untitled-2 untitled-2 untitled-2 jiims.cdr 52 headache is such a common disorder that its lifetime prevalence can safely be presumed to 100% in any population. in fact this is the commonest pain for which patients consult a doctor. humans are so much annoyed with this pain that they label every difficult problem as a “headache”. one of the punjabi proverb says, “bigger the head, bigger are the headaches” meaning people with more responsibilities have more problems to solve. human beliefs about headache and its treatment have been very interesting and human relation with headache dates back to 1 ancient times. about 7000 bc, people believed that headache occurred because of entrance of demons and evil spirits in head. they practiced trepanation (making a hole in skull bone) to release these spirits from head. neolithic skeletons have been found to have holes in their skulls. interestingly, at least some of these patients survived because of the evidence that some of these skulls had new bone formation at the edges of these holes. trepanning seems to continue till seventeenth century because in 1660, william harvey suggested trepanation to a patient who had intractable headache. around 1200 bc egyptians would bind a crocodile made of clay tightly around the head of headache patients. the linen with which this crocodile was tied displayed names of gods on it. it was believed that these gods would cure the headache. around 400 bc, hippocrates not only described aura of migraine as flashing light preceding headache, but also defined some of its triggering factors such as intercourse and exercise. he also believed that vapours arising from bile in the stomach rise to head to cause headache and that vomiting out of this bile relieve the headache. th in 12 century hildegard of bingen, a nun wrote a very vivid account of her headache. 1 she also made drawings of her visual aura. these manuscripts show that she was suffering from classical migraine. headaches are broadly classified into three 2 broad categories primary headaches secondary headaches and cranial neuralgias & other facial pains. most important in primary headaches are, among others, migraine, cluster headache and tension type headache. secondary headache is because of multiple causes, most common being intracranial tumors, aneurysms and giant cell arteritis. 3 fortunately most of headaches are primary , they are benign albeit very disturbing and annoying. they do not require extensive investigation. on the other hand, one should always remember that headache with serious sequel do occur. so which headache should be investigated is a very important question. why this question becomes important is because of following facts: headache being globally common, practically every human being will require investigation at some stage of life, if not filtered. investigations for headache are quiet costly so investigating every headache will not be a cost effective practice. investigations are unrewarding for editorial ------------------------------------------------correspondence: prof. ulfat bashir hod orthodontics department islamic international dental college islamabad headache who to be investigated? prof muhammad iqbal 53 most of primary headaches making it a futile exercise investigations per se are not free of harm, some of hazards are exposure to radiation, allergic reaction to contrasts, overdose of sedating drugs in case of claustrophobic patients undergoing mri etc. us headache consortium has laid down following principles for investigation of 4 headache. these principles are based on consensus, not any evidence. 1. testing should be avoided if it is not going to change the management of patient 2. testing is not recommended if patient is no more likely than general population to have a significant abnormality 3. exceptions can be made for individuals that are disabled for fears of serious pathology , even in the absence of known predictors of abnormalities on neuroimaging studies therefore people have identified certain features in history and physical examination which will help to identify patients who need further investigation. some of these featu res are t hunde rclap he ada che, headache with atypical aura, new onset headache in patients >50 years or <10 years, persistent morning headache with nausea, 5 p ro g re s s i v e l y w o r s e n i n g h e a d a c h e headache associated with postural change, headache in patients with cancer or hiv infection, history of head or neck injuy or weight loss. some abnormal physical findings like scalp tenderness, pyrexia, nuchal rigidity, pailloedema, abnormal mental status and neurological findings also 5,6,7 warrant for further investigation. apart from all above, there are at least two m o r e v e r y s t r o n g i n d i c a t i o n s f o r investigation of headache. they are patient's overwhelming concerns about his headache that are resistant to reassurance and physician's sixth sense feeling about probability of some serious underlying disorder. 1. lance j. history of headache. headache australia.org.au 2. headache classification subcommittee of i n t e r n a t i o n a l h e a d a c h e s o c i e t y. t h e international classification of headache nd disorders. 2 edition. cephalgia 2004;24(suppl 1):1-160. 3. rasmussen bk,jensen r, schroll m, oleson j. epidemiology of headache in a general population : a prevelance study. j clin epidemiol 1991; 44: 1147-57. 4. us headache consortium. evidence-based g u i d e l i n e s i n t h e p r i m a r y c a r e setting:neuroimaging in patients with nonacute headache 5. b a s h g u i d e l i n e s f o r a l l h e a l t h c a r e professionals in the diagnosis and management o f migraine, tension-type headache, cluster headache & medication-overuse headache 3rd e d (1st rev) 2010 6. de luca gc, bartleson jd. when and how to investigate the patient with headache. semin neurol. 30 2010. 131-44 7. bartleson jd. when and how to investigate the patient with headache. semin neurol. 2006 ;26:163-70. references: editorial social distancing and covid-19: is it ethical? noor-mah khan the cdc recommended social distancing of 6 feet in public and quarantine for exposed individuals for 1420 days at the start of the covid-19 pandemic. (centers for disease control and prevention) the vast history of public health validates the need and effectiveness of social distancing over the course of documented history. (qian 259-261) however, the widely debated question is whether it is ethical to impose the social and economic burdens that accompany social distancing, on the general population, in the midst of a pandemic such as covid-19? the value of imposing social distancing is not the conclusion of a debate rather the beginning of a very important discussion in the context of public health ethics. the burdens that come with social distancing fall disproportionately on different cohorts of society. while convenient for people in one domain of physical location, for example software engineers in the tech industry who have the privilege of working from home while having negligible effects on their work outcomes, it can take away the livelihood of a daily wage worker who has to go out every day in search of work and depends on engaging with strangers to be employed and earn a livelihood. this has highlighted the need of being sensitive to the distributive inequity associated with federal and public health policies related to policies regarding social distancing. the most important question we can bring up in trying to resolve this dilemma is to ask what do we as policy makers and public health professionals owe to the general public most affected by these policies? in trying to reach an answer, we need to categorize the individuals into two categories of harms incurred; the harm that an individual incurs in having to quarantine/isolate for a significant period of time and the harm the broader industries incur in having to implement social distancing as a policy. in trying to reach a balance where “fewest harms” are incurred, we need to address the responsibility that the government has towards the people. to lessen the socio-economic burdens of social distancing, we need to make sure that that person is cared for; food is provided, phone and internet is available for staying connected to loved ones, income is replaced and security is provided on an employer and government level. albeit a grand expectation, in my opinion it is not just the responsibility of the elected government but the due right of its people. the ethical theory of utilitarianism builds on the concept of consequential moral reasoning meaning the onus of reasoning relies on the consequence of the act. (sandel 31) it works to increase overall utility; defined as the net sum of pleasure over pain. (sandel 103) using the doctrine of utilitarianism in the context of the evident benefits of social distancing (qian), i believe imposing social distancing in a pandemic such as covid-19 is ethical. by forming policies to halt the spread of the virus, protect the most vulnerable in the society and attempt at containing a disease that little is known about in the setting of no vaccines or credible treatments, it is the overall beneficial choice to make. it aims to reduce death and debility of near ones, which is by far one of the most painful experiences humans can go through, it buys time for solutions to evolve, it helps people live long enough to figure a way past such a situation with minimal losses. for public health professionals and policy makers who find themselves consumed by the ethical dilemma of structuring and executing time-sensitive policies in a pandemic caused by a respiratory infection such as covid-19, they can take out a page from john rawls' book. john rawls created the thought experiment which he called, “the veil of ignorance” it is a moral reasoning method used to test whether an act is fair and impartial by disallowing the thinker to use any information that might potentially bias his/her decision in favor or against a certain people/situation. (huang) this experiment will allow the power holders to exercise a sense of consciousness when making policies and will help them analyze all their propositions through correspondence: dr. noor-mah khan mbbs, md 3585 monroe st, santa clara, ca95051, usa e-mail: noormahnk@gmail.com received: march 03,2022; accepted: march 14, 2022 1 2 the lens of fairness and justice. as rawls mentions, “ when addressing major decisions about the allocation of resources, we need only ask ourselves: 'how would i feel about this issue if i were stuck behind the veil of ignorance?” (huang) in the context of covid-19, it will help policy makers access the impartial state of the brain and allow them to reason beyond their position of privilege and from the point of view of the common man that makes up the larger part of the society. it will make it easier to help lead the population into a transitory phase of lockdown, ease their anxieties and provide for the basic necessities of living while socially distancing and isolating. it is important that policies such as social distancing, quarantine and isolation are imposed with the consciousness of distribution and its consequences. these policies need to be respected for the greater good and everyone's equal safety, provided that those people are given security of food, shelter, connection and financial and health coverage for that specified time. norman daniels wisely points out the matter of prioritizing the worse off and how it matters who is prioritized and how much. he also discusses how there is no sure way of knowing what is actually “just” and “fair” in allocating resources especially in settings such as a novel pandemic. norman daniels says and i quote, “ fairness is even more problematic because we don't have a criterion for what counts as fair and we have to accept the outcome of a fair process as what's fair.” (daniels 216) in a situation such as the outbreak of covid-19 and the ensuing pandemic, no government, public health officials or political party knew what to expect and how to go about imposing policies that were strict, safe and considerate enough for the general population. it was only after going through the process of forming and reforming policies while analyzing the outcomes on different strata of the society, did we get a clearer idea of the harms and benefits of the policies in short, 'the outcome of a process' regardless of the procedural fairness. daniels continues on to say, “ …how do we measure whether we get fairer decisions if we didn't have a prior agreement on what counts as fair? since we don't have that agreement we need a process but the outcome of that process might not comply with some people's judgements about fairness, and if so, what do we do about that and the answer is “i don't know.”” (daniels 2-16) in the case of mandating social distancing policies in covid-19, i agree with this statement. if we consider a collective societal and global benefit that may be gained through containing the spread of the virus, we need to consider that the policy will not be received well by all segments of the community and it might sit well with some while getting high criticism from others. in such a context, i believe, tying in the utilitarian perspective helps us justify this policy by arguing that as long as the benefit of the larger community outweighs the harm caused as collateral damage, the policies are fair. it is granted that no one policy can be the right policy. although it could be argued that it is every human's right to choose what they deem best for themselves, in a global situation such as a pandemic, it should also be weighed that one person's choice does not end up hurting other people's safety and health. thus, it is important that policies such as social distancing and isolation are respected for the greater good and everyone's equal safety. however, these avenues should only be employed provided that people are given security of food, shelter, connection with loved ones as well as financial, physical and mental health coverage for that specified time. governments need to plan ahead of time and be prepared to take on such a challenge if the need arises with the best interest of the people at its core. references 1. centers for disease control and prevention. “how to protect yourself & others.” cdc, https://www.cdc.gov/coronavirus/ 2 0 1 9 n c o v / p r e v e n t g e t t i n g s i c k / p r e v e n t i o n . h t m l . accessed 22 february 2022. 2. samuel k. “ treating persons as means (stanford encyclopedia of philosophy).” stanford encyclopedia of philosophy, 13 april 2019, https://plato.stanford.edu/ entries/persons-means/. accessed 22 february 2022. 3. qian m, jiang j. covid-19 and social distancing. z gesundh wiss. 2022;30(1):259-261. doi:10.1007/s10389-02001321-z. https://www.ncbi.nlm.nih.gov/pmc/articles/ pmc7247774/. 4. sandel mj. justice: what's the right thing to do. bul rev.2011; 91:1303. 5. daniels n. justice, health, and healthcare. american journal of bioethics. 2001 feb 1;1(2):2-16. 6. huang k, greene jd, bazerman m. veil-of-ignorance reasoning favors the greater good. proceedings of the national academy of sciences. 2019 nov 26;116(48):239899 5 . h t t p s : / / w w w. p n a s . o r g / d o i / 1 0 . 1 0 7 3 / p n a s . 1910125116#:~:text=the%20%e2%80%9cveil%20of%20ig norance%e2%80%9d%20is,least%20from%20the%20avail able%20options. jiimc 2022 vol. 17, no.1 jiims final.cdr 33 original article effects of lead toxicity on spermatogenesis in the testes of albino rats dr. saffia shaukat, dr. shabana ali, dr. fatima riaz abstract objective: the objective of this study was to observe changes in spermatogenesis in the testes of albino rats exposed to lead acetate. study design: an experimental animals study place of study and duration: this study was carried out in the department of anatomy, islamic international medical college rawalpindi and at national institute of health islamabad from january to april, 2009. materials and methods: male adult rats were exposed to lead acetate with intraperitoneal dose of 4mg/kg body weight for 5 days a week for 6 weeks. the animals in group a were used as control. the animals of groups b were treated with lead acetate with specified dose for 6 weeks. after 6 weeks the animals of subgroup b were sacrificed. the results of these two groups were then compared. results: after six weeks, it was observed that the number of spermatogenic cells had decreased in the test groups as compared with control group (p<0.05). conclusion: lead is toxic for cells of spermatogenic series, injurious to heaith and plays a significant role in reducing male fertility. key words: spermatogenesis, lead toxicity, rat fertility 3around 60 μgms/dl (khan, 1994) . lead is found in almost all agricultural food. lead present in air falls onto crops or soil which is absorbed by plants, thus entering the food chain and finally consumed by humans gaining entry into human blood (george, 41993). following are the major sources of lead:� i n s e c t i c i d e / p e s t i c i d e s p r a y s 5 (tollestrup, 1995). � lead can enter the water supply from lead solder in plumbing, lead service connections or lead pipes in home. lead is resistant to corrosion and hence old lead used as drains in the baths are still in service (lanphear, 62005). � lead based indoor and outdoor 7paints (lanphear, 1998). the study was carried out in the department of anatomy, islamic international medical college rawalpindi and national institute materials and methods introduction lead is a bluish-grey metal present in the earth's crust. it is one of the most ancient and commonest environmental pollutants, which has been reported to have caused damage in multiple body systems. it can be a cause of severe health problems such as high blood pressure, renal damage, nervous system breakdown, and anomalies in 1reproductive system (meyer, 2008). pakistan is a developing country. people here are specially exposed to lead pollution through three main sources i.e., air, soil, and 2water (rajendra, 1997). various researches carried out in pakistan, have stated that the majority of population has blood lead levels much above the internationally acceptable limits. another survey conducted in lead factory workers in pakistan showed blood lead levels hovering ------------------------------------------------dr. saffia shaukat, assistant professor anatomy department, iimct rawalpindi correspondence: 34 of health, islamabad. it was an analytical trial. the duration of study was 6 weeks. eight weeks old healthy male albino rats of sprague dawley strain weighing 200 ±10 gm. were selected for the study. a total of 30 adult male albino rats of sprague dawley strain were used in this study. these animals were randomly divided into two groups; one control (a)and one experimental group (b). the animals in group a (control) were given normal diet ad libitum. the animals in group b were treated with intraperitoneal lead acetate in the dosage of 4 mg / kg body weight / day, 5 days a week for a period of 6 weeks. these animals were sacrificed at the end of six weeks. all animals were kept in the animal house under standard conditions at a room temperature (180 c to 260 c) for six weeks. they were maintained on 12 hours light and dark cycle. the rats were fed ad libitum. day 0 was considered to be the starting day of experiment. pure lead acetate, taken from pharmaceutical laboratory in islamic international dental college (iidc), was used. it was purchased from the merck company (lot no. 107372). the temperature was maintained between 18°c to 26°c. the animals were sacrificed by an overdose of ether anesthesia. cotton soaked in ether was placed into the jar. the animal to be sacrificed was lifted by the tail and dropped into the jar. after sacrifice, the animal was taken out of the jar and placed on the dissecting board. the scrotal sac was then opened with the help of forceps and scissors. after fixation, histological sections were made and staining was done by haematoxylin and eosin. results fig.1: photomicrograph-section of testis of experimental group (group b) animal number 15, showing reduced germ cell count and reduced height of germinal epithelium. pas stain. x 420. fig. 2: photomicrograph; section of testis showing seminiferous tubule with normal germ cell count in group a, animal number 13, pas stain, x 400 data was entered in a data base using statistical package for social sciences (spss) for window version 13. the results were analyzed and considered significant with p value less than 0.05 (p <0.05) applying t test. only three cross sections of seminiferous tubules (randomly selected in different fields), were observed. total numbers of germ cells in the selected tubules were counted. histological examination: the following observations were made: number of spermatogenic cells/cross section of seminiferous tubule at 40 x. 35 germ cell count / cross section of seminiferous tubule) discussion the average germ cell count in group a was 304.53 cells/cross section of seminiferous tubule (sd + 28.46), in group b it was 116.91 cells/unit (sd + 32.66). the germ cell count was significantly higher in group a as compared to groups b (p < 0.001). (fig no. 1). the germ cell count was significantly lower in group b as compared to groups a (fig. 1) (p < 0.001). the present study was conducted to evaluate whether or not, lead has toxic effects in the rat's testes. for this purpose, albino rats of sprague dawley strain were selected. the animals were randomly divided into a control a and experimental group b. the animals of experimental group (b) were treated with intraperitoneal lead acetate in the dosage of 4 mg / kg body weight / day, 5 days a week for a period of 6 weeks. after 6 weeks, the animals of group b were sacrificed to see the toxic effects of lead in their testes. in lead toxic testes the seminiferous tubules decreased in size and had a wavy outline. the germ cell count was significantly reduced in group b, as compared to the control group a, which indicated the intensity of harm caused by lead on the cells of spermatogenic series. no effect on sertoli cells was observed. the population of leydig cells had become dispersed and they were sparingly seen in clumps. these findings are similar to those of chowdhury et al, saxena et al and hilderbrand et al.8, 9, 10. all these scientists described variety of toxic changes induced by lead in the testes depending upon dose and duration of the treatment which are in accordance with present study. at the end it is concluded that lead is injurious to the cells of spermatogenic series and the interstitial cells of leydig, while the sertoli cells are spared. chapin (2002) described in his study that cdc defines blood lead levels exceeding 10 micrograms/dl as elevated in children11. this may lead to cognitive and behavioral developmental changes. the researcher reported that lead induced reproductive abnormalities may occur in male rats at a dose as low as 10 μg/dl 11. manlay (1995) administered lead acetate to rats in the dose of 8mg/kg body weight, 5 days a week for 35 days 12. during past three decades, the decline in male reproductive health and fertility has been linked with environmental toxicants and xenobiotics. (sikka and wang, 2008)13. my present study validated the previous studies?, results and further added a new dimension to the existing literature by investigating lead-induced toxicity in the testes of sprague dawley rats. 1. meyer pa, brown mj, falk h. global approach to reducing lead exposure and poisoning. mutation research e pub 2008;50:166-75. 2. ramlogan a. environment and human health: a threat to all. environmental management and health, 1997; 8: 5166. 3. khan da, malik 1a, saleem m, hashmi r, bashir r. screening for chronic lead poisoning in lead factory workers. jpma1994;239-41. 4. george a. gellert ga. wagner, roberta m. maxwell, douglas m. faster i. lead poisoning among low-income children in orange county, california. jama 1993; 69-71. 5. tollestrup k, baling jr., allard j. mortality in a cohort of orchard workers exposed to lead references 36 a r s e n a t e p e s t i c i d e s p r a y. a r c h i v e s o f environmental health; 1995; 221-9. 6. lanphearbp. low-level environmental lead exposure and children's intellectual function: an international pooled analysis. environ. health percept 2005; 113: 894-99. 7. lanphear bp. matte td, rongers j. the contribution of lead-contaminated house dust and residential soil to children's blood lead levels. environment research 1998; 51-68. 8. eyden bp, maisin jr and mattelin g. long term effect of dietary lead acetate on survival, body weight and seminal cytology in mice. bull environ contam toxicol 1978; 19:266-72. 9. saxena dk, srivastara rs, lal b and chndra sv. the effects of lead exposure on the testis of growing rats. exp pathol 1987; 31: 240-52. jiims.cdr 74 original article abstract objective: to study the outcome of using improvised ventilating nasal packs compared with vaseline gauze packs in nasal surgery. study design: a comparative study. place and duration of study: department of ent, combined military hospital rawalpindi, from july 2011 to december 2012. materials and methods: one hundred and twenty patients undergoing nasal surgery were divided into two groups of sixty each. after surgery, group a was packed with improvised ventilating nasal packs and group b with vaseline gauze nasal packs. effects of nasal packs in both the groups were studied and compared in terms of control of bleeding, comfort level while in place, and discomfort level while packs were being removed. results: patient comfort level was significantly better in group a as compared to group b, while there was no significant difference in post operative bleeding control among the two groups. discomfort level while packs were being removed, was also similar among the two groups. conclusion: ventilating nasal packs provide a better alternative to conventional nasal packs in terms of patient comfort after nasal surgery, while they are as good in providing bleeding control. keywords: improvised nasal packs, nasal packing, ventilating nasal packs. from a few selected cases of septoplasty, where haemostasis can be achieved by stitching or fibrin glue, or other haemostatic agents, majority of cases require nasal packing as nasal packing provides 3 tamponade effect. it has been a long journey in search of an ideal nasal pack that not only controls b l e e d i n g , b u t a l s o c a u s e s m i n i m a l discomfort in terms of nasal breathing, good sleep and minimal pain and bleeding during its removal. traditional nasal packing methods using vaseline ribbon gauze or paraffin mesh may cause nasal obstruction, sleep disturbance, mouth dryness and adhesions formation due to the mucosal 4 abrasions caused by them. as these traditional packs do little in terms of patient comfort, especially patient is forced to breathe through mouth, they often result in an unsmooth recovery from anaesthesia, disturbance in sleep and distress. hence many innovations of nasal packs have been carried out to maintain nasal breathing so as 5 t o re d u c e p a t i e n t s ' i n c o n v i n i e n c e . ventilating nasal packs allow the patient to breathe through the nose thereby alleviating introduction nasal surgery is one of the corner stone's of o t o r h i n o l a r y n g o l o g y. i n t h e u s a approximately 600,000 patients underwent ambulatory sinonasal procedures in 2006 for 1 various nasal conditions. the foremost problem encountered after nasal surgery is bleeding, as nasal mucosa is one of the most vascular structures of the body being richly supplied both by the internal and external carotid system. hence post-operative nasal packing is required to control it. even if this bleeding is mild, it may clot resulting in adhesion formation. if the bleeding is severe, it may result in inhalation as well as swallowing causing aspiration and nausea 2 and vomiting respectively. but nasal packing is probably the most dreadful part of the nasal surgery from patients' perspective, as it results in discomfort causing nasal blockage and poor sleep while it is in place, and also causes severe discomfort while it is being removed. apart ------------------------------------------------comparison of improvised ventilating nasal packs with vaseline gauze packs in nasal surgery nasirullah khan, mirza khizer hameed, zeeshan ayub, muhammad junaid alam correspondence: dr. mirza khizer hameed ent deptarment combined military hospital, rawalpindi e-mail: mirzakhizar@yahoo.com 75 the patient's distress, resulting in smooth recovery from anaesthesia and offer better sleep as patient can breathe through nose. a l t h o u g h c o m m e r c i a l l y p r e p a r e d ventilating packs are available nowadays, but in our part of the world, the huge costs mark a question mark on their cost effectiveness. locally prepared ventilated nasal packs is not a new concept but has never been studied in our setup. therefore we carried out a prospective study to compare the improvised ventilating nasal packs with traditional gauze packs to see their effects in terms of post operative bleeding control, patients comfort while the packing was in place, and discomfort while removing the nasal packs. this study was carried out in ent department, combined military hospital rawalpindi from july 2011 to december 2012. a total of 120 patients undergoing nasal surgery were included in the study. patients were randomly divided into two groups a and b. group a consisted of patients who were postoperatively packed with improvised ventilating nasal packs, and group b patients were packed with t r a d i t i o n a l va s e l i n e g a u z e p a c k s . improvised ventilating nasal packs consisted of 9 cm long size 5 french endotracheal tube on which vaseline gauze was wrapped so as to give a cylindrical nasal pack with a breathing passage. they were secured by placing loose vaseline gauze around them. the traditional vaseline gauze pack consisted of 4 to 5 sheets of vaseline gauze rolled on it to form a cylindrical nasal pack. the packs were removed 24 hours after surgery. patients were observed in three parameters: 1. bleeding judged by any soakage/ change of pack 2. comfort level judged by comfortable sleep/ disturbed sleep 3. discomfort on pack removal, judged by pain/ bleeding. materials and methods the results were analyzed using spss 12. in this study one hundred and twenty patients were included. there were 31 females and 89 males in the study and ages varied from 18 to 55 years. mean for age in group a was 38 years (sd 7.5) and in group b was 41 years (sd 5.3). difference in bleeding control was found not to be significant using chi square test (p value > 0.05) as shown in table i. difference in comfort level was significantly better in group a (improvised ventilating pack) with p value< 0.05 as shown in table ii. difference in discomfort levels on pack removal was not significant with p value>0.05 as shown in table iii. results table i: bleeding episodes in patients (n=120) table ii: patient comfort level (n=120) table iii: pain on pack removal (n=120) 76 discussion nasal packing is routinely carried out primarily to control post operative bleeding, although some surgeons do not believe in 6 this concept. nasal packing currently being used consist of either vaseline gauze packs, finger glove stalls, or ribbon gauze packing. these packs though effective in stopping post operative bleeding but are extremely uncomfortable due to the fact that the patient is unable to breathe through the nose. furthermore these packs cause headache, throat dryness and local 7 discomfort. this study showed an excellent bleeding control in both these groups, probably bleeding control is more due to better packing technique rather than the nasal packing and the packing material. in our study we found that our improvised ventilating packs were superior to conventional vaseline gauze packs in terms of patient comfort as they reduced patients' inconvenience due to active nasal breathing. 8 similar results were shown by kim et al. but in other studies ventilating nasal packs are not found superior in maintaining 9 eustachian tube function. the ability to have a patent airway after nasal surgery is of the utmost importance as it provides a natural way of breathing, where as a blocked nose as in conventional nasal packs causes throat dryness and headache. in this study, discomfort in terms of pain and bleeding on removal of pack was not significant among both the groups. probably it was because of the material of the packing, as some packing materials like merocel packs cause much pain and bleeding when 10 removed. regarding materials to be used for nasal packing, biodegradable synthetic polyurethane foam has also found to be much superior as it causes less pain and 11 bleeding. commercially available ventilating packs like rapid rhino are available but when compared to improvised nasal packs the price is enormous. the ability to pack a patient's nostril helps the patient to breathe normally even though the patient has undergone nasal surgery. ventilating nasal packs provide a better alternative to conventional nasal packs in terms of patient comfort after nasal surgery, while they are as good in providing bleeding control. 1. bhattacharyya n. ambulatory sinus and nasal surgery in the united states: demographics and perioperative outcomes. laryngoscope 2010; 120: 635–8. 2. cruise as, amonoo-kuofi k, srouji i, kanagalingam j, georgalas c, patel nn et al. a randomized trial of rapid rhino riemann and telfa nasal packs following endoscopic sinus surgery. clin. otolaryngol 2006; 31: 25-32. 3. dhanasekar g, simmen d, briner hr. breathing straws. jlaryngol otol 2010; 124 : 73–4. 4. son km, yang jy, kim gb. the effect of nasal packing with rolled silastic sheet after closed reduction of nasal bone fracture. j korean soc plast reconstr surg 2011; 38 :602–8. 5. rhee sc, kim js. a simple method of fabricating nasal packing armed with ventilation tube. j craniofac surg 2008; 19: 1385–6. 6. orlandi rr, lanza dc. is nasal packing necessary following endoscopic sinus surgery?. the laryngoscope 2004; 114: 1541–4. 7. baig mn, malik aa, ajmal m, ashfaq ah. comparison of quilting of perichondrial flaps with routine nasal packing in patients undergoing septoplasty. rawal med j 2012; 37 : 187-90. 8. kim hy, kim sr, park jh, han ys. the usefulness of nasal packing with vaseline gauze and airway silicone splint after closed reduction of nasal bone fracture. arch plast surg 2012; 39 : 612–7. conclusion references 77 9. karahatay s, birkent h, demir d, ceyhan a, satar b. the effects of ventilated and non ventilated nasal packs on eustachian tube function: nine step inflation-deflation tests results. rhinology 2006; 44 :197-200. 10. acioglu e, edizer dt, yigit o, onur f, alkan z. nasal septal packing: which one? eur arch otorhinolaryngol 2012; 269: 1777–81. 11. moon sh, baek so, jung sn, seo bf, lee dc, kwon h. efficacy of biodegradable synthetic polyurethane foam for packing nasal bone fractures. j craniofac surg 2012; 23: 1848-50. 212 editorial recently discovered omicron: fifth wave of pandemic in pakistan. what strategies can be adopted to control its spread? prof. mulazim hussain bukhari since november 24, 2021, we are hearing about a new sars cov-2 variant of concern (voc) with 50 mutations (30 important) in spike proteins. “omicron” is the name given to it by who. literally th little “o” is the 16 letter of greek and b.1.1.529 is the name of the variant first detected in south africa, 1 botswana, in hiv patients. although, who first reported this variant of sarscov-2 on november 24, 2021, but originally it was reported in a specimen collected from a patient suffering from aids on november 9, 2021, in south africa. there is a lot of concern about more than 50 mutations in the new sars-cov-2 variant. the world is still waiting if it is more contagious, deadly, and will escape our existing 1-2 immunity due to previous infection or vaccines. it is believed that this new sars-cov-2 variant will spread all over the world very soon. it is likely that the virus may also reach pakistan in near future. who has learnt some lessons from the previous experience of sarscov-2; therefore, they are alert and vigilant to face the consequence of this new variant's spread. how bad will it behave? the r0 of this new variant is only 2 as compared to delta variant, which is 5-8. therefore, its possible spread is not expected to be as rapid as that of previous delta variant. at this stage, due to shortage of real-pathological/clinical data, we are unable to clearly predict the impact of this new variant on the covid-19 epidemiology. the world is already panic due to pandemic for the last 2 years and highly concerned about the efficacy of currently available vaccines against “omicron”, their side effects, and the requirement of booster doses. moreover, every new mutation in the virus further increases the concerns and worries of people as well as the healthcare providers. with this background the “omicron's” genetic profile has raised many concerns. it is spreading at a faster rate, but it is not possible to comment on the eventual consequences at this stage. if it is a milder virus, then there be less worries and let the people develop immunity against it. but as a pathologist, i believe, that it is not expected to cause much health problems by its rapid spread. why it has been included as a variant of concern (voc) by who? why who has kept it in the list of vocs like four previously identified alpha, beta, gamma, and delta variant, which appeared during this pandemic. we need to search the answers to the following questions before making an opinion about its future. · is there an increase in transmissibility or detrimental changes in epidemiology? · is there increase in its virulence or change in clinical presentation? · is there decrease in effectiveness of public health and social measure or available diagnostics, and vaccine effectiveness? 1-2 is there any increase in its transmission? we are looking at a mutation like delta on its spike proteins, which will enhance its efficiency of binding with ace2 receptor binding sites. one change p681h is at furin cleavage site (delta p681r), where enzymes tmpr ss2 will do its cleavage after attaching its s1 part of sp and will enable rapid fusion of s2 fusion site to ace2. on behalf of this, the binding affinity may be better and electromagnetic forces may be high. it takes one or more days for transmission and during that your immune system may ramp up. but the reported incubation period is prolonged, about up to 8 days, it means it is not a rapidly killing virus, better affinity does not mean, it is a more lethal virus. 1is it causing detrimental changes in epidemiology? 3 after its evolution from botswana, sa, the virus is now spreading to other countries of the world, but if we look on the world meter of covid-19, the correspondence: prof. mulazim hussain bukhari principal azad jammu kashmir medical college, muzaffarabad e-mail: mulazim.hussain@gmail.com received: november 05, 2021; accepted: december 05, 2021 department of pathology azad jammu kashmir medical college, muzaffarabad spreading it silently at home, during meals etc. therefore, the importance of following the sops like social distance, wearing face masks, frequent hand wash must be strictly observed. tiredness, muscle pain, fatigue and body aches are the more common symptoms. patients are mostly youngsters and recover at home in short period with less or no demand of oxygen. in older age group data is still not 5 clear. is there decrease in effectiveness of public health and social measure or available diagnostics and vaccine effectiveness? the changes in receptor binding domain which is interacting with ace2 are interesting and may raise the question about its escape from current available vaccines but still we are not looking such drastic change. all the changes are changing the dynamic of bindings of virus with ace2 receptors of human; they may make it more efficient? they may make the electromagnetic forces better. they may make them to be bad. they may make the phenotype be better and better fit or may make them? the 30 changes in sp and 20 others, which are making it voc, can make the virus unstable as who is expecting, and these changes may make the virus incompetent. vaccination and omicron the current vaccine is based on the important structural spike protein (sp) of the coronavirus. the sp is made up of 3831bp (1277 amino acids), while in “omicron” only 50 amino acids are changed, it means there is only 3.9% change in this new virus. while all other antigenic sites are like previous mother virus, therefore the available vaccines will still work against this strain. the people who have taken one dose must go for the second and those who have taken two doses about six months back, must go for the booster dose. what strategies can be adopted to stop the major mortalities in our population? the government of pakistan should increase the number of lab testing and the campaign of vaccination and booster dose, as it may prove to be a dangerous variant. hopefully, the vaccination will be effective against it. however, health authorities should be vigilant on the 'world tracing system' of its spread and all airports should be advised to take strict measures to reduce the escape of travelers without testing reports and follow up. it is also number of cases is not so much rapidly rising as we have seen with delta virus. the mutations like n679k, n501y, n679k, d614g, may enhance its ace2 binding affinity, with more infectivity, viral load and shedding of virus but still the cases are not advancing. we believe it will not cause any detrimental change in epidemiology. the currently available pcrs kits are still working to detect this new voc. many laboratories have indicated that for one widely used pcr test, one of the three target genes is not detected. it means there is s gene dropout or s gene target failure. this test can therefore be used as marker for this variant, pending sequencing confirmation. using this approach, this voc has been detected at faster rates than previous surges in infection, suggesting that this variant may have a growth advantage over previous mother virus. what is interesting is that the absolute increase in number is low and yet incubation period is seen as longer, which may perish it in future due to stability issues with large 50 mutations. is there increase in its virulence or change in clinical 1-5 presentation? there is still small data available to comment on this question, but based on current information, it has been observed that there are no increased cases of hospitalization, use of ventilators or admissions in icus. the daughter voc may behave aggressively, or it may be less efficient than the parent virus. on the available data from south africa, it has been learnt that the symptoms are entirely different from its other relative variants.there is some encouraging news and some mysteries are still associated with “omicron” symptoms. according to dr. angelique coetzee who is the chair of the south africa medical board and a practicing gp in pretoria, the symptoms are extremely mild. symptoms of this new variant are not clear, however in reported cases they are like previous south african variant and the beta indian variant. anosmia is not present, so it means it is not affecting olfactory bulbs. taste is also present. neurological symptoms may also be less, and long haul may not be there. there is no or very mild cough and only some mild scratchy throat symptoms, indicating less damage to the epithelium, so the direct spread is less. but as the patient is not aware of the disease, due to fewer symptoms so he may be 213 jiimc 2021 vol. 16, no.4 fight this voc, more definite information will reach in about 2 weeks. references 1. new covid variant: will new measures against omicron work? bbc. https://www.bbc.com/news/health-59448438. 1.12.2021 2. classification of omicron (b.1.1.529): sars-cov-2 variant of concern.https://www.who.int/news/item/26-11-2021classification-of-omicron-(b.1.1.529)-sars-cov-2-variant-ofconcern. 1.12.2021 3. voc omicron gr/484a (b.1.1.529) first detected in b o t s w a n a / h o n g k o n g / s o u t h a f r i c a . https://www.gisaid.org/hcov19-variants/. dated 1.12.2021 4. new virus variant stokes concern but vaccines still likely to work.https://www.nytimes.com/2021/11/26/health/omic ron-variant-vaccines.html. dated 1.12.2021 5. d r. c o e t z e e ' s i n t e r v i e w i n n e w s r o o m a f r i c a : https://youtu.be/zizwtcrjpay. dated 1.12.2021 important to ban the travel from the african countries to reduce the spread of virus to our country (e.g., usa, uk, canada, european union, and russia have already taken such steps). conclusion there are some encouraging news, that the new variant is infecting the youngsters and symptoms are very mild. the rate of infected people is increasing with this new voc, but the absolute number of cases are not rising. we must see the clinical outcomes, how rapidly are the patients deteriorating and becoming worse. it is not hugely damaging virus as compared to delta and the large number of mutations will make the virus unstable. it may not spread to the world like south african's previous beta and brazilian's p1 variants as initially feared the world. but we should remain prepared to jiimc 2021 vol. 16, no.4 214 original�article� abstract bilateral rectus sheath hematoma secondary to dengue fever is very rare. mainstay of treatment is conservative. surgical intervention is reserved for those who have expanding hematomas, infected hematomas, persistent pain, hemodynamic instability, etc. we present a rare case of spontaneous bilateral rectus sheath hematoma in a patient with dengue fever. patient was initially managed conservatively, and later drainage of bilateral rectus sheath hematoma was performed. key words: dengue fever, hematoma, rectus sheath. case a 39-year-old female with no known co-morbidities presented in emergency department with three days history of fever, epistaxis, heavy menstrual bleeding, lower abdominal fullness and pain. at presentation patient was tachycardiac, febrile and tachypneic. lower abdomen was mildly tender, more on left side as compared to right. patient had hemoglobin (hb) of 11.6 g/dl, white blood cells (wbcs) 2.14 x 103 /ul, 3 platelets count of 41,000 x 10 /ul, prothrombin time 11 seconds (control 10.8 seconds), activated partial thromboplastin time (aptt) 27.3 seconds (control 27 seconds) and international normalized ratio (inr) of 1. dengue virus non-structural protein 1 (ns1) antigen was positive while liver function tests were normal. ultrasound revealed 10.9ml left rectus sheath hematoma (rsh). after 12 hours of admission 3 patient had platelets count of 42000 x 10 /ul and hb of 9.7 g/dl while remaining hemodynamically stable. on second day morning platelets increased to 93000 3 x 10 /ul while hb decreased to 7.7 g/dl. a ct scan abdomen and pelvis with intravenous contrast was performed that showed hematoma involving bilateral rectus muscle measuring 9.7 x 6.5 cm on right side and 9.3 x 5.9 cm on left side (arrows in figure 1a, 1b and 2). there was no active bleeding from epigastric vessels a rare case: spontaneous bilateral rectus sheath hematoma in a patient with dengue fever muneeb ullah, aqsa adeel, adil shafi, muhammad faisal murad correspondence: dr. muneeb ullah assistant consultant department of surgery maroof international hospital, islamabad e-mail: muneebullah@gmail.com department of surgery maroof international hospital, islamabad received: february 04, 2022; revised: november 02, 2022 accepted: march 06, 2023 spontaneous bilateral rshjiimc 2023 vol. 18, no.1 figure 1a: ct scan (sagittal section) with red arrow showing right rectus sheath hematoma figure 1b: ct scan (sagittal section) with green arrow showing left rectus sheath hematoma figure 2: ct scan (axial section) image showing right (red arrow) and left (green arrow) rectus sheath hematoma or contrast extravasation, so the patient was continued on conservative management and blood products transfusion. at night hb was repeated and it came out to be 8.9 g/dl. follow up ultrasound on day three showed no interval increase in size of hematoma and a platelet count of 180,000 /ul. patient was discharged on day five after conservative management and followed up on outpatient basis. 75https://doi.org/10.57234/jiimc.march23.1275 patient remained well for four days at home and presented to us on day five with fever and lower abdominal pain for last 24 hours. patient was tachycardiac and had tenderness in lower abdomen. 3 hb was 9.8 g/dl with raised wbcs of 13.3 x 10 /ul. creactive proteins test was also raised (70mg/dl). patient had interval increase in rsh, 440ml on left side (figure 3) and 275ml on right side (figure 4). hemostasis, wound was kept open and daily dressings were continued. patient was discharged on day three and injectable antibiotics (tazobactam + piperacillin and metronidazole) were continued for two more days. patient was then shifted to oral antibiotics for five days according to culture sensitivity report. patient remained well and was completely settled in further three weeks. introduction dengue fever is a viral illness common in tropical and 1,2 subtropical regions of the world. it has four serotypes and it is transmitted to humans by bite of [1,3] aedes mosquito. the disease ranges from asymptomatic to serious dengue hemorrhagic fever or dengue shock syndrome that may cause bleeding 4 into retroperitoneal tissues or gastrointestinal tract. bleeding is due to complex pathophysiological pathways involving vasculopathy, thrombopathy and 5,6 disseminated intravascular coagulopathy. in very rare cases it may cause rectus sheath hematoma which is an uncommon disease itself. rsh may occur due to tear in rectus muscle or bleeding from 7 epigastric vessels. rectus sheath is deficient below arcuate line in abdomen so hematomas below the 8 arcuate line have the tendency to expland. it presents as abdominal pain or palpable abdominal 7,9 mass or fullness. predisposing factors for rsh include anticoagulation, old age, female gender, pregnancy, trauma, iatrogenic injury, intramuscular injection, hypertension, hematologic disease, 9,10 coughing or strenuous physical activity. the mainstay of treatment is conservative management. conservative management includes intravenous hydration, blood products transfusion, vitals and i n p u t o u t p u t m o n i t o r i n g , s t o p p a g e o f anticoagulation, etc. in case of hemodynamic instability, persistent pain, infective process or neurologic deficit, intervention is required. 11,13 intervention can be angioembolization or surgery. rectus sheath hematoma secondary to dengue fever is uncommon and in literature only few cases are 5 reported. bilateral rsh are even rarer. we discuss a case of spontaneous bilateral rectus sheath hematoma secondary to dengue fever requiring surgical intervention. discussion rsh associated with dengue fever is rare and only a few cases of bilateral rectus sheath hematoma figure 3: ultrasound image showing left rectus sheath hematoma (arrows) a (blue) transverse view b (red) longitudinal view figure 4: ultrasound showing right rectus sheath hematoma (arrows) a (red) longitudinal view b (blue) transverse view patient was admitted and bilateral separate incision and drainage of infected expanding hematoma was performed under spinal anesthesia. about 400ml hematoma was drained on the right side and 200ml hematoma was drained on the left side. specimen for culture sensitivity was sent. after securing spontaneous bilateral rshjiimc 2023 vol. 18, no.1 76 https://doi.org/10.57234/jiimc.march23.1275 5 complicated by dengue fever are known to date. bleeding complications in dengue hemorrhagic fever patients result from combination of thrombocytopenia, increased vascular fragility, increased fibrinolysis, immunological disturbance and unbalance between pro-coagulation and anti5,13 coagulation. persistent thrombocytopenia was seen in our patient. our patient presented with fever, abdominal fullness, leucopenia, and thrombocytopenia which is usual presentation of a 9,10 dengue fever patient with rsh. literature review shows female predisposition attributed to lesser 5,12 muscle mass, as was our case. ultrasound abdomen is the initial radiological investigation of choice. ct scan with intravenous contrast is superior to ultrasound since it gives accurate identification of bleeding vessels, contrast extravasation, hematoma, 7,13 its size, and extent. it has the disadvantage of need to transfer to ct room, radiation exposure and contrast induced nephrotoxicity. mri is superior to ct scan but needs more time. for mri our patient needed to be transferred to nearby facility due to non-availability at our setup and additionally our patient was claustrophobic. therefore, ct scan with intravenous contrast was performed to know the exact details of bilateral rsh, contrast extravasation, hemoperitoneum, hematoma size and extent. our patient was initially managed for dengue fever and rsh conservatively, including intravenous hydration, analgesia, blood transfusion and platelets transfusion. platelets transfusion is based on individual case, but transfusion is usually considered 5 when levels fall below 50,000 /ul. later expanding hematoma with fever and pain required surgical intervention in the form of bilateral incision and 7,12 drainage of hematoma. angioembolization is reserved for cases where active bleeding epigastric vessels are identified as well as the availability of interventional radiology services. conclusion dengue fever in complicated cases can present with rsh. these patients should be admitted and kept on strict observation. ct scan is the investigation of choice. rsh can be managed by conservative management. surgical intervention should be reserved for cases with expanding hematoma, infected hematoma, or hemodynamically unstable patients. outcomes are usually good with proper management. references 1. yue y, liu x, ren d, wu h, liu q: spatial dynamics of dengue fever in mainland. china, 2019. int j environ res public health. 2021, 18:2855. 10.3390/ijerph18062855 2. chan eyy, lo esk, huang z, lam hcy, yeung mp, kwok k et al.: sociodemographic predictors of knowledge, mosquito bite patterns and protective behaviors concerning vector borne disease: the case of dengue fever in chinese subtropical c i t y , h o n g k o n g . 2 0 2 1 , 1 5 : e 0 0 0 8 9 9 3 . 10.1371/journal.pntd.0008993 3. sarker mmr, khan f, mohammed in: dengue fever: therapeutic potential of carica papaya l. leaves. front. pharmacol. 2021, 12:610912. 10.3389/fphar.2021.610912 4. pan c, liu w, su m, chang t, ho h, shu p et al.: epidemiological analysis of the kaohsiung city strategy for dengue fever quarantine and epidemic prevention. bmc infect dis. 2020, 20:347. 10.1186/s12879-020-4942-y 5. rosa ct, navinan mr, samarawickrama s, hamza h, gunarathne m, arulanantham a et al.: bilateral rectus sheath haematoma complicating dengue virus infection in a patient on warfarin for mechanical aortic valve replacement: a case report. bmc res notes. 2017, 10:26. 10.1186/s13104-016-2330-x 6. anam am, rabbani r, shumy f: spontaneous calf haematoma in severe dengue. bmj case rep. 2018, 2018:bcr2017222932. 10.1136/bcr-2017-222932 7. pierro a, cilla s, modugno p, centritto em, filippo cmd, sallustio g: spontaneous rectus sheath hematoma: the utility of ct angiography. radiol case rep. 2018, 13:328332. 10.1016/j.radcr.2018.01.016 8. karapolat b, tasdelen ha, korkmaz hca: conservative treatment of spontaneous rectus sheath hematomas: single center experience and literature review. emerg med int. 2019, 2019: 2406873. 10.1155/2019/2406873 9. bello g, blanco p: giant rectus sheath hematoma. ultrasound j. 2019, 11:13. 10.1186/s13089-019-0129-4 10. nizam a, dua a, hameed t, jain sk: spontaneous rectus sheath hematoma masquerading as acute abdomen. a case report. maedica (bucur). 2020, 15:412-415. 10.26574/maedica.2020.15.3.412 11. landecy m, paquette b, revel l, behr j, badet n, delabrousse e: does iv contrast extravasation on ct in anticoagulant-related rectus sheath and iliopsoas hematoma predict hematoma expansion and patient outcomes? . abdom radiol (ny). 2016, 41:2241-2247. 10.1007/s00261-016-0818-4 12. hoe v, kinnear n, christidis d, o'connell h: rectus sheath haematoma causing ureteric obstruction. bmj case rep. 2018, 2018:bcr2018225671. 10.1136/bcr-2018-225671 13. nelwan ej, angelina f, adiwinata r, matondang s, andriono p: spontaneous rectus sheath hematomas in dengue hemorrhagic fever: a case report. idcases. 2017, 10:35-37. 10.1016/j.idcr.2017.08.004 spontaneous bilateral rshjiimc 2023 vol. 18, no.1 77https://doi.org/10.57234/jiimc.march23.1275 conflict of interest authors declared no conflicts of interest. grant support and financial disclosure authors have declared no specific grant for this research from any funding agency in public, commercial or nonprofit sector. data sharing statment the data that support the findings of this study are available from the corresponding author upon request. this is an open access article distributed under the terms of the creative commons attributionnoncommercial 2.0 generic license. spontaneous bilateral rshjiimc 2023 vol. 18, no.1 78 https://doi.org/10.57234/jiimc.march23.1275 original�article abstract objective: to assess the perception of students regarding the usefulness of formative assessments. study design: cross-sectional descriptive study. place and duration of study: islamic international medical college, from january to june 2015. materials and methods: a structured questionnaire was distributed to 150 medical students. response rate was 90%. there were six questions regarding the scheduling, strategy and components of formative assessment while four questions were regarding the effectiveness of formative assessment in learning. results: it was found out that majority of the students (60%) were satisfied with placement of formative assessments in each module while 76.3% agreed that assessment were arranged regularly, though 22% disagreed with assessment plan. about 64 % students agreed that it facilitates learning process and motivates students to learn more. on the other hand only 20% students disagreed with its role in learning. feedback and remedial were relatively weaker as only 33 % students thought that feedback was effective and timely while most of students disagreed but were satisfied with remedial offered by each discipline. conclusion: the medical students consider formative assessment an important tool to enhance their learning process. more efforts are required to enhance the usefulness of formative assessments by improving the quality of feedback and the remedial offered for improvement. key words: assessment, constructive feedback, learning, remedial measures. 2 a suitable curriculum. later on allal and lopez traced the history of formative assessment from scriven's original definition of “formative evaluation” of educational programs, found out that term “assessment” had “progressively replaced ‘evaluation’ during 1967. benjamin bloom used the term in 1968 in his book learning for mastery and he described the role of formative assessment as a tool for improving the teaching-learning processes for students and how it can be accommodated in 3 content. formative assessment is the only mean by which subsequent educational decisions can be altered. the true purpose of formative assessment is fulfilled when it is applied on a frequent and regular basis to see students’ progress and understanding and helps to identify their learning needs and adjusting the teaching appropriately. it is a midstream tool that is used by teachers to measure student understanding of specific topic or skill they are teaching. formative assessment is said formative because it leads to adjustments according to learners need to form new learning because every formative assessment is followed by feedback provided to students regarding their performance and taken from students regarding content, learning and teaching strategies etc. therefore it helps teacher to adjust or modify their learning strategy and student introduction formative assessment is the process used by teachers and students to recognise and respond to students’ learning in order to enhance learning. it helps in learning by generating feedback information that is beneficial for both students and teachers. it is suggested that feedback enables students to reconstruct their understanding and skills and hence improve their performance. rick stiggins concluded “most of the teacher change their instructional strategy according to the demand of the students or modify their teaching modalities according to their 1 students' needs, hence owning their own learning”. michael scriven derived the term in 1967, during those times information gathered through formative evaluation was used to assess the effectiveness of a curriculum and guide school system choices to adopt students' perception of formative assessment at iimc 1 2 3 komel zulfiqar , shabana ali , amena rahim correspondence: dr. komal zulfiqar assistant professor, community medicine islamic international medical college riphah international universiy, islamabad e-mail: komal.zulfiqar@riphah.edu.pk 1 2 department of community medicine/ anatomy / 3 biochemistry islamic international medical college riphah international universiy, islamabad funding source: nil; conflict of interest: nil received: aug 19, 2016; revised: mar 06, 2017 accepted: mar 06, 2017 formative assessment at iimcjiimc 2017 vol. 12, no.1 55 results response rate was 90% as 135 filled questionnaires were received. results were analyzed by using spss 21 for each while compiling the results male to female ratio was ignored. most of the students (60%) were satisfied with placement of assessments in each module by concerned disciplines. however 76.3% agreed that formative assessment were arranged regularly by each discipline although 22% disagreed with assessment plan. about 64 % students agreed that it always facilitates learning process and it also motivates students to learn more. on the other hand only 20% students disagreed with its role in learning. however very few number of students i.e. only 33% agreed that feedback was provided to them in time and remedial measures offered in each discipline were helpful in their learning. to improve their learning by provision of timely, 4 frequent and constructive feedback. this feedback h a s st ro n g i n f l u e n c e o n st u d e nt ' s f u t u re performance since it closes the gap between current and desired performance and delivers high quality information to students about their learning. it also 5 encourages and motivates student. at islamic international medical college, formal introduction of formative assessments in the modules was incorporated about two years ago, with the aim to support students learning. purpose of t h e s e a s s e s s m e n t s w a s t o e m b o d y t h e programmatic model of assessment in the students’ 6 curriculum. programmatic assessment model is based on the concept that arranged set of longitudinal assessment activities should be incorporated in order to enhance the effectiveness of formative assessments. every formative assessment must be complemented by certain assessment points which must be aggregated 7 towards the final or summative assessments. one important and critical component of formative assessment is the feedback which is used by students at one end to find out their deficiencies in their learning and teachers to tailor the teaching and learning strategies according to learners need at the other end. materials and methods this was a quantitative cross-sectional study. a structured questionnaire was designed on five point likert scale and construct validity was assured by expert opinion of four medical educationists. purposive sampling technique was applied for collection of data. fifty students each from 1st, 2nd and 3rd year mbbs students were selected randomly without the discrimination of gender. fourth year and final students were not included since these students were not available at basic science campus due to clinical rotations. students included were regularly taking their formative assessments. the students filled questionnaire in a given time. all the participants were given ten minutes to complete the questionnaire. questions were asked under three themes. ! the placement of formative assessments in each modules ! role of formative assessment in their learning ! effectiveness of feedback table i: frequency of students response on usefulness of forma�ve assessment es�mated by using 5-point likert scale (n=135) discussion formative assessment is strongly emphasized over summative assessment in a competency-based education program. it underscore the development of proficiency through conscious practice. this concept underlines the need for effective instruction, mentoring, and feedback to the students. the content, plan, rate and timing of assessment are important factors to establish an 8 assessment policy in any medical school. this study was designed to evaluate the process of formative assessment and perception of student' formative assessment at iimcjiimc 2017 vol. 12, no.1 56 therefore, formative assessment can be used in medical education to assess need, progress of medical students and to recognize and remediate the suboptimal performance of students. the optimum placement of formative assessment in each module for each subject with properly arranged effective constructive feedback to students may provide students to improve their learning. recommendations ! implementation: it should be the integral part of program design. it should be implemented gradually but consistently. ! enabling environment: the institution should provide an environment which nurtures the development of faculty and create awareness about need of formative assessment. ! faculty training: faculty should be trained to construct creative methods of assessment and to give timely and quality feedback. it has maximum effect on student's learning and future 14 performance. ! student's training: students must be informed about formative assessment and reason why it is carried out. they should know how to receive feedback and improve their weaker areas. ! student's feedback: it should be taken in routine to check the effectiveness of formative assessment in developing their concepts, modifying the way of delivery of content. ! role of department of medical education: they should incorporate formative assessment in curriculum without compromising the content. ! periodic evaluation of curriculum: regular formative assessment feedback given and taken from students may help in evaluation of 15 curriculum. conclusion expanded use of formative assessment should be followed by prompt feedback, and stress on remedial measures in order to enhance usefulness of formative assessments. references 1. david n, debra md. rethinking formative assessment in he: a theoretical model and seven principles of good feedback practice. studies in higher education. 2005; 50: 29-31. 2. william, dylan. "formative assessment: getting the focus right”. journal of educational assessment. 2006; 11: 283–9. regarding its usefulness in learning. study revealed that accurate and proper placement of formative assessment is assured in each module, but improvement in effective feedback with remediation offered is utmost need of the students. nijhuis et al. specified three elements of the learning environment which may affect student's learning. these elements are lucidity of the goals, aptness of the workload and the usefulness of the literature. the surface learners recognize these elements 9 negatively. academic reporting of achieved competencies has amplified the perplexity and decreased the motivation to learn in students. the current system of summative assessment encourages the students to find only right answers but opposes the true learning process. learning is not merely the collections of right and wrong facts. regular formative assessments have a greater impact on academic achievements in students. it entails the students about their deficiencies in studies. therefore proper scheduling of assessment is important. regular formative assessment (76.3%) in every module will facilitate learning process. the students get motivated (63.7%) to become involved in the learning process as it helps to promote their growth. regular formative assessment also increases the learning of students (63.7%) and hence the academic achievements as it guide them to the path of accomplishments. it has a great impact on student academic success, especially in constant low 10 achievers. feedback is taken for granted but it helps in selfcorrection and improvement. indirect forms of feedback maintain student motivation and 11 selfconfidence. it should be precise, positive, 12 encouraging, and frequent and substantial. successful feedback should clearly specify to the student what is wrong and right. effective feedback may be considered as a single most important tool 13 for professional development of students. the timely feedback was overlooked (33.3%) and was irregularly given (43%) to students. clear and suitable assessment criteria shall be given to the students to judge their own progress during taking the remedial. formative assessment assists the students to realize the standards that teachers may expect from them. formative assessment at iimcjiimc 2017 vol. 12, no.1 57 9. epstein mr, assessment in medical education. n england j med. 2007; 356: 387-96. 10. nijhuis jfh, segers msr, gijselaers whm. influence of redesigning a learning environment on student perceptions and learning strategies. learning environment research. 2005; 8: 67–93. 11. black p, harrison c, lee c, marshall b, william d. working inside the black box: assessment for learning in the classroom. journal phi delta kappan. 2004; 86: 8-21. 12. shepard la. the role of assessment in a learning culture. educational researcher. 2000; 29: 4-14. 13. yorke m. formative assessment in higher education: moves towards theory and the enhancement of pedagogic practice. studies of higher education. 2003; 45: 477–501. 14. hattie j, timperley h. the power of feedback. journal of educational psychology. 2007; 77: 81–112. 15. norcini jj. setting standards on medical education. blackwell publishing ltd medical education. 2003; 37: 464–9. 3. bloom bs, hasting jt, madaus gf. handbook of formative and summative evaluation of student learning. new york, usa: mcgraw-hill. 1971; pp: 923. 4. kluger an, denisi a. the effect of feedback interventions on performance: a historical review, a meta-analysis, and a preliminary feedback intervention theory. psychological bulletin. 1996; 119: 254-84. 5. masood a, hameed fm. formative assessment for undergraduate medical student. jiimc. 2014; 9: 56-8. 6. van der vleuten cpm, schuwirth lwt, driessen ew, dijkstra j, tigelaar d. a model for programmatic assessment fit for purpose. medical teacher. 2012; 34: 205–14. 7. butler r. task-involving and ego-involving properties of evaluation: effects of different feedback conditions on motivational perceptions, interest and performance. journal of educational psychology. 1987; 78: 210-6. 8. ericsson ka. an expert-performance perspective of research on medical expertise: the study of clinical performance. med education. 2007; 41: 1124–30. formative assessment at iimcjiimc 2017 vol. 12, no.1 58 jiimc december 2016 page 59 page 60 page 61 page 62 jiims final.cdr 3 original article results of myringoplasty in chindren: a comparison with an adult population muhammad azeem aslam, danyal rashid, ashfaq ahmed introduction myringoplasty in adults is now considered to be well established and rewarding 1procedure with high success rate but controversy still surrounds the advisability 2of tympanic membrane repair in children. the main concern regarding paediatric myringoplasty is that the child has an increased susceptibility to upper respiratory tract infections and eustachian tube dysfunction as compared to an adult leading 3to recurrent middle ear infection. this may j e o p a rd i z e t h e re s u l t s o f t y m p a n i c membrane grafting.moreover, tympanic membrane perforation may favor the child with poor eustachian tube function as it provides ventilation to middle ear resulting in decreased likelihood of development of 4,5effusion in it. if tympanic membrane grafting is done in these children with poor tubal function, negative pressure will develop in middle ear resulting in graft medialization or retraction minimizing the benefits of surgery. all these reservations about paediatric myringoplasty appear to be valid but we must take into account the effects of recurrent middle ear infections and decreased hearing associated with tympanic membrane perforation. childhood is a 6period of active learning and socialization. impaired hearing at this stage of active intellectual growth can be detrimental to 6child education and socialization. at the same time, repeated infections in the middle ear will further damage the hearing abstract objective: to find out validity of myringoplasty in children by comparing its anatomical and functional results with adult myringoplasty. study design: a descriptive cross sectional study place and duration of study: department of otolaryngology and head and neck surgery at a tertiary care teaching hospital in rawalpindi from january 2007 to december 2010. materials and methods: a total of 89 patients having dry central tympanic membrane perforation of various sizes secondary to chronic tubotympanic suppurative otitis media were included in the study. the patients were divided in two groups. first group comprised of children upto the age of 14 years whereas those above the age of 14 years were included in second group. myringoplasty was performed in all patients with temporalis fascia utilizing underlay technique. the two groups were compared regarding graft success rate and hearing improvement at the end of 6 months of follow up. results: out of 89 patients included in the study, 37 (41.6%) belonged to child group whereas 52 (58.4%) were included in adult group. among 37 patients in child group, 34(91.8 %) had successful graft take at the end of 6 months of follow up whereas 47 (90.3 %) patients out of 52 in adult group had successful graft. average air bone gap closure of 13.5 db was noted in child group whereas in adult group it was 12.5 db. the difference between graft success rate and average air bone gap closure was found to be statistically insignificant (p>0.05). conclusion: results of myringoplasty in paediatric and adult age group are comparable in terms of graft success rate and hearing improvement. key words: myringoplasty, tympanic membrane, paediatric, middle ear ---------------------------------------------------correspondence: dr. muhammad azeem aslam house no. 57, main road, sector g-8/2, islamabad. e-mail drazeemaslam@gmail.com phone: 0333 5131237 4 mechanism. in this study, we tried to solve the controversy regarding advisability of paediatric myringoplasty by comparing the results of tympanic membrane grafting in children to that of adults. t h i s s t u d y w a s c o n d u c t e d a t t h e department of otolaryngology and head & neck surgery at a tertiary care teaching hospital in rawalpindi during the period of january 2007 to december 2010. a non probability purposive sampling technique was adopted by including all patients coming to outpatient clinic of our department with dry central tympanic membrane perforation secondary to chronic tubotympanic suppurative otitis media, irrespective of age and gender. a detailed history was taken and thorough ear nose throat examination was done. all patients were examined under otomicroscope and findings were recorded in a pre-designed performa. the information obtained was age and sex of patient, duration of disease, size of tympanic membrane perforation, status of middle ear mucosa and ossicles, previous ear surgery and nasal complaints. patients with chronic rhinosinusitis, prior ear surgery, atticoantral type of disease were excluded from the study. pure tone audiometery with air and bone conduction threshold was done in all patients. patients selected according to the above mentioned criteria were divided in two groups according to age. first group comprised of children up to the age of 14 years and the second group consists of patients above 14 years of age. all the patients underwent myringoplasty under general anesthesia materials and methods using post aural approach and underlay technique of tympanic membrane grafting. post operative antibiotic cover was given for 5 days. patients were discharged on second postoperative day and were followed up after three weeks when bismuth iodoform paraffin paste pack was removed from the external auditory canal. status of graft (full take or failure) was noticed on that visit. they were then followed up at monthly interval for up to at least 6 months. during that period, they were observed for graft success. at the end of 6 months of follow up, pure tone audiogram with air and bone conduction thresholds was repeated. both groups of patients were compared in terms of graft success rate (anatomical gain) and hearing improvement (functional gain). graft take was defined as full, intact healing of tympanic membrane graft at 6 months postoperatively. hearing improvement was reviewed as the change in air-bone gap at the end of six months follow up period. gap change was defined as the difference between the pre and postoperative air-bone gap. air-bone gap was calculated as the average difference between air conduction and bone conduction at 0.5, 1 and 2 khz. results were statistically analyzed using spss version 10.0. chi square test was performed to find out the difference between graft success rates of both the groups. pre and postoperative air-bone gap change in db between the two groups was analyzed by using t test. statistical significance was accepted as p<0.05. a total of 89 patients fulfilled the inclusion criteria between january 2007 to december 2010. thirty seven of them, up to the age of results 5 14 years, were included in child group whereas 52 having more than 14 years of age w e r e i n c l u d e d i n a d u l t g r o u p . demographics of both the groups are shown in table i. average follow up duration was 8.8 months (range 6 to 29 months). graft success rates and hearing improvement (air-bone gap closure in successful graft) in both the groups are shown in table ii. the difference between graft success rate and air-bone gap closure in two groups were found to be statistically insignificant (p >0.05). overall hearing improvement was noted in all patients of both groups except those who met with graft failure. table-i: demographics of child and adult group child group adult group total no. of patients in each group 37 (41.6%) 52 (58.4%) male female mean age (years) age range (years) average duration of disease (years) size of tympanic membrane perforation 19 (51.4%) 18 (48.6%) 13 6 to 14 7.6 (1 to 13 small = 3 medium = 25 large = 9 16 (30.8%) 36 (69.2%) 28.5 15 to 57 12.5 (0.5 to 35) small = 1 medium = 32 large = 19 table-ii: graft success rates and air bone gap closure in both groups graft success rate child group n = 37 34 (91.8%) 47 (90.3%) 13.5 (range 5 to 33.3 12.5 (range 3 to 24) adults group n = 52 average air-bone gap closure (db) 6 discussion myringoplasty in children is still a controversial issue. although a number of studies appeared in literature on this subject in the recent past but opinions still differ on this subject. in the present study, we tried to solve this controversy by comparing the results of paediatric myringoplasty with that of same procedure in the adults. we obtained graft success rate of 91.8% in children between the ages of 6 to 14 years. comparable graft success rate (90.3%) were achieved in adult patients (> 14 yrs) utilizing the same underlay technique and graft i.e., temporalis fascia. the difference between graft success rates was statistically not significant. these results are similar to certain other studies in which adult and pediatric myringoplasty results were 7compared . in literature, we find wide variations between the graft success rates of paediatric m y r i n g o p l a s t y r a n g i n g f ro m 3 5 t o 8,9,10,11100%. one local study reported graft success rate of 72.96% at six months of follow up in a study of thirty cases of paediatric myringoplasty in children less 12than 18 years of age. another study reported graft success rate of 88% at one year of follow up, in 100 cases of myringoplasty performed in children less than 14 years of 13age. in another study of 231 cases of paediatric myringoplasty, 93.5% graft success rate was achieved at one year of 14follow up. few studies reported delayed perforations reducing the overall initial success rate. in one study, overall graft success rate of 87% was reported with 3 years of follow up whereas in another with longer follow up period, 80.5% graft success rate was re p o r t e d i n 4 1 c a s e s o f p e a d i a r t i c myringoplasty. the mean follow up period 9in that study was 39 months. we reported 91.8% graft success rate in children at 6 months of follow up. we suggest studies with long term follow up of at least three years to evaluate the issue of delayed graft failures in paediatric myringoplasty. the functional results of paediartic myringoplasty are not only promising but are also comparable to same procedure in adults. all of our patients in both child and adult group had hearing improvement after the surgery except those with graft failures. we noted an average air-bone gap closure of 13.5 db and 12.5 db in child and adult group respectively. the difference in air bone gap closure in both groups was statistically insignificant. these results showed that the functional results of paediatric and adult myringoplasty are comparable. this view is shared by number of other studies reported 13,15in literature. we believe that the results of our study may be of considerable importance in resolving the controversy of paediatric myringoplasty in favor of early surgical intervention. this will confer considerable benefits to children with tympanic membrane perforation in terms of improved hearing and decrease in number of recurrent ear discharge, which in turn leads to better overall academic and intellectual performance and socialization. in spite of our study results, we suggest that further studies should be carried out with larger number of patients and longer followups to resolve the controversy regarding paediatric myringoplasty. the success rate of myringoplasty in conclusion children is comparable to that of same in adults both in terms of anatomical and functional gains. 1. ashfaq m, aasim mu, khan n. myringoplasty: anatomical and functional results. pak armed forces med j 2004; 54:155-8. 2. sheahan p, dwyer t, blayney a. results of type 1 tympanoplasty in children and parental perceptions of outcome of surgery. j laryngol otol2002 ;116: 430-34. 3. kessler a, potsic wp, marsh rr. type 1 tympanoplasty in children. arch otolaryngol head neck surg. 1994;120: 487-90. 4. isaacson g. tympanoplasty in children. otolaryngol clin north am1994; 27: 593-605. 5. koch wm, friedman em, mcgill tj, healy gb. tympanoplasty in children. arch otolaryngol head neck surg 1989; 116:35-40. 6. mak d, mackendrick a, bulsana m et al. outcomes of myringoplasty in australian aboriginal children and factors associated with success: a prospective case series. clin otolaryngol allied sci. 2004; 29:606-11. 7. gersdorff m, garin p, decat m, juantequi m. myringoplasty : longterm results in adults and references children. am j otol 1995;16: 532-5. 8. bluestone cd, cantekin ei, douglas gs. eustachian tube function related to the results of tympanoplasty in children. laryngoscope 1979; 89: 450-8. 9. pignataro l, berta l, capaccio p, zaghis a. myringoplasty in children: anatomical and functional results. j laryngol otol 2001; 115: 36973. 10. chandrasekhar ss, house jw, devgan u. pediatric tympanoplasty. a 10 years experience. arch otolaryngol head neck surg 1995; 121: 8738. 11. p o t s i c w p, wi n a w e r m r , m a r s h r r . tympanoplasty for the anteriorsuperior perforation in children. amj otol 1996; 17:115-8. 12. rafi t. tympanoplasty in children-a study of 30 cases. j surg pakistan2001; 6:11-12. 13. umapathy n, dekker pj. myringoplasty: is it worth performing in children? arch otolaryngol head neck surg.2003;129:1053-5. 14. denoyelle f, roger g, chauvin p, garabedian en. myringoplasty in children: predictive factor of outcome. laryngoscope. 1999;109:47-51. 15. alberna r, riontino e, giordano l, gervasio cf et al. myringoplasty in children: a comparison with an adult population. acta otorhinolaryngol ital 1998; 18: 295-9. 7 original�article abstract objective: the objective of this study was to see the frequency and histological variants of endometrial metaplastic changes in benign endometrial curettage. study design: cross sectional descriptive study. place and duration of study: the study was conducted at pathology department of bannu medical college. the st st duration was five years. from january 1 , 2011 to december 31 , 2015. materials and methods: in this study a total of 530 endometrial curettage specimen were analysed. all the data was collected during these five years from pathology department register and the author was actively involved in examination and histopathology reporting. all benign endometrial curettage specimen from both pre and post-menopausal age were included. autolysed, malignant and insufficient biopsy specimen were not included. a minimum of one and maximum of three blocks were prepared. two to four 5 micron thick sections were taken, stained with h&e and pas where required. slides prepared were mounted and reported by histopathologist (author). the data was analysed in statistical package for social sciences (spss) version 20 for frequencies with percentages and mean with standered deviation. results: a total of 530 endometrial samples were collected in this study with mean age of 33.65 years and age range was from 21 to 63 years. the incidence of endometrial metaplasia was 4.90% amongst 530 endometrial samples. the metaplastic changes in order of frequency were tubal metaplasia followed by squamous metaplasia, clear cell metaplasia, ciliated cell metaplasia and mucinous metaplasia. conclusion: endometrial metaplasia is a recognized histological entity in endometrial curettage specimen with variable histological presentation. in this study tubal metaplasia was the commonest metaplasia followed by squamous metaplasia. key words: endometrial curettage, proliferative endometrium, morules, tubal metaplasia, histopathology. components are replaced by benign homologus or 4,5 heterologus elements inappropriate to the site. the epithelial emc occurs frequently, where as stromal emc are uncommon. the endometrial metaplasia 6 can occur in any age group. the emc terminology is still confusing as some of these metaplasia are merely cytoplasmic alterations better defined as cellular adaptation/changes rather than true metaplasia. this altered differentiation in endometrium is either due to degenerative/ reparative, hormonal or neoplastic processes and therefore must be mentioned in histopathology reports separate from from emc. this needs further work up, so that metaplasia and altered cellular 7 differentiation may be reported separately. this justification of this study is to provide awareness as well as to address and resolve the terminology gap between endometrial metaplasia and altered 8 cellular differentiation in future. presence of emc can significantly alert the reporting pathologist regarding their association with other primary lesions both benign as well as malignant. introduction endometrial metaplasia means replacement of normal endometrial epithelium by another type of 1 benign epithelium. the epithelium derived from mullerian duct which lines most of the female genital tract have the capacity to differentiate into different types of epithelium such as, ciliated, mucinous, endometrioid, transitional, clear and squamous cells 2 types. the endometrium show a spectrum of metaplastic changes. in endometrial metaplastic changes (emc) there occurs both epithelial as well as 3 stromal metaplasia. their epithelial or stromal frequency of metaplastic change in benign endometrial curettage specimen and its histological variants 1 2 3 mohammad sajjad khattak , mohammad akram khattak , sania tanveer khattak correspondence: dr. mohammad sajjad khattak associate professor, pathology bannu medical college, bannu e-mail: sajjadkhattak66@gmail.com 1 2 department of pathology/community medicine bannu medical college bannu, kpk 2 department of gynae/obs saidu medical college swat, kpk funding source: nil; conflict of interest: nil received: sep 24, 2016; revised: feb 17, 2017 accepted: feb 18, 2017 endometrial metaplastic changejiimc 2017 vol. 12, no.1 35 prepared. two to four 5 micron thick sections were taken, stained with h&e and pas where required. slides prepared mounted and reported by single histopathologist. data was analysed in statistical package for social scences (spss) version 20 for frequencies with percentages and mean with standard deviation. results a total of 530 endometrial curettage were included in this study. the mean age was 33.65 years with age range from 21 to 63 years. the incidence of endometrial metaplasia was 4.90% (n=26) cases amongst 530 endometrial curettage samples. the most common age group in metaplastic changes was between 46-55 years 34.61% (n=09) cases followed by 36-45 years 30.76% (n=08) cases. table i. tubal metaplasia was the commonest 34.61% (n=9) followed by squamous metaplasia 19.23% (n=5), mucinous 11.53% (n=3), hobnail 11.53% (n=3), clear cell 11.53% (n=3), eosinophillic 7.69% (n=2) and arias stella reaction 3.86% (n=1) cases. table ii. factors involved in emc are multiple physiological, reactive, neoplastic or genetic abnormalities. emcs occur in pure form or in combination with other 9 histological types in the same specimen. there are multiple risk factors of emcs may include the following: pubertal hormonal imbalance may induce m e t a p l a s t i c t r a n s f o r m a t i o n , a b n o r m a l endometrium including hyperplasia, endometritis, endometrial carcinoma, polycystic ovarian syndrome, tuberculous endometritis, foreign body such as intrauterine contraceptive device and 10 chronic trauma. the significance of emcs may present an indirect evidence of the presence of a causative factor. the underlying cause of emcs may present significant signs and symptoms or complications and treatment may be required for the underlying cause of metaplasia in endometrium. the prognosis is related 11 to the underlying cause and its treatment. t h e re a re d i ffe re nt t y p e s o f e n d o m et r i a l metaplasias, the most common is tubal metaplasia followed by squamous metaplasia, hobnail cell metaplasia, arias stella reaction/change, esinophilic cell change and mucinous metaplasia. other rare form of stromal metaplasia like clear cell metaplasia, cartilaginous, osseous, glial and smooth muscle can 12 also be seen in endometrium. the aim of this study was to see the frequency and histological variants of endometrial metaplastic changes in the southern districts of khyber pakhtunkhwa and to compare these with other studies. materials and methods this cross sectional descriptive study was carried out in pathology department bannu medical college bannu kpk. pakistan. the duration of this study was st st five years, from january 1 2011 to december 31 2015. the sample size was 530 endometrial curettage specimen. all the endometrial curettage samples were collected in 10% buffered formalin. the inclusion criteria was all endometrial curettage specimen of pre and postmenopausal age group, exclusion criteria was autolysed, insufficient and malignant specimen. all the specimen were overnight fixed in 10% buffered formalin, processed in various grades of alcohol, xyelene and wax. a minimum of one and maximum of three blocks were endometrial metaplastic changejiimc 2017 vol. 12, no.1 table i: distribu�on of age groups in endometrial metaplasia (n=26) table ii: frequency of histological variants of endometrial metaplasia (n=26) discussion endometrial metaplastic changes (emcs) are frequently overlooked and misdiagnosed. emcs by itself does not suggest a medical condition or an abnormality. however the cause of metaplasia may be of clinical significance and may require further 36 and mucinous metaplasia in 1.58% cases. another study conducted by firoiu et al16 show tubal metaplasia in 40.11% followed by eosinophillic metaplasia in 29.80%, squamous metaplasia in 21.72%, clear cell metaplasia in 6.40% and mucinous metaplasia in 1.94% cases. there are differences in the frequencies of different metaplasia in these studies. the reasons may be either variation in diagnosis and treatment modalities or background differences endometrial disease in different areas of the world. conclusion endometrial metaplasia is a recognized histological entity in endometrial curettage specimen with variable histological presentation. in this study tubal metaplasia was the commonest metaplasia followed by squamous metaplasia. refrences 1. rosai j. female genital tract. in: rosai and ackerman's surgical pathology. 10th edn. st. louis: elsevier mosby. 2013: 1878-88. 2. kumar v, abbass ak, astercj. female genital tract. in: robin's pathological basis of diseases. 9th ed. philadelphia: wb saunders. 2013; 628-704. 3. kaur p, kaur a, suri ak, sidhu h, hendrickson mr, kempson rl. a two year histopathological study of endometrial biopsies in a teaching hospital in northern india. indian journal of pathology and oncology, 2016; 3: 508-19. 4. hendrickson mr, kempson rl. endometrial epithelial metaplasias: proliferations frequently misdiagnosed as adenocarcinoma. am j surg pathol. 1980; 4: 525-42. 5. zaman ss, mazur mt. endometrial papillary syncytial change. a nonspecific alteration associated with active breakdown. am j clin pathol. 1993; 99: 741–5. 6. gersell dj. endometrial papillary syncytial change. another perspective, am j clin pathol. 1993; 99: 656-7. 7. rorat e, wallach rc. papillary metaplasia of the endometrium. clinical and histopathologic considerations. obstet gynecol. 1984; 64: 90-2. 8. lin mc, lomo l, baak jp. squamous morules are functionally inert elements of premalignant endometrial neoplasia. mod pathol. 2009; 22: 167-74. 9. chiarelli s, buriticá c, litta p, ciani s, guarch r, nogales ff. a n i m m u n o h i s t o c h e m i c a l s t u d y o f m o r u l e s i n endometrioid lesions of the female genital tract: cd10 is a characteristic marker of morular metaplasia. clin cancer res. 2006; 12: 4251-6. 10. suzuko moritani, ryoji kushima, shu ichihara, hidetoshi okabe, takanori hattori, kobayashi tk, et al. eosinophilic cell change of the endometrium: a possible relationship to mucinous differentiation. modern pathology. 2005; 18: 1243–8. 11. mccluggage wg, desai v, manek s. tamoxifen-associated investigation. also the prognosis is directly related to 13 the underlying cause and its treatment. emcs associated with atypical cytological findings and their persistence on repeated histopathological examination, may needs a careful workup to 14 determine the underlying cause. again it is important to note that atypical changes does not always mean an association with malignancy, such atypical changes may occur in 15 benign conditions as well. in this study the age range was 21 to 63 years. in 16 study conducted by firoiu et al the age range was from 22-75 years. another study conducted by 17 simon et al in taiwan in 2011 the age range was 2485 years. all almost have the same age range. in this study the most common age group was 46-55 years followed by 36-45 years with 34.61% and 30.76% cases respectively. in study conducted by 18 natheeu et al the most common age group was 4049 years followed by 30-39 years with 46.02% and 22.22% cases respectively. another study conducted by benyamen et al12 the common age group was 3039 years with 47% cases followed by 40-49 years with 26% cases. in this study the frequency of endometrial metaplasia was 26 (4.90%) cases amongst 530 endometrial curettage, where as in study conducted by natheeu et al17 the frequency of metaplasia was 11.62% higher than this study, another study conducted by benyamen et al12 show a very high frequency 60% of metaplastic changes. the reason for these frequencies in these both studies is due to the estimation of metaplasia in both benign as well as malignant lesions, where as in the present study the metaplasia is only estimated in benign endometrial lesions. in the later study of benyamen et al12 metaplastic changes of cervix are also included. in this study the endometrial metaplasia in order of frequency was tubal metaplasia 34.61% (n=9) followed by squamous metaplasia 19.23% (n=5), mucinous 11.53% (n=3), hobnail 11.53%(n=3), clear cell 11.53% (n=3), eosinophillic 7.69%(n=2) and arias stella reaction 3.86%(n=1) cases. in a study conducted by natheeu et al17 the frequency order was tubal metaplasia 52.38% followed by squamous metaplasia 17.46%, hobnail metaplasia 12.695, arias stella reaction 7.93%, eosinophilic metaplasia 4.76% endometrial metaplastic changejiimc 2017 vol. 12, no.1 37 15. firoiu c, simionnescu c, stanculescu d, chexnoiu f, stepan a. histopathological metaplasias in endometrial hyperplasia. current health sciences journal. 2009; 35: 449. 16. neethu gv, pawer jg. morphology of endometrial metaplasias and related reactive changes: a prospective study. 2014; 4: 1-4. 17. nicolae a, preda o, nogales ff. endometrial metaplasias and reactive changes: a spectrum of altered differentiation. j clin pathol. 2011; 64: 97-106. 18. simon ra, peng sl, liu f, quddus mr, zhang c, steinhoff mm, et al. tubal metaplasiaof endometrium with cytologic atypia: an analysis of p53, ki-67, tert and long tern follow up.modern pathology. 2011; 24: 1254-61. postmenopausal adenomyosis exhibits stromal fibrosis, glandular dilatation and epithelial metaplasias. histopathology. 2000; 37: 340-6. 12. banyameen m, masood i, aiman a, yasir m, mushtaq i, verma v. study of metaplastic lesions of different parts of the female genital tract: a prospective study. the internet journal of pathology. 2010; 2: 7. 13. carlson jw, mutter gl. endometrial intraepithelial neoplasia is associated with polyps and frequently has metaplastic change. histopathology 2008; 53: 325-32. 14. amin a, ali a, amin z, sani fn. justification for hysterectomies and frequency of histopathological lesions of hysterectomy at a teaching hospital in peshawar, pakistan. pak j med sci. 2013; 29: 170–2. endometrial metaplastic changejiimc 2017 vol. 12, no.1 38 jiimc december 2016 page 39 page 40 page 41 page 42 original�article abstract objective: the objective of this study was to evaluate the influence of storage media on the solubility of four different commercially available calcium hydroxide cements. study design: comparative experimental study st th place and duration of study: the study was conducted 1 august 2016 to 29 november 2016 at army medical college nums. materials and methods: the present study included four different commercially available calcium hydroxide cements. for each material 8 disc-shaped specimens were prepared according to manufacturer's instructions. then each material was further divided in to two groups on the basis of storage media. “group a” used distilled water (dw) and group b used saliva for the storage of specimens (n=4).solubility was noted using analytical balance after immersion. data was analyzed with analysis of variance (anova) and post hock tukey's test using spss 21. results: a significant difference (p≤0.05) between the results of solubility due to change in media of group a and b was observed. the difference in solubility between the various cements was significant. conclusion: the study confirmed the difference between the cements on the basis of solubility hence it highlighted the importance of solubility and provides a guideline for the clinician to choose the type of calcium hydroxide that is required in a particular situation on the basis of determined solubility. key words: calcium hydroxide, dental cavity lining, dental cements solubility. infections beyond short-term applications. infection and necrosis are quite common in breached seals (micro-leakages in caps and tunnel defects in dentin 6,7 bridges), within the first few years of application. this is mostly due to lower strength and higher 8 solubility than alternative products. available literature suggests that base/liner materials become unstable under restorations, possibly due to dissolution after exposure to dentinal fluid or other aqueous media. this results in loss of cavity 9,10 protection and physical support to restorations. evidence suggests that the solubility and water sorption properties have a direct impact on how well lining between teeth and their restorations endure. consequently, in the study of the quality of calcium hydroxide cements, their resistance to disintegration 11 is one of the most critical criterion. recent developments have seen an advent in the use of resin based calcium containing cements and methylcellulose based cements that have proven to have more resistant, robust and easier to cure compared to their non-resin based counterparts and 12-14 water based respectively. although, the results of pulp capping based on such cements seems to be encouraging, available evidence does not yet suggest that they would act as more resistant introduction the role of calcium hydroxide in the materials used as bases and cavity liners was identified in the early 1 twentieth century. they are used for pulp protection after injury caused either due to carious lesion or clinical intervention. also it prevents infiltration of dentinal fluid into the restoration or leaching of 2 restorative components into the oral tissue. furthermore the ability of calcium hydroxide based cements to simulate dentin recovery has seen an 3-5 expansion of their use as deep cavity cements. although, the use of calcium hydroxide cements to induce dentin bridges formation is well documented, their seals are known to be vulnerable to bacterial effect of storage media on the solubility of commercially available calcium hydroxide cements. a clear guideline for dentists 1 2 3 4 5 shahreen zahid , samie qadir , asfia saeed , muhammad kaleem , haroon ahmed khan correspondence: dr. shahreen zahid assistant professor, dental materials army medical college national university of medical sciences, rawalpindi 1,3,4 department of dental materials army medical college national university of medical sciences, rawalpindi 2 department of dental materials margalla institute of health sciences, rawalpindi 5 department of electrical engineering comsats institute of science and technology, islamabad funding source: nil; conflict of interest: nil received: dec 03, 2016; revised: mar 08, 2017 accepted: jun 04, 2017 effect of storage media on the solubility of calcium hydroxide cementsjiimc 2017 vol. 12, no.2 83 cured two paste system septocalcine ultra +, two with physical mode of activation system (calcipulp by septodont and cavity liner paste by produits dentaires ) and one resin-based light curing system cavity liner, (light cure calcium hydroxide paste by produits dentaires). details are given in the table i below: the iso 6876 specification was implemented with minor changes to develop the methodology used in this study. for the solubility tests a total of 32 discshaped specimens (6.2 mm diameter x 1 mm thick) were prepared according to manufacturer's instructions using a split mould of stainless steel (8 from each material given in figure 1). then each material was randomly divided by tossing a coin method in to two groups on the basis of different media for immersion. “group a” used distilled water (dw) and group b used saliva for the storage of specimens (n=4). the percentage difference in mass of the specimens before and after immersion in dw and saliva was determined. solubility was noted after 24 hours. the methodology has also been illustrated in figure 2.data was analyzed with analysis of variance (anova) and post hock tukey's test using spss 21. 14 barriers. consequently, there is an opportunity to conduct qualitative research to test resin based calcium cements. this study aimed to fill this gap in existing research by presenting a study in the observed performance of various commercially available resin based calcium cements. of special interest is the observation of their water solubility. the tests conducted focused on all possible factors that breach the cement integrity and their corresponding causes, over a period of time. considering the extensive use of calcium hydroxide in the field of dentistry and the varieties of formulation available by different companies with several claims, there was a need for a comprehensive comparison of the materials, particularly in the varying solubility media. the objective of this study was to evaluate the influence of storage media that is distilled water and saliva on the solubility of four different commercially available calcium hydroxide cements. materials and methods the materials used in the experimental in vitro study st th conducted from 1 august to 30 november 2016 at army medical college nums were four commercially available calcium hydroxide cements: one chemically tablei: materials used in the study along with composi�on and ac�va�on modes effect of storage media on the solubility of calcium hydroxide cementsjiimc 2017 vol. 12, no.2 84 resistance to oral solvents are necessary for the reliable support of restorations, especially the vertical stresses they have to face. further studies were needed to compensate the gap in current research with regards to loss of strength in bases and loss of hardness in liners, due to solubility of cements and the ph levels of the saliva. to maintain their protective effects, lining and base materials have to be resistant to dissolution in 18 organic oral solvents. the focus of this study is to identify vital quality indicators for the clinical validity of each tested material. hence, iso 6876 specification was used to test the solubility of various cements, not only in distil water but also in saliva. the results of present study were consistent with previous study which concluded that calcium hydroxide cement bases are significantly more 19 soluble in distilled water than in saliva, with exception of calcipulpe. this may be attributed to the excipients present in the cement. the manufacturers claim physical reliance and longevity due to low solubility. despite the several variations in their compositions, for all intents and purposes, pulp-capping materials are a mixture of 20 calcium hydroxide and an ester of salicylic acid. a selection of these compositions were evaluated and analysed for this study: (i) septocalcine ultra+ (chemically cured two-paste system) (ii) light cure calcium hydroxide paste by produits dentaires (resin-based light curing) (iii) calcipulp by septodont (physical mode of activation) (iv) cavity liner paste by produits dentaires(physical mode of activation) amongst the cements, light cure calcium hydroxide paste and cavity liner paste performed substantially better than the other two. the low solubility of the light cured system may be attributed to the presence of resin particles in its composition. on comparing the cements with the physical mode of activation, the single paste methyl cellulose based cement showed more resistance to solubility than water based system (figure 2). these observations about the resilience of resin-based lining materials in this 21,22 study have been validated by burke and watts, who demonstrated the higher resistance of resinbased lining materials compared to conventional results the results of solubility of group a and b and comparison between the groups are given in figure 2 and 3 respectively. there was a significant difference between the results of solubility due to change in storage media of group a and b (p < 0.01) while the difference in solubility between the various cements was also significant (p < 0.05). fig 1: methodology used for tes�ng solubility of calcium hydroxide based cements fig 2: means plot showing the effect of storage media on the solubility of various calcium hydroxide cements fig 3: the effect of environment on the se�ng �me of various calcium hydroxide cements discussion the subject of liners and bases has been controversial as there is no single guideline for clinicians, regarding the use of liners and bases. lot of research work has been done on the biological and 1 5 mechanical properties of these materials. 17 strength and low solubility are critical features of 13 base and lining materials. the strength and effect of storage media on the solubility of calcium hydroxide cementsjiimc 2017 vol. 12, no.2 85 hydration and bioactivity of radiopacified tricalcium silicate cement, biodentine and mta angelus. dental materials. 2013; 29: 580-93. 9. lowe ra. dental cements: an overview. dent today. 2011; 30: 140-3. 10. weiner r. liners, bases, cements: material selection and clinical applications. dent today. 2005; 24: 6-72. 11. mccabe jf, walls aw. applied dental materials: john wiley & sons. 2013. 12. estrela c, holland r. calcium hydroxide: study based on scientific evidences. journal of applied oral science. 2003; 11: 269-82. 13. desai s, chandler n. calcium hydroxide–based root canal sealers: a review. journal of endodontics. 2009; 35: 475-80. 14. madruga fc, ogliari fa, ramos ts, bueno m, moraes rr. calcium hydroxide, ph-neutralization and formulation of model self-adhesive resin cements. dental materials. 2013; 29: 413-8. 15. zmener o, pameijer ch, banegas g. an in vitro study of the ph of three calcium hydroxide dressing materials. dental traumatology : official publication of international association for dental traumatology. 2007; 23: 21-5. 16. mickenautsch s, yengopal v, banerjee a. pulp response to resin-modified glass ionomer and calcium hydroxide cements in deep cavities: a quantitative systematic review. dental materials : official publication of the academy of dental materials. 2010; 26: 761-70. 17. nasser m. evidence summary: which dental liners under amalgam restorations are more effective in reducing postoperative sensitivity? british dental journal. 2011; 210: 533-7. 18. von fraunhofer j, marshall k, holman b. the effect of base/liner use on restoration leakage. general dentistry. 2005; 54: 106-9. 19. driscoll c, woolsey g, reddy t, craig r. solubility of zinc oxide-eugenol and calcium hydroxide cements in simulated dentinal fluid. journal of oral rehabilitation. 1989; 16: 4515. 20. natale l, rodrigues m, xavier t, simoes a, souza d, braga r. ion release and mechanical properties of calcium silicate and calcium hydroxide materials used for pulp capping. international endodontic journal. 2015; 48: 89-94. 21. burke f, watts d. weight loss of four calcium hydroxidebased materials following a phosphoric acid etching and washing cycle. journal of dentistry. 1986; 14: 226-7. 22. burke f, watts d. weight loss of three resin-based lining materials containing calcium following a phosphoric acidetching and washing cycle. journal of dentistry. 1989; 17: 38-40. 23. hatton jf, ber bs, stewart gp. dental repair material. google patents; 2013. calcium hydroxide cements. the observation of the increase in resistance to solubility due to presence of methylcellulose has also been previously observed in 23 other cements. it would be pertinent to emphasise that the results of this study are strictly limited to the parameters and factors described and cannot be extended to other conditions without explicit tests. the need for high strength and low solubility in base materials has been established in this study. however, the solubility should not be low to an extent to hinder the ion exchange with the odontoblastic layer at the dentin-base interface. conclusion the present study characterized various calcium hydroxide cements on the basis of solubility. these results will be used as a guideline for the clinician to choose the type of calcium hydroxide that is required in a particular situation on the basis of determined solubility. references 1. hilton tj. keys to clinical success with pulp capping: a review of the literature. operative dentistry. 2009; 34: 615-25. 2. alhodiry w, lyons mf, chadwick rg. effect of saliva and blood contamination on the bi-axial flexural strength and setting time of two calcium-silicate based cements: portland cement and biodentine. the european journal of prosthodontics and restorative dentistry. 2014; 22: 20-3. 3. el meligy oa, avery dr. comparison of apexification with mineral trioxide aggregate and calcium hydroxide. pediatric dentistry. 2006; 28: 248-53. 4. andreasen jo, farik b, munksgaard ec. long-term calcium hydroxide as a root canal dressing may increase risk of root fracture. dental traumatology. 2002; 18: 134-7. 5. poggio c, ceci m, beltrami r, dagna a, colombo m, chiesa m. biocompatibility of a new pulp capping cement. annali di stomatologia. 2014; 5: 69-76. 6. bjorndal l, ricucci d. pulp inflammation: from the reversible pulpitis to pulp necrosis during caries progression. the dental pulp: springer; 2014. p. 125-39. 7. krastl g, zehnder ms, connert t, weiger r, kuhl s. guided endodontics: a novel treatment approach for teeth with pulp canal calcification and apical pathology. dental traumatology : official publication of international association for dental traumatology. 2016; 32: 240-6. 8. camilleri j, sorrentino f, damidot d. investigation of the effect of storage media on the solubility of calcium hydroxide cementsjiimc 2017 vol. 12, no.2 86 page 18 page 19 page 20 page 21 original�article abstract objective: to determine uptake of contraceptive methods by post abortion clients along with factors influencing the uptake. study design: descriptive cross sectional study. materials and methods: the study included 160 post abortion clients using two stage sampling technique. a questionnaire was designed based upon questions used in previous studies. part a of questionnaire was filled to record socio demographic details and part b to assess contraceptive uptake. chi square test was applied to determine association between independent and dependent variables. data were analyzed using spss version 22. p-value < 0.05 was considered significant. results: mean age of participants was 28.4 ± 6.04 years. only 38.1% clients adopted contraceptive method within one month. short term methods were adopted by 62.2% and long acting reversible contraceptives by 26.2% clients. male condom was the most frequently chosen method, adopted by 24.5% clients. fifty four percent clients having > 3 living children, 48.7% clients served by private sector, 61.7% clients reporting previous contraceptive use and 50.9% clients who received counseling, adopted the method. association between these factors and contraceptive uptake was statistically significant (p value <0.05). key words: contraception, contraceptive method, family planning, post abortion contraception. conclusion: post abortion contraceptive uptake was low. however private sector health facilities, previous contraceptive method use and counseling by health care providers were significantly affecting contraceptive uptake. place and duration of study: the study was conducted in three public and three private hospitals of sargodha from february to october 2018. important part of reproductive health care. healthy timing and spacing of pregnancy (htsp) is an intervention which enables women and couples delay or space their pregnancies, and hence ensure 3 healthiest outcomes for mother and neonate. in context to htsp, world health organization recommends at least 6 month interval to next 4 pregnancy after miscarriage or induced abortion. due to rapid return of fertility and early resumption of sexual activity, post abortion clients are exposed 5,6 to the risk of closely spaced pregnancy. counseling and provision of effective contraceptive method can protect post abortion client from this undesired 7 occurence. in pakistan, unmet need for contraception is as high as 17% and contraceptive prevalence rate is only 8 34%. incidence of abortions is also high and more 9 than 2 million pregnancies end annually. strategies for effective counseling and service provision must be implemented to address the contraceptive needs of post abortion clients. introduction access to comprehensive reproductive health care services enables women to pass through pregnancy and labour safely and to accomplish the best 1 reproductive outcomes. reproductive health care is one of the core components of the 3rd sustainable development goal which emphasizes on universal access to sexual and reproductive health-care services, including family planning, information and 2 education. contraception is an essential and contraceptive uptake among post abortion clients in local population of sargodha district, pakistan 1 2 3 saadia maqbool , hina shan , lubna shaheen correspondence: dr. saadia maqbool former head of training department green star social marketing, pakistan e-mail: maqboolsaadia@yahoo.com 1 green star social marketing, pakistan 2 department of community medicine hbs medical and dental college, islamabad 3 department of pathology sargodha medical college, sargodha funding source: nil; conflict of interest: nil received: april 17, 2019; revised: august 10, 2019 accepted: august 14, 2019 post abortion contraceptive uptakejiimc 2019 vol. 14, no.4 174 the mean age of 160 study participants was 28.4 ± 6.04 years. seventy eight clients (48.7%) received healthcare by public and 82 clients (51.2%) from private sector hospitals. details are in table i and table ii. the study. clients coming to hospital were assessed for eligibility criteria and those fulfilling the criteria were enrolled in the study after taking written voluntary informed consent. results data were entered and analyzed in spss version 22. descriptive statistics like frequency and percentage were used for categorical variables. mean and standard deviation were calculated for continuous variables. chi square test was applied to determine the association between categorical variables. a pvalue < 0.05 was taken as statistically significant. section a of questionnaire was filled on first contact with the client to record socio-demographic information and section b was filled after one month to record contraceptive uptake. research questionnaire was designed after extensive literature search by modifying the questions used in previous studies by pearson et al, abrah p, uwera d.j and thapa a. after review by two gynecologists and a public health specialist, questionnaire was piloted on 23 post abortion clients. research committees of national university of medical sciences and army medical college also approved it. gaps exist regarding awareness about post abortion contraception at client and health care provider's level. determination of post abortion contraceptive uptake is essential to know what percentage of post abortion clients get protection from the risk of unplanned pregnancies, poor perinatal outcome or repeat abortions. assessment of factors which affect post abortion contraceptive uptake would be helpful i n a d d r e s s i n g t h e h i g h u n m e t n e e d o f 11 contraception. there was paucity of data regarding post abortion contraceptive uptake in pakistan. the purpose of the study was to determine uptake of contraceptive methods by post abortion clients along with factors influencing the uptake. after obtaining approval from the ethical review committee of army medical college, this study was conducted at three public and three private sector hospitals of district sargodha from february 2018 to october 2018. study participants were 160 post abortion client, 78 from public sector hospital and 82 from private sector hospital. raosoft sample size calculator was used for sample size estimation. keeping 4% margin of error, 95% confidence level, a sample size of 115 was calculated initially. after adding 30% increase to cover the lost to follow-up and rounding off, sample size of 160 was finalized. two stage sampling technique was used. firstly, list of all hospitals providing reproductive health care was obtained from district health officer and sampling frames were constructed for private and public sector hospital strata. three hospitals were selected by simple random sampling technique using lottery method from each stratum. in the second stage of sampling, simple random sampling technique using computer generated random number was used to select hospital for that day to collect data. women aged 15–49 years who reported abortion before 20 weeks gestation and gave written consent were included and women with a desire for next pregnancy within 6 months and who developed life threatening complications were excluded from materials and methods post abortion woman must get the opportunity for discussion about contraceptive needs and her reproductive goals. she has a right to get comprehensive information and counseling about the benefits, usage, effectiveness and side effects of 10 a range of contraceptive methods. table i: socio demographic characteris�cs of the par�cipants (n=160) and their contracep�ve method uptake post abortion contraceptive uptakejiimc 2019 vol. 14, no.4 175 uptake uptake of contraception was significantly higher among clients served by private sector facilities (p value = 0.004). forty clients (48.7%) of private sector and 21 clients (26.9%) of public sector adopted the method. significant association was observed between contraceptive uptake and having >3 living children (p value < 0.001) as 33(54%) clients adopted the method. among 47 previous fp users 29 (61.7%) initiated contraceptive method while 32(28.3%) clients among 113 previous non users adopted contraception (p value < 0.001). fifty seven clients (96.4.7%) who received counseling while only 4 (8.3%) who received no counseling reported method uptake (p value < 0.001). dilation and curettage: d&c, manual vacuum aspiration: mva, medical treatment: mt, no treatment: nt,*statistically significant out of 160 clients, only 61 clients (38.1%) reported contraceptive method uptake within one month after abortion. among method adopters, 38(62.2%) clients adopted short term method while 16(26.2%) adopted larc. male condom was chosen by 15 (24.5%), iucd by 14 (22.9%) and pills by 12 (19.6%) clients. table ii: obstetric details of the par�cipants (n=160) and their contracep�ve method uptake fig 1: uptake of various contracep�ve methods (n=61) fig 2: contracep�ve method uptake in both sectors (n=160) (p value=0.004) majority of contraceptive method adopters have chosen the short term method. male condoms followed by pills were the most frequently chosen method. a brazilian study also indicated similar findings revealed that 38.1% clients adopted a contraceptive method which is higher than the 12 contraceptive prevalence rate in pakistan (34%). higher uptake could be due to increased felt need of contraception following an abortion. discussion post abortion contraceptive uptakejiimc 2019 vol. 14, no.4 176 2. starrs am, ezeh ac, barker g, basu a, bertrand jt, blum r, et al. accelerate progress—sexual and reproductive health and rights for all: report of the guttmacher–lancet commission. the lancet. 2018;391(10140):2642-92. use and counseling regarding contraception are significantly affecting contraceptive uptake. there is a need to strengthen post-abortion contraceptive services which can contribute in increasing the country's contraceptive prevalent rate. strategies for post abortion contraceptive provision as a part of post abortion care must be developed and implemented. capacity building of health care providers and availability of a range of contraceptive methods are essential to increase post abortion contraceptive uptake. references 5. gemzell-danielsson k, kallner hk. post abortion contraception. women's health. 2015; 11(6):779-84 6. g e m ze l l d a n i e l s s o n k , ka l l n e r h k , fa ú n d e s a . contraception following abortion and the treatment of incomplete abortion. international journal of gynecology & obstetrics. 2014; 126:s52-5. 7. roe ah, bartz d. contraception after surgical and medical abortion: a review. obstetrical & gynecological survey. 2017; 72(8):487-93 9. sathar z, singh s, rashida g, shah z, niazi r. induced abortions and unintended pregnancies in pakistan. studies in family planning. 2014; 45(4):471-91. 10. stanback j, steiner m, dorflinger l, solo j, cates w. who tiered-effectiveness counseling is rights-based family planning. global health: science and practice. 2015; 3(3):352-57. 11. samuel m, fetters t, desta d. strengthening post abortion family planning ser vices in ethiopia: expanding contraceptive choice and improving access to long-acting reversible contraception. global health: science and practice. 2016;4(supplement 2):s60-72. recommendations 3. allison a, basikoro ee. why world vision supports healthy timing and spacing of pregnancies to improve maternal and child health: a faith-based perspective. christian journal for global health. 2017;4(2):75-9. 1. dunn jt, lesyna k, zaret a. the role of human rights litigation in improving access to reproductive health care and achieving reductions in maternal mortality. bmc pregnancy and childbirth. 2017; 17(2):367. 4. agida te, akaba go, ekele ba, isah d. practice of healthy timing and spacing of pregnancy (hstp), experience from a low resource setting. tropical journal of obstetrics and gynecology. 2016;33(1):57-63. 8. national institute of population studies (nips) and icf. pakistan demographic and health survey 2017-18. islamabad, pakistan, and rockville, maryland, usa: nips and icf; 2018. available at https://dhsprogram.com /publications/publication-fr354-dhs-final-reports.cfm uptake of contraceptive method within one month after abortion is low although many clients express desire to limit fertility. however private sector health facilities, previous history of contraceptive method higher percentage of method adoption was noted in age groups more than 24 years with highest uptake among women more than 35 year (55%). these results are comparable to another study. benson et al. who also reported high uptake among women ≥25 15 years of age. in our study, uptake of contraceptive method was more among clients who had induced abortion (57.8%). findings of a study conducted in eight countries described higher odds of contraceptive method uptake in clients who had induced 16 abortion. choice of contraceptive methods. condom was the most frequently adopted method, followed by the 13 contraceptive pills. higher uptake of method was noted in women with more than 3 living children. another study also reported higher post abortion contraceptive use 17 among women with 3 or more children (83.8%). in our study uptake of contraception was significantly higher among clients served by private sector facilities results suggest that in private sector, clients are counseled and offered method provision more effectively. this finding is not similar with the study conducted at ethiopia. analysis of ethiopian study suggested that post abortion clients served in private health facilities were 72.4% less likely to adopt contraceptive method as compared to the 14 public facilities. different quality standards of private sector in both countries may be explain this disparity. conclusion most of clients who have been counseled, reported contraceptive uptake. very low adoption of fp method (8.3%) was seen among clients who received no counseling at all. in an ethiopian study, respondents who received contraceptive counseling were 4 times more likely to have post abortion 19 contraceptive method. contraceptive uptake was higher among clients who reported previous use of contraceptive method. significant association was also observed between the previous use of contraceptive and uptake of post 18 abortion contraception in a research at ghana. post abortion contraceptive uptakejiimc 2019 vol. 14, no.4 177 2017; 5(4):644-57. 17. pearson e, biswas kk, andersen kl, moreau c, chowdhury r, sultana s, et al. correlates of contraceptive use 4 months post abortion: findings from a prospective stud in bangladesh. contraception. 2017; 95(3):279-87. 19. kokeb l, admassu e, kassa h, seyoum t. utilization of post abortion contraceptive and associated factors among women who came for abortion service: a hospital based cross sectional study. j fam med dis prev. 2015; 1:022. 16. benson j, andersen k, brahmi d, healy j, mark a, ajode a, et al. what contraception do women use after abortion? an analysis of 319,385 cases from eight countries. global public health. 2018;13(1):35-50. 18. abrah p. predictors of post abortion family planning uptake in the new juaben municipality (doctoral dissertation). ghana: kwame nkrumah university of science and technology; 2015 15. benson j, andersen k, healy j, brahmi d. what factors contribute to post abortion contraceptive uptake by young women? a program evaluation in 10 countries in asia and sub-saharan africa. global health: science and practice. 12. national institute of population studies (nips) and icf. pakistan demographic and health survey 2017-18. islamabad, pakistan, and rockville, maryland, usa: nips and icf; 2018. available at https://dhsprogram.com /publications/publication-fr354-dhs-final-reports.cfm 13. borges al, monteiro rl, hoga la, fujimori e, chofakian cb, santos oa. post-abortion contraception: care and practices. revista latino-americana de enfermagem. 2014; 22(2):293300. 14. hagos g, tura g, kahsay g, haile k, grum t, araya t. family planning utilization and factors associated among women receiving abortion services in health facilities of central zone towns of tigray, northern ethiopia: a cross sectional study. bmc women's health. 2018; 18(1):83. post abortion contraceptive uptakejiimc 2019 vol. 14, no.4 178 original�article abstract objective: to compare the levels of depression, anxiety and stress between low and high achieving medical students. study design: a cross-sectional descriptive study place and duration of study: this research was carried out in islamic international medical college, pakistan, th th from 11 may to 30 december 2018. nd rd th th materials and methods: the study sample comprised of 160 medical students of 2 , 3 , 4 and 5 year mbbs classes. sampling was done by using purposive sampling technique. for comparison, the students were distributed in two groups depending upon their scores in recent professional examination. low scoring group comprised of 20 students from each class, who scored lowest marks in the recent professional examination and were placed at the bottom of result sheet, while high scoring group comprised of those 20 students who were placed at the top of result sheet in the same class. demographic data was obtained on a printed form and the depression anxiety stress scale (dass-21) was used to record clinical variables. statistical package for social sciences version 20(spss-20) was used for analysis of data. paired sample t-test was used to find the difference in the mean scores of clinical variables between two groups. results: the mean score for stress, anxiety and depression was 10.4, 16 and 15 respectively in low achievers. while the high achievers mean scores were 6.2, 8.7 and 9 on these variables respectively, with p-value below 0.05. the results revealed relatively high psychological morbidity in low achieving medical students. conclusion: the level of depression, anxiety and stress is found to be higher in low scoring students as compared to high scoring medical students. key words: depression, anxiety, stress, dass-21, low and high achieving medical students. worldthe levels of anxiety, stress and depression are 1-3 higher in medical students. in line with global trends, the prevalence of these issues is also higher 4-6 in pakistan. stress leads to physiological changes in the brain and body and can present with changes in behavioral profile, which might come and go initially. however, persistent and severe stress, might lead to depression and anxiety. clinical depression is characterized by persistent sadness, decreased capacity to enjoy, disturbed sleep impaired concentration, and ideas of suicide. anxiety produces fear of unknown, restlessness, worrying thoughts and palpitation. many studies have found that the life in medical colleges is quite stressful and can adversely affect the psychological health of 6-9 students. the stressors of medical college can adversely affect the academic progress of the 10 students . stressful factors commonly reported by students, are burden of studies, less sleep hours, unpleasant physical and emotional environment, 11 poor learning facilities and financial issues. it was found that student with low grades were having introduction for the achievement of academic milestones, the psychological and emotional health of students plays an important role. all over the world, medical colleges offer opportunities for intellectual and professional growth to their students. the intended aim is to prepare them as future healthcare professionals. however, these future health care providers undergo a tough journey, leading to psychological issues, which can affect their health, 1,2 morale and academic performance. all over the depression, anxiety and stress in low and high achieving medical students correspondence: muhammad masood khokhar associate professor department of psychiatry islamic international medical college riphah international university, islamabad e-mail: masoodkhokhar2@yahoo.com 1,2,3,4,5 6 department of psychiatry/surgery islamic international medical college riphah international university, islamabad funding source: nil; conflict of interest: nil received: june 11, 2019; revised: september 05, 2019 accepted: september 06, 2019 depression, anxiety and stress in low and high achieving medical studentsjiimc 2019 vol. 14, no.3 156 bottom of result sheet. while high scoring group consisted of 20 students scoring highest marks in the same professional examination and were placed at the top of score board. the depression anxiety stress scale (dass-21) was used to measure the clinical variable .e.g. depression, anxiety, and stress. dass-21 has 21-items, with seven items for each subscale. students scored each item from 0-3, where zero meant "did not apply" and three meant "applied strongly”. statistical package for social sciences version-20 (spss-20) was used to analyze the data and results were compiled accordingly. keeping the objectives of the study in mind difference in the mean scores of depression, anxiety and stress was calculated. for this purpose paired sample t-test was used to find the difference in the mean scores of clinical variables between two groups. statistical significance was based upon p-value of less than 0.05. results as shown in table-i, 160 students were divided into two groups, with 80 students in each group i.e. low and high scorning student. out of 160 students, 56(35%) were males and 104(65%) were females. regarding age, 104(65%) were below 23 years and 56 (35%) were above 23 years. majority (97.5%) of the students were unmarried. most of the students attributed their depression, anxiety and stress to their financial problems (46%), followed by study burden (26%). 12 severe stress, anxiety and depression. as compared to males the female students were found to have higher level of perceived stress and they attributed it 13-14 to academic burden. some studies found that the students do not seek professional treatment because of fear of stigma. thus only a small number 15-16 of students receive professional care. poor psychological health of students leads to poor performance in academics. follow up studies found that the level of stress in medical students is associated with academic performance of the 17-18 medical students. however, no published study was found to compare psychiatric morbidity and its impact on academic performance in pakistan. in the light of this knowledge gap a question arises in the mind of all interested stakeholders, and particularly the faculty members of our medical colleges, whether our medical students; whose academic performance is low are suffering from relatively severe psychological morbidity? if found correct then proper measures can be taken to facilitate and help the student and avoid academic failure and associated complications. the objective of this study was to compare level of depression, anxiety and stress between low and high achieving medical students. materials and methods this was a cross-sectional descriptive study carried out in islamic international medical college, th th pakistan, from 11 may to 30 december 2018. the study sample comprised of 160 medical students of nd rd th th 2 , 3 , 4 and 5 year mbbs classes. after approval of ethics review committee, data collection was done by using purposive sampling technique, by trained psychologists. forty students were selected from each of the four mbbs classes based on their marks in respective professional examination. the participants were provided with a consent form informing them about the purpose of study and voluntary participation. confidentiality and comfort was ensured. for the purpose of comparison, the students were distributed in two groups, the low and high scoring groups, which were operationally considered synonym to low and high achieving students, for the purpose of this study. low scoring group consisted of 20 students, from each mbbs class; who obtained lowest marks in the recent professional examination and were placed at the table: i demographic characteris�cs of par�cipants (n=160) depression, anxiety and stress in low and high achieving medical studentsjiimc 2019 vol. 14, no.3 157 1,8,14, 1921 psychological morbidity. however, exact cause and effect relationship of those factors, with psychological morbidity, could not be established because of the descriptive nature of our study. to the best of our knowledge no published study was found in the national literature, with focus on comparison of psychological morbidity in low and high achievers. therefore, for better understanding and management of psychological issues we need to explore whether the low achieving medical students are depressed and anxious before the respective professional examination. as psychological issues, may lead to poor concentration and difficulty in s c o r i n g b e tte r m a r ks i n t h e p ro fe s s i o n a l examinations. on the other hand it is possible that poor performance in professional examination may act as a stressful event, leading to anxiety and depression. moreover, some students may be having psychological morbidity before entering the medical college, which subsequently worsens due to pressure of academic demands and adjustment in the new environment. these questions need further reflection and exploration in order to comprehend the precise dynamics of psychological morbidity in future healthcare providers. therefore, we need further research with larger sample size, multiple settings and appropriate study designs to find the cause and effects relationship of different demographic and psychological variables. conclusion based upon our finding we conclude that the levels of depression, anxiety and stress are higher in medical students with poor academic performance. this observation provides a useful insight to better understand the higher prevalence of psychological morbidity in academically low performing medical students. it is possible that provision of appropriate psychological support to these students might improve their psychological well-being and academic performance. limitations a relatively small sample size, cross sectional design and single setting are the main limitations, therefore findings of this study cannot be generalized. declaration we declare that there was no conflict of interest involved in this research work and we did not receive any funds for its initiation and completion. the mean scores and standard deviations with regard to depression, anxiety, and stress were obtained for both the groups of medical students. as shown in table ii, there is statistically significant difference between the mean scores obtained by high and low achieving medical students on depression, anxiety and stress scale. it means that the low scoring (achieving) medical students had comparatively severe stress, anxiety and depression as compared to high (scoring) achieving medical students. discussion the finding of this research shows a significant difference in psychological morbidity in low scoring medical students, when compared to the high scoring ones. the findings of this study not only substantiate the previous research evidence on the psychological issues in medical students but it also adds a new dimension that the levels of psychological morbidity are comparatively much higher in low achieving medical students. a previous study done in malaysia concluded that low achieving students had increased depression, anxiety, and 17 stress than high achieving students. the results of this study and previous studies show the significance of psychological morbidity and its negative influence on academic performance of the medical students 18, 21 and the need for prevention of these issues. the perceived stressful factors, reported by students in this study are mainly socioeconomic, burden of various academic activities and problems in physical environment such as uncomfortable living and learning space. it is possible that students, who are depressed and anxious, perceive things differently than those who are healthy. moreover, the coping skills and personal resilience may also be different in students in both groups. previous studies have also identified various factors related to physical, social and psychological environment of medical college; which were reported by the medical students having table ii: differences in the mean scores of clinical variables between two groups. depression, anxiety and stress in low and high achieving medical studentsjiimc 2019 vol. 14, no.3 158 1997; 72(8):708-14. 13. dyrbye ln, thomas mr, massie fs, power dv, eacker a, harper w, durning s, moutier c, szydlo dw, novotny pj, sloan ja. burnout and suicidal ideation among us medical studentsmedical student burnout and suicidal ideation. annals of internal medicine. 2008; 149(5):334-41. 14. tyssen r, vaglum p, grønvold nt, ekeberg ø. suicidal ideation among medical students and young physicians: a nationwide and prospective study of prevalence and predictors. journal of affective disorders. 2001; 64(1):6979. 15. stewart sm, lam th, betson cl, wong cm, wong am. a prospective analysis of stress and academic performance in the first two years of medical school. medical educationoxford. 1999; 33(4):243-50. 16. newbury-birch d, white m, kamali f. factors influencing alcohol and illicit drug use amongst medical students. drug and alcohol dependence. 2000; 59(2):125-30. 17. yasin ma, dzulkifli ma. differences in depression, anxiety and stress between low-and high-achieving students. journal of sustainability science and management. 2011; 6(1):169-78. 18. a b d u l g h a n i h m , a l k a n h a l a a , m a h m o u d e s , ponnamperuma gg, alfaris ea. stress and its effects on medical students: a cross-sectional study at a college of medicine in saudi arabia. journal of health, population, and nutrition. 2011; 29(5):516-22. 19. dyrbye, liselotte n, thomas, matthew r, shanafelt, tait d. systematic review of depression, anxiety, and other indicators of psychological distress among u.s. and canadian medical students. 2006; 81(4):354-73 20. dyrbye ln, thomas mr, massie fs, power dv, eacker a, harper w, et al. burnout and suicidal ideation among u.s. medical students. ann intern med. 2008; 149:334-41. 21. suicidal ideation among medical students and young physicians: a nationwide and prospective study of prevalence and predictors. journal of affective disorders. 2001; 64(1):69-79. references 1. salam a, yousuf r, bakar sm, haque m. stress among medical students in malaysia: a systematic review of literatures. int med j. 2013; 20:649-655. 2. arab m, rafiei h, safarizadeh mh, ahmadi js, safarizadeh mm. stress, anxiety and depression among medical university students and its relationship with their level of happiness. j nurs health sci. 2016; 5:44-47. 3. menon v, sarkar s, kumar s: barriers to healthcare seeking among medical students: a cross sectional study from south india. postgrad med j. 2015; 91:477-482. 4. rab f, mamdou d, nasir s: rates of depression and anxiety among female medical students in pakistan. east mediterr heal j. 2008; 14:126-33. 5. inam sn, saqib a, alam e: prevalence of anxiety and depression among medical students of private university. j pak med assoc. 2003; 53(2):44-7. 6. rehmani n, khan qa, fatima ss: stress, anxiety and depression in students of a private medical school in karachi, pakistan. pak j med sci. 2018; 34:696-701. 7. alvi t, assad f, ramzan m, khan fa: depression, anxiety and their associated factors among medical students. j coll physicians surg pak. 2010; 20:122-26. 8. mahmood k: time to act-alarming rise in suicides among medical professionals in pakistan. j coll physicians surg pak. 2016; 26:947-949. 9. velayudhan a, gayatridevi s, bhattacharjee rr: efficacy of behavioral intervention in reducing anxiety and depression among medical students. ind psychiatry j. 2010; 19:41-46. 10. mosley th jr, perrin sg, neral sm, dubbert pm, grothues ca, pinto bm. stress, coping, and well-being among third year medical students. acad med. 1994; 70:152–156. 11. l e v e y r . s o u r c e s o f s t r e s s fo r r e s i d e n t s a n d recommendations for programs to assist them. acad med. 2001; 76:142–150. 12. helmers kf, danoff d, steinert y, leyton m, young sn. stress and depressed mood in medical students, law students, and graduate students at mcgill university. academic medicine. depression, anxiety and stress in low and high achieving medical studentsjiimc 2019 vol. 14, no.3 159 jiims final.cdr 3 original article abstract objective: the purpose of this study was to explore patient preferences in their dental treatment decision making and establish their role as active, passive or collaborative. study design: questionnaire based cross-sectional. place and duration of study: department of prosthodontics and the executive private clinics of the islamic st th international dental college, hospital from the 1 of february till the 30 of march 2012. materials and methods: a convenience sample of 80 patients, 40 recruited from the department of prosthodontics and 40 from the executive clinics at the islamic international dental college were interviewed and their preferences for participation in treatment decision making were established using a measurement tool designed to elicit decision-making preferences. patient preferences for participation in treatment decision making were established using a simplistic modification of the control preference scale (cps) tool. results: this study found that 45% clinic patients perceived active/semi-active roles in treatment decision making, 42.5% chose passive/semi-passive roles. 90% patients interviewed at the department of prosthodontics preferred passive/semi-passive roles. over all, out of 80 patients, 53 chose the passive/semipassive roles. conclusion: patients presenting at the private clinics prefer being actively involved in their treatments, having said that, majority of them choose to get treatment from private clinics because they expect better services and have more trust in their doctors. key words: control preference scale (cps), treatment decision making, patient preferences. participation preferences of any pakistani population in their dental decision making. it is pertinent to explore the elements of decision making in dental care, as patient participation is a field which has both ethical and legal implications in an increasingly user-focused, 'consumerist' health service, given that most dental care is paid for, in part or whole, by the patient. more importantly, b y i d e n t i f y i n g t h e p a t i e n t ' s d e n t a l preferences as active, passive or somewhere in-between, clinicians would obtain an insight not only into the outcome the patients have perceived but also in deciphering between different patient personalities. although, a number of methods have been used to examine patients' decisional role preferences, a modification of the control preferences scale would be used in this 5o b s e r v a t i o n a l s t u d y. t h i s s i m p l e introduction the demise of “single best treatments”, rise in multi-faceted chronic illnesses, variations in the provision of services, increasing costs and increasing availability of newer and easily accessible information are all cited as reasons contributing to patients getting actively involved in the decision making of their treatment plans. the shift in paternalistic decision-making where physicians play a more dominant role to one that actively involves patient involvement 1has been documented to be on the rise. studies on patient-doctor relationship along with elements addressing satisfaction have 2,3,4also been documented. no research so far has been conducted on assessing the ------------------------------------------------a study to evaluate patient preferences in the decision making of dental treatment faisal moeen, yawar hayat khan, uzma hasan correspondence: dr. faisal moeen asstt prof of dental material islamic international dental college, islamabad e.mail:faisal.moeen@riphah.edu.pk 3 4 m e t h o d o l o g y i n v o l v e s p r e s e n t i n g individuals with five options, each with a written statement. these options describe increasing levels of patient involvement in treatment decision-making, from the patient completely relinquishing control to c l i n i c i a n s , t h r o u g h t o t h e p a t i e n t maintaining complete control of treatment decision-making. patients are asked to choose one most preferred and one least preferred role from the five possible options which would determine whether the patient prefers a passive, collaborative or an active role. the aims of this study are to firstly evaluate patient preferences in the decision making of their dental treatments and secondly to compare the dental decision making preferences between patients presenting at the department of prosthodontics and the private, executive clinics both situated at the islamic international dental college, islamabad. patients were eligible for inclusion if they p r e s e n t e d a t t h e d e p a r t m e n t o f prosthodontics and the private clinics of the teaching hospital for elective replacement of missing teeth. they needed to be above the age of 18. patients were recruited consecutively and studied prospectively between february and march of 2012. the protocol of the study was approved by the ethics committee of the islamic international dental college and all patients gave informed consent. a convenience sample of 80 patients was r e c r u i t e d f o r t h i s s t u d y f ro m t h e prosthodontic department (40) and the executive clinics (40) of the islamic international dental college. each patient materials and methods was explained the objectives of the study and assured confidentiality of their responses. no patient declined to be a part of this study and no patient was excluded. patient preferences for participation in decision making were established using the 5control preference scale (cps). although, the cps enables identification of a role preference hierarchy for each respondent i.e. an order of preference from most preferred to least preferred role, our study for the sake of simplicity would not formulate a hierarchy of role preferences. patients would simply make choices as to the most preferred and least preferred options. the cards would however be presented to the patients in a mixed, randomly arranged 6 format. this would eliminate the possible introduction of bias which exists if the fixed order approach is used. once an option was selected, each patient was asked to give a rationale as to why that option was selected. the responses were recorded verbatim. by the end of the procedure, each patient would have chosen one option of the five and would be classed as either having an active, collaborative or passive decisional role preference. data from the control preferences scale can 5be analyzed in a number of ways. the simplest approach which is adopted here active role options collaborative role options passive role options 4 5 will be to extract the most and least preferred roles from each patient's response followed by a frequency count for each role. non-numerical data relating to patients' rationales for choice of role preference were content analyzed to enable identification of 7themes. all 80 patients appeared to understand the options presented in each of the five cards and their applicability to dental situations was confirmed. no further revision of the cards was necessary. each participant understood the concept of choosing the most and the least preferred options applicable to their treatments however some degree of explanation was required in a few situations. at the hospital setting, 21 patients out of the 40 (52.5%) chose card 'e' as the most preferred choice, leaving all decisions regarding their treatment planning and execution to the dentists. 15 patients (37.5%) chose card 'd' as their most preferred choice which is again following a similar trend as card 'e' i.e. the doctor deciding what is in the best interest of the patient although in consult with the patient. patients who were questioned at the executive clinics/private setting showed varied and mixed responses with choices leaning slightly more towards an active or a semi-active role. 6 patients (15%) chose option 'a', 12 (30%) chose o p t i o n ' b ' , h e n c e 4 5 % p a t i e n t s accumulatively chose between options 'a' and 'b'. five patients (12.5%) chose option 'c', 15 (37.5%) chose option 'd' and finally only 2 patients (5%) chose option 'e' as their most preferred choices. 42.5% patients hence choose between options 'd' and 'e'. results the two extreme choices 'a' and 'e' were overwhelmingly the least preferred at both sites, with the fully active role (card a) being particular unpopular. from the 40 patients questioned at the dental college, 30 patients (75%) chose option 'a' and 10 (25%) chose option 'e' as their least preferred choices. 22 patients (73.3%) and 18 (45%) chose options 'a' and 'e' respectively from the clinics. figure 1: distribution of the most preferred roles in treatment decision making. figure 2: distribution of the least preferred roles in treatment of decision making. 5 6 discussion previous studies using the control preferences scale have mainly been with patients suffering from cancer or other 8 1 0s e r i o u s i l l n e s s . h o w e v e r, t h e methodology has worked well in the dental context giving rise to interesting insights which are of great relevance to dental 11, 12practitioners. this would suggest that this extremely useful methodology is transferable to dental settings. although this study focuses on a select group of patients and the results obtained from such a small sample size does not represent the preferences in dental decision making of the general population, it does provide valuable information regarding the attitudes patients can have towards involvement in their treatments. dentists need to help patient participation in the decision making by explaining the nature of the disease, treatment options, benefits of the options, time required in completing the treatment and most importantly the cost incurred in achieving the desired treatment. analysis of the verbatim data regarding patients' rationales for their role preference revealed that 52 of the 80 patients interviewed mentioned lack of knowledge of the subject as influencing their ability to participate in treatment decisions, and several comments were: “i don't know the science behind medicine, so i'll leave the decision to someone who does”. patients presenting at the private clinics in particular mentioned that they were paying extra to get treated by a specialist and hence they would seriously consider the decisions of their doctor. trust was specifically referred to by 68 of the 80 patients, with comments like: “the doctor is a professional, therefore you should trust him/her”, “if you can't trust the doctor, there's something wrong”. therefore, either the patients lacked knowledge about health care and hence had no choice but to trust the healthcare provider or they knew the doctor before hand having genuine trust in his/her abilities and decision making skills. a further common theme amongst patients was lack of time for discussion. twenty nine of the 80 patients cited lack of time as a reason, and comments were: “there isn't enough time for the doctor to really consider my opinions”, “there's never enough time to sit and discuss everything”. in the part of preferences for patient participation in treatment decision making, the most preferred role in the private clinic is semi-active compared to a collaborative role in the hospital setting. it is interesting to see that 15% of patients at the private clinic choose option 'a' as their most preferred role with the rationale that they know beforehand the expenses involved in getting treatment from a private clinic and they would solely decide if or when is the correct time to proceed with the treatments. in this study an active role was more commonly perceived in clinics than in the teaching hospital. over-all lesser number of patients preferred an active rather than the passive role, however, there is no clear evidence that pakistani patients prefer more active roles than do their counterparts in advanced countries. finally, this finding suggests that a majority patients presenting at the islamic international dental college h a v e p o s i t i v e a t t i t u d e s t o w a r d s participation in dental decision making if they are fully informed. conclusion 6 7 references 1. national health service executive patient partnership: building a collaborative strategy department of health: london 1996. 2. charles c, gafni a, whelan . decision making in the physician-patient encounter: revisiting the shared treatment decision making model. soc sci med 1999; 49: 651-61. 3. levine mn, gafni g, markham b, macfarlane d. a bedside decision instrument to elicit a patient's preference concerning adjuvant chemotherapy for breast cancer. ann intern med 1992; 117: 53-8. 4. corah nl, o'shea rm, pace lf, seyrek sk. development of a patient measure of satisfaction with the dentist: the dental visit satisfaction scale. j behav med 1984; 7: 367-73. 5. degner lf, sloan jf, venkatesh p. the control preferences scale. can j nurs res 1997; 29: 21-43. 6. chapple h, shah s, caress al, kay ej. exploring dental patients' preferred roles in treatment decision-making a novel approach. br dent j 2003; 194:321-7. 7. hack tf, degner lf, dyck dg. relationship between preferences for decisional control and illness information among women with breast cancer: a quantitative and qualitative analysis. soc sci med 1994; 39: 279-89. 8. ende j, kazis l, ash a, moskowitz ma measuring patients' desire for autonomy: decision making and information seeking preferences among medical patients. j gen intern med 1989; 4: 23-30. 9. beaver k, luker ka, owens rg, leinster sj, degner lf, sloan ja treatment decision making in women newly diagnosed with breast cancer. cancer nurs 1996; 19: 8-19. 10. oates ajl, fitzgerald m, alexander g patient d e c i s i o n m a k i n g i n re l a t i o n t o e x t e n s i v e restorative treatment. part ii: evaluation of a patient decision making model. br dent j 1995; 179: 11-8. 11. redford m, gift hc dentist-patient interactions in treatment decision making: a qualitative study. j dent educ 1997; 61: 16-21. 7 original�article abstract objective: to determine the effect of sustained natural apophyseal glides (snags) along with muscle energy technique (met) on pain and range of motion in subjects with mechanical neck pain. study design: blinded randomized controlled trial. th th place and duration of study: kulsum international hospital islamabad, from july 16 to december 25 , 2018. materials and methods: the trial included 60 participants with mechanical neck pain who fulfilled inclusion criteria (mechanical neck pain, being vitally stable and physically independent without any serious psychological or systemic issue) and gave written and verbal consent. subjects were divided randomly by concealed envelope method into two groups: experimental and control with 30 participants each. experimental group was provided with met and snags, while control group received snags thrice a week for 8 weeks. numeric pain rating scale and inclinometer were used as outcome measures. data was taken at baseline and after 8 weeks of intervention. analysis was done by spss 21. results: pain improved from 7.14±0.88 to 2.33±0.73 (p=0.000) in experimental while 7.25±.98 to 3.18±.87 (p=0.009) in control group. ranges improved in experimental and control group as; flexion from 73.81±2.6 to 84.88±2.3 (p=0.000) and 73.25±2.8 to 77.00±2.5 (p=0.010), extension from 63.14±2.2 to 69.00±1.2 (p=0.000) and 62.07±1.8 to 65.66±1.5 (p=0.000), right side banding from 33.03±3.6 to 39.77±2.5 (p=0.000) and 32.25±3.0 to 36.00±2.5 (p=0.000), left side bending from 33.55±2.4 to 41.55±1.9 (p=0.000) and 32.44±2.1 to 37.48±1.6 (p=0.001), right side rotation from 79.96±2.70 to 88.48±1.5 (p=0.000) and 79.48±2.60 to 83.59±2.6 (p=0.000) and left side rotation from 80.37±2.4 to 88.92±1.9 (p=0.000) and 79.74±2.5 to 82.88±2.2 (p=0.005) respectively. conclusion: snags combined with met reduces pain and improves range of motion effectively in subjects with mechanical neck pain as compared to conventional treatments with snags alone. key words: muscle energy technique, neck pain, range of motion, sustained natural apophyseal glides. are least chances of tissue injuries associated with mechanical neck pain. common causes of mechanical neck pain are facet joint irritation or 1 dysfunction. majority of population worldwide must suffer disability throughout their lives because of neck and back pain. neck pain is fourth leading cause of disability and has the prevalence of 30%. it comes in episodes that resolve without any intervention, but in about 50% of population pain remains the same and causes limitation of 2 participation in daily activities. two third of the adult population experience neck pain at some point of their lives that causes high socioeconomic 3 impacts. patients with mechanical neck pain are usually offered symptomatic treatment which alleviates the symptoms temporarily, but the symptoms may reappear. the cases referred to physiotherapy are also less that ultimately leads to introduction mechanical neck pain also known as non-specific neck pain is diagnosed based on symptoms that are not caused by any serious cervical spine pathology i.e., malignancy, trauma, or radiculopathy etc. there muscle energy technique augmented with sustained natural apophyseal glides; an effective way to improve mechanical neck pain and range of motion: a randomized control trial 1 2 3 4 5 6 nasir sultan , kiran khushnood , shafaq altaf , malik muhammad ali awan , sidra qureshi , riafat mehmood correspondence: kiran khushnood isra institute of rehabilitation sciences isra university, ilsamabad e-mail: kirankhushnood@yahoo.com 1,3 department of rehabilitation shifa tameer-e-millat university, islamabad 2, 4 isra institute of rehabilitation sciences isra university, ilsamabad 5 foundation university institute of rehabilitation sciences, foundation university, islamabad 6 department of physiotherapy kulsum international hospital, islamabad funding source: nil; conflict of interest: nil received: november 21, 2019; revised: december 13, 2020 accepted: january 04, 2021 augmented approach of met and snags for mechanical neck pain and range of motionjiimc 2021 vol. 16, no.2 96 4 disability in patients with neck pain. the common interventions used in physical therapy to alleviate neck pain and improve range of motion are manual therapy techniques, exercises, and modalities. manual therapy has been observed to 5 improve pain and range in subjects with neck pain. manual therapy techniques focus on joint function, stability and range of motion as well as symptom 6 severity. evidences have shown effectiveness of manual therapy alone and in combination with other 3 exercises and modalities as well. transcutaneous electrical nerve stimulation, ultrasound and active exercise are considered to be best for combination with manual therapy for treatment of neck pain and improvement in range of motion. there are also evidences of strengthening exercises in mechanical 7 neck pain. one of the major manual therapy techniques is mulligan's sustained natural apophyseal glides (snags) used to manage various 8 spine dysfunctions. snags are observed to alleviate symptoms associated with cervical spine disorders 9 i.e. neck pain, headache and range restriction. another technique that has been observed to show p o s i t i v e e f fe c t s o n r e s t r i c t e d ra n g e a n d improvement in somatic function is muscle energy 10 technique (met). as both techniques have shown effects in improving restrictions and symptoms associated with cervical pain, it would be beneficial for the patient to have combination treatment comprising of snags and met for earlier relief and hence reducing costs of extended physical therapy sessions. so, study was aimed to determine the effect of sustained natural apophyseal glides (snags) augmented with muscle energy technique (met) on pain and range of motion in subjects with mechanical neck pain. materials and methods blinded randomized control trial was started after taking ethical approval from the study setting; th kulsum international hospital in july 16 to th december 25 2018. initially 83 subjects with mechanical neck pain aged 20 to 45 years were assessed; subjects with any history of head, neck or chest trauma, surgery or any serious systemic pathology were excluded. decision about sample size was done in accordance with evidence from 11-13 previous literature that was 45-60. the sampling method was non-probability purposive sampling and randomization was done using sealed envelope method. in the study 60 participants fulfilled inclusion criteria of having mechanical neck pain, being vitally stable, physically independent and without any serious psychological or systemic issue, were enrolled after taking written and verbal informed consent, participants were randomly divided into two groups; experimental (n=30) and control group (n=30). participants and outcome assessors were blinded, as the participants were explained about the whole procedure but were unaware about their inclusion in particular group. baseline assessment was done along with assessment of outcome measures which included numeric pain rating scale (nprs) and cervical range of motion through inclinometer for each participant. there were 3 dropouts from each group, who could not follow up the sessions. numeric pain rating scale was used to assess the intensity of pain on a scale of 0 to 10, where 0 is considered as no pain while 10 means worst pain ever felt. 2-point change in the scale is considered as clinically significant by clinicians as mentioned in the 14 literature. range of motion was measured through inclinometer, which is used for taking measurements 15 of spinal ranges and has good reliability. there was not much difference in measurements of outcome variables among the participants of both groups at baseline. pain was measured through nprs, while inclinometer was used to access the range of motion. after randomization, subjects in experimental group were provided with met and snags, while control group received snags thrice a week for 8 weeks. the intervention along with data collection was performed by trained physical therapist. group a was the experimental group who received met along with snag. for met, the subject was asked to sit in relaxed position, then end range of cervical muscles was achieved and subject was asked to contract the muscle voluntarily to 20% of total strength. the contraction was held for 6-10 seconds then released. there were 4 repetitions in each session. snags were performed at cervical spine in sitting position with 6-10 repetitions in two sets each in one session with 10 minutes rest between both sets. whereas group b was the control group and only received snags. inferential current for 15 minutes and postural education was provided to augmented approach of met and snags for mechanical neck pain and range of motionjiimc 2021 vol. 16, no.2 97 subjects of both intervention and control group. sessions were repeated for 3 times a week for 8 weeks, 6 subjects were dropped out of the study. data was evaluated using spss 21. as the data was parametric, paired sample test was used for within group analysis while independent t test was used for between group analysis of the data that was taken at baseline and after 8 weeks of interventions. results there were 54 participants who completed the study and were analyzed, although demographic data was taken initially from all the participants at the start of the study. gender distribution in both groups is shown in figure 1. (sd= standard deviation, n= number of participants, nprs= numeric pain rating scale) paired t test was applied for within group comparison of outcome measures as explained in table ii. fig 1: gender distribution figure 2 represents the baseline characteristics of participants from both groups, including past medical history, surgeries, allergies, and addictions. (git= gastrointestinal tract) independent t test was used for between group analysis of outcomes post intervention in experimental and control group, and results appeared as described in table i. discussion the study focused on two major symptoms of fig 2: baseline characteristics of participants table i: between group analysis (post intervention) – neck range of motion and pain table ii: within group analysis – neck range of motion and nprs (sd= standard deviation, n= number of participants, nprs= numeric pain rating scale) mechanical neck pain: pain and restricted range of motion and effect of snags with met on these symptoms. the techniques were found to be effective if given together according to the results augmented approach of met and snags for mechanical neck pain and range of motionjiimc 2021 vol. 16, no.2 98 obtained from the study. many studies have been conducted before to assess the effectiveness of both snags and met for neck pain. a randomized control trial conducted by apoorva phadke et al. in 2016 assessed the effect of muscle energy technique and static stretching on pain and functional disability in subjects with mechanical neck pain. the research showed that muscle energy technique is more effective for mechanical neck pain as compared to static stretching and conventional treatment techniques. muscle energy technique has gross effects in 16 subjects of mechanical neck pain. current study has shown that if combined with snags, met can bring even more positive changes in symptoms. a case report by sudarshan anandkumar to check the effect of sustained natural apophyseal glide combined with neurodynamics in the subject of cervical pain and radiculopathy showed that it can reduce symptoms of neck pain and radiculopathy and can improve cervical range of motion and functional abilities. present study has also shown reduction in symptoms in cervical pain with 17 combination of snags and met. current study has also shown that met can improves cervical range of motion, augmented with snags to amplify the effects of met. burns et al conducted a randomized control trial and studied effects of muscle energy technique on cervical spine and concluded that met is responsible for improving 18 cervical range of motion. another trial conducted by kanlayanaphotporn et al in 2008 studied effects of mobilization for relief of pain and improvement in range of motion in patients with mechanical neck pain and found that mobilization improved range and reduced pain in 19 subjects on immediate basis. present study also signifies that snags can reduce pain and improve range in mechanical neck pain; the difference was addition of met along with snags. patient's home activities and follow ups along with various other ergonomic and domestic factors also play role in prognosis and improvement. conclusion snags combined with met improves range of motion and are helpful in reducing pain in subjects with mechanical neck pain as compared to conventional treatments and snags alone, so the approach is recommended and can help the sufferers gaining the restricted range and help then with continuing their daily activities and functions with least hindrance. references 1. nakamaru k, aizawa j, kawarada k, uemura y, koyama t, nitta o. immediate effects of thoracic spine selfmobilization in patients with mechanical neck pain: a randomized controlled trial. journal of bodywork and movement therapies: 2019 apr 1; 23(2):417-24. 2. cohen sp. epidemiology, diagnosis, and treatment of neck pain. inmayo clinic proceedings: 2015; 90(2):284-299. 3. groeneweg r, van assen l, kropman h, leopold h, mulder j, smits-engelsman bc, ostelo rw, oostendorp ra, van tulder mw. manual therapy compared with physical therapy in patients with non-specific neck pain: a randomized controlled trial. chiropractic & manual therapies: 2017 dec 1; 25(1):12. 4. vos c, verhagen a, passchier j, koes b. management of acute neck pain in general practice: a prospective study. british journal of general practice: 2007 jan 1; 57(534):23-8. 5. langevin p, gross a, burnie s, bédard-brochu ms. manipulation and mobilisation for neck pain contrasted against an inactive control or another active treatment: update of a cochrane review. manual therapy: 2016; 100(25):e98-e99. 6. van de veen ea, de vet hc, pool jj, schuller w, de zoete a, bouter lm. variance in manual treatment of nonspecific low back pain between orthomanual physicians, manual therapists, and chiropractors. journal of manipulative and physiological therapeutics: 2005 feb 1; 28(2):108-116. 7. rush pj, shore a. physician perceptions of the value of physical modalities in the treatment of musculoskeletal disease. rheumatology: 1994 jun 1; 33(6):566-568. 8. exelby l. the mulligan concept: its application in the management of spinal conditions. manual therapy: 2002 may 1; 7(2):64-70. 9. shin ej, lee bh. the effect of sustained natural apophyseal glides on headache, duration, and cervical function in women with cervicogenic headache. journal of exercise rehabilitation: 2014 apr; 10(2):131. 10. fryer g. muscle energy concepts-a need for change. journal of osteopathic medicine: 2000; 3(2):54-59. 11. pérez hi, perez jl, martinez ag, la touche r, lerma-lara s, gonzalez nc, perez ha, bishop md, fernández-carnero j. is one better than another? a randomized clinical trial of manual therapy for patients with chronic neck pain. manual therapy: 2014 jun 1; 19(3):215-221. 12. mahajan r, kataria c, bansal k. comparative effectiveness of muscle energy technique and static stretching for treatment of subacute mechanical neck pain. int j health rehabil sci: 2012 jul; 1(1):16-21. 13. tank kd, choksi p, makwana p. to study the effect of muscle energy technique versus mulligan snags on pain, range of motion and func-tional disability for individuals with mechanical neck pain: a comparative study. int j physiother res: 2018; 6(1):2582-2587. 14. firdous s, mehta z, fernandez c, behm b, davis m. a augmented approach of met and snags for mechanical neck pain and range of motionjiimc 2021 vol. 16, no.2 99 comparison of numeric pain rating scale (nprs) and the visual analog scale (vas) in patients with chronic cancerassociated pain. journal of clinical oncology: 2017; 35(31):217. 15. ligorio g, sabatini am. a novel kalman filter for human motion tracking with an inertial-based dynamic inclinometer. ieee transactions on biomedical engineering: 2015 mar 9; 62(8):2033-43. 16. phadke a, bedekar n, shyam a, sancheti p. effect of muscle energy technique and static stretching on pain and functional disability in patients with mechanical neck pain: a randomized controlled trial. hong kong physiotherapy journal: 2016; 35:5-11. 17. anandkumar s. the effect of sustained natural apophyseal glide (snag) combined with neurodynamics in the management of a patient with cervical radiculopathy: a case report. physiotherapy theory and practice: 2015; 31(2):140145. 18. burns dk, wells mr. gross range of motion in the cervical spine: the effects of osteopathic muscle energy technique in asymptomatic subjects. the journal of the american osteopathic association: 2006; 106(3):137-42. 19. kanlayanaphotporn r, chiradejnant a, vachalathiti r. the immediate effects of mobilization technique on pain and range of motion in patients presenting with unilateral neck pain: a randomized controlled trial. archives of physical medicine and rehabilitation: 2009; 90(2):187-92. augmented approach of met and snags for mechanical neck pain and range of motionjiimc 2021 vol. 16, no.2 100 untitled-2 untitled-2 original�article abstract objective: to determine the co-relation between perceived social support and stress among nursing staff working in a covid-19 dedicated hospital setup. study design: cross-sectional study. place and duration of study: armed forces institute of mental health (afimh), rawalpindi from 30 aug 2020 to 02 march 2021. materials and methods: we consecutively sampled 128 subjects. all participants were requested to complete a brief demographic sheet, urdu version of the depression, anxiety and stress scale 21 (dass-21) to assess the level of severity of stress among nursing staff and the urdu version of the multidimensional scale of perceived social support (mspss). data analysis was done using spss version 23.0. results: the mean duration of stay of nursing staff in ward was 4.86 ± 2.28 weeks. sixty-two (48.44%) nurses had duration of 2 to 4 weeks while 66 (51.56%) nurses had duration of more than 4 weeks of stay in the ward. the mean total stress score was 6.86 ± 5.80. the mean multidimensional scale of perceived social support (mspss) score was 47.29 ± 22.53. there was significant negative correlation between mspss score and stress score (r= -0.396, p-value < 0.05). conclusion: results of this study highlighted that a significant negative co-relation is present between perceived social support and stress among nursing staff working in a covid-19 dedicated hospital setup. key words: anxiety, covid-19, depression, nursing staff, stress. protective equipment (ppe), which made their 3 routine tasks more arduous. in addition health care professionals had to make decision to selectively put certain patients on life support, while knowingly depriving other patients of these facilities due to lack 4 of available resources . to add to these issues, some staff required going themselves into quarantine while those who were pregnant or immunecompromised were not able to contribute as frontline workers and as a result feelings of guilt 5 surfaced in some individuals. in these difficult circumstances, having social support from colleagues, hospital administration (formal social support) and family (informal social support) may play a major role in deterring mental health challenges for the nursing staff. nurses who have increased perceived social support have been 6, 7 documented to have decreased stress levels. social support can have four different characteristics in the form of emotional, instrumental, informational and 8 evaluative support. every individual in his own way perceives his social network adequately supportive or not, is in simple terms “perceived social support”. evidence has shown that social support is correlated with mental health as it protects against mental introduction infectious disease caused by coronavirus (sars-cov2) reached the scale of a pandemic on march 11, 1 2020. covid-19 brought unprecedented challenges and catastrophic burden on healthcare services particularly health care workers were affected. nursing staff was at increased risk of getting infected with this virus, were continuously in danger of being infected while on duty and they also carried the same 2 risk for their families. long working hours at hospitals kept them away from their families, which further added to their stress, they also had the duty of caring for their colleagues who were covid-19 affected and they needed to work with personal level of stress among health care workers in covid-19 dedicated setup 1 2 3 4 asif azeem , sikandar ali , ayesha shabbir , tashfeen bin nazeer correspondence: dr. asif azeem department of psychiatry afimh, rawalpindi e-mail: drasifbajwa@yahoo.com 1,3 department of psychiatry afimh, rawalpindi 2 department of psychiatry cmh, mangla 4 department of psychiatry afpgmi rawalpindi received: september 14, 2022; revised: november 19, 2022 accepted: november 22, 2022 stress among health care workersjiimc 2022 vol. 17, no.4 269 doi: https://doi.org/10.57234/1530 health problems, thereby alleviating stress and 9 anxiety issues. in these circumstances, social support may be a highly effective factor in off-setting the effects of stressors for nursing staff, thereby protecting their mental health and ultimately contributing to their ability to provide an improved quality of patient care. currently, there is a paucity of literature investigating relationship between perceived support and level of stress among nursing staff of pakistan. therefore, this study aimed at finding evidence that social support protects the nursing staff from development of stress while serving covid-19 patients. materials and methods after approval of ethical committee vide erc ref (019/20), this cross-sectional study was done at armed forces institute of mental health (afimh), rawalpindi from 30 aug 2020 to 02 march 2021. a total sample size of 128 was estimated using 10 statistical formula n= [(zα+zβ)/c]2+3 by hulley 11 keeping results of study by xiao et al as reference. we consecutively sampled 128 subjects using convenience non probability sampling technique. both genders, age range 20-60 years, nurses working in covid-19 dedicated wards, hdus and icus at pemh, rawalpindi, nurses who had worked at least for a duration of 2 weeks in above settings were included in this study after consent. doctors and ancillary support staff, covid-19 infected nurses, nurses with pre-existing mental health problems were not included. participants completed a brief demographic sheet, depression, anxiety and 12 stress scale 21 (dass-21) urdu version and multidimensional scale of perceived social support 13 (mspss) urdu version. mspss a 12-item scale has subscales for family, friends and significant other 14 (each subscale having 4 items on the mspss). the respondents answered each item on a 7-point likert scale with the following responses, 1 for very strongly disagree, 2 for strongly disagree, 3 denoting i disagree, 4 representing neutral response, 5 meant i agree, 6 denoting i strongly agree while 7 meant i very strongly agree. total sum of all twelve items were calculated for all respondents for obtaining the mean score for perceived social support (range = 1 to 84). mean and standard deviation for psss score was described. the dass 21 has three sub scales for stress, anxiety, and depression with each subscale 15 having seven items on the scale. each item on the scale is required to be responded from 0 to 3 on likert scale where 0 denotes that it did not apply to me at all, 1 means it applied to me to some degree, or some of the time, 2 means it applied to me to a considerable degree or a good part of the time and 3 represents that it applied to me very much or most of the time. seven items of stress subscale were added and then multiplied by 2 to obtain a stress score representing 0 to 7 as normal, 8 to 9 as mild, 10 to 12 as moderate, 13 to 16 as severe while more than 17 as extremely severe. spss version 23.0 was used to analyze data. for age, duration inward, psss and stress score mean and standard deviation while frequency and percentages for categorical variables such as gender, and proportion of nurses in the various categories of perceived social support and stress were calculated. the outcome variable for the study was the perceived social support score (psss). the dependent variables for the study was the stress score (ss). pearson's correlation coefficient was calculated for the psss and ss. effect modifiers such as age, gender duration of work/stay in ward were controlled by stratification and post-stratification correlation was applied. post stratification chi squared test was used. statistical significance level was set to maximum of 5% (p<0.05). results the mean age of participants in this study was 30.81 ± 6.56 years (21 45 years), 80 (62.50%) were male and 48 (37.50%) female nurses with higher male to female ratio. the mean duration of stay of nursing staff in ward was 4.86 ± 2.28 with minimum and maximum duration in ward was from 2 to 8 weeks, 62 (48.44%) nurses had duration of 2 to 4 weeks while 66 (51.56%) nurses had duration of more than 4 weeks of stay in the ward. the mean total stress score was 6.86 ± 5.80, 72 (56.25%) nurses had normal scores, 19 (14.84%) had mild stress, 10 (7.81%) had moderate, 18 (14.06%) had severe while 9 (7.03%) had extremely severe stress. the mean mspss score was 47.29 ± 22.53 with significant negative correlation between mspss and stress scores r0.396, (p < 0.05). discussion current study findings show a significant negative correlation between mspss score and stress scores stress among health care workersjiimc 2022 vol. 17, no.4 270 doi: https://doi.org/10.57234/1530 table ii: comparison of stress score with demographic variables perceived from informal social support of friends, family and significant others, related to psychological health and quality of life which in turns improves the 19 mental health and quality of life. our findings are almost in agreement to another published study, i.e., xiao et al. which assessed the correlation between social support and stress of 180 health care workers involved in taking care of patients with covid-19 in a hospital in wuhan, china. their investigation found that social support had a negative weak correlation 11 with stress (standardized coefficient = 0.245). in another study done during covid pandemic by turkish investigators it was observed that the level of social support perceived by the nurses was very good while perceived psychological resilience level was moderately good which increased as the perception 20 of social support was increased. informal sources of social support have received less attention in 21 research as compared to formal sources of support. however, for most individuals, family and friends are the basic and foremost form of support and connection which they will turn to first in times of stress. they tend to utilize this resource before they turn to more formal sources of support i.e., superiors 22 and organizations . williams et al state that structure of informal social support network is an indicator of good social support therefore larger 23 support network is preferable. these results substantiate findings of other studies by uncovering the underlying mechanisms between social support and mental health. they have impact on mental health services for nurses working during the peak period of covid-19. during pandemic there is need to focus on availability of informal sources of table i: demographic variables fig. 1: severity of stress in nurses of nursing staff working in wards/icus of pemh rawalpindi, indicating psychological distress among nursing staff while dealing with covid-19 patients. these findings are like those of various other studies which have described psychological adverse effects among medical staff working during covid19 16,17,18 health crisis. this study has focused on co-relation of stress with stress among health care workersjiimc 2022 vol. 17, no.4 271 doi: https://doi.org/10.57234/1530 social support particularly for nursing staffs who serve in closer proximity to patients as compared to doctors. health care administrators need to be sensitive to these issues to address them in a better way. conclusion it is concluded that stress was seen in several staff nurses with significant negative co-relation between perceived social support and stress, whether formal or informal, has the capacity to impact the efficiency of nursing staff. hence, social support must be enhanced to reduce the stress levels among the nurses who have important role as spearheads in the fight against covid-19. refernces 1. cucinotta d, vanelli m. who declares covid-19 a pandemic. acta biomed. 2020;91(1):157-60. 2. 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;323(13):1239-42. 3. walton m, murray e, christian md. mental health care for medical staff and affiliated healthcare workers during the covid-19 pandemic. eur heart j acute cardiovasc care. 2020;9(3):241-7. 4. covid j. dashboard by the center for systems science and engineering (csse) at johns hopkins university (jhu). 2020 j h s u ; 2 0 2 0 a v a i l a b l e f r o m : https://coronavirus.jhu.edu/map.html. 5. maunder r, hunter j, vincent l, bennett j, peladeau n, leszcz m, et al. the immediate psychological and occupational impact of the 2003 sars outbreak in a teaching hospital. cmaj. 2003;168(10):1245-51. 6. shirey mr. social support in the workplace: nurse leader implications. nurs econ. 2004;22(6):313-9. 7. velando-soriano a, ortega-campos e, gómez-urquiza jl, ramírez-baena l, de la fuente ei, cañadas-de la fuente ga. impact of social support in preventing burnout syndrome in nurses: a systematic review. jpn j nurs sci. 2020;17(1):15. 8. liu x-x, liu w-h, ping m, li c-y, liu x-y, song p. correlation between resilience and social support and anxiety in obstetric nurses. frontiers of nursing. 2018;5(4):311-5. 9. samson p. stress, anxiety, and depression: role of campus connectedness, social support, and coping among nepalese nursing students. walden uni. 2018:1-219. 10. schmidt sa, lo s, hollestein lm. research techniques made simple: sample size estimation and power calculation. journal 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guo l, liu y, et al. the psychological impact of covid-19 pandemic on medical staff in guangdong, china: a cross-sectional study. psychol med. 2020:1-9. 17. dai y, hu g, xiong h, qiu h, yuan x. psychological impact of the coronavirus disease 2019 (covid-19) outbreak on healthcare workers in china. medrxiv. 2020. 18. de kock jh, latham ha, leslie sj, grindle m, munoz s-a, ellis l, et al. a rapid review of the impact of covid-19 on the mental health of healthcare workers: implications for supporting psychological well-being. bmc public health. 2021;21(1):1-18. 19. oztunc g, yesil p, paydas s, erdogan s. social support and hopelessness in patients with breast cancer. asian pacific journal of cancer prevention [internet]. 2013 jan 31;14(1):571–8. 20. kılınç t, sis çelik a. relationship between the social support and psychological resilience levels perceived by nurses during the covid-19 pandemic: a study from turkey. perspect psychiatr care. 2020. 21. esteban sánchez-moreno, iria-noa de la fuente roldán, lorena p. gallardo-peralta, ana barrón lópez de roda. burnout, informal social support and psychological distress among social workers, the british journal of social work, volume 45, issue 8, december 2015, pages 2368–2386. 22. jo billings, talya greene, tim kember, nick grey, sharif elleithy, deborah lee, helen kennerley, idit albert, mary robertson, chris r brewin, michael a p bloomfield, supporting hospital staff during covid-19: early interventions, occupational medicine, volume 70, issue 5, july 2020, pages 327–329. 23. sharon wallace williams, phd, peggye dilworth-anderson, phd, systems of social support in families who care for dependent african american elders, the gerontologist, volume 42, issue 2, 1 april 2002, pages 224–236 stress among health care workersjiimc 2022 vol. 17, no.4 272 doi: https://doi.org/10.57234/1530 conflict of interest authors declared no conflicts of interest. grant support and financial disclosure authors have declared no specific grant for this research from any funding agency in public, commercial or nonprofit sector. data sharing statment the data that support the findings of this study are available from the corresponding author upon request. this is an open access article distributed under the terms of the creative commons attributionnoncommercial 2.0 generic license. stress among health care workersjiimc 2022 vol. 17, no.4 273 doi: https://doi.org/10.57234/1530 abstract objective: to compare the complete healing of chronic anal fissure by using 2% nifedipine paste and 0.5% glyceryl trinitrate ointment each applied locally for 6 weeks. study design: randomized controlled trail. place and duration of study: surgical unit-i, pakistan railway hospital rawalpindi spanning over a period of 06 months starting from march 2011 to august 2011. materials and methods: seventy six patients of chronic anal fissure were included in the study. non-probability convenience sampling was used for the enrolment of patients. patients were divided equally into two treatment groups a & b. group 'a' was treated with topical 2% nifedipine paste and group 'b' was treated with 0.5% glyceryl trinirate ointment. patients were asked to come for the follow up after six weeks to look for symptomatic improvement and healing rate. results: all 38 patients included in the study completed the follow up after 06 weeks of treatment in either group. three patients from group b experienced intractable headache and were managed by analgesics accordingly but they went on to complete the treatment. none of the patient in group a had any significant side effect causing any adjustment in the treatment. at the end of 06 weeks of treatment, 28 patients in group a and 25 in group b showed complete healing of anal fissure. the overall healing rate was 69.75 %( n=76). there was statistically no significant difference at the end of 06 weeks of treatment (p=0.454). conclusion: it is concluded that 2% nifedipine paste is as effective as 0.5% gtn ointment in terms of healing of chronic anal fissure. key words: chronic anal fissure, gtn, nifedipine. 54 anal fissure are aimed to focus on high resting anal pressure. the underlying principle of treating anal fissure is to reduce internal anal sphincter tone, thus reducing 6 the resting anal pressure. this can be achieved both by pharmacological or 7 surgical means. s u rg i c a l o p e r a t i o n s i n c l u d i n g a n a l dilatation and internal sphincterotomy are effective in lowering the resting anal pressure and decreasing the anal tone but carry a significant risk of impaired level of 8 continence. therefore, there has been a significant change during the last decade in the treatment of anal fissure with major emphasis on the conservative treatment modalities. these pharmacological methods are aimed at reversible relaxation of anal 9 sphincter. glyceryl trinitrate is regarded as the first line agent, which is widely used for chemical 10 sphincterotomy. although it has high introduction anal fissure is one of the most common proctologic problems presenting with 1 painful bleeding per rectum estimated to be affecting 10% of the patients attending the 2 colorectal clinics. it is common condition affecting all age groups, but it is particularly seen in young and otherwise healthy adults 3 usually in third and fourth decade. chronic anal fissure is associated with persistent hypertonia of internal anal 4 sphincter and high resting anal pressure. the manometric evidence has confirmed that the high resting anal pressure is caused by internal anal sphincter spasm and hypertonicity of sphincter as the fissure bed 5 lies on the internal anal sphincter. all the current available treatment modalities of ------------------------------------------------correspondence: dr. maliha yunus assistant professor surgery iimc-t, pakistan railway hospital rawalpindi original article comparison of topical glyceryl trinitrate and nifedipine in management of chronic anal fissure maliha yunus, mumtaz akhtar, zeeshan ghani 54 55 healing rates but associated with major side 11 effects like headache. calcium channel blockers, e.g. nifedipine, diltiazem are the other class of drugs which are used for chemical sphincterotomy with comparable healing rates with fewer side effects 12 specially headache. there is no research conducted in our set up in which the efficacy of topical nifedipine for healing of chronic anal fissure is studied. though nifedipine has been recommended as first line treatment in the management of chronic anal fissure in united kingdom, it is neither dispensed nor used in tertiary care set ups due to lack of awareness and confidence about the drugs. its cost is also comparable to gtn. this study is based on very limited available data on the better healing with topical nifedipine as compared to glyceryl trinitrate for chronic anal fissure. this would help in building the confidence of surgeons in adapting nifedipine, as a new treatment modality which can be used in tertiary care hospitals in local population. it was randomized controlled trail conducted at surgical unit-i of iimc-t, pakistan railway hospital rawalpindi. the study was conducted on opd basis over a period of 06 months starting from march to august 2011. sample size of 76 patients was calculated by using who sample size calculator. the s a m p l e w a s s e l e c t e d b y u s i n g t h e consecutive (non-probability) sampling technique .first 76 adult patients, of both genders, having a history of anal pain, worsening with bowel movements, for duration more than 6 weeks, and on anal examination showing a longitudinal tear in the lining of distal anal canal below the dentate line, in the midline anteriorly or posteriorly and who gave consent to enter materials and methods the study were considered eligible for enrollment in the trial. patients with acute anal fissure, fissures occurring in locations other than the midline posteriorly or a n t e r i o r l y, a n d p a t i e n t s w i t h t b , i n f l a m m a t o r y b o w e l d i s e a s e , a n a l carcinoma and recurrent anal fissure were not included in the study. patients with multiple anal fissures and patients on other formulations of nitrates and calcium channel blockers for illness were also excluded from the study. after taking approval from hospital ethical committee and after explaining the purpose of the study, informed consent was obtained from the patients participating in the study. patients were randomly assigned using the lottery method, to either topical nifedipine paste (2%) [group a] or gtn ointment (0.5%) [group b] .the assigned medication was applied locally both externally and internally about the size of a pea every 12 hours for six weeks by the patient. the outcome was noted as 'complete healing' or 'incomplete / no healing' at the end of 06 weeks based on inspection on digital rectal examination of the anal canal. first e x a m i n a t i o n a s w e l l a s f o l l o w u p examination was done by consultants. data collected from the patients was entered on the performa. data was analyzed using the statistical package for social sciences (spss version 16). from march 2011 to august 2011, 76 consecutive outpatients were enrolled on a convenient sampling bases; 38 patients received 2% nifedipine paste (group a), and 38 patients received gtn ointment (group b).our study population was in age group of 11 to 60 years. mean age of patients in our study was 31.36 years .the duration of symptoms varied from 06 to 40 weeks. the results 55 56 maximum number of patients who fall in a specific duration were 14 (n=76) and that was 12 weeks followed by 11 patients in 08 weeks duration. mean for duration of symptoms was 14.83.standard deviation was 7.01. the distribution of duration of symptoms is shown in the figure 1. all the patients in the study completed the follow up of 06 weeks of treatment in both groupa and groupb. three patients (n=3) 3.94% from group b experienced intractable headache and were managed by analgesics in our study, 24 patients (31.6%) were male and 52 patients (68.4%) were female (n=76).there were 5 (6.67%) male and 33 (43.42%) female patients in the group a. on the other hand there were 19 (25%) male and 19 (25%) female patients in group b.the location of fissure is shown in the table i accordingly but they went on to complete the treatment. none of the patient in group a figure 1: duration of symptoms in weeks table i: position of fissures(n=76) table ii: outcome of treatment(n=76) procedures. incontinence is a major and irreversible complication. topical gtn remains the most widely used non-surgical 13 treatment for chronic anal fissure. gtn also remains the standard agent against which the other newer agents are compared 14 in terms of efficacy and compliance. aim of this study was to compare the efficacy of nifedipine treatment against the glyceryl trinirate in the management of chronic anal fissure. according to literature, anal fissure is particularly seen in young and otherwise 15,16 healthy individuals. fissures have a predilection for the posterior midline (90 %) but may also be located in the anterior midline or lateral. the explanation for this 56 57 phenomenon is both anatomic and 17,18 functional. calcium channel blockers such as nifedipine and diltiazem have been the focus of research in recent years regarding their role in fissure management. cook et al. demonstrated the reduction of resting anal tone, inhibition of contraction of internal anal sphincter and the healing of anal fissure 19 by using oral nifedipine. our study showed that 73% of patients with chronic anal fissure could achieve complete healing by using topical nifedipine. this finding is lower than a comparable study conducted by perrotti et al which showed the healing 20 rates of over 95%. they added topical lidocaine to nifedipine and compared it with the control. perhaps the addition of local anesthetic to topical nifedipine has 21 beneficial effect in lowering the anal tone. ezri and susmalliam showed better healing rates with topical nifedipine than gtn 22 when used for anal fissure. there were more side effects in gtn group than the nifedipine group many controlled clinical trials have shown varied results in terms of fissure healing with the topical gtn (4523 80%). the major side effect of topical gtn therapy for anal fissure is that almost 40% of 24 patients experienced headaches. masood et al demonstrated the healing of anal fissure in 82% of the patients with the use of topical gtn; however headache was experienced by 67% of the patients. another known considerable drawback to gtn therapy is 25 high recurrence rate. poor compliance with prescribed treatment often contributes to low outcome. the healing showed in the gtn group in our study was 65% which is comparable to other studies in term of efficacy. usman et al demonstrated the healing of anal fissure in 88% of patients after 06 weeks of topical treatment with gtn. they compared topical gtn with internal anal sphincterotomy in chronic anal fissure. however, headache of variable intensity was reported in 40% of the 17 patients. in a local study conducted at a tertiary care teaching hospital in pakistan, in which the effect of topical gtn was studied in acute anal fissure, the healing rate of 68% was 17 reported with gtn. in a prospective randomized trail which included 35 patients of anal fissure, bacher et al demonstrated complete fissure healing in 80% of the patients after 04 weeks of topical gtn 26 treatment against 40% of the controls. this result was better as compared to many other studies in which healing was reported 27 around 65-70% with gtn treatment. our study was unique in the way that a very few randomized trials available in the literature in which nifedipine was compared with the gtn in topical management of anal fissure. ezri et al compared topical nifedipine and gtn in a randomized trial involving 52 patients. they found that the healing was higher with nifedipine (89% vs. 58%) with less frequent side effects (5% vs. 22 40%). although the side effects profile was not made the part of work for which the study was conducted, but nevertheless, the number of headaches reported in our study were significantly lower in the nifedipine group than the gtn group. this had been 1 shown in many previous studies. we were unable to prove our hypothesis. although nifedipine failed to show any statistically significant difference over gtn in terms of efficacy, still the rates of healing are comparable to other studies showing its effectiveness. it is concluded that 2% nifedipine paste is as effective as 0.5% gtn ointment in terms of conclusion 57 58 efficacy in management of chronic anal fissure. . 1. gupta pj. a review of conservative and surgical management of anal fissure acta gastoenterol belg 2005; 68:446-50. 2. antonio a, francisco p, pilar s, fernando c, javier l, rafael c. surgical versus chemical (botulinum toxin) sphincterotomy for chronic anal fissure: long term results of a prospective randomized clinical and manometric study. am j surg 2005; 189: 429-34. 3. rohde h. the pathogenic mechanism causing anal fissure. intl j colorectal dis 2003; 18: 95. 4. klingensimth me, amos kd, green dg, halpin vj, hunt sr, editors: the washington manual of th surgery: 4 ed: usa: lipponcott williams & wilkins 2005;1114. 5. abraham a. ayantunde, samuel a debrah. current concepts in anal fissure. world j surg 2006; 30: 2246-60. 6. williams ns, bulstrode cjk, o'connel pr, editors: bailey & love's short practice of surgery: 25th ed; 2008: 1251-3. 7. jonas m, lund jn, scholefield jh. topical 0.2% glyceryl trinitrate ointment for anal fissures: long term efficacy in clinical practice. colorectal disease 2002; 4: 317-20. 8. gagliardi g, pascariello a, altomare df, arcana f, cafaro d, la torre f et al. optimal treatment duration of glyceryl trinitrate for chronic anal fissure: results of a prospective randomized multicenter trial. tech coloproctol 2010 ; 14: 2418. 9. steel rjc, cuschieri a. surgical biology and pathological examination. in: cuschieri a, steel rjc, moosa ar, essential surgical practice th vol.1.4 ed. london: butterworth-heinemann; 2000: 1-35. 10. doherty gm, way lw, editors: current surgical diagnosis and treatment.12th ed; 2006; 41-3. 11. nelson rl. nonsurgical therapy for anal fissure. cochrane database of systematic reviews 2006; 4: 3431-3. 12. medhi b, rao rs, prakash o, kaman l, pandhi p. refrences recent advances in the pharmacotherapy of chronic anal fissure: an update. asian j surg, 2008; 31: 154-63. 13. masood j, zubia m, manzar s. topical diltiazem hydrochloride and glyceryl trinitrate in the treatment of chronic anal fissure. jcpsp 2009; 19: 614-7. 14. sileri p, stolfi vm, franceschilli l, grande m, di giorgio a, d'ugo s, et al. conservative and surgical treatment of chronic anal fissure: prospective longer term results. j gastrointest surg 2010 ; 14: 773-80. 15. tranqui p, trotter dc, victor c, freeman jb. nonsurgical treatment of chronic anal fissure: nitroglycerin and dilatation versus nifedipine and botulinum toxin. can j surg 2006; 49: 41-5. 16. katsinelos p, kountouras j, paroutoglou g, beltsis a, chatzimavroudis g, zavos c, et al. aggressive treatment of acute and fissure with 0.5% nifedipine ointment prevents its evolution to chronicity. world j gastroenterol 2006; 12: 6203-06. 17. usman q, jahangir s k, arshad s m, muhammad m k. surgical versus nonsurgical treatment of chronic anal fissure: our local experience. ann. pak. inst.med.sci.2008; 4: 1937. 18. golfam f, golfam p, khalaj a, sayed mortaz ss. the effect of topical nifedipine in treatment of chronic anal fissure. acta med iran 2010 ; 48: 2959. 19. cook ta, smilgin humphreys mm, mortensen nj. oral nifedipine reduces resting anal pressure and heals chronic anal fissures. br j surg 1999; 86: 1269-73. 20. perrotti p, bove a, antropoli c, molino d, antropoli m, balzano a, et al. topical nifedipine with lidocaine ointment vs. active control for treatment of chronic anal fissure: results of a prospective, randomized, double-blind study. dis colon rectum 2002; 45: 1468-75. 21. festen s, gisbertz ss, van schaagen f, gerhards mf. blinded randomized clinical trial of botulinum toxin versus isosorbide dinitrate ointment for treatment of anal fissure.br j surg 2009; 96: 1393-9. 58 59 22. ezri t, susmalliam s. topical nifedipine vs. topical glyceryl trinitrate for treatment of chronic anal fissure. dis colon rectum 2003; 46: 805-8. 23. sanei b, mahmoodieh m, masoudpour h. comparison of topical glyceryl trinitrate with diltiazem ointment for the treatment of chronic anal fissure: a randomized clinical trial. acta chir belg 2009 ;109: 727-30. 24. sanei b, mahmoodieh m, masoudpour h. comparison of topical glyceryl trinitrate with diltiazem ointment for the treatment of chronic anal fissure: a randomized clinical trial. ann ital chir 2009 ; 80: 379-83. 25. hyman nh, cataldo pa. nitroglycerin ointment for anal fissures: effective treatment or just a headache. dis colon rectum 1999; 42: 3835. 26. bacher h, misclinger hj, werkgartner g e. local nitroglycerin for treatment of anal fissures: an alternative to lateral sphincterotomy. dis colon rectum 1997; 40: 840-5. 27. khan h, shakur i, munir s, ali i, akhtar s r. effect of topical glyceryl trinitrate on management of acute anal fissure. rawal med j 2006; 31: 70-2. 59 page 57 page 58 page 59 page 60 page 61 page 62 original�article abstract objective: to determine the prevalence of shoulder pain in spinal cord injury patient using manual wheelchairs in khyber pakhtunkhwa. study design: cross sectional. st place and duration of study: the study was carried out at paraplegic center peshawar from 1 january 2014 to th 30 june 2014. materials and methods: a cross sectional survey using convenience sampling method was used to determine the prevalence of shoulder pain in spinal cord injury patients using manual wheelchair at paraplegic center hayatabad peshawar. a total of one hundred and fifty traumatic paraplegic and tetraplegic patients using manual wheelchair post two weeks were included in this study. wheelchair user shoulder pain index (wuspi) was used as data collection tool. descriptive statistic was applied. frequencies and percentages were calculated for identifying the responses of patients to different questions, for level of injury, and identifying the prevalence. results: a total of one hundred and fifty (150) manual wheelchair user tetraplegic and paraplegic spinal cord injury patients were included in this study. among them 84% were male while 16% were female. the prevalence of shoulder pain was 34.7% while performing different activities in manual wheelchair users. from patient's responses, it was declared that shoulder pain was most common while pushing on inclined surfaces and ramps, pushing the wheelchair for 10 minutes or more, sleeping on the shoulder and transferring from bed into wheelchair. while at rest 89.3% of the subjects were free of pain. conclusion: most of the traumatic spinal cord injury (sci) manual wheelchair users (mwus) complain of shoulder pain during the course of their rehabilitation program. shoulder pain restricts most important activities of daily living like pushing wheelchair on inclined surfaces, ramps and transferring from bed to wheelchair and wheelchair to bed. key words: manual wheelchair user, spinal cord injury, shoulder pain, wheelchair user shoulder pain index. than 3 segments below the neurological level of injury while the incomplete injury means some preservation of sensory and/or motor function more than 3 segments below the neurological level of 2 injury. spinal cord injury (sci) is a devastating event that brings significant changes in life of the victims as well as their family. presently there is no sci registry at national level in pakistan. therefore, there is no accurate estimate of the number of individuals who suffer from sci in pakistan every year. the research on epidemiology of traumatic sci in pakistan is very limited. about 650-750 spinal cord 3 injuries occurred in october 2005 in pakistan. globally around 90 million individuals are suffering from spinal cord injury (sci). in developed countries sci incidence ranges from 1 to 5 persons per 4 100,000. the most common causes of spinal cord injury are automobile accidents (31.5%), fall from height (25.3%), gunshot injury (10.4%),motor cycle 5 accidents (6.8%) and diving (4.7%). the manual introduction any kind of neural disturbance in the spinal cord whether from trauma or disease is called spinal cord 1 injury. according to the standards for neurological classification published by the american spinal injury, the term complete injury means no preservation of motor and/or sensory function more the prevalence of shoulder pain in spinal cord injury patients using manual wheelchair in kpk (khyber pakhtunkhwa) 1 2 3 rafiullah , sayed zulfiqar ali shah , sajida mazhar correspondence: dr. sayed zulfiqar ali shah department of rehabilitation sciences rehman college of rehabilitation sciences rehman medical institute, peshawar e-mail: zulfiqar_kmu18@yahoo.com 1 department of physical therapy rafsan neuro rehabilitation center saddar peshawar 2 department of rehabilitation sciences rehman college of rehabilitation sciences rehman medical institute, peshawar 3 department of physical medicine and rehabilitation sciences institute of physical medicine and rehabilitation sciences khyber medical university, peshawar funding source: nil; conflict of interest: nil received: oct 27, 2016; revised: dec 13, 2016 accepted: feb 12, 2017 shoulder pain in manual wheel chair patientsjiimc 2017 vol. 12, no.2 101 the prevalence and study different aspects of shoulder pain experienced by spinal cord injury patients in khyber pakhtunkhwa (kpk), using manual wheelchairs. materials and methods a cross sectional survey was designed to identify the prevalence of shoulder pain in manual wheelchair users. the study was carried out at paraplegic center st th peshawar from 1 january 2014 to 30 june 2014. a total of 150 subjects both male and female with traumatic sci using mwc were included in this study. it was mandatory that subject have completed two weeks rehabilitation training in paraplegic center peshawar and rafsan neuro rehab center peshawar and currently. data was collected using wuspi with the help of follow up program team of paraplegic center peshawar and some subject were directly interviewed in rafsan neuro rehab center peshawar and paraplegic center peshawar. wuspi is a 15-items questioner specifically designed for independent mwcus scored from zero to ten with zero representing no interference of pain with daily activity and ten represents complete interference. inclusion criteria was independent manual wheelchair users, patients of both gender with traumatic spinal cord injury, c5 and below level quadriplegics subjects, age 18 -59 years, completed at least 2 weeks rehabilitation in an inpatient center. subjects with any of the following were excluded from the study: paraplegic and quadriplegics not using mwc, progressive diseases paraplegics, above c5 level tetraplegic, patients with age range below18 years and above 60 years, , pwc (power wheel chair) user subjects, subject having shoulder pain from a history of fall on affected shoulder after sci, subject experiencing referral pain from any other part of the body, subjects that are dependent for wheel chair propulsion and transferring. the wuspi was used for data collection which is a standard valid questioner. the covering letter was send along with the questioner to explain purpose of the study to the subjects. willing participants filled consent form and questionnaire. spss version 20 was used for data analysis. descriptive statistic was applied. frequencies and percentages were calculated for identifying the wheelchair ((mwc) is a potential enabling 6 technology for mobility impaired people. the mwc is a source of mobility and support to the body. it facilitate activities of daily living (adl), self-care and 7 recreation activities. in united states, around 1.7 million people were using wheelchair in 2000 in which 1.5million were mwus (manual wheelchair 8 users). the lifelong dependency of sci patient on mwc for their adls causes repetitive loading of shoulder joint and consequently results in shoulder 9 pain. the upper extremity repetitive use, high forces a n d a w k w a r d p o s t u r e l e a d s t o s h o u l d e r 10 impingement in mwcus. also the increase weight, high seat position and prolong disability may lead to 4 shoulder pain in these patients. shoulder pain in mwcus may result from shoulder impingement (75%), rotator cup tears (65%), aseptic humeral h e a d n e c r o s i s ( 2 2 % ) , t e n d i n i t i s a n d 11 bursitis. epidemiological studies have revealed that shoulder pain is common in mwc users and its 12 prevalence ranges from more than 32–78%. two third of mwus complain of shoulder pain after five 13 years of injury. after 20 years of injury almost all of 9 mwcus complain of shoulder pain. a study has reported that shoulder pain prevalence in tetraplegic is 59%and 42% in paraplegic mwcus sci 14 patient. shoulder pain in manual wheelchair users 15 result into decrease quality of life. initially mwc users adls may not be affected so much but later on it may result early fatigue, low level of endurance, lower work potential and reduced cardiopulmonary 16 endurance. the wheelchair users shoulder pain index (wuspi) is a 15 item tool for assessing shoulder pain while at rest and during activity. the pain intensity is measured through a 10cm line with zero (0) representing no pain and ten (10) representing the worse pain experienced on the basis of the past 17 week activities. spinal cord injury patients exclusively rely on upper limb for weight bearing activities like transfer and wheelchair propulsion, so it is necessary to keep them aware of proper wheelchair use, shoulder loading and shoulder complication in order to keep 18 them functional in society. shoulder pain in spinal cord injury patients in pakistan is under reported and up to author's knowledge no research has been found on this topic in pakistan. this study was designed to determine jiimc 2017 vol. 12, no.2 102 shoulder pain in manual wheel chair patients discussion postspinal cord injury (sci) life expectancy of the patient has improved as a result of advancement in medical care and followed up in specialized unit. the sci patient are compelled to go through repetitive weight bearing activity through their upper limb(ul) joints as a compensation for paralyzed lower limb (ll) and trunk muscle while performing different activity of daily life (adl), as a consequence, they develop shoulder joint pain at some stage of their life. very less number of patients (10.7 %) reported shoulder pain at rest while 34.7% reported shoulder pain with wheelchair related activities. most of the participants (41.3%) reported shoulder pain while pushing wheelchair on inclined surfaces and ramps. this study results revealed that 89.3% of the sci patients have no pain while it rests. a similar results were obtained from a study conducted it the united kingdom by dorsett (2001) showed that among sci responses of patients to different questions, for level of injury, and identifying the prevalence. results the wheelchair user shoulder pain index (wuspi) was used for data collection. a total of one hundred and fifty (150) manual wheelchair user tetraplegic and paraplegic spinal cord injury patients were included in this study. among them 84% were male while 16% were female. the age limit was from 19 to 58 years. among all 86.7% of the subjects were manual wheelchair users from one to five (1-5) years while the 13.3% were using wheelchair from the past five to twenty years. among the total recruited patients there were 64% with thoracic, 28% with lumber and 7% with cervical level of spinal cord injury patients. the shoulder pain noticed was as following. about 10.7 % of the subject reported shoulder pain even at rest while 89.3% of the subjects were free of shoulder pain while at rest. the prevalence of shoulder pain with wheelchair related activity was 34.7%. the shoulder pain was most common (41.3 %.) while pushing on inclined surfaces and ramps. among all 20% of the participants reported mild shoulder pain when pushing their wheelchair for ten minutes or more. some of the patients (24%) reported that they feel pain while washing their back while 17.3% reported that they feel pain during transferring from bed into wheelchair. the prevalence of shoulder pain while sleeping was 18.7%.the subjects were asked to mark their pain level on a 10cm line of visual analog scale (vas) according to their pain intensity while performing activities. the severity of the pain on vas was graded as“no pain, worse pain ever experienced and activity not performed”. table i: rehabilita�on dura�on of the study popula�on (n= 150) table ii: level of injury of the study popula�on (n= 150) table iii: pain at rest and on ac�vity jiimc 2017 vol. 12, no.2 103 shoulder pain in manual wheel chair patients wheelchair users 80% did not reported shoulder pain 19 while at rest. shoulder pain should be treated at priority it may later restrict patient's adls. conclusion this study concludes that the prevalence of activity related shoulder pain was high than pain at rest as many participants were having pain during activity. this study also concludes that most of the manual wheelchair users with spinal cord injury experience shoulder pain in activities which put more load on their shoulder joint and rotator cuff muscles, like profiling on inclined surfaces and transferring from bed to wheelchair. most of the patient experience shoulder pain in their later years of rehabilitation. recommendations this study recommends that the proper wheelchair training and upon experience of shoulder pain; proper treatment should be taken to facilitate further wheelchair use and combat immobility. patients should be taught not put abnormal weights on the shoulder and always ask for assistance for activities that demands high forces. references 1. maynard fm, bracken mb, creasey g, ditunno jf jr, donovan wh, ducker tb, et al. international standards for neurological and functional classification of spinal cord injury. spinal cord. 1997; 35: 266-74. 2. waters r, adkins r, yakura j. definition of complete spinal cord injury. spinal cord. 1991; 29: 573-81. 3. rathore mfa, hanif s, farooq f, ahmad n, mansoor sn. traumatic spinal cord injuries at a tertiary care rehabilitation institute in pakistan. jpma. the journal of the pakistan medical association. 2008; 58: 53-7. 4. hossain s. prevalence of shoulder pain among tetraplegia patients attended at crp, department of physiotherapy, bangladesh health professions institute, crp; 2013. 5. chen y, tang y, vogel l, devivo m. causes of spinal cord injury. topics in spinal cord injury rehabilitation. 2013;19: 18. 6. brubaker c, mcclay i, mclaurin c. effect of seat position on wheelchair propulsion efficiency. paper presented at: proceedings of the 2nd international conference on rehabilitation engineering 1984. 7. paul aj. biomechanical model of pediatric upper extremity dynamics during wheelchair mobility. 2012. 8. kaye hs, kang t, laplante mp. mobility device use in the united states. disability statistics report 14. 2000. 9. sawatzky bj, slobogean gp, reilly cw, chambers ct, hol at. prevalence of shoulder pain in adult-versus childhoodonset wheelchair users: a pilot study. journal of rehabilitation research and development. 2005; 42: 1-8. 10. shimada sd, robertson rn, bonninger ml, cooper ra. manual wheelchair users 80% have no shoulder pain 19 while at rest. this study's result showed that 41.3% of the clients experienced shoulder pain while pushing on inclined surfaces and ramps. these finding were supported by a study conducted by subbarao et al (1955) who conducted a study to find the prevalence of wrist and shoulder pain in sci patients and find that wheelchair transfer and propulsion activity exacerbated most of the shoulder 19 pain in mwus. this study result showed that pushing the wheelchair for 10 minutes or more produced shoulder pain in 20% of patients. these finding were supported by a study conducted by salisbury et al (2006) and reported that wheelchair 15 propulsion is the main cause of shoulder pain. also curtis et al, (1999) conducted a study about shoulder pain in wheelchair user tetraplegic and paraplegic patients and reported that most of the wheelchair users complain of shoulder pain while propelling on 17 ramps, inclined surfaces. this study result showed that 17.3% of patients were having pain during transferring from bed into wheelchair,8% of patients have pain in transferring from wheelchair to a tub or shower and 6.7% of patients have shoulder pain while transferring from wheelchair to a car. these finding were supported by a study conducted by gellman et al where they revealed that25% of the patient complain shoulder pain in post-traumatic 18 weight bearing ul while transferring activities. a survey has reported that 31 to 73% shoulder pain in wheelchair users rehabilitated patients increases continuously up to 20 years and then it begins to 11 declines. a study from the united kingdom by dorsett (2001) showed that among manual table iv: prevalence of spinal cord injuries jiimc 2017 vol. 12, no.2 104 shoulder pain in manual wheel chair patients sosnoff jj. shoulder pain and cycle to cycle kinematic spatial variability during recovery phase in manual wheelchair users: a pilot investigation. plos one. 2014; 9: e89794. 16. curtis ka, drysdale ga, lanza rd, kolber m, vitolo rs, west r. shoulder pain in wheelchair users with tetraplegia and p a ra p l e g i a . a rc h i ve s o f p hys i c a l m e d i c i n e a n d rehabilitation. 1999; 80: 453-7. 17. curtis k, roach k, applegate eb, amar t, benbow cs, genecco td, et al. reliability and validity of the wheelchair user's shoulder pain index (wuspi). paraplegia. 1995; 33: 595-601. 18. gellman h, sib i, waters rl. late complications of the weight-bearing upper extremity in the paraplegic patient. clinical orthopaedics and related research. 1988; 233: 1325. 19. dorsett p, geraghty t. health-related outcomes of people with spinal cord injury— a 10 year longitudinal study. spinal cord. 2008; 46: 386-91. kinematic characterization of wheelchair propulsion. journal of rehabilitation research and development. 1998; 35: 210-8. 11. cooper ra, boninger ml, spaeth dm, ding d, guo s, koontz am, et al. engineering better wheelchairs to enhance community participation. ieee transactions on neural systems and rehabilitation engineering. 2006;14: 438-55. 12. morrow mm, hurd wj, kaufman kr, an kn. shoulder demands in manual wheelchair users across a spectrum of activities. journal of electromyography and kinesiology. 2010; 20: 61-7. 13. souza ae. impact and usage of pushrim activated power assist wheelchair among individuals with tetraplegia, university of pittsburgh; 2007. 14. salisbury s, nitz j, souvlis t. shoulder pain following tetraplegia: a follow-up study 2 to 4 years after injury. spinal cord. 2009; 47: 350. 15. jayaraman c, moon y, rice im, wecksler eth, beck cl, jiimc 2017 vol. 12, no.2 105 shoulder pain in manual wheel chair patients page 36 page 37 page 38 page 39 page 40 untitled-2 original�article abstract objective: to determine the frequency and association of waist-hip ratio with acute coronary syndrome in local population of islamabad, pakistan. study design: analytical cross-sectional. place and duration of study: the study was carried out in the department of cardiology, pakistan institute of medical sciences, islamabad for the duration of six months (december 2014-june 2015). materials and methods: a total of 388 patients presented with acute coronary syndrome which included patients with unstable angina, non-st elevation and st elevation mi. non-probability purposive sampling was used for sample selection. after taking informed consent, a self-structured questionnaire was used to collect the data. waist-hip ratio was assessed using tape measure. waist circumference was measured between the last rib and iliac crest, whereas the measurement of hip circumference was done at the level of greater trochanters. a waist-hip ratio of >0.85 for females and >0.9 for males was taken as abnormal.data was analyzed on spss version 17.0. chi square test was applied to find out the association between waist-hip ratio and other variables whereas pvalue of < 0.05 was considered as significant. results: out of total 388 acute coronary syndrome patients, 70.9% patients were males and 29.1% were females. the mean age of these patients was 47.5±18.46 years. out of the total study population, 59.5% patients of acs had abnormal waist hip ratio (>0.9). among the patients having abnormal waist hip ratio, 62.9% were males and 51.3% were females. 71.6% patients presented with stemi, 18.8% with nstemi and 9.5% with unstable angina. chi square test depicted non-significant association of waist-hip ratio with acs (p>0.05). a significant association was found between whr and gender (p<0.05). conclusion: there is no significant association between waist-hip ratio and acute coronary syndrome. the frequency of acute coronary syndrome is highest among males, with maximum prevalence of stemi, followed by nstemi and unstable angina. key words: acute coronary syndrome, coronary artery disease, obesity, waist-hip ratio. (acs). acs is associated with myocardial infarction (mi) and is usually symptomatic such as the presence 1 of unstable angina. a report by the heart disease and stroke statistics update of the american heart association in 2016 showed that chd is prevalent in 15.5 million individuals aged > 20 years, and there was a proportional increase in prevalence with age in 2 both genders. one third of all the fatalities in 3 persons aged 35 years and above occurs due to chd. in pakistan, acute coronary syndrome is more 4 prevalent in males. risk of heart diseases increases in the presence of risk factors. a most common modifiable risk factor is sedentary lifestyle or physical inactivity leading to 5 obesity. globally, overweight and obesity are being considered as main public health issues due to their relation with various chronic diseases for instance type 2 diabetes, cardiovascular diseases and 6 cancers. there are multiple means of estimating the introduction one of the highest reasons of mortality in developing countries is attributed to cardiovascular diseases, which refer to a group of cardiac conditions which include coronary heart disease (chd), coronary artery disease (cad) and acute coronary syndrome association of acute coronary syndrome with waist hip ratio in local population of islamabad capital territory, pakistan 1 2 3 4 5 hesham naeem , farrah qayyum , hina qayyum , saba murad , zara khalid correspondence: dr. zara khalid department of rehabilitation foundation university, islamabad e-mail: zara_awan@hotmail.com 1 department of cardiology rawalpindi institute of cardiology, rawalpindi 2 department of medicine yusra medical and dental college, islamabad 3 department of paediatrics bahria university medical and dental college, karachi 4,5 department of rehabilitation foundation university, islamabad funding source: nil; conflict of interest: nil received: january 01, 2019; revised: march, 2019 accepted: july 15, 2019 association of acs with waist hip ratiojiimc 2019 vol. 14, no.3 111 body size or excess body weight, of which the most commonly used method, is the traditional measurement of body mass index (bmi). however in the last few years, alternative measures of central adiposity, namely waist-height ratio, waist circumference and waist-hip ratio (whr) have been found to be better for prediction of cvd risks as compared to bmi, due to their accurate depiction of 7,8 body fat distribution. it is also due to the fact that multiple metabolic abnormalities are associated with increased visceral adiposity. these include a decrease in glucose tolerance, reduction in insulin sensitivity and deranged lipid profile, all of which are 9 cvd and type 2 diabetes risk factors. there is found to be uncertainty and variation regarding the performance of these anthropometric measures across different ethnicities. among the asian population, central obesity is emerging as a problem, as these individuals have large waist circumference (wc), but a normal bmi. as per who 2 guidelines, bmi 25-29.9 kg/m which lies in overweight category, corresponds with a wc of 80.087.9 cm in women and 94.0-101.9 cm in men and a whr of 0.9 and 0.85 in males and females respectively. yet these values are derivative of caucasians, and might not be applicable for the noncaucasian population. it is still unclear that which of the afore-mentioned measures has a strong a s s o c i a t i o n w i t h t h e r i s k o f d e v e l o p i n g 6 cardiovascular disease in various ethnicities. it is reported in literature that waist hip ratio is the most useful and favored method of measuring obesity for the purpose of identification or 10,11 prediction of cvd risk factors. risk stratification is an essential part of initial diagnosis and management of acute coronary syndrome. hence the value of assessment of waist-hip ratio as a quantifiable measure of obesity, during physical examination of at-risk patients still needs to be determined in our population. as per our knowledge, data regarding the relation of these measures with cardiac diseases in pakistani population is still lacking. therefore, this study was carried out to determine the frequency and association of waist-hip ratio with acute coronary syndrome (acs) in local population of islamabad. materials and methods an analytical cross-sectional study was conducted on 388 patients with acute coronary syndrome reporting to cardiology department of pakistan institute of medical sciences, islamabad. this study spanned over duration of six months (december 2014-june 2015). sample calculation was done using rao soft sample size calculator, while keeping 95% confidence interval and 5% margin of error. nonprobability purposive sampling technique was employed. the inclusion criteria comprised of 30-70 years aged male and female patients, presenting with coronary artery disease or acute coronary syndrome consisting of non-st elevation myocardial infarction, st elevation mi and unstable angina. the patients with chronic kidney disease, compensated or decompensated liver disease or with gestation were not included the study. ethical approval was obtained from the ethics review committee of pakistan institute of medical sciences, islamabad. informed consent from all participants was taken after explaining the study procedure. demographic data was recorded using a self-structured questionnaire. waist-hip ratio was assessed by measuring the waist and hip circumference with a tape measure. the subjects were instructed to stand straight with feet closed together, arms at sides and even distribution of body weight. the measurement of waist circumference was done mid-way between the last rib and iliac crest, whereas hip circumference was measured at the level of greater trochanters, with legs close together. a waist-hip ratio of >0.85 for 12 females and >0.9 for males was taken as abnormal. statistical analysis of data was done on spss (version 17, spss inc, and usa). frequencies and percentages were used to express the categorical variables. chi square test was applied to find out the association between waist-hip ratio and other variables whereas pvalue of ≤ 0.05 was considered as significant. results the sample comprised of 388 acs patients including 275 (70.9%) males and 113 (29.1%) females. (table i) the mean age of the sample was 47.5±18.46 years. in this study the patients were divided into three categories according to their diagnosis. the results showed 278 (71.6%) patients presenting with st elevation myocardial infarction (stemi), 73 (18.8%) with non-st segment elevation myocardial infarction (nstemi) and 37 (9.5%) with unstable angina. gender wise distribution of the 3 types of acs association of acs with waist hip ratiojiimc 2019 vol. 14, no.3 112 presentation has been shown in table i. chi square test of association showed non-significant association of waist-hip ratio and acute coronary syndrome (p>0.05). (table ii) out of total 388 patients, 231 (59.5%) had abnormal waist hip ratio. among the patients having abnormal waist hip ratio, there were 173 (62.9%) males and 58 (51.3%) females. chi square test of association depicted significant association of gender with waisthip ratio (p<0.05). (table iii) hospital. we observed a majority of sample presenting with st elevation myocardial infarction (stemi) which was the most frequent type of acs among both genders, followed by non st elevation myocardial infarction (nstemi), and then unstable angina. these results are similar to the results of a study conducted in 2013 on the role of central obesity in risk stratification after an acute coronary event, in which total 285 patients were admitted wherein 96.1% reported myocardial infarction (stemi and nstemi) and 13 3.9% had unstable angina. regarding gender distribution, 71% of our sample comprised of male patients with acs and only approximately 29% females. as per a review article on gender differences in coronary heart diseases, the development of cardiovascular diseases occurs 7-10 years later in women as compared to men. the risk of d e ve l o p i n g h e a r t d i s e a s e s i s q u i te o f te n underestimated in women and the resulting underrecognition along with different clinical presentation leads to a reduced representation of females in 14 studies and clinical trials. there are various measures to assess abdominal adiposity as a means of predicting cvd risk factors, of which waist-hip ratio (whr) is the most favored. in the current study, more than half almost 60% of the sample had abnormal waist-hip ratio, higher than the normative standard. a study on central obesity and mortality risk in older adults with coronary artery disease concluded that higher values of waist 15 hip ratio are predictive of a greater risk of mortality. in our study, we found a non-significant association between waist hip ratio and acute coronary syndrome. our results support the findings of a study on relationship of physical fitness v/s bmi with cad and cardiovascular events in women which also showed that after adjusting for other risk factors, bmi and other abdominal obesity measures (whr, waist circumference) were not significantly associated with coronary artery disease or its adverse effects (p=0.05-0.88). rather physical fitness and functional capacity were more important and were significantly associated with cardiovascular 16 outcomes such as acs. no significant association was found between abnormal waist-hip ratio and acute coronary syndrome possibly because acute coronary syndrome is multi-factorial and depends on table i: demographics and presenta�on of acs subjects (n=388) table ii: associa�on of waist-hip ra�o with different types of acs **normal whr (< 0.85 for female, <0.9 for male) ***abnormal whr (> 0.85 for female & >0.9 for male) table iii: associa�on of waist-hip ra�o with gender (males & females) * shows significant value p < 0.05 **normal whr (< 0.85 for female, <0.9 for male) ***abnormal whr (> 0.85 for female & >0.9 for male) discussion this study was conducted to find out the frequency and association of waist-hip ratio with acute coronary syndrome (acs) in local population of islamabad. the patients were divided into three distinct categories according to the type of acute coronary syndrome with which they presented to association of acs with waist hip ratiojiimc 2019 vol. 14, no.3 113 other risk factors as well. contrary to this, a study on impact of body mass index and whr on clinical outcomes in patients with stemi showed that highest whr was one of the mortality risk factors due to acs. yet this study also recommended further observing these associations in larger population 17 cohort studies. the results of the current study also found that waist hip ratio was significantly associated with gender, wherein the proportion of males was higher in abnormal whr category as compared to females. this is in contradiction to a study done on southern chinese population which showed that abdominal obesity was more prevalent in females. gender differences could be explained by the hormonal changes and varying physical activity levels in males 18 and females. overweight and obesity, be it central or abdominal, poses many challenges for treatment of coronary heart diseases. the cornerstone of primary prevention is the assessment of atherosclerotic cardiovascular disease risk which includes estimation of multiple risk factors. management of obesity along with associated increase in physical activity and cardiorespiratory fitness levels is currently being recommended for a subsequent reduction in cardiovascular morbidity and mortality 19,20 burden. the current study has been conducted in only one hospital of islamabad limiting the generalization of the results to whole population. however, future studies on larger samples and in multiple settings are recommended to observe the association of acs with other probable risk factors using objective measures. conclusion based on the results of statistical data analysis we conclude that there is no significant association between waist-hip ratio and acute coronary syndrome. the frequency of acute coronary syndrome is highest among males, with maximum prevalence of stemi, followed by nstemi and unstable angina. furthermore, a significant association exists between whr and gender. references 1. lippi g, sanchis-gomar f, cervellin g. chest pain, dyspnea and other symptoms in patients with type 1 and 2 myocardial infarction. a literature review. international journal of cardiology. 2016;215:20-2. 2. mozaffarian d, benjamin ej, go as, arnett dk, blaha mj, cushman m, et al. executive summary: heart disease and stroke statistics-2016 update: a report from the american heart association. circulation. 2016;133(4):447-54. 3. rosamond w, flegal k, furie k, go a, greenlund k, haase n, et al. heart disease and stroke statistics—2008 update. circulation. 2008;117(4):e25-e146. 4. jafary mh, samad a, ishaq m, jawaid sa, ahmad m, vohra ea. profile of acute myocardial infarction (ami) in pakistan. pakistan journal of medical sciences. 2007;23(4):485. 5. leischik r, dworrak b, strauss m, przybylek b, schöne d, horlitz m, et al. plasticity of health. german journal of medicine. 2016;1:1-17. 6. huxley r, mendis s, zheleznyakov e, reddy s, chan j. body mass index, waist circumference and waist: hip ratio as predictors of cardiovascular risk—a review of the literature. european journal of clinical nutrition. 2010;64(1):16. 7. welborn t, dhaliwal s. preferred clinical measures of central obesity for predicting mortality. european journal of clinical nutrition. 2007;61(12):1373. 8. ashwell m, hsieh sd. six reasons why the waist-to-height ratio is a rapid and effective global indicator for health risks of obesity and how its use could simplify the international public health message on obesity. international journal of food sciences and nutrition. 2005;56(5):303-7. 9. organization wh. waist circumference and waist-hip ratio: report of a who expert consultation, geneva, 8-11 december 2008. 2011. 10. welborn ta, dhaliwal ss, bennett sa. waist-hip ratio is the dominant risk factor predicting cardiovascular death in a u 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netherlands heart journal. 2010;18(12):598-603. 15. sharma s, batsis ja, coutinho t, somers vk, hodge do, carter re, et al., editors. normal-weight central obesity and mortality risk in older adults with coronary artery disease. mayo clinic proceedings; 2016: elsevier. 16. wessel tr, arant cb, olson mb, johnson bd, reis se, sharaf bl, et al. relationship of physical fitness vs body mass index association of acs with waist hip ratiojiimc 2019 vol. 14, no.3 114 with coronary artery disease and cardiovascular events in women. jama. 2004;292(10):1179-87. 17. lee s-h, park j-s, kim w, shin d-g, kim y-j, kim d-s, et al. impact of body mass index and waist-to-hip ratio on clinical outcomes in patients with st-segment elevation acute myocardial infarction (from the korean acute myocardial infarction registry). the american journal of cardiology. 2008;102(8):957-65. 18. hu l, huang x, you c, li j, hong k, li p, et al. prevalence of overweight, obesity, abdominal obesity and obesity-related r i s k f a c t o r s i n s o u t h e r n c h i n a . p l o s o n e . 2017;12(9):e0183934. 19. lavie c, arena r, alpert m, milani r, ventura h. management of cardiovascular diseases in patients with obesity. nature reviews cardiology. 2018;15(1):45. 20. arnett dk, blumenthal rs, albert ma, michos ed, buroker ab, miedema md, et al. 2019 acc/aha guideline on the primary prevention of cardiovascular disease. journal of the american college of cardiology. 2019:26029. association of acs with waist hip ratiojiimc 2019 vol. 14, no.3 115 jiims final.cdr abstract objective:to compare the efficacy and safety of misoprostol with a foley's catheter and oxytocin for induction of labor at or beyond term. study design:quasi experimental study. place and duration of study:this study was carried out in the department of obstetrics and gynaecology, railway hospital rawalpindi from january 2008 december 2008. materials and methods: hundred patients requiring induction of labor at or beyond term with bishop less than 5 were randomized by lottery method to receive oral misoprostol or a cervical foley's plus oxytocin. patients in the misoprostol group (group a) received 50 microgram misoprostol at 6 hourly interval for a maximum of 4 doses or until an adequate contraction pattern developed. those in the foley's group (group b) had a foley's catheter inserted in the cervix. whereas oxytocin was administered intravenously by a standard incremental infusion protocol to a maximum dose of 36 milliunits/min. results:the mean induction delivery interval is 9.8 hours in group a while in group b the mean induction delivery interval was 17 hours. although all patients delivered in both groups within 24 hours but the mean induction delivery interval was prolonged in foley's group as compared to misoprostol group. the neonatal outcome was comparable in both the groups. conclusion: oral misoprostol at the dose 50 microgram is better than foley's group for induction of labor at term. key word: term, primigravida, induction of labour, misoprostol, induction delivery interval. 8 original article introduction labour is commonly induced in response to a number of fetal and maternal situations, including post term pregnancy, preeclampsia and rupture of the membranes w i t h o u t t h e o n s e t o f s p o n t a n e o u s 1contractions within the next 24 hours. different methods are used for induction of labor depending upon the bishop score. if bishop score is less than 5 then different methods of induction of labour are 2,3misoprostol, dinoprostone , sweeping of membrane and many other mechanical methods. results of different methods of induction of labor differ widely at different centers regarding their success rate, failure rate, complications and cost. prostaglandin are used to under labour in about 23% of all 4confinement. the prostaglandin e2 (pge2) dinoprostone, which is unstable at room temperature and requires refrigeration, is most commonly used. misoprostol a prostaglandin e-1 analogue manufactured for the prevention and treatment of gastric ulcer has also been evaluated as a cervical ripening agent. costs of misoprostol is approximately 300 times less per dose than pge2 ,stable at room temperature, easy to administer and may be given as an oral medication. there have been several meta-analysis and systemic reviews of randomized controlled trials evaluating the use of misoprostol for cervical ripening and labor induction. these reports are suggesting that misoprostol is effective ; but there is concern that ---------------------------------------------------a comparison of oral misoprostol and extra-amniotic foley's catheter with oxytocin for induction of labour at term asma shaheen, raazia rauf, attiqa zaigham, fareesa waqar correspondence: dr. raazia rauf senior registrar gynea/obs iimc-t, pakistan railway hospital rawalpindi 8 9 misoprostol may increase the rate of 5tachysystole and hyperstimulation. oral misoprostol reduces the need for oxytocin infusion from 51% to 13% and shortens 6delivery time by 8.7 hours. induction of labour with this analogue does not affect the frequency at which caesarean section is required. there is an increase in the rate of uterine hyperstimulation resulting in changes in fetal heart rate (fhr) pattern and staining of the amniotic fluid with meconium but without any apparent 7deleterious effect on the outcome. inflated foley's catheter has been used successfully as a mechanical device for ripening of unfavorable cervix because it is simple, in-expensive, reversible and has no 8systemic serious side effects compared to medical modes of cervical ripening. it has some association with an increase in caesarean section rate as compared to 9spontaneously laboring women. in the case of women who have previously undergone a caesarean section and thereby run an elevated risk for uterine rupture in connection with vaginal delivery, induction of labour with misoprostol may further 10enhance this risk and is not recommended. in a systemic review of 45 randomized trials, mechanical methods of labour induction were found to be less effective than prostaglandins and reduced the risk of uterine hyperstimulation; compared with oxytocin, there were fewer caesarean 11sections with mechanical methods. the purpose of this study was to evaluate the efficacy and safety of misoprostol versus extra amniotic foley's catheter and oxytocin for induction of labour at term. materials and methods this quasi experimental study comparing oral misoprostol and foley's catheter and oxytocin for induction of labour at term was carried out in the department of obstetrics and gynaecology, railway hospital rawalpindi from january 2008 december 2008. all women requiring induction of labour at or beyond term (> 37 weeks gestation) and bishop score <5 were included in the study. patients with previous caesarean section or any other uterine scars, multiple pregnancies, bishop score > 5, p l a c e n t a p re v i a , m a l p re s e n t a t i o n s , ruptured membranes were excluded from the trial. after informed consent, women were randomized by lottery method and assigned to receive oral misoprostol tablet in group a and foley's catheter in group b. after complete history and examination, a reassuring fetal heart tracing was confirmed w i t h a c a r d i o t o c o g r a p h . va g i n a l examination was performed to assess the bishop's score. misoprostol (50 micrograms) was given orally to patients in group a and repeated after six hours if required. a maximum of 4 doses were given. the use of oxytocin was according to the labour ward protocol and was not started less than 4 hours after the last dose of misoprostol. if cervix was not favourable for artificial rupture of membrane after 4 doses of misoprostol tablets, the induction was considered to have failed and the woman was offered caesarean section. a partogram was maintained for progress of labour. in group b; after bishop score, pre-packed sterile foley's catheter 20 f balloon was introduced and catheter balloon was inflated with 30 ml of sterile normal saline. patients were observed for 10-15 min for any 9 10 leakage of amniotic fluid or deflation of balloon. after 12 hours if it was not expelled then oxytocin infusion was also started along with it. all information collected was recorded in a pre-designed proforma. the data was entered on spss version 18 for statistical analysis. student's t test was applied to compare induction delivery interval between oral misoprostol and foley's catheter with oxytocin groups. statistical significance was assigned to pvalue < 0.05.percentage of indication of induction of labour ,use of oxytocin, mode of delivery ,maternal outcome such as hyperstimulation syndrome, tachysystole , hypertonus , nausea and vomiting ,pyrexia of 38 c, antepartum hemorrhage , uterine rupture and neonatal outcome such as assessment of 1 min and 5 min apgar score, need for intubation and nicu admission were calculated. results table i: mean age and birth weight table ii: induction delivery interval figure 1: induction delivery interval in both groups table iii: maternal outcome table iv: neonatal outcome the patients characteristics like age and parity were comparable in both the groups. the mean age in misoprostol group was 27 years and in the foley's group it was 29.7 years.the mean gestational age in group a was 39.6 weeks and in group b was 40.2 weeks. different indications for induction of route mean st. deviation st. error (mean) misoprostol n=50 foley’s catheter n=50 10 foley's catheteroral misoprostol (n=50) foley’s catheter ( n=50 ) oral misoprostol (n=50) oral misoprostol (n=50) 11 labor were summarized in table i .the commonest indication was postdated pregnancy in both the groups. table ii showed induction delivery interval. induction delivery interval was prolonged in foleys group as compared to misoprostol group. the mean induction delivery interval was 9.8 hours in group a and 17 hours in foley's group which statistically was not significant ( p value=0.654 ) .need of oxytocin infusion was more in group b (100% ) than in group a (21%). although all patients delivered within 24 hours but delivery occurred earlier in misoprostol group than foley's group. labour was interrupted by caesarean section in 8 (16%) women in group a and 17 (34%) in group b. the commonest indication of caesarean section in group a was fetal distress and in group b was failure to progress in active phase of labor.the incidence of failed induction was higher that is 17 (34%) in group b than group a, in which it was 3 (6%) . t h e re w a s i n c re a s e d i n c i d e n c e o f tachysystole in group a i.e., 7 (14%), while none in the foley's group. the incidence of pph was 3 (6%) each in both groups. three ( 6 % ) p a t i e n t s d e v e l o p e d f e v e r i n misoprostol group (table iii). for the neonates the mean birth weight, the incidence of 5 minute apgar score were similar. one baby developed meconium aspiration in misoprostol group and none in the foley's group (table iv). the incidence of n.i.c.u admission is almost similar in both groups misoprostol has been shown to be effective when given orally or vaginally for induction of labour. with vaginal administration doses of 50 μgm and more have been associated discussion with a higher incidence of excessive uterine 12contractility. the oral route may have advantages in terms of easier administration and lack of restriction of mobility. also, in keeping with the pharmacokinetics of drug, it may be associated with lower uterine 13hyperstimulation rate. there is attractive possibility of administering the drug without repeated vaginal examinations which would be of particular benefit in patients with prelabor spontaneous rupture of membranes. another study in which induction of labor using a foley's balloon with or without extra-amniotic saline infusion was compared. results showed shorter induction to vaginal delivery time in foley's with extraamniotic saline infusion than with foley's alone, without affecting 13cesarean delivery rates. cormi et al recently conducted a study for cervical ripening with foley's catheter concluded that transcervical use of foley's catheter is safe for pre-induction cervical ripening , and the associated risk of maternal and 13perinatal infections are negligible. shetty et al concluded that with most of the parameters of efficacy there was no statistical difference in the 50μg and 100 μg misoprostol groups. however, there were significantly more failed inductions in low dose groups with more doses of misoprostol required. in that study there was failed induction with misoprostol in 100 μg group is 6% while in our study there is 10% i n c i d e n c e o f f a i l e d i n d u c t i o n w i t h 14misoprostol using 50 μg dose. a large number of randomized trials suggest that vaginally administered misoprostol is an effective agent for cervical ripening and labor induction. the main concern with this technique is the incidence of excessive 11 12 uterine contractions, which appears to be dose related. the higher the misoprostol dose, the shorter the induction to delivery time but the higher rate of uterine 15hyperstimulation. tachysystole with or without fetal heart rate changes continues to be the most common complication of misoprostol for cervical ripening and induction of labor. in the current study where patients received serial 50μg doses of misoprostol six hourly; 13.3% of women were noted to have at least one episode of tachysystole. in our study, more oxytocin is required in foley's catheter group as compared to misoprostol group. in a study conducted in 2008, in which comparison between supracervical foley's catheter , intravaginal dinoprostone gel , supracervical foley's catheter and 100 μg oral doses of misoprostol or serial 100 μg oral doses of misoprostol showed that women in the balloon plus misoprostol group were 16treated with lower doses of oxytocin. in our study the induction delivery interval is prolonged in the foley's group as compared to misoprostol group, but it is not s t a t i s t i c a l l y s i g n i f i c a n t . w h i l e , t h e previously mentioned study showed that the median induction to delivery time was longer with misoprostol. the relevant neonatal out comes were comparable to both groups in our study as well as in the 17previously mentioned study. oral misoprostol has all the properties that constitute a viable technique for labor induction. it is effective, inexpensive, easily a d m i n i s t e r e d , a n d s t a b l e a t r o o m temperature and well tolerated by the mother and fetus. in contrast to oxytocin, misoprostol does not require to be mixed as solution and there is no requirement of an infusion pump thus reducing the possibility of drug errors. extra amniotic saline infusion (easi) with concomitant oxytocin administration was associated with a shorter interval from induction to delivery and a higher rate of successful vaginal delivery within 24 hours compared with intravaginal misoprostol with unfavorable cervix .in a study, easi with concomitant oxytocin administration appears more effective and is associated with fewer fhr tracing abnormalities than vaginally administered misoprostol for cervical ripening and labor induction. easi however, had more rapid cervical ripening 18and shorter induction delivery interval. in a local study in which trial of extra amniotic saline infusion with oxytocin versus prostaglandin e2 pessary for induction of labor, showed that both modes of induction were equally effective in terms 19of mode of delivery and apgar scores. another study showed that induction of labour using mechanical methods results in s i m i l a r c a e s a r e a n s e c t i o n r a t e s a s prostaglandins, with a lower risk of hyperstimulation. mechanical methods do not increase the overall number of women not delivered within 24 hours. however, the proportion of multiparous women who did not achieve vaginal delivery within 24 hours was higher when compared with vaginal pge2 and mechanical methods for 20induction of labour. according to olimpio et al., vaginal misoprostol is more effective than and as safe as foley's catheter and oxytocin for induction of labor in term and post-term 21pregnancy. another study conducted in 2 0 11 s h o w e d t h a t i n d u c t i o n w i t h 12 13 intravaginal misoprostol and transcervical foley's catheter have similar effectiveness and similar risk of caesarean section; but, with a reduced risk of tachysystole with 22transcervical foley's catheter. a transcervical balloon catheter can be used to achieve effective and safe induction of labour. induction with misoprostol is equally effective and safe. its cost effectiveness and easy storage due to its stability at room temperature favours its use especially where resources are limited. conclusion references 1. prager m, grimfors ee ,edlund m ,marions l. a randomized controlled trial of intravaginal dinoprostone,intravaginal misoprostol and transcervical ballon catheter for labour induction.br j obstet gynaecol 2008;115:1443-50. 2. hofmeyr gj, gulmezoglu am. vaginal misoprostol for cervical ripening and i n d u c t i o n of labour. cochrane database system rev 2003; 1: cd000941. 3. rehman k, nadira s. vaginal misoprostol: the revolutionary start switch in induction of labor. pak armed forces med j 2004; 54: 204. 4. dodal jm, crowther ca, robsinson js. oral misoprostol for induction of labour at term: randomized controlled trial, bmj 2006; 332:50913. 5. hofmyer gj . induction of labor with an unfavorable cervix. best pract res clin obstet gynacol 2003; 17: 777-94. 6. alfirevic z. oral misoprostol for induction of labour. cochrane database system rev 2003; 1: cd001338. 7. crane jm, butler b, young dc, hannah me. misoprostol compared with prostaglandin e2 for labour induction in women at term with intact membranes 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2006. 13. cromi a, ghezzi f, tomea s, ucella s, l i s c h e h , b o l i s p f. c e r v i c a l r i p e n i n g with foley catheter int j obstet gynecol 2007; 97: 105-9. 14. shetty a, martin m, danielian p, templeton a. a comparison of two dosage regimens of oral misoprostol for labour induction at term. acta obstet gynecol scand 2002;81: 337-42. 15. godinjak z, imsirija l, imsirija n. vaginal application of misoprostol for labor induction after 36 weeks of pregnancy . med arh 2007 ; 61: 218-20. 16. cheng sy,ming h,lee jc,titrated oral compared with vaginal misoprostol for l a b o r i n d u c t i o n . randomized controlled trial. obstet gynecol 2008; 111: 119-25. 17. h o f m e y r g j . m i s o p ro s t o l a d m i n i s t e re d vaginally for cervical ripening and labour induction in the third trimester oxford, england: cochrane library update software, 1998, issue 3. 18. saleem s. efficacy of dinoprostone, intracervical foleys and misoprostol in labour induction. j coll physicians surg pak 2006; 16:276-9. 19. mazher sb, alam k. induced labour: indications and outcome. pims experience. j surgical 2001; 23: 31-3. 20. jozwiak m, bloemenkamp kw, kelly aj. mechanical methods for induction of labour. cochrane database syst rev 2012 ;3:cd001233. 21. olimpio b,moraes f, rivaldo m. a randomized controlled trial comparing vaginal misoprostol 13 14 versus foley catheter plus oxytocin for labor induction. acta obstet gynecol scand 2010; 89: 1045-52. 22. fox ns, saltzman dh, roman as. intravaginal misoprostol versus foley catheter for labour induction: a metaanalysis .br j obstet gynecol 2011;118:647-54. 14 original�article abstract objective: to find out the pattern of tobacco use practices and the effects of chewable tobacco and other forms of tobacco use on oral mucosa. study design: retrospective observational study. st st place and duration of study: study was started from 1 july 2018 to 31 december 2018 and was conducted at maxillofacial surgery opd, isra dental hospital. materials and methods: samples of leukoplakia, erythroplakia or growth in oral cavity were collected from maxillofacial surgery opd. after taking detailed history including chewable tobacco habits, biopsy was taken and then results were analyzed by using spss version 22.0.the categorical data were expressed in terms of frequencies and percentages. the chi square test was used to determine the association of different variables. results: majority of the patients were found to have naswaar addiction followed by gutka, smoking, areca nut, mainpuri and paan. most of the patients i.e., 59% with oral lesions were having basic education at primary level and belonged to middle class monthly income category 35(39.77%) followed by low monthly income 28(31.8%).we noted significant association between various oral habits of tobacco use and biopsy reports and oral squamous cell carcinoma was observed as the common findings among study population. conclusion: we have reached to the conclusion that in our region chewable tobacco is most common and significantly associated with risk of development of oral lesions and subsequent oral squamous cell carcinoma. key words: chewabletobacco, gutka, mainpuri, naswar, oral lesions, squamous cell carcinoma. demographic variations are responsible for 2 differences in the incidence of oral lesions. tobacco use is directly linked with higher incidence of oral cancer as large proportion of our population is consuming the various forms of tobacco. tobacco is used in the form of cigarettes, pipe, bidi or chewable 3 form such as naswar, ghutka and paan. various studies have reported the presence of nearly 28 or more carcinogenic agents in chewable tobacco such as tobacco-specific nitrosamines (tsnas), polonium, formaldehyde, cadmium, lead and benzopyrene.the various forms of chewable tobacco have been reported to be linked with malignant tumors of head 4,5 and neck. most of the cases of oral lesionsinvolve prolonged usage of tobacco. such lesions also have chances of 6 malignant transformation at the rate of 3-5%. the type of oral lesionboth malignant and nonmalignant varies with the type of tobacco being consumed and 7 the way it is used. oral cancer is gaining attention as one of the most challenging dilemma for the world which is thought to be directly associated with 8 prolong tobacco usage. despite of modern therapeutic modalities, pakistan is still ultrareceptive to oral cancer. this can possibly be credited introduction in southeast asian countries including pakistan tobacco is easily available in open market and our 1 cultural norms are adding support to these habbits. the habits of chewing tobacco are also popular in younger age groups and females due to attractive appearance and easy availability of these products at cheaper rates. such habits are also supported by illiteracy and deficiency of knowledge about their devastating effects. the cultural norms and regional types of various oral mucosal lesions with respect to trends of chewable tobacco and their subsequent histopathological findings 1 2 3 4 5 6 abdul majid , shankar lal rathi , amin fahim , sarwat batool , waqas iqbal , bhawani shankar correspondence: prof. dr. amin fahim department of pathology pumhsw shaheed benazirabad e-mail:draminfahim@gmail.com 1,2 5 department of pathology/department of oral pathology isra university, hyderabad 3 department of pathology pumhsw shaheed benazirabad 4 department of pathology al-tibri medical college, isra university,karachi 6 department of pathology muhammad medical college, mirpurkhas received: july 16, 2021; revised: november 10, 2022 accepted: november 14, 2022 histopathology of oral mucosal lesionsjiimc 2022 vol. 17, no.4 245 doi: https://doi.org/10.57234/652 to the exposure to lower socioeconomic status, 9 illiteracy, and various environmental factors. looking at the co-morbidities associated with use of tobacco and its consequences, it is very sad to write here that at the country level no definitive measures are being taken. thereforeit is a real need for public awareness to curtail such tobacco addiction to reduce the incidence of different oral lesions as well 2 as oral squamouscell carcinoma. although we know that tobacco is linked with oral cancer but it is not clear in literature that which form of tobacco and tobacco chewing habits are more prone to cause which type of oral lesion; therefore the present study was designed with the objective to find out the patterns of tobacco use practices and the effects of chewable tobacco and other forms of tobacco use on oral mucosa. materials and methods this was a retrospective observational study done st st from 1 july 2018 to 31 december 2018.the study was approved by ethics review committee (erc), board of advanced studies and research (basr)isra university hyderabad. a total of 88 samples were collected from maxillofacial surgery opd, isra dental hospital by non-probability purposive sampling technique. samples from patients with leukoplakia, erythroplakia or growth in oral cavity were included in the study.both the male and female patients, belonging to all age groups and ethnic groups without socioeconomic discrimination were included in this study. medical records were studied for demographical data of the participants. samples with inadequate oral biopsy material were excluded from the study. informed consent was taken from all the participantsand biopsy was performed by standard protocols by dental surgeon. paraffin embedded blocks were prepared from all the biopsy samples and were cut into 5µ thin sections by microtome. thin sections were processed further by using haematoxylin and eosin stains and were focused under light microscope by experienced pathologists for the histopathological diagnosis. the data was analyzed through spss version 22.0. the categorical data were expressed in terms of frequencies and percentages. the chi square test was used to determine the association of different variables. results in present study 88 patients with leukoplakia, erythroplakia or growth in oral cavity were studied. in our study most of the patients i.e., 59% with oral lesions fall under the category of basic education level according to proforma designed (table-i). according to socioeconomic status patients were divided into four categories with respect to their monthly income as shown in table-i. most of the patients with oral lesions belonged to middle class monthly income category 35(39.77%) followed by low monthly income 28(31.8%). the biopsy findings based on histopathological diagnosis revealed; oral squamous cell carcinoma (oscc) being most common finding with 64(72.7%) cases (tableii).according to the various addiction trends majority of the patients were found to have naswar addiction 21(23.9%) followed by gutka 15(17%), smoking 15(17%), areca nut 13(14.8%), mainpuri 6(6.8%) and paan6(6.8%). however about 12(13.6%) patients were found with no use of chewable tobacco. this shows that most patients with oral lesions 61(69.3%) were addicted to smokeless tobacco use (tableiii).the association between various oral habits of tobacco use and biopsy findings were found statistically significant with p-value=0.01, as is shown in table-iii. tablei: the distribution of patients according to literacy level and economy status histopathology of oral mucosal lesionsjiimc 2022 vol. 17, no.4 246 doi: https://doi.org/10.57234/652 discussion tobacco induced oral mucosal lesions are result of damage to oral protective mechanism or presence of 10 carcinogen in tobacco products. in our study the most prevalent habit was naswaar chewing. similar results with little variations were given by saira et al 11 in 2019. inpresent study the second most common habit was smoking and gutka chewing which is in 12 consistent with the results of behura ss in 2015. however another study conducted in india by rooban has reported alcohol as most seen habit for 13 oral mucosal lesions. these differences might be due to cultural variations and increase alcohol misuse among individuals in their population. in another study, the second mostly reported chewing habits was betel quid which is in similarity with our study showing 17% cases with gutka or quid 14 chewers. according to our study most encountered oral lesions were oral squamous cell carcinoma which was in contrast with the results found by mohiuddin s in 2016 and priya mk in 2018 who found oral submucus fibrosis as most common tobacco induced 15,16 oral lesions. in present study majority of the patients i.e., 59% with oral lesions had primary education level. this finding is consistent with an egyptian cohort study in which they classified patients according to education level in three groups i.e. no education, basic education, and high education and their most of the patients were of 17 basic education (55.2%). in another study in iran has divided population in two groups i.e., illiterate and literate having 78.9% oral lesions in illiterate people. however, they did not define the term illiterate. as many people doesn't consider primary education as criteria of literacy; if it is that so then our 18 study is also consistent with this study. in present study majority of the patients with oral lesions belonged to middle class monthly income category 35(39.77%) followed by low monthly income 28(31.8%).it may be also because most of the population in our country is comprised of middle class that is low monthly income and middle monthly income. it may also be due to their working environment and easy availability or affordability of chewing tobacco to these proportions of population. the comparable findings by some other studies have reported the low socioeconomic status in majority of 19 the patients in other parts of the country. another national study conducted in karachi reported higher 45% of the cases with oscc with very low socioeconomic status which contrasts with the 20 findings of present study. our study revealed that most of the oscc cases were smokeless tobacco addicts;in the form of naswaar and ghutka which was in similarity with the results of studies done by younis s et al in 2016 and muange p 21,22 in 2014. however wang x has revealed that joint effect of tobacco and alcohol had a significant effect 23 on occurrenceof oscc. our study showed that second mostly seen risk factor for oral squamous cell carcinoma was smoking and areca nut which was in similarity with the results by khan et alwho have reported both smoking and betel nut chewing as most common related factors for oral submucus tableii: thedistribution of patients according to biopsy findings (n=88) table iii: association of biopsy findings with various chewable tobacco habits p value significant at < 0.05 histopathology of oral mucosal lesionsjiimc 2022 vol. 17, no.4 247 doi: https://doi.org/10.57234/652 24 fibrosis. according to present study tobacco induced reactive inflammatory lesions were about 7% which is also supported by kamble ka study, 25 conducted in india. but in contrast cebeci ar in 2009 reported that mostly oral mucosal lesions are 26 reactive in nature. this difference might be due to less frequent usage of tobacco among study groups and some cultural variations. our study proved the indication that unfortunately prevalence of tobacco induced oscc in our community is 17%. however other authors believed that tobacco induced oscc is only 1% in their 27 society. this variation might be due to adequate screening programs of oral precancerous lesions by timely biopsies done by oral practitioners in their society. but in our society oral soft tissue biopsies are 28 advised at very late stage. conclusion we reached to the conclusion that in our region chewable tobacco is most common and significant risk factor for development of oral lesions and subsequent oral squamous cell carcinoma. refferences 1. kaur j, rinkoo av. public health perspectives of smokeless 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malik s, khan mf, khattak mr. epidemiological and clinical correlates of oral squamous cell carcinoma in patients from north-west pakistan. jpma. the journal of the pakistan medical association. 2019 aug;69(8):1074-8. 12. behura ss, masthanmk, narayanasamy ab. oral mucosal lesions associated with smokers and chewers–a casecontrol study in chennai population. journal of clinical and diagnostic research: jcdr. 2015 jul;9(7):zc17. 13. rooban t, rao a, joshua e, ranganathan k. the prevalence of oral mucosal lesions in alcohol misusers in chennai, south india. indian journal of dental research. 2009 jan 1;20(1):41. 14. driemel o, kunkel m, hullmann m, kleinsasser n, staudenmaier r, muller-richter u, et al. performance of conventional oral brush biopsies. hno. 2008 feb;56(2):20510. 15. mohiuddin s, fatima n, hosein s, hosein m. high risk of malignant transformation of oral submucous fibrosis in pakistani females: a potential national disaster. j pak med assoc. 2016 nov 1;66(11):1362-6. 16. priya mk, srinivas p, devaki t. evaluation of the prevalence of oral mucosal lesions in a population of eastern coast of south india. journal of international society of preventive & community dentistry. 2018 sep;8(5):396. 17. el-aziz a, aboushousha a, ali s, zahran f. prevalence of potentially malignant lesions and oral cancer among smokers in an egyptian cohort: a hospital-based crosssectional study. advanced dental journal. 2020 jul 1;2(3):93-100. 18. saravani s, kadeh h, arbabi s. oral and dental status, oral health-related quality of life and associated factors among institutionalized elderly in southeast iran-a cross sectional study. journal of dental materials and techniques. 2020 dec 1;9(4):176-84. 19. yasser f, mushtaq s, ahmad a, tauseef a, yasser r. examine the prevalence of risk factors and causes of oral squamous c e l l c a rc i n o m a . m e d i ca l fo r u m m o nt h l y. 2 0 2 0 aug;31(8):97. 20. anwar n, pervez s, chundriger q, awan s, moatter t, ali ts. oral cancer: 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correlation of smoking and betel nut with the effect of survivin expression in oral submucous fibrosis in local population j pak dent assoc 2015; 24(3):121-128. 25. kamble ka, guddad ss, nayak ag, suragimath a, sanade ar. prevalence of oral mucosal lesions in western maharashtra: a prospective study. journal of indian academy of oral medicine and radiology. 2017;29(4):282. 26. cebeci ar, gulsahi a, kamburoglu k, orhan bk, oztas b. prevalence and distribution of oral mucosal lesions in an adult turkish population. med oral patol oral cir bucal. 2009;14(6):e272-7 27. do lg, spencer aj, dost f, farah cs. oral mucosal lesions: findings from the australian national survey of adult oral health. australian dental journal. 2014;59(1):114-20. 28. amjad k, anwar a, malik yr, sukhia hr. knowledge, attitude, and practice of dental practitioners in karachi regarding oral cancer. pakistan oral & dental journal. 2018;38(4):508-12. histopathology of oral mucosal lesionsjiimc 2022 vol. 17, no.4 conflict of interest authors declared no conflicts of interest. grant support and financial disclosure authors have declared no specific grant for this research from any funding agency in public, commercial or nonprofit sector. data sharing statment the data that support the findings of this study are available from the corresponding author upon request. this is an open access article distributed under the terms of the creative commons attributionnoncommercial 2.0 generic license. 249 doi: https://doi.org/10.57234/652 original�article abstract objective: to determine the presence of mandibular canal anterior loop and its length in patients reporting to a tertiary care center using computerized cone beam tomography (cbct). study design: descriptive cross-sectional. st place and duration of study: prosthodontics dept., armed forces institute of dentistry, from 1 february 2019 th to 30 november 2019 materials and methods: a total of 126 subjects, between the age of 16-60 years, were selected using nonprobability consecutive sampling technique from prosthodontics department. patients in whom cbct investigation was required were selected based on exclusion and inclusion criteria. with the help of nnt viewer software presence of mandibular canal anterior loop determined. the extent of anterior loop anteriorly into the mandible was analyzed using the measuring tool in the nnt viewer software. results: out of 126 patients, anterior loop was found in 19% (n=24) patients among which 7.1% (n=09) patients had on the left side and 3.9% (n=05) on the right side. a total of 7.9% (n=10) patients had anterior loop present bilaterally. the mean ± sd extent of anterior loop on left and right side were 3.87 ± 0.88 and 3.96 ± 0.84 respectively. conclusion: a low prevalence of mandibular canal anterior loop was observed in subjects of present study with variations in the extensions of anterior loop. computerized cone beam tomography (cbct) imaging modality was found to be effective in the detection of anterior loop. key words: cone beam, computerized tomography, mandible, mental foramen. terminal branch of inferior alveolar nerve (ian) which is known as the mental nerve. the ian may also continue into the anterior mandibular region in 3 the form of incisive nerve. certain studies have suggested that after giving off the incisive branch, it reaches postero-superiorly to the mental foramen to continue as the mental nerve, which can be seen in the form of radiolucent loop also known as anterior loop of mandibular canal (mc) or anterior loop of 4-7 mental nerve. in study conducted by pradeep out of 85 patients, anterior loop was found to be present in 4 11.76% patient with a mean length of 2.79 mm. in another study the mean extent of anterior loop was 8 found to be 0.89mm. yet in another study the mean length of anterior loop was found to 4.13mm (range 9 01 to 11mm). although these anatomical variations are rare but inadvertent damage during surgical implant placement can occur if such variations are ignored 10 thus leading to sensory dysfunction. therefore, it is of utmost importance to appreciate the anatomy of this region to avoid any injury to the neurovascular bundles. orthopantomograms (opg) is among one of the commonly advised investigation in dentistry to introduction the mandibular anterior/ para-symphyseal region is a common sight for surgical procedure like dental implant therapy, especially in edentulous mandible, thus sound knowledge about clinical anatomy is of great importance. even though the region between both the mental foramens anteriorly in mandible is a safe location for such procedures, but anatomical 1,2 variations do exist among different populations. these variations maybe in the form of accessory mental foramen (amf), anterior loop of mandibular canal or the presence of incisive branch of the nerve. mental foramen (mf) provides a pathway for the prevalence and extent of anterior loop of the mandibular canal using cone beam computerized tomography 1 2 3 4 5 6 shoaib rahim , nighat haroon khan , saira bilal , nadia hanif , uzma habib , fahad haroon correspondence: dr. shoaib rahim assistant professor department of prosthodontics foundation university, islamabad e-mail: shoaib_1402@yahoo.com 1 department of prosthodontics foundation university, islamabad 2,3,4,5,6 department of radiology, lahore general hospital, lahore funding source: nil; conflict of interest: nil received: september 25, 2020; revised: august 11, 2021 accepted: august 20, 2021 prevalence & extent of anterior loop of mandibular canaljiimc 2021 vol. 16, no.4 243 get an overview of all the dentition and its surrounding hard tissues. although the accuracy and precision of opg in detection of accurate location of mf and the presence of anterior loop of mc and amf 7 maybe considered questionable . study have also been done to determine the anatomical variability in the dried mandible of cadavers which is also 9 considered to be accurate for that population. it is therefore necessary to have a clear vision/image of the jaw to prevent these damages, which can be achieved with the 3d imaging technique, that is, cone beam computed tomography (cbct). cbct provides a better image quality/resolution and an accurate representation of the structures with a low radiation dose as well as the ability to use different 2,11,12 tools available in the software. keeping in view the above background, the rationale of our study was to use cbct imaging modality for determining the variability anterior loop of mc as it corresponds to clinical practice and provides images of greater accuracy and low dosage to satisfy the presurgical planning requirements and hence the present study was designed to determine the prevalence and extent of anterior loop of mc using cbct. materials and methods the data collection for this cross-sectional study (descriptive) was carried out in the prosthodontics department at armed forces institute of dentistry. the study duration was 09 months (february 2019 to november 2019). a sample size of 120 subjects was calculated to be the minimum sample for this study using the who calculator. a total of 126 patients were selected for this study. sampling technique used for collection of data was non-probability consecutive sampling. inclusion criteria consisted of patients of both male and female gender with age ranging from 16-60 years, patients for whom cbct has been advised as part of their treatment, patients with no history of mandibular symphyseal or para symphyseal fracture, both dentate and partially dentate patients with all lower anterior teeth and premolars present, patients with who had their cbct investigation done previously were also considered in this study provided they fulfill the criteria. exclusion criteria consisted of patients with a history of tumor, cyst or any other bony lesion or deformity involving the anterior portion of the mandible within the region of right and left mandibular, patients with a n y i d e n t i f i a b l e s y n d r o m e , p a t i e n t s o n bisphosphonate therapy, patients with osteoporosis and non-visualization of the mental foramen bilaterally, patients undergoing orthodontic treatment or patients with crowding of mandibular anterior teeth and/or root resorption. prior approval from ethical review board was obtained (ref. no. erc-5/25-2019). as a protocol all patients presenting to hospital were examined in dental opd/ diagnostics department and patients with prosthodontic needs were referred to prosthodontics department. those patients who fulfilled the criteria (exclusion and inclusion) were selected for the study. cbct investigation was advised to patients as a part of their treatment. cbct was recorded using newtom vgi cbct (verona, italy) and analyzed with the help of radiologist. position of mf was identified using multiplanar view, panorex view and or 3d model and its relationship with the teeth was noted. presence or absence of anterior loop of mc and amf was noted. patients in whom anterior loop was found to be present, its extent was measured using a measuring tool in cbct software (nnt viewer). spss version 20 was used analyze the data. for qualitative and quantitative variables descriptive statistics were calculated. for variables like position of mf, presence of anterior loop of mc, gender, and accessory mental foramen (qualitative). for quantitative variables like age, distance/extent of anterior loop mean + sd were calculated. to determine the association between the location of mf on left and right-side chi square test was applied. to analyze the difference in the extent of mandibular canal anterior loop independent sample t test was applied. results out of 126 patients, 52 (41.3%) were males and 74(58.7%) were females. the age range was 16 to 58 years. the mean of age of patients was 34.40±10.49 years. the location of mf in relation to the teeth on the left and right side have been given in table-i and table-ii. out of 126 patients, anterior loop of mandibular canal was found in 24 patients (19%). out of these 24 patients 19 (15.07%) were female and 5 (3.96%) were male. anterior loop was present in 10 patients (7.9%) bilaterally and 09 (7.1%) patients had anterior loop only on left side and 05 jiimc 2021 vol. 16, no.4 prevalence & extent of anterior loop of mandibular canal 244 (3.9%) had on right side. the mean distance/extent of anterior loop was 3.87±0.88 millimeters (mm) on left side and 3.95±0.84 mm on right side. the minimum and maximum extent of anterior loop on left side was 2.33 mm and 5.36 mm respectively and on right side it was 2.20 mm and 5.11 mm respectively. accessory mental foramen (amf) was found in 09 (7.1%) patients on left side and 06 (4.8%) on right side. to determine the association between the location of mf on left and right-side chi square test was applied and p value < 0.001 was found to be significant (table-iii). independent sample t-test was applied to determine the difference in the extent/distance of anterior loop of mandibular canal between left and right side. statistically no significant difference was found with p value of 0.784 (table-iv). discussion the results of current study show that the anterior loop of mandibular canal was present in 19% (n=24) of the patients with the maximum extension of 5.36 mm. no significant difference noted in the extension between left and right side among different patients (p value 0.784). it is critical to identify the exact position of mf along with extent of anterior loop of mc. the mf was most found to be in proximity with st the root of the 1 premolar tooth in most of the patients, both on left and right side. chi square test showed significant association between the location of left and right mf along with strong correlation (p value <0.001). amf was also found to be present in certain patients alongside mf. these results suggest that adequate investigations and treatment planning is required before proceeding with the surgical treatment in the mandibular interforaminal region to avoid any chance of possible injury to the nerve bundle and vessels during surgery. the precise position of these important structures becomes even important when performing surgical therapy in 13-15 completely edentulous patients. certain authors have conducted research to determine the incidence of mandibular canal anterior loop. in a study conducted by arati, who selected 32 cbct images of the patients for locating the anterior loop, it was reported to be extant in 41% (n=13) of the subjects with a mean extent of 16 2.90±2.79 mm. in another study conducted by pradeep who selected 85 patients, anterior loop was found to be present in 11.76% (n=10) patient with a 4 mean length of 2.79 mm. yet in another study conducted by dimirios on 93 patients, anterior loop was found to be present with a mean length of 0.89 8 mm in 48% (n=45) of cases. other studies have also reported difference in incidence of anterior loop of 17,18 mandibular canals. the findings in the above mentioned studies do not coincide with one another and neither does the findings of our study coincide with the finding of these studies, that is, 19% (n=24). this suggests that there is variation in the incidence table i: frequency of position of left mental foramen in relation to teeth (n= 126) table ii: frequency of position of right mental foramen in relation to teeth (n= 126) table iii: chi square test for location of mental foramen table iv: independent sample t-test for extent of anterior loop jiimc 2021 vol. 16, no.4 prevalence & extent of anterior loop of mandibular canal 245 of anterior loop among different population and geographic dysmorphism has been noted. it is therefore important to carefully observe the radiographic investigations of each patient for presence of anterior loop as its incidence is variable. an opinion from radiologist should always be considered in case of any doubt to avoid undue damage to neurovascular bundle during the surgical procedure. the mean length of mandibular canal anterior loop in our study was slightly more than the mean length reported in these studies. although the maximum range of length of anterior loop was 4,8,16-18 coinciding with our study. the difference in the mean values may be due to the difference in sample size, the incidence of anterior loop and the individual length of anterior loop being on the lower side. smrithi et al found that the anterior loop had more prevalence in male as compared to female whereas in our study it was more prevalent in females. one of the reasons for this difference maybe the gross difference in sample size between the study 17 conducted by smrithi and our study. another major reason for this difference is that, in our study more than half of the subjects were female so the resultant incidence might have higher because of that difference. numerous studies have been carried out in the past to determine the position of mf in relation to the st nd roots of a tooth namely canine, 1 premolar and 2 premolar. the limitations of such studies which is also common in our study is that they are only helpful in dentate patient. in our study the mf was most st found along the roots of mandibular 1 premolar on nd both sides followed by 2 premolar position. the results of our study do not coincide with the results of other studies as most of them report the common nd location of mental foramen to be coinciding with 2 st 19-21 premolar followed by 1 premolar. although further improvements in this finding can be made by increasing the sample size or utilizing more objective and stable landmarks for determining the position of the mf. whenever a landmark such as tooth is used to determine the position of mf, the factor of unreliability cannot be ignored as the position of teeth is not constant and difference can be expected because of mal-alignment, trauma, missing teeth and many more reasons. the limitations of our study were that we did not consider the variation in the size, shape and direction/classification of anterior loop of mandibular canal. numerous variations have been 22-24 reported in the literature. the information gained from this study suggests that anterior of the mandible is an area with a variety of anatomical variations when it comes to the vital structures. c a r e f u l t r e a t m e n t a l o n g w i t h a d e q u a t e investigations are keys requirements for safely placing dental implants in the interforaminal region without any chances of surgical complications. some advice from radiologist should always be considered when planning in such cases for better outcome of dental implant therapy. conclusion in conclusion, a low prevalence of the anterior loop of mandibular canal was noted in the present study, with variations in the length of extension of anterior loops. the maximum length observed was of 5.36 mm using cbct. keeping in view the limitations of the study it is therefore recommended that, for establishing a safety limit for implant surgical procedure an accurate evaluation using cbct is necessary. references 1. panjnoush m, rabiee zs, kheirandish y. assessment of location and anatomical characteristics of mental foramen, anterior loop, and mandibular incisive canal using cone beam computed tomography. j dent. 2016;13(2):126-32. 2. misch ce. contemporary implant dentistry. 3rd ed. st. louis: mosby; 2008. 8-15. 3. rodella l, buffoli b, labanca m, rezzani r. a review of the mandibular and maxillary nerve supplies and their clinical relevance. arch oral biol. 2012;57(4):323-34. 4. christopher jp, marimuthu t, c k, devadoss p, kumar sm. prevalence, and measurement of anterior loop of the mandibular canal using cbct: a cross sectional study. clin implant dent relat res. 2018;20(4):531-4. 5. torres mg, valverde lde f, vidal mt, crusoé-rebello im. accessory mental foramen: a rare anatomical variation detected by cone-beam computed tomography. imaging sci dent. 2015;45(1):61-65. 6. juodzbalys g, wang hl, sabalys g. anatomy of mandibular vital structures. part ii: mandibular incisive canal, mental foramen and associated neurovascular bundles in relation with dental implantology. j oral maxillofac res. 2010;1(1):1-10. 7. ahmed qn, khan mn, rehman a, shahid a, ghafoor w, kiani sg. a cone-beam computed tomography-based assessment of mental foramen position. pak armed forces med j. 2019;69(1):102-6. jiimc 2021 vol. 16, no.4 prevalence & extent of anterior loop of mandibular canal 246 8. apostolakis d, brown je. the anterior loop of the inferior alveolar nerve: prevalence, measurement of its length and a recommendation for interforaminal implant installation based on cone beam ct imaging. clin oral implants res. 2012 sep;23(9):1022-30. 9. neiva rf, gapski r, wang hl. morphometric analysis of implant-related anatomy in caucasian skulls. j periodontol. 2004;75(8):1061-7. 10. juodzbalys g, wang hl, sabalys g. injury of the inferior alveolar nerve during implant placement: a literature review. j oral maxillofac res. 2011;2(1):1-8. 11. parnia f, moslehifard e, hafezeqoran a, mahboub f, mojaver-kahnamoui h. characteristics of anatomical landmarks in the mandibular interforaminal region: a conebeam computed tomography study. med oral, patol oral cir bucal. 2012;17(3):5. 12. parnia f, moslehifard e, hafezeqoran a, mahboub f, mojaver-kahnamoui h. characteristics of anatomical landmarks in the mandibular interforaminal region: a conebeam computed tomography study. med oral patol oral cir bucal. 2012; 17: e420-5. 13. liang x, jacobs r, corpas l, semal p, lambrichts i. chronologic and geographic variability of neurovascular structures in the human mandible. forensic sci int. 2009;190(1-3):24-32. 14. igbigbi ps, lebona s. the position and dimensions of the mental foramen in adult malawian mandibles. west afr j med. 2005;24(3):184-9. 15. mbajiorgu ef mawera g, asala sa, zivanovic s. position of the mental foramen in adult black zimbabwean mandibles: a clinical anatomical study. cent afr j med. 1998;44(2):2430. 16. chaudhary a, kaur g, lalawat s. locating the anterior loop of the inferior alveolar nerve on cbct. ec dent sci. 2019;18(1):58-62. 17. sinha s, kandula s, sangamesh nc, rout p, mishra s, bajoria aa. assessment of the anterior loop of the mandibular canal using cone-beam computed tomography in eastern india: a record-based study. j int soc prevent communit dent. 2019; 9:290-5. 18. ngeow wc, dionysius dd, ishak h, nambiar p. aradiographic study on the visualization of the anterior loop in dentate subjects of different age groups.j oral sci. 2009;51(2):231-237. 19. al-mahalawy h, al-aithan h, al-kari b, al-jandan b, shujaat s. determination of the position of mental foramen and frequency of anterior loop in saudi population. a retrospective cbct study. saudi dent j. 2017;29(1):29-35. 20. alfaleh wm. location of the mental foramen using volumetrically rendered cbct images. j pak dent assoc. 2020;29(1):19-23. 21. budhiraja v, rastogi r, lalwani r, goel p, bose sc. study of position, shape and size of mental foramen utilizing various parameters in dry adult human mandibles from north india. int sch res notices. 2013; 2013:1-5. 22. iyengar ar, patil s, nagesh ks, mehkri s, manchanda a. detection of anterior loop and other patterns of entry of mental nerve into the mental foramen: a radiographic study in panoramic images. j dent implant 2013; 3:21-5. 23. shaban b, khajavi a, khaki n, mohiti y, mehri t, kermani h. assessment of the anterior loop of the inferior alveolar nerve via cone-beam computed tomography. j korean assoc oral maxillofac surg. 2017;43(6):395-400. 24. gupta s, mohan rp, goel s, mallik s, goel s, keswani t. a radiographic study of the anterior loop and mental foramen in a selected north indian population. west afr j radiol 2015; 22:86-91. jiimc 2021 vol. 16, no.4 prevalence & extent of anterior loop of mandibular canal 247 original�article abstract objective: to compare the day case laparoscopic cholecystectomy with conventional laparoscopic cholecystectomy in terms of early return to activities and intensity of postoperative pain. study design: randomized control trial (parallel). place and duration of study: department of surgery pakistan institute of medical sciences/ shaheed zulfiqar st th ali bhutto medical university islamabad. study was conducted from 1 nov 2014 to 30 april 2015. materials and methods: after approval of hospital ethical committee, patients who were fulfilling the inclusion criteria were included in study after taking informed and written consent. sample size was calculated using who sample size calculator, which turned out to be 42 for each group. patients were divided into two groups, group a and group b by lottery method. patients in group a had undergone day case laparoscopic cholecystectomy and patients in group b had undergone conventional laparoscopic cholecystectomy. data was collected and recorded on purposively designed performa. data was analyzed using spss 17; paired t test was used to calculate p-value. results: in group a, among 42 patients 13(31%) were on vas 4, 13(31%), on vas 5, 8(19%), in vas 3, 6(14.3%), in vas 2 and 2(4.8%), in vas 6. the minimum and maximum “number of days to return to activities” was 3 and 7 days respectively. among 42 patients, 20(47.6%) patients had returned to their home activities in 3 days, 13(31%) in 4 days, 5(11.9%) in 5 days, 2(4.8%) in 6 days and 2(4.8%) in 7 days. in group b the minimum and maximum intensity of pain on visual analogue scale was 2 and 6 respectively. among 42 patients 15(35.7%) were on vas 5, 14(33.3%) were on vas 3, 8(19%), in vas 4, 4(9.5%), in vas 6 and 1(2.4%), in vas 2. the minimum and maximum “number of days to return to activities” was 6 and 10 days respectively. out of 42 patients 17(40.5%) had returned to their home activities in 9 days, 17(40.5%) in 8 days, 4(9.5%) in 7 days, 3(7.1%) in 10 days and 1(2.4%) in 6 days. conclusion: patients undergoing day case lc do return to their routine activities earlier than those who undergo conventional lc, but there is no difference in terms of intensity of post-operative pain as measured on visual analogue scale. key words: cholelithiasis, day case surgery, laparoscopic, day case laparoscopic cholecystectomy, laparoscopic cholecystectomy. der weil was the first surgeon who found gall stone during surgery while operating upon a patient with 1 peritonitis in 1687. ever since the operative management of gall stones is in process of co ntin u o u s evo lu tio n . it was carl jo h an n langenbuch, who performed the first ever open 2 c h o l e c yste c to my i n g e r m a ny. l ate r o p e n cholecystectomy became the gold standard treatment for the management of symptomatic gall 3 stone disease. surgeons around the globe were trying to make the procedure as less invasive as possible. the technique of sils was introduced in which a single umbilical incision was used to insert three small ports. recently notes (natural orifices transluminal endo 4 surgery) has been introduced , in which natural introduction cholecystectomy is the commonest surgical 1 intervention in hepatobilliary system. stal pert von comparison of day case laparoscopic cholecystectomy versus conventional laparoscopic cholecystectomy 1 2 3 4 muhammad asad , aatif inam , muhammad burhan ul haq , zafar iqbal malik correspondence: dr. muhamnmad asad senior registrar department of general surgery islamic international medical college riphah international university, islamabad e-mail: tfortipu@gmail.com 1 department of general surgery islamic international medical college riphah international university, islamabad 2,3,4 department of general surgery pakistan institute of medical sciences, islamabad funding source: nil; conflict of interest: nil received: may 16, 2019; revised: august 13, 2019 accepted: august 15, 2019 day case vs conventional laparoscopic cholecystectomyjiimc 2019 vol. 14, no.3 131 orifices are used to gain access to the cavity. first notes was performed on a 43 years female with 5 symptomatic gall stones in 2007. evolution in surgery has led to the concept of day case surgery, which means patient is discharged on same day after surgery. day surgery is also called 6 outpatient surgery or ambulatory surgery. invention of laparoscopic surgery has made it possible to do number of procedure on day case basis, because of the small incision and less pain postoperatively. now a day's number of conventional procedures like laparoscopic hernia repair and laparoscopic cholecystectomy are being performed on day case basis worldwide. with the passage of time acceptability of day case surgery has increased among clinicians, patients, families and also 7 insurance agencies. shortage of medical services in most part of world and financial problems has made space for day case surgery, because of lowering the 8 treatment cost to less than 50%. study in pakistan showed reduction in treatment cost of pkr 6200 to 22800 in day case laparoscopic cholecystectomy 9 (lc). that is why day case surgery has gained worldwide acceptance. day case laparoscopic cholecystectomy is being 5 extensively performed in developed countries , but its scope in developing countries is still less. laparoscopic cholecystectomy has progressively shortened the hospital stay from 2 to 4 days to 6-8 9,10 hours. studies have also shown early return to 11 home activities in day case lc was 22 days. safety profile and technique of lc is making it an “ideal” for 12,13 day case surgery. recent literature review has shown laparoscopic cholecystectomy as safe as 10 conventional laparoscopic cholecystectomy. up to 70% of patients with symptomatic disease are ideal 14 for day case lc. while there is reasonable volume of data is available from developed world on safety and feasibility of day case lc, pakistan is lacking behind on this subject and more and more research work is required to establish the safety and feasibility of this procedure in our country. in developing countries like pakistan day case lc is still in eggshell. one of the most important reasons for this is inadequate published data on safety and feasibility of procedure. it is the need of hour to collect and publish data on safety and feasibility of day case surgery in our part of world. surgeons are very reluctant to offer day case lc to their patients in our part of world. quality local research data will give surgeons confidence in decision making for day case laparoscopic cholecystectomy. a study was planned to compare the day case lc with conventional lc in terms of mean of number of days of early return to activities and means of intensity of postoperative pain on vas. materials and methods study design was randomized controlled trial (parallel) with allocation ration of 1:1. study was conducted at department of general surgery, pims, shaheed zulfiqar ali bhutto medical university st th (szabmu) islamabad from 1 nov 2014 to 30 april 2015. sample size was calculated using who sample size calculator. taking 18(2-52) days as population mean+/-sd and 14(2-32) days as test value of population mean+/sd for early return to activities 15 from previous literature. level of significance was taken 5%. from given values 42 sample size was calculated for each group. consecutive sampling was done as per inclusion and exclusion criteria. operating surgeons were blinded and sampling was done by on floor post graduate trainee. permission was taken from hospital ethical review board after detailed discussion and defense before the ethical committee. inclusion criteria was to include all patients with uncomplicated cholelithiasis undergoing laparoscopic cholecystectomy in study from 14 years to 60 years of age, both female and male patients and patients in asa grade 1 and 2. patients with known co m p l i cat i o n s o f c h o l e l i t h i a s i s l i ke a c u te cholecystitis and acute pancreatitis, patients with known ihd, uncontrolled dm and uncontrolled htn, any bleeding disorder and patients who are unfit for ga, or in asa grade 3 and 4 were excluded from study. day case lc was defined as discharge from hospital within 12 hours of admission while conventional lc was defined as discharge from hospital after 24 hours of admission. return to home activities was calculated in days, from the time of admission to the time of return to routine home activities. patient was allowed to return to home activities if he was not having any surgical complications, able to move independently for eating, drinking and toilet, has no drain placed, was pain free and tolerating oral diet. jiimc 2019 vol. 14, no.3 132 day case vs conventional laparoscopic cholecystectomy intensity postoperative pain was assessed after 6 hours using visual analogue scale (vas). study population was all patients, who were booked for laparoscopic cholecystectomy during the period of study at surgical unit 3 of pims, szabmu. patients who were fulfilling the inclusion criteria were included in study after taking informed and written consent. patients were divided into two groups, group a and group b by lottery method. randomization was done by assigned on floor post graduate trainee. operating surgeons were blinded about group allocation of participants. patients in group a had undergone day case laparoscopic cholecystectomy and patients in group b had u n d e r g o n e c o n v e n t i o n a l l a p a r o s c o p i c cholecystectomy. pain was measured by vas (visual analogue score) at 6 hours postoperatively and number of days to return to home activities was asked to patient on follow up. for follow up contact numbers and addresses were recorded. data was collected and recorded on purposively designed performa. spss 17 was used for data entry and analysis. mean and standard deviation was calculated for numerical data (parametric) like age, number of days of return to activities and intensity of postoperative pain and frequencies were calculated for categorical data like sex. unpaired t test was used for numerical data like mean of no of days to return to home activities and mean of postoperative pain. p value <0.05 was considered significant. results total of 84 patients were included in study. in group a there were 42 patients who underwent day case laparoscopic cholecystectomy and in group b there were 42 patients who underwent conventional laparoscopic cholecystectomy. in group a, total number of female patients was 32(76.2%) and male were 10(23.8%). mean age was 38.95 years with sd of ±9.798. all the patients in group a underwent successful laparoscopic cholecystectomy without any major complications. out of 42 patients 40(95%) were discharged successfully on same day of admission, fulfilling the day case laparoscopic cholecystectomy criteria. rest of the two patients was discharged on second day of surgery. the reason for failure to discharge on same day of surgery was pain and nausea in both patients. the minimum and maximum intensity of pain on visual analogue scale was 2 and 6 respectively with mean of 3.93 and sd of ±1.135. among 42 patients 13(31%) were on vas 4, 13(31%) were on vas 5, 8(19%) were in vas 3, 6(14.3%) were in vas 2 and 2(4.8%) were in vas 6. the minimum and maximum “number of days to return to activities” was 3 and 7 days respectively, with mean of 3.88 and sd of ±1.109. out of 42 patients 20(47.6%) had returned to their home activities in 3 days, 13(31%) in 4 days, 5(11.9%) in 5 days, 2(4.8%) in 6 days and 2(4.8%) in 7 days. in group b, total number of female patients was 32(76.2%) and male were 10(23.8%). mean age was 44.83 years with sd of ±14.553. all the patients in group b underwent successful laparoscopic cholecystectomy without any major complication. all patients were discharged successfully on second day of admission. the minimum and maximum intensity of pain on visual analogue scale was 2 and 6 respectively with mean of 4.17 and sd of ±1.080. among 42 patients 15(35.7%) were on vas 5, 14(33.3%) were on vas 3, 8(19%) were in vas 4, 4(9.5%) were in vas 6 and 1(2.4%) were in vas 2. the minimum and maximum “number of days to return to activities” was 6 and 10 days respectively, with mean of 8.4 and sd of ±0.857. out of 42 patients 17(40.5%) had returned to their home activities in 9 days, 17(40.5%) in 8 days, 4(9.5%) in 7 days, 3(7.1%) in 10 days and 1(2.4%) in 6 days. there was no statistically significant difference between the two groups in terms of intensity of pain on vas, as p value was greater than 0.05 (p-value: table i: no of days to return to ac�vi�es table ii: intensity of post-opera�ve pain in both groups on vas jiimc 2019 vol. 14, no.3 133 day case vs conventional laparoscopic cholecystectomy 0.359 using paired t-test), while there was statistically significance difference in two groups in terms of no of days to return to routine activity as p value was less than 0.05 (p-value: 0.000 using paired t-test) discussion our study has demonstrated success rate of 92.5%, which is fairly consistent with the international reported figures, which is 95% as reported by hamad 16 et al. success rate is quite lower if proper patient selection is not done. careful patient selection base on the inclusion and exclusion criteria should significantly reduce the number of failed day case surgeries, as patient unfit for day case surgery was identified as leading cause of day case surgery failure 17 in literature. in our study, which has demonstrated success rate almost comparable to international literature, careful patient selection was done using preset inclusion and exclusion criteria. in our study we studied the two factors, one is postoperative pain and other one is the early return to home activities. postoperative pain is one of the most important reasons for failure to discharge patient on same day of surgery. literature has reported that postoperative pain and nausea is the reason for failure to discharge and even readmission 18 majority of patients undergoing day case surgery. as in our study, minimal post-operative pain has been included in criteria for discharge along with other parameters in almost all of the reported 19 literature on day case surgery. in our study failure to discharge rate after day case surgery was 5%. in all 5% of patients, reasons for delayed discharge was nausea and vomiting, which is again consistent with 18 reported literature. in our study visual analogue scale (vas) was used to assess the intensity of postoperative pain. vas is easy to record and easy to understand scale, which is being used by most of the 20 researcher around the globe. requirement for analgesics in both groups could have been a good variable to record, which our study lacks. our study also did not find any significant difference between the two groups in term of postoperative pain intensity as p value was more than 0.05, which translates into the fact that patients who are being discharged home on same day will not need extra care for pain management as compared to other group. early return to routine activities is quite an important factor in comparing the two groups. the more the patient stays in hospital; the delayed will be his return to normal life. our study has found significant difference between the two groups in term of early return to routine activities as the p value is less than 0.05. average of 10 days have been reported in literature for no of days to return to routine activities 21 after conventional laparoscopic cholecystectomy. our study has demonstrated 9 mean days for return to routine activities after conventional lc, while 3.88 mean days for day case lc, which was found to be statistically significant. this single variable shows that number of sick leaves days can be reduced by adopting day case surgery, where feasible, but more studies are warranted to validate and strengthen this claim. as it is evident from the above literature and from our study, that the lc can be performed with success and with safety on day case basis; as shorter hospital stay did not affect the outcomes and rate of complications after surgery. on the other hand day case surgeries have shortens the waiting list for surgeries and have reduced the total cost of surgery 22 because of shorter hospital stay. certain principles should be met for the success of day case surgery. careful selection of patients after setting inclusion and exclusion criteria and vigilant management of postoperative pain are the parameters for the success of day case surgery. conclusion patients undergoing day case lc do return to their routine activities earlier than those who undergo conventional lc, but there is no difference in terms of intensity of post-operative pain as measured on visual analogue scale. references 1. chalkoo m, ahanger s. the historical perspective, current advancements and innovations in laparoscopic cholecystectomy. j pioneer med sci. 2012; 2(3):86–7. 2. beal jm. historical perspective of gallstone disease. surg gynecol obstet. 1984; 158(3):181–9. 3. shaikh h, abbas a, aleem s, lakhani m. is mini-laparoscopic cholecystectomy any better than the gold standard? a comparative study. j minim access surg. 2016; 13(1):42. 4. khashab ma, kalloo an. natural orifice translumenal endoscopic surgery. curr opin gastroenterol. 2010; 26(5):471–7. jiimc 2019 vol. 14, no.3 134 day case vs conventional laparoscopic cholecystectomy 5. malik a, mellinger j, hazey j, dunkin b, macfadyen bj. endoluminal and transluminal surgery: current status and future possibilities. surg endosc. 2006; 20(8):1179–92. 6. jiang h, han j, lu a, liu x. day surgery management model in china: practical experience and initial evaluation. int j clin exp med. 2014; 7(11):4471–4. 7. an y, wang z. concept and basic problems of day surgery. chinese j pract surg. 2007; 27:38–40. 8. zhang z, yu t, li h. study on medical expenses and bed usage under day surgery model. hebei med j. 2007; 13:398–402. 9. chawla t, ali a, jamal a. ambulatory laparoscopic cholecystectomy: is it safe and cost effective? j minim access surg. 2009; 5(1):8. 10. briggs cd, irving gb, mann cd, cresswell a, englert l, peterson m, et al. introduction of a day-case laparoscopic cholecystectomy service in the uk: a critical analysis of factors influencing same-day discharge and contact with primary care providers. ann r coll surg engl. 2009; 91(7):583–90. 11. tamhankar ap, mazari f, olubaniyi j, everitt n, ravi k. postoperative symptoms, after-care, and return to routine activity after laparoscopic cholecystectomy. jsls j soc laparoendosc surg. 2011; 14(4):484–9. 12. ahn y, woods j, connor s. a systematic review of interventions to facilitate ambulatory laparoscopic cholecystectomy. hpb. 2011; 13(10):677–86. 13. mehraj a, naqvi ma, feroz sh, ur rasheed h. laparoscopic cholecystectomy: an audit of 500 patients. j ayub med coll abbottabad. 2011; 23(4):88–90. 14. sato a. ambulatory laparoscopic cholecystectomy: an audit of day case vs overnight surgery at a community hospital in japan. world j gastrointest surg. 2013; 4(12):296. 15. sharma a, hayden jd, reese ra, sedman pc, royston cms, o'boyle cj. prospective comparison of ambulatory with inpatient laparoscopic cholecystectomy: outcome, patient preference and satisfaction. ambul surg. 2004; 11(1–2):23–6. 16. al-qahtani hh, alam mk, asalamah s, akeely m, ibrar m. day-case laparoscopic cholecystectomy. saudi med j. 2015; 36(1):46–51. 17. dimitriadis pa, iyer s, evgeniou e. the challenge of cancellations on the day of surgery. int j surg [internet]. 2013; 11(10):1126–30. 18. al-omani s, almodhaiberi h, ali b, alballa a, alsowaina k, alhasan i, et al. feasibility and safety of day-surgery laparoscopic cholecystectomy: a single-institution 5-year experience of 1140 cases. korean j hepato-biliarypancreatic surg [internet]. 2015; 19(3):109. 19. hamid r, hakeem w, naiko z, malik m, resident s. annals of surgery: international feasibility of day care laparoscopic cholecystectomy in district hospital married doctors hostel room no= s2, a block, skims. ann surg int. 2016; 2(2):6–10. 20. tiryaki c, bayhan z, ertugrul e, alponat a. ambulatory laparoscopic cholecystectomy: a single center experience. j minim access surg. 2016; 12(1):47–53. 21. ito e, takai a, imai y, otani h, onishi y, yamamoto y, et al. quality of life after single-incision laparoscopic cholecystectomy : a randomized , clinical trial. surgery [internet]. 2019; 165(2):353–9. 22. ji w, ding k, li l, wang d, li j. outpatient versus inpatient laparoscopic cholecystectomy: a single center clinical analysis. hepatobiliary pancreat dis int. 2010; 9:60–4. jiimc 2019 vol. 14, no.3 135 day case vs conventional laparoscopic cholecystectomy original�article abstract objective: t ear peer-assisted learning (npal) in to o implement and evaluate n small group discussions (sgd) build correlation of anatomy and clinical sciences. study design: a quantitative descriptive study. place and duration of study: study was conducted in anatomy department for a period of 4 months. materials and methods: entire first year mbbs class (100 students) was included as near peer learners (npl) and 3 students of second year mbbs session who had secured more than 60% marks throughout first year assessments and in summative exam were included as near peer tutors (npt). npal was applied in small groups to correlate upper limb nerve injuries site of lesion with their symptoms. first year was divided into 6 batches with 12 to 15 students each. in first sgd 3, batches attended session with junior faculty while 3 with npts, both having same learning objectives regarding 4 upper limb nerves and their injuries. in second sgd the subgroups were flipped and exposed to same strategy where 3 new upper limb nerves and their injury sites were taught. thus entire first year students were taught seven upper limb nerves overall, half exposed to npal for one set of nerves and second half of class exposed to npal for second set of nerves. pre and post sgd mcqs were administered in each sgd to see the cognitive gain of learners. at the end of second sgd a 5 point likert scale questionnaire was used to assess learners' perception regarding npal. results: analysis of pre & post sgd mcq tests mean score of faculty and npt taught sessions in both sgds was found to be higher when taught by tutor though not statistically significant. paired t test and pearson correlation applied to questionnaire on spss version 21 showed that concept building and comprehension was almost equivalent in both while learning environment was found to be more conducive when taught by npts. the learners also felt better prepared for exam when taught by npt. conclusion: when used in small groups, is found to be equivalently useful and effective learning strategy npal, regarding concept building and comprehension of complex concepts of anatomy and its correlation with clinical sciences. the learners have shown cognitive gain and are satisfied with near peer tutors teaching in small groups. key words: anatomy in integration, near peer assisted learning, near peer learners, near peer tutors, small group discussions. 2 school in most of colleges. being mostly taught in modules and according to themes it becomes 3 difficult for student to make a concept. its vertical integration with clinical sciences, though interesting, becomes exhaustive for students. in addition lengthy reading hours from challenging text books make this 4 subject least interesting. the result is either students leave it on choice or have a higher failure 5 rate. teaching it in an innovative way removes the fears of new comers and develops learning skills in 6 them. in order to make the students understand the concepts and enhance their cognitive skills, the medical educationists are always in search of feasible new instructional strategies. one of them is peer assisted learning (pal). a working definition of pal is " people from similar social groupings who are not introduction medical curriculum delivery is in the phase of shifting from traditional system to integrated system in 1 pakistan. in integration gross anatomy, histology , general anatomy and embryology all has to be balanced with two basic sciences , preventive , legal and clinical subjects in first two years of medical an innovative way to teach anatomy in integration: near peer assisted learning 1 2 3 4 shazia muazam , ayesha baqar , zarmina sohail , samina anjum correspondence: dr. shazia muazam associate professor hbs medical and dental college, islamabad e-mail: shaziamuazam@gmail.com 1 department of anatomy hbs medical and dental college, islamabad 2,3,4 department of anatomy rawal institute of health sciences, islamabad funding source: nil; conflict of interest: nil received: february 15, 2020; revised: october 10, 2020 accepted: october 14, 2020 near peer assisted learning assisting in anatomy integrationjiimc 2021 vol. 16, no.2 122 professional teachers helping each other to learn 7 and learning themselves by teaching.” the general idea behind peer tutoring is students helping 8 students. help means providing support to others either in gaining knowledge or guiding others with new learning resources or helping in enhancing communication or competency skills. pal programs are not meant to replace instruction, but to 9 complement it. near-peer assisted learning (npal) is a type of pal in which the near peer tutors (npt) are someone at least one year senior to their near 10 peer learners (npl) regarding training. cognitive and social congruence, the basic idea in npal teaching, stands on the fact that near peer tutors, being one year senior, are familiar with difficulties the learners will face in their studies which the faculty cannot anticipate. student learners find it more convenient and relaxed to communicate with 11 near peer tutors as both have same social roles. globally npal has been accepted to inspire the learners to contribute to the learning activity giving learners ownership of their own learning ultimately leading to better understanding and concept 12 building. small group discussions is one of the teaching learning methodology for delivering integrated curriculum in which small number of learners get better chance of one is to one interaction and clarify 13 their concepts easily. delivery of integrated curriculum is resource intensive in terms of trained staff and logistics. there is paucity of trained junior faculty in basic sciences which is involved in small group teachings in most of the undergraduate medical institutes. in addition most of the colleges found it difficult to involve patient committed clinicians to deliver the clinical integration in preclinical years. anatomy, a high volume subject, becomes a formidable course when integrated with three or four subjects together. the need of hour is to apply some innovative teaching methodology capable of enhancing complex concept building in medical students and assisting the faculty 14 in faculty compensated medical institutes. work has already been done nationally and internationally using new teaching and learning strategies and comparing them with lecture format but there is no study using any teaching intervention in small group discussions side by side with faculty teaching in small groups to see its efficacy in terms of learners gain especially in an integrated curriculum. this pilot study was planned with an objective to implement and evaluate n ear peer-assisted learning (npal) in small group discussions (sgd) to build correlation of anatomy and clinical sciences. materials and methods this descriptive quantitative pilot study was conducted in anatomy department of a private medical college associated with shaeed zulfiqar ali bhutto university (szabmu), islamabad, pakistan. the study lasted for a period of 4 months. entire first year mbbs session comprising of 100 students was included as a convenience sample as npls and 3 students of second year mbbs session who had secured more than 60% marks throughout first year assessments and in summative exam were included as npts. after the approval by ethical review board of szabmu, the principal investigator (pi), an mphil in anatomy, took verbal consent from both npls and npts after explaining them the objectives and strategy. the curriculum in 1st and 2nd year mbbs is delivered in 3 blocks comprising of two, 6 weeks long, modules in our university. the basic sciences are horizontally integrated with each other and vertically integrated with clinical sciences. npal was introduced in small groups in second module of block 2 mainly concerned with integration of upper limb anatomy, nerve physiology, biochemical and clinical aspects. the npts were given a training session of 1 hour by pi on how to facilitate sgd and whom to contact in case 10 of any problem arising during or after the session. 1st year was divided into 6 batches: a, b, c, d, e and f with 12 to 15 students in each batch. in first sgd batch a, b and c attended sgd session with junior faculty while batch d, e and f with npts. the session lasted for 2 hours. both the npal assisted and nonassisted groups had similar learning objectives regarding four nerves, their injuries and correlation of symptoms with the site of lesion in upper limb. next week the batches were flipped and exposed to same strategy as above in second sgd where 3 new upper limb nerves and their injury sites were taught. thus entire first year students were taught seven upper limb nerves overall, half exposed to npal for one set of nerves and second half of class exposed to npal for second set of nerves . near peer assisted learning assisting in anatomy integrationjiimc 2021 vol. 16, no.2 123 a pre and post sgd mcq test (c2 and c3 level) was taken in each sgd, by pi, to assess the cognitive gain of npls. for recording learner's perception, a 5-point likert scale questionnaire was used which was modified by pi from a validated questionnaire, already used nationally and internationally, based on grounded 15 theory framework of peer assisted learning. it was modified from 7 to 5 points by removing the questions having duplication of responses. after modification it was validated by 2 medical educationists. at the end of second sgd the questionnaire was given to those npls who had attended both the sessions. it was collected on the same day. concept building and comprehension, learning skills development, interactive and cooperative learning and learning environment were four main domains of the questionnaire. the data was analyzed on spss version 21.paired t test and pearson correlation was applied with p value of ≤0.05 set as cut off point for statistical significance. results out of 100, 79 (79%) students participated in both sgds. analyses of pre & post mcq tests mean faculty taught score was 6.89 ± 1.69 while mean npt taught score was 7.29 ± 2.38 though not statistically significant (p= 0.18) regarding perceptions most of the individual parameters showed fair positive correlation. concept building and comprehension were almost e q u i va l e nt i n b o t h g ro u ps w h i l e l e a r n i n g environment was found to be more conducive when taught by npts (table i and ii). npls felt better prepared for solving short answer questions when taught by npts (table ii) 'the sessions provided opportunity to air concerns away from teaching staff and sessions provided an opportunity for learning with others' had a strong correlation when taught by npts (table ii). few parameters like 'sessions were helpful in improving my communication skills and session stimulated me to take part in active discussion', had mean responses which were close to neutral response. the learners were not clear about the learning skills development (table ii) discussion peer assisted learning helps by providing additional student support in curriculum delivery, in preparation of assessments, by providing feedback, table i: comparison of correlation of teaching by faculty and npts according to subtotal scores of 4 domains of questionnaire table ii: comparison of correlation of individual parameters of 4 domains between teaching by faculty and npts near peer assisted learning assisting in anatomy integrationjiimc 2021 vol. 16, no.2 npal: near peer-asisted learning 124 in our study we used near peer tutors to teach integration of anatomy with clinical science, in small groups, along with junior faculty. the leaners cognitive gain was found to be more with near peer teaching though not significant. the learners were satisfied with both the faculty and near peer teachers. there is not much difference in concept building of anatomy and its correlation with clinical sciences between tutors and faculty while learning environment was fairly positive in tutor taught group. worldwide, students perspective of acceptance of peer assisted learning is found out to be high. a study published showed that 82% of the learners showed satisfaction with peer teaching model used in skills training while only 1% were of the opinion that skills 20 training should be provided by faculty only. this strategy helps in building up course satisfaction in learners by removing subjective stress due to the social and psychological support provided by the 21 peer tutors. in current study the learners were satisfied with the teaching and integration of complex anatomical concepts by the tutors. npal 22 improves examination scores among learners. the result of current study also showed cognitive gain by the learners. learners find the learning environment 23 conducive in peer assisted learnings similar to current study. in pakistan, pal has been used formally in various studies either as a pilot or as a full fledge course. encouraging results are reported in terms of 15, 23,25 students' acceptance and learning. some studies have shown high score achievement by learners 26 when taught by npts as compared to faculty while some reports confirm at least same level of 8 knowledge gain. anatomy dissection when taught by pal helped the learners in building concepts and motivated them for 27 self-study. overall performance of students increased from 87 to 88% in a course of anatomy when delivered by npt and assessed by quizzes and question bank, over a period of four years.72% of the students responded in affirmation with enhanced understanding of anatomy concepts when taught by 28 npts. current study results also exhibited a better understanding anatomy as is assessed by mcqs though it was not significant. current study is different from other work done in 16 by mentoring and by re planning the curriculum. it 17 enhances cognitive gains , develops generic skills, 18 provides psychological support and leads to 19 attitude development. near peer assisted learning assisting in anatomy integrationjiimc 2021 vol. 16, no.2 125 pakistan as we have used near peer tutors and faculty simultaneously, in small group discussions, to teach complex anatomical concepts in integration with clinical signs and symptoms. our aim was not to find superiority of tutors over faculty but to see if near peer learners can understand the complex anatomical concepts in integration with clinical sciences when taught by near peer tutors. in the long run near peer tutors can be used to facilitate the faculty in faculty compensated medical institutes. limitation only two sgds were used for npal experimentation as it was a pilot study. we found it difficult to schedule the timetables of near peer learners and near peer tutors. learner's perception taken by a questionnaire could have been strengthened by arranging a focus group discussion at the end of intervention along with the questionnaire. our time constraint didn't allow us to conduct it. to see noticeable benefit among the learners, npal should be applied in different blocks, in all the sgds. the small group's timings in first year should be scheduled after adjusting the timings of classes of second year so that the tutors do not suffer academically. the cognitive gain after using such strategy should be assessed in a modular or summative exam as theory or in practical. conclusion this pilot study investigates experiences with near peer-assisted learning in delivering complex anatomical concepts in an integrated curriculum, in small groups. key findings indicate that learners are satisfied by near peer tutors teaching ,same as faculty teaching, regarding concept building and comprehension of anatomy and its correlation with clinical sciences when they are taught by both in small groups though better cognitive results are seen in near peer tutor taught groups. teaching by an expert cannot be surpassed solely but can be supported by an adjunct teaching strategy to deliver difficult concepts in small groups. references 1. pmc. curriculum. 2019 [cited 2020 feb 3rd]; available from: pmc.org.pk. 2. abid k, majid a, majeed f. stepping towards an integrated medical curriculum: a journey from talent to skills–a pilot study. jimdc. 2015; 4(2):81-4. 3. qurban s, saleem s, muntaha t. attitude of students towards introduction of integrated module system in undergraduate's medical curriculum. jrmc. 2017; 21(s1):45-8. 4. bruno pa, love green jk, illerbrun sl, holness da, illerbrun sj, haus ka, et al. students helping students: evaluating a pilot program of peer teaching for an undergraduate course in human anatomy. anat sci educ. 2016; 9(2):132-42. 5. papa v, vaccarezza m. teaching anatomy in the xxi century: new aspects and pitfalls. sci. world j. 2013; 13(2):5 pgs. 6. smith cf, martinez-álvarez c, mchanwell s. the context of learning anatomy: does it make a difference? j. anat. 2014;224(3):270-8. 7. topping kj. trends in peer learning. educational psychology. 2005;25(6):631-45. 8. sammaraiee y, mistry rd, lim j, wittner l, deepak s, lim g. peer-assisted learning: filling the gaps in basic science education for preclinical medical students. adv physiol educ. 2016;40(3):297-303. 9. de los ángeles cambrón-carmona m, de lara cnt, caracuel ir, cepas fl, gonzález rg, lozano sz, et al. near-peer teaching in histology laboratory. ijms. 2016;4(1):14-8. 10. aba alkhail b. near-peer-assisted learning (npal) in undergraduate medical students and their perception of having medical interns as their near peer teacher. med teach. 2015;37(sup1): s33-s9. 11. herrmann-werner a, gramer r, erschens r, nikendei c, wosnik a, griewatz j, et al. peer-assisted learning (pal) in undergraduate medical education: an overview. z evid fortbild qual gesundhwes. 2017; 121:74-81. 12. mann j, protty mb, duffy j, mohammed m, wiskin c. nearpeer teaching and exam results: the acceptability, impact, and assessment outcomes of a novel biological sciences revision programme taught by senior medical students. j biomed educ. 2014 nov 30;9. 13. ahmad rn, bhatti mm, khan ah, ghayur s, rafi s, naseem s, et al. small group discussion as a learning strategy for medical undergraduates. rmj. 2014;39(3):344-8. 14. hall s, stephens j, parton w, myers m, harrison c, elmansouri a, et al. identifying medical student perceptions on the difficulty of learning different topics of the undergraduate anatomy curriculum. med sci educ. 2018;28(3):469-72. 15. daud s, ali sk. perceptions of learners about peer assisted learning and lectures. int j sci res. 2014;3(11)1449-55. 16. yu tc, wilson nc, singh pp, lemanu dp, hawken sj, hill ag. medical students-as-teachers: a systematic review of peerassisted teaching during medical school. adv med educ pract. 2011; 2:157. 17. ali a, evans p. multi-resource peer assisted learning in postgraduate setting: a pilot study. jcpsp. 2013;23(4):2516. 18. burgess a, mcgregor d, mellis c. medical students as peer tutors: a systematic review. bmc med edu. 2014;14(1):1. 19. taheri m, amini m, delavari s, bazrafkan l, mazidimoradi j. effect of peer assisted learning (pal) education on knowledge, attitude and behavior related to prevention and control of diabetes. bmc res notes. 2019;12(1):227. 20. andrew jay e, starkman sj, pawlina w, lachman n. d e v e l o p i n g m e d i c a l s t u d e n t s a s t e a c h e r s : a n near peer assisted learning assisting in anatomy integrationjiimc 2021 vol. 16, no.2 126 anatomy-based student-as-teacher program with emphasis on core teaching competencies. anat sci educ. 2013;6(6):385-92. 21. bhatt jv. impact of peer assisted learning on year 1 medical students peer assisted learning module as a teaching learning method. ijabms. 2016;18(26):71-9. 22. nurmi a-m, kokkonen m. peers as teachers in physical education hip hop classes in finnish high school. j educ train stud. 2015;3(3):23-32. 23. manzoor i. peer assisted versus expert assisted learning: a comparison of effectiveness in terms of academic scores. jcpsp. 2014; 24(11):825-9. 24. naqi sa. peer assisted learning as a formal instructional tool. jcpsp. 2014;24(3):169-72. 25. ahsin s, abbas s, zaidi n, azad n, kaleem f. reciprocal benefit to senior and junior peers: an outcome of a pilot research workshop at medical university. jpma. 2015;65(8):882-4. 26. mueanploy w, editor. a study: effect of students peer assisted learning on magnetic field achievement. j phys conf ser 710 012025; 2016: iop publishing. 27. han e-r, chung e-k, nam k-i. peer-assisted learning in a gross anatomy dissection course. plos one. 2015;10(11): e0142988 28. jain a, michelotti m, mcdonald j, lee d, bohl m, fitzgerald j, et al. medical students as teaching assistants in an undergraduate anatomy course. med sci educ. 2012;22(2):50-2. near peer assisted learning assisting in anatomy integrationjiimc 2021 vol. 16, no.2 127 original�article abstract objective: to study the protective role of omega 3 fatty acids on the histomorphological changes in the area of the prostatic acini in rats, induced by sleep deprivation. study design: lab based randomized control trial. place and duration of study: the study was conducted at anatomy department, army medical college, rawalpindi, in collaboration with national institute of health (nih), rawalpindi for a duration of one year from th th 11 nov 2014 to 11 nov 2015. materials and methods: thirty male sprague dawley rats, 3-4 months of age with average weights of 200-300 grams (gm) were divided in three groups each having 10 rats .group a served as control with standard lab diet and regular sleep -wake cycle. group b was subjected to sleep deprivation of 16 hours followed by a sleep window of 8 hrs daily for 2 months and group c was administrated with omega 3 fatty acids and was sleep deprived as group b for 2 months. at the end of the experimental period rats were anesthetized and their blood sample was drawn for hormonal assay. they were dissected and the prostate gland was removed and fixed in 10 percent formalin. five micrometer sections were obtained after tissue processing and stained with haematoxylin and eosin (h&e) for histological study. results: microscopic examination revealed that the percentage area of the prostatic acini was decreased by 100% in group b and 30% in group c. this revealed that the area of the prostatic acini was decreased in the group b as compared to the control group a. decrease in the acinar area in the experimental group c was not that marked as compared to experimental group b. conclusion: it is concluded that sleep deprivation has deleterious effects on the area of the prostatic acini and that omega 3 fatty acids has an ameliorative effect on the area of the prostatic acini. key words: omega 3 fatty acids, prostate, rats, sleep deprivation. processes. it leads to biochemical, hormonal, behavioral and neurological alterations. therefore, it is imperative to apprehend the impact of sleep deprivation on the body. several experiments that have been conducted on rat models have established the physical effects of sleep deprivation such as dermatological findings, weight loss (in spite of regular food intake), decreased immunity followed by death in a couple of weeks proving that sleep is a basic biotic need that has impact on the operation of 3 many organ systems. as sleep deprivation has been proven to be a form of stress it exerts allostatic load i.e wear and tear of the systems in the body, circadian 4 disruption including increase in the cortisol levels. the increase in cortisol levels due to stress is associated with decrease in testosterone levels as sleep deprivation results in many alterations in the morphology of various organs and hormonal 5 abnormalities. it is strongly associated with alteration in the male sex hormone levels causing 6 detrimental effects on the prostate gland. testosterone plays a pivotal role in the development introduction sleep deprivation has become one of the leading forms of stress causing detrimental effects to the mind and body. prolonged sleep deprivation usually takes place in extreme situations or under 1 experimental conditions. the most common causes of sleep deprivation are those related to contemporary lifestyle and work-related factors; thus the condition affects a considerable number of people. sleep deficiency (insomnia) accompanies certain pathological states and may require 2 treatment it has become one of the greatest health risk factor that contributes to several disease effects of sleep deprivation on the area of the prostatic acini in rats and the protective effects of omega 3 fatty acids 1 2 3 nomana mahmood syed , kaukab anjum qureshi , humaira ali correspondence: dr. nomana mahmood syed assistant professor, anatomy wah medical college, wah cantt e-mail: mahmoodnomana@gmail.com 1,2 department of anatomy wah medical college, wah cantt 3 department of anatomy hitec institute of medical sciences, taxila funding source: nil; conflict of interest: nil received: feb 10, 2017; revised: apr 19, 2017 accepted: july 30, 2017 effects of sleep deprivation on prostatejiimc 2017 vol. 12, no.3 148 7 and functioning of the prostate gland. according to a latest study men with sleep problems have been 8 linked to the development of prostate cancers. sleep deprivation is strongly concomitant with 9 noticeable drop in the levels of androgens. this shows reduced steroidogenesis or lessened expression of androgens in the target glands. these effects can be counteracted by the addition of healthy fats like omega 3 fatty acids. these lessen the action of 5 alphareductase enzyme and have a protective role on the prostate gland. omega 3 fatty acids (omg 3 fa), an assembly of polyunsaturated essential fatty acids that are compulsory for human health but cannot be made de novo, so, they have to be attained from exogenous sources, found in enormous quantities in fish oil . the consistent use of omega 3 fatty acids greatly 10 diminishes the risk of developing prostate cancer. eicosapentaenoic acid (epa) a form of omega 3 fas is linked with reduction in the progression of prostate 11 cancer. it also results in the decline of oxidative 12 stress and cell apoptosis. chavarro proved that augmented blood levels of omega 3 fas were concomitant with a decreased likelihood of 13 development of prostate cancer. stress is known to cause inflammation which can impair tissues and organs if not controlled. exploring the positive e f f e c t s o f o m e g a 3 f a t t y a c i d s o n t h e histomorphology of sleep deprived rat prostates may be of great help. the modus operandi of current study was to ascertain the effects of sleep deprivation on the area of acini in the prostate gland of rats and to establish the beneficial effects of omega 3 fatty acids. the effects of sleep deprivation on the secondary sex glands especially in males e.g prostate gland, have not been focused upon. therefore, this study was aiming at the histological effects of sleep deprivation on the prostate gland in rats and the protective effects that omega 3 fatty acids brought about to minimize these detrimental changes. materials and methods the study was a laboratory based randomized control trial carried out in the department of anatomy, army medical college rawalpindi, in alliance with national institute of health (nih) islamabad and armed force institute of pathology th (afip), rawalpindi. it was spanned from 11 th november 2014 to 11 november 2015 with the a p p rova l o f et h i ca l co m m i tte e o n a n i m a l experiments, of the army medical college, rawalpindi. a total of thirty rats were used by random number table method, selected by nonprobability convenient sampling. the rats were 3-4 months of age and weighing 200-300 grams (gm). they were kept in a well ventilated room and under a temperature range of 22-26°c. rats were given nih laboratory diet for two months. water was provided ad libitum. rats were indiscriminately divided into three groups (10 animals in each group). the rats of group a served as controls, they were fed with standard lab diet and subjected to normal sleep wake cycle. the rats in group b were fed with regular lab diet and subjected to sleep deprivation for a period of 16 hours daily followed by a sleep window of 8 hours daily for 8 weeks. rats in group c were also subjected to sleep deprivation as group b and were administrated with omg 3 fa at a dose of 260 milligram/kilogram/day (mg/kg/day), through oral gavage in addition to the regular lab diet. the dose of omega 3 fatty acids was established based on prior 14 studies and it was obtained from good`n`natural, imported by route 2 health pvt ltd. the sleep deprivation apparatus was based on a modified pendulum technique and it consisted of a cage partitioned into 2 for each of group b and group c. it was fitted with an electrical device that caused to and fro jerky movements every 2 minutes set by a timer. this brought unrest in the rats causing sleep 15 deprivation. at the completion of 8 weeks, 5 milliliter (ml) blood was drawn from each rat via intracardiac puncture, for evaluating serum testosterone then rats were dissected under chloroform anesthesia. the prostate glands were excised and fixed in 10% formalin and processed in automatic tissue processor. the tissue was infiltrated and embedded with paraffin wax. cross sections of 5 micrometer (µm) thickness were obtained from the tissue blocks. all processing and staining procedures were done in histopathology lab at afip, rawalpindi. h&e stains were used for routine histological study. area of the acinar lumen was calculated by using a morphometric computer software “motic image plus 2.0” a software for c a l c u l a t i n g a r e a a n d o t h e r u s e r d e f i n e d 16 morphometric parameters. images of three effects of sleep deprivation on prostatejiimc 2017 vol. 12, no.3 149 selected fields were taken from each slide with the help of olympus digital camera (10 mega pixel), stylus 1010 were used through the ocular of the olympus dp21 light microscope. the images were then transferred in the computer. each image was opened in morphometric computer software “motic image plus 2.0”. a scale was set to measure the area in micrometer square at 10x. measurement tool for irregular shapes was selected and the area to be measured was outlined, the measurement was then analyzed and recorded. the final reading was recorded as the mean of area of 3 acini per three fields/slide per specimen. ibm-spss version 21 was used for data analysis. anova test was applied followed by post hoc tukey`s test, for intergroup comparison of quantitative variables which was taken as means and standard deviations (mean +sd). a p value <0.05 was considered significant. results thirty sprague dawley rats with an average age of 3-4 months and a mean weight of 220.16±10.80 grams were used in the experiment. after dissection and tissue processing, histological examination of the prostatic acini in group a showed that the mean area of the acini was 471.48±101.66 µm.² the mean area of the prostatic acini in group b was markedly decreased as compared to control group a, it was measured to be 246.69±17.08 µm.² the area of the prostatic acini in group c was observed to be 341.70±68.60 µm.² intergroup comparison of the area of the prostatic acini, after the application of post hoc tukey`s test, revealed a p value of <0.001, when group a was compared to group b which was statistically very significant. on comparison of groups a and c p value was found to be 0.001. when group b was compared to group c the p value= <0.016 which was also statistically highly significant. intergroup comparison of serum testosterone levels revealed a p value of 0.000 when group a was compared to group b and when group b was compared to group c, which was statistically significant. however, on comparison of group a with group c, p value= 0.526 which was statistically insignificant. discussion the difference in area among all the three groups was statistically significant (p<0.001). the group that was exposed to sleep deprivation showed marked changes in the histomorphology when the area of the prostatic acini was studied. this is because it has been found that the prostate is an androgen dependent organ. sleep deprivation results in decreased androgen levels in the blood which also effects the growth of prostate and hence, affects the prostatic acini. the decrease in area of the prostatic acini is a result of decrease in the testosterone levels in blood due to sleep deprivation. sleep deprivation is a form of stress and its effect on the sex hormones of rats was also proved in a study conducted where different stress modalities including sleep deprivation were inflicted on rats with resultant decrease in the testosterone levels. sleep deprivation causes alterations in hypothalamohypophyseal axis leading to decreased circulating 17 androgens in healthy individuals. omega 3 fatty acids are known to be responsible for the upsurge in luteinizing hormone (lh) formation, especially in animals ,this leads to the production of testosterone inside the leydig cells .this is one of the basic reasons why the area of the prostatic acini is not markedly decreased in rats of omega 3 administrated group c as compared to those of group b ,hence, proving the 18 objective of the study. sleep deprivation causes low levels of androgens and results in activation of apoptosis, hence, atrophy or decrease in size of the 19 acini due to cell death. the male sex hormone levels i.e testosterone levels were estimated which specified a noteworthy diminution in the hormonal level of the rats in the experimental group b when it was related with the control group a (p <0.001). n e ve r t h e l e s s , t h e va r i a n c e i n t h e s e r u m testosterone level in the experimental group c was not statistically significant when it was equated with the control group a. this is in agreement with the previous study which proved that the lack of sleep is associated with decrease in testosterone levels in rats. omg 3 fas are known to cause rise in luteinizing hormone (lh), especially in animals. this leads to the making of testosterone inside the leydig cells .this establishes why the levels of testosterone were increased in rats that were given omg 3 fas i.e group 20 c as compared to those of group b. conclusion it is concluded that sleep deprivation has harmful effects on the prostatic acini and that omega 3 fatty effects of sleep deprivation on prostatejiimc 2017 vol. 12, no.3 150 acids had a protective effect on the prostate gland in rats. references 1. gryglewska jo. consequences of sleep deprivation. international journal of occupational medicine and environmental health. 2010; 23: 95-114. 2. mander ba, winer jr, jagust wj, walker mp. sleep: a novel mechanistic pathway, biomarker, and treatment target in the 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of leydig cells and testosterone synthesis. 1990; 120: 610-8. effects of sleep deprivation on prostatejiimc 2017 vol. 12, no.3 152 page 31 page 32 page 33 page 34 page 35 original�article abstract objective: the objective of current research was to establish the validity and reliability of dysfunctional attitude scale-form a in pakistani population. study design: the present study incorporates the cross-sectional design based on confirmatory factor analysis. place and duration of study: the study was conducted in twin cities of rawalpindi and islamabad from march 2016 to february 2017. materials and methods: the data was collected through purposive convenient sampling. the dysfunctional attitude scaleform a (das-a) was translated in urdu language and construct validity of the instrument was tested by the aid of confirmatory factor analysis. it is a 40-items self-report instrument measuring both the dysfunctional and the adaptive aspects of attitudes. the study included a total sample of n=641 (324 male & 317 female) young adults aged above 18 years (m= 19.56; sd = 1.79) and selected from the normal population. results: the findings revealed significant alpha coefficients, homogeneity, and stability of the das-a. meanwhile, the confirmatory factor analysis provided strong support for a two-dimensional model. using the sample variance-covariance matrix as input and a maximum likelihood solution, the overall chi-square was statistically non-significant (cmin/df=1.24; p > .05), the tucker-lewis index was .90, the incremental fit index was .96, the normed fit index was .97, the comparative fit index was .96 and the root mean square residual / error (rmse) for the predicted minus observed correlation matrices was .03. all these values suggest good model fit for the das-a. conclusion: subsequently, findings suggest that das-a (urdu) is an efficient, reliable, and valid instrument for the assessment of dysfunctional attitudes which predispose to depression among young adults. meanwhile, this research laid the foundation for further research in clinically depressed population. key words: depression, dysfunctional attitudes, reliability, validity. depressive episodes or indirectly as a factor of 3 vulnerability under stressful conditions. previous studies revealed that dysfunctional attitudes are 4,5 related to the incidence of depression and that there was a correlation between high levels of dysfunctional attitude and the longer duration of 5,6,7 episode as well as shorter remissions in 8 depression. taken together, a reliable and valid measure is 9 necessary for understanding depression. thus, dysfunctional attitudes are measured with the 2, 10 dysfunctional attitudes scale (das) which has been one of the leading cognitive instruments in clinical research and diagnosis for measuring levels 11,12,13 of cognitive vulnerability to depression for more 14 than 30 years. das is one of the cognitive assessments that have a direct link or direction to 15 symptoms of depression. it is a self-report inventory designed to measure attitudes that can predispose a person to depression. das was originally a 100-item scale developed using a college student population. it was divided into two parallel introduction dysfunctional attitudes are an important risk factor 1 in the onset and maintenance of depression. beck proposed that dysfunctional attitudes are vulnerability factors that play a causal role in the onset of depression. in beck's theory, negative selfschemas that include irrational or dysfunctional beliefs are the core of vulnerability to depression. childhood experiences along with a negative stressor increase the risk of depression in those 2 individuals with maladaptive cognitive patterns. accordingly, these dysfunctional attitudes are considered as predisposing risk factors for measurement of vulnerability markers for depression: a study on translation, and validation of das-a meh para siddique, rubina hanif correspondence: meh para siddique ph.d. scholar national institute of psychology quaid-i-azam university, islamabad e-mail: mehpara1612@gmail.com national institute of psychology quaid-i-azam university, islamabad funding source: nil; conflict of interest: nil received: september 13, 2020; revised: february 25, 2021 accepted: february 26, 2021 translation and validation of das-ajiimc 2021 vol. 16, no.1 32 forms, 40-item forms a and b. the das form a (dasa) has been widely used in depression research, particularly in testing the cognitive theory of 16 depression. items were rated on a seven-point scale, ranging from totally agree (1) to totally disagree (7). total scores can ranges from 40 to 280, with higher scores indicating greater grace of negative beliefs. the original english version of this scale was found to have satisfactory reliability coefficients and could discriminate significantly between depressed and non-depressed groups. additional studies have further supported the adequacy of this scale in terms of internal c o n s i s t e n c y a n d v a l i d i t y a m o n g c o l l e g e 1,2,4,17,22 students. also, some researchers supported its adequacy in terms of internal consistency and 23 validity in the general population. the factor structure of the das has been studied 18, 24-27 with models consisting of two factors three 28,29 30,31 factors , and four factors. meanwhile, in pakistan previous research had explored the four32,34 factor model and unidimensional model of das-a english version, while the existing research is still scarce on adaptive attitudes. to date, no study has been designed to assess adaptive aspects of the instrument, although the ten items in the instrument 1,35 are designed in a functional way. consequently, valid and reliable cognitive measures are important for two reasons; first, to establish the adequacy of this instrument specially designed to assess depressive cognitions in a pakistani context and second, to further investigate the theoretical and empirical validity of the cognitive-behavioral approach in pakistan to measure both adaptive and dysfunctional attitudes. therefore, considering the current status of the das, the objective of current research was to establish the validity and reliability of dysfunctional attitude scale-form a in pakistani population, so that the das could be used with confidence to assess the vulnerability markers of depression. materials and methods the present study is a cross-sectional research which was being approved by the ethics committee of the national institute of psychology, quaid-i-azam university, islamabad, pakistan. data was collected by researcher from 641 community individuals of rawalpindi and islamabad through a purposive convenient sampling technique from march 04, 2016 to february 16, 2017. materials needed for the administration include the 40 items dysfunctional attitude scaleform a. the subject must be adequately motivated and in good physical and mental condition. the scale is administered without a time limit after all the necessary materials and adequate environmental conditions are provided. the 40 items of das are phrased as statements usually underlying depressive idiosyncratic thinking. each item elicits information on the individual's dysfunctional beliefs, which act as schemas used to 1,36-37. construct the world. these beliefs include approval, love, achievement, perfectionism, entitlement, omnipotence, and autonomy. subjects assess each statement, considering the way they usually think, by using a 7-point likert scale, where:1 = totally agree, 2 = agree very much, 3 = agree slightly, 4 = neutral, 5 = disagree slightly, 6 = disagree very much, 7 = totally disagree. meanwhile, the 10 items i.e., items 2, 6, 12, 17, 24, 29, 30, 35, 37, 40, were designed in an adaptive way. afterwards, the data was assessed to test the assumptions of normality, and it was found that the data was essentially suitable for parametric testing. thus, the first step to meet the study objectives was to translate the scale from english to urdu. after taking permission from the authors, the scale was 38 translated into urdu by following beaton's translation method. another essential phase in the translation of the scale was to establish that potential respondents could understand statements of the translated items. with this aim, the final translated scale was administered on 25 volunteer young adults. respondents of this pilot-testing confirmed that translated items were suitable and simple to comprehend. after translation, the instrument was validated into urdu language. the process of cross-language validation tries to produce equivalency between source and target language based on content. during this step 40 adults (13 male & 27 female) were tested. accordingly, the scales were administered twice to two researcher's identified groups of bilingual pakistani adults in english-urdu, and urdu-english sequences. the administration of the test was carried out individually on one to one basis. participants were randomly assigned to the two conditions in first translation and validation of das-ajiimc 2021 vol. 16, no.1 33 administration i.e., english test and urdu retest; urdu test and english retest, and these groups were made to control the experiences of learning that may take place due to the administration of urdu and english tests with two weeks apart retesting. afterward, the factor structure of the translated instrument was confirmed through a confirmatory factor analysis. the findings helped in determining the structure of factors for young adults and examined whether the construct has the same structure, or they depict a new pattern for the pakistani sample. cfa basically depends on multiple statistical tests to assess the acceptability of model fit to the data. cfa aimed to confirm to what extent the existing factor structure fits the present study 39-42 data. in the current study, the researcher has considered widely used model fit indices i.e., 43,44 cmin/df, cfi, nfi, tli, and rmesa and factor loading (.30 and above) as criteria to test the validity 45 46 of items. the data was analyzed through amos 24 and the statistical package for social sciences 25.0 47 for windows. results table i, ii, and iii show the findings of test-retest reliability, establishment of alpha coefficients reliability, and the confirmatory factor analysis. in order to determine cross-language validity and test-retest reliability of the scales (table i), moderate correlation coefficient ranging from .61 (p < .01) to .72 (p < .01) were found. afterward, the instrument was tested on a diverse group to confirm the factor structure in the pakistani population. using the whole sample, internal consistency, and validity analysis was conducted. the reliability of the two factors i.e., dysfunctional attitude and adaptive attitude was evaluated. table ii shows the internal consistency and descriptive values of the das-urdu. using cronbach's alpha to estimate the reliability coefficient, a high to moderate alpha was obtained for the dysfunctional attitude (.86), and the adaptive attitude (.62). cfa was subsequently utilized to examine the construct validity of the two-correlated factor model. the findings of cfa are presented in table iii. given these results, using maximum likelihood procedures to estimate the model, most 2 of the indices indicated a good fit (x = 357.60, df = 289; cmin/df=1.24, cfi=.96, ifi=.96, tli=.90, and rmesa=.03 which is indicating a good model fit. the cfa has confirmed the factor structure. these results depict that the translated version of the dysfunctional attitude scale is statistically valid for measuring the respective attitudes across pakistan. the inspection of non-standardized regression weights indicated significant loadings for all items that were above .30. table i: retest reliabilities of urdu and english version of the 2-factors of dysfunctional attitude scale (das) (n=40) note. ue = urdu english, eu = english urdu **p < .01, *p < .05 table ii: descriptive of subscales of dysfunctional attitude scale among young adults (n=641) table iii: confirmatory factor analysis (indices of model fit) for dysfunctional attitude scale (das) (n=641) note. cfi=comparative fit index, nfi= normed fit index, rmsea=root mean square error of approximation, tli =tucker-lewis index translation and validation of das-ajiimc 2021 vol. 16, no.1 34 discussion the purpose of the present research is to assess the factor structure, reliability, and validity of the dasurdu among the pakistani population. this paper shows that the dysfunctional attitudes are a hallmarks of depression. despite a central role for dysfunctional attitudes in cognitive theories of depression and the widespread use of the 1 dysfunctional attitude scale, form-a , the psychometric advancement of the das-a has been limited. few studies have been published which report its use as a measurement tool of the presence and intensity of dysfunctional attitude among the depressive individuals. it is a self-report instrument measuring both the dysfunctional and the functional (adaptive) aspects of attitudes. the present study establish that das-a is reliable and can assess the dysfunctional as well as adaptive attitudes. meanwhile, it is consistent with the previous 1.34-37 literature which asserted that 10 items are phrased in functional way. the strength of our study is that this tool is translated and validated in urdu to access dysfunctional and adaptive attitudes in the pakistani population, addressing a gap in the literature. one limitation of the study is geographical, as the data were collected from only two cities due to convenience sampling. in addition, our sample in this study was based on a higher educated population than the mean education level in the country. furthermore, in view of these limitations, further studies on diverse samples are required to achieve a higher level of validation of the urdu version of the das-a. accordingly, it was established that the das-a (urdu) is a reliable instrument for assessing the vulnerability markers of depression in pakistani population. it is a valid scale, appropriate to be used in clinical and research settings. it is a concise yet two-dimensional measure with solid psychometric properties to facilitate screening in both clinical and research settings. however, future research is strongly recommended to continue to assess the scale reliability and validity in clinically depressed population. conclusion taken together, it is concluded that the das-a (urdu) is an efficient, reliable, and valid instrument for the assessment of dysfunctional attitudes which predispose to depression among young adults. meanwhile, this research laid the foundation for further research in clinically depressed population. references 1. rosner r. manualizing psychotherapy: aaron t. beck and the origins of cognitive therapy of depression. european journal 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evaluating model fit: a synthesis of the structural equation modelling literature. in7th european conference on research methodology for business and management studies 2008 (pp. 195-200). 43. steiger jh. structural model evaluation and modification: an interval estimation approach. multivariate behavioral research. 1990;25(2):173-80. 44. mulaik sa, james lr, van alstine j, bennett n, lind s, stilwell cd. evaluation of goodness-of-fit indices for structural equation models. psychological bulletin. 1989;105(3):430445. th 45. ibm spss amos statistics for windows. 24 ed. armonk, ny: ibm.; 2016. th 46. ibm spss statistics for windows. 24 ed. armonk, ny: ibm.; 2016. translation and validation of das-ajiimc 2021 vol. 16, no.1 36 original�article abstract objective: to evaluate the effectiveness of lower uterine segment transverse purse string suture in patients with placenta previa and previous cesarean section to preserve uterus. study design: we conducted a descriptive cross-sectional study. place and duration of study: maternal and children hospital, arar in northern borders saudi arabia from 2016 to 2020. materials and methods: we included patients with previous cesarean section and complete placenta previa where we had applied transverse purse string suture in the lower uterine segment to control hemorrhage after the failure of preliminary measures of uterotonics' usage and figure of eight sutures at the site of placental bed. results: lower uterine segment purse string suture was applied in 40 patients during cesarean section after failure of preliminary measures, among them 13 patients were found to have placenta accreta spectrum including one with placenta percreta. in 37(92.5%) patients including all patients with placenta accreta spectrum except one patient with placenta percreta, hemorrhage was successfully secured, and the uterus was preserved. in three patients (7.5%) including one patient with placenta percreta, lower uterine segment transverse purse string suture failed to control hemorrhage and hysterectomy was performed. conclusion: lower uterine segment transverse purse string suture is an effective intervention in controlling hemorrhage to preserve uterus in patients with placenta previa and previous cesarean section. key words: complete placenta previa, purse string suture, cesarean section, hysterectomy, placenta accrete. trophoblastic invasion in the area of a uterine scar. the incidence of adherent or invasive placenta in such cases ranges from 24% to 67%. with each increasing scar on the uterus, the risk of placenta previa as well as the risk of morbidly adherent or 1, 3-5 invasive placenta increases. invasive placenta needs histopathology for its definitive diagnosis and actually this is a spectrum disorder that includes a range of abnormally adherent to deeply invasive placenta. the condition also varies in its extent, and it can be total, partial or focal. in fact, the severity of complications of this spectrum is directly proportional to the depth of placental invasion. depending on the degree of invasiveness it can be morbidly adherent only when it invades decidua basalis and the villi adhere superficially to the myometrium, placenta increta when it penetrates into the myometrium or placenta percreta when it penetrates through myometrium to serosa where it can also invade the adjacent pelvic 6-7, 11 organs mostly the bladder. with the rising rates of cesarean section, assisted reproductive techniques and increasing maternal age, the incidence of placenta previa and placenta accrete spectrum will continue to increase in the introduction pregnant women with placenta previa and previous cesarean section denote a very high-risk group of obstetric patients for major postpartum hemorrhage and peripartum hysterectomy. in women with scarred uterus the normal placental migration fails to occur, and the differential growth of uterine areas is hindered, contributing to high incidence of placenta 1-2 previa in such cases. moreover, it has been postulated that in a scarred uterus morbidly adherent or invasive placenta mainly results from deficiency of decidua basalis due to damage to endometrium. this secondary defect at the endometrium-myometrium interface enhances transverse purse string suture for placenta previa in the presence of previous cesarean section, experience in northern borders saudi arabia ayman khalil othman al-tarifi, nafees akhtar correspondence: dr. nafees akhtar consultant obstetrician and gynecologist department of obstetrics and gynecology maternal and children hospital, arar, kingdom of saudi arabia e-mail: akhtarnafees29@gmail.com department of obstetrics and gynecology maternal and children hospital, arar, kingdom of saudi arabia funding source: nil; conflict of interest: nil received: august 29, 2021; revised: february 24, 2021 accepted: march 02, 2022 transverse purse string suture for placenta previajiimc 2022 vol. 17, no.1 25 8,9 future. the appropriate management of these cases imposes a major challenge to experts in obstetric care. obstetricians managing such cases should be well aware of all the modalities for controlling intraoperative and post-operative h e m o r r h a ge i n c l u d i n g t i m e l y d e c i s i o n fo r hyste re c to my i n ca s e s o f l i fe t h re ate n i n g uncontrolled hemorrhage. tra d i t i o n a l m e t h o d s t o c o n t ro l exc e s s i v e intraoperative hemorrhage at cesarean include pelvic devascularization, balloon temponade and different types of compression sutures like b-lynch, cho suture or square suture and vertical parallel 12-15 compression sutures . none of such techniques has effectively decreased the rate of peripartum hysterectomy in patients with previous cesarean section and placenta previa particularly placenta 8 accreta . we here present a simple and effective technique of lower uterine segment transverse purse string suture to control intraoperative blood loss in such cases. this suture serves the dual purpose of directly occluding the vessels at the bleeding site as well as enhancing the function of weak myometrial fibers of scarred lower uterine segment by compressing them. the dual function of this suture controls the hemorrhage more efficiently and consequently the uterus can be preserved even in cases of placenta accreta spectrum. our study evaluated the effectiveness of lower uterine segment transverse purse string suture in patients with placenta previa and previous cesarean section to preserve uterus. materials and methods in northern borders saudi arabia, from september 2016 we started applying transverse purse string suture, in those cases of placenta previa where we were unable to control hemorrhage. to see the effectiveness of the technique we conducted a descriptive cross-sectional study at maternal and children hospital, arar. arar is the capital city of northern borders saudi arabia and almost all patients with placenta previa from the other cities of northern borders are also referred to maternal and children hospital, arar for management. ethical approval (h-09-a-51) for the study was taken from the local ethical research committee northern borders health affairs, ministry of heath saudi arabia. data was collected from september 2016 till november 2020. the primary outcome was peripartum hysterectomy. data were analyzed using simple mathematical computing techniques. data was collected from medical records of patients by the primary surgeon and his colleague obstetrician. they found forty (40) patients who had undergone this technique. the inclusion criteria were as below: 1. diagnosed with complete placenta previa antenatally 2. history of previous cesarean section 3. where we had applied transverse purse string suture to control hemorrhage exclusion criteria included: 1. patients with complete placenta previa without previous cesarean section 2. patients at less than 32 weeks gestation though transvaginal ultrasound is considered preferable for diagnosis of placenta previa but due to its unacceptability by most of our patients in third trimester we diagnosed placenta previa by trans abdominal ultrasound in the presence of full bladder, aided by color doppler imaging for signs of morbidly adherent placenta. four major signs looked for placental invasion on ultrasound included: vascular lacunae, loss of normal hypoechoic retroplacental zone, retroplacental myometrial thinness and placental thickness. elective cesarean section was planned between 36 weeks and 37 weeks of gestation unless some emergency arose. before cesarean section patients' hemoglobin level was strictly corrected to a level above 10g/dl. all patients were counseled in detail before surgery about the implications of the diagnosed condition, excessive intraoperative hemorrhage, risk of placenta accreta, need for blood transfusion, need to stay in high dependency area postoperatively, conservative surgical interventions to control hemorrhage as well as the risk of peripartum hysterectomy in case of uncontrolled hemorrhage. written informed consent for cesarean section and hysterectomy was taken from all patients. four to six units of blood were cross matched before surgery. the same primary surgeon applied the transverse purse string suture during cesarean in almost all these patients. at the time of cesarean section abdomen was opened through pfannenstiel incision at the site of previous scar. intra-abdominal adhesions especially 26 transverse purse string suture for placenta previajiimc 2022 vol. 17, no.1 adhesions between uterus and bladder, and signs of invasion including vascular engorgement of lower uterine segment were assessed and dealt with carefully [fig 2]. before incision on the uterus, bladder was well retracted down away from the uterus using sharp and blunt dissection. all patients received uterotonic drugs after the delivery of baby to control hemorrhage. oxytocin 5 iu intravenous bolus along with infusion of 20 iu oxytocin in 500 ml normal saline solution was started routinely in all cases, later on injection methylergometrine and injection prostagalndin f2 alpha were also used in cases where uterine atony occurred. placenta was removed completely by cord traction or in piece meal. if the placental tissue was found adherent at the scar site, the edges of the incision were excised along with the adherent placental tissue. once the baby and placenta were delivered the uterus was exteriorized. figure of eight sutures were taken in the placental bed as needed. in cases where hemorrhage could not be controlled with these preliminary measures transverse purse string suture was applied at the lower uterine segment, passing the needle as below as possible above the line of bladder reflection with vicryl (polyglactin) number 2 mounted on a large 75 mm needle using technique as shown in figures [fig1 & 3]. the two ends of the suture were held tight with an artery forceps. after closing the uterine incision in two layers the two ends of the purse string suture were pulled and tied together tightly. vagina was checked for blood loss. after ensuring the effective hemostasis, uterus was interiorized. an intraperitoneal drain was left in pouch of douglas in all cases. in case of inability to control hemorrhage despite transverse purse string suture, decision of hysterectomy was made by two consultants. the removed placenta and uterus were sent for histopathology. intra operatively and postoperatively blood and blood products transfusion were performed according to rcog guidelines “postpartum hemorrhage, prevention and management” and “blood transfusion in obstetrics”. postoperatively patient was kept in high dependency unit until stabilized. ultrasound abdomen was performed on all patients on next day after surgery to look for any collection. where the patients remained stable and without any complication urinary catheter was removed on next day of surgery and the drain was removed after 48 hours of surgery once the drain output was less than 100ml in 24 hours. once stabilized patient was shifted to the post-operative ward. at the time of discharge from hospital, all patients were provided with a phone number at which they could contact in case they develop any complaints like fever, excessive vaginal bleeding or discharge, or wound infection. on discharge, from hospital each patient was called for follow up in outpatient department (opd) within a week and then again at an interval of six weeks from the day of surgery. results we applied lower uterine segment transverse purse string suture on 40 patients with complete placenta previa and previous cesarean sections. among these, 26 patients had simple placenta previa while 13 patients had morbidly adherent or invasive placenta. among the latter group patients with placenta accreta spectrum other than placenta percreta were analyzed in one group. the main characteristics of the study group are listed in table1. majority of the patients have higher order cesarean sections with more than 4 cesarean sections. in three patient's bladder injury occurred due to excessive adhesions and bladder injury was repaired by the urologist. one patient was picked with a large hematoma on ultrasound performed after 24 hours of surgery. patient was taken to the operation theater and hysterectomy was performed. second patient, who underwent hysterectomy in our study, had eight previous cesarean sections and uterus was removed due to excessive uncontrolled hemorrhage caused by persistent uterine atony while the third patient who ended up in hysterectomy, had placenta percreta. among all patients with placenta accreta spectrum except placenta percreta, transverse purse string suture successfully controlled hemorrhage in this study [table 2]. most patients (24) had moderate major hemorrhage with blood loss between 1000-2000ml while 16 patients suffered severe major hemorrhage with a blood loss >2000ml. almost all patients received blood transfusion intra or postoperatively or both. there were two readmissions one with fever due to urinary tract infection and one with wound dehiscence [table 3]. no lochiometra was identified 27 transverse purse string suture for placenta previajiimc 2022 vol. 17, no.1 on ultrasound performed before discharge from hospital as well as on ultrasound performed on follow-up in opd. by using this technique of lower uterine segment transverse purse string suture, overall, we were able to secure hemostasis and preserve uterus in 92.5% of patients with complete placenta previa and previous cesarean sections. except placenta percreta, we successfully preserved uterus in all patients with placenta accreta using this simple technique. fig. 3: black arrows showing line of transverse purse string suture. blue arrow showing two ends of transverse purse string suture tied together table i: characteristics of study group table ii: primary outcome: peripartum hysterectomy table iii: secondary outcome: complications fig. 1: lower uterine segment transverse purse string suture fig. 2: showing bluish bulge of invasive placenta discussion our study had found the technique of transverse purse string suture quite effective in controlling hemorrhage in patients with placenta previa in the 28 transverse purse string suture for placenta previajiimc 2022 vol. 17, no.1 presence of previous cesarean section. controlling hemorrhage in this high-risk group is a major challenge for even experienced obstetricians. we had preserved the uterus in 92.5% patients by using our technique in this high-risk group. the abnormalities of placentation are grave conditions posing a major risk for peripartum hysterectomy, maternal morbidity, and mortality. peripartum hysterectomy has its inherent risks of surgical complications, inability to conceive in the future, post-traumatic stress disorder in 64% patients and maternal mortality in 2.6% patients. over the course of time several techniques have been demonstrated to control hemorrhage to preserve uterus in women with placenta previa, including compression sutures, balloon tamponade, pelvic devascularization and uterine artery 12-15 embolization. our study particularly involved those women with placenta previa who had scarred uterus and it also focused on a subgroup of women with placenta accreta spectrum. results of our study show that transverse purse string suture can effectively control hemorrhage and preserve uterus in women with complete placenta previa with or without morbid adherence, in the presence of a scarred uterus. we only had one patient with placenta percreta in our study but placenta percreta seems to be an exception, where it is safer to perform hysterectomy earlier to avoid excessive blood loss. though the number of patients in our study is small only 40, the results seem to be very encouraging to imply this technique in women with placenta previa in the presence of a previously scarred uterus. uterine temponade using bakri balloon, sengstaken blackmore tube or rusch balloon is an easy technique that can be performed by an average on duty obstetrician even in a resource poor setting. the technique is very effective to control postpartum hemorrhage with a success rate reported up to 78% 14 . the efficacy of this procedure yet to be tested in the scenario of complete placenta previa and placenta accreta. systematic pelvic devascularization is performed by ligation of uterine artery, infundibulopelvic vessels and internal iliac artery. the ligation of bilateral uterine arteries is technically easy, safe and effective to reduce the uterine blood flow. ligation of infundibulo-pelvic vessels further intends to reduce the uterine blood flow through utero-ovarian anastomosing vessels. furthermore, ligation of bilateral internal iliac arteries, embraces a success rate of 40-80%, however by this stage the patient may have suffered significant blood loss and coagulopathy. complexity of this procedure demanding substantial surgical skills and obligation of input from a vascular surgeon are additional hitches to this procedure. this procedure also carries 16, 17 the risk of injury to ureters and internal iliac veins . contrarily, pelvic arterial embolization carries a high median success rate of 89%, but the procedure involves an interventional radiologist and a wellequipped radiology unit. arterial embolization is also not without risks and patients may develop postembolization fever, vascular injury, infection, uterine 18-20 and bladder ischemia. several compression sutures have been devised to control hemorrhage and preserve uterus including blynch suture, cho suture or square suture, hayman suture, vertical compression sutures and transverse compression sutures. among these, b-lynch suture mainly intends to control bleeding from uterine atony and the technique is more successful to cause compression of myometrial fibers of upper uterine 21 segment to induce their contractility. cho suture technique involves placing square sutures to control bleeding from focal bleeding sites, but it may be difficult to apply such a relatively complex sequence of multiple sutures in the scenario of excessive 22 bleeding. hayman applied a simply modified blynch suture and additionally for placenta previa or accreta he suggested two transverse sutures at the level of isthmus or circular cervico-isthmic suture. this does not allow exploration of the uterine cavity 23 and impairs the drainage of lochia. on the other hand, vertical compression sutures applied for instance in the study by mohammed and muhammed in 2017 and later on by raitu and crisan in 2018 for placenta previa and accreta, showed excellent results with preservation of uterus in 24-26 around 98% cases. none of these studies involved such higher order cesarean sections as in our study where mean number of previous cesarean sections is 4. moreover, potentially any compression suture passing through both anterior and posterior uterine walls by close opposition of the two uterine walls carries the risk of uterine syneche, adhesions, 29 transverse purse string suture for placenta previajiimc 2022 vol. 17, no.1 impairment of uterine drainage and infection, ultimately resulting in problems related to menstruation and future conceptions. in our study, as the transverse purse string suture was passed only through the anterior uterine wall below the uterine incision and then tied above the uterine incision, it lacks such potential risks related to menstruation and fertility and the technique proved to be very effective by involving a large area of lower uterine segment both below and above the incision. our technique in this study is a modification of blynch transverse compression suture demonstrated by b-lynch c, et al in their study where they successfully secured hemostasis in cases of placenta 27 previa. in contrast, our study exclusively involved patients with scarred uterus and our technique is simpler, and thereupon can be rapidly performed even by an average on duty surgeon. our study has limitations of small sample size and absence of comparison group. we strongly recommend well-designed studies with larger sample size in future to look more closely at the effectiveness of this technique in such patients. we also recommend future studies to evaluate its longterm effects related to future conception and pregnancy outcome. conclusion despite the sample size being small, our results intimate the effectiveness of transverse purse string suture in a subgroup of patients very high risk for massive maternal hemorrhage who have scarred uterus inhabited with placenta previa and placenta accreta. references 1. klar m, michels kb. cesarean section and placental disorders in subsequent pregnancies–a meta-analysis. j perinat med. 2014; 42:571–83. 2. the global library of women's medicine. placenta previa and accreta [glown website]. 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ó«¹´·¿ ôöò î·­µ ±º °±­¬ ¬»®³ ¼»´·ª»®§ ¿º¬»® °±­¬ ¬»®³ ¼»´·ª»®§ò ß³»® ö ñ¾­¬»¬ ù§²»½±´ îððéå ïçêæ îìïóêò íí çò æ»·¬´·² öô þ´±²¼»´ þô ß´»¨¿²¼»® íô þ®»¿®¬ ùò ê¿®·¿¬·±² ·² ®¿¬»­ ±º °±­¬ ¬»®³ ¾·®¬¸ ·² û«®±°»æ ®»¿´·¬§ ±® ¿®¬·º¿½¬ò þ®·¬ ö ñ¾­¬»¬ ù§²»½±´ îððéå ïìæ ïðçéóïðíò ïðò õ¿®¿²¼» êýô ü»­¸³«µ¸ óßô ê·®µ«¼ ßßò 󿲿¹»³»²¬ ±º °±­¬ ¬»®³ °®»¹²¿²½§ò ö ð±­¬¹®¿¼ ó»¼ ïçèëå íïæ çèóïðïò ïïò ñ´»­»² ßéô é»­¬»®¹¿¿®¼ öùô ñ´­»² öò ð»®·²¿¬¿´ ¿²¼ ³¿¬»®²¿´ ½±³°´·½¿¬·±²­ ®»´¿¬»¼ ¬± °±­¬¬»®³ ¼»´·ª»®§æ ¿ ²¿¬·±²¿´ ®»¹·­¬»®ó¾¿­»¼ ­¬«¼§ô ïçéèó ïççíò ß³»® ö ñ¾­¬»¬ ù§²»½±´ îððíå ïèçæ îîîóé ïîò õ·­¬µ¿ æßô ð¿´±³¿® ôô þ¿­´¿«¹¸ íûô ü»¾¿«² óîô ü»º®¿²½± ûßô ó«¹´·¿ ôöò î·­µ ±º °±­¬ ¬»®³ ¼»´·ª»®§ ¿º¬»® °±­¬ ¬»®³ ¼»´·ª»®§ò ß³»® ö ñ¾­¬»¬ ù§²»½±´ îððéå ïçêæ îìïóêò ïíò ø¿²²¿¸ óûô ø¿²²¿¸ éöô ø»´´³¿² öô »¬ ¿´ò íí original�article abstract objective: to compare the effects of microwave and light emitting diode disinfection on the dimensional stability of two denture base materials; polymethyl methacrylate and polyamide. study design: in-vitro study place and duration of study: peshawar dental college and material research laboratories, university of th th peshawar from 10 june 2021 to 8 december 2021. materials and methods: fifteen specimens each for polymethylmethacrylate and polyamide were divided into three groups, control, microwave & light emitting diode. the specimens for microwave group were irradiated at 1000w for 3 minutes, thrice a week. the specimens for light emitting diode group were disinfected in a device for 30 minutes, thrice a week. the control group specimens were placed in distilled water for 4 weeks. dimensions were measured before disinfection, and four weeks after the assigned disinfection. the mean and the standard deviation of the differences between three groups were statistically analyzed using one-way anova and after obtaining significant values, through post hoc tukey hsd. results: for polymethylmethacrylate highest dimensional difference (-9.02mm) was noted for microwave disinfected group while the control group showed the lowest value (-6.99mm). for polyamide, the highest dimensional changes were recorded for light emitting diode group (8.66mm) and the lowest (-7mm) for the control group. statistical analysis showed that the differences were significant for both polymethylmethacrylate and polyamide when compared with the control (p<0.05) but insignificant when microwave disinfected group was compared with light emitting diode group (p>0.05) conclusion: no significant difference in dimensional stability of both the denture base resins was observed after disinfection with microwave and light emitting diode. key words: dimensional stability, disinfection, denture base resin, light emitting diode, microwave, polymethyl methacrylate, polyamide. with the adverse effects due to monomers present in 3 acrylic materials among patients and medical staff. in addition, the aesthetics of pmma based removable partial denture can be impaired by the appearance of metallic components. a viable or 4 possible alternative to pmma can be polyamide. polyamides (pa) are preferred for persons allergic to methyl methacrylate, bone undercuts, in thin mucosa and excessive resorption of bone, in production of temporary dentures after implants 5 placement surgeries. due to poor oral and denture hygiene, removable 6 prostheses provide a source for microbial growth , 7 and thus causing denture related stomatitis. denture hygiene is achieved both through chemical and mechanical methods which affect the physicomechanical properties of materials used to 8 make removable prosthesis. to overcome the introduction polymethyl methacrylate (pmma) is widely used for the fabrication of partial and complete dentures. even though implant treatments are on the rise, but still there is a vast majority of cases that need removable dentures in developed as well as 1 developing countries. therefore, the use of pmma in prosthetic dentistry remains substantial as it shows adequate material properties and ease of 2 application. however, concern has been expressed effects of microwave and light emitting diode as disinfection methods on the dimensional stability of polymethyl methacrylate and polyamide denture base resin 1 2 3 4 5 6 7 hina rehman , muhammad raza , amjad hanif , mehreen imran , zia-ur rehman khalil , salman khan , nida saeed , 8 zudia riaz correspondence: dr. hina rehman department of dental materials peshawar dental college, peshawar e-mail: drhr1979@gmail.com 1,3,4,6,7,8 2 department of dental materials/ prosthetics / 5 community dentistry peshawar dental college, peshawar received: august 06, 2022; revised: december 08, 2022 accepted: december 10, 2022 effects of disinfection methods on dimensions of base resins jiimc 2022 vol. 17, no.4 274 doi: https://doi.org/10.57234/1472 complications, microwave radiation has been advocated as an easy, safe, and effective way for 10 denture disinfection. in a recent review, microwave disinfection has been claimed as an efficient antifungal therapy for the treatment of denture 11 stomatitis. microwave disinfection is mostly carried 12 out in wet conditions where the denture base is placed in water in the microwave oven, this may 13 cause further polymerization of the resin. despite the effectiveness of microwave as denture disinfectant, researchers have reached contradictory findings regarding its harmful effects on some properties. these detrimental effects may be due to the heating of material during irradiation, which 14 could affect the structure of polymer. the consequences of microwave disinfection of denture base materials have been vastly studied, but no consensus could be developed regarding the deleterious effects of microwave on prosthodontic 11 materials . some of these studies showed notable 15 16 dimensional changes of upto -1.12% , & 3% after disinfection with microwave. blue led light in the visible spectrum of wavelength (405nm), has been found to have bactericidal/ 18 fungicidal effects. blue led light of this wavelength inhibits the candida biofilm production on prosthesis and can also disinfect denture surfaces swiftly than conventional disinfection methods. therefore, blue led light can be a promising technique for denture disinfection. however, there is very limited information available for the effects of led for disinfection of both pmma and pa denture base resins on their dimensional stability. similarly, no data is available to compare the effect of microwave and led disinfection of two denture base materials on their dimensional stability. the aim of this study was to compare the effects of microwave and led disinfection on the dimensional stability of polymethyl methacrylate and polyamide denture base resins. materials and methods th this was an in-vitro, study conducted from 10 june th 2021 to 8 december 2021, in peshawar dental college and material research laboratories, university of peshawar. a total of thirty specimens were made, fifteen each for the two materials used; polymethyl methacrylate (engropolymer, meadway, uk) and polyamide (vertex dental b.v, netherland). the specimens for each material were further subdivided into three groups: group (a) control (without treating either with mw or led), group b microwave (mw) and group c light emitting diode (led) disinfected 19 containing five specimens each (n=5) (table i). each specimen measuring 25×25×5mm was made in a stainless-steel split mold. four holes, measuring 0.5mm in depth, were engraved in the metal mold as index marks. after fabrication of specimens, wax patterns were invested in curing flask with dental stone type iii. the flasks were put in boiling water for about 10 minutes. after removal of wax, sodium alginate was applied to the mold. heat cure acrylic powder was mixed with 20 its monomer in a ratio of 2.5:1 w/v and was packed into the molds. the flasks were gradually heated to ° 100 c in a period of one and a half hour. this temperature was maintained for 30 minutes. the flasks were bench cooled overnight. the specimens were taken out and immersed in water for 48 hours. the specimens were then trimmed, using belt emery paper (400-800 grit). further refined with grade 1200 and finished with grade 2400 emery paper. final polishing was done with a motor driven revolving disc, with a velvet polishing cloth. wax patterns for pa specimens were made in stainless steel molds and invested in the flasks with dental stone (type iii), following the procedure adopted for pmma specimens. wax sprues were then attached to the wax patterns. the investment was coated with petroleum jelly. the flasks were then filled with dental stone and placed in boiling water. after dewaxing, the flasks were placed in the hydraulic injector for flexible denture base resin. molten polyamide was forced into the flask by using polyamide injection system at a pressure of 5 bars for 3 minutes. the flasks were bench cooled before 15 deflasking . following deflasking, finishing was performed with 600 and 800 grit silicon carbide paper, and then polished with white cotton yam wheel polishing brush. measurements were recorded with a digital caliper (mitutoyo, mfg co., japan), using elevated indentations labeled by letters a, b, c & d. six dimensions (distances ab, bc, cd, ad, ac and bd) were documented for each specimen. five measurements were recorded for each of the six effects of disinfection methods on dimensions of base resins jiimc 2022 vol. 17, no.4 275 doi: https://doi.org/10.57234/1472 dimensions before calculating the mean. the algebraic norm was calculated by taking the square 21 root of sum of squares of individual dimensions. 22 2 2 2 2 2 2 1/2 norm = [ab +bc +cd +ac +ad +bd ] for control group (a) specimens, after initial measurement were kept in distilled water at room te m p e rat u re a n d t h e wate r wa s c h a n ge d corresponding to the water change for the interventional groups (b & c). for group b, after taking the initial measurements, individual specimens were placed in 200ml of distilled water at room temperature in a microwave oven (dawlance, model: dw-162h, korea) and then subjected to disinfection at 1000w for 3 minutes, thrice a week for 4 weeks. for group c (led disinfection), after the initial measurements, the specimens were subjected to irradiation for 30 min, 3 times a week for 4 weeks. water for sample immersion was changed after conducting 2 disinfection protocols for groups b & c th and after every 4 day for group a. after completing 12 disinfection cycles, specimens were measured for final measurement. the percent difference was 21 determined as follow : percent difference = final measurement initial measurement / initial measurement × 100 mean and standard deviation values for the linear dimensions were determined. data collected before and after disinfection with microwave and led, were statistically analysed by one-way anova and post hoc tukey's test using spss version 26. p value less than 0.05 was considered as significant. results the mean values of the initial, final measurements and their differences for all the groups of pmma are given in table i. group b1 (disinfected using microwave) exhibited the highest change in dimensions (-9.02mm) while the control group (a1) displayed the lowest change in dimensions (6.99mm) (table i). one way anova showed highly significant difference (p=0.002) among the groups after disinfection protocol (table i). post hoc tukey's test for multiple comparison showed significant difference for both the groups b1&c1 when compared to control (a1) (p=0.004) &(p=0.006) respectively while the difference between group b1 & group c1 was insignificant (p=0.964) (table ii). the mean values of the initial, final measurements and their differences in mm with standard deviations for each group of pa are given in table iii. it can be seen from the table iii that group c2 exhibited the highest (-8.66mm) while the control group, displayed the lowest change in dimensions (7.0mm). one way anova showed statistically significant difference among the three groups ((p=0.013). post hoc tukey's test showed statistically significant difference between group b2 and the group a2, similarly the difference between group c2 and group a2 was significant (p=0.042). the difference between the group b2 and group c2 was also statistically insignificant (p=0.835). table i: comparison of dimensional changes in pmma* using one way anova * pmma: polymethylmethacrylate, ** m/w: microwave, *** led: light emitting diode. table ii: post hoc analysis (tukey's hsd) of dimensional changes in pmma table iii: comparison of dimensional changes in pa using one way anova effects of disinfection methods on dimensions of base resins jiimc 2022 vol. 17, no.4 276 doi: https://doi.org/10.57234/1472 discussion dimensional stability of denture bases during service is of great importance as it helps in retention of the 23 dentures and cuspal interdigitation. therefore, any effects of the adopted disinfection techniques on the dimensions of denture bases may pose problems. there are no standard specifications for measuring 24 linear dimensions of denture bases. wolfaardt et al stated, that many factors affect the dimensional changes of denture bases such as size and shape etc. it has been recommended to test specimens of 21 simple shapes for dimensional measurements. therefore, square shaped specimens were used in the present study. statistically significant difference was observed, when the interventional groups were compared with the control group whereas comparison of the mw with led showed insignificant results. therefore, the null hypothesis of this study was partially rejected as significant differences were observed for both the resins after disinfection with mw and led when compared with control. the contraction of resin for the control groups of this study could be attributed to the thermal contraction during storage and due to release of stresses that 25 were induced during polymerization. the storage of resin in water helps in residual monomer dispersion 26 in pmma. this elution of monomer continues for a 27 few days of storage in water. such loss of monomer from the polymerized specimens can be accredited for the shrinkage or decreased dimensions of specimens of control groups of pmma, after storage 25 in water for four weeks. the shrinkage in pa control group was recorded to be around 7mm. dimensional accuracy of pa is technique sensitive and require more precise and careful processing. it has been reported in literature that storage of nylon (pa) in water has shown 28 decrease in dimensions after about 24 hours. however, an increase in dimensions of the same pa used in the present study after storage in water has 29 also been reported by chuchulska & zlatev , which contrasts with the results of this study. this might be due to aging of the specimens for 5000 thermocycles. the change in dimensions of both denture base resins can be explained by the fact that microwave irradiation causes increase in temperature of the 17 specimens. despite all the precautions taken and careful processing of pmma, some monomer 30 content is left unreacted in the final product. this increase in temperature can cause reaction of the unreacted monomer at reactive sites of the polymer and thus cause further shrinkage due to 1 5 thiolymerization. resins can experience a plasticizing effect after their tg is exceeded, which 31 causes rearrangement of the polymer chains and thus this change in dimensions could be due to the plasticizing effect of resins above their tg. the highly significant result for mw disinfected pmma group in comparison with the control group of this study is in accordance with results reported 17 15 by wemken et al. polychronakis et al reported shrinkage of 0.35mm for heat cure pmma and 0.09mm for valplast after wet microwaving at 450 w for 3 minutes. this can be considered in accordance with the present investigation, as they had measured only the length of the specimens, while in this study, means were calculated for the six measurements of each specimen and the algebraic norm was calculated. 32 polyzois et al contradicts the results of the present study as disinfection of acrylic base resin specimens with a 500w mw for 3 minutes and 15 minutes manifested linear shrinkage of 0.005%. although the changes were significant statistically but were of no clinical importance. it can be noted in the arguments presented so far that the microwaves table iv: post hoc analysis (tukey hsd) of dimensional changes in pa *pa: polyamide effects of disinfection methods on dimensions of base resins jiimc 2022 vol. 17, no.4 277 doi: https://doi.org/10.57234/1472 used for disinfection of denture base resins specimens were of low powers. the power levels of mw ranged between 450w and 700w, with most studies conducted with 650w. this observation is consistent with a critical review by brondani & 33 siqueira. the microwave used in the present study had power of 1000w which is a normal domestic microwave device found in our part of the world. due to unavailability of studies on led disinfection in the literature, we were not able to compare the results of our study with other studies. conclusion within the limitations of this study, it is concluded that the dimensional stability of pmma and pa can be affected by disinfection with mw and led, and the dimensional changes observed for both m ate r i a l s a re co m p a ra b l e , t h e refo re , o n e disinfection procedure cannot be preferred over the other. references 1. clements jl, tantbirojn d, versluis a, cagna dr. do denture processing techniques affect the mechanical properties of denture teeth? the journal of prosthetic dentistry. 2018 aug 1; 120 (2):246-51. https://doi.org /10.1016/ j.prosdent.2017.10.025 2. anusavice kj, shen c, rawls hr, editors. phillips' science of dental materials. elsevier health 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(2021). the effect of chlorhexidine gels with anti-discoloration systems on color and mechanical properties of pmma resin for dental a p p l i c a t i o n s . p o l y m e r s 1 3 ( 1 1 ) , 1 8 0 0 . https://doi.org/10.3390/polym13111800 effects of disinfection methods on dimensions of base resins jiimc 2022 vol. 17, no.4 278 doi: https://doi.org/10.57234/1472 20. zafar ms. prosthodontic applications of polymethyl methacrylate (pmma): an update. polymers. 2020 o c t ; 1 2 ( 1 0 ) : 2 2 9 9 . h t t p s : / / d o i . o r g / 1 0 . 3 3 9 0 / polym12102299 21. gharechahi j, asadzadeh n, shahabian f, gharechahi m. effect of molding technique on two physical properties of acrylic resin specimens. ny state dent j. 2016 jun 1;82 (4):3844. 22. baydas, s., bayindir, f., & akyil, m. s. 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(2008). effect of microwave disinfection on physical and mechanical properties of acrylic resins. brazilian dental journal, 19(4), 348-353. https://doi.org/10.1590/s010364402008000400011 31. senna, p. m., jose da silva, w., faot, f., & antoninha del bel cury, a. (2011). microwave disinfection: cumulative effect of different power levels on physical properties of denture base resins. journal of prosthodontics: implant, esthetic a n d r e c o n s t r u c t i v e d e n t i s t r y, 2 0 ( 8 ) , 6 0 6 6 1 2 . https://doi.org/10.1111/j.1532-849x.2011.00770.x 32. polyzois gl, zissis aj, yannikakis sa. the effect of glutaraldehyde and microwave disinfection on some properties of acrylic denture resin. international journal of prosthodontics. 1995 mar 1;8(2). 33. brondani, m.a., & sequeira, a. r. (2018). a critical review of protocols for conventional microwave oven use for denture disinfection. community dental health; 35:228-234. https://doi.org/10.1922/cdh_4372brondani07 conflict of interest authors declared no conflicts of interest. grant support and financial disclosure authors have declared no specific grant for this research from any funding agency in public, commercial or nonprofit sector. data sharing statment the data that support the findings of this study are available from the corresponding author upon request. this is an open access article distributed under the terms of the creative commons attributionnoncommercial 2.0 generic license. effects of disinfection methods on dimensions of base resins jiimc 2022 vol. 17, no.4 279 doi: https://doi.org/10.57234/1472 jiims.cdr abstract objective: to identify the different clinical and biochemical presentations of patients having polycystic ovarian syndrome. study design: a descriptive observational study. place and duration of study: this study was carried out at obstetrics and gynaecology department of cmh rawalpindi, from october 2010 to sept 2011. materials and methods: this observational study was conducted to identify the different presentation of patients suffering from polycystic ovarian syndrome. seventy five cases of polycystic ovarian syndrome who reported in opd were selected for the study. results:the patients mostly presented between 20-30 years of age with symptoms of oligomenorrhea, infertility and hirsutism. ultrasonography showed the morphology of polycystic ovary and deranged fsh, lh and testosterone levels. keywords: polycystic ovarian syndrome, oligomenorrhea, infertility, hirsutism. 60 original article highlight the different symptoms and signs with which the patients reported in the gynaecology and obstetrics department of combined military hospital, rawalpindi over a period of one year. this descriptive study was carried out at obstetrics and gynecology department cmh rawalpindi. seventy five cases of polycystic ovarian syndrome were selected for the study. detailed menstrual history of the patient was taken. pelvic examination of all the married patients was carried out in all the patients. ultrasonography pelvis was carried out in all the patients. hormonal levels (fsh, lh, prolactin, testosterone, estradiol) were also carried out. baseline blood chemistry was done in all cases. patients who presented with complaints of m e n s t r u a l i r re g u l a r i t i e s , i n f e r t i l i t y, hirsutism and obesity were included in the s t u d y. p a t i e n t s h a v i n g m e n s t r u a l irregularities due to other causes, like menorrhagia, and other causes of infertility, like male causes, tubal occlusion, were excluded from the study. out of the 75 women selected for the study materials and methods results introduction polycystic ovarian syndrome (pcos) is associated with reproductive, metabolic and psychological dysfunction and affects 4-18% 1 of women in reproductive age group. it is the most common endocrinopathy affecting 2 women of reproductive age. there is an increased risk of diabetes, hypertension, metabolic syndrome, and endometrial 3 carcinoma. pcos adversely affects the female reproductive health leading to infertility and miscarriages. diagnosis of pcos is a challenge for the clinicians and with availability of more advanced diagnostic tools the prevalence has seen to be increased because most of the 4 cases remain undiagnosed clinically. pcos is a frequent condition in women of reproductive ageand has associated 5 metabolic dysfunction. this condition also has serious psychological implication as 6 well. the usual manifestations include irregular menses, androgen excess and 7 obesity. the aim of the present study is to ------------------------------------------------correspondence: dr nabila amin consultant gynecologist & obstetrician department of gynae/obs combined military hospital rawalpindi presentations of polycystic ovarian diseasestudy at tertiary care hospital nabila amin, shazia chohan, farhat kareem table i: presenting features of patients with pcos 61 51 (68%) had raised lh and fsh ratio while testosterone was mildly raised in 20 patients (table ii). on ultrasonography polycystic ovaries were found in 49 (65%) patients (table ii). most common presenting symptom wasoligomenorrhoea which was present in 75% cases (56 patients) (table i). fifty six perecent (42 patients) patients had infertility while hirsutism was present in 53% (39 patients) cases (table i). most of the patients presented in 20-30 years age group. 30 patients (40%) were found to be obese (table i). discussion it was in 1935 that stein and leventhal originally described the polycystic ovarian syndrome. pcos is diagnosed using the 8 rotterdam criteria, which declares that when at least two of the following three features are present the patient can be labeled as having pcos: � oligomenorrhea/ anovulation � hyperandrogenism � polycystic ovaries in the study rotterdam criteria was used for diagnosing the patients of pcos. the studyshows that the most common presenting symptom was oligomenorrhoea, this finding is similar to other studies carried out and was of almost similar level to the one 9,10 reported in us study. similarly infertility was a very common symptom being present in 65% of our patients. this shows that married women tend to report for their concern for infertility and are subsequently diagnosed as having pcos. the worldwide incidence of patients with infertility having 11 pcos is about 75%. hirsutism is again a very common symptom in patients of pcos, it being present in 35% patients in chinese 12 population. obesity is more commonly present in women with pcos of hispanic, black and white origin while its incidence is l o w e r i n w o m e n o f m e d i t e r r a n e a n d e s c e n t . 1 3 h y p e r a n d r o g e n i s m w a s exhibited by the deranged levels of fsh, lh and testosterone as in other studies these levels play an important role in diagnosis of table ii: investigations of patients with pcos figure 1: 62 1 4 pcos. transvaginal ultrasonography carried out showed the presence of 12 or more follicles measuring 2-9 mm in diameter and increased ovarian volume (more than 10cm3) in 65% patients, which is one of the features of pcos according to rotterdam criteria. the patients typically presented in 3rd decade of life. it can be concluded from this study that patients present with menstrual cyclical disturbances, infertility with and without m e n s t r u a l d i s t u r b a n c e s , a s s o c i a t e d h i r s u t i s m a n d o b e s i t y , ultrasonographicfeaturesandhormone level estimation play pivotal role in diagnosis of pcos. 1. moran lj, hutchison sk, norman rj, teede hj. lifestyle changes in women with polycystic ovary syndrome. cochrane database syst rev. [meta-analysis review]. 2011(2): cd007506. 2. knochenhauer es, key tj, kahsar-miller m, waggoner w, boots lr, azziz r. prevalence of the polycystic ovary syndrome in unselected black and white women of the southeastern united states: a prospective study. j clin endocrinol metab 1998 ; 83: 3078-82. 3. chen zj, shi y. polycystic ovary syndrome. front med china 2010; 4: 280-4. 4. march wa, moore vm, willson kj, phillips di, norman rj, davies mj. the prevalence of polycystic ovary syndrome in a community sample assessed under contrasting diagnostic conclusion references criteria. hum reprod; 25: 544-51. 5. moran lj, brinkworth gd, norman rj. dietary therapy in polycystic ovary syndrome. semin reprod med 2008; 26: 85-92. 6. teede h, deeks a, moran l. polycystic ovary s y n d ro m e : a c o m p l e x c o n d i t i o n w i t h psychological, reproductive and metabolic manifestations that impacts on health across the lifespan. bmc med 2010; 8: 41. 7. zarate a, moran c, hernandez m, saucedo r. [current criterion for diagnosing polycystic ovary syndrome]. ginecol obstet mex 2004; 72: 283-6. 8. isolauri e, huurre a, salminen s, impivaara o. the allergy epidemic extends beyond the past few decades. clin exp allergy 2004; 34: 1007-10. 9. najem f, elmehdawi r, swalem a. clinical and biochemical characteristics of polycystic ovary syndrome in benghazilibya; a retrospective study. libyan j med 2008; 3: 71-4. 10. richardson mr. current perspectives in polycystic ovary syndrome. am fam physician 2003 ; 68: 697-704. 11. lakhani k, seifalian am, atiomo wu, hardiman p. polycystic ovaries. br j radiol 2002; 75: 9-16. 12. li l, yang d, chen x, chen y, feng s, wang l. clinical and metabolic features of polycystic ovary syndrome. int j gynaecol obstet 2007; 97: 129-34. 13. carmina e, legro rs, stamets k, lowell j, lobo ra. difference in body weight between american and italian women with polycystic ovary syndrome: influence of the diet. hum reprod 2003; 18: 2289-93. 14. hunter mh, sterrett jj. polycystic ovary syndrome: it's not just infertility. am fam physician. 2000; 62:1079-88, 90. jiims final 1 infertility generally refers to women who have never conceived despite exposure to the chance of pregnancy and women who h a v e p r e v i o u s l y c o n c e i v e d b u t subsequently are unable to succeed. an infertile woman or a couple is constantly subjected to psychosocial stressors due to deep rooted cultural belief that children are continuation of family / pedigree and security of old age. parenthood is an inherent instinct and a passion of high order and thus culminates in diverse psychiatric and psychosomatic disorders if this passion does not translate into parenthood. these 1effects are described in a number of studies . typically the psychological response is that 2,3of loss and subsequent grief. one hypothesis suggests that unexplained psychogenic and physiologic infertility are 4the result of psychological stress. a terrible emotional complex of guilt, fear and anger is the major stress to which an infertile woman is continuously exposed to. a woman with this problem specifically blames herself and on occasions attributes her problem to past transgressions and a punishment. the infertility as such leads to strong guilt feelings, an uncertain future and fear of unknown. the fear that she possesses an imperfect body, fear of losing control over her life arouse feelings of anger directed towards self and therefore sense of worthlessness, h o p e l e s s n e s s , h e l p l e s s n e s s a n d t h e inappropriate projection of anger to the partner as unsupportive, callous and insensitive person emerge and usually generates marital disharmony as well as sexual problems. it is a common observation that women unable to conceive within a few months after marriage start visiting different general practitioners, specialists, homeopaths and more so the faith-healers on account of vague somatic complaints which are infect the manifestations related to their infertility. various studies have further emphasized that psychotherapeutic measures are more important for couples seeking help from infertility clinics since psychological factors largely affect the fertility rate which has also 5cultural and social impact. a number of other research studies have established that women with infertility are at higher risk of developing psychiatric illnesses as compared to general 6population. mahtstendt found that 80 % of their infertile sample described infertility as extremely stressful where as free man and her collogues found out 49 % of female sample considered as the most upsetting 7,8experience in their life. depressive disorders are the commonest morbidity followed by somatization disorder, d i s s o c i a t i v e ( c o n v e r s i o n ) d i s o r d e r s , generalized anxiety disorder, obsessive compulsive disorder and panic disorders editorial ------------------------------------------------psychosocial aspects of infertility wahid bakhsh sajid correspondence: brig® wahid bakhsh sajid si (m) professor of psychiatry and behavioral sciences islamic international medical college riphah international university islamabad 1 2 9and phobic disorders. it is thus high time to c r e a t e a w a r e n e s s a m o n g m e d i c a l professionals and the patients alike for understanding basic psychopathology and spectrum of symptoms of psychiatric d i s o r d e r s i n t h i s g r o u p o f f e m a l e population. 1. deanilik j, leader a & taylor pj. the psychological sequelae of infertility. the psychiatric implication of menstruation. washington; american psychiatric press 1985; 77-85. 2. karahasonglu a, barglow p & growe g. psychological aspects of infertility. j repord med 1972; 9: 241-47. 3. cabau a & de senalarens m. psychological references aspects of infertility. infertility; male and female. churchill livingstone london 1986; 648-72. 4. goldberg d. the detection of psychiatric illness by questionnaire. maudsley monograph no. 2; oxford university press 1972. 5. p kumar deka, s sarma. psychological aspects of infertility. bjmp. org 2010; 3 (3) : a 336 6. minhas fa mubasshar mh. validation of ghq in primary care setting of pakistan 1996; 6: 13336. 7. mahlstedt pp, maeduff s & bernstein j. emotional factors and the in vitro fertilization. j of in vitro fertilization and embryo transfer 1987; 4: 232-36. 8. freeman ew, boxer as, richels k & trench r. psychological evalution and sterility 1985; 43: 4854. 9. shoaib a, sajid wb, rashid s. psychiatric aspects of primary infertility in females. pak armed forces med j 2004; 54:37 20-41 2 july 2013.pdf í ñî×ù×òßô ßîì×ýôû ßþíìîßýì ñ¾¶»½¬·ª»æ ì± »ª¿´«¿¬» ¬¸» »ºº»½¬·ª»²»­­ ¿²¼ ­¿º»¬§ ±º »¿®´§ ò¿­±¹¿­¬®·½ û²¬»®¿´ ò«¬®·¬·±² ·² °¿¬·»²¬­ ©·¬¸ ß½«¬» 𿲽®»¿¬·¬·­ í¬«¼§ ü»­·¹²æ ¼±³·¦»¼ ½±²¬®±´´»¼ ¬®·¿´ò ð´¿½» ¿²¼ ü«®¿¬·±² ±º í¬«¼§æ 츻 ­¬«¼§ ©¿­ ½±²¼«½¬»¼ ¿¬ ××óý ø±­°·¬¿´ ×­´¿³¿¾¿¼ô ¿²¼ î¿·´©¿§­ ø±­°·¬¿´ î¿©¿´°·²¼· º®±³ ö«²» îððè ¬± ß°®·´ îðïïò 󿬻®·¿´­ ¿²¼ 󻬸±¼­æ ß ¬±¬¿´ 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°¿²½®»¿­òù¿­¬®±»²¬»®±´±¹§òîððëåïîçæïïîçóíðò íéò ý¿®®±´´ öõô ø»®®·½µ þô ù·°­±² ìô ô»» íðò ß½«¬» °¿ ² ½®» ¿ ¬ · ¬ ·­ æ ¼· ¿ ¹² ±­ · ­ ô ° ® ±¹² ±­ · ­ ô ¿ ² ¼ ¬®»¿¬³»²¬ò ß³ ú¿³ 𸧭·½·¿² îððéå éëæ ïëïíóîðò íèò 󷬽¸»´´ îóô þ§®²» óúô þ¿·´´·» öò 𿲽®»¿¬·¬·­ò ô¿²½»¬ îððíåíêïæ ïììéóëëò íçò õ¿´º¿®»²¬¦±­ úô õ»¸¿¹·¿­ öô 󻿼 òå û²¬»®¿´ ²«¬®·¬·±² ·­­«°»®·±® ¬± °¿®»²¬»®¿´ ²«¬®·¬·±² ·² ­» ª»®» ¿½«¬ » °¿ ²½®»¿ ¬· ¬ ·­ æ î»­ « ´¬ ­ ±º ¿ ®¿²¼±³·¦»¼ °®±­°»½¬·ª» ¬®·¿´ò þ® ö í«®¹ ïççéå èìæïêêëóçò ìðò û½µ»®©¿´´ ùûô ߨ»´­­±² öþô ß²¼»®­­±² îùò û¿®´§ ²¿­±¹¿­¬®·½ º»»¼·²¹ ·² °®»¼·½¬»¼ ­»ª»®» ¿½«¬» °¿²½®»¿¬·¬·­æ ß ½´·²·½¿´ô ®¿²¼±³·¦»¼ ­¬«¼§ò ß²² í«®¹ îððêå îììæ çëçóêëò ç original�article 4 staphylococcus aureus (mrsa) is on the rise. the occurrence of multidrug-resistant bacteria and the failure to develop new antibiotics has compounded 5 this public health issue. despite immense improvements in clinical diagnosis, blood culture remains the gold standard test for bsi detection. the spectrum of microorganisms isolated form hospitals and their antibiotic susceptibilities not only varies according to geography but even 6 within the same hospital setting. this holds true for pakistan as well, as we have recently seen a shift to a rise in gram negative bacteria as compared to gram positive bacteria. antimicrobial resistance (amr) has become a profoundly serious issue in pakistan, as there is a paucity of a good quality blood stream infection surveillance data that can influence policy change. the present study was undertaken to determine the pattern of bacterial isolates in blood stream infections and their antimicrobial susceptibility pattern. the aim of the study was to determine the recent trend in antimicrobial susceptibility pattern of microorganisms that cause bsi in our setup and to introduction infection caused by viable organisms is known as 1 blood stream infection (bsi). the clinical scale of bsi 2 ranges from mild bacteremia to severe septic shock. a scientific publication in 2017 reported that sepsis 3 accounted for almost 20% of all global deaths. these infections remain a significant cause of morbidity, mortality, prolonged periods of hospital stay, and higher health care cost worldwide. increased mortality of bsis is often attributed to inadequate diagnostic facilities and inappropriate, delayed, or 1 insufficient treatment. p r e v a l e n c e o f c a r b a p e n e m r e s i s t a n t enterobacteriaceae (cre) and methicillin-resistant assessment of bacterial profile and antimicrobial susceptibility pattern of blood culture isolates 1 2 3 4 5 kanwal hassan cheema , muhammad saeed anwar , fatima hameed , majid rauf ahmad , qanita fahim, 6 ayesha bashir correspondence: dr. kanwal hassan cheema department of pathology cmh lahore medical college, lahore e-mail: kanwalhassancheema@gmail.com 1,2,3,5,6 department of pathology cmh lahore medical college, lahore 4 department of pathology avicenna medical college, lahore funding source: nil; conflict of interest: nil received: february 10, 2021; revised: november 19, 2021 accepted: november 24, 2021 pattern of blood culture isolatesjiimc 2022 vol. 17, no.1 9 abstract objective : to determine the pattern of bacterial isolates in bloodstream infections and their antimicrobial susceptibility in a tertiary care hospital, lahore. study design: descriptive cross-sectional study. place and duration of study: the study was carried out at the pathology department of combined military hospital, lahore from november 2019 to january 2020. materials and methods: a total of 359 blood culture specimens were collected over a period of three months. organisms were identified by using api. antimicrobial susceptibility testing was carried out by modified kirby bauer disk diffusion method on mueller hinton agar and interpreted by clsi guidelines 2019. results: out of 359 bacterial isolates, only 11(3.1%) were gram-positive cocci, whereas 348 (96.9%) isolates were gram-negative rods (gnrs). amongst the gnrs, most commonly isolated organism was salmonella typhi (207; 59.5%) followed by salmonella paratyphi (60; 17.2%). twenty-seven (7.7%) acinetobacter sp., 20 (5.7%) e. coli and 20 (5.7%) klebsiella sp. were isolated. the antimicrobial resistance pattern of s. typhi showed 158 (76%) mdr and 106 (51%) xdr isolates. conclusion: the emergence of mdr and xdr bacteria especially amongst salmonella typhi is quite daunting. our study emphasizes the importance of antibacterial susceptibilities surveillance in determining the sensitivity pattern of microorganisms causing blood stream infections. key words: blood stream infections, multidrug resistance, blood cultures. prepare an antibiogram that will aid the clinicians in executing better decisions in treating their patients and can help to improve the antimicrobial stewardship programs in their hospital setting. material and methods this was a descriptive cross-sectional study done at the pathology department of cmh, lahore from november 2019 to january 2020 after getting approval from the ethical review committee of cmh lahore medical college (irb no: 532/erc/ cmh/lmc). simple convenient sampling technique was employed. a total of 359 samples of blood culture from patients with suspected signs of infection that presented to either opd or indoor facilities of combined military hospital were included in the study. duplicate samples were excluded. both adult and pediatric tryptic soya broth blood culture bottles were used to collect blood through aseptic blood collection technique. all the samples were collected before start of any antimicrobial drugs in the hospital. about 5 ml and 1 ml of blood was drawn and then inoculated into the adult and pediatric blood culture bottle. the blood culture bottles were transported to microbiology section of combined military hospital lahore and were placed in an incubator at 35±2 ºc overnight. first subculture from broth bottles was done on blood agar and macconkey agar plates. the subculture plates were incubated at 35±2 °c overnight and observed next day for any visible growth. if no growth occurred, then second and third subculture were done at day 4 and 7. the blood culture bottles were incubated for seven days in case of negative subculture. preliminary identification was based on gram staining, catalase test, oxidase test and motility. catalase positive and oxidase negative rods were identified by analytical profile index (api) 10s (biomerieux). oxidase positive rods were identified using api 20ne (biomerieux). gram positive, catalase positive cocci were identified by coagulase and deoxyribonuclease (dnase) tests. gram-positive cocci with a negative catalase test were further grouped by streptococcal grouping latex kit uk. antimicrobial susceptibility testing was carried out by modified kirby bauer disk diffusion method on mueller hinton agar and interpreted by clsi guidelines 2019. vancomycin and colistin susceptibility were tested by using e test method and broth microdilution method, respectively as per clsi 7 guidelines. statistical analysis was done by using spss 22. descriptive analysis of sample distribution, age, sex, and antimicrobial data was performed, and results are presented as frequencies and percentages. results the study was conducted over a period of three months and a total of 359 positive blood cultures were collected during this period. positivity was higher in males (233; 64.9%) as compared to females (126; 35.1%). majority of the samples with positive culture were isolated from patients visiting the opd 177 (49%) followed by medical ward 79 (22%), pediatric ward 69 (19%) and 34 (10%) from icu. out of 359 bacterial isolates, only 11(3.1%) were gram-positive cocci, whereas 348 (96.9%) isolates were gram-negative rods (gnrs). amongst the gnrs, most isolated organism was salmonella typhi (207; 59.5%) (table i). table i: breakup of gram positive and gram-negative isolates from positive blood cultures (n=359) 10 jiimc 2022 vol. 17, no.1 pattern of blood culture isolates out of the 11 gram-positive cocci isolated, 4 were staphylococcus aureus (2 methicillin sensitive staphylococcus aureus mssa strains and 2 methicillin sensitive staphylococcus aureus mrsa strains), 5 were coagulase negative staphylococci (cons). these were considered as contaminants and not processed further. two strains of enterococcus fecalis were isolated and were susceptible to vancomycin. the antimicrobial resistance pattern of salmonella typhi showed that out of the 207 isolates, 158 (76%) were mdr and 106 (51%) were xdr strains. no isolate was resistant to either meropenem or azithromycin (table ii). antimicrobial resistance pattern of e. coli and klebsiella sp. and acinetobacter sp. is shown in table iii. resistance to third generation cephalosporins was 85%, 70% and 52% respectively for e. coli, klebsiella and acinetobacter sp. overall fluoroquinolones were 100% resistant to e. coli. whereas they showed 75% and 52% resistance to klebsiella and acinetobacter sp. respectively. e. coli, klebsiella and acinetobacter sp. showed no resistance to colistin. table ii: amr pattern of s. typhi and s. para typhi isolates form positive blood cultures (n=267) *mdr s. typhi isolates (defined as resistant to ampicillin, chloramphenicol and trimethoprim-sulfamethoxazole) **xdr s. typhi isolates (defined as resistant to ampicillin, chloramphenicol and trimethoprim-sulfamethoxazole, fluoroquinolones and third generation cephalosporins) † 98% isolates were resistant to fluoroquinolones. it was observed (fig.1) that s. typhi was more commonly isolated in younger age groups, whereas, e. coli, acinetobacter sp. and klebsiella sp. were isolated from older age groups. fig. 1: distribution of positive blood cultures according to age group table iii: antimicrobial resistance pattern of e. coli, klebsiella sp. and acinetobacter sp. isolates form positive blood cultures (n=67) discussion the appropriate use of antibiotics by clinicians is paramount in preventing antimicrobial resistance. the challenges faced by the developing world in monitoring antimicrobial resistance are lack of surveillance systems, inadequate means, and indigent compliance to prevention of infection and 8 injudicious prescription as well as use of antibiotics. in the current study, 96.9% isolates were gramnegative rods (gnrs) while only 3.1% were gram11 jiimc 2022 vol. 17, no.1 pattern of blood culture isolates positive cocci. in another study conducted in lahore, out of a total of 267 positive blood cultures, 112 (41.9%) cases were of gram-positive cocci followed by 102 (38.2%) isolates of non-fermenters and 52 9 (19.47%) isolates were of enterobacteriaceae. in a 10 study conducted by kulkarni , a total of 720 samples showed growth on culture. 60.67% of the bacterial isolated were gram-positive whereas 39.33% were gram-negative bacteria. the most isolated organism isolated among the gnrs in the present study was salmonella typhi (59.5%) followed by salmonella paratyphi (17.2%). acinetobacter sp., e. coli and klebsiella sp. were isolated in the frequency of 7.7%, 5.7% and 5.7 % respectively. 9 a study conducted by imran et al showed staphylococcus aureus and coagulase negative staphylococcus sp. isolation as 56.25 % and 41.96 % r e s p e c t i v e l y . w h e r e a s , a m o n g s t t h e enterobacteriaceae, 55.76 % were e. coli and klebsiella species were 34.6 %. among 102 nonfermenters, 68.6 % were acinetobacter sp. and 31.37 % were pseudomonas sp. the antimicrobial resistance pattern of s. typhi showed 158 (76%) mdr and 106 (51%) xdr isolates. no isolate was resistant to either meropenem or azithromycin. this is comparable to a study 11 conducted by hussain et al in which isolation of multidrug-resistant (mdr) isolates was 76% in salmonella typhi and 34% in salmonella paratyphi. one hundred and fifteen (48%) isolates of salmonella typhi were extensively drug resistant. 12 another study conducted in rawalpindi showed isolation of mdr isolates of s. typhi to be 57% whereas in case of s. paratyphi a, it was 42%. ninetyeight percent strains of s. typhi were resistant to fluoroquinolones, a finding supported by regional studies as well as in india and bangladesh. a study 13 conducted by shrestha in nepal also showed 94.6% resistance to fluoroquinolones among salmonella species. the increase of mdr and xdr isolates of s. typhi has become one of the serious issues as the clinicians are left with few choices resulting in increased cost of treatment. the resistance pattern of escherichia coli in the current study was relatively greater in comparison to other studies performed in the region. a study in port 1 4 b l a i r, i n d i a s h o we d e . c o l i s e n s i t i ve to fluoroquinolones in 55.5% isolates, 50% sensitive to ceftriaxone, 90% sensitive to imipenem and 83% to meropenem, 75% sensitive to gentamicin and 90% to amikacin, respectively. in the current study, the resistant pattern of klebsiella species to third generation cephalosporins, fluoroquinolones, imipenem and meropenem was comparable to a study in nepal which showed klebsiella to be highly resistant to third generation c e p h a l o s p o r i n s , f l u o r o q u i n o l o n e s a n d aminoglycosides but showed better susceptibility to 15 colistin, carbapenems, and tigecycline. p r e v a l e n c e o f c a r b a p e n e m r e s i s t a n t enterobacteriaceae (cre) is rising. the present study showed 20% resistance to imipenem, 15% resistance to meropenem in strains of e. coli while resistance to imipenem and meropenem were seen in 60% of the isolates of klebsiella. the isolation of carbapenemresistant klebsiella pneumoniae rose from <0.1% in 16 2002 to 4.5% in 2010 in the united states. acinetobacter species are often multidrug resistant 17 and associated with life threatening infections. acinetobacter sp. isolated in the current study showed significant resistance to third generation cephalosporins, fluoroquinolones, gentamicin, and amikacin. no isolate was resistant to colistin. in a study conducted in delhi, 80.3% of the isolates of acinetobacter sp. revealed resistance to at least 18 three or more classes of antibiotics. the present study endorses the importance of antimicrobial surveillance as a valuable means in evaluating the load of amr. surveillances on a national scale are essential for providing decision makers with the information they need to develop appropriate action plans. antibiograms are more helpful for clinicians in making up to date decisions about optimum empirical therapy. this study emphasizes the need to motivate clinician to request antimicrobial sensitivity testing more frequently for better treatment outcome. the limitation of our study was that it was a single center study; hence more studies involving multiple hospitals should be carried out so that the results can be more reflective of the amr issue in our region. conclusion emergence of mdr and xdr salmonella along with cre is quite alarming. unfortunately, indiscriminate use, easy availability and over the counter use of 12 jiimc 2022 vol. 17, no.1 pattern of blood culture isolates antibiotics has compounded the issue of amr. the present study focuses on the significance of antimicrobial susceptibilities surveillance in determining sensitivity pattern of microorganisms causing blood stream infections to help the clinicians in making sound decisions when prescribing antibiotics to treat their patients. references 1. peker n, couto n, sinha b, rossen jw. diagnosis of bloodstream infections from positive blood cultures and directly from blood samples: recent developments in molecular approaches. clin microbiol infect. 2018 sep 1;24(9):944-55. 2. kreidl p, kirchner t, fille m, heller i, lass-flörl c, orth-höller d. antibiotic resistance of blood cultures in regional and tertiary hospital settings of tyrol, austria (2006-2015): impacts & trends. plos one. 2019 oct 10;14(10): e0223467. 3. banik a, bhat sh, kumar a, 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support the findings of this study are available from the corresponding author upon request. this is an open access article distributed under the terms of the creative commons attributionnoncommercial 2.0 generic license. pattern of blood culture isolates untitled-2 dec 2013.pdf ßþíìîßýì ñ¾¶»½¬·ª»æ ì± ­¬«¼§ ½´·²·½±ó¸¿»³¿¬±´±¹·½¿´ º»¿¬«®»­ô ô¿¾±®¿¬±®§ ®»­«´¬­ ¿²¼ °®±¹²±­¬·½ º¿½¬±®­ ·² °¿¬·»²¬­ ±º ¿½«¬» ´§³°¸±¾´¿­¬·½ ´»«µ¿»³·¿ò í¬«¼§ ü»­·¹²æ ü»­½®·°¬·ª» ­¬«¼§ò ð´¿½» ¿²¼ ü«®¿¬·±² ±º í¬«¼§æ 츷­ ­¬«¼§ ·²½´«¼»¼ ¿´´ ²»©´§ ¼·¿¹²±­»¼ ½¿­»­ ±º ¿½«¬» ´§³°¸±¾´¿­¬·½ ô»«µ¿»³·¿ ½±³·²¹ ¬± ß®³»¼ ú±®½»­ ײ­¬·¬«¬» ±º 𿬸±´±¹§ î¿©¿´°·²¼· º®±³ ö«² îððèóú»¾îðïðò 󿬻®·¿´­ ¿²¼ 󻬸±¼­æ 츻 ¼»¬¿·´»¼ ½´·²·½¿´ ¸·­¬±®§ ©·¬¸ °¸§­·½¿´ º·²¼·²¹­ ©»®» ½¸¿®¬»¼ ±² ¬¸» °®±º±®³¿ò ß¾±«¬ í³´ ¾´±±¼ º®±³ »¿½¸ °¿¬·»²¬ ©¿­ ¬¿µ»² ·² ûüìß ½±²¬¿·²»®ò 츻 ¾´±±¼ ©¿­ ¿²¿´§¦»¼ ±² ø¿»³¿¬±´±¹§ ¿²¿´§¦»® í§­³»¨ õè îïò ï«¿´·¬§ ½±²¬®±´ ©¿­ ³¿·²¬¿·²»¼ ¾§ ®«²²·²¹ ²±®³¿´ ¿²¼ ¿¾²±®³¿´ ½±²¬®±´­ò þ±²» ³¿®®±© ¿­°·®¿¬·±² ©¿­ ¼±²» ¿¬ ¬¸» ¬·³» ±º ¼·¿¹²±­·­ò ú·ª» 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îëîó êò îïò 𿬸¿µ îô ö¸¿ ßô í¿§¿³· ùò ûª¿´«¿¬·±² ±º ¾±²» ³¿®®±© ·² °¿¬·»²¬­ ©·¬¸ °¿²½§¬±°»²·¿ò ö±«®²¿´ ±º °¿¬¸±´±¹§ ±º ò»°¿´ îðïîå îæ îêëóéïò èè îîò ײ¿¾¿ øô ù®»¿ª»­ óô ó«´´·¹¸¿² ýùò ß½«¬» ´§³°¸±¾´¿­¬·½ ´»«µ¿»³·¿ò ô¿²½»¬ îðïíå íèïæ ïçìíóëëò îíò ð«· ýøô ù¿§²±² ðíô þ±§»¬¬ öóô ý¸»­­»´´­ öóô þ¿®«½¸»´ ßô õ¿³°­ éô »¬ ¿´ò ñ«¬½±³» ±º ¬®»¿¬³»²¬ ·² ½¸·´¼¸±±¼ ¿½«¬» ´§³°¸±¾´¿­¬·½ ´»«µ¿»³·¿ ©·¬¸ ®»¿®®¿²¹»³»²¬­ ±º ¬¸» ïï¯îí ½¸®±³±­±³¿´ ®»¹·±²ò ô¿²½»¬ îððîå íëçæ ïçðçóïëò îìò ð«· ýøô þ±§»¬¬ öóô î»´´·²¹ óêô î·ª»®¿ ùõô þ»¸³ úùò í»¨ ¼·ºº»®»²½»­ ·² °®±¹²±­·­ º±® ½¸·´¼®»² ©·¬¸ ¿½«¬» ´§³°¸±¾´¿­¬·½ ´»«µ»³·¿ò ö ý´·² ñ²½±´ ïçççå ïéæ èïèó îìò îëò  îô é±´¿½¸ ñ ô ê·¼¿´ ôô ù¿º¬»®óùª·´· ßô í¸°·´¾»®¹ ñô î¿¿²¿²· ðò ß¼±´»­½»²¬­ ¿²¼ §±«²¹ ¿¼«´¬­ ©·¬¸ ¿½«¬» ´§³°¸±¾´¿­¬·½ ´»«µ»³·¿ ¸¿ª» ¿ ¾»¬¬»® ±«¬½±³» ©¸»² ¬®»¿¬»¼ ©·¬¸ °»¼·¿¬®·½ó ·²­°·®»¼ ®»¹·³»²­æ í§­¬»³¿¬·½ ®»ª·»© ¿²¼ ³»¬¿ó ¿²¿´§­·­� ß³ò öò ø»³¿¬±´ îðïîå èéæ ìéî�èò îêò ú¿¼»®´ í ô þ®·»² íñ ô ð«· ýø ô í¬±½µ é ô 黬¦´»® óô ø±»´¦»® üò ß¼«´¬ ¿½ «¬» ´§³°¸±¾´¿­¬·½ ´»«µ»³·¿ò ý¿²½»® îðïðå ïïêæ ïïêë�éê îéò í³·¬¸ óô ß®¬¸«® üô ý¿³·¬¬¿ þôý¿®®±´´ ßöô ý®·­¬ éô ù¿§²±² 𠻬 ¿´ò ë²·º±®³ ¿°°®±¿½¸ ¬± ®·­µ ½´¿­­·º·½¿¬·±² ¿²¼ ¬®»¿¬³»²¬ ¿­­·¹²³»²¬ º±® ½¸·´¼®»² ©·¬¸ ¿½«¬» ´§³°¸±¾´¿­¬·½ ´»«µ»³·¿ò ö ý´·² ñ²½±´ ïççêå ïìæ ïèóîìò îèò î·½¸¿®¼ ß ô¿®­±²ô î·½¸¿®¼ õ ü±¼¹»ô ýò 𿬮·½µ þ«®²­ô û¼©¿®¼ ö ô»»ô î·½¸¿®¼ óò í¬±²»ô 𸷴·° í½¸«´³¿²ò ß ú·ª»óü®«¹ ·­­·±² ײ¼«½¬·±² · ³»² é·¬ ¸ × ²¬ »² ­ ·ª» ý±² ­ ±´ · ¼¿ ¬· ±² º ±® ß ¼« ´ ¬ ­ é· ¬ ¸ ß ½« ¬ » ô §³ °¸ ±¾ ´¿ ­ ¬ ·½ ô»«µ»³·¿æ ý¿²½»® ¿²¼ ô»«µ»³·¿ ù®±«° þ í¬«¼§ èèïïòþ´±±¼ ïççëå èëæ îðîëóíéò original�article abstract objective: this study was conducted to determine paediatric residents' perception, beliefs, and attitudes towards breastfeeding particularly by covid positive mothers and to assess the need for a breastfeeding teaching program. study design: a descriptive cross-sectional study place and duration of study: this study was conducted over 1 months (15 october 2021-15 november 2021) among the paediatric residents from different hospitals in rawalpindi/ islamabad. materials and methods: a total of 70 paediatric residents were included in the study. a self-administered online questionnaire was sent via email, comprising 19 items related to breastfeeding and its implications during the covid 19 pandemic. results were analysed on spss 20. results: out of 70 residents, 63 (90%) responses were obtained. most of the residents were supportive of breastfeeding and had a good perception as 100% of participants supported that breast milk is an ideal food for babies. however, huge uncertainty was noted in the answers to questions regarding breastfeeding in mothers with covid-19 infection as only a few (12.7%) residents believed that mothers with active covid 19 infection can breastfeed their baby. there was no difference among first and second year residents and third and fourth year residents (<0.5) conclusion: the participants' perception, beliefs, and overall knowledge about breast feeding is satisfactory but regarding breastfeeding in mothers who had covid-19 infection is inadequate. the authors' recommendation is to have more emphasis on support & promotion of breastfeeding in paediatric residency programs across pakistan. key words: breastfeeding, covid-19, pandemic , pediatric resident, perception. 4 0–5 months, which are still the leading causes of infant mortality in pakistan with a rate of 56/1000 5 live births. educating healthcare providers to be lactation advocates could be a useful strategy for p r o m o t i n g b r e a s t f e e d i n g i n u n d e r s e r v e d communities. the paediatricians with their leading role in provision of healthcare to children are re s p o n s i b l e fo r re c o g n i s i n g t h e va l u e o f breastfeeding, campaigning for it, and motivating & 6 helping mothers for breastfeeding. women who were encouraged by their perinatal care provider to 7 breastfeed more frequently initiated breastfeeding. according to who, breastfeeding should be encouraged for mothers with suspected or 2 confirmed covid-19. mothers should be reassured that the beneficial effects of breastfeeding greatly outweigh the dangers of transmission. none of the studies on the breast milk of women infected with covid-19 to date has found the virus in the breast 8,9 milk. whether they or their infants have suspected or confirmed covid-19, who, unicef, rcpch and ppa recommend rooming in with the practice of introduction breastfeeding has a pivotal role in infant nutrition, survival, and mother-infant bonding as breast milk is a wholesome source of nutrition for new-borns and 1 infants. exclusive breastfeeding for the first six months of life is recommended by the world health organization, american academy of paediatrics (aap) and pakistan paediatric association (ppa), followed by sustained breastfeeding along with 2,3 suitable supplemental foods for up to two years. non-exclusive breastfeeding will double the risk of death from diarrhoea and pneumonia in infants aged paediatric residents' perception of breastfeeding amidst covid 19 ammara ayub, saba afzal shaikh, fahim ahmed subhani, bilal ahmad, ghania sehar cheema, huma afzal correspondence: dr. saba afzal shaikh assistant professor department of pediatric islamic international medical college, riphah international university, islamabad e-mail: saba.afzal@riphah.edu.pk department of pediatric islamic international medical college, riphah international university, islamabad received: december 22, 2021; revised: july 21, 2022 accepted: july 28, 2022 residents' perception of breastfeedingjiimc 2022 vol. 17, no.3 192 hygienic measures unless the mother is too unwell or 10,11 the neonatal condition mandates intensive care. despite a thorough literature search, authors were unable to find any local studies on the knowledge of health care professionals on breastfeeding during covid-19. in this study, n addition to paediatric i residents' perception about basic concepts of breastfeeding, the authors also intended to find out their knowledge on breastfeeding recommendations in covid-19 positive mothers. materials and methods this cross-sectional, online survey was conducted at department of paediatrics, islamic international medical college/riphah international university. paediatric resident doctors were recruited from different training programs from teaching hospitals of twin cities of islamabad/rawalpindi over a period of 1 month. an online close-ended questionnaire comprising of 19 items related to perception, beliefs and knowledge about breastfeeding was designed & sent via email to the residents who agreed to participate in study. the questionnaire was validated by piloting. study was approved by institutional review board of riphah international university. results out of 70, 63 participants responded with a 90% response rate. majority (50%) of the participants belonged to the fcps residency programme, 40% from mcps and 10% from md, as depicted in table-1. nd most (38%) of them were from 2 year of residency. all of the participants are of the view that breastfeeding is the ideal food for the baby & is cheaper with 87% agreeing that breastfed babies are healthier than formula-fed babies. 84% of the residents agreed to the fact that breastfeeding is more convenient than formula feeding and 36.5 % of residents believed that working mothers should bottle-feed their babies. there is no significant relationship between the year of residency to the knowledge of breastfeeding (p-value insignificant). responses to questions linked to knowledge & perception of breastfeeding and formula feeding of paediatric residents are mentioned in table-ii and table-iii. knowledge and perception of the participants on breastfeeding amidst covid 19 is shown in table-iv. table i: distribution of degree program and year of residency (n=63) table ii: knowledge and perception of breastfeeding of paediatric residents (total responses=63) 193 table iii: knowledge and perception of formula feeding of paediatric residents (total responses=63) residents' perception of breastfeedingjiimc 2022 vol. 17, no.3 among all participants, 87.3 % were of the view that the mother can continue breastfeeding during active covid-19 infection if she takes proper precautions and medications, while 7.9% were unsure of what to do in such a situation and 11 % had the opinion that breastfeeding is contraindicated in such mothers. even though 58.7 % were of the view that such mothers can give expressed breast milk (ebm) to the baby, only 55% of the residents had the knowledge that breast milk protects against covid 19. discussion this study explored paediatric resident's perception & attitudes about breastfeeding amidst pandemic covid-19. response rate in present study was greater 12 13 (90%) as compared to 60% & 75% in international studies. the residents showed average knowledge about breastfeeding as is the case in the study on 12 spanish residents , although questions in both studies were different. while studies conducted on canadian paediatric residents showed opposite results with most residents lacking knowledge about 14,15 breastfeeding. all of the participants agreed that breast milk is an ideal and healthy food for a baby, with 75% of residents disagreeing that formula feeding is more convenient and cheaper than breastfeeding. this is in contrast to the study conducted by al-nassaj hh et al, in which only 57 % of the residents agreed that breast 13 milk is an ideal and healthy food for a baby. 50% of the residents agreed that working mothers should continue breastfeeding, which is similar to the 13 results by al-nassaj hh et al. majority (68% )agreed that exclusive breastfeeding should be extended for 4-6 months. in the present study, most of the residents agreed that breastfeeding should be given for the first 6 months, these results are similar to the results (92%) of a study conducted in brazil on 89 healthcare 16 professionals. 57.2% of residents agreed that breast milk contains sufficient iron which is similar to the perception of the doctors in a study conducted by 17 shaw et al. residents' responses to questions about covid-19 infection and breastfeeding revealed significant discrepancies, indicating a lack of adequate knowledge. similar results were obtained from a study conducted in india where only 54% of the participants have adequate knowledge amidst the 18 pandemic. in the present study, half of the residents agreed that breastfeeding is protective against covid -19. 12.7 % agreed that there is a risk of infection to the baby if breastfed by a mother suffering from covid-19, which is in contrast to the perception of doctors (85%) in a study carried out in 18 india . 87.3 % said that the mother can continue breastfeeding during active covid-19 infection if she takes proper precautions and medications, a response far better than the response of the 18 participants (47%) in the above-mentioned study. another study carried out in nepal on healthcare professionals about knowledge regarding covid 19 infection revealed that only 53.6% knew that 19 infected mothers can breastfeed. 58.7% of residents agreed that if a mother is confirmed case of covid-19 she should isolate herself and give ebm (expressed breast milk) to the baby. 22.2% agreed that formula feeding is a safer option in such cases, while 74.6% of indian doctors endorsed ebm & 12% 18 formula milk for such infants. there is no significant difference in the knowledge among various years of table iv: knowledge and perception of the participants on breastfeeding amidst covid 19 (total responses = 63) 194 residents' perception of breastfeedingjiimc 2022 vol. 17, no.3 residency. this study showed that knowledge & perception of paediatric residents about breastfeeding during covid 19 infection is average but there is still room for improvement. sars-cov-2 is a rapidly evolving infection and residents should have adequate knowledge about it so that they can manage and guide the parents accordingly. the limitations of the study are a small sample size and the fact that only paediatric residents were included. further studies with questions targetting technique & skills of breastfeeding as well as the inclusion of residents of obstetrics/gynaecology need to be done to identify the gaps in paediatric as well as obstetric residency to improve the training of future consultants, which will subsequently result in the promotion of breastfeeding. conclusion the participants' perceptions, beliefs, and breastfeeding knowledge are above average and acceptable but knowledge concerning breastfeeding in mothers who had covid-19 infection is inadequate. the authors' recommendation is to have more emphasis on support & promotion of breastfeeding amidst covid-19 in paediatric residency programs across pakistan. dedicated workshops and mandatory courses on breastfeeding during pandemic covid-19 should be offered to the residents to address this inadequacy. acknowledgement the author would like to pay special gratitude to all the residents who participated in this study and filled study questionnaire. the authors express their heartfelt gratitude to prof. samiya naeemullah for proofreading the manuscript and providing guidance throughout the project. prof. muhammad tahir deserves special recognition for his unwavering support and proofreading of the manuscript. references 1. victora cg, bahl r, barros ajd, frança gva, horton s, krasevec j, et al. breastfeeding in the 21st century: epidemiology, mechanisms, and lifelong effect. lancet. 2016;387:475–90. 2. world health organization. guideline protecting, promoting and supporting breastfeeding in facilities providing maternity and newborn services. geneva; 2017 [cited 2021 jul 12]. 3. breastfeeding and the use of human milk. pediatrics. 2012;129(3):e827–41. 4. lee mk, binns c. breastfeeding and the risk of infant illness in asia: a review. int j environ res public health. 2020;17(1): 2-10 5. unicef. pakistan (pak) demographics, health & infant mortality unicef data [internet]. [cited 2021 jul 12]. available from: https://data.unicef.org/country/pak/ 6. handa d, schanler rj. role of the pediatrician in breastfeeding management. pediatr clin north am. 2013;60(1):1–10. 7. lu mc, lange l, slusser w, hamilton j, halfon n. provider encouragement of breast-feeding: evidence from a national survey. obstet gynecol. 2001;97(2):290–5. 8. zhu h, wang l, fang c, peng s, zhang l, chang g, et al. clinical analysis of 10 neonates born to mothers with 2019ncov pneumonia. transl pediatr. 2020;9(1):51–60. 9. chen y, peng h, wang l, zhao y, zeng l, gao h, et al. infants born to mothers with a new coronavirus (covid-19). front pediatr. 2020; 16: 8. 10. who emro | breastfeeding advice during the covid-19 outbreak | covid-19 | nutrition site [internet]. available f ro m : h tt p : / / w w w. e m ro .w h o . i n t / n u t r i t i o n /c o v i d 1 9 / b r e a s t f e e d i n g a d v i c e d u r i n g t h e c o v i d 1 9 outbreak.html 11. wyckoff as. rooming-in, with precautions, now ok in revised aap newborn guidance. aap news. 2021 jul 3. 12. survey n, breastfeeding on, amongst k. original national survey on breastfeeding knowledge amongst breastmilk supplies newborn infants with the specific compounds they need to grow and centres and among different health workers . the bfhi strategy ( babyfriendly hospitals initiative ) promote. 2019;93:1–11. 13. al-nassaj hh, al-ward nja, al-awqati na. knowledge, attitudes and sources of information on breastfeeding among medical professionals in baghdad. east mediterr heal journal. 2004;10(6):871–8. 14. esselmont e, moreau k, aglipay m, pound cm. residents' breastfeeding knowledge, comfort, practices, and perceptions: results of the breastfeeding resident education study (brest). bmc pediatr. 2018;18(1):1–7. 15. pound cm, williams k, grenon r, aglipay m, plint ac. breastfeeding knowledge, confidence, beliefs, and attitudes of canadian physicians. j hum lact. 2014;30(3):298–309. 16. silvestre p, carvalhaes m. breastfeeding knowledge and practice of health professionals in public health care services. scielo bras [internet]. [cited 2021 jul 12]; a v a i l a b l e f r o m : h t t p s : / / w w w. s c i e l o . b r / j / r l a e / a / vtwkk5cx55ddy3cqh3cnvfd/?format=pdf&lang=en 17. shaw sc, devgan a. knowledge of breastfeeding practices in doctors and nurses: a questionnaire-based survey. med journal, armed forces india. 2018;74(3):217. 18. malik s, joshi p, gupta pk, sharma s. assessment of knowledge and opinion regarding breastfeeding practices during covid-19 pandemic among paediatricians and obstetricians in india: an online survey. sudan j paediatr. 2021;21(1):30. 19. neupane hc, shrestha n, adhikari s, angadi s, shrestha bk, gauli b. knowledge of health care professionals and medical students regarding covid-19 in a tertiary care hospital in nepal. j nepal med assoc. 2020;58(227):480. 195 residents' perception of breastfeedingjiimc 2022 vol. 17, no.3 conflict of interest authors declared no conflicts of interest. grant support and financial disclosure authors have declared no specific grant for this research from any funding agency in public, commercial or nonprofit sector. data sharing statment the data that support the findings of this study are available from the corresponding author upon request. this is an open access article distributed under the terms of the creative commons attributionnoncommercial 2.0 generic license. 196 residents' perception of breastfeedingjiimc 2022 vol. 17, no.3 microsoft word dr rahila modified final paper for submission in j 1 original article measuring and comparing educational environment of two education systems (integrated and traditional medical curriculum) running simultaneously at islamic international medical college with (dreem) inventory rahila yasmeen, masood anwar ______________________________________________________________________________ abstract objectives: measuring and comparing educational environment of two education systems (integrated and traditional medical curriculum), running simultaneously at islamic international medical college with (dreem) inventory study design: it was a quantitative descriptive study, a survey was conducted using dreem inventory. place and duration of study: the study was carried out at islamic international medical college from september 2011 to january 2012. materials and methods: total 137 out of 180 students filled the dundee ready education environment measure (dreem) inventory (roff et al., 1997) respectively. in traditional system, i.e. final year mbbs, the number of students who filled the inventory was n=63; out of which 46 were females and 17 were males. in integrated system mbbs i.e. 4th year, the number of students who filled the inventory were n=74 out of which 49 were females and 25 were males. response rate was 76%. mean age of the final year and 4th year students was 23 and 22 years respectively. results: on analysis of dreem inventory the overall score of integrated system was 130 and traditional system scored 114, fall in more positive than negative environment, but integrated system score was more towards excellent i.e.150-200, subscale of inventory revealed the following mean score results: perception of learning, 4th year scored 37-a more positive perception while traditional class had 25, just on border of teaching is viewed negatively. others subscales does not deviate more. conclusions: positive perceptions of integrated system’s students identified the strengths of the curriculum i.e. curriculum enhance their problem solving skills, competencies, student centeredness, teaching and learning strategies strengthened retention of their knowledge in long term memory on the other hand traditional system students scored negative to these areas. dreem inventory is a useful tool in measuring the learning environment and helps in finding the problems in it. key words: educational environment, dreem inventory, integrated curriculum _____________________________ correspondence: dr. rahila yasmeen assistant professor assistant dean medical educationfhms email: raheela.yasmin@riphah.edu.pk 2 introduction when students enter a new learning institution, they become aware of the curriculum they will follow through various explicit means such as the course syllabi, the classes they attend, the examinations they prepare for.1, 2 the teachers, of course, should be well aware of the curriculum they are expected to teach through the course documentation and through faculty meetings and discussions. 3 in addition to documented curriculum, students and teachers both should be aware of the educational environment’ or ‘climate’ of the institution as well. 4, 5 there are some important key questions in determining the nature of the learning experience these are; is the teaching and learning environment very competitive? is it authoritarian? is the atmosphere in classes and field placements relaxed or is it in various ways stressful, perhaps even intimidating? these expectations can be varied from course to course or from class to class and can be perceived as either formal or informal components of the educational experience and they can vary from individual to individual. 6, 7, 8 they can be motivating or de-motivating and individual students may respond differently to these subtle elements in their learning experience. 9 in order to enhance the learning experience in relation to teaching goal, it is of prime importance that institution should identify the basis for modifying the course by recognizing the elements operating in the educational environment of the institution or a course and evaluate how they are perceived by the students and teachers (strengths and weaknesses). 10 materials and methods in 2009, department of medical education of riphah international university initiated a major reform in its undergraduate medical curriculum with profound impact on the overall organization and delivery of educational strategies, after doing need analysis and piloting of project. the purpose of the paper is to identify and compare the educational environment of traditional and integrated system of undergraduate medical education by using dundee ready education environment measure1 (dreem) inventory (roff et al., 1997) in order to diagnose the strengths and weaknesses in the climate of both systems. the overall aim of the project was to improve the quality of medical education and providing a more holistic way of education to the medical students, which should be student centered and ultimately improves the health care delivery system. the educational strategy used in curriculum organization was integrated modular system (both vertical and horizontal) with problem-based learning used as a teaching and learning 3 strategy along with lectures, small group learning, role plays, skill lab and clinical clerkships. the curriculum reform project was implemented in 2009 on the newly inducted first year medical students; rest of the four years were on traditional medical education system, i.e. subject based, teacher centered. after completion of three years of new system, the two systems were compared in terms of its effectiveness by identifying the educational environment at the end of its users i.e. the students. we selected the two classes 4th year (senior most class of integrated system) and final year mbbs (traditional system), and asked them to fill the inventory named dreem (dundee ready environment measure).the dreem inventory ( roff et al.2001) was used, it contains 50 statements relating to a range of topics directly to educational climate. the inventory was administered by a survey face to face in the class room. students were asked to read each statement carefully and to respond using a 5 point likert-type scale ranging from strongly agree to strongly disagree. this inventory can produce global readings and diagnostic analysis of undergraduate educational environments in medical schools and other health professions institutions. results total 137 out of 180 students filled the dundee ready education environment measure (dreem) inventory (roff et al., 1997) respectively. in traditional system, i.e. final year mbbs, the number of students who filled the inventory was n=63; out of which 46 were females and 17 were males. in integrated system mbbs i.e. 4th year, the number of students who filled the inventory were n=74 out of which 49 were females and 25 were males. response rate was 76%. on analysis of dreem inventory the overall score of integrated system was 130 and traditional system scored 114, placed in more positive than negative environment, but integrated system score was more towards excellent i.e.150-200. subscale of inventory revealed the following mean score results: i: students’ perception of learning, 4th year scored 37, a more positive perception while traditional class had 25 that is just on border of teaching which is viewed negatively. ii: students’ perceptions of teachers 4th year scored 26 and traditional class have 25not much difference because same teachers are teaching i.e. moving in the right direction. 4 iii: students’ academic self –perception of 4th & 5th year is nearly same for both i.e. 19-20, means feeling more on the positive side. iv: students’ perception of atmosphere 4th and 5th years scored 30& 25; more towards positive but 5th year is on borderline. v: students’ social self perceptions of 4 th & 5th year scored 17 & 15 respectively which is on not too bad. discussion to pinpoint the specific strengths and weaknesses within the climate we look at the responses to individual items. no item falls in the mean score of 3.5 ( real positive points) for both years, 62% of items from 4th year and 34% from final year have the mean score between 2-3 (aspects of climate that can be enhanced),while 38% from 4th year and 66% of items from final year scores 2 or less indicate problems. among the problem areas 5th year ( traditional system) students identified that teaching is teacher centered, , teaching overemphasized factual knowledge, teachers ridicule the students, feeling about well prepared for the profession, i am able to memorize all i need on the other hand 4th year students rated high to their problem solving skills 5 are well develop, teaching helps in developing my competency and rated high to student centered teaching and long term learning is emphasized over short term learning. positive perceptions of integrated system’s students identified the following strengths of the curriculum i.e. curriculum enhance their problem solving skills, competencies, student centeredness, teaching and learning strategies strengthened retention of their knowledge in long term memory on the other hand traditional system students scored negative to these areas. but the problem areas identified by the new system need to be rectified i.e. teachers ridicule the students and are still authoritarian, teaching do not develop their confidence, teachers do not provide constructive criticism, the atmosphere is not relaxed during teaching, good support system for students who get stressed is not available, i am too tired to enjoy the course, hence dreem, inventory help in identifying the important areas which need to be modified in students perspective in order to enhance their learning.the ultimate aim of teaching... is to help students learn” and this will be achieved by enhancing the educational environment overall, scores reflect that both classes did not score excellent on subscales but 4th year scores (integrated curriculum) are little higher then 5th year and their self efficacy is higher because their attributes about their self are more towards positive hence their educational environment is little better than traditional education system. further exploration is required to justify it and identify the areas of strengths and weaknesses in both education systems. conclusion the dreem (roff et el., 1997) thus provides useful and powerful tool in providing diagnostic information about a particular education system of any institution. ‘considerations of climate in a medical school, along the lines of continuous quality improvement and innovation, are likely to further the medical school as a learning organization with attendant benefit’ (jack genn) and this can done by using dreem inventory. 11, 12, 13 to pinpoint the specific strengths and weaknesses within the climate we also looked into the individual items responses. positive perceptions of integrated system’s students identified the strengths of the curriculum i.e. curriculum enhance their problem solving skills, competencies, student centeredness, teaching and learning strategies strengthened retention of their knowledge in long term memory on the other hand traditional system students scored negative to these areas. 6 references 1. amee , education guide no.23,curriculum, environment, climate, quality and change in medical education: a unifying perspective 2. sue roff & sean mcaleer what is educational climate? medical teacher 2001; 23:68-73 3. block s. academia’s chilly climate for primary care, journal of the american medical association 1996; 276:677–82. 4. gilligan c & pollak s. the vulnerable and invulnerable physician, in: c. gilligan jv ward & jm taylor, mapping the moral domain, cambridge, ma, center for the study of gender, education and human development, harvard university press; 1988: 245– 62. 5. janz t a & pyke s a. a scale to assess student perceptions of academic climates, canadian journal of higher education, 2000; 30: 89–122. 6. kick s, adams i, o’brien-gonzales a. unique issues of older medical students, teaching and learning in medicine 2000; 12 : 150–5. 7. pimparyon p, roff s, mcaleer s. educational environment, student approaches to learning and academic achievement in a thai nursing school, medical teacher 2000; 22: 359–64. 8. pololi l & price j. validation and use of an instrument to measure the learning environment as perceived by medical students, teaching and learning in medicine 2000; 12 : 201–7. 9. maehr m l. meaning and motivation: toward a theory of personal investment. in ames, r.e., & ames, c. (eds.) motivation in education: student motivation, san diego: academic press. 1984; 1: 115 – 44. 10. prentice s. the conceptual politics of chilly climate controversies, gender and education 2000; 12: 195–207. 11. roff s, mcaleer s, harden r m. development and validation of the dundee ready education environment measure (dreem), medical teacher 1997; 19: 295–9. 12. roff s, mcaleer s, ifere os. a global diagnostic tool for measuring educational environment: comparing nigeria and nepal, medical teacher 2001; 23: 378–82. 13. bruning r h, schraw g j, & ronning r r. cognitive psychology and instruction 1999 (3ed.) . upper saddle river, nj: merrill, prentice hall. jiims final.cdr 40 introduction a d e n o m y o s i s i s a c o m m o n b e n i g n gynaecological disorder characterized by the heterotopic presence of endometrial glands and stroma within the myometrium, surrounded by smooth muscle proliferation. 1, 2, 3 the definite diagnosis of adenomyosis has traditionally been made after hysterectomy. because the junction between endometrium and myometrium in normal uteri is often irregular, the exact criteria for the histopathological diagnosis of adenomyosis are controversial. the traditional microscopic criteria commonly used by most pathologists is the identification of endometrial glands and stroma, at least one low-power field below the basal layer of endometrium and 3, 4surrounded by myometrium. the degree of myometrial invasion is variable and can involve the whole uterine wall up to the serosa. the prevalence of the condition in hysterectomy specimen varies depending on the diagnostic criteria chosen, from 8.8% 4to 61.5%. however with the advent of non-invasive imaging techniques e.g. transvaginal sonography (tvs) and magnetic resonance imaging (mri), diagnosis of adenomyosis is now possible with sufficient specificity and predictive value prior to any surgical 1t re a t m e n t . f u r t h e r m o re , t h e d i re c t visualization of the uterine cavity offered by hysteroscopy also broadens the possibilities o f r e l i a b l y d i a g n o s i n g t h e e n t i t y 1presurgically. thus the true prevalence of adenomyosis is still conflicting because of original article abstract objective:to determine the prevalence of adenomyosis in hysterectomy specimens and to correlate it with age, parity and associated pathologies. study design: descriptive study. place and duration of study: this study was carried out at the pathology department, railway hospital, islamic international medical college trust rawalpindi, from jan 2008-dec, 2010. materials and methods: two hundreds and four hysterectomy specimens were included in the study. standard histological techniques were followed and at least three sections were taken from the uterine wall. adenomyosis was diagnosed if endometrial glands and stroma were found at least one low-power field away from the endometrial-myometrial junction. results: out of 204 hysterectomy specimens received in the pathology laboratory during three year study period 47(23%) had adenomyosis. the age of patients with adenomyosis ranged from 32-64 years, a significantly higher prevalence being reported in those aged 40-59 years. a high prevalence of adenomyosis was found in multiparous women. no adenomyosis was found in nulliparous women. the analysis of other pathological entities (one or more in a single specimen), associated with adenomyosis showed uterine leiomyomas in 16 (34%), endometrial hyperplasia in 4 (8.5%) and endometrial polyps in 2 (4.2%) women. conclusion: adenomyosis is commonly found in multiparous women. definite association with fibroids, endometrial polyps and endometrial hyperplasia cannot be established. key words: hysterectomy, adenomyosis, histopathology. --------------------------------------------------correspondence: dr. samina iltaf associate prof. pathology department iimc, rawalpindi adenomyosis in hysterectomy specimens: prevalence and correlation with age, parity and associated pathology samina iltaf, madiha sajjad 40 41 different diagnostic modalities used. m o s t o f t h e w o m e n u n d e rg o i n g a hysterectomy which is followed by a confirmed diagnosis of adenomyosis are in their fourth and fifth decade of life. parity appears to be an important contributing factor as the majority (>80%) of these 5,6, 7women are multiparous. it has been commonly found in association with other pelvic pathologies for example leiomyomas, endometrial hyperplasias and 2,3endometrial polyps etc. the purpose of this study is to determine the prevalence of adenomyosis in hysterectomy specimens and its correlation with age, parity and associated pathologies. medical records were retrieved and histopathological material re-examined of 204 women who underwent hysterectomy procedure in railway hospital, islamic international medical college, rawalpindi in a three-year period from january 2008 to december 2010. all specimens had been studied in the surgical pathology laboratory using standard histological techniques. at least three sections were taken from the uterine wall. adenomyosis was diagnosed if endometrial glands and stroma were found at least one low-power field away from the 3endometrial-myometrial junction. the h i s t o p a t h o l o g i c a l a s s e s s m e n t o f a l l hysterectomy specimens received was reviewed by a consultant pathologist. other histopathological abnormalities were noted. age and parity were recorded from the medical records of these patients. data was analysed to study the prevalence of adenomyosis with regard to age, parity and associated pathology. materials and methods results two hundred and four hysterectomy specimens were received in the pathology laboratory during three year study period. of these, 47(23%) had adenomyosis according to the aforementioned criteria. the ages of patients with adenomyosis ranged from 32-64 years, a significantly higher prevalence being reported in those aged 40-59 years (table. i). no adenomyosis was found in nulliparous women. a higher prevalence of adenomyosis was found in multiparous women of parity >4 (57.4%) (table ii). the analysis of other pathological entities (one or more in a single specimen), associated with adenomyosis showed u t e r i n e l e i o m y o m a s i n 1 6 ( 3 4 % ) , endometrial hyperplasia in 4 (8.5%) and endometrial polyps in 2 (4.2%) (table iii). table i: age distribution of patients with adenomyosis prevalence per 100 patients undergoing hysterectomy in each age group. 41 42 prevalence per 100 patients undergoing hysterectomy in each parity group. discussion the conclusive diagnosis of adenomyosis at present still depends upon postsurgical histopathological examination of entire uterus. the prevalence of adenomyosis reported in the literature varies from 8% to 838% based on unselected hysterectomies. this wide variation in the reported prevalence is a result of the different diagnostic criteria used, which are based on the invasion of myometrium by glands and stroma either in terms of proportion of u t e r i n e w a l l t h i c k n e s s o r a b s o l u t e measurement. owing to the great variation in uterine wall thickness, we preferred to use the former. our study, using standard sampling techniques, found the prevalence to be 23%. this was in accordance with previously reported prevalence in most table ii: distribution of parity of patients with adenomyosis table iii: associated pathologic changes in patients with adenomyosis 7 ,8, 9studies. majority of our patients were between 40 to 59 years of age with maximum being in the 5 0 5 9 y e a r s a g e g r o u p ( ta b l e i ) . adenomyosis at younger age is unusual, but higher number of adenomyotic foci in older patients may be related to their higher 7hysterectomy rate. the peak incidence reported in most other studies is also 7, 8, 10between the 4th and 5th decades. all the adenomyotic uteri in our study were from multiparous women. no adenomyosis was identified in cases of nulliparity. these demographic trends in our study are similiar to those of hysterectomy peak incidence in the forties and a higher prevalence in multiparous women in 7,11previously published series. according to israel et al., with every pregnancy, the chance of endometrial 12penetration into myometrium is increased. in our study leiomyomas were the commonest associated lesions (34%) [table iii]. the reported incidence of concurrent 13, 14fibroids has ranged from 19% to 57%. many investigators have concluded that this high prevalence reflects an association between adenomyosis and fibroids. however, majority of these studies did not analyze the incidence of fibroids in the control specimens i.e. from women without adenomyosis. two previous studies by shaikh and khan. and vercellini et al., concluded that fibroids are equally common in the specimens with and without 7,15adenomyosis. in our study a similar pattern of prevalance of adenomyosis was observed in the presence and absence of fibroids endometrial hyperplasia has been noted to be more common in patients with 42 43 2, 4, 7adenomyosis. 1 8s o m e r e c e n t s t u d i e s f o u n d t h a t endometrial hyperplasia and uterine polyps w e re s i g n i f i c a n t l y a s s o c i a t e d w i t h 16,17adenomyosis. other studies have not 1 8 a l w a y s s u p p o r t e d t h i s f i n d i n g . hysterectomy continues to remain the single most important diagnostic and therapeutic procedure for adenomyosis, making it a retrospective diagnosis. it is equally common in women who have fibroids, endometrial hyperplasia polyps and women who do not. adenomyosis is commonly found in multiparous women.definite association with fibroids,endometrial polyps and e n d o m e t r i a l h y p e r p l a s i a c a n n o t b e established. conclusion references 1. molinas c r, campo r. office hysteroscopy and adenomyosis. best pract res clin obstet gynaecol 2006; 20:557-67 2. peric h, fraser i. s. the symptomatology of adenomyosis. best pract res clin obstet gynaecol 2006;20: 547-55 3. bergeron c, amant f, ferenczy a. pathology and physiopathology of adenomyosis. best pract res clin obstet gynaecol 2006; 20:511-21 4. bergholt t, eriksen l, berendt n, jacobson m, hertz j b. prevalence and risk factors of adenomyosis at hystrerectomy. hum reprod 2001; 16: 2418-21. 5. devlieger r, d'hooghe t, timmerman d. uterine adenomyosis in the infertility clinic. hum reprod update 2003; 2:139-47 6. templeman c, sarah f, marshall m.a, ursin g, horn-ross p l, clarke ca et.al. adenomyosis and endometriosis in the california teachers study. fertil steril 2008; 90:415-24. 7. shaikh h, khan k s. adenomyosis in pakistani women: four year experience at the aga khan university medical centre, karachi. j clin pathol 1990; 43:817-9. 8. thomas js, clark jf. adenomyosis: a retrospective view. j natl med assoc 1989; 81: 969-72. 9. bhosle a, fonseca m. eevaluation and histopathologic correlation of abnormal uterine bleeding in perimenopausal women. b h j 2010; 52 : 69-72 10. vora im, raizada rm, rawal my, chadda js. adenomyosis. j postgrad med 1981;27:7-11 11. ben hamouda s, ouerdiane n, ben zina h, masmoudi a, ennine i, bouquerra b, sfar r. adenomyosis at hysetrectomy tunis med 2007 ;85:559-62. 12. isreal s. l. and woultersz, t. b. adenomyosis--a neglected diagnosis. obstet. & gynecol 1959;14: 168-73 13. a l i a . i n c i d e n c e o f a d e n o m y o s i s i n hysterectomies pakistan j. med. res 2005; 1: 3844. 14. weiss g, maseelall p, schott ll, broockwell se, schocken m, johnston jm. adenomyosis a variant, not a disease? evidence from hystrectomized menopausal women in the study of women's health across the nation (swan). fertil steril 2009;91:201-6 15. vercellini p, parazzini f, oldani s. adenomyosis at hysterectomy: a study on frequency distribution and patient characteristics. hum reprod 1995; 10: 1160-2. 16. indraccolo u, barbieri f. relationship between adenomyosis and uterine polyps. eur j obstet gynecol reprod biol 2011; 157:185-9 17. vercelline p, viqano p, somiqliana e, daquati r, a b b i a t i a , f e d e l e l . a d e n o m y o s i s : epidemiologic factors. best pract res cl ob 2006; 20:465-77. 18. azziz r. adenomyosis:current perspectives. obstet gynecol clin north am 1989: 16 :221-35 43 jiims final.cdr 8 original article external cephalic version (ecv) for breech presentation at term -experience at railway hospital shamsunnisa sadia, shamsa rizwan, saadia sultana, fareesa waqar, raazia rauf, shaheena owais abstract objective: to assess the effectiveness of ecv in singleton breech presentation at term and to determine its effect on maternal, delivery and perinatal outcomes in women to whom the procedure was offered. study design: a quasi experimental study place and duration of study: the study was carried out in the department of obstetrics and gynaecology, railway hospital, rawalpindi, from august 2006 to december 2008. material and methods: eligible women, presenting with uncomplicated breech, between 37-41 weeks gestation, underwent ecv on day care basis. fifteen minutes before the procedure, injection salbutamol 0.5 mg was administered. cases with contraindication to ecv or salbutamol injection were excluded from the study. success rate of ecv (in terms of conversion from breech to cephalic presentation at the completion of procedure confirmed through ultrasound) along with maternal, delivery and perinatal outcomes were assessed. maternal and fetal demographic characteristics were also recorded as secondary outcome measures. for statistical analysis, spss version 10 was used and chi-square test applied with a p<0.05 taken as significant. results: of the 42 ecv procedures, 25 (59.5%) were successful. none of the patient suffered from serious maternal complications. seven (16.7%) parturients complained of severe palpitations and 4 (9.5%) of marked discomfort during the procedure. reversible fetal bradycardia was seen in 1 (2.4%) patient. reversion to a non cephalic presentation occurred in two cases. vaginal delivery was carried out in 21 patients out of the 25 who successfully underwent external cephalic version while all the patients with failed ecv underwent caesarean delivery. the 5 minute apgar score was more than 8 in all except one baby. conclusion: adverse maternal and fetal outcomes of breech presentation at term are rare and there was no increased risk of complications after external cephalic version. findings provide important data to quantify the frequency of adverse outcomes that will help facilitate informed decision-making and ensure optimal management of breech presentation. keywords: external cephalic version, breech presentation, pregnancy outcome introduction external cephalic version at more than or equal to 37 weeks gestation in suitable women with breech presentation was introduced in 1991 as a new management 1option. the rate of breech presentations in the general population of parturients at term has remained unchanged at 3-4%. however, the recent finding that the fetus has an increased morbidity during a vaginal delivery when compared with cesarean 2section has driven obstetricians towards the decision that all breech presentations will be delivered surgically .thus, the term breech trial (2000) has impacted management with 3-4% increase in overall c/s rate. this is further supported by the finding of survey of centre collaborators (2003) 92.5% report change in practice to planned c/s .the morbidity of the mother with a breech presentation is not increased with a vaginal delivery; in fact the maternal morbidity associated with surgery is higher than after a 3, 4 vaginal delivery. subsequent pregnancies are automatically deemed high risk due to 5the presence of a uterine scar. in an attempt to reduce the need for surgery with a breech presentation, the only option available in the current climate, where a vaginal delivery is out of the question, is to atempt to convert the fetal presentation from --------------------------------------------------------correspondance: dr. shamsunnisa sadia associate professor, gynae obs unit-i pakistan railway hospital iimc-t rawalpindi 9 a breech to a vertex (head) presentation. the success rates of ecv vary from 30% in nulliparous women, to 67% in multiparous 6women. the use of tocolytic agents has been shown to increase the success rate of 7ecv. this technique may result in the premature onset of labor, which would require emergent surgery, and there is also a risk of umbilical cord entanglement, prelabour rupture of membranes as well as placental 8abruption. following ecv, the fetus may spontaneously return to the breech position. overall complication rates have ranged from 1-2 % & in recent studies with strict inclusion criteria no significant fetal or maternal morbidity occurred as a result of 9ecv. in spite of these risks most women wish to avoid cs, preferring ecv the only effective intervention to convert a breech fetus to cephalic presentation with the potential to help women avoid cs. the royal college of obstetricians and gynecologists recommends that all women with an uncomplicated breech presentation at term should be offered ecv. survey of centre collaborators (2003) further support this rationale by reporting a change in practice with 13.8% more practitioners offering/performing ecv. unfortunately, the fact that versions are not practiced in all obstetrical departments is partly due to the embarrassing lack of expert knowledge on the part of some practitioners / clinicians and more importantly failure in adequately disseminating information regarding management options available to patients presenting with breech near term. probabilistic information on outcomes of breech presentation is important for clinical decision-making. the aim of the study was to assess the effectiveness of ecv in singleton breech presentation at term and to determine its effect on maternal, delivery and perinatal outcomes in women to whom the procedure was offered. it was a prospective study, carried out in the department of gynaecology and obsterics, islamic international medical college trust, railway hospital, rawalpindi. a total of 42 patients with singleton breech presentation but otherwise uncomplicated pregnancies, between 37-41 weeks gestation, were offered ecv from august 2006 to december 2008. type of breech was not considered a factor for suitability. exclusion criteria included m u l t i p l e p r e g n a n c y, a n t e p a r t u m haemorrhage, ruptured membranes, p l a c e n t a p r e v i a , k n o w n u t e r i n e malformation, oligohydramnios (afi < 8), fetal abnormality, previous caesarian section, active labour, intra uterine growth restriction, severe proteinuric hypertension, bad obstetric history, need for lscs for any other indication & any contraindication to tocolysis such as maternal diabetes mellitus, cardiac & thyroid disease and patient's wishes after thorough counseling. each patient was fully explained regarding the procedure, its possible complications and an informed consent was taken. immediately prior to the ecv procedure, the woman was reassessed to ensure she was still eligible for ecv, duration of pregnancy was between 37-41 weeks and the fetal presentation was confirmed by ultrasound. this ultrasound was used along with clinical assessments to determine any contraindications to ecv prior to each procedure. fetal well-being was assessed materials and methods 10 prior to the procedure by continuous fetal heart rate monitoring for 20 minutes. fetal heart rate assessment was required to reveal a normal baseline rate, good variability, and no evidence of decelerations prior to ecv. all ecv procedures were undertaken by e x p e r i e n c e d c l i n i c i a n s a n d i n a n environment where any complication could b e a p p r o p r i a t e l y m a n a g e d . tw o obstetricians, at least one of whom had experience with the procedure, performed the ecv, with the aid of ultrasound surveillance. the ecv procedure had to be halted if any of the following occurred: fetal bradycardia, placental abruption, and failure of ecv. i n j e c t i o n s a l b u t a m o l 0 . 5 m g w a s administered intravenously to 22 and subcutaneous to 20 patients. after detecting rise in maternal pulse, softening of uterus & easy palpation of fetal parts, external cephalic version was attempted under ultrasound guidance. continuous uterine pressure was limited to 5 minutes while total uterine manipulation was limited to a maximum of 10 minutes. no more than 2 attempts were tried. after successful version, attitude was maintained manually for a few minutes. fetal heart monitoring was done every 2 minutes throughout the procedure. the woman remained under supervision for at least one half hour following the procedure. fetal well-being was assessed following the procedure by confirming fetal movement on ultrasound and by recording a reactive fetal heart rate on continuous fetal heart rate m o n i t o r i n g f o r 2 0 m i n u t e s . f e t a l presentation was confirmed by ultrasound immediately following the procedure. since rhesus isoimmunization is a risk of ecv, non-sensitized rh negative women were required to be provided with anti-d immunoglobulin following the procedure. clinical parameters including age, height in centimeters, parity, duration of pregnancy in weeks, estimated fetal birth weight and placental location were recorded. the occurrence of any complication such as prom, aph, fetal distress, severe maternal t a c h y c a rd i a ( > 1 2 0 b e a t s / m i n ) w i t h palpitation, sweating with hypoglycaemia and reversion of fetus to breech presentation were noted. failure of ecv was followed by elective lower section caesarean section on completion of 38 weeks of gestation. on success of ecv women were discharged with weekly antenatal follow up to await spontaneous labor up to 41 weeks. care after external cephalic version including mode of delivery was determined by the attending obstetrician. the care in labour ward was guided by departmental protocols. mode of delivery, weight & sex of the baby was recorded at time of delivery. fetal outcome was measured in terms of apgar score at 5 mins. the principal outcome measures of the study were success rate of ecv, its overall effect on maternal/ perinatal outcome and mode of delivery. maternal and fetal demographic characteristics were also recorded as secondary outcome measures. for statistical analysis, spss version 17 was used and student ttest applied with a p<0.05 taken as significant. in our study 42 patients with singleton breech presentation between 37-41 weeks gestation but otherwise uncomplicated pregnancies fulfilled the inclusion criteria results 11 and were offered external cephalic version (ecv). overall success rate was 59.5% (25).reversion to breech occurred in 1 patient (2.4%) who was diagnosed on follow up visit and repeat ecv was successful but the patient had caesarean delivery due to intrapartum fetal distress. another patient had reversion to transverse lie after successful ecv but presented in labour and was found to have a bicornuate uterus on caesarean section. the mean age of our patients was 26.2 years (sd=5.9) while the mean height was 157cm (sd=4.7). the parity of patients is shown in table 1. the mean parity of the patients with successful ecv was 1.8 while that of unsuccessful ecv was 0.3.the mean gestation at which ecv was performed was 38 weeks (sd=1.2). intravenous tocolysis was done in 22 women (52.4%) while subcutaneous salbutamol was given to 20 patients (47.6%) prior to attempting ecv. similar frequencies had successful ecv's in both the groups. the ultrasonography carried out prior to the procedure revealed that the placenta was posterior / fundoposterior in 23 (54.8%), anterior / fundoanterior in 16 (38.1%) and fundal in position in only 3 (7.1%) cases. the mean estimated fetal birth weight (efbw) was 3 kg (sd0.33gm). the mean efbw of patients with successful ecv was 2.96kg while that of unsuccessful ecv was 3.1 kg. there was only 1 (2.4%) case of transient fetal bradycardia which recovered within 5 m i n u t e s . s e v e n ( 1 6 . 7 % ) p a r t u r i e n t complained of severe palpitations and 4 (9.5%) of marked discomfort during the procedure. about 28 (66.7%) did not have any complaint. vaginal delivery was carried out in 21 patients out of the 25 who successfully underwent external cephalic version. one patient was lost to follow up after successful ecv. caesarean delivery was necessary in rest of the three women, two of whom had reversion to non-cephalic presentation. all the patients with failed ecv underwent caesarean section. the 5 minute apgar score was more than 8 in all except one baby delivered by lscs due to fetal distress in whom it was 6, but the score improved to 10 at 10 mins of birth. twenty two (52.4%) babies were male while 19 (45.2%) had female sex. the mean weight at birth was 3.25 kg, minimum & maximum being 2.8 & 4 kg respectively. breech presentation is the most common malpresentation affecting at least 20 000 babies per year in the uk alone. it is the third most common indication for caesarean section (c/s) following previous caesarean section and labour dystocia. approximately 87% of breech presentations in the united 10states result in cesarean delivery. external cephalic version (ecv) has been clearly shown to decrease the incidence of breech presentation at term, thereby reducing the elective caesarean section rate. the royal discussion 12 college of obstetricians and gynaecologists ( r c o g ) a n d a m e r i c a n c o l l e g e o f obstetricians and gynecologists currently recommend that all women with an u n c o m p l i c a t e d s i n g l e t o n b r e e c h presentation at term should be offered ecv. trial of ecv is cost-effective when compared to a scheduled cesarean for b r e e c h p r e s e n t a t i o n p r o v i d e d t h e probability of successful ecv is at least more 11than 32%. this is in line with our case series where the success of ecv was 59.5%. in spite of this as well as recommendations by professional bodies, acceptance of ecv among both clinicians and consumers appears to be limited, apparently because of 12fears over safety. apart from only one case of reversible fetal bradycardia, there was no remarkable perinatal complication in our study. about 17% of patients complained of severe palpitations and 10% of marked discomfort during the procedure. the low frequency of complications in our series is matched by 13other studies which suggest that women should be counseled that ecv is extremely safe but has a 0.5% risk of emergency caesarean section at the time of the 14procedure. in fact women with a breechpresenting fetus at term and previous caesarean delivery, who desire a trial of labor, should be counseled regarding the accumulating evidence about the efficacy and apparently safety of this procedure and 15may be offered an ecv attempt. external cephalic version at 3435 weeks versus 37 or more weeks of gestation increases the likelihood of cephalic presentation at birth but does not reduce the rate of caesarean section and may increase 16the rate of preterm birth. so in our study, ecv was offered only to patients between 37-41 weeks. in our case series there was no significant d i f f e r e n c e i n m a t e r n a l a n d f e t a l demographic features. however, multipara tended to have a better chance of a 17successful ecv as in other studies. twenty one out of the 24 patients who were followed up after a successful ecv had a normal vaginal delivery in our study. this is in concordance with other studies exhibiting 18successful pregnancy outcome after ecv. however, certain other studies show that pregnancies after a successful external cephalic version at term are not the same as those with cephalic presentation. they are at higher risk of both dystocic labor and fetal distress and therefore require close 19intrapartum monitoring. in our case series there was no difference in the success of ecv whether tocolysis was carried out by subcutaneous or intravenous salbutamol. currently, various options to improve the success rate of ecv are being explored in research trials. moxibustion 20treatment due to its simplicity and combined spinal-epidural analgesia due to 21its efficacy are being extensively studied. adverse maternal and fetal outcomes of breech presentation at term are rare and there was no increased risk of complications after external cephalic version in our study. findings provide important data to quantify the frequency of adverse outcomes that will help facilitate informed decision-making and ensure optimal management of breech presentation. conclusion 13 references 1. hannah me, hannah wj, hewson sa. planned caesarean section versus planned vaginal birth for breech presentation at term: a randomized multicentre trial term breech collaborative group. lancet 2000 ;356:1368-9 2. rauf b, ayub t.maternal and perinatal outcome in term singleton breech presentation. j postgrad med inst 2004;18:373-9 3. sanchez-ramos l, wells tl, adair cd. route of breech delivery and maternal and neonatal outcomes. int j gynecol obstet 2001 ;73:7-14 4. jackson n, paterson-brown s. physical sequelae of caesarean section. best pract res clin obstet gynecol 2001; 15 :49-61 5. mozurkewitch el, hutton ek. elective repeat cesarean section versus trial of labor: a metaanalysisof the literature from 1989-1999. am j obstet gynecol 2000;183: 1187-97 6. ezra y, elram t, plotkin v, elchalal u. significance of success rate of external cephalic versions and vaginal breech deliveries in counseling women with breech presentation at term. eur j obstet gynecol reprod biol 2000;90 :63-6 7. yanny h, johanson r, baldwin kj, lucking l, fitzpatrick r, jones p.double blind randomized controlled trial of glyceryl trinitrate spray for external cephalic version. br j obstet gynecol 2000; 107:562-4 8. kasule j, chimbria th, brown im. controlled trial of external cephalic version. br j obstet gynaecol 1985;92:14-18 9. devendra k. introducing routine external cephalic version for the management of the malpresenting fetus near term. med j malaysia 2002;57: 454-9 10. martin ja, hamilton be, sutton pd, ventura sj, menacker f, munson ml.births: final data for 2002. natl vital stat rep 2003, 52:1-113 11. jonathan m tan, alex macario, brendan carvalho, maurice l druzin, yasser y el-s. costeffectiveness of external cephalic version for term breech presentation. bmc pregnancy and childbirth 2010, 10:3doi:10.1186/1471-2393-10-3 12. thomas j, callwood a, brocklehurst p, walker j. the national sentinel caesarean section audit. br j obstet gynaecol 2000;107:579-80. 13. grootscholten k, kok m, oei sg, mol bw, van der post ja. external cephalic versionrelated risks: a meta-analysis. obstet gynecol. 2008; 112:1143-51. 14. collins s, ellaway p, harrington d, pandit m, i m p e y l . s h o r t c o m m u n i c a t i o n : t h e complications of external cephalic version: results from 805 consecutive attempts. br j obstet gynaecol 2007;114: 636-8. 15. sela hy, fiegenberg t, ben-meir a, elchalal u, ezra y. safety and efficacy of external cephalic version for women with a previous cesarean delivery. eur j obstet gynecol reprod biol 2009; 142:111-4. 16. hutton ek, hannah me, ross sj, delisle mf, carson gd, windrim r,et sal. the early external cephalic version (ecv) 2 trial: an international multicentre randomised controlled trial of timing of ecv for breech pregnancies. br j obstet gynaecol. 2011;118: 564-77. 17. tasnim n, mahmud g, khurshid m.external cephalic version with salbutamol success rate and predictors of success. j coll physicians surg pak. 2009;19:91-4. 18. siddiqui d, robert j, stiller md, collins j, steven a, laifer md. pregnancy outcome after successful external cephalic version. am j obstet gynecol 1999;181:1092-5. 19. lau tk, kit lo kw, michael rogers m. pregnancy outcome after successful external cephalic version for breech presentation at term. am j obstet gynecol 1997;176:218-23. 20. manyande a, grabowska c. factors affecting the success of moxibustion in the management of a breech presentation as a preliminary treatment to external cephalic version. midwifery 2009;25: 77480. 21. sullivan j.t , grobman w.a, bauchat j.r , scavone b.m, grouper s, mccarthy rj et al. a randomized controlled trial of the effect of combined spinalepidural analgesia on the success of external cephalic version for breech presentation. 2009 intl jobstetanesth;18 : 32834. original�article abstract objective: to determine the perceptions of medical students about the effect of mentoring on professional development and to identify the problems faced during mentoring sessions in a private medical college. study design: it was a qualitative phenomenological study. place and duration of study: this study was conducted at islamic international medical college rawalpindi. it was completed in 6 months i.e., from feb. 2016 to 31 july 2016. materials and methods: it was a qualitative phenomenological study a sum of 32 students were included in . this study, 16 from third year mbbs and 16 from final year mbbs. students from each class were divided into two groups, each group comprising of 08 students. two focus group discussion were arranged. focus group discussions were audio recorded, transcribed and analyzed by thematic analysis with nvivo version 11. results: majority of the students found mentoring useful and a supportive program for their professional development, self-grooming, self-confidence and it helped them to increase their knowledge. students were of the opinion that mentoring sessions had been helpful for improving their behavior with the patients. students also highlighted that these sessions had positive effects on their professional and religious values. students identified certain problems faced during these sessions like irregularity in mentoring sessions, frequent change of mentors, lake of advice and guidance on their career development by the mentors. conclusion: medical students observe that mentoring has useful and beneficial effect on their professional development. however, they have highlighted certain shortcomings/problems of mentoring program run in iimc. these deficiencies include lack of a structured mentoring program, irregularity in mentoring sessions and change of mentors. key words: mentor, mentee, perceptions, carrier planning, carrier development, professionalism, professional development. the faculty encumbrance, in the meantime enabling professional cooperation and collaboration. it is constructive for academic institutions to introduce formal mentoring program, offer maintenance and 4 , 5 , 6 organize staff improvement for mentors mentoring skill is a respected possession for the faculty of academic medicine. it helps in shaping the professionalism of next group of physicians. mentors are basically role models acting as directors, in order to help students for their personal development and 7,8 carrier planning over time. mentors can be contributory in transmission of overt academic understandings necessary to master curriculum content. essentially, they can improve implied understanding about the “hidden curriculum” of ethics, values and the art of medicine not demonstrated from texts. mentors also provide 9,10,11 affectionate support and reinforcement. there was a need for formal mentoring program which socializes young doctors to meet their professional 12,13,14,15 needs. mentoring at islamic international medical college, introduction the conventional characterization of a mentor is a reliable and honest counselor. a mentor has the capability to direct, monitor and provokes his or her mentee by increasing his or her acquaintance, responsiveness, and vision. mentors are an influential force for developing successful professionals. medical faculty having mentors often viewed that mentoring positively facilitates the 1,2,3 personal development. effective mentoring surges carrier contentment in mentees. it reduces effect of mentoring on professional development of medical students medical students correspondence: dr. shamaila sharif associate professor department of gynecology islamic international medical college riphah international university, islamabad e-mail: shumaila.sharif@riphah.edu.pk 1,3,5 2 4 department of gynecology/medicine /surgery islamic international medical college riphah international university, islamabad funding source: nil; conflict of interest: nil received: december 10, 2018; revised: september 04, 2019 accepted: september 06, 2019 effects of mentoring program on professional developmentjiimc 2019 vol. 14, no.3 1 2 3 4 5 shamaila sharif , abdul ghani waseem , wajiha shadab , rehan ahmed khan , saadia sultana 160 coding was done using nvivo version 11. themes were selected and subthemes were identified. six steps were followed for data analysis and interpretation. transcripts were coded and themes confirmed. after identifying open codes, axial coding performed to find out subthemes. selective codes were identified, and interpretation of results was done. results majority of the students found mentoring useful and a supportive program for their professional development, self-grooming, and self-confidence. students agreed that it helped them to develop vision and increase their knowledge about life and living. students were of the opinion that mentoring sessions had been helpful for improving their behavior with the patients in the hospital. students highlighted that these sessions had positive effects on their professional duties and religious obligations and improved behavior towards peers, seniors and patients. they felt self-motivated and amended capabilities of teamwork and tolerance. students identified certain problems faced during these sessions like irregularity in mentoring sessions, frequent change of mentors, lack of advice and guidance on their career development by the mentors. the following themes and sub themes were extracted from the group discussion: medical students' perceptions themes and subthemes riphah international university is based on group mentoring where one senior and one or more junior mentors are assigned a group of students. the mentors are selected from the faculty and management staff of islamic international medical college. once selected, the mentors were trained and had to undertake special workshops on mentoring. the faculty members who had completed the “post graduate diploma in professional ethics and teaching methodology” for faculty members are preferred to take up mentoring. social sciences department run strategic vision workshop of medical students in the first semester to help understand life vision. this study will help us to explore the usefulness and effectiveness of mentoring program run for undergraduate medical students. the valued responses compiled by this research will help to highlight the importance of mentoring program and the improvements required to make it more useful and effective. a study was planned to determine the perceptions of medical students about the effect of mentoring on professional development and to identify the problems faced during mentoring sessions in a private medical college. materials and methods a qualitative phenomenological study was conducted at islamic international medical college rawalpindi from feb. 2016 to 31 july 2016 after an approval from ethical review committee of riphah international university. focus group discussion method was used. students who attended the mentoring classes in their previous sessions were included in the study. total 32 students were included, 16 from third year mbbs and 16 from final year mbbs. students from each class were divided into two groups, comprising 08 students in each group. in this study, maximum variation sampling technique was used. two focus group discussions (fgds) of mbbs students, were conducted to explore their understanding of the effectiveness, utility and problems of the mentoring sessions conducted in our institution. data was collected using questionnaire consisting of leading questions about their perceptions, attitudes and opinions. the group's composition and discussion was carefully planned to create a nonintimidating environment. data was transcript and effects of mentoring program on professional developmentjiimc 2019 vol. 14, no.3 161 impact on their mentees. as mentors convey wisdom indirectly through their approaches, outlooks and concepts, they have ability to engage with students at all levels and tolerate and guide the emotions of their mentees. on the other hand, it is also important that students make independent decisions and have their own experiences. it fosters their personality development and they work with their personal struggles. respondent 1 mentors were not role models so : they did not give us practical points which are impressive enough to improve ourselves. respondent 2: we can improve these classes by having role models as mentors. respondent 3: these can be further enhanced by providing us with trained mentors' because everyone cannot be a mentor. personal grooming: students involved in mentoring observed that their mentoring classes improved their tolerance, their understanding of teamwork and vision about life. they were able to formulate and express their vision of life according to their requirements and internal satisfaction. it also increased their interest in research work as they feel it easy and accessible to research on topics of their own interest. respondent 1: we discuss different aspects of life and it helps us in improving our attitude towards patients, empathy and awareness about religion. respondent 2: we discussed many queries with our teachers and after reading book adab e zindagi, we feel improved ourselves about daily life activities and attitude towards patients. respondent 3: it added a little to our ethics. respondent 4: may be we need separate classes on ethics. improving professionalism: many of the students a d m i tte d t h at m e nto r i n g h e l p e d t h e m i n understanding professionalism and it guided them to act upon its different aspects. respondent 1: mentoring helped us improving ourselves as a good doctor. it told us how we can be a doctor not only concerned about diseases of the patients but also about their psychological issues and social problems. respondent 2: it improved our self-motivation and workplace working. respondent 3: it increased our knowledge. as a result of two focused group discussion among the students, following seven major themes were identified. structured mentoring program students expressed that mentoring classes should be with the same mentor and on regular basis. they claimed that a structured program will ensure continuity and establish secure relationship of mentees with the mentors. students perceived mentoring as a personal relationship with faculty member engaged in helping the student in order to improve student's personal and professional prophecy. respondent 1: i don't feel any improvement but this can be improved by making these sessions more structured. respondent 2: mentoring sessions should be more frequent. may be for a limited time period but if teachers come prepared, it will be motivating. respondent 3: for better results, formal mentoring is necessary. respondent 4: only two sessions were conducted last year, which i think are insufficient even if we consulted our senior teachers many times but these were informal meetings and teacher cannot assess us. regular mentoring classes: students reflected that mentoring classes were interrupted and insufficient for any impact on them. there is need for regularity and punctuality for these classes so that program implementation is ensured and proper feedback can be taken. mentors also value the time they spend and mentee achieve guidance in most of the aspects of life through this affiliation. respondent 1: these sessions were insufficient. mentoring sessions should be at least one after every two months. respondent 2: number of sessions during the year was insufficient. we need more sessions with trained mentors for better results. respondent 3: actually, mentoring classes should be in succession and on weekly basis for may be a limited time period. respondent 4: we need regular sessions to avail benefits of mentoring. mentors as role models: students emphasized that if mentors are role models, it may be a better setting for them. it is evident that mentor's personality has effects of mentoring program on professional developmentjiimc 2019 vol. 14, no.3 162 a structured program ensures continuity and establishes secure relationships of mentees with the mentors. in this study, the student expressed that proper structuring of the mentoring program would ensure proper program implementation. similar results were found in a study that was conducted by 18 buddeberg fisher medteach 2006. the study showed that the majority of the mentoring programs lack a concrete structure, although the results of mentoring are promising, more formal programs 18 with clear setup goals are needed. in this study, student expressed that decrease regularity and punctuality leads to decrease in the impact of mentoring classes on them similar suggestions were . made in a study done by boyle preports on the development and assessment of mentoring programs. the study suggested that the sustained, involving relationships between mentor and mentee 19 for best outcomes. it is evident that mentor's personality has impact on their mentee. in this study, a small number of students emphasized that if mentors are role models, they may guide better for their professional development. in a study by allen td, meta-analysis was used to review and synthesize existing empirical research concerning the career benefits associated with mentoring comparisons of mentored versus nonmentored groups were made, the findings were generally supportive of the 20 benefits associated with mentoring. students involved in the present study perceived that mentoring sessions helped students in their personal grooming, improving tolerance, understanding of teamwork and vision about life. they were able to formulate and express their vision of life according to their requirements and internal satisfaction. in a study by ndwiga c, a qualitative assessment was conducted to assess provider experiences and perceptions about mentoring. mentees reported improved knowledge, skills, self-confidence, and 21,22 team work. many of the students admit that mentoring helped them in overall understanding of professionalism as well as guided them to act upon its different aspects. similar results are seen in a study by sambunjak d, they found that mentorship was reported to have an important influence on personal development, career guidance, career choice, and research productivity, including 24 publication and grant success. respondent 4: we have better communication with our peers. islamic values: students reflected that mentoring improved their knowledge about islamic values. they discussed their queries with the respective mentors and it, in turn had an impact on their daily life activities and now they are more empathetic towards patients. respondent 1: it only gave us knowledge about islamic values and did not give us practical points in team working. respondent 2: yes, it improved our religious and moral values. respondent 3: respondent 4: but we feel deficient regarding practical points, how to improve our self? and need more guidance in this aspect. career guidance: students had the opinion that their mentors were not much concerned about their carrier planning and only a short time talk was conducted during their sessions. if their teachers come prepared, they may give them valuable support in this aspect as well and it may become easier for them to choose the carrier according to their aptitude. respondent 1: it does increase our confidence and helped us in our future plans. respondent 2: it increased our confidence but did not help us in our future plans. respondent 3: these classes were not so much concerned about our preparation of our carrier. respondent 4: it improved self-motivation but not carrier planning. discussion in this study, conducted at islamic international medical college, most of the students found mentoring supportive for professional development, self-grooming and confidence. students reflected that these sessions fostered their professionalism and helped in improving their self-confidence. mentoring sessions were effective for improving behavior towards patients. however, these sessions did not help them in carrier development. the religious impact of these classes had also been significant. they emphasized that there was effective role of mentors and regular sessions were required for making it more beneficial. effects of mentoring program on professional developmentjiimc 2019 vol. 14, no.3 163 6. straus se, chatur f, taylor m. issues in the mentor-mentee relationship in academic medicine: a qualitative study. acad med. 2009, 84:135-9. 7. kram ke. phases of the mentor relationship, acad manage j. 1983; 608 26460825 8. kram k, eisabella la. mentoring alternatives: the role of peer relationships in career development acad manage j. 1985:7, 487-503. 9. rose gl, rukstalis mr, schuckit ma. informal mentoring between faculty and medical students. acad med, 2005; 80: 344–8. 10. connie e.cell. evolving as a scientist and a mentor. epub . 2019; 177:510-13. 11. newburger jw . reflections on mentoring. congenit heart dis. 2019; 14: 126-7. 12. milton cl . ethics with mentoring. nurs sci q. 2017; 30: 105-6. 13. block m, florczak kl.mentoring: an evolving relationship. nurs sci q. 2017; 30: 100-4. 14. byks-jazayeri c, samuels e, anderson ew, ellingro vl. implementing and measuring the impact of a clinical and translational research mentor recognition program. j clin transl sci. 2018; 2: 312-20. 15. gagliardi ar, perrier l,websterf, leslie k, bell ml ,evinson w. exploring mentorship as a strategy to build capacity for knowledge translation research and practice: protocol for a qualitative studyimplementsci . 2009; 1:14-98. 16. jacobi m. mentoring and undergraduate academic success: a literature review. 1991; 61:505–32. 17. chao gt, gardnerb p. formal and informalmentorship: a comparison on mentoringfunctions and contrast with nonmentoredcounterparts. pers psychol. 1992, 45:619 –36. 18. buddeberg-fischer b1, herta kd.formal mentoring programmes for medical students and doctors--a review of the medline literature. med teach. 2006 may;28 :248-57 19. boyle p, boice b.systematic mentoring for new faculty teachers and graduate teaching assistants.innovative higher education 1998, 22:157-179 . 20. allen td, eby lt, poteet ml, lentz e, lima l. career benefits associated with mentoring for protégeé: a metaanalysis. j appl psychol. 2004; 89:127-36. 21. thorndyke le, gusic me, milner rj. functional mentoring: a practical approach with multilevel outcomes. j contin educ health prof. 2008; 28:157-64. 22. ndwiga c1, abuya t, mutemwa r, kimani jk, colombini m, mayhew s, baird a, muia rw, kivunaga j, warren ce. exploring experiences in peer mentoring as a strategy for capacity building in sexual reproductive health and hiv service integration in kenya. bmc health serv res. 2014 1;14-98. 23. frei e , barbara m s, fischerr b. mentoring programs for medical students a review   of the pubmed literature 2000-2008.bmc medical education. 2010: 10 :32. 24. sambunjak d1, straus se, marusić a. mentoring in academic medicine: a systematic review.. jama. 2006 sep 6;296(9):1103-15. conclusion medical students observe that mentoring has useful and beneficial effect on their professional development. however, they highlighted certain shortcomings/problems of mentoring program being run in iimc causing hindrance. these deficiencies include lack of a structured mentoring program, irregularity in mentoring sessions and change of mentors. mentoring program is being implemented in most of the universities; there is need for a structured program according to local environment, facilities and social values. so that it fulfills our student's requirements and fosters their capabilities. regular classes with timely feedback would be beneficial for student's satisfaction and will make it more practical according to the needs of the students of different classes and gender. for effective mentoring, faculty development is necessary through workshops and seminars so that they may perform mentoring in appropriate manner, and it will satisfy the students as well. there should be incentives for faculty so that they do not feel it a burden and able to provide quality time for mentoring. assessment and evaluation are integral parts of this program. for improvement in future and removing flaws in this program, assessment at regular intervals with involvement of all stakeholders of institution is integral part of this program. references 1. anderson aj, sánchez b, mcmahon sd. natural mentoring, academic motivation, and values toward education among latinx adolescents. am j community psychol. 2019 ;63: 99109. 2. emery n, hund a, burks r, duffy m, scoffoni c, swei a. students as ecologists: strategies for successful mentorship of undergraduate researchers. ecol evol. 2019; 9: 4316-26. 3. boutjdir m , aromolaran as, de las fuentes l, boyington jea , arteaga ss, jobe j, jeffe db, et al. research education and mentoring program in cardiovascular diseases for u n d e r re p re s e n te d j u n i o r fa c u l t y f ro m n h l b i sipid/pride. j am coll cardiol. 2019; 73: 1861-65. 4. caruso tj, kung t, piro n, li j, katznelson l, dohn a. a sustainable and effective mentorship model for graduate medical education programs. j grad med educ. 2019; 11: 221 5. 5. fagenson-eland ea, marks ma, amendola kl. perceptions of mentoring relationships j voc behav 1997; 51: 29-42 effects of mentoring program on professional developmentjiimc 2019 vol. 14, no.3 164 original�article abstract objectives: to investigate the frequency and nature of various incidental findings and their relationship with presence or absence of sacroiliitis, observed on magnetic resonance imaging (mri) of sacroiliac joints (sij). study design: observational study. place and duration of study: fauji foundation hospital, rawalpindi, from january 2018 to march 2021. materials and methods: all patients undergoing mri of sij were included except those who could not lie down supine in mr gantry. data regarding age, gender, mri findings related to sij and other incidental findings were recorded. frequencies of findings in various groups were compared using chi-square test considering p value of <0.05 as significant. results: out of 302 patients, 126 (41.7%) showed incidental findings. among 201 females, 87 (43.3%), while among 101 males, 39 (38.6%) showed incidental findings (p=0.437, not significant). sacroiliitis (si) was seen in 58.7% and 45.5% of females and males respectively (p=0.030, significant). one hundred and sixty-four (54.3%) of 302 patients were grouped as having si on the basis of mri while 138 (45.7%) had normal sij. in the former group 64 (20.5%) showed at least one incidental finding. among the latter group, 62 (20.5%) had incidental findings (p= 0.300, not significant). most common incidental finding was lower lumbar disc degenerative disease (llddd), seen in 65 (21.5%) patients. conclusion: incidental findings are commonly observed on mri of sij. they were seen overall, in two-fifth of our patients. incidental findings must be reported, as these can have important clinical implications. there was no significant difference between patients with and without si with respect to prevalence of incidental findings. key words: ankylosing spondylitis, bone marrow oedema, lumbar disc degenerative disease, sacroiliac joint, sacroiliitis. 4 clinical suspicion of si. some of them can have important clinical significance in patients' management. the aim of this study was to identify the nature and analyze the frequencies of various incidental findings that were observed during the mri of sij in both the genders, and to compare their frequencies in different groups. materials and methods this observational study was carried out at radiology department of a tertiary care hospital in rawalpindi, pakistan, from january 2018 to march 2021, after approval from hospital's ethics review committee. all patients undergoing mri of sij were included, regardless of age or gender, employing consecutive, non-probability sampling technique. those patients were excluded who could not lie down supine in mr gantry to complete the examination. data regarding age, gender, mri findings related to sij and other tissues were recorded. si on plain mri was defined as sub-articular bone marrow oedema in at least two consecutive images, 5,6 or more than one lesion in a single slice. incidental findings were defined as all abnormal findings that introduction inflammation of sacroiliac joints (sij) is usually a 1 diagnosis of exclusion. magnetic resonance imaging (mri) has emerged as an important technique for diagnosis and follow-up of patients with sacroiliitis 2 (si). it can detect acute inflammatory changes across the joints even when plain radiographs are normal. initial changes of sub-chondral oedema are 3 picked up easily. there are multiple pathologies that can clinically mimic this disease, for example genitourinary, hip, muscle, and lower back pathologies and elicit request for mri of sij due to incidental findings observed on magnetic resonance imaging of sacroiliac joints 1 2 aasma nudrat zafar , saqib qayyum ahmad correspondence: dr. aasma nudrat zafar assistant professor department of radiology fauji foundation hospital & foundation university school of health sciences, islamabad, pakistan e-mail: aasmarad@gmail.com 1 department of radiology fauji foundation hospital & foundation university school of health sciences, islamabad, pakistan 2 department of pathology bahria international hospital, rawalpindi funding source: nil; conflict of interest: nil received: february 09, 2022; revised: august 16, 2022 accepted: september 13, 2022 sacroilic joints mrijiimc 2022 vol. 17, no.3 175 were seen other than or in addition to si, including clinically significant normal anatomical variants. scans were performed on 1.5 tesla mri unit (toshiba vintage titan), using body flexed array coil in supine position. the sequences included coronal stir (short-tau inversion recovery) along long axis of sacrum and perpendicular to second sacral vertebral body, axial t2-weighted (fat saturated), coronal obliques (t1 and t2-weighted) and sagittal t2 weighted. mri scans of patients were studied for presence or absence of si by radiologist having more than five years' experience of reporting. demographic data of all the patients was recorded. in addition to documenting presence or absence of si, data was also collected regarding the presence of any incidental finding. this included scrutiny of visualized lumbo-sacral spine, genitourinary organs, hip joints, muscles, and soft tissues. patients were arbitrarily divided, decade-wise into seven age groups, viz. group 1 (11-20 years), group 2 (21-30 years), group 3 (31-40 years), group 4 (41-50 years), group 5 (51-60 years), group 6 (61-70 years), and group 7 (71-80 years). the frequency of incidental findings was recorded for each age group. the data was entered into statistical package for social sciences version (version 21.0) for analysis. mean and standard deviation were calculated for quantitative variables. frequency and percentage we re ca l c u l ate d fo r q u a l i tat i ve va r i a b l e s . frequencies of si and incidental findings were compared in males and females using chi-square test considering p-value < 0.05 as significant. patients were also divided into those with, and those without si. frequencies of incidental findings were compared in both groups employing chi-square test, considering p-value < 0.05 as significant. results a total of 302 subjects were included in the study. patients' age ranged from 12 to 80 years with mean and median ages as 33.6 (sd+10.7) and 33 years respectively. most of the patients, i.e. 114 (37.7%) th out of 302, were in 4 decade of life. age distribution of patients and frequency of patients showing incidental finding on mri of sijs in different age groups are shown in the fig 1, and table i. female to male ratio was 1.9. mean ages for female and male were 35.3 (sd+ 10.52) and 30.2 (sd+ 10.51) respectively. si was seen in 118 (58.4%) of 202 females as compared 46 (45.5%) of 101 males. difference was significant with p-value 0.030 (table ii). among the females, 87 (43.3%) of 202, and among the males 39 (38.6%) of 101 showed incidental findings. difference was not significant with p-value 0.437 (table ii). fig 1: distribution of the frequency distribution of patients (shown along y-axis), subjected to magnetic resonance imaging of sacroiliac joints, according to decade-wise age groups (shown along x-axis). table i: frequency of patients showing incidental finding on magnetic resonance imaging of sacroiliac joints in different age groups (n=302) table ii: distribution of sacroiliitis and incidental findings in male and female patients jiimc 2022 vol. 17, no.3 176 sacroilic joints mri out of 302 patients, 164 (54.3%) were diagnosed as having si, according to mri criteria. in this group of patients, 64 (21.2%) showed at least one incidental finding. the second group of 138 (45.7%) patients revealed no mri evidence of si. among the latter group, 62 (20.5%) had incidental findings. no significant difference (p-value 0.300) was observed between the patients in two groups with respect to prevalence of incidental findings (table iii). discussion sij can be imaged using plain radiographs, fluoroscopy, computerized tomography, nuclear imaging, positron emission tomography, sonography 7 and mri. mri has revolutionized the diagnosis of si. it is superior to the rest of imaging modalities due to excellent depiction of bone marrow and soft tissue contrast; hence it enables detailed evaluation of tissues in addition to sij. moreover, it is radiationfree and can be safely used in younger patients and those of reproductive age. earliest changes of subchondral marrow oedema are well identified on mri. however, the imaging time is relatively longer than the rest of the modalities, rendering it difficult for the patients with severe pain to lie supine for the examination. on the other hand, radiographic manifestations of si occur much later in the course of the disease and the procedure is attended with risk of 2 irradiating pelvic organs. si can be due to multiple causes, e.g., infection, 8 inflammation, neoplasia, or trauma. early diagnosis of this entity is crucial in the management to prevent complications like chronic backache, hip pain and muscle wasting. due to complex pelvic anatomy, there is significant overlap of symptoms of bones, joints, soft tissues, genitourinary and gastrointestinal system diseases. a good clinical history and examination remains the mainstay of management 9 and must be obtained by the radiologist. differential diagnoses of sacroiliitis include ankylosing spondylitis, fractures around hip joint, tendinitis, piriformis syndrome, pyogenic infections, 4 tuberculosis, and trochanteric bursitis. the joints can show inflammatory changes in pregnancy and other hyperand hypomobile states. obesity is also a risk factor. malignant causes e.g. multiple myeloma and non-malignant etiologies such as osteitiscondensens-ilii can also be a cause of painful sij. we diagnosed one patient with latter condition during table iii: frequency of incidental findings in patients with and without sacroiliitis (si) on magnetic resonance imaging (mri) of sacroiliac joint (n=302) most common incidental finding was lower lumbar disc degenerative disease (llddd) that was present in 66 (21.5%) of 302 patients. it was seen in 37 (21.2%) patients with si and 29 (9.6%) patients without si (p=0.746, not significant). distribution of various incidental findings on mri, in groups of patients with and without evidence of si is shown in table iv. table iv: distribution of various incidental findings on magnetic resonance imaging (mri), in groups of patients with and without evidence of sacroiliitis (si). total number of patients=302 jiimc 2022 vol. 17, no.3 177 sacroilic joints mri this study. functional causes like scoliosis and leglength discrepancy can cause inflammatory changes at sij. hip degenerative and inflammatory arthritis 10 should also be looked for while interpreting sij. acute si manifests as bone marrow edema in subchondral location; this is the most important 11 criterion for defining active disease on mri. acute disease can show as joint fluid, sub-chondral or soft tissue edema. edema is manifested as hypo-intense signal on t1-weighted imaging and high signal intensity on t2 and stir sequences. earliest signs of cartilage and bone destruction can be picked up by 12 mri. active or acute si is best seen on fluidsensitive sequences like stir sequence; post 13 contrast imaging is not essential. features of chronic disease include structural changes such as new bone formation or sclerosis, fat deposition, erosions, joint space narrowing and ultimately, 14 ankylosis. erosions and ankylosis are best seen on t1-weighted images. a newer technique, mri-based synthetic computed tomography (sct) is reported to depict better details of erosions, sclerosis and ankylosis in comparison to t1 weighted mr 15 imaging. a multi-centric study was carried out in belgium, canada and poland to determine common incidental 16 findings on mri of sij in children. out of 540 children, 106 (20%) had si and 228 (42%) patients showed one or more incidental finding on mri. our study, though not limited to children only, shows a similar frequency (41.7%; n=302) of incidental findings. commonest incidental finding in both the studies was lumbar disc degenerative changes. a study was conducted in turkey, which included only the female subjects, mainly to see the frequency of pelvic congestion syndrome in patients who 17 underwent mri of sij for clinically suspected si. the study revealed that 285 (37%) of 774 patients had incidental findings which included pelvic congestion, various other genitourinary system disorders, and musculoskeletal system disorders. the percentage of patients showing incidental findings is not much different from the percentage of such patients seen in our study. this turkish study showed that in the group of patients without si, incidental findings were seen in 182 (24%) patients. on the other hand, in the group of patients with si, the incidental findings were less common and were seen in 103 (13%) patients. these findings are also concordant with the findings of our study. moreover, in both the studies the frequency of incidentally discovered musculoskeletal diseases was more in the group with si than the other group. during literature search, we found a case-report of 18 paget's disease with sacroiliitis. our study did not find this entity in any of our patients. jans et al showed in their six-year retrospective analysis that non-inflammatory disease entities were more common than si on mri in patients with 19 inflammatory type back pain. they found that out of 691 subjects, 249 (36%)showed si on mri, whereas more than half (54.3%) of our patients were diagnosed as suffering from si. a uk-based study investigated the incidence of transitional vertebrae and numerical variants of the spine using mri. they found transitional vertebrae in 20 14 (3.3%) of 418 subjects. we came across lumbosacral transitional vertebrae in 7 (2.3%) of 302 patients. the limitation of our study is that the size of the sample is relatively small. secondly, it has been carried out in a single centre; therefore the results cannot be generalized. thirdly, we did not receive any patient less than 10 years of age, with a request for mri of sij. more research is needed to diagnose incidental findings in this age group. in case of children it is important to keep a low threshold for selection with regards to imaging, for detecting pelvic and skeletal pathologies. this is because the u n d e r l y i n g co n d i t i o n s ca n h ave l o n g te r m implications if not diagnosed early. conclusion incidental features on mri of sij are common and were seen in approximately two-fifth of our patients. these must be reported, as these can have important clinical implications. commonest incidental finding in our study was lumbar degenerative disc disease. no significant difference was observed between the patients with si as compared to those without si with respect to prevalence of incidental findings. in suspected cases of sacroiliitis with negative mri findings, some other possible cause of symptoms should be looked for. these incidental findings may help in explaining the cause of symptoms and aid in management. jiimc 2022 vol. 17, no.3 178 sacroilic joints mri references 1. buchanan bk, varacallo m. sacroiliitis. [updated 2021 aug 11]. in: statpearls [internet]. treasure island (fl): statpearls p u b l i s h i n g ; 2 0 2 1 j a n . a v a i l a b l e f r o m : https://www.ncbi.nlm.nih.gov/books/nbk448141/ 2. braga mv, de oliveira sc, vasconcelos ahc, lopes jr, de macedo-filho cl, et al.ramos lma prevalence of sacroiliitis and acute and structural changes on mri in patients with psoriatic arthritis. sci rep2020; 10:11580. doi: https://doi.org/10.1038/s41598-020-68456-7 3. tsoi c, griffith jf, lee rkl, wong pch, tam ls. imaging of sacroiliitis: current status, limitations and pitfalls. quant i m a g i n g m e d s u r g 2 0 1 9 ; 9 ( 2 ) : 3 1 8 3 5 . doi:10.21037/qims.2018.11.10. 4. lin c, mackenzie jd, courtier jl, gu jt, milojevic d. magnetic resonance imaging findings in juvenile spondyloarthropathy and effects of treatment observed on subsequent imaging. paediatric rheumatology 2014; 12:25. doi: 10.1186/1546-0096-12-25. ecollection 2014. 5. herregods n, dehoorne j, van den bosch f, jaremco jl, vlaenderen jv, et al. asas definition for sacroiliitis on joos r mri in spa: applicable to children?. pediatr rheumatol online j 2017;15(1):24. doi:10.1186/s12969-017-0159-z 6. maksymowych wp, lambert rg, østergaard m, pedersen sj, machado pm, weber u et al. mri lesions in the sacroiliac joints of patients with spondyloarthritis: an update of definitions and validation by the asas mri working group. a n n r h e u m d i s 2 0 1 9 ; 7 8 ( 1 1 ) : 1 5 5 0 1 5 5 8 . d o i : 10.1136/annrheumdis-2019-215589. 7. slobodin g, hussein h, rosner i, eshed i. sacroiliitis – early diagnosis is key. j. inflamm. res 2018; 11:339-44. doi: 10.2147/jir.s149494. ecollection 2018. 8. kok hk, mumtaz a, o'brien c, kane d, torreggiani wc, delaney h. imaging the patient with sacroiliac pain. can assocradiol j. 2016;67(1):41-51. doi: 10.1016/j.carj. 2015.08.001. 9. casiano ve, dydykam, varacallo m. back pain. [updated 2021 may 12]. in: statpearls [internet]. treasure island (fl): statpearls publishing; 2021 jan-. available from: https://www.ncbi.nlm.nih.gov/books/nbk538173/ 10. soi c, griffith jf, lee rkl, wong pch, tam ls. imaging of sacroiliitis: current status, limitations and pitfalls. quant i m a g i n g m e d s u r g . 2 0 1 9 ; 9 ( 2 ) : 3 1 8 3 3 5 . doi:10.21037/qims.2018.11.10 11. rudwaleit m, jurik ag, hermann kg, landewé r, van der heijde d, et al. defining active sacroiliitis on baraliakos x magnetic resonance imaging (mri) for classification of axial spondyloarthritis: a consensual approach by the a s a s / o m e r a c t m r i g r o u p . a n n r h e u m d i s 2009;68(10):1520-7. doi: 10.1136/ard.2009.110767. 12. hermann kg, bollow m. magnetic resonance imaging of sacroiliitis in patients with spondyloarthritis: correlation with anatomy and histology. rofo. 2014;186(3):230-7. doi: 10.1055/s-0033-1350411. 13. de hooge m, van den berg r, navarro-compán v, van gaalen f, van der heijde d, et al magnetic resonance huizinga t . imaging of the sacroiliac joints in the early detection of spondyloarthritis: no added value of gadolinium compared with short tau inversion recovery sequence. rheumatology ( o x f o r d ) . 2 0 1 3 j u l ; 5 2 ( 7 ) : 1 2 2 0 4 . d o i : 10.1093/rheumatology/ket012. 14. tezcan me, temizkan s, ozal st, gul d, aydin k, et ozderya a al. evaluation of acute and chronic mri features of sacroiliitis in asymptomatic primary hyperparathyroid patients. clin rheumatol 2016;35(11):2777-2782. doi: 10.1007/s10067-016-3172-6. 15. jans l.b.o, chen m, elewaut d, bosch f.v.d, carron p, ozderya a et al. mri-based synthetic ct in the detection of structural lesions in patients with suspected sacroiliitis: comparison with mri. radiology 2021; 298:343–9. doi: https://doi.org/10.1148/radiol.2020201537 16. schiettecatte e, jaremko jl, sudoł-szopińska i, znajdek m, mandegaran r, et al.swami v common incidental findings on sacroiliac joint mri in children clinically suspected of juvenile spondyloarthritis. eur. j. radiol open. 2020; 7:100225. doi: https://doi.org/10.1016/j.ejro.2020.100225 17. cimsit c, yoldemir t, tureli d, aribal me. evaluation of sacroiliac joint mri for pelvic venous congestion signs in women clinically suspected of sacroiliitis. acta radiologica. 2017;58(7):849-855. doi:10.1177/0284185116675656 18. antonelli mj, magrey m. sacroiliitis mimics: a case report and review of the literature. bmc musculoskeletdisord 2017;18(1):170. doi: 10.1186/s12891-017-1525-1. 19. jans l, van praet l, elewaut d, van den bosch f, carron p, jaremko jl et al. mri of the si joints commonly shows noninflammatory disease in patients clinically suspected of sacroiliitis. eur j radiol 2014;83(1):179-84. doi: 10.1016/j.ejrad.2013.10.001. 20. tins bj, balain b. incidence of numerical variants and transitional lumbosacral vertebrae on whole-spine mri. i n s i g h t s i m a g i n g 2 0 1 6 ; 7 ( 2 ) : 1 9 9 – 2 0 3 . d o i : https://doi.org/10.1007/s13244-016-0468-7. jiimc 2022 vol. 17, no.3 179 sacroilic joints mri conflict of interest authors declared no conflicts of interest. grant support and financial disclosure authors have declared no specific grant for this research from any funding agency in public, commercial or nonprofit sector. data sharing statment the data that support the findings of this study are available from the corresponding author upon request. this is an open access article distributed under the terms of the creative commons attributionnoncommercial 2.0 generic license. jiimc 2022 vol. 17, no.3 180 sacroilic joints mri original�article abstract objective: to identify the effect of tcotrienols on adventitial changes induced by high cholesterol diet in descending thoracic aorta of rabbits. study design: laboratory based randomized control trial. place and duration of study: the anatomy department of army medical college rawalpindi in collaboration th th with national institute of health, islamabad. the study commenced on 10 march 2009 and completed on 10 september 2009. materials and methods: thirty adult male new zealand white rabbits were randomly divided into three equal groups (i, ii & iii). group-i consumed standard nih diet while group-ii was fed 2% high cholesterol diet. group-iii animals were given the same diet as to group ii, however, tocotrienols 6 mg/kg body wt/day were also added to the diet. following six weeks of experiment, aorta of every animal was dissected. cross sections were taken from descending thoracic aorta and processed for light microscopic examination. in h&e and verhoeff stained slides, adventitial histomorphological changes were compared among the three groups. results: in rabbits on standard diet, tunica adventitia was a thin layer composed of loose network of collagen and elastic fibers which lacked lamellar pattern as that of media. adventitial cells were relatively scanty. in contrast, aortic adventitia in group-ii was thickened with increased number of inflammatory cells characterized by central round nucleus and foamy cytoplasm. above mentioned histological changes were present in groupiii but were of lesser degree than group-ii. mean±sd thickness of adventitia and inflammatory cells score was significantly greater in group-ii &iii when either was compared with group-i. however, group-iii showed 19% (p<0.05) reduction in adventitial thickening and & 36% (p<0.05) lesser inflammatory cells score versus group-ii. conclusion: tocotrienols decrease adventitial thickening and inflammation induced by high cholesterol diet in aorta of cholesterol-fed rabbits. key words: adventitia, high cholesterol diet, rabbit aorta, tocotrienols. 4 event in the process of atherogenesis. majesky et al labeled adventitia as a dynamic interface harboring progenitor cells which respond to arterial injury and 5 then migrate into tunica intima. gutterman proposed that future managements for prevention of atherosclerosis should focus on drug therapies 6 targeting adventitia of vessels. vitamin e includes eight chemically distinct substances: four tocopherols and four tocotrienols (alpha, beta, gamma and delta). heath benefits of vitamin e in the prevention and treatment of atherosclerosis have been postulated with conflicting results but more than 95 per cent studies of vitamin e were directed towards tocopherols and 7 tocotrienols remain poorly understood. moreover, available data regarding tocotrienols is mainly limited to their potent hypocholesterolemic, 8,9 antioxidant and anti-inflammatory properties and thus addresses a major void in evaluation of their effect on histomorphological aspects of the atherosclerosis. therefore, this experimental study was designed to investigate the effect of this lesser known form of introduction atherosclerosis is considered to be the most 1 common physical burden globally. despite the use of dietary modifications and newer pharmacological approaches, very few effective measures exist for the prevention and treatment of this disease. antiatherogenic effects of tocotrienols (members of vitamin e family) are also unclear as yet. traditionally, atherosclerosis is considered as disease of intima with involvement of media in later stages of disease progression. accordingly, intimal and medial thickening was accepted as the most appropriate 2 predictor of atherosclerosis. with the advancement of new era, however, it was noted that features of atherosclerosis definitely exist in the tunica 3 adventitia and adventitial inflammation is an early effect of tocotrienols on aortic adventitia of cholesterol-fed rabbits uzma shahid, asma hafeez, kaukab anjum, zubia athar, nomana mahmood correspondence: dr. uzma shahid associate professor, anatomy wah medical college, wah cantt department of anatomy wah medical college, wah cantt funding source: nil; conflict of interest: nil received: nov 02, 2016; revised: feb 08, 2017 accepted: may 01, 2017 effect of tocotrienols on aortic adventitiajiimc 2017 vol. 12, no.2 87 scored accordoing to the following criteria: 0 = no inflammatory cells, 1 = inflammatory cells present in ≥ 25 to < 50 per cent circumference, 2 = inflammatory cells present in ≥50 to < 75 per cent circumference, 3 = inflammatory cells present in ≥ 75 per cent circumference. inflammation was defined as presence of ≥ 25 mononuclear round cells with foamy cytoplasm per field with 40x 13,14 magnification objective. parametric data was analyzed using spss (statistical package for social sciences) windows version 20. quantitative data was expressed as mean ± s.d. for each variable, group differences were compared by one way analysis of variance (anova) followed by post hoc tukey test for intergroup comparison of parameters. all the results were considered statistically significant at a p-value less than 0.05. results in rabbits on standard nih diet, tunica adventitia was a thin layer composed of loose network of collagen and elastic fibers which lack lamellar pattern as that of media. adventitial cells were relatively scanty and mainly suggestive of fibroblasts (figure 1-a). vasa vasora and nervi vascularis were also scattered amongst the fibers. in contrast, aortic adventitia in group-ii appeared to be thickened especially beneath the intimal lesions (figure 1-b). this thickening was associated with increased number of mononuclear round cells with central nucleus and foamy cytoplasm. these cells were forming a g g re ga t e s i n a d v e n t i t i a a n d p e n e t ra t i n g medioadventitial interface (figure 1-d). above mentioned changes were present in group-iii (figure 1-c) but were of lesser degree than group-ii mean±sd thickness of adventitia and inflammatory cells score was significantly greater in group-ii &iii when either was compared with group-i. however, group-iii showed 19 % reduction in adventitial thickening and & 36% lesser inflammatory cells score versus group-ii (table-ii). vitamin e (tocotrienols) on aortic adventitia of rabbits fed high cholesterol diet. materials and methods the present study was a laboratory based randomized control trial conducted in the anatomy department of army medical college rawalpindi in collaboration with national institute of health (nih), islamabad. all experimental procedures were approved by the institutional animal ethical th committee. the study commenced on 10 march th 2009 and completed on 10 september 2009. inclusion criteria were thirty adult male new zealand white (nzw) rabbits, 10-18 months old and weighing 1.5 to 2.5 kg. female rabbits and animals with any evident pathology were excluded from the study. each rabbit was kept in a separate cage, at a standard temperature of 21 ± 20c with 12 hour light/dark cycle at nih. each animal was given 100g/day standard nih diet. water was available ad libitum. after one week of acclimatization to experimental conditions, thirty rabbits were divided into three equal study groups (i, ii&iii) by using nonprobability convenient sampling technique. group-i continued standard nih diet (100g / head/day) while each animal in group-ii was given 2% high cholesterol diet {2g cholesterol powder (applichem, germany) 10 mixed with 100g standard nih diet/ head/day. group-iii animals were fed the same diet as to group ii, however, tocotrienols {mixture of 90% delta & 10% gamma (american river nutrition, inc. hadley, ma. 11 usa)} 6 mg/kg body wt/day were also added to the diet. composition of diet per animal in each group is given in table-i. after six weeks of experiment, rabbits were euthanized. cross sections were taken from descending thoracic aorta and placed in 10% formol calcium. after 48 hours, tissues were processed for light microscopic examination. h&e sta i n i n g wa s d o n e fo r h i sto m o r p h o l o g i ca l examination. for morphometry, verhoeff vangeisson stain was used for the delineation of collagen and elastin. under 40x objective, at three point of maximal luminal narrowing, adventitial thickness (at) was measured from media-adventitia interface (external elastic lamina) to the adventitiaperiadventitia interface (outer edge of collagen 12 containing dense fibrous tissue). mean of the three values was calculated for each cross section. inflammation in adventitia was semiquantitatively table i: showing composi�on of diet per animal per day in each group effect of tocotrienols on aortic adventitiajiimc 2017 vol. 12, no.2 88 which in turn produce increase amount of extracellular matrix. these fibrobasts also generate an inflammatory response by releasing cytokines 16,17 and chemokines. growth of vasa vasora further modulates arterial wall structure by acting as conduit 16 for inflammatory and progenitor cells. adventitial thickening and inflammation, in response to high cholesterol diet, as observed in the current experiment, supports the findings of gradus-pizlo et 17 al who found significantly greater thickness of adventitia in patients with coronary atherosclerosis than those with normal arteries. this adventitial thickening was associated with enhanced number of mononuclear vacuolated cells especially in the outer 18 half of vessel. according to dushkin, these cells are considered as an attribute to generate inflammation. 19 maillaro & taylor reported that population of these inflammatory cells include lymphocytes, monocytes, macrophages and fibroblasts which work in concert to elicit an inflammatory response that progresses towards tunica intima. in reviewing the immune and i n f l a m m a t o r y m e c h a n i s m s r e g a r d i n g 20 atherosclerosis, galkina and ley stated that these cells are found in normal adventitia but their number expands in atherosclerotic lesions. contrary to our 21 findings, deopujari and dixit reported that basic pathological changes occur in tunica intima and media and tunica adventitia is not affected in coronary artery disease. tocotrienols mediated substantial reduction in adventitial thickening is 22 quite close to the findings of qureshi et al whose striking results highlighted the atheroprotective properties of novel tocotrienols of rice bran by substantial reduction of 57 per cent, 33 per cent and 47 per cent in growth of atheromatous plaque in three genotypes of mice. comparable results were seen in a recent local study which showed that tocotrienols significantly decrease atheromatous 23 changes in diet induced diabetic balb/c mice. however, our findings are not consistent with ismail 2 4 et al who found no beneficial effect on atherosclerosis development in six rabbits given palm tocotrienols plus 2 per cent cholesterol for 10 weeks compared with the six rabbits given cholesterol alone and six rabbits on regular diet. the difference can be accredited to relatively small sample size in their study and more severe nature of the disease. discussion the present experimental study evaluated the effect of tcotrienols (mixture of 90% delta & 10% gamma) on adventitial atherosclerotic changes induced by high cholesterol diet in aorta of rabbits. our results suggested that tocotrienols supplementation significantly decrease adventitial thickening and inflammation. adventitial thickness displays a strong correlation with atherosclerosis risk factors 12,15 especially dyslipidemias. atherogenic stimuli excites adventitial cells particularly fibroblasts, table ii: showing comparison of adven��al thickness and inflammatory cells score between rabbits fed standard nih diet (group-i), 2% high cholesterol diet (group-ii), 2% high cholesterol diet+ tocotrienols (group-iii) for 6 weeks fig 1: aor�c cross sec�ons of rabbit fed standard nih diet (1-a), 2% high cholesterol diet (1-b, 1-d, ) & 2% high cholesterol diet+ tocotrienols (1-c) for 6 weeks (1-a, 1-b, 1-c: magnifica�on x400, verhoeff van geisson stain; 1-d: arrow indicates inflammatory cells, h&e stain). ti: tunica in�ma, tm: tunica media. ta: tunica adven��a effect of tocotrienols on aortic adventitiajiimc 2017 vol. 12, no.2 89 the other half of the natural vitamin e family. mol aspects med. 2007; 28: 692–728. 8. aggarwal bb, sundaram c, prasad s, kannappan r. tocotrienols, the vitamin e of the 21st century: its potential against cancer and other chronic diseases. biochemical pharmacology. 2010; 80: 1613-31. 9. qureshi aa, khan da, mahjabeen w, trias am, silswal n, qureshi n. impact of δ tocotrienol on inflammatory biomarkers and oxidative stress in hypercholesterolemic subjects. j clin exp cardiolog. 2015; 6: 367. 10. yang al, jen cj, chen hi. effects of high-cholesterol diet and parallel exercise training on the vascular function of rabbit aortas: a time course study. j appl physiol. 2003; 95: 1194–1200. 11. yu sg, thomas am, gapor a, tan b, qureshi n, qureshi aa. dose response impact of various tocotrienols on serum lipid parameters in 5 week old female chickens. lipids. 2006; 41: 453-61. 12. kazmierski r, watala c, podsiadly e, dorszewska j, kozubski w. association of atherosclerotic risk factors with carotid adventitial thickness assessed by ultrasonography. journal of clinical ultrasound. 2009; 37: 333-41. 13. moreno pr, purushothaman kr, sirol m, levy ap, fuster v. neovascularization in human atherosclerosis.circulation. 2006; 113: 2245-52. 14. phinikaridou a, hallock kj, qiao y, hamilton ja. a robust r a b b i t m o d e l o f h u m a n a t h e r o s c l e r o s i s a n d atherothrombosis. j lipid res. 2009; 50: 787–97. 15. skilton mr, sullivan tr, ayer jg, harmer ja, toelle bg, webb k, et al. carotid extra-medial thickness in childhood: early life effects on the arterial adventitia. atherosclerosis. 2012; 222: 478-82. 16. stenmark kr, frid mg, yeager m, li m, riddle s, mckinsey t, et al. targeting the adventitial microenvironment in pulmonary hypertension: a potential approach to therapy that considers epigenetic change. pulmonary circulation. 2012; 2: 3-14. 17. gradus pizlo i, bigelow b, mahomed y, sawada sg, rieger k, feigenbaum h. left anterior descending coronary artery wall thickness measured by high-frequency transthoracic and epicardial echocardiography includes adventitia. the american journal of cardiology. 2003; 91: 27-32. 18. dushkin m. macrophage/foam cell is an attribute of inflammation: mechanisms of formation and functional role. biochemistry (moscow). 2012; 77: 327-38. 19. maiellaro k , taylor wr. the role of the adventitia in vascular inflammation. cardiovascular research. 2007; 75: 640–8. 20. galkina e, ley k. immune and inflammatory mechanisms of atherosclerosis. annu rev immunol. 2009; 27: 165–97. 21. deopujari r, dixit a. the study of age related changes in coronary arteries and its relevance to the atherosclerosis. j anat soc india. 2010; 59: 192-6. 22. qureshi aa, salser wa, parmar r, emeson ee. novel tocotrienols of rice bran inhibit atherosclerotic lesions in c57bl/6 apoe deficient mice. j. nutr. 2001; 131: 2606-18. 23. kiani mrb, butt sa, arshad m. histological effects of tocotrienol on intima thickness in aorta of diabetic mice. pakistan armed forces medical journal. 2011: 61: 555-60. as inflammation is the hallmark of atherosclerotic 25 lesions. reduction in adventitial inflammatory cells, 26 in our study, is in supportive context with wu et al who concluded that tocotrienols possess potent anti-inflammatory activity by suppressing the expression of inflammatory mediators in human monocytic cells. many researchers have compared anti-inflammatory properties of various tocotrienols and tocopherols and found delta tocotrienol as the 2 7 , 2 8 m o s t p o t e n t i s o f o r m . i n a s t u d y o n hypercholesterolemic subjects, delta tocotrienol was given in doses of 125, 250, 500, 750 mg/day for 4 weeks. in each concentration, delta tocotrienol was therapeutically effective in reducing biomarkers of oxidative stress and inflammation including serum nitric oxide, c-reactive protein, malondialdehyde, 9 and δ-glutamyl-transferase. in conclusion, our experimental data suggests that tocotrienols exhibit significant potential in lowering adventitial atherosclerotic changes induced by high cholesterol diet in aorta of rabbits. the study had been carried out in an experimental model of atherosclerosis that differs from chronic lesions observed in human cases. therefore, human trials should be considered necessary for final elucidation of tocotrienols as atherosuppressive agents. moreover, mechanisms involved in suppression of a t h e r o s c l e r o t i c c h a n g e s w a r ra n t s f u r t h e r investigations. references 1. beaglehole r, bonita r. global public health: a scorecard. lancet. 2008; 372: 1988-96. 2. o'leary dh, bots ml. imaging of atherosclerosis: carotid intima–media thickness. european heart journal. 2010; 31: 1682-9. 3. ogeng'o j, ongeti k, obimbo m, olabu b, mwachaka p. features of atherosclerosis in the tunica adventitia of coronary and carotid arteries in a black kenyan population. anatomy research international. 2014; 45674: 1-5. 4. wang jl, ma sq, li l, liu gq, hu wc, ma r. correlation of inflammatory cells in adventitia and formation and extending of atherosclerotic lesions in coronary artery of apolipoprotein e gene knockout mice. chinese journal of physiology. 2013; 56: 77-82. 5. majesky mw, dong xr, hoglund v, mahoney wm, daum g. the adventitia a dynamic interface containing resident progenitor cells. arterioscler thromb vasc biol. 2011; 31: 1530-9. 6. gutterman dd. adventitia-dependent influences on vascular function. am j physiol 1999; 277: h1265. 7. sen ck, khanna s, roy s. tocotrienols in health and disease: effect of tocotrienols on aortic adventitiajiimc 2017 vol. 12, no.2 90 cells. mol nutr food res. 2008; 52: 921-9. 27. yam ml, rahma s, hafid a, cheng hm, nesaretnam k. tocotrienols suppress proinflammatory markers and cyclooxygenase-2 expression in raw264.7 macrophages. lipids. 2009; 44: 787–97. 28. wong wy, ward lc, fong cw, yap wn, brown l. antiinflammatory γ-and δ-tocotrienols improve cardiovascular, liver and metabolic function in diet-induced obese rats. european journal of nutrition. 2015; 56: 133-50. 24. ismail nm, ghafar na, jaarin k, khine jh, top gm. vitamin e and factors affecting atherosclerosis in rabbits fed a cholesterol rich diet. international journal of food sciences and nutrition. 2000; 51: 79-94. 25. l i b by p. h i sto r y o f d i s cove r y : i nf l a m m at i o n i n atherosclerosis. arterioscler thromb vasc biol. 2012; 32: 2045–51. 26. wu sj, liu pl, ng lt. tocotrienol-rich fraction of palm oil exhibits anti-inflammatory property by suppressing the expression of inflammatory mediators in human monocytic effect of tocotrienols on aortic adventitiajiimc 2017 vol. 12, no.2 91 page 22 page 23 page 24 page 25 page 26 original�article abstract objective: the objective of this study was to find out the prevalence of pregnancy related low back pain in the third trimester and evaluate its impact on the quality of life, functional limitation and physical disabilities of pregnant women. study design: a cross-sectional descriptive study. place and duration of study: the study was conducted at benazir bhutto women and children care hospital (dhq), abbottabad from jan 5, 2014 to feb 26, 2014. materials and methods: total 104 patients of 3rd trimester were selected on probabilistic sampling (simple random sampling). diseased, disabled, women with height less than 4.5 feet (137cm) and third grade obese were excluded. a structured pre-tested questionnaire was used to access rating of pain intensity, its effect on quality of life, functional limitation and daily activities. informed written consent was taken from the participants of study. statistical analysis was done by spss version-21. results: among 104, eight women data was not taken into account due to exclusion criteria. mean age of reaming n96 women was 24.56 (min 18-max 37) years and height was 160.39 (min 144max 176) cm. among n96, n66 (68.8%) had pregnancy-related low back pain (plbp). in which, n2 (3%) were totally dependent, n20 (20.8%) were physically inactive and n30 (31.3%) showed 61%-80% of disability scale. pain intensity of n36 (54.5%) women was moderate. conclusion: the prevalence of pregnancy related low back pain is quite high (68.8%) in abbottabad population. plbp adversely affect their quality of lives, limit their routine activities and productivities and even make them physically disable. there is a significant difference between women having pregnancy related low back pain and women without it. (p=0.452). women especially, young (p=0.390) and in first pregnancy (p=0.095) have severe pain intensity that interferes significantly with their daily living activities. key words: low back pain, physical disabilities, pregnancy. 5 always dull in quality. it restricts spine movement 6 and increases in its intensity on bending forward. in pregnant women, it is most common and 7 significantly affects their daily activates. during pregnancy, many factors like physiological, mechanical, hormonal and circulation changes cause 7,8 plbp. hormonal changes stretch ligaments and muscles attached to pelvic joints for accommodation of developing infant. all lumber and pelvic joints become more flexible. lumber lordosis that develops at later stages of pregnancy, gravity shifting, postural changing, and workload lead towards plbp. one study revealed that severe type of plbp at during sleeping is the result of venous engorgement in the pelvis. the enlarging uterus exerts pressure on inferior vena cava that results in venous congestion and hypoxia in lumber spine and 9 pelvis. plbp has been known and described many centuries ago. it has been mentioned for the first time by 1 0 h i p p o c rate s ( 4 0 0 . b .c . ) . l atte r, n u m e ro u s introduction during last decade, complains of pregnancy related low back pain (plbp) and pelvic girdle pain (pgp) has 1–4 become most common. low back pain (lbp) is a musculoskeletal symptom or simply a pain that is due to pelvic muscles stiffness in between 12th rib and inferior gluteal folds and/or symphysis pubis. it may or may not be associated to the referred pain of legs. lpb during the course of pregnancy is plbp. it is prevalence of pregnancy related low back pain in third trimester and its impact on quality of life and physical limitation 1 2 3 4 5 6 muhammad junaid khan , aamir israr , isma basharat , abaidullah shoukat , nazish mushtaq , hamza farooq correspondence: dr. muhammad junaid khan department of gyne & obs azad jammu & kashmir medical college muzaffarabad, ajk e-mail: drmjunaidkhan@yahoo.com 1,3,4,5,6 department of gyne & obs azad jammu & kashmir medical college muzaffarabad, ajk 2 deputy ms benazir bhutto women and children care (dhq) hospital, abbottabad funding source: nil; conflict of interest: nil received: sep 10, 2016; revised: feb 11, 2017 accepted: feb 14, 2017 prevalence of pregnancy related low back painjiimc 2017 vol. 12, no.1 39 less than 4.5 feet (137cm) and with third grade obesity were excluded from the research. third trimester pregnant women were first confirmed for the complaint of low back pain by a specialist, sitting in the same opd at same time. all the data and questions were recorded in a standardized subject profile. this profile was pretested at 10 patients and later on some unethical question were removed. each patient was interviewed individually for quality of life, routine work, effect of low back pain on their daily activates, pain intensity and to what extent their pain cause disability. socioeconomic data was also collected from each patient. other questions related to pregnancy were, gestational age, previous pregnancies, and mode of deliveries. height and weight was also taken for body mass index (bmi). the katz's activity's daily living index (adl), short form of who quality of life questionnaire (whoqolbref), urdu version, rating of pain intensity, and the oswestry low back pain disability index (odi) were also included. pain intensity was measured by a visual analog scale (vas), numeric pain intensity scale. functional pain scale (fps) was also used to reach the effect of pain severity on their daily activities. categorical variables were explained by percentages while numerical variables by histogram, mean, minimum and maximum. one-sample t-test was applied to reach the significance of different variables. all calculated data was computed according to validated scoring methods of each tool. statistical analysis was done by spss software (version 21). original patient's data were filed and was locked by principle author. informed written consent was taken from all patients. they were assured for maintaining their privileges and anonymity. the study was approved by ethical review board of aforementioned hospital. results a total of 104 third trimester pregnant women participated. eight women data was not taken into account due to exclusion criteria and only 96 were included in this study. mean age of these 96 women was 24.56 (18-37) years, height 160.39 (144-176)cm, weight 67.67 (45-86)kg, bmi 26.4 (1937), and mean duration of pregnancy was 8.08 (7-10)months. all women were housewives and most women were non-matriculated (n=48) and (n=30) were above matric. younger women aged 22-28 years (n=27) contributions was led by vesalins, ambroise pare, severin pinean, albinus of leyden, william hunter, luschkaamd and many others. their core of discussion was whether lbp and/or pgp was a constant/normal phenomena or exceptional/ 11 pathological. in 1870, snelling defined the pelvic syndrome and confirmed that lbp and/or pgp is not 12 pathologic at its own. it is actually caused by relaxation of pelvic articulation, which is due to the pressure of fetal head on pelvic bone, likewise, fetal size, physical and muscular weakness, a retroverted uterus and difficult labor causes painful sensation.6 in 1962 walde differentiated between pgp and lumbar pain (lp) and ostgaard et al. set the criteria 12 for diagnosis. studies show that its prevalence varies between 3,12 3.90%-89.88%. literature is full of the risk factors associated with plbp. the most common of them (in descending order) are previous lbp, increased weight (bmi), young age, strenuous work, 4 multiparous, lbp with menstruation and smoking. more than 80% pregnant women with plbp experience difficulties during their routine activates. it lowers their quality of life, makes them disable for 2,3 many activities and compel them for frequent bed 1,13 rest. whether they have back pain or not they have 3 functional disabilities. the aim of this study was to find out the prevalence of plbp and evaluate the impact of plbp (in the third trimester) on the quality of life and physical limitation of pregnant women. to compare the standard who values of quality of life with this study, and to analyze the correlations among physical ability, pain intensity and functional limitations of the pregnant women with plbp. materials and methods a cross-sectional descriptive study, conducted in benazir bhutto women and children care hospital (dhq), abbottabad, during 05 jan 2017 to march 2014. total 104 patients of 3rd trimester were selected by simple random sampling during opd timing. selected patients were screened for inclusion and exclusion criteria. the criterion for inclusion in the research was last trimester pregnant women and coming to the mentioned hospital for routine checkup, while those with preeclampsia, eclampsia, systemic disease and psychiatric problems, congenital or physical disable, patients with height jiimc 2017 vol. 12, no.1 40 prevalence of pregnancy related low back pain disability, i.e., their back pain impinged on all aspects of life and positive intervention is recommended for such patients (table v). 40.9% had greater prevalence of plbp than adolescent and middle aged (table i). jiimc 2017 vol. 12, no.1 table i: age categories versus pregnancy-related low back pain among them, 50 (52.1%) were living in city and almost all of them were using pulses, vegetable of different variety, mutton and rice once in a week. none of them was anemic or male nutritional. among 96 (100.0%) 3rd trimester pregnant women, 66 (68.8%) had pregnancy-related low back pain (plbp). all these 66 had suffered plbp in last two weeks. in other words, plbp was considered when patients experienced it during last two weeks. there was a significant different between those women that had plbp and those without plbp (p<0.005). among 66 women with plbp, katz activities of daily life resulted in two (3%) patients physically totally dependent on their care providers, 2 (3%) were neither dependent nor independent and remaining 62 (93%) were independent. all women without low back pain were totally independent. among 74 overweight women, 53 (80.3%) had plbp. (table ii) quality of life (qol) of n66 women with plbp was measured in four domain and their score were transformed to meet the standard results of who. table ii: bmi and pregnancy-related low back pain the domain were physical, psychological, social relationship and environmental with mean values of (95.00, 79.64, 48.03, 126.30) respectively. (table iii). pain intensity of n=96 has been showed in (table iv). among them, n=36 (54.5%) women was with moderate intensity which interferes significantly with their daily living activities. according to oswestry low back pain disability scoring, most women (n=30, 45.5%) showed 61–80% table iii: comparison of transformed domains of this study with whoqol-bref values. table iv: severity of low back pain (n=96) table v: oswestry low back pain disability scoring explained physical disabili�es due to plbp (n=66) when the same tool was applied to those women with moderate pain, majority of them n=23 (63.9%) also resulted in the same 61–80% disability index. functional pain scale values was computed for limitation of daily activities. among 66 patients, 61 patients had plbp at the time of interview and functional pain scale was used for their limitation of daily activities. in this scale, number of women are shown on y-axis and physical limitation on x-axis. (zero [0] is considered as no effect of pain on their daily lives and ten (10) as incapable of doing anything). its results are shown in figure 1. discussion to our best knowledge, this is the first ever study done in hazara population (pakistan) on the impact of quality of life, physical limitation and intensity of pregnancy-related low back pain (plbp). it has been 41 prevalence of pregnancy related low back pain this study strongly suggest that greater the weight of pregnant women, greater will be the chances for plbp. due to different criteria and tools used for pain intensity, very little data is found for comparison 3 6 purpose. two studies mentioned 33.3% and 44% women with moderate pain. whereas this study revealed n=36 (37.5%) suggesting that this moderate intensity of pain is more common and much enough to affect their routine lives. quality of life (qol) of n=66 women with plbp was measured in four domain and their score were transformed to meet the standard results of who. the domain were physical, psychological, social relationship and environmental. according to the results of the world health organization quality of life (whoqol bref) research, the mean scores of physical, psychological, social and environment domains for healthy women were found to be 13.4, 14 14.0, 14.1, 13.5 respectively and 14.5, 13.9, 15.3, 13.5 respectively in a study conducted on healthy 21 women in turkey , whereas our study resulted in (95.00, 79.64, 48.03, 126.30) respectively. study limitations included difficult patient relation while interviewing, small sample size and language barrier. in order to meet the standard of social and psychological relationship with this region, and of course, according to the guidelines of whooqolbref, few questions were omitted and the syntax of this tool was modified. it is recommended for gynecologists that they primarily educate their patients with plbp for its prevention. postural education, physical and alternative therapy and use of support belt, postural pillows and heating pad should always be encouraged. as plbp appeared the most common problem, therefore its evaluation and proper care should be included in antenatal care programs as well as preventive health programs. in order to alleviate plbp and reach the standard criteria of who for quality of life, researchers have to study further in large population and improve mother’s life. conclusion the prevalence of pregnancy related low back pain is quite high (68.8%) in abbottabad population. plbp is among the most common problems of pregnant women of abbottabad. plbp adversely affect their mentioned that plbp is a common problem in a 1-4 plethora of studies. its prevalence exists between 12 3.90%-89.88%. it usually starts as the pregnancy begins but gain its severity during sixth and ninth 4 month of pregnancy. that is why we studied third trimester pregnant women to reach for its maximum effect on quality of life and functional disability. in our study, it appears the most common problem among pregnant women in hazara population with prevalence rate of (n=66) 68.8%. among the 14 observed factors that lead to plbp are young age first pregnancy, strenuous activities, over weight and height ranges 155-164cm. average prevalence rate 15 of pregnancy related lpb is 50%. however due to recall bias, its prevalence differs for retrospective and perspective studies. our study resulted in 68.8%, 16 17 which is very close to 69%-italy , 66%-swedish. 1,18 19 68.6% and 67% usa. 71.3% spanish women and 3 68.5% new haven. according to oswestry disability index, (odi) n=30 (45.5%) are crippled (60%-80%). this is closer to a 20 study done on beninese women 33.33%. but another study mentioned it as 80% whose daily 3 activates are worsen by their plpb. the result of this study, i.e., n=21 (31.8%) women bound to bed, is 9 close to sabino j's study (30%). younger women had greater prevalence of plbp than 7 adolescent, middle aged and aged women. the relation of plbp with bmi is controversial. mostly overweight women n=53 (80.3%) complaint about plpb. morgen et al. also found that women between bmi 24 and 30 had plbp.7 some of the studies reported that bmi is not a risk factor for plpb4 but jiimc 2017 vol. 12, no.1 fig 1. func�onal pain scale values versus limita�on of daily ac�vi�es. y-axis=number of women and on x-axis=physical limita�on (zero [0] is considered as no effect of pain on their daily lives and ten (10) as incapable of doing anything). 42 prevalence of pregnancy related low back pain 8. vleeming a, albert hb, ostgaard hc, sturesson b, stuge b. european guidelines for the diagnosis and treatment of pelvic girdle pain. eur spine j. 2008; 17: 794-819. 9. sabino j, grauer jn. pregnancy and low back pain. curr rev musculoskeletal med: 2008; 1: 137-41. 10. nikolaos kk, craig sr, peter vg. pregnancy-related pelvic girdle pain: an update. bmc med: 2011; 9: 15. 11. abramson d, summer m, wilson p. relaxation of the pelvic joints in pregnancy. surg, gynecol obstet: 1934; 58: 595–613. 12. bastiaanssen jm, de bie ra, bastiaenen ch, essed gg, van den brandt pa. a historical perspective on pregnancyrelated low back and/or pelvic girdle pain. eur j obst gynecol reprod biol: 2005; 120: 3-14. 13. stuge b, hilde g, volestad n. physical therapy for pregnancy-related low back and pelvic pain: a systematic review. acta obstetricia et gynecoogical scandinavica: 2003; 82: 983-90. 14. what quality of life? the whoqol group. world health organization quality of life assessment. world health forum: 1996; 17: 354–6. 15. sihvonen tm, makkonen m, airaksinen o. functional changes in back muscle activity correlate with pain intensity and prediction of low back pain during pregnancy. arch phys med rehabil: 1998; 79: 1210-2. 16. padua l, padua r, bondi r, ceccarelli e, caliandro p, d'amico p, et al. patient-oriented assessment of back pain in pregnancy. europian spine journal: 2002; 11: 272–5. 17. biering-sorensen f. low back trouble in a general population of 30, 40, 50, and 60-year-old men and women: study design, representativeness, and basic results. dan med bull: 1982; 29: 289 –99. 18. skaggs cd, prather h, gross g, george jw, thompson pa, nelson dm. back and pelvic pain in an underserved united states pregnant population: a preliminary descriptive survey. journal of manipulative and physiological therapeutics: 2007; 30: 130–4. 19. francisco mk, emma g, ana r, lourdes g, víctor a. prevalence and factors associated with low back pain and pelvic girdle pain during pregnancy. pine 2012; 37: 1516–33. 20. charpentier k, leboucher j, lawani m, toumi h, dumas ga, pinti a. back pain during pregnancy and living conditions: a comparison between beninese and canadian women. ann phys rehabil med: 2012; 55: 148-59. 21. altparmak s, eser e. the quality of life in 15-49 years old who one married women. j fam soc: 2007; 3: 29-34. quality of lives, limit their routine activities and productivities and even make them physically disable. younger aged women with first parity are more prone to sever plbp. finally, this study underscore the fact that such worse condition of pregnant women over here is always ignored by both parties, patients as well as by the doctor. acknowledgements special regards and lot of thanks to 1. dr. rahul raul (dms, wch. benazir bhutto women and child care hospital (dhq ), abbottabad). 2. dr. kawsar inayat (obs,gynae. ap, women medical college abbottabad). 3. dr. nargis danish (obs, gynae. benazir bhutto women and child care hospital (dhq ) abbottabad). references 1. wang sm, dezinno p, maranets i, berman mr, caldwellandrews aa, kain zn. low back pain during pregnancy: prevalence, risk factors, and outcomes. obstetgynecol: 2004; 104: 65-70. 2. carragee ej. persistent low back pain. new england journal of medicine: 2005; 352: 1891–8. 3. katonis p, kampouroglou a, aggelopoulos a, kakavelakis k. pregnancy-related low back pain. hippokratia: 2011; 15: 205-10. 4. ansari nn, hasson s, naghdi s, keyhani s, jalaie s. low back pain during pregnancy in iranian women: prevalence and risk factors. physiotherapy theory and practice: 2010; 26: 40–8. 5. vermani e, mittal r, weeks a. pelvic girdle pain and low back pain in pregnancy: a review. pain pract: 2010; 10: 60–71. 6. bergstrom c, persson m, mogren i. pregnancy-related low back pain and pelvic girdle pain approximately 14 months after pregnancy pain status, self-rated health and family situation. bmc pregnancy and childbirth: 2014; 14: 48. 7. mogren im, pohjanen ai. low back pain and pelvic pain during pregnancy: prevalence and risk factors. spine: 2005; 30: 983-91. jiimc 2017 vol. 12, no.1 43 prevalence of pregnancy related low back pain jiimc december 2016 page 43 page 44 page 45 page 46 page 47 original�article abstract objective: to determine the effect of 30% hyperoxia on the weight, fasting blood glucose (fbg) and serum peptide yy (pyy) levels in sprague dawley rats and to see its potential role in treating obesity. study design: experimental, randomized control study. place and duration of study: it was carried out at the department of physiology, islamic international medical college, rawalpindi in collaboration with national institute of health, islamabad, pakistan from april 2015 to march 2016. materials and methods: total 40 male sprague dawley rats of 2-4 months weighing 250-520 g were taken. they were divided into two groups of 20 each: control group a exposed to 21% oxygen and group b exposed to 30% oxygen for a period of 7 days. before exposure to various oxygen concentrations the weight (g) of rats of both groups was taken and blood was collected for estimation of fasting blood glucose (fbg) (mg/dl) and serum peptide yy (pyy) (pg/ml).after exposure second sampling including weight, fbg and serum pyy was done. statistical analysis was done applying spss 21, comparisons among the two groups were analyzed using independent sample t-test and correlation among variables was determined using pearson's correlation coefficient. p value of <0.05 was considered significant in both analyses. results: group b rats had significantly (p<0.05) increased weight (g), increased fbg (mg/dl) levels (p<0.001) and low serum pyy (pg/ml) levels (p<0.001) in comparison with group a. conclusion: hyperoxia decreases pyy levels causing an increase in appetite leading to an increase in weight and fbg levels. therefore, hyperoxia may not be useful as a treatment for obesity. key words: fasting blood glucose, hyperoxia, peptide yy, weight . role in controlling the appetite and ultimately reducing the weight of the body have been identified 5 through recent research. peptide yy (pyy), the short 36 amino acid protein, is one such hormone. it is released from the gut and increases satiety resulting 6 in a decreased in food consumption. much study has been carried out on the role of exogenous pyy in reducing weight, but more research needs to be conducted on raising endogenously produced pyy as its levels have shown to be decreased in obese 7 individuals. oxygen is an odorless and colorless gas having a normal atmospheric concentration of 21% and is widely used for treating a number of medical 8 conditions. although exposure to a high level of hyperoxia for extensive periods has been shown to damage cells through the production of excessive 9 free radicals, low levels of hyperoxia produce lesser free radicals. these low levels of free radicals have shown to play an important role as signaling molecules that regulate various cellular processes and gene expression, such controlling fasting blood glucose levels through the production of glucose introduction obesity is a medical condition in which excess body fat has accumulated to the extent that it causes an 1 adverse effect on health and has become a global epidemic due to the readily available high calorie 2 diets and prevailing sedentary life style. the accumulated energy is stored mainly in the form of triglycerides in adipocytes leading to an increase in their size resulting in an increase in the overall body 3 weight. the increase in adipocyte size seen in obesity also leads to a decrease in insulin sensitivity hence raising blood glucose levels and increasing the 4 risk of diabetes. a number of circulating hormones that play a vital effect of hyperoxia on weight, fasting blood glucose and serum peptide yy levels in sprague dawley rats and its potential role in treating obesity muhammad raza, shazia ali correspondence: dr. muhammad raza department of physiology islamic international medical college riphah international university, islamabad department of physiology islamic international medical college riphah international university, islamabad funding source: nil; conflict of interest: nil received: may 04, 2016; revised: oct 24, 2016 accepted: march 25, 2017 effect of hyperoxia on weight, fbg and pyy in ratsjiimc 2017 vol. 12, no.2 78 laboratory where they were tested for serum pyy ( p g / m l ) l e v e l s u s i n g a n e n z y m e l i n k e d immunosorbent assay (elisa) kit (cusabio biotech 16 co. ltd., china). two transparent plastic chambers of dimensions 1.22 m x 0.72 m x 0.72 m were designed. the group a control chamber rats was not made air tight by keeping the upper two sides open allowing fresh air of a 21% oxygen concentration to enter freely. the group b chamber was made air tight with only two holes: an inlet for entry of oxygen and an outlet exit of air. two nitrogen cylinders of 6.8 m3 and three oxygen cylinders of 4.5 m3, 3.4 m3 and 3.4 m3 were used. two flow meters (richu medical regulator yr88e, ningbo beilun db marine co. ltd., china) were each attached to one nitrogen cylinder and one oxygen cylinder after which they were connected by a t-tube to allow oxygen and nitrogen to mix before 17 supplying the chamber. an oxygen sensor (cy-12c portable oxygen concentration tester, clever co. ltd., china) was also attached within the chamber to monitor the oxygen concentration. after 2 weeks given to the rats for replenishing their 18 blood volume to normal levels the experiment was started. to achieve an oxygen to nitrogen ratio of 3:7, the flow rate for oxygen was adjusted between 1-2 l/min and that for nitrogen between 3-4 l/minso that the chamber for group b rats was supplied with an oxygen concentration of 30 + 1%.17 upon reaching a value of 31% on the oxygen sensor the flow rates were readjusted to bring it back to a 30% oxygen concentration. the water in the flow meters provided the required air humidity and these 19 conditions were kept for 24 hours for 7 days except for two situations where the experiment was stopped for no more than 10 min: first for supplying food and water and to clean trays for waste matter, and second to refill gas cylinders. upon completion of 7 days of the experiment, second sample, comprising of weight, fasting blood glucose and serum pyy, was collected on the morning of day 8 similar to the method applied for the first sample collection. the labeled gel tubes containing the blood samples were centrifuged using a centrifuge machine (eba20 small centrifuge, andreas hettich gmbh & co. kg) at a speed of 3000 rpm for 15 min. the quantitative enzyme-linked immunosorbent assay (elisa) 10 11 membrane transporters and in healing wounds. the effect of hypoxia on serum pyy levels in humans has already been studied. hypoxia has shown to decrease serum pyy levels, but as the oxygen concentration is gradually raised back to a normoxic state of 21% oxygen, the serum pyy levels increase 12 again. studies showing the effect of hyperoxia on pyy levels, especially as a potential treatment for obesity and diabetes, still needs to be explored. the objective of this study was to see whether exposure to a low level of hyperoxia of 30% could be used as a treatment for obesity by raising endogenous pyy levels, ultimately decreasing the appetite leading to a reduction in weight and fasting blood glucose. materials and methods the experimental, randomized control study was carried out in the department of physiology, islamic international medical college, rawalpindi in collaboration with the animal house at national institute of health, islamabad, pakistan from april 2015 to march 2016. the study was approved by the ethics review committee of islamic international medical college, riphah international university. a total of 40 male sprague dawley rats of 2-4 months 13 weighing 250-520 g were included in the study. they were randomly divided into two groups: control group a (n=20) that was exposed to 21% oxygen and 14 group b (n=20) that was exposed to 30% oxygen. for 7 days the rats were allowed to acclimatize to the nih animal house environment. a standard diet in pellet form was prepared at the animal house of nih, islamabad according to the guidelines given by the 15 universities federation for animal welfare. the food and water was provided ad libitum. on the morning of day 8 the first sample was collected by anesthetizing each rat of group a and b by placing it in a jar containing cotton soaked in chloroform. its weight (g) was recorded using a weighing machine (ts200 electronic compact scale, jiangyin ditai electronic technology co. ltd., china) after which blood was drawn via intra cardiac sampling. one drop of blood was added onto the test strip of the glucometer (easy gluco ultra advance blood glucose meter, isotech co. ltd., south korea) and the fasting blood glucose (mg/dl) level was recorded. the blood was collected and stored in labeled gel tubes, protected from light and contamination and kept in a laboratory ice box at 2-8oc until shifted to the effect of hyperoxia on weight, fbg and pyy in ratsjiimc 2017 vol. 12, no.2 79 hypoxic environment influenced pyy levels. they concluded that the levels of serum pyy were lower in 12 hypoxia as compared to normoxia suggesting that as the oxygen concentration is increased from that of hypoxia to normoxia then serum pyy levels also increase. the aim of our present study was to see whether this pattern of increase in serum pyy levels was consistent after increasing the oxygen concentration beyond that of a normoxic state. according to our findings, a 7 day exposure to an oxygen concentration of 30% resulted in a significant decrease in serum pyy levels demonstrating that both hypoxia, as shown by wasseet al (2011), and hyperoxia, as shown by our present study, lowers the levels of serum pyy. our present results showed that exposure to hyperoxia led to a significant increase in weight which was in accordance with the study carried out by lakaniet al., (2012) who observed the effects of hypoxia, normoxia and hyperoxia on a total of 81 great sturgeon husohuso fish and concluded that the group exposed to hyperoxia led to the greatest 20 weight gain in the fish. the significantly increased weight seen in our study could have been due to an increase in appetite caused by the significant decrease in serum pyy levels observed as supported by the studies carried out by roth et al., (2005) who showed that fasting serum pyy levels are negatively 21 correlated with weight. on the other hand, our findings did not show a significant correlation of serum pyy levels with weight. stress is a situation in which the organisms' homeostasis is threatened by endogenous and 22 exogenous stimuli and cortisol is the most commonly measured indicator of stress that provides a good reflection of its duration and 23 severity. exposure to high levels of cortisol method was used to measure serum pyy (pg/ml) levels. statistical analysis was done applying the statistical package for social sciences version 21 (spss 21). results were documented as mean + sem. comparisons among the two groups was analyzed using the independent sample t-test and correlation among the variables was done using pearson's correlation coefficient. p value of <0.05 was considered significant for both analyses. results a total of 40 male sprague dawley rats were included in the study. during the experiment two rats died from group a and one from group b making the survival rate 92.5%. the weight of group b rats (309.08 + 10.71 g)was significantly higher (p<0.05) than the weight of group a rats (283.75 + 5.20 g) after exposure to 30% oxygen for seven days. the rats of group b had fasting blood glucose levels of 172.71 + 8.59 mg/dl which were significantly raised (p<0.001) as compared to those of the group a rats (132.06 + 4.66 mg/dl). on comparison the serum pyy levels of the group b rats was 14.62 + 6.14 pg/ml which was significantly lower (p<0.001) than those of the group a rats (256.87 + 25.48 pg/ml). mean ± sem of weight (g), fasting blood glucose (mg/dl) and serum pyy (pg/ml) for the two groups of male sprague dawley rats exposed to different concentrations of oxygen as are displayed in table i. no significant correlation was observed between serum pyy (pg/ml) levels, weight (g) and fasting blood glucose (mg/dl) levels in both groups using pearson's correlation coefficient as is displayed in table ii. table i: comparison of mean ± sem of parameters (weight, fas�ng blood glucose and pyy) for the exposed and control groups of male sprague dawley rats weight (wt), fas�ng blood glucose (fbg) pep�de yy (pyy) * = p<0.05 (value vs corresponding control) ** = p<0.001 (value vs corresponding control) table ii: correla�on of serum pyy (pg/ml) levels with weight (g) and fas�ng blood glucose (mg/dl) levels for the exposed and control groups of male sprague dawley rats pep�de yy (pyy), weight (wt) fas�ng blood glucose (fbg) discussion wasseet al, (2012) conducted an experimentin 10 male volunteers to explore how rest and exercise in a effect of hyperoxia on weight, fbg and pyy in ratsjiimc 2017 vol. 12, no.2 80 by adam et al., (2010) on 354 latino adolescents to determine the association between cortisol and insulin, in which they concluded that increased serum cortisol levels led to decreased insulin sensitivity and hence a raised fasting blood glucose 32 level. as we have already stated that hyperoxia induces oxidative stress and leads to an increased production of cortisol so maybe the increase in fasting blood glucose observed was due to an increase in serum cortisol levels produced on exposure to hyperoxia. as we did not measure other hormones apart from pyy, such as cortisol and ghrelin, so it remains unclear as to which hormone could have brought about the change observed in fasting blood glucose levels as seen in our study. on the other hand, the significant increase in fasting blood glucose observed can further be elaborated by the study carried out by stolicet al., (2002) to determine the influence of bmi, anatomical depot and body fat distribution on glucose uptake and insulin action in human adipose tissue in 68 subjects. they concluded that glucose uptake was increased in the omental adipose tissue of lean subjects, whereas it was decreased in the omental adipose tissue of obese subjects as their adipose tissue cells had 33 developed resistance towards insulin. hence it may be postulated that the increased fasting blood glucose levels observed in our study may have resulted from an increase in adipocyte size which occurs when there was an increase in weight. conclusion the conclusion derived from the results of the present study are thathyperoxia decreases serum pyy levels causing an increase in appetite leading to an increase in weight and fasting blood glucose. therefore, hyperoxia is not a useful option for the treatment of obesity and may be a precipitating factor for the development of diabetes mellitus. references 1. obesity, who. 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hubrecht rc, kirkwood j, editors. the ufaw handbook on the care and management of laboratory and other research animals. john wiley & sons. 2010. 17. mimura yo, yamakawa mi, furuya ki, oohara ta. effects of oxygen supply on protein metabolism in surgically injured rats. oxygen as a nutrient. annals of surgery. 1990; 212: 228. 18. diehl kh, hull r, morton d, pfister r, rabemampianina y, smith d, et al. a good practice guide to the administration of substances and removal of blood, including routes and volumes. journal of applied toxicology. 2001; 21: 15-23. 19. jones r, zapol wm, reid l. pulmonary artery remodeling and pulmonary hypertension after exposure to hyperoxia for 7 days. a morphometric and hemodynamic study. the effect of hyperoxia on weight, fbg and pyy in ratsjiimc 2017 vol. 12, no.2 82 page 13 page 14 page 15 page 16 page 17 original�article abstract objective: to identify low performers by utilizing individual readiness assurance test (i-rat) scores in first year mbbs students using team-based learning (tbl) strategy. study design: cross sectional observational study th place and duration of study: study was conducted in federal medical college islamabad from 10 january to st 31 march 2022. st materials and methods: tbl were introduced in 1 year mbbs. six tbl activities were practiced by anatomy department during the 12-week respiratory and cvs course program. premedical examination scores, first week individual readiness assurance scores and average i-rat scores of 6 weeks were gathered. mean and standard deviation were calculated. difference in the first week i-rat scores of three groups based on their premedical examination scores i.e., upper percentile group (a), middle percentile group (b) and lower percentile group (c). each group comprised of 37 students, was calculated using one way anova method. pearson correlation coefficient (r) was used to access strength and direction of linear association between premedical examination scores and i-rat scores. the data was analyzed in the statistical package for social sciences (spss) version 21 for analysis. results: high scorers in premedical examination (group a) showed lowest scores in first week irat (i-rat 1) and average i-rat when compared with group b and c with significant p value < 0.05. significant increase was seen in progressive i-rat scores in all 3 groups. negative linear association (r= -0.2) was found between premedical examination scores and i-rat 1 scores. a strong positive linear association with r= 0.54 was found between first i-rat and average i-rat scores. st conclusion: high achievers in premedical examinations struggled the most in 1 year of medicine. key words: individual reassurance test , mbbs, premedical scores, team based learning. exceptional scores. admission to medical college is extremely competitive. medical studies are associated with chronic and high stress, and evidence has shown that such stress is linked to worse performance, intentions to quit, and elevated 2 depression. literature has given the evidence that previous academic performance is used as a predictor for future performance in studies of selected students in a medical college though relation of antecedent scores with future performance in medical school years need to be 3 explored. studies have shown that pretest identifies low performers that might need extra support in learning and once the students at risk are identified educational intervention can help support such 4 students. for this purpose to identify low st performers in 1 academic year of medicine with high premedical scores i-rat is used in this study while conducting tbl exercises. introduction study of medicine is a challenging and tortuous course. it is declared as one of the lengthiest and 1 stressful academic programs. once entering mbbs, students require knowledge and skill to gain marks that will be sufficient for them to become good doctors in future. students are selected on merit in st 1 year mbbs but at the end of year show poor performance irrespective of their premedical utility of irat as a tool to identify low academic performers in 1st year mbbs with high scores in pre-medical examination sana malik, atteaya zaman, saima saleem, saima mumtaz khatak, anbreen aziz, madiha imran correspondence: dr. sana malik department of anatomy federal medical college, islamabad e-mail: sanamalik1211@gmail.com 1,3,4 2 department of anatomy/medical education federal medical college, islamabad 5 department of dentistry army medical college, rawalpindi 6 department of anatomy watim medical and dental college, rawat received: september 16, 2022; revised: may 30, 2023 accepted: june 03, 2023 jiimc 2023 vol. 18, no. 2 139 individual readiness assurance test (i-rat) https://doi.org/10.57234/jiimc.june23.1534 tbl is one of the popular and effective strategy used 5 in different educational systems. many medical collages have been using this strategy as primary 6 mode of learning in undergraduate medical setup. the benefits of tbl have been documented in literature many times stating that learning among students increases by active engagement in 7 teamwork and practical skill. medical curriculum can be strengthened by implementing this instructional approach format, in earlier phases of the first year program where the focus is on basic science, leading to clinical importance as students 8 move towards clinical years. team based learning exercise for implementation is divided into three phases; preparatory phase; where students study before they come to class, readiness assurance test; where students take both individual a n d te a m a s s u ra n c e te st to a s s e s s t h e i r understanding of pre-class material and application phases, where students apply learnt knowledge. in last phase students work as a team to share and 9, 10 improve learning. individual readiness assurance test (i-rat) helps to assess understanding of desired topic from pre class study directions and individual preparation. team readiness assurance test (t-rat) gives student an opportunity to get immediate feedback on assessment and team learning. the activity center around students being engaged in groups to solve 11 problem related to topic of concern. i-rat scores can be used to identify struggling 12 students. single tbl exercise exposure of first year students of medicine were helpful in identifying top 1 3 performers and struggling ones. individual readiness assurance test has significant value as literature suggests that it helps to pin down students that might not perform well in academic years of mbbs. tbl programs result in improvement in results of final examination of students interpreting that academically underperforming students are more 7 assisted by team bases learning methodology. research has been conducted previously to determine factors like personality, iq, peer and family pressure contributing to be responsible for st low performance in students of 1 year medical 14 college. less evidence is available how to identify these low performers especially those with high premedical examination scores. tbl activities help in tracking down students at peril to show low academic results. such students require early interventions to strengthen their performance and educational experience. tbl methodology can be used as a tool for early screening out of students that might perform below par in first year of mbbs irrespective of being high marks achievers in premedical examination. the purpose of carrying out this research project was to utilize an active learning strategy to identify low performers in medical school by utilizing irat scores in first year cvs and respiratory anatomy module. materials and methods it was a cross sectional observational study with the duration of 12 weeks. study was conducted for st students of 1 year mbbs (session 2021) of federal medical college islamabad. whole class of one hundred and eleven students participated using nonprobability convenient sampling technique. written consent was collected by all students before start of study. after ethical approval of fmti ethical review board t h ( 1 5 n o v e m b e r 2 0 2 1 l e t t e r n u m b e r ecpims/02/16).whole class was included with their consent. the team based learning activity was st introduced in 1 academic session in cvs and respiratory modules of 6-week duration each. six tbl activities were practiced by anatomy department during the course program which covered most of the taught anatomy content of the course. each tbl activity was conducted as a large group discussion engaging whole class at the beginning of week 2,4,6 ,8, 10 and 12. data was collected for 3 groups of students based on their premedical examination scores i.e., upper percentile group (a), middle percentile group (b) and lower percentile group (c). each group comprised of 37 students. following scores were gathered. 1. premedical examination scores 2. individual readiness assurance scores 3. average i-rat scores of 6 weeks the premedical scores were obtained from college administration listed on basis of merit, i-rat scores were maintained for each biweekly activity and documented on excel sheet and average i-rat was calculated at the end of 12 week by calculating average of i-rat scores obtained in six tbl activities. validity and reliability of the test was ensured as per jiimc 2023 vol. 18, no. 2 140 individual readiness assurance test (i-rat) https://doi.org/10.57234/jiimc.june23.1534 institutional policy. mean and standard division of first week irat scores and average irat scores in 6 tbl activities were calculated for the 3 groups as mentioned in methodology. difference in the first week i-rat scores of three groups was calculated using one way anova method. pearson correlation coefficient (r) was used to access strength and direction of linear association between premedical examination scores and i-rat scores. the data was analyzed in the statistical package for social sciences (spss) version 21 for analysis. result group a showed lowest scores in first week i-rat (irat 1) and average i-rat when compared with group b and c with significant p value< 0.05 indicating that the high achievers in premedical examinations st struggled the most in 1 year of medical studies as briefed in table i. association help fulfill the objective of identifying low performers in medical school by utilizing i-rat scores. a strong positive linear association with pearson coefficient r= 0.54 and significant p value of 0.01 was found between first i-rat scores and a v e r a g e i r at s c o r e s s h o w i n g p e r s i s t e n t improvement. discussion in early phase of the tbl activity i-rat assesses students independent learning ability to learning 15 materials shared before class . we found that consistent improvement in weekly i-rat in students performing in middle and lower percentile as compared to upper percentile students. studies have documented that premedical scores are high predictors of good academic performance but contradictory evidence is also available in literature that shows no correlation between entrance test 16 examination scores and academic performance. in this study we gathered scores of premedical examination and i-rat, we identified that the upper percentile students with highest scores in premedical examinations struggled the most in their first year of medical studies as indicated by their low i-rat scores in first week of team based learning activity. n e ga t i ve a s s o c i a t i o n b e t w e e n p re m e d i c a l examination scores and first week i-rat proved that high scorers lack in performing their best on entering medical college. literature is also in favor of our finding where the mdcat scores are not a determinant of good performance in initial 17 preclinical years. low scores in first week activity showed that high st scorers struggled in their 1 year of medical collages. this factor is documented as one of the tool to figure 1: comparison between i-rat 1 and premedical examination scores table i: intergroup comparison of p values of i-rat 1 and average i-rat significant increase is seen in progressive irat scores in all 3 groups, with maximum improvement seen in fifth and sixth week and minimum improvement is seen in upper percentile group when compared with the group b and c . negative linear association (r= -0.2) was found between premedical examination scores and i-rat 1 scores of whole class with significant p value < 0.05, while very minimal negative association (r= -0.15) was found between premedical examination scores and average i-rat with non-significant p value by using bivariate pearson correlation. negative figure 2: progressive i-rat scores in 6 weeks tbl activities jiimc 2023 vol. 18, no. 2 141 individual readiness assurance test (i-rat) https://doi.org/10.57234/jiimc.june23.1534 identify students who might be at risk to suffer in 18 initial academic years. individual readiness assurance test is utilized to identify these high scorers early in their academic years to give them early support to sustain their good performance in preceding clinical years. positive association between first week i-rat and average irat is in favor of the fact that the identified students maintain their performance and this factor can be taken as a tool to predict their future performance. to identify students who might struggle in first academic year of mbbs is only beginning to preview a n d st re a m l i n e a p p ro a c h e s i n te r m s o f m a n a g e m e n t , p o l i c y m a k i n g , te a c h i n g a n d counseling, to reduce failure, encourage and foster ways for students to success in beginning years of 19 medical studies. conclusion we concluded using i-rat that students with high scores in premedical examination don't perform well in medical colleges. references 1. wang l, lin c, han c, huang y, hsiao p, chen l. undergraduate nursing student academic resilience during medical surgical clinical practicum: a constructivist analysis of taiwanese experience. journal of professional nursing. 2 0 2 1 ; 3 7 ( 3 ) : 5 2 1 8 . h t t p s : / / d o i . o r g / 1 0 . 1 0 1 6 / j.profnurs.2021.02.004. 2. bergmann c, muth t, loerbroks a. medical students' perceptions of stress due to academic studies and its interrelationships with other domains of life: a qualitative study. medical education online. 2019;24(1):1603526. https://doi.org/10.1080/10872981.2019.1603526. 3. schneid sd, kelly cj, brandl k. relationships between preadmission variables and academic outcomes for postbaccalaureate students in medical school. advances in health sciences education. 2022;27(4):1033-48. ) https://doi.org/10.1007/s10459-022-10129-3. 4. aronson bd, eddy e, long b, welch ok, grundey j, hinson jl. identifying low pharmaceutical calculation performers using an algebra-based pretest. american journal of p h a r m a c e u t i c a l e d u c a t i o n . 2 0 2 2 ; 8 6 ( 1 ) . d o i : https://doi.org/10.5688/ajpe8473. 5. parmelee d. team-based learning. an introduction to medical teaching: the foundations of curriculum design, delivery, and assessment: springer; 2022. p. 77-84. doi: 10.1007/978-3-030-85524-6_6. 6. elshama ss. how to apply team-based learning in medical education? quantum journal of medical and health sciences. 2021;1(2):15-22. https://qjmhs.com/ index.php/qjmhs/article/view/15. 7. james m, baptista amt, barnabas d, sadza a, smith s, usmani o, et al. collaborative case-based learning with p ro g ra m m at i c te a m b a s e d a s s e s s m e nt : a n ove l methodology for developing advanced skills in early-years medical students. bmc medical education. 2022;22(1):81. https://doi.org/10.1186/s12909-022-03111-5. 8. burgess a, matar e, roberts c, haq i, wynter l, singer j, et al. scaffolding medical student knowledge and skills: teambased learning (tbl) and case-based learning (cbl). bmc medical education. 2021;21(1):1-14.https://doi.org / 10.1186/s12909-021-02638-3. 9. burgess a, matar e. team-based learning (tbl): theory, planning, practice, and implementation. clinical education for the health professions: theory and practice. 2020;20:129. https://doi.org/10.1007/978-981-13. 10. gullo c, ha tc, cook s. twelve tips for facilitating teambased learning. medical teacher. 2015;37(9):819-24. https://doi.org/10.3109/0142159x.2014.1001729. 11. hopper mk. alphabet soup of active learning: comparison of pbl, cbl, and tbl. haps educator. 2018;22(2):144-9. doi: 10.21692/haps.2018.019. 12. carrasco ga, behling kc, lopez oj. first year medical student performance on weekly team-based learning exercises in an infectious diseases course: insights from top performers and struggling students. bmc medical education. 2019;19(1):1-5. https://doi.org /10.1186/ s12909-019-1608-9. 13. carrasco ga, behling kc, gentile m, fischer bd, ferraro tn. effectiveness of a team-based learning exercise in the learning outcomes of a medical pharmacology course: insight from struggling students. naunyn-schmiedeberg's archives of pharmacology. 2021:1-8. https://doi.org/10/ 1007/s 00210-021-02093-3. 14. chakrabarti s, anand vv. factors contributing for decreased academic performance among first year medical students. european journal of molecular & clinical medicine. 2020;7(9):164-79. issn 2515-8260. 15. lin jw. the impact of team-based learning on students with different self-regulated learning abilities. journal of computer assisted learning. 2019;35(6):758-68. https://doi.org/10.1111/jcal.12382. 16. rocha badsr, toledo a. predictive factors of graduation delay in a medical program: a retrospective cohort study in brazil, 2010-2016. revista brasileira de educação médica. 2020;44. https://doi.org /10.1590/1981-5271v44.120190205.ing. 17. wu w, garcia k, chandrahas s, siddiqui a, baronia r, ibrahim y. predictors of performance on usmle step 1. the southwest respiratory and critical care chronicles. 2 0 2 1 ; 9 ( 3 9 ) : 6 3 7 2 . h t t p s : / / d o i . o r g / 10.12746/swrccc.v9i39.813. 18. christensen j, harrison jl, hollindale j, wood k. implementing team-based learning (tbl) in accounting courses. accounting education. 2019;28(2):195-219. https://doi.org/10.1080/09639284.2018.1535986. 19. ahmady s, khajeali n, sharifi f, mirmoghtadaei zs. factors related to academic failure in preclinical medical education: a systematic review. journal of advances in medical e d u c a t i o n & p r o f e s s i o n a l i s m . 2 0 1 9 ; 7 ( 2 ) : 7 4 . https://doi.org/10.30476%2fjamp.2019.44711. jiimc 2023 vol. 18, no. 2 142 individual readiness assurance test (i-rat) https://doi.org/10.57234/jiimc.june23.1534 conflict of interest authors declared no conflicts of interest. grant support and financial disclosure authors have declared no specific grant for this research from any funding agency in public, commercial or nonprofit sector. data sharing statment the data that support the findings of this study are available from the corresponding author upon request. this is an open access article distributed under the terms of the creative commons attributionnoncommercial 2.0 generic license. jiimc 2023 vol. 18, no. 2 143 individual readiness assurance test (i-rat) https://doi.org/10.57234/jiimc.june23.1534 original�article abstract objective: the aim was to find out frequency of nephropathy in subjects having type 2 diabetes mellitus; and to determine the effect of disease duration and blood glucose levels on the development of diabetic nephropathy. study design: cross-sectional. st th place and duration of study: pof hospital wah cantt, 1 january to 30 june 2018. materials and methods: two hundred and ten subjects were enrolled having type-2 diabetes for more than 5 years. a closed ended questionnaire was used to record information on disease duration, glycosylated hemoglobin level, blood pressure and albuminuria. the data was analyzed by spss v-19 and significance of results was studied by chi-square test. results: among 210 patients 126 were male and 84 were female. out of 210 people under study 54.76% had diabetic nephropathy. significantly a greater number of diabetic nephropathy was recorded among subjects having diabetes for more than 10 years (p-values 0.03), and whose blood sugar levels were never controlled (pvalues 0.000). conclusion: the frequency of diabetic nephropathy was found to be quite high. it was significantly higher among subjects having diabetes for longer duration and uncontrolled blood sugar levels. therefore, it is essential to monitor these patients regularly to prevent complications and improve their health. key words: albuminuria, diabetes mellitus, diabetic nephropathy, glycated hemoglobin a, hypertension, risk factors. complications; damage to large vessels causes macro vascular complications. long-standing blood glucose level is responsible for impairment of different organs leading to visual, neurological, 4,5 renal, and cardiovascular problems. dn remains an important common complication of diabetes. it is characterized by gradually increasing urine albumin excretion, accompanied by slowly rising blood pressure; the decline in glomerular 6,7 filtration rate occurs late. diabetes harms the kidneys by causing damage to tiny blood vessels of filtering units. with time, high blood sugar levels cause these vessels to become narrow and clogged. once the nephrons are damaged and reduction of functional renal mass reaches a certain point, the remaining nephrons begin a process of irreversible sclerosis esrd is the final stage of 8,9 leading to esrd. nephropathy, where kidney function has declined to the point that they can no longer function on their own; patients will need expensive procedures to live. 10,11 the possibility of cardiac diseases increases as urine albumin excretion increases and as gfr 6 decreases. esrd and cardiac problems lead to 7,12 decreased life expectation in these patients. introduction diabetes mellitus is progressively becoming a worldwide epidemic, about 8% (350 million) people are having dm, and this would rise to above 550 1 million by 2035. diabetes mellitus (dm) is a disease in which the body's ability to produce or respond to the hormone insulin is impaired, resulting in abnormal metabolism of carbohydrates and elevated levels of glucose in the blood. type-1 diabetes is due to autoimmune damage of pancreatic islets cells, while type 2 diabetes develops when the body becomes resistant to insulin or when the pancreas is unable to produce enough 2,3 insulin. over time, high blood glucose can damage the body's blood vessels, both tiny and large. damage to t i ny b l o o d ve s s e l s ca u s e s m i c ro va s c u l a r diabetic nephropathy: duration and glycemic control affect the outcome 1 2 3 4 robina mushtaq , ambreen ansar , anwar bibi , musarat ramzan correspondence: dr. robina mushtaq department of community medicine wah medical college, wah cantt e-mail: robina.mushtaq@yahoo.com department of community medicine wah medical college, wah cantt funding source: nil; conflict of interest: nil received: january 19, 2021; revised: november 08, 2021 accepted: february 24, 2022 diabetic nephropathyjiimc 2022 vol. 17, no.1 41 according to the international diabetes federation (idf), currently 7.5 million pakistani populations are 13 affected with dm , and almost 20% to 40% diabetics 1 in the long run have kidney disease. lots of diabetics with impaired renal function are ignorant of their condition, resulting in delayed management and increased morbidity due to esrd and cardiac 8 diseases. only a few studies have been conducted in our country to establish the effect of diabetes duration and glycemic control on kidney functions. well-timed testing of renal functions in patients having dm for longer duration would delay the 14 development of kidney disease. early detection and management holdup the disease process and lessen the risk of esrd, thus reducing the burden on health care delivery system. an easy approach to avoid or interrupt dn is adopting healthy way of living and good glycemic control. the aim was to find out frequency of nephropathy in subjects having type 2 diabetes mellitus; and to determine the effect of disease duration and blood glucose levels on the development of diabetic nephropathy. materials and methods a cross-sectional study was conducted at pof st th hospital wah cantt during 1 january to 30 june 2018. sample size was 210 based on 95% confidence 6 level, 5% precision and 16.4% anticipated proportion, subjects were selected by purposive sampling. prior permission to conduct this study was taken from the institutional review board. informed consent was taken from patients before data collection. patients having diabetes for more than 5 years were included. information regarding blood urea and creatinine levels, duration of diabetes, hba1c levels, family history, blood pressure and albuminuria was taken from the documents of selected patients by the researchers. a diabetic person having albuminuria and hypertension for the last 6 months (confirmed from patients record file) was labeled as having diabetic nephropathy. patients having blood pressure above 130/90 mmhg during last 6 months were labeled as having hypertension. on the basis of hba1c levels three categories of glycemic control were formed; always control (hba1c level < 7% during last 6 months), sometime control (hba1c level 7% 8% during last 6 months) and never control (hba1c level > 8% during last 6 months). the data analysis was done by spss v19 and chi-square test was applied to find out the relationship of diabetes duration and blood sugar levels with diabetic nephropathy (level of significance was 0.05). results mean age in this study was 55.77 + 13.68 years. out of 210 patients 126 (60%) and 84 (40%) were male and female respectively. ninety-eight (46.7%) patients had diabetes for 5-10 years and 112 (53.3%) patients had for >10 years. one hundred and thirtyseven (65.2%) patients had positive family history while 73 (34.8%) had no family history of diabetes mellitus. sixty-two (29.5%) had hba1c level below 7%, 123 (58.6%) had hba1c level between 7% and 8% while hba1c level of 25 (11.9%) patients was above 8%. one hundred and forty-six (69.5%) patients had blood pressure above 130/90 mmhg on average during last 6 months. one hundred and fifteen (54.8%) patients had albuminuria and hypertension for the last 6 months (fig. 1). fig. 1: frequency (%) of diabetic nephropathy mean blood creatinine and urea levels were 1.99+1.65 mg /dl and 65.26 + 29.62 mg /dl respectively. frequency of diabetic nephropathy among male was 70 (55.5%) and females was 45 (53.5%) which is statistically insignificant (p-value 0.7). seventy-nine (57.6%) patients with diabetic nephropathy had family history of dm as compared to 36 (49.3%) who had no family history (statistically insignificant p-value 0.24). nephropathy was reported notably more [69 (61.6%)] among patients having dm for more than 10 years, while frequency among those having dm for 5-10 years was [46 (46.9%), (p-value 0.033)]. the patients whose blood sugar levels were never controlled had high rate of 42 jiimc 2022 vol. 17, no.1 diabetic nephropathy nephropathy 21 (84%), in contrast to those having sometime [75 (61%)] and always controlled sugar levels [19 (30.6%)] (statistically significant p-value 0.000). nephropathy occurred more in hypertensive subjects [table i]. disease. the first sign of nephropathy is presence of albumin in urine. frequency of diabetic nephropathy (54.76%) was found similar to other studies by khalid 10 16 17 (43%) , machingura (45%) , wu (40%) , parving 18 19 (39%) and hasabi (45%) this frequency was high as 4 compared to the studies conducted in pakistan (20 6 15 %), mediterranean region (16.4%), china (30.9%), 8 9 20 usa (33%), saudi arab (10.8%), and india (26.9%). the high rate in our setting may be because the patients are diagnosed late due to shortage of medical facilities, high expenditure, low health risk awareness among populations and more priority is given to communicable diseases. type 2 diabetes is now equally prevalent among men and women in most populations and the effect of sex on nephropathy is not well established. in our study male and female were almost equally affected, while 15 in a study by zhou et al females had a significantly high rate of diabetic nephropathy. uncontrolled diabetes had increased the risk of development of nephropathy. there was some evidence that improved glucose control delayed the progression of albuminuria. with decrease of 1% hba1c level, there 21 was a 37% decreased possibility of nephropathy . in this study, the subjects having hba1c levels persistently above 8% had significantly high frequency of nephropathy (p-value 0.000). these results were consistent with other studies showing a relation of high hba1c levels to the progression of 15 8 nephropathy; china (p <0.001), usa (p< 0.001), 3 9 22 ethiopia (p< 0.002), saudi arab (or 1.17), india 16 (or 11.8), and zimbabwe (or 1.20). the likelihood of nephropathy among diabetics also 8 increases with the duration of disease. regardless of check on blood glucose and blood pressure the incidence of albuminuria increases as a consequence of increasing survival and duration of diabetes. the frequency of dn was found to be significantly higher among patients having diabetes for more than 10 years (p-value 0.033). the relationship of longstanding dm and nephropathy had been proved by 8 many studies; from usa (p-value 0.001) , pakistan (p4 9 value 0.05) , saudi arab (p< 0.0001) , zimbabwe (or= 16 20 22 1.03), and india (p = 0.046) (or = 4.69). hypertension is an invariable accompaniment of esrd and control of hypertension reduces the risk of developing albuminuria. a substantial association was found between presence of albuminuria and table i: relationship of diabetic nephropathy with different variables discussion diabetic nephropathy is diagnosed if albuminuria and impaired renal functions persist for at least 3 months. nephropathy is related to high mortality in common people as well as among diabetics. early findings will let insistent actions to be taken to impede the progression of disease to esrd. the number of diabetics is constantly rising in pakistan. type 2 diabetes can occur at any stage of life, even in children. however, it occurs most often in middle-aged and older people. in our study mean age of subjects was around 56 years, more than fifty percent subjects were having diabetic nephropathy; male and female were almost equally affected. the subjects having hba1c levels persistently above 8% and diabetes for more than 10 years had significantly high frequency of nephropathy. the mean age of subjects was comparable to other 15 4 studies made in shanghai (56 year), pakistan (55.2 5 year), and tanzania (45-60 year). in diabetics the organs are exposed to hyperglycemia. intracellular hyperglycemia causes collection of unstable oxygen radicals, resulting in damage to blood vessels. even with proper management and check on glucose level, diabetics can still develop renal pathological changes like glomerulosclerosis and chronic kidney 43 jiimc 2022 vol. 17, no.1 diabetic nephropathy hypertension (p = 0.015); similar association had 4 9 been studied by shera et. al. (p = 0.05), al-rubeaan 18 22 (p < 0.0001), parving (or = 1.10), and akheel (or = 2.06). educating patients on health risks associated with diabetes and changing their mode of living for better glycemic control can impede the disease process and lower the burden on health system of country. conclusion the frequency of diabetic nephropathy is found to be quite high. it is significantly higher among subjects having diabetes for longer duration and uncontrolled blood sugar levels. careful monitoring of diabetic patients can prevent complications and improve their quality of life. educating patients regarding the risk factors can reduce the burden of kidney diseases. references 1. gheith o, farouk n, nampoory n, halim ma, al-otaibi t. diabetic kidney disease: worldwide difference of prevalence and risk factors. j nephropharmacol. 2016; 5(1): 49–56. 2. magee c, grieve dj, watson cj, brazil dp. diabetic nephropathy: a tangled web to unweave. cardiovasc drugs ther. 2017; 31(5): 579–592.doi: 10.1007/s10557017-6755-9 3. hintsa s, dube l, abay m, angesom t, workicho a. determinants of diabetic nephropathy in ayder referral hospital, northern ethiopia: a case-control study. plos one. 2017; 12(4): e0173566.doi: 10.1371/journal. pone.0173566 4. shera as, jawad f, maqsood a, jamal s, azfar m, ahmed u. prevalence of chronic complications and associated factors in type 2 diabetes. jpma. 2004; 54(2): 54-9 5. janmohamed mn, kalluvya se, mueller a, kabangila r, smart lr, downs ja et al. prevalence of chronic kidney disease in diabetic adult out-patients in tanzania. bmc nephrology. 2013; 14:183.doi:10.1186/1471-2369-14-183 6. coll-de-tuero g, mata-cases m, rodriguez-poncelas a, pepio jma, roura p, benito b et al. chronic kidney disease in type 2 diabetic patients: prevalence and associated variables in a random sample of 2642 patients of a mediterranean area. bmc nephrology.2012;13:87. doi:10.1186/1471-2369-13-87 7. tziomalos k, athyros vg. diabetic nephropathy: new risk factors and 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disease among chinese patients with type 2 diabetes mellitus. european journal of medical research. 2013; 18:4. doi.org/10.1186/2047-783x-18-4 12. de boer ih, rue tc, hall yn, heagerty pj, weiss ns, himmelfarb j. temporal trends in the prevalence of diabetic kidney disease in the united states. jama. 2011; 305(24):2532-2539 13. uddin f, ali b, junaid n. prevalence of diabetic complications in newly diagnosed type 2 diabetes patients in pakistan: findings from national registry. j ayub med coll abbottabad. 2018; 30(4 suppl 1):652–8. 14. inassi j, vijayalakshmy r. role of duration of diabetes in the development of nephropathy in type 2diabetic patients. national journal of medical research. 2013; 3(1): 5-8 15. zhou y, echouffo-tcheugui jb, gu j, ruan x, zhao gm, zhang h et al. prevalence of chronic kidney disease across levels of glycemia among adults in pudong new area, shanghai, china. bmc nephrology. 2013; 14:253. doi:10.1186/14712369-14-253 16. machingura pi, chikwasha v, okwanga pn, gomo e. prevalence of and factors associated with nephropathy in diabetic patients attending an outpatient clinic in harare, zimbabwe. am j trop med hyg. 2017; 96(2): 477–482.doi: 10.4269/ajtmh.15-0827 17. wu ayt, kong nct, de leon fa, pan cy, tai ty, yeung vtf et al. an alarmingly high prevalence of diabetic nephropathy in asian type 2 diabetic patients: the micro albuminuria prevalence (map) study. diabetologia. 2005; 48(1): 17-26. doi.org/10.1007/s00125-004-1599-9 18. parving hh, lewis jb, ravid m, remuzzi g, hunsicker lg. prevalence and risk factors for microalbuminuria in a referred cohort of type ii diabetic patients: a global perspective. kidney international. 2006; 69:2057–2063. doi:10.1038/sj.ki.5000377 19. hasabi is, kardkal bl, bande us. the role of duration of diabetes in the development of nephropathy. journal of evidence based medicine and healthcare. 2017; 4: 60176021. doi 10.18410/jebmh/2017/1212 20. unnikrishnan r, rema m, pradeepa r, deepa m, shanthirani cs, deepa r, et al. prevalence and risk factors of diabetic nephropathy in an urban south indian population. diabetes care. 2007; 30(8):2019–2024 21. stratton im, adler ai , neil ha , matthews dr , manley se , cull ca , et al. association of glycemia with macrovascular and microvascular complications of type 2 diabetes (ukpds 35): prospective observational study. br med j. 2000; 321: 405 – 412 44 jiimc 2022 vol. 17, no.1 diabetic nephropathy 22. ahmed ma, kishore g, khader ha, kasturirangan mn. risk factors and management of diabetic nephropathy. saudi j kidney dis transpl. 2013; 24(6):1242-1247 45 jiimc 2022 vol. 17, no.1 conflict of interest authors declared no conflicts of interest. grant support and financial disclosure authors have declared no specific grant for this research from any funding agency in public, commercial or nonprofit sector. data sharing statment the data that support the findings of this study are available from the corresponding author upon request. this is an open access article distributed under the terms of the creative commons attributionnoncommercial 2.0 generic license. diabetic nephropathy original�article abstract objective: the aim of the study was to determine prevalence of urinary incontinence in post-partum females in tertiary care setups in hayatabad, peshawar. study design: cross-sectional. place and duration of study: tertiary care hospitals of hayatabad, peshawar from september 2016 to february 2017. materials and methods: a cross-sectional survey was conducted and a total of 296 females between 17 years and 40 years were recruited from september, 2016 to december 2016. the mean age of the population was 27.20 ± 4.46 years. participants were recruited by means of convenience sampling from tertiary care setups in hayatabad and were included in the study according to specified selection criteria. all of the participants completed bristol female lower urinary tract symptoms short form (bfluts-sf) after consent was taken and were evaluated accordingly. results: the prevalence of post-partum urinary incontinence in females coming to inand out-patients departments of tertiary care hospital hayatabad peshawar was 28.64%. out of total, 96% had moderate urinary incontinence i.e. between one third to two third of the time (1/3-2/3) and the remaining 4% had severe incontinence. majority of the women (84.4%) reported nocturia as their major symptom, while nocturnal incontinence/leakage was the lowest (9.8%). bladder pain (48.3%) and intermittency (36.5%) were the next highest reported symptoms. stress incontinence proved to be slightly more prevalent at 45.3%, whereas urge incontinence was at 43.9%. less than half of the population 36.2% women reported an adverse effect on their overall quality of life ranging from a little to a lot on the “bother” scale. conclusion: it can be concluded that urinary incontinence is a common condition in post-partum women in hayatabad with most patients reporting a mild to moderate effect on quality of life. key words: bfluts-sf, perpeurium, post-partum female, tertiary care, urinary incontinence. 3 counterpart's male population. although urinary incontinence is not a mortal condition, still the consequences are severely affecting quality of life of 4 all patients who are suffering from this condition. this issue is well documented and national and international networks have focused on this condition. however still organized, consistent and reliable data is deficient in developing country like pakistan where female population has limited access to health care services. urinary incontinence has various types which are mainly affected by specific conditions and therefore it may be described by specifying its relevant factors associated with those 5 conditions. the various forms of urinar y incontinence are stress, urge, and mixed urinary 6 incontinence. stress ui is the involuntary loss of urine during certain physical activities such as coughing, sneezing, laughing, jumping, or exercising etc., urge ui is the involuntary leakage of urine that is coupled with the lower urinary tract symptom urgency, and mixed ui is accompanied by urgency 1 and exercise, sneezing, or coughing. urinary introduction urinary incontinence is considered a significant health problem worldwide. according to the i n t e r n a t i o n a l c o n t i n e n c e s o c i e t y u r i n a r y incontinence is “the complaint of any involuntary 1 leakage of urine”. it can be associated with significant physical, psychological, social and 2 economic burden. as a result of urinary incontinence, a big portion of population get frustrated, socially isolated and are rendered incompetent. urinary incontinence is a common problem in woman population compared to their prevalence of urinary incontinence in post-partum females in hayatabad, peshawar 1 2 3 4 5 6 zoha gilani , haider darain , sadia aziz , mashal javed orakzai , laila raheem , musarrat jabeen correspondence: dr. haider darain assistant professor & director/principal institute of physical medicine and rehabilitation khyber medical university, peshawar 1,2,3,4,5 institute of physical medicine and rehabilitation khyber medical university, peshawar 6 kmu institute of medical sciences khyber medical university, peshawar funding source: nil; conflict of interest: nil received: jan 12, 2017; revised: mar 12, 2017 accepted: may 14, 2017 urinary incontinence in post-partum femalesjiimc 2017 vol. 12, no.2 106 majority of these studies have been carried out in developed countries. data regarding the prevalence of post-partum urinary incontinence in female population in countries like pakistani is scarce and need attention. therefore, this study was carried out in order to report intensity of the problem in female population living in the country. materials and methods a descriptive cross-sectional study was conducted in the inand out-patient gynaecology departments of tertiary care setups in hayatabad, peshawar. major tertiary care hospitals in hayatabad were included for this purpose. a total of 296 patients took part in the study after detailed information was provided to them and consent was taken. the participants all responded on standard questionnaire [bristol female lower urinary tract symptomsshort form (bfluts-sf)]. the questionnaire comprised of 5 parts and measured incontinence, severity of symptoms and its effect on the patient's quality of l i fe . t h e f i ve cate go r i e s a s s e s s e d by t h e questionnaire were a) filling symptoms which scored nocturia, urgency, bladder pain and frequency between voiding, b) voiding symptoms i.e. starring strain, hesitancy and intermittency c) incontinence symptoms i.e. pre-void dribbling, frequency daily, stress incontinence, unpredictable incontinence and nocturnal incontinence, d) sex symptoms i.e spoilt sex life and urine leakage during sex, e) quality of life symptoms which were scored on a “bother” scale. each question was scored from 0 to 4 with 0 pointing to no symptoms and 4 being worst possible symptoms. the last section i.e. the section consisting of questions pertaining to the quality of life assessed the degree of bother caused the symptoms caused. the sample was selected according to the inclusion criteria which consisted of female patients who were in the perpeurium period i.e. day 1-day 40, and had complaints of urinary incontinence. patients who had systemic diseases such as diabetes mellitus, previous urinary tract infection or any other n e u r o l o g i c a l d i s o r d e r l e a d i n g t o u r i n a r y incontinence were not included in the study. nonprobability sampling was carried out and patients were recruited according to convenience sampling. the total time duration for this study was 6 months. data was analysed using spss version 20. mean, range and standard deviation were measured for the incontinence is often associated with a variety of factors included pelvic floor muscles disorders, postmenopausal hypo-estrogenism, pregnancies and vaginal births, trauma of pelvic floor muscles, pelvic surgeries and the use of various medications like diuretics, chronic constipation, smoking, obesity 7 and diabetes mellitus. urinary incontinence is often considered a problem 8-10 that occurs mostly after pregnancy and childbirth. stanton et al. and allen and warell reported an increase in prevalence of stress urinary incontinence during pregnancy followed by a decrease after childbirth. the prevalence of urinary incontinence is around 20%-30% during pregnancy but it resolves 11 shortly after delivery. in contrast, in other trials, high prevalence of urinary incontinence was 12,13 reported after delivery before gestation. urinary incontinence is four times more common in women under 60 years age than in men of the same range of 14 age. it is noteworthy that prenatal incontinence increases the risk of postpartum incontinence suggesting an increased risk of long-term persistent 15-18 incontinence. the increased incidence rate of stress urinary incontinence during pregnancy and postpartum period is associated with low pelvic floor muscle strength. variation in the number of female population suffering from the condition may be 19,20 found in the literature ranging from 0.7% to 34%. similarly, in a systematic review prevalence of urinary incontinence during pregnancy was reported 16–60 % and after spontaneous and instrumental 21-23 vaginal delivery 16–34 %. the exact mechanism of urinary incontinence remained a dilemma, still, it is assumed that the condition develops at least in part as a result of 24 delivery trauma to the pelvic floor. pregnancy is a normal physiological phenomenon and many systemic changes occurring inside the body of a mother to meet the demands of a foetus. one of these changes included alteration in hormonal levels. it is well-known fact that the level of relaxing increases during pregnancy, which is thought to s t i m u l a t e c o n n e c t i v e t i s s u e r e m o d e l l i n g consequently playing a vital role in the modifications 25 female pelvis for delivery. as urinary incontinence remained a major problem during pregnancy, therefore, a huge number of trials may be found in the literature. it is noteworthy that 107 urinary incontinence in post-partum femalesjiimc 2017 vol. 12, no.2 them most of the time. cross tabulation between incontinence and other variables including age, parity, mode of delivery, duration of labor and bmi showed no significant differences suggesting that these factors have no major contributing role on incontinence in this population. the prevalence of urinary incontinence in this population was 85% with 82% moderately incontinent and 3% severely incontinent. discussion the aim of this study was to find out the prevalence of post-partum urinary incontinence amongst female population of hayatabad, peshawar in tertiary care settings. previous studies have shown post-partum urinary incontinence to be a significant problem with far reaching effects that considerably affects physical and psychological status of female population. a variation in the prevalence of postpartum urinary incontinence might be seen and it 19,20 has been reported between 0.7% to 34% in some trials. on the other hand its prevalence has been 21,22 reported between 16%-34%. in this study, we found the prevalence of post-partum urinary incontinence to be 28.% which in accordance to the previous trials carried out on the prevalence of the condition. finding of our trial suggested that stress i n c o n t i n e n c e r e m a i n e d h i g h e r t h a n u r g e incontinence. a disagreement about the type of incontinence may be found in the literature and higher ratio of developing post-partum stress incontinence in these patients have been 12,26 reported, while in the other trials, post-partum incontinence was reported a rarely occurring 13 situation in these patients. our study revealed that nocturia was one of the most cited symptoms in this population and 85% of the participants had nocturia; almost one fifth reported severe symptoms and more than half reported mild to moderate symptoms. this was followed by bladder pain which was experienced by almost half of the participants. other symptoms that also had high frequencies were intermittency, pre-void dribbling closely followed by starting strain, hesitancy and unpredictable miscellaneous incontinence. similar findings were reported in the trials carried out on urinary 27 incontinence in female population. quality of life assessment proved that the condition had severely affected quality of life in these patients. demographic data. results a total of 296 post-partum female patients with mean age 27.2 ± 4.4 years (range: 17-4 years) were included in this study. the mean marrying age of the participants was 21.32 ± 3.35 (range: 13-30). majority (53%) of this female population had undergone caesarean section while a small number (9%) had instrumental deliveries. the remaining (38%) had normal vaginal deliveries. majority of the female population (41%) was uneducated and the rest had completed their primary level (23%), secondary education (20%), graduation (15%) and post-graduation (1%). nutritional levels were determined by calculating bmis of the patients with most of them (38%) being in the overweight category. a total of 81% patients in this study were having moderately incontinence, while a small number of the patients (4%) were having severely incontinence and 15% of the patients had no symptom of incontinence i.e. they were continent. the mean total score for bfluts-sf was 12.0±10.0 with the following mean subscale scores fs=4.2 ± 3.2, vs= 1.5 ± 2.2, is= 3.6 ± 3.2, ss= 0.3 ± 0.8, qol= 2.3 ± 4.0. higher total sum scores were associated with higher chances of urinary incontinence. individually, nocturia remained the most reported symptom at 84% (64% moderate and 20% severe) while 16% reported no symptoms of nocturia. the lowest reported symptoms were 7% for the question pertaining to urine leakage during sex (see table 1 for frequency of severity of different symptoms). effects on quality of life subsection showed that 36% of the patients had reported an adverse effect on their quality of life (22% moderate14% severe). regarding changing their outer garments, 17% of the patients reported changing their outer garments once while 10% had to change them more frequently. water intake percentages showed that 11% of the population had decreased water intake to prevent frequent urination most of the time whereas 14% reported that they had reduced their water intake occasionally. in response to effects on daily activities, 10% of the patients responded 'quite a bit' and 14% reported a minor effect on their activities of daily living. avoidance of public places with no access to toilets was reported by 27% of the population with 18% avoiding them occasionally and 9% avoiding 108 urinary incontinence in post-partum femalesjiimc 2017 vol. 12, no.2 significantly affects overall quality of life in female population. it was found that the included population had reduced their water intake to help combat the problem while a quarter of the population confessed to avoiding public at places with no toilet facilities including markets or long journeys. the latter had severely affected their living style and majority of the population confined themselves to their homes or their movements were severely restricted. moreover, it was found that female population were using toileting facilities hourly up to multiple times an hour with a big number rushing to toilet in urgency. regarding the questions on sex, they appeared to not be applicable to one third of the population as it was their first pregnancy and they had not yet resumed the activity. regarding those who had it, a small number reported that their sexual life was adversely affects by incontinence. these findings are in accordance to the previous trials were sexual hypo or sexual dysfunction sexual was observed in female 28 population with urinary incontinence. t h e fa c t o rs a f fe c t i n g p o st p a r t u m u r i n a r y incontinence parity remained in accordance with other studies with multiparous women having more of a risk. other factors such as mode of delivery, duration of labour, number of pregnancy and bmi have been found to be significantly related to 20 postpartum urinary incontinence in some studies. however, in our trial no significant results were found for then mentioned factors. culturally, female population in pakistan especially in pathans culture is shy and we assumed that deviation of result from what is available in the literature might be caused by this issue. such issues may be covered by conducting large scale trials in the culture with questionnaires modified to the culture. this might be one of the l i m i t a t i o n s o f t h i s s t u d y. m o r e o v e r, t h e questionnaire used in this study was in english language and data collectors have to explain it to the participants. the responses of the participants were then recorded by the data collectors. conclusion in conclusion, the overall prevalence rate of postpartum urinary incontinence in perpeurial women in tertiary care setups in hayatabad, peshawar was within the range reported in other cultures. urinary incontinence may be regarded as one the major contributing factors that affects table i: showing the frequency values for severity of different symptoms references 1. abrams p, cardozo l, fall m, griffiths d, rosier p, ulmsten u, et al. he standardisation of terminology in lower urinary tract function: report from the standardisation subcommittee of the international continence society. urology. 2003; 61: 37-49. 2. yip sk, cardozo l. psychological morbidity and female urinary incontinence. best practice & research clinical obstetrics & gynaecology. 2007; 21: 321-9. 3. nitti vw. the 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journal of urology. 1990; 66: 12-5. 10. jolleys jv. reported prevalence of urinary incontinence in women in a general practice. bmj. 1988; 296: 1300-2. 11. nygaard i. urinary incontinence: is cesarean delivery protective? seminars in perinatology. 2006. 12. allen r, warell d. the role of pregnancy and childbirth in partial denervation of the pelvic floor. neurourol urodyn. 1987; 6: 183-4. 13. stanton s, kerr-wilson r, harris vg. the incidence of urological symptoms in normal pregnancy. bjog: an international journal of obstetrics & gynaecology. 1980; 87: 897-900. 14. sharifiaghdas f, tajalli f, taheri m, naji m, moghadasali r, aghdami n, et al. effect of autologous muscle-derived cells in the treatment of urinary incontinence in female patients with intrinsic sphincter deficiency and epispadias: a prospective study. international journal of urology. 2016; 7; 581-6. 15. groutz a, rimon e, peled s, gold r, pauzner d, lessing jb, et al. cesarean section: does it really prevent the development of postpartum stress urinary incontinence? a prospective study of 363 women one year after their first delivery. neurourology and urodynamics. 2004; 23: 2-6. 16. diez-itza i, arrue m, ibañez l, murgiondo a, paredes j, sarasqueta c. factors involved in stress urinary incontinence 1 year after first delivery. international urogynecology journal. 2010; 21: 439-45. 17. wesnes sl, hunskår s, bo k, rortveit g. the effect of urinary incontinence status during pregnancy and delivery mode on incontinence postpartum. a cohort study. bjog: an international journal of obstetrics & gynaecology. 2009; 116: 700-7. 18. fritel x, fauconnier a, levet c, bénifla jl. stress urinary incontinence 4 years after the first delivery: a retrospective cohort sur vey. acta obstetricia et gynecologica scandinavica. 2004; 83: 941-5. 19. viktrup l, lose g, rolf m, barfoed k. the frequency of 110 urinary incontinence in post-partum femalesjiimc 2017 vol. 12, no.2 page 41 page 42 page 43 page 44 page 45 original�article abstract objective: this study aimed to assess the effect of constraint induced movement therapy (cimt) augmented by virtual rehabilitation in improving upper extremity activity capacity and ability to perform activities of daily living (adl). study design: pre/post quasi experimental study. place and duration of study: it was carried out at the physiotherapy department at holy family hospital, rawalpindi in collaboration with islamic international medical college, riphah international university, islamabad, pakistan from march 2015 to march 2016. materials and methods: the study included 20 stroke patients who were subjected to constraint induced movement therapy augmented by virtual rehabilitation using nintendo wiitm four times a week for four weeks. upper extremity activity capacity and activities of daily living (adl) were measured preand postintervention using action research arm test (arat) and barthel index respectively. results: the arat improved from a pre-intervention mean score of 16.20+3.942 to 48.30+5.768 postintervention (p<0.001). barthel index showed improvement from the pre-intervention mean score of 9.05+2.544 to a post-intervention mean score of 16.80+1.609 (p<0.001). conclusion: virtual rehabilitation using nintendo wiitm has a positive impact on upper extremity motor recovery and subsequently the ability to carry out activities of daily living, if used as an adjunct to constraint induced movement therapy (cimt). key words: constraint induced movement therapy (cimt), nintendo wiitm, stroke, upper extremity motor capacity, virtual rehabilitation. lower limbs, speech difficulties, sensory deficits, impairment of genitourinary or bowel functions etcetera, that hinder activities of daily life and lower the chances of leading a normal, productive and 4 fulfilling existence. upper limb motor function impairment after stroke (the primary focus of this study) is one such complication that neurophysicians and physiotherapy specialists strive to improve as it allows the patients to, not only carry out daily life tasks with more ease and comfort but it has been shown to have a positive impact on the 5 psychological well-being of stroke survivors as well. regaining upper limb motor function post stroke by means of physical therapy has a corresponding positive impact on the ability to carry out routine tasks like bathing, dressing, toilet use, feeding and climbing up and down the stairs (collectively termed 6 as activities of daily living (adl)). constraintinduced movement therapy (cimt) is based on forced use of the affected limb by restraining the uncompromised limb for 90% of the waking hours and “shaping”, a form of behavioral conditioning in which certain task specific exercises are aimed at introduction stroke is the most common cause of disability 1 worldwide with 350,000 new cases per annum and a 2 prevalence of 4.8% in pakistan. thromboembolism of cerebral arteries and hemodynamic disturbances are the two main mechanisms involved in the pathophysiology of stroke. ischemic stroke accounts for 87% of the total burden of stroke while hemorrhagic strokes (spontaneous intracerebral and subarachnoid hemorrhage) comprise of the 3 remainder of all cases. survivors of stroke suffer debilitating sequelae like impairment of motor function of the upper and/or the effect of virtual rehabilitation and constraint induced movement therapy (cimt) on improving upper extremity motor activity post-stroke aiman farogh anjum, humaira fayyaz, arif siddiqui correspondence: dr. aiman farogh anjum department of physiology islamic international medical college riphah international university, islamabad e-mail: aiman.anjum@hotmail.com department of physiology islamic international medical college riphah international university, islamabad funding source: nil; conflict of interest: nil received: apr 22, 2016; revised: nov 05, 2016 accepted: jan 10, 2017 cimt based virtual rehabilitation post strokejiimc 2017 vol. 12, no.3 129 achieving a specific goal (such as movement of the impaired arm). the intensity of these tasks is increased in a step-ladder pattern according to the 7 patient's improvement. virtual rehabilitation is a novel technology that relies on the mirror-neuron system to bring about restructuring of the neuronal network in regions of the brain concerned with memory, learning and 8 motor function. in this aspect, nintendo wiitm is an innovative, cost-effective and ubiquitous technology which makes use of an on-screen “avatar” in order to incite “mirror-neurons” through “audio-visual” input to bring about neuronal re-organization and subsequent motor improvement. it has an added benefit of modifiable skill and speed which can be 9 tailored according to the user's needs. numerous studies have been conducted to shed some light on the effectiveness of virtual rehabilitation on motor improvement in stroke survivors but they have mainly focused on regaining lower limb function. furthermore, combination of vr with cimt for the purpose of improving the motor function profile in stroke survivors is an area that has 10 not been explored at length as yet. as far as the role of cimt augmented by motion capture consoles like nintendo wiitm in improving upper extremity motor function is concerned, a dearth of bonafide 11 research still remains. application of virtual reality based video games, nintendo wii in particular, for objectives other than stroke rehabilitation have shed some light on the effect of this console on improving hand-eye coordination. a study conducted at arizona state university by kullman, 2008, evaluating the efficacy of nintendo wii as a tool for improving hand-eye coordination in surgeons found that the use of n i n te n d o w i i a m o n g s u rg e o n s “ i m p ro ve s hand-to-eye coordination, strength and dexterity as the motion-sensitive controller allows some games to require very precise hand movements, similar to 12 those executed during surgery”. this effect might similarly manifest, albeit to a lesser extent, in the stroke survivor population undergoing “wii13 habilitation” allowing them to regain some level of coordinated hand and arm motion as well as a greater degree of strength and skill. data pertaining to upper extremity rehabilitation employing constraint induced movement therapy based on exergaming technology is scarce. this study aimed to assess the effect of constraint induced movement therapy (cimt) augmented by virtual rehabilitation in improving upper extremity activity capacity and ability to perform activities of daily living (adl). materials and methods this was a pre/post quasi experimental study with one year duration from march 2015 to march 2016. the study was conducted at medical unit i and ii and the physiotherapy department of holy family hospital rawalpindi in collaboration with islamic international medical college rawalpindi after the approval of ethical review committees at both institutions. the inclusion criteria were; first event of stroke, age ranging from 30 to 60 years, impairment of motor function in one arm, 1-4 months since the event of stroke, an understanding of computer/video game technology and clinically defined stroke by ct-scan or mri. patients of stroke with other neurological diseases, cognitive deficits, diagnosed dementia or epilepsy, language difficulty that would affect the capacity to receive information about the training procedure, visual impairment, orthopedic injuries that could impair locomotion, and inability to carry out voluntary arm movement were not included in the study. a total of 20 stroke patients were recruited in the study by purposive sampling. written informed consent was taken from all the subjects. the subjects were asked to report at physiotherapy department at holy family hospital rawalpindi in the morning. age, gender, blood pressure, hemisphere, type of stroke, and handedness of the subjects were recorded. “activities of daily living (adl)” were measured using the “10-item modified barthel index” which has a score of 0-20. upper extremity “activity capacity” was assessed using the “action research arm test (arat)”, scored from 0 to 57. the subjects were then subjected to constraint induced movement therapy/cimt for the upper extremity (a physiotherapy regimen where the use of the un-affected limb is limited by putting a weighted mitt over it for majority of the waking hours) using interactive video gaming technology (nintendo wiitm) for four sessions a week for four weeks (total 16 sessions) of 20 minute duration. the subjects cimt based virtual rehabilitation post strokejiimc 2017 vol. 12, no.3 130 were made to wear a weighted mitt on the unaffected arm during the course of the session. the speed and difficulty of each game was set according to each subject's level of comfort and the dexterity and mobility of the affected arm. the tasks each of the games demanded to be performed are listed in table i. they reported the time for which the unaffected was not used during the previous days before every session. “activities of daily living” and upper extremity “activity capacity” were assessed using the “barthel index” and “arat” respectively. statistical analysis was done using spss 21. results were documented as mean + sd. statistical significance was set at p < 0.05. paired-samples t-test was used to check difference in preand postintervention scores of arat and barthel index. results the demographic variables of the 20 subjects included in the study are given in table ii. highly significant (p<0.001) improvement was seen between the preand post-intervention scores of arat. all four subtests of arat i.e, grasp, grip, pinch and gross movement also showed highly significant improvement between the preand postintervention scores, given in table iii. the preintervention mean barthel index score was 9.05 +2.544. post-intervention barthel index scores improved to a mean value of 16.80 +1.609. the difference was highly significant (p<0.001), given in table iv. figures i, ii, iii and iv depict the comparisons of the items pertaining mainly to upper extremity function, namely “grooming, toilet use, feeding and dressing” in the barthel index, between the preand post-intervention scores of the subjects. the differences between the preand postintervention scores in the “grooming” item was significant (p<0.05) while it was highly significant in the “feeding”, “toilet use” and “dressing” (p<0.001). table i: tasks/movements demanded by each of the nintendo wiitm games employed in the study the gameplay was displayed on a projector screen. since the intervention pertained to the upper extremity only, the patients performed the tasks demanded by the games while sitting upright on a stool. the researcher herself carried out the intervention sessions, providing guidance to the subjects throughout the duration of the gameplay as well as assisting the subjects in case they encountered instability in maintaining sitting position (a rare occurrence). the gameplay sessions were scheduled for four days a week. ten minutes were designated to each of the two games mentioned. patients initially found it difficult to grasp the wii-mote optimally and were thus assisted by the velcro strap provided along with the wii-mote to cater for such difficulties. each subject's progress in terms of gameplay, speed and dexterity was charted along the course of the intervention phase. the level of difficulty of each game was progressively increased after the subjects showed improvement in performing the tasks demanded by the previous level of the videogames. the subjects were also asked to limit the use of the unaffected arm for the rest of the day and note the time for which they complied with this undertaking. table ii: demographic variables of the 20 stroke pa�ents in terms of mean ± sd of age (years), gender, type of stroke, stroke hemisphere, handedness and mean ± sd time since stroke (months) cimt based virtual rehabilitation post strokejiimc 2017 vol. 12, no.3 131 discussion the results showed that cimt augmented with virtual rehabilitation has a positive effect on improving upper extremity activity capacity which lends credibility to similar results seen in the single subject design trial by slijper et al. 2014, testing the effectiveness of computer game based upper extremity function showed marked improvement in arat scores in 11 of its 12 subjects after a five week 14 intervention phase. other similar trials have also shown improvements in arat scores following interventions based on computer, video game consoles as well as virtual rehabilitation. a pilot study aimed at evaluating the safety and effectiveness of nintendo wiitm as a rehabilitative tool for stroke survivors (christie et al., 2010) showed that although there was an overall improvement in arat scores in 6 out of the 9 total subjects after an intervention phase of 6 weeks, only the grip subscale showed significant improvement (p<0.05) in the affected arm. the finger pinch subscale also showed marked improvement but was not found to be 15 statistically significant. the improvement in arat scores in the current study could be attributed to two things. firstly, the current study employed not only nintendo wiitm but also subjected the patients to a detailed regimen of cimt while christie et al., used nintendo wiitm as the sole tool for improving motor function. secondly, the improved motor status of the upper extremity, is believed to be a consequence of long-term potentiation, as observed by saposnik et al. 2010 in the evrest trial, which results in the motor cortex retrieving old, and securing new patterns of motor function as a result of task repetition (one of the hallmarks of virtual 16 rehabilitation). it has been observed that the scores of arat, although consistently improved, are not statistically increased in majority of the trials that employ nintendo wiitm as the sole vehicle for upper extremity rehabilitation. however, studies that have used virtual rehabilitative tools as adjuncts to either 17 conventional therapy or to cimt have shown significant improvements in arat scores postintervention; findings supported by the current study's results. the highly significant improvement seen in the study group barthel index scores lend strength to a number o f s i m i l a r s t u d i e s t h a t e m p l o y e d v i r t u a l r e h a b i l i t a t i o n t o a c h i e v e m o t o r f u n c t i o n improvement for the upper extremity. one such study was the 12 week trial by cameirão et al. aimed at “using a multi-task adaptive vr system for upper limb rehabilitation in the acute phase of stroke” which showed significant improvement in barthel index, motricity and fugl-meyer scales for the upper extremity in the study group which underwent rehab therapy using a “rehabilitation gaming system 18 (rgs)”. trials conducted by kyoung-hee lee 2015, kwon js et al. 2012 and yoon j et al. 2015 were based on comparing the effectiveness of virtual rehabilitation as an adjunct to conventional therapy versus conventional therapy alone for upper extremity rehabilitation. all three trials exhibited significant improvement in the respective forms of barthel indices used in each study in the study 19-21 groups. evidence based on such data suggests a positive impact of virtual rehabilitation on the imp rovement in u p p er limb f u n ct io n a n d subsequently on the quality of everyday life. the possible explanation for the overwhelming improvement in the adl scale scores of the study groups in each of the trials mentioned as well as those of the current study could be the self-driven effort of the subjects in each study to adhere strictly to the therapy regimen, improvement in hand-eye table iii: comparison between the mean ± sd total scores of arat, grasp, grip, pinch and gross movement, pre and post interven�on ac�on research arm test (arat), gross movement (grosmt) * = p<0.05 (pre-interven�on vs post-interven�on) ** = p<0.001 (pre-interven�on vs post-interven�on) table iv: comparison between the mean ± sd barthel index scores between the preand post-interven�on assessment barthel index (bi) * = p<0.05 (pre-interven�on vs post-interven�on) ** = p<0.001 (pre-interven�on vs post-interven�on) cimt based virtual rehabilitation post strokejiimc 2017 vol. 12, no.3 132 coordination and overall increased therapy time (cimt plus time spent playing the virtual rehab games) in addition to the long term potentiation induced by repetitive tasks required to be performed during the gaming sessions. the role of cimt in bringing about significant improvement in motor function, as reflected by results of arat and barthel index in the current study cannot be ignored. according to langhorne et al., 2009 and van peppen et al., 2004, cimt has “a significant effect on increasing upper extremity (arm) function” and a “moderate effect on increasing performance of the activities of daily living immediately following treatment (sirtori et al., 22-25 2009).” conclusion virtual rehabilitation has a positive impact on upper extremity motor recovery if used as an adjunct to more robust models of therapy like constraint induced movement therapy (cimt). it is an effective and safe means of engaging stroke survivors in rehabilitative practices by increasing self-directed therapy time and improving motor function. however, there is a need for trials to be carried out on a larger scale, involving a greater population of stroke patients. references 1. feigin vl. stroke epidemiology in the developing world. the lancet. 2005; 365: 2160-1. 2. khealani ba, wasay m. the burden of stroke in pakistan. international journal of stroke. 2008; 3: 293-6. 3. sierra c, coca a, schiffrin el. vascular mechanisms in the pathogenesis of stroke. current hypertension reports. 2011; 13: 200-7. 4. whitall j, waller sm, silver kh, 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"bridging e-health and the internet of things: the sphere project." ieee intelligent systems. 2015; 4: 39-46. 14. kullman j. wii” bit of technology aids medical education. retrieved june. 2008; 9: 5-6. 15. winkels dg, kottink ai, temmink ra, nijlant jm, buurke jh. wii™-habilitation of upper extremity function in children with cerebral palsy. an explorative study. developmental neurorehabilitation. 2013; 16: 44-51. 16. slijper a, svensson ke, backlund p, engström h, sunnerhagen ks. computer game-based upper extremity training in the home environment in stroke persons: a single subject design. journal of neuroengineering and rehabilitation. 2014; 11: 1-4. 17. christie l, kennedy s, brennan k, ellis g, barber m. does stroke wii hab work? use of the nintendo wii for upper limb rehabilitation following stroke. cerebrovasc dis. 2010; 29: 254-5. 18. saposnik g, teasell r, mamdani m, hall j, mcilroy w, cheung d, et al. effectiveness of virtual reality using wii gaming technology in stroke rehabilitation a pilot randomized clinical trial and proof of principle. stroke. 2010; 41: 1477-84. 19. gordon am, okita sy. augmenting pediatric constraintinduced movement therapy and bimanual training with video gaming technology. technology and disability. 2010; 22: 179-91. 20. cameirão ms, oller ed, verschure pf, editors. using a multitask adaptive vr system for upper limb rehabilitation in the acute phase of stroke. virtual rehabilitation, 2008; 2008: ieee. 21. park hj, kim tu, hyun jk, kim jy. family history and functional outcome in korean stroke patients: a preliminary study. annals of rehabilitation medicine. 2015; 39: 980-5. 22. kwon js, park mj, yoon ij, park sh. effects of virtual reality on upper extremity function and activities of daily living performance in acute stroke: a double-blind randomized clinical trial. neurorehabilitation. 2012; 31: 379-85. 23. chen cc, chen yl, chen sc. application of rfid technology—upper extremity rehabilitation training. journal of physical therapy science. 2016; 28: 519-24. cimt based virtual rehabilitation post strokejiimc 2017 vol. 12, no.3 133 24. langhorne p, coupar f, pollock a. motor recovery after stroke: a systematic review. the lancet neurology. 2009; 8: 741-54. 25. sirtori v, corbetta d, moja l, gatti r. constraint-induced movement therapy for upper extremities in stroke patients. cochrane database syst rev. 2009; 4: 4-6. cimt based virtual rehabilitation post strokejiimc 2017 vol. 12, no.3 134 page 12 page 13 page 14 page 15 page 16 page 17 jiimc june 2021.cdr original�article abstract objective: to evaluate the effect of pioglitazone on anthropometric and metabolic parameters in infertile women suffering from polycystic ovarian syndrome (pcos). study design: randomized controlled trial. place and duration of study: the study was conducted in the pharmacology department of bahira university th medical and dental college in collaboration with infertility clinic, mamji hospital karachi from 24 september th 2018 to 30 march 2019. materials and methods: forty infertile women aged 20-40 years using non-probability convenient sampling technique were enrolled as per rotterdam criteria 2003. they had fasting insulin level > 9μu/ml, the fasting glucose level of 7 mmol/l or ≥126 mg/dl, and cyclical irregularity such as oligomenorrhoea/amenorrhea. they were given tablet pioglitazone 30 mg once daily per orally for three months. all participants were subjected to evaluation of anthropometric (weight, bmi, waist and hip circumference, and waist-hip ratio) and metabolic parameters (1. carbohydrate – fasting serum glucose and insulin, 2. lipids – total cholesterol, triglycerides, lowdensity lipoprotein cholesterol ldl-c), very-low-density lipoprotein cholesterol (vldl-c), high-density ( lipoprotein cholesterol (hdl-c), and 3. protein–serum hs-crp). the paired t-test was applied for comparison at the end of three months. data analysis was performed by spss version 23. results: thirty-one participants completed the study. we found a mean reduction of 3.17 kg in weight, bmi 1.2 2 kg/m , and w/h ratio 0.018 in anthropometric parameters. mean reduction of fasting serum glucose 19 mg/dl, insulin 6.61 µiu/ml, hdlc 3 mg/dl, ldl-c 7 mg/dl, vldlc 6 mg/dl, total cholesterol 14 mg/dl, triglycerides 32 mg/dl and serum hs-crp level 1.85 mg/l was found. conclusion: pioglitazone reduces anthropometric parameters and causes a significant reduction in metabolic parameters among polycystic ovarian syndrome infertile women. key words: infertility, insulin resistance, pioglitazone, polycystic ovarian syndrome. rotterdam criteria upon having 2 out of 3 characteristics: oligo or anovulation, increased serum androgen level & appearance of multiple cysts in the ovaries on ultrasound scan along with t h e o m i s s i o n o f o t h e r r e a s o n s f o r hyperandrogenism, such as the adrenal or pituitary malfunction. 3 more than half of the pcos patients have increased basal metabolic rate or are obese and thus have an increased risk of concomitant obesity4 related diseases. all these abnormal metabolic characteristics lead to infertility that includes insulin resistance, overweight/obesity, type 2 diabetes, dyslipidemia, and a greater chance of developing 5 heart disease. if left untreated pcos can cause endometrial cancer due to elevated level of estrogen and lower level of progesterone that predispose to 6 endometrial hyperplasia. pathophysiology of polycystic ovarian syndrome is complicated and vague, it is said that resistance develops against introduction polycystic ovarian syndrome (pcos) is a hormonal syndrome of females that affects reproductive life, 1 f o u n d i n 6 1 0 % o f f e m a l e s . i r r e g u l a r menstruation (oligomenorrhea/ amenorrhea), hyperandrogenism, polycystic ovaries, decreased sensitivity to insulin and persistent oligo2 anovulation are its main components. pcos is diagnosed by the internationally accepted impact of pioglitazone on anthropometric and metabolic parameters in pcosinfertile women 1 2 3 ayesha khan , nasim karim , jahan ara ainuddin correspondence: dr. ayesha khan senior lecturer bahria university medical and dental college, karachi e-mail: dr.ayeshakhan85@gmail.com 1,2 department of pharmacology bahria university medical and dental college, karachi 3 department of gynecology dow international medical college dow university of health sciences, karachi funding source: nil; conflict of interest: nil received: january 11, 2020; revised: november 17, 2020 accepted: november 18, 2020 impact of pioglitazone in pcos infertile women jiimc 2021 vol. 16, no.2 101 circulating insulin and is associated with hyperinsulinemia that plays a major part in the 7 endocrine and reproductive features of pcos. hypothalamus secrets gonadotropin-releasing hormone in an episodic manner that is often disrupted in pcos, leading to the excessive release of luteinizing hormone (lh) by the pituitary gland, causing ovulatory dysfunction and increased blood 8 androgen levels. pathogenesis of pcos is associated with the modification or alteration of the ppar-γ gene and thus drugs acting at this level can improve the anthropometric and metabolic characteristics of such women. ppar-γ agonists reduce the androgen synthesis in the ovaries indirectly and improve 9 resistance against insulin in peripheral tissues. pioglitazone, a thiazolidinedione effective for type two diabetes, is a highly selective agonist acting on ppar-γ receptors, located in the liver, fat tissues, skeletal muscle, etc. it is susceptible to insulin. there is a role of ppar-γ receptor in the expression of gene responsible for insulin release and metabolism of 10 carbohydrates, fat, and proteins. documented literature on anthropometric and metabolic parameters in polycystic ovarian syndrome infertile women following the use of pioglitazone is scarce, therefore this study was conducted to evaluate the effect of pioglitazone on anthropometric & metabolic parameters in pcos induced infertility. materials and methods this clinical trial was conducted after approval from erc of bahria university medical & dental college th vide (51/2018) for six months from 24 september th 2018 till 30 march 2019 at the pharmacology department of bahria university medical & dental college in collaboration with the infertility clinic of mamji hospital karachi. the sample size was calculated by using prevalence of pcos coded by 1 bozdag and his colleagues via www.openepi.com taking a 5% margin of error and 95% confidence interval. written informed consent was taken from all patients. the total sample size was 80 with 40 patients in each group. this manuscript is based on the data of group a only. diagnosed pcos infertile women were enrolled as per rotterdam criteria 8 2003. our patients had classic pcos phenotype " a”. i t i n c l u d e s c l i n i c a l a n d b i o c h e m i c a l hyperandrogenism (clinical hyperandrogenism was evaluated by modified ferriman-gallwey (mfg) scoring system for hirsutism (mean value in our patients = and 8 9.07±1.753, cutoff value ≥ 6) biochemical parameters (serum total testosterone level in our patients = 79.42 ± 17.40 ng/dl, cut off 11 value ≤ 67 ng/dl) , oligo-anovulation (serum progesterone level in our patients = 1.24 ± 0.50 12 ng/ml, cut off value of 3 ng/ml) , polycystic ovarian morphology (total number of follicles in our patients 13 = 13.06 ± 0.68, cut of value of 10-12 follicles). the inclusion criteria was infertile females, aged 20-40 years with fasting levels of serum insulin (>9μu/ml) 14 15 , glucose (7 mmol/l or ≥126 mg/dl) , and suffering from cyclical irregularity such as oligomenorrhea/ amenorrhea. women with endocrine disorders such as cushing's syndrome, hypothyroidism, congenital a d r e n a l h y p e r p l a s i a , h y p e r p r o l a c t i n e m i a , acromegaly, metabolic (familial hyperchole sterolemia) and organic diseases (diabetes, hepatic or renal insufficiencies), women using oral contraceptives/injectables, and females who had undergone oophorectomy/ovarian ablation 16 therapy were excluded from the study by biochemical tests (data not mentioned in the present manuscript) and clinical examination by the gynecologist. all patients were advised for 30-60 minutes daily walk, avoidance of oily foods, red meat, and bakery product. they were given tablet pioglitazone 30 mg orally once daily for three 17 months. anthropometric measurements–weight (kg) was measured by using a weighing scale, 2 quetelet index formula: bmi=weight / height (m ) was used to calculate bmi, as per asian criteria; bmi ≥ 25 and waist to hip ratio ≥ 0.80 in women is considered as obesity documented by hastuti and 18 his team, waist circumference was measured at the minimum circumference between the iliac crest and the rib cage in standing position at the end of normal expiration using a non-elastic tape, hip circumference was measured at the level of greater trochanters using a flexible tape, waist to hip ratio was calculated by dividing waist circumference (wc) to hip circumference (hc) as per the method 19 documented by chen and his colleagues. the blood sample was drawn from the cubital vein after an overnight fast of 12-14 hours for the detection of metabolic parameters – fasting serum glucose, insulin, lipid profile (hdl-c, ldl-c, vldl-c, impact of pioglitazone in pcos infertile women jiimc 2021 vol. 16, no.2 102 total cholesterol, triglycerides), and hs-crp. they w e r e m e a s u r e d b y c h e m i l u m i n e s c e n c e immunoassay. the glucose/insulin ratio was calculated by dividing fasting serum glucose value with insulin. vldl-c was estimated by friedewald's 20 equation. all parameters were assessed at baseline and at the end of 3 months. spss version 23 was used to analyze the data. data was normally distributed andpaired t-test was used for comparison at the end of treatment. results out of forty, nine patients failed to return, while 31 completed the study. anthropometric parameters of w e i g h t , b m i , w a i s t c i r c u m f e r e n c e , h i p circumference, and waist-to-hip ratio showed nonsignificant reduction as shown in table-i. metabolic parameters (carbohydrate, lipid profile, and protein metabolism) as shown in table-ii. in carbohydrate metabolism, parameters of fasting serum glucose and insulin showed a highly significant reduction. in lipid metabolism, hdl-c also showed a highly significant reduction whereas ldl-c, vldl-c, cholesterol, and triglycerides showed a significant reduction. serum hs-crp representing protein metabolism showed a highly significant reduction. problems such as hyperandrogenism (ha), menstrual irregularities, infertility, and pregnancy complications, but also causes long term complications such as dyslipidemia, insulin resistance, elevated risk of type two diabetes and 21 metabolic syndrome. we have found a reduction but non-significant in mean weight and bmi after 3 months of treatment with pioglitazone. this reduction may be due to a combination of lifestyle changes (one hour daily brisk walk) and dietary advice (avoidance of red meat, bakery products, and oily foods) given to all study participants along with the drug treatment. these findings are contradictory to sohrevardi et al. they have documented that pioglitazone produced weight gain after three 22 months of treatment. this is probably due to fluid retention that leads to weight gain or it might be due 23,24 to an increase in the mass of adipocytes. central obesity is more common in pcos; fat accumulates in the abdomen predominantly and is table i: anthropometric parameters (n=31) note: bmi: body mass index w / h ratio: waist to hip ratio < 0.05 p-value = significant table ii: comparison of metabolic parameters (n=31) hdl-c: high-density lipoprotein cholesterol ldl-c: low-density lipoprotein cholesterol vldl-c: very-low-density lipoprotein cholesterol hs-crp: high sensitivity c-reactive protein, g/i ration glucose / insulin ratio < 0.05 p-value = significant *= significant discussion polycystic ovarian syndrome (pcos) is a prevalent endocrine disorder and affects 6%–18% in reproductive age group females. it is not only in association with reproductive and obstetric impact of pioglitazone in pcos infertile women jiimc 2021 vol. 16, no.2 103 related directly to an increase in insulin resistance. 25 this can be measured by waist circumference. in our study, waist circumference (wc) and hip circumference (hc) were exhibited non-significantly reduced in the end and so do the waist-to-hip ratio because pioglitazone effectively decreases central obesity in polycystic ovarian syndrome (pcos) and these are similar to the findings reported by gupta 26 and colleagues. waist and hip circumference were significantly increased, documented by tanwar and his team and this is contradictory to our findings. it may be due to a decrease in visceral fat and an 23 increase in subcutaneous fat. pcos causes ovarian hyper-androgenemia due to increased sensitivity to insulin by the ovary as opposed to the resistance of the whole body. it is prevalent in 65-80% of patients. it increases the chances of diabetes mellitus as well as diseases of 27 heart and blood vessels. we have found a significant reduction in mean fasting serum glucose and insulin levels, which is coinciding with the study 28 done by rokade and colleagues. however, hwang and colleagues have documented a non-significant reduction in mean fasting serum glucose and insulin 29 levels and this is contradictory to our study. glucose to insulin ratio was significantly increased which is coinciding with the study conducted by narsing and 30 his team members. decreased sensitivity of insulin causes increased shunting of free fatty acids from fat tissues to the liver in adipocytes. free fatty acids induce hepatic synthesis of vldl-c resulting in increased levels of triglycerides and decreased level of hdl-c. these derangements in lipid parameters lead to atherogenic dyslipidemia. in our study, we have found significant reduction in ldl-c, vldl-c, total cholesterol, and triglycerides levels after three months of treatment with pioglitazone, which is like 31 the study done by devi and colleagues. c h o l e ste ro l l e v e l , l o w d e n s i t y l i p o p ro te i n cholesterol (vldl-c), and triglycerides also showed a significant decrease as documented by dawson and 32 his team which is similar to our finding. significant reduction is found in the serum high-density lipoprotein cholesterol level which is similar to the 17 study done by shahebrahimi and colleagues. however, the exact cause of the decrease in hdl-c could not be elucidated, whereas sangeeta has documented a significant increase in hdl-c which is contradictory to our study. this may be due to the anti-arteriosclerotic properties of pioglitazone and could also be due to a long duration of study that is six months in comparison to our study period of 33 three months. a non-significant reduction in all lipid parameters is observed by sohrevardi and his 22 colleagues which is contradictory to our study. it is probably due to the difference in ethnicity of study populations. c-reactive protein is produced by the liver. it is an a c u t e p h a s e r e a c t a n t , i n d i c a t e s c h r o n i c inflammation & its level is elevated in pcos because 34 of subclinical inflammation in pcos. we have found a significant reduction in serum hscrp which is like the study done by dawson and his colleagues. this is because pioglitazone decreases serum hs-crp level by modulating inflammation 32 through ppar-γ. present study was conducted at a single infertility clinic with an individual period of 3 months. large multicentric studies of longer duration should be conducted to authenticate our result findings and to produce generalize data for implementation. conclusion pioglitazone produces favorable effects on 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effects of metformin and pioglitazone on clinical symptoms in cases of polycystic ovarian syndrome. int j basic clinpharmacol. 2016;5(1):98-104. 24. filipova e, uzunova k, kalinov k, vekov t. effects of pioglitazone therapy on blood parameters, weight, and bmi: a meta-analysis.diabetolmetabsyndr. 2017; 9:90. 25. çakıroğlu y, vural f, vural, b. the inflammatory markers in polycystic ovary syndrome: association with obesity and ivf outcomes. j endocrinol invest. 2016;39(8):899-907. 26. gupta a, jakubowicz d, nestler je. pioglitazone therapy increases insulin-stimulated release of d-chiro-inositolcontaining inositol phosphoglycan mediator in women with polycystic ovary syndrome. metabsyndrrelatdisord. 2016;14(8):391-96. 27. shah d, rasool s. pcos and metabolic syndrome: the wo r r i s o m e tw o s o m e ? e n d o c r i n o l m e t a b s y n d . 2015;4(2):1-7. 28. rokade av, javdekar dp, patange rp. comparison of metformin and pioglitazone in pcos. journal of evolution of medical and dental sciences. 2013;2(15):2532-37. 29. hwang kr,choi ym, kim jj, chae sj, park ku, jeon hw. effects of insulin-sensitizing agents and insulin resistance in women with polycystic ovary syndrome. clinexpreprod med. 2013;40(2):100-105. 30. narsingrao l, jacob jj, paul tv, rajarathinam s, thomas n, seshadri ms. effects of pioglitazone on menstrual frequency, hyperandrogenism and insulin resistance in adoloscents and young adults with polycystic ovary syndrome. j pediatradolesc gynecol. 2009;22(2):91-95. 31. devi as, anuradha j. metformin and pioglitazone in polycystic ovarian syndrome: a comparative study. iaim. 2017;4(7):39-44. 32. dawson aj, kilpatrick es, coady am, elshewehy amm, dakroury y, ahmed l, et al. endocannabinoid receptor blockade reduces alanine aminotransferase in polycystic ovary syndrome independent of weight loss. bmc endocrdisord. 2017;17(1):41. 33. sangeeta s. metformin and pioglitazone in polycystic ovarian syndrome: a comparative study.j obstetgynaecol india. 2012;62(5):551-56. 34. ganie am, hassan s, nisar s, shamas n, rashid a, ahmed i, et al. high-sensitivity creactive protein (hs-crp) levels and its relationship with components of polycystic ovary syndrome in indian adolescent women with polycystic ovary syndrome (pcos). gynecolendocrinol, 2014; 30(11):781-84. impact of pioglitazone in pcos infertile women jiimc 2021 vol. 16, no.2 105 jiims.cdr abstract objective: to determine the effectiveness of intrasheath steroid injection in treating de quervain`s disease. study design: case series observational study. place and duration of study: outpatient department of orthopedics bbs [dhq] teaching hospital abbottabad from april 2006 to sept 2009 including a period of follow up of eighteen months. materials and methods: eighty patients with de quervain`s disease were diagnosed on the basis of positive finkelstein`s test and presence of severe pain for more than four weeks. these patients were given intrasheath injections of 40 mg methyl prednisolone mixed with one ml of lignocaine 2% in the first dorsal compartment of wrist. patients with trauma, infection and rheumatoid arthritis were excluded from study. results: seventy two patients i.e., 90% were cured and out of them 75% required only one injection .only two cases underwent surgical release. conclusion: intrasheath steroid injection is a safe, very useful and cost effective method in treating de quervain`s disease. key words: de quervain's disease, intra sheath injection, steroid injections 87 original article importance of non surgical options is not 4 emphasized. recently there have been a number of claims regarding the efficacy of intrasheath steroid injection. sawaizumi, et. al., reported an efficacy rate of 94% with intrasheath injection of 5 steroids. richie and eriner reviewing seven current reputable papers, concluded that the efficacy rate of injecting the steroid alone 6,7,8,9 was 83%. it is a safe and simple technique which can be carried out in outpatient 10 department. there is very little chance of 11 serious complications as well. hence this study was carried out to further strengthen this claim that injection treatment of de quervain's disease is the best option and it is not associated with any serious complication. this observational study was done in outpatient department of orthopedics of bbs [dhq] teaching hospital abbottabad from april 2006 to sept 2009 including a follow up period of eighteen months. eighty patients, who were diagnosed on the basis of positive finkelstein test, were included in this study. all patients had severe pain materials and methods introduction in a busy outpatient department of orthopedics or rheumatology we come across with a lady having a sore thumb and wrist, almost on daily basis. it was fritz de quervain, a swiss surgeon who in 1895, first described this condition as a tenosynovitis 1 of the first dorsal compartment. most of patients suffering from this problem first try different things either at their own or on the advice of their gp's ranging from natural to physical therapies and nsaid etc. but to their dismay most of these techniques fail and they have to seek the advice of specialist doctor. surgical release of the stenosing sheath is a good option in resistant de quervain's cases. although performed as a day case, it requires about two weeks for complete recovery, besides it is much costly and a s s o c i a t e d w i t h a n u m b e r o f 2,3 complications. surgical treatment is often chosen without careful consideration and ------------------------------------------------correspondence: dr. syed qasim mehmood assistant prof of orthopedics women medical college abbottabad email: sqmehmood@hotmail.com efficacy of intrasheath steroid injection in treating de quervain's disease syed qasim mehmood, johar ali, asif saeed, muhammad nawaz, rifat latif 88 which was interfering their daily activities for more than four weeks. besides other methods of treatment like rest, splints, physiotherapy and nsaids had not given much benefit. all patients with a history of rheumatoid arthritis, trauma or local infection were excluded. we injected 40 mg of methyl prednisolone mixed with one ml of lignocaine 2% in a 3 cc syringe. instead of giving vertical injections we bent the needle at 45 degrees and passed it from distal end proximally parallel to the involved tendon in the first dorsal compartment of wrist. slight ulnar deviation made it easy. intra sheathal status of the needle was ensured by the need of less force to push the syringe and absence of swelling in subcutaneous tissue. all patients were asked to report after two weeks if no complications occurred. success was measured by absence of pain on wrist movements and a negative finkelstein`s test. second injection was given after three weeks in patients who showed less improvement or recurrence. a third injection was given after another three weeks in cases who had still not responded to the treatment. out of 80 patients, 72 were considered to be cured as they remained symptom free after 18 months of follow up. in 75% of these cases only one injection was used (table ii). in others a second injection was given after 03 weeks. out of 80 patients, those who reported with recurrence even after second injection, a third injection has to be given i.e., 08 patients (10%). of these 08 cases, 02 finally underwent surgical release. the fear and doubts about injection were removed, to a large extent by proper counseling. after injection, 90% of patients were satisfied and ready to accept it again if required. slight increase in pain was reported by 70% of patients which however improved over a week in patients who were later declared results cured. depigmentation at the injection site was reported in five patients and atrophy of fat in subcutaneous tissue was seen in one patient only. no tendon rupture, infection or injury to radial nerve was seen. slight increase in pain was reported by 70% of patients which however improved over a week in patients who were letter declared cured depigmentation at the injection site was reported in five patients and atrophy of fat in subcutaneous tissue was seen in one patient only. no tendon rupture, infection or injury to radial nerve was seen. owing to de quervain's tenosynovitis common occurrence, there must be some treatment guidelines and recommendations so as to save time and cost. the brigham and women's hospital guidelines for treatment of de quervain's tenosynovitis, state that corticosteroid injection may be very helpful and that they should be considered if symptoms persist beyond 6 weeks of 1 2 conservative treatment. whereas orthopedic text books recommend corticosteroid injection for de quervain's tenosynovitis after 2 weeks of conservative 1 3 t re a t m e n t h a s f a i l e d . u p t o d a t e recommends steroid injection if pain persists for more than 2 to 6 weeks despite 14 splinting , icing and nsaid therapy. a pooled quantitative literature search concerning the treatment of de quervain's tenosynoritis compared 07 studies (a total of 459 wrists of the 226 cases) treated with steroid injection alone 83% were cured, though 30 of these needed a second injection. sixty one percent of those treated with injection and splint were cured, while 7 14% treated with splint alone reported cure. in another retrospective study comparing injection with splinting and non steroidal anti inflammatory drugs nsaids, authors discussion 89 stratified patients into minimal, mild, or moderate to severe, groups based on their severity of disease. of those cases treated with splinting and nsaids, 15 of 17 in the minimal group had resolution of symptoms, but only 4 of 20 in the mild group and 2 of 8 in the moderate to severe group had symptoms resolved. the injection group showed better results with 100% of cases in the minimal to mild groups resolving and 76% of those in the more severe group resolving completely with an additional 7% 15 reporting improvement. to make steroids more effective, injection needs to be properly placed in the tendon 16 compartment i.e. intra sheath. the efficacy can be enhanced and compilation rate reduced to almost nil by ultrasound guided 17 injections of steroids into tendon sheaths. however an earlier prospective study of 103 patients found suprafibrous injection to be easier to perform than intrasynovial 18 injection and to have the same effects. in our study we gave intra sheath injections and did not find it much difficult, besides it can also avoid potential complications of leakage of steroids in subcutaneous tissue or damage to superficial radial nerve by misplaced needle. we slightly modified the original technique by bending the needle to almost 45 degree and inserting it beneath the 19 tendons along there line proximately. an orthopedics study compared different techniques for injection and found that two point injections vertically in the indurated 5 area is better than injection at one point. but we think if it is properly placed in the sheath or compartment, it does not matter even if there is a septum with in the first dorsal 20, 21 compartment of wrist. this septum would be more effective than surgical as compared to injection as injection liquid would spill over or will he absorbed in the vicinity as well that is why taras js et. al., concluded that exact location of injection into the sheath may not be important in the 22 treatment of trigger digits. surgical release is not a bad option in de quervain's disease but it is not fair to choose an option which is invasive, costly and not without some serious complications, particularly when a simple injection of 23 steroids can cure almost 80-90% of cases. however in chronic cases with much thickening of the sheath and those not responding to repeated local injection can be treated by surgical release with good long 24, 25 term relief. intrasheath steroid injection is a safe, very useful and cost effective method in treating de quervain`s disease. conclusion table i: demographic data of study population (n= 80) table ii: number of injections and their response in the treatment of de quervain's disease (n= 80) 90 references 1. lapidus pw. stenosing tenosynovitis. surg clin north 1953:33:131747. 2. froimson a. tenosynovitis and tennis elbow. in: green dp (ed) operative hand surgery vol 2 3rd edn. churchill livingstone. new york: 1993. pp1989-2006. 3. tak t, eidelman d, thomson jg. patient satisfaction and outcomes of surgery for de quervain's tenosynovitis. j hand surg1999; 24: 1071-7. 4. ahuja nk, chung kc, fritz de quervain. stenosing tendovaginitive at the radial styloid process. hand surg 2004; 29:1164-70. 5. sawaizumi t, nanno m, ito h, de quervain's disease: efficacy of intrasheath triamcinolone injection. int orthop 2007; 31: 265-8. 6. harvey fj, harvey pm. de quervain's disease: surgical or non surgical treatment j hand surg 1990; 15:83-7. 7. richie ca iii, eriner ww jr. corticosteroid injection for treatment of de quervain's tenosynovitis a pooled quantitative literature evaluation. j am board fam pract 2003; 16:102-6. 8. weiss ac, abeiman e, tabatabai m. treatment of de quervain's disease. j hand surg 1994; 19:595-8. 9. zingas c, failla jm, holsbeeb mv. injection accuracy of clinical relief of de quervain's tendinitis. j hand surg 1998; 23: 89-96. 10. tallia. am fam physician 2003; 67:745-50. 11. avei. j hand surg 2002; 27:322-4. 12. brigham and women's hospital upper extremity musculo skeletal disorders: a guide to prevention, diagnosis and treatment. boston, mass: brigham and women's hospital 2003. 13. brinker mr, millor md. the adult wristin: fundamental of orthopeadics. philadelphia, pa: wb saunders; 1999: 179-95. 14. anderson bc, sheon rp. de quervain's tenosynovitis up to date [on line data base] (updated may 7, 2004) waltham, mass: up to date; 2004. 15. lane lb, boretz rs, stuchin sa. treatment of de quervain's disease: role of conservative management. j hand surgery 2001; 26:258-60. 16. ilyas am, astm, schaffer aa. de quervain's tenosynovitis of the wrist. j am acad orthop surg 2007; 15: 757-64. 17. jeyapalen k, chowdhary s. ultrasound guided injection of triamcinolne and bupivicaine in the management of de quervain's disease. skeletal radiol 2009; 38:1099-103. 18. apimonbutr p, budhraje n. suprafibrous injection with corticosteroid in de quervain's disease. j med assoc thai 2003; 86: 232-7. 19. lennard ta. fundamentals of procedural care. in : lannard ta , ed. physiatric procedures. in clinical practice. philadelphia, pa: hanley and belfus; 1995:1-13. 20. jachson wt, viegas sf, coon j mol. anatomical variation in the first extensor compartment of wrist: clinical and anatomical study. j bone joint surg 1986; 68:923-6. 21. leslie bm, ericson wb jr, more head jr. incidence of a septum with in the first dorsal compartment of the wrist. j hand surg 1990; 15:88-91. 22. taras js, rapheal js, pan wt. corticosteroide injections for trigger digits: is intra sheath injection necessary? j hand surg 1998; 23: 8891. 23. anderson bc, manthey r, mathew cb. treatment of de quervain's tenosynovitis with corticosteroids. a prospective study of response to local injection. arthritis rheum 1991; 34:7936. 24. scheller a, schuh r, honle w. long term results of surgical release of de querrain's stenosing tenosynovitis. int orthop 2009; 33: 1301-3. 25. a kt, eidelman d, thomson jg. patient satisfaction and outcomes of surgery for de quervain's tenosynovitis. j hand surg 1999; 24: 1071-7. untitled-2 original�article abstract objective: to find out the relationship of body mass index (bmi), dietary behavior and physical activity (pa) with bone mineral density (bmd) in students of rehabilitation sciences. study design: an analytical cross-sectional study. place and duration of study: it was conducted at department of rehabilitation sciences, shifa tameer-e-millat university, islamabad, pakistan within the duration of 4 months, from november 2019 to february 2020. materials and methods: this study included a sample size of 157 participants recruited through nonprobability convenient sampling. the students of rehabilitation sciences (males and females) of 18-25 years, who were independent in their activities of daily lives, were included, while those with any current or diagnosed medical condition, major surgery and students having any fracture or trauma were excluded. the physical activity was assessed using international physical activity questionnaire-short form (ipaq-sf), dietary behavior by eating attitude test (eat-26) and bmd by calcaneal ultrasound. data analysis was done on spss version 21. results: the mean age of the participants was 21.22 ±1.80 years, including 27(17.20%) males and 130(82.80%) females. according to the outcome measures, most of the participants had normal bmi 92(58.6%), normal eating behavior 122(77.7%), moderate activity level 84(53.5%) and were osteopenic 95(60.5%). the spearman's correlation showed that there is a weak negative but significant relationship between bmi and bmd (r = -0.238, p= 0.003), also weak negative relationship between dietary behavior and bmd (r=-0.002, p= 0.978). the physical activity level and bmd levels have weak positive relationship, (r= 0.002, p= 0.984). conclusion: the result of this study suggest that the bmi has significant relationship with the bone mineral status, whereas the physical activity and eating attitudes do not contribute directly to bone mineral status. key words: bone mineral density, dietary behaviour, osteopenia, osteoporosis, physical activity. to achieve ideal peak mineral density (pmd) during 2 childhood and pre-puberty age. in pakistan the asian audit (2009) revealed that about 40 million people were estimated to have osteopenia and number for osteoporosis being predicted to be ten 3 million. current statistics has shown that asians and caucasians getting osteoporosis are at advanced 4 risk. in relation to bone mineral density, body mass index is the one which is directly related to a person's physical fitness and is commonly associated with bmd in different anatomical regions, due to 5, 6 increased bone marrow adipocity. second major factor in maintaining bone mass is the dietary behavior, in that regards, calcium and vitamin d play a very vital role along with magnesium, vitamin c & k 7,8,9 also contribute to bone health. the world statistics depict that there is an increased proportion of young adults that rely on unbalanced, low energy and nutritionally-deficient diet that lead to decrease in introduction in the childhood and at puberty, the bone density and the maximum bone strength and density has already been achieved by the age of 18-20 years when the peak bone mass (pbm) has been maximally accumulated, followed by reduction in bone mass 1 with the passing time. it was generally believed that osteoporosis was a disease of older adults, but many former studies have pointed towards the relationship of low bone mineral density (bmd) in young age with the failure bone mineral density and its relationship with physical activity, dietary behavior and body mass index among rehabilitation students 2 sidra ali naqvi, fouzia batool , hania farheen, faisal saeed, muhammad ali, sheikh majid hussain correspondence: dr. sidra ali naqvi research assistant department of rehabilitation sciences shifa tameer-e-millat university, islamabad e-mail: sidifa94@gmail.com department of rehabilitation sciences shifa tameer-e-millat university, islamabad received: august 05, 2021; revised: september 15, 2022 accepted: september 19, 2022 bone mineral density study on rehabilitation studentsjiimc 2022 vol. 17, no.3 197 10 bone mass. lastly, the lack of physical activity in a person's life may lead to compromise in their 2 physical fitness. the strength of muscles and aerobic capacity are directly proportional to healthier bone mass. as stated by wolf's law; loading stress causes a modeling response, increasing bone mass and 11 strengthening of bones. from the above discussions and past literature, it has been depicted that the modifiable factors affecting bone health include body mass composition, physical activity and eating 1 behavior. due to the prevailing sedentary lifestyle and decrease physical activity in the young adults, the bone mineral density may be affected. there have been numerous studies conducted on the bone health in the old adult population, but limited data is available on young adults as rehabilitation students . must treat the patient physically in future, so they must have good body mass index, balanced diet and physical activity. therefore, a study was planned with an objective to find out the relationship of body mass index, dietary behaviour, and physical activity with bone mineral density in students of rehabilitation sciences. materials and methods it was a cross sectional analytical study conducted at department of rehabilitation sciences, shifa tameer-e-millat university islamabad, pakistan from november 2019 to february 2020. rao software calculator was used to the calculate the sample size with confidence interval level 95%, margin of error 5% and while assuming the students of rehabilitation sciences to be 3000 in the twin cities of pakistan, which came to be 341. while in this study data was collected from 157 participants using nonprobability convenient sampling due to low response rate. the approval was taken from institutional review board and ethics committee (irb & ec) shifa international hospital & shifa tameer-e-millat university islamabad, pakistan (ref: irb#073-563-2019 th received on 13 november 2019). students (males and females) of 18-25 years, who were independent in their activities of daily lives, were included, while students with any current or diagnosed medical condition, major surgery and those having any fracture or trauma were excluded. the data collection was done by manual distribution of selfadministered questionnaire in booklet form among the students. the questions were structured in english language. in addition, informed consent was attached with each questionnaire. the participants who were a part of the study had right to withdraw at any time during the study. the participants were informed that their confidentiality would be preserved, and no physical, psychological, and emotional harm is intended. demographic information was collected using selfconstructed questionnaire which included age, 2 gender, marital status, bmi (height in m and weight in kg). international physical activity questionnaireshort-form was used to record the level of physical activity in students which is a reliable and valid 12,13 tool. eating attitude test-26 questionnaire was used to assess the eating pattern in the 14 undergraduate students. eat-26 has reliable i n t e r n a l c o n s i s t e n c y ( c r o n b a c h ' s alpha = 0.822–0.922), test–retest reliability (interclass correlation coefficient = 0.817) and 14 convergent validity (r = 0.450–0.750). sonsot-3000 machine was used to check the bmd at the level of calcaneus. it is used previously in various studies and 1, 15 has been proven to be very reliable. t-scores were noted for each participant. t-values had three categories where t> -1.0 was considered normal, between 2.5 to -1.0 was considered osteopenia and t 1, 15 =< -2.5 was osteoporotic. data was entered and analyzed using spss 21. the descriptive analysis was reported as frequency, percentage and mean for age, dietary behavior, physical activity level and bmd. shapiro-wilk test showed p<0.05 representing that data was not n o r m a l l y d i s t r i b u t e d , t h e re fo re s p e a r m e n correlation test was used to find the relationship of bmi with bmd, pa and dietary behavior. the level of significance was taken as p<0.05 results out of 157 participants, 27(17.20%) were males and 130(82.80%) were females. the mean age of the participants was 21.22 ± 1.80years. majority of the participants were in the normal category of bmi 92 (58.6%), followed by underweight 33(21%), overweight 26(16.6%) and obese 6(3.8%). according to eat-26, 122(77.7%) participants showed normal eating behaviour while 35(22.3%) showed abnormal eating pattern. as stated by ipaq-sf results, 24(15.3%) showed vigorous activity levels, 84(53.5%) showed moderate activity level and 49(31.2%) jiimc 2022 vol. 17, no.3 198 bone mineral density study on rehabilitation students showed low activity levels. whereas, on the bmd scan 56(35.7%) participants were found to have normal bone mineral density, 95(60.5%) were osteopenic and 6(3.8%) were osteoporotic. mean and standard deviation of age, bmi, dietary behaviour, pa, and bmd. (table i) bmi showed a significant (p<0.05) relationship with bmd, while dietary behaviour and physical activity showed a non-significant (p<0.05) relationship with bmd respectively. (table ii) on bone, altering its microarchitecture but it also has the potential to increase the amount of atypical loading on the bone, which in turn can increase the 18 risk of fracture. hence, the findings of these three studies are in par with the results of this present study, supporting the fact that lower bmi has beneficial effects on bone mineral density of young adults. there was a negative and insignificant relationship between the eating attitude and bmd inferred that the higher score of the eat-26 (eating disorder attitude), the lower will be the bmd. although most of the respondents i.e., 122(77.7%) in this study were classified as normal, asymptomatic, or free of problem, while 35(22.3%) had a risk of developing eating disorders. work of bennell et al. indicated that the abnormal dietary behaviours can cause amenorrhea, low bmd, or maximised risk of stress fracture. thereby, this was in line with the past studies that examined eating attitude disorders with the bone mineral density and concluded that the bad eating behaviour is basically the reason for low bmd and is closely related to an increase in endogenous 15 cortisol production and decrease in bmd. on the other hand, the results of this study showed that the physical activity had a weak positive relationship with bmd. kopiczko et al. concluded that physical activity has the most significant effect on 19 bone status especially. this statement is consistent with the study findings proving that physical activity does have impact on bone mineral density. the lack of significant relationship between pa and bmd in the present study might be due to the difference in the level, duration and type of activity performed by the participants and that the sample size was not large. furthermore, majority of the participants who had moderate level of activity, reported walking being the most common activity of their daily life and that it was not habitual (not performed regularly) and non-continuous (consisted of large rest bouts). furthermore, such activity did not challenge the body's skeletal system to initiate an adaptive response in the bones to enhance bmd. evidence suggests that the resistance exercises which produce forces on bone tissue led to its proper development. high-intensity power training has shown to provide significant improvement for the hip, trochanter, and 19 lumbar spine bmd. this has been supported by the table i: mean and standard deviation of age, body mass index, dietary behavior, physical activity and bone mineral density table ii: correlation of body mass index, dietary behaviour and physical activity on bone mineral density discussion analysis of the study showed that bmi had a negative, weak, and significant relationship with bmd, proving that body mass of an individual is an important predictor of bone mineral which is consistent with previous study of hee-sook lim et al. that concluded body fat and consumption of fats had 16 a negative correlation with bone mineral status. according to the studies conducted by hervàs et al. and ho-pham et al. showed that lean bone mass had greater effect on bmd than higher bmi and also that lean bone mass was related with greater bmd in adults due to the combined effect of mechanical 1, 17 loading and biochemical actions. the study of iwaniec and his colleague turner, also concluded that higher body weight can increase mechanical loading jiimc 2022 vol. 17, no.3 199 bone mineral density study on rehabilitation students study of kim et al. which showed no association between moderate intensity pa and bmd in 20 women. limitations and recommendations of study in this study, we were unable to reach the estimated sample size due to low response rate so future studies should be conducted with a larger sample size. further, the objective way of assessing the physical activity of the participants should be considered. the study will help the clinicians to plan programs that can help in primary preventions for bone disorders for the university students. this study recommends that bmi is important for students of rehabilitation sciences, to prevent osteopenia and osteoporosis, therefore, students should be guided through lectures/ seminars about its importance in their well-being. conclusion it is concluded that the bmi has significant relationship with the bone mineral status, whereas the physical activity and eating attitudes do not contribute directly to bone mineral status among students of rehabilitation sciences. references 1. hervás g, ruiz-litago f, irazusta j, fernández-atutxa a, fraile-bermúdez ab, zarrazquin i. physical activity, physical fitness, body composition, and nutrition are associated with bone status in university students. nutrients. 2018;10(1): 61. 2. lim h-s, ji s-i, hwang h, kang j, park y-h, lee h-h, et al. relationship between bone density, eating habit, and nutritional intake in college students. journal of bone metabolism. 2018;25(3):181-6. 3. jalal s, younis mz. aging and elderly in pakistan. ageing international. 2014;39(1):4-12. 4. kruger mc, todd jm, schollum lm, kuhn-sherlock b, mclean dw, wylie k. bone health comparison in seven asian countries using calcaneal ultrasound. bmc musculoskeletal disorders. 2013;14(1):81. 5. hars m, trombetti a. body composition assessment in the prediction of osteoporotic fractures. current opinion in rheumatology. 2017;29(4):394-401. 6. moradi s, mirzaei k, abdurahman a, keshavarz s. adipokines may mediate the relationship between resting metabolic rates and bone mineral densities in obese women. osteoporosis international. 2017;28(5):1619-29. 7. karpiński m, popko j, maresz k, badmaev v, stohs sj. roles of vitamins d and k, nutrition, and lifestyle in low-energy bone fractures in children and young adults. journal of the american college of nutrition. 2017;36(5):399-412. 8. kunutsor sk, whitehouse mr, blom aw, laukkanen ja. low serum magnesium levels are associated with increased risk of fractures: a long-term prospective cohort study. european journal of epidemiology. 2017;32(7):593-603. 9. wang c, cao x, zhang y. a novel bioactive osteogenesis scaffold delivers ascorbic acid, β-glycerophosphate, and dexamethasone in vivo to promote bone regeneration. oncotarget. 2017;8(19):31612-25. 10. moreno la, gottrand f, huybrechts i, ruiz jr, gonzálezgross m, dehenauw s, et al. nutrition and lifestyle in european adolescents: the helena (healthy lifestyle in europe by nutrition in adolescence) study. advances in nutrition. 2014;5(5):615s-23s. 11. chen j-h, liu c, you l, simmons ca. boning up on wolff's law: mechanical regulation of the cells that make and maintain bone. journal of biomechanics. 2010;43(1):10818. 12. murphy jj, murphy mh, macdonncha c, murphy n, nevill am, woods cb. validity and reliability of three self-report instruments for assessing attainment of physical activity guidelines in university students. measurement in physical education and exercise science. 2017;21(3):134-41. 13. tran vd, do vv, pham nm, nguyen ct, xuong nt, jancey j, et al. validity of the international physical activity questionnaire–short form for application in asian countries: a study in vietnam. evaluation & the health professions. 2020;43(2):105-9. 14. gómez-bruton a, matute-llorente a, gonzález-agüero a, casajús ja, vicente-rodríguez g. plyometric exercise and bone health in children and adolescents: a systematic review. world journal of pediatrics. 2017;13(2):112-21. 15. dev ro, henry e. effects of body mass index (bmi), eating attitude and physical activity on bone health among undergraduate students in malaysia. international ejournal of advances in social sciences. 2016;2(5):591-7. 16. lim j-h, bae h-s, lee s-m, ahn h-s. dietary and non-dietary factors related to bone mineral density in female college students. korean journal of community nutrition. 2008;13(3):418-25.p 17. ho-pham lt, nguyen ud, nguyen tv. association between lean mass, fat mass, and bone mineral density: a metaanalysis. the journal of clinical endocrinology & metabolism. 2014;99(1):30-8. 18. iwaniec ut, turner rt. influence of body weight on bone mass, architecture and turnover. journal of endocrinology. 2016;230(3):r115-r30. 19. kopiczko a, łopuszańska-dawid m, gryko k. bone mineral density in young adults: the influence of vitamin d status, biochemical indicators, physical activity and body composition. archives of osteoporosis. 2020;15(1):1-9. 20. kim ya, lee y, lee jh, seo jh. effects of physical activity on bone mineral density in older adults: korea national health and nutrition examination survey, 2008–2011. archives of osteoporosis. 2019;14(1):1-10. jiimc 2022 vol. 17, no.3 200 bone mineral density study on rehabilitation students conflict of interest authors declared no conflicts of interest. grant support and financial disclosure authors have declared no specific grant for this research from any funding agency in public, commercial or nonprofit sector. data sharing statment the data that support the findings of this study are available from the corresponding author upon request. this is an open access article distributed under the terms of the creative commons attributionnoncommercial 2.0 generic license. jiimc 2022 vol. 17, no.3 201 bone mineral density study on rehabilitation students original�article abstract objective: to determine the prevalence and association of ponticulus posticus with dental and skeletal malocclusions in our local population. study design: cross sectional, observational study place and duration of study: orthodontics department of a tertiary care hospital based in islamabad using st st records between the duration of 1 march, 2014 – 31 february 2018. materials and methods: the study was conducted using lateral cephalograms of the patients visiting the orthodontic department which were analysed against age, gender, skeletal and dental malocclusions of the patients obtained from the patient records. for the incidence of ponticulus posticus a total of 1194 radiographs were obtained using convenience sampling and analysed using spss version 17 and pearson's chi-square test was applied. results: a combined frequency of pp was found to be 18.1% (181/817). a higher frequency in males 22.6% (77/264) as compared to females 15.8% (104/553) exhibited a significant difference (p < 0.05). partial type of ponticulus posticus was more frequent (61.3%) as compared to full (38.7%). partial variant expressed a higher frequency in skeletal (49.5%) and dental (48%) class ii malocclusion. whereas, the full variant of ponticulus posticus exhibited a higher frequency in dental class ii (48.6%) and skeletal class i (55.7%) respectively. conclusion: our data suggests that frequency of ponticulus posticus in our local population shows male preponderance in dental class ii malocclusion, however, no significance was established in relation to its association with skeletal or dental malocclusions. key words: arcuate foramen, atlas, dental and skeletal malocclusion, kimmerle anomaly , ponticulus posticus. articular process and posterolateral portion of 3 superior margin of the posterior arch of atlas. this anatomical anomaly has been termed in the literature using various terminologies such as arcuate foramen, kimmerle anomaly, foramen 4,5 atlantoideum being a few of them. origin of pp with 6 clinical implications is not yet fully understood and subjected to ongoing research with endochondral origin from the dorsal arch of atlas proposed in the 7 literature. 3 pp has prevalence ranging from 1.3% 60% with 8 ethnic variation. there is a lack of data on the asian 9 population, no such study is yet reportedly conducted in pakistan. recent meta-analysis shows preponderance in female gender (18.5%) as 8 compared to males (16.7%). the analysis is c o m m o n l y d o n e u s i n g va r i o u s a s s e s s i n g / 2 investigating tools such as cbct, dried specimens of 10,11 c1 (atlas) and most commonly employed method 12-14 comprising lateral cephalograms. using these investigative techniques, the establishment of presence of pp and types can be assessed which can introduction ponticulus positicus (pp) is a morphological variation of the atlas/c1 (the first cervical vertebra), famous for anatomical disparity leading to various clinical manifestations such as; migraine, neck pain, hearing loss and most importantly, incorrect assessment during orthopaedic surgery for atlanto-axial fixation 1 causing vertebral artery damage. ponticulus posticus is a latin word meaning “little posterior 1,2 bridge”. it is a membranous ossification found between the posterior portion of the superior prevalence of ponticulus posticus in orthodontic patients of the local population of islamabad, pakistan qurat ul ain, saqlain bin syed gilani, muhammad aamir ghafoor choudry, bakhtawar yaqoob awan correspondence: dr. saqlain bin syed gilani assistant professor department of dentistry islamic international dental college riphah international university, islamabad e-mail: saqlain.syed@riphah.edu.pk department of dentistry islamic international dental college riphah international university, islamabad funding source: nil; conflict of interest: nil received: october 23, 2018; revised: august 20, 2019 accepted: august 27, 2019 prevalence of ponticulus posticus in orthodontic patientsjiimc 2019 vol. 14, no.3 142 15-19 be partial (incomplete) and full (complete). skeletal deformities, head, neck, cervical posture and morphological deviation along with variable orthopaedic findings are believed to have an 20,21 association with malocclusion. studies have also reported a relationship between mandibular 22 positioning and cervical vertebral morphology. d'attilio et al presented a statistically significant correlation between mandibular plane angle, position, length and overjet to the cervical 23 curvature. all these studies showing an association of orthopaedic findings with certain orthodontic findings led us to investigate the prevalence and association of ponticulus posticus with dental and skeletal malocclusions in our local population. materials and methods a cross-sectional study was undertaken at the islamic interational dental hospital, using the records from the archives of the orthodontics department of patients who had undergone orthodontic treatment/consultation during a period of march 01, 2014 – february 31, 2018. a total of 1194 lateral cephalograms were acquired using nonprobability convenience sampling. the ethical approval was obtained from the institutional ethical review committee. a total of 196 radiographs were excluded, the exclusion criteria comprised of poor visualization of posterior arch of atlas and patients with congenital facial abnormalities and/or syndromes. radiographs were recorded using art plus dental x-ray fin-02150 and examined by direct visualization under adequate illumination for the presence of the anomaly, and if present whether complete or partial. gender, age, dental and skeletal malocclusions were noted. radiographs were examined by two observers twice on different occasions to reduce intra operative error. in case of a disagreement, a third observer from the radiology department was consulted. the observers followed the classification by miki et al which radiographically classifies the ponticulus 24 posticus into three types: “full type: it forms a complete bony ring. incomplete type: some portions of the bony ring are defective. calcified type: there is a linear or amorphous calcification.” due to many intermediate forms of partial (pp) which may range from a spicule to some being ossified but not completely encircling the posterior arch, the variations were dichotomized to complete and partial for this study. all data was entered and subjected to statistical analysis using spss version 17. using pearson's chisquare test, data was analysed to establish any association between occurrence, gender, age and malocclusions (skeletal & dental). results the mean age of the subjects was 17.76 ± 5.41 years (range 7 – 51 years) and catogarized into three groups, group i (7-14 years), group ii (15-20 years) & group iii (21 and above). highest prevalence of pp was found in group ii, partial form of pp was 44.1% and full form of pp was 37.1%. total number of pp detected were 181 with a prevalence of 18.1% out of 998 radiographs (partial: 61.3%, full: 38.7%). male patients showed a preponderance of pp n=77 (22.6%) as compared to females n=104 (15.8%) with significant difference (p<0.05) however, no significant difference (p>0.05) was observed between partial and full form of pp, age, skeletal & dental malocclusions. with the analysis of malocclusion groups, partial pp showed a relative predominance of dental 49 (48%) and skeletal 52 (49.5%) class ii malocclusions and conversely cases of complete/full pp showed a relative predominance of dental 32 (48.6%) class ii and skeletal 39 (55.7%) class i malocclusion. however, there was no significant difference between different malocclusion groups (skeletal or dental) (p>0.05). detail description available in table i & ii. table i: frequency of pp based on gender in local popula�on, p < 0.05 table ii: frequency of pp based on dental and skeletal malocclusions, p > 0.05 jiimc 2019 vol. 14, no.3 143 prevalence of ponticulus posticus in orthodontic patients discussion t h e c r o s s s e c t i o n a l s t u d y c o m p r i s e s o f cephalograms of the orthodontically treated patients, as shown in figures 1(a) & (b), of our local population, the evaluation showed a prevalence of 18.1% with partial 61.3% & full 38.7%. the analysis of malocclusion groups showed a predominance of partial type pp in dental class ii malocclusion and full type pp in skeletal class i. different methods have been used to investigate pp, that entail plain radiography, cbct, ct-scans and examination of dried specimens of atlas. various studies have been undertaken in different populations with highly variable results (1.3% – 60% prevalence), reported prevalences consist of a metaanalysis conducted by przemyslaw a. et al which states that the least amount of cases of pp were reported in asia as opposed to north america where 8 the frequency of pp was highest. compared to our population, similar prevalences 25 were reported by jae taek hong (15.6%), young et 26 al, (15.5%). kyeong hwan kim et al, elliot & tanweer 2 7 (16.6%) and yong jae (14%) and (15.5%) 4,28 29 respectively. however, v sharma et al. (4.3%), 9 chitrodka pk et al. (60%) showed contrasting results. a significant male predominance was observed in our local population (p < 0.05) which is in coherence with a study conducted by adisen and 3 misirlioglu. though a female predominance was also reported in a study with no significant difference 9 established between the genders (p>0.05). whereas, some studies also suggested that there is no significant difference in the prevalence of the pp 7,27 among the two genders. adisen and misirlioglu, in their attempt to study the relationship between mandibular position and cer vical vertebra morphology, no association could be established but it was recommended to investigate the presence of pp in different dentoskeletal patterns in future studies. middle anatolian population had a higher frequency of the anomaly (pp) detected in angle class iii patients (22.2 %). although no significant difference was observed between malocclusion 3 groups (p > 0.05) which is in coherence with the 2 results of this study. according to sevki et al 2017 in turkish population pp was most frequently detected in class iii patients (13.8%) followed by class ii (12.2%) and class i patients (10.5%). statistically significant differences between the different sagittal skeletal groups were observed (p = ˂ 0.05). in the turkish population, highest frequency of pp was found in angle class iii patients. both these findings are in accordance with the study conducted by sonnesen et al 2007 which showed significant (p = <0.001) relationship with mandibular overjet and cervical column morphological deviations as 30 compared to the control group. many studies have tried to find any association with age, but none has been able to do so, while some studies have gone as far as to negate any such 29 association. some claim it to be congenital, citing cadaveric and radiologic studies that have shown its presence in fetuses and children, with some still in the cartilaginous stage yet to ossify which supports the study conducted by geist whose findings oppose the theory of it being a degenerative phenomenon 18 which occurs as a result of aging. some studies have shown that in some cases it is able to ossify over the 31 years while in others it remains in a spicule/partial form throughout life, which suggests no association of the bridging process with life. one of the limitations in the study design was that the lack of extensive computated tomography which could have revealed the frequency more accurately by determining if the anomaly was bilaterally present or unilaterally. the observers were not trained radiologists and a trained radiologist was only consulted in cases where both the observers opinions differed. conclusion our data suggests that frequency of ponticulus posticus in our local population shows male preponderance in dental class ii malocclusion, however, no significance was established in relation to its association with skeletal or dental malocclusions. a larger sample should be taken in future studies conducted, cbct or ct scans are recommended to find the full extent of pp including unilaterally and bilaterally present variants. references 1. tassoker m, necmettin erbakan university k, turkey, kok h, necmettin erbakan university k, turkey, ozcan s, necmettin erbakan university k, turkey. investigation of the relationship between "sella turcica bridge" and "ponticulus posticus": a lateral cephalometric study. international journal of morphology. 2017;35(1):337-44. jiimc 2019 vol. 14, no.3 144 prevalence of ponticulus posticus in orthodontic patients 2. bayrakdar is, miloglu o, altun o, gumussoy i, durna d, yilmaz ab. cone beam computed tomography imaging of ponticulus posticus: prevalence, characteristics, and a review of the literature. oral surg oral med oral pathol oral radiol. 2014;118(6):e210-9. 3. adisen mz, misirlioglu m. prevalence of ponticulus posticus among patients with different dental malocclusions by digital lateral cephalogram: a comparative 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prevalence of foramen arcuale and its clinical significance: a meta-analysis of 55,985 subjects. journal of neurosurgery: spine.0(0):1-15. 9. chitroda pk, katti g, baba ia, najmudin m, ghali sr, kalmath b, et al. ponticulus posticus on the posterior arch of at l a s , p reva l e n c e a n a l ys i s i n sy m pto m at i c a n d asymptomatic patients of gulbarga population. j clin diagn res. 2013;7(12):3044-7. 10. gupta c, radhakrishnan p, palimar v, d'souza as, kiruba n. a quantitative analysis of atlas vertebrae and its abnormalities. j morphol sci. 2013;30(2):77-81. 11. patel dinesh k. saa, roy nilanjan, manvikar purushottam r., bharambe vaishaly. a study of foramen of arcuale i n at l a s v e rt e b r a : i n c i d e n c e a n d c l i n i c a l correlations -. international journal of current research and review. 2017;7(20):09-11. 12. hoenig jf, schoener wf. radiological survey of the cervical spine in cleft lip and palate. dentomaxillofac radiol. 1992;21(1):36-9. 13. haji ghadimi m, amini f, hamedi s, rakhshan v. associations among sella turcica bridging, atlas arcuate foramen (ponticulus posticus) development, atlas posterior arch deficiency, and the occurrence of palatally displaced canine impaction. am j orthod dentofacial orthop. 2017;151(3):513-20. 14. friedrich re. ponticulus posticus is a frequent radiographic finding on lateral cephalograms in nevoid basal cell carcinoma syndrome (gorlin-goltz syndrome). anticancer res. 2014;34(12):7395-9. 15. krishnamurthy a, nayak s, khan s, prabhu lv, ramanathan la, ganesh kumar c, et al. arcuate foramen of atlas: incidence, phylogenetic and clinical significance. rom j morphol embryol. 2007;48(3):263-6. 16. baeesa ss, bokhari rf, bajunaid km, al-sayyad mj. prevalence of the foramen arcuale of the atlas in a saudi population. neurosciences (riyadh). 2012;17:345-51. 17. rajani s. is variant anatomy of atlas clinically important? a review. basic sciences of medicine. 2014;3(1):1-7. 18. geist jr, geist sm, lin lm. a cone 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n : a c r o s s s e c t i o n a l s t u d y . http://dxdoiorg/101080/08869634200311746240. 2016. 23. d'attilio m, epifania e, ciuffolo f, salini v, filippi mr, dolci m, et al. cervical lordosis angle measured on lateral cephalograms; findings in skeletal class ii female subjects with and without tmd: a cross sectional study. cranio. 2004;22(1):27-44. 24. miki t, oka m, urushidani h, hirofuji e, tanaka s, iwamoto s. <originals>ponticulus posticus : its clinical significance. 25. jae taek hong, sang won lee, byung chul son, jae hoon sung, seung ho yang, il sub kim, et al. analysis of anatomical variations of bone and vascular structures around the posterior atlantal arch using three-dimensional c o m p u t e d t o m o g r a p h y a n g i o g r a p h y . http://dxdoiorg/103171/spi/2008/8/3/230. 2008. 26. young jp, young ph, ackermann mj, anderson pa, riew kd. the ponticulus posticus: implications for screw insertion into the first cervical lateral mass. jbjs. 2005;87(11):2495-8. 27. elliott re, tanweer o. the prevalence of the ponticulus posticus (arcuate foramen) and its importance in the goelharms procedure: meta-analysis and review of the literature. world neurosurgery. 2014;82(1). 28. cho yj. radiological analysis of ponticulus posticus in koreans. yonsei medical journal. 2009;50(1):45-9. 29. sharma v, chaudhary d, mitra r. prevalence of ponticulus posticus in indian orthodontic patients. dentomaxillofac radiol. 2010;39(5):277-83. 30. sonnesen l, kjaer i. cervical column morphology in patients with skeletal class iii malocclusion and mandibular overjet. am j orthod dentofacial orthop. 2007;132(4):427.e7-12. 31. paraskevas g, papaziogas b, tsonidis c, kapetanos g. gross morphology of the bridges over the vertebral artery groove on the atlas. surg radiol anat. 2005;27(2):129-36. jiimc 2019 vol. 14, no.3 145 prevalence of ponticulus posticus in orthodontic patients original�article abstract objective: to compare the effect of betulinic acid and simvastatin on triglycerides and low density lipoprotein cholesterol (ldl-c) in balb/c mice. study design: experimental randomized control trial. place and duration of study: study was conducted at biochemistry department islamic international medical college rawalpindi in collaboration with national institute of health islamabad from november 2017 to april 2018. materials and methods: a total of 40 mice were randomly divided into 4 groups. excluding one of the 4 groups as negative control, the remaining three were fed with high fat diet for 21 days to achieve raised levels of triglycerides and low density lipoprotein. after that out of the three high fat diet fed groups, one group was left untreated considering the positive control group and of the other 2 groups one was treated with simvastatin nd and 2nd one was given betulinic acid for the next 21 days. sampling was done by cardiac puncture on 42 day. triglycerides and ldl-c levels were measured in serum samples. data thus obtained was analyzed by one way anova through spss 21. results: study showed that positive control group showed a rise in mean triglycerides levels from 130mg/dl to 220mg/dl and mean ldl-c from 23mg/dl to 46mg/dl. betulinic acid showed significantly better control than simvastatin as mean serum levels of triglycerides were 146mg/dl as compared to 178mg/dl and mean serum levels of ldl-c were 28mg/dl as compared to 34mg/dl of simvastatin. considering the p<0.05, tgs had a (p<0.001) and ldl-c had a (p<0.001). conclusion: betulinic acid showed a far better control over the levels of triglycerides and ldl-c in hfd fed balb/c mice as compared to simvastatin. key words: betulinic acid, ldl-c; low density lipoprotein cholesterol, simvastatin. which results in increased risk of cardiovascular 5 complications. globally conducted estimation of deaths because of cvd by 'who' revealed 17.5 6 million deaths in the year 2012. while according to 2013 global burden of disease study, cvd is 7 responsible for 30% of deaths worldwide. in the last th half of the 20 century many epidemiological and experimental studies identified high levels of ldl-c as being atherogenic and advocated a linear relationship with rate of onset of chd; notable 8 among these are the “framingham heart study” , the “lipid research clinics” (lrc) trial by patsy and wies in 2014, and the “multiple risk factor intervention trial” (mrfit) in 2013. nla (national lipid association) expert panel advised lifestyle and drug therapies intended to reduce morbidity and 1 mortality associated with dyslipidemia. statins are the mainstay of treatment options in management of 1 hyperlipidemia. they block the de-novo synthesis of cholesterol by inhibiting “3-hydroxy-3-methylglutarylcoenzyme a reductase”, simultaneously upregulating the ldl-c receptors and enhancing the clearance of plasma lipoproteins thus, statins work . in a “self-limiting” manner and manage cholesterol introduction atherosclerosis is a “lipid-driven” inflammation of 1 the arterial wall , caused by the accumulation of 2 excess lipids into the arterial wall. it has been observed over the years that atherogenesis phenomenon is caused by triglyceride rich 3 lipoproteins (i.e low density lipoproteins ldl). triglycerides in the serum are derived from fats in our f o o d o r f r o m o t h e r e n e r g y s o u r c e s . hypertriglyceridemia is characterized by elevation in 4 triglyceride levels and is independently associated with cardiovascular disease (cvd). high levels of ldlcholesterol is an indication of extra lipids in blood, effect of betulinic acid vs simvastatin on hypelipidemic mice model abeerah zainub, farhana ayub, abdul khaliq naveed, saira jahan, saddaf ayub, aisha hasan correspondence: dr. abeerah zainub assistant professor department of biochemistry islamic international medical college riphah international university, islamabad e-mail: abeera@live.com department of biochemistry islamic international medical college riphah international university, islamabad funding source: nil; conflict of interest: nil received: february 01, 2019; revised: july 18, 2019 accepted: july 19, 2019 betulinic acid versus simvastatinjiimc 2019 vol. 14, no.3 121 9 levels in blood. although generally statins are 10 endured well but poor compliance with them may be caused by many of the side effects, including ga st ro i n te st i n a l d i st u r b a n c e s , b o d y a c h e s , respiratory problems, and headaches. of all these adverse effects liver and muscle related problems 11,12,13,14 are remarkably higher in numbers. recently, in blood, higher levels of glucose and glycosylated hemoglobin hb-a1c have also been reported in 13 association with administration of statins. as evidence gap is still there, the american college of cardiology/american heart association (acc/aha) blood cholesterol guidelines 2013 included dyslipidemia in the recommendations for high 15 priority research areas. keeping the recommendation in view we chose a noble compound named betulinic acid (ba), a triterpene with a pentacyclic structure. this is found 16 in the in leaves of ziziphus spina-christi as well as 17 from stem of white bark birch tree , and in various o t h e r p l a n t s i n t ro p i c a l re g i o n s s u c h a s tryphyllumpeltaum, ancistrocladusheyneaus, diospyorosleucomelas, tetraceraboliviana, and syzygiumformosanum. ba and its derivatives have been the subject of intense study which is primarily focused on their anti-cancer effects, anti-hiv, antibacterial, anti-inflammatory, antimalarial, anti18,19 helminthic, and other pharmaceutical properties. the direct effect of betulinic acid on lipid metabolism is recently being evaluated for the better treatment options available to treat dyslipidemia. as it proved to be beneficial in the treatment of 20 nonalcoholic fatty liver disease (nafld). in this study we compared the effect of betulinic acid and simvastatin on triglycerides and low density lipoprotein cholesterol in balb/c mice. materials and methods this experimental randomized control trial was conducted in department of biochemistry at islamic i n t e r n a t i o n a l m e d i c a l c o l l e g e o f r i p h a h international university in collaboration with national institute of health islamabad in 6 months duration from november 2017 to april 2018. after getting approval from the ethical review committee (erc) of islamic international medical college, and regulatory authority of national institute of health islamabad a total of 40 subjects were randomly selected from a population of male mice bred in the animal house of nih according to international standards for experimental purposes. for this our inclusion criteria was balb/c adult mice (6-7 weeks old). only healthy male mice weighing 30±5gms were selected under the guidance of a veterinary doctor and animal house supervisor appointed by nih. these 40 subjects were randomly divided into 4 groups where every member of the population had the same chance of being in any of the four groups and all four groups were exposed to 12 hour light/dark cycle while being provided with a temperature of 22±5°c, kept and maintained at nih with the help of nih approved animal handlers. subjects were equally divided into 4 groups. group i was named nc for negative control and was given normal rodent chow throughout the experiment (42 days). group ii named pc (positive control) was provided with high fat diet (hfd consisted of 25% fats, 25% sucrose and 50% standardized rodent 20,21 chow purchased from nih) throughout the experiment (42 days). group iii named ba (betulinic acid) was provided with hfd for 21 days. afterwards they were treated with betulinic acid while being fed with standardized rodent chow from day 22 to day 42 i.e the last day of experiment. group iv named sim (simvastatin) was also provided with hfd for 21 days. and from day 22 onwards they were treated with simvastatin while being fed with standardized rodent chow from day 22 to day 42 i.e last day of experiment. on day 21 after overnight fast serum samples of 2 subjects from hfd groups (i.e pc, ba and sim) were collected on random selection method to ensure established hyperlipidemia. after the confirmation of established hyperlipidemia, two groups i.e ba and sim were administered with treatment drugs betulinic acid and simvastatin respectively, at the dosage searched from literature (i.e; betulinic acid: 20 22 10mg/kg/day and simvastatin: 10mg/kg/day ). considering 30gm weight, their doses were 0.3mg per mouse. drugs obtained were in powder forms and readily soluble in water so they were administered in dissolved form through oral route. during this time hfd was discontinued for the treatment groups ba and sim. on the final day after an overnight fast samples were taken after anaesthetizing the mice in a closed lid glass jar containing cotton wool soaked in jiimc 2019 vol. 14, no.3 122 betulinic acid versus simvastatin chloroform. sampling was done through cardiac puncture 1.5±0.5ml of blood was collected from each subject and was stored in previously labeled sst (serum separating tube with clot activating gel) and were placed upright in a stand in a cold storage box. samples were analyzed within 24 hours of collection. after separating serum by centrifugation at 2500rpm for 10 min, samples were analyzed with reagents purchased from merck. protocol of technique used for triglycerides levels was endpoint direct method and for ldl-c levels was enzymatic direct endpoint method. semiautomated biochemical analyzer merck 300 was used for the analysis of triglycerides and ldl-c. collected data was analyzed using spss (statistical package for social sciences) software version 21, used for the analysis of data. normally distributed q u a n t i ta t i ve va r i a b l e s w e re ex p re s s e d a s means±s.e.m. as it was an analysis between 4 groups so one-way anova (analysis of variance) was applied and the differences among group means was observed while a p-value of <0.05 was set to be significant. results levels of serum triglycerides were compared in the form of mean±s.e.m. serum triglyceride in positive control group was 220 ±7.727 mg/dl as compared to negative control group 130.7 ±4.883 mg/dl with a p<0.001. while treatment groups ba with 146.2 ±16.03 mg/dl and sim with 178.8 ±6.959 mg/dl showed significant reduction with p<0.001 and p<0.05 respectively. this is evident in fig 1. pc. steric (*) denotes comparison of ba and sim with pc, our results showed *** p<0.001 when compared with pc. mean±s.e.m of serum ldl-c levels of positive control group was 46.86±1.844 mg/dl with a p<0.001 as compared to negative control group 23.17±2.088 mg/dl. while treatment group ba had 28.00±3.033 mg/dl with p<0.001 and sim had 34.83±1.537 mg/dl with p<0.01. the comparative analysis is depicted in fig 2. fig 1: graphical presenta�on of the results of serum triglycerides (mg/dl) in all 4 groups. hash (#) denotes comparison between nc and pc, our results showed p<0.001 comparison of nc and fig 2: graphical presenta�on of the results of serum ldl-c (mg/dl) in all 4 groups. hash (#) denotes comparison between nc and pc, our results showed p<0.001 comparison of nc and pc. steric (*) denotes comparison of ba and sim with pc, our results showed *** p<0.001 when compared with pc. discussion dyslipidemia has been responsible for a considerable 23 proportion of atherosclerotic cvd in the world. for its management a four step approach has been recommended to lower ascvd which include modification of life style, lowering blood cholesterol levels by the use of drugs (statins). however over the course of decades only approach that has shown overwhelming body of evidence is the drug (statins) 15 therapy approach. therefore in the guidelines for management of hyperlipidemia issued by american college of cardiology / american heart association (acc/aha), research in this field to the develop better treatment options for management of 15 hyperlipidemia has been recommended. so, we observed effects of betulinic acid on triglycerides and ldl levels in serum of hyperlipidemic balb/c mice. jiimc 2019 vol. 14, no.3 123 betulinic acid versus simvastatin our study demonstrated that ba treated group kept lipid levels in blood near normal which is in accordance with quan hy et al. who studied that betulinic acid alleviates non alcoholic fatty liver 20 disease (2013) and ahangarpour et al. who studied the effect of betulinic acid on leptin, adiponectin, hepatic enzyme levels and lipid profiles in streptozotocin–nicotinamide-induced diabetic mice 24 (2018). 25 triglycerides are absorbed from intestines. high levels of triglyceridess result in increased ldl formation by liver giving rise to ox-ldl and vascular 26 inflammation. betulinic acid was determined to 27 effectively lower down triglycerides. and in this study, at same dosage of 10mg/kg body wt, ba showed a better control of serum triglycerides (p<0.001) as compared to sim (p<0.05) in hyperlipidemic mice as evident in fig. 1. additional studies which were conducted by hai yan quan et 20,27 24 al and ahangarpour et al., backed our findings in their animal based researches. with hfd, ldlc level rise because of excess triglycerides absorption from intestines and their further accumulation in lipoprotein particle giving 25 rise to ldlc. it was observed that reducing ldlc 26 levels decreased endothelial inflammation. present study determined that serum ldl-c levels in ba and sim were found to be lowered when compared with pc (hyperlipidemic) group and ba showed significantly (p<0.001) better results as compared with sim (p<0.01). this is depicted in fig.2 and is in agreement with the findings of studies on mice by 24 28 ahangpour et al. and juan peng et al. conclusion it is concluded that, betulinic acid and simvastatin both have comparable effects in the rectification of hyperlipidemia in balb/c mice. simvastatin efficiently treats hypertriglyceridemia and lowers down ldl-c but betulinic acid shows an overall better control. hence it may be a good alternative to statins but further researches in this field are needed because betulinic acid is a novel compound whose safety profile is yet to be evaluated by the researchers. references 1. jacobson ta, ito mk, maki kc, orringer ce, bays he, jones ph, et al. national lipid association recommendations for patient-centered management of dyslipidemia: part 1—full report. j clin lipidol. 2015;9(2). 2. owens ap, byrnes jr, mackman n. hyperlipidemia, tissue factor, coagulation, and simvastatin. vol. 24, trends in cardiovascular medicine. 2014. p. 95–8. 3. nordestgaard bg. triglyceride-rich lipoproteins and atherosclerotic cardiovascular disease: new insights from e p i d e m i o l o g y, g e n et i c s , a n d b i o l o g y. c i rc re s . 2016;118(4):547–63. 4. ruchel jb, braun jbs, adefegha sa, guedes manzoni a, abdalla fh, de oliveira js, et al. guarana (paullinia cupana) ameliorates memory impairment and modulates acetylcholinesterase activity in poloxamer-407-induced hyperlipidemia in rat brain. physiol behav [internet]. 2017;168:11–9. available from: http://dx.doi.org / 10.1016/j.physbeh.2016.10.003 5. mann s, beedie c, jimenez a. differential effects of aerobic exercise, resistance training and combined exercise modalities on cholesterol and the lipid profile: review, synthesis and recommendations. vol. 44, sports medicine. 2014. p. 211–21. 6. rao w, su y, yang g, ma y, liu r, zhang s, et al. crosssectional associations between body mass index and hyperlipidemia among adults in northeastern china. int j environ res public health. 2016;13(5). 7. bhatnagar p, wickramasinghe k, williams j, rayner m, townsend n. the epidemiology of cardiovascular disease in the uk 2014. heart. 2015. 8. mahmood m, hoque h, mahmood sa, quayum ma. prevention of ischaemic heart disease. univ hear j. 2014;10(1). 9. zimmer m, bista p, benson el, lee dy, liu f, picarella d, et al. cat-2003: a novel sterol regulatory element-binding protein inhibitor that reduces steatohepatitis, plasma lipids, and atherosclerosis in apolipoprotein e*3-leiden mice. hepatol commun [internet]. 2017;1(4):311–25. available from: http://doi.wiley.com/10.1002/hep4.1042 10. de vera ma, bhole v, burns lc, lacaille d. impact of statin adherence on cardiovascular disease and mortality outcomes: a systematic review. br j clin pharmacol [ i n t e r n e t ] . 2 0 1 4 ; 7 8 ( 4 ) : 6 8 4 – 9 8 . av a i l a b l e f r o m : http://doi.wiley.com/10.1111/bcp.12339 11. el-salem k, ababneh b, rudnicki s, malkawi a, alrefai a, khader y, et al. prevalence and risk factors of muscle complications secondary to statins. muscle and nerve. 2011;44(6):877–81. 12. s c h a c h t e r m . c h e m i c a l , p h a r m a c o k i n e t i c a n d pharmacodynamic properties of statins: an update. fundam clin pharmacol. 2005;19(1):117–25. 13. park y, rha s-w, choi bg, choi sy, goud a, lee s, et al. impact of simvastatin on development of new-onset diabetes mellitus in asian population: three-year clinical follow up results. j am coll cardiol [internet]. 2014;63(12):a2128. av a i l a b l e f r o m : h t t p : / / l i n k i n g h u b . e l s e v i e r. c o m / retrieve/pii/s0735109714621318 14. aghasadeghi k, nabavi s, amirmoezi f, attar a. vitamin e supplementation for treatment of statin induced hepatocellular damage: a randomized, double-blind, p l a c e b o c o n t ro l l e d t r i a l . i n t c a rd i o va s c re s j . jiimc 2019 vol. 14, no.3 124 betulinic acid versus simvastatin 2018;12(1):29–33. 15. stone nj, robinson jg, lichtenstein ah, bairey merz cn, blum cb, eckel rh, et al. 2013 acc/aha guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the american college of cardiology/american heart association task force on practice guidelines. vol. 63, journal of the american college of cardiology. 2014. p. 2889–934. 16. nader ma, baraka hn. effect of betulinic acid on neutrophil recruitment and inflammatory mediator expression in lipopolysaccharide-induced lung inflammation in rats. eur j pharm sci. 2012; 17. lee sy, kim hh, un s, 3� p. letter to the editor: recent studies on betulinic acid and its biological and pharmacological activity. excli j [internet]. 2015;14:199–203. available from: http://dx.doi.org/ 10.17179/excli2015-150 18. kobayashi rk, gaziri lc, vidotto mc. functional activities of the tsh protein from avian pathogenic escherichia coli (apec) strains. j vet sci. 2010;11(4):315–9. 19. wu j, niu y, bakur a, li h, chen q. cell-free production of pentacyclic triterpenoid compound betulinic acid from betulin by the engineered saccharomyces cerevisiae. molecules. 2017;22(7). 20. quan hy, kim dy, kim sj, jo hk, kim gw, chung sh. betulinic acid alleviates non-alcoholic fatty liver by inhibiting srebp1 activity via the ampk-mtor-srebp signaling pathway. biochem pharmacol [internet]. 2013;85(9):1330–40. available from: http://dx.doi.org /10.1016/ j.bcp. 2013.02.007 21. del pozo r, mardones l, villagrán m, muñoz k, roa s, rozas f, et al. efecto de una dieta alta en grasas en el proceso de formación de cálculos biliares de colesterol. rev med chil. 2017;145(9):1099–105. 22. song x, wang j, wang p, tian n, yang m, kong l. 1h nmrbased metabolomics approach to evaluate the effect of xue-fu-zhu-yu decoction on hyperlipidemia rats induced by high-fat diet. j pharm biomed anal [internet]. 2013;78–79:202–10. available from: http://dx.doi.org/ 10.1016/j.jpba.2013.02.014 23. venkitachalam l, wang k, porath a, corbalan r, hirsch at, cohen dj, et al. global variation in the prevalence of elevated cholesterol in outpatients with established vascular disease or 3 cardiovascular risk factors according to national indices of economic development and health system performance. circulation. 2012;125(15):1858–69. 24. ahangarpour a, shabani r, farbood y. the effect of betulinic acid on leptin, adiponectin, hepatic enzyme levels and lipid profiles in streptozotocin-nicotinamide-induced diabetic mice. res pharm sci. 2018;13(2):142–8. 25. ta s k i n e n m r , b o ré n j . n e w i n s i g h t s i n t o t h e pathophysiology of dyslipidemia in type 2 diabetes. atherosclerosis. 2015;239(2):483–95. 26. caliceti c, rizzo p, ferrari r, fortini f, aquila g, leoncini e, et al. novel role of the nutraceutical bioactive compound berberine in lectin-like oxldl receptor 1-mediated endothelial dysfunction in comparison to lovastatin. nutr metab cardiovasc dis [internet]. 2017;27(6):552–63. a v a i l a b l e f r o m : h t t p : / / d x . d o i . o r g / 1 0 . 1 0 1 6 / j.numecd.2017.04.002 27. quan hy, kim dy, kim sj, jo hk, kim gw, chung sh. betulinic acid alleviates non-alcoholic fatty liver by inhibiting srebp1 activity via the ampk-mtor-srebp signaling pathway. biochem pharmacol. 2013;85(9):1330–40. 28. peng j, lv yc, he pp, tang yy, xie w, liu xy, et al. betulinic acid downregulates expression of oxidative stress-induced lipoprotein lipase via the pkc/erk/c-fos pathway in r aw 2 6 4 . 7 m a c r o p h a g e s . b i o c h i m i e [ i n t e r n e t ] . 2015;119:192–203. available from: http://dx.doi.org/ 10.1016/j.biochi.2015.10.020 jiimc 2019 vol. 14, no.3 125 betulinic acid versus simvastatin letter�to�editor marks or grades of students should be considered for their entry to this sacred profession but also the moral, ethical and behavioral principles of the candidate should be concerned. it is also necessary to incorporate the students with skill to deal the patients with cultural competency in their curricula and then their sensitivity and response according to needs and expectations of patients also taking account of patient's age, culture, gender, lifestyle, beliefs, race, and disability. therefore, it is the dire need of time to understand and implement the knowledge, practice and realization of emotional intelligence. 1. cherry mg, fletcher i, o'sullivan h, dornan t. emotional intelligence in medical education: a critical review. medical education. 2014;48(5):468-478. 2. council gm. tomorrow's doctors 2003: recommendations on undergraduate medical education. 3. hargie o, boohan m, mccoy m, murphy p. current trends in communication skills training in uk schools of medicine. medical teacher. 2010;32(5):385-391. dear sir/madam emotional intelligence (ei) describes a person's ability to assess and respond to emotions of his/ her 1 own or of others. it is a major contributor in daily life as well as health care delivery system. every person belonging to this sacred domain needs to be compassionate enough to understand the sufferings and should be able to deal and manage the patient's problem effectively. there is no formal system of ei assessment at the time of recruitment in health care profession. the individuals with compassionate attitude, value and behaviors should be given some priority for being selected. they then must be trained for patient interaction and communication using the principles of emotional intelligence. this is necessary to avoid the unpleasant incidents that happen because of improper dealing from the professional that leads to increasing dissatisfaction of patients towards the professionals. doctors, n u rs e s , p hys i c a l t h e ra p i st s a n d a l l o t h e r professionals should be educated for delivering empathetic care. all of them should be good communicators. the general medical council (gmc), the body that regulates and controls the medical education standards in the uk, states that doctors in future will commune with patients and their relatives clearly, sensitively and efficiently by 2 listening effectively, sharing and responding. they will keep the ethical and legal principles in their 2 behavior. all these areas are under the umbrella of ei. the uk and other developed countries have taken serious account in incorporating and teaching doctor-patient relationship and communication in all the curricula of health professions and it is taught 3 formally along with feedback system. it is recommended that the assessment prior to recruitment should be done and merely not the contribution of emotional intelligence in health professional education 1 2 kiran khushnood , nasir sultan correspondence: dr. kiran khushnood lecturer department of physical therapy shifa tameer e milat university, islamabad e-mail: kirankhushnood@yahoo.com 1 department of physical therapy shifa tameer-e-millat university, islamabad department of rehabilitation 2 shifa international hospital, islamabad jiimc 2019 vol. 14, no.3 165 original�article abstract objective: to determine caries frequency in mandibular second molars in proportion to level of angulation and depth of impaction of mandibular third molars established on winters and pell and gregory classification system. study design: this was a cross-sectional study. place and duration of study: this study was regulated in department of oral and maxillofacial surgery at st islamic international dental hospital, islamabad from 1 january 2018 to 30th june 2018. materials and methods: an overall 100 cases of caries were investigated on clinical and radiographic basis in mandibular second molars. each panoramic radiograph was studied for the presence of carious lesion in lower second molars. the depth and angulation of impacted third molars was being assessed using pell and gregory and winter's grouping respectively. chi square test was applied for analysis of data. results: the participants in this study had age range from 18 to 60 years old. mean age was 39.24 ±9.77 years. majority of the patients 59 (59.0%) were between the ages 18 and 40. among these patients, males were 83 (83.0%) and females 17 (17.0%) having a 4.9:1 male-to-female ratio. caries at the distal aspect of mandibular second molars were seen in 39 percent of individuals with impacted lower third molars and mesioangularly impacted teeth most resulted in caries. conclusion: this study concluded that 39% of the patients with impacted mandibular third molars caused distal cervical caries in second molars, with mesioangular impaction being the most prominent type causing caries. so, an attentive follow up of impacted mandibular third molars should be considered as health of lower mandibular second molar is influenced by pattern of impaction. key words: caries, lower second molar impaction, lower third molar impaction, mesioangular, preventive removal. crowding, and neoplastic lesions. distal caries on mandibular second molar are a frequently noted complication associated with impaction of mandibular third molar tooth. extraction of third molar is a commonly performed surgical procedure due to various reasons but removal due to caries on distal surface of mandibular second molars ranges 3 from 4.2 to 37.5%. the caries prevalence seems to be significantly influenced by the positioning of the impaction. there are numerous studies in literature regarding this subject highlighting the association of distal caries with mandibular third molar mostly related to 4,5 mesioangular impaction. also a statistically important link was found between horizontally impacted third molar and caries along with 6 mesioangular impaction. so, to preclude the development of caries and early loss of second molar teeth, removal of third molars should be given 7 consideration. introduction an impacted tooth is defined as being partially or totally embedded in the soft tissue or bone, having an obstruction in its eruption pathway and is unlikely 1 to erupt within the expected time frame. third molars are classified using pell and gregory (1933) and winters (1926) grouping that describes depth and angle of an impaction respectively relative to the 2 adjacent second molars. third molars are related to various complications such as tooth decay, root resorption, periodontal problems, pericoronitis, infections, cysts, dental pattern of impaction of mandibular third molar and its relation with caries in mandibular second molar numra mumtaz, jawaria bibi, hawa jabbar, mohsin fazal correspondence: dr. numra mumtaz department of oral and maxillofacial surgery islamic international dental college, islamabad e-mail: numramumtaz91@gmail.com department of oral and maxillofacial surgery islamic international dental college, islamabad e-mail: numramumtaz91@gmail.com received: august 29, 2021; revised: march 01, 2022 accepted: march 03, 2022 distal caries in mamdibular second molarjiimc 2022 vol. 17, no.4 260 doi: https://doi.org/10.57234/698 this study was conducted with an objective to determine the mandibular third molar impaction pattern and its consequences in causing carious lesions in mandibular second molars so a better practice can be formulated for early diagnosis to prevent caries in the adjacent tooth in our centre. materials and methods this cross-sectional study was conducted over a duration of 6 months, in the department of oral and maxillofacial surgery at islamic international dental hospital, islamabad commencing from 1st january to th 30 june 2018. total 100 subjects satisfying the criteria for inclusion and exclusion were included in this study with non probability, consecutive sampling method. the world health organization sample size calculator was used to compute sample size. after selecting patient informed consent and demographic details were recorded in a study pro forma. participants who were included in this study were 18 to 60 years old, having both mandibular second and third molars with caries present in lower mandibular second molars being identified clinically and r a d i o g r a p h i c a l l y. p a t i e n t s w i t h a l r e a d y missing/extracted mandibular second molars and filled mandibular second molars were not involved in this study. all the patients were approved from the opd of oral and maxillofacial surgery department in iidh. after patient selection associated complaints like pain, caries and pericoronitis were also documented. further, clinical examination was done to investigate the extent of caries clinically and then patient was s u b j e c t e d t o s t a n d a r d p r e o p e ra t i v e o p g (orthopantomograms) and periapical radiographs to confirm carious lesion. each radiograph was studied for presence of carious lesion in lower second molar and also depth and angulation of impacted third molar teeth was evaluated. the pell and gregory classification system was used to evaluate depth based on extent of tooth enclosed by anterior border of ramus (class i, ii, and iii), and when considering occlusal surface (class a, b and c). winter's classification was used to assess the angle by measurement of angle between second and third 8 molar, intersecting longitudinal axes . angles measurements were done using a protractor (180º) w i t h v e r t i c a l i m p a c t i o n a n g l e ( 1 0 º 1 0 º ) , mesioangular impaction(11º -79º), horizontal impaction(80º-100º) and distoangular impaction( 11º-79º). age, gender, impaction type, angulation and depth were study variables to assess carious lesions in lowers second molar teeth in relation with impaction pattern of third molar. the statistical analysis of data was done by ibm spss software version 16 (statistical package for the social sciences). for qualitative factors such as gender, caries presence, depth of impaction and type of angulation, frequency and percentage were determined. for all quantitative data such as age, the mean and standard deviation were computed. chi square test was applied to evaluate relation among caries in mandibular second molar to both depth and angle of impacted third molar. the effect modifiers like age and gender were measured by stratification. the post-stratification chi square test was used. confidence level was 95%. statistical significance was considered as p value ≤ 0.05. results the participants in this study were in age from 18 to 60 years old, with mean age 39.24 ± 9.77 years. majority of the patients 59 (59.0%) were between ages of 18 and 40. among these patients, males were 83 (83.0%) and females 17 (17.0%) having a 4.9:1 male-to-female ratio. table i shows the patient distribution according to angulation type and impaction depth. tables ii and iii indicate the relation between mandibular second molar caries and impaction depth and angulation type. in this study, cervical caries at the distal side of second molars occurred in 39% of patients having i m p a c t e d m a n d i b u l a r t h i r d m o l a r s , a n d mesioangular impaction was the most occurring as shown in figure i. table i: distribution of patients with respect to type of angulation distal caries in mamdibular second molarjiimc 2022 vol. 17, no.4 261 doi: https://doi.org/10.57234/698 discussion diverse patterns are seen in impacted third molars in relation to depth, position, and angle in comparison with mandible and plane of occlusion respectively. understanding of these pattern forms is essential as some of these are linked to greater caries risk in next 5 immediate tooth that is second molar , discomfort 8 and pericoronitis and early loss of second molar 9 tooth . according to a research distal caries was the highest stated pathology between the second and impacted third molars, second being the periodontal 10 pocketing . in light of the abovementioned issue, this study was conducted to determine frequency of caries in mandibular second molar in relation to level of angulation and depth of impaction, established on winter's and pell and gregory's categorization system so a close follow-up of impacted molars should be considered to protect the second molar tooth. in this study, of 100 patients, 83.0% were male gender and 17.0% female having a 4.9:1 male-tofemale ratio. majority of patients with impacted mandibular third molar showed in their second and third decade, that is, 59.0%. distal cervical caries in second molars occurred in 39 percent of patients having impacted mandibular third molar teeth, and mesioangular impaction the most commonly occurring. 5 a study carried by srivastava et al , supports the outcomes of our study, male predominance and majority of patients being in the second decade. although, numerous former studies advocate a 9 female predominance. a study shows consistent results reporting caries to be more common in those with mesioangular impaction, that is, 68.3%, then vertical with 25.4%, followed by horizontal being 4.2% and lastly 11 distoangular impaction 2.1% . also, third molars above the level of cemento-enamel junction of adjacent second molar were related to causing distal 12 cervical caries. several other studies show caries on the distal side of second molars occurred with unerupted mandibular third molars, and the 4,6,13 mesioangular impaction was the common kind. 3 according to pentapati et al caries on the distal surface of mandibular second molars may not be related with all impacted mandibular third molars but teeth with mesioangular and horizontal angulations may lead to caries on the distal aspect of second molars. some studies have shown increased risk of caries associated with other types of impactions, vertical 7,14 and horizontal mostlyx. altan et al suggested that prophylactic removal of mandibular third molar between 51º to 71º can lead 15 to avoidance of distal carious lesions. however, sample size and duration of our research work are the limitations of our study in view of these studies prophylactic removal of third molar can be beneficial for the health of second molar tooth but in our region, it can also be an economic burden for the patient. so, consideration should be given to keep follow up of an impacted molar and attempting its removal when required. further studies need to be carried out to devise a specific protocol for management and follow up of patients with impacted mandibular third molars to table ii: relation between the mandibular second molar caries to depth of impaction p value = 0.05* table iii: relation between the mandibular second molar caries to type of angulation figure 1: percentage of caries (n=100) distal caries in mamdibular second molarjiimc 2022 vol. 17, no.4 262 doi: https://doi.org/10.57234/698 maintain long term health of mandibular second molar. conclusion according to the findings, cervical caries is seen on the distal aspect of mandibular second molars in 39 percent of individuals and most common impaction was the mesioangular impaction. to ensure the continuing health of mandibular second molars next to impacted third molars with mesial angulation between 30° and 70°, notably located at level a and class i, should be called for an attentive follow-up of impacted mandibular third molar. references: 1. viqar s, rizwan s, faisal ss, hussain ss. the frequency of mandibular third molar impaction in different types of vertical skeletal faces. j pak dent assoc. 2021;30(2):118123. 2. pell gj, gregory gt. report on a ten-year study of a tooth division technique for the removal of impacted teeth. am j orthod oral surg. 1942;28:660-6. 3. pentapati kc, gadicherla s, smriti k, vineetha r. association of impacted mandibular third molar with caries on distal surface of second molar. pesquisa brasileira em odontopediatria e clinica integrada. 2019 jan 1;19(1). e4455. 4. altiparmak n, oguz y, neto rs, et al. prevalence of distal caries in mandibular second molars adjacent to impacted third molars: a retrospective study using panoramic radiography. j dent health oral disord ther. 2017;8(6):641645. 5. srivastava n, shetty a, goswami rd, apparaju v, bagga v, kale s. incidence of distal caries in mandibular second molars due to impacted third molars: nonintervention strategy of asymptomatic third molars cause harm? a retrospective study. int j appl basic med res. 2017 janmar;7(1):15-19. 6. prajapati vk, mitra r, vinayak km. pattern of mandibular third molar impaction and its association to caries in mandibular second molar: a clinical variant. dent res j. 2017 mar-apr;14(2):137-142. 7. ilyas m, kundi ja, noor ia, zeb o, khan s. correlationof mandibular second molar caries with patterns of mandibular third molar impaction: a retrospective study. j gandhara med dent sci. 2017;4(1):23-7. 8. hashemipour ma, tahmasbi-arashlow m, fahimi-hanzaei f. incidence of impacted mandibular and maxillary third molars: a radiographic study in a southeast iran population. med oral patol oral cir bucal. 2013;18(1):140-5. 9. yilmaz s, adisen mz, misirlioglu m, yorubulut s. assessment of third molar impaction patternand associated clinical symptoms in a central anatolian turkish population. j med princ pract. 2016; 25:169-75. 10. braimah ro, ali-alsuliman d, agbaje ho, alsalah y, sharma hk, alsawas nm. prevalence, sociodemographics, and indications for extraction of impacted mandibular third molar in najran, a southern saudi arabian city. saudi j oral sci 2021;(8):75-80 11. ali fm, khan ma, derrbishi aa, al-mughalis ga, almasrahi m, kinani a, darraj aa. study of prevalence of caries on distal side of second mandibular molar due to impacted mandibular third molar. ann. int. med. den. res. 2017; 3(3):41-43. 12. claudia a, barbu hm, adi l, gultekin a, reiser v, gultekin p, mijiritsky e. relationship between third mandibular molar angulation and distal cervical caries in the second molar. j craniofac surg. 2018;29(8):2267–71. 13. syed kb, alshahrani fs, alabsi ws, alqahtani za, hameed ms, mustafa ab, alam t. prevalence of distal caries in mandibular second molar due to impacted third molar. j clin diagn res. 2017 mar;11(3):28-30. 14. ashar t, shakoor a, ghazal s, parveen n, saleem mn, raja hz. prevalence of distal carious lesions in mandibular second molars due to mesio-angular impacted third molars. j pak dent assoc. 2021;30(1):50-55. 15. altan a, soylu e. the relationship between the slope of the mesioangular lower third molars and the presence of second molar distal caries: a retrospective study. cumhuriyet dent j. 2018;21:178-183. distal caries in mamdibular second molarjiimc 2022 vol. 17, no.4 conflict of interest authors declared no conflicts of interest. grant support and financial disclosure authors have declared no specific grant for this research from any funding agency in public, commercial or nonprofit sector. data sharing statment the data that support the findings of this study are available from the corresponding author upon request. this is an open access article distributed under the terms of the creative commons attributionnoncommercial 2.0 generic license. 263 doi: https://doi.org/10.57234/698 jiims.cdr abstract objective:to determine the ratio between width of hamular notches and maxillary central incisors' width at cervical, incisal and contact points. study design: cross–sectional descriptive study. place and duration of study: department of prosthodontics, armed forces institute of dentistry, rawalpindi from feb 2010 to aug 2010. materials and methods:impressions of the maxillary jaw of 125 subjects were made and casts were obtained. a precise caliper was used to make the measurement ofthe widths of the maxillary central incisors at three different levels; the incisal edge (iw), at the level of interdental contact points (conw) and in the cervical region(cerw). the hamular width (hw) was measured between the most mesial demarcation point of the left and the right hamular notches.the ratios between the hard palate width (hw) and maxillary central incisor widths at all the three levels (iw, conw, cerw) were calculated.data was analyzed using spss 16. results: of the125 subjects, 52 (41.6%) were males and 73 (58.4%) were females while mean age of the subjects was 26.56 years. ratios hw/cerw, hw/iw and hw/conwwere calculated as 6.08+0.18mm, 5.9+0.17mm and 5.81+ 0.17mm. conclusion: the hw can be used as a preliminary method for determining the width of the maxillary central incisor. keywords: incisor width, complete dentures, denture esthetics. 89 original article appropriately sized maxillary anterior 5 teeth. there is no single universally accepted that can be used reliably to help select artificial 6,7 teeth. many researchers haveadressed the correlation of dimensions of various facial landmarks and the size of a maxillary 8,9,10,11 anterior tooth. levin suggested the “golden proportion” to relate the width of the successive anterior teeth as viewed from 12 the labial aspect. snow proposed the “golden percentage” to evaluate the mesiodistal dimensions of anterior teeth. more recently, ward gave the concept of the “ r e c u r r i n g e s t h e t i c d e n t a l ( r e d ) proportion”. he described red as the proportion of the successive width of the teeth remaining constant when progressing 12 distally from the midline. various anatomic measurements have been suggested as guides to determine the correct size of the a n t e r i o r t e e t h i n c l u d i n g t h e i n t e rcommissural width, bi-zygomatic width, inter-alar width, and inter-pupillary distance.10in previous studies, the size and introduction a harmonious and natural smile is essential 1 in achieving a pleasant face. esthetics is the primary consideration for patients who seek 2 prosthodontic treatment. for the treatment to be successful, optimal facial esthetics 3 must be achieved. the ultimate objective of prosthodontic treatment in anterior segment of the mouth is to create a harmoniously balanced smile with ideal interaction of the 3,4 teeth, gingivae, lips and face. f o r d e n t u r e s t o b e e s t h e t i c a l l y acceptable,they should not vary from 4 natural teeth. this makes the selection of artificial teeth significant. many authors agree that the upper central incisors are the key determinants of anterior dental esthetics. therefore, one difficult and i m p o r t a n t a s p e c t o f p ro s t h o d o n t i c r e h a b i l i t a t i o n i s t h e s e l e c t i o n o f ------------------------------------------------selection of appropriate artificial maxillary central incisor size using dimensions of hard palate wasiq riaz, ayesha aslam, muhammad umer javed, azad ali azad correspondence: dr. muhammad umer javed dept. of prosthodontics armed forces institute of dentistry rawalpindi. email: umerjaved86@gmail.com 90 shape of maxillary central incisor has shownno significant correlation to the shape and dimensions of a patient's soft-tissue 6 landmarks. however, studies correlating the dimensions of the hard palate and the maxillary incisors are rare. the anterior portion of maxilla undergoes extensive resorptive changes following 5 tooth extractions. hamular notches, however, are not subject to resorption after 6 the extraction of teeth. studies reveal that a close relationship exists between the morphology and dimensions of maxillary central incisors and those of the hard 11 palate. in a study by petricevic n et al, the author correlated some dimensions of hard palate and the maxillary incisors. the various ratios calculated are: hamular width / cervical width of central incisor = 5.71, hamular width / incisal width of central incisor = 5.70, hamular width / contact point 6 width of central incisor = 5.51. the aim of this study is to determine the relationship between dimensions of maxillary anterior teeth and those of the hard palate. no recognizable work has yet been done on this subject on the local population. this study will be a step ahead in suggesting a single reliable biometric criteria for the selection of appropriately sized maxillary central incisors. this will enable the clinicians to achieve a dental appearance that is in accordance with overall facial esthetics. it will also give us an insight towards restoring the facial as well as dental esthetics in a more scientific way, thereby satisfying the patients up to their expectations. this case control study was carried out in department of prosthodontics, armed forces institute of dentistry, rawalpindi over a period of six months from feb 2010 to aug 2010.one hundred and twenty five subjects age between 18 to 35 years with intact anterior teeth and angle's class i materials and methods molar relationship were selected for participation in the study.subjects with one or more teeth missing (except the third molars), having any restorations or attrition of anterior teeth, any tooth size/ shape abnormalities, marginal periodontitis and gingival recession or had undergone orthodontic treatment were not included in the study. a written consent was obtained from each subject. a round end filling instrument was used to locate the hamular notch precisely and indelible pencil (0.1 mm point) was used for their demarcation.impressions of the maxillary jaw of each subject were made using irreversible hydrocolloid. casts were o b t a i n e d b y p o u r i n g t h e re c o rd e d impressions in hard stone. a precise caliper (0.1 mm precision) was used to measure distance between the two hamular notches and widths of right and left maxillary central incisors(mcis) on the dental cast. the measurements were made between incisal edge and the most apical point of marginal gingiva. the widths of the right and the left mcis were measured at three different levels, at the incisal edge, interdental contact points and between the tips of interdental papilla. mean for each dimension between right and left maxillary central incisor was calculated to obtain the incisal edge width (iw), the interdental contact point width (conw) and the cervical width (cerw) of the central incisor of the subject. the hamular width (hw) was measured between the most mesial demarcation point of the left and the right hamular notch. data was analyzed using spss version 16. mean±s.d was calculated for age, hamular width,central incisor width at incisal edge, contact point, andcervicallevel. frequencies and percentages were presented for gender. ratios (hamular width / cervical width of central incisor, hamular width / incisal width of central incisor, hamular width / 91 contact point width of central incisor) were then calculated. this study comprised of 125 subjects in total, out of which 52 (41.6%) were males and 73 (58.4%) were females (fig i).the minimum age of the patients was 18 years and maximum 35 years while mean age was 26.56 (table i). descriptive statistics for mean hw, cerw, incw and conw values and the three ratios n a m e l y h w / c e r w, h w / i n c w a n d hw/conware presented in table i. results the meanhw/cerw ratio is 6.08+0.18mm. gender-wise description reveals the mean hw/cerw for males to be 6.18±1.5mm and 6.00±1.6mm for females. the meanhw/incw ratio is 5.9+0.17mm. gender-wise description reveals the mean hw/incw for males to be 6.02±0.15mm and 5.84±0.15mm for females. the meanhw/conw ratio is 5.81+ 0.17mm. gender-wise description reveals the mean hw/incw for males to be 5.92±0.13mm and 5.74±1.6mm for females. data correlating the dimensions of hard palate with those of the maxillary incisors is scarce in literature. attempts made on this subject are few and far between. no appreciable work has been done in this discussion table i: gender-wise mean values fig 1: gender distribution of subjects regard on the local population. the present study used the dimensions of hard palate (hamular width) for the determination of artificial maxillary central incisor width during complete denture construction for edentulous patients. the results of the present study compare favorably with those reported by n. 6 petricevic et al. who included 80 dentate croatian subjects (24 male, 56 female) with a mean age of 24 years, while our study was carried out on 125 subjects with a mean age of 26.5 years.the ratio hw/incw recorded in the present study is 5.9mm that closely correlates with that of n. petricevic et 6 al (5.7mm). the ratio hw/cerw calculated by our study is 6.08mm while that reported by petricevic is 5.71mm. also, the ratio hw/conw by our study (5.81mm) closely approximates that of petricevic's study (5.51mm). the values of hw in the study conducted by 6 petricevic et al. ranged from 36 to 55mm with a mean of 47.1mm. in our study, the hw values ranged from a minimum of 43.5mm to a maximum of 63.4mm, with a mean of 51.7mm. this difference of 4.6mm in hw can be explained on the basis of the population groups studied. it can be inferred that the values of hw and hence, width of central incisors tend to be greater in a south-asian population. in a similar study carried out by petricevic et al and stipetic et al, the widths of maxillary 92 central incisor at the cervical, incisal and contact point areas were reported to be 8.26, 11 6.19 and 8.55 mm respectively. these values compare well with those of our study except for the incisal width which tends to be higher among our study group. cesario et al. conducted a study on 229 dentate saudi subjects (120 males, 109 females) mean age 21.16 years,and reportedthe central incisor width to be 15 8.9mm on average. the results match closely with those of our study. a comparable study conducted on 80 9 patients by s. wolfart et al. revealed maxillary central incisor width to be 9.1mm which is slightly larger than the values achieved in our study. dimensions of the all anterior teeth for most racial groups vary with gender, with men exhibiting wider anterior teeth than women 16,17,18 as reported in many studies. it was studied and reported by gillen et althat in both black and white populations, men hand wider as well as longer maxillary 16 anterior teeth in comparison to women. similarly, sterrett et al.postulated the average width and length of the crowns of t h e m a x i l l a r y a n t e r i o r t e e t h w a s significantly greater for white males than for 1 7 w h i t e f e m a l e s . i n t h e s t u d y o f hasanreisoglu et al. the averagecrown width and height values for the central incisors and the canines were significantly greater for men as compared to women, with the central incisors being the widest 7 teeth in both genders. hock da et al. measured the width of the maxillary central incisor in several racial groups and noted variations in most of them, with men, again 13 having wider central incisors than women. in our study the mean values for the width of central incisor at the cervical, incisal and contact point areas for males were 8.91, 9.15 and 9.29 mm respectively. for females, the v a l u e s w e r e 8 . 2 1 , 8 . 4 4 a n d 8 . 5 9 mmrespectively. this clearly indicates that the males have larger mesiodistal width of central incisors than females in our study population. these findings are in good agreement with the results of other related 13, 17 studies. the widths of maxillary central incisor vary considerably amongst different races. very few data is available on this subject in local population. there is a requirement of extensive local work on larger scale in order to evaluate orofacial biometric guides in our population. with the limitations of this study, the following conclusions were drawn: 1. hamular width can serve as a reliable and helpful landmark in order to determine the maxillary central incisor's dimensions. 2. maxillary central incisor's cervical (cerw), incisal (incw) and contact point width (conw) might be calculated by dividing hamular width (hw) by 6.08, 5.91 and 5.81 respectively. 3. the hw can only be used as a preliminary method for determining the width of the maxillary central incisor. the final decision regarding tooth selection should be made b y e m p l o y i n g v a r i o u s g u i d e l i n e s suggested in the literature regarding anterior tooth selection and should be confirmed by consultation with the patient. 1. paranhos lr, lima cs, silva rh, daruge junior e, torres fc. correlation between maxillary central incisor crown morphology and mandibular dental arch form in normal occlusion subjects. braz dent j 2012; 23: 149-53. 2. tozum tf, guncu gn, yildirim yd. evaluation of maxillary incisive canal characteristics related to dental implant treatment with c o m p u t e r i z e d t o m o g r a p h y : a c l i n i c a l multicenter study. j periodontol 2012; 83: 337conclusions references 93 43. 3. paranhos lr, joias rp, velasco lg, berzin f, daruge junior e. prevalence of the different maxillary central incisor shapes in individuals with natural normal occlusion. braz j oral sci 2010; 9: 104-7. 4. petricevic n, celebic a, seper li, kovacic i. appropriate proportions as guidelines in selection of anterior denture teeth. med glas 2008; 5: 103-8. 5. park ys, lee sp, paik ks. the three-dimensional relationship on a virtual model between the maxillary anterior teeth and incisive papilla. j prosthet dent 2007; 98: 312-8. 6. petricevic n, katunaric m, mehulic k, simeon p, rener-sitar k, celebic a. selection of appropriate artificial frontal teeth size using dimensions of hard palate. coll antropol 2006; 30: 573–7. 7. hasanreisoglu u, berksun s, aras k, arslan i. an analysis of maxillary anterior teeth: facial and dental proportions. j prosthet dent 2005; 94: 530-8. 8. amin wm, taha st, al-tarawneh sk, saleh mw, ghzawi a. the relationships of the maxillary central incisors and canines to the incisive papilla in jordanians. j contemp dent pract 2008; 9: 42-51. 9. wolfart s, quaas a c, freitag s, kropp p, gerber w d, kern m. subjective and objective perception of upper incisors. journal of oral rehabilitation 2006; 33: 489–95. 10. zlatariæ dk, kristek e, celebiæ a. analysis of width/length ratios of normal clinical crowns of the maxillary anterior dentition: correlation between dental proportions and facial measurements. int j prosthodont 2007; 20: 313-5. 11. petricevic n, stipetic j, antonic r, borcic j, strujic m, kovacic i, et al. relations between anterior permanent teeth, dental arches and hard palate. coll antropol 2008; 32: 1099–1104. 12. ali fayyad m, jamani kd, agrabawi j. geometric and mathematical proportions and their relations to maxillary anterior teeth. j contemp dent pract 2006; 7: 62-70. 13. hockda. qualitative and quantitative guides to the selection and arrangement of the maxillary anterior teeth. j prosthet dent 1992; 1: 106-11. 14. scandrett fr, kerber pe, umrigar zr. a clinical evaluation of techniques to determine the combined width of the maxillary anterior teeth and the maxillary central incisor. j prosthet dent 1982;48: 15-22. 15. cesario va jr, latta gh jr: relationship between the mesiodislal width of the maxillary central incisor and interpupillary distance. j prosthet dent 1984; 52: 641-3. 16. gillen rj, schwartz rs, hilton tj, evans db. an a n a l y s i s o f s e l e c t e d n o r m a t i v e t o o t h proportions. int j prosthodont 1994; 7 :410-7. 17. sterret jd, oliver t, robinson f, fortson w, knaak b, russel cm. width/length ratios of normal clinical crowns of the maxillary anterior dentition in man. j clin periodontol 1999; 26: 153-7. 18. sherfudhin h, abdullah ma, khan n. a crosssectional study of canine dimorphism in establishing sex identity: comparison of two statistical methods. j oral rehabil 1996; 23: 62731. 19. keng sb, foong kw. maxillary arch and central incisor dimensions of an ethnic chinese population in relation to complete denture prosthodontics.int dent j 1996; 46: 103-7. 20. ghoddousi h, edler r, haers p, wertheim d, greenhill d. comparison of three methods of facial measurements. int j oral maxillofac surg 2007; 3: 250-8. 21. ulhas et, shankar pd, arun nk. biometric relationship between intercanthal dimension and the widths of maxillary anterior teeth. j indian prosthod soc 2007: 123-5. jiims final.cdr 14 introduction the active phase of labor may be augmented routinely as in active management of labor or selecting when progress of labor is 1considered to be inadequate. prolonged labor is most common among nulliparous women and is related to increased caesarean section rate i.e. nearly 25% birth in england (pakistan-40-50% in some private institutes) of which 30% are 2due to failed progress. who recommend best outcome of mothers and babies to occur with c/section rates of 5-10%.the world health organization recommends the use of partogram with an alert line indication normal progress, defines as a cervical dilatation of 1cm/hr and an action line 4 hrs to the right to detect and treat prolonged 3labour. it has been argued for long time that active management reduces the duration of labour and incidence of labour lasting more than 12 hrs, as well as c/section rate however this is original article outcome of early versus delayed oxytocin augmentation in nulliparous women on the duration of labour and other obstetric and neonatal outcome a randomized controlled trial azra saeed awan, umber bakhtiar, ghazala amin abstract objectives: to determine the outcome of early versus delayed oxytocin augmentation in nulliparous women on the duration of labor and other obstetric and neonatal outcomes. study design: a prospective randomized trial. place and duration of study: the study was conducted at pakistan railways hospital, for the duration of 1 year with effect from january 2010 january, 2011. it is 400 bedded teaching hospital affiliated with iimc-t of riphah international university, islamabad materials and methods: in healthy nulliparous women with normal pregnancy,the progress of labor was thoroughly monitored and documented every 23 hours. if there was still no progress 1 hour after amniotomy, the woman was randomly allocated to either labor augmentation by oxytocin infusion or to postponement of oxytocin augmentation for 3 hours (expectant group, n = 158). women whose labors had progressed satisfactory (1 cm/hour) after amniotomy were not randomized. participants were managed according to a standard protocol entailing continuous documentation of the progress of labour, the amount of oxytocin administered, and obstetrical and neonatal outcomes. oxytocin infusion was started at 6 mu/minute and was raised by 6 mu/minute every 30 minutes until efficient contractions were established in the early oxytocin group. in the expectant group, if no progress occurred after 3 hours, the women were reassessed regarding the need for oxytocin augmentation. data were analyzed with spss 15.0. the mannwhitney u test was used to compare means. proportions of events were compared with fisher's exact test or chi-square analysis. statistical significance was set at a p value of <0.05. results: the caesarean section rate was 9% in the early oxytocin group and 10.7% in the expectant group (or 0.8, 95% ci 0.51.4), and instrumental vaginal delivery 17% in the early oxytocin versus 12% in the expectant group (or 1.5, 95% ci 0.972.4). early initiation of oxytocin resulted in a mean decrease of 85 minutes in the randomization to delivery interval. conclusion: early administration of oxytocin did not change the rate of caesarean section or instrumental vaginal delivery but shortened labor duration significantly in women with a 2-hour arrest in cervical dilatation. no other clear benefits or harms were seen between early and delayed administration of oxytocin. key words: oxytocin augmentation, prolonged labor, fetal distress. --------------------------------------------------correspondence: dr. prof azra saeed awan hod gynae obs unit-ii pakistan railways hospital rawalpindi 15 4not supported in recent meta analysis. aim of our study was to study effects of early augmentation versus post ponemant of oxytocin administration on obstetrical and neonatal outcomes in nulliparous women with spontaneous but prolonged labour. this prospective randomized trial was conducted pakistan railways hospital, iimc-t, riphah international university, islamabad. healthy nulliparous women with normal pregnancies received written information about the study in the third trimester at their antenatal clinics. inclusion criteria were nulliparity, a singleton fetus in cephalic presentation, spontaneous onset of active labour with regular contractions and an effaced cervix dilated between 4 and 9 cm, at a gestational age between 37 + 0 and 41 + 6 weeks. the choice of a minimum of 4-cm dilatation was to ensure that the active phase of labour was established at the time of inclusion into the study. the latent phase was defined as the interval between start of contractions (women's report) until active labour was established at inclusion into the study. women with spontaneous rupture of the membranes together with regular contractions were also included in the study. exclusion criteria were non-cephalic p re s e n t a t i o n , p re l a b o u r r u p t u re o f membranes, serious maternal disease and fetal death. during the study period 350 women fulfilled the inclusion criteria. at admission to the delivery ward, only the women given the study information antenatally were a s k e d t o p a r t i c i p a t e i n t h e s t u d y. material and methods participation into the study was accepted by 315women who were included in active labor. the progress of labour was thoroughly monitored and documented every 23 hours according to the departmental guidelines. slow progress of labour was defined as an arrest in cervical dilatation for two hours or a dilatation less than 1 cm for 3 hours in the first stage of active labour. if labour was slow and the membranes were intact amniotomy was first performed. if there was still no progress 1 hour after amniotomy, the woman was randomly allocated to either labour augmentation by oxytocin infusion within 20 minutes (early oxytocin group, n = 157) or to postponement of oxytocin augmentation for 3 hours (expectant group, n = 158). women whose labours had progressed satisfactory (1 cm/hour) after amniotomy were not randomized. participants were managed according to a standard protocol entailing continuous documentation of the progress of labour, the amount of oxytocin administered, and o b s t e t r i c a l a n d n e o n a t a l o u t c o m e s . oxytocin infusion was started at 6 m u / m i n u t e a n d w a s r a i s e d b y 6 mu/minute every 30 minutes until efficient contractions were established in the early oxytocin group. maximum dose of oxytocin infusion during the opening phase was 40 mu/minute. in the expectant group, if no progress occurred after 3 hours, the women were reassessed regarding the need for oxytocin augmentation. . data were analyzed with spss 15.0. the mannwhitney u test was used to compare means. proportions of events were compared with fisher's exact test or chi-square analysis. statistical significance was set at a p value of 16 <0.05. during the study period 315 consenting women were randomised. primary analysis was done according to intention to treat with all cases as randomized. the two study groups were well balanced against each o t h e r i n r e l a t i o n t o t h e b a s e l i n e characteristics, for example, maternal age, gestational age, proportion of women with spontaneous rupture of membranes before inclusion, intensity of labour pain and cervical dilatation at inclusion and at randomisation. in accord with the study protocol, oxytocin augmentation was started earlier, administered more often and in higher doses in the early oxytocin group. there were no significant differences in the primary outcome, mode of delivery. the instrumental vaginal deliveries were all vacuum extractions except two forceps deliveries in the early oxytocin group. the interval from randomisation to delivery was 85 minutes shorter in the early oxytocin group. there was no difference in duration of the second stage between the groups. shows the percentages of women giving birth from time of randomisation in both groups. the rate of postpartum blood transfusion did not differ significantly between the two groups. no neonatal outcome variable differed significantly between the study groups. birth weight is similar. there were no significant differences between the study groups in 5-minute apgar score below 7, admission to nicu or phototherapy for jaundice. there were no perinatal deaths. results 17 discussion s o m e o r a l l c o m p o n e n t s o f a c t i v e management of labor have been adopted 1since 1970's. several randomized control studies have been carried out different components of active management of labour are: strict diagnostic criteria for labour, early amniotomy, early use of oxytocin and 2continuous professional support. the rise of operative delivery particularly ceasarean section continous to be an obstetric concern. continuous increased caesarean section rate may have influence on maternal and neonatal mortality & 3morbidity. prolong labour has been described one of the leading indications for 18 4caesarean section. our study is relates to the oxytocin a u g m e n t a t i o n o f l a b o r. s i n c e t h e formulization of high dose protocol for oxytocin administration several papers have published on ability of oxytocin to fasten labor and decrease caesarean section 6, 11rate. in this protocol oxytocin infusion is started at equalent of 6miu/min and increasing 6miu every 30 minutes to maximum 40 miu/min. evidence of fetal distress on ctg or fbs is the only c o n t r a i n d i c a t i o n f o r o x y t o c i n administration. satin et al demonstrated that duration of labour may be decreased by 3 hours to lead less ceasarean section but his study included 6,both nulliparous and multiparous women. 13 other randomized controlled trial has not realized the decreased rate of ceasarean section but site similar reduction in duration of labor. our study has shown that although early or delayed use of oxytocin did not make any difference in mode of delivery but it is very obvious from results that every oxytocin group had a significant shortened length of labour and there was also a clear reduction in rate of operative vaginal deliveries. there was no significant difference in rate of pph, apgar score of neonatal and need for nicu admission. this study had the following weakness. obstetrician was not blinded to the treatment group. the decision to perform caesarean section or operative vaginal delivery may be tailored by knowledge of treatment arm. there is no current cochrane review of effect of oxytocin used as a single intervention in labour. there are only a few 10, 13, 15small trials for oxytocin alone. a meta analysis suggested that there was no 7, 13effect on caesarean section rate. our study also supported that a meta analysis by observing lack of any statistical difference in caesarean section rate. although the shortening of labour has long b e e n w i d e l y a s s u r e d w i t h a c t i v e 8, 14, 13management of labour. our study has reliably shown an 85 minutes reduction in total duration of labour, which is similar to previous studies which show 50-160minute reduction. in this study no significant differences were seen between early versus expectant administration of oxytocin stimulation in nulliparous women with slow labour in relation to the mode of delivery, postpartum h a e m o r r h a g e , p o s t p a r t u m b l o o d transfusions, neonates with a 5-minute apgar score below 7 or neonatal admission to nicu. the interval from randomization to delivery was 85 minutes shorter in the early oxytocin group. no other clear benefits or harms were seen between early administration and expectancy of oxytocin 1. waldenstrom u, hildingsson i, rubertsson c, radestad i. a negative birth experience: prevalence and risk factors in a national sample. birth2004; 31:17-27. 2. nystedt a, hogberg u, lundman b. some swedish women's experiences of prolonged labour. midwifery 2006; 22:56-65. 3. swedish national board of health and welfare. the swedish medical birth register, centre of epidemiology 4. florica m, stephansson o, nordstrom l. indications associated with increased cesarean section rates in a swedish hospital. int j gynaecol obstet 2006; 92:181-15. conclusion references 19 5. bugg gj, stanley e, baker pn, taggart mj, johnston ta. outcomes of labours augmented with oxytocin. eur j obstet gynecol reprod biol 2006; 124:37-41. 6. satin aj, levan kj, sherman ml et al high vs low dose oxytocin for labour stimulation. obstetric gynae 1992” 80: 111-16. 7. selin l, wallin g, berg m. dystocia in labour risk f a c t o r s , m a n a g e m e n t a n d o u t c o m e : a retrospective observational study in a swedish setting. acta obstet gynecol scand 2008; 87:21621. 8. fraser w, vendittelli f, krauss i, breart g. effects of early augmentation of labour with amniotomy and oxytocin in nulliparous women: a metaanalysis. br j obstet gynaecol 1998; 105:189-94. 9. sadler lc, davison t, mccowan lm. a randomised controlled trial and metaanalysis of active management of labour. bjog 2000; 107:909-15. 10. hodnett ed, gates s, hofmeyr gj, sakala c. c o n t i n u o u s s u p p o r t f o r w o m e n d u r i n g childbirth. cochrane database syst rev 2007;(3)cd003766. 11. lavender t, alfirevic z, walkinshaw s. effect of different partogram action lines on birth outcomes: a randomized controlled trial. obstet gynecol 2006; 108:295-302. 12. rogers rg, gardner mo, tool kj et al. active management of labour: a cast analysis of a randomized controlled trail west j med 2000”172: 240-3 13. hodnett ed, gates s, hofmeyr gj, et al; c o n t i n u o u s s u p p o r t f o r w o m e n du r i n g childbirth. cochrane database syst rev. 2003 ;(3):cd003766. 14. hofmeyr gj; evidence-basedintrapartum care. best pract res clin obstet gynaecol. 2005; 19(1):103-15. 15. wei s, wo bl, xu h, et al; early amniotomy and early oxytocin for prevention of, or therapy for, delay in cochrane database syst rev 2009 ;(2):cd006794. jiims final 3 original article introduction infertility is defined as failure to conceive after a year of regular intercourse without contraception. infertility is the major life crisis particularly in our society. it comes as a severe shock to couples who have probably taken their fertility for granted. it cannot be denied that infertility is a deeply 1distressing experience for many couples. couples suffering from infertility have a tough time admitting that they have a problem as they feel that they have failed in their basic role of reproduction. when they are not successful in treatments they feel that 2they and their marriage is a failure. this life crisis can lead to many emotional and psychological reactions. it presents them with one of their first major crises together. it may affect the couple's inter-personal relationships, marital, social and sexual aspects of life. infertility can cause depression, anxiety, 3, 4social isolation and sexual dysfunction. that is why the impact of infertility on the psychological well being of couples has been the object of increasing attention in recent y e a r m a n y s t u d i e s h a v e r e p o r t e d psychological symptoms and problems in infertile couples. these psychological symptoms can be the cause of infertility or the consequence of it or both. a study found that infertility has a significant effect on psychological health of couples. they suffer from loss of self-esteem, sadness of mood, fear, sexual dysfunction, depression, guilt, 5anxiety, frustration, emotional distress. a m o n g t h e p s y c h o l o g i c a l p r o b l e m depression, anxiety and stress are most abstract objective: to assess psychological morbidity amongst infertile couples. study design: cross-sectional study. place and duration of study: this study was carried out at mas infertility clinic, rawalpindi from august 2010 to january 2011. materials & methods: a total of 30 subjects (15 couples) were included in the study. after taking an informed consent, they were asked to complete a questionnaire. depression, anxiety and stress scale (dass) questionnaire was used for this study. data was analyzed using spss version-14 and t-test was applied to see the significance in differences. results: majority of couples were over 30 years of age and were married for more than 5 years. vast majority (73.3%) were living in joint family system. psychological morbidity, particularly anxiety and depression affected significantly (p=0.05) female partner. however no significant relationship was observed between the cause of infertility or duration of infertility and psychological manifestations. conclusion: this study presents pragmatic evidence regarding the psychological health of infertile couples in our society. findings suggest that high levels of stress and depression exist in these couples, which not only affects their physical health, but also their psychological well being. it highlights the importance of providing psychotherapeutic help along with treatment for the cause of infertility. key words: infertility, infertile couple, psychological morbidity, depression, anxiety and stress ---------------------------------------------------psychological morbidity amongst infertile couples shazia ali, fazaila sabih, farah rashid, sarwat jehan, masood anwar correspondence: dr. shazia ali department of physiology islamic international medical college, peshawar road, rawalpindi e-mail: alishazia259@gmail.com 3 4 commonly reported. several studies have demonstrated that anxiety has a detrimental 6effect on fertility. and the reduction of 7,8anxiety increases pregnancy rate. men and women with infertility experience poor self esteem and loss of physical potency and feeling of stigma in the society, which ultimately leads to elevated distress and 9great difficulties for the couple. different tools used for measurement of depression, anxiety and stress include depression 10,11anxiety stress scale (dass). beck 1 2d e p r e s s i o n i n v e n t o r y ( b d i ) . a n d 13symptom check list (scl-90-r). eventually these all yield comparable 11, 12, & 13results. we have used, in this study dass for the reason of convenience and simplicity. the present study focuses on the psychological morbidity of pakistani couples attending an infertility clinic. the depression anxiety stress scale (dass) is used to assess psychological morbidity which is increasingly used in diverse clinical settings. this was a cross-sectional study of psychological morbidity in infertile couples attending mas infertility clinic in rawalpindi, from august 2010 to january 2011. all infertile couples attending mas infertility clinic for the first time were asked to participate in this prospective, cross sectional study. thirty patients (15 women, 15 men) were entered into the study. the couples were asked, after informed consent to complete the questionnaire separately in the clinic. the depression anxiety stress scale (dass) questionnaire was used for the 11study. materials and methods study measures results the psychological morbidity was assessed using the depression anxiety stress scale 11(dass). the depression anxiety stress scale (dass) is a 42-item self-report measure of anxiety, depression and stress which is increasingly used in diverse settings. the dass has three sub-scales i.e. depression, anxiety and stress. each of the three dass scales contains 14 items and scores on each subscale range from zero to 3 indicating did not apply to me at all to applied to me very much. the alpha reliability of the instrument for this study was 93, which is highly significant. patients' demographic and clinical characteristics were also recorded on history taking proforma. data were analyzed through spss-14 by applying different statistical tests. student ttest was used to measure the significances. a total of 30 subjects, 15 male & 15 female (15 couples) were included in the study. age of the couples ranged from 25-30 years in 11, 31-35 years in 13 and more than 35 years in 6 subjects. only 8(26.7%) were living independently while 22(73.3%) were living in joint family system. eight (26.7%) couples were married for more than 10 years, ten (33.3%) for 6-10 years and 12 (40%) for up to 5 years. in majority (73.3%) both male and female factors were identified as the cause of infertility. female factor alone was responsible in 6(20%) females and no cause of infertility could be determined in 2(6.7%) couples. majority (28/30) of the subjects w e r e f o u n d t o h a v e p s y c h o l o g i c a l morbidity. however, manifestations were moderate in most (53.3%) of them. anxiety 4 5 and depression was observed in all affected (93.3%) subjects where is stress was seen in 86.6%. all three were seen in 66.7%. details are shown in figure 1. significant gender differences were observed. dass total score was significantly (p=0.05) higher in females and so, were the manifestations of anxiety and depression. details are shown in table-i. no significant relationship was observed between the cause of infertility and psychological manifestations in either of the gender (table-ii). there was also no significant relationship between the duration of infertility and psychological morbidity in both sexes (table-iii). this study investigated psychological m o r b i d i t y a m o n g i n f e r t i l e c o u p l e s attending infertility clinic. we observed that 93.3% of infertile couples suffered from different levels of depression anxiety and stress (figure-1). in the present study the psychological morbidity was assessed using the depression anxiety stress scale 11(dass). it is reported by siebel and taymor using beck depression inventory 1 2( b d i ) . t h a t o v e r a l l p e r c e n t a g e o f psychological problems in infertile couples 12range between 25 and 60%. another study carried out by downey j using symptom check list (scl-90-r) demonstrated that 74.6% patients reported changes in their 1 3m o o d . p r e v a l e n c e p s y c h o l o g i c a l morbidity appears to be much higher in our society. this may be the result specific religious and cultural effects. psychological difficulties of infertile patients are complex and influenced by a number of factors such as gender differences, cause and length of infertility. risk factors that predispose an discussion individual to anxiety and depression during infertility are being female, age over 30, l o w e r l e v e l o f e d u c a t i o n , l a c k o f occupational activity, a male cause for infertility, and infertility for 3-6 years. duration of infertility also affects the psychological state of the couple as 2-3 years infertility had more depression / anxiety than those couples who suffer from 14, 15infertility for more than 6 years. we also observed that it was female gender which was affected more. in our study there was also no significant relationship between the duration of infertility and psychological morbidity in both sexes similar results have 16,17,18also been reported by many others. one reason for such findings is due to the fact that usually women are more vulnerable to psychological problems. in our society women especially get more stigmatized regardless of the diagnosis of infertility and they carry more burden of being labeled as infertile from all sections of society. it causes more distress and decline in health-related quality of life amongst 19,20infertile females. in various studies it is observed that when the male partner is responsible for infertility in the couple the reaction of the male partner is very different from the couple in which the diagnosis was female, mixed or unexplained infertility. this was not observed in our study. this may be because in our study in majority there was a male as well a female cause for infertility. therefore, our study analysis showed that no significant differences in the psychological morbidity when aspects of duration of infertility and causes of infertility (table ii, iii) were considered. these results are in line with previous 21studies. a possible explanation might be 5 6 that the infertility leads to similar experiences by all men and women although they might express themselves in different ways. in the light of above we recommend that more attention should be given to health education and awareness about reproductive health for male and female both. couples should be advised to seek treatment early and should receive proper counseling and psycho-education. 1. guerra d, liobra a, veiga a, barri pn. psychiatric morbidity in couples attending a fertility service.hum reprod, 1998; 13:1733-36. 2. h. holter , l. anderheim, c. bergh1 and a. möller2 the psychological influence of gender infertility diagnoses among men about to start ivf or icsi treatment using their own sperm. 2007; 2559-65. 3. fassino s, piero a, boggio s, piccioni v, garzaro l. anxiety, depression and anger suppression in infertile couples. hum reprod. 2002;17:2986-94. 4. chen th, chang sp, tsai cf, juang kd. prevalence of depressive and anxiety disorders in an assisted reproductive technique clinic. hum reprod. 2004; 19:2313-18. 5. edelmann rg, connolly kj. psychological consequences of infertility. brit j med psychol, 1985; 59:202-19. 6. demyttenaere k, nijs p, steeno o, koninckx pr, everse-kiebooms g. anxiety and conception rates in donor in semi nation. j psychosom obstet gynaecol. 1988;8: 175-81. 7. sarrel p, decherney a. psychotherapeutic intervention for treatment of couples with secondary infertility. fertil steril, 1985;43:897900. 8. rodriguez b, bermudez l, poncede leon e, castro l. presented at the third world congress of behavior therapy. washington dc; the relationship between infertility and anxiety: some preliminary findings. december 811, 1983. 9. hämmerli k, znoj h, barth j. the efficacy of psychological interventions for infertile patients: a meta-analysis examining mental health and pregnancy rate. 2009; 15:279-95 10. covic a. depression and anxiety in patients with rheumatoid arthritis: prevalence rates based on a comparison of the depression, anxiety and stress scale (dass) and the hospital, anxiety and depression scale (hads) bmc psychiatry 2012; 12:6 11. lovibond s h & lovibond p f manual for the depression anxiety stress scales. sydney: psychology foundation. 12. seibel mm, taymor ml. emotional aspects of references figure 1: levels of depression, anxiety and stress amongst infertile couples table-i: mean, sd and t-value of infertile couples (male and female) on the total scores of dass and its subscales (n = 30) table-ii: mean, sd and t-value of causes of infertility on the scores on the total scores of dass and its subscales (n = 28) table-iii: mean, sd and t-value of duration of infertility on the total scores of dass and its subscales (n = 30) 6 7 infertility. fertil steril. 1982; 37:137-45. 13. downey j, yingling s, mckinney m, husami n, jewelewicz r, maidman j. mood disorders psychiatric, symptoms, and distress in women presenting for infertility evaluation. fertiles steril. 1989;52:425-32. 14. lok ih, lee dt, gheung lp, chung ws, lo wk, haines cj. psychiatric morbidity amongst infertile chinese women undergoing treatment with assisted reproductive technology and the impact of treatment failure. gynecol obstet invest. 2002; 53:195-9 15. domar ad, broome a, zuttermeister pc, seibel mm, friedman r. the prevalence and predictability of depression in infertile women. fertil steril. 1992; 58:1158-63 16. fekkes m, buitendijk se, verrips gh, braat dd, brewaeys am, dolfing jg,et al. health-related quality of life in relation to gender and age in couples planning ivf treatment. hum reprod. 2003; 18:1536-43. 17. van balen f, trimbos-kemper tc. factors influencing the well-being of long-term infertile c o u p l e s . j p s y c h o s o m o b s t e t g y n a e c o l . 1 9 9 4 ; 15:157-64. 18. donkor es, sandall j. the impact of perceived stigma and mediating social factors on infertilityrelated stress among women seeking infertility treatment in southern ghana. soc sci med. 2007;65:1683-94. 19. peronace la, boivin j, schmidt l. pattern of suffering and social interactions in infertile men: 12 months after unsuccessful treatment. j psychosom obstet gynecol 2007; 28:105-14. 20. batool rashidi, montazeri a, ramezanzadeh f, shariat m, abedinia n, and ashrafi m. healthrelated quality of life in infertile couples receiving ivf or icsi treatment 2008;8: 186. 7 original�article abstract objectives: to determine the frequency of metabolic syndrome in patients with acne vulgaris at unit of dermatology liaquat medical university hospital hyderabad. study design: case control study. st place and duration of study: the dermatology unit liaquat medical university hospital hyderabad from 1 st august 2018 to 31 december 2019. materials and methods: a total of 75 patients with acne vulgaris were included in this study. the demographic characteristics of patients have been carried out. after a detailed history and a full clinical review, the patients underwent relevant investigations, which were established earlier, for which overnight fasting blood sample of each patient was sent to the institutional pathology laboratory where the pathology consultant prepared each report and the data were collected on pre-designed proforma. confounders and effect modifiers including age, gender, bmi, occupation and socio-economic status were addressed through stratification and post stratification. statistical test conducted was chi-square. results: metabolic syndrome association in patients with acne vulgaris was observed in 13.33% (10/75) cases. stratification was performed and observed that, in patients with acne vulgaris, incidence of metabolic syndrome was not statistically significant with respect to age groups, bmi, duration of acne vulgaris, occupation, socio economic status and gender. conclusion: the frequency of metabolic syndrome in patients with acne vulgaris showed a weak positive association. key words: acne vulgaris, chronic inflammatory disease, insulin resistance, metabolic syndrome. resistance to insulin, different clinical symptoms can re s u l t i n c e l l s i g n a l i n g a n d u n c o n t ro l l e d 3 inflammation that includes acne vulgaris. it affects around 85% of adolescent patients and about 3% of the world's adult patients aged 35 and under about 4 44. it is not disease that threatens life, depression, low self-esteem and low living standards are associated with it. besides these results, it can also be associated with systemic disorders including chronic syndromes of hypovitaminosis, metabolic 5 syndrome, and behcet's syndrome. metabolic syndrome (ms) defined as an increased waist circumference with ethnicity-specific values plus any of the following four factors: triglyceride levels of at least 150 mg/dl; hdl cholesterol levels of at least 40 mg/dl for males and below 50 mg/dl for females; systolic bp levels of at least 130 mm hg or diastolic bp levels of at least 85 mm hg; and fasting plasma glucose levels of at least 100 mg/dl. it is a collection of predisposing factors, raising the risk of type 2 6 diabetes mellitus and heart disease. the main risk factors are elevated dyslipidemia, blood pressure, 7 central obesity and hyperglycemia. although introduction acne is a chronic inflammatory condition that occurs in age groups of teenagers. there is variety of misconceptions and misperceptions, in patients and also healthcare professionals, on the causes and 1 treatment of acne. acne is a common pilosebaceous unit multifactorial disease. the functions of s e b a c e o u s g l a n d a n d r o g e n i c s t i m u l a t i o n , hyperkeratosis of inflammation of the follicular infra infundibulum, and classically well-known etiological factors in acne pathogenesis are increased 2 colonization of propionic bacterium acnes. abnormalities in metabolism of androgenic steroids, metabolic syndrome frequency in patients with acne vulgaris 1 2 3 4 5 saima liaqat , hafiz bashir ahmed kalhoro , muhammad suleman pirzado , hira mughal , hira memon , 6 sikander munir memon correspondence: dr. sikander munir memon research officer department of medical research center liaquat university of medical and health sciences, jamshoro e-mail: drsikandermemon@gmail.com 1,2,4,5 3 department of dermatology/molecular biology and genetic/ 6 department of medical research center liaquat university of medical and health sciences, jamshoro funding source: nil; conflict of interest: nil received: january 07, 2020; revised: january 26, 2021 accepted: february 01, 2021 metabolic syndrome in acne vulgaris patientsjiimc 2021 vol. 16, no.1 24 metabolic syndrome in itself is not a dermatological diagnosis, many skin indications are a clinical predictor, increasing metabolic syndrome facilitating 8 early diagnosis. the rationale for the study was small national and international data, and therefore the findings of international data are not relevant to our population as we are genetically and geographically distinct. this research was carried out in our community to determine the frequency of metabolic syndrome in patients with acne vulgaris at unit of dermatology, liaquat medical university hospital hyderabad. materials and methods it was a case control study, conducted at unit of dermatology, liaquat medical university hospital st st hyderabad from 1 august 2018 to 31 december 2019. the sample size calculated for this study was 75. a non-probability consecutive sampling technique was used to select the patients. ethical approval was received from the research ethics committee of the college of physicians and surgeons of pakistan (cpsp) before the study was performed. inclusion criteria were confirmed cases of acne vulgaris for at least one year in both genders aged 18 to 30 years. the exclusion criteria were considered to be other skin disorders associated with metabolic syndrome such as psoriasis, patients already on medications that cause hyperglycemia, dyslipidemia or hypertension, and patients who were not willing to participate in the study. all the diagnosed cases of acne vulgaris presented in outdoor patients were enrolled in the study by the principal investigator. demographic characteristics like age, bmi, abdominal circumference in centimeter, blood pressure, weight, height, total cholesterol and fasting blood sugar of the patients were obtained on pre-designed proforma. after an extensive history and complete clinical examination (local and general), the patients undertook the requisite investigations described before, for that overnight, the fasting blood sample of each patient was sent to the institutional pathology laboratory where the pathology consultant drafted every sample. all patients received informed consent to participate in the study. an examination of metabolic syndrome in patients with acne vulgaris was the primary outcome variable. using spss (registered) version 22, the data was analyzed. for qualitative variables such metabolic syndrome, gender, occupation, socio economic status frequencies and %ages were calculated. quantitative data like age, weight, height, bmi and abdominal circumferences were presented as mean ± standard deviation. confounders and effect modifiers including age, gender, bmi, occupation and socio-economic status were addressed through stratification and post stratification. statistical test conducted was chisquare. confidence interval was set at 95% and probability value ≤0.05, as statistically significant. results this research included a total of 75 patients with acne vulgaris. table-i indicates the age distribution of the patients. the average age of the patients was 24.45±2.90 years. similarly, the other demographic characteristic of the patients is also shown in table i. there were 80% male and 20% female. most of the patients 56 (74.67%) were working in inside office and 19 (25.33%) doing field work. socio economic status of the patients was 26 (34.67%) were earning >30,000 and 49 (65.33%) were 15,000 to 30,000. average of abdominal circumference, serum triglyceride, hdl, sbp, dbp and blood fasting sugar are also reported in table ii. metabolic syndrome frequency in patients with acne vulgaris was observed in 13.33% (10/75) cases. stratification was performed and observed that, in patients with acne vulgaris, incidence of metabolic syndrome was not statistically significant with respect to age groups, bmi, duration of acne vulgaris, occupation, socio economic status and gender shown in table iii. table i: descrip�ve characteris�cs of pa�ent (n=75) metabolic syndrome in acne vulgaris patientsjiimc 2021 vol. 16, no.1 25 discussion in present study, most of the patients were under the age of 25 years, with a mean age of 24.45±2.90 years. a total of 80% male and 20% female were part of the study sample. the mean duration of acne vulgaris was 16.99 months and the mean bmi was found to 2 be 28.67 kg/m . although, 25.3% of field workers have been identified with it. the prevalence of office work as an occupational effect on acne vulgaris is shown by 74.67% of patients. in this study, a prevalence rate of 20.7% was found in the 26-30 years age group. the occurrence of metabolic syndrome was observed in 13.33% (10/75) cases. in their community-based research, alshammrie et 9 al recorded the age of respondents in a range of five years. much of the respondents were between 21 and 25 years of age. in comparison to our study, most of the respondents (84%) were female. thirty-eight percent had a body mass index (bmi) equal to more than 30%. most of the respondents were saudis (98%) and hail city residents (93%). 4 acne is seen in 85% of adolescents in the u.s. an overall prevalence of 60.7% was observed among 10 turkey's female secondary students. whereas another community-based research conducted in china found a prevalence of acne of 38% among 11 women aged 15-19 years. according to research conducted in saudi arabia, the overall prevalence of female secondary school students was 14.3 per cent. most of these studies were carried out in middle school or high school students and very few in 12 college or university. in similarity to our study, neupane et al. stated that, according to bmi, 65.5% were average, 12 % were overweight, 20.5 % were underweight, and 2 % were obese. much of the patients had grade 2 acne (52.6%). just 4.8% of the population had grade 4 acne. grade 2 and 3 acne were more prevalent in females, while grade 3 and 4 acne were more prevalent in males. 13 agreeing to current study, babar et al. reported that approximately half of the participants reported that their clothing was not affected by their skin. social and recreational habits of 60% of participants were influenced by acne at 9.7%, 14.5% a lot, 35.8% a little, and 40% not at all. the majority of participants 67.3% were not affected by their acne in sports. in addition, 73.9% of participants were not affected by acne when studying and working, and more than half of them did not have an acne impact on their relationship with their partners and close friends. in comparison to our research, the prevalence of metabolic syndrome was 39.0% in the indonesian population and 29.2% in the dutch population. the sex-stratified prevalence was 28.0% and 46.2% for men and women in indonesia and 36.2% and 23.8% for men and women in the netherlands. males had a higher prevalence than women of four out of five metabolic syndrome components in the netherlands population, with the exception of abdominal obesity 14 reported by sigit et al. the higher prevalence can be explained by the age of the studied populations in the present study: one study included elderly people 15,16 and the other younger. acne vulgaris is one of the world's most common skin disorders and is usually seen in teenagers. androgens have been identified as raising the size of the sebaceous glands, enhancing sebum production, inducing keratinocyte proliferation, which is what 13,17,18 triggers acne. the limitation of research is a small sample size and minimal study setting. by incorporating more table ii: clinical characteris�cs of pa�ents (n=75). table iii: frequency of metabolic syndrome in pa�ents with acne vulgaris in male and female (n =75) chi-square= 0.721 metabolic syndrome in acne vulgaris patientsjiimc 2021 vol. 16, no.1 26 research variables and wider study settings, it is recommended to design studies on a larger scale. conclusion in our research, the frequency of metabolic syndrome in patients with acne vulgaris showed a positive association in cases. references 1. hulmani m, bullappa a, kakar s, kengnal p. knowledge, attitude and practice towards acne vulgaris among acne patients. int j res dermatology. 2017;3(1):107. 2. el-tonsy tmk, mohammed ma, hamed yae-e, tawfik sh. bacteriological study of acne vulgaris in cairo egypt. egypt j hosp med. 2018;72(9):5203–9. 3. hu y, zhu y, lian n, chen m, bartke a, yuan r. metabolic syndrome and skin diseases. front endocrinol (lausanne). 2019;10(6):307–10. 4. skroza n, tolino e, mambrin a, zuber s, balduzzi v, marchesiello a, et al. adult acne versus adolescent acne: a retrospective study of 1,167 patients. j clin aesthet dermatol. 2018 jan;11(1):21–5. 5. emiroglu n. acne-associated syndromes. in: acne and acneiform eruptions. intech; 2017. p. 161–73. 6. parikh r, mohan v. changing definitions of metabolic syndrome. indian j endocrinol metab. 2012;16(1):7. 7. lu s, bao m-y, miao s-m, zhang x, jia q-q, jing s-q, et al. prevalence of hypertension, diabetes, and dyslipidemia, and their additive effects on myocardial infarction and stroke: a cross-sectional study in nanjing, china. ann transl med. 2019;7(18):436–436. 8. stefanadi ec, dimitrakakis g, antoniou c-k, challoumas d, punjabi n, dimitrakaki ia, et al. metabolic syndrome and the skin: a more than superficial association. reviewing the association between skin diseases and metabolic syndrome and a clinical decision algorithm for high risk patients. diabetol metab syndr. 2018;10(1):9. 9. alshammrie ff, alshammari r, alshammari r, khan fh, khan fh. epidemiology of acne vulgaris and its association with lifestyle among adolescents and young adults in hail, kingdom of saudi arabia: a community-based study. cureus. 2020;12(7). 10. koku aksu ae, metintas s, saracoglu zn, gurel g, sabuncu i, arikan i, et al. acne: prevalence and relationship with dietary habits in eskisehir, turkey. j eur acad dermatology venereol. 2012;26(12):1503–9. 11. zhang j, shen y, wang t, zhou c, wang x, ding x, et al. prevalence of acne vulgaris in chinese adolescents and adults: a community-based study of 17,345 subjects in six cities. acta derm venereol. 2012;92(1):40–4. 12. alanazi ms, hammad sm, mohamed ae. prevalence and psychological impact of acne vulgaris among female secondary school students in arar city, saudi arabia, in 2018. electron physician. 2018;10(8):7224–9. 13. babar o, mobeen a. prevalence and psychological impact of acne vulgaris in female undergraduate medical students of rawalpindi and islamabad, pakistan. cureus. 2019 sep 22;11(9):e5722. 14. sigit fs, tahapary dl, trompet s, sartono e, willems van dijk k, rosendaal fr, et al. the prevalence of metabolic syndrome and its association with body fat distribution in middle-aged individuals from indonesia and the netherlands: a cross-sectional analysis of two populationbased studies. diabetol metab syndr. 2020;12(1):2. 15. soewondo p, purnamasari d, oemardi m, waspadji s, soegondo s. prevalence of metabolic syndrome using ncep/atp iii criteria in jakarta, indonesia: the jakarta primar y non-communicable disease risk factors surveillance 2006. acta med indones. 2010;42(4):199–203. 16. kamso s. body mass index, total cholesterol, and ratio total to hdl cholesterol were determinants of metabolic syndrome in the indonesian elderly. med j indones. 2007;16(3):195–200. 17. kucharska a, szmurło a, sinska b. significance of diet in treated and untreated acne vulgaris. postep dermatologii i alergol. 2016;33(2):81–6. 18. park th, kim w il, park s, ahn j, cho mk, kim s. public interest in acne on the internet: comparison of search information from google trends and naver. j med internet res. 2020;22(10):e19427. metabolic syndrome in acne vulgaris patientsjiimc 2021 vol. 16, no.1 27 original�article abstract objective: to determine the effect of serum total cholesterol and triglyceride levels on stroke recovery in patients with acute ischemic stroke. study design: this was an observational cross sectional study. place and duration of study: the study was conducted at shifa international hospital islamabad. total duration th th of the study was 6 months starting from 5 august 2011 up till 4 february 2012. materials and methods: a total of 100 consecutive stroke patients fulfilling the inclusion criteria were recruited over a period of 6 months. stroke severity was clinically assessed using the national institute of health stroke scale (nihss) at the time of admission and then again at the time of discharge from the hospital. their blood sample were collected for serum cholesterol and triglyceride estimation within first 24 hours of admission. neurological improvement was assessed by the reduction in nihss score at discharge and was defined as good if it was ≥3. the data analysis was done by using spss version 20. cross tabulation and chi square tests were applied to analyze the data. results: out of the 100 patients, 63 were males and 37 were females with a mean age of 63.7 years (sd 11.9). patients with a normal or low cholesterol showed good recovery at the time of discharge in 41.3% of cases as compared to 68% of patients showing good recovery with a high total cholesterol levels. for the triglycerides level, there was good recovery in 49.2 % of patients with normal or low triglycerides levels while in patients with high triglyceride levels, good recovery was seen in 46.3% of patients. conclusion: our study shows a positive effect of high total cholesterol on early recovery following acute ischemic stroke but no positive or negative effect was evident with high serum triglycerides. this shows a possible role of serum cholesterol in prognosticating patients with acute ischemic stroke. key words: acute ischemic stroke, cholesterol and triglycerides, stroke recovery. becoming the leading cause of morbidity and 3 mortality. among the risk factors for stroke, hypertension and diabetes are more prevalent risk factors in the asians (44% and 35 % respectively) as compared to the caucasians (14% and 8% 4 respectively). dyslipidemia was also found to be more common among asian stroke population as compared to the western, but it was not statistically 2 significant. relation of high total cholesterol and triglycerides with ischemic heart disease is well established worldwide. high cholesterol level are estimated to 5 cause 56% of ischemic heart disease. however, dyslipidemia as a risk factor for ischemic stroke has been quite controversial in recent times. it has been observed in several studies that higher cholesterol and triglyceride levels are associated with better 6,7 outcome after ischemic stroke. many studies have demonstrated that patients with acute ischemic stroke who had a high serum cholesterol and triglycerides on admission showed a better recovery from stroke related disability as compared to those introduction stroke is a common disease worldwide resulting in significant morbidity and mortality. it is the second leading cause of death above the age of 60 years and the fifth leading cause in patients aged 15 to 59 years 1 old. globally the number of stroke patients each year is on the rise. according to who, up to 15 million people worldwide suffer from stroke each year. out of these 5 million die and another 5 million 1 are left permanently disabled. paradoxically, 80% people who suffer from stroke live in areas of low and 2 mid income countries. in pakistan also, stroke is the effect of total cholesterol and serum triglycerides level on recovery from acute ischemic stroke 1 2 3 adnan ghafoor , jahanzeb maqsood , syed assad nabi correspondence: dr. adnan ghafoor assistant professor, medicine fauji foundation hospital, rawalpindi e-mail: rockblaster80@yahoo.co.uk 1,3 department of medicine fauji foundation hospital, rawalpindi 2 department of medicine al nafees medical college, islamabad funding source: nil; conflict of interest: nil received: apr 28, 2016; revised: jan 26, 2017 accepted: jan 29, 2017 effect of lipid profile in stroke patientsjiimc 2017 vol. 12, no.1 20 stroke patients who had normal or low cholesterol and triglycerides at the time of admission. by determining a relationship of cholesterol and triglycerides with recovery of acute ischemic stroke; in terms of clinical improvement, we will be able to prognosticate the outcome of ischemic stroke in our patients. the purpose of this study is to find the effect of serum total cholesterol and triglyceride levels in patients with acute stroke on their recovery. materials and methods an observational cross sectional study was conducted at shifa international hospital islamabad which is a tertiary care hospital with 500 beds. the total study period was six months from august 2011 to february 2012. the sample size was calculated with the help of who sample size calculator and it was 100 patients. the study was started after permission from the hospital’s ethical committee. consecutive sampling was done. all the patients who were admitted in the neurology and medical departments of the hospital with the diagnosis of acute stroke were checked for the following inclusion and exclusion criteria. patients included in study were 18 years of age or above, having signs and symptoms of acute stroke within previous 48 hours and it was diagnosed radiologically as ischemic stroke confirmed by diffusion positive stroke on mri brain. patients with previous history of major stroke, hemorrhagic stroke, venous stroke and focal neurological deficit lasting for less than an hour were excluded from study. the two most common reasons for exclusion of patients from the study were delayed presentation after acute stroke (more than 48 hrs. after the onset of symptoms) and patients with history of previous stroke. all patients presenting to department of neurology or medicine at shifa international hospital, meeting the sample selection criteria were included in the study. written consent was taken from all the patients or their families. as a routine, all patients with stroke admitted at shifa international hospital undergo a set pattern of investigations according to the stroke pathway developed by a multidisciplinary team of our hospital. this includes fasting lipid profile and mri of brain with stroke protocol. other variables which have been included in data collection were age, gender, type and site of stroke, history of diabetes mellitus, ischemic heart disease, hypertension and smoking, duration of stay in the hospital and the stroke severity. for describing the type of stroke toast classification was used. for stroke severity, an initial clinical assessment of these patients was done by using nihss. on the day of discharge these patients were reassessed using the nihss score to measure clinical improvement. the data analysis was done by using spss version 20. cross tabulation and chi square tests were applied to analyze the data. results more than 170 patients were seen before the required sample size of 100 patients was met. out of the 100 patients who were selected for the study, 63 were males and 37 were females. the mean age of the patients was 63.7 years. the range of age was between the minimum of 36 and a maximum of 95 years. the total cholesterol level was normal or low in 75% of the patients and high in 25%. triglycerides levels were low or normal in 59% and high in 41%. (table ii and iii). regarding the stroke severity, 39% of the patients had a minor stroke, 44% had a moderate intensity stroke while 17% of the patient had a severe stoke. at the time of discharge, good recovery was seen in 48 patients while poor recovery was seen in 52 patients. when we compared the level of cholesterol and recovery, we found that 41.3% of patients with a normal or low cholesterol showed good recovery at discharge as compared to 68% of patients showing good recovery with a high total cholesterol levels (table ii). for the triglyceride levels, there was good recovery in 49.2 % of patients with normal or low triglyceride levels while in patients with high triglyceride levels, good recovery was seen in 46.3% of patients. (table iii). a total of 66% of patients had a history of hypertension. diabetes mellitus was seen in 54% of the patients. 18% of patients had a history of ischemic heart disease while 27% had a current or recent history of smoking. jiimc 2017 vol. 12, no.1 table i: details of lipid levels in the study group (n=100) 21 effect of lipid profile in stroke patients discussion stroke is a common neurological emergency presenting to the tertiary care hospitals all over the world. the risk factors and the factors affecting the stroke outcome are still poorly understood and controversial. high serum cholesterol and triglycerides have always been considered as a risk factor for the cardiovascular diseases including the ischemic 5 stroke. however, many studies conducted in patients with acute stoke have shown an opposite 5 effect of these risk factors on recovery from stroke. the patients with higher cholesterol and triglyceride did better in terms of recovery and mortality when compared with patients having normal or lower level of these substances. high admission cholesterol may be associated with increased long-term survival after 8,9 is. the data already available from other studies on this particular aspect of the stroke has mainly come from studies on patient population whose genetics and demographics are very different from the 10 patients presenting in the hospitals of pakistan. the severity of the stroke on admission was assessed using the nihss system. only 17% of the strokes fell under the category of severe stroke with nihss greater than 15. moderate intensity stroke was 44% with nihss score between 5 and 15. the percentage of minor stroke was 39% having a nihss stroke between 1 and 4. the recovery from the stroke at the time of discharge, which was the main outcome measure, was assessed by the improvement in nihss score on the day of discharge. an improvement of 3 or more points from the admission nihss score was considered as a good recovery while those showing improvement of 2 or less points on nihss at discharge were categorized as having a poor recovery. the results of this study showed that acute stroke patients with higher total cholesterol had a better recovery at the time of discharge as compared to the patients who had normal or low cholesterol on admission. out of the 100 patients, 25 had cholesterol that was higher than 200 mg/dl. out of these 25 patients, 17 (68%) patients showed good recovery from stroke that was improvement in nihss score by 3 or more points. when we compared this with the patients having normal or low serum cholesterol we saw a marked difference, with good recovery seen in only 41.3% of the patients and a poor recovery in 58.7% of patients (p value < 0.05). this is a significant finding and has also been seen in other studies. data from a chinese study on acute stroke patients showed that the levels of serum cholesterol in the good outcome group were significantly higher as compared to the patients with normal or low 11 cholesterol. although this study also included patients of intracranial hemorrhage, the beneficial effe c t wa s s e e n i n b o t h t y p e s o f st ro ke independently. another major difference of this study from the current one is that the prognosis of the patients with acute stroke was assessed at 3 months' interval after the stroke but in my study the outcome has been measured at the day of discharge which is somewhere between 5 to 7 days after admission. the effect of serum triglyceride on recovery from acute stroke was also compared with recovery from stroke. the results did not show any statistically significant difference in this regard. a total of 19 jiimc 2017 vol. 12, no.1 table iii: cross tabula�on between serum triglycerides (high vs. low) and recovery (good vs. poor (n= 100) table ii: cross tabula�on between serum cholesterol (high vs. low) and recovery (good vs. poor) (n= 100) 22 effect of lipid profile in stroke patients (48%) of patients with high triglyceride levels showed good recovery from acute ischemic stroke. similar good outcome (49.2%) was seen for patients with normal or low cholesterol levels. the mean hospital stay for the patients was 5.9 days. some patient stayed for 48 hours while the maximum hospital stay was 24 days. the reason of early discharge was usually because of less severity of stroke or early recovery, however many patients were discharged on request as their families wanted to take the patient home or shift to some other hospital due to personal and economic reasons. one study speculates a potential neuroprotective mechanism of high cholesterol by increasing gamaglutamyltransferase. gamma-glutamyl transferase (ggt) mediates intracellular intake of extracellular glutathione which is an important component of antioxidant mechanisms. glutathione is produced during normal metabolic processes and plays an important role in the protection of cells against 12 oxidative stress. another study suggested that this effect could be seen due to cofounding effect of 13 other prognostic factors. a study done by m jane et al concluded that lower triglyceride levels seem to 14 be associated with a worse prognosis in ais. low level of triglycerides predicts poor outcome following stroke and may be used as a prognostic marker for early mortality. some of the studies suggested that higher cholesterol level was associated with less severe stroke and hence a better outcome as compared to patients with normal or low cholesterol levels. the reason for this association was given that cholesterol played a role in the development of small vessel disease of the brain which results in minor strokes as compared to the disease process leading to occlusion of large vessels 9,11 of brain which results in more severe stroke. in our study, we have not catered for the other confounding factors that is age, presence or absence of modifiable risk factors for example smoking, htn, dm, ihd, diet and weather the patient was on lipid lowering drugs or not. all of these factors can have an independent as well as combined effect on stroke recovery which is difficult to measure. length of hospital stay is also an issue which needs to be looked into as it is difficult to assess the recovery of a patient in less than 6 days following acute stroke. although a positive correlation is seen between high cholesterol and good recovery following stroke, further studies are needed to confirm or reject this association. a better study design would be required with larger number of patients in both groups' i.e. acute stroke patients with and without high cholesterol levels. conclusion the study shows a positive relationship of high total cholesterol with early recovery following acute ischemic stroke but no positive or negative effect was evident of high serum triglyceride on early recovery from acute ischemic stroke. these findings are not likely to change the clinical practice regarding prevention and management of acute strokes any time soon, however there may be a role of serum cholesterol in prognosticating patients with acute ischemic stroke. this needs to be further investigated in larger studies. references 1. world health organization. mackay j, mensah ga. the atlas of heart disease and stroke [homepage on the internet]. 2004 [published on 2004 sep 23; cited 2010 jul 10] available f r o m h t t p : / / w w w . w h o . i n t / c a r d i o v a s c u l a r _ diseases/resources/atlas/en/. 2. thrift ag, arabshahi s. is stroke incidence in lowto middleincome countries driven by economics? int j stroke. 2012; 7: 307-8. 3. khan h, afridi ak, ashraf s. a hospital based study on stratification of risk factors of stroke in peshawar. pak j med sci. 2006; 22: 304-7. 4. tan ks, tan ct, churliv l, mackay m, donnan ga. ischaemic stroke in young adults: a comparative study between malaysia and australia. neurology asia. 2010; 15: 1 – 9. 5. gaziano ta, gaziano jm. epidemiology of cardiovascular disease. in: fauci as, braunwald e, kasper dl, hauser sl, longo dl, jameson jl, loscalzo j, editors. harrison's principles of internal medicine. new york: mc graw hill: 2008; p. 1375-9. 6. pan sl, lien in, chen th. is higher serum total cholesterol level associated with better long-term functional outcomes after noncardioembolic ischemic stroke? arch phys med rehabil. 2010; 91: 913-8. 7. oslen ts, christensen rh, kammersgaard lp, andersen kk. higher total serum cholesterol levels are associated with less severe strokes and lower all-cause mortality: ten-year follow-up of ischemic strokes in the copenhagen stroke study. stroke. 2007; 38: 2646-51. 8. markaki i, nilsson u, kostulas k, sjöstrand c. high cholesterol levels are associated with improved long term survival after acute ischemic stroke. j stroke cerebrovasc dis. 2014; 23: 47-53. 9. olson nc, cushman m, judd se, mcclure la, lakoski sg, folsom ar, et al. american heart association's life's simple jiimc 2017 vol. 12, no.1 23 effect of lipid profile in stroke patients 7 and risk of venous thromboembolism: the reasons for geographic and racial differences in stroke (regards) study. j am heart assoc. 2015; 4: e001494. 10. li w, liu m, wu b, liu h, wang l, tan s. serum lipid levels and 3-month prognosis in chinese patients with acute stroke. adv ther. 2008; 25: 329-41. 11. gurbuzer n, gozke e, basturk za. gamma-glutamyl transferase levels in patients with acute ischemic stroke. cardiovasc psychiatry neurol. 2014; 2014: 17026. 12. pan sl, lien in, chen th. is higher serum total cholesterol level associated with better long-term functional outcomes after noncardioembolic ischemic stroke? arch phys med rehabil. 2010; 91: 913-8. 13. jain m, jain a, yerragondu n, brown rd, rabinstein a, jahromi bs, et al. the triglyceride paradox in stroke survivors: a prospective study, neurosci j. 2013; 2013: 870608. jiimc 2017 vol. 12, no.1 24 effect of lipid profile in stroke patients jiimc december 2016 page 24 page 25 page 26 page 27 page 28 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××ò ì¸ »® ¿ °» « ¬· ½ »¨ »® ½· ­ »ò ß ½¬ ¿ ¾· ±ó ³» ¼· ½¿ ¼ » ôù߬»²»± °¿®³»²­» ïççðô êïô êéò èò ý«½«¦¦± ò ßô ú»®®¿²¼± ß ú ø»®²¼±² ü òò 츻 »ºº»½¬­ ±º »¨»®½·­» °®±¹®¿³³·²¹ ª­ ¬®¿¼·¬·±²¿´ ±«¬°¿¬·»²¬ ¬¸»®¿°§ ·² ¬¸» ®»¸¿¾·´·¬¿¬·±² ±º ­»ª»®»´§ ¾«®²»¼ ½¸·´¼®»²ò ö±«®²¿´ ±º þ«®² ý¿®» ú î»­»¿®½¸ îððïô îîæîïìóîðò çò í«³¿² ñ ûô í°·»­ î öô ý»´·­ ó óô 󴽿µ î ð ú ø»®²¼±² ü òò ûºº»½¬­ ±º ¿ ïîó©µ ®»­·­¬¿²½» »¨»®½·­» °®±¹®¿³ ±² ­µ»´»¬¿´ ³«­½´» ­¬®»²¹¬¸ ·² ½¸·´¼®»² ©·¬¸ ¾«®² ·²¶«®·»­ò ö±«®²¿´ ±º ¿°°´·»¼ °¸§­·±´±¹§ îððïå çïæïïêèóéëò ïðò í¸»®·¼¿² î ôô ø·²­±² ó ×ô ô·¿²¹ ó øô ò¿½µ»´ ß úô í½¸±»²º»´¼ ü ßô ² ý ó ú ì±³°µ·²­ô î ùò ô±²¹ó ¬»®³ ±«¬½±³» ±º ½¸·´¼®»² ­«®ª·ª·²¹ ³¿­­·ª» ¾«®²­ò ößóß îðððô îèíæêçóéíò ïì original�article abstract objective: to evaluate the effectiveness of faculty development workshop on “introduction & development of student's portfolio” using first two levels of kirkpatrick (kp) model. th study design: a quantitative evaluation study based on evaluation of one day workshop, conducted on 15 november 2019. place and duration of study: the study was conducted at islamic international medical college at department of medical education. materials and methods: the study aimed to evaluate the efficacy of faculty development workshop on kirkpatrick's model of program evaluation. a 4-hours workshop was carried at islamic international medical th college on 15 november 2019. sampling technique was purposive (n=21). the reaction of the study participants about the training experience was evaluated through a feedback evaluation proforma. the assessment of knowledge was done through mcqs and reflective writing skill was assessed through a checklist based upon framework of gibbs reflective cycle. both knowledge and skill were assessed before and after the workshop. the content of pre-test and post-test was same. results: the knowledge of the participants about portfolio was remarkably increased, from 3.95 ± 1.35 (median=4) in pre-test to 6.23 ±1.17 (median=6) in post-test. the improvement in reflective writing skill was also significant 2.14 ± 0.727 (median=2) in pre-workshop reflection to 4.23 ± 0.70 (median=4) in post-workshop reflection. the wilcoxon signed rank test showed a significant increase in both knowledge and skill (p-value <0.000). the reaction of the participants showed high percentages regarding content delivery (95%), learning environment (100%) and increase in knowledge (95%) measured on 5-point likert scale. conclusion: faculty development workshop on student's portfolio was highly valued by faculty members. most of the participants were convinced and ready to start portfolio for learning and assessment of students in the institution. key words: faculty development, kirkpatrick model, portfolio, reflective writing, students learning. 1 from experience by the process of reflection. the reflection is a metacognitive process that improves future course of action by creating deeper understanding about one's self and situation. it 2 makes students strategic life-long learners. the reflective writing is a fundamental skill required for development of portfolio which is not necessarily inherent for teachers and learners. hence the medical educators need to devise the strategies necessary to develop this skill among medical 3 teachers. thus teachers training on reflective writing is directly related to portfolio development by the students. for faculty development different activities can be arranged, among which workshops are most popular and desired ones. this may be due to an interactive ambiance in a small group, an ease of 4 communication and flexible environment. introduction portfolio is one of the most useful cognitive learning and assessment tool. it stimulates deeper learning effectiveness of faculty development workshop on introduction and development of student's portfolio: a pilot project 1 2 3 4 5 lubna rani faysal , raheela yasmin , ambreen ansar , shawana sharif , attia zaman correspondence: dr. lubna rani faysal assistant professor department of dermatology islamic international medical college riphah international university, islamabad e-mail: lubna.faysal@gmail.com 1 2 department of dermatology/medical education islamic international medical college riphah international university, islamabad 3 department of community medicine wah medical college, wah 4 department of dermatology rawalpindi medical college, rawalpindi 5 department of biochemistry federal medical and dental college, islamabad funding source: nil; conflict of interest: nil received: july 25, 2020; revised: december 14, 2020 accepted: january 28, 2021 faculty development on student's portfoliojiimc 2021 vol. 16, no.1 37 after the successful implementation of any workshop the next challenge is to measure its impact on the learning of the participants. the most suitable framework to evaluate the workshop training programs is the kirkpatrick's model. the evaluation of reaction, learning, behavior and results through different levels of the kirkpatrick model-kp is an invaluable tool to assess the achievement of an 5 outcome. the literature review has shown that the trainings on the development of reflective writing capacity are lacking in pakistan and this is the reason due to which the institutions are unable to use the effective tool of portfolio both for students learning and 6 assessment. portfolio is a regular part of undergraduate curriculum in majority of medical schools worldwide and the teachers are formally trained to achieve excellence in the skill of reflective writing through series of ongoing training programs. the purpose of current study is to evaluate the effectiveness of faculty development workshop on introduction and development of student's portfolio. the article will provide guidelines on faculty training in context of reflective writing in developing countries like pakistan. it will also be helpful to start with portfolio as an effective tool of learning and assessment in a curricular program. materials and methods it was a quantitative evaluation study carried at the department of medical education, islamic international medical college, rawalpindi on 15th november 2019. it was 4 hours workshop on introduction and development of student's portfolio the workshop evaluation was based on kp model. the workshop was attended by 21 participants and the sampling technique was purposive sampling. approval from the institutional ethical review committee was taken and informed written consent was obtained from all participants. the study participants were both from basic and clinical sciences, including professors, associate professors, assistant professors and senior registrars with certificate or master's degree in medical education. newly inducted faculty members and those without any background of medical education were not included in the workshop. the content delivered in the workshop was about the introduction of student's portfolio, the process of developing a sample portfolio and its importance in learning and student's assessment. the pre-existing knowledge of the participants about portfolio was assessed through a pretest consisting of 10 mcqs. it was followed by a reflective writing activity by the participants on any of the incident from their academic life experience. this was to assess the reflection writing skill of the participants before attending the workshop. the evaluation of learning of knowledge was done through mcqs and the reflective writing skill was assessed through a checklist based on gibbs reflective cycle (table i). both knowledge and skill were assessed by the workshop facilitator. the mcqs & reflective writing assessment checklist were approved from the expert in medical education. after the workshop, mcqs and reflective writing activity was repeated as post-test. mcqs and reflective writing activity were kept same in both pre-test and post-test. both the preand post-test mcqs and reflective writing scores were compared to see any change in the learning of participants. the reaction of the participants to workshop was collected on a pre-designed feedback evaluation proforma, given to the participants at the end of workshop. the feedback (reaction) was assessed on 5-point likert scale, where 1=strongly disagree (sd), 2=disagree (d), 3=do not know (dk) 4=agree (a) and 5=strongly agree (sa). for analysis of data, spss version 20 was used. the frequencies & percentages were calculated for the feedback evaluation of participants while mean & median scores were calculated for mcqs & reflective writing. for comparison of pre-test and post-test scores, wilcoxon signed-rank test was used as the data was non-parametric. table i: checklist for evaluation of reflective writing skill results the workshop was attended by 21 participants. there were 3 (14%) males & 18 (86%) female faculty development on student's portfoliojiimc 2021 vol. 16, no.1 38 participants, all appeared in pre & post-test. the reaction of the participants assessed through feedback evaluation proforma is given in figure 1. except for one domain “appropriate time allocation”, all the responses fall into the categories of 4 (a) & 5 (sa) on likert scale. both category 4 and 5 were considered positive response and sum of the percentages in each of these categories show a high satisfaction of the participants to the workshop regarding content delivery (95%), learning environment (100%), teaching strategy (90%) and increase in knowledge (95%). the knowledge of the participants about portfolio was remarkably increased, from 3.95 ± 1.35 (median=4) in pre-test to 6.23 ±1.17 (median=6) in post-test. the improvement in reflective writing skill was also significant 2.14 ± 0.727 (median=2) in preworkshop reflection to 4.23 ± 0.70 (median=4) in post-workshop reflection figure 2. the shapiro-wilk test showed the non-normal distribution of the scores and wilcoxon signed rank test confirmed remarkable improvement (p=0.000) in the postworkshop knowledge and reflective writing skill of the participants about student's portfolio (table-ii). discussion the knowledge of participants about portfolio and skill of reflective writing were remarkably improved after attending the workshop. the highly satisfactory response of the study participants further proved the effectiveness of workshop. such activities are necessary to develop the reflective writing skill of the medical teachers which is fundamental to the 7 process of portfolio development. the biggest challenge for health educators is the pedagogical tool to help students to write reflectively. portfolio is one such tool to develop reflective capacity of students to foster their critical thinking and problem-solving skills to prepare them 8 for informed clinical judgments. it helps them to perform better in written assessments and to develop decision making skills as a clinician. the implementation of any new strategy either for teaching or assessment of students is always very challenging. one of the biggest challenges is faculty resistance. the people do not feel comfortable to carry out the new responsibilities either due to inadequate exposure or lack of training. hence it is imperative to do capacity building of teachers at 9 first. the current study has implications for many institutions across the country, planning to begin with portfolio as an integral part of students teaching and assessment. there is not enough literature on the reflective capacity building of teachers in pakistan. the concept is relatively new in teachers training programmed on our set up. in a study conducted by m ilyas, shawana fazal & m amin, the comparison of perceptions of students and university teachers in pakistan and uk showed that majority of teachers and students here were not even well aware about 10 the notion of reflection. teachers represent one of the key resources for the academic success and investment in their training results in unceasing 11 success despite all challenges. teachers training fig 1: reaction of the participants to the workshop on 5-point likert scale 1=pre-test, 2=post-test table ii: improvement in knowledge and reflective writing skill fig 2: descriptive statistics of pre and post workshop knowledge and skill scores faculty development on student's portfoliojiimc 2021 vol. 16, no.1 39 always results in improvement of skills, motivation, and performance. it helps to boosts up one's selfconfidence and brings positive behavioral changes among teachers for educating students. in this study, an outcome-based workshop was conducted as apart of faculty development program, with targeted audience. the workshop was evaluated to assess the outcome at level i and level ii of kirkpatrick's model for reaction, improvement of knowledge and reflective writing skill of the participants. the study showed statistically significant increase in knowledge and reflective writing skill of all the participants after the workshop on student's portfolio. the pre workshop reflection was very ordinary, there was no framework followed by the participants, the coherence and flow of events was missing. after the workshop, all reflective writings improved significantly. the participants were trained to reflect using gibbs cycle of reflection and assessment was done on a checklist based on it. gibbs reflective cycle is an effective model for 12 teaching of reflection. after workshop, there was good reflection of description of situation along with feelings, critical analysis of the context and action plan. the evaluation of reaction of participants also showed good response with 95% satisfaction with content delivery and increase in knowledge. the participants valued and enjoyed all teaching and learning activities in the workshop on student's portfolio with 100% satisfaction on learning environment. they acknowledged the activities were interesting, informative, and contextual with less lecturing and more hands-on work. these findings highlighted the effective planning of the workshop. the pro-active measures in relation to expectations of the participants are of utmost 13 importance for an effective workshop. there are various other tools which can be used as valuable avenues to promote reflective writing. in another study conducted by karkabi k et al., the use of abstract paintings and narrative literature was used to develop reflective capacity in a multinational 14 faculty development workshop. the participants found this arts-narrative based workshop very useful to facilitate their reflective writing in context of educator-learner relationship. qualitative analysis of participants feedback was done. the sample size was small and no objective quantitative evaluation of the net gain in knowledge and skill about reflective writing of the participants before and after the workshop. also change in behavior was not evaluated. in another study by donald boudreau j et al., a workshop on reflective writing for clinical teachers, the evaluation of outcome was limited only to level i of kirkpatrick's model, quantitative data focused on patient satisfaction with qualitative analysis of their 15 narrative writings. narrative methods had been used successfully to nurture self-reflection through a half day interactive workshop. in comparison to current study, objective assessment of preand postworkshop reflective writings was lacking. in this study, the quantitative data interpretation was done before and after the workshop for both knowledge and reflective skills of participants along with their feedback evaluation. use of multiple tools like mcqs and reflective writing skill evaluation in a 4-hours workshop is another strength of this study. present study strongly emphasizes to initiate and continue these workshops for teachers training to promote their reflective writing skill. this is not only essential for portfolio development, but it is the need of hour to help our students to become critical thinkers and reflective life-long practitioners for 16 better health care services. conclusion the workshop on student's portfolio development was highly valued by the participants. there was remarkable improvement in knowledge and reflective writing skill of the participants required to develop a portfolio. such workshops are immensely needed for building reflective capacity of teachers which is one of the core competencies all health care professionals. limitations the results are generalized from the single workshop, which is main limitation of the study. further research is recommended with use of different validated qualitative and quantitative tools. disclaimer this manuscript has not been previously presented or published in any conference and it is not a part of research, phd or thesis project. conflict of interest it is declared that there are no personal, financial, and professional interests involved. faculty development on student's portfoliojiimc 2021 vol. 16, no.1 40 funding disclosure there are no funding sources to disclose. references 1. van tartwijk j, driessen ew. portfolios for assessment and learning: amee guide no. 45. medical teacher. 2009 jan 1;31(9):790-801. 2. huang jj, yang sj, chiang py, tzeng ls. building an eportfolio learning model: goal orientation and metacognitive strategies. knowledge management & elearning: an international journal. 2012;4(1):16-36. 3. wald hs, reis sp. beyond the margins: reflective writing and development of reflective capacity in medical education. journal of general internal medicine. 2010 jul 1;25(7):7469. 4. steinert y. faculty development: from workshops to communities of practice. medical teacher. 2010 jan 1;32(5):425-8. 5. rouse dn. employing kirkpatrick's evaluation framework to determine the effectiveness of health information management courses and programs. perspectives in health information management. 2011;8. 6. ashraf h, rarieya jf. teacher development through reflective conversations–possibilities and tensions: a pakistan case. reflective practice. 2008 aug 1;9(3):269-79. 7. tsingos c, bosnic-anticevich s, smith l. reflective practice and its implications for pharmacy education. american journal of pharmaceutical education. 2014 feb 12;78(1). 8. embo mp, driessen e, valcke m, van der vleuten cp. scaffolding reflective learning in clinical practice: a comparison of two types of reflective activities. medical teacher. 2014 jul 1;36(7):602-7. 9. raza sa, majid z, zia a. perceptions of pakistani university students about roles of academics engaged in imparting development skills: implications for faculty development. bulletin of education and research. 2010 dec 1;32(2). 10. fazal s, amin m. reflection in teacher education programmes in pakistan and the uk: a comparison. journal of research & reflections in education (jrre). 2014 dec 1;8(2). 11. breckwoldt j, svensson j, lingemann c, gruber h. does clinical teacher training always improve teaching effectiveness as opposed to no teacher training? a randomized controlled study. bmc medical education. 2014 dec 1;14(1):6. 12. adeani is, febriani rb, syafryadin s, mangana av, kurniawan e, ananda j, maryam s. using gibbs reflective cycle in making reflections of literary analysis. indonesian efl journal (ieflj).;6(2):139-48. 13. behar-horenstein ls, garvan cw, catalanotto fa, su y, feng x. assessing faculty development needs among florida's allied dental faculty. american dental hygienists' association. 2016 feb 1;90(1):52-9. 14. karkabi k, wald hs, castel oc. the use of abstract paintings and narratives to foster reflective capacity in medical educators: a multinational faculty development workshop. medical humanities. 2014 jun 1;40(1):44-8. 15. boudreau jd, liben s, fuks a. a faculty development wo rks h o p in n a rrat iveb a s ed ref lec t ive w rit in g. perspectives on medical education. 2012 aug 1;1(3):14354. 16. burdick w, amaral e, campos h, norcini j. a model for linkage between health professions education and health: faimer international faculty development initiatives. medical teacher. 2011 aug 1;33(8):632-7. faculty development on student's portfoliojiimc 2021 vol. 16, no.1 41 jiims final.cdr 44 original article abstract objective: to determine the age range, gender distribution, histological types, sites, neck node involvement, and surgery as modality of treatment in diagnosed cases of oral cavity tumours in a tertiary care centre. study design: descriptive study place and duration of study: the study was carried out in ent department, cmh rawalpindi for the duration from dec 2008dec 2011. materials and methods: data of 113 biopsy proven cases of oral cavity tumors who underwent surgery at cmh rawalpindi, were retrieved from armed forces institute of pathology's tumour registry and from head and neck oncology forum registry, and were evaluated. results: out of 113 patients with oral cavity tumours, 87 (77%) were male, while 26 (23%) were female, the male: female ratio being 3:1. the mean age of the patients was 59.4 years, ranging from 40 to 75 years. site distribution of the tumours was: tongue: 61(54%), buccal mucosa 24 (21%), floor of mouth 18 (16%), and hard palate 10 (9%). the histology of tumours showed squamous cell carcinoma in 102 (90%) and tumours of salivary gland origin in 11(10%). sixty four (56%) of these patients had n disease, 10 (9%) had n disease, 8 (7%) had n0 1 2a disease, 27 (25%) had n disease, 3(2%) had n disease, while 1 patient (1%) had n disease. resection of the2b 2c 3 tumour along with supra-omohyoid neck dissection was carried out in 64 (56%) patients, while resection with radical neck dissection was done in 49 (44%) patients. primary closure was carried out in 62 (55%) patients, while secondary reconstruction was done in 51 (45%) patients. conclusion: presentation of oral cavity tumours occur at an advanced age with male preponderance in our population. early presentation results in lesser local spread, leading to less aggressive surgical approach with selective neck dissection. key words: oral cavity tumors, squamous cell carcinoma, surgical treatment. 7countries. almost 90% of these tumours are squamous cell carcinomas, while rest comprise of salivary gland tumours, 8sarcomas and melanomas. commonest site 9is the tongue, usually the lateral border, followed by the buccal mucosa and floor of mouth. commonest presentation is of a nonhealing ulcer. in 30-80% of the patients, cervical lymph nodes may be involved on 10presentation. over the years the modalities of treatment has not significantly changed. surgery and radiotherapy alone are the treatment modality in the early cases, while combined therapy with surgical resection followed by radiotherapy or chemo-radiotherapy is the standard treatment modality in advanced 11disease. cervical lymph node metastasis is a main determinant in the staging and the 12choice of treatment modality. introduction head & neck cancers are the 6th commonest 1cancers. making 3% of all the cancers while oral cavity cancers represent approximately 48% of them, majority being squamous cell 2carcinoma (scc). head neck cancers are considered to be the commonest cancers in countries like india, pakistan, bangladesh etc. they usually occur in middle aged and old people. major risk factors are tobacco 3and alcohol intake. and both have a 4synergistic action. in south east asia its 5incidence is high due to betel quid chewing. generally incidence is 2-3 times higher in the 6males. but now almost equal gender distribution may be seen in many developed ------------------------------------------------oral cavity tumours, a clinical experience in a tertiary care center muhammad ashfaq, mirza khizer hameed, zeeshan ayub, kamran ashfaq correspondence: brig mirza khizer hameed ent department, combined military hospital, rawalpindi 44 45 consequently, neck dissection forms an integral aspect of the surgical treatment of oral squamous cell cancers, and has evolved from radical to more selective and functional procedures with our improved understanding of the distribution of 13regional metastasis. recent studies have shown that selective neck dissection is oncologically safe for head neck cancers 14with clinically negative node necks. successful reconstruction is mandatory for 15the success of any surgery for oral cancers. a descriptive study was carried out in ent department combined military hospital rawalpindi to determine the age range, gender distribution, histological types, subsites, neck node involvement, and surgery as modality of treatment in diagnosed cases of oral cavity tumours for the duration from december 2008 to december 2011. data of 113 biopsy proven patients of oral cavity tumours, operated upon, in the duration from december 2008december 2011, was retrieved from afip tumor registry and head and neck oncology forum registry and was evaluated. the data was entered in spss version 12 and the cases were evaluated for the age of patient, gender, histology of tumor, tumor site, neck node involvement, and the surgical procedure done. male to female ratio was found to be 3:1 as inferred from figure 1.the mean age of presentation was found to be 59.4 years ranging from 40-75 years. with regards to site, more than half of the patients had tumors of tongue, followed by tumors of buccal mucosa, tumors of floor of m o u t h a n d t u m o r s o f h a rd p a l a t e materials and methods results respectively as shown in table i. the most common histological diagnosis was squamous cell carcinoma followed by salivary gland tumours as shown in figure 2. neck nodes involvement in these 113 patients is shown in table ii. all these patients were staged according to tnm classification. sixty four (56%) patients were grouped into early stage cancer of the oral cavity (stage i & ii), while 49 (44%) were grouped as advanced disease (stage iii & iv). resection of the tumour along with supraomohyoid neck dissection was carried out in 64 (56%) patients, while resection with radical neck dissection was done in 49 (44%) patients. primary closure was carried out in 62 (55%) patients, while secondary reconstruction had to be carried out in 51 (45%) patients. with regards to secondary reconstruction, radial free forearm flap reconstruction was done in 27 (24%) cases, pectoralis major flap reconstruction in 14 (12%) patients, while osseo-cutaneous fibula flap reconstruction was carried out in 10 (9%) patients. oral cancer is the eighth commonest cancer in the developing countries and sixteenth commonest in developed countries. it is diagnosed usually at an advanced stage and approximately 30% of the patients delay seeking help for more than 3 months following the self discovery of symptoms. in pakistan, oral cavity cancers are found to be 17,18the leading tumours. in our study the mean age of the patients was found to be 59.4 years. almost similar mean age has 19been shown in another study. and it is probably due to prolonged exposure of the mucosa to tobacco, alcohol etc. but now, the discussion 45 46 incidence is increasing among relatively younger population. in our study the male to female ratio was 3:1 with 77% male and 23% female patients. carvalho et al also showed a similar gender distribution in the 7developing countries. as ours is a developing country, the same pattern prevails. in our study, the tongue was found to be the commonest site involved, followed by the buccal mucosa and floor of mouth respectively. a study carried out by razfer .et .al noted that 43.9% tumors involved the tongue, 27.3% involved the floor of mouth, 24.2% involved the alveolus and buccal 17mucosa while 3.8% involved hard palate. another study also showed tongue (58%) as 9the leading site of oral cancers. our results also showed a higher incidence of tongue tumours but with a higher percentage, and a relatively higher incidence of buccal mucosa tumours. similarly, we had a higher incidence of hard palate tumours. probably this slight difference is because of betel quid c h e w i n g a n d n a s w a r ( o r a l s n u ff ) placement. in our study commonest histological type of tumours was squamous cell carcinoma and it is similar to data given in a study by 17bhurguri et al. our results showed palpable cervical lymph nodes in 44% of the patients which are similar to a study by 10fukano et al. thus 56% patients presented to us at an earlier stage leading to expectation of a better prognosis as shown in 20study by elwood & gallagher. in patients with early stage disease, having n0 neck, tumour resection was carried out a l o n g w i t h s u p r a o m o h y o i d n e c k dissection. it is very logical because of much extensive lymphatic network draining the oral cavity. in rest of the cases with advanced disease, the surgical resection was carried out along with radical neck dissection. although there is recent trend for selective neck dissection even in advanced cases, but in our center, we adhere with radical neck dissection for better prognosis in advanced cases. presentation of oral cavity tumours occur at an advanced age with male preponderance as occurs in other developing countries. early presentation results in lesser local spread, leading to less aggressive surgical approach with selective neck dissection. conclusion figure 1: gender distribution in patients with oral cavity tumours gender distribution 46 47 references 1. parkin dm, pisani p, ferlay j. estimates of the worldwide incidence of eighteen major cancers in 1985. int j cancer 1993 ; 54 : 594-606. 2. ta n a k a t, ta n a k a m , ta n a k a t. o r a l c a r c i n o g e n e s i s a n d o r a l c a n c e r chemoprevention: a review. pathology research international, vol. 2011, article id 4 3 1 2 4 6 , 1 0 p a g e s , 2 0 1 1 . d o i : 10.4061/2011/431246. 3. petti s, scully c. determinants of oral cancer at the national level: just a question of smoking and alcohol drinking prevalence? odontology 2010 ; 98 :144-52. 4. sturgis em, wei q, spitz mr. “descriptive epidemiology and risk factors for head and neck cancer,” seminars in oncology 2004; 31 : 726-33. 5. jeng jh, chang mc, hahn lj. “role of areca nut in betel quid-associated chemical:current c a r c i n o g e n e s i s a w a r e n e s s a n d f u t u r e perspectives.” oral oncology 2001; 37 : 47792. 6. johnson n. tobacco use and oral cancer: a global perspective. j dent educ 2001 ; 65: 328-39. 7. carvalho al, singh b, spiro rh, kowalski lp, shah jp. cancer of the oral cavity: a comparison between institutions in a developing and a developed nation. head neck 2004 ; 26 : 31-8. 8. weber al, romo l, hashmi s. malignant tumours of the oral cavity and oropharynx: clinical, pathologic and radiologic evaluation. neuroimaging clin n am 2003 ; 13 : 443-64. table i: site distribution in patients with oral cavity tumours figure 2: histology of oral cavity tumours table ii: incidence of cervical nodes in oral cavity tumours site distribution (n= 113) histological diagnosis 47 48 9. riebero kcb, kowalski lp, latorre mrdo. impact of comorbidity, symptoms and patients' characteristics on prognosis of oral carcinomas. arch otolaryngol head neck surg 2000; 126: 1079-85. 10. fukano h, matsuura h, hasegawa y, nakamura s. depth of invasion as a predictive factor for cervical lymph node metastasis in tongue carcinoma. head neck 1997 ; 19 : 205-10. 11. fan k, lin c, kang c, huang s, wang h, chen ey et al. combined-modality treatment for advanced oral tongue squamous cell carcinoma. int. j radiation oncology biol phys 2007; 67 : 453-61. 12. myers jn, greenberg js, mo v. extracapsular spread. a signi?cant predictor of treatment failure in patients with squamous cell carcinoma of the tongue. cancer 2001; 92: 3030-6. 13. ozer e, karapinar u, ryoo c, agrawal a, schuller d e. when to address level i lymph nodes in neck dissections? otolaryngol head neck surg 2010; 142 : 355-8. 14. randall md, breau l, james md, suen y. management of the n0 neck. otolaryngologic clinics of north america 1998 ;31: 657-69. 15. rashid m, ahmad t, ansari tn, ahmed b, a h m e d s , g u l a a . m a n a g e m e n t o f oromandibular cancers. j coll physicians surg pak 2004 ;14 : 29-34. 16. scott se, grunfeld ea, mcgurk m. patient delay for potentially malignant oral symptoms. eur j oral sci 2008; 116: 141-7. 17. bhurgri y, bhurgri a, rahim a, bhutto k, pinjani p, usman a .et .al.the pattern of malignancies in karachi j pak med assoc 1999 ; 49 : 157-61. 18. ahmed u, akhter r, khawar a, bangash w, ajmal m. audit of head and neck cancer: hospital based statistics of islamabad. j surg pak 2007 ; 12 : 34-6. 19. razfa a, walvekar rr, melkane a, johnson jt, myers en. incidence and patterns of regional metastasis in early oral squamous cell cancers: feasibility of submandibular gland preservation. head neck 2009; 31: 1619-23. 20. elwood jm, gallagher rp. factors influencing early diagnosis of cancers of oral cavity. can med assoc j 1985 ;133 : 651-6. 48 original�article abstract objective: to describe the clinical, laboratory and antimicrobial susceptibility profile of enteric fever patients hospitalized at a tertiary care children hospital of karachi. study design: cross sectional study. place and duration of study: the study was conducted in three medical units of national institute of child health (nich) karachi from september 01, 2018 till february 28, 2019. materials and methods: patients of enteric fever diagnosed by positive blood culture for salmonella enterica serovar typhi, hospitalized at national institute of child health (nich) karachi were included. clinical history and physical examination findings were recorded in performa and routine laboratory tests and treatment was done according to hospital protocol. outcome of patients was recorded in terms of alive or died. data entry and analysis was done in spss 24.0. descriptive statistics were applied for statistical analysis. results: total 76 patients with culture proven typhoid were enrolled in the study including 39(51.3%) males and 37(48.7%) females. mean age of children was 5.7+ 2.81 years. mean duration of fever in these patients was 19.04+8.39 days. common symptoms were abdominal pain (64.5%), diarrhea (43.4%), vomiting (48.7%) and decreased appetite (67.1%). antibiotic resistance profile showed 98.7% to chloramphenicol and trimethoprimsulfamethoxazole, 96% resistance to ampicilline, 94.7% to cefixime and ceftriaxone, 82.2% to ciprofloxacin, 2.63% to azithromycine and no resistance to meropenam. all children were discharged with mean duration of hospital stay 8.296+3.33 days. conclusion: there are high rates of resistance against commonly used antibiotics for the treatment of enteric fever, including fluoroquinolones and cephalosporins leaving only extremely limited and costly options for treatment and prolonged length of hospital stay due to need of intravenous therapy. key words: antibiotic resistance, cephalosporins, enteric fever, salmonella typhi. may mimic any other febrile illness like influenza, malaria or dengue fever, which may cause delay in 1 the diagnosis and start of appropriate therapy. however most persistent feature is high grade 1 continuous fever. although a number of serological tests are available for diagnosis of typhoid fever but gold standard for 6 the diagnosis is blood culture. resistance to antimicrobials has been emerged in salmonella species. in 1970, main stay of treatment 3 was chloramphenicol. first epidemic of enteric fever which was resistant to chloramphenicol was 8,9 reported in 1972. by late 1980, multiple drug resistance (mdr) enteric fever defined as resistance to the traditionally used three first line antimicrobial drugs (chloramphenicol, ampicillin, trimethoprim and sulfamethoxazole) was reported from many 9 countries. this led to the use of fluororuinolones 8 (ciprofloxacin) as recommended first line therapy. by early 2000, the increasing non susceptibility to introduction enteric fever is one of the important cause of morbidity and mortality in countries with middle to 1-3 low income especially in south east asia. in global burden of disease 2010, enteric fever was included which accounted to cause 12.2 million illnesses and 3,4 190200 deaths. in 2015, it was estimated 17 million cases of typhoid and paratyphoid fever with highest incidence seen in south asia and other areas like 5,6,7 southeast asia and sub-saharan africa. the clinical features of enteric fever are variable and clinical spectrum, laboratory profile and antibiotic susceptibility pattern of children with enteric fever at a tertiary care hospital of karachi misbah anjum, shazia soomro, shazia kulsoom, safia bibi, sadaf asim, maira riaz correspondence: safia bibi research officer, phrc specialized research centre for child health national institute of child health (nich), karachi. e-mail: safiapmrc@gmail.com department of paediatric medicine national institute of child health (nich), karachi. funding source: nil; conflict of interest: nil received: january 02, 2020; revised: november 16, 2020 accepted: november 16, 2020 pattern of enteric fever at a children hospital of karachijiimc 2021 vol. 16, no.1 4 flouroquinolones including intermediate and full resistance occurred and in 2006 , 55% cases of 10,11 salmonella were resistant to ciprofloxacine. this led to the use of third generation cephalosporins 1,5 (ceftriaxone) as first line recommended therapy. most recently, an epidemic of extensively drug resistant (xdr) typhoid strain has been reported from sindh, pakistan, where resistance has been found to first line three antimicrobial drugs (chloramphenicol, ampicillin , trimethoprim and sulfamethoxazole), along with resistance to r d fluoroquinolone and also to 3 generation 1 0 c e p h a l o s p o r i n s . i n c a s e w h e re m d r a n d fluoroquinolone resistance is present, azithromycine has shown good efficacy by multiple trials, but by its widespread use in suspected cases of enteric fever, 9 there is risk of emergence of resistance to it as well. mortality due to enteric fever in pre-antibiotic era was 10-30%, but with the use of effective antibiotics, 2 it has been reduced to <1%. reported mortality rate 3 from pakistan is less than 2 % from enteric fever. considering high burden of enteric fever in developing countries like pakistan and recent epidemic of xdr typhoid, we conducted this study at a tertiary care hospital of karachi (sindh, pakistan) to assess clinical, laboratory profile and to check for antibiotic resistance pattern of s. typhi so that local data may be generated about recent trends on antimicrobial resistance in enteric fever cases and to modify local empirical treatment strategies and research priorities regarding typhoid fever. materials and methods this cross-sectional study was conducted in three medical units of national institute of child health st (nich) karachi over the period of 6 months, from 1 th september 2018 till 28 february 2019. the study was conducted in compliance with ethical standards on human subject research, informed consent was obtained from all patients' attendants. the study was approved by institutional ethical review board (ierb) of nich. national institute of child health is one of the largest tertiary care children hospitals of pakistan that provides health care service to pediatric patients mainly from sindh, balochistan and south punjab. patients hospitalized in nich during the study period with enteric fever proven by a positive blood culture for salmonella typhi were included. children with clinical suspicion of enteric fever but negative blood culture were excluded. similarly, patients who left hospital against medical advice before completion of treatment were also excluded. after explaining about the nature of the study informed consent was taken from parents or g u a r d i a n s . pa t i e n t h i s t o r y a n d p hy s i c a l s ' examination's findings were recorded in a semistructured performa by principal investigator and coinvestigators from their respective wards. results of routine laboratory tests including complete blood picture, serum urea, creatinine, electrolytes and liver function tests were also recorded in performa. blood culture and sensitivity testing was performed at the microbiology laboratory of nich. five ml blood sample of each child suspected for enteric fever was drawn and inoculated in blood culture bottle aseptically and sent to laboratory. at microbiology laboratory blood culture bottles were sub-cultured after every 18-24 hours for 3-days, identification of s. typhi was based on conventional biochemical tests and serotyping. sensitivity testing was performed using kirby bauer disk diffusion method as per clsi guidelines. other laboratory tests as needed according to the condition of child were also sent to laboratory as per nich protocol. antibiotic treatment started according to the hospital protocol and was recorded. outcome of patient along with total duration of hospital stay was recorded. outcome was recorded in terms of either recovered or died. all data was entered and analyzed through statistical package for social sciences (spss) version 24. descriptive statistics were applied. frequency and percentages were calculated for qualitative variables including clinical signs and symptoms, previous history, drug sensitivity pattern etc. mean± s.d was calculated for quantitative variables including age, fever history, duration of hospitalization, duration of antibiotic treatment, biochemical test results etc. results total 76 patients with culture proven enteric fever were enrolled in the study including 39(51.3%) males and 37(48.7%) females. mean age of children was 5.7+ 2.81 (range 0.83-12) years. only 5 (6.5%) patients were from interior sindh while 71 children (93.5%) were from karachi. mean duration of fever in these patients was pattern of enteric fever at a children hospital of karachijiimc 2021 vol. 16, no.1 5 19.04+8.39 days with minimum 4 days and maximum 45 days history of fever. thirty-six (47.37%) had fever duration of >20 days. other common symptoms among these patients were abdominal pain, diarrhea, vomiting and decreased appetite. frequency of different clinical symptoms along with mean duration at the time of hospitalization are summarized in table i. history of treatment before hospitalization with duration is presented in table ii, which shows most of the patients already had a history of using cephalosporins, fluoroquinolones and some had also taken antimalarial treatment. hematological and biochemical findings of patients are presented in table iii. ultrasound (usg) abdomen was done in 63(82.9%) cases, out of which, usg was normal in 50 cases (79.4%). major finding on s o n o g ra p hy wa s h e p a t o s p l e n o m e ga l y a n d lymphadenopathy found in 11(17.5%) cases, 1(1.6%) had cholecystitis, and 1(1.6%) had ascites with hepatosplenomegaly. all 76 children's blood culture was positive for salmonella enterica serovar typhi. antibiotic sensitivity profile of isolates is shown in figure 1 which showed high rates of resistance against all commonly used antibiotics for typhoid including fluoroquinolones and cephalosporins. however, none of the isolates showed resistance against meropenem. in the hospital, antibiotics were started according to culture and sensitivity. most of the patients were treated with intravenous meropenem with mean duration of 7.95+2.79 days out of which <7 days treatment was given in 10(25.6%) patients, 7-10 days treatment was received by 27(69.2%) patients while 2(5.1%) required treatment for >10 days to become afebrile. thirty-three (43.4%) children were treated with azithromycin (mean duration of 6.23+1.38 days). enteric fever related complications observed among st u d y p a r t i c i p a nt s i n c l u d e d b o n e m a r ro w suppression in 45(59.2%) with 35(46.1%) patients having moderate anemia (hb<9.0g%), 14(18.4%) 3 having leucopenia (tlc<4.5x10 /ul), while 3 thrombocytopenia (plt<150x10 /ul) was present in 31(40.8%). clinical jaundice was present in 4(5.3%), while subclinical hepatitis with raised sgpt (>40 iu) was present in 25(32.9%). acute kidney injury (based on deranged renal function) was present in 2(2.6%). hyponatremia (serum sodium <130meq) was seen in 7(9.2%), hypokalemia (serum potassium<3.5 meq) was seen in 9(11.8%). other complications included cholecystitis 1(1.3%), ascites 1(1.3%), meningitis 1(1.3%), sepsis 1(1.3%), hepatomegaly 29(38.2%) and abdominal distension 19(25%). outcome in term of mortality was nil and all children (100%) were discharged. mean duration of hospital stay was 8.296+3.33 days with range of 1-17 days. hospital stay of <5 days was found in 7.4%, 5-7 days in 37%, 8-10 days in 35.2% and >10 days in 20.37%. table i: clinical features of typhoid pa�ents hospitalized at nich. table ii: treatment history before culture and sensi�vity discussion in pakistan enteric fever is amongst the leading causes of febrile illnesses due to bacterial 1 2 pathogens. there are alarming reports of pattern of enteric fever at a children hospital of karachijiimc 2021 vol. 16, no.1 6 de ch ly ab antimicrobial resistance from pakistan with need of careful selection of antimicrobials in children with 13 enteric fever. in present study, mean duration of fever was19 days, therefore most of the patients were already in third week of illness where complications of enteric fever are expected. this suggests that there is need of early suspicion and early diagnosis in order to reduce complications and reduce mortality. common associated problems were decreased appetite, abdominal pain, clinical anemia, vomiting, diarrhea, hepatosplenomegaly, abdominal distension and chest congestion. thompsom et al also found the associated symptoms of anorexia, diarrhea and cough along with high grade fever in children of 13 enteric fever. in the present study results are alarming with 97.7% of mdr isolates, resistance to third generation cephalosporins as 93.4% and resistance to ciprofloxacin in 82.2% leading to serious limitation in therapeutic options, leaving only behind options of carbapenam and azithromycin. klemm et al in 2018 has reported the emergence of extensively drug r e s i s t a n t s . t y p h i s h o w i n g r e s i s t a n c e t o f l o u r o q u i n o l o n e s a n d t h i r d g e n e r a t i o n cephalosporin along with resistance to three first line 14 drugs in sindh pakistan. gene sequencing of mdr s. typhi revealed that it is haplotype h58, encoded by plasmid having additional resistant elements including extended spectrum beta lactamase and exhibited high identity to the plasmids of other enteric bacteria found worldwide highlighting ability of s. typhi to convert from mdr to xdr by plasmid 14 acquisition from other enteric bacteria. in the past there have been few sporadic reports of resistance to ceftriaxone where indian network for surveillance of antimicrobial resistance group has reported 3% resistance to third generation cephalosporin and jain et al has reported 2% 11,15 resistance to it. similar proportions of resistance has also been reported by abdullah et al from karachi 16 pakistan. in previous study from pakistan, in 2014, fluoroquinolone resistance was 82% and ceftriaxone 17 resistance was not reported. azithromycin is another oral option which has been reported as safe and effective against s. typhi but it can only be use d in uncomplicated early cases of enteric fever. resistance to azithromycin has been found in 2(2.63%) cases. resistance to azithromycin has also been reported by jain et al in new delhi where 7.3% isolates of salmonella has shown 11 resistance to azithromycin. most of the patients in present study were receiving cefixime (48.7%), ceftriaxone (51.3%) and ciprofloxacin (21.1%), indicating these medications may have been started on clinical grounds by suspicion of simple mdr s. typhi. many patients had a treatment history suggestive of their condition being diagnosed as upper respiratory tract infection and malaria as antimalarial was taken in 26.3% cases, and amoxicillin/amoxicillin+co-amoxiclav was given in 13.2% cases. these figures are indicating high rates of empirical antibiotic treatment without culture reports which may be a factor towards harboring of table iii: hematological and biochemical features of typhoid pa�ents hospitalized at nich fig 1: an�bio�c sensi�vity profile of s. typhi isolates pattern of enteric fever at a children hospital of karachijiimc 2021 vol. 16, no.1 7 xdr s. typhi and resistance to other pathogens, as we can look; intravenous ceftriaxone was received by 51.3% cases before culture reports. most common complications were bone marrow suppression was found in 59.2% and subclinical hepatitis in 32.9% and similar results have been 18 reported by iftikhar et al. we didn't find any case of intestinal perforation. one of its reasons may be that we only enrolled patients admitted in all medical units while enteric fever patients with perforation are usually admitted in pediatric surgical units. the limitations of the study are that it included only hospitalized patients. secondly, study enrolled only blood culture proven cases, so enteric fever patients treated with negative blood culture might have been missed. conclusion there are high rates of resistance against all commonly used antibiotics for typhoid including fluoroquinolones and cephalosporins. there is shift of antimicrobial susceptibility leaving only extremely limited and costly options for treatment and increases length of hospital stay due to need of intravenous therapy resulting in increased financial burden over families as well as government. recommendation in settings of poor sanitation, lack of vaccination coverage and the emergence of xdr s. typhi suggest the appropriate policies for antimicrobial usage, need for nationwide vaccination campaigns, and govt. based policies for provision of safe drinking water. there is also needed to revise guidelines for treatment of enteric fever in both empirical and in culture proven cases. treatment of enteric fever patients with two or more sensitive drugs may also be considered as this policy has been implemented in cases of malaria and tuberculosis to prevent further emergence of resistance. references 1. azmatullah a, qamar fn, thaver d, zaidi ak, bhutta za. systematic review of the global epidemiology, clinical and laboratory profile of enteric fever. journal of global health. 2015; 5(2): 020407. doi: 10.7189/jogh.05.020407. 2. dahiya s, malik r, sharma p, sashi a, lodha r, kabra sk et al. current antibiotic use in the treatment of enteric fever in children. the indian journal of medical research. 2019;149(2):263. 3. crump ja, sjölund-karlsson m, gordon ma, parry cm. epidemiology, clinical presentation, laboratory diagnosis, antimicrobial resistance, and antimicrobial management of invasive salmonella infections. clinical microbiology reviews. 2015;128(4):901-37. 4. lozano r, naghavi m, foreman k, lim s, shibuya k, aboyans v, et al. global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the global burden of disease study 2010. the lancet. 2012: 15;380(9859):2095-2128. 5. global burden of disease,2018. global burden of disease results tool gbd result tool/ ghdx available at: http://gbdx.healthdata.org/gbdresult tool. accessed on 12/10/2019. 6. budhathoki s, rimal s, shrestha s, lama l, sanjel s, amgain k. clinical profile of enteric fever in children of a tertiary care centre in kathmandu, nepal. journal of karnali academy of health sciences. 2020; 3(2). aavailable from http://jkahs.org.np/jkahs/index.php/jkahs/article/view/2 46. 7. voysey m, pant d, shakya m, liu x, colin-jones r, theissnyland k et al. under-detection of blood culture-positive enteric fever cases: the impact of missing data and methods for adjusting incidence estimates. plos neglected tropical diseases. 2020 jan 16;14(1): e0007805. 8. krishnasamy j, srinivasan a. sensitivity pattern of salmonella isolates from blood culture in children in a tertiary care hospital in western tamil nadu. eastern journal of medical sciences. 2020; 5(1):8-10. 9. parry cm, ribeiro i, walia k, rupali p, baker s, basnyat b. multidrug resistant enteric fever in south asia: unmet medical needs and opportunities. bmj. 2019;364: k5322. doi: https://doi.org/10.1136/bmj.k5322. 10. chatham-stephens k, medalla f, hughes m, appiah gd, aubert rd, caidi h et al. emergence of extensively drugresistant salmonella typhi infections among travelers to or from pakistan—united states, 2016–2018. morbidity and mortality weekly report. 2019 jan 11;68(1):11-13. d. 11. jain s, chugh td. antimicrobial resistance among blood culture isolates of salmonella enterica in new delhi. the j o u r n a l o f i n fe c t i o n i n d e v e l o p i n g c o u n t r i e s . 2013;7(11):788-95. 12. qamar fn, azmatullah a, kazi am, khan e, zaidi ak. a threeyear review of antimicrobial resistance of salmonella enterica serovars typhi and paratyphi a in pakistan. the j o u r n a l o f i n fe c t i o n i n d e v e l o p i n g c o u n t r i e s . 2014;8(08):981-6. 13. thompsom cn, karkey a, dongol s, ariyal a, wolbers m, darton t, et al. treatment response in enteric fever in an era of increasing antimicrobial resistance: an individual patient pattern of enteric fever at a children hospital of karachijiimc 2021 vol. 16, no.1 8 data analysis of 2092 participants enrolled into 4 randomized, controlled trials in nepal. clinical infectious diseases. 2017;64(11):1522-31. 14. klemm ej, shakoor s, page aj, qamar fn, judge k, saeed dk, et al. emergence of an extensively drug-resistant salmonella entericaserovartyphi clone harboring a p r o m i s c u o u s p l a s m i d e n c o d i n g r e s i s t a n c e t o fluoroquinolones and third generation cephalosporins. mbio. 2018;9(1): e00105-18. doi: 10.1128/mbio.0010518. 15. indian network for surveillance of antimicrobial resistance group. antibiogram of s. entericaserovartyphi and s. entericaserovarparatyphi a: a multi-centre study from india. who south-east asia journal of public health. 2012;1(2):182-8. 16. abdullah fe, haider f, fatima k, irfan s, iqbal ms. enteric fever in karachi: current antibiotic susceptibility of salmonellae isolates. j coll physicians surg pak, 2012; 22: 147-50. 17. basheer a. fluoroquinolone resistance in salmonella: a one year study of blood cultures at sheikh zayed hospital, lahore. proceeding szpgmi 2015;29(2):107-10. 18. iftikhar a, hamid mh, masood q. spectrum of risk factors associated with complications among children admitted with enteric fever. pak pediatr j. 2019;43(2):80-6. pattern of enteric fever at a children hospital of karachijiimc 2021 vol. 16, no.1 9 original�article abstract objective: to study the response of irritable bowel syndrome patients presenting with diarrhea and abdominal pain to the treatment with rifaximin. study design: observational descriptive study. st st place and duration of study: study was carried out from 1 february 2019 to 1 december 2019 at gastroenterology department of combined military hospital rawalakot. materials and methods: total of 113 patients were consecutively chosen from the gastroenterology outpatient department, sheikh khalifa bin zayed al nahyan hospital/ ak combined military hospital rawalakot. irritable bowel syndrome, diarrhea was diagnosed using rome iii criteria. all participants received 550 mg rifaximin in two divided doses for a period of fourteen days and were observed for six weeks. the assessed symptoms were diarrhea and abdominal pain, which were recorded at baseline and then at 6 week follow up. descriptive statistics were done to look for the response of patients' clinical symptoms to rifaximin. results: mean age of the participants was 26.96 years. out of 113 subjects, 45% were male (51/113) and 55% (62/113) females. rifaximin was found to be effective in relieving symptoms in 99(87.6%) cases while it did not relieve symptoms in 14 (12.4%) cases. only 14(12.4%) patients developed headache as a side effect, while the rest 99(87.6%) tolerated it well. conclusion: rifaximin is a useful, effective and a safe drug for the treatment of irritable bowel syndrome patients suffering from diarrhea and abdominal pain. key words: abdominal pain, diarrhea, irritable bowel syndrome, rifaximin. of ibs. in one of the studies from abbottabad, prevalence of 13% was found for this condition. a l t e r e d ga s t r o i n t e s t i n a l m o t i l i t y, v i s c e ra l hypersensitivity, post infectious reactivity, brain-gut interactions, alteration in fecal micro flora, bacterial overgrowth, food sensitivity, carbohydrate malabsorption, and intestinal inflammation all have 6 been implicated in the pathogenesis of ibs. due to unknown reasons, somehow irritable bowel syndrome presents more commonly amongst 6,7 females. an indian study however contradicts this finding showing a higher prevalence for males versus 8-9 females i.e., almost 8% males against 7% females. manning criteria, rome i, rome ii and rome iii criteria are used for diagnosis of this condition. rome iii criteria is more commonly used clinically but manning criteria has a better yield when compared 10 to rome i or ii criteria. all these criteria involve wide range of gastrointestinal symptoms and quality of life parameters. various treatment strategies have been available for the patients suffering from irritable bowel syndrome. in one of the placebo-controlled trials 41% patients showed marked improvement in introduction irritable bowel syndrome is marked by abdominal pain with disturbed defecation. it is amongst the most diagnosed conditions by health care physicians 1 across the world. epidemiological data suggest that there has been an increase in diagnosis of this 2 condition in all settings. in the western countries, prevalence of ibs is around 17-22%, while in asian 3-5 countries its around 2.3-34%. studies from pakistan have limited information regarding various aspects rifaximin: an option for the treatment of irritable bowel syndrome 1 2 3 4 5 muhammad abdul quddus , arslan shahzad , rukhsana munawar , khawaja tahir maqbool , amna mansoor , 6 7 naveed gani , sheikh muhammad taqqi anwer correspondence: dr. muhammad abdul quddus assistant professor department of gastroenterology poonch medical college, rawalakot e-mail: aquddus1@gmail.com 1,4,7 3 department of gastroenterology/ pharmacology poonch medical college, rawalakot 2 department of gastroenterology fazaia medical college islamabad 5 department of ophthalmology al shifa eye trust rawalpindi 6 department of psychiatry islam medical and dental college, sialkot funding source: nil; conflict of interest: nil received: january 02, 2021; revised: august 01, 2021 accepted: august 05, 2021 rifaxamin role in ibsjiimc 2021 vol. 16, no.4 215 symptoms with rifaximin versus 31% for the 11 placebo. another study that compared the efficacy of neomycin with rifaximin found that around 69% showed a remarkable clinical response with rifaximin versus only with 44% with neomycin and 12 other antibiotics. in another study patients of irritable bowel syndrome put on rifaximin were followed up for four weeks and showed marked 13 improvement in symptoms. limited data has been generated from patients of our own population regarding efficacy of rifaximin. therefore, this study was designed to assess the efficacy of rifaximin in treating diarrhea and abdominal pain in patients with irritable bowel syndrome. materials and methods this was an observational descriptive study conducted at the department of gastroenterology, sheikh khalifa bin zayed al nahyan hospital/ ak st combined military hospital rawalakot from 1 st february 2019 till 1 december 2019. duration of this study was ten months. sample size was calculated by using who sample size calculator by 12 using population prevalence proportion of 69% and margin of error as 10%. sample size turned out to be 83. nonprobability consecutive sampling technique was used to gather the sample for this study. the study was commenced after taking approval from hospital research ethical committee. we included patients of both genders with age between 18 and 35 years, diagnosed as suffering from irritable bowel syndrome for more than 6 months. irritable bowel syndrome was diagnosed based on rome iii criteria. according to rome iii criteria irritable bowel syndrome is characterized by repeated episodes of abdominal pain or discomfort for at least 3 days/month during last 3 months associated with two or more of the coming characteristics 14 : · which improve by passing stool and/or · attack associated with a change in frequency of stool. and/or · attack associated with a change in form (appearance) of stool. exclusion criteria were the patients with ulcerative colitis, crohn's disease, protozoal intestinal parasites entamoeba histolytica and giardia lamblia, duodenal or gastric ulcers, diverticulitis, bacterial and viral gastroenteritis. patients with history of use of antibiotic, probiotics, prebiotics, corticosteroids, proton-pump inhibitors, or patients on treatment of irritable bowel syndrome in last one month were excluded as well. detailed colonoscopic examination was undertaken to rule out any co morbid lower gastrointestinal problems. all participants received 550 mg rifaximin in two divided doses for fourteen days and were further followed for another fortytwo days to monitor drug efficacy. patients were called to outpatient department for follow up when examined at baseline. if they didn't show up, they were called as their contact numbers were taken at time of baseline interview. diarrhea and abdominal pain were recorded at baseline and then at 6 weeks follow up. the data was analyzed using spss 22.0. for the numerical values like age, mean± standard deviation and for the categorical, frequencies and percentages were presented. results a total was 113 patients who had ibs-diarrhea were included in the study after inclusion/exclusion criteria and dropouts. mean age of the participants was 26.96 ± s.d 4.606 with an age range of 20-34 years. out of 113 patients, 45% (51/113) were males while 55% (62/113) were females. regarding the efficacy of rifaximin, it was found that 99(87.6%) patients showed significant improvement in symptoms while 14 (12.4%) patients had no significant improvement in symptoms (table i). regarding the safety profile, it was found that only 14(12.4%) patients developed headache as a side effect, while the rest 99(87.6%) had no significant side effects (table ii). table i: improvement in symptoms with rifaximin among patients of irritable bowel syndrome table ii: safety profile of rifaximin rifaxamin role in ibsjiimc 2021 vol. 16, no.4 216 discussion timely managing irritable bowel syndrome is essential as there is considerable associated functional impairment leading to poor overall health 15,16,17 of the individual. a lot of research has been done in various parts of the world involving various pharmacological modalities to control the symptoms of ibs. this study was designed to assess the role of an antibiotic for this purpose. patients in our study showed a better response with rifaximin 550mg in a twice daily dosing offered for 2 weeks. we studied improvement in diarrhea and abdominal pain as primary outcome of our study and found significant improvement in both symptoms in response to rifaximin. this is in line with the study conducted by pimentel et al., where they found that around 41% patients responded well to rifaximin, in terms of overall improvement and also improving 11 diarrhea and bloating. there are other studies which support the use of rifaximin due to its efficacy 12,13, 18,19 in irritable bowel syndrome-diarrhea. considering this, there is sufficient support for rifaximin efficacy in improvement of physical disturbances of irritable bowel syndrome-diarrhea. it is a conveniently available, cost-effective, treatment, should be a part of future regimens for irritable bowel syndrome. our study showed that only about 11.5% patients had relapsed and did not show adequate response to rifaximin. this contradicts the findings from few other studies where most patients failed to show 20,21 adequate response to rifaximin. reason may be difference in pharmacokinetic or pharmacodynamic profiles of rifaximin in our population. it is worth mentioning here that we included a small sample which could lead to bias in our study. choosing a larger sample could have indeed helped in determining the exact efficacy and safety profile of rifaximin in our population. regarding the safety and tolerability, our study found that about 12.38% of our study participants experienced headache as a side effect, otherwise it was well tolerated. this is in line with the research by pimentel et al which showed that only 1.6% patients on rifaximin experienced serious adverse effects. similar safety profile has been reported in other 11 studies as well. therefore if efficacy of this agent gets established then side effects profile would not raise concerns for clinicians and hinder in the routine use of this medication. this study was useful in a sense that it provided sufficient evidence to suggest the rifaximin is an effective treatment for irritable bowel syndrome symptoms. in pakistan, it is a novel drug and holds a promise for treating this disorder effectively with minimum side-effects. this study had few limitations as well. due to small sample size and observational descriptive design; it lacks the generalizability of the findings to a larger population. therefore, the c o n c l u s i o n s s h o u l d b e d ra w n c a u t i o u s l y. furthermore, there was lack of control group for comparison and no randomization was done, which make it a methodologically weak study. conclusion rifaximin is a useful, effective and a safe drug for the treatment of irritable bowel syndrome patients suffering from diarrhea and abdominal pain. references 1. oka p, parr h, barberio b, black cj, savarino ev, ford ac. global prevalence of irritable bowel syndrome according to rome iii or iv criteria: a systematic review and metaanalysis. lancet gastroenterol hepatol. 2020;5(10):908917. 2. albutaysh of, alquraini aa, almukhaitah aa, alahmdi ym, alharbi fs. epidemiology of irritable bowel syndrome and its associated factors in saudi undergraduate students. saudi j gastroenterol. 2020;26(2):89-93. 3. ozer m, bengi g, colak r, cengiz o, akpinar h. prevalence of irritable bowel syndrome-like symptoms using rome iv criteria in patients with inactive inflammatory bowel disease and relation with quality of life. medicine (baltimore). 2020;99(19): e20067. 4. latif a, aziz memon f, asad m. irritable bowel syndrome in a population of a developing country: prevalence and association. cureus. 2020;12(5): e8112. 5. black cj, ford ac. global burden of irritable bowel syndrome: trends, predictions, and risk factors. nat rev gastroenterol hepatol. 2020;17(8):473-86. 6. bachani p, kumar l, kumar n, fatima m, naz s,memon mket al. prevalence of irritable bowel syndrome and frequency of symptoms in the general population of pakistan. cureus. 2021;13(1): e12541. 7. van kessel l, teunissen d, lagro-janssen t. sex-gender. differences in the effectiveness of treatment of irritable bowel syndrome: a systematic review. int j gen med. 2021; 14:867-84. 8. prevalence of irritable bowel syndrome in japan: internet survey using rome iii criteria. patient preference adherence. 2008; 2:143. 9. thabane m, kottachchi dt, marshall jk. systematic review and meta-analysis: the incidence and prognosis of postrifaxamin role in ibsjiimc 2021 vol. 16, no.4 217 infectious irritable bowel syndrome. aliment pharmacol ther. 2007;26(4):535–544. 10. black cj, craig o, gracie dj, ford ac. comparison of the rome iv criteria with the rome iii criteria for the diagnosis of irritable bowel syndrome in secondary care. gut. 2021;70(6):1110-16. 11. pimentel m, lembo a, chey wd, zakko s, ringel y, yu j et al. rifaximin therapy for patients with irritable bowel syndrome without constipation. n engl j med. 2011; 364(1):22-32. 12. yang j, lee hr, low k, chatterjee s, pimentel m. rifaximin versus other antibiotics in the primary treatment and retreatment of bacterial overgrowth in ibs. dig dis sci. 2008; 53(1):169-74. 13. meyrat p, safroneeva e, schoepfer am. rifaximin treatment for the irritable bowel syndrome with a positive lactulose hydrogen breath test improves symptoms for at least 3 months.aliment pharmacol ther. 2012; 36(11-12):1084-93. 14. camilleri m. irritable bowel syndrome: straightening the road from the rome criteria. neurogastroenterol motil. 2020;32(11): e13957. 15. farmer ad, wood e, ruffle jk. an approach to the care of patients with irritable bowel syndrome. cma j. 2020;192(11): e275-e282. 16. masuy i, pannemans j, tack j. irritable bowel syndrome: diagnosis and management. minerva gastroenterol dietol. 2020;66(2):136-150. 17. ferreira ai, garrido m, castro-poças f. irritable bowel syndrome: news from an old disorder. ge port j gastroenterol. 2020;27(4):255-268. 18. sharara ai, aoun e, abdul-baki h, mounzer r, sidani s, elhajj i. a randomized double-blind placebo-controlled trial of rifaximin in patients with abdominal bloating and flatulence. am j gastroenterol 2006; 101:326-33 19. brigidi p, swennen e, rizzello f, bozzolasco m, matteuzzi d. effects of rifaximin administration on the intestinal microbiota in patients with ulcerative colitis. j chemother 2002; 14:290-5 20. pimentel m. review of rifaximin as treatment for sibo and ibs. expert opin investig drugs 2009; 18:349-58. 21. pimentel m, park s, mirocha j, kane sv, kong y. the effect of a nonabsorbed oral antibiotic (rifaximin) on the symptoms of the irritable bowel syndrome: a randomized trial. ann intern med 2006; 145:557-63 22. lembo a, pimentel m, rao ss, schoenfeld p, cash b, weinstock lb et al. repeat treatment with rifaximin is safe and effective in patients with diarrhea-predominant i r r i t a b l e b o w e l s y n d r o m e . g a s t r o e n t e r o l o g y. 2016;151(6):1113-21. 23. menees sb, maneerattannaporn m, kim hm, chey wd. the efficacy and safety of rifaximin for the irritable bowel syndrome: a systematic review and meta-analysis. am j gastroenterol. 2012; 107:28–35. 24. noori my, khan g, abid i, baig s, zamir s, . sharafat s demographics of intestinal parasitic infections in karachi: an insight from positive stool samples.j islamic int med coll. 2016;11(1):20-3 25. haq mi, aziz sa, khan a, jehan a, farooq a. current maternal knowledge about diarrheal causes in children and role of oral rehydration salt.j islamic int med coll. 2011;6(2):25-8. rifaxamin role in ibsjiimc 2021 vol. 16, no.4 218 jiims.cdr abstract objective: to assess the knowledge, attitude and practices regarding dengue fever and its prevention in rawalpindi study design: a cross sectional survey. place and duration of study: community of rawalpindi, from july to sept. 2012. materials and methods: a total of 215 participants were selected through consecutive sampling technique. a structured questionnaire was self administered after informed consent was obtained from all the participants. knowledge of dengue was measured by asking questions related to disease symptoms and preventive measures. association between knowledge and awareness at p<0.05 was accepted as significant. results: it was found that the knowledge of the community regarding dengue fever was adequate (91%). the respondents' awareness about preventive measures for dengue was also satisfactory (88%). a significant association found between knowledge & awareness of dengue fever and preventive measures (p= 0.01). mass media was identified as an effective tool in raising awareness. however; adequate knowledge about prevention did not reflect in community practices (p=0.031); factors identified responsible for it, were like water storage for domestic use due to water shortage and excessive load shedding. conclusion: local community is well aware about dengue fever and its prevention; however it was found that good knowledge doesn't necessarily lead to good practice. health educational campaigns should be designed to improve behavior and practices of prevention & control measures against dengue fever. key words: dengue fever, viral hemorrhagic fever, healthcare. preventive measures. 69 original article 5 from srilanka in 1989. tropical season, periurbinization with ill planned and crowded a r e a s a n d i m p r o p e r w a s t e w a t e r management are supposedly responsible for df in this region. dhf was found in china, indonesia, malaysia, thailand, some studies have reported its epidemics occurred in 6,7,8,9 india and bangladesh. in pakistan dengue has been around for the past 20 years. the first documented report 10 was in 1985 whereby dengue type 2 virus was isolated in a sero-epidemiological study for encephalitis. the first major outbreak was reported in 1994-95, another epidemic has been witnessed in karachi following heavy rainfalls in 2006. during the previous two epidemics in karachi, dengue fever was more commonly seen in the 20 to 40 years 10,11 age group dengue vector control requires effective 12 participation of the local community. knowledge, attitude, and practice (kap) surveys provide a suitable format to evaluate existing programs and to identify effective strategies for behavior and introduction since the beginning of the 21st century, dengue fever (df)/ dengue hemorrhagic fever (dhf) is the emerging most important arboviral disease of humans, occurring in tropical countries of the world where >2.5 1,2 billion people are at risk of infection. it is still endemic in 112 countries around the world and dhf has been documented in 3 >60 of these countries. at the beginning of the 21st century it is estimated that between 50 -100 million cases of df and several hundred thousand cases of dhf occurred each year, depending on the epidemic activity. the case fatality rate (cfr) varies among countries, but can be as 4 high as 10–15% in some and <1% in others. dengue fever (df) is endemic in southeast asia. first major epidemic was reported ------------------------------------------------are we aware of dengue fever? a community based kap survey on dengue fever in rawalpindi farah rashid siddiqui, abdul qadir usmani, iffat atif, s. hassan bin usman, syed hammad haider correspondence: dr. farah rashid siddiqui associate professor yusra medical & dental college, islamabad. email: farahrashid@yahoo.com 70 environmental change in order to control disease effectively. it has been noticed such studies have been relatively rare in dengue 13,14 research . the present kap study was done with the aim of assessing knowledge regarding dengue fever among general population and to assess, whether knowledge of dengue symptoms and preventive measures contribute to better preventive practices. a cross sectional survey was conducted a m o n g s t t h e u r b a n c o m m u n i t y o f rawalpindi during july – september 2012. a total of 215 participants were selected through consecutive sampling technique. a s t r u c t u r e d q u e s t i o n n a i r e w a s s e l f administered after informed consent was obtained from all the participants. knowledge of dengue was measured by asking questions related to disease symptoms and preventive measures. regarding practices, questions were asked about the use of preventive measures against dengue fever. knowledge of symptoms was defined as the respondent mentioning at least two of the following s y m p t o m s : f e v e r , h e a d a c h e , nausea/vomiting, rash, bleeding, shock, or muscular pain. similarly, the criteria was set that the participants had knowledge of preventive measures if mentioned at least three of the following measures: using a mosquito net, using mosquito repellents, sprays, coils, changing and covering stored water and safe disposal of garbage. preventive practice was defined as using at least one of the following measures; using mosquito repellent, bed net or mosquito coils, screening on windows/doors, covering stored water for domestic use, checking the flower pots and coolers. overall the level of awareness about dengue fever was 91% and awareness about preventive measures was 88% which was materials and methods results f o u n d o u t a f t e r i n t e r v i e w i n g 2 1 5 participants. the study population was mainly comprised of adults; mean age of the population was 28 + 5 years; 66% female and 34% male; 67% of the participants were literate and 33% illiterate. table i; showed the details of demographic features of the study population and kap in relation with age, gender, education and socioeconomic status. kap has been categorized on the basis of the responses in to poor (one or no correct answer), fair (at least 2 correct answers), good (3 > 3 correct answers) about knowledge of symptoms, preventive measures and preventive practices against dengue fever. about mode of transmission of dengue, 99% of the participants knew that dengue fever is transmitted through mosquitoes. regarding knowledge about symptoms of dengue, 89%persons mentioned one symptom (fever), 72% persons specified 2 symptoms (fever, headache), 64% told 3 symptoms of dengue (fever, headache & muscular pain) and 24% specified 4 symptoms (fever, headache, muscular pain and bleeding). majority of the participants 89% reported that the knowledge and awareness of dengue fever was gained by mass media, tv, radio, internet, pamphlets and newspapers. regarding knowledge about preventive measures of dengue fever majority of the participants 89% were aware of at least one m e t h o d o f p r e v e n t i o n ( m o s q u i t o coil/spray/repellent), 80% knew about 2 p r e v e n t i v e m e a s u r e s ( m o s q u i t o coil/spray/repellent and bed nets), 75% were aware of 3 preventive measures (mosquito coil/spray/repellent, bed nets and safe disposal of garbage), although very few participants 18% were aware of covering and changing clean stored water. the association between knowledge of dengue and awareness about its preventive measures found statistically significant (p = 0.01) low-middle(10-20,000rs) 71 when the participants were asked about the preventive practices they have adopted 55% o f t h e m w e re p r a c t i c i n g m o s q u i t o coil/spray/repellent on & off, 12% bed nets, 10% safe garbage disposal and only 3% covering stored water for domestic use, checking the flower pots and coolers; 20% of the participants were not practicing any preventive measures. this shows adequate level of awareness about dengue symptoms and preventive measures wasn't successful in changing the practices of the community as preventive practices were poor as compare to knowledge, this finding is statistically significant (p = 0.03). discussion although the level of dengue knowledge and awareness about preventive measures table no i: kap (%ages) in relation to demographic features (n=215) of local community was satisfactory, however results of this study showed that this knowledge and awareness wasn't effectively put into practice. the personal preventive practices against dengue control weren't at satisfactory level. the focus should be now to motivate community to adopt the preventive practices against dengue. previous studies have reported conflicting results regarding the effects of knowledge on dengue prevention practices. some studies have shown that dengue knowledge was associated with an effective use of 15,16,17 preventive measures against the disease and a reduced number of development sites 18 for vector larvae. other studies found a s i g n i f i c a n t re d u c t i o n i n t h e v e c t o r upper-middle(>31,000rs) 72 infestation index after community-based 1 8 , 1 9 , 2 0 prevention campaigns. however, 21 22 studies in puerto rico, brazil, and 23 trinidad en tobago that found little or no correlation between knowledge of dengue and levels of preventive measures adopted by the communities, findings of these studies are in line with our results. our results indicated a weak association between dengue knowledge and preventive practices adopted by the community. better knowledge does not necessarily lead to better practice, presumably because it is difficult to change a person's behavior due to multiple social and cultural issues like water storages practices, sleeping outdoor due to load shedding, affordability and lack of resources to adopt preventive measures like covering windows with nets, large container with lids etc. adequate knowledge of preventive measures in our study could improve the preventive practices. mass media play a vital role in emphasizing preventive practices like reducing the numbers of unprotected containers. this suggests that more emphasis should be put on practical ways to prevent dengue in educational campaigns. although in our study it was not directly associated with better practice however, adequate knowledge of symptoms is important to recognize the severity of dengue at an early stage which can lead to proper case management and saves lives. conclusion it is concluded that the local community is well aware about dengue fever and its prevention; however it was found that good knowledge doesn't necessarily lead to good practice. health educational campaigns should be designed to improve behavior and practices of prevention & control m e a s u r e s a g a i n s t d e n g u e f e v e r. intersectoral collaboration is needed between different sectors of life like educational, religious and municipal corporation for stressing on adopting preventive measures and distributing low cost preventive material against dengue. closing the gap between knowledge and practice will remain an important challenge for public health to dengue control. 1. gubler dj. dengue and dengue hemorrhagic fever; its history and resurgence as a global public health problem. in dengue and dengue hemorrhagic fever (gubler, d.j.and kuno, g., eds), pp. 1–22, (1998) cab international press. 2. gubler, d.j. and meltzer, m. the impact of dengue/dengue hemorrhagic fever on the developing world. adv. virus res.1999;53:357 0 3 . w o r l d h e a l t h o r g a n i z a t i o n s t r e n g t h e n i n g i m p l e m e n t a t i o n o f t h e global strategy for dengue f e v e r / d e n g u e hemorrhagic fever prevention and control. report of the informal consultation, 18–20 october (2000),who, geneva. 4. ratageri vh, shepur ta, wari pk, chavan sc, mujahid ib, yergolkar pn. clinical profile and outcome of dengue fever cases. indian j pediator 2005; 72:705-6. 5. vijayakumar ts, chandy s, satish n, abraham m, abraham p, sridhavan g. is dengue emerging as a major public health problem? indian j med res 2005 121:100-7. 6. srivastava vk, suri s, bhasin a, srivastava l, bharadwaj m .an epidemic of dengue hemorrhagic fever and dengue shock syndrome in delhi: a clinical study. annl trop paediatr 1990, 10: 329-34. 7. kabilan l, balasurbramanian s, keshava sm, satyanavayana k. the 2001 dengue epidemic in chennai. indian j pediatr 2005; 72: 919-23. 8. ratho rk, mishra b, kaur j, kakkar n, sharma k. an outbreak of dengue fever in periurban slums of chandigarah, india, with special references 73 reference to entomological and climatic factor. india j med sci 2005; 59: 518-26 9. abu bakar, nazmul ahsan ham, ahsan m, mamun aa, kavin sr. emergence of dengue in bangladesh. pak armed forces med j 2004; 54; 147-50. 10. qureshi ja, notta nj, salahuddin n, zaman v, khan ja. an epidemic of dengue fever in karachi. associated clinical manifestations. j pak med assoc 1997, 47: 178-81. 11. ansari jk, siddiq m, hussain t, baig i, tariq wz. outbreak of dengue haemorrhagic fever in karachi. pak armed forces med j 2001; 51: 94 -8. 12. winch p, kendall c, gubler d, effectiveness of community participation in vector-borne disease control. health policy 2007; 7: 342–51. 13. guha-sapir d, schimmer b,. dengue fever: new paradigms for a changing epidemiology. emerg themes epidemiol 2005; 2: 1. 14. tram tt, anh nt, hung nt, lan nt, cam lt, chuong np, et al. heegaard ed. the impact of ` health education on mother's knowledge, attitude and practice (kap) of dengue haemorrhagic fever. dengue bull 2003; 27: 174–80. 15. swaddiwudhipong w, lerdlukanavonge p, khumklam p, koonchote s, nguntra p, chaovakiratipong c. a survey of knowledge, attitude and practice of the prevention of dengue hemorrhagic fever in an urban community of thailand. southeast asian j trop med public health 2006; 23: 207–11. 16. ayyamani ua, ying gc, san o g. a knowledge attitude and practice (kap) study on dengue/dengue haemorrhagic fever and the aedes mosquitoes. med j malaysia. 2007; 41: 108–15. 17. van benthem bhb, khantikul n, panart pj, kessels j, somboon p, oskam l. knowledge and use of prevention measures related to dengue in nothern thailand. trop med int health. 2009; 7: 993–1000. 18. chiaravalloti neto f, fiorin am, conversani dt, cesarino mb, barbosa aa, dibo mr et. a l . controle do vetor do dengue e participação da comunidade em catanduva, são pauo, brasil.cad saude publica 2003;19:1739-49. 19. fernandez e, lagos i, sherman c. advances in the aedes aegypti community-based control project in el progreso, honduras. j am mosq control assoc 2007; 9: 449. 20. espinoza-gómez f, hernández-suárez cm, coll-cárdenas r. educational campaign versus malathion spraying for the control of aedes aegypti in colima, mexico. j epidemiol community health 2002; 56: 148–52. 21. winch pj, leontsini e, rigau-perez jg, ruizp e r e z m , c l a r k g g , g u b l e r d j . c o m m u n i t y b a s e d d e n g u e p r e v e n t i o n programs in puerto rico: impact on knowledge, behavior, and residential mosquito infestation. am j trop med hyg 2002;67:363-70. 22. degallier n, vilarinhos pt, de carvalho ms, k n o x m b , c a e t a n o j j r . p e o p l e ' s knowledge and practice about dengue, its vectors, and control means in brasilia (df), brazil: its relevance with entomological factors. j am mosq control assoc 2000;16: 114–23. 23. rosenbaum j, nathan mb, ragoonanansingh r, rawlins s, gayle c, chadee dd, et. al. community participation in dengue prevention and control: a survey of knowledge, attitudes, and practice in trinidad and tobago. am j trop med hyg 1995;53:111-7. original�article abstract objective: to explore the mediating role of temperament traits in parenting styles and attention deficits hyperactive disorder (adhd) symptoms in young adults. study design: a cross-sectional research design. place and duration of study: this study was carried out in lahore from september 2019 to march 2020. materials and methods: a sample of 310 university students (men 38%, and women 63%) with the age range of 21 18-24 were given demographic performa, attention deficits hyperactive symptoms scale (adhss) , student 4 22 temperament scale (sts) and my memories of upbringing (embu-a). pearson correlation was used to find the association among parenting styles, adhd symptoms, and temperament traits and mediation analysis was used to investigate the mediating role of temperament traits between parental overprotection and adhd symptoms and model 4 was used. the level of significance was taken as p<.05, p<.01 and p<.001. results: women were 63% with higher percentage than men 38%. the mean of age was 20.12 years +1.60 sd. correlation analysis indicate that a significant positive relationship among temperament traits, parental overprotection and adhd symptoms. mediation analysis indicate that impulsivity, cautiousness, and apprehension were partially parallel mediated the relationship between parental over-protection and adhd symptoms. conclusion: the current study provides empirical evidence that temperament traits mediate the relationship between parental overprotection and adhd symptoms. key words: adhd, over protection, parenting, temperament traits, young adults. parenting styles and attention deficits hyperactive disorder symptoms: mediating role of temperament traits in young adults 1 2 rehana mushtaq , sadia saleem correspondence: rehana mushtaq department of clinical psychology school of professional psychology university of management and technology, lahore e-mail: rehanamushtaq93@yahoo.com department of clinical psychology school of professional psychology university of management and technology, lahore funding source: nil; conflict of interest: nil received: january 13, 2021; revised: september 19, 2021 accepted: september 20, 2021 parenting style and adhd symptoms jiimc 2021 vol. 16, no.4 10 performance and high self-esteem. parents who exert excessive control on individuals may promote resentment and hinder autonomy in their emerging adults that may create frustration, loneliness, 11 hyperactivity, shyness, careless and anxious . moreover, they expect parental support, and failure to receive may lead to inattention, hyperactivity, and 6 anxiousness. adhd is a neurodevelopmental disorder characterized by inattention, hyperactivity, 12 and impulsivity with the prevalence rate in adults 1 3 2.8%-3.4. inconsistent parenting manifests impairment in parenting control like lack of organized or planned household routines and appreciation of an individual's needs or failure to monitor the individual which leads to impulsiveness and adhd symptoms. adhd deficits may also disturb the development of adults which leads to mental 6 health problems. in emerging adults, a link is found between parental and offspring psychopathology like adhd symptoms, internalizing and externalizing 14 behaviors. a transitional period of adhd adults continuously displays impairments that are 6 associated with parenting . when noticing the 15 development of young adults with adhd jones introduction parenting and temperament are said to be two influential factors in the development of several 1 , 2 mental health concerns including anxiety, depression, adjustment problems, and attention 3,4,5,6 deficits hyperactive disorder (adhd) . adhd symptoms enhance due to lack of consistency in 7 parenting and temperament dimensions. parenting is a complex process that needs various skills to 8 9 influence the behavior of a child. wilmshurst explored that parenting style plays in the manifestation of the development of pathology and found that if parenting is warm, supportive, and e n c o u ra g i n g , a d u l t s h av e g o o d a c a d e m i c 255 explained the interaction between parent-childrelated factors and adhd symptoms. in the framework of developmental psychopathology, reciprocal and transitional relations are proposed b e t w e e n p ro b l e m s i n p a re n ta l e m o t i o n a l responsiveness or behavioral control and child maladjustment including adhd symptoms and closely related conditions like oppositional defiant 16 and conduit disorder. all individuals with adhd do not experience the same level of severity and type of symptoms but relevant factor temperament will identify as the 2 greatest risk for adverse results. temperament influences psychological functioning and a greater risk for mental health problems (depressive 3 symptoms, sleep problem, adhd symptoms). temperament traits are early markers of different 17 developmental pathways that lead to adhd and adhd is an extreme manifestation of temperament 2 traits . in temperament, two broader pathways apprehension and impulsivity were associated with 18 greater psychopathology. temperament traits are explored as possible ways to the emergence of adhd symptoms and may be relevant to the functioning of the parenting 11 domain. a link between certain temperament traits (impulsivity and apprehension) and adhd 2 symptoms was found . temperament traits are 16 related to the occurrence of adhd in adulthood . a link among parenting and temperament traits (impulsivity, apprehension, and cautiousness) was 19 also found . parenting, temperament, and adhd 1 9 sy m pto m s a re co r related . pa rent in g a n d 11 temperament traits are bidirectional correlated. parenting affects an individual's temperament and 19 20 behavior problem. gau reported that adhd adults perceive more overprotection and control from their 18,20 mothers. researches explained the relationship between parenting factors (overprotection) and child psychopathology. it can be concluded that parenting and temperament play a vital role in human development especially in psychopathologies like adhd. the current research was carried out to explore how parenting influence the temperament traits and adhd symptom in a sample of pakistani young adults. pakistani is collectivistic culture, where parents focus on overprotection and provide guidance and expect obedience from individuals. therefore, the present study was aimed to explore the relationship among parenting, temperament traits, and adhd symptom in a sample of pakistani young adults and find out the mediating role of temperament traits between parental overprotection warmth and adhd symptom. materials and methods a cross-sectional research design and government and private university settings were used. this study was carried out in lahore from september 2019 to march 2020. a sample of 310 undergraduate university students were taken from 2 government and 2 private universities of lahore through convinient sampling. the current research was approved by institutional review board (irb). only university students of bs hons and msc program were taken. university students of mphil and ph.d. were excluded from this study. demographic performa consists of age, gender, and academic class. attention deficits hyperactive 21 symptoms scale (adhss) was used to measure adhd symptoms in young adults. it is a self-report measure consisting of 40 items with 3 factors inattention, hyperactivity, and prosocial on 5 point likert scale such as 0 (not at all), 1 (too little), 2 (to some extent), 3 (often), and 4 (too much). in the current research, only 28 items of inattention and hyperactivity were used. the score of adhss (inattention and hyperactivity) lies between 0-112. a higher score represented more symptoms of adhd. internal consistency is inattention α=.85 and hyperactivity α=.79. 4 student temperament scale (sts) measures temperament styles in university students consist of 56 items with 6 factors, apprehension, impulsivity, cautiousness, introversion, submissiveness, and extroversion but in current research, only 38 items of apprehension, impulsivity, and cautiousness were used. the response options are on 4 point rating scale of 0(never), 1(sometimes), 2(often), and 3(most of the time). internal consistency is apprehension α=.82, impulsivity α=.81, cautiousness α=.80, introversion α=.77, submissiveness α=.72 and extroversion α=.70. my memories of upbringing 22 embu-a is a self-report measure that provides the individual perception of parental rearing practices. it parenting style and adhd symptoms jiimc 2021 vol. 16, no.4 256 has two forms for father and mother separately. it consisted of 27 items with 3 factors emotional warmth, rejection, and overprotection but in current research, only 6 items of overprotection subscale were used for both father and mother in urdu. the response options are 0 (never), 1 (sometimes), 2 (often) and 3 (always). the scoring range is between 0-18 and higher represent more perceived rejection from both parents. with ensuring confidentiality and privacy, researcher collected the data from the participant in the group with a debriefing session. they were asked to rate each statement to the extent to which it applies to them. mean and standard deviaoition and percentages were done through spss 21. data were analyzed in spss 21 for correlation and mediation analysis was carried out through process and model 4 was used. the level of significance was taken as p<.05, p<.01 and p<.001. results women were 63% with higher percentage than men 38%. the mean of age was 20.12 and standard deviatrion is 1.60. the relationship among parenting style, adhd symptoms and temperament traits were explored through pearson product moment correlation. finding indicated significant positive association among father over protection, impulsivity cautiousness, apprehension, adhd symptoms and mother overprotection moreover, results showed significant negative association between cautiousness and adhd symptoms. pearson product moment correlation indicates significant relationship among study variable, hence, the mediating role of apprehension, impulsivity and cautiousness in the relationship between parental overprotection and adhd symptoms was explored by conducting parallel mediation analysis through 23 hayes bootstrapping approach. figure 1 shows the mediating role of impulsivity, cautiousness and apprehension in the association between father overprotection and adhd symptoms. total effect of father overprotection on adhd symptoms (β = .23, 2 se = .06, p < .001, r = .05) was significant. f u r t h e r m o re , t h e d i re c t effe c t s o f fat h e r overprotection on impulsivity (β = .26, se = .06, p < 2 .001, r = .07), cautiousness (β = .23, se = .06, p < 2 .001, r = .06) and apprehension (β = .21, se = .06, p < 2 .01, r = .04) were significant. in contrast, an examination of the direct effects of the mediating variables on adhd symptoms exhibited that the direct effects of impulsivity (β = .40, se = .06, p < .001, 2 2 r = .32), cautiousness (β = -.23, se = .05, p < .001, r = 2 .32) and apprehension (β = .14, se = .06, p < .05, r = .32) were significant. findings suggests that impulsivity, cautiousness and apprehension partially m e d i a t e t h e a s s o c i a t i o n b e t w e e n f a t h e r overprotection and adhd symptoms as after controlling the mediating variables the direct effect of father overprotection on adhd symptoms is 2 reduced (β = .15, se = .05, p < .01, r = .32) but c' path is still significant. figure 2 shows the mediating role of impulsivity, cautiousness and apprehension in the association between mother overprotection and adhd symptoms. findings indicated that total effect of mother overprotection on adhd symptoms (β = 2 .15, se = .06, p < .01, r = .02) was significant. m o r e o v e r, t h e d i r e c t e f f e c t s o f m o t h e r overprotection on impulsivity (β = .15, se = .06, p < 2 .01, r = .02), cautiousness (β = .19, se = .06, p < .001, 2 r = .04) and apprehension (β = .11, se = .06, p < .05, 2 r = .01) were significant. furthermore, the direct effects of the mediating variables on adhd symptoms exhibited that the direct effects of 2 impulsivity (β = .42, se = .06, p < .001, r = .31), 2 cautiousness (β = -.22, se = .05, p < .001, r = .31) and 2 apprehension (β = .15, se = .06, p < .01, r = .31) were significant. findings suggests that impulsivity, cautiousness and apprehension partially mediate the association between mother overprotection and adhd symptoms as after controlling the mediating variables the direct effect of mother overprotection table i: summary of correlations of inter-factor parenting style, adhd symptoms and temperament traits (n=310) note. fop= father overprotection, mop= mother overprotection, adhss = attention deficits hyperactive symptoms scale *p<.05, **p<.01, ***p<.001.� parenting style and adhd symptoms jiimc 2021 vol. 16, no.4 257 on adhd symptoms is minimized (β = .11, se = .05, p < 2 .05, r = .31) but c' path is still significant. therefore, it can be concluded that temperament traits partially parallel mediate the association between parental overprotection and adhd symptoms. symptoms. the results revelaed that women were 63% with higher percentage than men 38%. the mean of age is 20.12 and standard deviatrion is 1.60. the greater ratio of women was found in university population. the finding of correlation anlysis revealed a significant correlation was found among p a r e n t a l o v e r p r o t e c t i o n a n d m a t e r n a l overprotection, temperament traits (impulsivity, cautiousness, and apprehension) adhd symptoms of inattention and hyperactivity at the .001, .01 and .05 level of significance. the previous literature 2,10,11,13,19 supports the results of the current study. the finding of mediation analysis revealed that temperament traits (impulsivity, cautiousness, and apprehension) partially parallel mediate the relationship between parental and maternal overprotection and adhd symptoms of inattention and hyperactivity at the .001, .01 and .05 level of significance. the previous literature supports the 2,10,11,13,15,16, 17,.18,19 results of the current study and indicated that parents who exert excessive control on their children may promote resentment and hinder autonomy in their emerging adults. it may create, 11 hyperactivity, shyness, careless and anxious and as a result of these consequences young adult could not pay attention to their studies, and increase impulsivity temperament trait (cautiousness). one interesting finding revealed that father overprotection is the most significant predictor of temperament and adhd symptoms. fathers are found to be an authoritative figure of the family and a sign of power. overprotection from fathers affects more on their temperament and inattention and hyperactivity. according to these findings, it can be said that parental overprotection may lead to a negative impact on an individual's life. conclusion the current study provides empirical evidence that temperament traits mediate the relationship between parental overprotection and adhd symptoms in young adults. parenting style plays an important in the manifestation of the development of pathology in a clinical setting. as well perceived parenting plays a crucial role in an individual's life. parent and child relationship is to be positive for decreasing their symptoms of adhd. in the current study, a cross-sectional research design was used. in the future longitudinal studies fig 1: mediation path framework of father over protection, temperament traits, and adhd symptoms fig 2: mediation path framework of mother over protection, temperament traits and adhd symptoms discussion family is the most significant context in the development of an individual. it plays an essential role in the upbringing process of an individual because parents provide a healthy relationship which is compulsory for the maturity of an 24 individual. parenting may influence an individual's behavior problems, which may increase or decrease 19 depending on the type of relationship . the parentchild relationship defines according to different approaches and individualistic and collectivistic 3 culture . parenting factors including warmth and overprotection may influence the relationship between parent and child psychopathology and 25 problems of young adults increased over time. parental overprotection may have different consequences in young adults with a difficult 25 temperament. therefore, the present research was aimed to explore the relalationship among parental overprotection, temperament traits and adhd symptoms and it was also aimed to explore the temperament traits that mediate the relationship between parental overprotection and adhd parenting style and adhd symptoms jiimc 2021 vol. 16, no.4 258 will be done for mediation. another limitation, data was taken from adults. in the future, data would be collected from both parents and adults for exploring parent-child bonding. the implication of this study is to understand the risk and protective of overprotection and counseling services needed 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2018. 24. montejo je, duran m, martínez m-dm, hilari a, roncalli n, vilaregut a, et. al. family functioning and parental bonding during childhood in adults diagnosed with adhd. j atten disord. 2015; 1–8. doi: 10.1177/1087054715596578 25. mckinney c. steele eh, story a-g. effects of parental internalizing problems on irritability in adolescents: moderation by parental warmth and overprotection. j child family studies. 2019; doi:10.1007/s10826-01901459-9. parenting style and adhd symptoms jiimc 2021 vol. 16, no.4 259 original�article abstract objective: the current study aimed to explore the sealing ability of commercially available root canal sealers after obturation by using stereomicroscope. study design: experimental laboratory-based study. place and duration of study: the study was conducted at zoology department, national centre of excellence in th st geology and department of pathology at college from 10 january 2021 to 31 march 2022. materials and methods: teeth used in this study were divided randomly into four experimental (four commercially available sealers) and one control group (only gutta percha without using sealer) (n=10) denoted by eg1, eg2, eg3, eg4 and cg5 respectively. after obturation, specimens were coated with varnish except for 12mm of apical area and immersed in 2% methylene blue for 1 week. specimens were analyzed using stereomicroscopy, scanning electron microscopy and energy dispersive x-ray analysis (sem, edx). kruskal wallis and mann-whitney u-tests were employed to measure statistical significance. results: fifty percent samples of endomethasone sealer had a score of 2 and the rest score 3. sixty percent of sealapex sealer had score of 2 and forty (40) percent had score of 3. fifty percent of adseal sealer had score of 2 and remaining fifty (50) percent of adseal sealer had score of 3. fifty percent of ah plus sealer had score of 2. forty (40) percent had a score of 1 and remaining ten percent had score of 3 (table. i). conclusion: ah plus proves to have better sealing ability with minimal dye penetration when compared to other endodontic sealers. key words: apical microleakage, dye penetration, gutta percha, root canal sealer. core filling materials. it should be radiopaque, act as lubricant, possess antibacterial properties, able to 2 , 1 flow easily into surface irregularities. an endodontic sealer is applied in conjunction with core filling material (gp), because the root canal system cannot be obturated completely by gutta-percha itself and avoid the infection of root canal by 1 providing seal both apically and laterally. sealers enhance the possibility of achieving an impermeable 4 seal and aids to act as fillers for canal irregularities. the leakage through a filled root canal occurs between the sealer and dentine interface, or the sealer and the gutta percha interface or through 5 voids within the sealer. although hermetic seal is not always possible with today's sealers, a fluid-tight seal 1 is at the very least preferable. the sealers used in root canal treatment are usually divided into groups depending on their constituents, for example sealers based on zinc oxide, sealers based on calcium hydroxide, glass ionomer cement sealers, formaldehyde containing sealers as well as 8 resin-based sealers. despite the tremendous progress, until today no material meets all re q u i re m e nt s a n d d e s i ra b l e p ro p e r t i e s to introduction the endodontic treatment comprises of eradication of bacterial load in the root canal and filling of the 1 entire root canal system three dimensionally. the anticipated outcomes of endodontic treatment rest on mechanical instrumentation, root canal disinfection, eradication of pathogens, absolute debridement of pulp remnants as well as filling the entire root canal. root canal filling should adequately seal the root canal and hinder the oozing of fluid into the root canal. thus, it stimulates the resolution of pathologies in the periapical area and ensures the cementum deposition to achieve the 1 biological seal. ideally root canal sealer should provide satisfactory adhesion between itself, root canal walls and the an in vitro study of sealing ability of commercially available root canal sealers wajahat hussain, amjad hanif correspondence: dr. amjad hanif associate professor department of dental materials peshawar dental college, peshawar e-mail: amjadhanif283@hotmail.com department of dental materials peshawar dental college, peshawar received: june 30, 2022; revised: january 03, 2023 accepted: january 11, 2023 sealing ability of root canal sealersjiimc 2023 vol. 18, no.1 9https://doi.org/10.57234/jiimc.march23.1388 hermetically seal the root canal system. apical leakage is still a common experience in root-filled teeth, which raises concern about the quality of obturation obtained with the presently available 7 root canal filling materials. literature search showed that many studies have been conducted in the past to determine the sealing ability of various commercially available sealers by using different techniques due to established concept that improper obturation can lead to reinfection, but the comparison of the efficacy of the sealing ability of various root canal sealers currently available in the local market was not carried out in the past therefore the aim of the present study was to evaluate the ability of different commercially available endodontic sealers to seal the root canal. materials and methods th this was an in-vitro, study conducted from 10 st january 2021 to 31 march 2022, in department of dental materials peshawar dental college, after approval by the institutional review board (prime/irb/2021-359). the materials used in the study are given in (table. i). sample size was determined based on iso standard (# 11405). a total of fifty (50) intact non-carious human permanent mandibular premolar teeth were selected. teeth were divided randomly into four experimental and one control group (n=10) denoted by eg1, eg2, eg3, eg4 and cg5 respectively (table i). mandibular premolar intact non-carious human extracted permanent teeth were included while carious, fractured teeth, teeth with open apices, root resorptions and teeth with bifurcating canals were excluded from the study. all the teeth were placed in 5.25% sodium 6 hypochlorite solution for 48 hours to clean the surface of teeth. coronectomy of all selected teeth was done by fissure bur (1.59 – 1.6mm shank diameter) at the cemento-enamel junction in ultra push type high-speed hand piece. protaper universal rotary system (foshan, guangdong, china, iso specification ceo197) was used to prepare root canals 1mm short of the length, until reaching to a size f2 (master apical file). barbed broaches were used to extirpate the pulp tissue from. sodium hypochlorite (5.25%) and 5ml of edta was used to irrigate the canals, prior to final irrigation by 5ml distilled water. canals were dried with paper points. each of the sealer was manipulated according to manufacturer's directions and was introduced into the canal using the lentulo-spiral fitted. hand spreader was used, and entire canal was obturated. then the teeth in all the groups were placed in an incubator (intelligent laboratory incubator, china) at 37 °c and 100% relative humidity for one week. two to three layers of clear nail varnish was applied on the root surface. apical area (1-2mm) covered with sticky wax was left uncoated. roots were completely immersed into the 2% methylene blue aqueous solution for 1 week. then sticky wax and coating was removed from the surface while rinsing under a tap water. the roots were vertically s e c t i o n e d b y u s i n g t e e t h c u t t i n g s a w. stereomicroscope was used to determine apical dye 1 leakage. the specimens were scored as follows . 1: (1-3 mm); 2: (3-5 mm); and 3: (>5 mm). the bond between the sealer and the dentin was examined using scanning electron microscopy. using a diamond disc on teeth cutting saw machine, the roots were sectioned perpendicular to the longitudinal axis to get 2mm thick samples. the samples were polished with sand discs and washed with distilled water. then, the samples were dried and fixed on aluminium stubs. sputter coating of the samples was performed with a gold–palladium alloy before being scanned with sem (japan, jsm-it 100). statistical analysis was done by using software version 23 of spss. mean and standard deviation values were determined. kruskal wallis and mann whitney test was applied to determine significant values. p value less than 0.05 was considered as significant. results the mean and standard deviation values for endomethasone, sealapex, adseal, ah plus, and control are 4.48±0.99, 5.06±0.98, 5.02±0.89, 3.75±1.21, 6.54±0.47 mm respectively (table i), while the table ii shows the distribution of samples for dye leakage based on scoring criteria. kruskal wallis test specified statistically significant difference among the various experimental groups (p=0.039). dye penetration was highest (5.06mm) in sealapex (eg2) and lowest (3.75mm) in ah plus (eg4). adseal (eg3) showed less dye penetration than sealapex (eg2) (p=0.970). ah-plus (eg4) showed lower amount of dye penetration when sealing ability of root canal sealersjiimc 2023 vol. 18, no.1 10 https://doi.org/10.57234/jiimc.march23.1388 compared to endomethasone (eg1), sealapex and adseal (eg3) (p<0.05). when endomethasone sealer was compared with sealapex, adseal and ah plus, no statistically significant difference was found (p>0.05). similarly, comparing sealapex (eg2) to adseal (eg3), no statistically significant difference was observed (p > 0.05). while comparing sealapex sealer with ah plus sealer, statistically significant difference (p < 0.05) was found. similarly, when adseal (eg3) was compared with ah plus (eg4), a statistically significant difference (p < 0.05) was noted. in sem analysis, endomethasone showed no gap (good adaptation) between the sealer and dentin at the interface. sealapex, showed gap (poor adaptation) between the dentin and sealer. epoxy resin based endodontic sealer (adseal) displayed no gap (reasonable adaptation) between dentin and sealer. also, ahplus displayed no gap (good adaptation) between the sealer and the dentin. sealer (50% had a score of 2 and the rest scored 3). the results of this study demonstrated that leakage was present in the apical area, between root canal walls and the sealers, between the sealer and gutta percha, and through the sealer. the dye penetration inside the sealers also indicated leakage in the sealer's body, opening up another avenue for leaking. the results of this study were also supported 15,16 by previous studies that all root canal fillings leak. the results of apical micro leakage are influenced by numerous factors. besides the sealing ability and properties of root-end materials, the technique of assessment, root canal morphology and the diameter of the root canal may influence the results 1 7 of sealing ability. several approaches of microleakage assessment have been employed, such as fluid filtration, dye penetration, bacterial leakage, radioactive isotopes and others. it is essential to highlight that no standard method of microleakage assessments exists, and there is a lack of technical standardization even when the same methodology is employed. the lack of standardization is possibly the table i: descriptive analysis of experimental groups showing mean, standard deviation, minimum and maximum values table ii: distribution of samples as per the dye leakage scoring criteria figure 1: (a). endomethasone, sem with 33x magnification. 'arrow' indicates no gap (good adaptation) between the dentin and sealer at the interfaces. (b) sealapex, sem with 230x magnification. 'arrow' indicates gap (poor adaptation) between the dentin and sealer (c) adseal, sem with 43x magnification. 'arrow' indicates no gap (reasonable adaptation) between the dentin and sealer. (d) ah plus, sem with 33x magnification. 'arrow' indicates no gap (good adaptation) between the dentin and sealer. s: sealer d: dentine discussion in experimental groups, mean dye penetration values for each group revealed that dye penetration was highest in sealapex sealer (60% of sealapex sealer had score of 2 and 40% percent had score of 3) and lowest in ah plus. afterwards, adseal sealer showed dye penetration less than sealapex (50% of adseal sealer had score of 2 and remaining 50% of adseal sealer had score of 3). ah plus shows lowest amount of dye penetration (50% of ah plus sealer had score of 2, 40% had a score of 1 and remaining 10% had score of 3) as compared to endomethasone sealing ability of root canal sealersjiimc 2023 vol. 18, no.1 11https://doi.org/10.57234/jiimc.march23.1388 main reason why there are so many different 17 methods to investigate the same phenomenon. in this study, sealapex demonstrated significantly higher leakage than ah plus sealer. sealer's porous nature allows for significant water intrusion, promoting the powder-binder reaction to continue. other study reported insignificant difference 1 between the sealapex and ah plus in apical leakage. because of water sorption due to the presence of calcium oxide, sealapex expands in volume during the setting process. this property may increase the solubility of the substance, increasing the danger of 19 leaking over time. zoe-based sealer (endomethasone) displayed the highest dye penetration when compared to sealer based on epoxy resin (ah plus), which is in 1,20 agreement with the previous findings. earlier studies have reported that sealers based on zoe have not good dentin adhesion and sealing qualities 21,22 and is highly permeable. the findings of the current study demonstrated that ah plus had a better sealing ability than the other types of sealers. these results are similar with the 6 findings of the patni et al which revealed that ahplus has a superior capability to seal than traditional zinc oxide eugenol and calcium hydroxide-based sealers. superior adaptation of ah plus is due to its ability to bond to root dentine chemically by reacting 10 with exposed amino groups in collagen. resin-based endodontic sealers (adseal) did not provide a superior seal than zoe-based sealers in the current study. this is since the specimens were kept at temperature and humidity level similar to the 23 human body . in the current study, ah plus was found to give low dye absorption values, implying less dye leakage, and impacting sealer's strategic advantage over the other sealers. finally, dye was seen in all sealers, regardless of kind, implying that a full airtight seal is impossible to achieve with contemporary sealers. linear dye penetration measurement is the most frequent, simple, and quick approach for 1,18 determining sealant microleakage. for obturation, lateral compaction technique was utilized in this work as it has been used as standard for 10 comparison . methylene blue (mb) is a commonly used dye with concentrations of 0.25, 1 and 2%. we selected 2% mb in our study, because it was the most 13 prevalent concentration and a reliable method. it was reported that mb penetrates more deeply along the root canal filling and exhibits greater penetration 12,14 than india ink due to low molecular. t h e s e m o f t h e e n d o m e t h a s o n e s e a l e r demonstrated uneven surface and a uniform distribution of components (fig. 1). the surface was entirely covered by huge granules. sem image of adseal sealer display rough surface and a homogenous distribution of components. it contains particles of variable morphology as shown in (fig. 1). 24 cakici and his coworkers stated, that for an epoxy resin sealer (adseal & ah plus), the apical area exhibits the highest bond strength when compared to other areas. ah plus, an epoxy resin-based sealer, displayed smooth surface and a consistent distribution of elements, with particles having 25 spherical shape and similar size. balaguerie et al reported deeper flow of ah plus sealer in tubules on sem examination. in this study, humidity and heat factor were not investigated; however, they are known to alter sealer flow and penetration. because o f t h e i r c r e e p c a p a b i l i t y a n d e x t e n d e d polymerization duration, epoxy-based sealers penetrate easier into micro irregularities. one of the limitations of this study was that it used the traditional dye-penetration approach. dye penetration approach is an invasive approach since the specimens were split vertically and during the splitting, there was a possibility that core material would be extruded from the specimens, influencing the outcome of this study. also, the linear dye penetration technique does not provide information about the volumetric data of the tracer penetrating the interface between the root filling and the root canal wall. additionally, due to lack of a simulated p e r i o d o n t a l l i g a m e n t a n d o t h e r c l i n i c a l characteristics, data obtained in in-vitro studies may not be applicable and instantly extrapolated to clinical conditions. furthermore, there is still a need for future work to compare different canal preparation methods, sealers and obturation skills since all of these factors may influence the seal of the root canal. it is also essential not to overlook the biocompatibility and cytotoxicity. other causes of leakage in this study might be linked to the presence of entrapped air or atypical anatomy which was not investigated in our sealing ability of root canal sealersjiimc 2023 vol. 18, no.1 12 https://doi.org/10.57234/jiimc.march23.1388 work and may be topic of research in future studies. conclusion within the limitation of this study, it can be concluded that among all the commercially available root canal sealers tested, epoxy resin-based sealer (ah plus) proves to have better sealing ability and good adaptation between the dentin and sealer at the interfaces with least amount of dye infiltration, implying minimal dye penetration and microleakage. references 1. ballullaya sv, vinay v, thumu j, devalla s, bollu ip, balla s. stereomicroscopic dye leakage measurement of six different root canal sealers. journal of clinical and diagnostic research: jcdr. 2017 jun;11(6): zc65-zc68. 2. asawaworarit w, pinyosopon t, kijsamanmith k. comparison of apical sealing ability of bioceramic sealer and epoxy resin-based sealer using the fluid filtration technique and scanning electron microscopy. journal of dental sciences. 2020 jun 1;15(2):186-92. 3. alghamdi f, abduljawad f. comparative evaluation of the apical sealing ability among different root canal obturation techniques and endodontic sealers by using fluid filtration method: a systematic review. idjsr. 2019 apr 15;7:1-8. 4. alenazy ms, mosadomi ha, al-nazhan s, rayyan mr. clinical considerations of nanobiomaterials in endodontics: a systematic review. saudi endodontic journal. 2018 sep 1;8(3):163-169. 5. khan ta, 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study. conservative dentistry and endodontic journal. 2020 sep 16;5(1):11-4. 19. moradi s, lomee m, gharechahi m. comparison of fluid filtration and bacterial leakage techniques for evaluation of microleakage in endodontics. dental research journal. 2015 apr 4;12(2). 20. anitha v. evaluation of the sealing ability of gutta percha with bioroot rcs, mta fillapex and sealapex: an sem study (doctoral dissertation, ragas dental college and hospital, chennai). 2020. 21. reddy n, teja gv, gowda mv. apical sealing ability of four different root canal sealers: an in vitro study. journal of international oral health. 2015 dec 1;7(12):47. 22. al-jawady j. evaluation of bioceramic sealer apical seal in dry and wet condition. journal of general dentistry. 2021 oct 27;3(1):1-3. 23. mokhtari h, shahi s, janani m, reyhani mf, zonouzi hr, rahimi s et al. evaluation of apical leakage in root canals obturated with three different sealers in presence or absence of smear layer. iranian endodontic journal. 2015;10(2):131. 24. cakici f, cakici eb, ceyhanli kt, celik e, kucukekenci ff, gunseren ao. evaluation of bond strength of various epoxy resin-based sealers in oval shaped root canals. bmc oral health. 2016 dec;16(1):1-5. 25. balguerie e, van der sluis l, vallaeys k, gurgel-georgelin m, diemer f. el hachem r, khalil i, le brun g, pellen f, le jeune b, daou m, el osta n, naaman a, abboud m. dentinal tubule penetration of ah plus, bc sealer and a novel tricalcium silicate sealer: a confocal laser scanning microscopy study. clinical oral investigations. 2019 apr;23(4):1871-6. sealing ability of root canal sealersjiimc 2023 vol. 18, no.1 13https://doi.org/10.57234/jiimc.march23.1388 conflict of interest authors declared no conflicts of interest. grant support and financial disclosure authors have declared no specific grant for this research from any funding agency in public, commercial or nonprofit sector. data sharing statment the data that support the findings of this study are available from the corresponding author upon request. this is an open access article distributed under the terms of the creative commons attributionnoncommercial 2.0 generic license. sealing ability of root canal sealersjiimc 2023 vol. 18, no.1 14 https://doi.org/10.57234/jiimc.march23.1388 original�article abstract objective: to identify the causes and risk factors leading to maternal mortality through verbal autopsy in the district of rawalpindi, pakistan. study design: a retrospective, descriptive study. place and duration of study: the study was carried out in community department of foundation university medical college islamabad from january 05, 2019, to december 25, 2019. materials and methods: data of 105 women died of causes related to death during pregnancy/ delivery between 01 april 2013 and 30 april 2018 was retrieved from the office of district health officer (dho) rawalpindi. a verbal autopsy was conducted to determine cause of death and the possible risk factors, through a structured questionnaire that was filled by close relatives of the deceased women. analysis of data was done using spss version 25.0. results: the mean age of the patients was 31 years, and it ranged from 15 to 49 years. in 26.7% of mothers cause of death could not be determined. overall, the major and most obvious cause of maternal death was delivery related hemorrhage in 58% cases. out of these, antepartum hemorrhage was the commonest cause occurring in 43.8% of the total cases. postpartum hemorrhage occurred in 11.4% cases, while fatal hemorrhage during the delivery occurred in 2.8% mothers. eclampsia was the next common cause that occurred in 11.4% mothers. difficult and prolonged labour was found to be cause of death in 2.8% cases, while 0.95% died of sepsis. among the risk factors, lack of antenatal care emerged as the leading risk factor, present in 62% mothers, followed by anemia being present in 46.6% mothers. multi-parity was found to be the next common risk factor being present in 26.6% mothers. reduced interval in successive pregnancies was found in 21% cases. systemic medical disorders like hypertension, renal disorders, diabetes mellitus, pneumonia, hepatic failure, were found in 6.66% mothers. history of complications in previous pregnancies was present in 3.8% cases. history of lack of proper medical services in the hospital as possible factor leading to death was present in only 5 (4.8%) cases. conclusion: hemorrhage related with delivery, especially the antepartum hemorrhage emerged as the commonest cause of maternal mortality, followed by eclampsia. at the same time, lack of antenatal care and anaemia emerged as the commonest risk factors in this regard. key words: delivery related hemorrhage, maternal mortality, maternal risk factors, unknown maternal deaths, verbal autopsy. sixth most populous country of the world as per the latest census conducted in the year 2017. the population growth rate recorded was 2.10 in 2016, and since then it has been increasing. this creates an overall burden on the economy of the country, where health indicators like maternal mortality remain a matter of great concern. most of the developing countries are facing maternal mortality as a major health issue. it is considered to be one of the top priority health issues in the formulation of health policies and research strategies in the developing world. it is a bitter reality that most of maternal deaths take place in the developing world and ironically, a vast majority of introduction pakistan, having a population of over 20 billion, is the verbal autopsy of maternal mortality in rawalpindi district 1 2 3 4 5 mahum khizar , aimen hafeez , ayesha saif khan , kinza awais , komal rashid correspondence: dr. mahum khizar bloomberg school of public health johns hopkins university, baltimore, united states e-mail: mahummirza99@outlook.com 1 mph student in bloomberg school of public health johns hopkins university us, 2 resident radiologist cmh rawalpindi, 3 cmo cmh risalpur, 4 mo hearts international hospital rawalpindi, 5 mo cda capital hospital islamabad received: august 10, 2022; revised: november 06, 2022 accepted: november 08, 2022 maternal mortality jiimc 2022 vol. 17, no.4 250 doi: https://doi.org/10.57234/1484 these are preventable. according to who, any non-accidental maternal death, occurring during the pregnancy or childbirth or within 6 weeks of delivery, is considered as 2 maternal mortality. it depicts the health and development status of a country. unfortunately, in pakistan it figures around 30000 maternal deaths, which is a very high number like any other developing country.thus the maternal mortality rate in pakistan is calculated as 276 per 100,000 live births th and it stand as 147 in the world for the year 2017. pregnancy related hemorrhage is found to be the commonest cause of maternal mortality, being present in 47.7% deaths. highest incidence of 35% was seen in 25–29-year age group. causes and risk factors leading to maternal mortality in developing countries vary greatly. according to who 75% of the causes of maternal mortality include hemorrhage, mostly post-partum, postpartum sepsis and eclampsia/ pre-eclampsia. though substantial decrease in maternal mortality in pakistan has occurred since 1990, but is far lower than the targets set by the un and also quite low as compared to other developing countries of the region. pakistan has also been declared as the most risky place for a birth to take place. this lack of achievement of the target of low maternal mortality rate is mostly due to many of the socioeconomic reasons like poverty, low female literacy rate, poor nutrition, and lack of access to the health facilities etc. a decrease of 44% in the maternal mortality has been observed all over the world from 1990 to 2015. it has been observed that almost all of the maternal deaths occur in the low income countries. even minimal modifications in the sops can lead to a decrease of 80% of maternal deaths even in the poor countries. un sdgs of less than 70 per 100 000 maternal deaths is achievable by implementing a better accountability system. many of the countries are moving towards achieving this goal by improving their accountability systems by introducing verbal autopsies and external enquiries to take measures to reduce maternal mortality. it is an irony that most of the factors leading to maternal mortality can be prevented simply by proper registration of the patients so that information can be obtained about these mothers. even in developed countries like uk, the actual number of maternal mortality is 60% higher than the reported figure. hence it is not surprising that a lot of maternal deaths in pakistan are not reported which makes it difficult to determine the exact numbers currently. this is mainly due to the lack of reporting of births and deaths to proper governing bodies. in order to fill the missing information, verbal autopsy is considered as an effective tool. verbal autopsy is defined by w h o as “a method to ascertain the cause of a death based on an interview with next of kin or other caregivers” and it is applicable on all those deaths where a death is not formally medically certified. hence verbal autopsy provides an effective alternate tool to record causes of maternal deaths and has been implemented at various levels. as many of the cases of maternal mortality are neither nor reported, it was felt that verbal autopsy can be carried out in such cases to determine the cause of maternal mortality. hence a retrospective, descriptive study was carried to find out the causes and risk factors leading to maternal mortality, through verbal autopsy in the district of rawalpindi, pakistan. materials and methods a retrospective descriptive study was carried out in community medicine department of foundation university medical college from january 05, 2019, to december 25, 2019. data of 105 women died of the causes related to death during pregnancy/ delivery was retrieved from the office of district health officer (dho) rawalpindi, pakistan by convenient sampling technique and evaluated. approval of the institutional ethical committee for this study was obtained beforehand. permission was obtained from dho office for this study. informed consent of the next of kin was obtained and data confidentiality was assured. data of all the women, who died of the causes related to pregnancy or delivery, from april 2013 to april 2018 was included in the study. the data was collected by the team of authors along with a senior staff nurse detailed by the dho. data of those subjects who could not be traced due to improper address entry or those women whose immediate family members did not cooperate during the study, were excluded. through a modified version of questionnaire, developed by the national maternal mortality jiimc 2022 vol. 17, no.4 251 doi: https://doi.org/10.57234/1484 committee for maternal and neonatal health (ncmnh) and validated by national institute of population studies pakistan & unicef, a verbal autopsy was conducted to determine the cause of death and the risk factors. this questionnaire was translated in urdu and was filled by a two-member team, comprising of a medical officer and a staff nurse who were well versed in local language, while interviewing close relatives (next of kin or those who remained close to the deceased during her illness) of the deceased women at their homes/ villages in selected rural and urban areas of rawalpindi district. in some cases, help of the local administration was also sought to convince the relatives for the interviews. analysis of data was done using spss version 25.0 and was analyzed for frequencies and percentages. results the mean age of the patients was 31 years, and it ranged from 15 to 49 years. regarding causes of maternal deaths as shown in figure: 1, in 28 (26.7%) mothers, cause of death could not be determined even after verbal autopsy. overall, the major and most obvious cause of maternal death was delivery related hemorrhage in 61 (58%) cases. out of these, antepartum hemorrhage was the commonest cause occurring in 46 (43.8%) of the total cases. postpartum hemorrhage occurred in 12 (11.4%) cases, while fatal hemorrhage during the delivery occurred in 3 (2.8%) mothers. delivery related hemorrhage was followed by eclampsia (fits) as the next common cause that occurred in 12 (11.4%) mothers. difficult and prolonged labour was found to be cause of death in 3 (2.8%) cases. one (0.95%) mother died of sepsis. among the risk factors, as shown in figure: 2, lack of antenatal care emerged as the leading risk factor, as 62 mothers (59%) had only 1-4 antenatal visits, while 2 mothers (1.9%) never visited antenatal clinic. anaemia followed it as the next commonest risk factor. it was present in 49 (46.6%) mothers. multiparity (≥ 4 children) was found to be the next common risk factor being present in 28 (26.6%) mothers. interval with previous pregnancy of 1 year or less was found in 22 (21%) cases. history of medical disorders like hypertension, renal disorders, diabetes mellitus, pneumonia, hepatic failure, was found in 7 (6.66%) mothers. history of pregnancy related complications in previous pregnancies was found in 4 (3.8%) cases. regarding lack of proper medical services in the hospital as possible factor leading to death, the answer was affirmative in only 5 (4.8%) cases. figure 1: causes of maternal mortality figure: 2 risk factors for maternal mortality discussion maternal mortality is one of the major health issues in the developing world, including pakistan. pakistan ranks 126 out of 149 on hdr-gender inequality index due to the low women empowerment, limited contributions, and lack of maternal healthcare facilities. data collection regarding maternal mortality serves to monitor and lower the rate. the purpose of our research was to identify the causes and risk factors leading to maternal mortality. hemorrhage, related to delivery, emerged as the commonest direct cause of maternal mortality, followed by eclampsia. among the risk factors, anaemia emerged as the biggest risk factor followed by multi-parity and reduced interval between successive pregnancies respectively. as shown by our findings, most of the causes of maternal mortality are modifiable and preventable. this information can help us elevate the health status of mothers in our country. maternal mortality jiimc 2022 vol. 17, no.4 252 doi: https://doi.org/10.57234/1484 results of our study correspond to the study carried out by sami & baloch (2002) in which maternal mortality ratio was calculated to be 560 out of 100000 live birds with delivery related hemorrhage accounting for 42% as the biggest cause of maternal deaths. similarly in another study carried out in four districts of afghanistan by bartlett et al (2005), delivery related hemorrhage emerged as the leading cause of maternal mortality in three of the four districts, as found in our study. yet in another study similar results showed hemorrhage to be the biggest cause of maternal mortality (36%) followed by eclampsia (17%). similarly, bhutta & black (2013) showed hemorrhage (22.9%) as the biggest cause of maternal mortality. in a similar study by perveen & ilyas (2017), eclampsia was shown as the most common cause of maternal mortality, followed very closely by hemorrhage. since this study was also carried out on a limited number of patients, such minor differences in data may not be considered very significant and the results are not much different than our study. in a study carried out in usa, after cardiac diseases, hemorrhage was still the most common cause of maternal mortality. results of most of these studies show hemorrhage as the most common or one of the most common causes of maternal mortality as shown in our study. a study conducted by akseer et al (2018) showed that though the millennium development goal (mdg) period saw immense achievements in health goals for improving child and maternal health, many of the muslim countries had much higher maternal mortality rates as compared to the rest of the world, due to very similar factors as shown in our study. a study carried out in jharkhand, india by khan & pradhan (2013) showed similar causes of maternal deaths as shown in our study, but this study attributed these deaths to preventable factors like ignorance, illiteracy, and lack of nursing facilities. according to yet another study by austin et al (2014), multiple factors contribute to maternal mortality, including lack of medical facilities and lack of affordability of the available health facilities, and of course illiteracy further aggravating it. as regards the risk factors, in our study, lack of antenatal care emerged as the biggest risk factor, followed by anaemia, multi-parity and reduced interval among successive pregnancies respectively. in a study by mahmood et al (2018) multiparity was shown as the biggest risk factor for maternal mortality, although it was the third common risk factor in our study. similar to our study, astuti et al (2017) also show lack of antenatal care as one of the important risk factors in maternal mortality. similar results regarding risk factors were shown in a study by masturoh et al (2017) that showed lack of antenatal care and obstetric problems as the leading risk factors in maternal mortality. in yet another study, bauserman et al (2015) showed lack of education, lack of antenatal care, obstetric causes and hypertension as the leading risk factors in maternal mortality. yet another study by diana et al (2020) showed anaemia and nutritional status, lack of antenatal care and obstetric complications as the leading risk factors for maternal mortality. it is evident from these comparisons that results of our study also correspond to these studies regarding causes and factors leading to maternal mortality. our study has certain limitations too. a major setback of verbal autopsy is the lack of requisite resources needed to successfully conduct it on a large scale. due to this shortcoming, we were compelled to keep the sample size limited to one district only. hence inference from this study cannot be generalized. moreover, reaching out for data collection in rural communities is particularly difficult owing to unfavorable conditions brought on by the reluctance of the locals to associate with outsiders regarding such sensitive matters. clearly, a general sentiment of mistrust towards outsiders prevails among these tightknit communities. this is reflected by the fact that family members or relatives of the deceased women were not very willing to give interviews. furthermore, at times, the volunteers were unable to recall events of the pregnancy that are pertinent to our research & many questions remained unanswered. in the light of our study following recommendations are made: 1. employment of trained birth attendants (tba): most of the deliveries in the developing countries like pakistan are carried out at domestic set up, in the absence of any skilled attendant. therefore, training of the traditional birth attendants should be ensured with adequate knowledge of midwifery skills along maternal mortality jiimc 2022 vol. 17, no.4 253 doi: https://doi.org/10.57234/1484 with emergency obstetric care so that the complications of labour are minimized. 2. proper prenatal care should be ensured to minimize risks and complications. conditions like hypertension, malnutrition, iron deficiency anemia should be addressed in prenatal assessments. free, disposable and easily usable delivery kits should be made available to avoid any transmission of infection from mother or surroundings to the newborn. 3. good antenatal care and obstetric care must be ensured. 4. most importantly an awareness campaign should be launched at national level to improve quality of life especially in girls and women. they should be educated about health, family planning and hygiene. moreover, communitybased intervention packages may be introduced to reduce maternal mortality as shown in a study by lassi & bhutta (2015). conclusions hemorrhage related with delivery, especially the a n t e p a r t u m h e m o r r h a g e e m e r g e d a s t h e commonest cause of maternal mortality, followed by eclampsia. at the same time, lack of antenatal care and anaemia emerged as the commonest risk factors in this regard. these are preventable and treatable causes. this information can help us elevate the health status of mothers in our country. although we could not establish cause of mortality in 28 patients even after the verbal autopsy, still this study establishes verbal autopsy as an effective tool in getting missing information about causes of maternal mortality. references 1. pakistan bureau of statistics. pakistan, 2018 2. national institute of population studies (nips) [pakistan] and icf. 2020. pakistan maternal mortality survey 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mortality. 2020, j public health res; 9 (2): 195-198. doi: 10.4081/jphr.2020.1842. pmid: 32728581; pmcid: pmc7376486. 30. lassi zs, bhutta za. community-based intervention packages for reducing maternal and neonatal morbidity and mortality and improving neonatal outcomes. cochrane database of systematic reviews, 2015; 3: art no cd007754. doi: 10.1002/14651858. cd007754.pub3. maternal mortality jiimc 2022 vol. 17, no.4 conflict of interest authors declared no conflicts of interest. grant support and financial disclosure authors have declared no specific grant for this research from any funding agency in public, commercial or nonprofit sector. data sharing statment the data that support the findings of this study are available from the corresponding author upon request. this is an open access article distributed under the terms of the creative commons attributionnoncommercial 2.0 generic license. 255 doi: https://doi.org/10.57234/1484 original�article abstract objective: this case series was carried out to determine the efficacy of ultrasound guided foam sclerotherapy as first line and minimally invasive treatment of varicose veins. study design: prospective case series. st place and duration of study: department of vascular surgery, combined military hospital, malir from 1 st january 2020 to 31 march 2021. materials and methods: total one hundred patients with varicosities mainly of great saphenous vein (gsv) were included after detailed history and examination. ultrasound doppler was done to rule out deep venous thrombosis (dvt) and any secondary reason for varicose vein. patients were followed up after 3 days, 10 days, 1month and 3 months with a doppler ultrasound. results: one hundred patients and 130 legs were studied. age ranges from 30-60 years with mean of 39.75 years, 70 (70%) of the patients were males and 30 (30%) were females. 98 legs (75.38%) had varicosities of gsv, 10 legs (7.692%) with mixed great and small saphenous vein and 22 legs (16.92%) with isolated small saphenous vein. 25 patients (25%) developed pain at cannula site, 3 patients (3%) had bradycardia following procedure and 4 (4%) developed ulceration on skin at the site of cannulation. all patients were followed up for 3 months with a doppler ultrasound and no recurrence was found post procedure. average return period to normal function and work was 15 days. in terms of leg pain and physical functioning, patients who underwent intervention achieved health better in short term. conclusion: ultrasound guided foam sclerotherapy is safe, least complicated, and efficacious management for varicose veins with minimal chance of technical failure. this being an outpatient procedure saves time and space for arterial casualties of a vascular surgeon. key words: deep venous thrombosis (dvt), great saphenous vein (gsv), small saphenous vein (ssv), sodium tetradecyl (std), ultrasound guided foam sclerotherapy (ugfs). subcutaneous veins not belonging to the main branches of the great or small saphenous vein. 3 telangiectasia are intradermal venules of <1 mm. underlying cause include weak or damaged valves of vein and are diagnosed by clinical examination in addition to ultrasound venous doppler for level of incompetent valve. risk factors include obesity, lack of exercise and leg trauma. they are significantly associated with increasing age, weight, female sex; prolonged standing, family history, number of 4 pregnancies and child birth. in history of surgeries performed for varicose veins preliminary method was ligation of the saphenofemoral junction, stripping up to knee level combined with phlebotomies and end up with the rapid rise of minimally invasive procedures, such as foam sclerotherapy, radiofrequency ablation, and 5 endovenous laser therapy. till now, gold standard treatment of varicose vein still is surgical ligation with stripping of the insufficient vein, however it may seldom be associated with substantial postintroduction varicose veins are tortuous, twisted, elongated 1 2 superficial veins. , the outnumbered group of varicose veins is primary; secondary varicose veins are mainly caused by conditions such as deep vein thrombosis, pregnancy and pelvic malignancies. truncal varices are varicosities in the line of great or small saphenous vein or their major branches; however reticular veins are dilated tortuous evaluation of foam sclerotherapy as minimally invasive and first line treatment of varicose veins in military setup 1 2 3 4 5 6 rafia zafar , khalid siddiqui , arslan sharif malik , muhammad imran , hatim khalid , khalid ibrahim correspondence: dr. rafia zafar trainee surgery department of surgery combined military hospital malir, karachi e-mail: rafia.zafarr@gmail.com 1,2,3,4 department of surgery combined military hospital malir, karachi 5 department of surgery combined military hospital, rawalpindi 6 department of surgery combined military hospital, jhelum received: august 21, 2021; revised: june 02, 2022 accepted: june 10, 2022 foam sclerotherapy as minimally invasive treatment for varicose veinsjiimc 2022 vol. 17, no.2 76 operative complications as bleeding, groin infections, thrombophlebitis and saphenous nerve 6 damage. sclerotherapy was introduced first time in 1920 and remained modality of treatment for next two decades, later due to high recanalization rates it was abandoned. tessari rejuvenated this method in late 90's. sodium tetradecyl sulphate (std), polidocanol, 5% alcohol and hypertonic saline are 7 generally used as sclerosant. to the best of author's knowledge the role of foam sclerotherapy in military setup was not extensively studied previously and thus no relevant literature was available. hence there was a need to address this research gap which provided the rationale for this study. materials and methods after hospital ethics committee approval, a prospective study design of case series with consecutive sampling for data collection was made. it was carried out over sample size of one hundred patients; data was collected primarily by vascular st st surgery team from 1 january 2020 to 31 march 2021 at combined military hospital, karachi. inclusion parameters were age between 30-60 years and symptomatic primary varicose veins. patients with secondary varicose vein, active or previous history of deep venous thrombosis, peripheral vascular disease, infection, active ulcer, thrombophlebitis, pulmonary embolism, pregnancy, patent foramen ovale and allergy to sclerosant were excluded from study. a comprehensive history was recorded about job type, duration, any history of dvt, aggravating or relieving factors affecting symptoms and any prior treatment for varicose vein. venous doppler ultrasound was advised to exclude dvt and establish the level of incompetence prior to booking for procedure. all cases were evaluated according to c l i n i c a l , e t i o l o g i c a l , a n a t o m i c a l a n d pathophysiological (ceap) classification with c3 and below selected for foam sclerotherapy. all cases were carried out in minor operation theater of vascular surgery opd. sodium tetradecyl sulphate (std) was used as sclerosant in every patient with maximum dose of 4ml. foam was mixed in 1:4 (std: air) ratio using modified tessari method by adding 1ml of liquid sclerosant and 4ml air in 5cc syringe.(8) ultrasound guided marking of main trunk and varices along with cannulation were done using 20g butterfly needles in slight reverse trendelenberg position with subsequent injection of foam in the cannulated sites. multilayered compression bandage was applied while keeping leg elevated at 45 degree. each of the patients was given intravenous 5000 i.u. of heparin at the end of the procedure followed by walking for few minutes. compression bandage was replaced by leg compression stockings on third day and continued for 2 weeks. re-checkup was carried out after 10 d ays to e va l u ate c o m p l i c at i o n s l i ke dv t, thrombophlebitis and pain. patients were advised to resume duty with light work for 5-7 days post procedure. follow-up was done at 1 month and 3 months for assessment of failure of treatment and extent of re-cannulation if present. documentation was done following results of ultrasound doppler for successful occlusion of varicose veins, any need of further session of ugfs, dvt or thrombophlebitis requiring medical intervention. this is a non-parametric study in which spss was used for data analysis and p value was not required since it's a case series. results patients examined in this study were exclusively military personals and their families. 100 consecutive patient and 130 legs were randomized. 70 (70%) were males and 30 (30%) were females with age ranging from 30-60 years and mean age of 39.75 years. the percentage distribution of patients with respect to clinical stage of the disease at the time of presentation is shown in (figure 1). varicose veins in region of gsv (75.38%), ssv (16.92%) and mixed type (7.692%) were noted. individuals with bilateral and recurrent disease were also included to be treated simultaneously in single session (table i). the number of legs with satisfactory occlusion of varicose veins recorded after one month of first session of foam sclerotherapy was 107 (82.30%), whereas 23 legs (17.69%) required second session of foam sclerotherapy for complete occlusion (figure 2). reason for failure or partial occlusion was either noncompliance to preventive measures prescribed or prolonged standing. all patients were followed up for 3 months with a doppler ultrasound and no recurrence was found post procedure. 25 patients (25%) complained of pain over the insertion site of cannula on first 10-day follow-up, which was foam sclerotherapy as minimally invasive treatment for varicose veinsjiimc 2022 vol. 17, no.2 77 discussion varicose veins are one of the most prevalent disorder of the vascular system among adults with 20–25% occurrence of visible varicosities in women and 9 10– 15 % in men . d elay in t reat ment ca n subsequently result into a number of complications, including venous ulceration and thrombosis. the 10 prone areas for development of varicose veins in saphenous tributaries suggest that there are s u s c e p t i b l e s i t e s w h e re c h a n g e s i n w a l l , hemodynamic pressure and orthostatic posture can initiate reflux. reflux of gsv calf tributaries are more common where majority of the limbs belong to 11 classes c1 and c2 of the ceap classification. in our military setup, soldiers face long orthostatic postures which results in early development and increased prevalence of varicose as compared to others. combined military hospital is a tertiary care referral center for vascular surgery which provides management for peripheral arterial diseases, vascular access surgery for hemodialysis, civilian and military vascular trauma, lymphatic, and venous diseases, in addition to it, heavy turnover of trauma cases requiring surgical and vascular attention and low availability of operation theaters; ugfs serves as safest, less time consuming, outpatient department based and definitive treatment option. many studies were conducted to compare the long term outcome of ugfs with great saphenous vein 12 stripping, in one study n. shadid concluded from randomized control trial of 230 patients treated by ugfs and 200 by gsv stripping , 2-year probability of recurrence was similar in the ugfs and surgery groups: 11.3% (24 of 213) and 9% (16 of 177). they concluded at 2-year follow-up, ugfs was not inferior to surgery and is a potential cost-effective approach which supports our aim of using foam sclerotherapy as first line method. the use of sodium tetradecyl sulphate in this study was primarily because of its superiority over other sclerosant in terms of better elimination of venous reflux, improved cosmetic appearance, minimum post procedure pain and fewer failure rates. efficacy rates of foam sclerotherapy over alternatives measures well with the values published in most studies. studies that compared foam to conventional sclerotherapy found negligible difference in failure rate or recurrence in varicosities. similarly recanalization rate was also not fig. 1: clinical stages at the time of presentation fig. 2: number of sessions of ugfs fig. 3: incidence of complications table i: demographic characteristics of patients foam sclerotherapy as minimally invasive treatment for varicose veinsjiimc 2022 vol. 17, no.2 completely settled by consecutive follow-up visits. 3 patients (3%) had bradycardia during the procedure and 4 patients (4%) developed wound at cannulation site after procedure which was managed conservatively (figure 3). 78 13,14 different between the two treatments. 15 a recent analysis by darval et al concluded advantages of minimally invasive ugfs over conventional surgery with respect to decrease in morbidity and faster recovery times. assessment was done by analyzing the result of questionnaire sent to patients of both groups after 4 weeks of procedure. individuals who had surgery were more likely to have substantial bruising and pain. those who underwent ugfs, 43.2% returned to work within a day compared with none who had surgery. patients who had ugfs were more likely to resume driving within 4 days with less association of pain, analgesia requirements and time off-work. number of sessions required for 82.30% of the patients for optimum elimination of varicosities in present study was single, which did not cross the mean volume of 4ml of std required for foam formation in 1:4 ratio. the protocol allowed an extra session if the gsv was found to be patent during the first month which resulted in a smaller number of failure rates in the long run, that can be due to larger volume of foam used than the mean of 4ml per leg. at a consensus meeting in europe it was recommended not to use 16 volumes of foam above 10ml per session. 17 stücker et al in his study appreciated the effectiveness of foam sclerotherapy over liquid. it is important to select the correct concentration and the correct foam volume and offers possibility of using lower sclerosant concentrations than with 18 liquids. jia et al did a systematic review to assess safety and effectiveness of foam sclerotherapy over sixty-nine studies which concluded that rate of critical adverse events, including pulmonary embolism, deep vein thrombosis and visual disturbance were less than 2 per cent. the median rate of headache, thrombophlebitis was less than 5% and pain at the site of injection measured 25.6%. individuals treated with ugfs experienced minimum post-operative pain, it also influences recovery, less time off work and early return to 19,20 normal work confirming previous observations. conclusion ultrasound guided foam sclerotherapy serves as a minimally invasive and less time-consuming method for treatment of varicose vein. due to high prevalence in our military setup this modality of treatment shares workspace of vascular surgeon with promising results and minimal technical failure rate. references 1. campbell b. varicose veins and their management. british m e d i c a l j o u r n a l . 2 0 0 6 ; 3 3 3 ( 7 5 6 2 ) : 2 8 7 . doi:10.1136/bmj.333.7562.287 . 2. bailey & love's short practice of surgery, 27th edition. 2018. 3. london n, nash r. abc of arterial and venous disease: v a r i c o s e v e i n s . b r i t i s h m e d i c a l j o u r n a l . 2 0 0 0 ; 3 2 0 ( 7 2 4 6 ) : 1 3 9 1 1 3 9 4 . d o i : 1 0 . 1 1 3 6 / bmj.320.7246.1391 . 4. laurikka jo, sisto t, tarkka mr, auvinen o, hakama m. risk indicators for varicose veins in fortyto sixty-year-olds in the tampere varicose vein study. world journal of surgery. 2002;26(6):648-651. doi:10.1007/s00268-001-0283-1. 5. van den bremer j, moll fl. historical overview of varicose vein surgery. annals of vascular surgery. 2010. doi:10.1016/j.avsg.2009.07.035. 6. rasmussen lh, lawaetz m, bjoern l, vennits b, blemings a, eklof b. randomized clinical trial comparing endovenous laser ablation, radiofrequency ablation, foam sclerotherapy and surgical stripping for great saphenous varicose veins. british journal of surgery. 2011;98(8):1079-1087. doi:10.1002/bjs.7555. 7. khan kharl ra, khan ni, pervaiz hk, ali k, haider fe, sattar s, et al. foam sclerotherapy: an emerging, minimally invasive and safe modality of treatment for varicose veins. journal of ayub medical college, abbottabad. 2019;31(4 suppl 1):s641-s645. 8. xu j, wang y fei, chen a wei, wang t, liu s hua. a modified tessari method for producing more foam. springerplus. 2016;5(1):1-3. doi:10.1186/s40064-016-1769-5. 9. callam mj. epidemiology of varicose veins. british journal of surgery. 1994. doi:10.1002/bjs.1800810204. 10. chwała m, szczeklik w, szczeklik m, aleksiejew-kleszczyński t, jagielska-chwała m. varicose veins of lower extremities, hemodynamics and treatment methods. advances in c l i n i c a l a n d e x p e r i m e n t a l m e d i c i n e . 2 0 1 5 . doi:10.17219/acem/31880. 11. seidel ac, miranda f, juliano y, novo nf, dos santos jh, de souza df. prevalence of varicose veins and venous anatomy in patients without truncal saphenous reflux. european j o u r n a l o f va s c u l a r a n d e n d o va s c u l a r s u rge r y. 2004;28(4):387-390. doi:10.1016/j.ejvs.2004.06.014. 12. shadid n, ceulen r, nelemans p, dirksen c, veraart j, schurink gw, et al. randomized clinical trial of ultrasoundguided foam sclerotherapy versus surgery for the incompetent great saphenous vein. br j surg. 2012. british j o u r n a l o f s u r g e r y . 2 0 1 2 ; 9 9 ( 8 ) : 1 0 6 2 1 0 7 0 . doi:10.1002/bjs.8781. 13. tisi p v, beverley c, rees a. injection sclerotherapy for varicose veins. cochrane database of systematic reviews. 2006. doi:10.1002/14651858.cd001732.pub2. 14. mcaree b, ikponmwosa a, brockbank k, abbott c, homervanniasinkam s, gough mj. comparative stability of sodium tetradecyl sulphate (std) and polidocanol foam: impact on foam sclerotherapy as minimally invasive treatment for varicose veinsjiimc 2022 vol. 17, no.2 79 vein damage in an in-vitro model. european journal of vascular and endovascular surgery. 2012;43(6):721-725. doi:10.1016/j.ejvs.2012.02.026. 15. darvall kal, bate gr, adam dj, bradbury aw. recovery after ultrasound-guided foam sclerotherapy compared with conventional surgery for varicose veins. british journal o f s u r g e r y . 2 0 0 9 ; 9 6 ( 1 1 ) : 1 2 6 2 1 2 6 7 . doi:10.1002/bjs.6754. 16. breu fx, guggenbichler s, wollmann jc. 2nd european consensus meeting on foam sclerotherapy 2006 tegernsee, germany. in: vasa journal of vascular diseases. 2008. vasa journal of vascular diseases. 2 0 0 8 ; 3 7 ( s u p p l . 7 1 ) : 3 2 9 . d o i : 1 0 . 1 0 2 4 / 0 3 0 1 1526.37.s71.3. 17. stücker m, kobus s, altmeyer p, reich-schupke s. review of p u b l i s h e d i n fo r m a t i o n o n fo a m s c l e ro t h e ra p y. dermatologic surgery. 2010. doi:10.1111/j.15244725.2009.01406. 18. jia x, mowatt g, burr jm, cassar k, cook j, fraser c. systematic review of foam sclerotherapy for varicose veins. british journal of surgery. 2007. doi:10.1002/bjs.5891. 19. coleridge smith p. sclerotherapy and foam sclerotherapy for varicose veins. phlebology. 2009;24(6):260-269. doi:10.1258/phleb.2009.009050. 20. lurie f, creton d, eklof b, kabnick ls, kistner rl, pichot o, et al. prospective randomized study of endovenous radiofrequency obliteration (closure procedure) versus ligation and stripping in a selected patient population (evolves study). journal of vascular surgery. 2003;38(2);207-214. doi:10.1016/s0741-5214(03)002283. conflict of interest authors declared no conflicts of interest. grant support and financial disclosure authors have declared no specific grant for this research from any funding agency in public, commercial or nonprofit sector. data sharing statment the data that support the findings of this study are available from the corresponding author upon request. this is an open access article distributed under the terms of the creative commons attributionnoncommercial 2.0 generic license. foam sclerotherapy as minimally invasive treatment for varicose veinsjiimc 2022 vol. 17, no.2 80 original�article abstract objective: to analyze the reno protective potential of berberis vulgaris on renal function by measuring renal biomarkers (serum urea and serum creatinine). study design: experimental lab-based study. th rd place and duration of study: study was done in baqai medical & dental university 4 july 2017 to 3 aug 2017. materials and methods: forty adult healthy male laboratory animals were randomly divided into four groups. group a was treated as control group. group b were administered with berberis vulgaris fruit extract 100 mg /kg/body wt. single oral dose for 21 days. group c were administered with gentamicin 100 mg/kg/day intraperitoneally single dose for 21 days. group d, animals received gentamicin intraperitoneally 100mg/kg/day along with berberis vulgaris fruit extract orally for 21 days. both kidneys were dissected, all sections obtained were stained with two dyes hematoxylin and eosin and periodic acid schiff stain for histomorphology. standard error of mean was used to express results. numerical data obtained from different groups were analyzed using spss version 21 p-value of 0.05 or less than 0.05 was considered statistically . significant. results: this study revealed that body weight, kidney weight has been reduced in gentamicin group whereas biomarkers and relative weight of kidney have shown significant increase in group d as compared to control group. conclusion: berberis vulgaris fruit extract ameliorates functional abnormalities along with biochemical parameters associated with gentamicin induced nephrotoxicity. key words: berberis vulgaris, gentamicin, nephrotoxicity, serum creatinine, serum urea. staphylococcus species is most commonly treated by 2 broad spectrum antibiotic gentamicin. clearance of gentamicin first rapidly by renal excretion but partially reabsorbed and accumulation occurred mostly within the proximal convoluted tubules, which are main site for renal toxicity. therefore, gentamicin has always been a restriction in clinical use for long term. renal insufficiency including renal end stage disease takes place in 30% of patients 3 treated with gentamicin. aminoglycoside has the potential to generate acute kidney failure due to tubular cell necrosis confined to proximal convoluted tubules by raising serum biomarkers creatinine and urea. additionally reactive oxygen species(ros)e.g., hydroxyl radicals (oh), hydrogen peroxide (h2o2), and superoxide anion (o2-) which are the most important mediators of tissue damage are produced by gentamicin. gentamicin renal toxicity also decreases the activity of renal tissue antioxidant 4 agents like catalase, superoxide dismutase content. tissue damage induced by gentamicin mainly caused by mitochondrial dysfunction as mitochondria are introduction kidneys play an important role for the removal of waste products, for maintenance of balanced body chemical and acid content of the body. substances produced by different metabolic reactions that occur in the body are excreted through kidneys include ammonia, bilirubin and creatinine in muscles and 1 also drugs and other xenobiotics. life threatening infections caused by different microorganisms such as proteus, e.coli, klebsiella, citrobacter species and a morphological and biochemical study of ethanolic fruit extract of berberis vulgaris against gentamicin induced renal damage in albino rats 1 2 3 4 5 6 lubna faisal , tabina urooj , zia ul islam , fatima rehman , sadia abdul qayyum , aaqiba rasheed correspondence: dr. lubna faisal assistant professor department of anatomy liaquat national hospital & medical college, karachi e-mail: drlubna.faisal@lnh.edu.pk 1,3,4 5 department of anatomy/forensic medicine liaquat national hospital & medical college, karachi 2 department of anatomy ziauddin medical university, karachi 6 department of anatomy islam medical & dental college, sialkot received: december 05, 2022; revised: june 04, 2023 accepted: june 06, 2023 jiimc 2023 vol. 18, no. 2 morphological & biochemical study of ethanolic fruit extract 98 https://doi.org/10.57234/jiimc.june23.1584 5 main sites of ros production. it is proved that g e n t a m i c i n re n a l a c c u m u l a t i o n fa c i l i t a t e s 6 nephrotoxicity. toxicity induced by gentamicin is mainly due to oxidative stress and this condition 7 could be antagonize by dietary antioxidant. berberis vulgaris medicinal herb belongs to the family berberidaceae found abundance in european countries, northwest africa and in few asian regions. fruit of berberis vulgaris commonly called barberry, (zereshk) in local language in iran are edible,they 8 contain large amount of vitamin c. barberry of both types dried and fresh have increased antioxidant activity and are rich in phenolic and anthocyanin 9,10 compounds, intake of both is recommended. berberis vulgaris also contains large percentage of 11 ascorbic acid which is antioxidant. fruit of berberis vulgaris is approved by fda and it is safe for 12 humans. considering reported therapeutic medicinal uses of berberis vulgaris fruit extract, the present study was conducted based on experiments to evaluate the probable protective role of berberis vulgaris fruit extract on renal parenchyma and to analyze the ameliorative potentials of berberis vulgaris fruit extract on renal function by measuring renal 13 biomarkers (serum urea and serum creatinine). materials and methods this experimental study was performed at baqai medical & dental university in anatomy department jointly with animal house of bm & du after ethical approval of experimental protocol (ref: bmuec/2016-04) from board of advanced research and th studies (bas&r) baqai medical university 4 july rd 2017 to 3 aug 2017. inclusion criteria for this study used were forty healthy male adult albino rats aged 10-12 weeks and weighted 180-250gms. exclusion criteria for this study used were any diseased rat or rat died during study. total four groups were made for this experimental study each having ten rats (n=10).group a required laboratory food and water, no drug or treatment was given to this group. group b animals were given fruit extract of berberis vulgarisorally100mg/kg rat bodywt./dayfor 21 consecutive days. gentamicin was injected intraperitoneal route to group c at a single dose of 100mg/kg rat body wt./day daily for 21 consecutive days to induce nephrotoxicity. group d were given g e n t a m i c i n 1 0 0 m g / k g r a t b o d y w t . / d a y intraperitonially daily once as company with berberis vulgaris ethanolic fruit extract 100 mg/kg rat body wt. daily once through gastric gavage for 21 days. before the commencement of this procedure all animals were weighted by using digital electronic balance, tagged, and kept in segregated cages in animal house of bm&du and allowed free access for fresh water& concentrated food (pellets) ad libitum. berberis vulgaris was purchased from local herbal m a r ke t o f ka ra c h i a n d a u t h e n t i c a t e d b y pharmacognosy department of karachi university. berberis vulgaris fruit obtained was dried to make it free from bacteria, fungus then it was chopped into small pieces to make refine powder. the grounded sample was retained in a sealed jar and then reserved for further extraction. grinded powdered fruit (1000g) was soaked in adequate volume of ethanol: water 70:30 ratio, stirred in a circular shaker at room temperature. the extract was kept for 7 days for further extraction. the decoction then separated from the remainder by filtration through whatmanno.1 filter paper. the remainder solvent of the concentrate removed by using rotar y 14 evaporator . after completion of dosing, all animals were anesthetized and then sacrificed. all animals weight was recorded at the beginning and at the time of sacrifice. effects of gentamicin related nephrotoxicity in albino rats was measured by kidney weight/100g rat body 15 weight , biomarkers serum creatinine and serum urea concentration in rats. 5ml whole blood samples were carefully collected at the end from each experimental rat by intracardiac puncture in a 10 ml capacity bottles for detailed estimation of biomarkers urea and creatinine levels. abdominal cavities were exposed by giving midline incisions. kidneys of both sides were obtained and divided into two equal-size length wise halves and were fixed for 24h in10% formalin (bfn). all fixed specimen of both kidneys were dehydrated with ascending grades of ethanol cleared in xylene solution and embedded in paraffin wax blocks.5um thick tissue sections were made. the architecture of all four groups slides a to d was observed. four randomly selected sections from each kidney were observed under a light microscope at 10 and 40x. two basic stains routine hematoxylin and eosin (h&e) and periodic acid schiff (pas) were used to jiimc 2023 vol. 18, no. 2 99 morphological & biochemical study of ethanolic fruit extract https://doi.org/10.57234/jiimc.june23.1584 notice the overall tissue architecture of both kidneys. standard error means (sem) was used to express results. numerical data obtained from different groups were analyzed using spss version 21 p-value . of 0.05 or less than 0.05 was considered statistically significant. the obtained data was analyzed by one way anova. results normal control mean for initial and final body weight were recorded as 207±4.26 and 210 ± 3.09 respectively. data showed highly significant increased (p-value 0.003) in the mean of final rat body weight of normal control group a (table i). berberis received group initial and final body weight were recorded as 196.50± 2.66 and 210.80±2.84 respectively. significant increase (p-value0.0001) in the mean of final rat body weight of group b was noticed. (table i).group c mean value for initial and final rat body weight were recorded as 196.2±2.26 and 183.8±1.93 respectively. significant decrease (pvalue 0.0001) (table i) in the mean of final rat body weight of group c was noticed. group d mean value for initial and final body weight were recorded as 203.30 ± and2.07 217.90 ± 2.09 respectively. data showed significant increase (pvalue0.0001) in the mean of final body weight of group d. (table i). the mean value of weight of rat kidneys (gm) in group a and b were .614±.018 and .639±.013 respectively. mean value of weight of rat kidney (gm) in gentamicin group was .962±.010 and mean value of weight of kidney in gentamicin along with berberis vulgaris treted group was .660±.009 (table ii). it was noticed in this study data revealed highly significant increament in the mean value of weight of kidneys (p-value 0.00) in gentamicin treated group.962±.010 when compared with normal control group.614±.018. the data of this study also showed highly significant increas in the mean of rat kidneys in gentamicin group (p-0.00) when compared with berberis group.639 ± .013. experimental data showed significant increment in the mean value of rat kidneys of group c .962 ±.010 (p-0.00) when compared with group d .660 ±.009. the mean values of relative weight of kidneys in normal group, berberis vulgaris fruit exract group, gentamicin treated group, and gentamicin along berberis vulgaris group are shown in (table iii a). significant increase was observed in the mean value of relative kidneys weight (p-0.000) in group c when compared with control normal group a, b and d (table iiib). interstingly our data showed highly significant increased (p-0.00) in the mean of biochemical parameters serum urea level (mg/dl) of gentamicin treated group in comparision with normal control group a. additionaly gentamicin along with berberis vulgaris treated group showed not much raised level of urea as compared to control group which revealed nephroprotective result of berberis vulgaris fruit extract against nephrotoxic drug gentamicin.(graph no 1). mean value of serum creatinine level (mg/dl) in group a and b were 0.655±.011, mean.635±.007 respectively. mean of serum creatinine level (mg/dl) in group c and d were 5.35±.186 and .688±.009. respectively (graph no 2). results of our study showed significant increament in the mean value of serum creatinine level (p-0.00) in gentamicin group 5.35±.186when compared with normal control group 0.655±.011.( graph no 2). the data showed significant increased in the mean value of serum creatinine level (p-0.00) in gentamicingroup c 5.35±.186 when compared with group d.688±.009. additionally, highly significant increase was observed in the mean value of serum creatinine level ( p 0 . 0 0 ) i n c o m p a r i s o n w i t h g e n t a m i c i n group5.35±.186 when compared with berberis group .635±.007. in contrast, tha data revealed no remarkable change in the mean value of serum creatinine level (p-0.869) in gentamicin treated along with berberis vulgaris fruit extract groupin comparision with control group a. table i : mean rat body weight (gm) in different treated groups jiimc 2023 vol. 18, no. 2 100 morphological & biochemical study of ethanolic fruit extract https://doi.org/10.57234/jiimc.june23.1584 discussion aminoglycoside brand gentamicin is one of an important and effective antibiotic due to its strong bactericidal properties, lower resistance rate and cost effectivness. aminoglycosides accounts for 10%-20% of nephrotoxicity which is its one of major 16 complication. gentamicin can be used both in humans as well as for animals in treating gram negative bacterial 17 infections. gentamicin induced nephrotoxicity is commonly used to study acute kidney failure in 18 animal model for research based experiments. gentamicin induced nephrotoxicity results in acute 19 kidney failure. akf is a complex series of event indicated by elevated serum creatinine level and blood urea including proximal tubular cell necrosis 20 resulting in renal failure. production of ros in mitochondria is directly increased by gentamicin as a result cellular damage occurred, decreased production of atp, apoptosis stimulating factor released from mitochondria, lipid per oxidation all these lead to cell hypertrophy and cell death by apoptosis thus resulting in decreased body weight. 21 sawardekar et al. showed same results which was observed in this study. berberis vulgaris fruit (bvf) can be used as an alternative medicine or as additive supplement food against nephrotoxicity generated table ii: mean rat kidney weight (gm) in study groups n=40 table iii a : mean relative weight of kidney in different groups table iii b analysis of differences in relative weight of kidneys between different groups. graph no 1. serum urea mean values comparision of different experimental groups. graph no 2. serum creatinine mean values comparison of different experimental groups. jiimc 2023 vol. 18, no. 2 101 rats’ morphological & biochemical study of ethanolic fruit extract https://doi.org/10.57234/jiimc.june23.1584 by gentamicin. berberis vulgaris (bv) and its important compound berberine have been used since for a long period in indigenous medicine. antioxidant results of berberis vulgaris are greater due to synergy of phenols and 22 berberine compounds. the most specific indicator for measuring adverse effects of divergent xenobiotics is the body weight,therefore it is considered as a principle parameter to test toxicity . significant decline in rat body weight gain was noted in group c.renal failure leads to acidosis, accompanied by anorexia and decreased food intake which later on results in body weight loss by gentamicin induced nephrotoxicity. 23 similar findings have been stated by erdem et al. in this study it was noted in berberis vulgaris protected group increase to some extent in body weight as 2 4 c o m p a re d t o g e n ta m i c i n t re a te d g ro u p . 25 tamilarasan et al also confirmed these findings. same energy levels were found in group d animals when compared with normal group. this is because berberis vulgaris fruit extract which has a potential to reduce oxidative stress, results in decline of free radicals scavenging activity. berberis vulgaris possess strong antioxidantal effects which help to improve physical strength consequently increased body weight this was in accordance with previously done . 26 study by laamech et al. marked increase in relative weight of kidney was observed in gentamicin treated group c as compared to control group due to decreased prostaglandine2 production which causes sodium retention resulting in renal hypertrophy and interstitial edema produced by gentamicin induced tubular necrosis resulted in significant increased 27 kidney weight as similar to noorani et al. prominent increased level of serum urea and creatinine concentrations are good signs of concentrated glomerular filtration and significant kidney failure. significant rise in levels of serum urea and creatinine concentrations resulted in powerful renal destruction produced by gentamicin 28 nephrotoxicity. serum creatinine is more authentic biomarker in the mechanism of pathogenesis of 29 renal disease as compared to urea. further more concentration of urea starts to develop right after injury of renal parenchyma. antioxidantal properties of tissue are decreased by gentamicin which is revealed by prominent decrease in enzymatic activity of superoxide dismutase and marked increase in per oxidation of lipids. due to this it generates oxidative stress to different organs. antioxidant agent can alter majority of the modifications in histological tissue sections of renal parenchyma generated by gentamicin related nephrotoxicity. the mechanism due to which serum urea and creatinine levels raised are because of the reason that gentamicin causes the ca+2 to enter more into the mesangial cells resulting in decreased 30 glomerular filtration rate. similar finding was 31 observed by w hozayen et al. it was clearly evident through results of our study that gentamicin at a dose of 100 mg/kg rat body wt/day generates nephrotoxic effects which was obvious by marked increase in pvalue (0.000 ) in serum urea and blood creatininelevel as compared to normal control group. berberis vulgaris fruit extract has strong antioxidant potential leading to nephroprotective effects 32 (jyothilakshmi et al., 2013). no significant increase in serum urea and blood creatinine concentration was found in berberis vulgaris treated group when compared with normal control group. in the light of above statistical analysis, figures, and facts. conclusion it is concluded that gentamicin produces oxidative nephrotoxic effects on renal parenchyma which can be limited and prevented by protective antioxidative e f fe c t o f b e r b e r i s v u l ga r i s t h a t re s t o re d histomorphological changes in renal tissue induced by gentamicin toxicity. limitations of study there will be no doubt if herbs will be used in future that will significantly benefit human beings. however sample size of this study is too small ,animal studies are time consuming and there will be chance of high failure in development of new drug. references 1. hall am, trepiccione f, unwin rj. drug toxicity in the proximal tubule: new models,methods, and mechanisms. pa e d i at r i c n e p h ro l o 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javed s, khan ja, khaliq t, javed i, abbas rz. experimental evaluation of nephroprotective potential of calotropis procera (ait) flowers against gentamicin-induced toxicity in albino rabbits. pak vet j. 2015;35:222-6. 31. hozayen w, bastawy m, elshafeey h. effects of aqueous purslane (portulaca oleracea) extract and fish oil on gentamicin nephrotoxicity in albino rats. nature and science. 2011;9(2):47-62. 32. jyothilakshmi v, thellamudhu g, kumar a, khurana a, nayak d, kalaiselvi p. preliminary investigation on ultra-high diluted b. vulgaris in experimental urolithiasis. h o m e o p a t h y . 2 0 1 3 j u l ; 1 0 2 ( 0 3 ) : 1 7 2 8 . d o i : 10.1016/j.homp.2013.05.004. conflict of interest authors declared no conflicts of interest. grant support and financial disclosure authors have declared no specific grant for this research from any funding agency in public, commercial or nonprofit sector. data sharing statment the data that support the findings of this study are available from the corresponding author upon request. this is an open access article distributed under the terms of the creative commons attributionnoncommercial 2.0 generic license. jiimc 2023 vol. 18, no. 2 104 morphological & biochemical study of ethanolic fruit extract https://doi.org/10.57234/jiimc.june23.1584 july 2013.pdf ßþíìîßýì ñ¾¶»½¬·ª»æ ì± ¿­­»­­ ¬¸» ú®»¯«»²½§ ¿²¼ ¬¸» ¬§°»­ ±º ð±­¬»®·±® ý¿°­«´¿® ñ°¿½·º·½¿¬·±² ¿º¬»® »¨¬®¿ ½¿°­«´¿® ½¿¬¿®¿½¬ »¨¬®¿½¬·±² ¿²¼ °±­¬»®·±® ½¸¿³¾»® ·²¬®¿±½«´¿® ´»²­ øðóóß÷ ·³°´¿²¬¿¬·±²ò í¬«¼§ ü»­·¹²æ ü»­½®·°¬·ª» ­¬«¼§ ð´¿½» ¿²¼ ü«®¿¬·±² ±º í¬«¼§æ ü»°¿®¬³»²¬ ±º ñ°¸¬¸¿´³±´±¹§ ø±´§ ú¿³·´§ ø±­°·¬¿´ô î¿©¿´°·²¼· º®±³ ó¿§ îððí ¬± ó¿§ îððëò 󿬻®·¿´­ ¿²¼ 󻬸±¼­æ 쩱 ¸«²¼®»¼ °¿¬·»²¬­ô ©·¬¸ ¿¹» ®¿²¹»­ º®±³ ëë ¬± è𠧻¿®­ô ¸¿ª·²¹ «²½±³°´·½¿¬»¼ ­»²·´» ³¿¬«®» ½¿¬¿®¿½¬­ ©¸± «²¼»®©»²¬ ûýýû ©·¬¸ ðý×ñô ±ª»® ¿ °»®·±¼ ±º ±²» §»¿® ©»®» ­»´»½¬»¼ º±® ¬¸» ­¬«¼§ò ߬ ꬸ 󱲬¸ °±­¬ ±°»®¿¬·ª»´§ ¬¸» °¿¬·»²¬­ ©»®» »¨¿³·²»¼ º±® ¿²§ »ª·¼»²½» ±º °±­¬»®·±® ½¿°­«´¿® ±°¿½·º·½¿¬·±² ©·¬¸·¬­ ¬§°» ¿²¼ ¬¸» ®»­«´¬­ ©»®» 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𿲼»§ íõò í»´»½¬·ª» ¿²¼ ­°»½·º·½ ¬¿®¹»¬·²¹ ±º ´»²­ »°·¬¸»´·¿´ ½»´´­ ¼«®·²¹ ½¿¬¿®¿½¬ ­«®¹»®§ «­·²¹ ­»¿´»¼ó ½¿°­«´» ·®®·¹¿¬·±²ò öò ý¿¬¿®¿½¬ ®¿½¬ îððíå îçæïëêóêèò îêò ß¾¼»´©¿¸¿¾ óìô õ«¹»´¾»®¹ óô í»®»¹¿®¼ íô 滬¬»®­¬®±³ ýò í¿º»¬§ ±º ·®®·¹¿¬·±² ©·¬¸ ëó º´«±®±«®¿½·´ ·² ¿ ­»¿´»¼ó½¿°­«´» ·®®·¹¿¬·±² ¼»ª·½» ·² ¬¸» ®¿¾¾·¬ »§»ò öò ý¿¬¿®¿½¬ ®¿½¬ í«®¹ îððéå ííæïêïçóîíò íè original�article abstract objective : to observe how loud noise affects the growth of new blood vessels in rat skin wounds. study design :quasi experimental study. th place and duration of study: the study was conducted at national institute of health islamabad from 28 june th 2017 to 28 february 2018. materials and methods: thirty male sprague dawley rats were split into control and experimental groups by convenient sampling, with 15 animals belonging to each leading group. on the dorsum of each rat, a 2 cm incision was created. while experimental subgroups endured 4h/d intermittent noise exposure of 85-95db five days a week for two consecutive weeks, control subgroup rats were left to heal with routine background noise exposure. on days 3, 7, and 14, five rats from each group were slaughtered. wounds were excised, repaired, and prepared for h&e stain before being able to see and count the freshly grown blood vessels. results: although difference in mean number of newly formed blood vessels among both control and experimental group was found with more numbers in control group but it was not statistically significant. conclusion: intermittent noise exposure has tendency to impair the process of angiogenesis thus delaying wound healing. key words: angiogenesis, noise, skin wound, stimulator, inhibitor. exposure between 70 and 100 db is believed to cause structural alterations in the vasculature as well as morphological changes due to an increase in stress 3 hormone and lipid peroxidation. the sympathetic nervous system is activated as a result of elevated levels of epinephrine and norepinephrine, 4 angiotensin ii. angiotensin ii in turn activates nadph oxidase, which is responsible for oxidation stress in vasculature. angiogenesis is integral to successful wound repair involves, budding from 5 capillaries of wound edge. soon after the invasion into damaged site newly formed vessels appear as a network to nourish the tissue and helps in formation 6 of granulation tissue. formation of granulation tissue from the wound edge involves immigration of 7 local fibroblast and lying down of fibrin network. sprouting of capillaries initiates neovascularization 8 and angiogenesis previously noise exposed . subjects showed more pronounced association 9 between noise and endothelial functions. although significant efforts have been made in the past to 10 address the issue of delayed wound healing , further research on the angiogenesis process is still required to identify all the factors that contribute to the delay. present study by demonstrating all stressors that harm the physical environment will aid in effective wound healing and, more specifically, by shedding light on noise-induced poor vascular regeneration. introduction restoration of skin integrity following injury is dependent on cell and ecm interaction and it can be hindered at any point during the process of wound 1 healing. multiple research models concluded that psychological stress may affect wound healing. it is evident from experimental work done in the past that aircraft noise is linked to stress-induced vascular damage, which is mediated by inflammatory cells infiltrating the blood vessels, endothelial nitric oxide synthetase being uncoupled, and nadph oxidase 2 being oxidized. transcriptome research has also revealed alterations in the expression of genes involved in controlling vascular function, re modelling, and cell death in the aortic tissues of animals exposed to noise. this explains how noiseinduced vascular damage works. white noise loud noise; wound angiogenic stimulator or inhibitor? 1 2 3 4 5 khalida moeed , jamshed khan , anum usman , fauzia siraj , waseem kausar correspondence: dr. khalida moeed department of anatomy loralai medical college, loralai e-mail: dr.khalidamoeed@gmail.com 1,2 5 department of anatomy/biochemistry loralai medical college, loralai 3 department of histopathology alnafees medical college, islamabad 4 department of anatomy wah medical college, wah received: september 23, 2022; revised: january 31, 2023 accepted: 16, february 2023 loud noise affects angiogenesisjiimc 2023 vol. 18, no.1 37https://doi.org/10.57234/jiimc.march23.1539 the objective of my study was to know how noise affects the growth of new blood vessels in rat skin wound. materials and methods study period of this quasi experiment was from 28th th june 2017 to 28 february 2018. institutional ethical review committee approved the research proposal via registration no,f.2/iuic-anmc /ec 64/2025 on june 23,2015. 30 sprague dawley male rats purchased from nih islamabad were included in the study aged between three and five months, they weighed between 250 and 300 grams, and rats with any skin conditions discovered during or after the trial were eliminated. the control and experimental groups of rats were housed in separate cages. each cage had five rats. the normal settings for temperature, light, and humidity were given to both groups. the animals were kept in 12-hour cycles of light and darkness, with lights on at 8 a.m. and off at 8 p.m, at a temperature of 23–27 °c, 30–40% humidity, and a normal pelleted feed with unlimited access to tap water. the animals were acclimatized to the surroundings for a week prior to the experiment to reduce handling and habitat-like stressors. two groups of thirty rats were created: control a (incised but not exposed to loud noise) .h&e stain was used to see the newly formed blood vessels.they were counted three times in incisional space in control a(incised but not exposed to white noise) and experimental b (incised and exposed to white noise). there were fifteen rats in each group (table i). the control and experimental groups were then separated into three subgroups, each with five rats (a1, a2, a3, and b1, b2, and b3). their days of exposure to noise (3, 7 and 14)—which consisted of white noise for the experimental groups and routine noise for the control groups—formed the basis for the grouping (table-i). the rats were put to sleep using intramuscular injections of xylazine and ketamine. the predicted dose for rats was 0.1ml/100g body weight and was created by mixing 5ml of ketamine and 0.5ml of xylazine. after shaving the back to produce a single 2 cm wound parallel to the right side of the vertebral column, a fullthickness incision was created. metallic clips were used to close wounds with a disposable skin stapler. five rats were housed in each cage, they were kept in a quiet environment, and they were only exposed to typical background noise at a volume of 40 to 50 db. after three days of exposure to noise, seven days for group a2 and fourteen days for group a3, rats were slaughtered. all rats in the test groups were subjected to white noise (85-95db). the exposure period began in the morning and lasted from 8 am until 4 am. the noise exposure was 4 hours per day with hourly breaks, followed by 5 days per week for two weeks straight (sub-acute stress) occasionally to prevent adaption. a sound player amplified and recorded the sound of pressure horns by an amplifier that was mounted 30 cm from the cages and connected to two 15 w loudspeakers. b1for three days, b2 seven days, and b3 fourteen days, the subgroup was exposed to loud noise. rats from group b1 were sacrificed on day 3, group b2 on day 7, and group b3 on day 14 after being exposed to noise (table i). wounds were repaired, histologically e x a m i n e d , i n p r e c a l i b r a t e d u n i t a r e a a t x100magnification.mean value of these readings was calculated. unit area was calculated by calibrating the stage and ocular micrometers. statistical analysis was performed according to standard methods (spss version 20). result was expressed as mean standard deviation (mean ± sd). mean of the two groups was compared using independent student's t test. p-value of ≤ 0.05 was considered statistically significant. table i: group distribution of rats results new blood vessels were counted at wound site for all three days of noise exposure. loud noise affects angiogenesisjiimc 2023 vol. 18, no.1 38 https://doi.org/10.57234/jiimc.march23.1539 blood vessels count per unit area in incisional space in control group. three days of white noise exposure to a1 resulted in (12%,1.20 ±0.44). (table ii ). in the experimental sub-group b1 exposed to white noise for three days, blood vessels were discovered to be present with a mean number (08%,0.80 ± 0.83). (table ii). process of angiogenesis was slower in noise exposed group than routine noise exposed group. comparison of mean number of blood vessels present per unit area showed insignificant p value (p=0.37) (table ii) on day three. mean number of newly formed blood vessels counted in group a2 on day seven was (16%,1.60 ± 0.89) and blood vessels in experimental group b2 were seen in number (14%,1.40 ± 0.89) (table ii). difference in mean number of newly formed blood vessels among both groups on day seven was not significant (p value= 0.73) (table ii). newly formed blood vessels were counted in control group (a3) on fourteenth day showed mean number (20%,2.00 ± 0.00) (table ii) while mean number of blood vessel in experimental group b3 was counted as (16%,0.70 ±.18) (table ii) per unit area, difference in mean number of blood vessels was not significant (p value= 0.14) (table ii). that as a normal phenomenon in intact tissue delivery of oxygen and nutrients equalizes the removal of waste products , hence maintaining the 13 vascular homeostasis. while in injured tissue disrupted microvasculature leads to inflammation and hypoxia which in turn activates endothelial 14,15 cells. thereafter; the new vessels differentiate into arteries and venules. the difference between capillaries and arterioles was made by the presence or absence of smooth muscles in their walls. when all control groups a1, a2 & a3 were compared with experimental groups b1, b2 & b3, on days three, seven, and fourteen. the difference was found to be insignificant (p >0.05) . these findings don't match with previous studies which said that most probable factor responsible for process of angiogenesis, were a protein called hypoxia inducible factor i (hif-1), table ii: number of blood vessels/unit area at different days of sacrifice figure 1: photomicrograph of specimen number 1's third day skin wound(group experiment b1). the arrow indicates how granulation tissue is growing and bridging the wound space. the h&e stain 10x10. figure 2: photomicrograph showing newly formed blood vessels at base of wound in specimen number 5 (control group a2). h&e stain.40x10 discussion non-healing of wounds drives patient morbidity and increases healthcare cost, became a major medical 11 problem. reduced vascular growth by the process of angiogenesis is found to be one among the key 12 factors of chronic non healing wounds. we observed and counted newly formed blood vessels at wound site in both control and experimental groups and found the fact mentioned previously, to be true loud noise affects angiogenesisjiimc 2023 vol. 18, no.1 39https://doi.org/10.57234/jiimc.march23.1539 16 thought to be inhibited by noise stress. this has been shown by another researcher that ''hif'' has a 17 key role in wound healing. another study done in past has also supported the above-mentioned conclusion that at the site of wound, proinflammatory cytokines were affected by stress, that might be a possible mechanism of inadequately formed blood vessels, resulted in delayed wound 18 healing in noise exposed group. another study showed not only difference in inflammatory cell count but significant inhibition of epidermal 19 regeneration in experimental rats too. in addition to count the proliferation and migration 0f fibroblast 20 and number of new vessels was also decelerated. underlying mechanism is explained by another author in terms of correlation of reduced number of inflammatory cytokines and enzymes involved in tissue repair with inhibition of regeneration of endothelial cells consequent on delayed wound 21 healing. any study in favor of our conclusion regarding formation of new blood vessels in experimental groups subjected to noise stress for fourteen days doesn't exist as per my knowledge. the matter of conflict might be the alternative exposure of noise, with (one hour exposure followed by one hour rest) as mentioned in ''subject and method'' in our study was quite different from previous above-mentioned studies. present study adopted the said pattern of noise exposure based upon the fact that prolonged repeated stress can be extremely harmful to auditory apparatus of rats as they are more sensitive to auditory stimuli than 22 humans. it is also a fact that harmfulness of noise to hearing or even healing depends not only on the sound level only, but there are some other factors like sensitivity of the exposed person or 23 experimental animal and the duration of exposure. conclusion intermittent noise exposure has tendency to impair the process of angiogenesis thus delaying wound healing. references 1. rown a wound management 1: phases of athe wound healing process. nursing times. 2015; 111: 46, 12-13. pmid: 26689053. 2. bodin t, björk j, ardö j, albin m . annoyance, sleep and concentration problems due to combined traffic noise and t h e b e n e f i t o f q u i e t s i d e . i n t e r j e n v i r o n .2015;12(2):1612–1628 .doi: 10.3390/ijerph120201612. 3. early s, du e, 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18, no.1 40 https://doi.org/10.57234/jiimc.march23.1539 exposure and the risk of cancer: a comprehensive systematic review. reviews on environmental health. 2022. https://doi.org/10.1515/reveh-2022-0021. 19. elbassyoni, s., kamoun, e.a., taha, t.h. et al. effect of egyptian attapulgite clay on the properties of pvahes–clay nanocomposite hydrogel membranes for wound dressing applications. arab j sci eng.2020”: 45: 4737–4749. https://doi.org/10.1007/s13369-020-04501-x. 20. rafi a, khan my, minhas la. quantitative analysis of macrophages in wound healing of rat skin subjected to loud n o i s e s t r e s s . j a m c . 2 0 1 4 ; 2 6 ( 2 ) : 1 1 5 1 1 7 . d o i : 10.1016/j.spinee.2005.12.005. 21. anuszyk m, kwon sk, wong vw, padmanabhan j, maan zn etal. the role of focal adhesion kinase in keratinocyte fibrogenic gene expression. int j mol sci .2017;18: 19151920 .https://doi.org/10.3390/ijms18091915. 22. he l, huang x, kanisicak o, li y, wang y etal. preexisting endothelial cells mediate cardiac neovascularization after i n j u r y. j c l i n i n v e s t . 2 0 1 7 ; 1 2 7 : 2 9 6 8 – 2 9 8 1 https://doi.org/10.1172/jci93868. 23. kamoun, e.a, kenawy, chen x. a review on polymeric hydrogel membranes for wound dressing applications: pvab a s e d h y d r o g e l d r e s s i n g s . j . a d v . r e s . 2 0 https://doi.org/10.1016/j.jare.2017.01.005. conflict of interest authors declared no conflicts of interest. grant support and financial disclosure authors have declared no specific grant for this research from any funding agency in public, commercial or nonprofit sector. data sharing statment the data that support the findings of this study are available from the corresponding author upon request. this is an open access article distributed under the terms of the creative commons attributionnoncommercial 2.0 generic license. loud noise affects angiogenesisjiimc 2023 vol. 18, no.1 41https://doi.org/10.57234/jiimc.march23.1539 jiims.cdr 54 original article abstract objective: to study the variations in gross appearance of ascending aortic fold, and relationship of vertical height of middle of fold to vertical height of heart and to the mean width of the fold. study design: this was a cross sectional study. place and duration of study: department of anatomy, rawalpindi medical college, rawalpindi, from jan 2010 to dec 2010. materials and methods: the present study was carried out on 24 hearts obtained from the dissection room of rawalpindi medical college, rawalpindi. all the cases cadavers available during the study period were included in the study. the ascending aorta was studied with respect to its length and presence of fold in each of the specimens. the direction of the fold was noted for the classic oblique form and other variations. results: the fold was present in all the specimens. it was oblique in 13 cases, horizontal in 6, oval in 2, vertical oblique in 2 and vertical horizontal in 1 individual. the vertical height of middle of fold was inversely proportional to vertical height of the heart and directly proportional to the mean width of the fold. conclusion: the present study provided new dimension and observation that the vertical height of the middle of fold and vertical height of heart are inversely proportional to each other. vertical height of the middle of fold and mean width of the fold are directly proportional to each other. keywords: ascending aortic fold, vertical height of heart, mean width of aortic fold. of fat was the result of collateral enlargement of blood vessels in the fat pads 5 to lessen the effect of coronary insufficiency. it was demonstrated by woodruff that opening of vasa vasorum of aorta was 6 present beneath the fat pads. vasa vasorum are contained in adventitia of large 7,8 arteries. it was reported by david j.davis (1927) that ascending aortic fold was constant in location, form and size. he suggested the name of periaortic fat bodies 9 for the fold. epicardial fat pad was another name used by robertson (1930) for the ascending aortic fold. he was of the opinion that the fold carried an arterial network to the vasa vasorum of aorta and a site of 10 anastomosis between the coronary arteries. the fold was found by parke and michels (1966) in adults, children and fetuses and was called by them as aortic ridge. they proposed that it relieves pressure and 11 friction between aorta and right auricle. a relatively recent study was carried out by g.t lebona (1993) in south africa. he proposed the name of ascending aortic fold. the fold has not been mentioned in the recent textbooks of anatomy. he observed that apart from classic oblique form other introduction the ascending aortic fold was described for the first time by rindfleisch (1984) as a fibrofatty epicardial fold, semilunar in shape, 1 to 3 cm long, 2 to 5 mm wide and directed obliquely across the middle of anterior surface of ascending aorta. he concluded that the fold enhanced the 1 e l a s t i c i t y o f v i s c e r a l p e r i c a rd i u m . epicardium is the visceral layer of pericardium. ascending aorta is enclosed in a sheath of serous pericardium. serous pericardium has parietal and visceral layer. p a r i e t a l l a y e r l i n e s t h e f i b r o u s 2,3 pericardium. accessory thyroid tissue was detected by swarts and thompson (1911) in 4 sub-epicardial preaortic fat. the term of periaortic fat pads was used by gross (1921) for the ascending aortic fold. he observed that these fat pads increase with age and myocardial pathology. he concluded that this progressive deposition ------------------------------------------------correspondence: dr amer qayum assistant prof of anatomy rawalpindi medical college, rawalpindi e. mail: aaau32@gmail.com a study of variations in human ascending aortic fold amer qayum, tahzeeb ul hassan, tassaduq hussain 55 varieties of ascending aortic fold also 12,13 exist. different views were given about the structure of ascending aortic fold. the knowledge about the fold was limited. moreover no more studies could be found to confirm or refute the work done by g.t lebona, which needs to be studied and explored more. this inspired me to work for this difficult task and to conduct the present study. this was cross sectional study carried out in rawalpindi medical college from jan 2010 to dec 2010. all the cadavers dissected during this period were used for this study. for the data collection a structured questionnaire was developed mentioning the important variables about length, width, position, type's and shapes/axis of fold etc. data was analyzed by using microsoft excel and statistical package for social sciences version 17.mean and standard deviation were calculated; cross tabs were done and mentioned in tables and graphs. the material consisted of 24 hearts obtained from the dissection hall of rawalpindi medical college, rawalpindi. obese adult, putrefied and macerated specimens, gross pathological findings like aortic aneurysms, myocardial infarction and congenital anomalies were not included. the ascending aorta was studied with respect to its length and presence of fold in each of the specimens. the direction of the fold was noted for the classic oblique form and other variations. mean width of the fold was calculated by taking the average of maximum and minimum width in each of the specimens. the vertical height of the middle of fold was measured from middle of its upper border to its lower border. vertical height of the heart was measured from middle of the upper border of fold to the inferior border of heart. height of the fold as materials and methods percentage of height of heart was also calculated in each of the specimen. a comparison of the vertical height of the heart and vertical height of the fold was made in e a c h o f t h e s p e c i m e n . s i m i l a r l y a comparison of mean width and vertical height of the middle of the fold was made. the ascending aortic fold was present in all the 24 specimens. it was obliquely oriented in 13 specimens as shown in figure 1. horizontal variety was present in 6 specimens as shown in figure 2. the fold was oval in 2 hearts as shown in figure 3. in remaining 3 specimens combination of axis was observed. it was vertical oblique in 2 specimens as shown in figure 4. vertical horizontal form was seen in only 1 heart as shown in figure 5. the frequency of variations of ascending aortic fold is shown in table 1. length of ascending aorta ranged between 4.40 to 5.40 cm. the mean length of ascending aorta came out to be 4.90cm as shown in table 1. the mean width of the fold ranged between 0.19 cm and 1.07 cm. the mean of the mean width was 0.41 cm with sd of 0.17 as shown in table 1.the vertical height of the middle of fold ranged between 0.21 cm to 0.82 cm, with mean value of 0.39 and sd of 0.14 as shown in table 1.the vertical height of the heart ranged between 7.80 cm and 9.82 cm with mean value of 8.66 cm and sd of 0.62 as shown in table 1. height of the fold as percentage of height of the heart ranged from 2.23% to 8.81% with mean of 4.61% as shown in figure 6 and table 1. the vertical height of the fold decreased as the height of the heart increased as shown in figure 7. the vertical heights of the middle of fold and mean width of fold generally remained in the similar ranges as shown in figure 8. results 56 figure 1: anterior aspect of ascending aorta showing oblique type of ascending aortic fold (yellow arrows). figure 2: anterior aspect of ascending aorta showing horizontal type of ascending aortic fold (yellow arrows). figure 3: anterior aspect of ascending aorta showing oval type of ascending aortic fold (yellow arrows). figure 4: anterior aspect of ascending aorta showing vertical oblique type of ascending aortic fold (yellow arrows). figure 5: anterior aspect of ascending aorta showing vertical horizontal type of ascending aortic fold (yellow arrows) figure 6: the height of the fold as percentage of height of the heart. 57 table i: gross parameters of ascending aortic fold 58 discussion the present study has shown that the ascending aortic fold is a constant feature and confirmed the findings of previous 1,9,11,12 workers. during the present study mean length of aorta (4.90cm) was approximately the same as given in 14 literature. earlier the literature identified only oblique semilunar form of the ascending aortic fold. later on, it was reported by g.t lebona that a wide 12,13 variation in gross anatomy of fold exists. he observed classic oblique form in 51 out of 90 specimens. horizontal form was seen in 17, vertical form in 5 and oval in 2 hearts. in the remaining 15 hearts the fold was seen in the form of a combined axial pattern. it was horizontal-oblique in 4, vertical-oblique in 6, vertical-horizontal in 3, vertical-horizontaloblique in 1 and oval-oblique in 1. the present study has confirmed that variations are present in the gross anatomy of ascending aortic fold. classic oblique form was present in 13 out of 24 hearts. it was oval in 2 hearts and horizontal in 6 hearts. the remaining 3 hearts showed a combination of axis. the fold was vertical-oblique in 2 and vertical-horizontal in 1 of the hearts. however the variations noted in the present study were not as wide as seen by g.t lebona in black south africans. thus the present study is the first to agree with the work of g.t lebona. during the present study it was found that height of the fold as percentage of the height of heart ranged from 2.23% to 8.81% with mean value of 4.61%. a trend was noted that as the vertical height of heart increase there was no increase in vertical height of middle of fold, rather it decreased. to our knowledge no such study has been carried out before this. the present study provides new dimension and observation that the vertical height of the middle of fold and mean width of the fold are directly proportional to each other. 1. daniel a, anne mb. dorland's medical dictionary. 32nd ed. united states of america. elsevier wb saunder's company; 2012. p1648. 2. snell, richard s. the thoracic cavity. in t h c l i n i c a l a n a t o m y b y re g i o n s . 9 e d . philadelphia: lippincot williams and wilkins, 2012. p95. 3. chummy s. sinnatamby. middle mediastinum t h and heart. 12 ed. london: churchill livingstone elsevier; 2011. p197. 4. swarts and thompson: aberrant thyroids in pericardium in the dog. j.m research 1911; 24: 299. 5. louis gross. age period changes in the blood supply to the heart and their pathogenic relations. in: the blood supply to the heart and its anatomical and clinical aspects. new york: paul b.hoeber; 1921. p109. 6. woodruff, ce. studies on the vasa vasorum. am j path1926; 2: 567-75. 7. anthony l mescher. the circulatory system. in th junqueiras basic histology. 12 ed. new york. mc graw hill companies, 2010, p190. 8. michael h. ross & wojciech pawlina. reference figure 7: scatter graph showing the comparison of vertical height of the fold and the vertical height of the heart. figure 8: scatter graph showing the comparison of vertical height of middle of fold and its mean width. 59 cardiovascular system. text book and atlas of th histology 6 ed. lippincot williams and wilkins; 2011. p417. 9. davis dj. the periaortic fat bodies. archives of pathology and laboratory medicine 1927; 4: 937-42. 10. robertson h f. the vascularization of the epicardial and periaortic fat pads. am j path 1930; 6: 209-15. 11. parke ww & michels na. the human aortic ridge and cushion. anatomical record 1966; 154; 185-93. 12. lebona gt. morphological variations of the human ascending aortic fold. j anat 1993; 182: 275-9. 13. lebona gt. the presence of paraganglia in the human ascending arotic fold: histological and ultra structural studies. j anat 1993; 183: 35-41. 14. gerard j. tortora, bryan derrickson. the cardiovascular system; blood vessels and haemodynamics. principles of anatomy and th physiology. 13 ed. hoboken jhon wiley and sons. 2011. p831. original�article abstract objective: to determine noise related health issues prevailing in the residents of high traffic flow areas of rawalpindi and islamabad. study design: cross sectional study. th place and duration of study: high traffic flow residential areas of rawalpindi and islamabad from 15 may to th 18 october, 2015. th th materials and methods: a cross-sectional study was carried out from 15 may to 18 october, 2015. a total of 352 respondents in the age group 25-65 years from high traffic flow residential areas of rawalpindi and islamabad were selected through non-probability convenience sampling technique. a structured closed ended questionnaire was administered and the collected data was analyzed through spss version 22. results: among the various findings of our study, difficulty in sleeping was a significant problem (87%), irrespective of the age of respondents. the annoyance (69%), stress (63.4%), easy fatigability (61.4%) and poor digestion (60.5%) were also significant predicaments owing to excessive noise exposure. the residents complained that noise was interfering with their speech (58.2%) and reducing their productivity leading to difficulty in concentrating on a task (55.1%) and reduced task performance (52.3%). conclusion: the current study revealed that there are certain health issues attributed to noise, posing a major threat to the health of community and gradually worsening the burden of non-communicable diseases. key words: health issues, high traffic flow, noise pollution, residents. and physiological effects including reduce performance and provoke annoyance responses and 5,6 changes in social behavior. an insight into noise pollution in our opinion is a daunting combination of many factors. the formidable wrath of poverty has influenced migration of individuals inspiring a shift from rural to 6 urban areas. this shift has not only lead to noise pollution but serves as a nidus for various other complexities and has proved rather grave instead of 7 being bounteous. population explosion and overcrowding has led to congestion of residential and commercial areas in its vicinity and this in turn postulates and dictates rise in traffic; deemed by some theorists as a "forerunner and a preposterous 8 cause of noise pollution”. at least one million healthy life years are lost every year from traffic related noise in the western part of 9 europe. most of the areas, particularly the urban side, are subjected to unacceptable noise conditions due to construction, manufacturing, traffic and 10 recreational activities. the road traffic noise is another source of noise nuisance in urban areas of pakistan; the situation is getting alarming with 9-11 increase in traffic density on city roads. there is no introduction in an ever changing environment, a new man-made epidemic breed, a pernicious agent of many physiologic and psychological aliments as it grows, hailed by many theorists as "slow agent of death", the environmental noise devours its prey as time 1,2 courses forward. it is a significant problem all over 2 the world especially in urban territories. environmental noise particularly high traffic noise is increasing day by day in urban areas over the period of past few years. noise health effects are the health 3 consequences of elevated sound levels. increased traffic noise alone is harming the human health and interferes with people's daily activities at school, at 4 work, at home and during leisure time. noise exposure has been known to induce auditory and 5 non-auditory effects. it can disturb sleep, can cause cardiovascular, autonomic and other psychological noise related health issues among residents of high traffic flow areas of rawalpindi and islamabad iffat atif, adeela mustafa, ishaq ahmed, farah rashid, mohsin javaid, shahroz saud ahmed, muhammad ausaf saleem, waqas ahmed correspondence: dr. iffat atif assistant professor, community medicine yusra medical and dental college, islamabad department of community medicine yusra medical and dental college, islamabad funding source: nil; conflict of interest: nil received: nov 11, 2016; revised: jan 10, 2017 accepted: april 25, 2017 noise related health issuesjiimc 2017 vol. 12, no.2 73 results the mean age of respondents in this survey was 35.4 years with a standard deviation of ± 10.2. the majority (65.3%) spends 9 hours daily in high traffic flow areas and 58.8% lived for more than 4 years or more in their noise affected residential areas. among various findings of our study, difficulty in sleeping was a more prevalent problem showing magnitude of the effect of noise has on the sleep alone, affecting respondents of all ages. the annoyance, stress, easy fatigability and poor digestion were also considerable predicaments owing to noise exposure. the residents complained that ambient noise was interfering with their speech, provided a barrier for proper communication and reducing their productivity leading to difficulty in concentrating on a task and reduced task performance. the people experienced trouble in hearing, buzzing noise in ears and difficulty in understanding spoken words. they also complained of headache and palpitations but to a lesser extent, the findings being presented in figure 1. specific and detailed legislation to deal with the emergingdilemma of noise nuisance in urban areas of pakistan, no national survey has been conducted to assess the noise level in cities and no national standards for prescribing noise limits for residential areas, industrial areas, commercial areas or silence 12-14 zones. there has been a lapse of effort to glean sufficient information on the health hazards caused by 15,16, noise therefore, this study was conducted to determine associated health issues, primarily to highlight the importance of a possible linkage between noise pollution and ill health and provide a growing evidence of effects of noise on community health. the objective of this study was to determine noise related health issues prevailing in the residents of high traffic flow areas of rawalpindi and islamabad. materials and methods a cross sectional study was conducted in high traffic flow residential areas of rawalpindi and islamabad th th from 15 may to 18 october 2015. the present study focused on road traffic noise therefore air traffic noise, railway stations, people living near railway tracks and industrial area were all excluded from the study. occupational and household noise exposures also ruled out. a total of 352 respondents in the age group 25-65 years from these localities were selected through non-probability convenience sampling technique. the sample size was calculated by who sample size calculator. for the purpose of noise exposure assessment, a structured closed ended questionnaire was administered, mainly dealt with duration of residential status and health effects of noise pollution from road traffic noise. the persons were interviewed for auditory and nonauditory effects including annoyance, sleeplessness, interference with communication and other harmful effects. informed consent was taken from the respondents explaining them the purpose of this study and confidentiality of data was ensured. the collected data was analyzed using spss version 22. standard descriptive and analytical statistics were used to analyze the data. frequency distributions were calculated. chi-square test was used to ascertain the association between qualitative variables and p-value less than 0.05 was considered significant. fig 1: frequency of health issues caused by noise the problems faced during sleeping or primary sleep disturbances were frequent awakening, the most significant finding, followed by difficulty falling asleep, waking too early, alteration in sleep stages e s p e c i a l l y r e d u c t i o n i n r e m s l e e p a n d uncomfortable sensations in the body as shown in figure 2. fig 2: problems faced during sleeping due to noise it was appreciated that sleep disturbance prevails in all age groups and this finding was statistically highly significant (table 1). noise related health issuesjiimc 2017 vol. 12, no.2 74 discussion this study was conducted to reveal existing status of potential health effects caused by exposure to noise. the study found that there are certain adverse health effects that can be linked to exposure to traffic noise. excessive noise seriously harms human health. noise can be perceived as being abhorrent by some individuals, which may not pose the same 6 impact on others in the respective vicinity. the results of the study indicate that persons residing in high traffic flow areas and exposed to noise pollution showed sleep disturbance, annoyance, fatigue, difficulty in hearing, stress, lack of concentration, 9,10 reduced task performance and poor digestion. our study suggested that the most significant health issues related to noise exposure were sleeping problems at night and annoyance, a finding 7,9,10 consistent with other studies. uninterrupted sleep is known to be a prerequisite for good physiological and mental functioning of healthy individuals in the present study it was proved that individuals were suffering from sleeplessness due to 10 noise. when sleep disruption becomes chronic the results are long term effects on health and 11,12 wellbeing. studies conducted internationally, suggests that there was a significant relationship between noise annoyance at night and sleeping problem, moreover there is no association between noise and cardiovascular problems, these results were similar 15-18 to our research. in another study it has been reported that majority of the respondents was suffering by frequent irritation, fatigue, and lack of sleep due to noise pollution, the results comparable 19 to our research findings. an important finding of the present study was indigestion or poor digestion suffered by majority (60.5%) of the participants, 9,10,19 inconsistent with other studies. this finding can be explained by the fact that environmental factors like noise can increase the levels of stress hormones in the body causing hyperacidity and alteration in gastrointestinal motility. noise pollution also assumed to hasten and exaggerate the development of latent mental disorders including anxiety, mood changes, nausea, headache, neurosis, psychosis and behavioral 19 changes. our findings showed noise impairs task performance at school and work, increases errors it was also found that participants having exposure to noise for a longer duration with an increment in the time span spent every year, the participants experienced more health issues related to noise. the maximum frequency of health issues was observed among those who spend 9 hours or more daily at high traffic flow areas, as observed with gradually increasing years spent in the high traffic flow residential areas(table 2). table i: frequency of sleep disturbances in all age groups table ii: health issues related to dura�on of exposureat high traffic flow areas noise related health issuesjiimc 2017 vol. 12, no.2 75 who european centre for environment and health. bonn office. 2011. 2. welch d, shepherd d, dirks kn, mc bride d, marsh s. road traffic noise and health-related quality of life: a crosssectional study. noise and health. 2013; 15: 224-30. 3. roswall n, hogh v, envold-bidstrup p, raaschou-nielsen o, ketzel m, overvad k, et al. residential exposure to traffic noise and health-related quality of life—a populationbased study. plos one. 2015; 10: e0120199. 4. riedel n, scheiner j, muller g, kockler h. assessing the relationship between objective and subjective indicators of residential exposure to road traffic noise in the context of environmental justice. journal of environmental planning and management. 2014; 57: 1398-421. 5. clark c, crombie r, head j, kamp iv, kempen ev, stansfeld sa. does traffic-related air pollution explain associations of aircraft and road traffic noise exposure on children's health and cognition? a secondary analysis of the united kingdom sample from the ranch project. american journal of epidemiology. 2012; 176: 327-37. 6. riedel n, kockler h, scheiner j, berger k. objective exposure to road traffic noise, noise annoyance and self-rated poor health–framing the relationship between noise and health as a matter of multiple stressors and resources in urban neighbourhoods. journal of environmental planning and management. 2015; 58: 336-56. 7. frei p, mohler e, roosli m. effect of nocturnal road traffic noise exposure and annoyance on objective and subjective sleep quality. international journal of hygiene and environmental health. 2014; 217: 188-95. 8. foraster m. is it traffic-related air pollution or road traffic noise, or both? key questions not yet settled. int j public health. 2013; 58: 647-8. 9. ali l, zehra t. the ringing bells: perspective of karachi it's regarding noise pollution. journal of the college of physicians and surgeons pakistan. 2014; 24: 940-3. 10. farid m, ali s, shakoor mb. comparative study of noise levels in various areas of faisalabad, pakistan. greener journal of environmental management and public safety. 2013; 2: 166-71. 11. dratva j, zemp e, dietrich df, bridevaux po, rochat t, schindler c, et al. impact of road traffic noise annoyance on health-related quality of life: results from a populationbased study. quality of life research. 2010; 19: 37-46. 12. shepherd d, welch d, dirks kn, mcbride d. do quiet areas afford greater health-related quality of life than noisy areas?. international journal of environmental research and public health. 2013; 10: 1284-303. 13. urban j, maca v. linking traffic noise, noise annoyance and life satisfaction: a case study. international journal of environmental research and public health. 2013; 10: 1895915. 14. shepherd d, welch d, dirks kn, mathews r. exploring the relationship between noise sensitivity, annoyance and health-related quality of life in a sample of adults exposed to environmental noise. international journal of environmental research and public health. 2010; 7: 357994. 15. dekluizenaar y, van lenthe fj, visschedijk aj, zandveld py, and decreases motivation, initially causing concentration lapse, poor understanding and progressively leading to decreased efficiency at 19 work. hearing loss is a key feature observed in other 5,9,10,19 researches in comparison. the problem of experiencing trouble in hearing was most likely due to the direct effect of long and continuous exposure to noise, causing sensor neural hearing loss. early detection of symptoms could yield better prognosis and a definitive treatment strategy could be 19 formed. the assessment of road traffic noise by noise dosimeter (sound meter) was done in a study done in iran but in our study new technological gadgets could not be used to suffice adequate sound measurement which could have effectively yielded masterful 20 results. ignorance or lack of education had been a prime cause to hamper positive results although the symptoms perceived were mostly directing towards particular disease process. this was observed when people highlighted they were suffering from health problems but could not invariably correlate the 21 disease process to noise pollution. since there had been inadequate knowledge on the subject of health hazards of noise pollution as highlighted by our research; the main crux of the problem lies in the fact that general public does not appreciate this problem and do not perceive noise pollution to have negative effects on health due to 21 lack of awareness and ignorance. conclusion the current study concluded that certain health issues are especially attributed to noise pollution posing a major threat to the health of community and gradually worsening the burden of noncommunicable diseases. the most significant findings were sleep disturbance, annoyance, stress, fatigue, indigestion, headache, hearing problems and inefficient daily activities. health education measures should be directed to highlight noise pollution as a public health issue and raise awareness among general public in order to reduce the consequences of noise on human health. references 1. fritschi l, brown l, kim r, schwela d, kephalopoulos s. b u r d e n o f d i s e a s e f r o m e n v i r o n m e n t a l noise—quantification of healthy life years lost in europe, noise related health issuesjiimc 2017 vol. 12, no.2 76 19. shahid m, bashir h. psychological and physiological effects of noise pollution on the residents of major cities of punjab (pakistan). peak journal of physical and environmental science research. 2013; 1: 41-50. 20. dehrashid ss, nassiri p. traffic noise assessment in the main roads of sanandaj, iran. journal of low frequency noise, vibration and active control. 2015; 34: 39-48. 21. jamir l, nongkynrih b, gupta sk. community noise pollution in urban india: need for public health action. indian journal of community medicine: official publication of indian association of preventive & social medicine. 2014; 39: 8-12. miedema hm, mackenbach jp. road traffic noise, air pollution components and cardiovascular events. noise and health. 2013; 15: 388. 16. schmit c, lorant v. noise nuisance and health inequalities in belgium: a population study. archives of public health. 2009; 67: 52-61. 17. kang ts, lee lk, kang sc, yoon cs, park du. assessment of noise measurements made with a continuous monitoring in time. the journal of the acoustical society of america. 2013; 134: 822-31. 18. nitschke m, tucker g, simon dl, hansen al, pisaniello dl. the link between noise perception and quality of life in south australia. noise and health. 2014; 16: 137-42. noise related health issuesjiimc 2017 vol. 12, no.2 77 page 8 page 9 page 10 page 11 page 12 172 editorial history of contraception saadia sultana in primitive societies, perhaps, a couple had 6 to 8 children in total. around half of these offspring perished before they might reproduce, & the population grew very sluggishly. mothers lactated for 3–4 years, and gestations were physiologically according to aristotle, “if you would understand a n y t h i n g , o b s e r v e i t s b e g i n n i n g a n d i t s development”. history can never be unwritten, but familiarity with the past can enlighten the contemporary issues. societal/religious attitudes, o f te n re p re s s e d t h e a c k n o w l e d ge m e nt o f complications related to fertility. globally, people were blinded by the beliefs which were not pertinent to this crucial situation of twentieth century explosion of population. the society has faltered in searching for organizational & technical solutions to control fertility rate even in the west. scientific ideas were not entirely exploited, identified technologies went unapplied, and recent resources that might have made prominent differences were held back. only forthcoming history will decide whether these interruptions, will verify a crippling, or the mortal setback to cultured living. the imbalance between diffusion of contraceptive awareness/regulations and the means to treat disease has produced a burst in global inhabitants which is hard to accommodate. it has, now, contributed to excessive discriminations in affluence and individual misery. the human fertility controlling factors/treatments are not certainly more problematic to comprehend than the cure of bacterial illnesses, i.e. iud insertion/tubal ligation are simpler than instrumental delivery or appendicectomy. valuable understandings into contemporary malfunctions can be achieved by observing the history of 'fertility-control' practices. spaced. with urban civilization, puberty started at an earlier phase of life and breastfeeding was reduced in duration or additional food introduced earlier. hence the fertility improved. without artificially restraining fertility, if a couple starts relationship when the female is above twenty & continues till menopause, she can expect to procreate around 1011 children. therefore, ultimately, all human cultures have to implement some limits on family size. written archives of contraceptive remedies and techniques of abortion are present in the latin writings of pliny elder (23–79 ad), the egyptian ebers papyrus (1550 bc),) and dioscorides (58–64 ad), and the works of soranus (greek-gynaecology, 100 ad). throughout 10th century, while the blossoming of a ra b i c m e d i ca l p ro fe s s i o n , a d i ve rs i t y o f contraceptive endorsements was mentioned, predominantly in the writings of al-razi (rhazes, 923 /924 ad,), avicenna (ibn sina, d. 1037 ad) and alabbas (the royal book 994 ad). 2. reasonable & conceivably effective (honey, lactic acid, alum, pepper etc. used as barriers in the form of pessaries (dioscorides, ebers papyrus) 1. those that nowadays are recognized to be unsuccessful, appeared practical at the time e.g., wiping after vaginal intercourse (soranus). 3. manufacturing vaginal pessaries from the animal's dung, e.g. crocodiles (papyrus), mice (pliny) or elephants (rhazes). jewish references of contraception were closer to few modern approaches e.g. “cohabit with a sponge.” the prevalence of a common method of 'coitus interruptus' for ancient and contemporary societies differs; both old & modern references are fairly common in islamic, christian & jewish manuscripts. the only biblical reference (genesis 38:7) about c o i t u s i n t e r r u p t u s i s v a g u e . o n a n i s m (masturbation/withdrawal), abortion and additional co nt ra c e p t i ve p ra c t i c e s , re c e i ve d g ro w i n g condemnation. nonvaginal intercourse as fertilitycontrol method is rarely conversed, nevertheless it the earliest scholars refer to 3 general groups of methods: correspondence: prof. dr. saadia sultana professor of obstetrics & gynaecology islamic international medical college riphah international university, islamabad e-mail: saadia.sultana@riphah.edu.pk received: november 02, 2019; accepted: december 01, 2019 department of obstetrics & gynaecology islamic international medical college riphah international university, islamabad the foot, or the wooden pestle/rice grinder. 1. podalsky e. medicine marches on. harper, new york. 1902. 5. kuczynski rr. population movements. oxford, new york. 1936 8. curtis ah. textbook of gynaecology. saunders, philadelphia. because of the unequal dissemination of 'death control' & 'birth control', global population is destined to multiply around 3 and 4 times between 1950 & 2050. much of that increase continues to be determined by unplanned pregnancies. around the world, the national family planning programs took enormous time to develop, and the response of developed countries in providing aid/technical assistance was irregular & delayed. it is now the vital obligation to have more focused approach of making people more knowledgeable about fertility control & to make birth spacing widely acceptable. literature also witnessed abstinence as a means of contraception. the sentiments were expressed about 2 centuries ago in a letter by the famous queen victoria (born 1819). victoria was to deliver 9 children before the premature death of prince consort. like millions of common people, she would have benefited, if the '19th century history of contraception' had been different. specifically, she never thought that she was hurrying ovulation by giving all her off-springs to a lactating nurse after birth. it was very difficult for the medical/political systems to extend altruism/selflessness to those stressed to regulate their fertility than to those suffering from diseases. important developments, such as intra uterine devices (iuds) and oral/injectable contraceptives, developed more slowly than they might otherwise have done. 4. mcdaniel wb. the medical and magical significance in ancient medicine of things connected with reproduction and its organs. hist. med. & allied sc. 3: 1948. 6. malkin hj. observations on social conditions, fertility and family survival in the past. proc. roy. soc. med. 53: 1960. references 2. graham h. eternal eve. heinemann, london, england. 1939. 3. simmons a. human infertility. new england med. 1956. 7. price fa textbook of the practice of medicine. oxford medical publications. 9. historical review of british obstetrics and gynaecology. livingstone, london, england. 1800-1950. 'massage abortion' is a cruel technique usually tried when the lady is 4-5 months pregnant. the method has been described in thailand, burma, philippines, malaysia, & indonesia. woman lies on her back, attendant tries to stabilize the uterus and at that moment presses it very hard with the hands, heel of throughout the middle ages, 'induced abortion' & 'coitus interruptus' were acknowledged approaches of birth spacing in married people. in west, some couples managed to postpone conception and few babies were delivered in july/august, when the crucial harvest labour took place. in 1959, archaeologists, while unearthing the skeleton of a 25-year-old girl from a gallo-roman times (first century bc to fifth century ad) in netherlands identified a bone stylet 10.5 cm long in her pelvis. it was interpreted as a lady who died due to an attempt to induce abortion. mechanical abortion and embyotomy (to save the woman's life in childbirth), is cited in olden jewish literatures. seems to have frequently been used in different cultures (550–850 ad). it was narrated by jaabir ibn' abdullah (allah be pleased with him), “we used to practice 'azl' (or coitus interruptus) at the time of prophet mohammed ملسو هيلع هللا ىلص, when the quran was being revealed. (sahih muslim, vol. 3, book of marriage, hadith 3386). it was also mentioned at some places that the wife's permission is a prerequisite for its use as birth spacing method. jaabir (allah be pleased with him) reported: we used to practise 'azl during the lifetime of allah's messenger ملسو هيلع هللا ىلص. this (the news of this practise) reached allah's apostle ملسو هيلع هللا ىلص, and he did not forbid us(sahih muslim, vol. 3, book of marriage, hadith 3388). history is bursting with 'herbal preparations' (for delayed menstruation), and same is being practiced in modern-day culture. one unique ancient method was the herb named 'silphion' transferred from the early greek city cyrene. the plant was extremely precious and worth more than silver. no one is certain if it was an oral contraceptive/abortifacient. 'silphion' was also shown on the cyrene coins. huge efforts were put to cultivate it in other areas of the mediterranean, but remained unsuccessful, & the plant was picked to extinction. 173 jiimc 2019 vol. 14, no.4 original�article abstract objective: to compare the efficacy of epi-off and epi-on collagen cross-linkage procedure in terms of visual outcomes and astigmatism during one-year period. study design: prospective study. place and duration of study: amanat eye hospital from may 2014 to april 2015. materials and methods: eighty patients (102 eyes) with keratoconus were included in this study. there were forty patients (51 eyes) presented with epi-on collagen cross-linkage procedure (group i) and forty patients (51 eyes) with epi-off collagen cross-linkage procedure (group ii). epi-off procedure involved epithelial removal comprised of isotonic riboflavin solution 0.1% with 20% dextran, whereas epi-on procedure involved intact epithelium utilized hypotonic 0.25% riboflavin solution. results: in group i, the mean age of patients was 21.83 years± 3.83 sd. there were 27 (67.5%) male and 13 (32.5%) female patients. in group ii, the mean age of patients was 20.75years ± 4sd. there were 22 (55%) male and 18 (45%) female patients. uncorrected visual acuity improved to 0.04 log mar in epi-on and 0.03 log mar in epi-off procedure with p-value=0.7(statistically insignificant), whereas best corrected visual acuity improved to 0.06 log mar in epi-on and 0.02logmar in epi-off technique with p-value=0.28 (statistically insignificant) respectively. however, mean pre-operative topographic astigmatism were (5.51± 2.58) with epi-on procedure and (3.98 ±2.30) with epi-off procedure, improvement of mean post-topographic astigmatism were improved in epi-on procedure (5.10 ±2.42) than epi-off procedure (3.96± 2.20). conclusion: there was insignificant difference between both cxl procedures. however, improvement of mean topographic astigmatism were observed in epi-on as compared to epi-off collagen cross linkage procedure. key words: epi-on cxl, epi-off cxl, keratoconus, riboflavin. through slit lamp examination, corneal topography, measurement of visual acuity and refraction. since slit lamp examination is unable to show the signs of keratoconus in the early stages and visual acuity may not be affected, corneal topography is the only 7,8 reliable criterion, recent advances in corneal imaging and the possibility of the assessment of the corneal surface with the help of anterior or posterior e l e v a t i o n m e a s u r e m e n t s h a v e p r o v i d e d 9,10 ophthalmologists with valuable information. pentacam employs the scheimpflug imaging technique to present the corneal topographic indices 11 with an acceptable accuracy and repeatability. in the mildest form of keratoconus, spectacles or soft contact lenses may help. but as the disease progresses, with the thinning of the cornea and more irregularity in shape, glasses and regular soft contact lens no longer provide adequate vision correction. corneal cross-linking has made it possible to arrest keratoconus, especially in the early stages, hence significantly reduce the need for corneal 12 transplantation (keratoplasty). therefore, early diagnosis is of vital importance. introduction ke ra t o c o n u s i s d e g e n e ra t i v e e y e d i s e a s e characterized by localized thinning and conical protrusion of the cornea, which typically develops in 1 the inferior-temporal and central zones . it results in distorted, blurred vision, glare and photophobia. consequently, visual acuity is reduced due to irregular astigmatism and high myopia resulting from asymmetric topographical changes in the anterior corneal surface. keratoconus is the most prevalent form of corneal ectasia and affects all 2,3,4,5 ethnicities. it is a progressive condition with a heavy burden for patients as a result of aggravation 6 in the third decade of life. a diagnosis of keratoconus is most commonly made efficacy of epi-off and epi-on collagen cross-linkage procedure in terms of visual acuity and astigmatism in keratoconus patients sumaira amir, aamir asrar correspondence: ms. sumaira amir department of ophthalmology combined military hospital, rawalpindi e-mail: sumairajoya321@gmail.com department of ophthalmology combined military hospital, rawalpindi funding source: nil; conflict of interest: nil received: sep 30, 2016; revised: feb 10, 2017 accepted: march 08, 2017 efficacy of epi-off and epi-on collagen cross-linkjiimc 2017 vol. 12, no.2 92 distance visual acuity (cdva), slit-lamp examination, corneal topography (oculus pentacam). udva and cdva were recorded using log mar early treatment diabetic retinopathy study vision chart at distance of 4m. pentacam topography was used to evaluate preand postoperative corneal topography and pachymetry.silt-lamp examination was done by an ophthalmologist. the selection criteria for cxl procedure includes high k-readings >47.0 d and corneal thickness <450microns .those with kreadings >49.0 d and corneal thickness < 400 microns undergo epi-on cxl procedure,as thin corneas can be best treated with epi-on technique. e p i o f f c x l t e c h n i q u e i nv o l v e d e p i t h e l i a l debridement performed under topical anesthetic drops followed by instillation of isotonic riboflavin drops 0.1% in 20% dextran solution topically for 30 minutes. the cornea was exposed to uva 370 nm light for 3 minutes at an irradiance of 30mw/cm2, bandaged contact lenses were applied for 5 days after the procedure. new intervention for the treatment of keratoconus in regards to patient comfort and safety is epi-on cxl procedure (trans-epi).epi-on cxl involved intact epithelium followed by instillation of hypotonic riboflavin drops 0.25% solution for one hour, then cornea was subjected to uva radiation for 3 minutes with a wavelength of 370 nm at the intensity of 30mw/cm2 within a circular diameter of 9 mm which increases collagen cross-linkages and stiffens the cornea. pre-operatively and post-operative data of visual acuity and astigmatism were measured by using log mar chart and corneal topography (pentacam) at baseline, three and twelve months respectively. the statistical package for social sciences software (spss, version 22) was applied to organize and tabulate the data collected. pre and post-operative data of visual acuity and astigmatism were calculated by using independent sample t-test. all the results were evaluated at a confidence interval of 95%. pvalue <0.05 considered to be statistically significant. results eighty patients (102 eyes) presented with mean age (in years) ± sd as 21.29 ± 4.07. there were forty patients (51 eyes) with epi-on cxl procedure (group i) and forty patients (51 eyes) with epi-off cxl procedure (group ii). in group i, the mean age of corneal collagen cross-linking (cxl) with riboflavin and ultraviolet-a is a new technique of corneal tissue strengthening by using riboflavin as a photosensitizer and uva to increase the formation of intra and inter fibrillar covalent bonds by photosensitized oxidation. there are two procedures introduced for treating keratoconus,epi-off collagen cross-linkage(standard cxl) and epi-on collagen cross-linkage(trans-epi cxl). epi-off cxl involved epithelium removal followed by instillation of 0.1% isotonic riboflavin drops with 20% dextran solutions. however, the epi-on cxl procedure involved intact epithelium with hypotonic riboflavin drops 0.25% solution.long-term clinical reports showed that both t h e s e m e t h o d s h a l t s t h e p r o g r e s s i o n o f 13,14 keratoconus and to some extent improves 1 5 , 1 6 , 1 7 refractive and topographic parameters. recently introduced technique epi-on cxl that involves intact epithelium targets to reduce postoperative pain, reduced chances of infections 18 and early visual recovery. the aim of this study was to find the efficacy of epioff and epi-on collagen cross-linkage in terms of visual outcome and astigmatism in keratoconus patients in order to better define the validity of both techniques. materials and methods a prospective study conducted in the settings of amanat eye hospital, rawalpindi. consecutive sampling technique was used to collect the sample of eighty patients (102eyes) from may 2014 to april 2015 with age group 14-31 years. an informed consent was obtained from all the patients enrolled in the study. an approval was taken from the hospital ethical committee. there were forty patients (51 eyes) with epi-on cxl procedure (group i) and forty patients (51 eyes) with epi-off cxl procedure (group ii). the inclusion criteria included 14-31 years of age, history of vigorous eye rubbing, intolerant to contact lenses, patients with the complaint of unstable refraction, vision deterioration, pentacam corneal thickness 450microns 380 microns depending upon k-readings on the basis of mild<48d, moderate 48-54d and advanced keratoconus>54d.the exclusion criteria included systemic diseases affecting ocular conditions and corneal scarring. pre and post-operative testing included uncorrected distance visual acuity (udva), best-corrected efficacy of epi-off and epi-on collagen cross-linkjiimc 2017 vol. 12, no.2 93 after stratification of keratoconus as mild, moderate and severe, independent samples t-tests revealed that there were statistically insignificant difference between group 1 (epi-on cxl) and group 2 (epi-off cxl) procedure in terms of improvement in astigmatism after three months, twelve months and between three to twelve months of treatment among all three grades of keratoconus, with p values > 0.05 (table iii and iv). patients (in years) ± sd was 21.83 ± 3.83 (range 14 to 31). there were 27 (67.5%) male and 13 (32.5%) female patients. right eye was affected in 15 (37.5%) patients, left eye was affected in 14 (35%) patients while there were 11 (27.5%) patients with both their eyes affected. in group ii, the mean age of patients (in years) ± sd was 20.75 ± 4.27(range 14-31). there were 22 (55%) male and 18 (45%) female patients. the right eye was affected in 17 (42.5%) patients, left eye was affected in 12 (30%) patients while there were 11 (27.5%) patients with both their eyes affected. the independent sample t-test reported no significant statistical difference between epi-on cxl and epi-off cxl procedure in terms of improvement in un-corrected visual acuity after three months, twelve months and between three to twelve months of treatment, with p values > 0.05. there was also statistically insignificant difference among group 1(cxl epi-on) and group 2 (cxl epi-off) procedure on the basis of improvement in best corrected visual acuity with p-value > 0.05 (table i and ii). table i: un-corrected visual acuity a�er epi-on and epi-off cxl procedure table ii: best-corrected visual acuity a�er epi-on and epi-off cxl procedure table iii: as�gma�sm results on the basis of grades of keratoconus a�er epi-on cxl procedure fig 1. graphical representa�on of grades of keratoconus a�er epi-on cxl procedure table iv: as�gma�sm results on the basis of grades of keratoconus a�er epi-off cxl procedure fig 2.graphical representa�on of grades of keratoconus a�er epi-off cxl procedure efficacy of epi-off and epi-on collagen cross-linkjiimc 2017 vol. 12, no.2 94 treating keratoconus. at 12 months post treatment results showed that both procedures proved to be useful and effective in halting the progression of 19 20 keratoconus. caporossi et al and magli et al reported a study of 26 eyes treated by epi-on cxl, and they observed an initial, although not statistically significant, increase in udva and cdva in the first 3 months. however, this study showed no statistically significant difference between both cxl procedures on the basis of uncorrected visual improvement after three months, twelve months and between three to twelve months of treatment. the person who lost 2lines of log mar chart of best-corrected visual acuity (bcva) was 18 years old female who at baseline had un-corrected distance visual acuity (udva) of 0.6 log mar, bcdva of 0.2 log mar and maximum k-value of 56.70d. after 12 months she was noted to had further deterioration of vision, ucdva was 1.0log mar, bcdva was 0.6 log mar and the maximum k value had increased slightly to 57.30d. 21 wollensek et al reported regression with reduction of maximum k readings by 2.01d after epithelial removal in 70% of eyes with mean follow-ups of 23.2 months. in this study we analyzed no change in mean keratometric readings in case of the steep and flat m e r i d i a n w i t h e p i o f f p ro c e d u re . s e v e ra l complications were reported in the literature, especially after epi-off cxl procedure such as corneal 22, 23, 24 edema and endothelial damage. in this study we observed significantly greater postoperative pain in the epi-off cxl group compared to epi-on cxl group with no complications in both treatment groups. an overall analysis of the clinical outcomes after epioff and epi-on cxl showed that keratoconus was relatively stable after 12 months, and no differences were observed comparing the two procedures. the main aim of the cxl procedure initially was to stabilize the keratoconic cornea. stabilization was achieved with extra benefits like more symmetric corneas, which not only increased visual acuity but made the cornea easier to fit with contact lenses. it is reported that the cornea still tolerates contact lenses after the 25 procedure. some investigations indicate that keratoconus leads to keratoplasty in approximately 26,27 20% of patients. collagen cross linkage (cxl) will 28, 29 significantly decrease the need for keratoplasty or at least delay the need for it. mean pre-operative topographic astigmatism were (5.51± 2.58) with epi-on procedure and (3.98 ±2.30) with epi-off procedure, improvement of mean posttopographic astigmatism were improved in epi-on procedure (4.84 ±2.42) than epi-off procedure (3.96± 2.20) after six months as shown in figure iv. table v: the descrip�ve sta�s�cs of keratometric readings a�er epi-on and epi-off cxl procedure fig 3: mean pre-opera�ve topographic as�gma�sm a�er epi-on and epi-off cxl procedure fig 4: mean post-topographic as�gma�sm a�er epi-on and epi-off cxl procedure discussion this study analyzed comparison of cxl procedure in two homogenous groups (epi-on and epi-off cxl) for efficacy of epi-off and epi-on collagen cross-linkjiimc 2017 vol. 12, no.2 95 long-term follow-up of riboflavin/ultraviolet a (370 nm) corneal collagen cross-linking to halt the progression of keratoconus. br j ophthalmol. 2013; 97: 433–7. 15. caporossi a, mazzotta c, baiocchi s, caporossi t. long-term results of riboflavin ultraviolet a corneal collagen crosslinking for keratoconus in italy: the siena eye cross study. am j ophthalmol. 2010; 149: 585–93. 16. magli a, forte r, tortori a, capasso l, marsico g, piozzi e. epithelium-off corneal collagen cross-linking versus trans epithelial cross-linking for pediatric keratoconus. cornea. 2013; 32: 597–601. 17. grewal ds, brar gs, jain r, sood v, singla m, grewal sp. corneal collagen cross linking using riboflavin and ultraviolet-a light for keratoconus: one-year analysis using scheimpflug imaging. j cataract refract surg. 2009; 35: 425–56. 18. filippello m, stagni e, o'brart d. trans epithelial corneal collagen cross linking: bilateral study. j cataract refract surg. 2012; 38: 283–291. 19. caporossi a, mazzotta c, paradiso al, baiocchi s, marigliani d, caporossi t. trans epithelial corneal collagen cross linking for progressive keratoconus: 24-month clinical results. j cataract refract surg. 2013; 39: 1157–63. 20. magli a, forte r, tortori a, capasso l, marsico g, piozzi e. epithelium-off corneal collagen cross-linking versus transepithelial cross-linking for pediatric keratoconus. cornea. 2013; 32: 597–601. 21. wollensak g, spoerl e, seiler t. riboflavin/ultraviolet-ainduced collagen crosslinking for the treatment of keratoconus. am j ophthalmol. 2003; 135: 620-27. 22. rama p, di matteo f, matuska s, paganoni g, spinelli a. acanthamoeba keratitis with perforation after corneal crosslinking and bandage contact lens use. j cataract refract surg. 2009; 35: 788–91. 23. rama p, di matteo f, matuska s, insacco c, paganoni g. severe keratitis following corneal cross-linking for keratoconus. acta ophthalmol. 2011; 89: 658–9. 24. greenstein sa, hersh ps. characteristics influencing outcomes of corneal collagen crosslinking for keratoconus and ectasia: implications for patient selection. j cataract refract surg. 2013; 39: 1133–40. 25. wollensak g, spoerl e, seiler t. riboflavin/ultravioletinduced collagen crosslinking for the treatment of keratoconus.am j ophthalmol. 2003; 29: 620-7. 26. vinciguerra p, albe e, trazza s, rosetta p, vinciguerra r, seiler t, et al. refractive, topographic, tomographic, and aberrometric analysis of keratoconic eyes undergoing corneal cross-linking. ophthalmol. 2009; 32: 369-78. 27. spoerl e, huhle m, seiler t. induction of cross-links in corneal tissue. exp eye res. 2005; 66: 97-103. 28. goldich y, barkana y, morad y, hartstein m, avni i, zadok d. can we measure corneal biomechanical changes after collagen cross-linking in eyes with keratoconus – a pilot study. cornea. 2009; 28: 498-502. 29. kohlhaas m, spoerl e, schilde t, unger g, wittig c, pillunat l. biomechanical evidence of distribution of crosslinks in corneas treated with riboflavin and ultraviolet a light. j cat ref surg. 2006; 32: 279-83. however, limitations of this study include limited treated eyes and shorter follow-ups (12 months). conclusion one year followup study showed that in terms of visual outcomes and topographic parameters, there were statistically insignificant differences between both cxl procedures. however, mean topographic astigmatism tends to improved in epi-on procedure as compared to epi-off cxl procedure. above all, the added advantage of patient comfort reduced postoperative infection and early visual recovery gave epi-on cxl, the best treatment of choice. references 1. auffarth gu, wang l, volcker he. keratoconus evaluation using the orbscan topography system. j cataract refract surg. 2000; 26: 222–8. 2. rabinowitz ys. keratoconus. surv ophthalmol. 2002; 42: 297–319. 3. wagner h, barr jt, zadnik k. collaborative longitudinal evaluation of keratoconus (clek). contact lens anterior eye. 2007; 30: 223–32. 4. weed kh, macewen cj, giles t, low j, mcghee cn. the d u n d e e u n i ve rs i t y s c o tt i s h ke rato c o n u s st u d y : demographics, corneal signs, associated diseases, and eye rubbing. eye (lond). 2008; 22: 534–41. 5. owens h, gamble gd, bjornholdt mc, boyce nk, keung l. topographic indications of emerging keratoconus in teenage new zealanders. cornea. 2007; 26: 312–8. 6. rebenitsch rl, kymes sm, walline jj. the lifetime economic burden of keratoconus: a decision analysis using a markov model. am j ophthalmol. 2011; 151: 768–73. 7. dahl bj, spotts e, truong jq. corneal collagen cross-linking: an introduction and literature review. optometry. 2012; 83: 33–42. 8. randleman jb, trattler wb, stulting rd. validation of the ectasia risk score system for preoperative laser in situ keratomileusis screening. am j ophthalmol. 2008; 145: 813–18. 9. binder ps. analysis of ectasia after laser in situ keratomileusis: risk factors. j cataract refract surg. 2007; 33: 1530–38. 10. belin mw, khachikian ss. an introduction to understanding elevation-based topography: how elevation data are displayed – a review. clin exp ophthalmol. 2009; 37: 14–29. 11. ambrosio r jr, belin mw. imaging of the cornea: topography vs tomography. j refract surg. 2010; 26: 847–9. 12. chen d, lam ak. reliability and repeatability of the pentacam on corneal curvatures. clin exp optom. 2009; 92: 110–8. 13. vinciguerra r, romano mr, camesasca fi. corneal crosslinking as a treatment for keratoconus: four-year morphologic and clinical outcomes with respect to patient age. ophthalmology. 2013; 120: 908–16. 14. o'brart dp, kwong tq, patel p, mcdonald rj, o'brart na. efficacy of epi-off and epi-on collagen cross-linkjiimc 2017 vol. 12, no.2 96 page 27 page 28 page 29 page 30 page 31 original�article abstract objective: the aim of this study was to evaluate the diagnostic utility of calretinin immunostaining in colonic biopsy specimens in patients having a clinical suspicion of hirschsprung's disease. study design: this study was a cross sectional validation study. place and duration of study: the study was conducted at pakistan institute of medical sciences, shaheed zulfiqar ali bhutto medical university (szabmu), islamabad, for a period of 11 months (december 2018 to november 2019). materials and methods: sixty specimens from patients including multiple colonic biopsies and biopsies from rectum for doubted hirschsprung's disease were evaluated. the biopsies were processed in histopathology lab and hematoxylin and eosin slides were examined. 30 ganglionic segments and 30 aganglionic segments along with control specimens were further stained with calretinin immunohistochemical marker and evaluated. results: on hematoxylin and eosin staining, 30 biopsies showed ganglion cells and 30 biopsies showed absence of ganglion cells. calretinin immunohistochemistry was then evaluated on these ganglionic and aganglionic segments. in this study, sensitivity was found to be 91.4 % and a 100% of specificity was established. the positive predictive value and negative predictive value was found to be 100% and 89.2% respectively. conclusion: calretinin immunohistochemical marker can be applied on colonic and rectal biopsy specimens as a dependable and adjunctive tool for diagnosing hirschsprung's disease, as it is easy and reliable to be used in daily practice. key words: calretinin, hirschsprung's disease, immunohistochemistry. absence of ganglion cells in the colon, along with their disrupted proliferation and differentiation. two types of hd are identified: type 1 or short-segment disease that is identified in 60% to 85% of patients with hd. it is characterized by aganglionosis which is limited to the rectum, reaching up to the large gut distal to the splenic flexure. type 2 is labeled as longsegment disease, that is found in 15% to 25% of the patients having widespread aganglionosis of the r e c t u m a n d c o l o n . a g a n g l i o n o s i s i n t h e gastrointestinal tract is demonstrated by the lack of the ganglion cells in the two plexuses of gut wall, the 2,3 submucosal and myenteric plexuses. a combination of clinical symptoms help in diagnosing the hd including, contrast enema, 1 anorectal manometry and histologic findings. histopathological absence of ganglion cells and nerve plexus of submucosa and muscularis propria showing hypertrophy and hyperplasia constitute the diagnostic criteria for hd. hematoxylin and eosin (h & e) staining is conventionally used for the diagnosis of hirschsprung's disease but it requires serial sectioning and also depends on observer's capability introduction obstruction of large gut in infants is commonly caused by hirschsprung's disease (hd). the disease occurrence is about 1 per 5000 live births, with a predicted disease frequency of 1.4 per 5000 live 1 births in asian populations. the etiology of hd is explained by the disruption of migration of neural crest cells, resulting in congenital diagnostic utility of calretinin immunohistochemistry for the diagnosis of hirschsprung's disease 1 2 3 4 5 6 maryam qaiser , saira javeed , rabiya fawad , ayesha sarwar , iram kehkashan khurshid , abrar ul haq satti correspondence: dr. maryam qaiser assistant professor histopathology ,department of pathology hbs medical and dental college, islamabad e-mail: maryamsherazi110@gmail.com 1,4 department of histopathology, hbs medical and dental college, islamabad 2 department of histopathology, islam medical and dental college, sialkot 3 department of histopathology, quetta institute of medical sciences, quetta 5 department of histopathology, cmh medical college, khariyan cantt 6 department of pediatrics rawal institute of health sciences, islamabad received: february 18, 2022; revised: august 17, 2022 accepted: september 10, 2022 diagnostic utility of calretinin ihc in hdjiimc 2022 vol. 17, no.3 170 3 t o e v a l u a t e t h e b i o p s y s p e c i m e n . immunohistochemistry (ihc) in the recent years has been proven to be an additional tool in the diagnosis 4 of hd, with increased diagnostic yield. calretinin is one of the many markers used for diagnosing hd. it is a calcium binding protein which is vitamin d dependent and richly expressed in neurons, steroid producing cells, testicular cells, and neuroendocrine 4, 5 cells etc. ganglion cells in submucosal and myenteric plexus of a normal gut show a positive calretinin expression whereas aganglionic regions of d i s e a s e d g u t s h o w a b s e n c e o f c a l re t i n i n 6,7 expression. in contrast to routine h & e, calretinin ihc staining has become frequently applied immune-marker to identify ganglion cells in colonic biopsies with suspicion of hirschsprung's disease. calretinin carries several advantages in this regard. it is easily performed on paraffin-embedded sections, staining pattern is simple, pattern of interpretation is easy, and it is cost effective. many studies in literature demonstrated a high sensitivity (96%) and specificity (100%) for 8 calretinin. calretinin highlights ganglion cells which are not very apparent on h & e-stained sections, thereby preventing unnecessary surgeries. it is found to be a cost effective and valuable diagnostic support 9 in hd. the study was carried out to determine the diagnostic utility of calretinin immunohistochemical marker for the diagnosis of hirschsprung's disease in order to benefit the clinicians for the management of the patients. materials and methods the place of study was pathology department, conducted at the pakistan institute of medical sciences, shaheed zulfiqar ali bhutto medical university (szabmu), islamabad, pakistan. duration of the study was 11 months, from december 2018 to november 2019. it was a cross sectional validation study. multiple colonic and rectal biopsies from 60 suspected patients of hirschsprung's disease were evaluated. the biopsies were processed in histopathology lab and hematoxylin and eosin slides were examined. biopsies including 30 ganglionic segments, 30 aganglionic segments and control s p e c i m e n s w e r e s t a i n e d w i t h c a l r e t i n i n immunohistochemical marker. calretinin showed a granulated staining of neuronal fibers in lamina propria and submucosal layer of ganglionic segments, whereas ganglion cells showed a dark nuclear and cytoplasmic staining which was seen in the ganglionic segments in both meissner and myenteric plexuses. negative staining shown by neuronal fibers and ganglion cells in all the gut layers was considered as negative for calretinin immunohistochemical maker. inclusion criteria: all colonic biopsies with full thickness sections with suspicion of hirschsprung's disease were included. exclusion criteria: inadequate biopsies which showed only the superficial mucosa without submucosa and muscularis propria were exempted from the study. statistical package for social sciences (spss16) software was applied for performing the statistical analysis. different variables including sex, h&e staining patterns and immunohistochemical results were calculated as frequency and percentages. sensitivity, specificity, positive and negative predictive values were considered by means of 2x2 tables. · sensitivity = true positives / true positives + false negatives x 100 · specificity = true negatives / true negatives + fp x 100 · positive predictive value = true positives / true positives + fp x 100 · negative predictive value = true negatives / true negatives + fn x 100 results colonic biopsies were taken from 60 patients showing an age range from two months to 10 years. male to female ratio was 3.2 to 1. most common presenting complaint was constipation (93%) while some of them presented with abdominal distention and delayed passage of meconium. out of total 60 biopsies (n=60), fifteen biopsies (25%) were from rectosigmoid junction and fourteen (23%) were rectal wall biopsies. on h & e, 30 biopsies showed ganglion cells and the other 30 biopsies showed that ganglion cells were absent. in 16 cases (26.7%), ganglion cells were present in myenteric plexus and 14 (23.3%) cases showed the presence of ganglion cells in both messeiner's and myenteric plexus. out of 30 aganglionic segments, 13 cases diagnostic utility of calretinin ihc in hdjiimc 2022 vol. 17, no.3 171 (21.7%) showed nerve bundle hyperplasia. calretinin ihc was then applied on all ganglionic and aganglionic biopsies. out of the 30 ganglionic segments, calretinin immunoexpression was seen in 27 segments but 3 ganglionic segments were negative for calretinin despite the existence of ganglion cells on routine h&e staining (10%). out of 3 0 a g a n g l i o n i c s e g m e n t s c a l r e t i n i n immunoexpression was seen in five cases (16.6%). all the other 25 cases were negative for calretinin. ( p h o t o m i c r o g r a p h s h o w i n g c a l r e t i n i n immunostaining) therefore 32 cases {27 cases (90%) having ganglion cells on both h & e and calretinin and 5 (16.6 %) cases which showed ganglion cells positive based on calretinin, but h & e declared it negative} were true positives. 25 (83.3%) cases were true negatives showing no ganglion cells on h & e and calretinin. 3 (10%) cases are false negatives which are negative on calretinin but having ganglion cells on h & e. so, this method showed a sensitivity of 91.4 % and specificity was found to be 100%. the positive predictive value was found to be 100% and negative predictive value was 89.2 %. (table i) discussion as diagnosis of hd depends upon the demonstration of the aganglionosis in the colonic biopsy specimens, sometimes it becomes very difficult and tiresome; necessitating furthermore serial cut sections on 10 h&e. to overcome these problems calretinin ihc is 5 now widely used in the diagnosis of hd. the age range of the patients in the current study (n=60) was 2 months to 10 years. rakhshani et al in their study showed that age range of patients with 11 hd was, one day to 12 yr. similarly anbardar et al demonstrated that age of patients suffering from the 5 disease was ranging from 2 days to 10 years. the current study showed a male predominance (75%). collins et al in their study showed that 82% of the 12 patients were male. the study conducted by rakhshani et al also pointed male predominance 11 (67.1%). joseph et al in his study showed that constipation was the most common complaint 13 (94.5%). this was comparable to the current study in which constipation (93%) was most common presenting symptom. in present study out of the total 30 ganglionic segments (which showed ganglion cells on h&e), 27 cases (90%) showed staining of ganglion cells by calretinin. out of the 30 aganglionic segments calretinin ihc was able to pick 5 (16.6 %) cases which were negative on h & e. this study indicated a sensitivity of 91.4 % and specificity was found to be 100%. the results were comparable to the study conducted by mukhopadhyay et al (n=80) and it was shown that calretinin ihc marker had sensitivity equals to 96% and a specificity of value 100%. the positive predictive value was found to be 14 100% and negative predictive value was 92.59%. musa et al and kazemi et al in their studies concluded that calretinin immunostaining, is a very sensitive (100%) and specific (100%) diagnostic tool to the histopathological analysis in the suspected cases of 15,16 hd. in adequate biopsy specimens calretinin ihc is confirmatory, but in case of inadequate biopsies it is 17 decisive, and diagnostic as compared to h&e. in present study, out of 13 cases of nerve bundle hyperplasia, not a single case showed positivity of calretinin. similar was the finding observed by gabal et al in their study that the nerve fibers showing calretinin positivity alone was not sufficient to consider the colonic biopsies as positive for 18 innervation to exclude hirschsprung's disease. table i: utility of calretinin compared to h & e photomicrograph: a: h & e showing ganglion cells in myenteric plexus (400x) arrow points ganglion cell b: calretinin iimmunopositivity of ganglionic segment. (400x) diagnostic utility of calretinin ihc in hdjiimc 2022 vol. 17, no.3 172 3(10%) cases in the current study were classified as false negative which were positive for ganglion cells on h & e but did not show immunoreactivity with calretinin. many studies conducted describe the reasons for false negative results of ihc in the 19 laboratories. human inaccuracy leading to false negative results comprise “wrong on slide control,” “no on-slide control,” and “wrong protocol run,”. it is predicted that the explanations for unsuccessful ihc staining, and their incidences are inconstant among variable laboratories based on test list, platforms, regularity of use, conservation, and obviously the value of the 19,20 control materials in place. many researchers applied calretinin along with other markers as ancillary techniques on rectal biopsies to rule out aganglionosis. study conducted by takawira et al has demonstrated that calretinin is superior to acetylcholinesterase (ache) as an ancillary technique because it is readily available, can be utilized on paraffin embedded tissue and helpful in 3 improving the diagnostic accuracy. zani et al observed in the survey study that as the loss of calretinin staining is a marker of ganglion cell absence in the colon of hd patients and can be easily utilized on paraffin embedded tissue, it has widely replaced ache staining which is applied on frozen 21 sections. similar observation was made by kovach et al showing more significance of calretinin to 22 ache. chisholm km et al also reported that calretinin is easier to accomplish and understand and increases the investigative accurateness in patients 23 of hd. there are few limitations in the study including: small sample size, anatomical subtyping of the lesion into short or long segment or total colonic aganglionosis was not done and the data regarding clinical follow-up was lacking. further studies with large sample size are suggested. research should be directed to describe the calretinin immunostaining configurations of the variable gut portions including transitional zone, rare t y p e s o f h i r s c h s p r u n g ' s d i s e a s e , t o t a l hypoganglionosis patients, and the anorectal junction. genetic studies for mutational analysis in cases of hd should also be carried out. conclusion calretinin immunohistochemistry is an important and reliable diagnostic tool showing high sensitivity and specificity that aids histopathological examination in suspected hd. hence based on sensitivity and specificity we strongly recommend the use of calretinin stain especially in cases where ganglion cells are not seen on routine hematoxylin and eosin staining. references: 1 ali a, haider f, alhindi s. the prevalence and clinical profile of hirschsprung's disease at a tertiary hospital in bahrain. cureus.2021;13:(1): e12480. doi:10.7759/cureus.12480 2 anderson je, vanover ma, saadai p. epidemiology of hirschsprung disease in california from 1995 to 2013. pediatr surg int. 2018, 34:1299-1303. 10.1007/s00383-0184363-9 3 bradnock tj, knight m, kenny s. hirschsprung's disease in the uk and ireland: incidence and anomalies. arch dis child. 2017; 102:722-27. 10.1136/archdischild-2016-311872 4 yan bl, bi lw, yang qy. transanal endorectal pull-through procedure versus transabdominal surgery for hirschsprung disease: a systematic review and meta-analysis. medicine b a l t i m o r e . 2 0 1 9 , 9 8 : e 1 6 7 7 7 . 1 0 . 1 0 9 7 / md.0000000000016777 5 musa za, qasim bj, ghazi hf. diagnostic roles of calretinin in hirschsprung disease: a comparison to neuron-specific enolase. saudi j gastroenterol. 2017; 23:60-6 6 mukhopadhyay b, sengupta m, das c, mukhopadhyay m, barman s, mukhopadhyay b. immunohistochemistry-based comparative study in detection of hirschsprung's disease in infants in a tertiary care center. journal of laboratory physicians. 2017;9(2):76. 7 jiang m, li k, li s, yang l, yang d, zhang x, et al. calretinin, s100 and protein gene product 9.5 immunostaining of rectal suction biopsies in the diagnosis of hirschsprung'disease. american journal of translational research. 2016;8(7):3159 8 jeong j, kim sp, jung e, choi so. the usefulness of calretinin immunohistochemistry for rectal suction biopsy to diagnose hirschsprung's disease. journal of the korean association of pediatric surgeons. 2016;22(2):23-8 9 sikandar m, nagi ah, sikandar k, naseem n, qureshi i. calretinin expression in hirschsprung's disease–a potential marker of ganglion cells. annals of punjab medical college. 2017;11(3):181-6. 10 najjar s, ahn s, kasago i, zuo c, umrau k, ainechi s, et al. image processing and analysis of mucosal calretinin staining to define the transition zone in hirschsprung disease: a pilot study. european journal of pediatric surgery. 2019 ;29(02):179-87. 11 rakhshani n, araste m, imanzade f, panahi m, tameshkel fs, sohrabi mr, et al. hirschsprung disease diagnosis: calretinin marker role in determining the presence or absence of ganglion cells. iranian journal of pathology. 2016;11(4):409. 12 collins l, collis b, trajanovska m, khanal r, hutson jm, teague wj, et al. quality of life outcomes in children with hirschsprung disease. journal of pediatric surgery. 2017;52(12):2006-10. 13 joseph b m, neema m, mange m, alphonce b c, peter f r, diagnostic utility of calretinin ihc in hdjiimc 2022 vol. 17, no.3 173 phillipo l c hirschsprung's disease in children: a five-year experience at a university teaching hospital in northwestern tanzania. bmc res notes. 2014; 7: 410 14 mukhopadhyay m, das c, kumari m, mukhopadhyay b, saha ak. evaluation of calretinin expression in diagnosis of hirschsprung's disease: as an adjunct to histopathological diagnosis. international journal of scientific research. 2019;8(3). 15 musa za, qasim bj, ghazi hf, al shaikhly aw. diagnostic roles of calretinin in hirschsprung disease: a comparison to neuron-specific enolase. saudi journal of gastroenterology: official journal of the saudi gastroenterology association. 2017;23(1):60 16 kazemi aghdam m, khoddami m, mollasharifi t, almasihashiani a. diagnostic value of calretinin and s100 immunohistochemistry in hirschsprung's disease. international journal of pediatrics. 2019;7(6):9577-89. 17 sheir m, samaka rm, fakhry t, albatanony aa. comparative study between use of calretinin and synaptophysin immunostaining in diagnosis of hirschsprung disease. international surgery journal. 2019;6(3):658-63. 18 gabal hh, osman wm, el atti rm. effectiveness of calretinin immunohistochemistry with digital morphometry in mapping of different segments of hirschsprung disease. egyptian journal of pathology. 2016;36(1):9-18. 19 cheung cc, taylor cr, torlakovic ee. an audit of failed immunohistochemical slides in a clinical laboratory: the role of on-slide controls. applied immunohistochemistry & molecular morphology. 2017;25(5):308-12. 20 cates jm, troutman ka. quality management of the immunohistochemistry laboratory: a practical guide. applied immunohistochemistry & molecular morphology. 2015;23(7):471-80. 21 zani a, eaton s, morini f, puri p, rintala r, van heurn e, et al. european paediatric surgeons' association survey on the management of hirschsprung disease. european journal of pediatric surgery. 2017;27(01):096-101. 22 kovach ae, pacheco mc. ganglion cells are frequently present in pediatric mucosal colorectal biopsies: h&e sections and calretinin immunohistochemistry in the evaluation of children with chronic constipation. pediatric and developmental pathology. 2018;21(1):48-53. 23 chisholm km, longacre ta. utility of peripherin versus map2 and calretinin in the evaluation of hirschsprung disease. applied immunohistochemistry & molecular morphology. 2016;24(9):627-32. diagnostic utility of calretinin ihc in hdjiimc 2022 vol. 17, no.3 conflict of interest authors declared no conflicts of interest. grant support and financial disclosure authors have declared no specific grant for this research from any funding agency in public, commercial or nonprofit sector. data sharing statment the data that support the findings of this study are available from the corresponding author upon request. this is an open access article distributed under the terms of the creative commons attributionnoncommercial 2.0 generic license. 174 original�article abstract objective: the aim of the study was to determine prevalence of urinary incontinence in post-partum females in tertiary care setups in hayatabad, peshawar. study design: cross-sectional. place and duration of study: tertiary care hospitals of hayatabad, peshawar from september 2016 to february 2017. materials and methods: a cross-sectional survey was conducted and a total of 296 females between 17 years and 40 years were recruited from september, 2016 to december 2016. the mean age of the population was 27.20 ± 4.46 years. participants were recruited by means of convenience sampling from tertiary care setups in hayatabad and were included in the study according to specified selection criteria. all of the participants completed bristol female lower urinary tract symptoms short form (bfluts-sf) after consent was taken and were evaluated accordingly. results: the prevalence of post-partum urinary incontinence in females coming to inand out-patients departments of tertiary care hospital hayatabad peshawar was 28.64%. out of total, 96% had moderate urinary incontinence i.e. between one third to two third of the time (1/3-2/3) and the remaining 4% had severe incontinence. majority of the women (84.4%) reported nocturia as their major symptom, while nocturnal incontinence/leakage was the lowest (9.8%). bladder pain (48.3%) and intermittency (36.5%) were the next highest reported symptoms. stress incontinence proved to be slightly more prevalent at 45.3%, whereas urge incontinence was at 43.9%. less than half of the population 36.2% women reported an adverse effect on their overall quality of life ranging from a little to a lot on the “bother” scale. conclusion: it can be concluded that urinary incontinence is a common condition in post-partum women in hayatabad with most patients reporting a mild to moderate effect on quality of life. key words: bfluts-sf, perpeurium, post-partum female, tertiary care, urinary incontinence. 3 counterpart's male population. although urinary incontinence is not a mortal condition, still the consequences are severely affecting quality of life of 4 all patients who are suffering from this condition. this issue is well documented and national and international networks have focused on this condition. however still organized, consistent and reliable data is deficient in developing country like pakistan where female population has limited access to health care services. urinary incontinence has various types which are mainly affected by specific conditions and therefore it may be described by specifying its relevant factors associated with those 5 conditions. the various forms of urinar y incontinence are stress, urge, and mixed urinary 6 incontinence. stress ui is the involuntary loss of urine during certain physical activities such as coughing, sneezing, laughing, jumping, or exercising etc., urge ui is the involuntary leakage of urine that is coupled with the lower urinary tract symptom urgency, and mixed ui is accompanied by urgency 1 and exercise, sneezing, or coughing. urinary introduction urinary incontinence is considered a significant health problem worldwide. according to the i n t e r n a t i o n a l c o n t i n e n c e s o c i e t y u r i n a r y incontinence is “the complaint of any involuntary 1 leakage of urine”. it can be associated with significant physical, psychological, social and 2 economic burden. as a result of urinary incontinence, a big portion of population get frustrated, socially isolated and are rendered incompetent. urinary incontinence is a common problem in woman population compared to their prevalence of urinary incontinence in post-partum females in hayatabad, peshawar 1 2 3 4 5 6 zoha gilani , haider darain , sadia aziz , mashal javed orakzai , laila raheem , musarrat jabeen correspondence: dr. haider darain assistant professor & director/principal institute of physical medicine and rehabilitation khyber medical university, peshawar 1,2,3,4,5 institute of physical medicine and rehabilitation khyber medical university, peshawar 6 kmu institute of medical sciences khyber medical university, peshawar funding source: nil; conflict of interest: nil received: jan 12, 2017; revised: mar 12, 2017 accepted: may 14, 2017 urinary incontinence in post-partum femalesjiimc 2017 vol. 12, no.2 106 majority of these studies have been carried out in developed countries. data regarding the prevalence of post-partum urinary incontinence in female population in countries like pakistani is scarce and need attention. therefore, this study was carried out in order to report intensity of the problem in female population living in the country. materials and methods a descriptive cross-sectional study was conducted in the inand out-patient gynaecology departments of tertiary care setups in hayatabad, peshawar. major tertiary care hospitals in hayatabad were included for this purpose. a total of 296 patients took part in the study after detailed information was provided to them and consent was taken. the participants all responded on standard questionnaire [bristol female lower urinary tract symptomsshort form (bfluts-sf)]. the questionnaire comprised of 5 parts and measured incontinence, severity of symptoms and its effect on the patient's quality of l i fe . t h e f i ve cate go r i e s a s s e s s e d by t h e questionnaire were a) filling symptoms which scored nocturia, urgency, bladder pain and frequency between voiding, b) voiding symptoms i.e. starring strain, hesitancy and intermittency c) incontinence symptoms i.e. pre-void dribbling, frequency daily, stress incontinence, unpredictable incontinence and nocturnal incontinence, d) sex symptoms i.e spoilt sex life and urine leakage during sex, e) quality of life symptoms which were scored on a “bother” scale. each question was scored from 0 to 4 with 0 pointing to no symptoms and 4 being worst possible symptoms. the last section i.e. the section consisting of questions pertaining to the quality of life assessed the degree of bother caused the symptoms caused. the sample was selected according to the inclusion criteria which consisted of female patients who were in the perpeurium period i.e. day 1-day 40, and had complaints of urinary incontinence. patients who had systemic diseases such as diabetes mellitus, previous urinary tract infection or any other n e u r o l o g i c a l d i s o r d e r l e a d i n g t o u r i n a r y incontinence were not included in the study. nonprobability sampling was carried out and patients were recruited according to convenience sampling. the total time duration for this study was 6 months. data was analysed using spss version 20. mean, range and standard deviation were measured for the incontinence is often associated with a variety of factors included pelvic floor muscles disorders, postmenopausal hypo-estrogenism, pregnancies and vaginal births, trauma of pelvic floor muscles, pelvic surgeries and the use of various medications like diuretics, chronic constipation, smoking, obesity 7 and diabetes mellitus. urinary incontinence is often considered a problem 8-10 that occurs mostly after pregnancy and childbirth. stanton et al. and allen and warell reported an increase in prevalence of stress urinary incontinence during pregnancy followed by a decrease after childbirth. the prevalence of urinary incontinence is around 20%-30% during pregnancy but it resolves 11 shortly after delivery. in contrast, in other trials, high prevalence of urinary incontinence was 12,13 reported after delivery before gestation. urinary incontinence is four times more common in women under 60 years age than in men of the same range of 14 age. it is noteworthy that prenatal incontinence increases the risk of postpartum incontinence suggesting an increased risk of long-term persistent 15-18 incontinence. the increased incidence rate of stress urinary incontinence during pregnancy and postpartum period is associated with low pelvic floor muscle strength. variation in the number of female population suffering from the condition may be 19,20 found in the literature ranging from 0.7% to 34%. similarly, in a systematic review prevalence of urinary incontinence during pregnancy was reported 16–60 % and after spontaneous and instrumental 21-23 vaginal delivery 16–34 %. the exact mechanism of urinary incontinence remained a dilemma, still, it is assumed that the condition develops at least in part as a result of 24 delivery trauma to the pelvic floor. pregnancy is a normal physiological phenomenon and many systemic changes occurring inside the body of a mother to meet the demands of a foetus. one of these changes included alteration in hormonal levels. it is well-known fact that the level of relaxing increases during pregnancy, which is thought to s t i m u l a t e c o n n e c t i v e t i s s u e r e m o d e l l i n g consequently playing a vital role in the modifications 25 female pelvis for delivery. as urinary incontinence remained a major problem during pregnancy, therefore, a huge number of trials may be found in the literature. it is noteworthy that 107 urinary incontinence in post-partum femalesjiimc 2017 vol. 12, no.2 them most of the time. cross tabulation between incontinence and other variables including age, parity, mode of delivery, duration of labor and bmi showed no significant differences suggesting that these factors have no major contributing role on incontinence in this population. the prevalence of urinary incontinence in this population was 85% with 82% moderately incontinent and 3% severely incontinent. discussion the aim of this study was to find out the prevalence of post-partum urinary incontinence amongst female population of hayatabad, peshawar in tertiary care settings. previous studies have shown post-partum urinary incontinence to be a significant problem with far reaching effects that considerably affects physical and psychological status of female population. a variation in the prevalence of postpartum urinary incontinence might be seen and it 19,20 has been reported between 0.7% to 34% in some trials. on the other hand its prevalence has been 21,22 reported between 16%-34%. in this study, we found the prevalence of post-partum urinary incontinence to be 28.% which in accordance to the previous trials carried out on the prevalence of the condition. finding of our trial suggested that stress i n c o n t i n e n c e r e m a i n e d h i g h e r t h a n u r g e incontinence. a disagreement about the type of incontinence may be found in the literature and higher ratio of developing post-partum stress incontinence in these patients have been 12,26 reported, while in the other trials, post-partum incontinence was reported a rarely occurring 13 situation in these patients. our study revealed that nocturia was one of the most cited symptoms in this population and 85% of the participants had nocturia; almost one fifth reported severe symptoms and more than half reported mild to moderate symptoms. this was followed by bladder pain which was experienced by almost half of the participants. other symptoms that also had high frequencies were intermittency, pre-void dribbling closely followed by starting strain, hesitancy and unpredictable miscellaneous incontinence. similar findings were reported in the trials carried out on urinary 27 incontinence in female population. quality of life assessment proved that the condition had severely affected quality of life in these patients. demographic data. results a total of 296 post-partum female patients with mean age 27.2 ± 4.4 years (range: 17-4 years) were included in this study. the mean marrying age of the participants was 21.32 ± 3.35 (range: 13-30). majority (53%) of this female population had undergone caesarean section while a small number (9%) had instrumental deliveries. the remaining (38%) had normal vaginal deliveries. majority of the female population (41%) was uneducated and the rest had completed their primary level (23%), secondary education (20%), graduation (15%) and post-graduation (1%). nutritional levels were determined by calculating bmis of the patients with most of them (38%) being in the overweight category. a total of 81% patients in this study were having moderately incontinence, while a small number of the patients (4%) were having severely incontinence and 15% of the patients had no symptom of incontinence i.e. they were continent. the mean total score for bfluts-sf was 12.0±10.0 with the following mean subscale scores fs=4.2 ± 3.2, vs= 1.5 ± 2.2, is= 3.6 ± 3.2, ss= 0.3 ± 0.8, qol= 2.3 ± 4.0. higher total sum scores were associated with higher chances of urinary incontinence. individually, nocturia remained the most reported symptom at 84% (64% moderate and 20% severe) while 16% reported no symptoms of nocturia. the lowest reported symptoms were 7% for the question pertaining to urine leakage during sex (see table 1 for frequency of severity of different symptoms). effects on quality of life subsection showed that 36% of the patients had reported an adverse effect on their quality of life (22% moderate14% severe). regarding changing their outer garments, 17% of the patients reported changing their outer garments once while 10% had to change them more frequently. water intake percentages showed that 11% of the population had decreased water intake to prevent frequent urination most of the time whereas 14% reported that they had reduced their water intake occasionally. in response to effects on daily activities, 10% of the patients responded 'quite a bit' and 14% reported a minor effect on their activities of daily living. avoidance of public places with no access to toilets was reported by 27% of the population with 18% avoiding them occasionally and 9% avoiding 108 urinary incontinence in post-partum femalesjiimc 2017 vol. 12, no.2 significantly affects overall quality of life in female population. it was found that the included population had reduced their water intake to help combat the problem while a quarter of the population confessed to avoiding public at places with no toilet facilities including markets or long journeys. the latter had severely affected their living style and majority of the population confined themselves to their homes or their movements were severely restricted. moreover, it was found that female population were using toileting facilities hourly up to multiple times an hour with a big number rushing to toilet in urgency. regarding the questions on sex, they appeared to not be applicable to one third of the population as it was their first pregnancy and they had not yet resumed the activity. regarding those who had it, a small number reported that their sexual life was adversely affects by incontinence. these findings are in accordance to the previous trials were sexual hypo or sexual dysfunction sexual was observed in female 28 population with urinary incontinence. t h e fa c t o rs a f fe c t i n g p o st p a r t u m u r i n a r y incontinence parity remained in accordance with other studies with multiparous women having more of a risk. other factors such as mode of delivery, duration of labour, number of pregnancy and bmi have been found to be significantly related to 20 postpartum urinary incontinence in some studies. however, in our trial no significant results were found for then mentioned factors. culturally, female population in pakistan especially in pathans culture is shy and we assumed that deviation of result from what is available in the literature might be caused by this issue. such issues may be covered by conducting large scale trials in the culture with questionnaires modified to the culture. this might be one of the l i m i t a t i o n s o f t h i s s t u d y. m o r e o v e r, t h e questionnaire used in this study was in english language and data collectors have to explain it to the participants. the responses of the participants were then recorded by the data collectors. conclusion in conclusion, the overall prevalence rate of postpartum urinary incontinence in perpeurial women in tertiary care setups in hayatabad, peshawar was within the range reported in other cultures. urinary incontinence may be regarded as one the major contributing factors that affects table i: showing the frequency values for severity of different symptoms references 1. abrams p, cardozo l, fall m, griffiths d, rosier p, ulmsten u, et al. he standardisation of terminology in lower urinary tract function: report from the standardisation subcommittee of the international continence society. urology. 2003; 61: 37-49. 2. yip sk, cardozo l. psychological morbidity and female urinary incontinence. best practice & research clinical obstetrics & gynaecology. 2007; 21: 321-9. 3. nitti vw. the prevalence of urinary incontinence. reviews in urology. 2001; 3: s2. 4. szymona-pałkowska k, janowski k, pedrycz a, mucha d, ambroży t, siermontowski p, et al. knowledge of the disease, perceived social support, and cognitive appraisals in women with urinary incontinence. biomed research international. 2016; 2016: 12-7. 5. sumeh as, tan ce, jaffar a. types of urinary incontinence, its symptoms bother and effect on quality of life among older women in penampang health clinic. 2014; 8: 13–9. 6. wilson ja. the management of urinary incontinence. us pharm. 2016; 41: 22-6. 7. tanriverdi ha, hakan s, akbulut v. üriner inkontinans ve pelvik prolapsusun epidemiyoloji, etiyoloji ve risk faktörleri. turkiye klinikleri journal of gynecology and obstetrics. 2004; 14: 231-8. 8. thomas tm, plymat kr, blannin j, meade t. prevalence of urinary incontinence. br med j. 1980; 281: 1243-5. 9. sommer p, bauer t, nielsen k, kristensen e, hermann g, 109 urinary incontinence in post-partum femalesjiimc 2017 vol. 12, no.2 urinary symptoms during pregnancy and puerperium in the primipara. international urogynecology journal. 1993; 4: 27-30. 20. wilson p, herbison r, herbison g. obstetric practice and the prevalence of urinary incontinence three months after delivery. bjog: an international journal of obstetrics & gynaecology. 1996; 103: 154-61. 21. thom dh, rortveit g. prevalence of postpartum urinary incontinence: a systematic review. acta obstetricia et gynecologica scandinavica. 2010; 89: 1511-22. 22. burgio kl, zyczynski h, locher jl, richter he, redden dt, wright kc. urinary incontinence in the 12-month postpartum period. obstetrics & gynecology. 2003; 102: 1291-8. 23. brown sj, donath s, macarthur c, mcdonald ea, krastev ah. urinary incontinence in nulliparous women before and during pregnancy: prevalence, 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results of a cross-sectional study. european urology. 2004; 45: 642-8. steven k, et al. voiding patterns and prevalence of incontinence in women.: a questionnaire survey. british journal of urology. 1990; 66: 12-5. 10. jolleys jv. reported prevalence of urinary incontinence in women in a general practice. bmj. 1988; 296: 1300-2. 11. nygaard i. urinary incontinence: is cesarean delivery protective? seminars in perinatology. 2006. 12. allen r, warell d. the role of pregnancy and childbirth in partial denervation of the pelvic floor. neurourol urodyn. 1987; 6: 183-4. 13. stanton s, kerr-wilson r, harris vg. the incidence of urological symptoms in normal pregnancy. bjog: an international journal of obstetrics & gynaecology. 1980; 87: 897-900. 14. sharifiaghdas f, tajalli f, taheri m, naji m, moghadasali r, aghdami n, et al. effect of autologous muscle-derived cells in the treatment of urinary incontinence in female patients with intrinsic sphincter deficiency and epispadias: a prospective study. international journal of urology. 2016; 7; 581-6. 15. groutz a, rimon e, peled s, gold r, pauzner d, lessing jb, et al. cesarean section: does it really prevent the development of postpartum stress urinary incontinence? a prospective study of 363 women one year after their first delivery. neurourology and urodynamics. 2004; 23: 2-6. 16. diez-itza i, arrue m, ibañez l, murgiondo a, paredes j, sarasqueta c. factors involved in stress urinary incontinence 1 year after first delivery. international urogynecology journal. 2010; 21: 439-45. 17. wesnes sl, hunskår s, bo k, rortveit g. the effect of urinary incontinence status during pregnancy and delivery mode on incontinence postpartum. a cohort study. bjog: an international journal of obstetrics & gynaecology. 2009; 116: 700-7. 18. fritel x, fauconnier a, levet c, bénifla jl. stress urinary incontinence 4 years after the first delivery: a retrospective cohort sur vey. acta obstetricia et gynecologica scandinavica. 2004; 83: 941-5. 19. viktrup l, lose g, rolf m, barfoed k. the frequency of 110 urinary incontinence in post-partum femalesjiimc 2017 vol. 12, no.2 page 41 page 42 page 43 page 44 page 45 original�article abstract objective: this study aimed to assess the effect of constraint induced movement therapy (cimt) augmented by virtual rehabilitation in improving upper extremity activity capacity and ability to perform activities of daily living (adl). study design: pre/post quasi experimental study. place and duration of study: it was carried out at the physiotherapy department at holy family hospital, rawalpindi in collaboration with islamic international medical college, riphah international university, islamabad, pakistan from march 2015 to march 2016. materials and methods: the study included 20 stroke patients who were subjected to constraint induced movement therapy augmented by virtual rehabilitation using nintendo wiitm four times a week for four weeks. upper extremity activity capacity and activities of daily living (adl) were measured preand postintervention using action research arm test (arat) and barthel index respectively. results: the arat improved from a pre-intervention mean score of 16.20+3.942 to 48.30+5.768 postintervention (p<0.001). barthel index showed improvement from the pre-intervention mean score of 9.05+2.544 to a post-intervention mean score of 16.80+1.609 (p<0.001). conclusion: virtual rehabilitation using nintendo wiitm has a positive impact on upper extremity motor recovery and subsequently the ability to carry out activities of daily living, if used as an adjunct to constraint induced movement therapy (cimt). key words: constraint induced movement therapy (cimt), nintendo wiitm, stroke, upper extremity motor capacity, virtual rehabilitation. lower limbs, speech difficulties, sensory deficits, impairment of genitourinary or bowel functions etcetera, that hinder activities of daily life and lower the chances of leading a normal, productive and 4 fulfilling existence. upper limb motor function impairment after stroke (the primary focus of this study) is one such complication that neurophysicians and physiotherapy specialists strive to improve as it allows the patients to, not only carry out daily life tasks with more ease and comfort but it has been shown to have a positive impact on the 5 psychological well-being of stroke survivors as well. regaining upper limb motor function post stroke by means of physical therapy has a corresponding positive impact on the ability to carry out routine tasks like bathing, dressing, toilet use, feeding and climbing up and down the stairs (collectively termed 6 as activities of daily living (adl)). constraintinduced movement therapy (cimt) is based on forced use of the affected limb by restraining the uncompromised limb for 90% of the waking hours and “shaping”, a form of behavioral conditioning in which certain task specific exercises are aimed at introduction stroke is the most common cause of disability 1 worldwide with 350,000 new cases per annum and a 2 prevalence of 4.8% in pakistan. thromboembolism of cerebral arteries and hemodynamic disturbances are the two main mechanisms involved in the pathophysiology of stroke. ischemic stroke accounts for 87% of the total burden of stroke while hemorrhagic strokes (spontaneous intracerebral and subarachnoid hemorrhage) comprise of the 3 remainder of all cases. survivors of stroke suffer debilitating sequelae like impairment of motor function of the upper and/or the effect of virtual rehabilitation and constraint induced movement therapy (cimt) on improving upper extremity motor activity post-stroke aiman farogh anjum, humaira fayyaz, arif siddiqui correspondence: dr. aiman farogh anjum department of physiology islamic international medical college riphah international university, islamabad e-mail: aiman.anjum@hotmail.com department of physiology islamic international medical college riphah international university, islamabad funding source: nil; conflict of interest: nil received: apr 22, 2016; revised: nov 05, 2016 accepted: jan 10, 2017 cimt based virtual rehabilitation post strokejiimc 2017 vol. 12, no.3 129 achieving a specific goal (such as movement of the impaired arm). the intensity of these tasks is increased in a step-ladder pattern according to the 7 patient's improvement. virtual rehabilitation is a novel technology that relies on the mirror-neuron system to bring about restructuring of the neuronal network in regions of the brain concerned with memory, learning and 8 motor function. in this aspect, nintendo wiitm is an innovative, cost-effective and ubiquitous technology which makes use of an on-screen “avatar” in order to incite “mirror-neurons” through “audio-visual” input to bring about neuronal re-organization and subsequent motor improvement. it has an added benefit of modifiable skill and speed which can be 9 tailored according to the user's needs. numerous studies have been conducted to shed some light on the effectiveness of virtual rehabilitation on motor improvement in stroke survivors but they have mainly focused on regaining lower limb function. furthermore, combination of vr with cimt for the purpose of improving the motor function profile in stroke survivors is an area that has 10 not been explored at length as yet. as far as the role of cimt augmented by motion capture consoles like nintendo wiitm in improving upper extremity motor function is concerned, a dearth of bonafide 11 research still remains. application of virtual reality based video games, nintendo wii in particular, for objectives other than stroke rehabilitation have shed some light on the effect of this console on improving hand-eye coordination. a study conducted at arizona state university by kullman, 2008, evaluating the efficacy of nintendo wii as a tool for improving hand-eye coordination in surgeons found that the use of n i n te n d o w i i a m o n g s u rg e o n s “ i m p ro ve s hand-to-eye coordination, strength and dexterity as the motion-sensitive controller allows some games to require very precise hand movements, similar to 12 those executed during surgery”. this effect might similarly manifest, albeit to a lesser extent, in the stroke survivor population undergoing “wii13 habilitation” allowing them to regain some level of coordinated hand and arm motion as well as a greater degree of strength and skill. data pertaining to upper extremity rehabilitation employing constraint induced movement therapy based on exergaming technology is scarce. this study aimed to assess the effect of constraint induced movement therapy (cimt) augmented by virtual rehabilitation in improving upper extremity activity capacity and ability to perform activities of daily living (adl). materials and methods this was a pre/post quasi experimental study with one year duration from march 2015 to march 2016. the study was conducted at medical unit i and ii and the physiotherapy department of holy family hospital rawalpindi in collaboration with islamic international medical college rawalpindi after the approval of ethical review committees at both institutions. the inclusion criteria were; first event of stroke, age ranging from 30 to 60 years, impairment of motor function in one arm, 1-4 months since the event of stroke, an understanding of computer/video game technology and clinically defined stroke by ct-scan or mri. patients of stroke with other neurological diseases, cognitive deficits, diagnosed dementia or epilepsy, language difficulty that would affect the capacity to receive information about the training procedure, visual impairment, orthopedic injuries that could impair locomotion, and inability to carry out voluntary arm movement were not included in the study. a total of 20 stroke patients were recruited in the study by purposive sampling. written informed consent was taken from all the subjects. the subjects were asked to report at physiotherapy department at holy family hospital rawalpindi in the morning. age, gender, blood pressure, hemisphere, type of stroke, and handedness of the subjects were recorded. “activities of daily living (adl)” were measured using the “10-item modified barthel index” which has a score of 0-20. upper extremity “activity capacity” was assessed using the “action research arm test (arat)”, scored from 0 to 57. the subjects were then subjected to constraint induced movement therapy/cimt for the upper extremity (a physiotherapy regimen where the use of the un-affected limb is limited by putting a weighted mitt over it for majority of the waking hours) using interactive video gaming technology (nintendo wiitm) for four sessions a week for four weeks (total 16 sessions) of 20 minute duration. the subjects cimt based virtual rehabilitation post strokejiimc 2017 vol. 12, no.3 130 were made to wear a weighted mitt on the unaffected arm during the course of the session. the speed and difficulty of each game was set according to each subject's level of comfort and the dexterity and mobility of the affected arm. the tasks each of the games demanded to be performed are listed in table i. they reported the time for which the unaffected was not used during the previous days before every session. “activities of daily living” and upper extremity “activity capacity” were assessed using the “barthel index” and “arat” respectively. statistical analysis was done using spss 21. results were documented as mean + sd. statistical significance was set at p < 0.05. paired-samples t-test was used to check difference in preand postintervention scores of arat and barthel index. results the demographic variables of the 20 subjects included in the study are given in table ii. highly significant (p<0.001) improvement was seen between the preand post-intervention scores of arat. all four subtests of arat i.e, grasp, grip, pinch and gross movement also showed highly significant improvement between the preand postintervention scores, given in table iii. the preintervention mean barthel index score was 9.05 +2.544. post-intervention barthel index scores improved to a mean value of 16.80 +1.609. the difference was highly significant (p<0.001), given in table iv. figures i, ii, iii and iv depict the comparisons of the items pertaining mainly to upper extremity function, namely “grooming, toilet use, feeding and dressing” in the barthel index, between the preand post-intervention scores of the subjects. the differences between the preand postintervention scores in the “grooming” item was significant (p<0.05) while it was highly significant in the “feeding”, “toilet use” and “dressing” (p<0.001). table i: tasks/movements demanded by each of the nintendo wiitm games employed in the study the gameplay was displayed on a projector screen. since the intervention pertained to the upper extremity only, the patients performed the tasks demanded by the games while sitting upright on a stool. the researcher herself carried out the intervention sessions, providing guidance to the subjects throughout the duration of the gameplay as well as assisting the subjects in case they encountered instability in maintaining sitting position (a rare occurrence). the gameplay sessions were scheduled for four days a week. ten minutes were designated to each of the two games mentioned. patients initially found it difficult to grasp the wii-mote optimally and were thus assisted by the velcro strap provided along with the wii-mote to cater for such difficulties. each subject's progress in terms of gameplay, speed and dexterity was charted along the course of the intervention phase. the level of difficulty of each game was progressively increased after the subjects showed improvement in performing the tasks demanded by the previous level of the videogames. the subjects were also asked to limit the use of the unaffected arm for the rest of the day and note the time for which they complied with this undertaking. table ii: demographic variables of the 20 stroke pa�ents in terms of mean ± sd of age (years), gender, type of stroke, stroke hemisphere, handedness and mean ± sd time since stroke (months) cimt based virtual rehabilitation post strokejiimc 2017 vol. 12, no.3 131 discussion the results showed that cimt augmented with virtual rehabilitation has a positive effect on improving upper extremity activity capacity which lends credibility to similar results seen in the single subject design trial by slijper et al. 2014, testing the effectiveness of computer game based upper extremity function showed marked improvement in arat scores in 11 of its 12 subjects after a five week 14 intervention phase. other similar trials have also shown improvements in arat scores following interventions based on computer, video game consoles as well as virtual rehabilitation. a pilot study aimed at evaluating the safety and effectiveness of nintendo wiitm as a rehabilitative tool for stroke survivors (christie et al., 2010) showed that although there was an overall improvement in arat scores in 6 out of the 9 total subjects after an intervention phase of 6 weeks, only the grip subscale showed significant improvement (p<0.05) in the affected arm. the finger pinch subscale also showed marked improvement but was not found to be 15 statistically significant. the improvement in arat scores in the current study could be attributed to two things. firstly, the current study employed not only nintendo wiitm but also subjected the patients to a detailed regimen of cimt while christie et al., used nintendo wiitm as the sole tool for improving motor function. secondly, the improved motor status of the upper extremity, is believed to be a consequence of long-term potentiation, as observed by saposnik et al. 2010 in the evrest trial, which results in the motor cortex retrieving old, and securing new patterns of motor function as a result of task repetition (one of the hallmarks of virtual 16 rehabilitation). it has been observed that the scores of arat, although consistently improved, are not statistically increased in majority of the trials that employ nintendo wiitm as the sole vehicle for upper extremity rehabilitation. however, studies that have used virtual rehabilitative tools as adjuncts to either 17 conventional therapy or to cimt have shown significant improvements in arat scores postintervention; findings supported by the current study's results. the highly significant improvement seen in the study group barthel index scores lend strength to a number o f s i m i l a r s t u d i e s t h a t e m p l o y e d v i r t u a l r e h a b i l i t a t i o n t o a c h i e v e m o t o r f u n c t i o n improvement for the upper extremity. one such study was the 12 week trial by cameirão et al. aimed at “using a multi-task adaptive vr system for upper limb rehabilitation in the acute phase of stroke” which showed significant improvement in barthel index, motricity and fugl-meyer scales for the upper extremity in the study group which underwent rehab therapy using a “rehabilitation gaming system 18 (rgs)”. trials conducted by kyoung-hee lee 2015, kwon js et al. 2012 and yoon j et al. 2015 were based on comparing the effectiveness of virtual rehabilitation as an adjunct to conventional therapy versus conventional therapy alone for upper extremity rehabilitation. all three trials exhibited significant improvement in the respective forms of barthel indices used in each study in the study 19-21 groups. evidence based on such data suggests a positive impact of virtual rehabilitation on the imp rovement in u p p er limb f u n ct io n a n d subsequently on the quality of everyday life. the possible explanation for the overwhelming improvement in the adl scale scores of the study groups in each of the trials mentioned as well as those of the current study could be the self-driven effort of the subjects in each study to adhere strictly to the therapy regimen, improvement in hand-eye table iii: comparison between the mean ± sd total scores of arat, grasp, grip, pinch and gross movement, pre and post interven�on ac�on research arm test (arat), gross movement (grosmt) * = p<0.05 (pre-interven�on vs post-interven�on) ** = p<0.001 (pre-interven�on vs post-interven�on) table iv: comparison between the mean ± sd barthel index scores between the preand post-interven�on assessment barthel index (bi) * = p<0.05 (pre-interven�on vs post-interven�on) ** = p<0.001 (pre-interven�on vs post-interven�on) cimt based virtual rehabilitation post strokejiimc 2017 vol. 12, no.3 132 coordination and overall increased therapy time (cimt plus time spent playing the virtual rehab games) in addition to the long term potentiation induced by repetitive tasks required to be performed during the gaming sessions. the role of cimt in bringing about significant improvement in motor function, as reflected by results of arat and barthel index in the current study cannot be ignored. according to langhorne et al., 2009 and van peppen et al., 2004, cimt has “a significant effect on increasing upper extremity (arm) function” and a “moderate effect on increasing performance of the activities of daily living immediately following treatment (sirtori et al., 22-25 2009).” conclusion virtual rehabilitation has a positive impact on upper extremity motor recovery if used as an adjunct to more robust models of therapy like constraint induced movement therapy (cimt). it is an effective and safe means of engaging stroke survivors in rehabilitative practices by increasing self-directed therapy time and improving motor function. however, there is a need for trials to be carried out on a larger scale, involving a greater population of stroke patients. references 1. feigin vl. stroke epidemiology in the developing world. the lancet. 2005; 365: 2160-1. 2. khealani ba, wasay m. the burden of stroke in pakistan. international journal of stroke. 2008; 3: 293-6. 3. 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8: 741-54. 25. sirtori v, corbetta d, moja l, gatti r. constraint-induced movement therapy for upper extremities in stroke patients. cochrane database syst rev. 2009; 4: 4-6. cimt based virtual rehabilitation post strokejiimc 2017 vol. 12, no.3 134 page 12 page 13 page 14 page 15 page 16 page 17 original�article abstract objective: to determine the frequency of dyslipidemia among patients suffering from rheumatoid arthritis. study design: descriptive study. place and duration of study: the study was conducted in medicine department in collaboration with pathology department of khalifa gul nawaz teaching hospital bannu, khyber pakhtunkhwa. the duration of study was two years from january 2016 to december 2017. materials and methods: a total of 187 cases were included. inclusion criteria were all diagnosed patient of rheumatoid arthritis of any age and sex. exclusion criteria were patients with history of diabetes mellitus, hypertension, endocrinopathies, alcohol intake and use of oral contraceptive. fasting blood samples were analyzed to measure various fractions of lipids, blood sugar, cholesterol, thyroid hormones, and liver and kidney functions. the data collected was analyzed in spss version 20 for various variables. the results were presented in tables and graphs where required. results: in this study male to female ratio was 0.5:1. the age range was from 22 to 60 years. average age was 43.49 years + 10.94. dyslipidemia was present in 48(25.67%) patients of rheumatoid arthritis; whereas 139(74.33%) patients didn't have dyslipidemia. conclusion: rheumatoid arthritis patients have significant dyslipidemias which may leads to increased risk of cardiovascular diseases. early diagnosis and treatment is mandatory to reduce morbidity and mortality. dyslipidemia must be considered an essential part of ra and may be managed appropriately and in time to avoid/ minimize complications of cardiovascular diseases. key words: cholesterol, dylipidemia, high density lipoprotein, low density lipoprotein, rheumatoid arthritis, triglycerides. 3 cardiovascular diseases. the pattern of cvd in ra is different from general population. they usually have silent ischemic heart disease, sudden death and heart failure. the inflammation of rheumatoid a r t h r i t i s i s a s s o c i a t e d w i t h a c c e l e r a t e d atherosclerosis. recent evidences show that high inflammatory status of ra is associated with lipid paradox especially serum cholesterol, inversely related to risk of cvd in untreated patients of ra. it is noted that inflammation influences lipid profile in ra patients and have a complex relationship between 4,5 inflammatory burden of ra and cvd risk. in general population evidences show that inflammation contributes to the onset and pathogenesis of atherosclerosis leading to cvd, where as inflammation underlies progression of atherosclerosis in ra. the impact of inflammation on dyslipidemia in ra is associated with inverse relationship between cvd risk and lipids levels. a similar relation is observed in other chronic inflammatory diseases like malignancy, sepsis and post myocardial infarction cases. the mechanisms introduction rheumatoid arthritis is a chronic systemic inflammatory disease which mainly manifest as synovitis of multiple joints. it has prevalence of 1% 1 with females more affected than males in 3:1 ratio. rd th 2 peak age of onset is between 3 to 5 decade. the frequency of dyslipidemia in general population is variable in different age groups, more in adults as compared to young. rheumatoid arthritis patients are at 2-3 fold higher risk of atherosclerosis leading to cardiovascular diseases (cvd). as high as 50% deaths in rheumatoid arthritis are due to dyslipidemia among patients of rheumatoid arthritis 1 2 3 4 naseeb ur rehman shah , mohammad sajjad khattak , sami ullah , asim muhammad correspondence: mohammad sajjad khattak associate professor department of pathology bannu medical college, bannu e-mail: sajjadkhattak66@gmail.com 1,3 department of medicine khalifa gul nawaz teaching hospital, bannu 2,4 department of pathology bannu medical college, bannu funding source: nil; conflict of interest: nil received: january 15, 2019; revised: august 10, 2019 accepted: august 12, 2019 dyslipidemia in rheumatoid arthritisjiimc 2019 vol. 14, no.3 146 involved in lipid changes in this inflammatory 6-9 process are not yet clear. the inflammation of ra is also associated with qualitative and quantitative changes of lipids profile. the hdl-c which is having a high protective role in cvd in general population is impaired in ra, leading to accentuation of cvd. genetic studies show that fractional composition of hdl-c isolated from ra 1 0 reveals significant changes. these findings regarding lipid paradox and qualitative and quantitative changes in ra needs further assessment to be addressed in future. in our country we have limited research in this field, and are lacking national consensus regarding lipid monitoring in rheumatoid patients. this study will provide us with local statistics of dyslipidemias in patients of rheumatoid arthritis. the objective of the study was to determine the frequency of dyslipidemia in patients suffering from rheumatoid arthritis patients in southern region of khyber pakhtunkhwa pakistan. materials and methods: this descriptive study was conducted in department of medicine in collaboration with pathology department of khalifa gul nawaz teaching hospital bannu pakistan. the duration of study was two years from january, 2016 to december, 2017. a total of 187 cases were included. inclusion criteria was all patients of rheumatoid arthritis both males and females of any age of more than five years disease duration as per acr criteria 2010 were included. exclusion criteria was patients with history of diabetes mellitus, hypertension, endocrinopathies, chronic kidney diseases, alcohol intake and use of oral contraceptive. all these diseases were excluded either by clinical manifestation or by performing relevant laboratory tests. data was collected after approval from hospitals ethical and research committee. all patients meeting the inclusion criteria were enrolled in the study after their written informed consent from the in and out patient department. aseptic blood sampling was performed from all patients after overnight fasting to measure total cholesterol, high density lipoprotein (hdl-c), low density lipoprotein (ldl-c) and triglyceride to confirm dyslipidemia. all these investigations were performed by a single laboratory under supervision of pathologist. all the relevant information was recorded in a pre designed proforma. the data collected was analysed for frequency with percentages and mean with standard deviation for different variables like age, total cholesterol, hdl-c, ldl-c and triglycerides. the results were presented in tables and graphs where required. operational definition: rheumatoid arthritis: american college of rheumatology (acr) criteria was used for diagnosis. 1. number and types of joints involvement. 2. serological tests like rheumatoid factor and anti citrulinated cyclic protein antibody (anti ccp antibody). 3. acute phase reactants i.e. er y throcy te sedimentation rate (esr) and c-reactive protein (crp). 4. duration of arthritis lasting six weeks or longer. dyslipidemia is defined as marked abnormal 11 concentration of lipoproteins or lipids in the blood. 1. total cholesterol >200 mg/dl 2. high density lipoprotein (hdl) cholesterol <40mg/dl 3. low density lipoprotein (ldl) cholesterol >130mg/dl 4. triglycerides >150mg/dl results in this study the age range of patients was from 21 to 60 years with mean age 43.49+ 10.94 years. male were 66 (35.29%) and female 121 (64.71%) with male to female ratio was 0.5:1. (table 1) the disease was more common in age group of more than 50 years 57(30.5%) followed by age group of 41 -50 years 55(29.4%), 31-40 years 48 (25.7%) and 27 (14.4%) in age group of less than 30 years. (table ii). dyslipidemia was present in 48 (25.67%) patients of rheumatoid arthritis, where as 139(74.33%) ra patients were free of dyslipidemia. (fig: 1).total cholesterol was ranged from 168-330 mg/dl with mean 212±34.96 mg/dl, hdlc was from 23-60 mg/dl with mean 39.9±12.57 mg/dl, ldlc was from 76-156 mg/dl with mean 99.2+ 29.60 mg/dl and triglycerides was 158-285 with mean 196+ 30.64 md/dl.(table iii). male suffered dyslipidemia relatively more common as compared to female. in male 21(31.8%) patients were suffering from dyslipidemia and in females 27(22.3%) patients were suffering from dyslipidemia and 94(77.7%) didn't have dyslipidemia. dyslipidemia in rheumatoid arthritisjiimc 2019 vol. 14, no.3 147 discussion: dyslipidemia is frequently associated with rheumatoid arthritis. in general, in inflammation including active ra have a lipid lowering effect on 12 blood lipid level. also ra patients have increased risk of cvd in relatively low blood cholesterol level in contrast to general population. rheumatoid arthritis increases mortality primarily due to cvd and can reduce life expectancy by about 8-15 years. this increase mortality is mainly due to atherosclerosis and dyslipidemia is a well major recognized risk 13 factor of atherosclerosis. in this study there is diffuse derangement of lipid levels in 25.67% cases. the most common was total cholesterol in 39.58% patients followed by ldl-c in 22.92% cases and hdlc and triglyceride both in 18.75% cases. the age range of patients was from 22 to 60 years with mean age 43.49 years + 10.94 years. in a study conducted 20 by erum et al in 2017 in karachi the age range is from 20-60 years with mean age of 36.31±10.46 21 years. another study conducted by attar et al in 2015 in saudi arabia the mean age is 40.49±12.19 years. the common age group was from 51-60 years 57(30.5%) followed by 41 -50 years 55(29.4%), 31-40 years 48 (25.7%) and 27 (14.4%) in age group of less 20 than 30 years. in a study conducted by erum et al the common age group is 31-40 years 37.5% followed by 20-30 years 32%, 41-50 years 24% and 51-60 years 6.5%. another study conducted by 19 hameed et al in 2017 in iraq the common age group is 50-59 years 345 followed by 40-49 years 22%, 3039 years 16%, 60-69 years 13% and less than 30 years 12%. male patients were 66 (35.29%) and female 121(64.71%) and male to female ratio of 0.5:1. in a 20 study conducted by erum et al male are 11.5% and female 88.5% with male to female ratio of 0.12:1. table i: gender distribu�on of dyslipidemic pa�ents suffering from rheumatoid arthri�s (n=48) fig 1: frequency of dyslipidemia in pa�ents suffering from rheumatoid arthri�s table ii: different age groups of rheumatoid arthri�s pa�ents suffering from dyslipidemia (n=48) table iii: lipid profile of dyslipidemic pa�ents suffering from rheumatoid arthri�s (n=48) table: iv. comparison of frequency of dyslipidemia in various studies this comparison of dyslipidemia in rheumatoid a r t h r i t i s s h ow a l m o st s a m e f re q u e n c y o f 14 dyslipidemia in study done by willerson et al and 15 scott et al. all other studies in above table show high frequency of dyslipidemia as compared to the present study. the reason may be difference in activity of disease during sample collection, different treatment modalities used, patients food habits, epidemiology and life style. amongst the dyslipidemic patients the total cholesterol was 212.3±34.96 mg/dl, hdl-c was 39.9±12.57 mg/dl, ldl-c was 99.2+ 29.60 mg/dl and 14 triglycerides was 196+ 30.64 mg/dl. erum et al show total cholesterol as 169.68±36.68 mg/dl, hdlc 40.02±10.23 mg/dl and ldl-c 93.28±26.17 mg/dl. 16 in hammed et al total cholesterol is 177.6±39.2 mg/dl, hdl-c 44.6±10.9 mg/dl, ldl-c 101.7±30.9 mg/dl and triglyceride is 148.8±70.9 mg/dl. these studies like present study show low level of hdl-c amongst the dyslipidemic patients of ra, which in dyslipidemia in rheumatoid arthritisjiimc 2019 vol. 14, no.3 148 high level is cardio protective. also these studies like present study show high level of ldl-c which is associated with increased risk of cvd in ra patients and the same is true for tc and tg in high level. the small sample size, current laboratory assessment tools and lack of causal relationship between lipid level and inflammatory activities of ra are the limitation of this study. it is suggested to incorporate modern laboratory technique in routine practice for assessment of various fractions of lipids. this study confirms dyslipidemia in ra patients, there might be differences in pattern of dyslipidemia amongst different racial and ethnic group as well as from country to country depending on food habits, religious belief and life style. conclusion: rheumatoid arthritis patients have significant dyslipidemias which may leads to increased risk of cardiovascular diseases. early diagnosis and treatment is mandatory to reduce morbidity and mortality. dyslipidemia must be considered an essential part of ra and may be managed appropriately and in time to avoid/ minimize complications of cardiovascular diseases. references 1. vinapamula ks, manohar sm, bitla ar, kanduri r, bhattaram sk, pemmaraju sr. evaluation of dyslipidaemia in patients with rheumatoid arthritis in south indian population.indian journal of rheumatology 2013; 8 (4):155-60. 2. bahlas s, ahmed mm. lipid levels and association with disease activity in ra and sle in saudi arabia 2013; 11 (7)16. 3. al-zaidi gh, abdulsamad t. serum lipids in patients with active rheumatoid arthritis and its relation to drug therapy: j fac med baghdad 2005; 47(1): 35-9. 4. david b hellmann, john b, imboden jr. musculoskelatal & immunologic disorders. in: stephen j mcphee, maxine a. papadakis. current medical diagnosis & treatment. 49th ed. new york: mc graw hill. 2010; 747. 5. choy e, ganeshalimgam k, semb ag, szekanecz z, nurmohamed m. cardiovascular risk in rheumatoid arthritis: recent advances in the understanding of the pivotal role of inflammation, risk predictors and the impact of treatment. rheumatology 2014; 53:2143-54. 6. tracey e, panoulas ve, smith jp, douglas kmj, metsios1 gs, stavropoulos-la;ompg as et al. rheumatoid arthritis susceptibility genes associate with lipid levels in patients with rheumatoid arthritis. ann rheum dis. 2011; 70:102532. 7. robert b. baron. lipid abnormalities. in: stephen j. mcphee, maxine a. papadakis. current medical diagnosis & treatment, 49th ed. new york: mc graw hill; 2010: 8. brown t. fda approves intravenous golimumab (simponi aria) for rheumatoid arthritis. medscape medical news [serial online]. july 18, 2013; accessed july 30, 2013. a v a i l a b l e a t : h t t p : / / w w w . m e d s c a p e . c o m / viewarticle/807965. 9. aletaha d, neogi t, silman aj, funovits j, felson dt, bingham co 3rd, et al. 2010 rheumatoid arthritis classification criteria: an american college of rheumatology/european league against rheumatism collaborative initiative. arthritis rheum. 2010;62(9):2569-81. 10. shoenfeld y, gerli r, doria a, matsuura e, cerinic mm, ronda n, et al. accelerated atherosclerosis in autoimmune rheumatic diseases. circulation 2005; 112:3337-47. 11. national cholesterol education program (necp) expert panel on detection, evaluation and treatment of high blood cholesterol in adults (adult panel iii). final report. circulation2002; 106:3143-421. 12. turesson c, jacobsson lt, matteson el. cardiovascular comorbidity in rheumatic diseases. vasc health risk manag. 2008; 4:605-14. 13. toms te, symmons dp, kitas gd. dyslipidaemia in rheumatoid arthritis: the role of inflammation, drugs, lifestyle and genetic factors. curr vasc pharmacol. 2010a;8(3):301-26. 14. willerson jt, ridker pm. inflammation as a cardiovascular risk factor.circulation 2004; 109(21suppl 1):112-1110. 15. scott ic, ibrahim f, johnson d, scott dl, kingsley gh. current limitation in the management of cardiovascular risk in rheumatoid arthritis. clin exp rheumatol 2012; 30:228232. 16. hadda v, handa r, aggrawal p, lakshmiy r, umar uk, pandey rm. disease activity and lipid in rheumatoid arthritis: aprospective study. indian j rheum 2007;2:13740 17. soubrier m, zerkak d, dougados m. indication for lowering ldl cholesterol in rheumatoid arthritis an unrecognized problem. j rheumatol 2006; 33:1766-69. 18. nisar a, rasheed u, aziz w,farooqi az. prevalence of dyslipidemia in autoimmune rheumatic diseases.journal of the college of physicians and surgeons pakistan 2012;22 (4):235-9. 19. hameed sb, barzinjy nj. prevalence of dyslipidemia and its association with disease activity in patients with rheumatoid arthritis attending rizgary teaching hospital in erbil city. zanco j med sci 2017;21(2):1781-88 20. erum u, ahsan t, khowaja d. lipid abnormalities in patients with rheumatoid arthritis. pak j med sci. 2017; 33(1):22730. 21. attar sm. hyperlipidemia in rheumatoid arthritis patients in saudi arabia. saudi med j.2015; 36(6):685-90. 22. zrour sh, neffeti fh, sakly n, saoussen h,korbaa y, et al. lipid profile in tunisian patients with rheumatoid arthritis. 2011; 30 (10):1325-31. 23. toms te, panoulas vf, kitas gd. dyslipidemia in rheumatological autoimmune diseases.open cardiovasc med j. 2011;5:64-75. 24. shah sza, devrajani br, devrajani i, bibi i. frequency of dyslipidemia in obese verus non obese in relation to body mass index (bmi) and waist hip ratio (whr) and waist circumference (wc). pak j sci.2010; 61(2):27-31. dyslipidemia in rheumatoid arthritisjiimc 2019 vol. 14, no.3 149 jiims.cdr abstract objective: study design: it was a quasi experimental study. place and duration of study: the study was conducted at the department of orthopedics, pakistan railway hospital, rawalpindi, from august 2011 to september 2012. materials and methods: results: conclusion: key words: frozen shoulder, suprascapular nerve block, intra-articular injection. the objective of this study was to compare the effect of supra scapular nerve block and intra articular injection to relieve pain and reduce disability in the patients of frozen shoulder. patients diagnosed as the cases of frozen shoulder in outpatient department of orthopedics irrespective of their gender were included in the study. forty patients and 50 shoulders were divided into two groups by randomization, one group received single suprascapular nerve block and second group received single intra-articular steroid injection. both groups were advised for physiotherapy after injection. patients' pain levels and ranges of movement were assessed over a period of twelve weeks. the study included 40 patients and 50 shoulders to a single suprascapular nerve block and intra articular steroid injection. the mean age of the patients was 49.4 + 9.97 and the range was 40-60 years. there were 16 females and 24 male patients. post injection assessment of patients was done at two, six, eight and twelve weeks. there was a significant decrease in pain and marked improvement in range of movement with supra scapular nerve block than with intra articular injection. patients' pain levels and ranges of movement were assessed over a twelve week period. suprascapular nerve block produced a faster and more complete resolution of pain and restoration of range of movement than intra articular injection. 76 original article s p o n d y l o a r t h r o p a t h i e s a n d c r y s t a l 2 arthropathies. frozen shoulder or adhesive capsulitis, is a common problem in general practice presenting as pain that may be severe, accompanied by a progressive loss of 3 movements resulting in a loss of function. w h i l e m a n y t re a t m e n t s h a v e b e e n employed, few have been proven in randomized controlled trials such as simple analgesia, nsaids, intra-articular steroid injection and surgery, all have their 4 limitations. physiotherapy is often the first line of management for shoulder pain, it can help in early stages but in established cases, physiotherapy seems to be of little benefit 5 and its efficacy has not been established. the suprascapular nerve supplies sensory fibers to about 70% of the shoulder joint, including the superior and postero-superior introduction shoulder pain has a prevalence of 15%30% in the adult population. it is a common complaint especially amongst the elderly and may lead to functional disability and 1 d e c r e a s e i n q u a l i t y o f l i f e . b o t h suprascapular nerve block (ssnb) and intraarticular injection are effective methods for the treatment of frozen shoulder. shoulder pain is a common cause of morbidity in the community and most common causes of that pain include d e g e n e r a t i v e d i s e a s e a ff e c t i n g t h e glenohumeral and acromioclavicular joints and supporting soft tissue structures in addition to inflammatory diseases such as rheumatoid arthritis (ra), seronegative ------------------------------------------------correspondence: dr. sohail iqbal sheikh hod orthopaedics iimc-t, pakistan railway hospital rawalpindi comparison of suprascapular nerve block & intra-articular injection in the treatment of frozen shoulder sohail iqbal sheikh, awais ahmed, shahid javaid, abdul basit , imran sohail sheikh saba sohail sheikh, zara s. sheikh 77 regions of the shoulder joint and capsule, and the acromioclavicular joint. in addition i t s u p p l i e s m o t o r b r a n c h e s t o t h e 6 supraspinatus and infraspinatus muscles. ssnb performed in conjunction with rehabilitation program can provide the window of opportunity to proceed with 7 effective rehabilitation program. regional nerve block is effective for 8, 9 managing acute or chronic pain. among v a r i o u s n e r v e b l o c k t e c h n i q u e s , suprascapular nerve block is an effective, simple, and practical method for the 8,10-12 management of shoulder pain. it can be performed in the clinic using anatomical 13 landmarks to determine needle placement. the aim of the study was to compare the effectiveness of ssnb versus intraarticular steroid injection, in management of chronic shoulder pain and to assess the effectiveness of these methods, improve range of m o v e m e n t o f t h e s h o u l d e r a n d t o demonstrate the most suitable method for treatment of such patients. materials and methods this quasi experimental study was conducted over duration of 1 year and 2 months from august 2011 to september 2012 in the orthopedic unit of pakistan railway hospital rawalpindi. as such, they had a loss of movement (most loss of external rotation, then abduction, and least loss of internal rotation). with pain that was constant, radiated beyond the elbow, or disturbed sleep. all resisted movements produced no pain. serious pathology was excluded by measurement of esr, random blood glucose, and rheumatoid factor. suprascapular nerve block: a mixture of 40 mg triamcinolone acetonide and 9.5 ml 0.5% bupivacaine hydrochloride (marcain) was injected using the technique described by 7 dangoisse et. al. (figure1). a 21g × 1.5'' needle was introduced through the skin 2 cm cephaloid to the midpoint of the spine of the scapula (figure 1). the needle was advanced parallel to the blade of the scapula until boney contact was made in the floor of the suprascapular fossa. this technique has previously been demonstrated to be safe and to effectively block the articular branches of the suprascapular nerve. the injection was not repeated. the need to include a steroid in the injection has been 9 debated; we chose to include it to minimize the differences between the treatment groups. following each treatment, all patients were given verbal and written instructions regarding a home exercise programme of self-mobilization, joint-stretching, and static rotator cuff strengthening. patients were asked to take only paracetamol for pain relief. intraarticular injection: the solution injected contained 1cc of 2% lidocaine hcl and 2cc (80 mg) methylprednisolone acetate .all patients were injected once. the posterior approach was used to inject glenohumeral joint. the site of entry was same as used for traditional posterior portal for arthroscopy of shoulder. this portal is located 2 to 3 cm inferior and 1 cm medial to the posterolateral tip of the acromion. at this site the attempt was made to pass through the posterior soft spot between the infraspinatus and teres minor muscles. an 18 gauge spinal needle was inserted in this site with tip pointing towards coracoids process anteriorly. the index and middle finger was placed on the coracoid process to direct the tip of needle anteromedially towards the coracoid. when in right direction, the needle faces little resistance on entering the joint. 78 assessment pain levels and range of movement were recorded at initial attendance and after two weeks, six weeks, eight weeks, and twelve weeks. to avoid bias, patients graded their pain using the scale in table i. the sum of the three columns was recorded as the total pain score. range of movement was measured using a goniometer in three planes: abduction and external rotation. no attempt was made to isolate gleno-humeral movement, as total shoulder movement gave more reproducible results and is a better gauge of function. data was entered into performa and was analysed using spss 12. results the study included 40 frozen shoulder patients. the mean age of the patients was 49.4 + 9.97 years and the range was between 40-60 years. there were 16 (40%) females and 24 (60%) males. all patients diagnosed as cases of frozen shoulder were divided into two groups randomly. patients were placed alternately into the two groups. the group i patients received ssnb while group ii received intraarticular injection. after the injections all patients were advised home exercises. patients were serially followed for three months after 2, 6, 8 and 12 weeks time. group i had 13 males and 7 females, their ages were 49.4 + 9.97 with disease duration ranged between 3-12 months. while the ages of group ii was also the same, disease duration ranged between 3.5-12months and it included 12 males and 8 females. both groups did not differ significantly at baseline for personal characteristics as age, sex, disease duration. all the patients recovered in the mean time of six weeks. (range 3 weeks to 12 weeks). three patients did not meet the recovery criteria within three months after injection. these patients did not strictly follow the home exercise routine advised after ssnb and intraartriculer injection. at base time, no significant difference was found between two groups as regard to pain, disability and total pain scores. pain improved significantly in all times of follow up with best improvement in group i. range of active movements showed no significant differences at base time between the two groups. over the 4 time periods, abduction & flexion and external rotation showed significant differences in all groups with gradual improvement from week 2 to week 6 to week 8 to week 12. no complication occurred in ssnb group. table i. scale used to grade severity of pain. tableii: comparison of the two treatment groups at initial assessment table iii: pain scores and range of movement in suprascapular nerve block (snb) and intraarticular groups (ia). 79 while four patients in intra-articular injection complained of shoulder pain anteriorly. three patients claimed that the pain relieved in 2 to 3 days time. but only one patient remained in distress at first assessment. at final assessment no patient claimed of any side effects of the intervention. statistical analysis revealed a significant difference in the recovery of the patients of two groups of frozen shoulder. both the methods used are significant as per statistical value but ssnb give early and long term pain relief and range of motion than intra-articular nerve block. intra-articular oss tabulation suprascapular oss tabulation intra-articular oss tabulation table vii: site of injection suprascapular * range of motion cross tabulation figure 1: dangoisse technique. posterior shoulder view; the needle is inserted 1 cm above the middle of the spine of scapula to the floor of the supraspinatus fossa. ac: acromion; cl: clavicle; ss: spine of scapula. discussion the results of our study show a clear benefit from the use of suprascapular nerve block using bupivacaine and methylprednisolone over intraarticular steroid injection in patients w i t h f r o z e n s h o u l d e r. t h e r e w e r e statistically and clinically significant reduction in pain and disability. this benefit was prolonged, with benefit still present at th 12 week. the improvement in these 80 parameters are better or at least comparable with published studies examining nsaids 14-16or intra-articular steroid injection. not much literature is present on the comparison study of ssnb and intra-articular steroid injection for the treatment of frozen shoulder there were no significant side effects from the injection, which was well tolerated by most of the patients. the ssnb is an effective and safe pain treatment in chronic diseases that affects the shoulder, and has been widely used by professionals in clinical practice such as rheumatologists, orthopedists, neurologists, and pain specialists. the pain in this joint is a frequent complaint and leads to significant functional disability and reduced quality of life of the affected patients. when properly indicated, ssnb should be considered. s h o u l d e r p a i n a n d r e s t r i c t i o n o f glenohumeral movements are the main clinical findings in frozen shoulder. three sequential phases are described in its clinical 8 course. after the painful and stiff phases, the last phase, the resolution phase, is a selfl i m i t e d m e m b r a n e o f t h e j o i n t a re innervated via axillary, suprascapular, subscapular, and musculocutaneous nerves. the suprascapular nerve, which provides sensory fibers to approximately 70% of the shoulder joint has afferent, efferent, and 12 sympathetic fibers. the efferent fibers i n n e r v a t e t h e s u p r a s p i n a t u s a n d infraspinatus muscles. the afferent fibers distribute to the articular capsule and ligaments of the glenohumeral and acromioclavicular (ac) joints and to the periosteum and tendons of the scapula. significant pain relief can be produced if the nerve block can be performed before it gives 8, 12 off to its articular branches. the most appropriate site is around the suprascapular notch, in which the nerve can also be located easily. prominent pain relief is a natural consequence of the regional block of the suprascapular nerve that innervates a wide 8 portion of the shoulder joint. va r i o u s s u p r a s c a p u l a r n e r v e b l o c k techniques have been described by several 11, 12, 14investigators. dangoisse et al described indirect suprascapular nerve blocks, using 14anatomical landmark. we have demonstrated that suprascapular nerve block is efficacious over intra-articular steroid injection without the need to image the area, by ultrasound or fluoroscopy during the procedure. this study shows that this treatment not only reduces pain but also decreases disability and gives clinicians a proven efficacious treatment for patients with frozen shoulder. whether the efficacy would be further improved with guidance of the needle under direct imaging is unknown. longer period of pain relief and combination of nerve block with other approaches to pain relief would also be a potentially worthwhile area to study. it is not clear how the nerve block acts to produce a resolution of the symptoms. as the direct action of bupivacaine cannot extend beyond a few hours or days there must be an effect on the underlying pathology, which owes in part to the patient's ability to perform an adequate exercise programme. the triamcinolone included in the injection may have a systemic anti-inflammatory effect, but this should be the same in both groups. a more definitive study could also have a third group of patients treated by nerve block without steroid. since the nerve block produces a faster resolution, its widespread use could produce a saving of time and 81 further economic benefits if patients are able to return to work sooner. conclusion references combination of physical treatments with suprascapular nerve block significantly improve outcome in chronic shoulder pain, and can be more effective than conventional treatments, offering clear advantages (ease of application, low cost, rare side effects) considering that the top priority of a pain control program is restoring the function of the affected area. further, it may prove to be a useful treatment for patients who are unfit or unwilling to consider manipulation under anesthesia. 1. taskaynatan ma, yilmaz b, ozgul a, yazicioglu k, kalyon ta. suprascapular nerve block versus steroid injection for non-specifi c shoulder pain. tohoku j exp med 2005; 205:1925. 2. edward l, bell l and theodore a. inflammation and shoulder pain. a perspective on rotator cuff disease, adhesive capsulitis and osteoarthritis. business briefing: us orthopedic review2006; 55:233-42. 3. dahan t, fortin l, pelletir m. double blind randomized clinical trial examining the efficacy of bupivacaine 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manipulation following regional interscalene anesthetic block for shoulder adhesive capsulitis: a case series. man ther 2005; 10: 80-7. 10. dahan th, fortinl, pelletier m, petit m, vadeboncoeur r, suissa s. double blind randomized clinical trial examining the efficacy of bupivacaine suprascapular nerve blocks in frozen shoulder. j rheumatol 2000; 27:1464-9. 11. wassef mr. suprascapular nerve block: a new approach for the management of frozen shoulder. anaesthesia 1992; 47: 120-4. 12. shanahan em, smith md, wetherall m, lott cw, slavotinek j, fitzgerald o et. al. suprascapular nerve block in chronic shoulder pain: are the radiologists better? ann rheum dis 2004; 63:1035-40. 13. yasar e, vural d, safaz i, balaban b, ahmet y, goktepe as et. al. which treatment approach is better for hemiplegic shoulder pain in stroke patients: intra-articular steroid or suprascapular nerve block? a randomized controlled trial. clin rehabil 2011; 25: 60-8. 14. dangoisse mj, wilson dj, glynn cj. mri and clinical study of an easy safe technique of suprascapular nerve blockade. acta anaesth belg1994; 45:49-54. 15. bal a, eksioglu e, gulec b, aydog e, gurcay e, cakci a. effectiveness of corticosteroid injection in adhesive capsulitis. clin rehabil 2008; 22: 50312. 16. ryans i, montgomery a, galway r. a randomized controlled trial of intra-articular triamcinolone and/or physiotherapy in shoulder capsulitis. rheumatology 2005; 44:52935. original�article abstract objective: to assess the knowledge, attitudes and deworming practice regarding soil-transmitted helminthiasis among parents of school-going children in rawalpindi. study design: descriptive cross sectional study. place and duration of study: the study was conducted at general outpatient department (opd) of holy th th family hospital, rawalpindi, from 20 february 2019 to 15 july 2019. materials and methods: a pilot-tested, self-structured interview sheet was used to collect data from 350 parents who had at least one school going child. non-probability consecutive sampling technique was used. associations between socio-demographic variables and knowledge and between treatment beliefs and deworming practice were explored. the data analysis was done using statistical software program spss version 25.0. results: most of the participants (71.7%) had adequate overall knowledge about soil-transmitted helminthiasis. majority (84.3%) believed soil-transmitted helminthiasis to be harmful for children's health and wanted more awareness to be raised about the topic. significant associations were found between the better educational status of parents (p=0.040), family/friends as sources of information (p=0.000) and adequate knowledge about soil-transmitted helminthiasis. parents who said it was safe to give deworming medicines to children without sth had significantly higher odds (4.513, p=0.000) of giving deworming medicines to their children than those parents who believed it to be unsafe. conclusion: this study shows that most parents have adequate overall knowledge and correct attitude towards soil-transmitted helminthiasis. however, many parents have a misconception regarding the safety of deworming medicines and this significantly affects their deworming practice. key words: children's health, helminthiasis, parents, public health. of albendazole and mebendazole as safe, efficacious 1 and cost effective antihelminthic drugs. according to global estimates, roundworm infections are the most prevalent (ascaris lumbricoides; about 820 million) followed by hookworm (necator americanus and ancylostoma duodenale; about 460 million) and whipworm 1,2 infections (trichuris trichuria; about 440 million). according to pakistan's first nationwide sth survey conducted in late 2016,19 million school age children were in need of annual treatment throughout the country. rawalpindi and gujrat represented the areas of highest prevalence (56% and 31%, 3,4 respectively). chronic sth of heavy intensity leads to anemia, malnutrition and impaired mental and physical development, especially among children, resulting in l o w s c h o o l a t t e n d a n c e a n d p o o r s c h o o l 5, 6 performance. as a more far reaching consequence, sth can reduce economic productivity and trap introduction soil-transmitted helminthiasis (sth) is a term referring to a group of parasitic diseases caused by nematode worms that are transmitted to humans by soil contaminated with feces. soil-transmitted helminths infect almost 2 billion people worldwide. school-age children (5-14 years) are one of the three high risk groups for sth (along with preschool age 1 children and women of reproductive age). the world health organization (who) advocates the use knowledge, attitudes and deworming practice regarding soil-transmitted helminthiaisis among the parents of school going children 1 2 3 maheen nazir , aqiba malik , faizania shabbir correspondence: maheen nazir rd 3 year mbbs student rawalpindi medical university, rawalpindi e-mail: maheennazir32@gmail.com 1,2 mbbs student rawalpindi medical university, rawalpindi 3 department of physiology gujranwala medical college, gujranwala funding source: nil; conflict of interest: nil received: february 21, 2020; revised: august 18, 2020 accepted: august 27, 2020 knowledge regarding soil-transmitted helminthiasisjiimc 2021 vol. 16, no.2 106 6 countries in poverty cycles. the prevalence rate of sth in pakistan has not 7 decreased over the last two and a half decades. there can be several reasons for this. insufficient knowledge about sth among parents was a predominant reason for the high prevalence among 8 children in china. deficient knowledge is likely to be an easier causative agent to ameliorate compared to other factors linked to sth. these other factors, such as low socioeconomic status, insufficient sanitation and waste disposal, and a lack of clean water, require a much greater input of time and finances to 9 improve. despite this, no study has been conducted so far in the rawalpindi region to evaluate the various aspects of knowledge about sth among parents and the misconceptions regarding this disease that need to be overcome. furthermore, the government of pakistan has recently launched a school-based deworming program in islamabad and 10 rawalpindi to counter the prevalence of sth. a study that explores the awareness and possible misconceptions of parents regarding sth can be used by the concerned authorities to devise an effective awareness campaign, which may then lead to better results from the actual deworming campaigns. thus, this study was planned with an objective to assess the knowledge, attitudes and deworming practice regarding soil-transmitted helminthiasis among parents of school-going children in rawalpindi. materials and methods this was a descriptive cross-sectional study th th conducted from 20 february 2019 to 15 july 2019 at general out-patient department (opd) of holy family hospital, rawalpindi, after the institutional ethical approval was taken from institute research forum (irf). parents of both genders, willing to participate, with at least one school-going child falling under the age group of 5-14 years, were included in the study. parents working as doctors, nurses, and health workers were excluded from the study. sample size was calculated to be 350, for a confidence level of 95% and margin of error 5%, based on the prevalence of knowledge about sth (65.3%) from a similar study conducted in 11 bangladesh. non-probability consecutive sampling technique was used. every patient who arrived at the opd between 8:00 am to 12:00pm and met the aforementioned criteria to be a participant was approached for the interview by the administrators. the interviews were conducted over a period of about 6 months till data from 175 mothers and 175 fathers had been collected. verbal informed consent w a s o b t a i n e d f r o m a l l p a r t i c i p a n t s a n d confidentiality was assured. the data collection tool was a 10-15 minute, pilottested, self-structured interview sheet in urdu with questions that were adopted from related studies 11,12 conducted in bangladesh and malaysia. the i n t e r v i e w s h e e t c o n t a i n e d q u e s t i o n s o n demographic variables (age, highest level of education, socioeconomic status, number of children) and on knowledge regarding transmission, signs and symptoms, prevention and treatment of sth. in the attitudes section, parents were asked about whether they believed sth to be harmful for their children and wanted more awareness to be spread about sth. lastly, parents were asked if they had ever administered deworming medicines to their child. the questions on knowledge were openended. participants were not given options so as to eliminate the bias due to guessing. instead, several possible responses to the questions were prerecorded from previous studies and an initial pilot study. the answers to the knowledge questions during the actual data collection were usually one of these pre-recorded answers. in knowledge about transmission, signs and symptoms and prevention, a maximum score of 2 was awarded for more than one correct pre-coded answer given by the parent; 1 mark was awarded for 1 correct answer and 0 marks were awarded for no correct answer. for knowledge about treatment, a correct response to each of the 3 questions was worth 1 mark. thus, the highest achievable score was 9. parents with a score of 5-9 were categorized as having adequate knowledge, whereas parents having scores below 5 were categorized as having inadequate knowledge. to assess various aspects of knowledge, frequencies and percentages were calculated. chi-square test was used to check for any significant associations. binomial logistic regression was applied on the significant association found between treatment beliefs and deworming practice. p-value ≤0.05 was considered significant. the data analysis was done knowledge regarding soil-transmitted helminthiasisjiimc 2021 vol. 16, no.2 107 using statistical software program spss version 25.0. results the mean age of the parents was 36.2 ± 9.2 years. most parents 263(75.1%) had received some degree of formal education, while 87(24.9%) had received no formal education. most participants belonged to low socio-economic status (165, 47.1%), followed by middle (128, 36.6%) and high socio-economic status (57, 16.3%). the majority of parents (223, 63.7%) had less than 3 children whereas 127(36.3%) had more than 3 children. out of the 350 parents, 314 (89.7%) had heard about sth, whereas only 36 parents (10.3%) had never heard of the disease before. the most common sources of information about sth for participants were friends and family members (187, 53.4%). table i shows that educated participants and those who heard about sth from friends or family were significantly more likely to have adequate knowledge about sth. table ii indicates that out of 314 parents who had at least heard about sth, the majority correctly stated that ingestion of soil led to sth. only about 17% incorrectly stated that eating sweet things led to sth. the common signs and symptoms told by the parents were mostly abdominal pain, anemia, pallor, and reduced growth despite overeating. the most commonly stated means of prevention by the participants was taking deworming medicines fig. 1 shows knowledge about treatment of sth. of the 314 participants, 285(90.8%) knew that medicines were available in pharmacies to treat sth. only 85(27.1%) parents correctly stated that it was safe to give deworming medicines even to those children who do not have sth. only 60(19.1%) table i: association between demographic characteristics and knowledge of respondent about sth (n=350) table ii: knowledge about various aspects of sth. knowledge regarding soil-transmitted helminthiasisjiimc 2021 vol. 16, no.2 108 sth = soil transmitted helminthiasis sth = soil transmitted helminthiasis parents were of the incorrect opinion that a life time cure is provided by administering the medication only once. overall, 251(71.7%) of the 350 participants had adequate knowledge about sth while 99(28.3%) had inadequate knowledge. from varied socio-demographic backgrounds was assessed. education was found to be significantly associated with adequate knowledge. this is in accordance with a study conducted in south 13 africa. an educated person is compelled to learn more about diseases from reliable sources such as internet articles and pamphlets. most parents in our study obtained their information from friends or relatives and this was significantly associated with adequate knowledge. this is probably because, as shown by our study, most parents have sufficient knowledge about sth and can serve as reliable dissemination channels themselves. in south africa, where below 50% of the participants had adequate knowledge about sth, parents who accessed health information through mass media were more likely to 13 have adequate knowledge. although most parents in our study (71.7%) were found to have adequate knowledge, only one other study, conducted in kenya, reported that a reasonable proportion of participants had sufficient 14 knowledge. the rest of the surveys from china, bangladesh, malaysia, south africa, western côte d'ivoire, islamabad (pakistan) and nigeria reported 8,11,13,15,7 poor knowledge about sth. misconceptions about sth were common in these studies. for example, 90% of the participants in a western côte d'ivoire village incorrectly stated that the consumption of particular eatables such as 15 sweetened foods was the main cause of sth. in our study, only 16.9% of the parents incorrectly mentioned eating sweet things as a cause of sth and 9.9% mentioned avoidance of eating sweet things for prevention. contact with soil as a cause for sth was correctly stated by very few of the participants (8.7% ) in bangladesh, whereas in present study, children eating soil was the most commonly cited cause 11 (50.3%). fatima et al reported that among the 151 mothers living in urban slums of islamabad, 50% respondents did not know about the source of worm infection and only 13.9% knew about the medicine 16 for worm infestation. in contrast, only 21% of the participants in our study did not know about the source of infection and almost 91% knew about the medicine in nigeria, 88.4% of the study population . did not know what preventive measures could be adopted for sth whereas only 13.7% of our study fig 1: knowledge of parents about treatment of sth (n=314). sth: soil-transmitted helminthiasis out of the 350 parents, 295(84.3%) held the correct attitude that sth was harmful for children's health, 46(13.1%) did not know whether it was harmful and 9(2.6%) did not think it was harmful. most participants (329, 94.0%) wanted more awareness to be spread about sth via mass media. slightly more parents had previously given deworming medicine to their child (178, 50.9%) than those who had not (172, 49.1%). in table iii, binomial regression analysis shows that parents who said it was safe to give deworming medicines to children without sth had significantly higher odds (4.513, pvalue=0.000) of giving deworming medicines to their children than those parents who believed it to be unsafe. table iii: binomial logistic regression analysis of treatment beliefs and deworming practice discussion in this study, the knowledge, attitudes and deworming practice regarding sth among parents knowledge regarding soil-transmitted helminthiasisjiimc 2021 vol. 16, no.2 109 population did not know any means of prevention for 17 sth. to summarize, most other studies reported inadequate knowledge about transmission, signs and symptoms, and prevention of sth as opposed to our study which showed adequate knowledge in these areas. this may be attributed to the better education level of the parents in our study (75.1% were educated), compared to other studies (as in the survey conducted by fatima et al in islamabad, where 64% of the mothers were illiterate). some of the surveys, such as the one in south africa, also tested knowledge about the life-cycle of helminths, which was not tested in our survey. the difference in study setting could also have contributed to the discrepancy of results; in the other studies, parents were interviewed in a location other than the hospital, for example, in their households or in schools. in our study, they were interviewed in a tertiary hospital, where it is more likely that they had acquired knowledge about the disease from other patients or health professionals. the most commonly stated means of prevention was taking deworming medicines (36.9%), but this percentage was lower in comparison to bangladesh 11 (94.2%). over the years, bangladesh has had several more mass deworming campaigns compared to pakistan, so it is understandable why more parents there knew that anti-helminthic drugs can serve as preventive chemotherapy. about 81% of the participants in our study agreed that administration of deworming medicines once was not enough to provide a lifetime cure. this suggests that most parents would approve of the who recommended biannual administration of antihelminthic medicines in areas where baseline prevalence is more than 50%. despite the overall adequacy of knowledge, a large majority (72.9%) had the misconception that it was unsafe to administer deworming medicines to school-age children who did not have sth. this is possibly due to lack of confidence in the efficacy of the drugs used and widespread fear of adverse side 18 effects. a similar mindset was reported in rural china where deworming medicines were thought to be unsafe for children and to cause infertility, despite the safety of medicines like albendazole for schoolage children being extensively confirmed in 8 literature. our study showed that parents who believed it to be unsafe to administer deworming medicines to children without sth were less likely to administer deworming medicines to their children. in who recommended deworming programs, children are given deworming medicines irrespective of whether they have a diagnosed worm infection or not. if parents consider these medicines to be unsafe, they may not allow their children to take part in such programs. therefore, targeted campaigns to clear any misconceptions regarding the safety of deworming medicines before the launch of deworming programs may lead to maximum participation of children in school-based as well as doortodoor health worker based deworming programs. the limitation of this study is that the study setting is restricted to a single tertiary-care hospital and does not provide insight into level of knowledge about sth based on area of residence (rural or urban). further studies should be conducted, especially in rural areas of pakistan, to have a broader view on adequacy of knowledge and misconceptions regarding sth. conclusion this study shows that most parents have adequate overall knowledge and correct attitude towards soiltransmitted helminthiasis. however, many parents have a misconception regarding the safety of deworming medicines and this significantly affects their deworming practice. references 1. world health organisation. guideline: preventive chemotherapy to control soil-transmitted helminth infections in at-risk population groups 2017. report no.: 9241550112. 2. pullan rl, smith jl, jasrasaria r, brooker sj. global numbers of infection and disease burden of soil transmitted helminth infections in 2010. parasit vectors. 2014; 7:37. 3. monohagan p. pakistan's first nationwide sth survey: determining the intensity and prevalence of worm infections. [internet]: evidence action; 2017 [cited 2019 march 27]; available from: https://www.evidenceaction. org/blog-full/first-sth-survey-pakistan. 4. world health organization, ird pakistan, indus health network, institute of development and economic alternatives, evidence action (2017) baseline survey report of soil-transmitted helminthes prevalence in pakistan;2017 [ c i t e d 2 0 1 9 m a r c h 2 7 ] ; av a i l a b l e f ro m : h t t p s : / / pndajk.gov.pk/uploadfiles/downloads/baseline%20sth%2 knowledge regarding soil-transmitted helminthiasisjiimc 2021 vol. 16, no.2 110 0survey_pakistan_final%20%20%20survey%20report.pd. 5. al-mekhlafi hm, azlin m, aini un, shaik a, sa'iah a, fatmah ms, et al. protein-energy malnutrition and soil-transmitted helminthiases among orang asli children in selangor, malaysia. asia pac j clin nutr. 2005;14(2):188-94. 6. hotez pj, fenwick a, savioli l, molyneux dh. rescuing the bottom billion through control of neglected tropical diseases. the lancet. 2009;373(9674):1570-5. 7. blum aj, majid mf, hotez pj. pakistan: a nation held back by ntds. plos negl trop dis. 2018; 12(10):e0006751. 8. lu l, liu c, zhang l, medina a, smith s,rozelle s. gut instincts: knowledge, attitudes, and practices regarding soil-transmitted helminths in rural china. plos negl trop dis. 2015; 9(3): e0003643. 9. de silva nr, brooker s, hotez pj, montresor a, engels d, savioli l. soil-transmitted helminth infections: updating the global picture. trends parasitol. 2003;19(12):547-51. 10. the express tribune. 17m children targeted for massdeworming. [internet]; 2019 [cited 2020 july 27]; available from: https://tribune.com.pk/story/2123851/17mchildren-targeted-mass-deworming 11. nath tc, padmawati rs, alam ms, das s, murhandarwati eh. elimination of soil-transmitted helminthiasis infection in bangladesh: knowledge, attitudes, and practices regarding mass drug administration. j glob health rep 2018; 2: e2018017. 12. nasr na, al-mekhlafi hm, ahmed a, roslan ma, bulgiba a. towards an effective control programme of soil-transmitted helminth infections among orang asli in rural malaysia. part 2: knowledge, attitude, and practices. parasit vectors. 2013;6(1):28. 13. sacolo-gwebu h, kabuyaya m, chimbari m. knowledge, attitudes and practices on schistosomiasis and soiltransmitted helminths among caregivers in ingwavuma area in umkhanyakude district, south africa. bmc infectious diseases. 2019;19(1):734. 14. masaku j, mwende f, odhiambo g, musuva r, matey e, kihara jh, et al. knowledge, practices and perceptions of geo-helminthes infection among parents of pre-school age children of coastal region, kenya. plos negl trop dis. 2017; 11(3): e0005514. 15. ackaca, raso g, n'goran ek, tschannen ab, bogoch ii, seraphin e, et.al. parasitic worms: knowledge, attitudes, and practices in western côte d'ivoire with implications for integrated control. plos negl trop dis. 2010;4(12): e910. 16. fatima sr, qureshi ah, kumar r, naveed i, khushik ia, ronis k. assessment of knowledge attitude and practice (kap) about worm infestation and deworming among mothers of children under-5years of age living in the slum of islamabad pakistan. isra med j. 2016;8(1):23-19. 17. oyebamiji da, ebisike an, egede jo, hassan aa. knowledge, attitude and practice with respect to soil contamination by soil-transmitted helminths in ibadan, southwestern nigeria. parasite epidemiol control. 2018;3(4): e00075. 18. lorenzo pj, manzanilla dr, cortel dk, tangog e. community perceptions of mass drug administration for soiltransmitted helminthiasis and schistosomiasis in selected schools in the philippines. infectious diseases of poverty. 2019;8(1):87. knowledge regarding soil-transmitted helminthiasisjiimc 2021 vol. 16, no.2 111 original�article abstract objective: to evaluate the effectiveness of hiv pre-exposure prophylaxis (prep) in hiv clinic of a tertiary care hospital in pakistan. study design: a descriptive study covering the data of clients who were offered prep. place and duration of study: hiv treatment center pakistan institute of medical sciences (pims) islamabad, pakistan, from october 2019 to september 2022. materials and methods: total of 118 people without hiv from various high-risk population groups were reported in hiv treatment center pims during a period of 3 years including 39 females from serodiscordant couples, 16 transgender females, and 63 men having sex with men (msm). all of them were given oral prep after necessary screening, investigations, and evaluation. these clients were prescribed a fixed drug combination of tenofovir/lamivudine (tdf/3tc) one tablet daily as prep. the alternate regimen used was event-driven prep (edp) for msm. monthly follow-up was performed, and all patients were found to be hiv negative. results: all 118 clients receiving prep remained seronegative on regular monthly follow-ups after a sufficiently long period of unsafe sexual practices that frequently exposed them to hiv-positive sex partners. based on their age mean age of the clients in young group below 35 years was 27 + 6, all 62 young clients had 100% protection. similarly, 41 middle aged (mean age 43 + 6) and 15 old clients (mean age 56 + 5) had 100% protection with prep. six women from serodiscordant couples while receiving prep became pregnant with partners who had completely suppressed viral load (<50 copies). conclusion: oral prep has offered complete protection to all seronegative individuals belonging to high-risk population groups despite their frequent exposure to hiv-positive partners. all 118 individuals who received prep remained seronegative. key words: hiv, pre-exposure prophylaxis, serodiscordant couples, event-driven prep. hiv prevention, ms. data from randomized trials found no significant differences in the efficacy of lamivudine and emtricitabine, consistent with very similar chemical 13 structures of these two nucleoside analogues. there has been a growing need to find effective methods to stop spread of hiv infection to healthy individuals. prep is an effective and safe method of prevention of hiv transmission in high-risk population groups. while the incidence of hiv has declined worldwide over the past decade, many new hiv infections occur globally highlighting the ongoing need for new and effective hiv prevention initiatives. oral pre-exposure prophylaxis of hiv (prep) is the use of antiretroviral drugs (arvs) by hiv seronegative individuals from high-risk population 1 groups to block the acquisition of hiv . the us food and drug administration approved tdf with emtricitabine (ftc) for oral prep in 2012. in 2015, who recommended once-daily oral prep to population susceptible of hiv. however, for msm, introduction hiv/aids is a global public health problem. there is no cure for the disease and once the hiv infection is acquired by an individual, he needs life-long treatment with arvs to keep the viral load 1 6 suppressed. most common ways for hiv transmission are unsafe sex practices and injection drug use with shared syringes. despite a global awareness campaign, many people tend to ignore the risks involved and indulge in unsafe sex practices or share syringes with other injection drug users. a systematic review of published and unpublished effectiveness of hiv pre-exposure prophylaxis (prep) in pakistan 1 2 3 4 5 6 muhammad waqar aslam khan , usman nawaz , ali faheem , mehwish memon , mahak memon , aleem ul haq correspondence: dr. ali faheem department of pharmacology cmh kharian medical college, kharian e-mail: alif49218@gmail.com 1,2 3,4,5,6 department of pharmacology/biochemistry cmh kharian medical college, kharian received: october 13, 2022; revised: february 20, 2023 accepted: february 23, 2023 pre-exposure prophylaxis(prep) of hivjiimc 2023 vol. 18, no.1 27https://doi.org/10.57234/jiimc.march23.1550 the 2019 who guidance include options for event 14 driven dosing (on demand prep). oral prep trials have shown evidence of effectiveness in certain high-risk population groups in society including serodiscordant couples, msm, transgender females, 5. and injection drug users (idus) in pakistan, the prep regimen consists of a fixed-dose combination of tenofovir with lamivudine in place of emtricitabine. 3 oral prep containing tdf co-formulated with ftc or 3tc is recommended as an additional prevention option for persons at substantial risk of hiv infection by both who and the us president's emergency plan 2 1 for aids relief (pepfar). clinically 3tc is interchangeable with ftc for prep given comparable pharmacologic equivalence, resistance, and toxicity 2 patterns , and indirect clinical trial evidence from 1 2 tdf-containing studies. prep has provided significant protection to these high-risk population 4 groups . daily oral prep with tenofovir/emtricitabine is highly efficacious in preventing hiv infection with high adherence and safe to use during pregnancy 9 and breast-feeding. therefore we design our study to evaluate the effectiveness of hiv pre-exposure prophylaxis (prep) in hiv clinic of a tertiary care hospital in pakistan. materials and methods this descriptive study was carried out in a tertiary care hospital in the federal capital of pakistan after obtaining approval from institutional ethical committee ref no 6/9/22 (1). this study covers a period of 3 years from october 2019 to september 2022. behavioral therapy was conducted by experienced counselors of the hiv clinic before initiating the prep therapy, and biomedical 8 interventions were explained to the clients. as per who guidelines, seronegative males, females, and transgender women of all ages from key population groups and those with unsafe sex practices were offered prep. during the last 3 years, 118 individuals from high-risk population groups were given prep including 63 msm, 39 female members of serodiscordant couples, and 16 transgender 15 females. selection criteria were strictly followed as per the who guidelines for offering prep. after initiation of arvs, regular follow-up of individuals was ensured and compliance/adverse effects as well as the hiv-negative status of clients monitored. the following three eligibility criteria were necessary for offering prep: confirmed hiv-negative status, no signs, and symptoms of acute hiv infection, and acknowledged being at substantial risk for hiv. exclusion criteria for prep include hiv infection, adolescents less than 35 kg, impaired renal function, allergy, or contraindication to any drug in the prep regimen, refusal to follow up, and pregnancy. prep regimen: i. fdc (fixed dose combination; lamivudine 300 mg + tenofovir (tdf) 300 mg ii. daily dosing prep 15 iii. edp (event driven prep) or 3-day prep following lab investigations were performed to determine the eligibility status of the individual for prep:1. rapid test: negative 2. rfts: normal 3. pregnancy test for the female client: negative clients receiving prep were divided into three groups based on gender i.e., males, females, and transgender women. another division was made based on age i.e., clients less than 35 years, 35 to 60 years, and more than 60 years. another grouping was done according to the high-risk population groups i.e., msm, hiv-negative members of serodiscordant couples, and heterosexual sex workers. follow-up was done regularly for an uninterrupted supply of medicines. a rapid test was performed after every 3 months. serum creatinine was also checked after every 3 months. prep was discontinued in 6 females temporarily due to pregnancy and resumed after childbirth with the mother's consent. results a total of 118 seronegative clients from high-risk 7 population groups were given prep . all individuals remained seronegative on regular follow-up tests with rapid test kits. these clients were msm, female m e m b e rs o f s e ro d i s c o rd a n t c o u p l e s , a n d transgender women. the total number of clients were divided in three groups based on their ages : <35 y, 35-50 y, and >50 y. based on their age (table-1), mean age of the clients in young group below 35 years was 27 + 6, all 62 young clients had 100% protection. similarly, 41 middle aged (mean age 43 + 6) and 15 old clients (mean age 56 + 5) had 100% protection with prep. another comparison based on gender (table -1) pre-exposure prophylaxis(prep) of hivjiimc 2023 vol. 18, no.1 28 https://doi.org/10.57234/jiimc.march23.1550 table i: age, gender, and risk population-based data of study participants (n= 118) 12 (300 mg) is used mostly as a daily single dose . in the case of msm, edp is offered as it needs less frequent dosing and provides an option to the individual to 11 administer the prep as per his sexual practices . this regimen is supposed to provide better compliance by 17 the client. an uninfected member of a serodiscordant couple is offered prep after behavioral therapy and counseling of the hiv-positive partner to use arvs and ensure compliance to keep the viral load at an undetectable level (<50 copies on pcr). in case the female is on prep and the couple meets the above criteria, then pregnancy is permitted, and according to who guidelines pregnant female is given a choice to discontinue prep to avoid any adverse effects on the fetus. prep is restored after the delivery of the baby. in our study 6 females from serodiscordant couples became pregnant, their prep was stopped during pregnancy and all 6 delivered healthy babies. their prep was restored after delivery and all of them were advised to breastfeed their babies since it is a safe 9 practice. transgender female clients were advised daily prep regimen because of their unsafe practice and a lifestyle that makes them vulnerable to acquiring hiv infection from multiple sex partners. these clients are mostly registered with ngos due to which they remain under continuous surveillance by the dedicated staff. their compliance is good and regular follow-up is expected. most clients from the msm group were referred by ngos that deal with hiv/aids population. they are reluctant to show up and need a lot of persuasion, encouragement, and a guarantee of complete confidentiality to convince them for starting prep. due to efforts of ngos, this group constitutes the biggest proportion of clients receiving prep from hiv treatment center pims. it was noted with interest while conducting the analysis that no client was registered in prep from population groups like idus and female sex workers. on further investigation main reason was the fact that idus are mostly hiv positive and therefore do not fit into the inclusion criteria for prep. moreover, some msm may be using injection drugs but there is a possibility that they did not disclose because most of these clients were reluctant to seek prep and reported voluntarily only due to motivation by ngos msm: men who have sex with men idu: injection drug use. shows all three groups have 100% protection from hiv with prep. another group based on high-risk population groups (figure-1) shows complete protection for msm, discordant couples and transgenders. however, there was no client in idus group since no one opted to get prep from idus, those who are registered with hiv clinic are all hiv positive and do not fulfill criteria to administer prep. figure 1: comparison of prep clients according to highrisk population groups discussion the centers for disease control and prevention (cdc) reports that studies on prep effectiveness have shown that consistent use of prep reduces the risk of 15 getting hiv from sex by about 99%. certain hiv seronegative population groups are more at risk of acquiring hiv infection because of their marital relationship with an hiv-positive spouse or due to their adopted unsafe practices. such individuals need protection against the potential transmission of infection by physical methods like the use of 10,19 condoms and avoidance of unsafe sex practices. however, this approach is seldom adopted either by these vulnerable people themselves or by their sex partners resulting in the transmission of hiv to a previously uninfected individual. to avoid this risk, prep was introduced by fda and who. prep is offered to people who are hiv-negative but are at risk of getting hiv through sex or injection drug use, they take arvs daily to prevent hiv infection. the fixed drug combination of tdf (300 mg) with 3tc pre-exposure prophylaxis(prep) of hivjiimc 2023 vol. 18, no.1 29https://doi.org/10.57234/jiimc.march23.1550 to use prep. female sex workers do not agree to document their activities by disclosing their 20 profession or activities. prep has been providing safety to 118 registered clients since 2019. some of them are using arvs for 2 to 3 years and are still hiv-negative. the analysis of the study and results obtained show complete safety to the clients on prep. their regular follow-up and investigations provide a pattern of the efficacy of arvs as well as the safety of the regimen used. it has been a useful tool so far for the prevention of hiv transmission to vulnerable population groups who are frequently exposed to sexual contact with hivpositive patients. conclusion results compiled from this study showed that prep therapy is highly effective to prevent hiv in different risk groups of different ages. high-risk population groups are benefiting from this program which is successfully working since october 2019. there were no reports of any serious side effects of arvs, no therapeutic failure, no case of loss to follow-up, no issue of compliance, and no evidence of resistance to used drugs. there is a need to initiate prep in other hiv clinics in pakistan after a successful launch in islamabad. references 1. nicholls e, rosengarten m. prep (hiv pre-exposure prophylaxis) and its possibilities for clinical practice. sexualities. 2019;23(8):1327-1342. 2. pilkington v, hill a, hughes s, nwokolo n, pozniak a. how safe is tdf/ftc as prep? a systematic review and metaanalysis of the risk of adverse events in 13 randomised trials of prep. journal of virus eradication. 2018;4(4):215-224. 3. baldwin a, light b, allison we. pre-exposure prophylaxis (prep) for hiv infection in cisgender and transgender women in the u.s.: a narrative review of the literature. archives of sexual behavior. 2021;50(4):1713–28. 4. jongen v, reyniers t, ypma z, schim van der loeff m, davidovich u, zimmermann h et al. choosing event-driven and daily hiv pre-exposure prophylaxis – data from two european prep demonstration projects among men who have sex with men. journal of the international aids society. 2021;24(8): 1213-1220. 5. baeten j, haberer j, liu a, sista n. preexposure prophylaxis for hiv prevention. jaids journal of acquired immune deficiency syndromes. 2013;63(supplement 2):s122-s129. 6. murchu e, marshall l, teljeur c, harrington p, hayes c, moran p et al. oral pre-exposure prophylaxis (prep) to prevent hiv: a systematic review and meta-analysis of clinical effectiveness, safety, adherence, and risk c o m p e n s a t i o n i n a l l p o p u l a t i o n s . b m j o p e n . 2022;12(5):e048478. 7. kamitani e, johnson a, wichser m, mizuno y, deluca j, higa d. mapping the study topics and characteristics of hiv preexposure prophylaxis research literature: a protocol for a scoping review. bmj open. 2019;9(5):e024212. 8. hong c, abrams l, holloway i. technology-based interventions to promote the hiv preexposure prophylaxis (prep) care continuum: protocol for a systematic review. jmir research protocols. 2022;11(3):e33045. 9. hill l, golin c, saidi f, phanga t, tseka j, young a et al. understanding prep decision making among pregnant women in lilongwe, malawi: a mixed-methods study. journal of the international aids society. 2022;25(9): 90816. 10. franks j, teasdale c, olsen h, wang c, mushimebele n, tenda mazala r et al. prep for key populations: results from the first prep demonstration project in the democratic republic of the congo. aids care. 2021;34(3):359-362. 11. mutua g, sanders e, mugo p, anzala o, haberer j, bangsberg d et al. safety and adherence to intermittent pre-exposure prophylaxis (prep) for hiv-1 in african men who have sex with men and female sex workers. plos one. 2012;7(4):e33103. 12. mujugira a, baeten j, hodges-mameletzis i, haberer j. lamivudine/tenofovir disoproxil fumarate is an appropriate prep regimen. drugs. 2020;80(18):1881-1888. 13. orkin c, squires ke, molina j-m, sax pe, sussmann o, lin g, et al. doravirine/lamivudine/tenofovir disoproxil fumarate (tdf) versus efavirenz/emtricitabine/tdf in treatmentnaive adults with human immunodeficiency virus type 1 infection: week 96 results of the randomized, double-blind, phase 3 drive-ahead noninferiority trial. clinical infectious diseases. 2020. 14. schaefer r, schmidt h, ravasi g, mozalevskis a, rewari b, lule f et al. adoption of guidelines on and use of oral preexposure prophylaxis: a global summary and forecasting study. the lancet hiv. 2021;8(8):e502-e510. 15. 2022. [online] available at: <https://www.cdc.gov/ hiv/pdf/risk/prep/cdc-hiv-prep-guidelines-2021.pdf> [accessed 22 september 2022]. 16. pillay t, cornell m, fox m, euvrard j, fatti g, technau k et al. recording of hiv viral loads and viral suppression in south african patients receiving antiretroviral treatment: a m u l t i c e n t r e c o h o r t s t u d y. a n t i v i r a l t h e r a p y. 2019;25(5):257-266. 17. vuylsteke b, reyniers t, de baetselier i, nöstlinger c, crucitti t, buyze j, et al. daily and event-driven pre-exposure prophylaxis for men who have sex with men in belgium: results of a prospective cohort measuring adherence, sexual behaviour and sti incidence. journal of the international aids society. 2019;22(10):54–7. 18. mujugira a, baeten jm, hodges-mameletzis i, haberer je. lamivudine/tenofovir disoproxil fumarate is an appropriate prep regimen. drugs. 2020;80(18):1881–8. 19. hillis a, germain j, hope v, mcveigh j, van hout mc. preexposure prophylaxis (prep) for hiv prevention among men who have sex with men (msm): a scoping review on prep service delivery and programming. aids and behavior. pre-exposure prophylaxis(prep) of hivjiimc 2023 vol. 18, no.1 30 https://doi.org/10.57234/jiimc.march23.1550 2020;24(11):3056–70. 20. pinto rm, lacombe-duncan a, kay es, berringer kr. expanding knowledge about implementation of preexposure prophylaxis (prep): a methodological review. aids and behavior. 2019;23(10):2761–78. 21. padian ns, holmes cb, mccoy si, lyerla r, bouey pd, goosby ep. implementation science for the us president's emergency plan for aids relief (pepfar). jaids journal of a c q u i r e d i m m u n e d e f i c i e n c y s y n d r o m e s . 2011;56(3):199–203. conflict of interest authors declared no conflicts of interest. grant support and financial disclosure authors have declared no specific grant for this research from any funding agency in public, commercial or nonprofit sector. data sharing statment the data that support the findings of this study are available from the corresponding author upon request. this is an open access article distributed under the terms of the creative commons attributionnoncommercial 2.0 generic license. pre-exposure prophylaxis(prep) of hivjiimc 2023 vol. 18, no.1 31https://doi.org/10.57234/jiimc.march23.1550 original�article abstract objective: to assess the experience of loneliness and suicidal ideations among young adults. study design: descriptive cross-sectional study. place and duration of study: the study was conducted from march 2015 to february 2016 across the young adults residing in rawalpindi and islamabad. materials and methods: purposive sampling technique was used for data collection from community sample young adults (n=308; aged between 18-25 years). self-report measures that are, de jong gierveld loneliness 1,2 scale and scale for suicidal ideation were used for the data collection. participants were categorized as suicide ideators and non-ideators through independent sample t-test. bivariate pearson correlation was also calculated. afterward, the moderating role of gender was assessed in the relationship between suicidal ideation and loneliness. results: loneliness was positively correlated with suicidal ideations. individuals identified as suicide ideators scored significantly higher on both of social and emotional loneliness as compare to non-ideators. in an alliance, gender significantly moderated the relationship between suicidal ideations and emotional loneliness where females with a higher level of emotional loneliness were more prone to develop the suicidal ideations. conclusion: in general young adult population suicidal ideation is significantly associated with loneliness. this point outs the desired significance of efforts to minimize loneliness with regards to diminishing its detrimental effects on well-being as well as general health of young adults. key words: loneliness, suicidal ideation, young adults. are interrelated in a way to decline the ratio of 8,9 suicide. one-fourth significant indicator in lieu of attempting or committing suicide is the existence of 8–12 suicidal ideation. such ideations can transpire all the way through the lifetime and are the second most prominent reason of death amongst 15-29 year 3 olds worldwide. for the meantime, loneliness is an associative risk factor along with suicidal ideations for morbidity and mortality. both non-case-control and case-control designs studies where relatives of persons who committed suicide depicted loneliness as often one 13,14 of the major factor leading to suicidal death. meanwhile, previous studies also revealed the existence of an association among feelings of being alone and involving in suicidal activities. for instance, greater levels of loneliness were assessed, 15 amongst under treatment suicide attempters. certainly, more or less evidence recommends that loneliness can remain a significant risk element for suicidal behavior throughout the lifespan as research amongst adolescents, middle-aged, and aging adults have altogether interconnected it to be a introduction agreeing to world health organization every year around 800000 individuals die because of suicide, 3 constituting one individual in every 40 seconds. every single case of such death itself establishes a tragedy. above all, they also intensely affect the mental health of surrounding individuals along with the social order of society, thus such affected individuals often require the desired psychosocial 4 support. numerous risk dynamics for suicidal behavior was recognized, given as lower class economic status, history of child neglect and abuse, 5-7 and mental illness. protecting elements as social support, religious associations, and life contentment experience of loneliness and suicidal ideation among young adults: the moderating role of gender meh para siddique, rubina hanif correspondence: meh para sidddique phd schalor national institute of psychology, quaid-i-azam university, islamabad e-mail: mehpara1612@gmail.com national institute of psychology, quaid-i-azam university, islamabad funding source: nil; conflict of interest: nil received: january 01, 2019; revised: february 01, 2019 accepted: june 15, 2019 loneliness and suicidal ideation among young adultsjiimc 2019 vol. 14, no.3 126 contributing risk for suicidal ideation in addition to 16-18,33 suicide attempts. while evidence on countless features of the relationship between loneliness and suicidal ideations nonetheless leftovers is limited. in specific, most of the empirical studies carried out up till now were accompanied within precise subpopulations like high school students, indoor patients, and the aging individuals, whereas little focus was found to assess this specific association in the general young adult population. although young 19 adults are more prone to mental illness. this is an essential research gap as previous research data provide an indication that the frequency of loneliness among adults can be elevating in few countries probably as a consequence of fluctuations in lifestyles resultant of greater divorce rates, inhabitants aging, along with smaller-sized 20,21 families. therefore research is required to fill this gap as establishing this association between loneliness and suicidal ideations can lay an evidencebased foundation to address preventive measures to minimize the loneliness as well the suicidal ideations. simultaneously, this research will provide an enhanced understanding of the psychological phenomenon that subsidies to suicidal behavior, and will manage for mental health experts with clear criteria for classifying those at risk, then contribute to the establishment of in effect suicide prevention and intervention approaches. taken together, the main aims of the current study was to assess the experience of loneliness and suicidal ideations among young adults. furthermore, the foremost objectives of study were: (1) to address the association between loneliness and suicidal ideation in general young adult population; (2) to scrutinize the level of loneliness among suicidal ideators and non-ideators; and (3) to examine the moderation role of gender in association of suicidal ideations and loneliness. materials and methods the present cross sectional study was conducted from march 2015 to february 2016 across the young adults residing in rawalpindi and islamabad. the study protocol for current research was being approved from the ethical board of national institute of psychology, quaid-i-azam university islamabad. sample to address study objectives comprising of 308 young adults (126 male & 182 female) within an age range of > 18 and < 25 years was obtained by means of purposive sampling. they were all pakistani nationals and native urdu speakers having no problem with urdu language (talking, reading, understanding, and writing) respectively. individuals at current or previously diagnosed with any psychiatric ailments were instantly excluded from the study sample. if the inclusion and exclusion criteria were met, then each participant was being tested individually in two steps. during step i, the informed consent was signed from the participant. after rapport building, the researcher filled the d e m o g ra p h i c s h e et w h i l e q u e st i o n i n g t h e participant. next, the participants were requested to fill the set of questionnaires by providing their genuine response. finally, participants were thanked for their participation. this set of questionnaires consisted of self-report measures. in order to measure the level of loneliness the de jong gierveld loneliness scale was utilized whereas, the suicidal ideation scale was used to 1,2 examine the suicidal ideations. the loneliness scale is grounded on a cognitive theoretical characterization of loneliness, which highlights the incongruity among what person desires in positions of interpersonal liking and intimacy, and what person actually has; the more the difference, the more the loneliness. thus, loneliness is understood as an individual experience which is not openly linked to 1 situational aspects. it is a 06-item instrument to be scored on a 4-point scale ranging from “no” to “yes”. it has two subfactors, the emotional loneliness scale, and the social loneliness scale, and the sum of their scores provides the total loneliness score. instrument reliability ranges from .70 to .74 1 (cronbach's α). the suicidal ideation scale was designed to screen individuals in the community for presence of suicidal thoughts and assess the severity of these thoughts. it targets an attribute of suicidal thoughts: frequency, controllability, closeness to attempt, level of distress associated with the thoughts and impact on daily functioning. the i n st r u m e nt h a d h i g h i nte r n a l co n s i ste n c y 2 (cronbach's α = 0.91). the parametric data was analyzed with the help of 22 spss 24. at first, we calculated descriptive statistics cronbach's alpha reliability's followed by inferential statistical analysis i.e., pearson bivariate correlation loneliness and suicidal ideation among young adultsjiimc 2019 vol. 14, no.3 127 (p < .01; p < .05), independendent sample “t” test ( p < .001; p < .01; p < .05 ) and moderation analysis (p < .01) . moreover, pearson bivariate correlation coefficients were calculated to address the relationship between suicidal ideation and loneliness. at the same time, individuals were categorized into two groups that are, suicide ideator and non-ideators, based on their score on the the suicidal ideation scale. furthermore, differences were explored on emotional and social loneliness across two groups of suicide ideators and nonideators via computation of independent sample ttest, and cohen's d were calculated to examine the 23 strength of the group differences. finally, the moderating part of gender was measured by using process macro version 2.16 for the effect of suicidal 24 ideations on emotional loneliness. given that majority of participants are middle born, and belonging to middle socioeconomic status (ses) in our sample, so birth order and ses was used as a control in the moderation analysis to counterweight the gender groups through birth order and socioeconomic status. results taken together, first of all, cronbach's reliabilities, mean values, standard deviation, and pearson bivariate correlation amongst study variables are grouped together in table i. afterward, in table ii differences of social and emotional loneliness among suicide ideators and non-ideators are presented. finally, table iii and figure 1. explain the moderating role of gender across the relationship between emotional loneliness and suicidal ideations. at first, results from the table i depicted that there is a significant positive correlation between emotional loneliness and social loneliness (r = .67, p < .01) as well as the emotional loneliness and that of suicidal ideations (r = .49, p < .05). meanwhile, in alliance with our predictions, social loneliness is also positively associated with the suicidal ideations (r = .38, p < .01). as expected, results from an i n d e p e n d e n t s a m p l e s t t e s t s h o w e d t h a t participants clustered as suicide ideators (m = 7.62, sd = 2.29, n = 86) scored significantly higher on the emotional loneliness as compared to that of nonideators (m = 6.71, sd = 1.99, n = 222), t (306) = 3.43, p < .001, two-tailed. the change of .91 scale points was large (d = .43), and the 95% confidence interval around difference between the group means was relatively precise (.39 to 1.43). similarly, on loneliness suicide ideators (m = 8.73, sd = 2.21, n = 86) had elevated scored than that of non-ideators (m = 8.14, sd = 2.06, n = 222), t (306) = 2.15, p < .05, twotailed. finally, the results of the moderation analyses showed that after controlling the effect of birth order and socioeconomic status, gender moderated the effect of emotional loneliness on suicidal ideations. the results presented in table iii show a significant interaction effect (b interaction = 1.23, p < .01) explaining 12% additional and 57% total variance in emotional loneliness. the moderating effect of gender is additionally explained in figure 1. the figure demonstrates that emotional loneliness increases suicidal ideations amongst both men and women young adults, yet the slope for the females is much steeper than for males, suggesting that females are more prone to develop suicidal ideations as a consequence of emotional loneliness. additionally, a fan effect appearing approximately in the center of the figure suggests a reversal role of low versus high suicidal ideations. the fan effect suggests that while facing low levels of emotional loneliness, male become more suicidal. contrary to that while facing high levels of emotional loneliness, females are more prone to develop suicidal ideations. table i: cronbach's reliabili�es, mean, standard devia�on, and pearson bivariate correla�on among study variables (n=308). *p < .05, **p < .01. table ii: differences in social and emo�onal loneliness among suicide ideators and non-ideators (n=308). *p < .05, **p < .001. loneliness and suicidal ideation among young adultsjiimc 2019 vol. 14, no.3 128 m sd m sd t ll ul cohen’s d discussion regardless of the emergent body of research on suicidal ideations and loneliness, as such, slight farscale research is present in the general young sample that focused on this relationship. the current study has addressed this research gap after considering the emerging young adult population. at first, our results depicts a relationship between suicidal ideations and loneliness. in an alliance, both forms of the loneliness that is., social and emotional loneliness significantly positively correlates with suicidal ideations. this association laids the foundation that more the person feels lonely more s/he is susceptible to develop the suicidal ideations. in the same way, as predicted suicide ideators are high on social and emotional loneliness as compare to that of non-ideators. this is in alliance with previous research findings that loneliness predicts 14,17,19,25-29 suicide ideations. finally, after controlling a few probable confounders that are, birth order, and socio-economic status it is establised that the gender is moderating the relationship between the suicidal ideations and emotional loneliness. this association is suggestive of the fact emotionally lonely girls are 30,31 more susceptible to develop suicidal ideation. thus based on these findings it is necessary to discuss that the prevention and intervention techniques are need to be designed to restrict the suicidal behavior. meanwhile, establishment of the crises management cells, and personal skills grooming units are desired in a way to accomplish a mandate in healthcare-associated with suicidal ideation, along with other mental health 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environmental research and public health. 2017 jul;14(7):791. loneliness and suicidal ideation among young adultsjiimc 2019 vol. 14, no.3 130 jiims final.cdr 1 dengue fever is fast emerging as one of the common arthropode borne diseases. viral th aetiology of dengue was established in 20 century but dengue like illness could be traced back 200 years. in 1950s the infection was being reported by 9 countries, today a wide array of countries, report regular outbreaks. pakistan is one of those countries which have been in the grip of outbreaks since 1990s. first reported epidemic could be traced back to 1994. it is evident that dengue fever is not a very recent phenomena in pakistan. it has had its history but 2011 witnessed hyperbole and press hype of gigantic magnitude. this created scare and irrational response to the outbreak. somehow the outbreak was pinned on or attributed to collapse of health services, whereas established wisdom attributes this emergence of dengue fever to uncontrolled population growth, rapid urbanization and s l u m f o r m a t i o n , i n a p p ro p r i a t e a n d inadequate waste water management, refugee movement and to erosion of vector control program, non of this falls in the domain of health sector. the hype created by the press this year was a cause of daily headlines on the news channels, resultant response to this outbreak could at best be described as misdirected. lot of fallacy and misplaced response was undertaken. for example, cases of fever were subjected to virological diagnoses with resultant increase in cost and unnecessary effort. similarly isolation wards were put up in hospitals and a pressure created by fever patients to get admitted in them. a misplaced efficacy of platelet transfusion in every case was advocated with the result that demand for cell separators and platelets skyrocketed. health education on the lack of specific treatment was not common knowledge and this outbreak was somehow thought of as fault of medical and health professionals and a cause of consternation for the profession in the country in general and lahore in particular. dengue fever outbreak was reported not for the first time and surely it will not be for the last time. as we square upto the fact that dengue fever epidemics are here to stay, it is already recognized that the countries reporting dengue fever outbreaks suffer from the same every five to six months in different regions and report major outbreaks every three years. it is hoped that the experience gained in 2011 will give rise to saner voices and prudent response after all the mayhem created by the press. a judicious response would have to be tailored for the long term and most of the action has to be taken by the government functionaries other than the health and medical professionals. some of the steps that need to be advocated are, firstly population management and population control and policies to curb rapid urbanization and slum f o r m a t i o n , s e c o n d l y g e a r i n g u p o f municipal services in the cities and slums to editorial dengue fever outbreak maqsood-ulhassan ------------------------------------------------dr. maqsood-ul-hassan dph, mcps, msc(med adm) islamic international medical college rawalpindi 2 avoid waste water accumulation and ensuring appropriate drainage in and around human habitations. in case of outbreak the press will also have to be tutored to play its role of educating the general public on general and personal protective measures rather than be a harbinger of scare. people will have to be told before and during outbreaks to manage water collections in and around their residences, be it waste water or fresh water, and role of press can be invaluable. there is also a need to have a robust vector control program in terms of mosquito surveillance and surveillance of its larvae to map out areas with high density of vector, so as to undertake selective spraying of locales with high density so as to be aware of areas at risk of outbreaks and avoid consequences of environmental degradation and insecticide resistance of universal spraying. these are measures to be taken by sectors other than health and medical professionals, in case of outbreak through an important role is to be played by medical professionals in managing the cases. health/ medical professionals will have to propagate conventional wisdom that not every case needs virological confirmation once epidemiological data and testing of index and initial cases have confirmed the outbreak. primary health care physician will have to be trained on risk management of cases, in that most of the cases will be treated outdoors, but high index of suspicion on bleeding diathesis due to platelet lowering and or evidence of leaking plasma causing dengue shock syndrome be readily recognized. as these merit hospital handling of the cases. the public and medical profession will have to be made aware of screening fever cases so as to avoid mosquito bites both in the houses as well as hospitals. use of aspirin during the outbreak will have to curbbed/stopped. a proactive approach though may not eliminate dengue fever, dengue shock syndrome, dengue hemorrhagic fever but can minimize its consequences. society as a whole, needs to make concerted efforts to prevent outbreaks of the disease. a political will to undertake measures prior to outbreak is imperative. jiims.cdr abstract objective: to determine safety of diode laser by studying post operative complications after endourological procedures in co-morbid patients. study design: a descriptive study. place & duration of study: shalamar hospital, lahore from june 2009 to june 2012. materials and methods: we studied post-operative complications (up to 3 months) in 3 groups (prostatic obstruction, bladder growths ,urethral strictures) of total180 patients with asa iii & iv. we assessed hematuria, uti, abdominal pain, suprapubic discomfort, urinary retention, dysuria, incomplete procedure, cardiac or respiratory compromise, fluid overload, mortality, catheterization times and mean postoperative hospital stay results: in prostate group, mean age was 70.8±8.6 years and follow-up period was 3 months. complications were: mild transient haematuria in 65 (100%), creamy urine in 50 (77%), urinary tract infection in 25 (38.4%), dysuria in 16 (24.6%), retreatment required in 06 (9.2%), suprapubic discomfort in 3 (4.5%), turp syndrome in 1 (1.5%) and significant hemorrhage requiring blood transfusion in 1 (1.5%),. in urethral strictures, the complications were: microscopic hematuria in 80 (100%), urinary tract infection in 52 (65%) suprapubic discomfort in 9 (11.2%), dysuria in 6 (7.4%) mild transient hematuria in 5 (6.2%). in bladder growths, the complications were: mild transient haematuria in 30 (85.7%), creamy urine in 19 (54.2%), suprapubic discomfort in 18 (51.`4%), dysuria in 9 (25.7%), urinary uti in 8 (22.8%) , ablation performed in two sittings in 1 (2.8%). no mortality in any group. conclusion: diode laser is a safe and useful modality in patients with co-morbidities (asa iii and iv). key words: diode laser, endourology, co-morbidity. 98 original article introduction elderly patients with coexisting medical conditions undergoing complex or major surgery are high-risk. range of surgery and patient-related factors including ischaemic h e a r t d i s e a s e , c h r o n i c o b s t r u c t i v e pulmonary disease (copd), advanced age, poor exercise tolerance determine the 1 overall risk b l e e d i n g re m a i n s a c o n c e r n i n a l l endoscopic procedures, like morbidity and mortality for transurethral resection of prostate (turp) have not changed for 2,3 decades. potential advantages of laser therapy over traditional procedures include appreciably good hemostasis, decreased morbidity, minimal cardiac stress, and shorter hospital ------------------------------------------------complications of diode laser in endourological procedures in co-morbid patients farooq hameed, mohammad imran zahoor, javed aziz, saadat hashmi, abdul jalil, abdul rehman correspondence: dr. farooq hameed consultant urologist shalamar hoapital, lahore e-mail:farooqhameed4@gmail.com 4 stay. high-powered diode laser systems are 5 available for endoscopic procedures. it has a compact size, easy portability, and a potential for lower capital and maintenance 3 costs. the current system (biolitec) allows a continuous wave mode to a flexible and customizable pulsing regime with side or bare end fire fibre . diode laser has similar wavelength characteristics to the nd: yag laser (neodymium:yttrium-aluminumgarnett), but scatters less in tissue, high simultaneous absorption in water and hemoglobin and it is postulated to combine high tissue ablative properties with good hemostasis with significantly lower energy 3,6 consumption . safety measures are similar to nd: yag laser. clinical data regarding safety of diode laser in endoscopic surgery is not frequently available. we studied the post operative complications (up to 3 months) in 180 patients between materials and methods 99 june 2009 and june 2012 in shalamar h o s p i t a l , l a h o re . d e p e n d i n g u p o n diagnosis, patients were divided into 3 groups (with prostatic obstruction, bladder growths and urethral strictures) and complications in each group were studied. in all cases of bph, pharmacological treatment had been tried. physical examination including digital rectal examination (dre), prostate specific antigen (psa), abdominal ultrasound scan ( t r a n s r e c t a l s c a n o n l y i n c a s e o f disagreement between dre and the abdominal ultrasound scan) were carried out for prostatic obstruction and bladder growth. retrograde urethrogram was done for urethral strictures. all operations were done in spinal (60 %) or combined spinal/epidural, epidural alone or general anesthesia.) we used 980 nm diode laser (biolitec, germany) with 1000 ìm core optical fibers (side-fire), 600 ìm end fire with a spot diameter of 1 mm. the output power ranged from 50 w to 140 w during the surgery. the mean applied energy was 130 ± 70 kj. vapo-resection (coagulation and resection of bigger prostates, vaporization and sample collection for small lesions) was performed using laseroscope / resectoscope of 26 fr. the strictures were dealt with by vaporizing the tissue when passing, using the contact technique or non-contact mode depending on the characteristics of the tissue. saline solution was used as irrigation during ablation and 1.5% glycine during sample collection. the antibiotic prophylaxis consisted of three intravenous doses of 1g of cefoperazone /sulbactam , at induction, at 12 and 24 hrs post operative period respectively. patients needing anticoagulation were switched over to enoxaprin 4000 i.u. sub cutaneous injection before the procedure. all procedures were performed by a single experienced surgeon with a dedicated team. in post operative period, patients were a s s e s s e d f o r t r a n s i e n t , s i g n i f i c a n t h a e m o r r h a g e n e e d i n g t r a n s f u s i o n , microscopic hematuria, urinary tract infection, abdominal or flank pain, suprapubic discomfort, urinary retention, dysuria, incomplete procedure, cardiac or respiratory compromise, fluid overload , mortality, catheterization times and mean postoperative hospital stay. patients were discharged from the hospital within 48 hours when urine was bloodless. patients from all age groups needing endoscopic laser treatment for bph, bladder growths, and urethral strictures having 1. co-morbidities a. altered renal function, (creatinine > 2.0) b. copd c. bleeding / clotting disorders with international normalization ratio (inr) >1.5 d. myocardial dysfunction, ejection fraction up to 30%) 2. american society of anesthesiologists (asa) grade iii and iv 3. refused surgical treatment due to high risk exclusion criteria: patients with asa grade i & ii follow up: follow up intervals postoperatively in out patient clinic were within 5 days for removal of catheter, 15 days, one month, 2 month and 3 months. any clinical event, adverse effects and additional interventions or repeat surgery was noted. for cases of ablation of prostate and bladder growths, follow up intervals were within 5 days for removal of catheter (upto 7 days for some cases of bladder growths), 15 days, one month, 2 month and 3 months. in case of urethral strictures, the catheter was removed depending upon the severity of the condition and were followed upto 3 months. inclusion criteria: 100 results prostate group: mean age of patients was 70.8±8.6 years. one patient having prostate >260 gms developed significant post operative haemorrhage and needed transfusion. the patients having prostates >100 gms developed retention within 1 week and were re-operated. dysuria was moderate, disappeared in all cases by s y m p t o m a t i c t re a t m e n t w i t h i n t h e following two weeks. uti was noted in patients having indwelling catheter for > 3 months. patient with turp syndrome was readmitted and electrolyte imbalance was corrected. further results are in table i. stricture urethra group: microscopic hematuria and gross hematuria both settled within 24 hrs in all patients. post operative infection was noted in already infected urine which settled by two weeks antibiotics followed by suppressive dose. further results are in table ii. bladder growth group: urinary retention occurred only in cases of indwelling catheter > 3 months. creamy urine lasted for 2-3 months and settled. dysuria persisting up to 2 weeks was noted in widespread bladder tumours. further results are in table iii. table i. complications in prostate group (n= 65) table ii. complications in urethral stricture (n = 80) table iii. complications in bladder growths n = 35 table iv. mean hospital stay and catheterization time 101 discussion use of laser for the treatment of bph and bladder tumours is the most commonly used alternative to tur to decrease 7,8 morbidities. for nd:yag, laser, it required longer catheterization periods because of the longer time required for expelling the necrotic tissue. reports of long 9 term results with ktp laser are limited. we removed catheter within 3 days because of effective coagulation and hemostasis except for prostatic obstruction with indwelling catheter for > 3months or complicated strictures of posterior and bulbar urethra . rapid vaporization and hemostasis is 9,10,11 possible by diode laser. we easily obtained tissues of prostate and bladder growths for biopsy. the architectural pattern in resected tissue was well m a i n t a i n e d f o r h i s t o p a t h o l o g i c a l evaluation. an ex vivo study showed that diode laser has a higher tissue ablation capacity than ktp laser, and shorter 9 operative time. using vapo-resection technique ,we obtained clean sharp cuts with almost blood-less field. w. cecchetti et al obtained a bloodless sharp cut and easy vaporization with minimum carbonization and edema in 22 cases. they found diode laser a good compromise between absorption and coagulative effects 11 on the tissue . seitz et al treated 10 patients with bph with diode laser. ten patients were followed up at 1 month and 8 patients were followed up at 6 and 12 months. no serious postoperative 12 haematuria was reported. we found, mild transient hematuria in almost all patients which settled within 4 hours. erol et al (2009) studied 47 patients with diode laser prostatectomy. the commonest complication was mild-moderate irritative symptoms (23%) which resolved within the f i r s t t w o w e e k s . a l a t e b l e e d i n g complication (requiring hospitalisation) was encountered in one patient at 4 weeks. 13 mean operative time was 53 minutes. chen et al (2010) treated 55 patients of bph. they reported 10 patients with transient dysuria. acute urinary retention in two men was resolved by removal of sloughed tissue via turp. two patients underwent turp due to insufficient vaporisation or regrowth of prostatic tissue (reoperation rate 7%). the three studies (seitz et al; erol et al; chen et al) reported no serious intraoperative complications or postoperative haematuria. lengths of hospital stay were 4.7 (sd 2.3) days in seitz et al (2007) and 2.8 (sd 1.8) days 12,14 in chen et al (2010). in our study, almost all patients were discharged within 48 hours after surgery.clemente ramos and luis 15 miguel evaluated diode laser treatment of bph, focused on the peri-operative m o r b i d i t y. t h e y f o u n d p r o s t a t e vaporization effective with minimal 15 morbidity. the application of lasers in treating urologic disorders has gained widespread clinical a c c e p t a n c e i n m u l t i p l e s u r g i c a l indications.15 safety has also been demonstrated in patients with large prostates and patients receiving anti 16 coagulant therapy or in retention. the early results showed a virtually bloodless surgery with sharp cut. with acceptable complication rate, diode laser is relatively safe and useful modality in patients with co-morbidities (renal failure, chronic obstructive pulmonary disease, myocardial dysfunction, ( asa iii & iv). 1 pearse r m. perioperative management of the high-risk surgical patient in bailey and love's short practice of surgery. 25th ed © 2008 edward arnold (publishers) ltd, p215 2 lanzafame rj. applications of lasers in laparoscopic cholecystectomy. j laparoendosc surg 1990;1:33-6. 3 mulligan ed, lynch th, mulvin d, greene d, conclusion references 102 smith jm, fitzpatrick jm. high-intensity focused ultrasound in the treatment of benign prostatic hyperplasia. british journal of urology 1997; 79: 177-80. 4 http://tau.sagepub.com/content/1/2/85, chung d e, te a e. new techniques for laser p ro s t a t e c t o m y : a n u p d a t e t h e r a p e u t i c advances in urology 2009; 1: 85. 5 nordahl g, huckele s, honeck p, alken p, knoll t, michel ms et al. 980-nm diode laser: a novel laser technology for vaporization of the prostate. european urology 2007; 52:1723-8. 6 madersbacher s, alivizatos g, nordling j, sanz cr, emberton m, de la rosette jj. eau 2004 guidelines on assessment, therapy and followup of men with lower urinary tract symptoms suggestive of benign prostatic obstruction (bph guidelines). eur urol 2004;46:547-54. 7 bülent oktay, hakan kýlýçarslan, hasan serkan doðan. diode laser in the treatment of benign prostatic enlargement: a preliminary study, turkish journal of urology 2011;37:25-9 8 seitz m, ruszat r, bayer t, tilki d, bachmann a, stief c et al. ex vivo and in vivo investigations of the novel 1,470 nm diode laser for potential treatment of benign prostatic enlargement. lasers med sci 2009;24:419-24. 9 seitz m, bayer t, ruszat r, tilki d, bachmann a, gratzke c, et al. preliminary evaluation of a novel sidefire diode laser emitting light at 940 nm, for the potential treatment of benign prostatic hyperplasia: ex-vivo and in-vivo investigations. bju int 2009;103:770-5. 10 wendt-nordahl g, huckele s, honeck p, alken p, knoll t, michel ms, et al. 980-nm diode laser: a novel laser technology for vaporization of the prostate. eur urol 2007;52:1723-8. 11 cecchetti w, guazzieri s, tasca a, dal bianco m, zattoni3 f, pagano f, european biomedical optics week, bios europe '96 12 seitz m, sroka r, gratzke c. the diode laser: a novel side-findding approach for laser vaporisation of the human prostate-inmediate efficacy and 1 –year follow up. eur urol 2007; 52:1717-22. 13 erol a, cam k, tekin a, memik o, coban s, ozer y. high power diode laser vaporization of the prostate: preliminary results of benign prostatic hyperplasia. the journal of urology 2009; 182: 1078-82. 14 chen ch, chiang ph, chuang yc, lee wc, chen yt, lee wc. preliminary results of prostate vaporization in the treatment of benign prostatic hyperplasia by using a 200-w highintensity diode laser. urology 2010; 75: 658-63. 15 ramos c, miguel l. high power diode laser at 980 nm: preliminary results in the treatment of the benign prostatic hyperplasia. urology 2011; 70: 734-43. 16 thomas r.w. evangelos n. olivier t. eau guidelines on laser technologies, european urology 2012; 61: 23-40. original�article abstract objective: to explore effect of coenzyme q10 (co q10) on serum ldl-cholesterol and compare its hypolipidemic efficacy with the normal control. study design: randomized control trial. st th place and duration of study: the study was conducted from 1 february 2013 to 30 june 2013 at the department of chemical pathology, army medical college and national institute of health sciences (nih) islamabad. materials and methods: eighteen rabbits were divided into three groups of six rabbits each. base line lipid profile was estimated for serum ldl cholesterol in mmol/l. leaving one group as normal control, the other two groups were given high cholesterol diet to produce hyperlipidemia. of the two hyperlipidemic groups, one group was treated with coq10 orally for 30 days. blood samples were drawn for lipid biochemistry, 24 hours after administration of the last dose. the means of serum analysis were calculated and compared using spss version 20. results: serum ldl-cholesterol (ldl-c) was reduced in the group taking coq10 as compared to the group with no coq10 treatment. the p value was significant for ldl-c in treatment group, (p<0.0001). conclusion: it is concluded that coenzyme q10 plays a vital role in hyperlipidemic rabbits in reducing serum ldl cholesterol levels. key words: coq10, hyperlipidemia, ldl-cholesterol. more agents to cope with the major determinant of 5 cvd i.e. hyperlipidemia. in order to prevent the unavoidable adverse reactions with traditional antihyperlipidemic agents, monodrug therapy with vitamin like substance exhibiting properties of controlling blood cholesterol in addition to acting as 6 supernutrient may offer valuable consequences. coenzyme q10 (coq10) is a fat soluble, vitamin like enzyme and is an important supernutrient. it is 7 synthesized in all the tissues of body especially liver. coq10 is recommended to prescribe nowadays along with the conventional treatment of 8,9 cardiovascular diseases as a supplement. coqi0 is found in wide variety of foods and is richly present in meat, poultry, fish products, nuts, broccoli, soy bean 10 and spinach. coq10 is available in different formulations like tablet, gel, capsules as well as in injection form. coq10 is a large molecular weight 11 substance and is hydrophobic in nature. absorption of dietary coq10 is slow and limited but increases 12 with meal. solubilized formulations show enhanced 13 bioavailability with tmax of approx. 6 hrs. it has 14 elimination half-life of 33 hours. coq10 is taken up by all the tissues including heart and brain 15 mitochondria. it also undergoes enterohepatic circulation as it is reabsorbed from small intestine introduction the increasing incidence of deaths due to cardiovascular diseases (cvd) have become a foremost current health issue and are accountable for 76 percent of deaths and disabilities due to 1 myocardial infarction, atherosclerosis and stroke. the most vital risk factor for coronary heart disease is high blood ldl-c levels that accumulate on the walls 2,3 of the arteries. trials have shown that there is 30 p e r c e n t d e c l i n e i n t h e r i s k o f c v d b y pharmacologically lowering serum ldl cholesterol. therefore it has been stressed that lowering the blood lipids are beneficial in cardiovascular patients. blood cholesterol levels are maintained within normal range via antihyperlipidemic drugs exhibiting 4 different lipid lowering mechanisms. therefore majority of patients need a combination of two or new insights into the role of coenzyme q10 in serum ldlcholesterol reduction sabeen shakir, zunnera rashid, naureen hafeez correspondence: dr. sabeen shakir assistant professor, pharmacology rawal institute of health sciences, islamabad e-mail: sabeen.ali@live.com department of pharmacology rawal institute of health sciences rawalpindi funding source: nil; conflict of interest: nil received: oct 19, 2016; revised: jan 31, 2017 accepted: feb 06, 2017 effect of coenzyme q10 on serum ldl-cholesteroljiimc 2017 vol. 12, no.1 25 16 instead of exceretion. coq10 is incorporated in its reduced form i.e. ubiquinol, into the mitochondria of almost all the body tissues especially brain and heart mitochondria and allow these tissues to produce 17,18 more energy in the form of atp. this energy is required to maintain basic metabolic functions such as to take up and utilize nutrients, to synthesize new proteins and to discard waste materials. coq10 also acts as a potent antioxidant by mopping up 19 potentially harmful free radicals. unstable free floating electrons when not attached to other molecules are capable of causing damage to cell membranes. as an antioxidant, it causes the regeneration of vitamin e and vitamin c and prevents prooxidant effects of vitamin e. once it gives up its free electron to stabilize a free radical, it needs to be regenerated in order to become functional again. for this, drug hands over electrons to oxidized version of vitamin e and c, and thus converts back to its 20 reduced form, ubiquinol (reduced coq10). in this way it protects mitochondrial dna from oxidative stress. an important mechanism of action of coq10 involves the decrease in the oxidation of ldl cholesterol thereby reducing the risk of developing a t h e r o s c l e r o s i s a n d o t h e r c a r d i o v a s c u l a r 21,22 diseases. unlike traditional antihyperlipidemics, no adverse drug reactions have been documented with coq10 so far, the objective of my study is to observe the potential of coenzyme q10 in ldl-cholesterol reduction in hyperlipidemic rabbits to see wheather this provitamin can be used in cardiovascular patients effectively. materials and methods it was a randomized control study. the approval for the study was sought from the ethics committee of centre for research in experimental and applied medicine (cream). the study was conducted from st th 1 february 2013 to 30 june 2013 at the department of chemical pathology, army medical college and national institute of health sciences (nih) islamabad. study included eighteen healthy adult rabbits having a weight of 1.5 to 2.0 kg. they were of mixed breed with equal distribution of male and female rabbits in three different groups. animals under 1.5 years of age and pregnant females were excluded from the study. standard laboratory conditions were maintained in animal house of national institute of health and were provided with controlled environment assuring twelve hours day and night cycle and an average temperature of 24oc. rabbits 23 were acclimatized for one week before the study. after acclimatization, the study period comprised of twenty weeks. blood samples (n=6.0) were drawn from the dorsal surface of rabbit's marginal ear vein with the help of a 5cc syringe according to standard described techniques. all the samples were transferred to separate plain clot activator tube were centrifuged at 4500 rounds per minutes for 10 minutes. serum was separated via an automatic micropipette and then shifted in clean dry vials for estimation of serum cholesterol, serum triglycerides and serum hdl-cholesterol in mmol/l. all tubes were labelled accordingly. the rabbits were randomly assigned into three groups of six animals each. group a was the control group and received normal diet and water ad libitum for 150 days. group b (hyperlipidemic control; n=6) animals received cholesterol powder (1g/day) mixed in a diet comprising of grain whole and wheat bran for 120 days. cholesterol powder was excluded from the diet for the next 30 days. rabbits were also given tap water ad libitum for drinking. group c (hyperlipidemic+coenzyme q10; n=6) animals received the high cholesterol diet (1g/day) as per group b for 120 days and then fed on normal/routine diet without cholesterol along with coenzyme q10 (10mg/kg) once daily via gavage for a period of 30 days. serum ldl was calculated in (mmol/l) by using the formula:24 ldl=tc-hdl-tg/ 2.20 + hdl – cholesterol. the statistical analysis was carried out using spss version 20. the results of serum analysis were 25 established as means + standard error of mean. the difference was taken as significant for a p value of 0.05 or less. results group a (normal control) showed unchanged levels of serum ldl-c when recorded on day 120 and on day 150 in contrast to the levels recorded on day zero. in group b (hyperlipidemic control), serum ldl-c levels on day 120 were increased significantly as compared to day zero with p=0.0005. the levels jiimc 2017 vol. 12, no.1 26 effect of coenzyme q10 on serum ldl-cholesterol remained unchanged on day 150 in comparison to day 120 in this group so p>0.05, but were increased on day 150 in comparison to group a (normal control) hence p<0.0005. group c (coq10) ldl-c levels were also recorded on day zero and day 150. when this treatment group was compared with group b (hyperlipidemic control) to assess the post treatment reduction in serum ldl levels on day 150, a statistically remarkable decrease was recorded, i.e. group c (coq10) p value equal to 0.0001. lowering high serum ldl-c levels in hyperlipidemia. coenzyme q10, a provitamin as it is a safe and highly tolerable drug, so can be used without the fear of adverse drug reactions that otherwise would occur with other traditional antihyperlipidemic agents. future studies are required to observe the antihyperlipidemic potential of this vary super nutrient in human subjects so that it can be used to prevent or to treat cardiovascular diseases. conclusion after conducting this experimental study on eighteen rabbits and assessing the results of serum analysis statistically, it is concluded that coq10 has a potential to reduce serum ldl-cholesterol in hyperlipidemic rabbits. further studies in humans are needed, however, to prove its action of improving serum lipid profile to be used effectively for the prevention and treatment of cardiovascular diseases. references 1. lim ss, vos t, flaxman ad, danaei g, shibuya k, adairrohani h. a comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990-2010: a systematic analysis for the global burden of disease study 2010. lancet. 2012; 380: 2224–60. 2. stella mg, kyvelou gp, vyssoulis ea, karpanou dn, adamopoulos ai, zervoudaki pg, et al. effects of antihypertensive treatment with angiotensin ii receptor blockers on lipid profile: an open multi-drug comparison trial. hellenic j cardiol. 2006; 47: 21-8. 3. padilla e, sanz m, ganado p, tejerina ty. effects of irbesartan and losartan in cholesterol-fed rabbits. clin invest arterioscl. 2002; 14: 230-8. 4. pahan k. lipid-lowering drugs. cell mol life sci. 2006; 63: 1165–78. 5. ghibaudi l, cook j, frarley c, van heek m. fat inktake affects adiposity comorbid factors, and energy metabolism of sprague-dawley rats. obes res. 2002; 10: 956-63. 6. chapman n. new evidence in hypertension and hyperlipidaemia. heart. 2004; 90: 14-7. 7. modi kp, vishwakarma sl, goyal rk, bhatt pa. effects of coenzyme q10 on lipid levels and antioxidant defenses in rat s w i t h f r u c to s e i n d u c e d hy p e r l i p i d e m i a a n d hyperinsulinaemia. the internet journal of pharmacology. 2007; 5: 1531-2976. 8. weant ka, smith km. (2005). pharmacokinetics of coenzyme q10. ann pharmacother. 2005; 39: 1522-6. 9. wyman m, leonard m, morledge t. coenzyme q10: a therapy for hypertension and statin-induced myalgia? cleve clin j med. 2010; 77: 435-42. 10. pravst i, zmitek k, zmitek j. coenzyme q10 contents in foods and fortification strategies. crit rev food sci nutr. jiimc 2017 vol. 12, no.1 table 1: means ± sem of serum ldl-c (in mmol/l) in group a, group b and group c in rabbits (n=6) discussion in our study we found that coq10 has the ability to reduce serum ldl cholesterol significantly in high cholesterol diet fed rabbits. this favors the dual role of coenzyme q10, i.e. although it is a supernutrient, coq10 also serves as an antihyperlipidemic agent. similar results were also shown by ketan et al., 26 (2006). they established that coq10 has a potential of lowering all the parameters of lipid profile including serum total cholesterol, tgs, vldl, and ldl with the exception of serum hdl which increases with the use of coq10. the only difference with our study is that, they used rats instead of rabbits as an experimental model. our results are also consistent with the inference of hiroshi et al., (2007). they certified from their study that treatment with coq10 27 significantly improves plasma lipid biochemistry. coq10 has the ability to decrease even aortic cholesterol and triglycerides in transfatty rich diet. singh et al., (2000) explained the reduction in aortic and coronary artery plaque sizes along with the decrease in aortic and coronary artery scars in high 28 fat diet induced rabbits. keeping all this in view, our inference is that coq10 reduces the serum ldl-c in high cholesterol diet fed rabbits. administration of this vitamin like substance can be used effectively in 1 n=6, results are expressed as mean ± sem (standard error of mean) 27 effect of coenzyme q10 on serum ldl-cholesterol 2010; 50: 269-80. 11. kalenikova ei, gorodetskaya ea , medvedev os. pharmacokinetics of coenzyme q10. exp biol med. 2008; 146: 288-91. 12. ullman u, metzner j, schulz c. pharmacokinetics of coenzyme q10. j. med. food. 2005; 8: 397-9. 13. bhagavan hn, chopra rk. pharmacokinetics of coenzyme q10. free radic res. 2006; 40: 445-53. 14. aronov dm. pharmacokinetics of coenzyme q10. rus. med. zh. 2004; 12: 905-9. 15. haas rh. the evidence basis for coenzyme q10 therapy in oxidative phosphorylation disease. mitochondrion. 2007; 7: 154-67. 16. zaghloul a, gurley b, khan m. pharmacokinetics of coenzyme q10. drug dev ind pharm. 2002; 28: 1195-1200. 17. ketan pm, vishwakarma sl, goyal rk, bhatt pa. beneficial effects of coenzyme q10 in streptozotocin-induced type i diabetic rats. ijpt. 2006; 5: 61-5. 18. o'keefe, j. potential benefits of coq10. cardiotab. 2013; 2: 41-55. 19. rocha m, victor vm. targeting antioxidants to mitochondria and cardiovascular diseases: the effects of mitoquinone. med sci monit. 2007; 13: 132-45. 20. modi kp, vishwakarma sl, goyal rk, bhatt pa. beneficial effects of coenzyme q10 in streptozotocin-induced type i diabetic rats. ijpt. 2006; 5: 61-5. 21. rauscher fm, sanders ra, watkins jb. effects of coenzyme q10 treatment on antioxidant pathways in normal and streptozotocin-induced diabetic rats. j biochem mol toxicol. 2001; 15: 41-6. 22. ketan pm, vishwakarma sl, goyal rk, bhatt pa. beneficial effects of coenzyme q10 in streptozotocin-induced type i diabetic rats. ijpt. 2006; 5: 61-5. 23. durand m, godier a, notet v, hacquard m, collignon o, corbonnois g, et al. recombinant activated factor vii attenuates major arterial bleeding in noncoagulopathic rabbits. eja. 2011; 28: 51-6. 24. bimenya sg, kasolo j, okwi la, othieno i, ochieng j, kalule b, et al. determination of ldl-cholesterol: direct measurement by homogenous assay versus friedewald calculation among makerere university undergraduate fasting student. int j biol chem. 2010; 4: 464-70. 25. jaykaran. “mean + sem” or “mean (sd)”? indian j pharmacol. 2010; 42: 329. 26. ketan pm, vishwakarma sl, goyal rk, bhatt pa. beneficial effects of coenzyme q10 in streptozotocin-induced type i diabetic rats. ijpt. 2006; 5: 61-5. 27. hiroshi m, afsushi n, junji k, mesa aki k, shuji k, akhiro i, et al. effects of coq10 supplementation on plasma lipoprotein lipid, coq10 and liver and muscle enzyme levels in hypercholesterolemic patients treated with atorvastatin: a randomized double-blind study. atherosclerosis. 2007; 195: 82-9. 28. singh s, nautiyal a, dolan jg. recurrent acute pancreatitis possibly induced by atorvastatin and rosuvastatin. is statin induced pancreatitis a class effect?. j pancreas. 2004; 5: 502-4. jiimc 2017 vol. 12, no.1 28 effect of coenzyme q10 on serum ldl-cholesterol jiimc december 2016 page 29 page 30 page 31 page 32 original�article abstract objective: to determine the frequency of temporomandibular disorders (tmds) among 18to 24-year-old university students of islamabad. study design: descriptive cross-sectional study. place and duration of study: sample was chosen from quaid e azam university, bahria university and riphah international university. duration of the study was from january to march 2020. materials and methods: the study comprised of 160 candidates from various universities in islamabad including both males and females aged 18 to 24 years. data was collected using a self-reported questionnaire and clinical examination. age, gender, socio-economic status, and history of symptoms of tmds were assessed. clinical examination of the temporomandibular joint was carried out by the investigator to assess any clicking sounds, tenderness in the myofascial muscles and any evidence of osteoarthritis. the data was analyzed by using ibm spss 23. the results and frequencies were calculated using the chi-squared test. with a p value of <0.05, a significant relationship of tmd with gender and its clinical conditions, was determined. results: out of the 160 examined, 88 were males and 72 were females. tmds were more prevalent amongst candidates aged 22 years, with a percentage of 31.3%. prevalence of tmds among the participants was calculated at 61.3%. out of those 61.3%, 58.1% had internal derangements 15% had myofascial pain and 2.5% had osteoarthritis. conclusion: our study shows a high prevalence of tmds in 18to 24-year-old individuals. there was an overall prevalence of 61.3% among the total participants. it was found to be most prevalent among 22-year-old individuals with a percentage of 31.3%. key words: internal derangement, myofascial pain, osteoarthritis, temporomandibular joint disorders. factors such as personality and behavior, occlusal discrepancies, improper dental treatment, joint l ax i t y, co nt i n u o u s m i c ro t ra u m a to j o i nt , overloading /overusing joint structures, and parafunctional habits. stress, behavioral, social, and 3 emotional conditions are also considered . common symptoms include jaw tenderness, headaches, 4 earaches and facial pain . the symptoms vary greatly with the classification of tmds. the classification of tmds by okeson p. jeffrey, which is based on the management and diagnosis of tmj disorders, is divided into three clinical conditions i.e., 1. 3 degenerative joint disease, 2. myofascial pain. 5 internal derangement. one or more of these conditions can prevail at the same time in an individual. the investigators of our research had a set of symptoms documented on the questionnaire with respect to each condition. the degenerative joint disease included osteoarthritis and rheumatoid arthritis in the temporomandibular joint (tmj). myofascial pain included pain in the fascia covering introduction temporomandibular disorders (tmd) are disorders of the jaw muscles, temporomandibular joint (tmj) and the nerves associated with chronic facial pain. anything that prevents the complex system of muscles, bones and joints from working together in h a r m o n y m a y r e s u l t i n d i s h a r m o n y a n d 1 temporomandibular disorder (tmd). etiology and pathogenesis of tmd is poorly understood, therefore treatment of temporomandibular joint diseases is sometimes difficult but it is thought to be 2 multifactorial. different etiological factors of tmd documented in the literature are psychological frequency of temporomandibular joint disorders (tmds) among university students from islamabad, pakistan mohsin fazal, nimrah umair, fahad masud, syeda ayesha absar hussain, muhammad talha ashfaq, usman khan correspondence: dr. syeda ayesha absar hussain demonstrator, department of oral and maxillofacial surgery islamic international dental college, islamabad e-mail: ayesha.absar@gmail.com department of oral and maxillofacial surgery islamic international dental college, islamabad received: september 17, 2021; revised: september 12, 2022 accepted: september 18, 2022 frequency of temporomandibular joint disordersjiimc 2022 vol. 17, no.3 202 the muscles that control the normal functions of jaw, neck, and shoulders. internal derangement included a dislocated jaw, disk displacement or an injured 1 condyle. tmds are commonly found among individuals from 20 to 40 years of age but it is also reported in the 6 younger population as well. a systematic review has investigated the prevalence of tmds among the general population, using the diagnostic criteria 7, 8 'dc/tmd', which is recognized worldwide. emerging studies regarding genetics and hormones have shown evidence of tmds more prevalent in 6 women than in men. tmds are prevalent in around 31% of adults/elderly people and 11% of children/adolescents. furthermore, most common tmd is disc displacement with reduction, accounting for roughly 26% of adults/elders and 7.5 percent of 9, 10 children/adolescents. in recent years, a lot of youngsters are presenting with the complaint of headache and jaw pains in dental hospitals. these are mostly found to be associated with tmd which often times gets overlooked. since tmds are a degenerative condition that exacerbates over time, early detection and management are extremely 1,2,11, 12 important. i n a s u r v e y o f u n i v e r s i t y s t u d e n t s , temporomandibular joint disorders were shown to 13 be widespread among university going students. these students usually fall under the age range of 18 to 24 years old in most undergraduate universities. during the course of their undergraduate studies, students face all sorts of academic stresses and social pressures that lead to the development of certain parafunctional habits like bruxism, clenching etc. resulting in one of the three clinical conditions of 8 tmds. in this cross-sectional study, the authors investigated the prevalence of tmds among university going individuals aged 18 to 24. prevalence of the most common condition of tmd was also assessed among those individuals. incidence of the most common signs and symptoms was also assessed based on respective conditions of tmds. most health care professionals receive minimal or no training in diagnosis of tmds and have difficulty in distinguishing the pain associated with tmd and pain originating from surrounding structures, due to which it goes undetected in most individuals. several researches have reported the misdiagnosis of severe pain due to tmds with migraines, neck-ache, 14 musculoskeletal pain due to other reasons . the aim of this study was to take tmds into account as a public health issue since it was an under-reported condition among students. our objective was to highlight orofacial pain disorder as a disease for its early detection and management as it effects the quality of an individual's life. materials and methods a descriptive cross-sectional study was conducted in three institutions of islamabad, namely 'quaid e azam university', 'bahria university' and 'riphah international university'. students from these three institutions were sampled for our study. duration of the study was from january to march 2020. a total of 160 participants were examined and given self-reported questionnaires to fill out. the sample size was calculated using the who calculator, confidence level=95%, confidence interval 5%, population=infinite and population proportion=10%. 15 this generated a sample size of 130. the data st collection was carried out from 1 january 2020 to th 14 march 2020. during the survey, the students were explained the terminologies and an informed consent was taken with the assurance that the privacy of their information would be maintained. the study was permitted by the institution's ethical review committee (ref. no. iidc/irc/2 0211007 1008). inclusion criteria for our study was university students from age 18 to 24 years. their age was verified through university identity cards. our study included university students aged 18 to 24. data was collected using a self-reported questionnaires and physical examination of the temporomandibular joints was carried out. the physical examination by the investigators comprised of palpation of the tmj on mouth closing and opening, to assess the presence of any crepitation or clicking. furthermore, the muscles of mastication were palpated to assess any tenderness that might be present due to undiagnosed tmds. the participants were then interviewed and asked about their symptoms relating to temporomandibular disorders. our self-reported questionnaire was adapted from 7,8 the 'dc/tmd' criteria it consisted of five parts. the first part comprised history of the participant jiimc 2022 vol. 17, no.3 203 frequency of temporomandibular joint disorders including demographic details and socio-economic status. the second part consisted of causative factors such as depression, anxiety, arthritis, stress plus symptoms such as headaches and earaches. any significant previous dental treatment linked to the tmj, was also recorded for example prior orthodontic treatment or third molar extractions. presence of osteoarthritis was assessed in the third part of the questionnaire. symptoms like pain in the jaw, pre-auricular area, jaw lock, limited mouth opening and headaches in the temple areas were evaluated. for those presenting with any of the above symptoms, were to identify the aggravating f a c t o r s s u c h a s c h e w i n g h a r d f o o d a n d parafunctional habits such as clenching and grinding of teeth. in the fourth part, internal derangements within the tmj, which presents as opening and closing jaw clicking in both tmjs and crepitation, was mentioned. this was assessed through palpation and auscultation of the joints by the investigator. the fifth and final part of the form was to evaluate myofascial pain through palpation of the muscles of mastication and muscles of the neck. spss 23 software was used to analyze the data. for each variable, the frequency and percentages were determined. chi-square test was used to compare factors such as tmd signs and symptoms among age groups, genders, and clinical situations. p value less than 0.05 was taken statistically significant. results a total of 160 participants were included in the study who filled questionnaires. they were interviewed and examined. these 160 participants were between the age ranges of 18 to 24. individuals younger than 18 and older than 24 were not included in the study. all the participants were healthy, and their socioeconomic status was assessed based on the level of income as chosen by participants in the questionnaire. individuals were informed that the questionnaires would be kept confidential, to avoid any bias in their selection of income level. out of 160 participants, 88(55%) were males and 72(45%) were females. 98 participants out of 160 were found to be positive for having one of the tmds. among the tmd positive 98 participants, 45(46%) were males and 53(54%) were females. thus, an overall 61.3% prevalence rate was found. we found a statistically significant relationship table i: prevalence of tmds amongst different genders between gender and the presence of tmds with a pvalue of 0.005. a generalized prevalence of tmds was assessed in a manner of present or absent status in the participants. our participants were also assessed for the type of tmds present via manual examination by the researchers and the signs and symptoms marked by the participants in the questionnaires. table ii: prevalence of the various types of tmds amongst participants table ii shows that out of the three clinical conditions of tmds, 70(71.4%) individuals had internal derangement only, 5(5.1%) had tmpds only and 3(3.06%) individuals had both internal derangement and osteoarthritis. 19(19.3%) individuals had both internal derangement and tmpds and only 1(1.02%) individual had all three conditions. furthermore, about 48.9% of people who had tmd were found to have a click on mouth opening after examination. 78.5% of tmd positive subjects showed a click on closing. and 25% of these subjects manifested crepitation. assessment of other variables was also conducted via questionnaire like depression, arthritis, periodontal disease, headaches, migraines, neck ache, earache, stressful work environment, marital problems, trouble sleeping and shoulder pain etc. despite depression being the most frequent variable found in our study population and marital problems being the closest (0.6) to statistically significant value (0.005), the results did not show a statistically significant relationship with any of these variables. other variables related to oral and maxillofacial aspect included orthodontic treatment, jaw trauma, parafunctional habits, wisdom tooth extraction, jiimc 2022 vol. 17, no.3 204 frequency of temporomandibular joint disorders previous treatment for tmpds and dental treatment. dental treatment was found to be the most frequent variable among the oral and maxillofacial factors, giving a percentage of 30% among tmd positive individuals, yet not statistically significant. examination and history of tmpds included pain in (jaw, temple, in the ear, in front of ear), limitation in function (jaw closing, ability to eat), jaw lock, jaw stiffness, clicking sounds, headache in temple areas, pain on chewing hard or tough food, side to side pain, pain on opening of mouth, on parafunctional jaw habits (clenching, grinding, pen chewing, chewing gum) and pain on yawning or while talking. none of these had a statistically significant relationship with tmpds either. lastly, investigators examined the muscles of mastication and neck manually. among all the muscles examined (masseter, temporalis, medial pterygoid, lateral pterygoid, anterior neck, posterior neck, and sternocleidomastoid), temporalis was the most common muscle found tender on palpation i.e. 14.4%. since our research focused on a specific range of age of individuals, a prevalence of tmds was also found with respect to age. table iii shows that the mean age of the participants was 21 years in the age group of 18to 24-year-olds. tmd was found to be most prevalent in 22-year-olds followed by 21-year-olds and then 20 year old. in order of prevalence, headache, temporal pain, and clicking were observed to be the most common symptoms. a previous study conducted at abdul wali khan university in mardan observed headache to be the most common symptom as these findings were 15 found to be in line with our study . however, a study by okeson et al. revealed clicking to be the most 5, 15 common symptom . it is likely that students mix up ear issues and tmd symptoms since it is easier to say "earache" compared to "joint discomfort." this is further supported by the fact that otolaryngologists examined 50% of tmd patients from the lebanese 16 and italian subpopulations , which is the reason why our study also aimed at its awareness so that its findings can guide in the diagnosis, prevention, and treatment of tmds by respective specialists. our study further revealed that the female subgroup showed a higher prevalence of tmpds than their male counterparts. this is supported by similar 17 results observed in a study at qassim university . the findings of the present study also showed similar results in the presence of tmd symptoms between the two genders. furthermore, the subgroup of students who had previous dental treatments showed the highest prevalence of tmpds. the most common sign on examination was the clicking sound on the closing of the jaw followed by a clicking sound on opening and crepitation. almost half of the people who had tmd were found to have a click upon mouth opening during the examination. more than half of tmd-positive subjects revealed clicking upon mouth closing, and a quarter of these subjects experienced crepitation. our study observed that out of seven muscles that we examined, the temporalis muscle was the most affected muscle in tmds patients, with the masseter being the second most common. according to research, tmd affects the jaw elevator muscles, such as the temporalis and masseter 18 muscles. another correlation derived from our study was depression and stress as aggravating and risk factors for tmds. out of the 46 individuals who claimed to be subject to stress and depression, more than half of them exhibited signs and symptoms of tmds. this result was in line with a study conducted at the mayo hospital, pakistan, that investigated the 19 correlation between depression and tmds. finally, a study conducted in china investigated the frequency of tmds amongst medical students and table iii: prevalence of tmds amongst 18to 24-yearold participants discussion our study revealed that more than half of the total participants had tmd symptoms. this is in line with findings from the college of medicine and medical sciences at holy spirit university of kaslik (usek) in jounieh, lebanon, which revealed that a similar 8 number of patients in a clinic sample had tmds . jiimc 2022 vol. 17, no.3 205 frequency of temporomandibular joint disorders the psychological risk factors associated with it. their study found a high frequency of tmds (31.7%) amongst the participants, this result is in line with our findings as our study also demonstrated a high prevalence of tmds with psychological influences as 20 possible risk factors. despite positive findings there were some limitations to our study. firstly, our study only included 18to 24-year-old individuals, hence leaving out a big portion of the younger generation. secondly, we could not examine the subjects in a clinical setting with radiographic aids, which would have proved to be far more accurate and reliable. to accurately assess the correlation between stress and depression with tmds, subjects diagnosed with stress and depression could be added to the study. furthermore, our study does not reveal the future implications of tmds since the study was crosssectional. future longitudinal studies should be conducted to include a wider range of youth, to reveal the true impact of undiagnosed tmds. moreover, if ignored at an early age, tmds aggravate and can consequently affect the quality of life of an individual. our study hopes to aid and encourage further research on this topic, to diagnose, prevent, and treat these disorders timely and to spread awareness regarding these conditions. moreover, future studies should be conducted with a proportionate number of male and female participants to maximize the accuracy of the results. in conclusion, among all the variables assessed i.e type of tmd, gender, age, environmental and dental factors, the only statistically significant relationship found between a variable and its effect on presence or absence of tmds, was gender. it is accepted that 21,22 tmd symptoms are more common in females. conclusion our study shows a high prevalence of tmds in 18 to 24 year old individuals. there was an overall prevalence of 61.3% among the total participants. it was found to be most prevalent among 22-year-old individuals with a percentage of 31.3%. references 1. ferneini em. temporomandibular joint 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2018;27(03):100. 20. wu j, huang z, chen y, chen y, pan z, gu y. temporomandibular disorders among medical students in china: prevalence, biological and psychological risk factors. bmc oral health. 2021;21(1):1-8. 21. conti pca, ferreira pm, pegoraro lf, conti jv, salvador mc. a cross-sectional study of prevalence and etiology of signs and symptoms of temporomandibular disorders in high school and university students. journal of orofacial pain. 1996;10(3). 22. poveda roda r, bagán jv, díaz fernández jm, hernández bazán s, jiménez soriano y. review of temporomandibular joint pathology: part i: classification, epidemiology and risk factors. medicina oral, patología oral y cirugía bucal (internet). 2007;12(4):292-8. conflict of interest authors declared no conflicts of interest. grant support and financial disclosure authors have declared no specific grant for this research from any funding agency in public, commercial or nonprofit sector. data sharing statment the data that support the findings of this study are available from the corresponding author upon request. this is an open access article distributed under the terms of the creative commons attributionnoncommercial 2.0 generic license. jiimc 2022 vol. 17, no.3 207 frequency of temporomandibular joint disorders jiims.cdr abstract objective: to determine effects of early mobilization in reducing post operative wound infection after lower extremity orthopedic surgeries. study design: quasi experimental study. place and duration of study: this study was carried out at department of orthopedics pakistan railway general hospital rawalpindi, from august 2010 to july 2012. materials & methods: eighty nine patients who had undergone lower extremity surgery were conveniently placed into early mobilization group a and delayed mobilization group b. all the patients mobilized within first week after surgery were included in group a, and those mobilized after one week of surgery were included in group b. patients' wound infection was defined as local redness, pain, and pus discharge within three weeks after surgery. results were analyzed using chi-square test with spss-16.0. results: minimum age of patients in this study was 10 and maximum 90 years with a mean of 45 in group a and 44 in group b. the total number of the cases of wound infections was 6 (6.74%); 2 (4.4%) in the early mobilized group and 4(9%) in the delayed mobilized group. statistical analysis showed significant difference in the number of wound infections in both groups and the result for group a was statistically more significant (p value=0.03) as compared to result) for group b (p value =0.06) conclusions: we conclude that after lower extremity orthopedic surgeries, early mobilization is needed, as it significantly reduces the postoperative wound infection rates, and early mobility is achieved. key words: lower extremity orthopedic surgeries, early mobilization, post wound infection 63 original article include: the state of hydration, nutrition and existing medical conditions as well as extrinsic factors, the pre-, intra-, and post4 operative care. it is always the top priority of each orthopedic surgeon to mobilize the patient as soon as possible after every lower extremity orthopedic surgery. sometimes it is very difficult to mobilize the patient due to factors like patient's age, loss of joint integrity, general body weakness, and some comorbid psychiatric or neurological conditions. the type of mobilization depends upon the surgical procedure, patient's age, bone density and patient's mental health. the types of mobilization are full, partial and non weight bearing. some equipments, assistive devices, and walking aids are also c o m m o n l y u s e d l i k e t i l t i n g t a b l e , immobilizers and crutches, walkers and canes. the patient's mobility is always the responsibility of the physical therapist with introduction the risk of postoperative complications is associated with every orthopedic surgery. the wound infection is one of the major complications that could occur after any orthopedic surgery and always threats the patient's prognosis by delaying recovery 1 and increasing hospital stay. it has been estimated that each patient with a surgical site infection will require an additional 6.5 days in hospital, which results in the doubling of hospital costs associated with 2 that patient. the complex of many factor are responsible for the development of the wound infection 3 after orthopedic surgery. the contributing factors for the development of postoperative wound infection after orthopedic surgery ------------------------------------------------correspondence: syed shakilurrehman department of physiotherapy riphah international university rawalpindi the role of early mobilization in the prevention of post operative wound infection after lower extremity orthopedic surgeries syed shakil-ur-rehman, sohail iqbal sheikh, khalid farooq danish 64 the consent of orthopedic surgeon. this was a quasi experimental study done in the department of orthopedics iimct pak. railway general hospital rawalpindi. duration of the study was one year, from august 2010 to july 2012. 89 patients were included in the study and divided in two groups (45 in group a and 44 in group b).convenient technique was applied. all patients of lower extremity surgeries above the age of 10 years, admitted and operated in the orthopedic unit were included in the surgery. a l l p a t i e n t s w i t h c l o s e d re d u c t i o n procedures, arthroscopically assisted surgeries and with any surgical procedure done in the upper extremity were excluded from the study. the patients mobilized within one week after surgery were placed in the group a, the early mobilized group and all the patients mobilized after the one week of surgery were placed in group b , the delayed mobilized group. the patients' data was analyzed by the statistical software spss version 16. number of patients having postoperative wound infection was recorded in both groups. percentages were calculated and compared using chi-square test. p value < 0.05 was considered significant. out of a total 89 patients, 55 were males and 34 were females. minimum age of patients in this study was 10 and maximum 90 years with a mean of 44 in group a and 49 in group b. the total number of wound infections was 6 (6.74%); 2 (4.4%) in the early mobilized group and 4 (5.6%) in the delayed mobilized group, as shown in table: i. the statistical analysis shows significant difference in number of infection in both groups and the statistical results for group a was (p value=0.03) statistically significant as material and methods results compared to result (p value=0.06) for group b, which is statistically not significant. (table i) table i: frequency of postoperative wound infection after lower extremity orthopedic sugery(n= 89) discussion these results are supported by many international studies. stockton ka and mengersen ka conducted a clinical trial on 57 patients who had undergone total hip replacement. they concluded that the patients, who received physical therapy treatment twice a day, achieved the functional milestones earlier as compared to the other group, who received physical therapy treatment once a day. the result of this study shows that early mobilization and physical therapy treatment can achieve early mobility and decreases the hospital 5 stay. study done by brasher pa et al added that early mobility can decrease post operative complications after cardiac surgery. this clinical trial was conducted on two hundred and thirty patients and this study supports our results that early mobility can decrease 6 postoperative infection. another clinical trial conducted by cinar n et al department of physical medicine and rehabilitation, ankara numune training and research hospital, ankara, turkey on fifty seven patients with modified radical mastectomy. they concluded that early 65 onset rehabilitation program after modified radical mastectomy provides improvement in shoulder mobility and functional capacity w i t h o u t c a u s i n g a d v e r s e e ff e c t i n 7 postoperative period. a randomized controlled trial done by bendz i, fagevik olsen, and m title on two hundred and thirty women who had undergone surgery for breast cancer were randomized to a prospective study. at the end of this study they concluded that mobility of the shoulder girdle is restored in the immediate exercise group as compared 8 to the delayed exercise group. stovall m et al conducted a randomized controlled trail on 199 patients. they compared the improved performance in activities of daily l i v i n g w i t h m o b i l i t y a f t e r a m u l t i d i s c i p l i n a r y p o s t o p e r a t i v e rehabilitation in older people with femoral neck fracture: a randomized controlled trial with 1-year follow-up. the intervention consisted of staff education, individualized care planning and rehabilitation, active prevention, detection and treatment of p o s t o p e r a t i v e c o m p l i c a t i o n s . t h e y c o n c l u d e d t h a t a m u l t i d i s c i p l i n a r y postoperative intervention programme e n h a n c e s a c t i v i t i e s o f d a i l y l i v i n g performance and mobility after hip fracture, from both a short-term and long-term perspective. this study supports the key r o l e o f a p h y s i c a l t h e r a p i s t a n d rehabilitation after lower extremity 9 orthopedic surgeries. budny pg, lavelle j, regan pj, and roberts ah conducted a randomized clinical trial on sixty one patients with pretibial injuries. in group a they traditionally advised bed rest to 40 patients and in group b they early mobilized the 21 patients. comparison of the outcome suggested that the hospital stay in group a was 12 days and group b only 2 days. they concluded that early mobility can decrease the hospital stay and post 10 injury complications. in a contemporary study, khan ms et al. showed 5.76% infection rate in their patients who had undergone orthopedic surgical procedures, supports our results. however they did not relate it to post operative immobilization time or early mobilization 11 time. we conclude that after lower extremity orthopedic surgeries, early mobilization is needed, as it significantly reduces the postoperative wound infection rates, and early mobility is achieved. 1. national prescribing centre. supplementary prescribing: a resource to help healthcare professionals to understand the framework and opportunities. national health service, 2003. 2. ninss. surveillance of surgical site infection in english hospitals: a national surveillance and quality improvement programme. public health laboratory service, 2002. 3. calvin m. cutaneous wound repair. wounds 1998; 10: 12-32. 4. heinzelmann m, scott m, lam t. factors predisposing to bacterial invasion and infection. am j surg 2002; 183: 179-90. 5. stockton ka, mengersen ka. effect of multiple physiotherapy sessions on functional outcomes in the initial postoperative period after primary total hip replacement. archives of physical medicine and rehabilitation 2009; 90:1652-7. 6. brasher pa. does removal of deep breathing exercises from a physiotherapy program including pre-operative education and early mobilization after cardiac surgery alter patient outcomes? australian journal of physiotherapy 2003; 49:165-73. 7. cinar n. the effectiveness of early rehabilitation in patients with modified radical mastectomy. cancer nursing 2008; 31:160-5. 8. bendz i, fagevik olsen, m. evaluation of conclusion references 66 immediate versus delayed shoulder exercises after breast cancer surgery including lymph node dissection. the breast 2002; 11:241-8. 9. stovall m. improved performance in activities o f d a i l y l i v i n g a n d m o b i l i t y a f t e r a multidisciplinary postoperative rehabilitation in older people with femoral neck fracture. journal of rehabilitation medicine 2007; 39:2328. 10. budny pg, lavelle j, regan pj, roberts ah. pretibial injuries in the elderly. british journal of plastic surgery 1993;46:594-8. 11. khan ms, ur rehman s, ali ma, sultan b, sultan s. infection in orthopedic implant surgery, its risk factors and outcome. j ayub med coll abbottabad 2008; 20:23-5. original�article abstract objective: to study the frequency of head injuries in pediatric population at dhq hospital haripur. study design: descriptive cross-sectional study. place and duration of study: we carried out this study for six months from 01.09.2018 to 28.02.2019 at the department of surgery, dhq teaching hospital haripur. materials and methods: in this study,110 children aged upto12 years who sustained head trauma were included in this study. after initial assessment (conscious levels was checked by using glasgow coma scale, any changes in pupils were noted and ct scan was performed wherever indicated), patients were shifted to the department of surgery for admission. those needing surgery were operated after further clinical evaluation and ct scan findings. results: total number of patients was 110. age ranged from 1 to 12 years with a mean age of 5.7 years. out of the total 110 patients, 75% presented between 3 to 8 years. the presenting symptoms were vomiting in 52.7%, peri-orbital swelling in 14.5%, scalp swelling in 20.9% and 36.3% had loss of consciousness. conclusion: it is concluded that the frequency of head injury is quite common in our community. children of younger age with male preponderance are more vulnerable to acquire this injury and fall from height and road traffic accidents are major preventable causes. key words: brain injuries, coma, head trauma, unconsciousness. because of several known reasons head is most frequent part of the body affected by traumatic insults in children and the reason for hospitalization. 5 however, majority of head injuries are minor. road traffic accident (rta) and falling from heightened places are most common causes of traumatic head trauma. in developing countries like pakistan, some important causes include ignorance of traffic rules, badly maintained vehicles, limited zebra crossings, nonfunctioning air bags, less use of seatbelts and overcrowded roads. this and similar studies can help to set protocols for early recognition of potentially treatable causes of mortality and morbidity and will 6 help in better usage of available resources. severity of traumatic brain injury is assessed with glasgow coma scale (gcs) along with other parameters and is characterized as minor, moderate, and severe brain injuries on the basis of score with little changes in scoring for children. a gcs sore of 9 or less indicates serious head injury, 13 and above denotes minor head injury and in between is taken as 7 moderate injury. another way of assessing severity of head trauma is to locate part of tissue damaged. bleeding from scalp vessels can severely affect hemostasis of child. similarly subdural hemorrhage, intracranial hemorrhage and injury to brain parenchyma or its introduction head trauma is a frequent occurrence in children and on most occasions, it results in traumatic brain injury needing active intervention and emergency management. it is a common cause of the loss of consciousness, long term functional problems and 1,2 mortality in trauma patients. head injury is defined as an injury to the cranium, 3 meninges and/or brain. children with their proportionately large heads and flexible consistency 4 of skull bones frequently sustain head injuries. many protective measures have been adapted to reduce head injuries in pediatric population but still it is major health threat because of above mentioned facts. head injuries in pediatric population at dhq teaching hospital haripur 1 2 3 4 5 6 javed iqbal khan , hassan nasir , tahir iqbal khan , noreen sultan , tahir angez khan , mehwish naz correspondence: dr. muhammad javed iqbal khan assistant professor department of surgery abbottabad international medical college, abbottabad e-mail: drjavedikhan@gmail.com 1,6 5 department of surgery/medicine abbottabad international medical college, abbottabad 2 3 department of pediatric/radiology dhq teaching hospital, haripur 4 department of biochemistry ayub medical college, abbottabad funding source: nil; conflict of interest: nil received: june 01, 2020; revised: september 30, 2021 accepted: october 06, 2021 frequency of head injuries in childrenjiimc 2021 vol. 16, no.4 232 edema can threaten child's survival. in the same way hemorrhage below galea can spread around and lead to significant loss of blood which can cause hypovolemic shock and hence endanger the life of a 8 child and must not be ignored. a lot of research has been conducted and being conducted to improve the assessment of severity of brain injury, devise protocols for prompt resuscitation and immediate intervention in indicated patients and all this has contributed significantly in the management of such 9,10 injuries. hemorrhage inside brain parenchyma or its direct tear, bleeding in sub arachnoid space, sub dural or extra dural space can lead to coma and later death or disability. even in minor head trauma, 6 to 30 % cases 8 have injuries to brain or its coverings. in all cases of head injuries, one common mode of damage to brain tissue is loss of either complete or partial blood supply and this single factor has most 11,12 important impact on outcome of poor child. after identifying this factor, efforts are being made to determine methods to urgent revascularization if ischemic area in the hope of recovering its 13,14 function. head injury patients usually require x-ray skull, ct scan, mri and other routine investigations to access clinical evaluation for their proper management. this study will help to outline different types of brain injuries and to set protocols for their early management and better prognosis of these children a n d w i l l a c h i e v e o b j e c t i v e o f i m p r o v i n g understanding and management of head injuries in children and will open gates for further research in this context. hence, a study was planned to study the frequency of head injuries in pediatric population at department of surgery, dhq hospital haripur materials and methods it was a cross sectional descriptive study in which 110 children aged below 12 years with head injury who presented in emergency department at dhq st teaching hospital haripur from 1 september2018 to t h 28 february 2019 were included through convenient sampling technique after permission from hospital ethical review committee. children with other comorbidities were excluded. a quick primary survey and emergency resuscitation was performed on all patients wherever indicated. this was followed by a detailed secondary survey to look for the associated injuries. data was collected by the medical officers through already designed proforma. complete blood count, and x-ray skull, ct scan was done. provisional diagnosis was made in the emergency department and necessary treatment was instituted. complications like meningitis, posttraumatic seizures, csf fistula, epilepsy and hemiplegia were all documented. statistical analysis was done using spss version 20.0. frequencies and percentages were calculated for categorical variables such as gender, mechanism of injury, clinical presentation, skull injury, associated injuries, investigations, provisional diagnosis, treatment, and complications. mean with standard deviations were reported for continuous variables. results the mean age of study patients was 5.7 + 2.7 years ranging from 1 to 12 years. almost 75% of the children were between 3 and 8 years. out of the total, 11 (10.0%) were between 1 and 2 years while 18 (16.4%) were between 9 and 12 years. in our study majority of the cases 62 (56.4%) were males as compared to 48 (43.6%) females. the male to female ratio was 1.3: 1. on average patients remained hospitalized for 1.9 + 1.2 days, ranging from 1 to 8 days. almost 80% of the study patients required 1 to 2 days of hospital stay while 25 (22.7%) of the patients needed 3 or more days of hospital stay. the mechanism of injury is illustrated in table 1. the gcs level was noted in the study patients. in 3 (2.7%) cases it was less than or equals to 8. in 10 (9.1%) cases the gcs level was between 9 and 12. however, in majority of the cases 97 (88.2%) the gcs level was between 13 and 15. vomiting was the presenting symptom in 58 (52.7%) patients, orbital swelling in 16 (14.5%) cases and scalp swelling in 23 (20.9%) patients. forty (36.3%) patients had history of loss of consciousness. other complaints included nasal bleeding and convulsions in 3 (2.7%) patients, ear bleeding in 4 (3.6%) patients. the mean systolic bp was 98.8 + 11.4 while the diastolic bp was 66.0 + 8.5 mmhg. the average heart rate in the study patients was 78.8 + 10.5 ranging from 60 to 136. similarly, the average respiratory rate was 29.2 + 6.2 ranging from 20 to 45. out of total, 44 patients had skull injuries, 32 (29.1%) jiimc 2021 vol. 16, no.4 frequency of head injuries in children 233 had single skull fracture, 6 (5.4%) had linear fracture, whereas 5 (4.5%) had multiple fractures. one (0.9%) patient had wound on the right temporal and frontal region. out of the total 110 patients, 53 (48.1%) had no fracture on x-ray skull. twenty-eight (25.4%) patients had linear fracture, 21 (19.1%) had single fracture while 6 (5.4%) had depressed fracture and 2 (1.8%) had multiple fractures. ct scan was done in 93 patients and ct scan findings are illustrated in table 2. different management options needed by the patients are illustrated in table 3. sustain minor injuries (in this study97% children were having gcs of 13-15). in our study, most (75%) of children were in age group from3-8 years and fall from height was major cause (47.3%). according to most of the previous reports, male gender has 22 suffered more than females. in third world countries incidence of head injuries is on the rise and most important contributing factors include increased traffic, ignorance about road sense, decreased safety protocols in major industries, falls from heights and firearm penetrating injuries. road traffic injuries are an increasing dilemma globally but the incidence in south and east asia is increasing rapidly and need special 15 attention. trauma to brain is responsible for 25 to 35 % of all deaths resulting from accidents and is a cause of most deaths in trauma patient in different hospitals 16 worldwide as reported by some studies. one major cause of head injuries is accident caused by motor cars, trolleys, and motorcycle injuries. fall from heighted places like mountains or high-rise buildings, physical attacks from enemies and firearm penetrating injuries to skull are another important causes of head injuries which is well depicted in present study. sometime injury to brain is a part of poly trauma involving many organs, but it can also occur in isolation which is comparable to present 17 study. there is evidence from different parts of the world indicating that incidence of head injuries is rising 18 steadily. a study by sosin et. al. reported that a huge proportion (28%) of deaths in trauma patients 19 were caused by traumatic brain injury alone. another report from indian held kashmir who worked on head injury related morbidity and mortality, revealed that pediatric population of age less than 10 years was major sufferer of these catastrophes which is very much like present study 20,21 satistics. these statistics are comparable to present study. in one report rtas (44.4%) were mainly responsible for sustaining traumatic head injury followed by falls from heighted places which were responsible for 20 approximately 32.2% cases. different types of physical assaults accounted for 19.0% cases of head injury. comparatively in our study fall from roof was most common (47.3%) mode of head injury and rtas table i: mode of injury in the study (n = 110) table ii: ct findings in patients (n=93) table iii: mode of treatment given to patients (n=110) discussion head injury is common occurrence in children and presents to the accident and emergency (a&e) department quite frequently but majority of them jiimc 2021 vol. 16, no.4 frequency of head injuries in children 234 were responsible for many patients (24%) to land in emergency department with head injuries, while other significant modes of injury were also fall either from tree, stairs, or bed. this very well may be attributed to our living styles. in most of the cases minor and moderate head injured patients required up to 2 days of hospital 23 stay. in our study, the average hospital stay was 1.9 days with almost 80% had hospital stay of 1 to 2 days. this could be due to grading of injury, as in our case, most of the head injuries were diagnosed as concussions. the study by yattoo gh and colleagues reported that 80% of their patients had gcs score of 15 while 10% had 13-14 and 5.3% had 8 to 12 gcs level while 20 another 5% had gcs score less than 8. in our study almost 88% patients had gcs between 13 and 15, 9% had it between 9 and 12 while 3% had gcs level below or equals to 8. again, this could be due to severity of injury as mentioned most of the patients had concussions in our study. ct scan findings were also comparable. the nature of head injuries in our study was mostly minor to moderate. none of our patients died. those patients (6%) having depressed fracture were elevated and in 5% of the patient's evacuation and debridement was done via surgery. no significant side effects or complications were witnessed in our patients except for headache in 2.7% and hemiplegia in 1% children was witnessed. one of the limitations of our study was its descriptive methodology. the strengths and advantages of the current study are the scope of information gathered. in the current study data regarding patient's demographics, hospital stay, mechanism of head injury, presenting complaints, physical examination, nature of skull injuries and associated injuries, radiography in the form of both x-rays and ct scan were recorded. this is one of the few studies auditing head injuries in children in the local settings. the details of present study suggest that we should focus on prevention of head injuries in pediatric population by educating children at different stages of their life. this can be started at home by parents, later by teachers in school going children and can be supplemented by social organization working for children in liaison with health care workers. anticipatory counseling of caretakers can be done to understand the patterns and priorities during early age of a child. conclusion it is concluded that fall from height is a common cause of injury and early radiographic evaluation specially, ct scan is very important in determining nature of head injury and its management. there is a need of initiatives for careful planning to prevent head injuries in children with active involvement of people responsible for their care at different stages of their development and growth. references 1. lecourse a,sirois mj,ouellet mc,boivin k,simard jf.long term functional outcomes of older adults after a traumatic brain injury. journal of head trauma rehabilitation. 2012; 27:379-90. 2. wilkes s, mccormack e, kenney k, stephens b, passo r, harburg l et al. evolution of traumatic parenchymal intracranial hematomas: comparison of hematoma and edema components.front. neurol.2018; 9:527. 3. shekar c, gupta ln, premsagar ic, sinha m, kishore j. an epidemiological study of traumatic brain injury cases in a truma centre of new delhi (india). j emerg trauma shock. 2015;8(3):131-9. 4. young sj, barnett plj, oakley ea. fractures, and minor head injuries. minor injuries in children ii. med j aust.2005; 182: 644-8. 5. retting ra, ferguson sa, mccartt at. a review of evidencebased vehicle crashes. am j public health 2003; 93: 145663. 6. krug, sharma gk, lozano r. the global burden of injuries. am j public health 2000; 90: 523-6. 7. gedeit r. head injury. pediatr rev. 2001; 22(4): 118-24. 8. atabaki sm. pediatric head injury. pediatr rev. 2007; 28(6): 215-24. 9. bonfield cm, naran s, adetayo oa, pollack ib, losee je. pediatric skull fractures: the need for surgical intervention, charecteristics, complications and outcomes. j neurosurg pediatr. 2018;14(2):205-11. 10. acosta ja, yang jc, winchell rj, simons rk, fortlage da, hollingsworth-fridlund et al. lethal injuries and time to death in a level 1 trauma center. j am coll surg 1998;86: 528-33. 11. martin na, patwardhan rv, alexander mj, afrik cz, lee jh, shalmon e et al. characterization of cerebral hemodynamic phases following severe head trauma: hypoperfusion, hyperemia and vasospasm. j neurosurg 1997; 87: 9-19. 12. broderick jp, adams hp, barsan w, feinberg w, feldmann e, grotta j et al. guidelines for the management of spontaneous intracerebral hemorrhage. stroke 1999; 30:905-915 13. wise j. new clinical guidelines for stroke. bmj 2000; 320: 23. jiimc 2021 vol. 16, no.4 frequency of head injuries in children 235 14. grabz tj. in: barnet hjm eds: stroke: pathophysiology, diagnosis and management, new york, churchill livingstone, 1992; 29. 15. charles m, manjul j: the essential trauma care project – relevance in southeast asia. regional health form who southeast asia region 2004, 8(1):29-38. 16. fulkerson dh, white ik, rees jm, baumanis mm, smith jl, ackermam ll et al. analysis of longterm (median 10.5 years) outcomes in children presenting with traumatic brain injury and an initial glasgow coma scale score of 3 or 4. j neurosurg pediatr 2015;16(4):410-9. 17. grenvik a, stephen ma, ayres sm, holbrook pr, shaemaker wc. management of traumatic brain injury in the intensive care unit. critical care. 2000;4: 322-26. 18. tabish sa, shah s, bhat as, bhat fa, shoukat h, mir my. clinical profile and mortality pattern in patients of ballistic trauma. jimsa. 2004;13(4):247-50. 19. yattoo gh, tabish a. the profile of head injuries and traumatic brain injury deaths in kashmir. j trauma management & outcome 2008; 2:5. 20. kirmani ma, sexena rk, wani ma. the spectrum of head injury in the valley of kashmir as seen at sher-i-kashmir institute of medical sciences, srinagar, kashmir. thesis submitted for m.s (general surgery) 1986. 21. tasker rc, morris kp, forsyth rj, hawley ca, parslow rc. emerg med j 2006; 23: 519-22. 22. wani aa, sarmast ah, ahangar m, malik nk, chhibber ss, arif sh, ramzan au, dar ba, ali z. pediatric head injury: a study of 403 cases in a tertiary care hospital in a developing country. journal of pediatric neurosciences. 2017 oct;12(4):332. jiimc 2021 vol. 16, no.4 frequency of head injuries in children 236 original�article abstract objective: to analyze the serum electrolyte imbalance in children with severe acute malnutrition (sam) aged 159 months. study design: it was a cross sectional study. st th place and duration of study: six months from 1 march 2018 to 30 august 2018 at nutrition stabilization centre of the children's hospital and institute of child health multan. materials and methods: all the children between age group 1-59 months and admitted in stabilization centre of the hospital and institute of child health multan with diagnosis of severe acute malnutrition during the study duration were included in this study. after inclusion criteria fulfilled sample was collected from 100 different patients and sent to pathology department of children's hospital and institute of child health multan 2+ 2+ + + for biochemical assessment. the serum was analyzed for mg , ca , k and na by spectrophotometric method. all the data was entered and analyzed by using spss version 21. the percentages were calculated through spss. results: total 100 children with severe acute malnutrition were included in current study. 60 (60%) were male and 40 (40%) were female, mean age reported was 23.65 months. there were 66% cases presented with diarrhea. hypokalemia was found in 23 (23%) children and hyponatremia was present in 28 (28%) children. mean of sodium & potassium were 138.96 (8.692) and 3.06 (+1.7517) respectively. mean (s.d) of calcium and magnesium were 8.51 (1.58) and 2.23 (2.38) respectively. conclusion: electrolyte imbalance is common in children with severe acute malnutrition with or without diarrhea. determination of electrolyte profile of children with severe acute malnutrition admitted at stabilization centers in pakistan should be ensured to reduce the mortality and morbidity. key words: diarrhea, electrolytes imbalance, severe acute malnutrition (sam). healthy child, sodium potassium pump exists, which maintains the potassium concentration in the cell by pumping sodium out and potassium in to the cell. when a child is suffering from severe acute malnutrition, the sodium potassium movement become impaired. the level of sodium inside the cell became high and potassium is lost. when the child is treated, na+, k+ levels are maintained. therefore, feeding must be very slow otherwise it will cause fluid overload, metabolic disturbances and system will be disturbed. magnesium is essential for potassium to enter the cell. potassium and magnesium are recommended according to world health organization (who) 3-4mmol/kg/day and 5 0.4-0.6mmol/kg/day respectively. the children with severe acute malnutrition occasionally suffer from diarrhea which leads to the 6 electrolyte imbalance. the children suffering from severe acute malnutrition may have low serum level of potassium (hypokalemia), high level of sodium (hypernatremia) and altered level of calcium. rehydration solution for severely malnourished children (resomal) is recommended which is less in introduction malnutrition is the big contributor of illness in 1 children worldwide. malnutrition especially under nutrition is the cause of mortality and morbidity and results in 45% of child mortality (under 5 years of 2 age) worldwide. pakistan is the fifth country having 3 higher cases of severe acute malnutrition. severe acute malnutrition leads to major complications in the body along with electrolyte 4 imbalances which may worsen with diarrhea. in a the serum electrolyte imbalance in children with severe acute malnutrition 1 2 3 4 5 6 saadia khan , zille rubab , ibad ali , reema arshad , asad abbas , erum akhtar correspondence: reema arshad research associate department of pediatrics and child health, aga khan university karachi e-mail: reemaarshad0@gmail.com 1,3,6 department of preventive pediatrics/ department of 2 pediatrics hematology the children's hospital and the institute of child health, multan 4 department of pediatrics and child health aga khan university karachi 5 institute of food sciences and nutrition bahauddin zakariya university, multan funding source: nil; conflict of interest: nil received: october 25, 2019; revised: february 09, 2021 accepted: february 10, 2021 the serum electrolyte levels in children with samjiimc 2021 vol. 16, no.1 10 sodium and more in potassium. serum electrolyte imbalances in sam children can be due to numerous 7 reasons but are more evident during diarrhea. the malnourished children are more susceptible to morbidities and mortalities related to electrolyte balance. the findings of this study will help to determine the extent of electrolyte imbalance in children suffering from sam and further researches can be conducted for detailed analysis. the purpose of current study was to analyze the serum electrolyte imbalance in children with severe acute malnutrition (sam) aged 1-59 months admitted to the children's hospital and institute of child health multan. materials and methods the current study was cross sectional study, conducted in nutrition stabilization centre of the children's hospital and institute of child health multan from march 2018 to august 2018. simple random sampling technique was used. all the children between age 1-59 months and admitted in stabilization centre of the children's hospital and institute of child health multan during the duration of study period and diagnosed with severe acute malnutrition were included in this study. a total of 110 children were admitted during the study period. severe acute malnutrition was defined as children having mid upper arm circumference less than 11.5cm, weight-for-height/length ratio less than 3sd and bilateral edema or anyone out of above. all children admitted with severe acute malnutrition aged between 1-59 months with or without diarrhea were included in this study. the study was started after getting permission from irb committee of the hospital. written consent was taken from the parents/guardians of the admitted patients. out of 110 patients only 100 gave consent and were thus enrolled for the study. the children whose parents refused to give consent were excluded from this study. a self-made questionnaire was designed by the principal researcher and filled by the trained nursing staff of stabilization center. the demographic data ( a g e , g e n d e r, a n d n a m e ) wa s c o l l e c t e d . anthropometric assessment (weight, height, muac, weight/height or length ratio) was done and noted by the nurses. about 2ml blood sample was collected from 100 patients admitted in stabilization centre ward and sent to pathology department of children's hospital and institute of child health multan for biochemical assessment. sodium and potassium analysis were performed by using patient's serum on a fully automated electrolyte analyzer diestro 103 ap, that work on the principle of ion selective electrode (ise) while serum calcium and magnesium levels were measured on a fully automated chemistry analyzer beckman coulter au-680, that works on the principle of spectrophotometry. the biochemical assessment was performed by lab technicians of the pathology department and results were recorded on the questionnaire by the nurses. the data collected was nonparametric. all data was computed and analyzed by using spss version 21. descriptive cross-sectional analysis of complete data was analyzed, and results are reported as frequencies and percentages. mean sd and averages were calculated where required. results total 100 children with severe acute malnutrition were included in current study. 60 (60%) were male and the mean age in months was 23.65. there were 66% cases presented with diarrhea. mostly children 93 (93%) belong to poor socio-economic status (table i). the serum level of potassium was low in 23 (23%) and high in 12 (12%) patients. the serum level of potassium was normal in 65 (65%) children. the serum level of sodium was low in 28 (28%) and high in 15 (15%). the serum level of potassium was normal in 57 (57%) children. the serum level of magnesium was low in 16 (16%). 2+ the serum level of mg was normal in 73 (73%) children. the serum level of calcium was low in 28(28%) and high in 3 (3%). the serum level of potassium was normal in 69 (69%) children (table ii). the mean serum potassium and sodium was 3.06 ± 1.75 mmol/l and 138.96 ± mmol/l respectively. (table iii) discussion current study was intended to explain the electrolyte profile with severe acute malnutrition, admitted in stabilization centre of the children's hospital and institute of child health multan and their age were 159 months. this age group is very critical group because weaning is initiated, and children have higher risk of developing severe acute malnutrition. according to the findings of this study, in severe the serum electrolyte levels in children with samjiimc 2021 vol. 16, no.1 11 acute malnutrition, hypokalemia and hyponatremia were significant risk factor for acute diarrhea. serum electrolyte balance along with diarrhea may results in increased mortality and morbidity in sam children. in current study, 86 (86%) children were of age 25-59 months. this study included 60% males and 40% females. current results were comparable with the 8 previous study conducted in india . it may also indicate that despite gender discrimination, male children were at more risk of severe acute malnutrition than female child or perhaps more male children were admitted to hospitals for treatment than female child. there were 66% cases presented with diarrhea and 34% cases without diarrhea which is comparable with a study conducted in zambia (64% cases 9 presented with diarrhea). according to previous studies, diarrhea is directly linked to severe acute malnutrition and have a major impact on serum 10 electrolyte balance as well. these findings were also confirmed by the current study. chronic and persistent diarrhea leads to severe acute malnutrition and sam children were more prone to diarrhea due to low immunity and prolonged 11 infections. in this study almost one third of cases had hyponatremia and these results were supported by another study conducted by zulqarnain et al. which reported hyponatremia in 31.1% cases and 22.6% 5,12 cases were reported by bilal at al. our study included serum sodium level less than 136mmol/l as standard hyponatremia but negussie at al. included serum sodium level less than 130mmol/l as 13 hyponatremia. there were 23% cases of hypokalemia in current study, but previous studies included 55% and 13.7% 5,12 cases of hypokalemia. in current study, 12% and 15% cases were hyperkalemia and hypernatremia respectively. current results included higher cases of hyperkalemia and hypernatremia as compared to 12,14 previous studies. the cases of hypocalcemia in current study were much higher than the previous 14 studies. this also indicated that the samples enrolled in our study were at much higher risk for 15 complications regarding hypocalcemia. this research, however, is subject to limitations, the primary limitation was short time duration of six months, due to which random sampling technique was used. all the patients registered at the hospital during those six months, fulfilling the inclusion criteria were recruited. a study done for longer table i: gender, age, socio-economic status of children with sam (n= 100) table ii: serum electrolyte profile of children with severe acute malnutri�on table iii: mean serum electrolyte profile of children with severe acute malnutri�on the serum electrolyte levels in children with samjiimc 2021 vol. 16, no.1 12 period of time may include more samples and provide more concrete results to strengthen the findings of this study. according to the findings of this study, in severe acute malnutrition, hypokalemia and hyponatremia were significant risk factor for acute diarrhea. conclusion electrolyte imbalance is common in children with severe acute malnutrition with or without diarrhea. determination of electrolyte profile of children with severe acute malnutrition admitted at stabilization centers in pakistan should be ensured to reduce the mortality and morbidity. references 1. tesfay w, abay m, hintsa s, zafu t. length of stay to recover from severe acute malnutrition and associated factors among under-five years children admitted to public hospitals in aksum, ethiopia. plos one. 2020;15(9):238311. 2. fanzo j, hawkes c, udomkesmalee e, afshin a, allemandi l, assery o, et al. global nutrition report. unicef. new york, 2018.website:[http://openaccess.city.ac.uk/id/eprint/227 97/] accessed on: june 15, 2012. 3. ministry of national health services, regulations and coordination. government of pakistan. national nutrition sur vey 2018. pakistan: unicef; 2018. website: [ h t t p s : / / w w w . u n i c e f . o r g / p a k i s t a n / n a t i o n a l nutritionsurvey-2018]. retrieved on: june 14, 2020. 4. prost a, nair n, copas a, pradhan h, saville n, tripathy p, et al. mortality and recovery following moderate and severe acute malnutrition in children aged 6-18 months in rural jharkhand and odisha, eastern india: a cohort study. plos med. 2019;16(10):2-934. 5. zulqarnain a, jaffar z, iqbal i. malnourished children with diarrhea. tpmj. 2017;22(05):610-4. 6. world health organization. pocket book of hospital care for children: guidelines for the management of common childhood illnesses. 2nd ed. geneva: world health organization; 2013. 7. girum t, kote m, tariku b, bekele h. survival status and predictors of mortality among severely acute malnourished children< 5 years of age admitted to stabilization centers in gedeo zone: a retrospective cohort study. ther clin risk manag. 2017; 13:101. 8. gangaraj s, das g, madhulata s. electrolytes and blood sugar changes in severely acute malnourished children and its association with diarrhoea and vomiting. int j pharm sci invent. 2013;2(5):33-6. 9. irena ah, mwambazi m, mulenga v. diarrhea is a major killer of children with severe acute malnutrition admitted to inpatient set-up in lusaka, zambia. int j nutr. 2011;10(1):110. 10. mahfuz m, alam ma, islam sb, naila nn, chisti mj, alam nh, et al. treatment outcome of children with persistent diarrhoea admitted to an urban hospital, dhaka during 2012–2013. bmc pediatr. 2017;17(1):142. 11. trehan i, goldbach hs, lagrone ln, meuli gj, wang rj, maleta km, et al. research article (new england journal of medicine) antibiotics as part of the management of severe acute malnutrition. malawi med j. 2016;28(3):123-30. 12. bilal a, sadiq ma, haider n. frequency of hyponatraemia and hypokalaemia in malnourished children with acute diarrhoea. j pak med assoc. 2016;66(9):1077-80. 13. negussie as, tadesse aw. predictors of undesirable treatment outcomes of severe acute malnutrition among inpatient children in addis ababa, ethiopia: a retrospective cohort study. bmc public health. 2020; 20(1):1-0. 14. kamberi t, azemi m, avdiu m, jaha v, uka v. 675 malnourished children with acute diarrhea. arch dis child. 2018;97(suppl 2):a195-a. 15. sameen if, moorani kn. morbidity patterns of severely malnourished children at tertiary care hospital. pak paed j. 2014; 38:3-8. the serum electrolyte levels in children with samjiimc 2021 vol. 16, no.1 13 original�article abstract objective: to determine the frequency of p53 and ki-67 staining in cases of papillary urothelial carcinomas of urinary bladder and to correlate staining frequencies of p53 and ki 67 in lowand high-grade carcinomas. study design: a cross sectional study. place and duration of study: the study was conducted in department of histopathology, foundation st th university medical college and hospital rawalpindi for duration of six months, from 1 september 2017 to 28 february 2018. materials and methods: eighty-five patients of both genders undergoing trans urethral resection of bladder tumor were included in the study. the bladder biopsies were collected after turbt and placed in 10% formalsaline for twenty-four hours. after tissue fixation, representative sections were taken and processed routinely for histology and immunohistochemistry at histopathology lab. patients with histological diagnosis of low and high grade papillary urothelial carcinoma were included in the study. results: among 85 patients, 64 were females and 21 were males. the most frequent tumor was low grade papillary urothelial carcinoma seen in 44 patients while 41 patients had high grade carcinoma. positive p53 expression was more in high grade carcinoma (32.94%) as compared to low grade carcinoma (27.1%) and negative p53 expression was more in low grade carcinoma (23.5%) as compared to high grade carcinoma (14.1%). however, a statistically non-significant p value of 0.132 was obtained on comparison of p53 expression with chi square test. similarly, positive ki-67 expression was seen in 45.9% of low-grade carcinomas and 37.65% of high-grade carcinomas and negative expression was seen in 9.4% of low-grade carcinomas and 7.06% of high-grade carcinomas which did not correlate with our histopathological diagnosis. p value calculated by chi square test for ki-67 was 0.659 which is also non-significant in our study. conclusion: our study concluded that p53 and ki-67 immunostaining does not significantly correlate with histopathological grades of urothelial papillary carcinoma of urinary bladder in our local population. therefore, immunohistochemistry expression of these markers cannot be solely relied upon for determining the grading of urothelial carcinomas. key words: immunohistochemistry, ki-67, p53, tumor markers, urinary bladder neoplasms. th 1 frequent malignancies in men and 17 in women. the reported incidence of new bladder carcinoma 2 cases is about 1 in 10 people before 75 years of age. the most frequent tumor type of bladder carcinoma is urothelial (transitional cell) carcinoma comprising 90% of all cases followed by squamous cell 3,4 carcinoma and adenocarcinoma clinically, bladder carcinomas are divided into superficial non-muscle 3,5,6,7 invasive tumors and invasive tumors. in nonmuscle invasive carcinomas, mainstay of treatment is local resection while invasive tumors require cystectomy (bladder removal) or additional adjuvant 2,8 therapies. early diagnosis of bladder carcinoma by pelvic ultrasound and cystoscopy (by urologist) helped in early treatment, reducing tumor 9 morbidity. urine cytology is also used for diagnosis introduction th bladder carcinoma is a 6 most frequent malignant th neoplasm in the world with 7 amongst most p53 and ki-67 expression in papillary urothelial carcinomas of urinary bladder, an experience at foundation university medical college islamabad, pakistan 1 2 3 4 5 6 iram kehkashan khurshid , mumtaz ahmad , sarah javed , saba aneeqa , atiya gardezi , maryam waqar correspondence: dr. iram kehkashan khurshid senior lecturer mohi-ud-din islamic medical college, mirpur ajk e-mail: iramkhurshidpath@gmail.com 1 department of pathology mohi-ud-din islamic medical college, mirpur ajk 2,3,4 department of pathology foundation university medical college, islamabad 5 department of pathology united medical and dental college, karachi 6 department of pathology hbs medical and dental college, islamabad funding source: nil; conflict of interest: nil received: february 25, 2021; revised: may 25, 2021 accepted: may 27, 2021 p53 and ki-67 expression in bladder carcinomasjiimc 2021 vol. 16, no.2 74 as it is cost effective but less sensitive diagnostic 10 modality. so coordinated efforts of urologists and the histopathologists for detection of lesion is 11 essential for management of patients. apart from depth of invasion, the stage and grade of urothelial 11 carcinoma has significant prognostic value. immunohistochemical expression of p53 and ki-67 can be utilized for grading and staging of urothelial 12,13 carcinomas and also as important prognostic 13,14 markers. a thorough search of literature showed that not much work is done on bladder carcinoma diagnosis with correlation of its histological grade and immunohistochemical markers expression in local pakistani population. this study was an effort to identify the histological grade of bladder tumor in small biopsies using h i s t o p a t h o l o g y a n d i t s c o r r e l a t i o n w i t h immunohistochemical expression of p53 and ki-67 among local pakistani population which acted as a guide for clinicians in determining therapeutic management plan for patients. materials and methods after approval by the ethical committee, this comparative cross-sectional study was carried out. it was conducted at department of histopathology and urology, foundation university medical college and hospital, rawalpindi. the study spanned 6 months st th duration from 1 september 2017 to 28 february 2018. the study population comprised eighty-five patients of both genders undergoing turbt, selected by consecutive (nonprobability) sampling technique. sample size was calculated using who sample size calculator. patients with histological diagnosis of low and high grade papillary urothelial carcinoma were included in the study. patients with histological diagnosis of papillary urothelial carcinoma of low m a l i g n a n t p o t e n t i a l a n d t h o s e r e c e i v i n g chemotherapy or radiotherapy prior to surgery and biopsies with insufficient material were excluded from the study. the bladder biopsies were collected after turbt and placed in 10% formal-saline for twenty-four hours. after tissue fixation, representative sections were taken and processed routinely for histology and immunohistochemistry at histopathology lab. an indirect ihc staining protocol was used consisting of four main steps: (1) fixation – to keep everything in its place, (2) antigen retrieval – to increase availability of proteins for detection, (3) blocking – to minimize pesky background signals and (4) antibody labeling (primary and secondary antibodies by dako) and visualization. the h&e-stained sections of bladder tissue was examined simultaneously by me and a senior consultant histopathologist under 10 and 40 objectives in the histopathology department, foundation university medical college, giving the exact histologic grade of the papillary urothelial tumor. the ihc slides of ki-67 and p53 were also examined under 10 and 40 objectives by another consultant histopathologist. the low power examination i.e., 10 objectives helped to find the field with maximum positive cells. then that area was examined under 40 objectives to calculate the cells with positive nuclear staining (brown to black) dividing it with the total number of cells in that area (positive and negative) and multiplying result with 100. both markers give nuclear staining. p53 and ki67 were considered positive when more than 10% of the total tumor cells gave positive (brown) nuclear staining. the person who reported ihc slides was blinded to histopathological slide results and viceversa. spss version 17 was used for data analysis including frequencies and percentages for age, gender, tumor grade (low, high), p53 and ki-67 expression. chi –square test was used to compare frequency of p53 and ki-67 expression among low and high grade papillary urothelial carcinomas of the urinary bladder. p value of ≤ 0.05 was considered significant. results a total of 85 patients were diagnosed with papillary urothelial carcinoma of bladder. maximum number of patients 27(31.8%) were in the age range of 6170years. 64 (75.3%) were female and 21(24.7%) were male, with a female to male ratio of 3:1. among all patients 58 (68.24%) patients presented with bladder growth on cystoscopy followed by hematuria in 25 patients (29.41%) and flank pain in 2 patients (2.35%). on histological diagnosis 44 (51.8%) patients revealed low grade carcinoma and 41(48.2%) patients had high grade carcinoma. (figure -1). in this series, positive p53 expression was seen in 32.94% of high-grade carcinoma and 27.06% cases of low-grade carcinoma. negative p53 expression was p53 and ki-67 expression in bladder carcinomasjiimc 2021 vol. 16, no.2 75 present in 23.5% of low-grade carcinoma and 14.1%cases of high-grade carcinoma. on comparing histopathological diagnosis with p53 expression by chi square test the p value was non-significant p=0.132. positive ki-67 expression was seen in 45.9% of low-grade carcinomas and 37.65% of highgrade carcinomas and negative expression was seen in 9.4% of low-grade carcinomas and 7.06% of highgrade carcinomas which did not correlate with the histopathological diagnosis. p value calculated by chi square test for ki-67 was 0.659 which is proved nonsignificant. discussion urinary bladder carcinoma is amongst the most frequently occurring carcinomas in pakistan causing significant morbidity and mortality. for these reasons, patient's diagnostic workup is very important as it guides the clinicians about the treatment modalities. immunohistochemistry is an adjunctive tool to confirm the histopathological 12 grade of bladder carcinoma. mutations in p53 and k i 6 7 a re a m o n g t h e key co nt r i b u to rs i n 13 carcinogenesis of bladder cancers. in the current study, the urothelial carcinoma was more frequent in females (75.3%) however worldwide bladder carcinoma is more frequent in males. this discrepancy may partly be due to the fact that female patient's turnover was more in our hospital. a research done by rukhsana parveen samo et al in 2019 states higher incidence of bladder carcinoma in 15 males (61.4%) as compared to females (38.6%). in their study, more subjects had high grade bladder carcinoma (65.10%) with highest number of patients 15 in age range of 46-60 years while in our study, low grade carcinoma was more frequent and highest number of patients were in 61-70 years age bracket. another study done in 2014 by telli showed results comparable to our study, exhibiting low grade bladder carcinoma to be more frequent bladder 16 tumor. a study done by rafal stec et al., in 2019 on 134 patients showed positive correlation of p53 and fig 1: relatively bland nuclear features of low-grade carcinoma (100x) a; as compared to pleomorphic nuclei and prominent nucleoli in high-grade bladder carcinoma (400 x) b h&e. fig 2: positive nuclear staining of p53 (400x) ihc fig 3: positive nuclear staining for ki-67 (200x) ihc table i. frequency of p53 and ki-67 expression among lowand high-grade urothelial neoplasms p53 and ki-67 expression in bladder carcinomasjiimc 2021 vol. 16, no.2 76 17 ki-67 with tumor grade unlike our study. mirja geelvink et al., in 2018 took higher percentage of tumor cells to be positive, i.e ki-67 >15% was taken as 12 positive for high grade bladder carcinomas. a study done by dipti gajjar et al in 2019 0n 314 patients of bladder pathologies revealed immunohistochemistry requirement for diagnosis in 48 cases. out of those 48 cases, 16 cases were of low-grade bladder carcinomas exhibiting p53 expression of >10% in 15 cases (93.75%) and ki-67 of 15-40% in all 18 16 cases (100%) unlike our study. a study by stanislav ziaran et al., in 2020 on p53, ki67 expression in bladder carcinomas took p53>10% and ki-67>15% as positive. ki-67 showed positive correlation with high grade morphology (unlike our study) as well as predictor of tumor recurrence while p53 did not prove to be significantly correlated with 19 tumor progression or recurrence. a brazilian study conducted on 43 patients of transitional cell carcinoma of urinary bladder revealed 20 patients of high grade while 23 patients with of low-grade carcinomas. the ki-67 positivity was observed in total of 25 patients (58.1%), out of which 18 patients were of high-grade carcinomas (41.9%), while 7 patients were of low-grade carcinomas (16.2%). the ki-67 was negative in 18 patients (41.9%), out of which 2 patients were of high-grade carcinomas (4.7%) and 16 patients were of low-grade carcinomas (37.2%). the expression of p53 was observed in total of 11 patients (25.6%), all of which were having high grade carcinomas, while expression was negative in 32 patients (74.4%) out of which 9 patients were of carcinomas (20.9%) and 23 20 patients were of low-grade carcinomas (53.5%). a study by thakur et al., in 2017 showed majority male patients (88.2%) with only 11.8% females. cases reported as low grade were less (44.5%) as compared to high grade (55.5%). high expression of p53 and ki-67 were seen in high grade carcinomas with statistically significant p value, contrary to our 4 study. conclusion this study concluded that p53 and ki-67 immunostaining is not significantly correlated with histopathological grades of urothelial papillary carcinoma of urinary bladder in our local population. therefore, immunohistochemistry expression of these markers cannot be solely relied upon for determining the grading of urothelial carcinomas. references 1. gandomani hs, tarazoj aa, siri fh, karimi rozveh a, hosseini s, borujeni nn, et al. essentials of bladder cancer worldwide: incidence, mortality rate and risk factors. biomedical research and therapy. 2017;4(9):1638-55. 2. richters a, aben kkh, kiemeney lalm. the global burden of urinary bladder cancer: an update. world journal of urology. 2020;38(8):1895-904. 3. miyazaki j, nishiyama h. epidemiology of urothelial carcinoma. 2017;24(10):730-4. 4. thakur b, kishore s, dutta k, kaushik s, bhardwaj ajijop, microbiology. role of p53 and ki-67 immunomarkers in carcinoma of urinary bladder. indian j pathol microbiol. 2017;60(4). 5. sanli o, dobruch j, knowles ma, burger m, alemozaffar m, nielsen me, et al. bladder cancer. nature reviews disease primers. 2017;3(1):17022. 6. inamura kjc. bladder cancer: new insights into its molecular pathology. cancers (basel). 2018;10(4):100. 7. tan tz, rouanne m, tan kt, huang ry-j, thiery j-p. molecular subtypes of urothelial bladder cancer: results from a meta-cohort analysis of 2411 tumors. european urology. 2019;75(3):423-32. 8. degeorge kc, holt hr, hodges scjafp. bladder cancer: d i a g n o s i s a n d t r e a t m e n t . a m fa m p h y s i c i a n . 2017;96(8):507-14. 9. khan mr, naser f, hossain m, rahman mjbjou. flexible cystoscopy a valuable diagnostic lool for lower urinary tract pathology. bangladesh journal of urology. 2020;23(2):151-3. 10. oeyen e, hoekx l, de wachter s, baldewijns m, ameye f, mertens i. bladder cancer diagnosis and follow-up: the current status and possible role of extracellular vesicles. int j mol sci. 2019;20(4):821. 11. compérat e, varinot j, moroch j, eymerit-morin c, brimo f. a practical guide to bladder cancer pathology. nature reviews urology. 2018;15(3):143-54. 12. geelvink m, babmorad a, maurer a, stöhr r, grimm t, bach c, et al. diagnostic and prognostic implications of f g f r 3 h i g h / k i 6 7 h i g h pa p i l l a r y b l a d d e r c a n c e rs . 2018;19(9):2548. 13. agrawal r. immunohistochemical and molecular markers in urothelial carcinoma. 2017;60(4):462-3. 14. el-gendi s, abu-sheasha g. ki-67 and cell cycle regulators p53, p63 and cyclind1 as prognostic markers for recurrence/ progression of bladder urothelial carcinoma. pathology & oncology research. 2018;24(2):309-22. 15. samo rp, dal na, das b, shaikh ap, kashif sjtpmj. urothelial carcinoma and its association with age and gender. the professional medical journal. 2019;26(10):1719-23. 16. telli o, sarici h, ozgur bc, doluoglu og, sunay mm, bozkurt s, et al. urothelial cancer of bladder in young versus older adults: clinical and pathological characteristics and outcomes. 2014;30(9):466-70. 17. stec r, cierniak s, lubas a, brzóskowska u, syryło t, zieliński h, et al. intensity of nuclear staining for ki-67, p53 and p53 and ki-67 expression in bladder carcinomasjiimc 2021 vol. 16, no.2 77 survivin as a new prognostic factor in non-muscle invasive bladder cancer. pathology & oncology research. 2020;26(2):1211-9. 18. gajjar d, mansi faujdar d, jain r, gupta s. diagnostic utility of ck20, p53 and ki67 to differentiate between papillomas/non-invasive papillary urothelial neoplasm of low malignant potential/non-invasive papillary urothelial carcinoma, low grade. international journal of clinical and diagnostic pathology. 2019;2 (1):86-91. 19. ziaran s, harsanyi s, bevizova k, varchulova novakova z, trebaticky b, bujdak p, et al. expression of e-cadherin, ki-67, and p53 in urinary bladder cancer in relation to progression, s u r v i va l , a n d re c u r re n c e . e u ro p e a n j o u r n a l o f histochemistry: ejh. 2020;64(2):3098. 20. wang l, feng c, ding g, ding q, zhou z, jiang h, et al. ki67 and tp53 expressions predict recurrence of non-muscleinvasive bladder cancer. tumor biology. 2014;35(4):298995. p53 and ki-67 expression in bladder carcinomasjiimc 2021 vol. 16, no.2 78 166 editorial student empowerment in medical education 1 2 rehan ahmed khan , madiha sajjad correspondence: dr. rehan ahmed khan professor of surgery assistant dean, medical education islamic international medical college riphah international university, islamabad e-mail: rehan.ahmed@riphah.edu.pk received: nov 05, 2017; accepted: nov 08, 2017 becoming a doctor is an arduous task. this journey of becoming a doctor from a student is guided by the medical curriculum, which is defined by kern as an 1 educational experience. curriculum has various components comprising of mission and outcomes, educational strategy and content, teaching and learning methods, assessment, student support, faculty development, program evaluation and 2 governance. one of the main stake holders of the curriculum are students. in advanced countries, students have been empowered to make decisions 3 regarding their curricula. however, in authors observation, pakistani medical students have minimal or no input in designing their curriculum. student empowerment is defined as 'any attitudinal, structural, and cultural activity, process or outcome where students of any age gain the ability, authority and agency to make decisions and implement changes in their own schools, learning and education, and in the education of other people, including fellow students of any age and adults 4 throughout education. student involvement in medical curriculum has been stressed by world federation for medical education (wfme), liaison committee for medical education 5 6 (lcme) and aspire excellence initiatives. wfme has designed quality standards for basic medical education, which describe the basic standard for attainment of student engagement as “the medical school must have a policy on student representation and appropriate participation in the design, management and evaluation of the curriculum, and 7 in other matters relevant to students”. in the 1980's, harden introduced the concept of 8 'spices' model which is being employed as an educational strategy in many medical schools across the globe. 's' in this model emphasizes on student centred approach as opposed to teacher centred learning. psychologists have also advocated 'selfdirected learning' in which students take control of 9 their learning. one of such strategies employed is 'problem based learning' in which students identify learning issues themselves and then find answers to 10 the questions developed. this, however, is the minimal level of students being empowered. 'aspire', which targets excellence in education, demands involvement of students in different committees pertaining to curriculum, assessment 6 and student affairs. in medical schools, where students are involved in these committees, improvement in learning of students is expected. in curriculum committees, students can offer their feedback and opinion on mission and vison of medical school, matters of admission test, content volume and difficulty, teaching and learning methodology, time tabling and provision of electives, whereas in assessment committees student's feedback would be of utmost importance regarding qualitative feedback offered to students by their teachers, frequency of assessment and inclusion of newer assessment techniques. student affairs committee can provide feedback to the medical school administrators, regarding the infrastructure, educational environment and quality of education provided to them. role of students in research and mentoring committees is no less important. references 1. kern de , thomas pa, howard dm, bass eb. curriculum development for medical education. a six step approach. baltimore and london, johns hopkins university press; 1998. 1. p. 2. lilley pm, harden rm. standards and medical education. med teach. 2003; 25: 349–51. 3. baird j, bracken k, grierson lem. the relationship between perceived preceptor power use and student empowerment during clerkship rotations: a study of hidden curriculum. med educ. 2016; 50: 778–85. 4. soundout.org. student empowerment and meaningful student involvement – soundout school consulting [internet]. [cited 2017 dec 8]. available from: https://soundout.org/studentempowerment/. 5. van zanten m, boulet jr, greaves i. the importance of medical education accreditation standards. med teach. 2012; 34: 136–45. 6. drees s, peters h. aspire-to-excellence academy. educ médica [internet]. elsevier. 2017; 17: 115–8. 7. world federation for medical education. basic medical ed u cat i o n w f m e g l o b a l s ta n d a rd s fo r q u a l i t y improvement [internet]. 2012 [cited 2015 feb 2]. available from: www.wfme.org 1 2 department of surgery/histopathology islamic international medical college riphah international university, islamabad 167 jiimc 2017 vol. 12, no.3 8. harden rm, sowden s, dunn wr. educational strategies in curriculum development: the spices model. med educ. 1984; 18: 284–97. 9. sandars j, cleary tj. self-regulation theory: applications to medical education: amee guide no. 58. med teach [internet]. 2011; 33: 875–86. 10. bate e, hommes j, duvivier r, taylor dcm. problem-based learning (pbl): getting the most out of your students their roles and responsibilities: amee guide no. 84. med teach [internet]. 2014; 36: 1–12 page 6 page 7 review�article abstract ocimum basilicum l. is an annual plant found in the wild tropical, subtropical and temperate regions of the world. it is member of family labiatae (lamiaceae). it contains wide variety of constituents of medicinal importance. ocimum basilicum l. is a common herb, grown in many households with a broad range of therapeutic properties. it would be a blessing in disguise if this herb becomes a medicine for the common man. various plant parts such as leaves, seeds and roots are recommended for the common people as folk medicines. ocimum basilicum l., has reputed medicinal uses as antioxidant, antibacterial, antimicrobial, antifungal, antiviral, cytoprotective, anticonvulsant, hypoglycaemic, hypolipidemic, hepatoprotective, renoprotective, neuroprotective, spermicidal, dermatologic and insectisidal. from mid to late summer. the plant appear pubescent from the base to the upside. leaves are opposite, glabrous, lanceolate, lanceolate-ovate or oblong, lightly toothed, shinny, with markings on veins. they are petiolate, narrow at the tips, unusually with angulate or entire-margined. the leaves have a typical aroma. inflorescence often in terminal clusters of whorled flowers (called – vertcilillasters). flowers are often white, labiate (like lips), and are six in numbers, pedicel is almost sessile. calyx 5-lobed, upper lobe expanded into a lid or cap over others, often bilabiate. phytochemical investigation of whole ocimum basilicum l. plant or its specific part have been done by many research workers and a number of active constituents have been identified. these include volatile oils, saponins, coumarins, alkaloids, tannins, anthra-quinones, anthocyanins, flavonoides, d i t e r p e n o i d e s , t r i t e r p e n o i d e s , p y re d i n e s , pyrolidines, polyphenols, irridoides, quinones, 5-8 sugars and insect moulting hormones. flavones apogenin, such as luteolin and chrysoeriol were also present in several members of plant family labiatae including o. basilicum. in addition to these compounds; 6-hydroxy and hydroxyl-flavones in glycosidic combination and lipophilic flavones; such 5 , 6 , 4 7 , 3 as -trihydroxy-dimethoxy-flavone in the members of 24 genera of this family have also been detected.6 among coumarin; scopoletin, astol and 9,10 andelicin were isolated and identified along with 11 3-p-coumarylglucoside-5-monoglucoside. z. e. and e. e., isomer of enolic ester were isolated by the condensation of dopaldehyde with caffeic acid. these esters efficiently formed complexes with iron 1 1 a n d a c te d a s p o we r f u l f u n g i c i d e s . a c i d introduction ocimum basilicum l. is an annual plant (figure 1) found wild in the tropical, subtropical and temperate regions of the world, specially established itself in ceylon, hot west asia, africa, malayan and pacific islands. it is also found in tropical and hot temperate regions of india and pakistan. it is indigenous in punjab and in low hilly areas of kpk. it is also 1,2 cultivated in punjab and in lower part of pakistan; and its worldwide distribution is in tropical africa, arabia, pakistan, kashmir, himalayas to nepal, sri 3-5 lanka and malaysia. the bushy stems grow to about two feet in height, with an upright stalk, herbaceous, branching on all sides with two leaves at every joint, a little snipped about the edges, strongly aromatic and sometime bushy. it is grown in gardens biomedical description of ocimum basilicum l. 1 2 3 4 5 6 saima rubab , irshad hussain , barkat ali khan ayaz ali unar , khawaja asad abbas , zawar hussain khichi , 7 8 9 10 mour khan , shazea khanum , khalil ur rehman haroon khan correspondence: dr. irshad hussain department of pharmacy smbb medical university, larkana e-mail: irshadpharmacist@yahoo.com 1 department of pharmacognosy lahore pharmacy college, lahore 2,4 department of pharmacy smbb medical university, larkana 3,10 department of pharmaceutics gomal university, dera ismail khan 5 department of botany sadiq egerton college, bahawalpur 6 department of forensic medicine smbb medical university, larkana 7 department of dermatology smbb medical university, larkana 8 department of pharmacy mayo hospital, lahore, 9 department of surgery multan medical and dental college, multan funding source: nil; conflict of interest: nil received: jul 12, 2016; revised: feb 02, 2017 accepted: feb 07, 2017 a review on ocimum basilicum l.jiimc 2017 vol. 12, no.1 59 basilicum, obtained from its seeds, leaves and other parts, either by using glc alone, or by glc-ms 17-19 analytical techniques. this entire work came to the conclusion that the ‘basil oil’ and ‘basil camphor’ contained more than 41 constituents. these researchers detected following compounds on qualitative or quantitative bases. few of such compounds with their quantity have been outlined 17-19 as follow: α-guaiene, α-bulnescene, eugenol, ocimene, cadinene, perillyl alcohol, methyl chavicol, linalool, camphor, and limonene were identified from the seed oil. while methyl chavicol, linalool, and 18-20 citral were identified from the leaf oil by glc. these researchers also isolated β-caryophyllene, germacrene-d, α-copaene, humulene, β-elemene, β b o u r b o n e n e , γ m u u r o l e n e a n d a sesquiterpenegratissimene from the leaf oil of o. 17-19 basilicum and identified by gc-ms. in other 19-21 investigations, the oil content of whole plant, flower and leaves, were determined, which later on, after analysis by glc-ms, the following components were determined and identified. eugenol, methyl eugenol, carophyllene, un-identified sesquiterpenes 1-8 and terpenes. limonene, cineole, p-cymene, linalool, thymol, linalyl acetate and β-carophyllene were also identified. in these findings, the seeds of the plant furnished essential oil, mostly composed of phenols engenol, nerol, methyl engenol, methyl e t h e r ; c a r o p h y l l e n e ; t e r p i n e n e ; 4 o l deacetaldehyde; α-selinene, α-pinene; β-pinene; 19-21 camphor and carvacol. in some plants, leaves contained the highest percentage of essential oil, whose major constituents were eugenol, carvacrol, 17 methyl eugenol and caryophyllene. -osilicum leaves also contained ascorbic acid, carotene, calcium, 17-22 phosphorus and insoluble oxalates. seed oil was further fractionated into polar and neutral lipids fractions. neutral lipid afforded hydrocarbons; wax ester; tri-glycerides; free fatty acids; sterols and monoglycerides. free fatty acid composition of the neutral lipids, as determined by glc or glc-ms, were caphic; lauric, myristic, palmatic, stearic acid, linoleic acid, linolenic and arachidonic acid. fixed oil, procured from the seeds of o. basilicum was found to contain four major fatty acids i.e., palmatic acid, 23 stearic acid, oleic acid and linoleic acid. mucilage of the seeds composed of d-glucose; d-galactose; dm a n o s e ; d a b r a b i n o s e ; d z y l o s e a n d l 12 polysaccharides from the seeds of o. adscendens and quercetin, isoquercetin, quercetin-3-0diglucoside, rutin, kaempferol, kaempferol-3rutinoside, caffeic acid, esculin, thymol and xenthonucrol from the seeds of o. basilicum were also 8-12 isolated and identified. it was further investigated that the sweet taste of the seeds of o. basilicum was jiimc 2017 vol. 12, no.1 fig. 1 plant of ocimum basilicum l. due to the presence of high concentration of trans10 anethole and esragole. many members of family labiataeproduced significant amount of essential 13 oils. shafiqet al. (1987) isolated and identified caryophyllene, carvacrol, methyl eugenol, and eugenol, alcohols as linalool, minor amount of cineole, sesquiterpenes and d-terpene from the 13 essential oil of o. santum. leaves provided yellow green volatile oil which is crystalized out after some 14 time, and called 'basil camphor'. leaf contains 11-13 14 volatile oil, and terpenes. keita et al., (2000) , 15 16 politeoet al., (2007) and bozinet al., (2006) identified — diterpenoid; pyridine and pyrrolidine alkaloids; polyphenols and tannins; iridoids and their glycosides; quinones; furanoids; cyclitols; coumarin; sugar — like stachyose; methyl cinnamate; methyl chavicol; linalool; cineole; estragole; ocimene; borneol; sabulene; cyclohexanone; myrecenol; safrole; 1-epi-bi-cyclo-sesqui-phellandrene; ocimol; gratissimin; that was characterized as dimethyl ester of α-truxillic acid; nevadedsin; salvigenin; ursolic acid; oleanolic acid and galacturonic acid together with traces of galactose and glucose from different 14-16 samples of the plant's oil. lee, adam and jirovet carried out investigations on the essential oils of o. 60 a review on ocimum basilicum l. common people as folk medicines as exhilarants (demulcent), expectorant, antiperiodics and emmenagogues. its leaves are often fragrant, aromatic (antiseptic) and are also used as an expectorant. decoction of the leaves, given in gastric and hepatic disorders and is useful in catarrh, bronchitis, in cough (due to heat), acts as diuretic and emmenagogues as well as tonic for stomach. its leaves are brushed into paste and applied over the inflammations. its seeds are mucilaginous and demulcent, used for heat, as a household remedy when utilized in the form of syrups particularly in summer season. seeds are also recommended as folk medicines for urino-genital complaints, such as gonorrhoea. oil of seeds is employed in syphilis, otitis and otorrhoea, whereas the fragrant oil of basil leaves and seeds (obtained after steam distillation) is used in perfumes and toiletries. syrup in which seeds are added become mucilaginous within minutes, which is effective against cardiac debility and palpitation. decoction of roots is useful in malarial fever as antiperiodics. extract of leaves is useful in earache (as drops). pharmacological effects and clinical applications followings are the pharmacological effects and clinical applications. antioxidant activity ocimum basilicum l. is an important medicinal and culinary herb, that contains several highly 15-58,22,30 antioxidants compounds. solvent extracts of o. basilicum have been demonstrated to exhibit a significant effect at cellular level, including the platelet anti-aggregate property and inhibitory 27 action against hiv-1 reverse transcriptase. in one of the patient's study with chronic bronchitis, exposure to volatile oil of o. basilicum, induced lowering of plasma levels of dienic-conjugates and ketones along with the activation of catalase in red cells, which 28 were typical features of antioxidant actions. 29 nitureet al. (2006) , further reported that the solvent extracts of o. basilicum were able to raise the o 6 m e t h y l g u a n i n e d n a m e t h y l t ra n s fe ra s e 29 (mgmt) levels. increased levels of mgmt–mrna were capable of increasing the activity of dna repair protein. the solvent extracts of o. basilicum were also effective for an increase in glutathione-stransferase-pi (gstp1) expression, but to a lesser extent than mgmt. the authors concluded that rhamnosealong with d-galactouronic acid and d12 mannuranic acid. main constituents of the oil, obtained from the flower of o. basilicum were methyl cinnamate and linalool, while the oil from both the leaves and flowers, comprised the compounds pinene, ocimene, linolene, cineole, pcymene, terpinene, methyl heptanone, nonyl aldehyde, linalool, farnescene, borneol, gerinol and 13,21 22 methyl cinnamate. hussain et al. (2008) ; da-silva 23 24 et al. (2003) ; muller-riebauet al.(1997) and 25 kofidiset al. (2006) further investigated that the chemical composition and the pharmacological activities of the four seasons, effected the volatile oils of aerial parts of o. basilicum. it was further detected that the contents of most of the chemical constituents altered significantly during different seasons of the year. these workers ascertained that the hydro-distilled essential oil contents were ranged from 0.5% to 0.8%; the maximum amount was recovered in winter and minimum amount in summer. the volatile oils in this season, consisted of linalool as the abundant ingredient, that was espoused by epi-α-cadinol, α-bergamotene and γcadinene. these research workers further demonstrated that those samples which were accumulated during winter season, were abundant in oxygenated monoterpenes, while those samples that were collected in summer, were bacciferous in sesquiterpene hydrocarbons. these workers further determined that the biological / pharmacological activities; such as antioxidant and antimicrobial activities (which were assessed by determining the minimum inhibitory concentration (mic) against both gram positive and gram negative bacterial strains, as well as against a number of strains of 26 fungi. medicinal uses ocimum basilicum l. is a common herb, grown in many households with a wide range of therapeutic properties. it would be a blessing in disguise if this herb becomes a medicine for the common man. more clinical trials are needed to be conducted to support its medicinal and therapeutic uses. since the basil plant (o. basilicum) is cultivated in our plane areas and as a garden ornamental plant, its various parts, particularly its leaves, seeds and roots are commonly used as daily household remedies. various plant parts are recommended for the jiimc 2017 vol. 12, no.1 61 a review on ocimum basilicum l. 22,34,38-40,42-45 well as the localized infections. antifungal activity many infections of skin, hair, nail, and subcutaneous tissues, in animals and human beings, are induced by several organisms, mainly different species of fungi. these organism were named dermatophytes and the 46,47,48 crusade diseases were called dermatophytoses. a number of dermatophytes had been separated 49,50 from animals by many workers use of synthetic antifungal drugs is restrained to treat human or 51 animal due to their high perniciousness. few of the antifungal agents, from plants and their natural products are at liberty and licensed for employing in the veterinary practice or for human being treatment in various countries of the world. it is said that most of the antifungal plant products are quite safe for the human as well as for animal 51 consumption. antifungal effectiveness of the solvent extracts of aerial parts, root extracts, basil oil and the isolated phytochemical compounds of o. basilicum were investigated by many authors and 52-58 compared with the standard antiseptics. in some of the findings, it was concluded that the minimum inhibitory concentration (mic) of the solvent extracts of aerial parts, root extracts, basil oil and their isolated phytochemical compounds, when compared with that of the standard antiseptics, showed that higher concentrations are needed to 52inhibit the growth of wide ranges of test organisms. 58 further, it was demonstrated that the ethanol extract of aerial parts of the plant and its isolated phytochemical compounds, showed higher degree of antifungal activities than the root extracts, thus suggesting that the antifungal agents were most 48-56 probably polar in nature. the essential oils also showed significant antifungal activity against many 52 plant pathogenic fungi. antiviral activity many research workers have conducted various laboratory experimental studies for investigating the demeanour of basil (o. basilicum) for its antiviral activities. nevertheless, each of the study indicated different compounds, responsible for its antiviral effects. in vitro studies of various plant parts of o. basilicum, exhibited substantial inhibitory actions against hiv-1 induced cytopathogenicity in mt-4 57 cells. the active factors present in the solvent extracted samples were found to be water-soluble plant constituents regulate human mgmt and probably elevated the dietary approach for fading 27-30 alkylations-induced carcinogenesis. bravo et al. 31 (2008), further indicated a protective consequence of basil (o. basilicum) against oxidative dna damage 31 and mutagenesis , with a decreasing outcome in the cholesterol synthesis and lipid accumulation in 31 human macro-phages by ethanolic extract. antibacterial activity antibacterial potentials of various parts of o. basilicum have been investigated by many 16,19,32-38 authors. o. basilicum exhibited foreboding antibacterial action against salmonella spp., escherichai coli, campylobacter jejunii and 32 clostridium perferingens. similarly, opalchenova 33 and obreshkova (2003) indicated that the volatile oil procured from the aerial parts of o. basilicum also demonstrated a marked action against drug immune clinical isolates from different species of staphylococcus, enterococcus, and pseudomonas 34 genera minimum inhibitory concentrations (mics) between 0.0030% and 0.0007% (v/v) were described 33 by these authors. antibacterial activities of various parts and essential oil of o. basilicum have also been ascertained by many other research workers 34 including— tomaret al. (2010) , gupta et al. 35 36 37 (2009) , tomoko et al. (2002) , durgaet al. (2010) 38 and ahmet et al. (2005). antimicrobial activity different plant parts of basil (o. basilicum) have been exploited for its antimicrobial effects in the laboratory experimental studies and concluded with 22,34,38,39,40 significant results. in india, basil is used for dental ailments due to its proposed antimicrobial effects but the mechanism of its action is not clear. research workers found that the essential oils extracted from different plant parts, particularly the leaves and seeds of different species of genus ocimum inhibited the growth of wide range of 22,38-40,42-45 bacteria and other microbes. they further investigated that the whole samples of essential oil, as well as its individual phytochemical constituents proved to have strong curbing properties in vitro and in vivo, in relation to the microbes of various diseases 22,34,38and to infection in animals and in human beings. 40,42,45 both organic solvent and water extracts of various plant parts of o. basilicum and basil oil are helpful in treating many serious systemic diseases, as jiimc 2017 vol. 12, no.1 62 a review on ocimum basilicum l. 61 lines. anticonvulsant activity in one of the reports of who, it was observed that about 450 million people in the entire world have endured mental, neurological, or behavioural 62 problems at some time in their life. large-scale research on plants, their active photochemical compounds and their derivatives have taken place in recent years that could furnish some new alternative treatments and therapeutic uses, for various diseases of central nervous system (cns) in human beings. epilepsy (a neurological disorder marked by sudden recurrent episodes of sensory disturbance, loss of consciousness, or convulsions, associated with abnormal electrical activity in the brain) is a group of disorders, delimited by repeated selfgenerated attacks that manifested from complex processes, implying various neurotransmitter systems such the glutamatergic, cholinergic, and gabaergic system. the estimation of the prevalence rate for epilepsy according to who is about 1–2% of 62,63 the world population. although a number of classic and more modern anticonvulsant drugs are available for the treatment of epilepsy patients worldwide, the seizures remained uncontrolled in more than 20% of the cases. moreover, nearly all the existing anti-epileptic drugs, — such as hydantoins, deoxybarbiturates, succinimides, benzodiazepines, iminostilbenes and carboxylic acids, were obtained 62,63 through chemical synthesis. on the other hand, many species of aromatic plants are medicinally used, due to the occurrence of essential oils and phytochemical compounds; some of them possessed certain cns properties, including anti-epileptic action with history of usage in folk medicines. recent studies on essential oils and their main phytochemical compounds have drawn the attention of many scientists for screening the natural products for such purposes and study their chemical and pharmacological aspects, which might potentially extend further, for the development of new anti-convulsant compounds having advantages 64 over current synthetic drugs. for this purpose, the basil oil and its phytochemical compounds, obtained from the leaves and seed of o. basilicum were used 62 64 by many research workers. almeida et al. (2003) , demonstrated that the o. basilicum essential oil, at higher doses, produced substantial increased in a polar substances. furthermore, other than aqueous extracts, inhabitation of giant cell formation in coculture of molt-4 cells with and without hiv-1 infection, also demonstrated inhibitory activity 57 against hiv-1 reverse transcriptase. in another laboratory experimental studies, chiang et al. (2005), demonstrated that both the aqueous and ethanolic extracts of o. basilicum aerial parts, along with its phytochemical compounds, like apigenin, linalool, and ursolicacid, revealed a wide ranges of 58 antiviral activity. these authors further ascertained that — ursolic acid displayed a pronounced action against herpes-viruses(ec50=6.6mg/l., selectivity index (si)=15.2);adeno-viruses (ec50=4.2mg/l., si=23.8); coxsackie-virus-b1 (ec50=0.4mg /l; si=251.3); and entero-virus-71 (ec50=0.5mg/l., si=201). apigenin possessed the highest activity against herpes-viruses (ec50=9.7mg/l., si=6.2); adeno-viruses (ec50=11.1mg/l., si=5.4); hepatitisb-surface antigen (ec50=7.1mg/l., si=2.3); and hepatitis-b-e-antigen (ec50=12.8mg/l., si=1.3) and linalool pointed out the potent activity against avdii (ec50=16.9mg/l., si=10.5).57no activeness was noted by these research workers, for carvone, cineole, β-caryophyllene, farnesol, fenchone, 57 geraniol, β-myrcene, and α-thujone. they also found that the antiviral action of these compounds against cvb1 and ev71 was to take place during the 58,59 initial infection levels and at the replication phase. cytoprotectiveeffects 60 renzulliet al. (2004) demonstrated that rosmarinic acid is a natural phenolic compound, which is probably present in many herbs of the family labiatae (lamiaceae). this compound is also present in o. basilicum, which is said to inhibit the c o m p l e m e n t d e p e n d e n t i n f l a m m a t o r y 60 processes. in vitro studies showed that rosmarinic acid was able to cut down oxygen species production, protein and dna synthesis inhibition, which were induced by two types of mycotoxins. the cell death was thus prevented. it was established by the reduction of dna fragmentation and also by the 60 inhibition of caspase-3 activation. manosroiet al. 61 (2006) also carried out an investigation that the anti-proliferative activity of o. basilicum essential oil on kb and p388 cell lines. they concluded that o. basilicum oil had an ic50 value of 0.0362mg/ml (12.7 times less powerful than 5-fu) in p388 cell jiimc 2017 vol. 12, no.1 63 a review on ocimum basilicum l. ascertained that the administration of combination of o. sanctum aqueous leaf extract and gentamicin, significantly prevented rise in levels of serum creatinine and blood urea when compared to the 72 gentamicin alone treated group in rats. aqueous leaf and seed extracts of o. sanctum plant have also been described to cut down the blood and urinary uric acid level in albino rabbits and also exhibited 73 74 diuretic property. rodrigues et al. (2001) also found that the aqueous leaf extract of o. sanctum prevents stress induced dendritic deficiency in hippocampal neurons in albino rats. all these researches indicated that the extracts of various parts of both o. basilicum and o. sanctum had a very high safety margin and very low toxic profile, providing safe beneficial effects at low doses without 69-74 any undesirable side effects. spermicidal effects 75 buchet al. (1988) , studied the effects of extracts of leaves and seeds of basil (o. basilicum) on human spermatozoa in vitro. they concluded that the basil 75 plant had potent spermicidal action. dermatologic effects 76 balambalet al. (1985) studied the effects of extracts of various plant parts of basil (ocimum basilicum l.) in humans, against acne vulgaris. they concluded that these extracts were quite effective in acne vulgaris, but the mechanism of their action was not 76 clear. insecticidal effects 77 erleret al. (2006) studied the mosquito repellent activities of five essential oils, including the 'basil oil'. since culexpipiens was very common pest mosquito in most of the urban and suburban regions; they used mosquito species — culexpipiens for such purposes and found that this oil was very effective to 72 repel these mosquitos. conclusion ocimum basilicum l., has reputed medicinal uses as antioxidant, antibacterial, antimicrobial, antifungal, a n t i v i r a l , c y t o p r o t e c t i v e , a n t i c o n v u l s a n t , hypoglycaemic, hypolipidemic, hepatoprotective, renoprotective, neuroprotective, spermicidal, 77 dermatologic and insectisidal. references 1. sabnis ts. (1986). “the flora of punjab plains and the associated hill region”, scientific publishers, jodhpur342001, india. 1986; p. 352. dose dependent reaction time of convulsion and the 65 percentage of mice displaying clonic seizures it also reduced lethal effects in response to different 64,65 stimulants of convulsions used in this study. it was further indicated that the essential oil increased the latent period for growing of paroxysms in 65 pentylenetetrazol and pic tests. for pentylenetetrazol, the effects of essential oil were reversed by flumazenil. moreover, it was also observed by these workers that the essential oil did not intervene 64-66 with the convulsions induced by strychnine. 67 oliveira et al. (2009) isolated a number of phytochemical compounds from the o. basilicum essential oil and pointed out that 1.8-cineole, linalool, and geraniol were the main constituents, comprising about 92.9% of the total oil. these compounds were obligated for blocking the clonic seizures produced by pentylenetetrazole, picrotoxin 67,68 or strychnine in mice. hypoglycaemic and hypolipidemiceffects 69 recently, mohan et al. 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24: 163-5. 72. muglikar ag, kothekar ma, chilwant ks, jaju jb. effect of ocimum sanctum (os) aqueous leaf extract on gentamicin induced nephrotoxicity in rats. ind. j. pharmacol. 2004; 36: 123. 73. sarkar a, pandey dn, pant mc. a report on the effect of ocimum sanctum (tulsi) leaves and seeds on blood and urinary uric acid, urea and urine volume in normal albino rabbits. ind. j. physiol. pharmacol. 1994; 34: 61–2. 74. rodrigues v, rao ms, satish n, rao gm. ocimumnsanctum jiimc 2017 vol. 12, no.1 67 a review on ocimum basilicum l. jiimc december 2016 page 63 page 64 page 65 page 66 page 67 page 68 page 69 page 70 page 71 original�article abstract objective: to study the protective effects of turmeric against hepatic damage brought on by methotrexate. study design: randomized controlled trial. place and duration of study: this experimental research was conducted at animal house of institute of basic medical science (ibms), khyber medical university, peshawar from 10june 2017 to 25 june 2018. materials and methods: a total of 28 adult albino mice were divided into four groups. group a was control group. control group received no medication. group b received a daily dose of turmeric extract (400 mg/kg) for 14 days. group c received an intraperitoneally (i.p) injection of methotrexate (40 mg/kg) on day 7. group d received oral administration of turmeric extract (400mg/kg) for 14 days and injection methotrexate (40mg/kg) was administered intraperitoneally (i.p) on day 7. all mice were sacrificed on day 14. weight of liver of all the animal was recorded. for data analysis statistical package for social sciences (spss) version 21 was used. quantitative variables were expressed as mean ±standard deviation and the significant difference was assessed using anova test. the chi square test was used to determine statistical significance based on the categorical variables. p value <.05 was significant statistically. results: on microscopic examination of liver tissue, abundant inflammatory cells were observed around the portal area in all mice (100%) of methotrexate group (group c) with increase in liver weight. in methotrexate + turmeric group (group d) few inflammatory cells were observed with slight decrease in liver weight as compared to group c in all mice (100%). conclusion: the results of this study revealed that turmeric (curcuma longa) treatment protects liver tissue against methotrexate-induced damage. key words: curcuma longa, hepatotoxicity, inflammatory cells, methotrexate, reactive oxygen species methotrexate is effective in the treatment of sy s t e m i c l u p u s e r y t h e m a t o s u s , va s c u l i t i s , inflammatory bowel syndrome and several other 3 diseases of connective tissue. it is also used for the treatment of leukemia and malignancies of different 4 organs such as breast and lung. the most frequent side effects of methotrexate are nausea, vomiting, loss of appetite, ulcers of mucosa, 5 when taken in low doses. after used as a continuous therapy, its other side effects are alopecia, low white cell count, increased risk of infection, gi bleeding, bone marrow suppression, hepatotoxicity and renal 6,7,8 failure. methotrexate and its metabolite-polyglutamated inhibit the dihydrofolate reductase enzyme, which converts dihydrofolate into tetrahydrofolate (the folic acid's active form). the nucleoside thymidine denovo can only be produced with folic acid. methotrexate thus has an indirect effect on the thymidylate synthesis, which is required for 9 synthesis of dna . hepatocytes are damaged by introduction methotrexate is one of folic acid antagonists. it was initially used for acute leukemia in children. the effective use in treating other cancers followed 1 thereafter. methotrexate has been commonly used in the treatment of a rheumatoid arthritis, psoriasis and other autoimmune disorders such as juvenile 2 idiopathic arthritis for more than 40 years. protective effects of turmeric (curcuma longa) against methotrexate induced liver toxicity in the albino mice 1 2 3 4 5 6 farah deeba , ronaq zaman , shehla khatoon , fatima daud , maqbool illahi farzana begum, correspondence: dr. ronaq zaman assistant professor department of pathology kabir medical college, peshawar e-mail: drronaq@live.com 1,4 department of anatomy pak international medical college, peshawar 2 3 department of pathology/anatomy kabir medical college, peshawar 5 department of anatomy northwest school of medicine, peshawar 6 department of radiology peshawar institute of medical science, peshawar received: august 16, 2022; revised: march 03, 2023 accepted: 03, march 2023 curcuma longa in methotrexate induced hepatotoxicity jiimc 2023 vol. 18, no.1 32 https://doi.org/10.57234/jiimc.march23.1504 reactive oxygen molecules such as hydrogen peroxide, hydroxyl radicals, and superoxide. methotrexate inhibits nadp, which is needed by the glutathione reductase enzyme to neutralize reactive 10 oxygen species. herbs have a key part in the treatment of many liver i l l n e s s e s b e c a u s e t h e r e a r e n o e f fe c t i v e pharmaceuticals that can protect the liver in 11 allopathic medical procedures. numerous studies have demonstrated the significance of plant extracts 12 in liver diseases . the use of turmeric in chinese and indian medicine 13 has a long history. there are more than 300 i n g re d i e nt s i n tu r m e r i c , d i a r y l h e pta n o i d s , monoterpenes, diterpenes, sesquiterpenes, phenyl propene, alkaloids, and curcuminoids are some of 14 these ingredients. it is used to treat inflammatory disorders, cancer, hepatitis and other hepatic disorders, alzheimer's disease, skin diseases and 15 rheumatoid arthritis . the generation of reactive oxygen species (ros), such as hydroxyl radicals and hydrogen peroxide, is inhibited by turmeric. turmeric's antioxidant properties thereby prevent the liver damage caused 16,17 by free radicals. limited studies have been conducted to know the role of turmeric in protection against methotrexate hepatic damage. therefore, this study was planned to assess the defensive effects of turmeric on methotrexate induced hepatic toxicity in mice. materials and methods this randomized controlled study was conducted at the animal house of institute of basic medical sciences, kmu, and peshawar from 10 june 2017 to 25 june 2018. sampling technique was convenient sampling. ethical clearance was taken from the ethical review board of postgraduate medical department, khyber girls medical college with reference number.3325/pgmed/kgmc. male albino mice were included in study. female albino mice were excluded. adult male albino mice weighing 25 to 45 grams (5 to 7 weeks) were acclimated for two weeks in a 12-hour cycle of darkness and light at 0 temperature of 22 c. mice were split between the control group (group a) and the experimental groups b, c, and d. there were four mice in the control group (a) and eight mice each in groups b, c, and d. group a received no medication. group b was given turmeric extract orally (400mg /kg) for 14 days. group c received injection methotrexate (40mg/kg) intraperitoneally on day 7. both turmeric and methotrexate given to group d. turmeric extract (400mg /kg) daily for 14 days was given to group d. on day 7, injection of methotrexate (40mg/kg) was 17 administered intraperitoneally to group d . all mice were sacrificed on day 14. weight of the livers of all the animal was recorded. analytic balance was used to measure liver organ weight. the liver was preserved in formalin. by tissue processing, various liver sections were made. eosin and hematoxylin were used to stain the slides. to observe the histological parameters, tissues were seen under a light microscope. slides were examined by histopathologist. (assistant professor, mphil histopathology). for data analysis statistical package for social sciences (spss) version 21 was used in this study. quantitative variables were expressed as mean ±standard deviation and the significant difference was assessed using anova test. the chi square test was used to determine statistical significance based on the categorical variables and results. p value <.05 was significant statistically. results the mean value of liver weight was significantly increased in methotrexate group i.e. 1.650 ± 0.17gm as compared to control group i.e. 1.352 ± 0.20gm. whereas mean value of liver weight of mice treated with methotrexate and turmeric was significantly reduced i.e. 1.464 ± .016gm as compared to group receiving methotrexate (p< 0.00). the weight of liver of different groups is shown in figure 1. on gross examination of mice liver in methotrexate and methotrexate + turmeric group, there was no change in color, texture and consistency as compared to control group. on histological examination of liver tissue, no periportal inflammation was present in all animals of control as well group b (turmeric). abundant inflammatory cells were present around portal area in all eight animals receiving methotrexate group c (figure 2) with p value < 0.00 (table 1) which is statistically significant, where as in the group d (methotrexate plus turmeric) few inflammatory cells were seen as compared to group c with p< 0.00 (figure 3). curcuma longa in methotrexate induced hepatotoxicity jiimc 2023 vol. 18, no.1 33https://doi.org/10.57234/jiimc.march23.1504 figure 1: increase in weight of liver of methotrexate group liver weight was significantly increased in methotrexate group. whereas in methotrexate turmeric group administration of turmeric causes significant reduction in liver weight as compared to methotrexate group. liver weight increased because of diffuse inflammatory cellular infiltration, collagen deposition, mild hepatic edema and fatty 22,23 infiltration. our findings concur with those made by tag et al, who observed that administration of mulberry leaves extract causes significant reduction in liver weight of mice as compared to methotrexate 24 group. significant periportal inflammation was observed in all eight animals in methotrexate group. few inflammatory cells are observed in methotrexate turmeric group. our results correlate with the result of adel rezaei et al. in his study he also observed that periportal inflammation induced by methotrexate is significant reduced by ethanolic extract of turmeric 19 (curcuma longa) . the protecting effects of curcumin against liver damage were also observed 25 by a study conducted by erenoğlu etal. conclusion in conclusion, turmeric (curcuma longa) treatment protects liver tissue against methotrexate-induced damage. recommendations it is feasible to use turmeric as a potential addition to a methotrexate therapy regimen by conducting clinical trials to examine the herb's effects on human. table i: the effect of methotrexate and turmeric on periportal inflammation c figure 2: photomicrograph of liver tissue of (mtx group) where “ c” shows abundant inflammatory cells around portal area at 40x figure 3: photomicrograph of liver tissue of (mtx+ turmeric group) where few inflammatory cells round portal area at 40x discussion methotrexate has been highly criticized for its hepatotoxicity. if a medicine is used with a good ameliorative agent, the liver may be protected. several researchers scientifically demonstrated that curcuma longa (turmeric) has anti-inflammatory, a nt i m i c ro b i a l , a nt i ca n c e r a n d a nt i ox i d a nt 18,19 properties . thus, curcuma longa (turmeric) have capability to provide protection against oxidative .20,21 stress induced by methotrexate curcuma longa in methotrexate induced hepatotoxicity jiimc 2023 vol. 18, no.1 34 https://doi.org/10.57234/jiimc.march23.1504 references 1. conway r, carey jj. risk of liver disease in 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15(1):1-9. 25. erenoğlu c, kanter m, burhan ak, sağiroğlu t, ayvaz s, aktaş c, erboğa m. protective effect of curcumin on liver damage induced by biliary obstruction in rats. balkan med j. 2011 dec 1; 2011(4):352-7. curcuma longa in methotrexate induced hepatotoxicity jiimc 2023 vol. 18, no.1 35https://doi.org/10.57234/jiimc.march23.1504 conflict of interest authors declared no conflicts of interest. grant support and financial disclosure authors have declared no specific grant for this research from any funding agency in public, commercial or nonprofit sector. data sharing statment the data that support the findings of this study are available from the corresponding author upon request. this is an open access article distributed under the terms of the creative commons attributionnoncommercial 2.0 generic license. curcuma longa in methotrexate induced hepatotoxicity jiimc 2023 vol. 18, no.1 36 https://doi.org/10.57234/jiimc.march23.1504 original�article abstract objective: this study was conducted to determine awareness, attitude, and knowledge about thalassemia among the students of urban educational institutions of rawalpindi/islamabad. study design: a cross sectional study. place and duration of study: institutions of rawalpindi and islamabad from december 2018 to june 2019. materials and methods: there were four major groups of students, which included newly inducted medical students, fsc. students, engineering students and students of biomedical sciences. a questionnaire consisting of 20 yes/no responses and 6 multiple choice questions was given. spss 23.0 software was used for analysis of data using frequency and chi-square tests and p<0.05 was considered statistically significant. results: among the 500 subjects recruited in this cross-sectional study, a total of 434(86.8%) had some idea about thalassemia. the p-value was less than 0.05 (p<0.05) the range of percentage of correct answers was between 35.6% (about iron rich diet) and 95.2% (about the affected cells). the attitudinal patterns of all the students towards thalassemia revealed that 93.2% students wanted to be informed about the disease at their respective institution. 90.6% were willing to learn their carrier status and 91.4% were ready to amend their future in case of risky prospects. conclusion: the awareness regarding the general aspects of thalassemia is reasonably sufficient among the students in urban educational institutions of rawalpindi/islamabad, there is some level of disparity in the degree of knowledge between different groups of students. there is need of sessions based on knowledge of thalassemia among non-medical students also. key words: thalassemia, awareness, gene disorder, prevention, premarital screening. 4,6,7 (1-9%). the term thalassemia originated from the greek, 6 thalassa(sea) and haima (blood). thalassemia is an inherited disorder resulting from either the absence or reduced synthesis of alpha (α) or beta (β) globin 2,7 chains that are integral components of hemoglobin an oxygen carrying protein in red blood cells (rbcs). it is an autosomal recessive disorder and is categorized as α or β thalassemia based on the type of globin chain affected. β thalassemia is further 7 classified as thalassemia major or minor. β thalassemia occurs due to a defect in the autosomal chromosome 11. it is thalassemia major if both the copies of this chromosome are affected and if only 8 one copy is affected it is thalassemia minor. the affected and carrier population varies in different countries. malaysia has about 4.5% carrier frequency with 2.1 affected births out of 1000 3 annually with 5600 transfusion dependent patients. 4 in turkey carrier frequency is about 4.3%. egypt has 9-10% carrier frequency with approx. 1000 out of 9 1.5million annual thalassemic births. netherlands introduction t h a l a s s e m i a i s t h e m o s t w i d e s p r e a d hemoglobinopathy worldwide affecting about 5% of total population of world with gene frequencies 1,2 ranging from 2.5% to 16.2%. worldwide there are about 240 million carriers and about 200,000 – 400,000 infants are born with severe disease 3,5 annually. it is most common in the areas of africa, southeast asia, equator, mediterranean, the middle east, central asia, southern china, far east as well in south america. the maximum carrier frequency was found in cyprus (14%), sardinia (10.3%) and southeast asia awareness, attitude and knowledge about thalassemia among students of different disciplines 1 2 3 4 h m sanaullah sialvi , gulrez umar , sidra hamid , ghulam khadija correspondence: h m sanaullah sialvi final year mbbs student rawalpindi medical university, rawalpindi e-mail: sialvi827@gmail.com 1,2 3 final year mbbs student/ department of physiology/ 4 general surgery rawalpindi medical university, rawalpindi funding source: nil; conflict of interest: nil received: august 08, 2019; revised: may 01, 2021 accepted: may 04, 2021 thalassemia awareness among studentsjiimc 2021 vol. 16, no.2 117 10 has got 140,000 carriers. in thailand, about 40% are carriers, while 1% of the population is afflicted with 11 this disease. thalassemia gene in different regions of india varies from 1 to 17% with a mean prevalence 12 of about 3.3%. iran has approximately 3,750,000 carriers and 20,000 persons with a diagnosis of beta 13 thalassemia major (b-tm). in pakistan, thalassemia is the most common inherited single gene disorder causing serious health 14 issues. the carrier frequency is about 5-8% that are more than 9 million. at present time pakistan has 100,000 estimated cases of thalassemia, which makes up almost 5% of the total cases of the world and each year nearly 5,000-9,000 affected children 7,15,16 are born in the country there is no therapeutic cure for thalassemia, who introduced control program consisting of general public awareness, screening and genetic counseling 4,17 to avoid affected births. different countries initiated these programs and remain successful. fortunately no thalassemic baby has been born in 17 cyprus since 2001. sardinia has reduced the birth rate of thalassemia major from 1:250 live births to 4 1:4000. the disease can only be prevented through proper screening, awareness, public enlightenment about disease and genetic counseling. blood analysis and 6,7 electrophoresis is used to identify carriers. lack of awareness and knowledge only fuels the increase in 4 prevalence of this disease. in this study, we wanted to explore the knowledge of fsc, biomedical, newly inducted medical and engineering students about thalassemia in islamabad and rawalpindi. our aim was to assess the level of awareness to determine awareness, attitude, and knowledge about thalassemia among the students of urban educational institutions of rawalpindi/islamabad. materials and methods this was a cross sectional study aiming to gauge the knowledge and attitude about thalassemia among undergraduate students in the institutions of islamabad and rawalpindi conducted from december 2018 to june 2019. there were four major groups which included newly inducted medical students, fsc students, engineering students and students of biomedical sciences. a total of 500 students took part in this study. out of which 200 of them were in their 1st year of mbbs, 100 each from fsc, biomedical sciences and non-medical undergraduates in which there were equal numbers of males and females and the average age of the subjects was around 19 years. the data from newly inducted medical students was collected from rawalpindi medical university (rmu), islamabad medical and dental college and hbs medical college. the f.sc. students were from opf college for boys h-8/4 and islamabad model college for girls g-10/4, islamabad. the nonmedical undergraduates and biomedical students were from comsats and fast university. a questionnaire consisting of 20 yes/no responses and 6 multiple choice questions regarding the disease and their attitude towards it was applied to gather data. we did not give any knowledge regarding thalassemia while collecting data and we ensured that medical students had not yet studied thalassemia in their curriculum as well. the data analysis was done using spss software and results were analyzed with frequency and chi-square tests and p<0.05 was statistically significant. results among the 500 subjects recruited in this crosssectional study, a total of 434(86.8%) had some idea about thalassemia. a significant relationship between the student's academic field and their awareness regarding this disease was observed (p<0.05, table i). however, only 182(36.3%) students had ever seen a thalassemic patient and 36(7.2%) had a family member suffering from the disease. table i: general perspective about thalassemia a the values are in n (%) the level of awareness regarding the general facts about thalassemia and its complications was checked after classifying students into their respective groups. in totality, 94.8% of the students knew about the body system affected by the disease and 95.2% knew about the cells affected by it. thalassemia awareness among studentsjiimc 2021 vol. 16, no.2 118 moreover, 89% knew that it has a genetic mode of transmission while 88.8% were aware that cousin marriages are a risk factor in causing thalassemia. only 39.6% students understood that it is not curable, 72.4% said that it is preventable, and 67.2% students understood that both genders have an equal risk of being affected. regarding the relationship of iron rich diets with thalassemia, a general perception among 64.4% of the total subjects responded that iron rich diets are beneficial for thalassemic patients. table shows the total frequency of correct responses by students of different groups along with their p values. the table also shows the expected and observed counts of the correct answers, indicating an obvious disparity between the two. queries associated with the attitudinal patterns of all the students towards thalassemia revealed that 93.2% students wanted to be informed about the disease at their respective institution. 90.6% were willing to learn their carrier status and 91.4% were ready to amend their future plans in case of risky prospects. table ii: correct student's responses a the values are in n(%) a total of 121(24.2%) students in the entire sample had attended a discussion or awareness seminar about thalassemia before this study was conducted and the remaining 379(75.8%) had never been to any such event. among those who had been previously informed, 32% were mbbs undergraduates, 10% were enrolled in some non-medical graduation program, 11% were fsc students and 36% were students of biomedical sciences as shown in table iii. another significant relationship was observed between the aforementioned academic fields of the students and their status of being previously informed with a p value of less than 0.05 as reported in table. surprisingly, no significant relationship was recorded between the awareness of subjects after attending seminars/discussions on thalassemia and the frequency of blood donations among them. (p>0.05) as shown in table iv. table iii: students who attended awareness sessions previously table iv: relationship between blood donation and previously informed students table v: attitude and behavioral pattern of students regarding thalassemia. a the values are in n (%) thalassemia awareness among studentsjiimc 2021 vol. 16, no.2 119 discussion this study began in the light of the fact that there is a high prevalence of thalassemia in rural and urban areas of pakistan. an estimated 5000-9000 children are born with β-thalassemia in pakistan. this shows a carrier frequency of 5-8% i.e. 9.8 million people in an 2,15 approximate population 180 million. to unravel the causes of this occurrence, awareness of young individuals was checked regarding the disease, its complications, transmission, risk factors, prevention and treatment. we found that even though the awareness regarding the general aspects of thalassemia was reasonably sufficient among the students in urban educational institutions of rawalpindi/islamabad, there was some level of disparity in the degree of knowledge between different groups of students that were analyzed separately. even though about 86.8% of the subjects said that they had heard or had some idea about thalassemia, only 24.2% of them had actually attended a discussion or an awareness seminar about it. in a similar study conducted on students at antioch in turkey, 37.3% students had been previously 17 informed about thalassemia. regarding the characteristics of thalassemia, 89% of the participants knew that this disease has hereditary mode of transmission and 39.6% gave the correct answer about its cure and 72.4% that it is preventable. these findings are comparable to the research carried out in antioch where 82% of the previously informed students knew about the mode of transmission, only 37% gave correct answers about treatment and 60.7% knew that it is 18 preventable. according to a research, iron overload in beta thalassemia major and intermedia patients, 87.4% of thalassemic patients showed high ferritin (a protein used store iron and indicate iron levels in the 19 body) levels. in our study when asked if iron rich diets are helpful for thalassemic patients only 35.6% of the total participants responded correctly. moreover, a significant disparity was observed between the level of knowledge about the disease and the academic courses of the subjects. students enrolled in medical programs i.e. mbbs and bioscience scored higher than those enrolled in nonmedical programs which is comparable to a study carried out on 1st and 2nd year medical students to assess the knowledge and attitude towards thalassemia in delhi where 75.25% of the p a r t i c i p a n t s h a d g o o d k n o w l e d g e a b o u t 20 thalassemia. another study carried out by mirza a in pakistan on thalassemia and premarital screening at non-medical universities showed that only 54.5% of the students had ever heard about beta 21 thalassemia. the attitudinal patterns of students towards thalassemia were observed to be well above satisfactory and sufficient. 93.2% students stated that they would like to be informed about thalassemia at their college/university. 90.6% were willing to know about their carrier status checked and 91.4% agreed to change their future plans in case of a risky situation. these results are higher than other studies. 87% students wanted to be educated on hemoglobinopathies at their school in a study 4 carried out on young students in turkey. in the same study, 81.6% students wanted to learn about their carrier status and 70.4% said that they were willing to change their future decisions in case these diseases could harm them or their families. in a study in antioch, turkey 89.1% participants also wanted to 17 know about their carrier status. conclusion the awareness regarding the general aspects of thalassemia is reasonably sufficient among the students in urban educational institutions of rawalpindi/islamabad, there is some level of difference in the degree of knowledge between different groups of students. there is need of sessions based on knowledge of thalassemia among non-medical students also. although awareness was quite sufficient but there is still high prevalence in the country that refers the need of study and awareness in rural areas of the country thalassemia awareness among studentsjiimc 2021 vol. 16, no.2 120 references 1. mustafa, i., et al., genetic epidemiology of betathalassemia in the maldives: 23 years of a beta-thalassemia screening program. gene, 2020: p. 144544. 2. al sabbah, h., et al., factors associated with continuing emergence of β-thalassemia major despite prenatal testing: a cross-sectional survey. international journal of women's health, 2017. 9: p. 673. 3. wong, l.p., e. george, and j.-a.m.a. tan, public perceptions and attitudes toward thalassaemia: influencing factors in a multi-racial population. bmc public health, 2011. 11(1): p. 193. 4. okyay, r.a., et al., haemoglobinopathy awareness among young students in turkey: outcomes of a city-wide survey. plos one, 2016. 11(7): p. e0159816. 5. ayub, r., et al., prevention of thalassemia. the professional medical journal, 2017. 24(02): p. 249-251. 6. galanello, r. and r. origa, beta-thalassemia. orphanet journal of rare diseases, 2010. 5(1): p. 11. 7. ghafoor, m.b., et al., level of awareness about thalassemia among parents of thalassaemic children. journal of rawalpindi medical college (jrmc), 2016. 20(3): p. 209211. 8. ishfaq, k., et al., impact of thalassemia major on patients; families in south punjab, pakistan. professional medical journal, 2015. 22(5). 9. el-shanshory, m., et al., spectrum of beta globin gene mutations in egyptian children with β-thalassemia. mediterranean journal of hematology and infectious diseases, 2014. 6(1). 10. oerlemans, a.j., l.a. kluijtmans, and s. van der burg, the moral life of professionals in newborn screening in the netherlands: a qualitative study. public health ethics, 2017. 10(1): p. 19-34. 11. apidechkul, t., prevalence of thalassemia carriers among the lahu hill tribe population, chiang rai, thailand. asian biomedicine, 2017. 9(4): p. 527-533. 12. dhirar, n., et al., thalassemia major: how do we improve quality of life? springerplus, 2016. 5(1): p. 1895. 13. hadipour dehshal, m., et al., β-thalassemia in iran: things everyone needs to know about this disease. hemoglobin, 2019. 43(3): p. 166-173. 14. saba shahid, m.n., et al., alpha thalassemia deletions found in suspected cases of beta thalassemia major in pakistani population. pakistan journal of medical sciences, 2017. 33(2): p. 411. 15. ansari, s.h., et al., molecular epidemiology of βthalassemia in pakistan: far reaching implications. indian journal of human genetics, 2012. 18(2): p. 193. 16. baig, s.m., et al., β-thalassemia in pakistan: a pilot program on prenatal diagnosis in multan. journal of pediatric hematology/oncology, 2012. 34(2): p. 90-92. 17. savas, n., et al., hemoglobinopathy awareness among high school students in antakya (antioch), turkey. vol. 91. 2010. 413-8. 18. fibach, e. and e.a. rachmilewitz, pathophysiology and treatment of patients with beta-thalassemia–an update. f1000research, 2017. 6. 19. mishra, a.k. and a. tiwari, iron overload in beta thalassaemia major and intermedia patients. maedica, 2013. 8(4): p. 328. 20. pujani, m., et al., knowledge and attitude among indian medical students towards thalassemia: a study in delhi ncr. international journal of research in medical sciences int j res med sci, 2017. 55(10): p. 4470-4477. 21. mirza, a., et al., thalassemia and premarital screening: potential for implementation of a screening program among young people in pakistan. hemoglobin, 2013. 37(2): p. 160-170. thalassemia awareness among studentsjiimc 2021 vol. 16, no.2 121 original�article abstract objective: to evaluate the activity of ranitidine at neuromuscular junction with and without pancuronium. study design: experimental randomized control study. place and duration of study: department of pharmacology, islamic international medical college, riu rawalpindi from october 2018 to september 2019. materials and methods: changes in the length (contraction) of rectus abdomininis muscle of frog were recorded using students oscillograph and cumulative dose response curve with acetylcholine was obtained (control group). the effect of ranitidine before and after adding pancuronium was observed using three groups. statistical analysis of variance (anova) between the groups was performed by using the student's 't' test and a p-value < 0.05 was considered statistically significant. results: ranitidine in a dose of 1mm concentration produced a shift of the curve to the left with mean deviation of 61.5% (sem ± 20.5) showing an enhancement of effects of acetylcholine. ranitidine also produced a shift of the curve to the left in the presence of 1µg pancuronium with the mean deviation of 104.5% (sem ± 39.7). the shift was statistically significant (p < 0.05) showing the antagonistic effect of ranitidine on neuromuscular junction (nmj) blockers like pancuronium at this concentration. conclusion: ranitidine in a concentration of 1mm increases the effects of acetylcholine at neuromuscular junction (nmj) and antagonizes the effects of nmj blockers like pancuronium at this concentration. key words: acetylcholine, neuromuscular junction, pancuronium, ranitidine. oesophagitis, and other conditions where gastric 4 acid reduction is beneficial. also used for prophylaxis of gastric acid aspiration during 5,6 anaesthesia. in the past there is conflicting evidence regarding the interaction between h receptor blockers and various 2 neuromuscular junction blockers. there is evidence that ranitidine can inhibit acetylcholinesterase in low dose and at high doses 7 produce neuromuscular blockade. also in a study ranitidine potentiated the effects of neuro muscular 8 junction blocker. this is of particular interest to anesthesiologists as non-depolarizing neuromuscular junction blockers like pancuronium are administered during various 9,10 surgical procedures for muscle relaxation. a potential for synergism / potentiation with neuromuscular junction (nmj) blockers exist in such situations. thus, there may be a chance of side effects during surgery. this would be clinically relevant because of respiratory depression and prolonged apnoea. it was therefore pertinent to determine the activity of ranitidine at neuromuscular junction and its interaction with neuromuscular junction blocker like pancuronium. introduction histamine h receptor blockers are widely used in 2 medicine for the treatment of acid peptic disease as 1 they reduce the basal and stimulated acid secretion. they are also used pre-operatively before general anaesthesia for prophylaxis of gastric acid 2 aspiration. ranitidine is a competitive antagonist at h -2 3 receptors. ranitidine is therapeutically used in the treatment of duodenal ulcer, benign gastric ulcer, stress ulcer, zollinger ellison syndrome, reflux potentiation effects of acetylcholine at neuromuscular junction by ranitidine 1 2 3 4 5 6 abdul azeem , akbar waheed , sidra mumal , salman bakhtiar , jawaria iftikhar , talal zafar correspondence: dr. abdul azeem assistant professor department of pharmacology watim medical & dental college, rawat, rawalpindi e-mail: azeemhaseeb079@gmail.com 1 department of pharmacology watim medical & dental college, rawat, rawalpindi 2,3 ,5 department of pharmacology islamic international medical college, riphah international university, islamabad 4 department of pharmacology sharif medical & dental college, lahore. 6 department of pediatrics hbs medical & dental college, islamabad funding source: nil; conflict of interest: nil received: february 02, 2021; revised: november 01, 2021 accepted: november 09, 2021 ranitidine potentiates acetylcholine effects at nm junction jiimc 2021 vol. 16, no.4 237 so, the present study was performed to evaluate the activity of ranitidine at neuromuscular junction with and without pancuronium. materials and methods the experimental randomized control study was carried out in the department of pharmacology and therapeutics, islamic international medical college, rawalpindi from october 2018 to september 2019 in collaboration with department of pharmacology and therapeutics, rawalpindi medical university rawalpindi. accredited ethical review committee of islamic international medical college approved the research proposal before starting the study. a total of 24 frogs selected randomly, six rectus abdominis 11 muscles in each group were used. both male and 12 female adult frogs (rana-tigrina). weighing 100 to 13,14 150 gm were included in the study. frogs weighing less than 100gm and more than 150 gm were excluded. -3 the drugs used were acetylcholine solutions of 10 , -4 -5 10 and 10 strength, 1g of pancuronium bromide 4 (molecular weight 732.7), 1mm concentration of 15 ranitidine (molecular weight 350.9), frog ringer 16 solution with the following composition. nacl 6.493 g/l, kcl 142mg/l, cacl 133mg/l, 2 nah po 7.68mg/l, nahco 197mg/l, dextrose 2 4 3 198mg/l. six rectus abdominis muscles from randomly selected frogs were used for recording the observations in each group. each frog was dissected. the two rectus abdominis muscles were cut across just above the sternum, dissected and shifted to a 17 dish containing frog ringer at room temperature. one muscle was mounted in the organ bath aerated 18,19 with oxygen and connected to the oscillograph. the effects of different drugs were recorded as changes in the muscle length (contraction) via isotonic transducer according to the following schedule. in group-i (control), 1 g acetylcholine was added to the organ bath and the contraction of the frog's rectus abdominis muscle was recorded on the graph paper for 3 minutes. next reading with 2g of acetylcholine was obtained and similarly a cumulative dose response relationship was observed and recorded by doubling the dose of acetylcholine after every 3 minutes till the maximum or ceiling effect was obtained. oscillograph was stopped and the ringer solution was drained and replaced. the nd tissue was given a rest for 30 minutes and 2 cumulative dose response curve was obtained on the same rectus abdominis muscle in a similar manner. muscles of six different animals were used for the recording as mentioned above. this group was used as a control group for the study. in group-ii (pancuronium), cumulative dose response curve was obtained on each of the six preparations with acetylcholine as already described above. the tissues were given a rest for 30 minutes and a fixed dose of 1 g of pancuronium was added to the organ bath. after a reaction time of 15 minutes another cumulative dose response curve with acetylcholine was recorded in the presence of pancuronium for every preparation. in group-iii (ranitidine), cumulative dose response curve was obtained on each of the six preparations with acetylcholine as already described above. the tissues were given a rest for 30 minutes and a fixed dose of 1 mm solution of ranitidine was added to the organ bath. after a reaction time of 15 minutes another cumulative dose response curve with acetylcholine was recorded in the presence of ranitidine for every preparation. in group-iv (pancuronium + ranitidine), cumulative dose response curve was obtained on each of the six preparations with acetylcholine as already described above. the tissues were given a rest for 30 minutes and a fixed dose of 1 g pancuronium and 1 mm ranitidine were added to the organ bath. after a reaction time of 15 minutes another cumulative dose response curve with acetylcholine was recorded in the presence of pancuronium and ranitidine for every preparation. statistical analysis of variance (anova) between the groups was performed by using the student's 't' test and a p-value < 0.05 was considered statistically significant. results observations of groups group i (control group) in a series of six experiments the mean ± sem values of responses for 1, 2, 4, 8, 16, and 32 µg of acetylcholine were recorded. percent responses were calculated by taking the response with 32 µg as 100% and were 12%, 31%, 57%, 82%, 95%, and 100% for the above-mentioned doses respectively. after ranitidine potentiates acetylcholine effects at nm junction jiimc 2021 vol. 16, no.4 238 washing the preparations with frog-ringer solution and after an interval of 30 minutes the percent responses were 8, 24, 50, 80, 92 and 96 % for each dose respectively. semi log dose response curves were plotted by taking the percentage responses which showed that the second curve i.e., after washing with frog-ringer solution and rest on an average shifted to the right and downwards. the st deviation was slight which started with the 1 dose of 1 µg and continued in the entire extent of the curve. percent deviation was calculated for each dose and was 29.4 %, 23.9%, 11.9%, 2.5%, 2.9%, and 4.1% respectively, with mean 12.45%. (sem± 4.77). p > 0.05. -40 -20 0 20 40 60 80 100 120 140 0 0.301 0.602 0.903 1.204 1.505 log dose p e rc e n t m a x im u m r e s p o n s e before after fig 1: semi log dose percent response bars for acetylcholine induced contractions group ii (pancuronium) in a series of six experiments the mean ± sem values of responses for 1, 2, 4, 8, 16, 32, 64, and 128 µg, of acetylcholine were recorded. percent responses were calculated by taking the response with 128 µg as 100% and were 6%, 24%, 42%, 62%, 83%, 91%, 98% and 100% for each dose respectively. after washing the preparations, giving them a rest of 30 minutes, and adding a fixed dose of 1µgm of pancuronium the percent responses were 1%, 1%, 9%, 19%, 47%, 75%, 90%, and 96% for each dose respectively. semi log dose response curve were plotted by taking the percent responses which showed that the second curve i.e., after washing with frog-ringer solution and rest and adding 1µg of pancuronium shifted to the right and downwards. st the deviation started with the 1 dose of 1 µg and continued in almost the entire extent of the curve, minimizing at the higher doses. percentage deviation was calculated for each dose and was 88%, 94%, 79.7%, 69.0%, 43.1%, 17.3%, 8.0% and 4.3% respectively with mean 50.4%. (sem ± 15.17). p < 0.05. fig 2: semi log dose percent response bars for acetylcholine-induced contractions, before and after adding 1µg pancuronium group iii (ranitidine) in a series of six experiments the mean ± sem values of responses for 1, 2, 4, 8, 16, 32, 64, and 128, µg of acetylcholine were recorded. percent responses were calculated by taking the response with 128 µg as 100% and were 2%, 9%, 25%, 48%, 66%, 87%, 95%, and 100% for each dose respectively. the same experiment was repeated on the same tissue preparation using similar concentration and doses of acetylcholine after washing the preparations, giving them a rest of 30 minutes, and adding a fixed dose of 1mm concentration of ranitidine. the percentage responses with the same doses were 6%, 16%, 47%, 70%, 93%, 111%, 117%, and 117%, for each dose respectively. semi log dose response curves were plotted by taking the percent responses which showed that the second curve i.e., after washing with frog-ringer solution and rest and adding 1µm ranitidine on an average shifted to the left and st upwards. the deviation started with the 1 dose and continued in the entire extent of the curve. percentage deviation was calculated for each dose and was 166%, 83%, 90.9%, 44.6.%, 42.0%, 25.6%, 22.7%, and 17.2% respectively with mean 61%. (sem ± 20.59). p < 0.05 fig 3: semi log dose percent response bars for acetylcholine-induced contractions before and after adding 1mm ranitidine ranitidine potentiates acetylcholine effects at nm junction jiimc 2021 vol. 16, no.4 239 group iv (pancuronium+ ranitidine) in a series of six experiments the mean ± sem values of responses for 1, 2, 4, 8, 16, 32, 64, and 128 µg of acetylcholine were recorded. percent responses calculated by taking response with 128 µg as 100% and were 1%, 6%, 15%, 30%, 57%, 89%, 95%, and 100% for each dose respectively. after washing the preparations and adding a fixed dose of 1µg pancuronium and 1mm ranitidine the percent responses were 3.2%, 11%, 37%, 71%, 97%, 114%, 120%, and 121% for each dose respectively. semi log dose response curve were plotted by taking the percentage responses which showed that the second curve i.e., after washing with frog-ringer's solution and rest and adding pancuronium and ranitidine shifted to the left and upwards. the deviation started after the 2nd dose and continued in the entire extent of the curve. percentage deviation was calculated for each dose and was 312.5%, 100.86%, 142.4%, 135.3%, 69.8%, 28.4%, 25.6%, and 21.1% with mean 104.5%. (sem ± 39.7). p < 0.05. comparison of group ii (acetylcholine + pancuronium) and group iv (acetylcholine + pancuronium + ranitidine) the difference in the percent deviation of response to acetylcholine in the two groups fig 6 (p < 0.05). fig 4: semi log dose percent response bars for acetylcholine-induced contractions, before and after adding 1µg pancuronium and 1mm ranitidine comparison of control group i (acetylcholine) and group iii (acetylcholine + ranitidine). the difference in the percent deviation of response to acetylcholine in the two groups. fig 5 (p < 0.05). fig 5: comparison of percent deviation of group i (acetylcholine) with percentage deviation of group iii (ranitidine) fig 6: comparison of percent deviation of group ii (acetylcholine + pancuronium) and group iv (acetylcholine + pancuronium + ranitidine) comparison of group ii (acetylcholine + pancuronium) and group iv (acetylcholine + pancuronium + ranitidine) the difference in the percent deviation of response to acetylcholine in the two groups fig 6 (p < 0.05). discussion in the present study ranitidine in a dose of 1mm concentration produced a shift of the curve to the left with mean deviation of 61.5% (sem ± 20.5) showing an enhancement of effects of acetylcholine. ranitidine also produced a shift of the curve to the left in the presence of 1µg pancuronium with the mean deviation of 104.5% (sem ± 39.7). the shift was statistically significant (p < 0.05) showing the antagonistic effect of ranitidine on neuromuscular junction (nmj) blocker pancuronium at this concentration. the difference in the percent deviation of response to acetylcholine in the two groups (control group i and group iii) was highly significant (p < 0.05). the difference in the percent deviation of response to acetylcholine in the two groups (group ii and group iv) was also highly significant (p < 0.05). this was consistent with previous studies by mishra and kounenis and a clinical case report of resistance to non-depolarizing blocking agents in a patient on a 20,21, 22 prolonged treatment with ranitidine. this reversal is concentration dependent and is seen only at lower doses while at higher doses the effect is reversed and ranitidine enhances the effects of nmj blockers possibly by its ion channel blocking ranitidine potentiates acetylcholine effects at nm junction jiimc 2021 vol. 16, no.4 240 20 activity. ranitidine induced reversal of the effects of pancuronium may be due to the anti-cholinesterase activity of the drug whereby it enhances the effects 15 of acetylcholine by interfering with its metabolism. this is further reinforced by the fact that ranitidine does not enhance the tissue responses and conversely shifts the curve to right when carbachol is used instead of acetylcholine. carbachol is resistant 23 to hydrolysis by cholinesterase and in such situations ranitidine decreases the response to 24 carbachol in dose range of 0.25mm to 01mm. this nmj blocking activity of ranitidine may be due to direct blockade of the ion channel independent of its 22 anti-cholinesterase inhibiting activity. due to this effect of ranitidine with carbachol, it can be inferred that the anti-cholinesterase activity of ranitidine is relatively stronger as compared to its ion channel blocking properties. moreover, in actual clinical situations it is acetylcholine which serves as neurotransmitter at neuromuscular junction, consequently this antagonistic effect of ranitidine may have important interactions with nmj blockers in anaesthetic practice. conclusion the present study concludes that ranitidine in a concentration of 1mm increases the effects of acetylcholine at nmj and antagonize the effects of nmj blocker pancuronium at this concentration. references 1. � bhuse kv. fixed dose combination of ranitidine and dicyclomine. world j pharm pharm sci. 2017;6(8):426–9. 2. � nason ks. acute intraoperative pulmonary aspiration. thorac surg clin. 2015;25(3):301–7. 3. � herrera-mozo i, sanz-gallen p, martí-amengual g. occupational contact allergy to omeprazole and ranitidine. med pr. 2017;68(3):433–5. 4. � brunton l, randa hilal-dandan, knollmann bc, editors. goodman & gilman's the pharmacological bases of terapheutics、13th. mcgraw-hill medical; 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t i ve effe c t s o f s a l b u ta m o l a n d beclomethasone against insulin induced airway hyperreactivity on isolated tracheal smooth muscle. ncbi.nlm.nih.gov. 20. � mishra y, torda t, ramzan i, graham g. in-vitro interaction between h2 antagonists and vecuronium. j pharm pharmacol. 1994;46(3):205–8. 21. � kounenis g, koutsoviti-papadopoulou m, elezoglou v. effect of nizatidine and ranitidine on the d-tubocurarine neuromuscular blockade in the toad rectus abdominis muscle. pharmacol res. 1994;29(2):155–61. 22. � keleş g, kara e, tok d, dergisi ta-ft, 2007 u. resistance to nondepolarizing blocking agents in a patient prolonged treatment with ranitidine. firattipdergisi.com. 23. � masuoka t, uwada j, kudo m, yoshiki h, yamashita y, taniguchi t, et al. augmentation of endogenous acetylcholine uptake and cholinergic facilitation of h i p p o c a m p a l l o n g t e r m p o t e n t i a t i o n b y ranitidine potentiates acetylcholine effects at nm junction jiimc 2021 vol. 16, no.4 241 acetylcholinesterase inhibition. neuroscience. 2019 apr 15;404:39–47. 24. � cheah ls, lee hs, gwee mce. anticholinesterase activity of and possible ion-channel block by cimetidine, ranitidine and oxamitidine in the toad isolated rectus abdominis muscle. clin exp pharmacol physiol. 1985;12(4):353–7. ranitidine potentiates acetylcholine effects at nm junction jiimc 2021 vol. 16, no.4 242 original�article abstract objective: the purpose of the study was to determine the association between the media exposure and the aggression levels in the students of 13-24 years residing in wah cantt. study design: cross-sectional place and duration of study: educational institutes of wah cantt for 1 year from january 2019 to january 2020. materials and methods: the standardized questionnaires i.e., cme-scale & bus-perry scale were used to measure media exposure and aggression levels besides basic demographic data. data was analyzed by using spss version 20. media exposure and aggression exhibited by the students was categorized into low, medium, and high levels. results: majority of students had low or medium levels of media exposure (59.4%) and low or medium aggression scores (84.1%). there was no difference in level of aggression between males and females (p=0.230). association of aggression with media exposure was significant (p=0.000) and the pearson correlation was weakly positive (r= 0.393, p= 0.000). although a majority (80.6%) of participants possessed electronic devices, but they were mostly (55.9%) monitored by parents. hours spent per day on screen were positively skewed with mean hours of 4.58±3.8. conclusion: there was a weak positive correlation between media exposure & aggression. a longitudinal study might be done to assess the possible effect of the cultural and societal values of indulgence in sports and scholarship by the citizens of this area on the levels of media exposure and aggression levels in youth. key words: adolescent, aggression, education, media, primary prevention primary prevention of aggression induced by media exposure: a cross sectional study 1 2 3 4 5 6 ambreen ansar , sadia nadeem , amna sajjad , aleena sohail , aisha bukhari , aima akhtar correspondence: dr. ambreen ansar associate professor department of community medicine wah medical college, wah cantt e-mail: ansarambreen@gmail.com 1,2 department of community medicine wah medical college, wah cantt 3,5 department of gynecology pof wah hospital, wah cantt 4,6 department of surgery bahawal victoria hospital, bahawalpur funding source: nil; conflict of interest: nil received: june 17, 2020; revised: september 11, 2021 accepted: september 19, 2021 aggression and media exposure in wahjiimc 2021 vol. 16, no.4 role in almost every field of life. through this people can communicate with each other at different platforms. media exposure is defined as the extent to which audience members have encountered specific 3 messages or classes of messages/media content. media makes remarkable contributions but, regretfully the negative effects of social media cannot be kept far aside. concerns have been raised that social media deeply impact behaviors and adolescents who are exposed to violent behaviors through media are more likely to participate in 4 violence. several news reports of cyber bullying, criminal activity on social media or through it, gang violence and suicide have surfaced and social media 5 appears to fuel these troubling incidents. the influence of media on psychological development of 6 children is repeatedly documented in literature. violent media are defined as “those that depict intentional attempts by individuals to inflict harm on other, an individual can be non-human cartoon 7 character, a real person or anything in between”. the evidence also reveals that exposure to violent media is associated with physical and psychological problems including aggression, bullying, fear, introduction social psychologists define aggression as behavior that is intended to harm another individual who does not wish to be harmed. aggression is caused by the 1 thoughts and feeling lying in our subconscious mind. this is the reason why exposure to violent media put children's and adolescent's health and wellbeing at risk. relationship between exposure to violent media and aggressive behaviors are well explained by general aggression model, externally stimulated 2 aggression and the learned aggression theory. in an era of technology, social media plays dynamic 260 8 depression, nightmares & sleep disturbances. the problem is not only confined to violent media exposure. even the excessive recreational use of computer and video games and long screen hours >2-3/day increase the odds of mental health two 9 times. pakistani youth is also facing the same threat from media exposure. social science literature and news blogs are regularly narrating media's advantages and disadvantages and suggesting a change required in media content to create good impact on changing minds. control to media exposure needs to be promoted and practiced. as an educated community we have to work together to find and eliminate these 10 triggers. to counter these negative consequences protective and mediating factors like parental involvement, parental monitoring, restrictive and active measures 11 taken by the parents and as whitney and christopher reported that violent media exposure is not a single or very promising predictor of youth aggression. their empirical research based on large sample size (n=5133) and a diverse youth group concludes that family and social variables are more influential factors implying that preventive measures targeted at community level like promotion of sports and scholarship among youth might play a very 12 important role. in lieu of the above evidence by whitney et al. this research is aimed to explore the effects of social media on aggressive behavior of college students in wah cantt. wah cantonment is a military city located in the punjab province of pakistan, near taxila 30 km to the north west of islamabad. according to the 2017 census of pakistan, its population is 380,103. the most distinct feature of the town is its very high literacy rate reaching up to 99%. wah cantt, having an area of about 35 square kilometers, has the highest number of educational institutes per square kilometer. apart from many private and government schools up to 12th level, foundations of professional 13 universities have been laid down in past 5 years. in addition to the educational institutes with big playing grounds there are parks and grounds for hockey, cricket, football, basketball, and athletics as well as the swimming pool and a large golf club. with this background we expect the levels of media exposure and aggression in youth of wah cantt to be lower than what is found elsewhere. this study was aimed to measure the levels of media exposure and a g g re s s i o n a m o n g yo u t h re s i d i n g i n wa h cantonment and quantify the association between these two. material and methodss a descriptive cross-sectional study was conducted in wah cantonment from jan 2019 to jan 2020 on a sample of 323 students -95% level of confidence and expected proportion to be 70%after taking permission from irb of wmc. all the male & female students ranging from 13-24 years of age residing in wah cantt were included using convenient sampling. the study participants were contacted either directly or through school/college teachers who were in contact of all the researchers. students not resident of wah cantt but studying in this area were excluded. all the researchers explained the study objectives a n d q u e s t i o n s i n t h e q u e s t i o n n a i r e s t o school/college teachers they knew personally who then provided us the time & opportunity to reach the different cohort of students, take their informed consent and collect the data. the university students were contacted directly via various social contacts. after taking informed consent and ensuring anonymity and confidentiality questionnaires were filled by the researchers in english. as english is the medium of teaching in all schools and colleges of wah cantt so there was no need to translate the questionnaire. it comprised of three parts; demographic information, media exposure measured by using content-based media exposure 14 scale (c-me scale) an 8-item inventory for measuring anti-social and risk behavior content and 9 neutral filler items; buss-perry aggression scale to 15 measure level of aggression. data was analyzed using spss version 20. descriptive statistics was calculated for all the variables. the association between levels of aggression and levels of media exposure was tested using chi-square test keeping alpha at 0.05. media exposure was categorized into: high exposure = those scoring from 32 to 40, medium exposure =those scoring between 24-31 and low exposure = those scoring <23. total score was 85 on cme-scale but the items on anti-social and risk behavior content had maximum score of 40. the aggression levels were also categorized into 3: high aggression = those aggression and media exposure in wahjiimc 2021 vol. 16, no.4 261 scoring 80% or more on buss-perry scale, medium aggression = those scoring between 60-80% and low aggression = those scoring 60% and below. results age of the students ranged from 13 to 24 years and mean was 18.3±3.1 and half of population was male. eighty-point six percent (n=258) students owned electronic devise mobile being the most common possessed by 68% (n=217) students followed by mobile & laptops 27% (n=86) students. fifty-fivepoint nine percent students (n= 179) were monitored by their parents for media content. total hours spent on screen were positively skewed with mean duration of 4.58± 3.89 hours & skewness =2.53 ± 0.139. overall, the levels of both aggression and media exposure were low among youth of wah cantt in both genders. violent, non-punitive behaviors of adult; a type of 16 primordial prevention, in shaping behaviors. both the levels of media exposure and aggression were low in majority of students in our sample which could be attributed to above-mentioned factors in wah cantt. this cultural value, very much unique to this geographical location, has a profound effect on thinking patterns and goal setting process of the 6,17 youth. unlike most of the cited literature , there were lower aggression scores strongly associated with lower media exposure in this study most probably related to the context in which this youth was brought up. according khurana & padilla-walker understanding certain aspects helps to predict the aggressive behavior at an adult age, one of which is less 11 interaction of children with parents. padilla-walker et al. in their latest study reported controlled media exposure especially maternal monitoring can bring 17 about decrease in aggression. highly literate maternal population i.e., 81.9% in our sample along with majority of them being i.e., 87.8% housewives should also have contributed to low levels of aggressions and media exposure but unexpectedly children of working mothers had significantly lesser aggression & media exposure levels and maternal education was not associated with either aggression or media exposure. fathers, however, seem to have important role in shaping children's behaviors in our culture. higher the education of father lesser are the aggression & media exposure scores in children. these results correlated well with the findings of table i: age and gender-wise distribution of aggression levels and media exposure levels in wah youth (n= 372) association of aggression with media exposure was 2 statistically significant (x = 63.446, df=4, p= 0.000) and pearson correlation was positive (r=0.393, p=0.000). aggression was also positively correlated with hours spent on electronic devices (r=0.125, p=0.028). significant associations were found between aggression levels and student's education, father's education & occupation, parental monitoring. whereas media exposure was significantly associated with all these independent variables as shown in table 2. discussion literature proves that media provokes violent behavior in youth, and it leaves deep psychological impacts on their minds. authors have highlighted various protective factors against violent media 11 exposure but very few highlighted the effect of cultural background, peaceful societies, and nontable ii: measure of association between aggression score (dependent variable) and independent predictors besides media exposure aggression and media exposure in wahjiimc 2021 vol. 16, no.4 262 18 jaynes & rebecca. a three year longitudinal study reports an association between viewing relational aggression on tv and exhibiting it in the future, even when controlling for existing levels of multiple forms of 6, 19, 20, 21 aggression. but parental monitoring can mediate these effects positively as proved in meta 22 reviews. parental monitoring in our context was 35.9% and was positively correlated with hours spent on ed, and negatively associated with aggression & media exposure scores. although cross sectional study design has hampered the complete understanding of interplay of various factors in shaping aggression among youth but in the context of wah cantt it can be postulated that the significant associations could be due to strong bonding and increased level of interaction between parents and their children, leading to close surveillance of the activities of children which controls any addiction to media exposure. another limitation was the students themselves answering the questions for aggression which might not provide the authentic results because aggression is predominantly determined by observation and the reported media exposure could have been confirmed by the parents & teachers. behavior is a complex combination of physical, psychological, and physiological dimensions in human beings. it is defined as “the internally coordinated responses (actions or inactions) of whole living organisms (individuals or groups) to internal and/or external stimuli, excluding responses more easily understood 23, 24 as developmental changes”. it is important therefore to conduct physical, neurophysiologic, behavioral, cognitive, and environmental studies to understand the inter relationship between students' behaviours and contextual factors. among other non-negotiable risk factors like poverty was not the (25) case in our sample . there is a deep and subtle relationship between aggression and its social & genetic predictors. all these factors open new research areas in our unique educational culture. it would be interesting to see the role of these factors in media and aggression equation in a community with such low levels of aggression. conclusion the levels of aggression and media exposure are both low in our society. there is a positive correlation between the two variables. the role of the cultural and societal values of indulgence in sports and scholarship by the citizens of this area on youth behaviors should be studied in a longitudinal study to confirm the association. the primary prevention model in vogue at wah cantonment i.e., may contain some positive lessons which could be implemented to lessen the evil of media exposure and hence aggression levels in youth in extended societies. references 1. � munsaka t. sigmund freud's psychodynamic theory. the origins of aggression. grin verlag; 2014 jun 11. 2. � anderson ca, bushman bj. media violence and the general aggression model. journal of social issues. 2018 jun;74(2):386-413. 3. � de vreese ch, neijens p. measuring media exposure in a changing communications environment. 4. � allen jj, anderson ca, bushman bj. the general aggression models. current opinion in psychology. 2018 feb 1; 19:7580. 5. � the digital age, s.o.c.i.a.l.m.e.d.i.a. the digital age at the 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c i e n c e d i r e c t . c o m /science/article/pii/s0190740919312319. aggression and media exposure in wahjiimc 2021 vol. 16, no.4 264 jiims final.cdr 20 original article the reno-protective effect of ethanolic extract of cassia fistula (amaltas) leaves on streptozotocin induced diabetic nephropathy in rats farhana adnan, soban sadiq, adnan jehangir abstract objective: to determine the reno-protective effect of ethanolic extract of cassia fistula (amaltas) leaves on streptozotocin induced diabetic nephropathy in rats. study design: an animal experimental study place of study: the study was done in biochemistry department, islamic international medical college,rawalpindi and nih.islamabad. materials and methods: single injection of stz was given intraperitoneally to rats and those rats that showed fasting blood glucose level over 280mg/dl were included in the study. after induction of diabetes all rats were divided into, normal control group (a), diabetes positive control group (b), and the two groups (c and d) served as experimental groups while group e served as standard as it received glibenclamide. group c and d diabetic experimental rats received ethanolic extract of cassia fistula leaves at 400 mg/kg and 500mg/kg of body weight orally for eight weeks on daily basis. on the other hand group e rats received glibenclamide at 0.5 mg/kg body weight orally for eight weeks. blood samples were collected after eight weeks to find reno-protection against stz induced diabetic nephropathy. results: the diabetic positive group rats showed variable increase in levels of serum glucose, serum urea, serum creatinine, total urinary protein and microalbuminuric levels. body weight decreased and urine volume increased in diabetic groups. cassia fistula ethanolic extract of 400mg/kg and 500mg/kg body weight dose and glibenclamide significantly decreased the levels of these parameters in rats. on comparison cassia fistula ethanolic extract of 500mg/kg dose reduced levels of biochemical parameters more effectively than the 400mg/kg dose of cassia fistula and glibenclamide. cassia fistula constituents, especially polyphenols and flavonoids have strong anti-oxidant activity which might be involved in reno-protection. conclusion: cassia fistula ethanolic leaf extract showed reno-protection against stz induced diabetic nephropathy in rats. key words: reno-protection, streptozotocin , cassia fistula, diabetic nephropathy, oxidative stress 3of diabetes mellitus. diabetic nephropathy is the leading cause of end stage renal diseases (esrd) in western societies and accounts for 30 to 35% of patients on renal replacement therapy in north america. type 1 and type 2 dm affect approximately 0.5 and 4% of the population, respectively. nephropathy complicates 30% of cases of type 1 dm and approximately 20% of cases of type 2 dm. however most diabetic patients with esrd have type 2 dm because of the greater prevalence of type 2 dm 4worldwide. the level of hyperglycaemia seems to be quantitatively linked to risk of developing renal lesions. hyperglycaemia introduction diabetes mellitus (dm) is a syndrome characterized by chronic hyperglycaemia and relative insulin deficiency, resistance or 1both. diabetes mellitus is not a single disease but basically a group of disorder which is characterized by hyperglycemia, hyperlipidemia, glycosuria, ketonemia and if prolonged leads to diabetic complications such as nephropathy, neuropathy and 2retinopathy. nephropathy is one of the important microangiopathic complications --------------------------------------------------correspondence: dr. farhana adnan assistant professor department of biochemistry iimct rawalpindi 21 enhances the non-enzymatic glycosylation of proteins; hence advanced glycosylation end-products (age) are formed. increased serum levels of age seem to predict changes in kidney morphology such as expansion of mesangial cell matrix and glomerular 5basement membrane thickening. the activation of hyperglycaemia-induced secondary mediators, such as protein kinase c and mitogen-activated protein kinase, and cytokine production are also responsible for oxidative stress induced renal injury in the 6diabetic condition. various experimental animals have been utilized to investigate diabetic nephropathy, however stz induced hyperglycaemic rats have been used in this model of diabetic nephropathy. stz is synthesized by streptomycetes achromogenes and is used 7to induce both type 1 and type 2 dm. cassia fistula belonging to the family leguminosae casesalpinaceae is commonly called as amaltas, an indian labernum and is native to india, sri lanka and is 8extensively diffused in various countries. its main property being that of a mild laxative suitable for children and pregnant women. it has been used to treat many 9-10intestinal disorders like ulcers. the plant has a high therapeutic value and it exerts 11antipyretic and analgesic effects. cassia fistula leaf extract is also used for its anti12-13tussive and wound healing properties. it has been concluded that plant parts could be used as a therapeutic agent in the treatment of hypercholesterolemia partially due to 14their fibre and mucilage content. it has 15been reported to possess antitumor 1 6,hepatoprotective, antifertility and 17antioxidant properties. the cassia fistula leaves are known to be an important source of secondary metabolites, notably phenolic compounds. the purpose of the present experimental model was to observe the effect of cassia fistula on streptozotocin induced diabetic nephropathy when given together to wistar rats. the study was done in biochemistry department, islamic international medical college,rawalpindi and nih.islamabad. the present study was carried out on 50 male wistar rats, each weighing 200 250g and were divided into 5 groups (10 each). each group was kept in a separate cage, in t h e s a m e ro o m a n d u n d e r s i m i l a r physiological conditions in animal house of national institute of health (nih) islamabad. initially all groups were fed on normal rat chow (consisting of wed, starch, choline, methionine, vitamin, mineral mixture and fat) and water for a period of one week for a c c l i m a t i z a t i o n b e f o re s t a r t i n g t h e experiment the care and handling of rats were in accordance with the internationally accepted standard guidelines for use of experimental animals. commercially available kits (randox ) for biochemical analysis of glucose, urea, c r e a t i n i n e , t o t a l u r i n a r y p r o t e i n , microalbuminuria, 95% ethanol, pre-coated tlc(thin layer chromatography) plate silica gel gf254 and toluene. the standard compounds used are ellagic acid, gallic acid and protocatechuic acid. the instruments used were soxhlet and rotary evaporator, centrifuge (germany), clinical chemistry material and methods animals: chemicals/instruments: 22 analyzer and tlc scanner iii (camag, switzerland) with win cats software. leaves of cassia fistula were collected from jinnah park, rawalpindi and authenticated from a botanist. ethanolic leaf extract (ele) was prepared from cassia fistula. freshly collected leaves were washed in tap water and then distilled water and were shade dried for about 1 week. the dried leaves were crushed into a coarse powder. one hundred gram of the powder was soaked in 1 liter of ethanol for 30 days with occasional shaking. after 30 days this ele was filtered and evaporated to dryness over a water bath 18at 60°c .the yield of ethanolic leaf extract was 19-20%.this (ele) of cassia fistula was got standardized from nih, islamabad. tlc (thin layer chromatography) was used for standardization. tlc was performed on a pre-coated tlc plate silica gel gf254. sample was applied on the plate as 8 mm wide bands with an automatic tlc sampler. the development was carried out in trough chamber (20 cm × 10 cm),which w a s p r e s a t u r a t e d w i t h m o b i l e phase(solvent system, toluene-ethyl acetateformic acid-methanol ( 30:30:8:2), for 20 min at room temperature (25 ± 2°cand 40% relative humidity). subsequent to the development, tlc plates were dried under stream of hot air and then subjected to densitometric scanning using a tlc scanner iii (camag, switzerland) with win cats software (version 1.4.1) in the absorbancereflectance scan mode. quantitative evaluation of the plate was performed in absorption-reflection mode at 338 nm. the plant materials and preparation of the extract standardization of plant extract: standard compounds used are ellagic acid, gallic acid and protocatechuic acid. after acclimatization, 10 rats were labeled as control. all other rats were starved for 16 hours and diabetes was induced using a single intraperitoneal injection of freshly dissolved streptozotocin (60 mg/kg) in 0.01m citrate buffer (ph 4.5). one week after the streptozotocin injection, rats were assessed for diabetes and those with fasting blood glucose over 280 mg/dl were 19included in this study. thereafter, all rats were divided into five groups each having 10 animals. the control rats (group a) were fed on standard diet with tap water and received no drug. group b i.e. diabetic control rats received 60 mg/kg of stz as a single intraperitoneal injection and were fed on standard diet and tap water. group c i.e. experimental group rats received 60 mg/kg of stz as a single intraperitoneal injection and ele in a daily oral dose of 400 mg/kg for a period of sixty days. group d i.e. experimental group rats received 60 mg/kg of stz as a single intraperitoneal injection and ele using a dose of 500 mg/kg body weight daily (orally) for a period of sixty days.16, 18 group e i.e. standard group rats received 60 mg/kg of stz as a single intraperitoneal injection and glibenclamide 0.5mg/kg body weight orally for a period of sixty days. timings: (day 0, day 60th). blood samples were taken at day 0 to establish that all rats had normal glucose and renal profile. twenty four hour after administration of the last dose of extract i.e. on 60th day and after overnight fasting, the animals were weighed and anaesthetized under ether vapours. a experimental procedure sample collection: 23 sample of 2ml blood was drawn from tail vein from all animals. blood was transferred to the sterile vacuotainers with gel and allowed to clot at room temperature for one hour. it was then centrifuged for ten minutes at a speed of 3000 rpm. serum was separated and stored in sterile eppendorf tubes at 2 0 ° c f o r a n a l y s i s o f b i o c h e m i c a l 20parameters. twenty four hour urine samples were collected using metabolic cages and a n a l y z e d . t h e a n i m a l s w e r e k e p t individually in metabolic cages, they were given only water. the urine was then collected in 24 hours and measured. body weight also measured initially and at the end of experiment. glucose levels were estimated using commercially available kit (randox, uk) 21based on glucose oxidase method. serum urea was estimated by commercially available kits (randox, uk), based on 22enzymatic colorimetric method while serum creatinine using jaffe alkaline picrate 23method (randox, uk). total urinary protein was estimated by colorimetric method and microalbumin level based on 24-25immunoturbimetric assay (randox, uk). the data was entered and analyzed using spss 17.0 (statistical package for social sciences). all data are shown as mean ± s.e.m. one way anova was applied to observe group mean differences. post hoc tukey test was applied to observe mean differences among the groups. a p-value of <0.05 was considered as statistically significant. biochemical analysis statistical analysis results the biochemical parameters showed that the injection of stz caused a significantly (p<0.05) increased serum glucose, serum creatinine and total urinary protein levels in the rats of group b, c, d and e as compared to control group. on the other hand, simultaneous administration of ethanolic extract of cassia fistula to group c and d and glibenclamide to group e resulted in a significant (p<0.01) decrease in the serum glucose, serum creatinine and total urinary protein levels in groups c ,d and e when compared with that of group b. the urea levels showed that the injection of stz caused a significantly (p<0.05) increased urea levels in the rats of group b, c, d and e as compared to the control. on t h e o t h e r h a n d , t h e s i m u l t a n e o u s administration of ethanolic extract of cassia fistula resulted in a significant (p<0.01) decrease in urea levels in the rats of group c and d when compared with that of group b. when group b was compared with group e, no significant difference was observed in urea levels (p = 0.05). the microalbuminuric levels showed that the injection of stz caused a significantly (p<0.05) increased microalbuminuric levels in the rats of group b, c, d and e as compared to the control. on the other hand, the simultaneous administration of ethanolic extract of cassia fistula resulted in a significant (p<0.01) decrease in the microalbuminuria in the rats in group d when compared with that of group b. when group b was compared with group c (p=0.07) and e (p=0.06), no significant d i f f e r e n c e w a s o b s e r v e d i n microalbuminuric levels. the urine volume showed that the injection of stz caused a significantly (p<0.05) 24 increased levels of urine volume in the rats of group b, c, d and e as compared to the control group. on the other hand, the simultaneous administration of ethanolic extract of cassia fistula resulted in a significant (p<0.01) decrease in the levels of urine volume of the rats in group c and d when compared with that of group b. when group b was compared with group e, no significant difference was observed in urine volume levels (p =0.08). the body weight showed that the injection of stz caused a significant (p<0.05) decrease in body weight in the rats of group b, c, d and e as compared to the control. on the other hand, the simultaneous administration of ethanolic extract of cassia fistula resulted in an increase in the body weight of the rats in group d. when group b was compared with group c (p= 0.63) and e (p=0.55), no significant difference was observed in body weight. t h e e a r l i e s t c l i n i c a l e v i d e n c e o f nephropathy is the appearance of low but a b n o r m a l l e v e l s ( = 3 0 m g / d a y o r 20mcg/min) of albumin in the urine referred as microalbuminuria and patients with microalbuminuria are referred to as 2 6n e p h r o p a t h y. o x i d a t i v e s t r e s s i s c o n s i d e r e d t o b e t h e m a j o r pathophysiological mechanisms involved in the development of diabetic nephropathy. high glucose directly increases hydrogen peroxide production by mesangial cells and also causes lipid peroxidation of glomeruli 27and glomerular mesangial cells. effective control of blood glucose level is a key step in reversing diabetic complications and improving the quality of life in diabetic discussion patients. currently available drugs for the treatment of dm have a number of limitations including adverse effects and high rate of secondary failure. a number of plants are being assessed for their therapeutic potential as there is a growing trend towards the use of natural remedies as 28adjuncts to conventional therapy. 25 the present study showed a significant elevation observed in the levels of serum glucose, urea, creatinine, total urinary protein and urinary albumin excretion in group b diabetic rats as compared to group 29a normal rats. urine volume was also elevated in group b rats while body weight reduced in group b rats as compared to group a rats. elevated levels of these parameters in serum and urine are presumptive markers of diabetes associated lesions in kidneys of rats. co-administration of ethanolic extract of cassia fistula leaves brought the levels of these diagnostic parameters in the serum and urine of group c, d and e animals towards normal as compared to group b rats (table i). when we compared mean values of group c with group d, although both decrease glucose and renal parameters levels, but group d reduced the levels more as compared to group c. when we compare mean values of group c and d with group e, although glibenclamide decrease levels, but cassia fistula ethanolic leaf extract reduced t h e l e v e l s m o r e a s c o m p a r e d t o glibenclamide. cassia fistula also improved t h e b o d y w e i g h t a s c o m p a r e d t o glibenclamide (table i), showing better effectiveness of cassia fistula ethanolic leaf extract over glibenclamide. our results are in accordance with the reports by others who used chemical antioxidants and diet of 30-31natural antioxidant plants. the main constituents in cassia fistula are polyphenols (quercetin), anthraquinones, flavonoids and flavan-3-ol derivatives. the proposed mechanism of cassia fistula in renoprotection could be due to the antioxidant mechanism. anjaneyulu and chopra observed that quercetin is a strong 27antioxidant. it is likely that the scavenging effects of quercetin on free radicals and the inhibition of lipid peroxidation may play a role in improving renal dysfunction in 32diabetes. robards and antolovich in 1997 have critically reviewed the analytical chemistry of bioflavonoid and it was found that flavonoids possess antioxidant activity, they are potent free radical scavengers and metal chelators and they also inhibit lipid 3 3oxidation .therefore, in our study flavonoids and quercetin in cassia fistula might have a role in the recovery in stz induced diabetic nephropathy in rats. further studies are needed to observe histopathological examination and also to see effect of higher doses and variable routes of administration for its protective effect on the kidneys of diabetic nephropathy subjects. the results of the present study show that the co-treatment of cassia fistula ethanolic leaf extract prevents stz induced diabetic nephropathy in rats. the high dose (500mg/kg) cassia fistula leaf extract, showed better results as compared to low dose (400mg/kg) cassia fistula leaf extract and glibenclamide. the authors would like to thank the principal iimc maj.gen(retd) dr. masood anwar for his continuous supervision and nih animal house incharge mr.hussain ali for helping in instrument handling and biochemical analysis. 1. gale ea, anderson jv. diabetes mellitus and conclusion acknowledgments references: 26 other disorder of metabolism. in:kumar p, clark m, eds. kumar and clark clinical medicine (fifth edition). philadelphia: w.b.saunders, 2002:10691104. 2. silawat n, jarald ee, jain n, yadav a, deshmukh pt. the mechanism of hypoglycemic and antidiabetic action of hydroalcoholic extracts of cassia fistula in rats. the pharma research 2009; 1:82-92. 3. baynes jw. role of oxidative stress in the development of complications in diabetes. diabetes 1991; 40:405-12. 4. brady hr, o'meara ym, brenner 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microdetermination of creatinine. clin chim acta 1971; 32:81. 24. o r s o n n e a u j l , d o v e t p, m a s s o u b re c , lustenberger p, bernard s. an improved p y r o g a l l o l r e d m o l y b d a t e m e t h o d f o r determining total urinary protein. clin chem 1989; 35:22-33. 25. bakker aj. immunoturbidimetry of urinary albumin: prevention of adsorption of albumin; influence of other urinary constituents. clin chem 1988; 34:82-6. 26. american diabetes association: nephropathy in diabetes. diabetes care 2004; 27 :79-83. 27. anjaneyulu m, chopra k. quercetin, an antioxidant bioflavonoids, attenuates diabetic nephropathy in rats. clin exp pharmacol physiol 27 2004; 31:244-8. 28. evans jl, goldfine id, maddux ba, grodsky gm. oxidative stress and stress-activated signalling pathways: a unifying hypothesis of type 2 diabetes. endocr re 2002; 23:599-622 29. suradkar sg, ghodasara dj, vihol p, patel j,jaiswal v,prajapati ks.haemato-biochemical alterations induced by lead acetate toxicity in wistar rats. veterinary world 2009;2:429-31. 30. sharma sb, nasir a, prabhu km, murthy ps, dev g. hypoglycaemic and hypolipidemic effect of ethanolic extract of seeds of eugenia jambolana in a l l o x a n i n d u c e d d i a b e t i c r a b b i t s . j . ethnopharmacol 2003; 85:201-6. 31. akpanabiatu mi, umoh ib, udoh ae, edet ef. . rats serum electrolytes, lipid profile and cardiovascular activity on nuclea latifolia leaf extract administration. indian j clin biochem 2005; 20: 29-34. 32. chan ec, pannangpeth p, woodman ol. relaxation to flavones and flavonols in rat isolated thoracic aorta: mechanism of action and structure activity relationship. cardiovasc pharmacol 2000;35:326-33 33. robards k, antolovich m. analytical chemistry of fruit bioflavonoids. a review. analyst 1997; 122:11-30. original�article abstract objective: to compare the awareness among medical and non-medical students about the practice of periodic medical examination. study design: cross sectional descriptive study. st th place and duration of study: the study was conducted between 1 february 2016 to 30 april 2016 among the students enrolled in universities and colleges of rawalpindi and islamabad. materials and methods: it was a cross-sectional comparative study. data was collected through structured, pre-validated questionnaire. eight colleges of rawalpindi and islamabad were selected, four were related to medical profession and four were non-medical. on the basis of simple random sampling, 271 students enrolled in bachelor program were selected among these institutes. the data was analyzed through spss version 20. results: overall 63 % of the students, both from medical and non-medical institutions, had awareness about the knowledge and practice of periodic medical examination. among medical students 68% and 61% among nonmedical students had knowledge about periodic medical examination. no major difference was found in knowledge and practice among medical versus non-medical students. conclusion: this study concludes that medical and non-medical students are aware about the importance of periodic medical examination with trivial difference and lack of practice and reasons of not following the medical advice are busy schedules and heavy costs of investigations. from public health perspective there is a great need to raise health awareness amongst those who do not have awareness about periodic medical examination to prevent our future generation from chronic illnesses. key words: awareness, medical examination, medical students, non-medical students. highlighted their role in global health issues, including high blood pressure, stroke, diabetes and 2 cancer. notably 60% of deaths were observed due to these diseases worldwide. however 80% of these deaths emerged in developing countries including pakistan. in 2020 approximately 13.9 million people with diabetes will drag up pakistan to 4th most populous 3 country in the world. in the present world, pakistan is ranked 6th among countries, who have high burden of diseases. communicable diseases have share of 40% in pakistan which means every 3rd 4 individual has some sort of communicable disease. childhood infectious diseases were responsible for 5 two thirds of the burden of disease in pakistan. these statistics emphasize to save future through raising awareness about health seeking behavior and practicing periodical medical examination. that will lead a developed society because of the availability and productivity of workable human resources. it will reduce medical expenditure in household bucket and will increase economic productivity of workable adults accordingly. periodic medical examination (pme) is essential for introduction healthy environment, good knowledge, practicing attitude and approachable availability of health services for all individuals are essential for prevention of diseases. it is progressively more recognized now a days that health is preserved and enriched not only through the development and application of health advancements but also through the efforts adopted for intelligent lifestyle choices by the individuals and community. staying physically active and conscious about health can help prevent or delay certain diseases, including some cancers, 1 heart diseases and diabetes. in 2005 world health organization emphasized on chronic diseases and awareness among medical and non-medical students about the practice of periodic medical examination 1 2 3 tahira sadiq , muhammad asim , shahzad akhtar aziz correspondence: dr. tahira sadiq assistant professor, community medicine islamic international medical college riphah international university, islamabad 1,3 department of community medicine islamic international medical college riphah international university, islamabad 2 department of training character education foundation, islamabad funding source: nil; conflict of interest: nil received: feb 07, 2017; revised: mar 31, 2017 accepted: may 20, 2017 practice of periodic medical examinationjiimc 2017 vol. 12, no.2 116 mortality. this study will highlight the level of awareness among medical and non-medical students about the practice of periodical medical examination and the factors which are considered as causes for not practicing would be the future recommendations. materials and methods this cross-sectional descriptive study was conducted st in three months duration from 1 february 2016 to th 30 april 2016 among the students enrolled in 8 colleges and universities of rawalpindi and islamabad. four institutes selected from public sector and four from private sector were included in the study. wherein four were related to medical profession and remaining four were related to nonmedical profession. sample size was based on who calculator by using following figures. ci 95%, anticipated population proportion (p value) was 0.20, absolute precision required was 0.05 so the sample size turned out 246 and the actual sample size for the current study was 271. sampling technique used was simple random sampling. a structured, pre validated questionnaire was used for data collection. after the validation of questionnaire, pilot testing was done at riphah international university islamabad, before the actual study was carried out. questionnaire had different variables about periodic medical examination like knowledge, practice, source of information, and gap between pme, trends in family regarding pme and finally identifying the reason in those students who don't practice it. data was collected by authors themselves. statistical analysis was done through chi square test (non-parametric). p value less than 0.05 was considered as significant. results a total of 271 students from medical and nonmedical profession were included in the study. 131 were male and 140 were female students. a total 132 (48.7%) respondent were between age interval of 18-21, 116 (42.8%) were of 21-23 and 23 (8.5%) were of 24-26. total 127 respondents were from the medical colleges and 144 from non-medical institutes. 246 (90.7 %) were single, only 21 (7.8%) were married and four (1.5%) were separated. among all 81% of respondents marked pme important for health, whereas others think that it is wastage of resources as well as time. respondents 6 early detection of an illness. it plays vital role to keep human resource healthy and productive. as individual are considered basic entity in any society, they should give priority to health and allocate time for health facilities and for this purpose two utmost aspects are good healthy food and regular checks on 7 health conditions. periodic medical examination is defined as a thorough study or examination of the 8 health of an individual. some studies have also shown in their results that people who undergo regular medical examinations have decreased the 9 rates of invasive cancers and mortality respectively. it shows that developing societies should be more concerned and sensitive towards the health needs of its members. in modern day life, health care has made significant improvement in management of various diseases but it is still hard to understand the rise of mortalities and morbidities. according to 1998 census pakistan has placed sixth populous country with 180 million individuals. if percentage who suffered with different diseases translated into figures then estimation will be alike 40 million individuals suffer from high blood pressure, 32 million cardiovascular diseases, 24 million from obesity, 18 million from high cholesterol, 8 million from diabetes and about 50 10 million from mental health disorders respectively. this is the reason that life expediency in pakistan is 11 still low if we compare it with developed countries. main goal of periodic medical examinations is to diagnose treatable asymptomatic diseases. in pa k i s t a n r e s e a r c h e s o n p e r i o d i c m e d i c a l examination are done mainly on workers in different 12,13 industries, hospital workers and food handlers. limited work is available on students especially who have strong educational background and studying in renowned medical and non-medical fields. purpose of this study was to raise awareness about health through addressing the gap between knowledge and practice of periodic medical examination. youth considered as cream of the nation is expected to be more conscious about health seeking behavior and practices as compared to other age groups, especially medical students who are the future health care providers. it is therefore important to raise awareness on periodic medical examination so that diseases can be detected and managed at early stages to reduce morbidity and practice of periodic medical examinationjiimc 2017 vol. 12, no.2 117 peers and friends as their source of information.who practice regular periodic medical examination, 89% of their family members also practice it. table i highlights the fact that the 170 respondents including medical and non-medical were aware of the periodic medical examination. 101 respondents including 53 males and 48 females had no knowledge about it. table i: knowledge about periodic medical examina�on according table ii highlights the differences between knowledge of periodic medical examination and its practice. most of the respondents who know the importance of periodic medical examination, actually practice it. table ii: difference between knowledge and prac�ce of periodic medical examina�on table iii highlights the comparison of knowledge of periodic medical examination among medical and non-medical students. there is no major difference but still medical students are more knowledgeable then non-medical students. this difference could be because of their study fields. table iii: comparison of knowledge about periodic medical examina�on in medical vs non-medical students p value = < 0.01 in figure 1, 76 (28 %) respondents reported internet as their source of information about medical examination, while 60 (22 %) respondents reported fig 1: sources of informa�on about periodic medical examina�on in figure 2, important reason among those who don't practice pme is ignorance (33%). some others are not practicing because of their busy schedules (25%) and cost of investigations (20%) fig 2: reasons for not prac�cing periodic medical examina�on discussion developing world is facing double burden of diseases. it is need of the time as well as cost effective measure to prevent chronic illness by raising awareness of periodic medical examination. current study shows that 62 % respondents had the knowledge of periodic medical examination. among those, 54% practice and 46 % don't practice, although they know the importance of periodic medical examination. there is no significant difference in their knowledge due to their educational profession. as per figure 3 health education alone is not sufficient if health behavior is 14 not changed. the female respondents knew about periodical medical examination, but were not practice of periodic medical examinationjiimc 2017 vol. 12, no.2 118 3. wasay m, jabbar a. fight against chronic diseases (high blood pressure, stroke, diabetes and cancer) in pakistan; cost-effective interventions. 4. p a k i s t a n e c o n o m i c s u r v e y 2 0 1 4 1 5 . http://www.finance.gov.pk/survey_1415.html. 5. hyder aa, morrow rh. applying burden of disease methods in developing countries: a case study from pakistan. american journal of public health. 2000; 90: 1235-40. 6. drewnowski a, eichelsdoerfer p. can low-income americans afford a healthy diet? nutrition today. 2010; 44: 246-9. 7. chen mf. attitude toward organic foods among taiwanese as related to health consciousness, environmental attitudes, and the mediating effects of a healthy lifestyle. british food journal. 2009; 111: 165-78. 8. wang n, iwasaki m, otani t, hayashi r, miyazaki h, xiao l, et al. perceived health as related to income, socio-economic status, lifestyle, and social support factors in a middle-aged japanese. journal of epidemiology. 2005; 15: 155-62. 9. eke co, eke no, joe-ikechebelu nn, okoye sc. perception and practice of periodic medical examination by traders in south east nigeria. afrimedic journal. 2012; 3: 24-9. 10. jafar th, haaland ba, rahman a, razzak ja, bilger m, naghavi m, et al. non-communicable diseases and injuries in pakistan: strategic priorities. the lancet. 2013; 381: 2281-90. 11. world health organization. global status report on alcohol and health. 2014. 12. musa o, bamidele j, salaudeen a, saromi h, omi a. occupational hazard awareness and safety practices among cement factory workers at obajana, kogi state, nigeria. elixir bio-diversity. 2012; 47: 9013-8. 13. verbeek j, husman k, van dijk f, jauhiainen m, pasternack i, vainio h. building an evidence base for occupational health interventions. scandinavian journal of work, environment & health. 2004; 30: 164-8. 14. glanz k, rimer bk, viswanath k. health behavior and health education: theory, research, and practice. john wiley & sons. 2008; 28; 231-48. 15. oboler sk, prochazka av, gonzales r, xu s, anderson rj. public expectations and attitudes for annual physical examinations and testing. annals of internal medicine. 2002; 136: 652-9. 16. smith he, herbert cp. preventive practice among primary care physicians in british columbia: relation to recommendations of the canadian task force on the periodic health examination. cmaj: canadian medical association journal. 1993; 149: 1795-1800. 17. steptoe, andrew, jane wardle. "health behaviour, risk awareness and emotional well-being in students from eastern europe and western europe." social science & medicine. 2001; 53: 1621-30. practicing it. however these findings were not similar to other researches done with different 15 prospective in world wide. there are multiple reasons mentioned by respondents not to have periodic medical examination. 33 % respondents marked in appropriate knowledge about pme and few mentioned reasons like lack of facilities and cost of investigations. world health organization's annual 16 reports support this data. most of the respondents gave credit of knowledge for pme to the internet and f r i e n d s . m e d i c a l s t u d e n t s s e e m m o r e knowledgeable (68%) then non-medical students (61 %). although the medical students should be more aware of health behavior and risk awareness, as 17 concluded in other studies. it is clear sign that curriculum of all profession is lacking in providing knowledge on periodic medical examination. current study suggests that the periodic medical examination serves a purpose of screening for diseases and the awareness and practice of proven beneficial components of such examinations be increased among students. conclusion the present study concludes that awareness is present among medical and non-medical students, however the practices are low. there is no major difference between medical and non-medical students in terms of their knowledge and practice. periodic medical examination being a cost effective measure as compared to actual treatment expenses, should be practiced in routine by youth. efforts should be made by the government and other health agencies, especially students/youth representative societies to educate them on the periodic medical examination on regular basis especially for newly enrolled students. references 1. williams cl, hayman ll, daniels sr, robinson tn, steinberger j, paridon s, et al. cardiovascular health in childhood. circulation. 2002; 106: 143-60. 2. ghaffar a, reddy ks, singhi m. burden of noncommunicable diseases in south asia. bmj: british medical journal. 2004; 328: 807-10 practice of periodic medical examinationjiimc 2017 vol. 12, no.2 119 page 51 page 52 page 53 page 54 original�article abstract objective: to correlate maternal albumin levels with neonatal weight. study design: cross-sectional study. place and duration of study: the study was carried out in obstetrics and gynecology unit and laboratory of railway hospital, rawalpindi from june 2015 to march 2016. materials and methods: eighty-five mother -baby pairs were selected using systematic random sampling method, they were divided into two groups. group i included mothers with serum albumin level in the acceptable range (3.5-5.0) gm/dl and group ii included mothers with serum albumin level less than 3.5gm/dl. maternal venous blood was collected before delivery, serum was separated by centrifuge method. information regarding the monthly income and dietary protein was recorded from patients. quantitative in vitro determination of serum albumin was done by calorimetric biuret on photometric system. (micro lab).birth weight of neonates was assessed using the laica weighing scale. comparison of baby weight in group i and group ii was done by mann whitney u test. p-value of < 0.05 was considered significant. correlation of maternal albumin with baby weight was done by spearman correlation. results: in group i the median of 3.00 kg baby weight and in group ii the median of 2.30 kg baby weight. spearman correlatin showed a significant correlation coefficient between maternal albumin and baby weight with p value less than 0.05. conclusion: the weight of the babies born to mothers with serum albumin level < 3.5gm/dl was low as compared to the weight of the babies born to mothers with serum albumin level of (3.5-5.0 gm/dl). key words: animal protein, maternal albumin, mother baby pair, neonatal weight. blood plasma. it is soluble and is produced in the 3 liver. it has a major role in modulating the distribution of fluids between compartments and keeps the plasma inside the blood vessels, also causes transportation of molecules including fatty 3 acid to liver. albumin attaches to and carry bilirubin, drugs, thyroid hormone, it competitively binds with calcium, prevents photo degradation of folic acid and 4 helps maintain the blood acidity in a narrow range. increased dietary protein intake promotes the synthesis of more albumin and raises albumin levels 4 in the blood. albumin also has free radical scavenging ability. there is one free sulfhydryl group in albumin that reacts with thiol compounds and 5 reduces inflammation. during pregnancy one kilogram of extra protein is required with half going to the fetus and placenta and another half going to uterine contractile proteins, breast glandular tissue, 6 plasma protein, and haemoglobin. there is increased plasma volume by 50% and cardiac output 7 by 30-50% leading to low albumin level. increased water retention causes reduction in plasma 8 osmolality. it has been reported that poor nutrition of mother and low albumin level in late gestation was 9 associated with low birth weight in babies. this decreased birth weight is an important determinant introduction the rate of low birth weight neonates have increased in the recent years. metabolic demand increase in pregnancy. reduced dietary protein during pregnancy causes decreased maternal albumin and low weight of babies. nutritional reserves including 1 protein , and vitamins are low in these babies. reduced baby weight leads to neonatal mortality, morbidity, subsequent growth and developmental 1 retardation. in developing countries women living in poverty have poor albumin status and are at 2 increased risk of having low birth weight babies. identification before delivery of such mothers is important for the better outcome of babies. serum albumin is the most abundant protein in human correlation of maternal albumin levels with neonatal birth weight 1 2 3 erum rasheed chaudhry , zunnera rashid chaudhry , sana rasheed chaudhry correspondence: dr. zunnera rashid chaudhry assistant professor, pharmacology rawal institute of health sciences, islamabad 1 department of biochemistry islamic international medical college riphah international university, islamabad 2 department of pharmacology rawal institute of health sciences, islamabad 3 department of physiology post graduate medical institution, lahore funding source: nil; conflict of interest: nil received: jul 23, 2016; revised: aug 23, 2016 accepted: feb 05, 2017 meternal albumin and neonatal birth weightjiimc 2017 vol. 12, no.2 97 results table i shows 51 mothers in group i and 34 mothers in group ii. comparison of baby weight in group i and group ii was done by mann whitney u test which showed in group i the median iqr of baby weight was 3.00 (2.80-3.50) kg and in group ii the median iqr of baby weight was 2.30 (2.23-2.50) kg. this comparison showed a significant difference with p value less than 0.05. mann whitney u test indicated that increased maternal albumin causes increase in baby weight. table ii shows the correlation of maternal albumin with baby weight by spearman correlation showing rho value of 0.71 and indicating a significant correlation between maternal albumin and neonatal weight with p value less than 0.001. table iii shows that 40 % of women in group i were taking animal protein and 60% were taking non animal protein. in group ii 80% of women were taking animal protein and 20% were taking non animal protein. thus from the above results we can say that group i mothers with acceptable albumin level had improved baby weight as compared to group ii mothers with low albumin level and low baby weight. most mothers in group i were taking non animal protein while majority of mothers in group ii were taking animal protein. 10 of infant mortality and morbidity worldwide. low albumin level in neonates is associated with various adverse clinical conditions, including necrotizing 11 enterocolitis, and sepsis. diet rich in protein include meat, chicken , cheese, beans, lentils, milk , yogurt, 12 eggs, nuts, and seeds. if protein rich diet is given to the mothers during pregnancy it can improve the 13 weight of neonates. present study was conducted to find out the level of maternal albumin and its relation with neonatal weight. materials and methods this cross-sectional study was carried out in the obstetrics and gynecology unit and laboratory of railway hospital rawalpindi from june 2015 to march 2016. eighty-five mother -baby pairs were selected using systematic random sampling method. women of age more than 18 years and less than 45 years with single full term pregnancy based on fundal 14 height or naegele's rule. irrespective of any mode of delivery were included in our study. women with pregnancy complications including intrauterine g r o w t h r e t a r d a t i o n , p r e g n a n c y i n d u c e d hypertension, gestational diabetes mellitus, rh , abo incompatibility, sepsis or having twins or triplets at the time of delivery were excluded from the study. information regarding socio economic status, belonging to urban or rural area, dietary proteins, antenatal care ,delivery outcome were collected the birth weight of babies in kg was recorded using the 15 laica weighing scale. babies weighing < 2.5 kg were considered as low birth weight babies and those weighing ≥ 2.5 kg were taken as acceptable birth weight for this study. under aseptic technique two milliliters of maternal venous blood was collected and placed in vacutainer. sera were separated from maternal venous blood by centrifuging these blood samples at 5000 revolutions per minute (rpm) for five minutes. the sera were used to estimate maternal albumin in (gram/dl) by using calorimetric 15 biuret on photometric system. (micro lab). all sera collected was kept in a refrigerator at -20°c until the time of maternal albumin assay. statistical analysis was performed using statistical package for social science (spss) statistical software version 20, statistical significance was defined as a p value <0.05. correlation of maternal albumin with baby weight was done by spearman correlation method. table i: comparison of baby weight in group i and group ii by mann whitney u test group i = albumin level (3.5-5.0) gm/dl group ii= albumin level < 3.5 gm/dl ***p<0.05 is considered significant table ii: spearman correla�on of maternal albumin with baby weight (n=85) ***p<0.001 is considered significant table iii: frequency distribu�on of animal and non animal protein in both groups jiimc 2017 vol. 12, no.2 98 meternal albumin and neonatal birth weight 21 dairy products 80-90%, cereals and beans 60-70 %. animal products contain less protein as compared to dairy and vegetable products. animal products contain all the essential amino acid but not in the concentrated form as compared to vegetables and 21 beans. chris et al., 2007 in one of his study suggested that amino acids increased whole-body protein synthesis including albumin. albumin function as building blocks for bones, muscles, 22 cartilage, skin, blood, enzymes and hormones. according to neil osterweil., 2016 albumin is also 23 used for building and repairing tissues. it is seen in our study that neonates of the mothers of group ii had low weight, improving the maternal albumin level will increase the weight of neonates as albumin act as a building block for many structures of body and causes tissue growth and repair . in our study a positive correlation is seen between maternal albumin and neonatal weight indicating that increased maternal albumin is associated with increase in neonatal weight. the mothers belonging to low income class can easily buy the diet containing non animal proteins and had high albumin level indicating that vegetables and cereals proteins improves maternal albumin and neonatal weight more as compared to animal protein. conclusion it is seen that maternal albumin is directly proportional to neonatal weight and a positive correlation exists between maternal albumin and neonatal weight. for the better outcome of growth of neonates it is essential that mothers should be advised to take proper protein diet during pregnancy including cereals and vegetables in increased amount as compared to animal protein. this will improve the albumin of mother and weight of neonates preventing them from intrauterine neonatal stress and disease of fetal origin. references 1. krishna k, moniqa a, wahid a. umblical cord blood nutrients among low birth weight and normal birth weight babies in primary health care set up in lucknow india. general of biological and scientific opinion. 2013; 1: 300-3. 2. eltahir me, gerd s. the effect of maternal anthropometric characteristics and social factors on gestational age and birth weight in sudanese newborn infants. bmc.pub. h, 2008; 8: 244-51. 3. merlot am, kalinowski ds, richardson dr. unraveling the mysteries of serum albumin more than just a serum protein. discussion in the developing countries the relationship between maternal albumin and birth weight outcome of neonates is of major public health importance. in this study, majority of neonates and mothers had acceptable birth weight and maternal albumin respectively. similar observation was made by baba usman et al., 2010 who observed high percentage of mother-baby pair with acceptable maternal albumin levels and birth weight of babies. he further attributed that this high percentage is a good indicator not only of mother's health and nutritional status, but also of the good outcome for survival, growth, long-term health and psycho social 15 development of babies. in our study it was seen that neonates (34) in number had low weight and their mothers were having albumin level < 3.5 gm/dl. saleem,2014 in one of his study said that reduction in nutritional diet of mother causes intrauterine stress and disturbance of metabolic system leading to 16 reduction in baby weight. rucker et al.,2011.in one of his research said that health insults in utero may lead to greater physiological deterioration of 17 metabolic and immune systems. these less weight neonates develop many diseases in adult life, carlos et al., 2013 concluded that low baby weight and under-nutrition in utero causes adult diseases with 18 fetal origin. eriksson, 2005 said that neonates with low weight are at increased risk of obstructive lung disease, high blood cholesterol and renal 1 9 damage. betty et al., 2010 suggested that intrauterine stress also contribute to the risk of 20 increased blood pressure in later life. in our study neonates (51) in number had acceptable weight and their mother were having albumin level in the acceptable range 3.5-5.0 gm/dl. about 60% of these mothers were taking diet containing cereals , beans, milk, yogurt and vegetables frequently and fish, beef, mutton and chicken once a month. most of these mothers belonged to rural areas and had a monthly income of less than 50,000 pkr. the mothers with low albumin level mostly belonged to urban area and had monthly income of more than 50,000 pkr, 80% were frequently taking beef, mutton, chicken, potatoes in their diet and were seldom taking cereals, beans and vegetables. the percentage of usable protein in beef, meat and poultry is 20-40 %. vegetables 75-80%, rice 85-90%, jiimc 2017 vol. 12, no.2 99 meternal albumin and neonatal birth weight 14. basket tf, nagele f. nagele's rule: a reappraisal. british journal obsgynae. 2000; 107: 1433-35. 15. baba u, adebayo a, haruna n, usman j, kyari s. correlation of maternal albumin and birth weight of babies in a nigerian teaching hospital. international journal of public health and epidemiology. 2012; 1: 10-13. 16. saleem b, naveen s, michael p. immune responses in neonates. expert rev clin immunol. 2014; 10: 1171–84. 17. rucker c, robert f. early-life origins of adult disease: national longitudinal population-based study of the united statesamerican j public health. 2011; 101: 2317–24. 18. carlos a, marilia b. low birth weight: causes and consequences diabetology & metabolic syndrome. 2013; 5: 49-50. 19. eriksson jg. the fetal origins hypothesis-10 years.british medical journal. 2005; 330: 1096-97. 20. betty r, walter a, karol h, karen c, laura r. early predictors of hypertension in prematurely born adolescents. acta paediatr. 2010; 99: 1812–18. 21. www.nutribodyprotein.com/protein-types.php. 22. chris h, frans w, henk s, trinet r, darcos j, jan e, et. al. albumin synthesis in premature neonates is stimulated by parenterally administered amino acids during the first days of life. american journal of clinical nutrition.2007; 86: 1003-8. 23. neil osterweil. the benefits of protein. nutrional journal. 2016; 6: 24-6. journal of physiology. 2014; 15: 3580-95. 4. michael e, dietary protein, serum albumin and health 2007. https://proteinpower.com. 5. judy h. the role of albumin in fluid and electrolyte balance. journal of infusion nursing. 2006; 29: 260-5. 6. seong wj, chong go, hong dg, lee th, lee ys, cho yl, et.al. clinical significance of serum albumin level in pregnancyrelated hypertension.2010; 36: 1165–73. 7. thornburg kl, jacobson sl, giraud gd. hemodynamic changes in pregnancy. semin perinatol. 2000; 24: 11-4. 8. nancy f, william w, margarita s, kenneth j, brian s. energy requirements during pregnancy based on total energy expenditure and energy deposition. american journal clinical nutrition. 2004; 79: 1078-87. 9. stephenson t, symonds me. maternal nutrition as a determinant of birth weight. arch. dis. child. fetal. neonatal. 2002; 86: 4-6. 10. riza s. perinatal mortality and morbidity among low birth weight babies. international journal community med public health. 2015; 2: 51-8. 11. morris i, molly ej. albumin administration in the management of neonatal hypoalbuminaemia arch dis child fetal neonatal.2008; 93: 326. 12. elizabeth o. the best sources of protein for pregnant woman. 2014. www.livestrong.com. 13. fatemeh b,kambiz a, shanuak sk. milk and protein intake by pregnant women affects growth of foetus. journal health popul nutr. 2013; 31: 435–45. jiimc 2017 vol. 12, no.2 100 meternal albumin and neonatal birth weight page 32 page 33 page 34 page 35 review�article abstract atopic dermatitis (ad) is a long-lasting dermatological disease that is associated with ophthalmic complications in the long run. those having ad are more likely at risk of developing comorbidities in eye as compared to normal persons. this review encompasses the clinical manifestations, pathophysiology and treatment of common ophthalmic complications presented with ad i.e., blepharitis, kerato-conjunctivitis, corneal ectasias, glaucomatous eyes, lens opacification, detachment of retina, herpetic eye disease (hed) and dupilumab associated eye toxicities. it is necessary for dermatology colleagues to be vigilant enough not to miss ophthalmic problems associated with ad, as an early detection and management can save the vision. key words: atopic dermatitis, atopic keratoconjunctivitis, blepharitis, corneal ectasias, herpetic eye disease. course of the disease as compared to normal people, 2,3 with varying range of severities. notable ocular m o r b i d i t i e s i n c l u d e b l e p h a r i t i s , k e r a t o conjunctivitis, corneal ectasias, glaucomatous eyes, lens opacification, retinal detachments, herpetic eye 3 disease and dupilumab associated eye toxicities. the pathophysiological basis for these ocular morbidities is myriad and involves multiple mechanisms. innate immunity dysfunction, excessive eye rubbing due to itching, steroid induced ocular toxicities and genetic susceptibility all have 2 been implicated. some ocular conditions develop lately in the course of disease, while some presents acutely, however if not picked up early and managed appropriately can result in severe visual impairment. this review encompasses the clinical manifestations, pathophysiology and treatment of common ophthalmic problems associated with ad. blepharitis this inflammatory/infective lid margin disease affects approximately more than 5% of people with 2 ad as compared to normal people. it is divided into an anterior and posterior types, based upon the anatomical landmark of meibomian gland orifices at the lid margins. patient complains of ocular itching and irritation of the lids, watering of eyes, ocular grittiness or feeling of burning, lid crusts, and light 4 sensitivity. anterior blepharitis is mostly caused by staphylococci, while posterior one is secondary to meibomian gland dysfunction (mgd). though pathophysiology is still unclear, tissue desiccation in atopic patients is accompanied by barrier disruption and trans-epidermal desiccation, 4,5 causing eyelid dermatitis. introduction atopic dermatitis (ad) is a long-standing dermatitis with a disease burden ranging from 12% to 22% in 1 developed countries. it typically affects the face (cheeks), neck, arms, and legs but usually spares the groin and axillary regions. ad usually starts in early infancy, but it also affects number of adults. ad is commonly associated with elevated levels of immunoglobulin e (ig-e) resulting in allergic diathesis which may include food allergies, asthmatic events and atopic rhinitis in sequence referred as “atopic march” theory, which suggests that it is a part of progression that may lead to subsequent allergic 2,3 disease at other epithelial barrier surfaces. any age group can be affected but it predominantly affects adults in their second and third decade manifested as dry skin patches with itching that remits and exacerbates. primary physical findings include 2 xerosis, lichenification and eczema. recently, evidence have shown that ad can present with extra-cutaneous features. epidemiological surveys have revealed that an enormous proportion of patients develop ocular comorbidities in the ophthalmic complications associated with atopic dermatitis: a review 1 2 3 4 jamal hussain , shams ul haq , adnan ahmad , javed rasul correspondence: dr. adnan ahmed department of ophthalmology nowshera medical college, nowshera e-mail: dradnanahmad@hotmail.com 1,2 department of ophthalmology dhq hospital, timergara, lower dir 3 department of ophthalmology nowshera medical college, nowshera 4 department of ophthalmology pak international medical college, peshawar. received: july 07, 2022; revised: december 01, 2022 accepted: december 05, 2022 atopic dermatitis with ocular comorbidities: a reviewjiimc 2022 vol. 17, no.4 286 doi: https://doi.org/10.57234/1396 the conventional therapy of ad associated blepharitis consists of conventional lid-hygiene measures, such as warm compresses and gentle scrubbing of the lid margins to remove crust and debris, which can be done with non-prescription cleansers, lid-scrubs, and baby shampoos. acute flare needs topical antibiotics, topical calcineurin inhibitors (i.e., cyclosporine 0.05%), or low-strength 5 topical steroids. due to possible toxicities of medication especially topical steroids, ophthalmic consultation is mandatory for early diagnosis and treatment. kerato-conjunctivitis atopic kerato-conjunctivitis (akc) is a non-infectious inflammatory condition involving the corneal and conjunctival tissues with a prevalence ranging from 6,7 23% to 43% of patients with ad. mostly present in the late teens and peaks from the third to fifth 8 decade. the symptoms of akc include itching, red eyes, stringy mucous secretion, burning sensation, light sensitivity and decrease vision. long standing disease can cause corneal vascularization, punctate epithelial erosions and secondary bacterial keratitis, repeated corneal trauma can lead to scarring and 7 corneal blindness. pathophysiology of kerato-conjunctivitis involves inflammatory involvement of the conjunctiva by eosinophil, mast cells and other inflammatory cells. it has been reported in studies that patients having peri-orbital ad is linked with the development of severe form of atopic kerato-conjunctivitis, which in the long run can turn into development of entropion 7 if not properly mananged. eye consultation is very important in akc for its proper management in order to avoid ocular complications ultimately leading to 7.8 visual impairment. conservative measures include cool compresses and treatment with ophthalmic eye drops containing antihistamines (i.e., ketotifen 0.025%) and mast-cell inhibitors (i.e. olopatadine 8 0.2% drops). atopic kerato-conjunctivitis flare ups may require short-term use of topical steroids or calcineurin inhibitors, or systemic steroids/ immune6 suppressants for refractory cases. in the long run patients with akc needs maintenance therapy with long acting anti-inflammatory agents in the form of c a l c i n e u r i n i n h i b i t o rs w h i c h c o n t ro l s t h e inflammatory component of the disease without 8 having steroid induced complications. corneal involvement resulting from chronic inflammation requires steroids, calcineurin inhibitors, amniotic membrane grafting and in severe cases may need 7 limbal stem cell transplantation. keratoconus keratoconus (kc) is a non-inflammatory ectatic corneal disease characterized by slowly advancing ectasia and cone-like bulging of the cornea. corneal topography reveals changes in the thickness profile characteristic of kc along with irregular astigmatism depending upon the severity of condition clinically manifested as diminished vision with distorted 2,9 images. numerous studies have shown positive 10,11 link between kc and akc. the exact mechanism of kc development in akc is ambiguous and thought to be multi-factorial. excessive eye rubbing from peri-ocular itch and 12 irritation has been shown to be responsible for kc. furthermore, immune deregulation and altered synthesis of inflammatory mediators have also been 13 implicated in the causation of kc. kc is dynamic in its course with significant effect on visual acuity, making it imperative to detect it earlier on before its lead to severe visual impairment. certain risks predisposes the person to develop kc includes, akc, ad involving the lids, excessive eye rubbing and familial kc. any of these conditions make it prudent to seek ophthalmic consultation for 10,11,12 screening and visual assessment. early management of kc includes spectacles and rigid gas permeable (rgp) contact lenses for refractive correction. for severe kc, specially designed contact lenses are used. the rgp contacts are custom made lenses to vault over the ectatic 9 corneal surface. for moderate cases of kc without apical corneal scarring, a technique developed to strengthen the bond between the corneal collagen fibers to prevent its progressive thinning by using riboflavin and uv-a irradiation to make firm bonds between collagens in the corneal tissue, this is known as corneal cross linking. studies have shown its efficacy and safety in halting the progression of kc, especially if undertaken earlier in the disease, and has been given 9,10,11 fda approval in 2015. glaucoma glaucoma development is common during the therapy of ad and can cause irreversible damage to atopic dermatitis with ocular comorbidities: a reviewjiimc 2022 vol. 17, no.4 287 doi: https://doi.org/10.57234/1396 the nerve fiber layer of the retina and optic discs. steroids used in the treatment of ad is mainly 14 responsible for its causation. n u m e r o u s c a s e r e p o r t s h a v e a t t r i b u t e d glaucomatous risk to chronic use of high potency topical steroids in the peri-ocular areas, which is mainly responsible for it to direct absorption by ocular tissues, as glaucoma seldom develops with topical steroid application anywhere else in the 15-17 body. oral steroids (i.e. betamethasone) taken for more than 2 months is also associated with very high 18 intra-ocular pressure (iop). predisposing factors for raised iop, includes preexisting glaucoma, diabetes, connective tissue 15,19 disorders, and high myopes. steroid responders and younger lot also shows hypersensitivity to 20 steroids. as glaucoma progresses silently until advanced, earlier diagnosis is important from the management point of view. patients who are showing exaggerated clinical response (raised iop) to optimal dose of steroids as compared to normal individuals, patients on long standing steroids via different routes for their medical conditions and those having positive family history of glaucoma should be screened for 1 7 glaucoma assessment. in addition to that, individuals having simultaneous glaucoma and ad s h o u l d s e e k c o n s u l t a t i o n f r o m b o t h t h e ophthalmologist and dermatologist for their management, and preferably steroid sparing agents should be used in such cases to avoid steroid induced 21,22,23 complications. cataracts prevalence of cataract ranges from 6% to 23% with 21,24 ad. pre-senile cataracts are quite common in patients of ad, which can be attributed to both steroids use and disease process itself. cataract development can sometimes become abrupt and number of evidences from studies have shown it to 25,26 be associated with flare ups of ad. sub-capsular variants of cataract are quite common in ad, in contrast to nuclear and cortical ones, which 27,28 mostly effect normal elderly population. anterior sub-capsular cataract is more specific to ad, whereas posterior sub-capsular ones are specific to long27 standing steroids use in ad. younger age group are more prone to steroid induced cataract development with short duration of therapy and even less potent 29 ones as compared to elderly people. the patho-physiology of cataract development in ad is multi-factorial. evidence based scientific reports have shown that patients with ad have breached blood retinal barrier and high levels of free radicals in 30,31 the lens suggestive of oxidative damage. steroids in any form can cause cataract formation but mostly the oral form are strongly associated with cataractous changes in the lens, however steroids in the form of inhalers and topical creams/ointments 26,32 are also responsible for cataract development. patients with early onset peri-orbital ad, long standing steroids use, and positive family history need to be reviewed periodically. anterior and posterior sub-capsular lens opacities are detected with red-reflex assessment that can readily be 33 performed by the optometrists or ophthalmologist. retinal detachment retinal detachment (rd) is a vision threatening ocular comorbidity of atopic dermatitis that hits younger people more than 5 years old. the prevalence of rd in patients with ad is in the range 34 from 3% to 7%. patients with rd presents with loss of vision, photopsia, floaters and curtain like field 35,36 defects. many studies have reported that involvement of peri-orbital region by ad along with long standing history of eye rubbing is strongly associated with retinal detachment. rd is also accompanied with other ocular pathologies such as proliferative vitreo34retinopathy, ectopia lentis, and lens opacifications. 38 the underlying development of rd is thought to be due to ocular distortions from forceful ocular rubbings, also the morphological appearance of rd in ad-associated rd versus traumatic rd both are 37 characterized by retinal breaks at vitreous base. avoiding eye-rubbing and optimal therapy for periorbital ad can reduce the risk of developing rd. in addition to that, all patients with symptoms of rd should seek ophthalmic consultation. herpetic eye disease herpetic eye disease (hed) presents with potential ocular morbidity, as recurrent attacks can lead to corneal scarring and neo-vascularization. individuals with atopic dermatitis are more prone to develop severe herpetic ocular infection and mostly of atypical variants with more complication and refractory to conventional therapy as compared to atopic dermatitis with ocular comorbidities: a reviewjiimc 2022 vol. 17, no.4 288 doi: https://doi.org/10.57234/1396 38,39 normal indivisuals. additionally, atopic disorders are associated with frequent herpetic recurrences 38,39,40 leading to neurotropic keratitis . these observations suggests that atopic dermatitis patients with a prior hed should be carefully observed and treated with anti-virals and topical steroids in case of dendritic keratitis or topical steroids only in disciform keratitis, while for recurrences prophylaxis with acyclovir is needed for 39,40 few months. addionally, active hed warrants urgent ophthalmic consultation. dupilumab associated ocular complications dupilumab, is a monoclonal antibody that inhibits il6 and il-12 transduction pathways. it is one of the first biologics given approval for treatment of moderate to severe ad. some studies have reported a higher incidence of anterior conjunctivitis in dupilumab treated ad patients (6%–26%) compared 41 to placebo (1%–9%). surprisingly, the incidence 42 may go as high as 68%, reported in some literature. however, in some other studies it has been found that dupilumab given in asthmatics, nasal polyposis and eosinophilic-granulomas didn't show any rise in the incidence of dupilumab associated conjunctivitis in dupilumab treated patients when compared with control group, emphasizing upon an ad-specific 43 mechanism. main findings of dupilumab associated conjunctivitis includes conjunctival congestion and limbal hyperemia, along with eye symptoms such as watering, itching and blurring of vision. its use has been associated with reduced goblet cell density in conjunctiva on histological and spectroscopic 44 specimens. blepharo-conjunctivitis is also reported 45 in some literature due to dupilumab therapy. standard treatment protocol for dupilumab associated ocular complications hasn't yet been established. it is noteworthy that anti-histamine eyedrops are ineffective in the treatment of dupilumab 42 associated conjunctivitis. but, topical less potent steroids and tacrolimus ointment 0.03% has shown 41 some promising results in its management. lifitegrast, an immunosuppressant agent has been granted approval in the treatment of keratoconjunctivitis sicca, in patients who are resistant to 45 topical steroids. as a last resort, stopping of the therapy is the only way to get rid of therapy induced 43,44 ocular toxicities in ad patients. those taking dupilumab, who develop eye problems should seek ophthalmic consultation. recommendations dermatologists who are dealing with ad should be made aware of possible ocular comorbidities that develops in due course of time. they should be educated via conducting joint clinco-pathological sessions by increasing their knowledge with inputs from both the ophthalmologists and dermatologists, mutual clinical rotations of the postgraduate residents of both specialties, interdisciplinary and multidisciplinary approach towards managing such patients and making joint protocols/ guidelines for ad patients with liaison between both specialties. references 1. weidinger s, beck la, bieber t, kabashima k, irvine ad. atopic dermatitis. nat rev dis primers. 2018 jun 21; 4(1):1. doi: 10.1038/s41572-018-0001-z. pmid: 29930242. 2. govind k, whang k, khanna r, scott aw, kwatra sg. atopic dermatitis is associated with increased prevalence of multiple ocular comorbidities. j allergy clin immunol pract. 2019 jan; 7(1):298-299. doi: 10.1016/j.jaip.2018.10.009. epub 2018 oct 17. pmid: 30339855. 3. thyssen jp, toft pb, halling-overgaard as, gislason gh, skov l, egeberg a. incidence, prevalence, and risk of selected ocular disease in adults with atopic dermatitis. j am acad d e r m a t o l . 2 0 1 7 a u g ; 7 7 ( 2 ) : 2 8 0 2 8 6 . e 1 . d o i : 10.1016/j.jaad.2017.03.003. pmid: 28601391. 4. putnam cm. diagnosis and management of blepharitis: an optometrist's perspective. clin optom (auckl). 2016; 8:7178. 5. amescua g, akpek ek, farid m, et al. blepharitis preferred practice pattern®. ophthalmology. 2019; 126:p56-p93. 6. b i e l o r y b , b i e l o r y l . a t o p i c d e r m a t i t i s a n d keratoconjunctivitis. immunol allergy clin north am. 2010; 30:323-336. 7. guglielmetti s, dart jk, calder v. atopic keratoconjunctivitis and atopic dermatitis. curr opin allergy clin immunol. 2010; 10:478-485 8. chen jj, applebaum ds, sun gs, et al. atopic keratoconjunctivitis: a review. j am acad dermatol. 2014; 70:569-575. 9. andreanos kd, hashemi k, petrelli m, et al. keratoconus treatment algorithm. ophthalmol ther. 2017; 6:245-262. 10. rahi a, davies p, ruben m, et al. keratoconus and coexisting atopic disease. br j ophthalmol. 1977; 61:761-764. 11. gasset ar, hinson wa, frias jl. keratoconus and atopic diseases. ann ophthalmol. 1978; 10:991-994. 12. bawazeer am, hodge wg, lorimer b. atopy, and keratoconus: a multivariate analysis. br j ophthalmol. 2000; 84:834-836. 13. galvis v, sherwin t, tello a, et al. keratoconus: an inflammatory disorder? eye (lond). 2015; 29:843-859. atopic dermatitis with ocular comorbidities: a reviewjiimc 2022 vol. 17, no.4 289 doi: https://doi.org/10.57234/1396 14. clark af, wordinger rj. the role of steroids in outflow resistance. exp eye res. 2009; 88:752-759. 15. daniel bs, orchard d. ocular side-effects of topical corticosteroids: what a dermatologist needs to know. australas j dermatol. 2015; 56:164-169. 16. garrott hm, walland mj. glaucoma from topical corticosteroids to the eyelids. clin exp ophthalmol. 2004; 32:224-226. 17. aggarwal rk, potamitis t, chong nh, et al. extensive visual loss with topical facial steroids. eye (lond). 1993; 7(pt 5):664-666. 18. mandapati js, metta ak. intraocular pressure variation in patients on long-term corticosteroids. indian dermatol online j. 2011; 2:67-69. 19. jones r 3rd, rhee dj. corticosteroid-induced ocular hypertension and glaucoma: a brief review and update of the literature. curr opin ophthalmol. 2006; 17:163-167. 20. tamagawa-mineoka r, yasuoka n, ueta m, et al. influence of topical steroids on intraocular pressure in patients with atopic dermatitis. allergol int. 2018; 67:388-391. 21. bercovitch l. screening for ocular complications in atopic dermatitis. arch dermatol. 2011; 147:588-589. 22. abramovits w, hung p, tong kb. efficacy and economics of topical calcineurin inhibitors for the treatment of atopic dermatitis. am j clin dermatol. 2006; 7:213-222. 23. takakuwa k, hamanaka t, mori k, et al. atopic glaucoma: clinical and pathophysiological analysis. j glaucoma. 2015; 24:662-668. 24. haeck im, rouwen tj, timmer-de mik l, et al. topical corticosteroids in atopic dermatitis and the risk of glaucoma and cataracts. j am acad dermatol. 2011; 64:275-281. 25. amemiya t, matsuda h, uehara m. ocular findings in atopic dermatitis with special reference to the clinical features of atopic cataract. ophthalmologica. 1980; 180:129-132. 26. tatham a. atopic dermatitis, cutaneous steroids and cataracts in children: two case reports. j med case rep. 2008; 2:124. 27. chew m, chiang pp, zheng y, et al. the impact of cataract, cataract types, and cataract grades on vision-specific functioning using rasch analysis. am j ophthalmol. 2012; 154:29-38. 28. nagaki y, hayasaka s, kadoi c. cataract progression in patients with atopic dermatitis. j cataract refract surg. 1999; 25:96-99. 29. kaye ld, kalenak jw, price rl, et al. ocular implications of long-term prednisone therapy in children. j pediatr ophthalmol strabismus. 1993; 30:142-144. 30. matsuo t, saito h, matsuo n. cataract and aqueous flare levels in patients with atopic dermatitis. am j ophthalmol. 1997; 124:36-39. 31. namazi mr, handjani f, amirahmadi m. increased oxidative activity from hydrogen peroxide may be the cause of the predisposition to cataracts among patients with atopic dermatitis. med hypotheses. 2006; 66:863-864. 32. james er. the etiology of steroid cataract. j ocul pharmacol ther. 2007; 23:403-420. 33. lambert sr, teng jmc. assessing whether the cataracts associated with atopic dermatitis are associated with steroids or inflammatory factors. jama ophthalmol. 2018; 136:918-919. 34. sasoh m, mizutani h, matsubara h, et al. incidence of retinal detachment associated with atopic dermatitis in japan: review of cases from 1992 to 2011. clin ophthalmol. 2015; 9:1129-1134. 35. yoneda k, okamoto h, wada y, et al. atopic retinal detachment. report of four cases and a review of the literature. br j dermatol. 1995; 133:586-591. 36. gnana jothi v, mcgimpsey s, sharkey ja, et al. retinal detachment repair and cataract surgery in patients with atopic dermatitis. eye (lond). 2017; 31:1296-1301. 37. oka c, ideta h, nagasaki h, et al. retinal detachment with atopic dermatitis similar to traumatic retinal detachment. ophthalmology. 1994; 101:1050-1054. 38. prabriputaloong t, margolis tp, lietman tm, et al. atopic disease and herpes simplex eye disease: a populationbased case-control study. am j ophthalmol. 2006; 142:745749. 39. borkar ds, gonzales ja, tham vm, et al. association between atopy and herpetic eye disease: results from the pacific ocular inflammation study. jama ophthalmol. 2014; 132:326-331. 40. rezende ra, hammersmith k, bisol t, et al. comparative study of ocular herpes simplex virus in patients with and without self-reported atopy. am j ophthalmol. 2006; 141:1120-1125. 41. wollenberg a, ariens l, thurau s, et al. conjunctivitis occurring in atopic dermatitis patients treated with dupilumab-clinical characteristics and treatment. j allergy clin immunol pract. 2018; 6:1778-1780.e1. 42. ivert lu, wahlgren cf, ivert l, et al. eye complications during dupilumab treatment for severe atopic dermatitis. acta derm venereol. 2019; 99:375-378. 43. akinlade b, guttman-yassky e, de bruin-weller m, et al. conjunctivitis in dupilumab clinical trials [published online march 9, 2019]. br j dermatol. doi:10.1111/bjd.17869. 44. bakker ds, ariens lfm, van luijk c, et al. goblet cell scarcity and conjunctival inflammation during treatment with dupilumab in patients with atopic dermatitis. br j dermatol. 2019; 180:1248-1249. 45. zirwas mj, wulff k, beckman k. lifitegrast add-on treatment for dupilumab-induced ocular surface disease (diosd): a novel case report. jaad case rep. 2019; 5:34-36. atopic dermatitis with ocular comorbidities: a reviewjiimc 2022 vol. 17, no.4 290 doi: https://doi.org/10.57234/1396 conflict of interest authors declared no conflicts of interest. grant support and financial disclosure authors have declared no specific grant for this research from any funding agency in public, commercial or nonprofit sector. data sharing statment the data that support the findings of this study are available from the corresponding author upon request. this is an open access article distributed under the terms of the creative commons attributionnoncommercial 2.0 generic license. atopic dermatitis with ocular comorbidities: a reviewjiimc 2022 vol. 17, no.4 291 doi: https://doi.org/10.57234/1396 original�article abstract objective: to evaluate the safety and efficacy of parental iron therapy to treat iron deficiency anemia in malnourished children. study design: quasi experimental design. place and duration of study: stabilization centre, children hospital and the institute of child health, multan st st from 1 december 2014 to 31 december 2020. materials and methods: a total of 250 malnourished children with iron deficiency were included in the study. the laboratory parameters i.e., hemoglobin, hematocrit, red blood cells count, mean corpuscular hemoglobin, mean corpuscular volume, and serum ferritin of all patients were done. using the iron deficit formula, all participants were given the measured iron sucrose complex. the iron sucrose complex was diluted with 0.9% normal saline and administered steadily for 3-4 hours. after 6 weeks of therapy, hemoglobin, rbc count , ferritin was measured. comparison of mean ±sd of baseline laboratory parameters and after 6 weeks of iron supplementation was analyzed by using t-test. results: a total of 250 participants were registered, male patients (57.2%) were more than female patients (42.8 %). most of the 92(36.8%) participants were 12-24 months old. the key cause of anemia among 102(40.8%) admitted patients was inadequate diet or excessive milk consumption. the mean ±sd value of the hb level at admission was 7.5±1.9 and it increased to 11±1.15g/dl after 6 weeks of active supplementation which is statistically significant (p-value < 0.05). six weeks after giving intravenous iron therapy mean serum ferritin increased from 11.5ml to 21.61 ng/ml. conclusion: current study concluded that controlled administration of iv iron sucrose for treatment of iron deficiency anemia among inpatients is efficacious and safe. iv iron sucrose should be considered for patient with severe ida, those who are not compliant with oral formulations, and patients with malabsorption. key words: hemoglobin, intravenous iron sucrose, iron deficiency anemia, red blood cells, severe acute malnutrition, serum ferritin. deficiency anemia is prevalent in children up to 63% in pakistan. according to pakistan national nutritional survey 2018, 17% children were wasted, 24% children were stunted and 31% were 1 underweight. anemia is interpreted as a low red blood cell concentration along with low hemoglobin, or hematocrit, in a routine blood test. the main causes of iron deficiency anemia are poor infant and young child feeding practices (iycf) practices, poor diet, and consumption of over diluted milk and worm infections. poor serum iron concentration in blood can lead to growth failure, developmental delay, behavioral and cognitive issues, learning disabilities 2-5 and immune dysfunction. oral iron therapy is the global standard for the 6 management of anemia. it is mostly well tolerated by well-nourished children but in under-nourished children particularly severe acute malnutrition ( sa m ) c h ild ren b o d y u n d ergo es red u c t ive introduction protein energy malnutrition is a prime concern of developing countries, and it is often linked with iron deficiency anemia (ida) among children. iron parental iron therapy to treat iron deficiency anemia in malnourished children 1 2 3 4 5 6 7 saadia khan , imran iqbal , asad abbas , reema arshad , ibad ali , sabeeha khan , adan ijaz correspondence: reema arshad research associate department of pediatrics and child health, aga khan university karachi e-mail: reemaarshad0@gmail.com 1,5 2 department of preventive pediatrics/department of medicine the children's hospital and the institute of child health, multan 3 department of human nutrition bahauddin zakariya university, multan 4 department of pediatrics and child health, aga khan university karachi 6 department of pediatrics medicine dhq hospital, multan 7 department of nutrition and dietetics, multan medical and dental college , multan. received: august 25, 2021; revised: december 04, 2022 accepted: 06, december 2022 parental iron therapy and iron deficiency anemia jiimc 2022 vol. 17, no.4 239 doi: https://doi.org/10.57234/691 a d a ptat i o n s , g u t a bs o r pt i ve a b i l i t i e s a l s o 7,8 compromised. previous studies suggested that iron supplementation by malnourished children mostly presents with complications of diarrhea and vomiting that leads to poor compliance of iron in children with severe acute malnutrition which may 6,8 be especially due to git dysfunction. moreover, young children are non-compliant with the oral iron supplements, therefore, other alternatives such as the parenteral route of iron administration must be sought. for decades parenteral iron has been used to treat iron deficiency unresponsive to oral iron therapy. iron preparations, including low molecular weight (lmw) iron dextran, iron sucrose, ferric gluconate, and the newest formulation, ferumoxytol, have generally replaced hmw iron dextran for use in both adults and children with chronic kidney disease due 7 to their more favorable safety profiles. intravenous (iv) iron sucrose was approved by the fda in 2000 for patients. iron sucrose has been reported to be safe and effective in adults with iron deficiency due various non-renal causes, including pregnancy or 9 inflammatory bowel disease. blood transfusions is not a solution to overcome this problem in children particularly with mild and moderate anemia with low 9 iron residues. previous studies documented that iv iron sucrose therapy can help in improving hb level to a variable extent. previous international as well as national studies documented that intravenous (iv) iron therapy is safe for the management of anemia in 10-14 children. a study conducted at ben-gurion university of the negev, israel showed hemoglobin (hb) rise to 9.27±1.23g/dl with intravenous (iv) iron sucrose therapy in children with iron deficiency anemia ida. unfortunately, some adverse effects 15 have limited its use in children. to this date, only a few studies from pakistan have emerged evaluating the safety and efficacy of parental iron therapy in malnourished children. hence, the current study will have significant clinical implications enhancing our understanding and our capability to tackle the malnourished children with iron deficiency anemia. so current study was planned to evaluate the safety and efficacy of parental iron therapy to treat iron deficiency anemia in malnourished children. this study will help establish the usefulness of intravenous iron sucrose in malnourished children with anemia in resourceconstrained countries like pakistan. materials and methods this was a quasi-experimental study conducted in preventive pediatrics department children hospital st and the institute of child health, multan from 1 st january 2014 to 31 december 2020. registration of patients was started after taking approval from institutional ethical committee (ref. no. 794, dated: 16.12.2013). simple convenient sampling technique was used. informed consent was taken from parents and guardians after explaining risk and benefits of iv iron therapy. a total of 250 participants were registered in current study by fulfilling inclusion criteria i.e., all the children were included with age group 1 year to 5 years with primary severe acute malnutrition (sam) with wt/ht z-score <-3sd or muac 11.5cm or presence of any bilateral pedal edema and/or primary moderate acute malnutrition (mam) children wt/ht z-score <-2sd or muac 11.512.5 cm with anemia categorized as: serum hb levels 6-10g/dl was classified as anemic, 6-8g/dl was classified as moderate anemic, 8-10g/dl was classified as mild anemic and <6g/dl was categorized as severely malnourished and serum ferritin levels <20ng/ml. exclusion criteria was defined as critically ill children with anemia less than 6g/dl and any previous iron therapy during last 3 months, hemolytic anemia, those who refused consent, children with chronic illnesses or secondary malnutrition. a planned questionnaire was designed by trained medical staff and required variables were noted. the laboratory parameters i.e., hemoglobin, hematocrit, red blood cells count, serum ferritin, mean corpuscular hemoglobin, mean corpuscular volume of all patients were done once at admission and again 6 weeks after the intervention. injectable iron is available in 5ml ampule that contains 100mg of iron in it. dose of iv iron was 10 calculated by using following standard formula normal hb levels for age-initial hb levels ×body blood volume× 3.4×1.5 100 here:3.4 is converting factor for hb in mg of iron,1.5 is constant to replenish iron stores and 80ml/kg blood volume. derived dose from formula was injected 2ml/day for parental iron therapy and iron deficiency anemia jiimc 2022 vol. 17, no.4 240 doi: https://doi.org/10.57234/691 consecutive two days but not more than 3ml/day was given. after proper available aseptic measures calculated dose diluted in 100ml normal saline in peds chamber with precautions and cannot comixed with other medications and tpn. unlike other forms of injectable iron viable of anaphylactic reaction are minimum with iron sucrose but were not overloaded. so, test doze was given initially over 15 minutes for any reaction. required calculated dose added to 100 ml normal saline with the help of infusion pump. 100 ml fluid was adjusted over 4 hours. after 15 minutes infusion stopped and assessed for any reaction for 30 minutes. if no anaphylactic reaction occurs in 15 minutes infusion was started again. hypotension, anaphylaxis, nausea, vomiting, diarrhea, abdominal pain, headache, edema, muscle cramps, fatigue and dizziness were common side effects of iv iron that were monitored throughout the infusion. post and parental iron sucrose therapy was started and changes in ferritin levels were accurately measured within 48 hours even. data shows 18-68% iv iron 2 dose incorporated into erythrocytes within 2 weeks. after completion of initial dose over two consecutive days, mms (multi micronutrient sachet) with iron content one per day was started. after 15 days repeat samples of cbc and serum ferritin was sent and compared with initial baseline levels. all the patients turned up for follow up and no lapse was noted. comparison of mean ±sd of baseline laboratory parameters and after 6 weeks of iron supplementation was analyzed by using t-test. after completion of study duration, this data was entered in spss version 21.0 for analysis. frequency distribution of qualitative variables was done. descriptive statistics was applied to analyze the significance of study. mean comparison of quantitative variables was analyzed by using t-test and p-value less than 0.05 was considered as statistically significant. results a total of 250 malnourished patients were enrolled in present study, from which 150(60%) patients were severely malnourished and 100(40%) were moderately malnourished. male/female was 1.3:1. male participants (57.2%) were more than female participants (42.8%). the majority of 92(36.8%) participants belonged to 12-24 months, followed by 72(28.8%) from age group 36-48 months and 47(18.8%) were from age group 36-48 months respectively (table ii). table i: gender, age and nutritional status distribution of all participants ( n= 250) mam: moderate acute malnutrition, sam: severe acute malnutrition the feeding history and diagnosis of admitted patients was noted in table ii. most of the participants were on mother feed along with formula feed after birth (39.2%) and only 23.2% admitted patients were exclusively on breast milk and 37.6% were on formula milk only. poor diet or excessive milk intake was the major cause of anemia among 102(40.8%) admitted patients and another reason behind anemia was mal absorption in 58(23.2%). table ii :feeding history and diagnosis at the time of admission iycf: infant and young child feeding practices severe acute malnutrition with edema was present in 13.3% enrolled subjects and without edema was observed in 86.67% enrolled subjects. anemic status (moderate and severe anemia) compared to nutritional status of admitted patients was statistically significant as p-values was <0.05 analyzed (table iii). parental iron therapy and iron deficiency anemia jiimc 2022 vol. 17, no.4 241 doi: https://doi.org/10.57234/691 common side effects were analyzed of all studied participants; fever was highly prevalent in 25(10%) patients (table v) therefore, it is imperative that iron deficiency anemia should be treated promptly and effectively, more so in malnourished children. some children with severe acute malnutrition may be intolerant, non-complaint or non-responsive to oral iron therapy. as blood transfusion carries some hazards, parenteral iron therapy was assessed for its safety as well as efficacy in malnourished iron deficient children. current study reported that iv iron sucrose in pediatric patients with ida leads to clinical meaningful and statistically significant increases in hemoglobin, rbcs, mch, and serum ferritin. we carried out this study in malnourished children who were having iron deficiency anemia current study reported children were 60% severely malnourished and 40% were moderately malnourished. similar trends were also observed in another study, where 79% children were severely malnourished and were intolerant, non-compliant or unresponsive to oral 11 iron therapy. all these patients were treated for malnutrition according to who guidelines in 13 addition to intravenous iron therapy. male were prominent participants of our study. another study also shares the same results where male 12 outnumbered than females. the significant cause of anemia among 40% admitted patients was poor iycf practices, excessive milk intake 35.6% and celiac disease 14.8%. while similar findings suggested that most of the participants were on mother feed along with formula feed after birth (39.2%) and only 23.2% admitted patients were feeding exclusively mother milk and 16 37.6% were feeding only formula milk. this study revealed that serum hb levels improved up to 11±1.15g/dl by intravenous iron sucrose therapy. another national study documented that parenteral iron sucrose therapy improved mean hb level from 6.65±0.65g/dl to 10.35±1.17g/dl in 14 malnourished children with ida. a pakistani study reported hb rise to 9.21±1.13g/dl with iv iron 10 sucrose therapy. these findings were lower than current study however they also concluded that iv iron sucrose therapy in malnourished children with 6,17 ida is safe and efficient. an international study conducted at ben-gurion university of the negev, israel showed hemoglobin (hb) rise to 9.27±1.23g/ dl with intravenous (iv) iron sucrose therapy in 15 children with ida. current study reported that iv table iii: distribution of anemia according to nutritional status (n=250) mean ±sd value of hb level was 7.5±1.9 at admission and it improved up to 11±1.15g/dl after successful supplementation of 6 weeks. mean levels of hb, rbcs count, mch and ferritin levels was significantly correlated (table iv). table iv: comparison of base line and after 6 weeks laboratory parameters (n=250) table v: common side effects observed in studied subjects discussion iron deficiency anemia has a significant impact on health and survival of children under five years of age. it is the leading cause of global burden of 1 disease. according to unicef report 2020, over 149 million children less than 5 years of age in developing 11 countries have significantly impaired growth. parental iron therapy and iron deficiency anemia jiimc 2022 vol. 17, no.4 242 doi: https://doi.org/10.57234/691 iron sucrose in pediatric patients with ida leads to clinical meaningful and statistically significant increases in hemoglobin, rbcs, mch, and serum ferritin. similar findings were also reported by kaneva et al., 2017 where significant association with hemoglobin, ferritin and iron therapy was 16 documented. a rise in posttreatment hemoglobin levels implies that erythropoietic recovery is achieved with intravenous iron sucrose which also 16,18 strengthens the findings of our study. the most common side effect in our study is fever 10% whereas the study by mantadakis et al. reported the most common adverse effect of parental iron to be injection site extravasation followed by a 19 transient alteration in taste. papadopoulos et al. found that rash following infusion and the urticarial rash was a common adverse effect following 20 therapy. no side effects were noted in children during follow up and the objective of follow up was to analyze hematocrit profile only. iron sucrose complex therapy appears to be highly 21 and rapidly effective without major side effects. this makes it convenient and cost effective in iron deficient, malnourished children. we followed-up patients till 6weeks for study purpose but we recommend further trials with prolonged follow-ups to rectify the ida completely and achieve normal hemoglobin level. it should be emphasized that iron deficiency even without a n e m i a s h o u l d b e p r e v e n t e d b e f o r e i t s development. in other words, to treat patients when they become anemic is too late. conclusion c u r r e n t s t u d y c o n c l u d e d t h a t c o n t r o l l e d administration of iv iron sucrose for treatment of iron deficiency anemia among inpatients is efficacious and safe. iv iron sucrose should be considered for patient with severe ida, those who are not compliant with oral formulations, and patients with malabsorption. references 1. national nutrition survey 2018. planning commission, planning and development division government of pakistan. 2. allali s, brousse v, sacri as, chalumeau m, de montalembert m. anemia in children: prevalence, causes, diagnostic work-up, and long-term 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children with iron deficiency anemia. parental iron therapy and iron deficiency anemia jiimc 2022 vol. 17, no.4 243 doi: https://doi.org/10.57234/691 professional med j 2020; 27(9):1867-1871. doi: 10.29309/tpmj/2020.27.09.4107 19. mantadakis e, tsouvala e, xanthopoulou v, chatzimichael a. intravenous iron sucrose for children with iron deficiency anemia: a single institution study. world j pediatr 2019; 12(1): 109-13. 20. papadopoulos m, patel d, korologou-linden r, goto e, soondrum k, fell jm, et al. safety and efficacy of parenteral iron in children with inflammatory bowel disease. br j clin pharmacol 2018; 84(4): 694-9. 21. khan ms, khan a, hussain u, khan a, tahir m, bilal m, et al. effectiveness and safety of intravenous iron sucrose therapy in children with iron deficiency anemia. lnjpc 2022; 4(1): 2-5. conflict of interest authors declared no conflicts of interest. grant support and financial disclosure authors have declared no specific grant for this research from any funding agency in public, commercial or nonprofit sector. data sharing statment the data that support the findings of this study are available from the corresponding author upon request. this is an open access article distributed under the terms of the creative commons attributionnoncommercial 2.0 generic license. parental iron therapy and iron deficiency anemia jiimc 2022 vol. 17, no.4 244 doi: https://doi.org/10.57234/691 original�article abstract objective: to study the histomorphological changes in cerebellar purkinje cells after exposure to fine particulate matter in c57bl/6j mice. study design: laboratory based experimental study. place and duration of study: the study was conducted in the anatomy department of the army medical college, rawalpindi, from 15 june to 15 september 2020, in coordination with the military hospital, rawalpindi, and the national institute of health (nih), islamabad. materials and methods: thirty male and female c57bl/6 mice, 8 weeks of age, weighing 37± 2 gm were obtained from nih, islamabad. the animals were divided in two groups, 15 mice in each group (8 male and 7 female) group a were marked as control, received regular diet and water ad libitum. group b (experimental group) received dynamic inhalation of 3mg/m³ fine particles (soot) through air circulation for 6h/d for 12 weeks, in plastic cabin measuring 2x2x2 feet fitted with two small fans for evenly distribution of particulate matter. after exposure period, the animals were sacrificed. after sectioning the tissue and staining, the microscopic analysis was carried out. purkinje cell margins were evaluated. number of purkinje cells and changes in purkinje cell size were noted. data was collected, analyzed with the statistical package for social sciences version 23. a p value ≤ 0.05 was considered significant. result: the purkinje cell margins were observed to become irregular and corrugated in the experimental groups b when compared with control group a. the number and size of purkinje cells also showed difference when compared to the control group a. conclusion: the present study concluded that fine particulate matter induces changes in histomorphological features of mice cerebellar tissue including purkinje cells. key words: air pollution, cerebellum, fine particulate matter, purkinje cells. particulate matter is responsible for more damage to 3,4 human health as compared to ground level ozone. aerodynamic diameter is usually known as particulate matter (pm), ranging from coarse (between 2.5 and 10μm pm10) to fine (<2.5μm pm2.5) to ultrafine (<100nm or 0.1μm; ufp). ambient ufps, which result mainly from ignition processes, include the burning of fossil fuels, has primary source in the form of automobile 5 , 6 emissions. in several parts of the world, atmospheric air quality remains a most important concern, despite attempts to regulate atmospheric pollutant pollution. total percentage of world's population exposed to pollutant concentrations above the recommended level of the world health organization (who) is more than eighty percent and from household related sources it accounts for about 4 million and about 3.6 million deaths can be due to environmental air pollution. in addition, air pollution can alter habitats, destroy constructions and introduction air pollution is a major public concern that has adverse health and economic effects. fine particulate matter containing many chemical components within these gradients, which can differ dynamically with time and space and with an aerodynamic diameter of < 10μm, is often associated with air pollution in large cities. the presence of to study the histomorphological changes in cerebellar purkinje cells after exposure to fine particulate matter in c57bl/6j mice 1 2 3 4 5 saima saleem , shabnam hamid , abdul basit jilani , sana malik , saima mumtaz khatak correspondence: dr. saima saleem department of anatomy federal medical college, islamabad e-mail: dr.saimasaleem.75@gmail.com 1,4,5 department of anatomy federal medical college, islamabad 2 department of anatomy army medical college, nums, rawalpindi 3 department of atmospheric dispersion modeling and experimentation group, pieas, islamabad. received: august 11, 2022; revised: june 07, 2023 accepted: june 09, 2023 jiimc 2023 vol. 18, no. 2 fine particulate matter exposure in c57bl/6j mice 109https://doi.org/10.57234/jiimc.june23.1495 memorials, as well as affect the energy balance of 7 the planet and thus causes change in climate. pm can be released directly into the atmosphere, called primary pm or it can be produced from gaseous precursors known as secondary pm. the scale of pm ranges from groups of molecules with a diameter of a few nanometers up to abrasion products of a micrometer. in the varying composition and characteristics of pm measured at source and receptor sites, this large dimensional range is expressed. particulate matter species are important atmospheric components and play a role in the climate system of the earth. some components of pm species absorb visible light and make the atmosphere warm i.e. black carbon, while other species, i.e. organic substances and sulphates reflect 8 sunlight back into space and cool the environment. air pollution is a multidimensional environmental toxin which through various pathways can attack the cns. inflammation and oxidative stress have been re co g n i ze d a s t h e co m m o n a n d e s s e nt i a l mechanisms by which air pollution causes harm, including adverse effects in the cns. it is known that black carbon can cause inflammation or that exposure to particulate matter in mice induces the development of pro-inflammatory cytokines (il1-b, 9,10 tnfa, and ifng) in olfactory bulbs. when neuroinflammation has started, it causes neuron damage and loss, stimulates microglia, leading to cytokine and ros production, and causes damage and dysfunction of the blood brain barrier. both of these events contribute to lipid peroxidation, 11 astrogliosis, and damage to dna and cns diseases. epidemiological studies have linked air pollution with cognitive impairments reduced mental development index and iq scores, attention-related disorders, anxiety/depression , nonverbal reasoning deficits, autism spectrum disorder (asd) and delayed psychomotor development. programmed cell death, or apoptosis, is an evolutionarily conserved process 12 triggered by a variety of stimuli. exposure to pm has been associated with neuronal shrinkage, micro 1 abscesses, and cerebellar edema. studies have focused the histological effect of fine particulate matter on multiple organs for example lungs, heart, nasal mucosa, maternal exposure, and some components of brain. despite considerable literature there is still a need for studies, which should investigate the histomorphological changes in brain because of rapidly increasing rate of dispersion of air pollutants, especially in the developing country like pakistan. so, a research was planned to study the histomorphological changes in cerebellar purkinje cells after exposure to fine particulate matter in c57bl/6j mice. materials and methods this study was conducted in rawalpindi, department of anatomy, army medical college, in collaboration with the national institute of health (nih), islamabad, from june 2020 to september 2020, after getting approval by the army medical college, rawalpindi, and the national university of medical sciences, islamabad, ethical review committee (erc/ id/ 10). laboratory based experimental study was carried out and non-probability convenience sampling technique was used. thirty male and female c57bl/6 mice, 8 weeks of age, weighing 37± 2 gram were procured from nih, islamabad. they were kept in separate cages in animal house of nih under standard laboratory conditions with temperature 22 ± 2° c and 12-hour light/dark cycle. the animals were fed on standard laboratory rat chow and water ad libitum. mice with any obvious injury and disease were excluded. the animals were divided in two groups, 15 mice in each group (8 male and 7 female). group a served as control. they received standard diet and water ad libitum. group b (experimental group). mice in experimental group b received dynamic inhalation of 3mg/m³ fine particles in the form of carbon soot through air 13, 14 circulation for 6h/d for 12 weeks. 15 mice (8 males and 7 females) in two separate cages were placed in a plastic cabin measuring 2x2x2 feet fitted with two small fans opposite each other in nih islamabad. air circulation was maintained by fan running at moderate speed. the particulate matter was evenly 15, 16 dispersed in the cabin through fan. the dose of particulate matter was calculated in mg/number of breaths in one minute. the dose was weighed by using digital precision balance. fine particulate matter was purchased from amazon.com. the particle name was carbon powder with normal sensitivity and refractive index of 2.4. the size of the particle ranged from 0.020 to 2000.000µm with 2 specific surface area of 0.555m /g. at the end of 03 months, after 18hrs of last exposure the animals jiimc 2023 vol. 18, no. 2 fine particulate matter exposure in c57bl/6j mice 110 https://doi.org/10.57234/jiimc.june23.1495 were euthanized by placing the animals in the jar 17 with cotton soaked in ether. the animals were positioned on a dissecting board and decapitated by cutting the neck close to the head with the help of a sharp blade. skin of the skull was removed by giving a longitudinal incision in the midline of the head. with the help of a bone cutter the cranium was opened along the sagittal suture and the bones were cracked open by using a forceps in the center. brain was exposed and carefully lifted at its anterior end. optic nerves were identified, and brain was separated from them and removed from the cranium by detaching from the spinal cord. the brain was placed on the dissection board and the cerebellum was identified. the cerebellum was separated from the cerebrum by locating and cutting through the layer of duramater (tentorium cerebelli) between the two. the middle cerebellar peduncle was identified, and the cerebellum was separated from the brain stem by cutting through this peduncle. after washing the specimens with normal saline, the entire cerebellum was put into 10% formalin enough to cover all the tissue (about 3times the volume of tissue). from each cerebellum, splitting it into upper and lower halves, three transverse sections were obtained. all parts have been stored in tissue tek cassettes and processed in the automated tissue processor leica tp 1020. sections were processed and cleared in xylene through the rising concentration of alcohol from 70 percent to 100 percent. for penetration and embedding, paraffin wax was used with a melting point of 58oc. leica eg 1160 paraffin embedding center was used for this purpose. the blocks were allowed on a cold plate to 18 solidify. the rotary microtome (leica rm 255) was used to cut 5μm thick cross sections. at 45˚c, pieces were floated in a hot water bath and then placed on glass slides. for 30 minutes, the slides were held in a slanting position to remove excess water and o sections were dried at 65 c in a hot air oven for 60 minutes. identification details were inscribed using the diamond tip pencil at the extreme corner of the glass slides. with the leica auto-stainer x, the sections were stained. hematoxylin and eosin (h&e) stains have been used to study cerebellum histology. purkinje cell margins were observed in complete purkinje cell layer in one slide per specimen at 40x magnification. the cell margins were recorded as regular (having normal pyriform somata with pale nuclei and prominent nucleoli) or irregular (having shrunken purkinje cell bodies with irregular outline, deeply stained cytoplasm and hardly identified 19 nuclei). number of cells was counted at high power field in complete purkinje cell layer in one slide per 20 specimen. size of purkinje cells was measured by taking ten consecutive high-power fields from left to right and three cells per field were considered. both length and width of purkinje cell was calculated with the help of micrometry and mean was taken. it was 21 compared with the control. micrometry is a technique to measure microscopic organisms and parameters using calibrated scale i.e., ocular micrometer and stage micrometer. the linear unit of measurement in micrometry is micron. one micron is equal to 1/1000mm. with the help of the stage micrometer, the eyepiece scale was calibrated, and the former was then used for measurements. by comparing the ocular micrometer scale with a calibrated stage micrometer, the eyepiece micrometer was calibrated. once calibrated the ocular micrometer was used for measurement. 0.25 micrometer calibration factor was obtained for 40x and was valid for the optical combination. the stage micrometer was removed and on the microscope stage, slides of the cerebellum were placed. for the purkinje cell size, the number of eyepiece divisions was counted and multiplied by 0.25. using the eyepiece of the olympus dp22 light microscope, the sony digital camera (16 megapixels) was used. the zoom of camera was 3x. the images were corrected and modified by photo scape software. the magnification was calculated according to the formula below: magnification � power of eye piece (10) x power of objective (10&40) x camera zoom (3x) statistical package for data analysis spss version 23 was used to analyze data. intergroup comparison for quantitative variables was done by independent sample t-test. a p value ≤ 0.05 was considered significant. results were represented as mean ± standard deviation (mean ± sd). qualitative variables were presented by frequency and percentage. chi-square test was applied for comparison of qualitative variables jiimc 2023 vol. 18, no. 2 fine particulate matter exposure in c57bl/6j mice 111https://doi.org/10.57234/jiimc.june23.1495 results between the periods of 15 june 2020 to 15 september 2020, 15 out of 30 mice with average weight of 37±2 gram were given dynamic inhalation of 3mg/m³ fine particles through air circulation for 6h/d for 12 weeks. the mice were placed in a plastic cabin measuring 2x2x2 feet fitted with two small fans opposite each other in nih islamabad. air circulation was maintained by fans running at moderate speed. the particulate matter was evenly dispersed in the cabin through fans. till the end of the experiment, all the animals remained alive. the purkinje cells in control group a showed regular margins i.e., irregularity ratio was 0%.whereas in experimental group b 73% of purkinje cells had irregular and distorted margins and 27% had regular margins (fig l ). the intergroup comparison between a and b was done by fisher's exact test which showed significant results with p-value 0.000 (table i). mean ± sd number of purkinje cell number in control yielded significant result with p-value 0.012 (table ll). mean ± sd size of purkinje cells in control group a fig. 1: photomicrograph of histological section of cerebellum in b2f showing purkinje cell layer (black arrowhead). purkinje cell margin is shown by yellow arrowhead. h&e 1200x table l frequency of purkinje cell margin among the control group a and experimental groups b. p-value ≤0.05significant* p-value <0.001highly significant** group a was 392 ± 62 whereas in experimental group b the mean ± sd of purkinje cell number was 328 ± 67 ( fig. ll). the intergroup comparison between group a and b was done by independent sample t-test which fig. 2 : bar chart showing intergroup comparison of mean number of purkinje cells among control group a and experimental group b ( pvalue 0.012) was 6.0 ± 0.4 µm whereas in experimental group b the mean ± sd size of purkinje cells was 3.2 ± 0.36 µm (fig iii). the intergroup comparison between group a and b was done by independent sample t-test which showed significant result with p-value 0.000 (table ll). fig. 3 : bar chart showing intergroup comparison of mean size of purkinje cells among control group a and experimental groups b (p-value 0.000) table ll: mean cell count and cell size of the control group a and experimental groups b. p value < 0.05 significant* p value < 0.01 highly significant** jiimc 2023 vol. 18, no. 2 fine particulate matter exposure in c57bl/6j mice 112 https://doi.org/10.57234/jiimc.june23.1495 discussion the aim of this study was to assess the effects of fine particulate matter exposure on the histomorphology of mice cerebellar purkinje cells for which thirty c57bl/6 mice of 8 weeks of age were selected. all animals remained alive during the experimental p e r i o d . re ga rd i n g t h e h i sto m o r p h o l o g i c a l examination the purkinje cell margins were found to be smooth and regular in control group a, whereas in experimental groups b they were found to be highly irregular and corrugated, shrunken with deeply stained cytoplasm (p<0.05). these results were 19-22 similar to a study conducted by el-dien in which the purkinje cell margins were irregular after exposure to fluoride which has same mechanism of action as particulate matter i.e. oxidative stress leading to neurodegenerative diseases. there was decreased number of purkinje cells in experimental group b as compared to control group a with p-value 0.012. the decrease in number of purkinje cells is most probably due to degenerative changes and stress imposed by exposure to fpm and also due to process of apoptosis stimulated by exposure to fine particulate matter as documented by xiaozheng 23 zhu . also, there is an assumption that due to presence of spongiosis the purkinje cells might have displaced from their normal place creating empty spaces in purkinje cell layer. these results are in 20 correlation with a study conducted wallauer in which there is decreased number of purkinje cells after exposure to tobacco smoke. in another study 21-24 done by kivrak in which there was reduced number of purkinje cells after exposure to radiation which has similar mode of action as particulate matter. the size of purkinje cells was decreased in experimental group b as compared to control group a with p-value 0.000. this is most probably due to degenerative changes in cells and stress imposed by exposure to particulate matter and due to development of spongiosis which compresses the cells. the results are similar to a study in which there is decrease in size of cells after exposure to 21 radiation with p-value <0.01 and also to a study conducted to find out quantitative analysis of 25 purkinje cells in nude mice . conclusion the present study concluded that fine particulate matter in the form of carbon soot induces changes in histomorphological features of mice cerebellar tissue. the major effects of exposure included both neurodegenerative and neuroinflammatory changes along with decreased size and number of purkinje cells, which were presented by irregular and distorted margins. ethics statement the rules and regulations regarding the handling and care of animal set forth by the ethics committee of the army medical college / national university of medical sciences were followed for the research nd (dated: 2 feb 2020, no: erc/id/10). author contribution sh designed the project, sm & smk helped in experimental procedure, abj analyzed the data. all authors approved the final version of manuscript. conflict of interest author has no conflict of interest to declare disclosure authors are extremely obliged to the national university of medical sciences, islamabad for providing funds for our project. references 1. ku t, ji x, zhang y, li g, sang n. pm2. 5, so2 and no2 coe x p o s u r e i m p a i r s n e u r o b e h a v i o r a n d i n d u c e s mitochondrial injuries in the mouse brain. chemosphere. 2 0 1 6 ;1 6 3 :2 7 3 4 . d o i.o rg / 1 0 .1 0 1 6 / j .c h em o s p h ere. 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request. this is an open access article distributed under the terms of the creative commons attributionnoncommercial 2.0 generic license. jiimc 2023 vol. 18, no. 2 fine particulate matter exposure in c57bl/6j mice 115https://doi.org/10.57234/jiimc.june23.1495 original article abstract objective: purpose of this study was to know any existing correlation between haemoglobin and lung function tests for respiratory status evaluation in young healthy individuals. study design: cross sectional study. place and duration of study: physiology laboratory of yusra medical and dental college, islamabad from january 2012 to january 2013. materials and methods: one hundred and sixty students of yusra medical and dental college were included in the study. blood samples of the subjects were collected for haemoglobin (hb) estimation by sahli method and measurement of the lung function tests was done by spirometry using volume spirometer. lung function tests included tidal volume (tv), inspiratory reserve volume (irv), expiratory reserve volume (erv) and vital capacity (vc).data was analysed using spss 15and correlation was calculated using pearson's correlation co-efficient between haemoglobin and the lung functions tests. results: the p value indicates significant positive relation exist between haemoglobin and inspiratory reserve volume(r = 0.39, p < 0.0001), expiratory reserve volume(r = 0.43, p < 0.0001) however, no significant relation exists between vital capacity and haemoglobin (p=0.242). conclusion: there is positive correlation between haemoglobin and lung function tests. key words: spirometry, haemoglobin, vital capacity, lung function tests. 1,2,3 abnormal lung functions so in this study we chose 4 hemoglobin as second entity for direct comparison with irv, erv and vc. in a developing country like 12 13 pakistan, where lung functions tests are too costly 14 for an average person and according to study conducted in urban areas of pakistan anemia is quite common, our study was carried out with an aim to find any co-relation that exists between haemoglobin and lung function tests so in future by 15 knowing hb level of a person indirect assessment of functioning of lung could be made. materials and methods the study was conducted at physiology laboratory of yusra medical and dental college, islamabad from january 2012 to january 2013. it was an analytical (cross sectional) study. a total of 160 healthy young adults of both sexes between ages 18 to 24 selected through purposive sampling, were included in the study. patients with existing lung diseases of asthma, dyspnoea, pneumonia were excluded from study. before starting the study, formal approval from ymdc medical ethics committee was obtained. data for haemoglobin (hb) and lung function tests was analysed using pearson co-relation co-efficient that give numeral values between two variables that are measured on same interval and results were calculated using spss 15. we approached potentially healthy students regularly attending classes in ymdc. participants provided signed informed introduction 1 various studies have shown that restrictive and 2 obstructive lung pathologies are accountable for 3 million deaths every year world widely with estimated mortality rate of 71 deaths per 100,000 in 3 pakistan. respiratory status of patient is evaluated 4 using lung function tests, that are non-invasive diagnostic tests and helps in monitoring of functioning of lung and also gives an overall idea of prognosis for diseases. though there are several different kinds of lung function tests, recent data 5,6 suggests spirometry, is first and most commonly 7 used method. spirometer monitors lung function by measuring amount of gas inhaled and exhaled that 2,4 shows how effectively gas travels from the lungs into the blood which allows to estimate how well the 8 lungs move oxygen that is carried by haemoglobin from the air into the blood stream. different studies have shown that due to decrease haemoglobin concentration poor delivery of oxygen to lungs 9 10 makes, anaemic patients usually lethargic and 11 breathless, thus, they are more prone to have correlation of hemoglobin with lung function tests sidra jahangir, ambreen asad, idrees farooq butt correlation of hb with lung function testsjiimc 2015 vol. 10, no.2 151 received: april 11, 2015; accepted: may 21, 2015 department of physiology yusra medical and dental college, rawalpindi correspondence: dr. ambreen asad associate professor of physiology yusra medical & dental college, rawalpindi e-mail: drambreenasad@yahoo.com consent, predesigned questionnaire performa and underwent blood sample collection for haemoglobin (g/dl),blood group, bleeding time, red blood cell count, white blood count cell count, and lung function tests that is spirometer testing includes tidal volume, inspiratory reserve volume, expiratory reserve volume and total lung capacity. erythrocyte sedimentation rate (mm at end of first hour) was measured using westergren method. haemoglobin 16 of participants was estimated using sahli method due to its simplicity and cost effectiveness. haemometer kit of sahli method included in it a comparator tube, hb pipette and acid. sahli haemometer method utilizes the conversion of haemoglobin into acid haematin which has a brown colour in solution. the intensity of the colour is related to the amount of haemoglobin in the blood sample. water is added to dilute the brown solution until it matches that of a standard. the more haemoglobin, the more water required to obtain a 17 colour match . haemoglobin values are read at the meniscus of the brown solution. hence, haemoglobin levels of individuals were taken and 17 estimated. lung function test swere measured 18 using spirometer with its accessories that included a mouth piece, soda lime container, floating drum and the results were obtained on kymograph. data was noted from the recorded spirogram for inspiratory reserve volume, tidal volume and expiratory reserve volume were recorded where as vital capacity values were calculated. analysis of covariance was performed to compare the levels of different pulmonary function parameters in relation to haemoglobin. data for haemoglobin (hb) and lung function tests was analysed using pearson corelation co-efficient which give numeral values between two variables that are measured on same interval and results were calculated using spss 15. though, our approach of using pearson co-efficient is quite novel in biomedical field, however, in other fields such as statistics, pearson method is well known for tackling co-relation financial phenomena. results the lung function tests and haemoglobin are compared by taking lung function tests (irv, erv,vc) on y axis whereas, haemoglobin is taken on x axis and results were calculated using pearson correlation co-efficient as shown in table ii. for inspiratory reserve volume and haemoglobin comparison variance is 3.9001, standard deviation of 0.1623, whereas, co-relation co-efficient 'r' was evaluated as 0.3862 which showed significance level p<0.0001 and 95% confidence interval for 'r' calculated as 0.2398 to 0.5154 hence the p value indicated the significant positive relation exist between inspiratory reserve volume and haemoglobin as shown in table ii and figure 1. the 95% confidence interval for mean is 12.8995 to 13.5411. fig 1: scatter plot showing significant positive correlation between the hb & irv on comparing expiratory reserve volume and haemoglobin, variance is 3.8515, standard deviation of 1.9625, whereas, the co-relation co-efficient r value is 0.4321 ,significance level of p<0.0001 and 95%confidence interval for r calculated as 0.2910 to 0.5547 therefore, a positive relation co-exist among haemoglobin and expiratory reserve volume. the confidence interval for mean is 12.8828 to 13.5226.results are shown in table ii. when vital capacity was compared with haemoglobin, it showed variance of 3.8710, standard deviation of 1.9675, whereas, co-relation co-efficient calculated to be 0.2110, significance level of p=0.242 and the confidence interval for 'r' calculated as 0.02816 to 0.3801. hence results showed no significant relation exists between vc and haemoglobin, shown in table ii. the 95% confidence interval for the mean is 12.8852 to 13.5201. the positive relation of haemoglobin with inspiratory reserve volume and correlation of hb with lung function testsjiimc 2015 vol. 10, no.2 152 expiratory reserve volume indicates that by knowing one parameter either haemoglobin or lung function test one can predict about working of other. the statistical summary is given in table i. table i: statistical analysis of hb and lung function tests 95% ci: 95% confidence interval. sd: standard deviation discussion when the co-relation of haemoglobin with lung function test parameters (inspiratory reserve volume, expiratory reserve volume and vital capacity) is done using pearson co-relation coefficient method, there exists positive relation of 19 haemoglobin with inspiratory reserve volume (p value<0.0001) and expiratory reserve volume (p value<0.0001). haemoglobin and lung function test are separate parameters and usually evaluated out separately however, it is found by our study results that with having just haemoglobin values of an individual one can predict about his lung function. decrease haemoglobin concentration results in poor delivery of oxygen to lungs disturbing breathing 9,10,11 mechanism, thus, anaemic patients are lethargic and dyspnoeic being more prone to have abnormal lung function tests. as in poor countries, it is difficult for people to go for lung function tests due to expenses, hence by taking blood samples for haemoglobin, fair prediction about functioning of lung could be done and if any doubt still persists regarding poor functioning of lung, then for confirmation, lung function tests such as 20 spirometry could be prescribed for such patients. in accordance to best of our knowledge, no direct national or international study has yet been carried out on comparison of haemoglobin with lung function test, however, there is evidence of matching of our study results with that, conducted in year 2012 by j.n. oko-ose et al. in university of benin teaching 21 hospital, which compared lung function test in 22 sickle cell patient. though the sample size was less than half of that what we chose for our study(160) ,as they chose 60 subjects, however the analysis of data was done using t test and pearson co-relation that we have also utilized for results. in that study, other parameters such as forced expiratory volume in one second (fev1) and forced vital capacity (fvc) were also included, though they have not been utilized in our study, but we have future plans of exploring these areas also. according to the study, the lung function indices were lower in females than males in sickle cell 23 patient, that differs greatly with our results as they were same for both genders in regards, that low haemoglobin values for both genders will predict equally for poor lung functioning, however, this area needs further extensive exploration and the difference in gender result may be due to different geographical areas and different races being examined in both studies. further recommendation regarding our study is that haemoglobin estimation by drapkin method, forced expiratory volume, forced vital capacity and diseased individuals should also be included. conclusion haemoglobin level in future can serve as good indicator for assessing lung function of the patients without history of any lung disease especially in poor socioeconomic conditions and environment where anaemia is more prevalent, patients are prone to have abnormal lung function tests. table ii: correlation between hb & lung function tests correlation of hb with lung function tests *for haemoglobin and inspiratory reserve volume, the “r” value is 0.38 so there exists fair co-relation among them. **for haemoglobin and expiratory reserve volume, the “r'' value 0.43 depicts a good significant relation between the two. ***for haemoglobin and vital capacity, the “r” value of 0.2 shows a weak co-relation among them. irv: inspiratory reserve volume. erv: expiratory reserve volume vc: vital capacity correlation of hb with lung function testsjiimc 2015 vol. 10, no.2 153 references 1. stam h, splinter ta, versprille a. evaluation of diffusing capacity in patients with a restrictive lungdisease. chest journal2000; 117:752-7. 0.3862* <0.0001 0.4321** <0.0001 0.2110*** 0.0242 2. qaseem a, wilt tj ann. diagnosis and management of stable chronic obstructive pulmonary disease: a clinical practice guideline update from the american college of physicians. american college of chest physicians 2011; 155: 179-91. 3. tazeen h jafar, benjamin a haaland, atif rahman noncommunicable diseases and injuries in pakistan: strategic priorities. the lancet 2013; 381: p2281-90. 4. miller mr, crapo ro, hankinson jl, general considerations of lung function testing. european respiratory journal 2005; 26: 319-38. 5. hyatt re, scanlon pd, nakamura m. spirometry, dynamic lung volumes. interpretation of pulmonary function tests: a practical guide. philadelphia: lippincott-raven; 1997. 6. stanojevic s, wade a, stocks j, hankinson jl, coates al, pan h et al. reference ranges for spirometry across all ages. a new approach. american journal of respiratory and critical care medicine 2008; 177: 253-60. 7. gold wm. pulmonary function testing. in: murray jf, nadel ja, eds. textbook of respiratory medicine, 3rd ed. philadelphia: wb saunders, 2000:781-882. 8. quan-zhou feng, yu-sheng zhao and yu-feng li. effect of haemoglobin concentration on the clinical outcomes in patients with acute myocardial infarction and the factors related to haemoglobin. british medical journal 2011; 4:142. 9. driskell ja. nutritional anemia: the guidebook: nutritional anemia. journal of the american medical association 2008; 299: 2690-1. 10. william mcclellan, stephen l aronoff, w kline bolton. the prevalence of anemia in patients with chronic kidney disease. journal of the american medical association 2004; 20: 1501-10. 11. pasricha sr, flecknoe-brown sc , allen kj, gibson, et al. diagnosis and management of iron deficiency anaemia: a clinical update. the medical journal of australia, 2010; 193: 525-32. 12. nicole beydon, isabelle pin, regis matran. pulmonary function tests in preschool children with asthma. american journal of respiratory and critical care medicine, 2003; 168: 640-4. correlation of hb with lung function testsjiimc 2015 vol. 10, no.2 154 13. luis puente maestú. lung function tests in clinical decision-making. arch bronconeumol. 2012; 48: 161-9. 14. baig-ansari n, badruddin sh, karmaliani r, harris h, jehan i, pasha o, et al. anemia prevalence and risk factors in pregnant women in an urban area of pakistan. food and nutritional bulletin 2008; 29: 132-9. 15. may c, rivella s, callegari j, heller g, gaensler km, luzzatto l. therapeutic haemoglobin synthesis in beta-thalassaemic mice expressing lentivirus-encoded human beta-globin. british medical journal 2000 july 6; 406: 82-6. 16. prashant jijabrao patil, girish vithal thakare. variability and accuracy of sahli's method in estimation of haemoglobin concentration. national journal of integrated research in medicine 2013; 4: 38-44. 17. harpreetranu, michael wilde, brendan madden. pulmonary function tests. the ulster medical journal may 2011; 80: 84-90. 18. hnizdo e, glindmeyer hw, petsonk el. workplace spirometry monitoring for respiratory disease prevention. international journal of tuberculosis and lung disease 2010; 14:796-805. 19. otto jm, doherty afo. association between preoperative haemoglobin concentration and cardiopulmonary exercise variables: a multicentre study. perioperative medicine journal 2013; 1:2-18. 20. quanjer ph, borsboom gj, kivastik j, merkus pj, hankinson jl, houthuijs d, et al. cross-sectional and longitudinal spirometry in children and adolescents: interpretative strategies. american journal of respiratory and critical care medicine 2008; 178:1262-70. 21. oko-ose jn, iyawe v, egbagbe e, ebomoyi m. lung function tests in sickle-cell patients in benin city. pulmonology 2012; 210:1-5. 22. ohara dg, ruas g, walsh ia, castro ss, jamami m. lung function and six-minute walk test performance in individuals with sickle cell disease. brazilian journal of physical therapy 2013; 18: 79-87. 23. connes p, machado r, hue o, reid h. exercise limitation, exercise testing and exercise recommendations in sickle cell anemia. canadian medical association journal 2011; 49:151-63. abstract objective: to assess patient compliance in systemic hypertension and to identify the causes of non-compliance. study design: a descriptive observational study. place and duration of study: the study was conducted in the department of medicine unit i and unit ii at th th pakistan railway hospital, rawalpindi, for 1 month from 5 of september, 2012 to 5 of october, 2012. materials and methods: semi structured interviews of 32 patients with primary hypertension who were admitted in medical ward were done along with their blood pressure readings and their compliance was assessed. morisky 1 8-item medication adherence questionnaire was used to assess the adherence to anti-hypertensive medication. scores of less than 3 out of 8 were termed as compliant while scores of 3 or more were termed as non-compliant. non-compliance was defined as missing at least two days of medications per week. this definition was arrived at from the general understanding that a minimum compliance of 80% is needed to achieve an adequate 2 reduction in blood pressure in the treatment of hypertension. results: among 32 patients, 18 were male while 14 were female with mean age of 56 years. twenty six out of thirty two (81.25%) patients did not comply with their antihypertensive medications. in majority of the patients (42.3%), misperception about disease and management due to inadequate education by health care providers was found to be the cause of non-compliance. other causes were considering medication unnecessary (15.3%) or ineffective (11.5%), forgetting to take them regularly (11.5%), unaffordable drug prices (11.5%) and unpleasant side effects (7.7%). conclusion: patients compliance in hypertension was sub-optimal and misperceptions of the disease and its management seemed to play a major role for non-compliance. physician-patient relationship, effective communication and better understanding of the disease can result in adequate control of hypertension and its complications. key words: patient compliance, hypertension, physician patient relationship 48 original article p e r i p h e r a l v a s c u l a r d i s e a s e , a o r t i c dissection, atrial fibrillation and end-stage kidney disease. in a world health organization report, blood pressure was responsible for approximately half of all 5 cardiovascular disease worldwide. despite this knowledge and unequivocal s c i e n t i f i c p r o o f t h a t t r e a t m e n t o f hypertension can prevent many of its lifealtering complications, hypertension remains untreated or undertreated in the majority of affected individuals in all countries, including those with the most advanced systems of medical care. inadequate treatment of hypertension is a major factor contributing to some of the adverse secular trends since the early 1990s, introduction hypertension is defined as a blood pressure of 140/90 mm hg or more than 130/85 mm hg if diabetic or having chronic kidney disease (ckd), stage iii, measured in a proper setting on at least two different 3 o c c a s i o n s . h y p e r t e n s i o n i s a n overwhelming global challenge, which ranks third as a means of reduction in 4 disability-adjusted life-years. it affects 1 billion people worldwide and is the most easily recognized treatable risk factor for stroke, myocardial infarction, heart failure, ------------------------------------------------patient compliance in systemic hypertension and to identify causes of non-compliance muhammad ali, jawad hameed, muhammad hamza zia, raja adil masood, aamir shahzad correspondence: muhammad ali (final year mbbs)iimc flat no. 8,doctor's colony, saidpur scheme 2 rawalpindi (03335721188) (postmuhammadali@yahoo.com) 48 49 including an increased incidence of stroke, heart failure, and kidney failure plus a leveling off of the decline in coronary heart disease mortality. the asymptomatic nature of the condition impedes early detection, which requires regular blood pressure measurement. because most cases of hypertension cannot be cured, blood pressure control requires lifelong treatment with prescription medication, which is costly and often causes more symptoms 6 than the underlying disease process. compliance with treatment is an important i s s u e i n t h e s u c c e s s f u l c o n t ro l o f h y p e r t e n s i o n a n d p r e v e n t i o n o f complications. according to the world h e a l t h o rg a n i z a t i o n ( w h o ) , p o o r adherence to antihypertensive medication is the most important cause of uncontrolled blood pressure and estimates that 50-70% of t h e p a t i e n t s d o n ' t t a k e t h e i r antihypertensive medication as prescribed 7 by their health care providers. this study was done to assess the patient compliance in systemic hypertension and to identify the causes of non-compliance in our settings. railway hospital caters to the railway employees along with general public. railway employees are entitled for free investigations/ treatment, so lack of financial resources can't be a major factor for non-compliance. this observational study was performed at iimct-pakistan railway hospital; a 400 bedded teaching hospital located in west ridge, affiliated with islamic international medical college, rawalpindi.a total of 32 patients who were admitted in medical unit i and ii with various medical conditions were included in this study. 12 patients presented with medical conditions resulting as the complications of hypertension mostly stroke, myocardial infarction and heart failure while rest of the patients were having materials and methods hypertension as co-morbidity. all the patients were previously diagnosed cases of hypertension and had been prescribed with a n t i h y p e r t e n s i v e m e d i c a t i o n . s e m i structured interviews were conducted and morisky 8-item medication adherence 1 questionnaire was used to assess their adherence to anti-hypertensive medication. scores of less than 3 out of 8 were termed as compliant while scores of 3 or more were termed as non-compliant. the noncompliance was defined as missing at least two days of medications per week. this definition was arrived at from the general understanding that a minimum compliance of 80% is needed to achieve an adequate reduction in blood pressure in the treatment 2 of hypertension. blood pressures of all the patients were measured at the time of interview and they were within normal limits due to the fact that they were given antihypertensive medication regularly during their management in the ward. out of 32 patients, 18 were male and 14 were female. 25 patients were above the age of 50 years with the age range of 43 years to 68 years and the mean age was 56 years. 26 out of 32 (81.25%) patients did not comply with their antihypertensive medications. noncompliance in males was found to be 77.7% while in females it was 85.7%. 11 patients were of the view that their blood pressures were controlled as they experienced no symptoms so they stopped taking their medicines. 4 patients considered medication unnecessary and believed they do not need it. 3 patients considered them ineffective. 3 patients forgot to take medication regularly. 3 patients cited unaffordable drug prices as the main reason for noncompliance. 2 patients experienced unpleasant side effects. majority of the patients considered the necessity of taking antihypertensive medication only when they experienced symptoms like headache etc and believed results 49 50 that they do not need the medication when they are asymptomatic. non-adherence was an active decision, partly based on misunderstandings of the condition and general disapproval of medication. table i: frequency of causes of non-compliance discussion despite improvements in the management of hypertension in the past several years, nearly 70% of patients with hypertension are 8 not adequately controlled. one of the major contributors to the large number of uncontrolled hypertensive patients appears to be non-compliance with prescribed regimens. in prescribing medication, compliance usually means “the extent to which the patient takes the medication as 9 prescribed”. non-adherence to prescribed drugs schedule has been and continues to be a major problem the world over. the world health organization (who) describes poor adherence as the most important cause of uncontrolled blood pressure and estimates that 50-70% of people do not take their antihypertensive 7 medication as prescribed. data from the national health and nutrition examination survey in usa indicates that approximately 40% of hypertensive individuals are untreated, and 65% do not have their hypertension controlled to a blood pressure 10 level of 140/90 mm hg. as with the treatment of other chronic illnesses in which long-term treatment is r e q u i r e d , a d h e r e n c e t o p r e s c r i b e d medications for hypertension is also a problem. studies have shown that almost 5 0 % o f i n d i v i d u a l s d i s c o n t i n u e antihypertensive medications within 6 to 12 11 months of their initiation. according to the national health survey of pakistan, the prevalence rate of hypertension is 18% in the pakistani population of more than 15 years o f a g e , w i t h a p re v a l e n c e r a t e o f hypertension of 16.2% and 21.6% in rural and urban population respectively and it also showed that among all hypertensive patients in pakistan, more than 70% are 12 unaware of their disease. a study done by saleem et al in 2011 at quetta, pakistan showed 13 that 64.7% of the patients were non-compliant and a study done by nazir et al in 2008 at abbottabad showed that 51.7% of the 14 patients were non-compliant. another study from agha khan university karachi by hashmi et al showed compliance to be significantly higher around 77% in 15 hypertensive patients. in our study 81.25% of the patients were found to be noncompliant. this poor compliance was mainly due to the fact that patients were not given adequate education about their disease and its management. consequently they stopped taking their medication although majority of them were entitled for free treatment by railway hospital. the free treatment by the railway hospital also excludes unaffordable drug prices as the major cause in our study as this cause was only found in 11.5% of the patients mainly in those who were railway non-entitled but this cause cannot be ignored in general 50 51 population as we have a substantial poor population in our country. patients' beliefs and attitudes have been explored in studies worldwide to explain not taking medication as prescribed. egan et al found forgetfulness, adverse effects and not liking to take medication among the reasons for poor 16 adherence in the united states. commonly encouraging factors, such as understanding the need and effectiveness of medication, a good support system and employing methods to reduce forgetfulness such as keeping medication in sight, were all significantly associated with better adherence in our population. similarly, among the discouraging factors cited in literature, most commonly reported in our population was forgetfulness (48%) followed by cost (40%) and fear of getting used to medication (27%). these were, however, factors that reduced adherence among the adherent (>80% adherence) population. this was different from the major factors reducing adherence in the non-adherent (<80% adherence) patients, w h o s e m a i n i s s u e s w e r e l a c k o f understanding of need of medication (70%) and lack of understanding of effectiveness of 17 medication (59%). in our study 42.3% of the patients believed that one should only take medication when there are symptoms and had strong concerns about the potential adverse effects of taking medication every day or did not see the need for taking medication when one is not feeling ill. this finding also provides a preliminary insight into the mechanism by which beliefs relating to medication might influence compliance. a study done by saleem et al in quetta, pakistan showed that patients were unsure of the benefits of continuous medication use which resulted 13 in non-adherence (64.7%) to regimens. the same study showed that out of the 385 patients 37.9 % of the patients were within the poor knowledge range, 61.3 % of the patients moderate and only 0.8 % of the p a t i e n t s s h o w e d a d e q u a t e g e n e r a l 13 knowledge about hypertension . some of these findings were similar to those reported 18, 19 in previous studies. familoni et al., in a 2004 study in nigeria, reported that only about one-third of patients knew that hypertension should ideally be treated for life, and 58.3% believed that antihypertensive drugs should be used only where there are 'symptoms' while the remaining 6.3% believed that the treatment should be for a period of time and not for 20 life. hayrettin k. in his study showed that there is a positive relationship between patient's levels of knowledge of treatment and better 21 adherence. it was found in the same study that 43.7% of patients believed that antihypertensive drugs can be stopped once the blood pressure has stabilized. this shows how the lack of knowledge about treatment contributes to patient low adherence behavior. patients cannot 21-23 necessarily be blamed for this as studies have shown that patients' poor knowledge about disease and medication is often related to the effectiveness of the health education they receive. there are many studies which describe the role of physicianpatient communication in enhancing 24-26 patients' adherence to medication. the o u t c o m e o f ' p a t i e n t c e n t e r e d ' communication between patients and health care providers is that it contributes to increase patients' understanding about their illnesses and adherence to treatments. although the interpersonal communication process in the patient-physician relationship has a potentially positive impact on patients' 51 52 health outcomes, physicians usually do not ask their patients about medication-taking b e h a v i o r o r m a y u s e i n e f f e c t i v e 24 communication approaches. it is argued that non-collaborative communication on the part of healthcare providers often result i n p o o r p a t i e n t a d h e r e n c e t o 25 antihypertensive treatments. in our study population 81.25 % of were non-adherent to the treatment regimen which is similar to the study “prevalence, awareness, treatment and control of hypertension among the elderly in bangladesh and india: a multicentre study” where 90% patients were 27 estimated as being non-adherent. patient knowledge is critical in the management of hypertension and yet is an area that is frequently neglected. in our study the most important factor resulting in non-adherence was found to be lack of patient education about disease, its management and side effects. patients who have been educated and understand their disease process, the goal of controlling blood pressures, potential side effects associated with antihypertensive medication (and the fact the medication can be changed if there are side effects), and the consequences of poor adherence and inadequate bp control tend to be more adherent with the medical 28 regimen. a recent systematic review of 59 papers in july 2012 from 16 countries (united states, united kingdom, brazil, sweden, canada, new zealand, denmark, finland, ghana, iran, israel, netherlands, south korea, spain, tanzania, and thailand) by marshall ij, wolfe cd, mckevitt c., showed that nonadherence to hypertension treatment often resulted from patients' understanding of the causes and effects of hypertension; particularly relying on the presence of stress or symptoms to determine if blood pressure was raised. these beliefs were remarkably similar across ethnic and geographical 29 groups. to improve adherence, clinicians and educational interventions must better understand and engage with patients' ideas about causality, experiences of symptoms, and concerns about drug side effects. although it has been suggested that it is sometimes possible to withdraw drug therapy and continue lifestyle-modification after several years, the consensus is that almost all who are hypertensive before treatment will become hypertensive again if 30 treatment is stopped. misperception of disease understanding and its management is a significant cause of n o n c o m p l i a n c e i n h y p e r t e n s i o n . e d u c a t i o n a l e ff o r t s a n d b e h a v i o r a l techniques can improve patient compliance in chronic, asymptomatic conditions. effective management requires continuity of care by a regular and knowledgeable physician as well as sustained active involvement by an educated patient. health care providers need to educate, counsel and motivate their patients in this regard. further studies should be carried out to identify major causes of non-compliance. conclusion references 1. morisky de, ang a, krousel-wood ma, ward h. predictive validity of a medication adherence measure in an outpatient setting. j clin hypertens 2008; 10:348-54. 2. guerrero d, rudd p, bryant kosling c. a n t i h y p e r t e n s i v e m e d i c a t i o n t a k i n g . investigation of a simple regimen. 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e n t a n d c o n t r o l o f hypertension among the elderly in bangladesh and india: a multicentre study. bull who 2001; 79: 327-33. 28. neutel j m, smith dhg. improving patient compliance: a major goal in the management of hypertension. j clin hypertens 2003; 5: 12732. 29. marshall i j, wolfe c d, mckevitt c. lay perspectives on hypertension and drug adherence: systematic review of qualitative research. bmj 2012; 345:e3953. 30. salako la. treatment of hypertension. cardiovascular diseases in africa 1979; 2:2-7. 53 page 51 page 52 page 53 page 54 page 55 page 56 jiims.cdr abstract objective: to examine the utility of clinical features in detecting serious underlying causes of headache in patients presenting to an emergency room. study design: descriptive observational study. place and duration of study: pakistan railway hospital spanning over a period of one year from july 2010 to june 2011. materials and methods: medical records of the patients attending the emergency room with headache as the major complaint were studied. results: 312 patients presented to er with a complaint of headache. of these 7.7% (n=24) had malignant headache and 92.3% (n=288) had benign headache. one hundred and ninety six patients (62.8%) were women and 116(37.2%) were men. in males there were 86.2% patients with benign headache and 13.8% with malignant headache. while in females 94.9% had benign and 4.1% malignant headache. ninety percent of patients had altered consciousness at presentation proved to have malignant cause for their headache. this figure was 91% for limb weakness, 100% for papillary and gaze abnormalities, 89% for extensor plantar response, and 85% each for papilledema and neck rigidity. conclusions: females present at younger age with headache and tend to have benign than malignant headache in majority of cases. males present at relatively older age and tend to have malignant than benign headache in majority of cases. younger patients presenting with headache usually have benign and elderly patients usually have malignant illness as the cause of their headache. with a good history and thorough physical examination imaging like ct scan and mri can be avoided. key words: benign headache, malignant headache, neck rigidity. 82 original article 3 received a pathological diagnosis. assessing the pretest probability with detailed history and physical examination will help reducing the cost of expensive tests 4 unduly ordered. a thorough neurological assessment is not only necessary for a correct diagnosis but it also enables the clinician to identify the seriousness of the problem by distinguishing between primary and secondary headaches and to make a definite plan for the additional w o r k u p f o r t h e s a f e a n d e ff e c t i v e 5 management of patients with headache. in 2008 the policy of the american college of emergency physicians on evaluation and management of adult patients presenting to the emergency department with acute nontraumatic headache was revised. in this policy there are recommendations for imaging in all headaches with abnormal neurological examination, new onset severe headache, hiv patients presenting with severe headache and patients more than 50 introduction most of the patients who visit the emergency department for headache prove to have a benign cause for their complaint but physician has to rule out an unexpected and potentially serious disease such as 1 subarachnoid hemorrhage. a thoughtful approach complemented by the judicious selection of tests is compatible with that goal as well as achieving the desired outcome of 2 accurate diagnosis and relief of pain. there is a tendency to order expensive investigations in the emergency department in the fear of missing a diagnosis. the national hospital ambulatory medical care survey for the years 19922001 revealed that in usa of the total of patients who underwent neuro imaging only 5.5% ------------------------------------------------correspondence: dr. asim zulfiqar associate prof. of medicine iimc-t, pakistan railway hospital contact number: 0300-504-6434 headache: a useful clinical feature in detecting serious underlying cause mohammad masood savul, iffat sultana, asim zulfiqar, lubna meraj 83 years of age presenting with new type of 6 severe headache. the purpose of this study is to highlight the importance of clinical examination in the evaluation of a patient with headache in emergency department. a lot of work has been done in the west in this regard to help an er physician in quick evaluation of a patient with headache with least possibility of missing a diagnosis without ordering too many investigations. such studies are lacking in our setting. medical records of 312 patients, who had presented to er with headache as their major complaint during the study period, were studied. a performa was filled depicting the details about age, sex, occupation, marital status, history of the headache with special emphasis on duration, onset, mode of presentation, location, associated features like fever, aura, impairment of consciousness, nasal c o n g e s t i o n , l a c r i m a t i o n , v i s u a l disturbances, photophobia, irritability, nausea, vomiting, vertigo, dizziness etc. there were also details about physical e x a m i n a t i o n i n c l u d i n g p u l s e , b p, temperature, general physical examination, abnormal neurological findings like limb weakness, altered mental status, brisk deep tendon reflexes, extensor plantar responses, pupillary abnormalities, conjugate gaze deviation, signs of meningeal irritation and other details in examination of the nervous system. a note was also made of the investigation carried out in the er and the final diagnosis at the time of discharge. we divided our patients into two groups: group 1: comprised those patients who had spent less than two hours in the er. group 2: comprised those patients who had spent more than two hours in the er and underwent thorough clinical examination and investigations. material and methods we then studied the charts for follow-up in opd for the next six months and made a note of the final diagnosis after six months of follow-up was made. inclusion criteria: all the patients attending the er whose major complaint was headache. exclusion criteria: �patients with vague complaints. �headache being the part of illness like flue or febrile illness. �patient discharged immediately or triaged to opd and not retained in er. three hundred and twelve patients presented to er with a complaint of headache. of these 196(62.8%) were women and 116(37.2%) were men. most patients 217(70.2%) spent less than 2 hours in the er. 95 patients (29.8%) stayed for more than 2 hours. of 312 patients 24 (7.7%) had malignant headache and 288 (92.3%) had benign headache. the mean age of presentation in males was 41.43 years (range 3-78years), while the mean age in females was 33.17 years (range 2-75 years). in males there were 86.2% (n=100) patients with benign headache and 13.8% (n=16) with malignant headache while in females 94.9% (n=188) had benign and 4.1% (n=8) malignant headache. there were 245 patients in the age group between 11-50 years. out of these only 3% (n=7) patients had malignant headache while 97% patients (n=238) had benign headache. there were 32 patients between the age of 51 and 60 years and amongst them 87.5% (n=28) had benign headache and 12.5% (n= 4) had malignant headache. there were 21 patients between the age of 61 and 70 years and amongst them 12.5% (n= 4) had malignant headache and 66.66% (n=14) had benign headache. at extremes of ages there were more patients results 84 with malignant than with benign headache. below age 10 years there were 9 patients, 33.3% (n=3) who had malignant headache while above 71 years of age there were 5 patients and 66.66% (n=3) had malignant headache out of 196 females who presented to er with headache 122 (62%) had severe headache and 96 (49%) had a history of recurrent attacks with similar pattern in the past. there was sudden onset of severe headache in 176 patients but out of these only 18 (10.2%) had proved to have a serious cause to their headache. photophobia was an associated feature with headache in 56 patients but 40 out of these had migraine as their final diagnosis. all the patients who had meningitis as their final diagnosis had photophobia as prominent associated feature with their headache. the frequency of signs on physical examination in malignant headache was as follows: 90% of those who had altered consciousness at presentation proved to have malignant cause for their headache. this figure was 91% for limb weakness, 100% for pupillary and gaze abnormalities, 89% for extensor plantar response, and 85% each for papilledema and neck rigidity. thirty eight ct scan head were performed. only 8 were reported as positive. of these positive ct scan patients there were 6 males between the age of 51 to 60 years and 2 females above the age of 70 years. a total of 10 lumber punctures were performed. out of these 5 (50%) were positive. out of those who tested positive 3 (71.5%) were from the age group of below 10 years. the final diagnosis made in the er was as follows: total of 24 patients had some malignant cause for their headache. out of these subarachnoid haemorrhage 1.6% (n=5), intracranial hemorrhage 3 % (n=9), meningitis 1.6% % (n=5), venous sinus thrombosis 0.32% (n=1), benign intracranial hypertension 0.32% (n=1), space occupying lesions 0.96% (n=3). headache management especially in an discussion table i: frequency of variables in the study population (n= 312) emergency setting needs lot of expertise. most of the er physicians are trained in internal and emergency medicine and are expert enough to deal with the headache as a 7 medical emergency. in a busy tertiary care centre er where at least 2-3% of patients are admitted with headache as their chief complaint, a quick clinical assessment and a prompt diagnosis is essential for proper management. sometimes, although rarely, the er physicians cannot face satisfactorily the diagnostic challenge concerning the benign 8 etiology of referred headache. the major critical issue in er is to distinguish subtle primary headaches from more serious secondary headaches like subarachnoid haemorrhage, intracerebral haemorrhage, subdural haematoma, 85 hypertensive encephalopathy, brain tumor, and other space occupying lesions, artery dissection, cerebral venous thrombosis, temporal arteritis etc. missing any of these 9 could prove hazardous. all these situations demand both a careful evaluation and a correct diagnostic algorithm and can be grouped in subtypes such as severe-onset secondary thunderclap headache, transient neurological deficits, neurological deteriorations, headache 10 associated with infections, etc. there are many clinical features which can distinguish between primary and secondary headaches. benign headaches tend to occur in younger patients and predominantly in female. they are mostly unilateral and there is long history of constellation of similar features in each episode which usually have a triggering factor. on the other hand secondary headaches occur at an older age, males are the usual sufferers, are usually generalized, neurological examination is 11 abnormal. the time course of a headache can give a 7 good clue to the etiology of headache. a new onset severe headache with abnormal neurological examination and presentation due to associated features is usually due to a secondary cause and should be investigated 8 in er with imaging. an excruciatingly painful headache with a sudden onset can reflect vascular pathology, such as 12,13 subarachnoid hemorrhage. survivors of subarachnoid hemorrhage often describe the pain as the worst 14 headache ever encountered. headaches that occurs on at least 15 days per month for 4 or more hours per day, for at least three consecutive months is called chronic daily headache. if the attacks last for less than 4 hours per day then likely diagnosis is chronic cluster headache or trigeminal autonomic cephalalgia which includes episodic and chronic cluster headache, episodic and chronic paroxysmal hemicranias etc. if the duration is =4 hours then differential diagnosis encompasses chronic migraine and chronic tension-type 15 headache. for a long time physicians have been using favorable response to analgesics as an indicator of benign type of headache. 12 studies have proved that it is not a good predictor of severity rather, at times, it could 16 be hazardous. much work has been done in this regard to find out a relationship between clinical presentation and diagnosis of headache. work of detsky me et. al. to find out cardinal signs pointing towards migraine and other benign headaches is worth mentioning. four signs which predict migraine are unilateral, pulsating headache, of 4-72 hours duration 1 associated with nausea. in the study by ertan mert et. al., three important correlations were found. unilateral location and having any trigger increased 1.431 and 1.44 fold increase respectively in primary headache risk. having an associated co-morbid medical disorder caused 4.643 fold increases in 17 secondary headache risk. in the famous study by ramirez-lassepas m it was concluded that abnormal results from neurological examination are the best clinical parameters to predict structural intracranial pathology. however, in patients over age 55 years an imaging is strongly recommended specially if headache in the 18 occipitonuchal region . in our study abnormal neurological findings had strong association with secondary causes of headache. we conclude that: �females present at younger age with headache and tend to have benign than malignant headache in majority of cases �males present at relatively older age and conclusions 86 tend to have malignant than benign headache in majority of cases er stay is prolonged because of: �severity of symptoms �investigations �difficulty in reaching a diagnosis �severity of headache is not an indicator of malignant headache. �photophobia and phonophobia are not necessarily present in fulminant headache �abnormal neurological signs indicate malignant headache �most of the investigations done are unnecessary �with a good history and thorough physical examination imaging like ct scan and mri can be avoided 1. detsky me, mc donald dr, baerlocher mo, tomlinson ga, mccrory dc, booth cm. does this patient with headache have a migraine or need neuroimaging? jama 2006; 296: 1274 83. 2. ward tn; levin m; phillips jm. evaluation and management of headache in the emergency department. med clin north am 2001; 85: 97185. 3. goldstein jn, camargo ca jr, pelletier aj. headache in united states emergency departments: demographics, work-up and f r e q u e n c y o f p a t h o l o g i c a l d i a g n o s e s . cephalalgia 2006; 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í¿ª±´¿·²»² íô ö±«­·³·»­óí±³»® øîô ó¿µ·¬·» ßßô ç´·µ±­µ· öíò ð»®·¬±²­·´´¿® ¿¾­½»­­ò ý´·²·½¿´ ¿²¼ ³·½®± ¾·±´±¹·½¿´ ¿­°»½¬­ ¿²¼ ¬®»¿¬³»²¬ ®»¹·³»²¬­ ß®½¸ ñ¬±´¿®§²¹±´ ø»¿¼ ò»½µ í«®¹ ïççíå ïïîæëîïóìò ïìò 翲± öô ñµ·¬¿ éò ð»®·¬±²­·´´¿® ß¾­½»­­ò ¿ ½±³°¿®·­±² ±º ¬®»¿¬³»²¬ ¾§ ¿­°·®¿¬·±² ú ·²½·­·±²ò ò·°°±² ö ·¾··²µ±µ¿ ù¿µµ¿· õ ¿·¸± ïççíåçêæîïçóîìò ïëò ö¿µ±¾­»² óøò ð»®·¬±²­·´´¿® ß¾­½»­­ ¬®»¿¬»¼ ©·¬¸ °«²½¬«®» ¿²¼ ß­°·®¿¬·±²ó¿ °®±­°»½¬·ª» í §»¿®­ º±´´±©ó«°ò ë¹»­µ® ´¿»¹»® ïççíåïëëæíìèðóîò ìî original�article 112 abstract objective: to study the radiological features of sinusitis, its intracranial and orbital complications. study design: a case series design. place and duration of study: radiology department, shifa international hospital, from march 16, 2016, to june 28, 2018. materials and methods: a total of 7 patients were selected from the radiology database retrospectively from march 16, 2016, to june 28, 2018.of these patients had their mri and ct scans done at shifa international hospital. ct scan was performed on toshiba aquilion1, double detector 320 slices, and mri was performed on toshiba-titan 1.5 tesla. the literature review was also done to identify different complications of sinusitis. result: out of 7 patients, 3 patients showed pansinusitis with meningitis and intra-orbital extension causing cellulitis and inflammation, all of them showed bony erosions and developed cavernous sinus thrombosis. amongst these a 32-year-old female patient developed left cavernous sinus thrombosis, with ophthalmic vein occlusion with loss of the left eye and was followed by enucleation, she developed left ica thrombosis with watershed ischemic infarcts in the left cerebral hemisphere. the remaining 4 patients had pansinusitis with intra-orbital and intracranial extension, without cavernous sinus thrombosis one amongst the 7 patients had severe sphenoid sinusitis with evidence of fungal infection on mri with intracranial and intra-orbital extension. conclusion: imaging plays a vital role in the diagnosis of sinusitis. it displays all the details of paranasal sinuses and surrounding structures including orbits and the brain. though ct scan depicts the involvement of the bones, yet mri is more accurate for the extension of the disease into the orbital apex, cavernous sinus, and brain. key words: sinusitis, complications, imaging modalities. modalities can be used for diagnosing sinusitis and complications of sinusitis. plain radiograph talks only about the presence of sinusitis yet has no role in 6 detecting its complications. ct scan is the modality of choice for detection of bony complications whereas mri gives a detailed assessment of intra7 orbital and intra-cranial complications of sinusitis. many diseases can mimic sinusitis clinically. thus, radiology through its imaging modalities can assist 8 the clinician to diagnose accurately. materials and methods a case series study in which total of 7 patients were selected from the radiology database retrospectively in radiology department, shifa international hospital, from march 16, 2016, to june 28, 2018. all these patients had their mri and ct scans done at shifa international hospital. ct scan was performed on toshiba aquilion1, double detector 320 slices, and mri was performed on toshiba-titan 1.5 tesla. the literature review was also done to identify different complications of sinusitis. ethical review letter from the institutional review board was taken. introduction inflammation of the mucosa of any of the paranasal sinuses is called sinusitis. it can be acute, subacute or 1 chronic, depending on the duration of symptoms. symptoms include nasal blockage and discharge 2 associated with fever and headache. if left 3 untreated, this can lead to various complications. these complications can be intracranial or 4 intraorbital. the sinusitis itself though very common rarely presents with life-threatening complications which can be local like erosion through bone, subperiosteal abscess or intracranial like meningitis, encephalitis, subdural empyema, subdural abscess, cavernous sinus thrombosis or intra-orbital like preseptal cellulitis, subperiosteal abscess, orbital 5 cellulitis, and orbital abscess. different imaging imaging features of sinusitis and its complications belqees yawar faiz, zainab malik, khurram khaliq bhinder correspondence: dr. khurram khaliq bhinder resident radiologist department of radiology shifa international hospital, islamabad e-mail: kkbhinder@yahoo.com department of radiology shifa international hospital, islamabad intraorbital and intracranial complications of sinusitisjiimc 2021 vol. 16, no.2 case presentation case 1: a 32-year-old female who presented with left orbital cellulitis and uncontrolled gestational diabetes, shows extensive soft tissue opacification involving nasal cavity and paranasal sinuses. (figure 1). her follow up imaging showed loss of signal void of cavernous part of left ica, consistent with thrombosis. (figure 2). patient then underwent enucleation. biopsy was done which revealed mixed fungal infestation. case 2: a 42-year-old male came to our hospital with active complaints of left sided body numbness and dizziness for 5 days. mri brain was ordered which showed multiple bright t2 and flair signal foci in watershed distribution in right cerebral hemisphere. patient is status post fess with extensive opacification of ethmoid, left frontal and left sphenoid sinuses with intracranial extension of the infective process resulting in thickening and enhancement of dura and meninges in floor of anterior and middle cranial fossa on left as well as abnormal enhancement of the cavernous sinuses. further workup by contrast enhanced ct paranasal sinuses confirmed these findings. the patient then underwent medical as well as surgical management. case 3: a 58-year-old male who presented with history of headache for 6 weeks associated with weight loss, vertigo and dizziness. ethmoid, sphenoid sinus and mastoid mucosal disease suggesting acute sinusitis and mastoiditis bilaterally with fluid levels in left mastoid air cells. t2/flair high signal foci in peri ventricular and subcortical white matter, left temporal lobe, midbrain and pons intraorbital and intracranial complications of sinusitisjiimc 2021 vol. 16, no.2 113 could be suggestive of chronic microvascular angiopathy. however, osmotic demyelination was kept in mind. enhancement of leptomeninges in left temporal fossa, cavernous/paracavernous region, orbital apices, more on the left and left subtemporal soft tissues consistent with intracranial extension of sinus and mastoid disease process causing leptomeningitis. the patient was managed medically with iv amphotericin. case 5: a patient with history of stroke, showing extensive mucosal thickening in the right maxillary, sphenoid, ethmoid and the frontal sinus with hypointense signal with post contrast enhancement. asymmetric dural enhancement along the right temporal lobe was seen suggesting sinusitis with intracranial extension. iv amphotericin was the main line of treatment initiated in this patient. case 4: a 58-year-old female showing abnormal accentuated post contrast enhancement of leptomeninges at cavernous, para cavernous region and orbital apices. extensive paranasal sinus disease was seen with t2 low signal containing retention cyst in sphenoid sinus which seems to be extending laterally eroding pterygoid plates and reaching medial inferior temporal fossae. abnormal appearing accentuated postcontrast enhancement of leptomeninges at cavernous, paracavernous region and orbital apices was noted. accentuated enhancing venous channels noted at vertex passing through diploic space. relatively small sized ventricles and partially empty sella was seen, raising suspicion of increased intracranial pressure. numerous t2/flair bright signal foci in bilateral periventricular and subcortical white matter suggesting microvascular angiopathy. overall findings may be sequelae of intracranial extension of sinus disease and requires further confirmation with clinical correlation, analysis of csf and additional workup including post contrast ct. the patient was confirmed to have fungal infection and non-surgical treatment was initiated. case 6: a 50-year-old female with cld and history of right maxillary swelling, pain and epistaxis. mri showed extensive opacification involving the right maxillary sinus, bilateral ethmoid, sphenoid and frontal sinus more so of right with soft tissue edematous changes in the premaxillary and infratemporal region also extending to pre-septal soft tissues on right. mild right proptosis with retrobulbar involvement of disease process with edematous changes and thickening of extraocular muscles more so of medial rectus; the constellations of findings were more in favor of overall infective sinonasal disease process with right intraorbital extension and soft tissues as described above. illintraorbital and intracranial complications of sinusitisjiimc 2021 vol. 16, no.2 114 defined high signal foci in the right anterior basifrontal lobe as well likely suggested intracranial extension of the disease process. the patient was managed surgically in ent department. discussion inflammation of the mucosa of any of the paranasal sinuses is called sinusitis. many complications are 5 known to it, which can be intracranial or intraorbital. different modalities like plain radiograph, ct scan and mri help in different ways in identifying these 6,9 complications. it can be acute or chronic depending upon the duration. acute sinusitis can occur following an upper respiratory tract infection or it can spread via oral/dental infection. recurrent infections in cystic fibrosis and those having allergic sinusitis, immuno-compromised states, and diabetes mellitus predispose an individual to complications. the incidence of intracranial complications is reported to have decreased in recent years to only 3.7 % in patients admitted for 10 acute or chronic sinusitis. for reasons not known it has been observed that males are more prone to develop intracranial complications than females the 11,13,14,15 ratio roughly being 2:1. its complication is said to have occurred when the disease process spreads beyond the confines of the sinus cavity to involve the sinus wall and/or surrounding structures like the brain or orbit. it usually presents with fever, headache, nasal congestion, postnasal discharge, 16,17 and an altered sense of smell . the complicated case can be asymptomatic or can present with neurological deficit, blurring of vision, altered state 18,19 of consciousness, fits, or even coma. though with prompt use of antibiotics, the complications of sinusitis have become rare, yet when they occur, they are potentially life10 threatening . the complications are mainly divided into three groups; local complications, intracranial complications which include subdural empyema, epidural and intracerebral abscess, meningitis, and 1 1 venous sinus thrombosis , and intra-orbital complications which include pre-septal cellulitis, subperiosteal abscess, orbital cellulitis, and orbital abscess. different imaging modalities have a different management role in diagnosing sinusitis and complications. plain radiograph assessment gives only about the presence of sinusitis yet has no role in 6 detecting its complications. ct is the modality of choice in the detection of bony complications whereas mr being the modality of choice gives a detailed assessment of intra-orbital and intracranial case 7: a 20-year-old male came to our hospital with active complains of severe left sided headache, visual disturbances, nausea and vomiting. ct brain outside facility showed no evidence of abnormal leptomeningeal enhancemnet. h/o frontal sinus abscess. iv antibiotics were given in hospital. ultrasound face showed preseptal soft tissue swelling and subcutaneous edema around left orbit, upper nose and forehead. complained of severe left sided headache, visual disturbances, nausea and vomiting. mri revealed complete opacification and marginal enhancement of the maxillary, ethmoid and frontal sinuses suggesting acute sinusitis. moderate pachymeningeal enhancement in left frontal region with a small subdural empyema indenting the left frontal lobe was seen. subtle loss of normal signal void of left lamina papyracea and impingement of medial rectus muscle raised suspicion for intraorbital extension of the disease process. medical management with drainage of abscess/ empyema remained the initial treatment. intraorbital and intracranial complications of sinusitisjiimc 2021 vol. 16, no.2 115 complications. xray's are the first modality that is used in patients who present with non-complicated sinusitis, which shows opacification of sinuses and air-fluid levels. but it does not tell about the extent of 6 the disease. ct scan gives a better idea about disease extent and complications. it is more sensitive than plain radiography for detecting sinus pathology, 9 especially within the sphenoid and ethmoid sinuses. features suggesting sinusitis are peripheral mucosal thickening, air-fluid level, gas bubbles within the fluid and obstruction of the ostiomeatal complexes, and in complicated cases pressure erosion/ deossification of bones. mri is the modality of choice to look for intracranial as well as intra-orbital 16,17,18,19 extension. conclusions the imaging plays a crucial role in the diagnosis of sinusitis it displays all the details of paranasal sinuses and surrounding structures including orbits and brain. though ct scan depicts the involvement of the bones, yet mri is more accurate for the extension of the disease into the orbital apex, cavernous sinus, and brain. references 1. deboer dl, kwon e. acute sinusitis. in: statpearls [internet]. treasure island (fl): statpearls publishing; 2021. pmid: 31613481. 2. wilson m, wilson pj. acute sinusitis. close encounters of the microbial kind. everything you need to know about st common infections. ; springer, cham. 1 ed 2021 publishing (pp. 213-224). doi.org/10.1007/978-3-030-56978-5 3. kim m, pearlman a, kacker a, stewart mg. acute sinusitis, and its complications. textbook of clinical otolaryngology. springer, cham. https://doi.org/10.1007/978-3-03054088-3_23 2021:253-9. 4. ziegler a, patadia m, stankiewicz j. neurological complications of acute and chronic sinusitis. current neurology and neuroscience reports. 2018;18(2):1-8. 5. dankbaar jw, van bemmel aj, pameijer fa. imaging findings of the orbital and intracranial complications of acute b a c t e r i a l r h i n o s i n u s i t i s . i n s i g h t s i n t o i m a g i n g . 2015;6(5):509-18. 6. mafee mf, tran bh, chapa ar. imaging of rhinosinusitis and its complications. clinical reviews in allergy & immunology. 2006;30(3):165-85. 7. waqar s, ameer s, naeem m, bajwa ma, bajwa sm, bajwa gr. diagnostic accuracy of magnetic resonance imaging for diagnosis of acute invasive fungal sinusitis taking histopathology as a gold standard. pakistan armed forces medical journal. 2020 dec 16;70(6):1810-4. 8. mccann mr, kessler at, bhatt aa. emergency radiologic approach to sinus disease. emergency radiology. 2021 may 19:1-8. 9. okuyemi ks, tsue t. radiologic imaging in the management of sinusitis. american family physician. 2002 ;66(10):1882. 10. germiller d, monin dl, sparano et al: intracranial complication of sinusitis in children and adolescents and their outcomes. arch otolaryngol head neck surg 2006; 132:969–976. 11. kombogiorgas d, seth r, athwal r et al: suppurative intracranial complications of sinusitis in adolescence. single institute experience and review of literature. br j neurosurg 2007; 21:603– 609. 12. clayman gl, adams gl, paugh dr et al: intracranial complications of paranasal sinusitis: a combined institutional review. laryngoscope 1991; 101:234–239. 13. blumfield e, misra m: pott's puffy tumor, intracranial, and orbital complications as the initial presentation of sinusitis in healthy adolescents, a case series. emerg radiol 2011; 18:203– 210. 14. hicks cw, weber jg, reid jr et al: identifying and managing intracranial complications of sinusitis in children: a retrospective series. pediatr infect dis j 2011; 30:222–226. 15. younis rt, lazar rh, anand vk: intracranial complications of sinusitis: a 15-year review of 39 cases. ear nose throat j. 2002; 81:636–644. 16. cornelius rs, martin j, wippold fj, aiken ah, angtuaco ej, berger kl et al. acr appropriateness criteria sinonasal disease. journal of the american college of radiology. 2013;10(4):241-6. 17. yousem dm. imaging of sinonasal inflammatory disease. radiology. 1993 188(2):303-14. 18. sadhu vk, handel sf, pinto rs, glass tf. neuroradiologic diagnosis of subdural empyema and ct limitations. american journal of neuroradiology. 1980 ;1(1):39-44. 19. miller es, dias ps, uttley d. management of subdural empyema: a series of 24 cases. journal of neurology, neurosurgery & psychiatry. 1987;50(11):1415-8. intraorbital and intracranial complications of sinusitisjiimc 2021 vol. 16, no.2 116 dec 2013.pdf éè ñî×ù×òßô ßîì×ýôû ßþíìîßýì ñ¾¶»½¬·ª»æ ì± ¼»¬»®³·²» ¬¸» °¿¬¬»®² ±º ­µ·²¼·­±®¼»®­ ­»»² ¿³±²¹ ½¸·´¼®»² ¿¬¬»²¼·²¹ ¿ó»¼·½¿´ ý±´´»¹» ø±­°·¬¿´ò í¬«¼§ ü»­·¹²æ ß¼»­½®·°¬·ª» í¬«¼§ ò ð´¿½» ¿²¼ ü«®¿¬·±² ±º í¬«¼§æ 츻 ­¬«¼§ ©¿­ ½±²¼«½¬»¼ ¿¬ ü»®³¿¬±´±¹§ ü»°¬ò 𿵷­¬¿² î¿·´©¿§ ø±­°·¬¿´ º®±³ ü»½îðïï ¬± ö«´§ îðïîò 󿬻®·¿´­ ¿²¼ 󻬸±¼­æ ß´´ ½¸·´¼®»² ïí §»¿®­ ¿²¼ ¾»´±© ¿¬¬»²¼·²¹ ¬¸» ü»®³¿¬±´±¹§ ñðü ©·¬¸ ­µ·² ¼·­»¿­»­ ©»®» ·²½´«¼»¼ ¾»¬©»»² ¬¸» °»®·±¼ ±º ü»½»³¾»® îðïï ¬± ö«´§ îðïîò ß ¼»¬¿·´»¼ ¸·­¬±®§ ©¿­ ¬¿µ»²å ¬¸±®±«¹¸ ½´·²·½¿´ »¨¿³·²¿¬·±² ©¿­ ¼±²» ¿²¼ ©¿­ ­«°°±®¬»¼ ¾§ ·²ª»­¬·¹¿¬·±²­ ©¸»®»ª»® ²»½»­­¿®§ò 츻 ¼·­»¿­»­ ©»®» ¬¿¾«´¿¬»¼ ¾¿­»¼ ±² ¬¸» ª¿®·±«­ ¹®±«°­ ¿²¼ ®»­«´¬­ ©»®» ¿²¿´§­»¼ò î»­«´¬­æß ¬±¬¿´ ±º îíëé ½¿­»­ ø¾±§­ ïðíéå ¹·®´­ ïíîð÷ ©·¬¸ ¼·ºº»®»²¬ ¼»®³¿¬±­·­ ©»®» ·²½´«¼»¼ ·² ¬¸» ­¬«¼§òò ó±­¬ ±º ¬¸» ¼·­±®¼»®­ ©»®» ­»»² ¾»¬©»»² ï ¬± ë §»¿®­ ±º ¿¹»ò 츻 ³±­¬ 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îêæêëí�éò îîò ú·²¼´¿§ ùøô ê·­³»® øúô í±°¸·¿²±­ ìò 츻 ­°»½¬®«³ ±º °»¼·¿¬®·½ ¼»®³¿¬±´±¹§ò ß²¿´§­·­ ±º ïðôðð𠽿­»­ò þ® ö ü»®³¿¬±´ ïçéìå çïæíéçóèéò îíò ß´ó ú±«¦¿² ßí ú ò¿²¼¿ ßò ß ­«®ª»§ ±º ½¸ ·´¼ ¸±±¼ °­ ±®·¿ ­· ­ ·² õ« ©¿ ·¬ ò ð »¼· ¿¬ ® ü»®³¿¬±´ ïççìå ïïæïïê óçò îìò ö¿ª»¼ óô ö¿·®¿³¿²· ýò 𻼷¿¬®·½ ¼»®³¿¬±´±¹§æ ¿² ¿«¼·¬ ¿¬ ø¿³¼¿®¼ ë²·ª»®­·¬§ ø±­°·¬¿´ô õ¿®¿½¸·ò ö 𿵠߭­±½ü»®³¿¬±´ îððêåïêæçí�êò îëò í¸¿®³¿ êõô õ«³¿® þô ü¿©² ùò ß ½´·²·½¿´ ­¬«¼§ ±º ½¸·´¼¸±±¼ ¿´±°»½·¿ ¿®»¿¬¿ ·² ý¸¿²¼·¹¿®¸ô ײ¼·¿ò 𻼷¿¬® ü»®³¿¬±´ ïççêåïíæ íéîóó éò îêò ù±­¸ íõô í¿¸¿ üõô  ßõò ß ½´·²·½± »¬·±´±¹·½¿´ ­¬«¼§ ±º ¼»®³¿¬±­»­ ·² °»¼·¿¬®·½ ¿¹» ¹®±«°ò ײ¼·¿² ö ü»®³¿¬±´ ïççëåìðæ îç�íïò original�article abstract objective: to study the effects of iron supplementation in pregnancy on the height of zones of epiphyseal growth plates of off springs. study design: laboratory based randomized control trial. place and duration of study: this study was conducted at department of anatomy, army medical college rawalpindi in collaboration with national institute of health (nih) islamabad from march 2016 to november 2016. materials and methods: five lactating rats with ten pups were selected for control group a1and experimental groups b1 and b2 each. experimental groups were given iron supplementation daily throughout the pregnancy. mothers of group b2 were given oral iron during pregnancy as well as during lactation. control group was on normal diet throughout the pregnancy. the infant rats were allowed to reach seven weeks of age till dissection. they were weighed before euthanasia. right femur of each rat was removed for the epiphyseal growth plate analysis. femurs were processed, embedded and stained with hematoxylin & eosin, perl's stain, and toluidine stain for histological study. the heights of hypertrophy and proliferative zones were analyzed histologically and statistically. results: the height of hypertrophy zone and proliferative zone of epiphyseal plates of long bones were measured. mean values of the heights of hypertrophy in group a1 276.19 ±43.61, b1 136.73±3.58and b2 205.00±12.76. mean values of the heights of proliferative zones in group a1 377.29±50.73, b1 202.89±11.56 and b2 281.07±11.96 were taken. the heights in hypertrophy and proliferative zones were statistically decreased in group b1 and b2 as compared to group a1. conclusion: indiscriminate iron supplementation during pregnancy and lactation can decrease the height of hypertrophy zone and proliferative zone of epiphyseal growth plates of long bones of the off spring. key words: growth plate, hypertrophy zone, iron supplementation, proliferative zone. fortification and the use of iron supplementation are methods which can correct iron deficiency anemia. iron excess in body may be associated with excess dietary intake. iron overload is associated with problems like ineffective erythropoiesis. clinically, systemic iron overload can present as liver disease, diabetes mellitus, gonadal insufficiency and other e n d o c r i n e d i s o rd e rs , c a rd i a c d y s f u n c t i o n , 2 arthropathy, and increased skin pigmentation. there is a negative effect of excess iron on bone 3 structure, which exposes patients to fractures. there is a decrease in osteoblast activity due to iron . iron supplementation is given during pregnancy as well as during lactation routinely even in 4 nonanemics. excess iron intake during pregnancy is associated with reduced fetal growth. fetuses of pregnant women with iron intake in the third trimester have a significantly lower biparietal diameter, abdominal circumference and femur length than the fetuses of mothers taking iron in the 5 second trimester. excessive iron can lead to oxidative damage and decrease in the absorption of introduction iron is an essential nutrient required by each cell of the body. the deficiency as well as excess of iron in 1 the body has clinically significant effects. iron deficiency can be due to either increased requirements of body as in pregnancy and period of rapid growth or inadequate iron supply. iron 1 deficiency is the most common cause of anemia. availability of iron in the diet, with the food effects of iron supplementation on the height of the zones of growth cartilage of rat 1 2 3 4 faiza umbreen , aamna khalil , saadia rashid , khadija qamar correspondence: dr. faiza umbreen department of anatomy army medical college national university of medical sciences (nums), rawalpindi e-mail: faizaumbreen46@gmail.com 1,4 department of anatomy army medical college national university of medical sciences (nums), rawalpindi 2 department of anatomy rawal institute of health sciences, islamabad 3 department of anatomy fauji foundation medical college, islamabad funding source: nil; conflict of interest: nil received: apr 25, 2017; revised: june 24, 2016 accepted: aug 17, 2017 effects of iron supplementation on the height of growth cartilagejiimc 2017 vol. 12, no.3 135 copper and zinc, which are the important 5 micronutrients for fetal growth. there is an association between elevated maternal hemoglobin and adverse birth outcome, including low birth weight, preterm birth, and small for gestational age 6 at birth in addition to anemia. effects of iron supplementation on the growth plate need to be evaluated further . growth plate is responsible for 7,8 the elongation of bones. as iron supplementation is given as a routine during pregnancy and lactation so its effects on the height of hypertrophy and proliferative zones of epiphyseal growth plate of femur of new born will be determined with the help of present study. materials and methods this laboratory based randomized controlled trial was approved by ethical committee, of the army medical college rawalpindi. it was conducted at the anatomy department of amc rawalpindi from march 2016 to september 2016 in collaboration with the national institute of health (nih) islamabad. twenty adult sprauge dawley rats (sixteen female and four male) with average weight of 250gms and average age of seven weeks were selected for the study. the animals were kept at standard temperature21±2 ċ in a room maintained on 12 hour 9 light/dark cycle. a battery powered fan was used to maintain the temperature. they were fed on standard lab diet and water ad libitum. 10 they were kept on breeding. presence of vaginal 11 plug was checked in the dames daily. its presence confirms mating and considering it the first day the pregnant rats of both experimental groups b1 and b2 were started with oral iron supplementation daily in water. sytron syrup was given in a dose of 0.5ml once daily for each pregnant rat throughout pregnancy till the day rat delivers through spontaneous delivery. the pups of group b2 were separated with the mothers on iron supplementation throughout the 12 lactation as well. ten pups were separated as control group which was group a1, ten pups in experimental group b1and ten pups in experimental group b2. control group was kept on normal laboratory diet. on completion of 7 weeks of age the rats of all the three groups were weighed and killed by euthanasia by ether inhalation. right femurs were removed. bones were fixed in 10% formalin decalcified in 2% edta solution. lower ends of femurs were separated for evaluation of growth plate. processed into 5micron thick sections using rotary microtome. 13 staining with hematoxylin & eosin, perl's stain (for detection of iron deposition), and toluidine stain was 14 done. slides were observed under the light microscope for histological analysis of the height of hypertrophy and proliferative zones and measured 1 5 with image j.software. the height of the hypertrophy and proliferative zones was measured at three different areas of epiphyseal plate (in the centre and two extreme zones). average of these three readings was recorded as final height. firstly the boundary between reserve and proliferative zone and proliferative hypertrophic zone had to be identified first. between the proliferative and hypertrophy zone it was identified by the first considerably enlarged chondrocytes proportional to the proliferative cells. the limit between the reserve and the proliferative zones was also recognized by the upper border of the proliferative columnar organization, till the beginning of hypertrophy 16 zone. data was analyzed using spss version 21. parameter was expressed as mean and standard deviation. the means were compared for significance among groups using one way analysis of variance (anova) followed by post hoc tukey test for comparison. p value less than 0.05 was considered significant. results the mean ±sd of height of hypertrophy zone in groupa2 (figure-1) was 276.19 ±43.61, mean± sd of group b1 (figure-3) was 136.76±3.58um (table-1). the mean ±sd of group b2 was 205.00±12.76um (table-i). the p-value for the height of hypertrophy zone was < 0.005 (table-ii) which is statistically significant. in proliferative zone mean ±sd of group a2 was 377.29±50.73um (table-1), mean± sd of group b1 (figure-2) was 202.89± 11.56um and mean ±sd of groupb2 (figure-2) was 281.07 ±11.96 (table-1), the p-value for height of proliferative zone was < 0.005(table-1) which is statistically significant. discussion supplementation of mothers with iron during pregnancy and lactation without checking the serum iron level can have damaging effect on the effects of iron supplementation on the height of growth cartilagejiimc 2017 vol. 12, no.3 136 longitudinal growth of the long bones of the offspring via its effects on epiphyseal growth plate. in the current study iron administration during pregnancy and lactation resulted in the reduction of height of the hypertrophy zone and proliferative zone of growth plate of long bones of the off spring as compared to the control group of rats. effects on the height of hypertrophy and proliferative zones of growth plates of experimental groups b1 and b2 are significant statistically. the body has limited capacity to excrete iron, and iron in excess can lead to long17 term damage to tissues. iron supplementation in non-anaemic pregnant women may not be beneficial. this may permit the consideration of a p e rs o n a l i ze d a p p ro a c h fo r a nte n ata l i ro n supplementation, especially in non-anaemic 18 women. current study shows that injudicious iron supplementation of mothers during pregnancy and lactation significantly reduces. the height of hypertrophy and proliferative zones of epiphyseal growth cartilages of long bones of the off springs. it is in accordance with the previous researches showing the orally supplemented iron can easily cross the placental barrier and accumulates in the fetal tissues. a study shows that multiple doses of positively-charged nanoparticles given over several days resulted in significantly increased fetal deaths and accumulation of iron in the fetal liver and 19 placenta. it is also in accordance with the previous studies showing the height of the hypertrophy zone is the 20 main contributor of the growth plate height. the growing cartilages are affected more as compare to the adult cartilage. iron can be detected in isolated chondrocytes after a short culture period in the presence of either iron or haemoglobin, which negatively influences dna content and proteoglycan synthesis rate. this inhibiting effect is reversible in 21 the absence of a pro-inflammatory signal. the decrease in the height of hypertrophy zone and the h e i g h t o f p r o l i fe ra t i v e zo n e i n t h e i r o n supplementation groups are comparable with the earlier study which shows the effects of iron on the 22 bone. conclusion this study recommends that indiscriminate iron supplementation of rats throughout pregnancy and lactation without checking serum iron levels can p value <0.05 is sta�s�cally significant fig 1: h&e stain at 10x. photomicrograph of histological sec�on of growth plate of control group a1 showing height of hypertrophy and prolifera�ve zones fig 2: h & e at 10x. photomicrograph of histological sec�on of growth plate of experimental groups b1 (b) and group b2(c) showing hypertrophy zone(h) and prolifera�ve zone (p) fig 3: cluster bar chart showing comparison of mean values of height of hypertrophy and prolifera�ve zones in micrometers ( along y-axis) among the groups (along x-axis), control group a1 and experimental groups b1 and b2 table i: showing comparison of mean value of height of hypertrophy and prolifera�ve zones effects of iron supplementation on the height of growth cartilagejiimc 2017 vol. 12, no.3 137 affect the height of the hypertrophy and proliferative zones of epiphyseal growth plate of long bones of the off springs. refferences 1. hoffman r, benz jr ej, silberstein le, heslop h, weitz j, anastasi j. hematology: basic principles and practice, expert consult premium edition-enhanced online features. 6th ed. philadelphia: elsevier health sciences. 2013; 6: 239-47. 2. guggenbuhl p, filmon r, mabilleau g, baslé mf, chappard d. iron inhibits 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2015; 68: 592600. 22. tsay j, yang z, ross fp, cunningham-rundles s, lin h, coleman r, et al. bone loss caused by iron overload in a murine model: importance of oxidative stress. blood. 2010; 116: 2582-9. effects of iron supplementation on the height of growth cartilagejiimc 2017 vol. 12, no.3 138 page 18 page 19 page 20 page 21 original�article abstract objective: to assess the resemblance of lip prints among the members of biological families, involving identical twins. study design: descriptive study. place and duration of study: department of forensic medicine & toxicology, post-graduate medical institute/university of health sciences lahore december 22, 2014, to december 22, 2016. materials and methods: a total of 216 individuals (father, mother and both the children), who underwent observational study of lip impression collection without any anesthesia or drug, were enrolled into the present study. father, mother and both identical twins of each family were selected. lip prints of father, mother and both twins of each family were recorded. each lip of 54 twin offspring was compared with the corresponding lip of his/her father, mother, and other identical twin in the same family twin. results: out of 54-total families, monozygotic twins of 19(35.18%) families observed resemblance with father, whereas monozygotic twins of 35(64.81%) families observed resemblance with mother. there was no definite identical lip print pattern observed in any of the children. furthermore, the prevalence of type ii lip prints was higher type present in males and in females. conclusion: lip prints of study participants do not match with each other. they are not identical with other twin baby or either parents but have some resemblance features. like fingerprints, lip print patterns are unique, and it is considered feasible to apply lip prints features in personal identification. key words: cheiloscopy; lip prints; monozygotic twins family, personal identification. amongst the inner labial mucosa and external skin there is zone of transition on which lip patterns are present in the form of wrinkle and grooves in the form of normal lines and fissures. like fingerprints, the pattern of wrinkles on the lips has individual characteristics. the wrinkles and grooves on the labial mucosa (called sulci labiorum) form a characteristic pattern called lip prints, the study of 2 which is referred to as cheiloscopy. lip patterns can be identified as early as the sixth th week of intra uterine life. after 6 week of fetal intra uterine life, lip prints are well developed and can be 3 recognized. the duration of lip print's reliability on paper may be up to 12 weeks even if exposed to ambient conditions, but duration of reliability on glass may be up to 9th week if kept in closed o container in temperature adjusted around 25 c, but if exposed to ambient conditions it may be up to 6th week. clear and identifiable lip prints can be 4 obtained if taken less than 24 hrs. after death . a study was conducted on two matching twins in 1972 which stated that twins are indistinguishable by every other means, but their lip prints were diverse. lip print analysis of family members suggest that introduction personal identification is necessary for unknown deceased person in homicide, suicide, accident, mass disaster etc. identification of a missing individual can aid immensely in the process of grief resolution by family and friends. in universal declaration human rights, article 06 states that “before the law, it is the right of every person to be 1 identified as individual person. on human lips hereditary resemblances of lip prints among the members of biological families 1 2 3 4 5 6 aftab alam tanoli ,ijaz aziz , khalil ur rehman , nayella nijat bangesh , qurrat ul ain , farrukh iqbal correspondence: dr. aftab alam tanoli, department of forensic medicine women medical college, abbottabad 1,4 department of forensic medicine women medical college, abbottabad 2 department of forensic medicine makran medical college, turbat 3 department of forensic medicine rehman medical college, peshawar 5 department of gynae/obs unit-2, holy family hospital unit 2, rawalpindi 6 department of medicine, federal polyclinic hospital, islamabad funding source: nil; conflict of interest: nil received: november 06, 2021; revised: june 06, 2022 accepted: june 06, 2022 lip prints among biological familiesjiimc 2022 vol. 17, no.3 164 offspring do receive similar type of lip prints features as of their mother / father, but location of these lines are different, and no two prints are the same even in 5 twins. development of modern techniques of crime detection has cautioned the criminals for taking sufficient precautions like the use of gloves. in such circumstances, accurate methods like fingerprint analysis fails to establish a positive identity. any method that owns the probability of supporting the forensic field in identifying a dubious should be chased and if revealed applicable then it should be utilized for criminal investigations and legal proceedings. crime detectors mostly don't utilize the benefits of using lip prints for the purpose of identifying the suspects. detailed anti-mortem records of both lips can be used for matching the details of post-mortem lip prints for personal identification. a lip print established at the scene of crime can be a source for inferences as to the character of the cosmetics used, number of people involved, sex, habits, occupational traits and the 6 diseased changes in lips themselves. lip prints were recorded among 54 biological families with siblings involving identical twin, to ascertain inheritance resemblance of lip prints, and to analyze the characteristics of lip prints for positive identification, so that to make it an investigatory tool of identification in forensic sciences. the findings of these studies can be utilized to motivate crime scene investigators to analyze the characteristics of lip prints for positive identification as fingerprints in crime scenes, so that to make it an investigatory tool of identification in forensic sciences. materials and methods a descriptive study was conducted in the department of forensic medicine & toxicology, postgraduate medical institute/university of health sciences lahore from december 22, 2014, to december 22, 2016. a total of 216 individuals (father, mother, both children's), who underwent nonprobability / convenience sampling of lip impression collection without any anesthesia or drug, were enrolled into the present study. before starting the research work, i presented my proposal in institutional ethical review committee and advance studies and research board. ethical review committee approved on 02-07-2014 and advance studies and research board approved on 05-07-2014. only individuals having lips with normal transition zone of mucosa and skin were included in the study. i n d i v i d u a l s h a v i n g i n f l a m m a t i o n o f l i p s , malformation, deformity, surgical scars, active lesions, and hypersensitive to impression material were not included in the study. no drugs or chemical was used in study subjects. the subjects were residents of abbottabad & mansehra (kpk), rawalpindi (punjab) & islamabad surrounding villages. written informed consent was obtained. all participants were given brief details of our objectives and answered the questions relating to procedure. a thin layer of lipstick was applied in a single motion evenly on the lips of everyone. after two minutes, the individuals were advised to maintain a relaxed lip position. negligible pressure was sustained on lips touching cellophane tape the while making the lip impression and subsequently the glued portion of the cellophane tape fixed on to the white bond paper to retain the lip impression. the impressions were afterward visualized with the magnifying lens. to minimize the chances of error, which could most likely occur with manual magnifying lens, a digital method (indirect method) was used to analyze the lip marking. the lip impressions were scanned and exported on adobe photoshop-7 software at 256 gray scales configuration. a 300-dpi resolution was used to enhance the imagining quality of lip prints. collected data values were recorded and analyzed using spss 20.0. p-value was taken as < 0.05. confidence level was taken as 95%. mean, standard deviation, minimum and maximum values were calculated for continuous variables in all quadrants of individual lips. frequency and percentages were calculated for resemblance among biological families and for gender. two-way anova test applied for substantial variance in type of lip prints. z-test was applied to test the resemblance of lip prints to mother and father separately in the family. microsoft word and excel have been used to form tables and figures. results the available data was used to generate the profile of resemblance of lip prints among various family members. the percentage of resemblance of lip prints of father and mother with their identical twins jiimc 2022 vol. 17, no.3 165 lip prints among biological families st nd and resemblance of 1 identical twin with 2 identical twin with their father and mother in all of 54 families (216 individuals) are described in graph. resemblance between first twin and second twin was found to be 58.335. maximum resemblance of twin babies with father and mother was87.51% & 91.67% respectively, whereas minimum resemblance of twin babies with father and mother 25% & 33% respectively st nd in 54 families, father resemblance with 1 and 2 twin baby was calculated, and then mother st nd resemblance with 1 and 2 twin baby was calculated. in 19 families, off-springs found to be having higher resemblance with father 35.18% (z=0.4978, p<0.05), whereas in 35 families, children's lip impressions showed higher resembling with fig. 1: percent resemblance of 54 families the x-axis shows family coded number. the y-axis shows resemblance among the families. a-c corresponds to father verses first twin a-d corresponds to father verses second twin b-c corresponds to mother verses first twin b-d corresponds to mother verses second twin c-d corresponds to first twin verses second twin lip print pattern of all identical twin babies along with their parents were analyzed. lip print type-1 was 116 (4.44%), lip print type-2 was 1870 (71.6%), lip print type-3 was 52 (1.99%), lip print type-4 was 567 (21.7%) and lip print type-5 was 05(0.19%) in all the quadrants of lips. the mean resemblance between father and both twin was found to be 58.335 while between mother and first twin was as 58.335 and between mother and second twin was as 70.835. the mean fig. 2: percent distribution of types of lip prints in male and female table i: lip prints quadrant wise in male gender table ii: lip prints quadrant wise in female gender jiimc 2022 vol. 17, no.3 166 lip prints among biological families mothers 64.81% (z=0.49917, p<0.05). lip prints showed a strong positive and statistically significant correlation between parents and their offspring. we observed that mother resemblance towards twin babies was at higher level as compared with father resemblance. father to mother resemblance ratio is 1:1.8. no lip print pattern was found specific to any lip quadrant and mostly mix types of lip print pattern were present in all the 04quadrants of lips. none of the gender had any specific lip print pattern in any specific lip quadrant. discussion our research study with 54-pairs of identical twin babies along with their mother and father in a family is unique and valuable addition on chelioscopic data. lip prints are not identical in case of identical twins but similarities of lip prints between parents and children were found accounting for the hereditary to play a major role. study on18-pairs of monozygotic twins and 22-pairs of monozygotic twins found that families with identical twin babies pointed to have a considerable genetic factor. uni-ovular twins share same proteins, same genetic information so lip can be used as a primary biometric modality for 7 successful identification purpose. lip print pattern type ii was the commonest finding in the study. in male and female gender participants lip print type ii was 70.88% and 72.3%, lip print type iv was 22.9% and 20.4%, lip print type i was 3.8% and 5.06%, lip print type iii was 2.32% and 1.66%, and lip print type v was 0.0% and 0.37%, respectively. in our study lip print type ii was most common pattern in all the quadrants of lip in both males and females. the predominance of type ii lip print is in accordance of the findings of a researcher, who studied 208 individuals and found type ii (47.6%) as predominant 8 lip print type. the result finding of other research 9,10,11 articles are also consistent with our data. the findings of another study has also shown type ii lip print pattern of both sexes in all of the 0412 quadrents. in female study subjects, lip print type ii was most common dominant finding, which is 13 consistent with the results of other findings. studies conducted by other organizers found that lip print type i was highest percentage in male and females 14,15 subjects. lip prints show differences according to race and ethnic origins of persons. in contrast to our observation previous work demonstrated that lip print type ii with (26%) was second most studied type 16 in both sex. studies regarding prevalence of lip print pattern in different races or ethnic origin have been reported to show variations of pattern not only in 17 population but also in male and female subjects. similarly the second most common type observed was lip print type iv which is in accordance to the 18,19,20 previous studies. but in contrast to the other studies where lip print type iv was most common 6,5 type of lip prints. other lip print pattern observed in our research were lip print type iv, i, iii and v respectively in prevalence which is in contrast to findings of other research where they found the 21 succession of lip print as type iii , iv, i and v. these findings are consistent with the study on 496 subjects and twins with families. no two identical lip 22 prints were found in their study. these findings are also like the study performed on 20-pairs of monozygotic twins and 20-pairs of non-twin 23 siblings. overall, the results of the study are found to be consistent with the previous studies. current study shares several features common with other published data in literature, where parents and monozygotic twins were studied, and it was found that they shared some similarity in the grooves, but the detail features of lip prints were not same. they found that neither between the twins nor the twins 24,25 with their parents had the similarity. also lip prints were not identical in case of identical twins but the similarities of lip prints between parents and children were found accounting for the hereditary to play a major role. identical twin babies had shown more percentage of similarities with each other in comparison to non-identical twins. also, inheritance fig. 3: parents maximum and minimum resemblance with twins jiimc 2022 vol. 17, no.3 167 lip prints among biological families pattern was significant for twin babies in case of their 11 lip prints. however, the findings of the study are inconsistent with the findings where they found no significant correlation with parents and twin 16 offspring. the most important feature of the current study is that the level of resemblance of parents with the offspring is studied. when individuals were compared for resemblance among biological family, there was no significant difference in parents and off springs as revealed by z-test 17 (z=0.4978 and z=0.499 for father and mother respectively) showing positive association with both parents. the finding is important as it could be used in forensic identification of missing persons in a family as phenotypic marker especially in cases of mass disaster. conclusion comparison of lip print pattern of identical twin babies shows that they are unique to each individual(father, mother, each twin baby) and among identical twin lip print patterns have some similarities with each other. they are not identical with other twin baby or either parents but have some resemblance features. there is no definite identical lip print pattern observation in any of the children. the prevalence of type-2 lip print is higher type, present in male and females of studied population. it concludes that lip print pattern is nonspecific indicator of gender determination. operational definition resemblance when off springs will receive at-least one same types of lip prints characteristic as their parents (either father or mother) in each quadrant of lip, but placement of lip prints characteristics may or may not be in the exact location as their either parents will be labeled as resemblance. study limitations when the subjects press his or her lips, there is a possibility that only the central area of lip come in contact while the rest relaxed portion stay away of cellophane tape, which leads to distortion of the prints. identifying the biological family tree with identical twins is really hard work and time consuming. family members especially fathers are mostly out of house due to business or job earning reasons and we must wait a lot and sometime travel a lot. families are reluctant to participate voluntarily and concerned of giving their personal details and samples. ethical approval the ethical approval from ethical committee of postgraduate medical institute, lahore was obtained prior to initiation of the research work. participants' consent the informed consents have been obtained from volunteer individuals or guardians to publish the data concerning this case. funding source authors declared no funding from any source. conflict of interest authors declared no conflict of 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the corresponding author upon request. this is an open access article distributed under the terms of the creative commons attributionnoncommercial 2.0 generic license. jiimc 2022 vol. 17, no.3 169 lip prints among biological families original�article abstract objective: to compare serum gamma-glutamyl transferase and serum c-reactive protein as biomarker of oxidative stress in patients of type 2 diabetes mellitus. study design: comparative cross-sectional study. place and duration of study: the study was conducted at armed forces institute of pathology, department of chemical pathology and endocrinology rawalpindi. the duration of study was 6 months i.e., 17 nov 2021 – 17 may 2022 after approval from institutional review board fc-chp21-12/read-irb/22/846. materials and methods: an analytical, cross-sectional research was carried out at armed forces institute of pathology rawalpindi. an overall 300 diabetic patients were included between ages of 45 – 65 years. group i had 100 nondiabetic individuals of 45 – 65 years of age with hba1c < 5.7 %. group ii and iii included 100 patients each of dm of matched age with hba1c 6.5 – 7 % and greater than 7 % respectively, without any other chronic disease. serum gamma-glutamyl transferase, hba1c, serum c-reactive protein were analyzed. moreover, some more biochemical investigations such as serum liver enzymes were measured to rule out any liver disease. one-way anova was followed up by post-hoc tukey analysis for intergroup comparison. results: mean serum gamma-glutamyl transferase levels were markedly increased in group iii patients followed by group ii and normal in group i. the mean of serum gamma-glutamyl transferase in group i was (9.38+4.05u/l), group ii (34.27+15.07 u/l) and group iii (47.08+20.56 u/l). the mean of serum c-reactive protein in group i was (11+6.02 mg/l), group ii (62.07+ 26.94 mg/l) and group iii (107.73+57.03 mg/l). pearson correlation revealed prominent positive correlation between hba1c, serum gamma-glutamyl transferase and serum c-reactive protein with r value of serum gamma-glutamyl transferase (0.838367) and serum c-reactive protein (0.684722). one-way anova and post-hoc tukey analysis had p value of < 0.05 which was statistically significant. conclusion: serum gamma-glutamyl transferase is better marker of oxidative stress in patients of type 2 diabetes mellitus as compared to serum c-reactive protein. the r value of serum gamma-glutamyl transferase is (0.838367) and serum c-reactive protein is (0.684722) indicating strong positive correlation of serum gamma-glutamyl transferase with hba1c. therefore, serum gamma-glutamyl transferase can be used for the prevention and monitoring of complications of type 2 diabetes mellitus. key words: armed forces institute of pathology (afip), c reactive protein (crp), diabetes mellitus (dm), gamma glutamyl transferase (ggt), institutional review board (irb). recognizable symptoms and long-term problems are caused by hyperglycemia, which also serves as the disease's definition. the main objectives of diabetes mellitus research have been to comprehend the pathophysiology and prevent long-term consequences. unquestionably, one of the most difficult health issues of the twenty-first century is diabetes. recent studies have established role o f i n f l a m m a t i o n a n d o x i d a t i v e s t r e s s i n 1,3 pathophysiology of complications of dm. serum ggt is a cell-surface enzyme that contributes to glutathione's extracellular degradation (gsh). the introduction diabetes mellitus (dm) is a collective term for several m eta b o l i c co n d i t i o n s t h at a l l ex h i b i t t h e hyperglycemia phenotype. the disease's most association of serum gamma-glutamyl transferase and c-reactive protein as a biomarkers of oxidative stress in patients of type 2 diabetes mellitus ammar ul hassan, zujaja hina haroon, sobia irum kirmani, muhammad anwar, muhammad younas, muhammad usman munir correspondence: dr. ammar ul hassan registrar department of chemical pathology armed forces institute of pathology, rawalpindi e-mail: drammarhassan27@gmail.com department of chemical pathology armed forces institute of pathology, rawalpindi received: november 17, 2022; revised: april 26, 2023 accepted: may 05, 2023 jiimc 2023 vol. 18, no. 2 ggt & crp: biomarkers of oxidative stress 93https://doi.org/10.57234/jiimc.june23.1570 enzyme is produced in numerous tissues, although 2 most of the serum ggt are synthesized in the liver. the role of serum ggt in controlling extracellular glutathione (gsh) transport system serves as basis of intracellular antioxidant defenses. several pathogenic diseases, including aging, carcinogenesis, inflammation, reperfusion injury and atherosclerosis relate to oxidative stress. additionally, oxidative stress might also be a contributing factor to the development and 4,5 pathophysiology of diabetes. the majority of research examines the part oxidative stress plays in the development of cardiovascular problems in 3 diabetic individuals. in addition, increased levels of serum ggt is linked with increased body weight and a liver disease called nonalcoholic fatty liver disease “nafld”. it is caused when excessive fat is deposited in a liver. nafld is believed to be main contributory factor responsible for hepatic insulin resistance and ultimately development of hyperinsulinemia and systemic insulin resistance. thus, serum ggt may reflect metabolic changes and may serve as diagnostic for the syndrome of insulin resistance. several potential explanations explain the link between elevated serum ggt levels and glycemic control in patients with type 2 diabetes with 5,18 excellent and poor control. in the pathophysiology of diabetes, serum ggt may therefore play the role of the insulin resistance syndrome marker. moreover, serum ggt may leak into the serum due to regular cellular turnover and cellular stressors. there are multiple putative reasons for serum ggt leakage, including oxidative stress, protein degradation, glycosylation, and endothelial cell injury. thus, elevated serum ggt levels may identify individuals with a minimal but constant increase in 16,17 oxidative and other cellular stress. serum ggt is an upcoming biomarker of oxidative stress monitoring in disease progression from very beginning. the rationale of study is to evaluate serum ggt as an early marker of oxidative stress in patients of type 2 diabetes mellitus. the main objective of this study is to compare serum gammaglutamyl transferase and serum c-reactive protein as biomarker of oxidative stress in patients of type 2 diabetes mellitus. materials and methods an analytical, cross-sectional research was carried out at armed forces institute of pathology rawalpindi. the duration of study was 6 months. an overall 300 diabetic patients were included between ages of 45 – 65 years. nonprobability convenient sampling technique was used. the study started after the approval of ethical review committee i.e., 17 nov 2021 – 17 may 2022 (fc-chp21-12/readirb/22/846.) group i had 100 nondiabetic individuals of 45 – 65 years of age with hba1c < 5.7 %. group ii and iii included 100 patients each of dm of matched age with hba1c 6.5 – 7 % and greater than 7 % respectively, without any other chronic disease. we excluded patients with deranged liver enzymes and chronic disorders, as they could interfere with our results by falsely altering the concentration of serum ggt. the patients taking hepatotoxic drugs were also excluded. all eligible participants in this study were informed of the study's goals. detailed history was taken in endocrine clinic department of chemical pathology and endocrinology afip. group i included 100 nondiabetics individuals with 45 – 65 years of age with hba1c < 5.7 %. group ii and iii included 100 patients each of dm of matched age with hba1c 6.5 – 7 % and greater than 7 % respectively, without any other chronic disease. detailed history was followed up by review of patient's past medical reports from laboratory information management system (lims). for participation in research groups and venipuncture, informed written agreement was obtained from all study participants. the emphasis was placed on the voluntary nature of participation in this study. during a standardized interview, the questions also focused on sociodemographic variables and the characteristics in the background diabetes has (length and type of dm, mode of treatment used for dm, and any complications). in addition, each participant got a comprehensive, standardized medical checkup, which included blood collection. under fasting conditions, 5 ml of each participant's venous blood was collected using a disposable vacutainer equipment (plain and edta). serum and plasma were separated within a halfhour and kept at 2-8°c for analysis of serum crp and plasma hba1c. samples were analyzed in multiple batches. glycosylated hemoglobin (hba1c) was analyzed by turbidimetric inhibition immunoassay (tinia) jiimc 2023 vol. 18, no. 2 94 ggt & crp: biomarkers of oxidative stress https://doi.org/10.57234/jiimc.june23.1570 method on sebia capillary octa-3. carboxy substrate kinetic method was used to determine the activity of serum ggt on chemistry analyzer advia 1800. one-way anova was conducted among three group for comparison of means. post-hoc tukey analysis was used to compare the intergroup mean. pearson linear correlation was used to study correlation between hba1c, serum ggt and serum crp. statistically speaking, p-value of < 0.05 and r value of > 0.75 was considered as significant. results mean of serum ggt were strikingly increased in the patients of group iii followed by group ii and normal in group i. the mean of serum ggt in group i was (9.38+4.05u/l), group ii (34.27+15.07 u/l) and group iii (47.08+20.56 u/l). the mean of serum crp in group i was (11+6.02 mg/l), group ii (62.07+ 26.94 mg/l) and group iii (107.73+57.03 mg/l). pearson correlation revealed prominent positive correlation among hba1c, serum ggt and serum crp with r value of serum ggt (0.838367) and serum crp (0.684722). one-way anova and post-hoc tukey analysis was conducted to compare the mean. statistically speaking, p-value of < 0.05 was significant. discussion patients of type 2 dm having poor glycemic control have considerably higher concentrations of serum ggt and hba1c compared to healthy individuals and those with tightly regulated glycemic control. in addition, we found a substantial positive linear correlation between serum ggt and hba1c. these results imply a correlation between oxidative stress (as evidenced by a higher serum ggt) and glycemic management with type 2 diabetic patients and associated comorbidities. this shows that oxidative stress and chronic inflammation have a major role in 19-21 the pathogenesis of type 2 diabetes. mean of serum ggt was lowest in control group i.e individuals with normal glycemic control (hba1c < 5.7 %) and significantly increased in group ii (hba1c 6.5 – 7 %) and group iii (hba1c > 7 %). the mean of serum ggt in group i was (9.38 u/l), group ii (34.27 u/l) and group iii (47.08 u/l). r value of serum ggt was (0.838367) indicating positive correlation between serum ggt and hba1c. a serum ggt elevation may be indicative of nonalcoholic fatty liver disease, which is characterized by an excessive accumulation of fat in the liver. it is believed that a fatty liver results into hepatic insulin resistance 22 leading to hyperinsulinemia. serum crp is a well-known marker of inflammation, however its role in oxidative stress secondary to type 2 diabetes mellitus has not been established. the mean of serum crp in group i was (11 mg/l), group ii (62.07 mg/l) and group iii (107.73 mg/l). however, table i: mean serum ggt and serum crp among study groups (n = 300) table ii: comparison of serum ggt among groups (n = 300) *p value < 0.05 considered as statistically significant table iii : comparison of serum crp among groups (n = 300) *p value < 0.05 considered as statistically significant figure 1: pearson correlation scatterplot of serum ggt & serum crp (n = 300) jiimc 2023 vol. 18, no. 2 95 ggt & crp: biomarkers of oxidative stress https://doi.org/10.57234/jiimc.june23.1570 pe a rs o n co r re l at i o n re ve a l e d i n s i g n i f i ca nt correlation of serum crp and hba1c with r value of (0.684722). there are other studies supporting our results and findings. r sharma et al. demonstrate a strong correlation of serum hscrp and serum ggt in diabetic with poor glycemic control, which may be due to oxidative stress and inflammation in 9 diabetes. the findings of thamer c et al. and andre p et al. seconds a correlation between high serum ggt, uncontrolled diabetes and metabolic syndrome. elevated levels of ggt are associated with increased insulin resistance, an increased risk of developing type 2 diabetes, and inadequate glycemic control. moreover, serum ggt may leak into the serum due to regular cellular turnover and cellular stressors. there are multiple putative reasons for serum ggt leakage, including oxidative stress, protein degradation, glycosylation, and endothelial cell 23,24 injury. marchesini g et al. and silventoinen k et al. determined that the close affiliation of serum ggt activity with other metabolic disorders related to dm, such as atherosclerosis, cardiovascular diseases, and dyslipidemia. increased oxidative stress, fatty liver and insulin resistance may be responsible for the pathogenesis of disease increased activity of serum ggt. increasing evidence suggests that serum ggt is a measure of both fatty 12,13 liver and oxidative stress. study revealed that serum ggt plays a crucial role in the maintenance of intracellular antioxidant defenses by mediating the transport of extracellular glutathione into most cell types. it is an enzyme generally found on the outside of the cell membrane whose major job is to maintain intracellular concentrations of glutathione (gsh), the cell's most important antioxidant defense. growth in serum ggt activity may be a reaction to oxidative stress, allowing for an increase in the gsh 25 precursors' movement into cells. our research had numerous limitations. first, this was a cross-sectional study that reports no causal effect. in addition, serum ggt levels in the follow-up were not included in the analysis. in addition, some confounding variables, such as fasting insulin concentration and markers other than serum crp that can assess the inflammatory status of the patient in correlation with serum ggt, could not be included in this study. conclusion it can be concluded that serum ggt is a better and more specific marker of oxidative stress in patients of type 2 dm as compared to serum crp. serum ggt can be used for prevention and monitoring of complications of type 2 diabetes mellitus. references 1. powers ac, niswender kd, evans-molina c. diabetes mellitus: diagnosis, classification, and pathophysiology. harrison's principles of internal medicine. 2018;2:2399407. bookid=2129&sectionid=192288322 2. bandara d, thennakoon s, dias p, withanage n. association of serum gamma glutamyltransferase with diabetes mellitus, random blood sugar and body mass index in selected sri lankan subjects. ceylon journal of medical science. 2022 dec 28;57(1). doi: 10.4038/cjms.v57i1.4970 3. ohiagu fo, chikezie pc, chikezie cm. pathophysiology of diabetes mellitus complications: metabolic events and control. biomedical research and therapy. 2021 mar 31;8(3):4243-57. doi : 10.15419/bmrat.v8i3.663 4. oyakhire f, emokpae ma, ogie e, valentine ee. effect of diabetes mellitus on the excretory function of the liver. medical laboratory technology journal. 2021 dec 3 1 ; 7 ( 2 ) : 1 5 5 6 3 . d o i : h t t p s : / / d o i . o r g / 10.31964/mltj.v0i0.416 5. sharmin f, junaed mt. association of obesity and serum gamma glutamyl transferase with impaired fasting glucose in adults at a tertiary level hospital of bangladesh. mymensingh medical journal: mmj. 2022 jul 1;31(3):61421. 6. darenskaya ma, kolesnikova li, kolesnikov si. oxidative stress: pathogenetic role in diabetes mellitus and its complications and therapeutic approaches to correction. bulletin of experimental biology and medicine. 2021 may;171(2):179-89. doi: 10.1007/s10517-021-05191-7 7. wan jy, yang lz. liver enzymes are associated with hyperglycemia in diabetes: a three-year retrospective study. diabetes, metabolic syndrome and obesity: targets a n d t h e r a p y . 2 0 2 2 f e b 2 3 ; 1 5 : 5 4 5 5 5 . d o i https://doi.org/10.2147/dmso.s350426 8. rösen p, nawroth pp, king g, möller w, tritschler hj, packer l. the role of oxidative stress in the onset and progression of diabetes and its complications: asummary of a congress series sponsored byunesco-mcbn, the american diabetes association and the german diabetes society. diabetes/metabolism research and reviews. 2001 may;17(3):189-212. doi: 10.1002/dmrr.196. 9. marchesini g, brizi m, bianchi g, tomassetti s, bugianesi e, lenzi m, mccullough aj, natale s, forlani g, melchionda n. nonalcoholic fatty liver disease: a feature of the metabolic syndrome. diabetes. 2001 aug 1;50(8):1844-50. doi: 10.2337/diabetes.50.8.1844 10. lee dh, ha mh, kim jh, christiani dc, gross md, steffes m, jiimc 2023 vol. 18, no. 2 96 ggt & crp: biomarkers of oxidative stress https://doi.org/10.57234/jiimc.june23.1570 blomhoff r, jacobs dr. gamma-glutamyltransferase and diabetes—a 4 year follow-up study. diabetologia. 2003 mar;46(3):359-64. doi: 10.1007/s00125-003-1036-5 11. s h a r m a r , s h a r m a s , k a u s h i k g g . g a m m a glutamyltransferase (ggt)–a novel marker of endothelial dysfunction. jiacm. 2010;11(1):26-30. 12. thamer c, tschritter o, haap m, shirkavand f, machann j, fritsche a, schick f, häring h, stumvoll m. elevated serum ggt concentrations predict reduced insulin sensitivity and increased intrahepatic lipids. hormone and metabolic research. 2012 apr;37(04):246-51. doi: 10.1055/s-2005861411 13. andré p, balkau b, born c, charles ma, eschwège e. threeyear increase of gamma-glutamyltransferase level and development of type 2 diabetes in middle-aged men and wo m e n : t h e d es i r co h o r t . d i a b e to l o g i a . 2 0 1 5 nov;49(11):2599-603. doi: 10.1007/s00125-006-0418-x 14. marchesini g, avagnina s, barantani eg, ciccarone am, corica f, dall'aglio e, dalle grave r, morpurgo ps, tomasi f, vitacolonna e. aminotransferase and gamma-glutamyl transpeptidase levels in obesity are associated with insulin resistance and the metabolic syndrome. journal of endocrinological investigation. 2005 jun;28(6):333-9. doi: 10.1007/bf03347199 15. lee dh, silventoinen k, jacobs jr dr, jousilahti p, tuomileto j. γ-glutamyltransferase, obesity, and the risk of type 2 diabetes: observational cohort study among 20,158 middle-aged men and women. the journal of clinical endocrinology & metabolism. 2004 nov 1;89(11):5410-4. doi: 10.1210/jc.2004-0505 16. krishnamurthy v, patted as, kumar a, jayaram sk, magaji bs. evaluation of serum gamma-glutamyl transferase and highly sensitive c-reactive protein as biomarkers of oxidative stress and inflammation in type 2 diabetes mellitus patients with good and poor glycemic control. int j a d v m e d . 2 0 1 9 m a y ; 6 ( 3 ) : 6 5 0 . d o i : https://doi.org/10.18203/2349-3933.ijam20191494 17. bs m, patted da, krishnamurthy dv, dak t, jayaram ds. pdb9 serum ggt and hscrp: early predictors of oxidative stress and inflammation in type 2 diabetes mellitus patients with good and poor glycemic contorl. value in health. 2019 nov 1;22:s573. doi: 10.1186/2251-6581-1256 18. elimam h, abdulla am, taha im. inflammatory markers and control of type 2 diabetes mellitus. diabetes & metabolic syndrome: clinical research & reviews. 2019 jan 1;13(1):800-4. doi: 10.1016/j.dsx.2018.11.061 19. lee jh, lee hs, lee yj. serum γ-glutamyltransferase as an independent predictor for incident type 2 diabetes in middle-aged and older adults: findings from the koges over 12 years of follow-up. nutrition, metabolism and cardiovascular diseases. 2020 aug 28;30(9):1484-91. doi: 10.1016/j.numecd.2020.04.027 20. nagalakshmi cs, savadi b, santhosh nu, shaikh sb, javarappa d. can gamma glutamyl transferase serve as a marker to predict the risk of metabolic syndrome in patients with type 2 diabetes mellitus?. indian journal of medical biochemistry. 2019 sep;23(3):347-9. doi: 10.5005/jp-journals-10054-0116 21. neuman mg, malnick s, chertin l. gamma glutamyl transferase–an underestimated marker for cardiovascular disease and the metabolic syndrome. journal of pharmacy & pharmaceutical sciences. 2020 apr 19;23:65-74. doi: 10.18433/jpps30923 22. mohapatra e, priya r, nanda r, patel s. serum ggt and serum ferritin as early markers for metabolic syndrome. journal of family medicine and primary care. 2020 jul;9(7):3458. doi: 10.4103/jfmpc.jfmpc_570_20 23. dai h, zhu l, pan b, li h, dai z, su x. the relationship between serum γ-glutamyltransferase (ggt) and diabetic nephropathy in patients with type 2 diabetes mellitus: a cross-sectional study. clinical and experimental medicine. 2023 jan 11:1-2. doi: 10.1007/s10238-023-00991-9 24. shibabaw t, dessie g, molla md, zerihun mf, ayelign b. assessment of liver marker enzymes and its association with type 2 diabetes mellitus in northwest ethiopia. bmc research notes. 2019 dec;12:1-5. doi: 10.1186/s13104019-4742-x agarwal h, jha op, meena pk. role of serum γglutamyl transpeptidase (ggt) level as a marker for the detection of type-2 diabetes mellitus. conflict of interest authors declared no conflicts of interest. grant support and financial disclosure authors have declared no specific grant for this research from any funding agency in public, commercial or nonprofit sector. data sharing statment the data that support the findings of this study are available from the corresponding author upon request. this is an open access article distributed under the terms of the creative commons attributionnoncommercial 2.0 generic license. jiimc 2023 vol. 18, no. 2 97 ggt & crp: biomarkers of oxidative stress https://doi.org/10.57234/jiimc.june23.1570 original�article abstract objective: to study the frequency of periodontitis in diabetes mellitus patients and the impact of glycaemic control on the severity of periodontitis. study design: a descriptive observational study. place and duration of study: this study was completed in six months from may2018 to november2018 in department of medicine in collaboration with dental department of railway general hospital, rawalpindi. materials and methods: this study included 150 participants. participants were divided in two groups with 75 individuals placed in each group. the study group comprised of well controlled and poorly controlled diabetics referred from medical opd and medical wards, selected through non-probability consecutive sampling. the control group involved normal healthy individuals. glycemic control was evaluated by hba1c level. community periodontal index (cpi) was recorded to compare the periodontal status of both groups using perioprobe. confounders like personal and oral hygiene habits along with diabetes profile, treatment and duration were also recorded. data analysis was done using spss, version 21. results: the frequency of periodontitis in diabetics and non-diabetics was 87.49 % and 8.51% respectively. mean-cpi was higher in diabetics (2.76 ± .78) compared to non-diabetics (1.88± .56) and was statistically significant. tooth loss was 59.8% in diabetics and 15% in non-diabetics. poorly controlled diabetics had higher mean-cpi (3.23± .38 vs2.24± .45, p <0.001) compared to well controlled diabetics. mean-cpi score increased with increase in duration of diabetes, 1.89± .51, 3.15± .56 and 3.32± .46 in patients with 1-5, 6-10 and >10 years of diabetes respectively. conclusion: diabetes mellitus patients have higher frequency of periodontitis as compared to non-diabetics. its severity increases as glycemic control worsens. moreover, its severity also increases with duration of diabetes. key words: community periodontal index, diabetes mellitus, hb a1c, periodontitis. microbes. the exaggerated host immune response in attempt to destroy microbes results in continued 2 destruction. 3 periodontitis is most common in elderly. severe periodontitis affects about 10% to 15% of population mainly adults around the age of 50-60.periodontitis causes economic burden of about 54 billion us 4 dollars per year. diabetes mellitusa rapidly growing epidemic, is a chronic metabolic disorder characterized by hyperglycemia leading to complications like diabetic 5 nephropathy, retinopathy, and neuropathy. periodontitis is regarded as sixth complication of 6 diabetes. t1dm previously called iddm and type 2 diabetes (niddm) are associated with increased risk 7,8,9,10 of periodontitis. the risk increases tremendously 11,12 as glycemic control worsens. each 1% reduction in hba1c level is associated with significant decline in micro and macro vascular complications of 9 diabetes. research has shown that reductions in hba1c of up to 0.40% could be achieved with 13 periodontal treatment. introduction periodontitis is the chronic inflammation of periodontium (gingival tissue and its supporting 1 bone). plaque is a biofilm which accumulate on teeth near and below gums. when plaque is not taken care of by cleaning, it becomes hard tartar (calculus) and leads to gingivitis and periodontitis. current research has suggested important role of frequency of periodontitis in diabetes patients. a hospital based study 1 2 3 4 5 6 samia kausar , shamaila burney , khalil ur rehman , zunera jahanzab , asim zulfiqar , amna shoaib correspondence: dr. samia kausar assistant professor department of medicine islamic international medical college riphah international university, islamabad e-mail :samia.kausar@riphah 1,2,4,5 3 department of medicine/dentistry islamic international medical college riphah international university, islamabad 6 department of dentistry punjab dental hospital, lahore funding source: nil; conflict of interest: nil received: february 01, 2019; revised: july 18, 2019 accepted: july 19, 2019 periodontitis in adult diabetes patientsjiimc 2019 vol. 14, no.3 150 the mechanisms underlying the link between the two diseases involve inflammation. diabetes mellitus for both type-1 and type-2 were found to 14 have elevated levels il-6 and tnf-alpha. serum levels of il-6 correlate well with severity of 15 periodontitis. chronic hyperglycemia causes structural and functional damage to blood vessels 16 and tissues. moreover age and rage interaction 17 result in local cytokine release. local cytokine 7,8 release increases insulin resistance. impaired apoptosis and neutrophil function in diabetes is 7,8 associated with increase tissue destruction. moreover presence of diabetes enhances the 1 8 pathogenicity of oral flora. so continued inflammation in periodontitis can adversely affect metabolic control of diabetes, and persistent hyperglycemia in turn potentiates periodontitis 10 suggesting bidirectional relationship. a large body of evidence is available in current literature which confirms that uncontrolled diabetes 7,8,9 worsens periodontitis and vice versa. controlling diabetes is likely to improve periodontitis and vice 9,11 versa. teeuwet al. have suggested periodontitis as 10 a possible early sign of diabetes mellitus. this fact could be exploited for better management of both conditions. the latest studies suggest that better glycemic control may be achieved by resolution of periodontal inflammation by regular periodontal treatment. non-surgical treatment of periodontitis reduces insulin requirements, systemic inflammation and 13 leads to better metabolic profile. although large randomized control studies are required to validate these results. there is need to further explore the relationship between diabetes mellitus and periodontitis as the prevalence of diabetes is expected to increase in next few decades. the beneficial effect of periodontal management on diabetes and its complications i l l u m i n a t e s p o t e n t i a l v a l u e o f e n h a n c e d understanding of relation between two conditions. t h e r e i s a d e a r t h o f c o m m u n i t y b a s e d epidemiological data from pakistan on this association. no separate guidelines/protocols for screening of diabetes in patients with periodontitis and vice versa exist. the objective of study was to find the frequency of periodontitis in diabetes mellitus patients and to determine the effect of glycemic control on severity of periodontitis. material and methods this was a descriptive observational study. it was conducted at department of medicine and department of dentistry at railway general hospital from may2018 to november2018. sample size was 150 patients. patients with type2diabetes (duration>1 year) were included into the study group using consecutive non-probability sampling. they were referred to dental department for examination from medical in and out patient department. non-diabetic patients visiting the dental department were randomly selected for the control group while ensuring the age and sex matched the diabetic-study group patients. inclusion criteria for both groups were individuals having no fewer than 20 teeth. patients on prophylactic antibiotics for rheumatic fever, drug causing gum hypertrophy (phenytoin, cyclosporine), heart problem, type-1 diabetes mellitus, pregnant and lactating mothers were excluded. the study was initiated after approval from the institutional ethical review committee of riphah international university. informed written consent was taken from all participants. a brief patient history was taken along with examination. relevant information about the age, sex, personal habits (pan, chewing tobacco, smoking, naswar, gutka), oral hygiene aids (toothbrush, toothpaste, mouth washes, tooth powder, tongue cleaner) frequency of tooth brushing (occasional, once, twice daily) were recorded. the diabetes status (hba1c values), diabetes duration (1-5 years, 6-10 years, >10 years) and the detail of diabetes treatment (diet restriction, physical exercise, oral hypoglycemic drugs and or insulin) were entered in specially designed performa. periodontal status was assessed by single trained examiner for both groups. perioprobe (single ended probe by marquis dental) with blunt rounded tip and millimeter marking, was used for examination. ten index teeth (11, 16, 17,26,27,31,36,37,46, and 47) were examined. cpi was applied in each six sextants 19 as per laid down criteria by who. 5 diagnosis of diabetes was made per who criteria. h e m o g l o b i n a 1 c ( ro c h e d i a g n o st i c , b a s e l , switzerland) was checked once in all participant of jiimc 2019 vol. 14, no.3 151 periodontitis in adult diabetes patients study group to assess glycemic control. diabetic patients were divided based on hba1c level into two c a t e g o r i e s : < 7 % w e l l c o n t r o l l e d , > 7 % 20 poorlycontrolled. data (parametric) was analyzed by spss-21. descriptive statistics including patient's age, gender and admission number were entered. mean and standard deviation was calculated for age and cpi. frequency of qualitative variable was expressed as frequencies and percentages. independent samplettest was used to compare quantitative data. results one hundred and fifty individuals were selected for study after meeting inclusion and exclusion criteria. 75 (40 females and 35 males) were diabetics and 75 were non-diabetics who were age and sex matched. the mean age was 53.91 ±9.50 in diabetic group and 49.15±8.7 in non-diabetic group. the age range was 18-70 years. the frequency of periodontitis in diabetic was 87.49%.the mean-cpi score was 2.78±.78 in diabetic group and 1.88± .95 in nondiabetic group. periodontal status of diabetic and non-diabetics is shown in figure 1 and table 1.patients with well controlled and poorly controlled diabetes groups had mean-cpi score of 2.24±.45 and 3.33±.56 respectively. periodontal status of well controlled vs. poorly controlled was also statistically significant (table 3, figure 2). most of the patients, 48% had diabetes duration of 15 years while26.6% and 25.3% patients had diabetes for 6-10 years and >10 years respectively. cpi score in these groups were, 1.89± .51, 3.15±.56 and 3.32±.46 respectively as shown in figure 3. in our study tooth loss was present in 59.5% in diabetic vs. 15% of non-diabetic. there were 12% smokers in diabetic group vs. 11.5% in non-diabetics. none of the study participant used gutka, pan or naswar. in both groups tooth brush was most frequently practiced for oral hygiene. fewer participants were finger user. few patients used tooth powder, miswak and mouthwash. most of diabetics brushed only once a day 85% compared to 83% non-diabetics. about 8% participants brushed occasionally. majority of diabetics, 60%, were on both insulin and oral hypoglycemic drugs. 25% were taking only oral hypoglycemic drugs and rest 15% were using insulin only. mode of therapy, both insulin and oral hypoglycemic drugs did not affect periodontal status. table i: distribu�on of study popula�on according to age and sex. (pa�ents n=150) table ii: comparison of periodontal status of diabe�c and non-diabe�c pa�ents table iii: comparison of periodontal status of well controlled and poorly controlled diabe�cs fig 1: mean community periodontal index in diabe�cs and non-diabe�cs. fig 2: community periodontal index score with glycated haemoglobin jiimc 2019 vol. 14, no.3 152 periodontitis in adult diabetes patients discussion results of our study showed high prevalence of periodontitis (87.49%) in diabetics. diabetics had higher mean-cpi score (2.76±.78) as compared to non-diabetics (1.88± .95). poor glycemic control was associated with worse periodontal status as compared to good glycemic control in diabetics. worldwide studies have shown that diabetic patients have increased prevalence of periodontal disease. a study from eastern mediterranean region 21 in lebanon has shown prevalence of 94.5%, while 22 23 yeluriet al. and rajhanset al. have reported from india 84.5% and 86.4% of diabetics had periodontitis respectively. our study has shown that 87.49% diabetics had periodontits. the association of diabetes with periodontal inflammation has been subject of various studies. diabetes has been implicated in initiation, 9,10 progression as well as severity of periodontitis. diabetes increases the risk of developing p e r i o d o n t i t i s a b o u t t h re e fo l d . t h i s w a s demonstrated by emrich et al. in a study on pima indians, who have highest prevalence of type-2 diabetes mellitus in the world. he used probing attachment loss and alveolar bone loss parameters for this purpose. the odd ratio for diabetic subjects was 2.81 when attachment loss was used as 24 parameter and 3.43 when bone loss was used. studies from pakistan also confirmed increased frequency of periodontitis in patients with 25,26 diabetes. in study done by fatima et al., using different parameters for periodontal disease showed higher deposition of plaques (87% vs.13%) and mobility index (85.5% vs.65%) in diabetics as 25 compared to non-diabetics. approva et al. performed a study in bangalore involving patients from all ethnic groups and found that diabetics had higher cpi score compared to non-diabetics and the 27 difference was statistically significant. our results are in agreement with above mentioned studies as mean-cpi scores were higher in diabetics as compared to non-diabetics. another aspect our study was to observe how severity of periodontitis is related to glycemic control. many studies have confirmed that periodontal status deteriorates with 7,11,28 poor glycemic control. in this study higher cpi scores were observed with rise in hba1c levels. a study was done at services hospital lahore by haseeb et al. where they included study subjects with good oral hygiene only. they analyzed the periodontal status of individual tooth in each study subject, using different parameter like probing depth, gingival recession and attachment loss. results showed that periodontitis was significantly (p <0.001) more severe in poorly controlled diabetic 29 group compared to well controlled diabetics. similarly other studies showed glycemic control was 23,27 significantly related to severity of periodontitis. however basic et al. were unable to confirm this 30 association. longer the duration of diabetes greater will be the severity of periodontal inflammation. possible explanation is long standing hyperglycemia. rajhans 23 et al. had declared that it was significant factor. approva et al. observed that cpi score was 2.658±0.635when diabetes duration was less than 5 years, and it rose up to 2.940±0.562 and 3.000±0.576 in patients with diabetes duration of 6-10 and >10 27 years respectively. we observed high cpi score with longer duration of diabetes, 1.89± .51, 3.15± .56 and 3.32± .46 in patients with diabetes duration of 1-5, 610 and >10 years respectively. contrary to these results bacic et al. and yeluri et al. were unable to demonstrate significant effect of diabetes duration 22,30 on severity of periodontitis. altered immune response with decreased neutrophil phagocytosis and fibroblast function in 7,8 diabetes causes enhanced tissue destruction. this is stated to be responsible for high frequency of tooth mortality observed in diabetics. in this study, 59.8% diabetics had missing teeth as compared to15% of healthy volunteers. a study from pakistan reported tooth loss of 58.4% in diabetics and 10.7% 25 became edentulous. similarly other studies showed fig 3: mean community periodontal index score against diabetes dura�on jiimc 2019 vol. 14, no.3 153 periodontitis in adult diabetes patients that periodontitis is major cause of tooth loss in 22,23,27 diabetics. number of missing teeth increased 24 significantly with time in diabetes mellitus patients. it has been demonstrated that infrequent brushing is associated with severity of periodontitis. higher cpi score was seen in individuals who brushed once daily 31 compared with those who brushed twice daily. majority of patients in both groups (brushed once a day) had poor oral hygiene so nullifying its confounding effect. thus diabetes was an added risk 23 for population already at risk for periodontitis. 26 similar observation was made by tanweer et al. the high prevalence 87.49% in this study suggests that there is connection between the two chronic diseases. as both condition aggravate each other, recognition and treatment of periodontitis is essential. importance of oral health should be emphasized in diabetic patients. it should be an essential element of diabetes management plan. there is a need for in depth patient education and c o n s i s t e n t r e i n fo r c e m e n t b y h e a l t h c a r e professionals. limitation of our study was that we possibly overlooked the confounding factors like age and poor oral hygiene as periodontitis severity increases 23 with age and poor oral hygiene. present study was hospital based study with small sample size. further large community based studies are required to investigate this important association. conclusion diabetes mellitus patients have higher frequency of periodontitis as compared to non-diabetics. its severity increases as glycemic control worsens. moreover, its severity increases with duration of diabetes. references 1. william rc. periodontal disease. n engl j med. 1990; 322(6):373. 2. kinane df, stathopoulou pg, papapanou pn. periodontal diseases. nature reviews disease primers. 2017; 3 (1):1703 3. holm-pederson p, müller f, lang n. pathology and treatment of gingivitis and periodontitis in the aging individual. in: holm-pedersen p, walls a, ship ja. textbook of geriatric dentistry. 3rd ed. john wiley & sons; 2015. p. 211-23 4. listl s, galloway j, mossey pa, marcenesw. global economic impact of dental diseases. journal of dental research. 2015; 94: 1355–61. 5. american diabetes association. classification and diagnosis of diabetes. diabetes care. 2015 ;(suppl 38):s8–16. 6. loe, h. periodontal disease: the sixth 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periodontitis in us a d u l t s : n h a n e s 2 0 0 9 t o 2 0 1 2 . j o u r n a l o f periodontology.2016; 87(10):1174-85. 13. borgnakke ws, chapple il, genco rj, armitage g, bartold pm, d'aiuto f, et al.the multi-center randomized controlled trial (rct) published by the journal of the american medical association (jama) on the effect of periodontal therapy on glycated hemoglobin (hba1c) has fundamental problems. journal of evidence based dental practice. 2014; 14(3):12732. 14. dandona p, aljada a, bandyopadhyaya. inflammation: the link between insulin resistance, o besity and diabetes. trends in immunology, 2004 1; 25(!): 4-7 15. paraskevas s, huizinga jd, loos bg.asystematic review and meta-analyses on c-reactive protein in relation to periodontitis. j clin periodontol2008; 35:277–90 16. brownlee m.the pathobiology of diabetic complications: a unifying mechanism. diabetes. 2005; 54:1615–25 17. vlassara h the age-receptor in the pathogenesis of diabetic complications. diabetes metab 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patients periodontal disease. j indian socperiodontol 2011;15:3889224. emrich lj, shlossman m, genco rj. j periodontal disease in non-insulin-dependent diabetes mellitus.jperiodontol. 1991 feb; 62(2):123-31. 25. fatima g, akhtar mj, naveed n, ahmd m, tariq m, khawaja ar. diabetic patients and periodontitis: a study. pakistan oral & dental journal. 2017;37(2):290-3. 26. tanwir f, altamash m, gustafsson a. effect of diabetes onperiodontal status of a population with poor oral health.actaodontol scand2009; 67:129-33. 27. apoorva sm, sridhar n, suchethaa.prevalence and severity of periodontal disease in type 2 diabetes mellitus (noninsulin-dependent diabetes mellitus) patients in bangalore city: an epidemiological study. j indian socperiodontol 2013; 17:25-9. 28. tsai c, hayes c, taylor gw.glycemic control of type 2diabetes and severe periodontal disease in the us adult population.community dent oral epidemiol . 2002; 30:182–92 29. haseeb m, khawaja ki, ataullah k, munir mb, fatima a. periodontal disease in type 2 diabetes mellitus. j coll physicians surg pak 2012; 22:514-8. 30. bacic m, plancak d, granic m. cpitn assessment of periodontaldisease in diabetic patients. j periodontol 1988; 59:816-22. 31. akhionbare o, ojehanon pi. a studyof the effect of frequency of tooth brushing on the prevalence of inflammatory periodontal diseases. port harcourt med j 2016; 10:119-23 jiimc 2019 vol. 14, no.3 155 periodontitis in adult diabetes patients original�article abstract objective: to identify reasons for the refusal of spectacle usage among medical students of rawalpindi and islamabad. study design: cross sectional study. th th place and duration of study: different medical colleges of rawalpindi and islamabad from 15 april to 18 september 2018. materials and methods: a total of 254 medical students who were prescribed constant use of spectacles were selected through simple random sampling technique. a structured close ended questionnaire was administered and collected data was analyzed through spss version 22. results: mean age of the participants was 22.5 + 1.4 years, female students were 60.7% and 39.3% were male. it was found that majority of female participants do not use spectacles due to cosmetic reason (64.5%). unwillingness to use spectacles was the next most common reason for not using spectacles i.e., 57.2%. the students who reported that they face inconvenience and difficulty in managing the glasses were 47.9%. 31.8% of students were not using spectacles due to social stigma. many students either lost their spectacle or not using spectacles due to breakage of glasses (23.1%). the gender differences among various reasons were found to be statistically significant. conclusion: the current study concludes that various reasons leading to refusal and inadequate usage of spectacles among medical students are cosmetic unacceptability, unwillingness, social stigma and inconvenience. targeted health education measures are imperative to formulate comprehensive corrective strategies. key words: medical students, reasons, refusal, spectacle usage. errors, prevalence being 1.11%. the prevalence of ure varies widely around the globe, showing higher 3 among east asian countries. the prevalence of uncorrected refractive errors in pakistan has been 4 found as 23.9% in males and 20% in females. in pakistan, 3% of blindness can be attributed to 5 uncorrected refractive errors. the high prevalence rate of uncorrected refractive errors among medical students has led to a mounting concern for this 6 problem. the dilemma of continuously escalating burden of disease due to refractive errors is growing, regardless of the availability of a reasonably simple and cost7,8 effective interventions. spectacles are mainly used method for correcting vision in developing as well as 9 in developed countries. in spite of the fact that spectacles are the easiest preference for vision correction, however, several factors determine compliance with prescribed glasses and for the reason that ignorance, stigmas, taboos, cultural 10 beliefs and cost related issues, it is underutilized. at introduction the global enormity of visual impairment that can be ascribed to uncorrected refractive errors is on rise. refractive errors are the most frequent cause of visual disorders and blindness among young adults 1 following cataract globally. the uncorrected refractive errors (ure) pose a considerable consequence on daily life impairment, education and future economic anticipation of a student, 2 particularly medical students. worldwide, about 27.1 million in age group 16-39 years develop visual impairment due to refractive reasons for the refusal of spectacle usage among medical students of rawalpindi and islamabad 1 2 3 khadija mohammad , iffat atif , farah rashid correspondence: dr. iffat atif assistant professor department of community medicine yusra medical and dental college, islamabad e-mail: iffat.atif@hotmail.com 1 2,3 department of ophthalmology/community medicine yusra medical and dental college, islamabad spectacle usage refusal among medical studentsjiimc 2020 vol. 15, no.3 funding source: nil; conflict of interest: nil received: december 06, 2017; revised: july 04, 2020 accepted: july 04, 2020 188 ended questionnaire was self-administered and the data was analyzed using spss version 22. frequency distributions were calculated using descriptive statistics. chi-square test was employed to establish the association between qualitative variables and a p-value less than 0.05 was considered as significant. results there were a total of 254 participants with a mean age of 22.5 + 1.4 years. female students were 60.7% (n=155) and males were 39.3% (n=99). it was found that out of 254 individuals, 16.2% participated from st nd rd 1 year, 13.4% from 2 year, 19.2% from 3 year, th 40.7% from 4th year and 10.5% from 5 year. out of 254 respondents, 18% were from high socioeconomic status while 74.8% from upper middle, 1.9% from middle and 4.7% belonged to low socioeconomic status. the time duration of spectacle wear by respondents shown in figure 1. present knowledge about various causes leading to influence compliance with spectacle usage is very trivial particularly in our setting, therefore this study was carried out to highlight the importance of these issues and embark upon the problem. the literature search has revealed that many studies have been focused on primary and secondary school children neglecting the university students such as medical students. although numerous studies had been carried out to determine the prevalence of refractive errors, there is comparatively insufficient data available on the causes and associated factors acting as barriers to spectacle wear. the current study has been conducted to identify reasons of refusal and issues related to low usage of spectacles among medical students for effective interventions to prevent vision deterioration in future. materials and methods a cross-sectional study was conducted in different medical colleges of rawalpindi and islamabad from th th 15 april to 18 september 2018. sample size was calculated by who sample size calculator, keeping confidence interval at 95%, and prevalence of uncorrected refractive errors to be 21% (found in literature review), the calculated sample size was 254 selected through simple random sampling technique from these institutions. ethical approval was taken from ethical review board of yusra medical & dental college. permission was taken from administration of the medical colleges; the response rate of students was 100%. informed consent was taken from the respondents explaining them the purpose of this study and confidentiality of data was ensured. in this study, the medical students who had already been diagnosed with res were included, out of these who were strictly compliant were excluded from the study and a total of 254 non-compliant students who had been prescribed spectacles for constant use, were included in this study. the contact lens users and those with refractive surgery were also excluded, the reason being they have already left spectacle use and opted for an alternative choice, focusing on the students whose main modality of treatment was spectacles. the noncompliance with spectacle usage was defined as refusal to the use of spectacles prescribed for refractive errors, assessed either by observation or by interviewing the student. structured closed fig. 1: time dura�on for par�cipants who were prescribed spectacle usage the various reasons of refusal as shown in figure 2, it was found that majority of participants (64.5%) perceived that wearing spectacles was unacceptable aesthetically and awkward to use in social gatherings. 57.2% of the respondents showed unwillingness and they refrained from using spectacles even if they are in need of using them. the students who faced inconvenience while wearing spectacles along with issues related to managing the glasses were 47.9%. various students did not wear spectacles due to social stigma and unacceptability, many students lost their spectacle or not using due to breakage of glasses and some students forgot spectacles at home. jiimc 2020 vol. 15, no.3 189 spectacle usage refusal among medical students by nose pad and distort the overall image and appearance. the participants think that their use may lead to low self-esteem and decreased confidence level, more evident in female students, hence, have a propensity to incline towards supplementary alternatives accessible to them. this 5 finding is similar to the study done in pakistan. the second reason showed by this study is unwillingness or intolerance towards spectacle use. 57.2% of respondents were not willing just for the reason that they simply just did not like to wear glasses. this 6-8 result is quite higher as compared to other studies. the others reasons mentioned for not using was the stigma attached to the use of spectacles especially for females in a social set up like ours where there is cultural as well as social unacceptability of spectacle use tends to be higher than other societies and therefore the problem is aggravated, similar with the 9,10 study results reported from other countries. a proportion of students did not feel spectacles use convenient or at ease while using these. they consider use of spectacles as hindrance in daily routine activities and vigilance in handling, placing and maintenance, similar with the findings of other 11,12,13 studies. some students stopped using due to breakage or they lost their glasses and had difficulty in picking a new one. some showed the habit of forgetting spectacles at home, a behavior found more common in males as compared to the females, 14,15 a finding consistent with other studies. a small proportion felt that they do not require spectacles and they have no issue of vision without 16,17 spectacles, a finding in contrast to other studies. only a small percentage did not use spectacles due to being teased by their colleagues, this finding is 18 inconsistent with other studies. the measures taken to tackle with this situation should be broad based like health education intervention to promote 19,20 spectacle use like done in other countries. the main limitation of our study was that information about certain potential confounders such as severity of refractive errors could not be collected as most of the students did not know their present refractive status, needs to be considered while interpreting findings of this study. in the current study only quantitative approach was adopted but in future a mixed method approach with qualitative element including open ended questions cosmetic unacceptability, social stigma and unwillingness were recognized as the foremost reasons of refusal in female students and broken/lost glasses and forgetfulness were the most important causes of refusal to spectacle usage among male students, found to be statistically significant (table i). fig 2: frequency of various reasons of spectacle usage refusal table i: gender differences among various reasons discussion this study was conducted to address the issue of refusal of spectacle wear and its various causes and associated factors among medical students. the consistently high prevalence rates among medical students are attributable to extensive and intensive 2,4 study duration and lengthened use of near vision. the focal problem causing refusal and low usage among the participants found to be cosmetic factors i.e., frames leaving impressions/indentations on face jiimc 2020 vol. 15, no.3 190 spectacle usage refusal among medical students res... 2013; 2:150-4. 9. dhoble p, agarwal r, patel c, anand g, sharma j, sabde y. study to assess the psychosocial aspects of refractive errors and effectiveness of health education in correcting stigmas related to spectacle use in high-school students of rural india. int j med sci public health. 2013 jul 1; 2(3):716-9. 10. ak sm. awareness and attitude toward refractive error correction methods: a population based study in mashhad. journal of patient safety & quality improvement. 2013; 1(1):23-29. 11. ebeigbe ja, kio f, okafor li. attitude and beliefs of nigerian undergraduates to spectacle wear. ghana medical journal. 2013; 47(2):70-3. 12. gogate p, mukhopadhyaya d, mahadik a, naduvilath tj, sane s, shinde a, holden b. spectacle compliance amongst rural secondary school children in pune district, india. indian journal of ophthalmology. 2013 jan; 61(1):8. 13. megbelayin eo, asana ue, nkanga dg, duke re, ibanga aa, etim ba, okonkwo sn. refractive errors and spectacle use behavior among medical students in a nigerian medical school. british journal of medicine and medical research. 2014 may 1; 4(13):2581-2589. 14. aldebasi yh. a descriptive study on compliance of spectacle-wear in children of primary schools at qassim province, saudi arabia. international journal of health sciences. 2013 nov; 7(3):291. 15. bhatt nk, rathi m, dhull cs, sachdeva s, phogat j. spectacle compliance amongst school children of rohtak, haryana, india. international journal of community medicine and public health. 2017 feb 22; 4(3):734-7. 16. barria von-bischhoffshausen f, munoz b, riquelme a, ormeno mj, silva jc. spectacle-wear compliance in school children in concepcion chile. ophthalmic epidemiology. 2014 dec 1; 21(6):362-9. 17. basu m, ray s, mazumdar m, gupta ak, sengupta p, chatterjee s. refractive errors and its determinants among medical students of kolkata: a descriptive study. international journal of preventive and public health sciences. 2016 jan 30; 2(1):11-7. 18. alruwaili ws, alruwaili ms, alkuwaykibi mk, zaky ka. prevalence and awareness of refractive errors among aljouf university medical students. egyptian journal of hospital medicine. 2018 jan 1; 70(1). 19. khandekar rb, gogri up, al harby s. the impact of spectacle wear compliance on the visual function related quality of life of omani students: a historical cohort study. oman journal of ophthalmology. 2013 sep; 6(3):199. 20. morjaria p, bastawrous a, murthy gv, evans j, and gilbert c. effectiveness of a novel mobile health education intervention (peek) on spectacle wear among children in india: study protocol for a randomized controlled trial. trials. 2017 dec; 18(1):168. as well as focus group discussions will give an indepth analysis in identifying reasons for refusal of spectacle use. conclusion the current study concludes that several sociocultural reasons leading to refusal and inadequate use of spectacles among medical students include cosmetic unacceptability, unwillingness, social stigma and inconvenience. these factors tend to contribute towards raising the burden of visual impairment owing to refractive errors. targeted health education measures directing to cultural beliefs and social barriers pertaining to spectacle wear, early screenings and community ophthalmology involvement are imperative to formulate effective and comprehensive corrective strategies. references 1. desalegn a, tsegaw a, shiferaw d, woretaw h. knowledge, attitude, practice and associated factors towards spectacles use among adults in gondar town, northwest ethiopia. bmc ophthalmology. 2016 dec; 16(1):184. 2. al-batanony ma. refractive errors among saudi medical and pharmacy female students: a questionnaire survey study. journal of advances in medical and pharmaceutical sciences. 2016 mar 14:1-8. 3. dandona l, dandona r. estimation of global visual impairment due to uncorrected refractive error. bulletin of the world health organization. 2008; 86: b-c. 4. abdullah as, jadoon mz, akram m, awan zh, azam m, safdar m, nigar m. prevalence of uncorrected refractive errors in adults aged 30 years and above in a rural population in pakistan. journal of ayub medical college abbottabad. 2015 mar 1; 27(1):8-12. 5. yasmin s, officer p, minto h, advisor lv. community perceptions of refractive errors in pakistan. community eye health. 2007 sep; 20(63):52. 6. salih aa. prevalence and progression of refractive errors among el-mustansiriyah medical students. eurasian journal of medicine and oncology. 2018; 2(2):79-83. 7. kumar n, jangra b, jangra ms, pawar n. risk factors associated with refractive error among medical students. international journal of community medicine and public health. 2018 jan 24; 5(2):634-8. 8. agarwal r, dhoble p. study of the knowledge, attitude and practices of refractive error with emphasis on spectacle usages in students of rural central india. j. biomed. pharm. jiimc 2020 vol. 15, no.3 191 spectacle usage refusal among medical students july 2013.pdf ßþíìîßýì ñ¾¶»½¬·ª»æì± ½±®®»´¿¬» ½±´°±­½±°·½ º·²¼·²¹­ ©·¬¸ ¬¸» ®»­«´¬­ ±º ½»®ª·½¿´ ¾·±°­§ ¿²¼ ¬± °®±ª» ½±´°±­½±°§ ¿­ ¿ ª¿´«¿¾´» ­½®»»²·²¹ ¬±±´ º±® ¬¸» ¼·¿¹²±­·­ ±º °®»³¿´·¹²¿²¬ ¿²¼ ³¿´·¹²¿²¬ ½»®ª·½¿´ °¿¬¸±´±¹·»­ò í¬«¼§ ü»­·¹²æ ß ¯«¿­· »¨°»®·³»²¬¿´ ­¬«¼§ ð´¿½» ¿²¼ ü«®¿¬·±² ±º í¬«¼§æ í¬«¼§ ©¿­ ½±²¼«½¬»¼ º®±³ ö¿²«¿®§ 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¿½»¬·½ ¿½·¼ò ײ¬ò öò ý¿²½»® îðïðå ïîêæ ïëêóêïò îî untitled-2 original�article conclusion: nepafenac is superior to prednisolone in controlling iop after cataract surgery, with adequate and comparable control of post-surgical inflammation. key words: intraocular pressure, nepafenac, prednisolone. abstract objective: to compare the effect of topical 0.1% nepafenac and 1% prednisolone in control of inflammation and maintenance of intraocular pressure (iop) after cataract surgery. study design: randomized control trial. th th place and duration of study: department of ophthalmology, from 4 june 2018 to 30 june 2019. materials and methods: total sample size of study population was 400, including all patients getting phacoemulsification cataract surgery. study population was equally divided in two groups. group 1 was nepafenac group, and group 2 was prednisolone group. both groups underwent cataract extraction, and were started on topical 0.1% nepafenac or 1% prednisolone along with topical antibiotics after surgery. postoperative iop and activity and flare was checked in all patients on day 1, 7 and 28 after surgery and compared between both groups. results: the study population had a mean age of 60.97±4.91 years. the proportion of male and female patients in study population was 51% and 49% respectively. difference in mean post-operative iop and mean change from pre-operative value between both groups was statistically significant (p=0.003 and 0.004 respectively). there was statistically significant difference between both groups in terms of anterior chamber cells and flare respectively at 1st week post-operatively (p=0.002, and 0.003). however, there was no statistically significant difference between both groups in terms of anterior chamber cells and flare respectively after 28 days postoperatively (p=0.12, and 0.71). 2 are inflammation, infection and refractive errors. post-operative inflammation after cataract surgery remains a grave concern. this manifests as cells in anterior chamber (ac), proteins (flare), corneal 3 edema and iritis. this is responsible for sufficient stress to patient as well as surgeon, as post-operative surgical outcome remain compromised till settling of inflammation, which usually requires a long term management with topical and local or systemic drugs. inflammation is managed by variety of therapeutic agents like drugs corticosteroids and other anti-inflammatory drugs. corticosteroids are commonly used agents, which manage inflammation very well with reasonable safety. post-operative inflammation is managed by prescription of topical corticosteroids or local steroid injections, former being commonly practiced. the drugs are safely discontinued, upon return of eye to inflammation4 free state, manifested by variety of clinical signs. different corticosteroids are commonly used to treat post-cataract surgery inflammation, with different introduction cataract surgery is the most commonly performed 1 surgery all over the world in ophthalmic eye care. however like any other surgical procedure; it is also associated with a number of complications. commonly observed post-operative complications to compare the effect of nepafenac versus prednisolone on post-operative inflammation and intraocular pressure after cataract surgery 1 2 3 4 5 6 asim mehboob , muhammad usman arshad , faran bin afzal , sohail zia , aneeq ullah baig mirza , masud ul hassan correspondence: usman arshad senior registrar department of opthalmology islamic international medical college riphah international university, islamabad e-mail: usmanqureshi_cancer@yahoo.com 1 department of ophthalmology combined military hospital, kharian 2,4,5 department of ophthalmology islamic international medical college riphah international university, islamabad 3, department of ophthalmology alshifa trust eye hospital, rawalpindi 6 department of ophthalmology bashiran umer eye hospital, rawalpindi funding source: nil; conflict of interest: nil received: november 07, 2019; revised: february 05, 2020 accepted: february 07, 2020 topical 0.1% nepafenac versus 1% prednisolonejiimc 2020 vol. 15, no.1 23 5 safety and therapeutic profiles. c o n v e n t i o n a l l y, t o p i c a l d e x a m e t h a s o n e , p r e d n i s o l o n e , l o t e p r e d n o l e t a b o n a t e a n d flouromethalone are given to control inflammation after cataract surgery. a commonly observed side effect of these agents is raised intra ocular pressure (iop). although a number of factors can result in raised iop after cataract surgery, but in un-eventful and complication free surgery with restoration of visual acuity within days, steroids can result in raised iop. increased iop can result in compression of the optic nerve leading to progressive irreversible neuropathy. researches are being carried out internationally to recommend a safe compound which can provide anti-inflammatory effects but with no side effects as compared to traditional steroids. non-steroidal anti inflammatory drugs (nsaid) is widely prescribed to manage post-operative inflammation and also to provide analgesia after phacoemulsification cataract surgery. they are also shown to be beneficial in control of iop while managing inflammation. the role of nsaids is also well established in prevention 6, 7 of post pseudophakic surgery macular oedema. therefore we tried to conduct a study on comparison of efficacy and safety of nepafenac and prednisolone after cataract surgery. the aim of the study was to compare the effect of topical 0.1% nepafenac and 1% prednisolone in control of inflammation and maintenance of intraocular pressure (iop) after cataract surgery. materials and methods this randomized control trial was carried out after permission from hospital ethical review board in the department of ophthalmology, from 04 june 2018 to 30 june 2019. written informed consent was mandatory from all patients prior to inclusion in the study. approval from hospital's ethical review committee and written informed consent was taken from all participants. the sample size was calculated keeping level of significance as 5%, and power of the test as 80%, using world health organization calculator. for ease of analysis, a total sample size of 400, with 200 patients in each group was strength of study. non-probability consecutive sampling technique was used, and all patients divided in group 1 or 2 using lottery method. patients with visually significant cataract undergoing cataract surgery, aged between 40-60 years from either gender were included. patients with pre-existing glaucoma or uveitis, complicated cataract, prolonged surgery, increased phaco time, per and post-operative complications, systemic diseases e.g., diabetes, hypertension, asthma, arthritis, were excluded. all patients underwent thorough eye examination and iop measurement was by the single researcher to exclude bias. all the patients underwent a slit lamp examination of anterior segment and assessment of iop using applanation tonometer. all patients underwent radical and conventional phacoemulsification surgery, and all were implanted with posterior chamber intraocular lens after surgery by a single surgeon. both groups were prescribed with 0.5% topical moxifloxacin eye drops, three times daily for 2 weeks. group 1 was costarted with topical 0.1% nepafenac eye drops, thrice daily for four weeks after cataract surgery. group 2 was started with topical 1% prednisolone eye drops thrice daily after cataract surgery for four weeks. iop, ac cells and flare were checked on day 1, 7 and 28 after surgery. the data collected was entered in pre-devised proforma. the data was entered and analyzed using spss software version 20.0. the mean and standard deviations were used to evaluate ordinal data while frequencies and percentages were calculated for nominal data variables. normality of data was checked. post stratification, independent't' test was used to compare mean iop and mean change in iop between both groups. iop of <19mmhg after cataract surgery was considered efficacy of topical drug to control iop. chi square test was used to compare grading of cells and flare between both groups. p value of ≤ 0.05 was taken as statistically significant. results in this study a total of 400 cases meeting the inclusion criteria were evaluated and analyzed. the groups had equal number of participants (200 each). group 1 was nepafenac group, in which patients we re g i ve n n e p a fe n a c a n d g ro u p 2 wa s prednisolone group. the clinical data of study population is given in table (i) the comparison between both groups in terms of age, gender and laterality of eyes was statistically unremarkable. mean pre-operative iop and post-operative iop along with mean change in iop in both groups is jiimc 2020 vol. 15, no.1 24 topical 0.1% nepafenac versus 1% prednisolone given in table( i) difference between both groups in terms of post-operative iop and mean change in iop was statistically significant (p=0.003 and 0.004 respectively). a higher number of patients (102/200) showed iop control efficacy (iop<19mmhg) in group 1 as compared to group 2 (88/200). however, the difference was not statistically significant (p=0.182). the comparison of ac cells and flare between both groups at 1 week and 28 days is given in table (iii) the difference in ac flare and cells grading between both groups at 1 week was statistically significantly different (p=0.023 and 0.002 respectively). however, the difference in flare and cells grading at 28 days (4 weeks) after surgery was not statistically significant (p=0.216 and 0.137 respectively). discussion the corticosteroids are widely used after cataract surgery to control post-operative inflammation, but rise in iop is a known complication of their use. injudicious and prolonged use, especially in already compromised individuals puts optic nerve at risk of damage. this has been managed by limited use or 8 use of alternative therapeutic agents. we observed a mean rise of 1.23±0.18 mmhg in iop in patients receiving nepafenac eye drops, while a mean rise of 2.79±1.19 mmhg was observed in prednisolone group. in a study conducted for evaluation of iop rise after prednisolone use after cataract surgery, it was observed that 3% of patients has high iop after 9 cataract surgery. since the difference in change in iop was significant between groups, we recommend use of nepafenac in patients particularly susceptible to glaucomatous damage. there have been multiple researches evaluating safety, performance and analysis of nsaids after phacoemulsification table i: demography and clinical data of study popula�on (n=400) table ii: comparison of pre and post-opera�ve iop table iii: comparison of post-opera�ve ac cells and flare between group (n=400) jiimc 2020 vol. 15, no.1 25 topical 0.1% nepafenac versus 1% prednisolone surgery. in a study evaluating post-operative inflammation by laser photometry, it was observed that nepafenac was superior to other nsaids in 10 controlling post-operative inflammation. we used topical nepafenac in concentration of 0.1%, given thrice daily for four weeks. some studies evaluated the dose of nepafenac, and found out that 0.1% nepafenac was equally effective to 0.3% nepafenac 11 with less adverse effects. in another study comparing efficacy of nepafenac with placebo drug, it was observed that nepafenac was far superior in 12 managing post-surgical inflammation. in the most reliable meta-analysis evaluating 19 controlled trials, it was observed that nepafenac was superior to all nsaids in managing post-operative pain, while management of ac inflammation after cataract surgery was superior by diclofenac followed by 13 nepafenac eye drops. there have been some studies mentioning the superiority of steroids in maintaining mydriasis during cataract surgery if used before surgery. however some studies have shown equal efficacy of nepafenac and prednisolone in maintaining 14 mydriasis during phacoemulsification. this is to prove non-inferiority of nsaids to steroids in managing per-operative mydriasis. in another study conducted for comparison of nepafenac and prednisolone in controlling inflammation after small gauge vitrectomy, it was obser ved that nepafenac was superior to prednisolone in managing post-operative pain, and was equal in efficacy in management of post15 operative inflammation. in other studies comparing safety profile of nsaids and steroids in management of inflammation after cataract surgery, it was observed that diclofenac was equal to prednisolone in management of inflammation, and was equally 16 safe and well-tolerated. similar findings were observed by malik a and colleagues, who observed that nsaids like nepafenac, bromfenac and ketorolac are a good alternative to steroids in 17 management post-operative ocular inflammation. we observed that there was statistically significant difference in grading of ac cells and flare between both groups at 1 week after surgery. however, the difference was not statistically significant at 4 weeks after surgery. this is in connection with results found out by simone jn et al who found out that prednisolone was superior to nepafenac in management of ocular inflammation at 1 week, 18 which was comparable at one month after surgery. we used either nepafenac or prednisolone along with antibiotic after surgery. in another study, it was revealed that diclofenac alone, or used in combination with dexamethasone was superior to dexamethasone alone in prevention of development of pseudophakic macular edema, and change in 19 central retinal thickness. there have been conflicting results with regards to superiority of nsaids in post-operative pain and inflammation. in one meta-analysis, gross results showed the superiority of nsaids in management of post-operative inflammation as compared to corticosteroids. however, the results also showed the better results of nsaids in prevention of irvine gass syndrome (pseudophakic cystoid macular 20 oedema). in one meta-analysis evaluating 48 randomized control trials, no conclusion was found regarding superiority of nsaids to steroids in management of post-operative inflammation or 21 pain. our study has limitation of not having a group using c o m b i n a t i o n o f n s a i d s a n d s t e r o i d s fo r management of inflammation and evaluation of iop. the management of post-operative pain using visual analogue score could also have been beneficial. the follow up time of 4 weeks after surgery was also slightly shorter, considering that inflammation might continue for 6 to 8 weeks after surgery. conclusion we conclude that nepafenac was safer in control of iop after phacoemulsification cataract extraction surgery. the control of post-operative inflammation is better with use of steroids immediately after cataract surgery. however, in long term, both drugs show equal efficacy in management of postoperative inflammation. nepafenac is thus a safe and efficient alternative to prednisolone in patients undergoing un-eventful cataract surgery. references 1. amon m, busin m. loteprednol etabonate ophthalmic suspension 0.5 %: efficacy and safety for postoperative antiinflammatory use. int ophthalmol.2012; 32:507-17. 2. pleyer u, ursell pg, rama p. intraocular pressure effects of common topical steroids for post-cataract inflammation: are they all the same? ophthalmol ther. 2013; 2:55-72. jiimc 2020 vol. 15, no.1 26 topical 0.1% nepafenac versus 1% prednisolone 3. comstock tl, decory hh. advances in corticosteroid therapy for ocular inflammation: loteprednol etabonate. int j inflam. 2012; 2012:789623. 4. lane ss, holland ej. loteprednol etabonate 0.5% versus prednisolone acetate 1.0% for the treatment of inflammation after cataract surgery. j cataract refract surg. 2013; 32:168-73. 5. el-harazi sm, feldman rm. control of intra-ocular inflammation associated with cataract surgery. curr opin ophthalmol. 2001; 12:4-8. 6. el gharbawy sa, darwish ea, abu eleinen kg, osman mh. efficacy of addition of nepafenac 0.1% to steroid eye drops in prevention of post-phaco macular edema in high-risk eyes. eur j ophthalmol. 2019; 29:453-7. 7. chinchurreta capote am, lorenzo soto m, rivas ruiz f, caso peláez e, garcía vazquez, group oftacosta,et al. comparative study of the efficacy and safety of bromfenac, nepafenac and diclofenac sodium for the prevention of cystoid macular edema after phacoemulsification. int j ophthalmol. 2018; 11:1210-6. 8. tijunelis ma, person e, niziol lm, musch dc, ernest p, mcbain m, et al. comparison of prednisolone acetate 1.0% and difluprednate ophthalmic emulsion 0.05% after cataract surgery: incidence of postoperative steroidinduced ocular hypertension. j cataract refract surg. 2017; 43:223-7. 9. kusne y, kang p, fintelmann re. a retrospective analysis of intraocular pressure changes after cataract surgery with the use of prednisolone acetate 1% versus difluprednate 0.05%. clin ophthalmol. 2016; 10:2329-36. ecollection 2016. 10. sahu s, ram j, bansal r, pandav ss, gupta a. effect of topical ketorolac 0.4%, nepafenac 0.1%, and bromfenac 0.09% on postoperative inflammation using laser flare photometry in patients having phacoemulsification. j cataract refract surg. 2015; 41:2043-8. 11. jones bm, neville mw. nepafenac: an ophthalmic nonsteroidal anti-inflammatory drug for pain after cataract surgery. ann pharmacother. 2013; 47:892-6. 12. lane ss, modi ss, lehmann rp, holland ej. nepafenac ophthalmic suspension 0.1% for the prevention and treatment of ocular inflammation associated with cataract surgery. j cataract refract surg. 2007; 33:53–8 13. duan p, liu y, li j. the comparative efficacy and safety of topical non-steroidal anti-inflammatory drugs for the treatment of anterior chamber inflammation after cataract surgery: a systematic review and network meta-analysis. graefes arch clin exp ophthalmol. 2017; 255:639-49. 14. zanetti fr, fulco ea, chaves fr, da costa pinto ap, arieta ce, lira rp. effect of preoperative use of topical prednisolone acetate, ketorolac tromethamine, nepafenac and placebo, on the maintenance of intraoperative mydriasis during cataract surgery: a randomized trial. indian j ophthalmol. 2012; 60:277-81. 15. nagpal m, lambat s, mehrotra n, paranjpe g, yadav h, bhardwaj s. topical nepafenac 0.1% alone versus prednisolone acetate 1% as postoperative antiinflammatory agents in small gauge vitrectomy. indian j ophthalmol. 2014; 62:606-9. 16. demco ta, sutton h, demco cj, raj ps. topical diclofenac sodium compared with prednisolone acetate after phacoemulsification-lens implant surger y. eur j ophthalmol. 1997; 7:236–40. 17. malik a, sadafale a, gupta yk, gupta a. a comparative study of various topical nonsteroidal anti-inflammatory drugs to steroid drops for control of post cataract surgery inflammation. oman j ophthalmol. 2016; 9:150-6. 18. simone jn, pendelton ra, jenkins je. comparison of the efficacy and safety of ketorolac tromethamine 0.5% and prednisolone acetate 1% after cataract surgery. j cataract refract surg. 1999; 25:699–704. 19. ylinen p, holmström e, laine i, lindholm jm, tuuminen r. anti-inflammatory medication following cataract surgery: a r a n d o m i z e d t r i a l b e t w e e n p r e s e r v a t i v e f r e e dexamethasone, diclofenac and their combination. acta ophthalmol. 2018; 96:486-93. 20. kessel l, tendal b, jørgensen kj, erngaard d, flesner p, andresen jl, et al. post-cataract prevention of inflammation and macular edema by steroid and nonsteroidal anti-inflammatory eye drops: a systematic review. ophthalmology. 2014; 121:1915-24. 21. juthani vv, clearfield e, chuck rs. non-steroidal antiinflammatory drugs versus corticosteroids for controlling inflammation after uncomplicated cataract surgery. cochrane database syst rev. 2017; 7:cd010516. jiimc 2020 vol. 15, no.1 27 topical 0.1% nepafenac versus 1% prednisolone editorial peripheral arterial disease-more than just numbers: lack of disease awareness and hurdles in management jahangir sarwar khan global population is going through a serious epidemiological shift inside which the load of peripheral arterial disease (pad) is converting towards third world countries. therefore, we ought to shift our recognition toward prevention and control of this disease. over the last decade, treatment plan has been advanced, such as early diagnosis, greater common utilization of diagnostic investigations and advanced revascularization techniques. in this writing i emphasize the need to expand the vision and know-how of peripheral a r t e r i a l d i s e a s e , e n h a n c e i t s d i a g n o s t i c considerations and to analyze and control this disease. lower limbs pad is atherosclerotic disorder involving the arterial system of lower limbs. it is a prevailing condition considered to take hold of around 250 million people internationally and is related to expanded danger of numerous detrimental scientific effects such as amputations and mi. amputation is the accidental loss or removal of part of the body . it is a transformative incident which influence one's capacity to be mobile, to do his routine chores , engage with people around and keep their selfdetermination. the word burden of disease is a -ive term as it focuses more on the adversities and losses related with disease, disability, and death. 4 critical limb ischemia is a drastic variety of arterial disease which is frequently described as peripheral arterial disease with associated limb pain at rest, 2,5 non-healing ulcers, or gangrene. a study showed the 1-12 months incidence proportion for mortality as well as amputation is around twenty percent in 6 patients with critical limb ischemia. in three different studies done at three different setups, there is an established relationship between lower socioeconomic group and high amputation rate in patients with cli. despite being widespread and having unfortunate clinical outcomes in phrases of impaired workout and decreased physical function, pad is still underrepresented and not thoroughly studied as in comparison with other related diseases. this little to no know-how is the reason behind disastrous approach to patients with pad round the globe. in a latest systematic review by bridgwood et al about pad expertise and understanding, 61% of gps were doing patients screening for arterial diseases and only 6% were treating patients according to the set 1 guidelines. during the same setup, the data of knowledge testing of undergraduate students and post graduate trainees validated negative to little overall knowledge regarding disease presentation and management. disease awareness rate is 21% 61% among general population, according to this study. this lack of know-how and understanding is one of the motives towards delayed or underused treatment. there seems to be many possible grounds for this underestimation of peripheral arterial disease. firstly, it's a diagnostic dilemma thanks to broad 13 spectrum of disease presentation. only 10%-30% presented with classical symptoms of intermittent claudication which is pain in calves that improved on rest of at least ten minutes, 20-50% are asymptomatic, whereas 40-50% having atypical 3 presentation. secondly, the first-line investigation is the ankle-brachial index (abi) and abi ≤0.90 is 2,7,8 diagnostic. research proved that ladies tend to own lower abis than males, mainly attributed 9,10 towards their shorter height. the abi are often falsely high because of stiffened ankle arteries in dm 11,12 or chronic kidney disease. so here it is best to record the toe-brachial index i.e., measurements of 2,7,12 toe and brachial systolic blood pressures. as luck would have it, in our setups due to increased patient load, non-availability of resources and lack of expertise this is often not routinely done. also, many of us assume that morbidity and mortality related to leg diseases is lowered as correspondence: prof. jahangir sarwar khan dean postgraduate education rawalpindi medical university, rawalpindi e-mail: jskdr@hotmail.com received: june 03,2022; accepted: june 18, 2022 74 75 compared to other atherosclerotic diseases. in conclusion, pad is prevalent in our society and needs to be addressed properly considering in mind the cost and maintenance of prosthesis after amputation is not a piece of cake for our people. in my opinion we can take steps towards attention of our healthcare workers within the shape of seminars and workshops. also, we can distribute pamphlets in outpatient department for patient awareness. there should be screening of all high-risk patients with or without symptoms of pad. an early and prompt referral of those patients to specialized clinics are going to be of great help. we should always stress more on prevention of disease instead of prevention of amputation. references 1. bridgwood bm, nickinson at, houghton js, pepper cj, sayers rd. knowledge of peripheral artery disease: what do the public, healthcare practitioners, and trainees know? va s c m e d . 2 0 2 0 ; 2 5 : 2 6 3 – 2 7 3 . d o i : 1 0 . 1 1 7 7 / 1358863x19893003 2. gerhard-herman md, gornik hl, barrett c, barshes nr, corriere ma, drachman de, fleisher la, fowkes fg, hamburg nm, kinlay s, et al. 2016 aha/acc guideline on the management of patients with lower extremity peripheral artery disease: a report of the american college of cardiology/american heart association task force on c l i n i c a l p r a c t i c e g u i d e l i n e s . c i r c u l a t i o n . 2 0 1 7 ; 135:e726–e779. doi: 10.1161/cir.0000000000000471 3. hirsch at, criqui mh, treat-jacobson d, regensteiner jg, creager ma, olin jw, krook sh, hunninghake db, comerota aj, walsh me, et al. peripheral arterial disease detection, awareness, and treatment in primary care.jama. 2001; 286:1317–1324. doi: 10.1001/jama.286.11.1317 4. conte ms, bradbury aw, kolh p, white jv, dick f, fitridge r, mills jl, ricco jb, suresh kr, murad mh; gvg writing group. global vascular guidelines on the management of chronic limb-threatening ischemia.j vasc surg. 2019; 69(6s):3s–125s.e40. doi: 10.1016/j.jvs.2019.02.016 5. mustapha ja, katzen bt, neville rf, lookstein ra, zeller t, miller le, driver vr, jaff mr. critical limb ischemia: a threat to life and limb.endovasc today. 2019; 18:80–82. 6. abu dabrh am, steffen mw, undavalli c, asi n, wang z, elamin mb, conte ms, murad mh. the natural history of untreated severe or critical limb ischemia.j vasc surg. 2015; 62:1642–1651.e3. doi: 10.1016/j.jvs.2015.07.065 7. aboyans v, ricco jb, bartelink mel, björck m, brodmann m, cohnert t, collet jp, czerny m, de carlo m, debus s, et al.; esc scientific document group. 2017 esc guidelines on the diagnosis and treatment of peripheral arterial diseases, in collaboration with the european society for vascular surgery (esvs): document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteries.eur heart j. 2018; 39:763–816. doi: 10.1093/eurheartj/ehx095 8. aboyans v, criqui mh, abraham p, allison ma, creager ma, diehm c, fowkes fg, hiatt wr, jönsson b, lacroix p, et al.; on behalf of the american heart association council on peripheral vascular disease; council on epidemiology and prevention; council on clinical cardiology; council on cardiovascular nursing; council on cardiovascular radiology and intervention, and council on cardiovascular surgery and anesthesia. measurement and interpretation of the ankle-brachial index: a scientific statement from the a m e r i c a n h e a r t a s s o c i a t i o n . c i r c u l a t i o n . 2 0 1 2 ; 126:2890–2909. doi: 10.1161/cir.0b013e318276fbcb 9. allison ma, cushman m, solomon c, aboyans v, mcdermott mm, goff dc, criqui mh. ethnicity and risk factors for change in the ankle-brachial index: the multi-ethnic study of atherosclerosis.j vasc surg. 2009; 50:1049–1056. doi: 10.1016/j.jvs.2009.05.061 10. kapoor r, ayers c, visotcky a, mason p, kulinski j. association of sex and height with a lower ankle brachial index in the general population.vasc med. 2018; 23:534–540. doi: 10.1177/1358863x18774845 11. potier l, abi khalil c, mohammedi k, roussel r. use and utility of ankle brachial index in patients with diabetes.eur j va s c e n d o v a s c s u r g . 2 0 1 1 ; 4 1 : 1 1 0 – 1 1 6 . d o i : 10.1016/j.ejvs.2010.09.020 12. aburahma af, adams e, aburahma j, mata la, dean ls, caron c, sloan j. critical analysis, and limitations of resting ankle-brachial index in the diagnosis of symptomatic peripheral arterial disease patients and the role of diabetes mellitus and chronic kidney disease.j vasc surg. 2020; 71:937–945. doi: 10.1016/j.jvs.2019.05.050 13. mcdermott mm. lower extremity manifestations of peripheral artery disease: the pathophysiologic and functional implications of leg ischemia.circ res. 2015; 116:1540–1550. doi: 10.1161/circresaha.114.303517 jiimc 2022 vol. 17, no.2 103 editorial patient safety a 'right or privilege' saima aslam, paul barach, zakiuddin ahmed correspondence: dr. saima aslam assistant director riphah institute of healthcare improvement & safety riphah international university, islamabad e-mail: saima.aslam @riphah.edu.pk funding source: nil; conflict of interest: nil received: july 28, 2019; revised: august 06, 2019 accepted: august 10, 2019 is patient safety a 'right or a privilege'? the intention while treating patients is always to “do no harm” and yet, it does not always turn out that way. healthcare interventions are meant to benefit people and promote wellness; unfortunately many times they present a risk of harm. patients still suffer from wrong treatment or medications, preventable falls in hospitals, hospital acquired infections and many other events that are harmful. an international report published in 2018, reported that 1/10 of all patients suffer preventable adverse events, two decades after the institute of medicine found that 98,000 people die in hospitals in the us each year because of medical errors that could have been 1,2 prevented. patient safety has now emerged as a fundamental 3 concept in healthcare. it is defined by the institute of medicine as “the prevention of harm to patients”. a growing emphasis is being put on the system of healthcare delivery that 1) prevents errors, 2) learns from the errors that occur, and 3) is built around a culture of safety that supports and enables and involves healthcare professionals, organizations and 3,4 patients. the history of patient safety goes back more than a century. in 1854, florence nightingale, a nurse and s t a t i s t i c i a n , u s e d e v i d e n c e b a s e d q u a l i t y improvement to reduce preventable harm in the crimean war. a century later in 1964, schimmel in his paper “the hazards of hospitalization” reported that 20% of the patients admitted to the medical wards experienced one or more untoward episode 5 and 10% had a prolonged or unresolved episode. the agency for healthcare research and quality, known as ahrq, was formed in 1989, to produce evidence to make health care safer, higher quality, more accessible, equitable, and affordable, and to 6 ensure that the evidence is understood and used. patient safety initiatives in the uk emerged from a wide set of influences and events during the 1970s and 1980s. finally, in 1999, all chief executives of health care trusts were given a statutory duty and framework, known as clinical governance, to manage and actively promote risk management, quality, and safety. this resulted in considerable 7 progress in addressing patient harm. now there is much greater awareness to the problem, a more reflective approach to error and harm, policy initiatives to address safety, a dedicated research program, and a more humane approach to injured 7,8 patients and their families. there is little information on the existing culture and 9,10,11 practices regarding patient safety in pakistan. in pakistan, we need to focus first on assessing the culture of care and on creating an increased awareness for patient safety among healthcare professionals. this will create a critical mass of healthcare workers to lead the patient safety journey. on a larger scale the healthcare system is weak and fragmented in pakistan. the government is rapidly promoting health network formation at the local level, but they rarely provide guidance on how to assemble or succeed. there is no central or n a t i o n a l g o v e r n i n g b o d y f o r h e a l t h c a r e management. it is primarily the responsibility of provincial governments. during the past 5 years, the punjab and sindh healthcare commission bodies 12,13 have been formed. the commissions have formulated local acts known, respectively, as the punjab and sindh health commission acts. the acts contain a defined set of regulations for the healthcare facilities in punjab and sindh, respectively. the prime aim of these acts is to register all healthcare facilities in pakistan followed 12,13,14 by licensing and accreditation. some of the specific challenges for pakistan's healthcare commission quality initiatives are a lack of national healthcare accreditation system and integrated national guidelines, policies, procedures department of riphah institute of healthcare improvement & safety riphah international university, islamabad this should include setting minimal standards for healthcare delivery, a central reporting and audit and accreditation system, as well as mandating patient safety education at all levels of healthcare training and practice. references: 1. national academies of sciences, engineering, and medicine. (2018). crossing the global quality chasm: improving health care worldwide. national academies press. 2. global priorities for patient safety research. (n.d.). world h e a l t h o r g a n i z a t i o n . r e t r i e v e d f r o m http://whlibdoc.who.int/publicaton/2009/97892415986_ eng.pdf. 3. 10 facts on patient safety. (n.d.).retrieved from http://www.who.int/features/factfiles/patient_safety/en/i ndex.html 4. erickson, s. m., wolcott, j., corrigan, j. m., & aspden, p. (eds.). (2003). patient safety: achieving a new standard for care. national academies press. 5. schimmel, e. m. (1964). the hazards of hospitalization. annals of internal medicine, 60(1), 100-110. 6. rockville, m. (march 2018). agency for healthcare research and quality: a profile. content last reviewed march 2018. agency for healthcare research and quality. retrieved from https://www.ahrq.gov/cpi/about/profile/index.html 7. small, s. d., & barach, p. (2002). patient safety and health policy: a history and review. hematology and oncology clinics of north america, 16(6), 1463-1482. 8. barach, p. (2003). the end of the beginning. journal of legal medicine, 24(1), 7-27. 9. jafree, s. r., zakar, r., zakar, m. z., & fischer, f. (2017). assessing the patient safety culture and ward error reporting in public sector hospitals of pakistan. safety in health, 3(1), 10. 10. shah, n., jawaid, m., shah, n., & ali, s. m. (2015). patient safety: perceptions of medical students of dow medical college, karachi. j pak med assoc, 65(12), 1261-1265. 11. gille, l. (2018). mycoplasma bovis: sources of infection, prevalence and risk factors (doctoral dissertation, ghent university). 12. sindh healthcare commission act 2013. (2015 june 08) r e t r i e v e d f r o m h t t p : / / w w w . p a s . g o v . p k / uploads/acts/sindhact no.vii 2014. pdf. 13. punjab, g. o. (30 july 2010). punjab healthcare commission act 2010. punjab gazette, 465-477. 14. h t t p : / / w w w . n a c p . g o v . p k / i n t r o d u c t i o n /national_heath_policy/nationalhealthpolicy-2001.pdf 15. shaikh, j. m., devrajani, b. r., shah, s. z., akhund, t., & bibi, i. (2008). frequency, pattern and etiology of nosocomial infection in intensive care unit: an experience at a tertiary care hospital. j ayub med coll abbottabad, 20(4), 37-40 on healthcare quality and patient safety which as 12,13 mentioned on the patient safety acts. in a recent study jafree et. al. reported that “nurses” perceive the culture in public hospitals of pakistan to be punitive and that individuals are not supported or 9 made to feel comfortable in reporting errors. the fear and lack of psychological safety is not very different in the private sector. hospital acquired infections is one of the highest problems in pakistani hospitals. as reported by shaikh et. al in 2008, data from a tertiary care hospital in sindh showed that the frequency of hospital acquired infections was 29% with urinary tract infections being the most prevalent at 39%, followed by respiratory tract infections 30.1% and blood stream infection in 23.7% of patients admitted to icu. other infections identified were skin, soft tissue, wound and gastrointestinal tract infections. infection control and prevention measures are essential components of quality healthcare quality 11,15 and patient safety. pakistan's first national infection guidelines were established in 2006, with the help of the national aids control program. it was noted that hand hygiene is rarely practiced as 11 observed in government hospitals. self-assessment of trainee physicians at a tertiary hospital revealed t h a t o n l y 1 7 % w e re a wa re o f t h e w h o recommendations for hand hygiene and hospital 11 acquired infection risks. there are many challenges in addressing the national levels of quality and patient safety in pakistan. one way to overcome these challenges is to d e ve l o p re g i o n a l a n d n at i o n a l g ro u p s o f improvement-minded leaders. these local leaders can be mentored to build trust and lasting relationships, share ideas and expertise, and learn from successes of others. there is an urgent need to address patient safety as a priority in our system. we recommend funding research at all levels of healthcare to address the gaps that exist in our system regarding the delivery of safe medical care. the pakistani government and the ministry of health need to focus on policy development for patient safety as a national priority. 104 original�article abstract objective: to appraise the preventive effect of turmeric on anti-mosquito coil smoke induced interstitial fibrosis in lungs of sprague dawley rats. study design: randomized control trial. st th place and duration of study: this study was completed in 10 months from 1 august 2014 to 28 may 2015; conducted at islamic international medical college, rawalpindi and national institute of health (nih), islamabad, pakistan. material and methods: three equal groups of 21 adult albino rats were made. control group x was retained in fresh air. experimental groups m & t inhaled mosquito coil smoke for 12 weeks. group t also had oral turmeric 300mg/kg body weight. after 12 weeks rats were dissected, and their lung tissues were studied microscopically for the presence of fibrosis. results: interstitial fibrosis was markedly present in the histological sections of lung tissues from experimental group m showing thickened fibrotic alveolar walls and inflammatory cell infiltrate with reduced air spaces in all animals (100%) in group m. fibrosis was present in 2 out of 7 rats in group t showing a significant protection with only 28.5% of animals with fibrotic lungs. no interstitial fibrosis (0%) was seen in the lung tissues of animals in control group x; all 7 rats showed well-formed alveoli. conclusions: interstitial lung fibrosis caused by anti-mosquito coil smoke can be protected with the use of turmeric. key words: covid-19, curcuma, mosquito coil, pulmonary fibrosis, turmeric. nutraceutical. turmeric has significant anti3 inflammatory and anti-oxidant properties. it has gained value as a digestive aid, treatment for fever, wounds, infections and blood disorders. data from animal and pharmacological studies also supports that active ingredients in turmeric play a protective role in various diseases like acute respiratory distress syndrome, chronic obstructive pulmonary disease and allergic asthma and also have proven antiviral properties against para-influenza type 3, respiratory 4,5,6 syncytial virus and herpes simplex virus, its therapeutic action is based on the inflection or prevention of oxidative stress and inflammation confirmed with the studies done at molecular & 7,8 cellular levels. the findings in these researches give substance to the possibility of testing turmeric for the prevention of pulmonary fibrosis caused by allethrins released from burning anti-mosquito coils. mosquitoes and the transmission of the mosquito borne diseases have been historically controlled by the use of chemical insecticides and mosquito repelling agents like anti-mosquito coil containing pyrethroids (allethrins), which play a central role in introduction modern medicine to a large extent has failed in its ambition to control both acute and chronic diseases. traditional herbal medicines have been found effective for the treatment and prevention of several 1 diseases. turmeric is a traditional herbal medicine. it's broad reaching mechanism of action and lack of systemic toxicity may make it best suited as an adjuvant therapy for various viral and other respiratory disorders like tobacco smoke induced epithelial damage and acute lung injury that are 2 resistant to currently available therapies. several diseases have been found to have inflammatory origin. turmeric is safe, affordable and efficacious preventive effect of turmeric against anti-mosquito smoke induced pulmonary fibrosis in laboratory rat saira jawed, wafa omer 1 2 correspondence: dr. saira jawed assistant professor department of anatomy hbs medical and dental college, islamabad e-mail: sairajawed371@gmail.com 1 2 department of anatomy /pathology hbs medical and dental college, islamabad funding source: nil; conflict of interest: nil received: february 11, 2020; revised: october 01, 2020 accepted: october 10, 2020 preventive effect of turmericjiimc 2020 vol. 15, no.4 222 9 mosquito control programs. more toxic products having higher concentration of allethrins are predominating the market due to the rapid spread of 10 resistance worldwide. the use of allethrins in higher concentrations and a complicated mixture of metallic vapors to tackle the resistant mosquitoes, 11 exposes the consumer to a severe health risk. it has already been addressed in the literature that exposure to mosquito coil smoke can have toxic effects on the lungs and can induce histopathological changes like severe emphysema, hyperplasia, chronic obstructive pulmonary disease, edema, hemorrhage & fibrosis, necrosis, hyperemia, connective tissue infiltration by inflammatory cells and obstruction by hyaline material within the lung 12,13 tissue. the objective of the current research was to demonstrate the efficacy of turmeric in preventing pulmonary fibrosis as there is insufficient literature on the preventive characteristics of turmeric against anti-mosquito allethrins present in coil smoke. material and methods this randomized control trial conducted at islamic international medical college, rawalpindi and national institute of health (nih), islamabad and was completed in 10 months. a total of 21 sprague dawley male rats weighing 250-300g were purchased from the animal house of national institute of health (nih) islamabad and were randomly divided into three groups; control group x and experimental groups m & t. the study was performed after an ethical approval from the institutional review committee of riphah international university. female rats and the rats having a weight of less than 250 g or having a physical disability were excluded from the study. groups m & t rats were placed in smoke exposure cabins at a temperature of 27±3ºc with a 12hr light/dark cycle along with standard laboratory diet and water. experimental groups were exposed to mosquito coil smoke for 7 hours per day for 12 weeks; group t received 300mg/kg body weight oral turmeric as well. all rats were sacrificed at the end of 12 weeks and left lungs of all were dissected out and preserved in 10% formalin. after tissue processing slides were prepared and stained with masson's trichrome to be studied microscopically first at low power, x10, and then at high power, x40 objective. the histological slides were interpreted by the pathologist. slides were studied for presence of interstitial fibrosis. masson's trichrome stained collagen fibers causing thickening of alveolar septa & alveolar spaces filled with proteinaceous fluid and inflammatory cell infiltrate causing reduction in alveolar spaces was taken as a criterion for interstitial fibrosis. results the lung tissue of all rats (100%) in group m (fig 2a) had a masson's trichrome stained dense fibrous connective tissue with collagen fibrils & thickening of alveolar walls with cellular infiltration, proliferation & airspaces filled with proteinaceous fluid. the interstitial infiltrate consisted of lymphocytes, plasma cells, mast cells and eosinophils resulting in interstitial fibrosis. interstitial pulmonary fibrosis was present in 2 out of 7 rats in group t; thus rats in group t showed a remarkable protection from pulmonary fibrosis with only 28.5% of animals developing fibrosis (fig 2b). the result is shown in table (fig 1). the masson's trichrome stained histological slides from the rats in control group x had normal honeycomb like alveolar structure with well-formed alveolar walls (fig 2c). table i: table represen�ng percentage of inters��al lung fibrosis in control and experimental groups jiimc 2020 vol. 15, no.4 223 preventive effect of turmeric discussion pulmonary fibrosis is a pattern of reaction to parenchymal damage in which lung has unusually high collagen fiber content per unit volume of 14 tissue. in the present study histological sections of the lungs of rats are stained with masson's trichrome in order to observe the fibrotic thickening of alveolar septa, reduced air spaces and presence of proteinaceous fluid. 100% of rats in group m showed thickened alveolar walls & proteinaceous fluid accumulated in interstitial space along with interstitial fibrosis. in group t, only 28.5% of rats showed the said histopathological parameters. inflammation is one of the etiological factor for the 14 development of fibrosis. as inflammatory reaction is observed in this case, it can be correlated to the development of fibrosis. fibrosis in the pulmonary interstitium is usually a result of alveolar damage due 14 to physical, chemical or microbial agents. allethrin in the coil smoke can be linked to the interstitial fibrosis observed in this study. the process of interstitial fibrosis is characterized by thickened alveolar walls that are fibrotic and contain an inflammatory cell infiltrate with reduced air spaces. macrophages are thought to be responsible for expressing fibroblast growth factor, resulting in the proliferation of fibroblasts and subsequent development of fibrosis. the excessive deposition of collagen fibers reflects reduced lung capacity leading to respiratory distress which is the main effect of air pollutant exposure. earlier study mentions that smoke induces lung destruction with inflammatory reaction, more fibroblasts are brought to the irritated area leading to more collagen fiber 15,16 deposition. in another study, fibrotic change was observed in lung parenchyma of rats after 6 weeks of exposure to mosquito coil smoke. similar histological appearance was seen in the lungs exposed to 17 asbestos and cigarette smoke. excessive deposition of collagen fiber has also been observed in the lungs 18 of rats in similar inhalational studies. turmeric is one of the herbal compounds that has been 19,20 investigated in fibrosis research. in the present research only 28.5 % of histological sections of rat lungs in the group t showed fibrous reaction. the result of this study is consistent with the previous studies. turmeric administration can inhibit 21 abnormal lung collagen formation. turmeric supplementation suppresses alveolar macrophages, expression of fibroblast growth factor by the macrophages and other inflammatory cells thereby ameliorating the inflammatory responses in the 22 lungs which prevents fibrosis in the lung tissue. the histopathological findings of the current research can further be utilized to test turmeric for the prophylaxis and treatment of covid-19 induced pulmonary fibrosis; which is considered to be the 23 most devastating outcome of this viral infection. conclusion interstitial lung fibrosis caused by anti-mosquito coil smoke can be protected with the use of turmeric. fig 2: (a) histological sec�on of a rat lung from group m showing thickened fibro�c alveolar septa (arrow), proteinaceous fluid (star) with reduced air space (double headed arrow) (b) histological sec�on of a rat lung from group t showing less thickened alveolar septa (arrow) with a few cellular infiltrates (star), well-formed alveoli and preserved air space (double headed arrow) (c) histological sec�on of a rat lung from group x showing normal alveolar septa (arrow) and alveoli showing honeycomb like pa�ern (double headed arrow) jiimc 2020 vol. 15, no.4 224 preventive effect of turmeric references 1. kant s, lohiya a, ahamed f, abdulkader rs, singh ak, silan v. comparative morbidity profile of patients attending an ayurveda clinic and a modern medicine clinic of a primary health center in rural haryana, india. j fam med prim care. 2018;7(2):374. 2. liang z, wu r, xie w, zhu m, xie c, li x, et al. curcumin reverses tobacco smoke-induced epithelial-mesenchymal transition by suppressing the mapk pathway in the lungs of mice. mol med rep. 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corah's dental anxiety scale. the qualitative variables were described as frequencies and percentages and the quantitative variables were expressed as mean ± standard deviation. data was subjected to descriptive statistical analysis and significance testing between the variables was done using independent samples t t test and analysis of variance (anova). level of significance was set at 0.05. results: dental anxiety was prevalent in 29.7% patients, mostly children with a mean dental anxiety score of 7.23 (±3.78). the incidence of dental anxiety among the patients was 70.3% non-anxious, 15.3 % moderate anxiety, 6.7 % high anxiety and 7.7 % severe anxiety. females recorded a higher mean dental anxiety score, 7.89 (±4.07) as compared to males 6.44 (±3.39). there was a highly significant (p<0.05) difference in dental anxiety scores based on age, gender, and past dental experiences. conclusion: the dental anxiety levels reported in the study population were low and the high level of anxiety was seen mostly in children. this highlights the importance of developing a comfortable dentist-patient relationship to help anxious patients and support them during the course of the treatment. key words: corahs dental anxiety scale, dental anxiety, dental fear, dental survey, past dental experience. them and make a treatment plan specifically for such patients 4 . according to epidemiological data, between 3% and 20% people worldwide suffer from 5 dental anxiety which is a cause for concern. around 10-20% of the population in the united states suffers 1 from dental anxiety. dental anxiety has also been linked to deteriorating oral health and lack of timely 5 treatment. it has been found that people suffering from dental anxiety have more decayed or missing 2 teeth as compared to those in non-anxious patients. although advancements in dental technology have been made but no change in dental scores has been 1 observed over the years. previously, limited studies have been done on the prevalence of dental anxiety in patients in pakistan 3,6 and there was a need for a study in our population. the objective was to relate dental anxiety scores with age, gender and past dental experiences. this could help dentists in anticipating the responses of their patients when they report to the clinic. the corah's dental anxiety scale (das) was used to create a 20-point questionnaire. das is the most introduction dental anxiety refers to a state of fear in regard to something bad happening during dental treatment, whereas dental fear is the normal response to a 1 particular threatening stimulus in a dental setting. dental anxiety (da) is considered a major factor which results in patients avoiding treatment ultimately leading to an increase in the severity of 2 the disease. such patients may be more uncooperative during the visit and may respond to 3 pain stimuli differently. it is imperative for dentists to address dental anxiety in patients so that they can develop empathy for dental anxiety in patients in lahore medical and dental college: a cross sectional study fatima suhaib, usman mahmood, uzair abu bakar, aqib sohail, shyreen liaqat correspondence: dr. fatima suhaib assistant professor department of dentistry lahore medical and dental college, lahore e-mail: fatimasuhaib83@hotmail.com department of dentistry lahore medical and dental college, lahore funding source: nil; conflict of interest: nil received: september 14, 2020; revised: february 12, 2021 accepted: february 15, 2021 dental anxiety in patients of lmdcjiimc 2021 vol. 16, no.1 28 commonly and widely used scale for measuring 7 dental anxiety. if the level of anxiety experienced by patients is known then the dentist can be better , prepared to deal with such patients. the aim of our study was to determine the prevalence and level of dental anxiety in patients reporting to the outpatient department (opd) in lahore medical and dental college. materials and methods this cross-sectional comparative study was done at lahore medical and dental college (lmdc), lahore, st th pakistan starting from 1 august to 30 september 2019. a formal permission was obtained from the ethical review board of the college to conduct the study. all consecutive patients who came for treatment in the opd of the college were enrolled in the study. the patients were asked to fill a questionnaire. those patients who refused to participate were excluded from the study. informed consent as a standard procedure was taken and confidentiality and anonymity of their responses was ensured. the study sample consisted of 300 patients. the sample population comprised of non-probability convenience sampling. all the patients belonged to a low socioeconomic background. the data was collected using the following method. a questionnaire was prepared to measure the level of anxiety of the patients before a dental visit. a bilingual translator translated the questionnaire into urdu language. the first part of the questionnaire consisted of questions regarding age, gender, and previous dental experience. the second part consisted of questions based on corah's dental anxiety scale. this is a 20-point scale where each response is given a set score. it is based on 4 questions each having 5 options. each question may have a total maximum score of 20 or a minimum score of 4. this is calculated as a sum of all the scores of the five multiple choice items. a score of 9-12 was considered moderate anxiety, 13-14 was high anxiety, 15-20 as severe anxiety or phobia. 4 was the lowest score indicating no anxiety. the data was collected, and statistical package for social sciences (spss) version 21.0 was used to do the statistical analysis. the qualitative variables were described as frequencies and percentages. data was subjected to descriptive statistical analysis and presented as mean ± standard deviation. the independent student t test was used to compare the mean das score in both the genders and groups with previous dental experiences. analysis of variance (anova) and post hoc analysis was done to compare the das scores in the different age groups. level of significance was set at 0.05. results a total of 300 (170 females and 130 males) patients were involved in the study out of which 56.7% were females and 43.3% were males. the ages of the patients ranged from 4 years to 73 years with a mean age of 28.2 (±12.27). the total number of patients in each group and mean ±standard deviation (sd) of age, gender, previous dental experience, and dental anxiety scale are given in table i. each variable with its statistical significance to dental anxiety is also given in table i. table i: bivariate rela�onship between dental anxiety and sociodemographic variables the prevalence of dental anxiety among the patients was 70.3% non-anxious, 15.3 % moderate anxiety, 6.7 % high anxiety and 7.7 % severe anxiety. females recorded a higher dental anxiety score (das) 7.89 (±4.07) as compared to males 6.44 (±3.39). the bar chart in figure 1 shows the dental anxiety level for each of the items of the questionnaire. there was a highly significant (p<0.05) difference in das scores based on age, gender, and past dental experiences. discussion this cross-sectional study was done to find the prevalence and dental anxiety levels in patients reporting to the opd of lahore medical and dental college, lahore. the prevalence of dental anxiety was found to be 29.7% with a mean dental anxiety score of 7.23 (±3.78). around 70.3% population was c l a s s i f i e d a s n o n a n x i o u s . a s s o c i a t i o n o f demographic variables with dental anxiety were dental anxiety in patients of lmdcjiimc 2021 vol. 16, no.1 29 identified using bivariate analysis. these findings are comparable to other studies done for the same region like shimla, india where incidence of dental anxiety was found to be 29.2% 8 and mean dental anxiety score was 9.22 (±4.5). similarly in an australian population, the das score 9 recorded was 9.04 (± 3.45). in a nigerian study the dental anxiety score was similar to our study, 7.33 (± 3.20) and 92.5% of the population was found to be 10 non-anxious. an iranian study showed higher das score, 12.34 (±4.74) where prevalence of dental 2 anxiety was 58.8%. in a similar study done in a teaching hospital in karachi, the mean das score 5 recorded was much lower, 2.73. there was a highly significant difference (p ≤ 0.05) between the anxiety levels based on age, gender, and past dental experiences. females had a higher dental anxiety score than males (7.89 and 6.44 respectively) and similar association has been 2,5,9,12 extensively documented in other studies too. it was found that younger female patients with past unpleasant experiences had a greater chance of 13 developing anxiety before a dental procedure. there are multiple reasons reported for this difference mainly because of a difference in the genetic makeup as females have a more developed fight and flight response due to presence of 5 progesterone and estrogen. in addition females may also find it easier to express their emotions and fears 14 openly. it has been reported that as the age of the patient becomes more, the anxiety experienced by them 14 before dental treatment also becomes less. the reason could be a level of maturity that comes with age and the result of forming a good rapport with the dentist over time that ensures more confidence. this was also true for our study as higher das score (12.47 ±3.85) was seen in children as compared to adults' ≥ 51 years of age (5.00 ±2.00) (p<0.001). it has been extensively documented that children have more anxiety before a dental procedure and higher das 15,17 scores have been reported in many studies. in a study in iran, no difference in das score based on age 2 was found. in an australian study, highest das score 9 was found in the 35-44 years age group. this anxiety could be due to diverse factors like the sociocultural background, child's age, personality and nature of 16 the parent's dental experiences. anxiety in young children can lead to an increased incidence of decayed teeth and more oral health related 18 problems in life. our study also showed that there was a highly significant association between das scores and past unpleasant experiences of the patients. higher das score was observed in patients previously having a bad experience with the dentist (12.16 ±3.77) than the other group (6.46 ±3.24). this trend is expected and underlines the importance of a healthy patient and dentist relationship. the dentist's positive attitude and reassurance can make a patient feel safe and secure. similar findings have also been highlighted in a study in iran, where a statistically significant association was seen between the two variables thus further highlighting the role of the 2 dental care givers in reassuring the patient. limitations of our study were due to the small sample size confined to one hospital only where patients belonging to a low socioeconomic and educational background reported. it was felt by the authors that the avoidance of dental treatment despite low das score was due to low dental awareness rather than anxiety. however, further data is needed from diverse populations and people from all kinds of backgrounds to fully understand the factors responsible for dental anxiety and fear. conclusion it is concluded that most patients are non-anxious and the high level of anxiety that is seen is mostly in children. dental anxiety is prevalent in a small percentage of people and dental anxiety scores recorded are low. female patients are more anxious and those patients with previous unpleasant dental experiences have higher levels of anxiety. this highlights the importance of developing a fig 1: associa�on of level of anxiety with the items in the dental anxiety scale dental anxiety in patients of lmdcjiimc 2021 vol. 16, no.1 30 comfortable dentist-patient relationship in order to help anxious patients and support them during the course of the treatment. adequate measures must be taken to help children overcome their fear and anxiety so that they are not scarred for life. references 1. tellez m, kinner dg, heimberg rg, lim s, ismail ai. prevalence and correlates of dental anxiety in patients seeking dental care. community dentistry and oral epidemiology. 2015;43(2):135-42. 2. saatchi m, abtahi m, mohammadi g, mirdamadi m, binandeh es. the prevalence of dental anxiety and fear in patients referred to isfahan dental school, iran. dental research journal. 2015;12(3):248. 3. khokhar na, abdullah j, shinwari ms, anwar a, farid h. dental fear and anxiety among orthodontic patients a pakistani sample. pakistan oral & dental journal. 2015;35(2). 4. sardar kp, raza i, shafi m. dental anxiety level in patients attending dental outpatient department at dow university of health sciences. j pak dent assoc. 2015;24(03):145-51. 5. wali a, ali sa, siddiqui tm, 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𸷴¿¼»´°¸·¿æ úòßò ü¿ª·­ ý±³°¿²§å îððéò ëò ø ¬ ¬° æñ ñ © © ©ò² ½¾· ò²´ ³ ò²· ¸ò ¹±ªñ ° « ¾³» ¼ ñïîçéððïî ®»¬®·»ª»¼ ±² îéñêñîðïí »®»²½»­ î original�article abstract objective: to determine the effect of caffeine on the weight and length of femur of balb/c mice. study design: a laboratory based randomized control trial. place and duration of study: the study was conducted at anatomy department, army medical college, th rawalpindi in collaboration with national institute of health, islamabad for a duration of one year from 6 th october 2014 to 5 october 2015. materials and methods: twenty balb/c mice (10 male, 10 female) , three weeks old, weighing 12-14 g, were taken and divided into two groups with 10 mice (5 male, 5 female) in each group. the control group g1 was given normal diet and water ad libitum. each animal in the experimental group g2 was given 10mg of caffeine per 100g body weight on alternate day, three days in a week by oral gavage for 60 days. the effect of caffeine was evaluated by measuring the weight and length of femur of the balb/c mice at the end of study. ibm-spss version 20 was used for data analysis. the student's t-test was applied for intergroup comparison of quantitative variable, which was taken as means and standard deviations (mean ± sd). a p value < 0.05 was taken as significant. results: the mean femur weight of balb/c mice of control group g1 was observed as 0.387±0.019 g while the mean femur weight of experimental group g2 was found to be 0.316±0.020 g. however, the mean femur length of control group g1 was 20.70±0.609 mm and experimental group g2 was 24.382±1.087mm. the weight of femur was decreased in experimental group g2 while the length of femur was increased in experimental group g2 as compared to control group g1. conclusion: caffeine consumption causes reduction in femur weight and increase in femur length. key words: caffeine, femur, length, weight. that caffeine impairs bone development by decreasing the mineral content and calcium a b s o r p t i o n . t h e l o w b o n e m a s s a n d microarchitectural deterioration of osseous tissue that leads to bone fragility as well as an increased 3 susceptibility to fractures. caffeine is antiproliferative towards osteoblasts and it debilitates 4 some important events in osteogenesis. the excessive coffee consumption was associated with a small but significant reduction in number of teeth 5 with periodontal bone loss. there is a significant association between caffeinated beverages and 6 dental erosion. the intake of caffeine in amounts >300 mg/day (514 g, or 18 oz, brewed coffee) accelerated bone loss at the spine in elderly 7 postmenopausal women. it is also investigated that if young, rapidly growing rats are exposed to caffeine, disruption of osteoblasts and retarded bone development occur. an in-vitro study showed that caffeine may enhance the rate of osteoblast apoptosis and has potential deleterious effect on the 8 osteoblast viability . caffeine could easily permeate through placenta and introduction caffeine is the most commonly consumed stimulant in the world. it is found in coffee, tea, cocoa products, soft drinks and energy drinks. caffeine (1, 3, 7trimethylxanthine), in addition to being food 1 constituent, is also a common analgesic adjuvant. the pandemic consumption of caffeine in food, beverages, and pharmaceutical preparations, such as decongestants, muscle relaxants, and allergy drugs, has developed special attention in demonstrating the multitude of effects and 2 mechanisms of action of this drug of daily life. the laboratories based researches have illustrated the effect of caffeine on the weight and length of femur of balb/c mice 1 2 maimoona khan , shadab ahmed butt correspondence: dr. maimoona khan assistant professor, anatomy hitec institute of medical sciences taxila e-mail: maimoonakhan@hotmail.com 1 department of anatomy hitec institute of medical sciences, taxila 2 department of anatomy army medical college, rawalpindi funding source: nil; conflict of interest: nil received: sep 02, 2016; revised: feb 18, 2017 accepted: feb 18, 2017 effect of caffeine on femur of balb/c micejiimc 2017 vol. 12, no.1 44 control trial. it was carried out at anatomy department, army medical college, rawalpindi in collaboration with national institute of health, th islamabad. it was spanned from 6 october 2014 to th 5 october 2015 with the approval of ethical committee on animal experiments. the healthy three week old male and female balb/c mice were taken for the experiment. the total number was twenty (20), 10 male and 10 female weighing 12-14 g. the simple random sampling technique was applied. they were kept in a well ventilated room and under a temperature range of 20-260c. mice were randomly divided by lottery method into two groups. each group contained 5 male and 5 female mice (10 animals in each group). male and female mice were kept in separate cages to avoid 16 pregnancy. the mice of group g1 served as controls, they were given standard laboratory diet for 60 days. mice in g2 group were given caffeine at a dose of 10mg/100gm body weight, on alternate day, 3 days a week for 60 days by oral gavage. at the end of experiment, the animals were euthanized with ether anesthesia. they were dissected and right femur was removed after separating from hip and knee joints. femur was weighed by electrical balance while its length was measured by digital vernier calliper from 17 greater trochanter to lateral condyle (fig 1). ibmspss version 20 was used for data analysis. student's t test was applied for intergroup comparison of quantitative variable which was taken as means and standard deviations (mean ±sd). a p value < 0.05 was considered significant. results the mean femur weight of mice in experimental group g2 was considerably decreased as compared to control group g1. however, the mean femur length of experimental group g2 was appreciably increased as compared to control group g1 (table i). the p-values of both femur weight and length of group g2 in comparison with group g1 were calculated to be < 0.05 and therefore found statistically significant (table i). it could interrupt the development as well as mineralization of the osseous tissue. consequently the process of skeletal ossification was delayed in 9 fetal animals. during lactation, maternal exposure to caffeine resulted into specific effects on the enamel of the molar teeth of young animals and enhanced the sensitivity to dental caries. there would be fewer osteocytes per area of femur cross section, retarded structural remodeling of the lateral tibial metaphysis, abnormal osteoblasts and 10 osteocytes with swollen mitrochondria. caffeine invariably lowered the zn content and altered the bone tissue mass that caused fragility as well as 11 predisposition to fractures. the excessive dietary caffeine is responsible to increase urinary calcium output, most probably as a result of the acidic load which is favored by it. the bones counterbalance against acidosis by the buffering capacity of a large 12 reservoir of calcium salts. the effects of coffee on bone metabolism are contentious, although caffeine intake is associated with an eloquent increase in risk of periodental 13 disease, osteoporosis and fracture. the animal studies have evaluated that rats exposed to caffeine during gestational period exhibited structural disturbances of bone with a decreased number of osteocytes and smaller cross-sectional area of bone. the histological manifestations showed immature bone trabeculae and inhibition of osteoblasts 14 proliferation. caffeine reduces calcium balance which is either by increased urinary excretion or 15 decreased intestinal calcium absorption. caffeine is consumed in pakistan in different forms through foods as well as beverages. over the past decades, intake of caffeine is increasing day by day and it has become a part of our daily diet. however, the society is generally unaware regarding its deleterious effects on human health especially the bony tissues. this is because of non-availability of data on its various adverse effects. until now, there have been limited local studies on the subject of amount of caffeine consumption and its effects on health. the present study is an effort towards generating this understanding by gathering information and demonstrating detrimental effect of high caffeine consumption on the developing thigh bone of animals (balb/c mice). materials and methods the study was a laboratory based randomized jiimc 2017 vol. 12, no.1 table i: mean values of weight and length of femur in control group g1 and experimental group g2 *p value < 0.05 is sta�s�cally significant 45 effect of caffeine on femur of balb/c mice of growth hormone (gh) through different m e c h a n i s m s . m e t h y l x a n t h i n e s i n h i b i t phosphodiesterase (pde), which leads to an increase in pituitary cyclic adenosine monophosphate (camp) 22 responsible for growth hormone release. caffeine also effects neurotransmitters. caffeine increases 23 24 the turnover of norepinephrine and serotonin in the brain. norepinephrine as well as serotonin cause 25 gh secretion in adult rats and humans. the weight of femur was found less in experimental group g2 than control group g1. an earlier international study shows that caffeine reduces the 26 weight of the leg bones of rat. yet another study illustrates that intake of caffeine diminishes the 27 volume and weight of femur. the caffeine consumption lowers the bmd and hence weight of 8 skeletal bones. there is impairment of weight and 28 longitudinal growth of bones by caffeine. the excessive caffeine ingestion is usually a marker for a 15 low calcium intake. caffeine decreases mineral and hydroxyproline content in bones. the amount of hydroxyproline in-turn indicates the collagen 2 content of bones. caffeine consumption effects the normal metabolism of bones, including lower bone mineral density (bmd), lighter bone weight and 27 decrease in calcium content of the bone. the lower calcium content is also connected with caffeine induced defective development of bone.8 moreover, caffeine has negative effects on normal 28 growth and development of the osseous tissue. caffeine also decreases zinc levels in several tissues 2 9 i n c l u d i n g b o n e s . t h e d e f i c i e n c y i n z i n c concentration in caffeine fed animals changes bone m eta b o l i s m a n d p e r m a n e nt l y a l te rs b o n e 13 cytoarchitecture. the future work can be conducted by using different doses/duration of caffeine and studying the teratogenic effect of caffeine on genetic / chromosomal changes. conclusion it was observed in the present study that caffeine altered the development of femur of balb/c mice. high intake of caffeine caused increase in femur length and decrease in femur weight. references 1. mitchell dc, hockenberry j, teplansky r, hartman tj. caffeine intakes from beverages in the 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tomaszewski m, olchowik g, tomaszewska m, burdan f. use of x-ray microprobe to diagnose bone tissue demineralization after caffeine administration. folia histochem. cytobiol. 2012; 50: 436-43. 11. schulman rc, weiss aj, mechanick ji. nutrition, bone, and aging: an integrative physiology approach. current osteoporosis reports. 2011; 9: 184-95. 12. choi ej, kim kh, koh yj, lee js, lee dr, park sm. coffee consumption and bone mineral density in korean premenopausal women. korean journal of family medicine. 2014; 35: 11-8. 13. liu sh, chen c, yang rs, yen yp, yang yt, tsai c. caffeine enhances osteoclast differentiation from bone marrow hematopoietic cells and reduces bone mineral density in growing rats. journal of orthopaedic research. 2011; 29: 954-60. 14. su sj, chang kl, su sh, yeh yt, shyu hw, chen km. caffeine regulates osteogenic differentiation and mineralization of primary adipose-derived stem cells and a bone marrow stromal cell line. international journal of food sciences and nutrition. 2013; 64: 429-36. 15. ross ac, taylor cl, yaktine al, del valle hb, editors. dietary reference intakes for calcium and vitamin d. national academies press; 2011. 16. furukawa s, hayashi s, usuda k, abe m, ogawa i. histopathological effect of ketoconazole on rat placenta. journal of veterinary medical science. 2008; 70: 1179-84. jiimc 2017 vol. 12, no.1 47 effect of caffeine on femur of balb/c mice jiimc december 2016 page 48 page 49 page 50 page 51 editorial artificial intelligence in dentistry: hype or hope? ulfat bashir, kanwal zulfiqar artificial intelligence is one of the most significant contributions to the fourth industrial revolution, which ushers in a new digital era. it is defined as “the study of intelligent agents, which includes any machine that can comprehend its environment and 1 respond to increase its chances of success.” the term "ai" is used informally when a machine imitates cognitive processes that people often connect with other human minds, such as "learning and problem1 solving." mathematician john mccarthy created the concept of "artificial intelligence" in 1955. mccarthy is widely considered the founder of the field. to explain how machines might be able to perform what can be referred to as "intelligent" activities, he 2 introduced this phrase. numerous industrial sectors, including robotics, transportation, smart cities, financial analysis, etc., have incorporated ai. as an example, medical and dental imaging diagnostics, decision support, precision and digital medicine, drug discovery, wearable technologies, hospital monitoring, robotic and virtual assistants have all been employed in medicine and dentistry. in many instances, artificial intelligence (ai) can be seen as a helpful tool for physicians and dentists to lessen their labor. ai may learn from various information sources (multi-modal data) to diagnose diseases beyond the capability of humans, in addition to identifying diseases by means of a single information source that 3 is focused on a particular illness. the introduction of ai platforms such as chat gpt has completely revolutionized the dynamics of information being available within seconds. similarly, health professionals are eagerly contemplating its 3 effects in the medical and dental health profession. the dentists all over the world are also rapidly embracing the advancements in ai and machine 4 learning. one of the biggest advantages of ai in dentistry is its ability to diagnose oral diseases with high accuracy and precision. ai algorithms can analyze dental images and detect early signs of oral cancer, periodontitis, and other oral diseases, allowing for early treatment and prevention of 5 further complications. ai has been heavily utilized in periodontology to investigate, comprehend, and build periodontal applications, such as detecting periodontal bone loss, identifying gingivitis inflammation, and evaluating connective tissues and other periodontal 4 cavities. endodontic treatment planning has been greatly aided by ai in recent years. different types of ai can aid dentists in the diagnosis and management of endodontic issues while fostering performance and assuring improved and precise patient care. the review's main objectives are to extract and evaluate ai-based methods for disease diagnosis and therapy 4 planning. when teeth exhibit periapical lesions and/or associated symptoms, it may be challenging for doctors to make a diagnosis and formulate a 6 treatment plan. the common disease known as apical periodontitis is responsible for about 75% of 7 cases with radiolucent jaw lesions. early detection could improve the effectiveness of care, stop it from spreading to other tissues, and lessen potential 8 difficulties. another benefit of ai in dentistry is its ability to improve the planning and execution of 5 dental procedures. ai algorithms can help dentists plan complex procedures such as implants, orthodontics, and restorations with high accuracy, reducing the risk of complications and ensuring the 4 best possible outcome for the patient. due to its capacity to improve the efficiency and accuracy of the diagnostic process, artificial intelligence (ai) has become extremely popular in orthodontics in recent years. since orthodontic treatments are frequently drawn-out processes, more effective planning calls for more effective and efficient solutions. dentists can make judgments more precisely and quickly in a time-constrained context by using ai-based knowledge to automate disease diagnosis and treatment prognosis processes. through their capacity to learn and make correspondence: prof. ulfat bashir department of orthodontics islamic international dental college, riphah international university islamabad e-mail: ulfat.bashir@riphah.edu.pk received: february 27,2023; accepted: march 01, 2023 1 department of orthodontics islamic international dental college, riphah international university islamabad https://doi.org/10.57234/jiimc.march23.1666 automobile decisions, ai solutions can further aid in the prevention of human errors. numerous studies have looked into using ai to diagnose and design 9,10 treatments for orthodontic diseases. in the area of dental education, ai is extensively used. the preclinical virtual patient input to the students has been much enhanced. the interactive interphase develops top-notch learning environments by letting pupils assess their own work and contrast it with the ideal. numerous studies on the efficiency of these systems have revealed that, in comparison to conventional simulator units, these systems enable students to reach a competency-based skill level 11 more quickly. artificial intelligence-powered virtual dental assistants can perform a variety of tasks in dental offices with greater accuracy and fewer errors. it is very helpful when discussing the patient's medical history and any habits they may have, such as smoking and drinking, with the dentist. the patient can choose to receive urgent teleassistance in dental crises, particularly if the practitioner is not 12 readily available. in recent years, there has been a noticeable increase in the number of research investigating the 13,14 application of ai in restorative dentistry. various studies investigated the application of ai in helping caries detection, vertical tooth fracture prediction, and treatment planning. to accurately plan therapy utilizing clinical examples, lee et al. suggested a machine learning method based on a decision tree to evaluate the tooth prognosis. the model's precision 13 was 84.1%. however, despite the rapid progress made in ai research in dentistry, there are still many challenges that need to be addressed. one of the biggest challenges is the lack of data standardization and interoperability between ai systems and existing dental systems. also there is lack of understanding and adoption by dental professionals. while some dentists have embraced ai and its benefits, others are still skeptical about the technology and its ability to replace human expertise. additionally, the high cost of ai technology can also limit its widespread adoption, particularly in resource-limited settings like pakistan. this can lead to the inability to share data and collaborate on research thus limiting the advancement of the field. additionally, there is a need for further research on the ethical and legal implications of ai in dentistry, such as data privacy and patient consent. it is still necessary to use appropriate external data gathered from freshly enrolled patients or gathered from other dental facilities to confirm the generalizability and dependability of the offered ai models, even though their results have been 15 encouraging. administration and exchange of clinical data are two major barriers to the use of ai systems in the healthcare sector. patients' personal data is needed for both the initial training of ai algorithms as well as for ongoing training, validation, and improvement. the development of ai will also promote data sharing across multiple institutions and, in some circumstances, across international borders. ai must be integrated into healthcare operations while modifying systems that protect 16 patient confidentiality and privacy. personal data must therefore be anonymized before considering a 17 wider distribution. even if these protections are technically possible, the medical community has doubts about secure data sharing. despite these limitations, the future of ai in dentistry looks bright. as ai technology continues to advance and become more accessible, we can expect to see an increased adoption of the technology by dental professionals and patients alike. furthermore, the development of ai-powered devices and tools will revolutionize the way dentists diagnose and treat oral diseases, leading to improved patient outcomes and a more efficient and effective delivery of dental care. computer learning researchers will be better able to comprehend some multifactorial diseases with the aid of deep learning, and it will be feasible to increase our collective understanding of oral diseases and conditions that are not yet fully known. artificial intelligence can undoubtedly be a tool for delivering improved healthcare to patients, but it cannot in any way take the place of human knowledge, skills, and 18 capacity of judgment. despite the difficulties, there is a good probability that ai will be used in dentistry in the future, and as we adopt these exciting innovations, patient care will only improve. however, for this to happen in the dental sector, new finance resources are required, along with debt and an understanding that open systems lead to innovations that are good for the sector. the possibilities are endless if these problems can be fixed. in conclusion, ai is the next paradigm shift in the healthcare. we as healthcare jiimc 2023 vol. 18, no.1 2 artificial intelligence in dentistry https://doi.org/10.57234/jiimc.march23.1666 professionals need to carefully evaluate the challenges we face when moving towards this new age of transformation.ai is not absolute and cannot replace human judgement. it is imperative that we adapt to ai to improve patient care but also be watchful of its limitations. references 1. russel s, norvig p. artificial intelligence: a modern approach. 3rd ed. new jersey: pearson education; 2010. back to cited text no. 2. 2. rajaraman v. john mccarthy—father of artificial intelligence. resonance. 2014 mar;19:198-207. 3. poplin r, varadarajan av, blumer k, liu y, mcconnell mv, corrado gs, et al. prediction of cardiovascular risk factors from retinal fundus photographs via deep learning. nat biomed eng. (2018) 2(3):158–64. doi: 10.1038/s41551018-0195-0 pubmed abstract | crossref full text | google scholar. 4. fatima a, shafi i, afzal h, díez id, lourdes dr, breñosa j, espinosa jc, ashraf i. advancements in dentistry with artificial intelligence: current clinical applications and future perspectives. inhealthcare 2022 oct 31 (vol. 10, no. 11, p. 2188). mdpi. 5. agrawal p, nikhade p. artificial intelligence in dentistry: p a s t , p r e s e n t , a n d f u t u r e . c u r e u s . 2 0 2 2 j u l 28;14(7):e27405. doi: 10.7759/cureus.27405. pmid: 36046326; pmcid: pmc9418762. 6. artificial intelligence in endodontics: current applications and future directions. aminoshariae a, kulild j, nagendrababu v. j endod. 2021;47:1352–1357. [pubmed] [google scholar]. 7. radiolucent inflammatory jaw lesions: a twenty-year analysis. becconsall-ryan k, tong d, love rm. int endod j. 2010;43:859–865. 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[pmc free article] [pubmed] [google scholar]. 16. char ds, shah nh, magnus d. implementing machine learning in healthcare — addressing ethical challenges. n eng j med. 2018;378(11):981-3. 17. he j, baxter sl, xu j, xu j, zhou x, zhang k. the practical implementation of artificial intelligence technologies in medicine. nat med. 2019 jan;25(1):30-36. doi: 10.1038/s41591-018-0307-0. epub 2019 jan 7. pmid: 30617336; pmcid: pmc6995276. 18. israni st, verghese a. 2019. humanizing artificial intelligence. jama. 321(1):29–30. jiimc 2023 vol. 18, no.1 3 artificial intelligence in dentistry conflict of interest authors declared no conflicts of interest. grant support and financial disclosure authors have declared no specific grant for this research from any funding agency in public, commercial or nonprofit sector. data sharing statment the data that support the findings of this study are available from the corresponding author upon request. this is an open access article distributed under the terms of the creative commons attributionnoncommercial 2.0 generic license. https://doi.org/10.57234/jiimc.march23.1666 jiims final 19 introduction the tibia is commonly fractured bone frequently caused by high-energy trauma leading to the complications and major 1disabilities. surgeons have employed different types of intramedullary nails over past 500 years. today, the intramedullary interlocking tibial nailing is the leading modality of treatment because of its biomechanical advantage over the other 2modalities. this procedure is done in the advanced centers under the image 3,4,5intensifier. however, there is no facility of carm image intensifier in the operation theatre at most of the tertiary level hospitals in pakistan. most of the peripheral hospitals do not even have portable xray facility. the purpose of this study was to study the success rate of intramedullary nailing of tibial shaft fractures without the aid of image intensifier. tanna et al reported a method for locked tibial nailing without image intensifier in 1994, using hollow t u b u l a r n a i l s w i t h n o s l i t a n d anteroposterior holes for the locking 6screws. with newly designed interlocking nails, it is now feasible to achieve interlocking nail i n s e r t i o n w i t h o u t t h e a i d o f a n intraoperative image intensifier, simply by the use of an external jig and slot finder eg the sign (surgical implant generation network) system. successful interlocking nailing using such method should not only improve the quality of fracture care, but should also lead to a reduction of exposure 7,8,9to intra-operative ionizing radiation. sign nail is not freely available in our original article abstract introduction: internal fixation with interlocking nails is commonly performed using an image intensifier which is expensive and is not readily available in most resource-poor countries of the world. objective: the aim of this study was to achieve internal fixation with interlocking nail without the use of an image intensifier and to study the mean union time and complications in these patients. study design: it was a quasi-experimental study. place and duration of study: this study was carried out at railway general hospital (rgh), rawalpindi over duration of two years from january 2010 till december 2011. materials and methods: 22 closed tibial shaft fractures were fixed with interlocking intramedullary nails without using an image intensifier. results: the study included 22 closed tibial shaft fractures. the mean age of the patients was 39.4±9.97 years and the range was 2255 years. there were 8 females and 14 males. postoperative plain radiographs confirmed that all of the cases had satisfactory positioning of the inserted nails and interlocking screws. the mean union time was 13.8±4.2 weeks. two cases of delayed union were seen (union occurred at 24 and 28 weeks). one case of infection occurred and presented with an infrapatellar abscess. shortening of 12 mm and valgus deformity occurred in one case due to loosening of distal screw. conclusion: internal fixation with interlocking of tibial shaft fractures can be achieved successfully without an image intensifier. key words: tibial fracture, interlocking, intramedullary nails --------------------------------------------------closed interlocking tibial nailing without using an image intensifier sohail iqbal sheikh, muhammadullah, arab khan, javed iqbal correspondence: prof. dr sohail iqbal sheikh head of orthopedics department islamic international medical college pakistan railway general hospital, rawalpindi 19 20 region and if available it is expensive, so we started doing interlocking nailing of tibia w i t h o r d i n a r y t i b i a l i n t e r l o c k i n g instruments which are freely available and inexpensive. this work, which describes my experience in using this method, is expected to contribute to knowledge in our sub region, since there is a paucity of literature on this subject matter. this work will also help to introduce this mode of treating fractures in resource-poor regions of the world, where image intensifiers are not widely available. t h i s q u a s i e x p e r i m e n t a l s t u d y w a s conducted over duration of two years from january 2010 to december 2011 in the orthopedic unit of railway general hospital (rgh) rawalpindi. the study was conducted after approval from the hospital ethical committee.tibial shaft fracture patients presenting to the emergency department were recruited into the study by consecutive non-probability sampling and a n i n f o r m e d c o n s e n t w a s t a k e n . anteroposterior (ap) and lateral view radiographs of tibial shaft incorporating the entire length of the lower leg from knee to ankle were obtained. closed tibial shaft fractures with significant malrotation (=10 degrees of rotation in any plane), malalignment (angulated =10 degrees), and displacement (=5 mm of displacement) were opted for operative management by interlocking nailing. open fractures or severely comminuted fractures were excluded. moreover fractures with evidence of neurovascular injury, compartment syndrome and fractures with dislocation of the knee or ankle were excluded. closed, material and methods well-aligned, no displaced tibial shaft fractures were treated with a long leg cast and also were not included in our study. patients were operated under spinal anesthesia. the interlocking nails were inserted as follows; under tourniquet the patient is placed supine and the leg of the patient hangs downwards over the edge of the table making 90 degrees of flexion at knee joint. a skin incision is made over patellar tendon and the patellar tendon is split longitudinally. hole is made in upper end of tibia with bone awl, after this guide wire is inserted into the medullary cavity. one assistant pulls distal end of fracture downwards and guide wire is pushed through distal end of fracture. grating feeling is appreciated while guide wire passes into distal fragment and stability is confirmed. reaming of medullary cavity is done in increasing numbers. after this, size of nail is measured by putting nail over leg from tibial tuberosity to just above ankle. then another nail of similar size is kept aside. one of the nails is inserted into medullary cavity after attaching it to proximal jig of tibial interlocking nail. second nail is placed outside the tibia closed to skin and drill bit is passed through jig and then it passes through nail placed outside and then through skin and is drilled into bone. this is checked by passing guide wire through medullary cavity. the drill bit is retrieved and guide wire is passed distally till the lower end of nail. then upper end of guide wire is marked with help of artery forceps. another hole is drilled through distal i/l hole by passing drill bit through distal hole in the nail placed over skin, then it is drilled into the inner nail which is confirmed by pushing guide wire, if the 20 21 artery forceps mark is lying away from jig, it confirms that the drill is in the hole of inner nail. then screw is passed, guide wire is removed and screw through upper hole is passed. finally wound is closed. all patients had a similar preoperative regimen of intravenous cephradine continued for 5 days postoperatively. early physiotherapy of all involved joints, as well as early weight bearing, was encouraged. no cast or brace was applied. analysis of the outcome of treatment with respect to the time of fracture union and the presence of complications was performed. fracture union was assessed clinically and radiologically at 6 weeks and 3 months, and then subsequently at monthly intervals. the fracture was considered to have united when there was no pain or tenderness, when there was no abnormal movement at the fracture site and when bridging callus was visible on a plain radiograph. a fracture was considered to have normal union if there was osseous union in four months or less and delayed union if the fracture healed between four and eight months post operatively. a fracture that had not healed by eight months was considered to have a non-union. all of our patients were followed-up for at least 12 months. data was entered into a proforma and was analyzed using spss 12. the study included 22 closed tibial shaft fractures. the mean age of the patients was 39.4±9.97 years and the range was 2255 years. there were 8 (36.4%) females and 14 ( 6 3 . 6 % ) m a l e s . p o s t o p e r a t i v e p l a i n radiographs confirmed that all of the cases had satisfactory positioning of the inserted nails and interlocking screws. the mean results union time was 13.8±4.2 weeks. two (9.1%) cases of delayed union were seen (union occurred at 24 and 28 weeks). this was in comminuted fractures of distal one third of tibia. one case (4.5%) of infection occurred nine months after union and presented with an infrapatellar abscess, which did not communicate with the knee joint. this was drained and the nail removed. shortening of 12 mm and valgus deformity occurred in one (4.5%) due to loosening of distal screw. the most common cause of morbidity and mortality in the most productive period of life worldwide are road traffic accidents 10causing fractures. it is not surprising, therefore, that these fractures occur mostly in people aged between 20 and 50 years. the sex ratio distribution of 1.75:1 for male:female is also in keeping with other 11reports and further emphasizes the greater vulnerability of males to trauma. the availability of the appropriate treatment modality could be of utmost concern to any practicing orthopaedic surgeon in most resource-poor countries of the world, including the indian subcontinent. the use of interlocking nails for fractures of long bones has increased and indeed has become the gold standard for care of unstable long b o n e f r a c t u r e s . h o w e v e r , i t s m a i n drawbacks are cost and the need for a reliable intraoperative image intensifier 12,13support. there are now nails that can be 14locked with the aid of external jigs. in our study, 100% of the fractures were fixed without the use of an image intensifier with the satisfactory placement of nails and screws in all cases. complications were few and mild. infection could have been avoided discussion 21 22 by improving the aseptic technique. delayed union occurred in the distal third fracture of a tibia with severely comminuted fracture line. the blood supply to this region is very precarious and could be associated with an increase in the incidence of nonunion. there was no case of nail or screw breakage in this study, however screw loosening resulted in valgus deformity and shortening in one case.our results are in 15,16,17agreement with other works. only few studies were available for comparison. ikem et al15 recorded two cases of superficial wound infection, two cases of delayed union 16and a case of screw loosening giri. in 2007 reported the success of distal locking in the intramedullary nailing of tibial shaft fractures with the aid of distal aiming device, where the distal hole was directly visualized after proper drilling. the union 17time in an average was 4 months. giri. in 2008 in another study reported that after using interlocking nails for fractures of tibial shaft the complication was distal screw loosening leading to valgus deformity and shortening in one case. however, no local study is available for comparison.the e x c l u s i o n o f a n i m a g e i n t e n s i f i e r automatically eliminates the harmful effect of an increased dose of radiation to both the orthopaedic surgeon and the patient. radiation times were recorded to average table-i: complications after closed tibial nailing about eight seconds, the longest time being 36 seconds in the study by court et al during interlocking nailing of tibial fractures.3 it has the added advantage of reduced cost to the patient whilst, at the same time, ensuring high-quality fracture care. we conclude that internal fixation with interlocking of tibial shaft fractures can be achieved successfully without an image intensifier. however, proficiency in the use conclusion figure 1reaming of medullary cavity after insertion of guide wire figure 2measurement of the length of the nail and the site of holes 22 23 of interlocking nail instrumentation without use of image intensifier will come with practice. 1. schmidt ah, finkemeier cg, tornetta p. treatment of closed tibial fractures. instr course lect 2003;52:607. 2. abdlslam km, bonnaire f. experimental model for a new distal locking aiming device for solid intramedullary tibia nails. injury 2003;34:3636. 3. court-brawn cm, christie j, mcqueen mm. closed intramedullary tibial nailing: its use in closed and type i open fractures. j bone joint surg 1990;72:60. 4. muller me, allgower m, schneider r, willenegger h. manual of internal fixation: techniques recommended by the ao-asif group. third ed. berlin, etc: springer-verlag, 1990:332-65. 5. paige whittle a, russell ta, taylor jc, lavelle dg. treatment of open fractures of the tibial shaft with the use of interlocking nailing without reaming. j bonejoint surg [am] 1992; 74-a:1 16271. 6. tanna dd. interlocking tibial nailing without an image intensifier. j bone joint surg [br] 1994;76:670. 7. azer sn, krause wr, salman nn. self-guiding interlocking intramedullary nail. contemp orthop 1992;25:228. 8. shah rk, moehring hd, singh rp, dhakal a. surgical implant generation network (sign) intramedullary nailing of open fractures of the tibia. int orthop 2004;28:1636. 9. steriopoulos ka, kontakis gm, katonis pg, galanakis ia, dretakis ek. placement of the d i s t a l l o c k i n g s c r e w s o f t h e f e m o r a l intramedullary nail without radiation. arch orthop trauma surg 1996;115:434. 10. gaebler c, mcqueen mm, vécsei v, courtbrown cm. reamed versus minimally reamed nailing: a prospectively randomized study of 100 patients with closed fractures of the tibia. injury 2011;42:17-21. 11. madadi f, eajazi a, madadi f, daftari besheli l, sadeghian r, nasri lari m. adult tibial shaft fractures different patterns, various treatments references figure 3drilling of the hole in the distal interlocking hole figure 4insertion of the nail into the medullary cavity of tibia over the guide wire figure 5the healed fracture 23 24 and complications. med sci monit 2011;17:640-5. 12. xiang z, guo zh. minimally invasive treatment for bilateral tibia shaft fractures with interlocking intramedullary nails. zhongguo gu shang 2009;22:58-9. 13. vidyadhara s, sharath kr. prospective study of the clinico-radiological outcome of interlocked nailing in proximal third tibial shaftfractures. injury 2006;37:536-42. 14. ogunlusi jd, st rose rs, davids t. interlocking nailing without imaging: the challenges of locating distal slots and how to overcome them in sign intramedullary nailing. int orthop 2010;34:891-5. 15. ikem ic, ogunlusi jd, ine hr. achieving interlocking nails without using an image intensifier. int orthop 2007;31:487-90. 16. giri sk. achieving distal locking without an image intensifier. nepal med coll j 2007;9:275-7. 17. giri sk, adhikari br, gurung gb, rc d, bajracharya ar, khatri k. mini-open reduction and intramedullary interlocking nailing offracture shaft of tibia without an image intensifier. nepal med coll j 2008;10:123-5. 24 jiims final.cdr 26 original article abstract objective: to evaluate and compare the radiological and functional results of immobilization of colle's fracture treated conservatively in two different positions of wrist i.e. palmarflexion(pf) & dorsiflexion (df). study design: a descriptive cross sectional study. materials & methods: sixty patients with closed colle's fracture who were treated conservatively by close reduction and below elbow cast application were included in this study. the study was conducted at department of orthopedics, railway hospital, westridge, rawalpindi from november 2008 to may 2011. the patients were alternately allocated to dorsal or palmar flexed immobilized position of wrist. patients were followed up for a minimum six-month period. the radial tilt, palmar tilt and ulnar variance were measured at 6 month follow up. the results were scored by demerit scoring system of saito. results: all fractures were united. individual movement of dorsiflexion, palmar flexion, supination, and radialulnar deviation (except pronation) were all significantly better in the dorsiflexed-immobilized group as compared with the palmar flexed immobilized group. grip strength recovery with subjective assessment was better in the dorsiflexed group as compared to the pf group. radiological parameters were markedly better in the dorsiflexed group. 100% of patients in the dorsiflexed group had overall excellent results as compared to 23.3% in the palmar flexed group in terms of radiological & functional outcome. conclusion: functional & radiological results of colle's fractures are superior if the fractures after reduction are immobilized in dorsiflexion of wrist rather than in conventional palmar flexion position. keywords: colle's fracture, immobilization, dorsiflexion. possible. accurate assessment of standard radiographs is essential for appropriate 3management. and includes true posterior4anterior (pa) and true lateral projections. each view contains a small number of important landmarks and measurements for proper interpretation. distal radius fractures can be described using either a fragment-specific classification or the standard frykman classification. the frykman classification system divides the fractures among four main groups based upon joint involvement. for immobilization we generally need to avoid positions of marked palmar flexion a n d u l n a r d e v i a t i o n ( c o t t o n l o d e r position); a truly stable fracture will probably be stable in any position once it is reduced; fractures which are stable in only extreme positions, should be considered to be unstable and probably require additional methods of fixation (pins, external fixation, 5orif). while most orthopedists probably introduction about 200 years have passed since colle's described a fracture of the distal end of the radius, and it is one of the most common fractures encountered by the orthopedic 1surgeon. such injuries account for approximately one-sixth of fractures treated 2in emergency departments. the majority of distal radius fractures occur as isolated injuries in two distinct populations: youth involved in sports who sustain a relatively high-energy fall, and seniors with osteoporotic bone who sustain a low-energy fall. fracture examination includes an assessment of neurovascular status. range of motion of the wrist, including supination, pronation, flexion, and extension should be evaluated if ------------------------------------------------treatment of colle's fracture with wrist immobilization in palmar flexed & dorsiflexed position sohail iqbal shaikh, abdul basit, javed iqbal, saba sohail shaikh, imran sohail shaikh correspondence: prof. sohail iqbal shaikh hod orthopedics department iimc-t, pakistan railway hospital rawalpindi. e-mail: tazysheikh@hotmail.com 26 27 immobilize distal radius fractures in slight flexion and pronation, but there is some evidence to suggest that distal radius fractures should be immobilized with the wrist extended; as noted by gupta et al. position of wrist made no difference with regards displacement, in displaced extraarticular fractures with no comminution; in comminuted fractures, both extra articular and intra articular, best results occurred in fractures treated in dorsiflexion; functional results were superior when fractures were treated in dorsiflexion and in contrast palmar flexion was associated with higher rate of fractures displacement. dorsiflexion is also a better position for rehabilitation of 6the fingers. numerous previous studies have taken the amount of displacement into consideration but very few have dwelt on the role of the position of immobilization as a parameter for comparing radiological and functional 7,8,9,10outcome. the present study was undertaken to evaluate the functional and radiological outcome of conservatively treated extra-articular fractures when wrist was immobilized in df compared to immobilization in pf. this prospective study included 60 patients in the age group of 16-75 years with closed extra-articular fractures of the lower end radius from november 2008 to may 2011 in the orthopedics unit of railway general hospital (rgh) rawalpindi. the study was conducted after approval from the hospital ethical committee. the study included extra-articular fractures of frykman category i and ii. extra-articular fractures with extreme displacement or grossly comminuted fractures that were not materials and methods amenable to reduction by manipulation were treated surgically were not included in the study. patients who did not complete a six month follow up were also excluded. standard anteroposterior (ap) and lateral radiographs of injured wrist were taken. all were treated initially by below elbow plaster of paris (pop) slab for a period of approximately five days followed by closed reduction and below elbow cast application under general anesthesia. reduction of fractures was done under image intensifier guidance using appropriate reduction maneuver. dorsal bending type fractures ( c o l l e ’ s ) h a v i n g i n c r e a s e d d o r s a l a n g u l a t i o n s , s h o r t e n i n g a n d r a d i a l deviation of distal fragment were reduced by applying longitudinal traction, ulnar deviation and palmar flexion at fracture site. similarly palmar bending fractures (smiths) having a reverse deformity of palmar a n g u l a t i o n s , s h o r t e n i n g a n d r a d i a l deviation were reduced by producing opposite deformity by giving longitudinal traction, ulnar deviation and extension at fracture site. once the fracture was reduced as seen under c-arm, the patients were allocated dorsal or palmar flexed attitude of the wrist alternately, irrespective of the fracture geometry and immobilized with a below e l b o w p o p c a s t . t h e d e g r e e o f immobilization was either 15° pf or 15° df. plaster removal was done at four weeks. it was followed by active exercises during the first week and following active and passive exercises one week later. during the first two weeks of cast removal a crepe support was given. the results were scored by demerit scoring system of saito and by taking ap and lateral 27 28 radiographs. assessment of pain, disability, i.e. limitation of motion, subjective e v a l u a t i o n w a s d o n e . r a d i o l o g i c a l parameters, radial tilt, palmar tilt and ulnar variance were measured at 6 month follow up. radial tilt: is the angle between one line drawn perpendicular to the long axis of the radius and a second line drawn between the distal tip of the radial styloid and the central reference point (crp). the crp lies midway between the palmar ulnar corner and the dorsal ulnar corner of the distal radius. the average angle is approximately 20 to 25 degrees. palmar tilt: is the angle formed by the intersection of one line perpendicular to the longitudinal axis of the radial shaft and a second line drawn through the apices of the palmar and the dorsal rims of the radius. the normal palmar tilt on a standard lateral projection averages 11.2 ± 4.6 degrees. ulnar variance: is the distance between two l i n e s d r a w n p e r p e n d i c u l a r t o t h e longitudinal axis of the radial shaft: one through the distal articular surface of the ulnar head and the second through the crp. normally, the radial surface is distal to the ulnar surface by 1 to 2 mm (negative ulnar variance). movements were measured in degrees from neutral position with the help of goniometer. grip strength was measured as mm of hg with the help of a dynamometer. the functional results of both groups using the saito's scoring system were calculated by adding all the points and were finally graded as follows: excellent 0-3, good 4-9, fair 10-15 and poor 16-26. both the df group and pf group were compared with each other on the above mentioned parameters of saito. the study included 60 patients with frykman category i/ii colles fractures. the age ranged from 16-75 years with a mean age of 55.2512.34 years. thirteen (21.7%) were males, whereas 47 (78.3%) were females. forty two (70%) fractures were on right side. a f t e r r e d u c t i o n 3 0 p a t i e n t s w e r e immobilized in pf and 30 patients immobilized in df. these patients were scored at the end of 6 month follow up. subjective evaluation: it was done on the basis of pain, restriction of movements and disability. at final followup out of 30 patients of df immobilized group 23, 7, 0 and 0 had excellent, good, fair and poor results respectively as compared to 12, 15, 2 and 1 patient in pf immobilized group; this difference was statistically significant (p value = 0.025). objective evaluation: residual deformity radial tilt: at final follow-up 27 (90%) patients of df group had 13 to 33° radial tilt as compared to 17 (56.7%) patients in pf group (p value = 0.004). palmar tilt: at six months 23 (76.6%) patients of df immobilized group had 1 to 21° palmar tilt as compared to 11 (36.6%) patients in the pf immobilized group (p value = 0.002). ulnar variance: at six months 28 patients (93.3%) in the df group had normal variance i.e. -2 to 0 mm. in the pf group only 15 patients (50%) had normal ulnar variance (p value = 0.00). range of movements: dorsiflexion: at six months all 30 patients (100%) in the df group had dorsiflexion more than 45° as compared to 11 patients results 28 29 (36.6%) in the palmarflexion group (p value = 0.00). palmar flexion: at final follow-up all 30 (100%) patients of the df group had palmar flexion more than 30° as compared to 21 patients (70%) in the pf group (p value = 0.001). supination: 30 patients (100%) had more than 50° supination in the df group as compared to 24 patients (80%) in the pf group (p value = 0.010). pronation: 28 patients (93.3%) in the df group had more than 50° pronation as compared to 24 patients (80%) in the pf group (p value = 0.129). ulnar deviation: 29 patients (96.6%) in the df group had more than 15° ulnar deviation as compared to 20 patients (66.7%) in the pf group (p value = 0.003). radial deviation: 28 patients (93.3%) in the df group had more than 15° ulnar deviation as compared to 18 patients (60%) in the pf group (p value = 0.002). grip strength it was measured in both dominant and non-dominant hand and scoring was done accordingly in the final follow-up. there were 27 patients (90%) in the df group with more than two third grip recovery of normal side as compared to only 15 patients (50 %) in the pf group (p value = 0.003). arthritis changes they were not seen in any of the cases in both the pf as well as df group as the follow up was short. complications none of the patients in either group showed any complication at final follow-up. final follow-up : at the final follow-up, 30 (100%) patients in the df group showed overall excellent results in terms of radiological & functional outcome as compared to 7 (23.3%), 22 (73.3%) and 1 (3.3%) patient with excellent, good and fair results respectively in the pf group (p value = 0.000) no clear consensus exists as to the best position for immobilizing the wrist in a cast in extra-articular fracture of lower end radius. sarmentio et al, advocated immobilization in the position of supination to decrease the deforming force of the brachioradialis, which may cause loss of 12,13reduction. in contrast, wahlstrom recommends immobilization in pronation because he claims that the pronator quadratus causes the deforming force and is responsible for 14loss of reduction. according to the john charnley. colle's fracture should be treated in palmar flexion and ulnar deviation as dorsal periosteal hinge provides stability. following this, traditionally, extra-articular fractures of the lower end of radius were classically treated by closed reduction, cast immobilization in palmar flexion and ulnar deviation. but this conventional position has higher chance of redisplacement, inhibits hand functions and has greater associated complications like 15median nerve compression. van der linden conducted a study by applying cast in different positions of wrist and compared between complete cast and splint. he studied the anatomical and functional outcome and found that the results were surprisingly same; thereby c o n c l u d i n g t h a t t h e t e c h n i q u e o f 16immobilization plays a subordinate role. the concept of our study was influenced by t h e o r i g i n a l r e c o m m e n d a t i o n by zuppinger in 1910 and bohler in 1929 discussion 29 30 proposed that the position of the wrist should be changed from slight palmar flexion at initial post reduction to neutral or slight extension but maintaining ulnar 17,18deviation at 10 to 14 days post reduction. our study resembles to some extent the 12study done by gupta a in 1991 on 204 patients in which displaced colles' fractures were subjected to closed reduction and plaster immobilization randomly allocated to one of the three groups with respect to wrist position. palmar flexion, neutral or dorsiflexion. they reported that in displaced extra-articular fractures with no comminution the position of the wrist made no significant difference in regards to later displacement. in comminuted fractures, both extra-articular and intra-articular, the best anatomical results were in fractures treated in dorsiflexion. functional results in all fractures, regardless of the classification were superior if the fractures were treated in dorsiflexion. in this study we compared the functional and radiological results of extra-articular fractures of lower end radius treated conservatively in two groups, one with wrist immobilized in df and the other in pf, we found that individual movements of df, pf, supination, ulnar and radial deviation are significantly better when the wrist is immobilized in df as concluded by gupta a. further, grip strength recovery and subjective assessment of pain, disability and limitation of the movements was also better as well as faster in df immobilized patients. radiological parameters as measured by ulnar variance, palmar tilt and radial tilt were significantly better in the df group as compared to the pf group. the residual deformity seemed to be greater in the pf group. although arthritic changes were not seen in any of the groups possibly in view of very short follow up. complications were also not seen at final follow up in both groups. according to gupta a the reasons for the better results in the df immobilized wrist can be understood by understanding the biomechanics of the wrist joint and fracture reduction. in the pf group the dorsal carpal ligament is taut, but cannot stabilize the fracture because of its lack of attachment to the distal carpal row. thus the deforming forces and the potential displacement of the f r a c t u re a re p a r a l l e l . w h i l e i n d f immobilization the volar ligament is taut which has attachment to the distal as well as proximal carpal row and tends to pull the fracture anteriorly. the deforming forces act at an angle that tends to reduce the displacement of the fracture thus preventing redisplacement. since the wrist in extension is the optimal position for hand function and rehabilitation of the fingers, along with the fact that pf is associated with a higher rate of fracture displacement, gupta concluded that flexion at the fracture site is important to make use of the dorsal periosteal hinge but the flexed position need not be maintained at the wrist joint. it is concluded that in conservatively treated colle's fractures, the wrist should be i m m o b i l i z e d i n p o s i t i o n o f s l i g h t d o r s i f l e x i o n . b e t t e r r e s u l t s i n d f immobilized wrist are perhaps because df is needed for the rehabilitation of fingers, and the optimal functional position for the hand is wrist in extension. conclusion 30 31 table i: frykman categories table ii: demerit point system (saito) figure 1: modes of immobilization figure 2: measurement used for the anatomical results 31 32 ap view lateral view figure 3: colle's fracture (frykman i distal radius fracture) figure 4:cast with wrist immobilization in dorsiflexed position figure 5: result after healing of fracture in dorsiflexed position 32 33 references 1. fujii k, henmi t, kanematsu y, mishiro t, sakai t, terai t. fractures of the distal end of radius in elderly patients: a comparative study of anatomical and functional results. journal of orthopaedic surgery 2002;10: 915. 2. chung, kc, spilson, sv. the frequency and epidemiology of hand and forearm fractures in the united states. j hand surg am 2001;26:908. 3. bozentka, dj, beredjiklian, pk, westawski, d, steinberg, dr. digital radiographs in the assessment of distal radius fracture parameters. clin orthop relat res 2002;12:409. 4. medoff, rj. essential radiographic evaluation for distal radius fractures. hand clin 2005;21:279. 5. batra, s, gupta, a. the effect of fracture-related factors on the functional outcome at 1 year in distal radius fractures. injury 2002;33:499. 6. gliatis, jd, plessas, sj, davis, tr. outcome of distal radial fractures in young adults. j hand surg 2000; 25:535. 7. fujii k, henmi t, kenematsu y, mishiro t, sakai t, terai t. fractures of distal end of radius in elderly patients: a comparative study of anatomical and functional results. j orthop 2002;10:9-15. 8. mae kenney pj, me queen mm, elton r. predictions of instability of fractures of the distal radius. j orthop trauma 2000;14:121-2. 9. young bt, rayan gm. outcome following nonoperative treatment of displaced distal radius fractures in low -demand patient older than 60 years. j hand surg am 2000;25:19-28. 10. van der linden w, erison r. colles fracture: how should its displacement be measured and how should it be immobilized? j bone joint surg am 1981;63:1285-8 11. fernandez, jj, gruen, gs, herndon, jh. outcome of distal radius fractures using the short form 36 health survey. clin orthop relat res 1997; 341: 36-41 12. macdermid, jc, donner, a, richads, rs,, roth, jh. patient versus injury factors as predictors of pain and disability six months after a distal radius fracture. j clin epidemiol 2002; 55:849 13. fernandez dl, jupiter jb. fracture of distal radius a practical approach to management. first ed. new york: springer and verlag; 1996. p. 54-65. figure 6: subjective evaluation figure 7: objective evaluation. table iii: end result at final follow-up according to saito's scoring system 33 34 14. sarmentio a, latta ll. the evolution of functional bracing of fractures. j bone joint surg br 1995;88:141-8. 15. sarmiento a, zagorski jb, sinclair wf. functional bracing of colles' fractures: a prospective study of immobilization in supination vs. pronation. clin orthop relat res 1980;146:175-83. 16. wahlstrom o. treatment of colles fracture. acta orthop scand 1982;53:225-8. 17. charnley j. the colles' fracture: the closed treatment of common fractures 4th ed. vol 4, 1999. p. 128-42. 18. van der linden w, erison r. colle's fracture: how should its displacement be measured and how should it be immobilized? j bone joint surg am 1981; 63:1285-8. 19. fernandez dl, jupiter jb. fracture of distal radius -a practical approach to management. first ed. new york: springer and verlag; 1996. p.23-52. 20. bohler l. the treatment of fractures, 3 rd ed. new york: grune and stratton; 1932. p. 90-6. 21. gupta a. the treatment of colles fracture immobilization with the wrist in dorsiflexion. j bone joint surg br 1991;73:312-5. 34 case�report abstract a 65 year old female patient suffering from rheumatoid arthritis reported with multiple joint pains, malaise, fatigue, difficulty in breathing, difficulty in opening jaw, difficulty in holding objects and menopausal symptoms. she had been taking multiple medications including indomethacin, aspirin, prednisolone, methotrexate etc. treatment at al-sayed hospital rawalpindi included autologous bone marrow derived stem cell transplantation and exercise training program. specific exercises were given four weeks before and eight weeks after stem cell transplant at our center. after one year of treatment, the patient had improvement in all of her signs and symptoms, which enabled her to discontinue several medications. there was marked improvement in her joint pain, range of motion, muscle power, grip function, functional activities and activities of daily living (adls). key words: bone marrow derived stem cells, exercise training, rheumatoid arthritis. available for public use. it was only then that these pioneering endeavors saw their first introduction, thus dramatically changing the lives of rheumatoid a r t h r i t i s p a t i e n t s w i t h h i g h l y s e l e c t i v e 5 immunotherapy. in a vast majority of patients, who were given anti-tumor necrosis factor (tnf) therapy, significant improvement was noted clinically with minimal adverse effects right after the treatment. of late, the first antiinter leukin1 (il-1) therapy has been approved for use clinically as an il6 1 receptor antagonist (anakinra). bone marrow derived stem cell transplant is a promising treatment choice for patients suffering from ra. it is suggested that hematopoietic stem cell transplantation (hsct) is a useful therapy for severe ra on the basis of animal models and case reports of patients undergoing the procedure for other indications. case report a sixty five year old female came to us with the history of multiple joint pains since she was 19 years old and was diagnosed with rheumatoid arthritis 01 year later. she had taken multiple medicines including indomethacin, aspirin, prednisone, methotrexate, and gold. she was complaining of severe pain, decreased range of motion (rom) decreased mostly in lower limbs, muscle tightness, deformities, functional limitations, unable to change posture from lying to sitting and sitting to standing, muscle wasting, pulmonary problems, difficulty in opening jaw, difficulty in holding objects. muscle introduction “rheumatoid arthritis is a chronic progressive inflammatory disease of the joints resulting in painful deformities and immobility, especially in the small joints”. it decreases red blood cell count and causes inflammation around lungs and heart. it also 1 presents with fever and low energy. middle age women are affected 2.5 times more than men. the diagnosis is made mostly on the basis of a patient's 2,3 signs and symptoms. the main objective of the treatment is to reduce pain and inflammation, and improve a person's overall daily activities. this may be assisted by ensuring proper balance between rest and exercise, by using splints and assistive devices. the progression of the disease may be delayed by the use of a class of medicines known as disease-modifying antirheumatic drugs (dmards). in certain cases surgery to repair, replace, or fuse joints is opted for and 4 proves useful. alternative medicine and related treatments are not yet supported by evidence. before the year 1999 biological treatments were not effects of autologous bone marrow derived stem cell transplant and exercise training program on rheumatoid arthritis 1 2 3 4 syed salman naeem gilani , muhammad naeem , tauseef bukhari , muhammad asad ullah correspondence: dr. syed salman naeem gilani hod, stem cell al sayed hospital, rawalpindi e-mail: alsayedstemcell@gmail.com 1 2 3 department of stem cell/ physiotherapy / director hospital al sayed hospital, rawalpindi 4 department of physiotherapy funding source: nil; conflict of interest: nil received: jan 17, 2017; revised: apr 15, 2017 accepted: aug 27, 2017 effects of stem cells and exercise on rheumatoid arthritisjiimc 2017 vol. 12, no.3 157 power is given in table i. lab investigations showed: hemoglobin: 11.1 g/dl, esr: 84, ra factor and anti-ccp (cyclic citrullinated peptide) antibodies: positive, hba1c: 9.2. exercise training program included active and passive range of motion, stretching of tight musculoskeletal structures, isometrics, deep breathing exercises, cycle ergometry for upper and lower limbs to improve endurance and aerobics was given at our hospital for four weeks before and eight weeks after stem cell transplant. this session was given twice a day with twenty to thirty repetitions of each activity. patient was then transitioned to home exercise management and followed up at three, six and twelve months after the procedure. stem cell extraction and transplant procedure: patient was given injection filgrastim (granulocyte colony stimulating factor analog) 10 µg per kg body w e i g h t s u b c u t a n e o u s l y w i t h o u t m e t h y l prednisolone or cyclophosphamide and baseline cbc with hpc (hematopoietic progenitor cells) was performed. two days later cbc with hpc was repeated and patient's bone marrow stem cells were harvested by apheresis. a total of 100cc of autologous bone marrow stem cells were harvested. cbc with hpc was repeated at the end of apheresis to confirm the total number of hematopoietic stem cells. harvested stem cells were t h e n i n j e c t e d i n t o h e r k n e e , s h o u l d e r, metacarpophalyngeal and inter-phalyngeal joints bilaterally in the procedure room under aseptic technique. afterwards stem cells were transfused to the patient intravenously. outcome measurements patient showed marked improvement in muscle power one year after the stem cell transplant. a comparison of muscle power before starting the treatment at our center and one year after stem cell transplant is given in table i. patient's pain was reduced from severe to pain free. range of motion (rom) significantly increased. range of motion (rom) was measured by goniometry. grip function was measured by the “sollerman test”. the results of sollerman test are given in table ii. modified hss (hospital for special surgery) score for both knees were measured that improved from 57 to 90 for her left knee and 57 to 87 for her right knee. discussion bone marrow contains hematopoietic and nonhematopoietic (mesenchymal) stem cells, the latter being with immunoregulator properties. it is suggested that adult mesenchymal stem cells (msc) are useful as cellular therapy in several inflammatory 7 diseases, including ra. as msc may transfer to sites of injury in vivo, it is suggested that inflamed joints are targeted by cells which might have a therapeutic effect o n a rt h rit is t h ro u gh m sc med iated 8 immunosuppression. leeds group presented a study in 1997 in which g-csf was used at a dose of 5µg/kg/day to mobilize stem cells in five patients. in peripheral blood cd34+ count was checked to establish good efficacy. patients remained stable after the treatment but we observed that administering methylprednisolone (median 80mg, table i: muscle power before and one year a�er bone marrow derived stem cell transplant table ii. “sollerman test” result. performance is graded from 4 (best) to 0 (worst). grade 04 is used for correct grip and performance of the ac�vity within 20 seconds. grip strength was measured in newton's by means of an electronic hand dynamometer effects of stem cells and exercise on rheumatoid arthritisjiimc 2017 vol. 12, no.3 158 range 40–120mg) intramuscular or intra-articular diminished any pro-inflammatory effects of filgrastim. a phase i placebo controlled 1110 study was conducted in australia to investigate the efficacy of g-csf in patients suffering from active form of ra 9 for the use of stem cell collection. in paris, four patients had their stem cells mobilized with cyclophosphamide 4g/m2 followed by g-csf 5µg/kg/day. probably, in three of the patients cd34+ cell yields were higher with g-csf along with cyclophosphamide than with g-csf alone. arthritis and extra-articular manifestations improved markedly in these patients. to some extent the disease activity persisted in three patients, although it never went back to the same level even two years 10 after the procedure. in this case, the patient presented with inflammatory arthritis of almost forty five years' duration. she described the pain in her hands, wrists, elbows, shoulders and knees as frequently unbearable. she had significant muscle wasting, decreased muscle power, deformities, and weak grip strength. one year after autologous bone marrow stem cell transplant, the patient felt significant decrease in all subjective symptoms and discontinued her medications. esr had normalized, indicative of clinical reduction of arthritis. she also felt improvement in adls. in our study autologous bone marrow derived stem cells combined with exercises showed that it is a safe and effective treatment option for the patient suffering from rheumatoid arthritis and warrants a larger scale phase i / ii clinical study. references 1. tugwell p, pincus t, yocum d, stein m, gluck o, kraag g, et al. combination therapy with cyclosporine and methotrexate in severe rheumatoid arthritis. new england journal of medicine. 1995; 333: 137-42. 2. de punder ym, hendrikx j, den broeder aa, pascual ev, van riel pl, fransen j. should we redefine treatment targets in rheumatoid arthritis? low disease activity is sufficiently strict for patients who are anticitrullinated protein antibody-negative. the journal of rheumatology. 2013; 40: 1268-74. 3. van nies ja, krabben a, schoones jw, huizinga tw, kloppenburg m, van der helm-van mil ah. what is the evidence for the presence of a therapeutic window of opportunity in rheumatoid arthritis? a systematic literature review. annals of the rheumatic diseases. 2014; 73: 861-70. 4. smolen js, landewé r, breedveld fc, dougados m, emery p, gaujoux-viala c, et al. eular recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs. annals of the rheumatic diseases. 2010; 69: 964-75. 5. maini r, st clair ew, breedveld f, furst d, kalden j, weisman m, et al. infliximab (chimeric anti-tumour necrosis factor alpha monoclonal antibody) versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate: a randomised phase iii trial. lancet. 1999; 354: 1932–9. 6. snowden ja, brooks pm, biggs jc. haemopoietic stem cell transplantation for autoimmune diseases. british journal of haematology. 1997; 99: 9-22. 7. wang y, chen x, cao w, shi y. plasticity of mesenchymal stem cells in immunomodulation: pathological and therapeutic implications. nature immunology. 2014; 15: 1009-16. 8. bouffi c, bony c, courties g, jorgensen c, noel d. il-6dependent pge2 secretion by mesenchymal stem cells inhibits local inflammation in experimental arthritis. plos one. 2010; 5: e14247. 9. snowden ja, biggs jc, milliken st, fuller a, staniforth d, passuello f, et al. a randomised, blinded, placebocontrolled, dose escalation study of the tolerability and efficacy of filgrastim for haemopoietic stem cell mobilisation in patients with severe active rheumatoid arthritis. bone marrow transplantation. 1998; 22: 1035-41. 10. moore j, brooks p, milliken s, biggs j, ma d, handel m, et al. a pilot randomized trial comparing cd34-selected versus unmanipulated hemopoietic stem cell transplantation for severe, refractory rheumatoid arthritis. arthritis & rheumatism. 2002; 46: 2301-9. effects of stem cells and exercise on rheumatoid arthritisjiimc 2017 vol. 12, no.3 159 page 40 page 41 page 42 original�article abstract objective: the current study was aimed to assess the role of modified constraint induced movement therapy (mcimt) on hand function of hemiplegic patients. study design: an experimental randomized control trial. place and duration of study: the study was conducted in rural health care hospital and almeraj clinic, st th nankana sahib from 1 may 2019 to 29 september 2019. material and methods: total 30 patients were recruited through non probability convenient sampling. experimental group (15 subjects) received mcimt and conventional therapy, while control group received only conventional treatment for 2 weeks. fugl meyer assessment scale and motor assessment scale were used for assessment of treatment and control groups. paired sample t-test was used for the comparison of before and after results of treatment and control groups. mann-whitney u test was used further to compare treatment and control groups independently. results: in upper arm function, the mean rank of control group and treatment groups were 9.37 and 21.63. the mean ranks of hand movements in control and treatment groups were 8.97 and 22.03 respectively. advanced hand activities had mean rank of 10.07 and 20.93 in control and treatment groups respectively. motor function had mean ranks of 9.07 and 21.93 in control and treatment groups respectively. here the p value of mannwhitney u test is 0.00 which is less than 0.05, this shows that the test is highly significant. conclusion: it is concluded that modified constraint induced movement therapy has presented improved upper arm function, hand movements, advanced hand activities and motor function. key words: fugl meyer assessment scale, hemiplegia, modified constraint induced movement therapy. treatment each day, below four hours per day for two weeks and no treatment to the abnormal extremity respectively. the affected limb performs tasks like lifting, throwing, holding objects, buttoning and catching. these approaches lead to improvements in 2,3 motor activity and adls. modified constraint induced movement therapy (mcimt) does not follow the same protocol as cimt but has other sets of exercises after limiting the working hand with a splint and series of task oriented movements were performed with the weaker arm. it is not performed for 6 hours and patients don't need to wear splint for 90% of waking hours. modified constraint induced movement therapy (mcimt) considered to be best task specific approach for improving hand function, range of motion, quality of life, amount of improvement and advanced hand activities when measured with motor assessment scale, motor activity log and fugl meyer assessment 4 scale as opposed to cimt. constraint induced movement therapy is based on two approaches: one is limiting the normal limb and introduction constraint means “to limit” induced means “leading to do something ” thus constraint induced movement therapy means to restrict the one normal limb with a mitt or glove and use the other affected limb for activities. this technique is more beneficial 1 in patients of cerebrovascular accident. there are different methods used for cimt and different treatment timings which affect the results of the study, which includes modified constraint induced movement therapy (mcimt), massed practice and forced use. in all these methods, the unaffected extremity is limited with a mitt and the abnormal limb received below three hours of effect of modified constraint induced movement therapy on improving hand function of stroke patients shaheen noor, syeda nida bukhari, rabia tariq, awais bin inam correspondence: shaheen noor department of physical therapy university of faisalabad e-mail: shaheennoor147@gmail.com department of physical therapy university of faisalabad funding source: nil; conflict of interest: nil received: december 18, 2019; revised: september 04, 2020 accepted: september 27, 2020 modified cimt in strokejiimc 2020 vol. 15, no.4 236 second one is forceful practice of the abnormal extremity. this approach leads to permanent improved behavior of the abnormal extremity. this technique was developed after experimenting on monkeys, constraining the monkey's normal upper limb with the glove for days. monkeys were able to use the affected limb for feeding and then they were able to achieve some of the functions with abnormal extremity. in the past, the affected limbs were not used and all the activities were performed by the healthy extremity which makes the affected limb 5 even more prone to permanent disability. more than 24% of subjects having upper limb dysfunction, due to cva, can get better by constraining the normal limb and utilizing the damaged extremity with different tasks. modified constraint induced movement therapy has different results than constraint induced movement therapy that needs to 6 be learned. stroke is the major problem which causes functional disability in adults. nine out of ten people described 75% permanent disability due to hemiplegia that leads to dependent living. increasing number (300\130000) of stroke cases in pakistan focused on great need of therapeutic rehabilitation of hemiplegic hands to improve their fine motor skills. modified constraint induced movement therapy (mcimt) is a newer therapy technique and has 7 prospective of enhancement of function. the objective of this study was to assess the role of modified constraint induced movement therapy (mcimt) on hand function of hemiplegic patients. material and methods this experimental randomized controlled study was conducted on hemiplegic patients (3 to 8 months) in rural health care hospital and almeraj clinic, nankana sahib from may 2019 to september 2019. total 30 patients recruited through non probability convenient sampling, aged between 40 to 60 years having minor spasticity of upper limb, able to extend wrist about 20 degree and interphalangeal joints about 10 degree were included for data collection. while those having pain (more than 4 on vas), previous hand trauma and any psychological condition were excluded from the study. the subjects were enrolled after taking an informed consent for willingness to include in the study. 30 subjects (15 in each group) were divided in to two groups by lottery method; experimental group was treated by modified constraint induced movement therapy (mcimt) and by conventional therapy while control group was treated by only conventional therapy (pnf techniques, grasp release and range of motion exercises) for 2 weeks. in the experimental group modified cimt was done by limiting the normal hand with glove and series of functional tasks were performed with affected hand. non parametric data was collected by using motor assessment scale (upper arm function, hand movements and advanced hand activities) and fugl meyer assessment scale (motor function) before and after the treatment, paired sample t-test was used to check pre and post effects in control and treatment groups and mann-whitney u test was used to measure the difference between treatment and control groups. the results were then evaluated by spss (v. 20). results thirty subjects were treated through modified cimt (treatment group) and conventional therapy (control group) after division into two groups. the mean and standard deviation values of pre control group are 43.80± 4.195, while 50.40± 4.014 is the mean and s d of post control group treated by only conventional therapy. 42.33± 5.715 is the mean and standard deviations of pretreatment group while 61.33± 5.790 is the mean and standard deviations of post treatment group which is highest mean and standard deviations than all the other values. this depicts that *frequency distribu�on of fugl meyer assessment scale. fig 1: frequency distribu�on of motor func�on in control and treatment group (n= 30) modified cimt in strokejiimc 2020 vol. 15, no.4 237 mcimt (treatment) group showed better results as the mean and standard deviation of mcimt group after application of therapy is 61.33± 5.790 which is higher than conventional group (50.40± 4.014). and 21.93 respectively. control group showed less values of mean ranks than treatment group, which shows that there is increase in upper arm function, hand movements, advanced hand activities and motor function in treatment group. here the p value of mann-whitney u test is 0.00 which is less than 0.05, this shows that the test is highly significant. discussion modified constraint induced movement therapy when used with conventional therapy shows better results in performing complex hand movements and functional tasks than other treatment options like pnf techniques, grasp release exercises combined with range of motion. there were improvements in upper arm function, hand movements, advanced hand activities and motor function in the affected table i: frequency distribu�on between control (pre and post) and treatment group (pre and post) (n= 30) *paired sample t-test comparing pre and post values of treatment and control groups. *s d = standard devia�on. paired sample t-test collectively shows the level of improvements in the results of patients who were treated with modified cimt in treatment group. firstly upper arm function in post conventional group showed mean and standard deviation of 4.20± 1.146 which is less than post treatment group (5.80± 0.561). secondly hand movements improved with mean of 2.87 and standard deviation 0.834 in post control group which is less than the mean and standard deviation of post mcimt group (4.80± 0.862), thirdly advanced hand activities are more advanced form of activities in motor assessment scale and its values are higher in post treatment group which is 3.47± 0.990 and post conventional group have values of 1.93± 0.961, which is less than post treatment values. here the p value for both groups is 0.000, which is less than 0.05.there is statistically significant difference exist between motor assessments scales of post control and post treatment groups. after comparing pre and post treatment and pre and post control groups. now compare the difference between treatment and control groups. in upper arm function the mean rank of control group is 9.37, while in treatment group it is 21.63 which is higher than control group. the mean ranks of hand movements; in control and treatment group are 8.97 and 22.03 respectively. advanced hand activities have mean rank of 10.07 and 20.93 in control and treatment group respectively. in the control and treatment group motor function have values of 9.07 table ii: comparison between treatment and control groups (n= 30) uaf = upper arm func�on hm = hand movements aha = advanced hand ac�vi�es table iii: mann-whitney u test comparing treatment and control groups (n= 30) *mann-whitney u test used for comparison between independent groups. *p < 0.05 was taken as level of significance. uaf = upper arm func�on hm = hand movements aha = advanced hand ac�vi�es modified cimt in strokejiimc 2020 vol. 15, no.4 238 upper arm func�on hand and fewer improvements in control group. in upper arm function the mean rank of control group and treatment groups were 9.37 and 21.63, which was higher than control group. in the same manner, the mean rank of hand movements; in control and treatment group were 8.97 and 22.03 respectively. advanced hand activities have mean rank of 10.07 and 20.93 in control and treatment group respectively. motor function had values of 9.07 and 21.93 in control and treatment groups respectively. control group showed less value of mean ranks than treatment group. here the p value of mannwhitney u test is 0.00 which is less than 0.05, this shows that the test is highly significant. the results of the study 8 are same as suggested by taub, et al. that upper arm function, hand movements and advanced activities are improved; when normal hand is immobilized with a mitt and series of tasks are being performed by affected hand with conventional therapy. collecting the beans, holding objects and placing them to the desired point have been made easy by 2 weeks exercise session and following follow up. our 9 results are also supported by priyanka and bijayeta. they conducted a randomized controlled trial on hemiplegic patients of sub-acute stage. 20 subjects have been treated by modified constraint induced movement therapy mcimt (normal hand was covered by a glove) for 2 hours and control group has been treated by conventional therapy for 2 hours. motor function and daily functional activities got better in affected hand through mcimt. fugl-meyer assessment (fma) explained the mean and standard deviation increased in treatment group (77.11± 2.22) than control group. while on the contrary, hartman, 10 et al. compared the effects of constraint induced movement therapy with mirror therapy on upper extremity dysfunction due to cerebrovascular accident in sub-acute and chronic stage. visual feedback has been given through mirror therapy and leads to illusion of both arms function normally. while there has been fewer improvements in other group treated by cimt and conventional treatment as there is no visual feedback and upper limb remained in previous state of immobility with minor changes. the patients who received cimt with mirror therapy have been improved (p value 0.0001) while others showed minor improvements in stroke patients. similar results were reported by other researcher that cimt alone showed better results when compared with conventional therapy for one month. it has better outcomes in improving daily task specific activities even in chronic stage of learned 11 nonuse of the immobile limb. the same results 12 have been explained by sirtori, et al. in a systemic review that when comparison occur among cimt, modified constraint induced movement therapy, forced used phenomenon and conservative therapy or no treatment. there is improvement in those patients treated by modified constraint induced therapy as those patients were wearing mitt for not more than 2 hours and there was no specific two hour training which make them tired and stressed. there is significant increase in the mean and standard deviations (61.44± 2.33) of mcimt group. in the same way, a meta-analysis has been 13 conducted by coleman, et al. the goal of the study is to find out the importance of modified constraint induced movement therapy (mcimt) in ischemic stroke survivors when comparing with traditional therapy. evaluation of data has been done by fugl meyer assessment scale, motor activity log, action research arm test and wolf motor function test, to measure how well, how much quality of hand and wrist movement improved. the results of the study are supporting that mcimt is much better technique with mean and standard deviation of 20.77± 1.00 which is higher than control group (18.99± 1.22). a randomized control trial was conducted on acute post cva patients to check the effectiveness of constraint induced movement therapy. fugl meyer assessment scale was used before and after the treatment session on 30 patients for 2 weeks, which showed improved behavior of patients treated by cimt as tms showed parts of improvement in 14,15 cerebral hemisphere. but a single blinded study 16 was conducted by dromerick, et al. on 40 stroke patients. they performed exercise sessions in hospital for 4 weeks and outcomes were different, which explained that the abnormal hand function improved in flexion but no increase in extension and functi0onal activities improved in other group. due to limited time duration, small sample size was selected to check the effects of modified constraint induced movement therapy (mcimt) in stroke survivors. further only single upper limb was modified cimt in strokejiimc 2020 vol. 15, no.4 239 selected; there was no inclusion of quadriplegic patients. this study included only hemiplegic patients who had stroke in 3 to 8 months and age between 40 to 60 years, while stroke effects on younger population also who is below 35. further there was no follow up assessments (feedback) were followed in this study which shows for how long improvements persists after quitting exercise. there were less coordinated movements present in hand due to stroke, which need more weight bearing and core stability exercises. recommendations this study can help in further studies on mcimt. upcoming authors can also compare the effects of mcimt with other exercise therapies to find out the best possible treatment for stroke. further younger population can also affected by stroke which can be included in future studies. only single upper limb was selected in hemiplegic patients, while studies can be performed on quadriplegic patients. we selected only small sample size of hemiplegic patients who had stroke in 3 to 8 months; studies can be performed on large sample size in acute or chronic stroke patients and other than stroke. conclusion it is concluded that modified constraint induced movement therapy provides improved upper arm function, hand movements, advanced hand activities and motor function than conventional therapy for the patients with hemiplegic stroke. references 1. baldwin cr, harry aj, power lj, pope kl, harding ke. modified constraint-induced movement therapy is a feasible and potentially useful addition to the community rehabilitation tool kit after stroke: a pilot randomised control trial. australian occupational therapy journal. 2018; 65(6):503-11. 2. batool s, soomro n, amjad f, fauz r. to compare the effectiveness of constraint induced movement therapy versus motor relearning programme to improve motor function of hemiplegic upper extremity after stroke. pakistan journal of medical sciences. 2015; 31(5):1167. 3. kwakkel g, veerbeek jm, van wegen ee, wolf sl. constraint-induced movement therapy after stroke. the lancet neurology. 2015; 14(2):224-34. 4. liu xh, huai j, gao j, zhang y, and yue sw. constraintinduced movement therapy in treatment of acute and subacute stroke: a meta-analysis of 16 randomized controlled trials. neural regeneration research. 2017; 12(9):1443. 5. aloraini sm, mackay-lyons m, boe s, mcdonald a. constraint-induced movement therapy to improve paretic upper-extremity motor skills and function of a patient in the subacute stage of stroke. physiotherapy canada. 2014; 66(1):56-9. 6. wolf sl, winstein cj, miller jp, thompson pa, taub e, uswatte g, et al. retention of upper limb function in stroke survivors who have received constraint-induced movement therapy: the excite randomised trial. the lancet neurology. 2008; 7(1):33-40. 7. rahman g, darain h, farooqi s. the effects of constraint induced movement therapy in improving functions of upper limb in patients with stroke. 2017; 12(9):1443. 8. taub e, uswatte g, bowman mh, mark vw, delgado a, bryson c, et al. constraint-induced movement therapy combined with conventional neurorehabilitation techniques in chronic stroke patients with plegic hands: a case series. archives of physical medicine and rehabilitation. 2013; 94(1):86-94. 9. singh p, pradhan b. study to assess the effectiveness of modified constraint-induced movement therapy in stroke subjects: a randomized controlled trial. annals of indian academy of neurology. 2013; 16(2):180. 10. hartman k, altschuler el. mirror therapy for hemiparesis following stroke: a review. current physical medicine and rehabilitation reports. 2016; 4(4):237-48. 11. jin, y., jin, x. li, j., fu's subcutaneous needling and constraint-induced movement therapy for a patient with chronic stroke: one-year follow-up case report. medicine, 2019; 98(8). 12. sirtori v, corbetta d, moja l, gatti r. constraint-induced movement therapy for upper extremities in stroke patients. cochrane database of systematic reviews. 2009(4). 13. coleman er, moudgal r, lang k, hyacinth hi, awosika oo, kissela bm, et al. early rehabilitation after stroke: a narrative review. current atherosclerosis reports. 2017; 19(12):59. 14. boake c, noser ea, ro t, baraniuk s, gaber m, johnson r, et al. constraint-induced movement therapy during early stroke rehabilitation. neurorehabilitation and neural repair. 2007; 21(1):14-24. 15. kim, j.h. and chang. effects of modified constraint-induced movement therapy on upper extremity function and occupational performance of stroke patients. journal of physical therapy science. 2018; 30(8): 2-4. 16. dromerick aw, lang ce, birkenmeier rl, wagner jm, miller jp, videen to, et al. very early constraint-induced movement during stroke rehabilitation (vectors): a singlecenter rct. neurology. 2009; 73(3):195-201. modified cimt in strokejiimc 2020 vol. 15, no.4 240 original�article abstract objective: to identify the key challenges faced by senior faculty members in the implementation of an integrated curriculum in developing countries study design: quantitative descriptive cross-sectional place and duration of study: foundation university medical college islamabad and women medical college abbottabad. four months duration (jun 2017-sep 2017) materials and methods: the study was conducted in two private medical colleges. the sampling technique employed was a purposeful non-probability sampling technique. a total of 60 senior faculty members (associate professors and professors) participated in the study. data collection was carried out using a selfdeveloped, validated questionnaire (closed-ended), consisting of 20 items based on the likert scale format of strongly agree (sa) =4 points, agree (a) = 3 points, neutral, 0 disagree (d) = 2 points, and strongly disagree (sd) = 1 point. results: descriptive analytics were run on spss version 21. the common challenges confronted by senior faculty members in the implementation of an integrated curriculum consisted of; lack of sequential planning of the integrated curriculum (66.5%), insufficient continuous medical education (cme) activities for faculty (56.5%) along with ineffective communication among faculty members (53.5%), lack of effective teamwork (42.6%) and lastly, deteriorating quality of students in medical colleges (48.6%). conclusion: senior faculty members faced diverse challenges while their institutes decided to implement the modular integrated curriculum. the lack of a collaborative approach in curriculum planning adversely affected curriculum organization and sequencing. lack of interdepartmental communication and collaboration and deficient faculty development programmes together with the deteriorating quality of medical students were the major challenges faced by senior faculty members in implementing an integrated curriculum. key words: challenges in integrated curriculum, curriculum implementation, faculty development, integrated curriculum, medical education. a c c o r d i n g t o i v o w i ( 2 0 0 4 ) c u r r i c u l u m implementation implies putting “theory into practice” or “proposal into action”. even after investing enormous proportions of money and effort into implementing an integrated curriculum, its successful accomplishment remains a dream yet to be realized in most medical colleges at the national 2 level. the students who have experienced an integrated curriculum perceive it as a strength in terms of enhancing problem-solving skills, and 3 student-centred teaching and learning, therefore, there is a dire need for designing effective policies for successful curriculum implementation. hence, it is i m p e r a t i v e t h a t m e t h o d s o f c u r r i c u l u m 4 implementation are addressed and focused upon. according to muller et al (2008) and shaheen et al (2021), curriculum integration is a complex process understood and implemented differently at different introduction curriculum development is a dynamic process. the medical curriculum has gone through many reforms. these reforms are never easy, but they are 1 inevitable. the problems arising at different levels of the educational system do not lie in the curriculum formulation, but rather in its implementation. challenges faced by senior faculty in the implementation of integrated curriculum in developing countries 1 2 3 madeeha rehan , neelofar shaheen , noushaba sadiq correspondence: dr. madeeha rehan associate professor department of pathology foundation university medical college, islamabad 1 department of pathology foundation university medical college, islamabad 2 department of health professions education & research peshawar medical college, riphah international university 3 department of medical education national university of medical sciences, rawalpindi received: march 30, 2021; revised: august 06, 2022 accepted: september 15, 2022 integrated curriculum; challengesjiimc 2022 vol. 17, no.3 214 5,6 rates in different contexts. it is an undeniable fact that no educational policy can be successfully implemented unless teachers' problems are taken into consideration before initiating decision-making and planning of 7 curriculum. the teacher is the most qualified resource person and is the best candidate to be consulted in all stages of curriculum development. nevertheless, it has been observed that when it comes to decision-making in education, teachers' opinions are not given their due weightage, which in turn negatively impacts curriculum implementation. this issue, therefore, calls for careful consideration by the stakeholders involved in designing and 8 implementing the integrated curriculum. as per the literature review, relatively younger faculty members are more willing, open, and adaptive to change as compared to their senior counterparts. undoubtedly, senior faculty members are integral to the success of any academic institution. they are consistently growing professionally and contributing to their discipline, 9 and they also serve as mentors to the junior faculty. vital features of an organization such as leadership, maintenance of cohesive culture and a positive climate depend upon the senior members of the faculty. it takes determination, will and participation 10 to lead the change of curricular reforms. faculty face diverse challenges everywhere in the world and literature reports even the challenges related to 11 infrastructure, space, and administrative issues. thus, it is of utmost importance to identify first and then try to resolve the problems and the needs of senior faculty to nurture their desired characteristics 12 over the career continuum. this study aimed to identify the major challenges encountered by senior faculty members during the implementation of the integrated curriculum in their institutes. materials and methods this quantitative study of the cross-sectional design was carried out in two private medical colleges in different provinces where an integrated curriculum was already implemented. ethical approval was acquired from the ethical review committee of the respective institution. the sampling technique employed was the purposeful sampling technique. it included the associate professors and professors as their participants. the 60 senior faculty members were all those who had been part of the transition from traditional to integrated curriculum. all assistant professors and the faculty of the medical education department were not included in the study. written informed consent was taken from all the participants. data collection was done via the use of a selfdeveloped descriptive questionnaire. the main questions were related to intrinsic motivation, mindsets, interdepartmental and intradepartmental issues, cme activities, lack of teamwork and curriculum organization. it was validated by 4 medical educationists. it consisted of 20 items in total, based on the likert scale format of strongly agree (sa) = 4 points, agree (a) = 3 points, neutral, 0 disagree (d) = 2 points, and strongly disagree (sd) =1 point. data were analysed using spss version 21. results a total of sixty senior faculty members including associate professors (63.3%) and professors (36.6%) were included in the study. out of the sixty participants', forty were females and twenty were males (table i). table i: demographics of the participants amongst various major challenges identified, most common were lack of sequential planning of integrated curriculum, insufficient continuous medical education (cme) activities for faculty, lack of effective teamwork, lack of interdepartmental communication, lack of collaborative approach in designing the table of specifications, deteriorating quality of students in medical colleges and lastly inadequate infrastructure (table ii). integrated curriculum; challengesjiimc 2022 vol. 17, no.3 215 50% of the faculty members believed an integrated curriculum is associated with a reduction in rote curriculum. however, most of the faculty members are of the opinion that there is a lack of faculty development approaches to polish their skills which could allow them to adopt advanced teaching strategies. in a systematic review, it is recommended t h a t va r i o u s fo r m a l a n d i n fo r m a l fa c u l t y development approaches including workshops, seminars, experiential learning, timely feedback and effective peer coaching should be incorporated into 15 faculty development programmes. in a study conducted in nigeria, inadequate faculty training and interdepartmental issues were found to be the most common causes which are consistent with our study 16 findings. while in contrast to our study, time constraints and temporal restrictions were the main issues faced by the faculty in curriculum implementation. most of the senior faculty members believed that there is a dearth of coordination and communication at the interdepartmental and intradepartmental levels about curriculum designing and changes done in the curriculum later. it is a matter of urgency to formulate a well-structured curriculum committee consisting of senior faculty members and a qualified medical educationist. though caution needs to be exercised and overambitious attempts must be avoided. it is best, to begin with, modular integration under the supervision of modular integration committees followed by a module coordinator for every committee. representatives from different departments including clinical teachers and a medical educationist should be members of 14 committees. also, for the successful implementation of an integrated curriculum monthly and fortnightly meetings of the faculty should be arranged to finalize the teaching-learning schedule. the reason for transitioning to an integrated system, including its advantages and disadvantages should be explained 15 to the faculty. in our study, most of the faculty members believed there were no incentives or rewards for competent and hardworking faculty members. in one study, it has been mentioned that there should be incentives and rewards for the faculty members involved in curriculum development through a collaborative approach and skilful conflict resolution. this strategy of improving extrinsic motivation can boost the table ii: major challenges faced by senior faculty in transition from traditional to an integrated curriculum learning as compared to a discipline-based curriculum, and 17.9% strongly agreed that integrated curriculum results in the production of more competent doctors as compared to the discipline-based curriculum. similarly, 23.2% of the participants agreed that after having practised traditional teaching and learning methodologies for a long period of time, they did not feel motivated to adopt new teaching and learning strategies in an integrated curriculum. on the flip side, 32% agreed that a student-centred approach in an integrated curriculum limits a teacher's authority over students. discussion according to asebiomo (2009), not only a wellformulated curriculum is important but its effective implementation is necessary to achieve the desired 13 goals of education. a study conducted at the 2 national level, concluded that the design and implementation of an integrated curriculum in public sector institutions with established curricula is a difficult process, and resistance by faculty was the most common issue in this context where changing the mindset of faculty members at senior level is 14 mandatory. this is in contrast to our findings because most of the senior faculty members were more than willing to adapt to the change and strongly agreed that an integrated curriculum enhances problem-solving and critical-thinking skills as compared to a traditional disciplined-based integrated curriculum; challengesjiimc 2022 vol. 17, no.3 216 17 curricular change process. while extrinsic motivation is important, intrinsic motivation has also an important role to play. according to literature intrinsic motivations of faculty and their professional and ethical values are often ignored while using different faculty development approaches. therefore, it is essential to re-design faculty development approaches not only for skill enhancement but also as an opportunity for the 14 renewal of personal and professional growth. in most western countries medical education is a characterized trend toward student-centred learning, however in most eastern and developing countries medical education remains a more 18 traditional teacher-centred process. this trend is changing now and many developing countries are adopting integrated curricula where faculty have 19 multiple roles to play. a vast majority of the faculty members were of the view that there is an inadequate infrastructure which is a huge obstacle to the implementation of the integrated curriculum. this is in accordance with a study conducted at a national level in which it was concluded that good infrastructure is required for 1 successful curriculum implementation. in fact the infrastructure, serves as the necessity to be considered before implementing the integrated 20 curriculum. in our study, most of the faculty members agreed that selection criteria for admission of medical students in medical colleges need reviewing. this is consistent with another study in which it was reported that awareness should be provided to medical teachers and students regarding integrated 2 curriculum. the integrated curriculum necessitates the involvement of students in the curriculum implementation, review, and assessments to make sure that the students take responsibility for their own learning and provide valuable input to the 21 faculty and administrators. limitations of the study 1. sample size was small but we had only senior faculty as our target population and there were only two institutions so the results can be considered applicable to other similar settings. 2. a close-ended questionnaire was designed therefore opinions of faculty members could not be taken. conclusion in conclusion, curriculum implementation is the lifeblood of an educational institution and is critical to the success of any medical college. there is a dire need to design an innovative and creative faculty policy to simplify integration, enhance faculty development approaches and collaborate at the political, institutional, and 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education in ondo state, nigeria. 2014;1:264 18. findyartini a, hawthorne l, mccoll g, chiavaroli n. how clinical reasoning is taught and learned : cultural perspectives from the university of melbourne and universitas indonesia. bmc med educ. 2016;1–10. 19. nawabi s, shaikh ss, javed mq, riaz a. faculty's perception of their role as a medical teacher at qassim university, saudi arabia. cureus. 2020 jul 9;12(7). 20. owolabi r. adoption of integrated curriculum development as a tool to promote information profession, nigeria. library philosophy and practice. 2021 jan 14:121. khan ra, sajjad m. student empowerment in medical education. journal of islamic international medical college (jiimc). 2017 dec 1;12(4):166-7. integrated curriculum; challengesjiimc 2022 vol. 17, no.3 conflict of interest authors declared no conflicts of interest. grant support and financial disclosure authors have declared no specific grant for this research from any funding agency in public, commercial or nonprofit sector. data sharing statment the data that support the findings of this study are available from the corresponding author upon request. this is an open access article distributed under the terms of the creative commons attributionnoncommercial 2.0 generic license. 218 65 editorial fatal angioinvasive mucormycosis 'black fungus', a co-infection in covid-19 patients, requiring a vigilant eye watch irfan ali mirza the pandemic of corona viral infection disease-19 (covid-19) had become a challenging task for the clinicians around the globe. despite the passage of near about one and a half year, yet many mysterious requires exploration to contain this fatal infection. the researchers and scientist are trying level best to identify ways for the reduction of morbidity and mortality rates from the said infection. but with the availability of vaccine things are heading towards betterment. the covid patients are found to be at risk of many serious complications. presence of serious fungal infections is one of them. few published studies are highlighting strong correlation amongst presence of superimposed angioinvasive mucormycocsis (black fungus) in either acute illness or even in recovered patients. this rapidly progressing infection attacks the blood vessel and live tissues resulting in necrosis and blackening of area. thus, giving it a name 'black fungus'. this superimposed infection requires somber attention, because it prolongs the recovery time of patients. the negligence can even lead to 1 fatal outcomes. the early case recognition and timely management for mucormycosis will be the only way out to reduce the miseries of covid sufferers. mucormycosis or zygomycosis (older name), belongs to a category of opportunistic invasive fungal infection (ifis). either of the three commonly responsible fungi i.e rhizopus, mucor, or lichtheimia belongs to the phylum zygomycota, subphylum mucoromycotina, order mucorales and the family mucoraceae. the members of this order are also well known as pin molds. these are congregated as saprophytic molds in environment like soil , putrefying organic matter i.e dung piles, 2 vegetable matter, leaves, rotten wood, etc. mucormycosis is a third communal, rare and fatal angioinvasive fungal infection i.e 2–6% of all ifis. however, candidiasis and aspergillosis rank on first and second numbers. according to a published report for the year 2021, species wise frequency in patients with mucormycosis is 34% for rhizopus species, 19% for both mucor and lichtheimia species. the reported mortality rate showed a range of 50% 80% especially for the intraorbital or intracranial complications. however, country wise variation was observed as well. in india, rhizopus, apophysomyces elegans, anabaeana variabilis and rhizopus homothallicus, were identified to be the evolving responsible species. while less frequently identified species includes mucor irregularis and thamnostylum lucknowense. a mexican study reported a new commonly responsible species of 3 apophysomyces i.e apophysomyces mexicanus. other less frequently reported fungal infections includes oropharyngeal candidiasis, candidemia, pulmonary aspergillosis and pneumocystis jiroveci 4 pneumonia. mucormycosis is usually a coinfection in conditions like pulmonary diseases, renal disorders, septic arthritis, dialysis-associated, peritonitis, gastritis, rhinocerebral and cranifacial mycormycosis. the involvement of mucous layer of skin, precisely cutaneous layer, predisposes to 5 mucormycosis. in chronic state, the predisposing factors includes prolonged and severe neutropenia due to chemotherapeutic drugs, immunosuppression, hematologic malignancies, stem cell transplantation, and solid organ transplant recipients (sotrs). other factors can be previous respiratory pathology, uncontrolled diabetes mellitus (dm), iron overload, deferoxamine therapy, prolonged corticosteroid use, premature neonates, intravenous drug use, malnutrition, major trauma or burns, and 6 impending nosocomial sources. the available data strongly supports that covid correspondence: prof. dr. irfan ali mirza hod microbiology department armed forces institute of pathology, rawalpindi e-mail: irfanmirza651@hotmail.com received: may 16, 2021; accepted: may21, 2021 department of microbiology armed forces institute of pathology, rawalpindi 1 sinusitis with headache and fever. involvement of eyes or jawbone and osteomyelitis of the craniofacial skeleton, requires emergency surgical intervention to prevent the spread to brain. however, hyphal invasion of sinuses may follow a slow course of spread, even upto 04 weeks of time. the examination finding of nasal cavity or hard palate shows presence of black 3 eschar due to necrosis of affected tissues. as soon establishment of provisional diagnosis, confirmation can be done by taking samples from tissue debridement, tissue biopsy, nasal or upper respiratory tract by diagnostic nasal endoscopy. in case of severity of illness, early diagnosis can be done on direct microscopy with potassium hydroxide (koh) to identify the presence of 5 hyphae. use of optical brighteners such as blankophor and calcofluor have proven effective for diagnosis on direct microscopy. while definitive diagnosis can be established by histological studies and fungal culture. the presence of broad aseptate, irregular, and ribbon-like, 6-15μm, broad hyphae, branching at right angles is the hall mark for confirmation. hematoxylin and eosin (h&e), periodic acidschiff (pas) or grocott-gomori's methenamine, and silver staining are commonly used satin to evaluate morphology on histopathology. regarding the culture, mucorales grow rapidly within 03 to 07 days of incubation on sabouraud agar at 25°c to 30°c. while extent of infection can be identified with radiological support. the presence of multiple (≥10) nodules, reverse halo sign (rhs), and pleural effusion supports the diagnosis by computerized tomography (ct) 2,3 scan. enzyme-linked immunosorbent assays (elisa), immunoblots, immunodiffusion tests, and mucorales specific t cells by enzyme-linked immunospot (elispot) assay are the surrogate diagnostic markers. molecular characterization can be studied by conventional polymerase chain reaction (pcr), restriction fragment length 19 is a life-threatening illness. the pathogenesis involved over expression of inflammatory cytokines, and diminished cell-mediated immunity. a key factor for correlation amongst covid-19 and mucormycosis is the decline in cluster of differentiation 4 and 8 positive thelper (cd4+ t and cd8+ t) cell counts. while super added factors include hospital admissions in intensive care units (icus) requiring mechanical ventilation, prolonged hospital stays (>50 days), use of glucocorticoids and anti-viral 7 drug remdesvir. the situation further gets w o r s e n e d w i t h s i m u l t a n e o u s u s e o f immunomodulatory drugs like tocilizumab. all these promotes secondary infection in covid patients. the common routes for acquiring m u c o r my c o s i s i s i n h a l a t i o n o f f u n ga l sporangiospores from environment or air. direct inoculation into disrupted skin or mucosa of gastrointestinal tract can be the other source. afterwards invasion to adjacent fat, muscle, fascia, and even bone. while secondary vascular invasion and hematogenous spread is common for cutaneous mucormycosis, which leads to 2,3 high fatality rates. the penetration of fungal hyphae to the orbits, brain, and meninges will cause infarction and necrosis of the involved 2,6 tissues. therefore four recommended general principles harbors significance for managing mucormycosis i.e rapid diagnosis, elimination of predisposing factors, surgical debridement of infected tissue and appropriate antifungal therapy. a european study reported the common clinical presentations of mucormycosis i.e rhino-orbital (34%), cerebral (34%), pulmonary (21%), c u t a n e o u s ( 2 0 % ) , a n d d i s s e m i n a t e d mucormycosis (14%). the infection can rapidly progress to serious outcomes in <03 days' time. therefore, a wise approach much be there for recognizing red flags of severity. these can be informed of neurological deficit, cranial nerve palsy, sinus pain, diplopia, periorbital swelling, proptosis, ulcers of the palate, complicated 66 jiimc 2021 vol. 16, no.2 government should provide updated protocols for appropriate diagnostic and management option for this co existing mucormycosis. it will be the frontward step to combat this lethal infection. references 1. fekkar a, lampros a, mayaux j, poignon c, demeret s, constantin jm, etal. occurrence of invasive pulmonary fungal infections in patients with severe covid-19 admitted to the icu. am j respir crit care med. 2021 feb 1; 203(3): 307–317. doi: 10.1164/rccm.202009-3400oc. 2. khudyakov a, ahmed r, huynh cd, dehghani a, li z, rose m, etal. a rare indolent course of rhinocerebral mucormycosis. c a s e re p o r t s i nfe c t d i s . 2 0 2 1 ; 4 3 8 1 2 5 4 1 : 5 d o i : https://doi.org/10.1155/2021/4381254 website:[https:// w w w. h i n d a w i . co m / j o u r n a l s /c r i i d / 2 0 2 1 / 4 3 8 1 2 5 4 / ] th accessed on may 13 2021 3. skiada a, floerl cl, klimko n, ibrahim a, roilides e, petrikkos g, etal. challenges in the diagnosis and treatment of mucormycosis. med mycol. 2018; 56(1): 93–101. doi: 10.1093/mmy/myx101 4. li z, lu g, meng g. pathogenic fungal infection in the lung. f r o n t i m m u n o l . 2 0 1 9 ; 1 0 : 1 5 2 4 . d o i : 10.3389/fimmu.2019.015240154 5. verma dk, bali rk. covid-19 and mucormycosis of the craniofacial skeleton: causal, contributory or coincidental? j m a x f a c o r a l s u r g . 2 0 2 1 ; 2 0 : 1 6 5 6 6 doi: https://doi.org/10.1007/s12663-021-01547-8. 6. khatri a, chang km, berlinrut i, wallach f. mucormycosis after coronavirus disease 2019 infection in a heart transplant recipient – case report and review of literature. j m y c o l m e d . 2 0 2 1 ; 3 1 ( 2 ) : 1 0 1 1 2 5 . d o i : 10.1016/j.mycmed.2021.101125 7. chen n, zhou m, dong x. epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in wuhan, china: a descriptive study.. lancet. 2020;395:507–513. doi: https://doi.org/10.1016/ s01406736(20)30211-7 8. garg d, muthu v, sehgal is, ramachandran r, kaur h, bhalla a, etal. coronavirus disease (covid-19) associated mucormycosis (cam): case report and systematic review of literature. mycopathologia. 2021; 186(2): 289-298. doi: 10.1007/s11046-021-00528-2 polymorphism analyses (rflp), and dna sequencing. most of the molecular assays targets internal transcribed spacer or the 18s 3 rrna genes. t h e re c o ve r y o f c ov i d p a t i e n t s w i t h mucormycosis is dependent upon early case recognition and prompt management. a combination of anti fungals and surgical debridement can improve treatment outcomes and patient's survival. intra venous (i/v) amphotericin b is the recommended drug of choice for initial therapy for mucormycosis. another study report concluded that synergistic effect achieved by a combination of i/v amphotericin b and caspofungin had proven more effective. posaconazole oral suspension or isavuconazonium (iv or oral) can be the other anti fungals for management. while intraorbital irrigation with amphotericin had been declared supportive for preventing the spread of 2 craniofacial infection. mucormycosis belongs to a category of highly invasive and rapidly progressing severe fungal infection. the secondary origin of this coinfection with covid7 19 can lead to fatal outcome. covid-19 itself had taken more than one million lives around the globe. until the successful completion of phase three trials for many vaccines or specific antiviral therapy, supportive care plays a pivotal 8 role in covid management. as per recommended guidelines, timely tallying of broad-spectrum antibiotics, for covid m a n a g e m e n t o f fe rs u p r i g h t c o v e r fo r superimposed bacterial infection. while for fungal infections, due care is deficient. adoption of a vigilant approach for early diagnosis and management is the only way out, to reduce high morbidity and mortality rate from this fatal coinfection. the clinicians should be well aware for the possibility of its presence in covid patients. while health policy makers from the jiimc 2021 vol. 16, no.2 67 editorial coping with contagious diseases: a global perspective meh para siddique historically, when compared to other ailments, contagious infectious have been feared greater in contrast to other diseases. a contagious disease is an infectious condition that spreads easily (i.e., is communicated) when a pathogen is exposed through direct or indirect contact with an infected 1 person. this infection has peculiar properties that elucidate the exaggerated level of anxiety; it spreads quickly and covertly; generally, it has been responsible for significant sickness and mortality; old forms reappear; new forms arise; and both the 2 media and society are frequently in awe. such infection could be viral, bacterial, parasitic, fungal or any other such as, severe acute respiratory 3 syndrome (sars), middle east respiratory syndrome 4 5 6 7 ( m e rs ) , e b o l a , tu b e rc u l o s i s , cov i d 1 9 , 8 carbapenem-resistant enterobacter ales (cre), 9 10 enterovirus d68, flu, human immunodeficiency virus infection and acquired immune deficiency 11 12 syndrome (hiv/aids), hepatitis (a and b), 13 14 15 16 measles, hantavirus, monkeypox, pertussis, 17 18 19 rabies, sexually transmitted disease, shigellosis, 20 21,22 west nile virus, and zika. the occurrence, and swift spread of such contagious diseases as a pandemic provides a challenge worldwide. though the spread of contagious disease is undoubtedly a scientific phenomenon linked to a particular pathogen, understanding the pandemic requires a consideration of the culture-mind relationship, which is at the core of mental health. in terms of relative mortality, transmission rates, behavioral responses, official policies, compliance with authorities, and even the degree to which disease-spread beliefs have been politicized across diverse communities and cultures, startling discrepancies have been seen. everyone may find these outbreaks upsetting, but especially those who are thought to be more sensitive to certain 23 pandemics. additionally, cultural context has an impact on individual differences, for instance, intolerance of uncertainty, optimism, conspiratorial thinking, or collectivist orientation, which has implications for actions related to the spread and impact of contagious diseases, such as mask-wearing 24 and social distancing. with a few justifiable exceptions, people must remain confined to their homes during such pandemic conditions. moreover, this scenario altered people's lives profoundly and worry, stress, depression emerged as emotional, cognitive, and behavioral symptoms, which can have a wide range 25 of psychosocial effects. thus, subsequent factors were associated to person's mental health: (1) demographics; (2) level of pandemic concern; (3) home confinement environmental conditions; (4) changes in daily life as a result of the disease outbreak; (5) contact with said communicable disease; (6) perceived and real severity of the emergency; (7) information about the disease; (8) perceived health status; and (9) participation in 23 leisure activities. such infectious diseases might have a deleterious emotional resonance on those who are vulnerable, causing anxiety, denial, stigmatization, loss, distress, and fear that are all made worse by uncertainty, as well as depression, post-traumatic stress disorder ailments, general 2 psychiatric morbidity, doubts about infection, concerns about treatment, disruption of routines, financial and occupational worries, and upset expectations of healthcare. it was frequently noted that there was heightened awareness of nonpharmaceutical protective activities. social support can be a protective factor for poor mental health although during an outbreak may be difficult to 23 access. although time is an eternal physician, but it takes time to heal the emotional scars that surfaced in patient diagnosed with infectious diseases. intensity, and severity of these scars varies from individual to individual depending upon their level of exposure to certain contagious diseases. primarily, there are three certain levels of exposure, firstly, is an infected correspondence: dr. meh para siddique deputy director, research and analysis, government of khyber pakhtunkhwan e-mail: mehpara1612@gmail.com received: august 13,2022; accepted: september 10, 2022 148 149 individual being walking at double edged sword as it is possible to violate someone's privacy when attempting to manage an infection epidemic since the patient in an outbreak serves being both a victim 2 and a transmission vector equally. secondly, a man becomes apprehensive after watching the news. his heartbeat raises, and his hands start to perspire. hearing about a potential epidemic makes him feel anxious. the media bombards him with fragmented images of people running to emergencies, discussions on the necessity and prospective shortfall of antimicrobial drugs, media people reporting the death toll of prior epidemics, the hundreds of millions of expected victims worldwide, the extraordinary cost of the control of previous outbreaks, and the anticipated expense superficially required to improve preparedness. the amount of knowledge feels overwhelming to the man. because of this, the whole public, particularly caregivers that are not infected, are not exempt from the 26-29 psychological effects of such epidemics, which may be caused by several things, such as disruptions 30 31 to daily routines, loss and grief, considering the 32,33 shame associated with such epidemics. these psychological responses affect the well-being of the individual and community and can persist long after 34,35 the outbreak. thirdly, an emergency department health care provider in a nearby hospital considers requesting a long-term leave of absence as he wants to be away when an outbreak occurs. he is worried about his family and believes he is unprepared to handle and be protected from deadly infection. meanwhile, an infectious disease expert is flying home from an international infectious diseases congress after attending a lecture about the then evolving severe epidemic outbreak. these three clusters of people, among many others, regularly experience varying degrees of fear related to contagious diseases. in addition to having chronic stress, health care professionals who were at high risk of getting infectious patients also seem to have higher levels of sadness and anxiety. stress management could be helpful for front-line employees as they get ready for upcoming 36 outbreaks. they share the anxiety, the uncertainty, and the potential for irrational behavior due to fear of an unknown disease. there are self-management approaches to improve psychological well-being for the psychic symptoms of anxiety, despair, fear, and discomfort since they are common, manifest in different ways, and they are widely felt. these facts need to be known by clinicians. health systems must put into place the short and long-term psychological 37 support for clinicians providing covid-19 care. additionally, the psychological responses shared by survivors, caregivers, professionals, and the public included anxiety/fears, despair, anger, guilt, grief and l o s s , p o s t t ra u m a t i c s t r e s s d i s o r d e r, a n d stigmatization, but also a greater sense of 23, 38. empowerment and concern for others. when faced with an infectious disease, a person will typically adopt one of three coping mechanisms: 25 avoidance, surrender, or overcompensation. these coping mechanisms include problem-focused coping (looking for alternatives, protecting oneself and others), avoidance, and positive situational 39,41-45 analysis. a growing body of evidence, however, is needed to support the theory that immune system activation and infections may be responsible for the initiation, activation, and development of serious psychiatric illnesses. additionally, attempts to combat stigmatization and prejudice through activism may have unintended consequences because these problems may also include ethical considerations. by raising health literacy, public health programmers can allay the public's apprehensions and help to lessen the negative psycho-social effects of infectious diseases. references 1. who. communicable diseases. world health organization. available from: https://www.afro.who.int/health-topics/ communicable-diseases. 2. pappas g, kiriaze j, giannakis p, falagas e. psychosocial consequences of infectious diseases. clinical microbiology and infection. 2009;15(8):743-747. 3. who. severe acute respiratory syndrome (sars). world h e a l t h o r g a n i z 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2009;23(4):714-725. 42. jones a, fitness j. moral hypervigilance: the influence of disgust sensitivity in the moral domain. emotion. 2008;8(5):613-627. 43. murray d, schaller m. the behavioral immune system: implications for social cognition, social interaction, and social influence. in advances in experimental social psychology 2016 (vol. 53, pp. 75-129). academic press. 44. wu b, chang l. the social impact of pathogen threat: how disease salience influences conformity. personality and individual differences. 2012;53(1):50-54. 45. muller n. infectious diseases and mental health. comorbidity of mental and physical disorders. 2014; 179, pp 99–113 (doi: 10.1159/000365542). jiimc 2022 vol. 17, no.3 151 original�article abstract objective: to evaluate the efficacy and safety of collagen cross linking in stabilizing the visual acuity and keratometric readings one year after the procedure. study design: a case series. place and duration of study: all the procedures were performed at amanat eye hospital rawalpindi from january to june 2011. materials and methods: sixteen cases suffering from progressive keratoconus which underwent collagen cross-linking were analyzed retrospectively. after epitheliectomy and instillation of topical riboflavin, uv light exposure was given for 30 min. a bandage contact lens was applied postoperatively for 5 days. the patients were followed up after 5 days, one month, 3 months, 6 months and then one year. during all the postoperative visits, visual acuity, slit lamp examination and keratometry were performed. results: sixteen cases completed one year's follow-up. un-corrected visual acuity improved in 12 out of 16 eyes, remained stable in 4 out of 16 and deteriorated in none. best-corrected visual acuity improved in 9 out of 16 eyes, remained stable in 6 out of 16 and deteriorated in one out of 16. mean pre-operative keratometry was 50.23 d which reduced to 49.77 d after one year. progression of original disease (increase in k-value by > 0.50 d) was seen in only 2/16 eyes after one year of follow-up. keratometric improvement (decrease in k-value by > 0.50 d) was seen in 6/16 eyes while 8/16 eyes (50%) showed keratometric stability (i.e. k-value within 0.50 d of the preoperative value). conclusion: collagen cross-linking is effective and safe in providing visual and keratometric stability for keratoconus. key words: collagen cross linking, keratoconus, efficacy. in cases of corneal opacification. none of these procedures corrects the underlying problem. collagen cross-linking (cxl) emerged as a promising procedure. it is indicated in cases having clear cornea but evidence of progression. cxl is the only procedure which addresses the underlying pathophysiology of keratoconus i.e. corneal collagen 2 structural weakness. 3 it was introduced by wollensak et al with the idea of providing mechanical and biochemical stability to the corneal collagen structure.“dresden protocol” was established, which provided the safety 4 measures for the procedure. according to this protocol, after epitheliectomy, the residual thickness must be at least 400 µm. this would protect the underlying endothelium, lens and retina from the harmful effects of uva radiation. isoosmolar 0.1% riboflavin in 20% dextran solution is used for 30 min and exposed to uva radiation of 370 nm at 3 mw/cm2for 30 min.cxl utilizes riboflavin eye drops (as photosensitizer) and ultraviolet radiation to 5 strengthen the corneal collagen structure. riboflavin also acts as a shield to protect the introduction progressive myopia with astigmatism and frequent changes in glasses during the teen years is the hallmark of keratoconus. it is caused by thinning and ectasia of corneal stroma. its association with other genetic conditions like marfan’s and down’s syndrome and family history suggest genetic factors 1 in its etiology. the treatment of keratoconus includes refraction and prescription of glasses, rigid gas-permeable hard contact lenses, intacs (to correct the ectasia and irregular astigmatism) and penetrating keratoplasty efficacy and safety of corneal collagen cross-linking in keratoconus; a one year follow-up 1 2 3 aneeq ullah baig mirza , aamir asrar , bisma ikram correspondence: dr. aneeq ullah baig mirza professor & hod, ophthalmology islamic international medical college riphah international university, islamabad e-mail: aneeqmirza07@gmail.com 1 department of ophthalmology islamic international medical college riphah international university, islamabad 2,3 amanat eye hospital, rawalpindi funding source: nil; conflict of interest: nil received: aug 03, 2016; revised: jan 05, 2017 accepted: jan 19, 2017 efficacy and safety of corneal collagen cross-linkingjiimc 2017 vol. 12, no.1 15 underlying structures from the harmful effects of uv radiation. cxl can be performed both with epithelium on and epithelium off. however, the epithelium-on technique results in some reduction of uv penetration into the corneal stroma. epithelium-on cxl can be utilized in cases with thin cornea (<400µm), where epitheliectomy would result in further thinning and more penetration of uv light. other methods of cxl in thin corneas can be pachymetry-guided epithelial debridement before cross-linking, parameters modification (conc. of riboflavin, intensity/wavelength of uv radiation and exposure time) and utilization of hypo-osmolar 2 riboflavin for cxl. studies have shown stabilization in un-corrected visual acuity (ucva), improvement in best-corrected visual acuity (bcva) and reduction in keratometry after cxl. all these factors suggest stabilization of keratoconus. safety of the procedure is suggested by stable corneal thickness, endothelial cell density and 6 foveal thickness. haze and increased density of anterior stroma have been cited as the only direct 7 complications of the procedure. there is scarcity of literature about cxl results in keratoconus in our population. the present study was conducted to evaluate the efficacy and safety of cxl in achieving visual and keratometric stability, one year after the procedure. materials and methods this is a case series of sixteen cases of progressive keratoconus which underwent collagen cross-linking with uva light and riboflavin. all the cases completed one year's follow-up. the procedure was performed at amanat eye hospital, rawalpindi by a single surgeon from january to june 2011. the keratoconus was diagnosed by history, refraction, slit-lamp examination, keratometry and orbscan ii. those with evidence of progression of keratoconus and clear cornea underwent cxl. all the cases with stable keratoconus or corneal scarring were excluded from the procedure. the procedure was performed with standard epitheliectomy. this was followed by instillation of 0.1% riboflavin eye drops in 20% dextran solution for 30 min. uva radiation exposure (370 nm at 3 mw/cm2) was given for 30 min. a bandage contact lens was placed for 5 days. postoperative treatment consisted of antibiotic/steroid combination alongwith lubricant, given for two weeks. follow-up visits were conducted after 5 days, one month, 3 months, 6 months and one year. on followup visits, ucva, bcva, slit-lamp examination, refraction and keratometry were performed. in the final visit, alongwith the above, orbscan ii was also performed. efficacy was determined with respect to ucva, bcva, average and steepest meridian k e r a t o m e t r y. s a f e t y w a s d e t e r m i n e d b y complications recorded. results a total of 16 cases of cxl which had completed one year of follow-up were included in the study. 8 were male and 8 female eyes. the age range was 14 to 32 years. ucva improved in 12 out of 16 eyes, remained stable in 4 out of 16 and deteriorated in none (fig 1). there was improvement in bcva in 9/16 eyes. bcva remained stable in 6/16 and deteriorated in only 1/16 eyes (fig 2). 5/16 eyes showed improvement in visual acuity by 2 or more lines. preoperative mean k-reading was 50.23d which reduced to 49.77d one year after the procedure. progression of original disease was defined as increase in k-reading by >0.50 d and stability as keratometric reading within 0.50 d of original kreading. according to that criteria, only 2/16 eyes showed progression. stability of original disease was seen in 8/16 and improvement in 6/16 eyes, one year post-operatively (table i). k-value in steepest meridian remained stable in 9/16 eyes, improved in 5/16 eyes and deteriorated in 2/16 eyes (table ii).mean steepest meridian k-reading reduced from 52.38 d (sd 5.27) to 52.09 d (sd 5.08)and flattest meridian k-reading decreased from 48.06 d (sd 4.56) to 47.80 d (sd 3.44)during the same time period (table iv). none of the eyes developed corneal haze or infection postoperatively. jiimc 2017 vol. 12, no.1 fig 1: comparison of pre-opera�ve vs post-opera�ve ucva 16 efficacy and safety of corneal collagen cross-linking discussion in our study, the male and female ratio was 50:50. both ucva and bcva showed improvement in jiimc 2017 vol. 12, no.1 fig 2: comparison of pre-opera�ve vs post-opera�ve bcva table i: comparison of pre-opera�ve vs one year post -opera�ve mean keratometry table ii: comparison of pre-opera�ve vs one year postopera�ve steepest meridian keratometry table iii: comparison of pre-opera�ve vs one year postopera�ve fla�est meridian keratometry table no. iv: mean reduc�on in keratometric readings and p value 17 efficacy and safety of corneal collagen cross-linking majority of cases. un-corrected visual acuity improved in 12 out of 16 eyes, remained stable in 4 out of 16 and deteriorated in none. best-corrected visual acuity improved in 9 out of 16 eyes, remained stable in 6 out of 16 and deteriorated in one out of 16 eyes.the pre-operative mean cylinder was 3.97±2.29 d which improved to -3.60±2.40 d, one year postoperatively. majority of the cases showed keratometric stability. mean pre-operative keratometry was 50.23 d which reduced to 49.77 d after one year. progression of original disease (increase in k-value by > 0.50 d) was seen in only 2/16 eyes after one year of follow-up.keratometric improvement (decrease in k-value by > 0.50 d) was seen in 6/16 eyes while 8/16 eyes (50%) showed keratometric stability (i.e. k-value within 0.50 d of the preoperative value). safety of the procedure was established by lack of corneal haze and infection in any of the cases. 8 razmjoo et al completed topographical corneal changes on 66 patients. just like our study, their cases also completed one year of follow-up. the age range was 1829 years. the mean age was 22.4 ± 5.4 years. the age range resembled our study i.e. 14-32 years since keratoconus starts in teanage and continues till mid thirties. there were 54.55% males and 45.45% females. 9 frederiket al conducted the long-term study regarding dampening effect of riboflavin and uv-a on progressive keratoconus by collagen crosslinking. 6 months of follow-up was completed by 241 eyes. in the first year, there was a decrease in steepening by 2.68 d. it further decreased by 2.21 d in the second year and 4.48 d in the third year. there was a significant improvement in bcva by ≥ i line in 53% among 142 eyes (in first year), 57% of 66 eyes in the year falling and 58% among 33 eyes in the third year. in the first year, bcva remained stable in 20% of 142 eyes. in second year, 24% of 66 eyes and in third year, 29% of 33 eyes showed stable bcva. only two patients experienced continued progression and needed another cxl. the study proved a long-term stabilization and improvement after cxl. a study of cxl with corneal de-epithelialization was conducted on 14 eyes of 14 patients by goldichyakov et al.6 as compared to pre-operative bcva, 24 months postoperative bcva showed significant improvement (0.21± 0.1 to 0.14±0.1, p=0.002). the steepest meridian k-reading showed a significant decrease i.e. 53.9±5.9 to 51.5±5.4(p=0.001). the mean cylinder also showed significant decrease i.e. 10.2±4.1 to 8.1±3.4(p=0.001). there was no significant alteration in foveal reflex. according to their conclusion, ucva showed stability, bcva showed improvement and keratometry depicted reduction after 2 years of cxl. safety of the procedure was proved by stability in corneal thickness, density of corneal endothelial cells and thickness of fovea. 10 deepa viswanathan and john males evaluated long-term efficacy of cxl in 51 eyes of 35 patients. the mean follow-up was 14.38±9.36 months. the treated patients were compared with a control group of 25 fellow eyes which were not treated. the treated group showed significant flattening of maximum keratometry by 0.96±2.33 d(p=0.005).the bcva showed significant improvement i.e. 0.05±0.13 logmar(p=0.04). the maximum kreading increased significantly in control group i.e. 0.43±0.85 d (p=0.05) and bcva decreased by mean 0.05±0.14 (p=0.2). their study concluded that cxl decreases corneal curvature and improves visual acuity in keratoconus. in young patients with keratoconus, there are more chances of rapid progression and they are more likely to require penetrating keratoplasty for visual 11 improvement. 18 paedietric patients (25 eyes) were evaluated for efficacy of cxl in progressive 12 keratoconus. the paedietric age was defined as 18 years of age or younger. the mean age of the patients was 14.3±2.4 years and mean follow-up of 20.1±14.25 months. pre-operative mean k-reading in flattest meridian which was 46.34 d reduced postoperatively after 20 months to 45.67 d(p=0.03). preoperative mean k-reading in the steepest meridian which was 50.06 d reduced to 49.34 d (p= 0.005). there was a reduction in topometric astigmatism from mean 3.50 d to 3.25 d (p=0.51). their study concluded that cxl is an effective option for paedietric patients with progressive keratoconus. a twenty four months follow-up prospective study of 13 cxl cases was performed in 57 eyes of 55 patients. as compared to our study where orbscan was used, they examined the patients with pentacam, iol master and ocular response analyzer. our study focused on visual acuity, mean keratometry, steepest jiimc 2017 vol. 12, no.1 18 efficacy and safety of corneal collagen cross-linking & flattest meridian keratometry. their study additionally concentrated on thinnest point keratometry. twenty four months after cxl, there was a significant improvement in bcva (p<0.01), a significant decrease in corneal thinnest point keratometry readings at the corneal apex and corneal volume (p<0.01). the limitations of our study are smaller sample size and shorter duration of follow-up. future studies with a three to five year follow-up should be conducted to evaluate the long-term effects of cxl. conclusion cxl is effective and safe procedure in providing visual and keratometric stability for keratoconus. references 1. edwards m, mc ghee cn, dean s. the genetics of keratoconus. clinical & experimental ophthalmology. 2001; 29: 345-51. 2. padmanabhan p, dave a. collagen cross-linking in thin corneas. indian j. ophthalmol. 2013; 61: 422-4. 3. wollensak g, spoerl e, seiler t. riboflavin/ultraviolet-ainduced collagen cross linking for the treatment of keratoconus. am j ophthalmol. 2003; 135: 620-7. 4. spoerl e, mrochen m, sliney d, trokel s, seiler t. safety of uva-riboflavin cross-linking of the cornea. 2007; 26: 385-9. 5. mirko r, jancov ii, jovanovic v, delevic s, coskunseven e. corneal collagen cross -linking outcomes: review. the open ophthalmology journal. 2011; 5: 19-20. 6. yakov g, marcovich al, yaniv b, yossi m, ami h, yair m, et al. clinical and corneal biomechanical changes after collagen cross-linking with riboflavin and uv irradiation in patients with progressive keratoconus: results after 2 years of follow-up. cornea. 2012; 6: 609-14. 7. dhawan s, rao k, natrajan s. complications of corneal collagen cross-linking. hindawi publication corporation. journal of ophthalmology. 2011; 8690: 1-5. 8. razmjoo h, nasrollahi apk, salam h, karbasi n, najarzadegan mr. topographical corneal changes after collagen cross-linking in patients with corneal keratoconus. j res med sci. 2013; 18: 882-6. 9. raiskup wf, hoyer a, spoerl e, pillunat le. collagen crosslinking with riboflavin and ultraviolet-a light in keratoconus: long-term results. j cataract refract surgery. 2008; 34: 796-801. 10. viswanathan d, males j. prospective longitudinal study of c o r n e a l c o l l a g e n c r o s s l i n k i n g i n p r o g r e s s i v e keratoconus.clinical and experimental ophthalmology. 2013; 41: 531-6. 11. reeves sw, stinnets, adelman ra, afshari na. risk factors for progression to penetrating keratoplasty in patients withkeratoconus. american journal of ophthalmology. 2005; 140: 607-11. 12. viswanathan d, kumar nl, males jj. outcome of corneal collagen cross-linking for progressive keratoconus in paedietric patients. biomed research international. 2014; 140461: 5. 13. bernardo md, capasso l, lanza m, tortori a, iaccarino s, cennamo m, et al. long-term results of corneal collagen crosslinking for progressive keratoconus. j optom. 2015; 8: 180-6. jiimc 2017 vol. 12, no.1 19 efficacy and safety of corneal collagen cross-linking jiimc december 2016 page 19 page 20 page 21 page 22 page 23 original�article abstract objective: to assess the impact of fibroids on pregnancy outcome. study design: a retrospective descriptive study. place and duration of study: the study was conducted at department of obstetrics & gynecology during a st st period of 2 years from 1 january 2017 to 31 december 2018. materials and methods: all pregnant patients with fibroids > 3cm either diagnosed during antenatal period or incidentally during cesarean section were included in this study. data regarding obstetrical outcome was extracted from the maternity ward record. maternal age, parity, obstetrical complications, mode of delivery and indications for caesarean section were noted. neonatal outcomes were ascertained from the maternity record and chart review. results were summarized as %age, average and presented as tables using ms excel version 13. results: during the study period 38 pregnant women with fibroid are included in the study. major proportion of patients with fibroid were in age group of 30-35 years. obstetrical complications observed were; placental abruption (5.26%), pph (15.78%), obstructed labor (5.26%), prolonged labor (28.94%), abdominal pain nd (10.52%), preterm labor (2.63%) and malpresentation (2.63%). miscarriages during early 2 trimester were recorded in (5.26%) cases. caesarean section was required in 69.44% cases. one lady ended up in cesarean hysterectomy due to intractable bleeding during c/section. during the course of pregnancy (21.05%) women with fibroid uterus remained asymptomatic. fetal outcome was good with (88.88 %) alive babies, (5.55%) nnd, (2.77%) iud and (2.77%) neonatal intensive care unit (nicu) admission were recorded. conclusion: pregnancies with fibroids are associated with increased risk of fetomaternal complications. pregnant women with myoma may have frequent antenatal visits in a consultant led clinic and well defined care pathways. significant number of still birth due to placental abruption associated with large myoma may warrant elective caesarean section at relatively earlier gestational age. key words: caesarean hysterectomy, fibroid, myoma, neonatal outcome, obstetrical outcome. outcome of pregnancy. the incidence of fibroids in pregnancy reported ranges from 0.1 to 10.7% of all pregnancies and increases with increasing maternal 4 age. fibroids may negatively affect fertility and 1 outcome of pregnancy. myoma are associated with increased risk of spontaneous abortion, antepartum hemorrhage, placental abruption, malposition of the fetus, foeto-pelvic disproportion, premature rupture of membranes, retention of the placenta, postpartum hemorrhage (pph), preterm delivery, low birth weight infants, dysfunctional labor, and 5,6,7,8 increased need to cesarean deliveries. about 1040% of women with fibroid uterus developed 9 complications during pregnancy. large size fibroids and submucosal fibroids are associated with more 10 complications. although fibroid uterus is associated with many adverse events during pregnancy, but still the perinatal outcomes in these patients tend to be 11 fair. as an increasing number of women with fibroid introduction fibroid is the most common benign tumor of the female internal genital organs, affecting 20% –60% of 1 young women. incidence of fibroids varies from 2 0.1% to 12.5% as most fibroids are asymptomatic, the true prevalence of fibroids may be greatly 3 higher. fibroid is the most common smooth muscle tumor of the uterus seen in child baring age and if associated with pregnancy may adversely affect the to assess the impact of fibroids on pregnancy outcome 1 2 3 4 5 rakshinda mushtaq , uzma afridi , pari gul , shama jogezai , rukhsana neelofer correspondence: dr. rakhshinda neelofer department of obstetrics and gynecology bolon medical college, quetta e-mail: dr.rakhshinda.mushtaq@gmail.com 1,2,3,4 department of obstetrics and gynecology bolon medical college, quetta 5 department of radiology civil hospital, quetta pregnancy outcome with fibroid uterus jiimc 2020 vol. 15, no.3 funding source: nil; conflict of interest: nil received: may 27, 2019; revised: december 27, 2019 accepted: january 31, 2020 173 1(2.63%) and malpresentation 1(2.63%) [table, ii]. two women (5.26%) had miscarriages during early nd 2 trimester [table iii]. out of 36, about 25 women (69.44%) required caesarean section and 4 of them had technically difficult procedure [table iii]. in 12 cases (48%) of fibroid uterus cesarean section was done for non-progress of labor. other indications for caesarean section were malpresentation 2(8%), fetal distress 4(16%) obstructed labor 2(8%), placental abruption 1(4%) and repeat section d/t previous c/section 4(16%). 6 women (15.78%) developed pph [table ii]. one lady ended up in cesarean hysterectomy due to intractable bleeding during cesarean section. 8(21.05%) women with fibroid uterus remain asymptomatic during the course of pregnancy. fetal outcome was good with 32 (88.88 %) alive babies.2 (5.55%) nnd, 1(2.77%) iud and 1(2.77%) nicu admission [table iv]. during pregnancy is observed, therefore the study was aimed to find out the obstetrical outcome of the pregnancies complicated with fibroid presenting in bmch quetta to help developing local guidelines and protocols for management of these women in order to reduce the risk associated with myoma. so, a study was planned to assess the impact of fibroids on pregnancy outcome in a local set up. materials and methods this retrospective study was carried out at department of obstetrics & gynecology bolan medical complex hospital, quetta, for the period of 2 st st years from 1 january 2017 to 31 december 2018. all pregnant patients with fibroids > 3cm either diagnosed during antenatal period or incidentally during cesarean section were included in this study. patients with subserous fibroids of less than 3cm were excluded from the study. the permission of institutional ethical review committee was obtained and all ethical issues were addressed. data regarding obstetrical outcome was extracted from the maternity ward record. maternal age, parity, obstetrical complications (miscarriage, preterm labor, abdominal pain, prolonged labor, malpresentation, cesarean hysterectomy, pph, placental abruption), mode of delivery and indications for caesarean section were noted. neonatal outcomes (alive, iud, nnd, admissions in neonatal ward) were ascertained from the maternity record and chart review. results were summarized as %age, average and presented as tables using ms excel version 13. results during the study period, 38 women were identified with fibroid uterus during pregnancy. during antenatal visits, 32 women (84.21%) were diagnosed with fibroid uterus, while in 6 women (15.78%), myoma was an incidental finding during cesarean section; contributory to the cause of operative delivery most of the women in our study population . (34.21%) were in 30-35 years age group as shown in table i. fibroids were more frequent (86.84 %) in multigravida as compared to primigravida (13.15%) shown in table i. common obstetrical complications encountered in pregnancies with myoma were; placental abruption 2(5.26%), pph 6(15.78%), obstructed labor 2(5.26%), prolonged labor 11 (28.94%), abdominal pain 4(10.52%), preterm labor table i: parity wise distribu�on of women with fibroids table ii: obstetrical outcome in women with fibroids table iii: mode of delivery in women with fibroids table iv: fetal outcome in women with fibroids discussion fibroids are the most common benign tumors of child bearing age with an overall incidence of 4012 60%. pregnancy with fibroid is potentially serious problem. the aim of this study was to find out the pregnancy outcome with fibroid uterus jiimc 2020 vol. 15, no.3 174 period. findings of our study in case of placental abruption are conflicting with a study conducted in china which found no association between fibroid 16 and placental abruption. out of 36, 25 (69.44%) women required caesarean section and 4 of them had technically difficult procedure. the most common indication for caesarean section was non progress of labour 12(48%). the rate of cesarean section found in our study was comparable with 11 other studies conducted by klatsky et al, and irum et 17 al. the results of placental abruption and pph found in this study are comparable with the study 18 conducted by saha m et al. another study by zhao r et al also confirm the results of this study by reporting increased risk of caesarean section and 16 pph associated with fibroid uterus. contrary to findings of this study, another study conducted by wang et al deny any association between fibroid 19 uterus and adverse obstetrical outcome. fetal outcome was good with (88.88 %) alive babies.(5.55%) nnd, (2.77%) iud and (2.77%) nicu admission. this study has its limitations. as this was a retrospective study which has its own inherent limitation of availability of information. furthermore it was a small scale study and the findings are to be interpreted with caution in the presence of small sample size. however, this study will provide useful data to help clinicians in counseling and management of pregnant women with fibroid uterus. elective cesarean section at an earlier gestation in case of large myoma and lower segment myoma may reduce the risk of placental abruption and obstructed labour. a study may be conducted in future to see the effect of elective caesarean section in reducing the obstetrical complications of fibroid uterus. conclusion pregnancies with fibroids are associated with increased risk of fetomaternal complications. pregnant women with myoma may have frequent antenatal visits in a consultant led clinic and well defined care pathways. significant number of still birth due to placental abruption associated with large myoma may warrant elective cesarean section at relatively earlier gestational age. references 1. shannon k laughlin-tommaso, jane c schroeder, donna obstetrical outcome of pregnancies complicated by leiomyomas, with special emphasis on following outcomes measures, such as preterm delivery, malpresentation, mode of delivery and postpartum haemorrhage. furthermore. the efforts were made to estimate the magnitude of the problem to help formulate guide lines regarding management of pregnancies with fibroid in our set up. the clinical data of obstetrical outcome of 38 pregnant women with fibroid were evaluated. about 84.21% women were diagnosed during routine antenatal visits while in 15.78% women, myoma was an incidental finding during cesarean section. these cases were also included in this study because fibroids seemed contributory to the pathology leading to cesarean section owing to their size and location. mean maternal age in our study was 33 years which is comparable with national and 13,14 international studies. fibroids were more frequently found in multigravida, 33 (86.84 %) as compared to primigravida 5(13.15%) which is in consistent with the study conducted by sheinner et 14 a. out of total about 8(21.05%) women with fibroid uterus remained asymptomatic during the course of nd pregnancy. miscarriages during early 2 trimester were found as 5.26%. one patient presented with sudden unexplained iud at 35 weeks of gestation. she had a large lower segment intramural fibroid and no other identifiable cause for iud.6 (15.78%), women developed pph, 3 during cesarean section and 3 after vaginal birth. 4 women were managed conservatively but one woman ended up in obstetrical hysterectomy (2.63%) due to uncontrolled pph during caesarian section. the increased incidence of pph noted in the study is consistent with findings of study conducted 15 by kremer ms et al. 2 (5.26%) women with fibroid presented with placental abruption at term gestation. one of these women was diagnosed during antenatal visits with multiple fibroids. she presented at 38 weeks of gestation with placental abruption. a large anterior upper segment myoma was an incidental finding during caesarean section in another women who was undergoing c/section for severe aph due to placental abruption. both of these women had no other identifiable risk factor for placental abruption other than myoma. both of them lost their newborns during early neonatal pregnancy outcome with fibroid uterus jiimc 2020 vol. 15, no.3 175 11. klatsky pc, tran nd, caughey ab, et al. fibroids and reproductive outcomes: a systematic literature review from conception to delivery. american journal of obstetrics and gynecology. 2008; 198(4):357–66. 12. baird dd, dunson db, hill mc, et al. high cumulative incidence of uterine leiomyoma in black and white women: ultrasound evidence. am j obstet gynecol. 2003; 188(2):100-107. 13. sarwar i, habib s, bibi a, et al. clinical audit of foeto maternal outcome in pregnancies with fibroid uterus. journal of ayub medical college, abbottabad: jamc. 2012; 24(1):79–82. 14. sheiner e, bashiri a, levy a et al. obstetric characteristics and perinatal outcome of pregnancies with uterine leiomyomas. the journal of reproductive medicine 2004, 49(3):182–186. 15. kramer ms, berg c, abenhaim h, et al: incidence, risk factors, and temporal trends in severe postpartum hemorrhage. american journal of obstetrics and gynecology 2013, 209(5):441–447. 16. zhao r, wang x, zou l, li g, et al. adverse obstetric outcomes in pregnant women with uterine fibroids in china: a multicenter survey involving 112,403 deliveries plos one. 2017 12(11): 3-9. 17. sarwar i, habib bibi attiya et al. clinical audit of foetomaternal outcome in pregnancies with fibroid uterus. journal of ayub med college abbottabad 2012; 24(1):1317. 18. saha m, mondal d and biswas sc. pregnancy with leiomyoma uteri and feto-maternal outcomes; al ameen j med sci 2016; 9(2):96-100. 19. hm wang, yc tian, zf xue, et al. “associations between uterine fibroids and obstetric outcomes in twin pregnancies,” international journal of gynecology and obstetrics, 2016, 135(1): 22–27. day baird. new directions in the epidemiology of uterine fibroids. seminars in reproductive medicine, 2010; 28(3): 204–217. 2. laughlin sk, baird dd, savitz da et al. prevalence of uterine leiomyomas in the first trimester of pregnancy: an ultrasound-screening study. obstetrics and gynecology. 2009; 113(3): 630–35. 3. guo, segars, the impact and management of fibroids for fertility: an evidence-based approach,” obstetrics and gynecology clinics of north america, 2012; 39(4):521–533. 4. somigliana, vercellini, and r daguati, “fibroids and female reproduction: a critical analysis of the evidence,” human reproduction update, 2007; 13(5): 465–476. 5. hasan f, arumugam k, sivanesaratnam v. uterine leiomyomata in pregnancy. international journal of gynecology and obstetrics. 1991; 34(1):45–48. 6. hend, saleh, hala e et al. does uterine fibroid adversely affect obstetric outcome of pregnancy. biomed research international; 2018; 18(1): 1-5. 7. klatsky, tran nd, caughey ab et al. fibroids and reproductive outcomes: a systematic literature review from conception to delivery. american journal of obstetrics and gynecology. 2008; 98(4): 357–66. 8. mj stout, ao odibo, as graseck, leiomyomas at routine second-trimester ultrasound examination and adverse obstetric outcomes, obstetrics gynecology, 2010 ; 116(1): 1056–63. 9. cu eze, ea odumeru, k ochie et al. “sonographic assessment of pregnancy co-existing with uterine leiomyoma in owerri, nigeria,” african health sciences, 2011, 13( 2): 453–460. 10. ciavattini a, clemente n, delli carpini,et al, number and size of uterine fibroids and obstetric outcomes. the journal of maternal-fetal & neonatal medicine. 2015; 28(4):484–88. pregnancy outcome with fibroid uterus jiimc 2020 vol. 15, no.3 176 original�article abstract objective: to determine the protective role of pomegranate juice (pj) and pomegranate peel extract (ppe) on steroid induced serum creatinine level in mice. study design: randomized control trial. place and duration of study: department of anatomy, army medical college rawalpindi, in collaboration with st th the national institute of health (nih), islamabad, from may 1 to june 30 , 2015. materials and methods: forty healthy mice (balb/c strain), weighing 25-30 gms on average were randomly divided into four groups, each group having five male and female mice. group a was control group and groups b, c and d were experimental groups. mice in experimental groups were injected nandrolone decanoate, 1 mg/100 gm body weight, intramuscularly in the hind limb once a week for 8 weeks. mice in experimental group c were also given pomegranate juice daily, 3ml/kg body weight by oral gavage tube for 8 weeks. mice in experimental group d were given pomegranate peel extract daily, 200mg/kg bodyweight through oral gavage tube for 8 weeks. after eight weeks 5ml blood was drawn from mice through cardiac puncture just before the sacrifice of animals. data were entered and analyzed by using spss version 21. anova test was applied for intergroup comparison of quantitative variables. p-value of <0.05 was taken as significant. results: serum creatinine level was significantly higher in experimental group b. it was improved statistically when compared with pomegranate juice and pomegranate peel extract 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 equally ameliorate the steroid induced effects on serum creatinine level in mice. key words: androgenic anabolic steroids, pomegranate juice, pomegranate peel extract, serum creatinine level. generally considered as those associated with masculinization. recently, more than hundred aas drugs have been developed. androgens and other appearance and performance enhancing substances are abused worldwide. survey among people attending gyms equipped for bodybuilding, the proportion of aas's users was around 25–50%. aas drugs cause ethical problems when they are used to increase performance by sportsmen in competitions and are often misused and self-administered by bodybuilders to rapidly increase muscle mass. androgen abuse first spread from elite athletics and into the general population in the 1980s, and thus the oldest users – those who began androgens as youths in the 1980s – are only now reaching middle age, with consequently increasing risk of long-term adverse effects. restrained usage of aas may also induce serious side effects such as cardiovascular system failure, prostate gland diseases, lipid metabolic disorders or 1 insulin sensitivity. introduction androgenic anabolic steroids (aas) are synthetic drugs closely related to the hormone testosterone, capable of increasing muscle mass and physical strength. the anabolic effects of aas are associated with protein synthesis in bone and skeletal muscle while androgenic effects of these hormones can be protective role of pomegranate juice and its peel extract on steroid induced raised serum creatinine in mice 1 2 3 4 5 humaira ali , nomana mahmood , gulshan trali , khadija qamar , zarmina saga correspondence: dr. col khadija qamar professor & hod, anatomy army medical college national university of medical sciences, rawalpindi 1 3 department of anatomy/biochemistry hi-tech medical college national university of medical sciences, rawalpindi 2 department of anatomy wah medical college national university of medical sciences, rawalpindi 4 department of anatomy army medical college national university of medical sciences, rawalpindi 5 department of anatomy rawal institute of health sciences, islamabad funding source: nil; conflict of interest: nil received: dec 30, 2016; revised: mar 10, 2017 accepted: mar 10, 2017 pomegranate juice and serum creatinine leveljiimc 2017 vol. 12, no.1 29 nandrolone decanoate (nd) is the conjugation of nandrolone and decanoic acid. chemical name of nandrolone decanoate is 19-nortestosteron decanoate. its trade names are decadurabolin (dd), deca-durabol and retabolil. nd is available as both intramuscular (i/m) and subcutaneous (s/c) injections, dissolved in a vegetable oil vehicle and 2 produced under 25-200mg /ml dose range. such injections provide continuous androgen release into the blood stream and have remained the main route of pharmacological androgen therapy (pat) for the last few decades. therapeutic uses of these substances include the treatment of hypogonadism, as in men, androgens are necessary for reproductive function as well as they play a vital role in cognitive function and a feeling of well-being. they are also beneficial in bone mineralization, some muscle wasting disorders, bone marrow failure syndromes, osteoporosis in 3 postmenopausal women and aplastic anemias. besides having therapeutic effects, aas have been recognized to produce some undesirable effects, most documented of which include elevated blood pressure, cardiac arrhythmias, myocardial infarction, altered rbc morphology, cholestatic jaundice, h e p a t o c e l l u l a r hy p e r p l a s i a a n d a d e n o m a . furthermore, male reproductive side effects are testicular atrophy, gynecomastia, compromised spermatogenesis, masculinization and menstrual 4 disorders in female. although aas are taken only on prescription, but in some countries they are sold illegally. athletes use these drugs to improve their stamina and performance; this is known as “doping”, which is banned by international olympic committee. a variety of aas are often taken simultaneously, this is called “stacking” and drugs are taken in doses that cause ten to hundred times increase in androgen concentrations, and this apparently describes the 5 increase in toxic effects. pomegranate is the figure and icon of the historical city of “granada” in spain – from which the city acquires its name. in earliest times it was mentioned as possessing powers of fertility, abundance and good luck. apart from being eaten fresh, pomegranates are used to make juice, which is a worldwide popular beverage as well. about 100 g arils provide 72kcal of energy, 7mg vitamin c, 16.6g carbohydrate, 1.0g protein, 1mg sodium, 379mg potassium, 12mg magnesium, 13mg calcium, 0.7mg iron, 0.17mg copper and 0.3mg niacin. pomegranate peel is a great natural source of phenolic compounds such as gallotannins, anthocyanins, free ellagic acid, ellagic acid glycosides, ellagitannins, punicalagin and punicalin. numerous studies have demonstrated the antihelminthic, antimicrobial, and antioxidant potentials of pomegranate juice and peel extract ingredients, suggesting their protective and 6 curative role. pathophysiology in kidney, liver and heart are often associated to oxidative stress, as these are major organs involved in drugs metabolism, detoxification and excretion. this oxidative stress is described by interruption of control regarding redox signaling. a cellular damage and lipid peroxidation products lead to an inflammatory response. this study was conducted to observe the nephrotoxic effects of aas, to cause awareness especially, in young abusers. when prescribed in chronic illnesses, aas have both therapeutic as well as undesirable effects side by side. the present study was planned to determine the protective role of pomegranate juice (pj) and pomegranate peel extract (ppe) on steroid induced serum creatinine level in mice. materials and methods this randomized control trial was conducted in the department of anatomy, army medical college, rawalpindi, in collaboration with national institute st th of health (nih), islamabad from 1 may30 june 2015. experimental protocols were carried out with the approval of ethical committee of centre for research in experimental and applied medicine (cream), army medical college, rawalpindi. forty healthy male and female balb/c mice average weighing 25-30 gms, were randomly divided into four groups, each having five male and five female animals. they were housed in nih under controlled environment of light and temperature, and were fed with nih standard laboratory diet for eight weeks. group a served as a control group and groups b, c and d served as experimental groups. mice in experimental groups b, c and d were injected nd at the dose of 1 mg/100 gm body weight, as a single intramuscular injection in the hind limb once a week 7 for 8 weeks. in addition, mice in experimental group jiimc 2017 vol. 12, no.1 30 pomegranate juice and serum creatinine level c was also given pj at the dose of 3ml/kg body weight 8 by oral gavage tube for 8 weeks daily, and mice in experimental group d was given ppe at the dose of 200mg/kg body weight by oral gavage tube for 8 9 weeks daily. preparation of pomegranate juice: the fresh and seasoned pomegranate fruits were purchased from a local market. they were washed thoroughly and peeled manually. juice was prepared by using an electrical blender. as seeds cannot be manually separated, juice was filtered through a filter paper. it was stored at-20°c after diluting with distilled water 10 to volume of 1:3, at-20°c. in this study, 3ml of juice is dissolved in 27ml of plain water to make 30ml solution and 1ml was given to each mouse by gastric tube. preparation of pomegranate peel extract: pomegranate peels were manually separated, sun dried and grounded to powder. extract was prepared by mixing the powder (25g), by using a magnetic stirrer, with 100ml of methanol at 30°c for 1hr. first it was was filtered to remove the peel particles, and then the extracts was pooled and concentrated 11 under vaccum at 40°c. in this study, 5.6mg of extract was dissolved in 2ml of plain water and was given to each mouse by a gastric tube. five ml sample of blood was taken through cardiac 12 puncture in a test tube (figure 1), for the quantitative measurement of serum creatinine level just before the sacrifice of the animals. after collection, the blood was centrifuged and serum was collected. the blood samples were labeled according to the groups as control group a and experimental groups b, c and d. serum creatinine level were measured on spectrophotometer using enzymatic method. data was entered and analyzed by using spss version 21. anova test was applied for intergroup comparison of quantitative variables. pvalue of <0.05 was taken as significant. results results of experimental groups b, c and d were compared with control group a and with each other. mean serum creatinine level ±sd of control group a was 0.130±0.048mg/dl, and in experimental groups b , c a n d d i t w a s 1 . 0 9 ± 0 . 2 8 0 m g / d l , 0 . 3 6 0 ± 0 . 1 4 2 m g / d l a n d 0 . 3 5 0 ± 0 . 2 1 7 m g / d l respectively (table i). intergroup comparison was statistically significant when control group a was co m p a re d w i t h ex p e r i m e nta l g ro u p b ( p value=0.000*) and experimental group c (pvalue=0.053) but there was no significant difference when compared with experimental group d (pvalue=0.069). statistical significance was seen when experimental group b was compared with experimental groups c and d (p=0.000* in both cases). when experimental group c was compared with control group a (pvalue=0.053) statistical difference was noted but no statistically significant difference was seen when experimental groups c and d were compared with each other (p-value=0.999). jiimc 2017 vol. 12, no.1 table i: mean values of serum crea�nine level in control group a and experimental groups b, c and d. fig 1: blood sample collec�on for serum crea�nine es�ma�on discussion the father of medicine, hippocrates, about 25 centuries ago, stated, “let food be the medicine and let medicine be the food”. in regard to this statement, globally, the interest in nutraceuticals has increased widely, and this plays a vital role in health management. numerous studies have shown the beneficial effects of many vegetables, fruits, pulses, 13 spices and herbs. pomegranate has achieved the title of “superfood'', due to its presumed safety and potential nutritional as well as therapeutic benefits. pomegranate juice contains phenolic compounds such as anthocyanins, 31 pomegranate juice and serum creatinine level improvement in experimental groups c and d is attributed to pomegranate's ability to lower the oxidative stress. edible part of pomegranate fruit is rich in vitamin c and phenolic compounds, which are 17 strong antioxidants , and this was verified by riezzo et al., 2014 who reported an increase in the malondialdehyde (mda) level (marker of lipid peroxidation) as well as enhanced activity of antioxidant enzymes (gr and gpx) in the pomegranate administered groups, resulting in the increased ability of the kidneys to scavenge toxic free radicals such as hydrogen peroxide and lipid 18 peroxides. furthermore, pj considerably reduced the concentration of pro-inflammatory chemokines like il-6, il-12p40, il-1βand cytokines, thus reducing inflammation and markedly improved kidney and 19 liver functions. this was also in agreement with the results of study conducted by balbir et al., 2011, who described that oxidative stress plays a vital role in developing chronic complications in case of interstitial nephritis and it is related to increased lipid peroxidation, which can induce fragmentation of dna leading to apoptosis in renal tubules causing an end stage renal disease. pomegranate peel extract consumption at the dose of 0.5ml/day for 12 weeks considerably reduced both the occurrence and severity of collagen-induced interstitial nephritis in mice. high l e v e l o f p hy t o c h e m i c a l s ( a n t i ox i d a n t s ) i n pomegranate could enhance the reduction of free radicals inside the cells, to protect the kidney tissue 20 from oxidative stress damage. these findings were in accordance with another study conducted by sastravaha and colleagues who demonstrated the beneficial effect of ppe by reducing cytokine activity, in patients having periodontitis. patients suffering from this type of oral i n f l a m m a t i o n r e c e i v e d i n t r a g i n g i v a l p p e impregnated chips which resulted in reduced inflammatory cytotoxic cytokines (il-1beta, il-6 and 21 tnf-α) levels few months after treatment. the reno-protective roles of pomegranate in clinical trials were chiefly associated to its antioxidant and antiinflammatory properties. this opinion was also reinforced by the findings of viuda-martos et al., 2013 who suggested that ppe activates the antiinflammatory responses of the immune system 22 within the cells. jiimc 2017 vol. 12, no.1 ellagic acid, gallic acid, glucose, ascorbic acid, rutin, iron, and amino acids which have been shown to scavenge free radicals, decrease lipid peroxidation and macrophage oxidative stress, as well as increase 14 the plasma antioxidant capability in humans. the objective of this study was to observe the ameliorative effect of two forms of pomegranate on the steroid induced changes in serum creatinine level in mice. it was found that the difference of serum creatinine level in all animals of experimental group b in comparison with control group a was statistically significant. statistical significance was also seen when experimental groups c and d were compared with control animals, although marked improvement was seen in both these experimental groups. drug related renal damage is acquiring a lot of attention these days as it is the commonest cause of crd (chronic renal disease) in teenagers. it has been reported that seven out of ten bodybuilders abusing high doses of aas's were diagnosed with end-stage 15 renal disease. pathophysiology in kidney, liver and heart are often associated with oxidative stress, as these are major organs responsible for drugs detoxification, metabolism and excretion. this oxidative stress causes interruption of control regarding redox signaling. a cellular damage and lipid peroxidation products lead to an activation of inflammatory signaling cascades and increases pro inflammatory cytokine production, causing noticeable decrease in capability of some organs to tolerate injury. reactive oxygen species (ros), e.g. superoxide and hydrogen peroxide (h o ), can be 2 2 formed by xanthine-oxidase, mitochondrial electron transport chain or cytochrome p-450, as a product of metabolism, or directly by the nicotinamide adenine dinucleotide phosphate-oxidase (nadph-oxidase) (nox) group of enzymes. the biological functions of nox are known in various cellular processes, such as cellular differentiation and multiplication, synthesis and release of h o r m o n e s , e n z y m e f o r m a t i o n , b u t t h e i r overexpression is related to pathophysiology of various diseases. nox enzymes are transmembrane proteins and are situated at nuclear membrane, near to dna, increasing the possibility of its damage. antioxidant systems react with these molecules forming less reactive compounds to maintain ros 16 levels in limits. 32 pomegranate juice and serum creatinine level 28:273-83. 6. saad h, charrier-el bouhtoury f, pizzi a, rode k, charrier b, ayed n. characterization of pomegranate peels tannin extractives. industrial crops and products. 2012; 40: 23946. 7. frankenfeld sp, de oliveira lp, ignacio dl, coelho rg, mattos mn, ferreira ac, et al. nandrolone decanoate inhibits gluconeogenesis and decreases fasting glucose in wistar male rats. journal of endocrinology. 2014; 220: 14353. 8. moneim ae, dkhil ma, al-quraishy s. studies on the effect of pomegranate (punica granatum) juice and peel on liver and kidney in adult male rats. journal of medicinal plants research. 2011; 5: 5083-8. 9. parmar hs, kar a. medicinal values of fruit peels from citrus sinensis, punica granatum, 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: 376-81. 10. faria a, monteiro r, mateus n, azevedo i, calhau c. effect of pomegranate (punica granatum) juice intake on hepatic oxidative stress. european journal of nutrition. 2007 ; 46: 271-8. 11. el-habibi em. renoprotective effects of punica granatum (pomegranate) against adenine-induced chronic renal failure in male rats. life sci j. 2013; 10: 2059-69. 12. beeton c, garcia a, chandy kg. drawing blood from rats through the saphenous vein and by cardiac puncture. jove (journal of visualized experiments). 2007; 7: 266. 13. cristofori v, caruso d, latini g, dell'agli m, cammilli c, rugini e, et al. fruit quality of italian pomegranate (punica granatum l.) autochthonous varieties. european food research and technology. 2011; 232: 397-403. 14. arun n, singh dp. punica granatum: a review on pharmacological and therapeutic properties. international journal of pharmaceutical sciences and research. 2012; 3: 1240. 15. herlitz lc, markowitz gs, farris ab, schwimmer ja, stokes mb, kunis c, et al. development of focal segmental glomerulosclerosis after anabolic steroid abuse. journal of the american society of nephrology. 2010; 21: 163-72. 16. turillazzi e, perilli g, di paolo m, neri m, riezzo i, fineschi v. side effects of aas abuse: an overview. mini reviews in medicinal chemistry. 2011; 11: 374-89. 17. jilanchi s, nematbakhsh m, mazaheri s, talebi a, zolfaghari b, pezeshki z, et al. pomegranate flower extract does not prevent cisplatin-induced nephrotoxicity in female rats. international journal of preventive medicine. 2014; 5: 1621–5. 18. riezzo i, turillazzi e, bello s, cantatore s, cerretani d, di paolo m, et al. 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: 97-106. 19. dahlawi h, mahy nj, clench mr, le maitre cl. bioactive actions of pomegranate fruit extracts on leukemia cell lines in vitro hold promise for new therapeutic agents for leukemia. nutrition and cancer. 2012; 64: 100-10. jiimc 2017 vol. 12, no.1 future researchers may focus their attention to explain aas's (anabolic androgenic steroids) and punica granatum interactions in conditions of long term co-exposure and their consequences for health in human population. additional studies are recommended to see if the effects noticed in the current study are transitory or long-lasting in order to evaluate the use of punica granatum as a potential agent to be used as antidote along with anabolic steroids in clinical settings. conclusion there was significant increase in serum creatinine level of animals in experimental group b, indicating renal damage, and improvement was seen in pomegranate administered experimental groups c and d. therefore, it is concluded that pomegranate in both forms has equal antitoxic effects on steroid induced renal damage. advance studies are required to be conducted to explain the exact mechanism of action, in protection provided by punica granatum, on histomorphology of kidneys during steroid induced renal damage. acknowledgement special thanks to dr hussain ali, scientific officer animal house, nih, islamabad for his expert advices and support in conducting this study, and mr. muhammad saad shoaib for his assistance in animal handling both during drug administration and dissection. references 1. hijazi mm, azmi ma, hussain a, naqvi sn, perveen r, hijazi s. androgenic anabolic steroidal-based effects on the morphology of testicular structures of albino rats. pakistan j. zool. 2012; 44: 1529-37. 2. erdal t, seyfullah h. the administration of nandrolone decanoate may cause multiple organ failure. ovidius university annals, series physical education and sport/science, movement and health. 2013; 13: 784. 3. brenu ew, mcnaughton l, marshall-gradisnik sm. is there a potential immune dysfunction with anabolic androgenic steroid use?: a review. mini reviews in medicinal chemistry. 2011; 11: 438-45. 4. mutalip ss, singh gks, shah am, mohamad m, mani v, hussin sn. histological changes in testes of rats treated with testosterone, nandrolone, and stanozolol. international journal of reproductive biomedicine. 2013; 11: 653-8. 5. hassan na, salem mf, sayed ma. doping and effects of anabolic androgenic steroids on the heart: histological, ultrastructural, and echocardiographic assessment in strength athletes. human & experimental toxicology. 2009; 33 pomegranate juice and serum creatinine level therapy. j int acad periodontol. 2005; 7: 70-9. 22. v i u d a m a r to s m a , pé rez a l va rez ja , s e n d ra e , fernández-lópez ju. in vitro antioxidant properties of pomegranate (punica granatum) peel powder extract obtained as coproduct in the juice extraction process. journal of food processing and preservation. 2013; 37: 7726. jiimc 2017 vol. 12, no.1 20. gurman ab, fuhrman b, moscovici yb, markovits d, aviram m. consumption of pomegranate decreases serum oxidative stress and reduces disease activity in patients with active rheumatoid arthritis: a pilot study. the israel medical association journal: imaj. 2011; 13: 474-9. 21. sastravaha g, gassmann g, sangtherapitikul p, grimm wd. adjunctive periodontal treatment with centella asiatica and punica granatum extracts in supportive periodontal 34 pomegranate juice and serum creatinine level jiimc december 2016 page 33 page 34 page 35 page 36 page 37 page 38 original�article abstract objective: to determine the combined cardioprotective effects of nigella sativa and enalapril in doxorubicininduced cardiotoxicity in rats. study design: experimental randomized control trials. place and duration of study: this research was carried out from september 2020 to august 2021, in the department of pharmacology, in collaboration with the national institute of health (nih) islamabad, pakistan. materials and methods: for this experiment, 4 groups of adult male rats were taken, each containing 10 rats. group 1 rats acquired a normal diet without any medication throughout the experiment. on day 8 (after acclimatization) cardiotoxicity was induced in groups 2, 3, and 4 rats by administering doxorubicin 5mg/kg intraperitoneally for 3 consecutive days. after the confirmation of cardiotoxicity, group 3 rats were administered only angiotensin-converting enzyme inhibitors (acei) enalapril 2mg/kg, while group 4 rats were given a combination of nigella sativa 100mg/kg and enalapril 2mg/kg orally for 14 days. baseline blood samples were taken on day 0 to obtain normal values of cardiac troponin t ( ctnt), cardiac troponin i (ctnt), and ck-mb enzyme. to confirm cardiotoxicity 2nd sampling was done on day 11, and the final sampling was done through cardiac puncture on day 26. serum biochemical estimation was done and data were analyzed through spss 22 by using one-way anova and paired t-test. a p-value < 0.05 was believed statistically considerable. results: enalapril alone produced significant cardioprotective effects as shown by the marked reduction in ctnt, ctni, and ckmb levels in group 3 (p<0.05), but combined administration of nigella sativa and enalapril in group 4 mice produced a more significant reduction in trop t, trop i, and ck-mb levels (p <0.05). conclusion: nigella sativa and enalapril in combination significantly lower cardiac enzyme in doxorubicininduced cardiotoxicity in rats. key words: cardiotoxicity, doxorubicin, enalapril, nigella sativa. malignancies for years. the main concern about the use of this drug is its cardiac adverse effects because about twenty percent of patients who receive 1 doxorubicin can develop adverse cardiac effects. cardiomyocytes have a lesser capability to regenerate therefore, they are potentially more vulnerable to the long-term adverse effects of 2 doxorubicin. its cardiotoxicity occurs because of its quinone group-based metabolites that produce 3 reactive oxygen species and free radicals. cardiomyocytes are intrinsically more susceptible to oxidative stress, so these free radicals & reactive oxygen species impose mitochondrial and nuclear 4,5 dna lesions in cardiomyocytes. doxorubicinmediated reactive oxygen species also stimulate mitogen-activated protein kinases, which induce the expression of several proapoptotic proteins. these processes lead to cardiomyocyte death either by necrosis or apoptosis and cause the release of introduction doxorubicin is an extensively used anthracycline for the treatment of several solid tumors and childhood cardioprotective effects of nigella sativa and enalapril in doxorubicin-induced cardiotoxicity 1 2 3 4 5 6 uzma naeem , salma saleem , rabia iftikhar malik , alia rehman , nimra ijaz , aqsa tazarat correspondence: dr. uzma naeem department of pharmacology islamic international medical college riphah international university, islamabad e-mail: uzma.naeem@riphah.edu.pk 1 department of pharmacology islamic international medical college riphah international university, islamabad 2,6 department of pharmacology mohi ud din islamic medical college, mirpur ajk 3 department of pharmacology shifa college of medicine, islamabad 4 department of pharmacology muhtarma benazir bhutto medical college, mirpur, ajk. 5 department of pharmacology fazaya medical college, islamabad received: july 28, 2022; revised: november 27, 2022 accepted: november 29, 2022 cardioprotection with nigella sativa jiimc 2022 vol. 17, no.4 264 doi: https://doi.org/10.57234/1426 cardio-specific contractile proteins; cardiac troponins i (ctni), cardiac troponin t (ctnt), and 6 creatinine kinase mb into the circulation. cardiotoxicity is more specifically expressed by ctni and ctnt because they are exclusively expressed in the myocardium and are more abundant than ck-mb in the myocardium. therefore, the quantitative approximation of these sensitive biomarkers is used for the presence of cardiotoxicity at the subclinical as 7,8 well as clinical stages. several strategies have been recommended for the prevention of doxorubicininduced cardiotoxicity. still, the protection deliberated is not always effective and is expensive 9 as well. several clinical studies and meta-analyses assessing the use of angiotensin-converting enzyme inhibitors (aceis) in anthracycline-induced cardiotoxicity have recently been revealed, and these studies suggested that aceis are effective as cardioprotective agents because of their antioxidant 10,11 and anti-inflammatory properties. nigella sativa has been used medicinally for decades because it is a marvel herb with a wide range of pharmacological properties and astonishing 12 religious background. this herb has proven antioxidant, anti-inflammatory, cardioprotective, hepatoprotective, antidiabetic, neuroprotective, 13 and anticancer, effects among others. the cardioprotective effects of both nigella sativa and enalapril have been studied and proved separately, but according to the best of our knowledge, their combined effects are not yet explored. so, this study aimed to evaluate the extent of the protective role exerted by nigella sativa in the prevention of cardiotoxic effects of doxorubicin in combination with an acei enalapril. materials and methods this experimental randomized controlled study was performed from september 2020 to august 2021 in the department of pharmacology, after getting approval from the institutional review committee. this study was initiated on a total of 40 healthy male albino rats weighing 200-250 g, 8 weeks of age, and with normal ctni, ctnt, and ckmb levels. rats were placed in well-aerated cages for acclimatization, a room temperature of 22 ± 2 ° c, and a 12-hour light14 dark cycle was maintained. rats were randomly divided into 4 groups of 10 rats each. group 1, the control group, consumed a normal diet and tap water throughout the experiment while group 2, 3, and 4 rats were given three intraperitoneal injections of doxorubicin at a dose of 5mg/kg for three 15 consecutive days (cumulative dose 15 mg/kg). after the confirmation of cardiotoxicity by measuring and analyzing ctni, ctnt, and ck-mb levels; group 3 rats 16 were given enalapril 2mg/kg/day alone while group 4 rats were given nigella sativa seed powder 17 100mg/kg/day and enalapril 2mg/kg/day dissolved 16 in distal water for 14 days. nigella sativa and enalapril powders were prepared at the riphah pharmaceutical science institute (rips) in islamabad. on day 0, blood samples were taken for a baseline evaluation, and on day 11, a second sampling was done for the confirmation of cardiotoxicity in groups 2, 3, and 4. the final sampling th happened on the 26 day of the experiment, all samplings were accomplished by cardiac puncture. the sample was centrifuged at 3000 rpm for 5 minutes, and the serum was separated and stored at -8 ºc in eppendorf tubes for further biochemical analysis. ctnt, ctni, and ck-mb were assessed using the chemistry analyzer, micro lab 200 (merck). these parametric data were statistically analyzed by using spss 22. the mean and standard error of the mean was calculated for all four groups. one way anovas were done for comparison among different groups while comparison between two groups was done by using the paired t-test. results were considered significant at a p-value less than 0.05. results cardiac troponin i (ctni) and cardiac troponin t (ctnt) were measured in ng/l ±sd while ck-mb activity was measured in u/i ±sd. on day 11 the confirmation of cardiotoxicity in groups 2, 3, & 4 was figure 1: comparison of biomarkers among groups on days 0 & 11. cardioprotection with nigella sativa jiimc 2022 vol. 17, no.4 265 doi: https://doi.org/10.57234/1426 done by the results shown in figure 1. the p-values for ctni, ctnt, and ckmb were 0.001, 0.003, and 0.000 respectively. when we analyzed the 26th-day results of all groups, remarkably significant improvement was found in the cardiotoxic profiles of groups 3 & 4, their parameters were almost equal to normal control values and their day 0 levels (table 1). doxorubicin's cardiotoxicity is a piece of evidence u s e d by n u m e ro u s re s e a rc h e rs to i n d u c e cardiotoxicity in different animal models. lin and his associates induce cardiotoxicity in rats with doxorubicin, they use an accumulative dose of 18 18mg/kg over 2 weeks. aziz and his colleagues observed similar changes in biomarkers following the use of doxorubicin as a single intraperitoneal 19 injection in rats. sawyer and his colleagues observed such kinds of effects in their preclinical st u d i e s b o t h i n v i t ro a n d i n v i vo, w h i l e georgakopoulos and coworkers observed the effects of doxorubicin in clinical studies on lymphoma patients and established that doxorubicin caused a significant and dose-dependent cardiomyocyte 20,21 apoptosis and myocytes death. another study by eisvand et al also supported the cardiac enzyme disruption after introducing a single dose of 22 doxorubicin in rats. in our study the rationale behind the measurement of ckmb was its historical value but our stress remained on ctni & t as more specific and sensitive biomarkers, these markers are considered the gold standard biomarker of cardiac 23 injury in all mammalian species. the second part of our study was a comparative analysis of the cardioprotection provided by enalapril alone and in combination with nigella sativa. the group 3 animals were treated with e n a l a p r i l f o r 1 4 d a y s a n d t h e y c o n f e r cardioprotection. the cardioprotective effects of enalapril and other aceis are well established. in a r e c e n t s t u d y, g h a s e m i a n d h i s f e l l o w s comprehensively review the clinical trials performed on the prevention of doxorubicin-induced cardiotoxicity. they conclude that aceis plus doxorubicin are the best treatment for preventing 24 cardiotoxicity in these patients. divergent effects of enalapril and eplerenone in primary prevention against doxorubicin-induced cardiotoxicity were studied by hullin et al and they concluded that primary prevention with enalapril preserves left 25 ventricular morphology and function in mice. georgakopoulos et al studied the cardioprotective effects of metoprolol and enalapril in lymphoma 21 patients. adıyaman used the same dose of nigella sativa seed powder for the prevention of doxorubicin17 induced toxicity while we use it for the treatment table i: comparison among serum biomarkers of all groups on days 0 and 26. *significant p-value to confirm our hypothesis, we further compared the serum markers of group 3, & 4 and we observed pvalues of 0.000, 0.023, and 0.000 respectively for trop t, trop i, & ckmb levels. these results showed that nigella sativa increased the efficacy of enalapril. figure 2: comparison of serum markers of groups 3 & 4 on day 26. discussion in the present study, we observed that nigella sativa potentiates the cardioprotective effects of enalapril in doxorubicin-induced cardiotoxic rats as represented by the comparison of the cardiotoxicity indicating biomarkers. enalapril alone also proved cardioprotective. we artificially induced acute cardiotoxicity by a cumulative dose of doxorubicin 15 mg/kg/day in groups 2, 3, and 4 rats, this cardiotoxicity was confirmed by significant rises in serum biomarkers of cardiac injury including ctni, ctnt, & ckmb. cardioprotection with nigella sativa jiimc 2022 vol. 17, no.4 266 doi: https://doi.org/10.57234/1426 and in combination with enalapril to define their combined effects. a study conducted by el-kerdasy also showed the beneficial effects of nigella sativa and aceis on myocardial fibrosis induced by 26 lipopolysaccharide. cardioprotective effects of the ethanolic extract of nigella sativa (800mg/kg/day) were studied by hassan and his colleagues, they observed improvement in different cardiac 27 markers. extensive literature is present regarding the use of this herb in animals but very few studies have been done on humans and this is the need of time. conclusion nigella sativa and enalapril in combination significantly lower cardiac enzyme in doxorubicininduced cardiotoxicity in rats. so, nigella sativa can be used as an adjunct with enalapril in the treatment of doxorubicin-induced cardiotoxicity. references 1. khalilzadeh m, abdollahi a, abdolahi f, abdolghaffari ah, dehpour ar, jazaeri f. protective effects of magnesium sulfate against doxorubicin-induced cardiotoxicity in rats. life sci. 2018;207:436-441. doi:10.1016/j.lfs.2018.06.022 2. koleini n, kardami e. autophagy and mitophagy in the context of doxorubicin-induced cardiotoxicity. oncotarget. 2017;8(28):46663-46680. doi:10.18632/oncotarget.16944 3. bhagat a, kleinerman es. anthracycline-induced cardiotoxicity: causes, mechanisms, and prevention. adv exp med biol. 2020;1257:181-192. doi: 10.1007/978-3030-43032-0_15. pmid: 32483740. 4. mcgowan jv, chung r, maulik a, piotrowska i, walker jm, 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suter tm. modulation of anthracycline-induced myofibrillar disarray in rat ventricular myocytes by neuregulin-1β and cardioprotection with nigella sativa jiimc 2022 vol. 17, no.4 267 doi: https://doi.org/10.57234/1426 anti-erbb2:potential mechanism for trastuzumab-induced cardiotoxicity. circulation. 2010;105:1551-1554. 21. georgakopoulos p, kyriakidis m, perpinia a, karavidas a, zimeras s, mamalis n, et al. the role of metoprolol and enalapril in the prevention of doxorubicin-induced cardiotoxicity in lymphoma patients. anticancer res. 2019 oct;39(10):5703-5707. doi: 10.21873/anticanres.13769. pmid: 31570470. 22. eisvand f, imenshahidi m, ghasemzadeh rahbardar m, tabatabaei yazdi sa, rameshrad m, razavi bm, et al. cardioprotective effects of alpha-mangostin on doxorubicin-induced cardiotoxicity in rats. phytother res. 2022 jan;36(1):506-524. doi: 10.1002/ptr.7356. epub 2021 dec 27. pmid: 34962009. 23. ding l, li d, li m, zhao d, govindhan a, santhoshkumar m, et al. an in vivo and in 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benha med j. 2021;0(0):0–0. 27. hassan mq, akhtar m, ahmed s, ahmad a, najmi ak. nigella sativa protects against isoproterenol-induced myocardial infarction by alleviating oxidative stress, biochemical alterations, and histological damage. asian pac j trop biomed [internet]. 2017;7(4):294–9. available from:http://dx.doi.org/10.1016/j.apjtb.2016.12.020 cardioprotection with nigella sativa jiimc 2022 vol. 17, no.4 conflict of interest authors declared no conflicts of interest. grant support and financial disclosure authors have declared no specific grant for this research from any funding agency in public, commercial or nonprofit sector. data sharing statment the data that support the findings of this study are available from the corresponding author upon request. this is an open access article distributed under the terms of the creative commons attributionnoncommercial 2.0 generic license. 268 doi: https://doi.org/10.57234/1426 original�article abstract objective: to evaluate the combined effect of dexamethasone, and a phosphodiesterase inhibitor, pentoxifylline, in aversion of lps/endotoxin induced hepatotoxicity in balb/c mice. study design: an experimental study. place and duration of study: department of pharmacology and therapeutics, army medical college, nust, rawalpindi over a period of 3 months (march 2015-june 2015). materials and methods: thirty animals were divided into 5 groups, each group having six animals. the animals were injected intraperitoneally with normal saline (group 1), lipopolysaccharide(lps) of serotype e.coli (group2), low dose steroid-dexamethasone after lps (3mg/kg of body weight)(group 3) , pentoxifylline (ptx) (75 mg/kg of body weight) (group 4) after lps and in the last group coadministration of dexamethasone and pentoxifylline after lps (group 5).the extent of liver damage was adjudged via serum alanine aminotransferases (alt) and aspartate aminotransferase (ast) estimation along with histopathological examination of liver tissue. results: lipopolysaccharide administration in animals of group 2 resulted in marked hepatotoxicity as evident by statistically significantly escalated serum aminotransferases and pronounced inflammation on liver tissue cross section examination. dexamethasone (group 3). pentoxifylline (group 4) and combined treatment (group 5) abated considerably serum alt levels at 17 hours when compared to lps group (group 1) yielding a p value of ≤ 0.01 for each group. serum ast levels also declined statistically significantly giving a p value of ≤ 0.01 when lps group (group 1) is compared to group 3, 4 and 5 respectively. histological examination revealed that dexamethasone (group 3). pentoxifylline (group 4) and combined treatment (group 5) reduced inflammation and necrosis produced by lps in group 2. however combined treatment results were akin to individual drug therapy alteration. conclusion: treatment of lipopolysaccharide (lps/endotoxin) induced hepatotoxicity with dexamethasone, and phosphodiesterase inhibitor, pentoxifylline in lps/endotoxin showed encouraging results in our study. key words: dexamethasone, endotoxin, hepatotoxicity, lipopolysaccharides, pentoxifylline. causing systemic inflammation, tissue damage and sepsis. sepsis and related organ failure are a global health crisis leading to high morbidity and mortality. though difficult to determine the disease burden, almost 30 million people suffer from sepsis annually and 6 million lose their lives to this deadly disease and risk is likely highest in low and middle-income 1,2 countries. those who do survive are left with lifechanging effects, such as post-traumatic stress disorder (ptsd), chronic pain and fatigue, and organ dysfunction and/or amputations. initially gram-negative bacteria were the main culprit of sepsis and associated organ failure but with the more utilization of invasive procedures and increasing ratios of hospital acquired infection, gram 3 positive bacterial infections are also common. the eventual death in sepsis results from organ introduction human immune system where functions to protect our race from deadly infections, can also produce an exaggerated and overwhelming immune response dexamethasone and pentoxifylline combination therapy in aversion of lipopolysaccharide induced hepatotoxicity in balb/c mice 1 2 3 ammara khan , zahid azam chaudry , akbar waheed correspondence: ammara khan assistant professor department of pharmacology nawaz sharif medical college university of gujrat, gujrat e-mail: drammara19@gmail.com 1 department of pharmacology/ department of community 2 medicine nawaz sharif medical college, university of gujrat, gujrat 3 department of pharmacology islamic international medical college riphah international university, islamabad funding source: nil; conflict of interest: nil received: february 06, 2020; revised: february 03, 2021 accepted: february 09, 2021 dexamethasone and ptx in lps induced hepatoxicityjiimc 2021 vol. 16, no.2 79 failure and liver injury plays a pivotal role in commencement and augmentation of multiple organ failure. liver via hepatocytes (hcs), küpffer cells (kcs), and sinusoidal endothelial cells (secs plays a crucial part in endotoxin /bacteria scavenging, detoxification, and synthesizing proteins for metabolic, immune, and coagulation functions. the pathological part of gram-negative bacterial cell wall called lipopolysaccharide (lps), through its interaction with toll like receptors on kupffer cells, elicit production of inflammatory cytokines including tnf-alpha, various interleukins (ils), reactive oxygen-nitrogen species, lipid mediators like thromboxane a2, and proteases; all producing 4,7 hepatocytes dysfunction in counteraction to lps. studies document that low dose steroid therapy (300mg/day hydrocortisone or equivalent) expedite 8,10 shock reversal. it amends hemodynamic instability through up regulation of catecholamine receptors which were desensitized by high cortisol levels and 10,11 decline production of nitrous oxide. also reported that it markedly decreases inflammatory mediators tnf-alpha, il-10, il-6, il-8, c-reactive proteins, decline release of hydrogen peroxide from neutrophils, improves endothelial dysfunction, ameliorates coagulation disorder and reduces the 10,5 severity of organ failure including hepatotoxicity. pentoxifylline (ptx) is an all-around and wide range phosphodiesterase inhibitor and adenosine receptor agonist/antagonist. studies have demonstrated that pentoxifylline beneficial effects are attributed to reduction of lps induced production of tnf-α followed by decline in il-1β, il-12, il-8 and inducible nitric oxide synthase production with up-gradation of anti-inflammator y circle through il-10. pentoxifylline has demonstrated to reduce expression of icam-1 adhesion molecules on e n d o t h e l i a l c e l l s , d i m i n i s h e d n e u t r o p h i l s polarization, chemotaxis and degranulation, abated cytotoxicity of natural killer cells, contracted tlymphocytes cell proliferation, adhesion and trans endothelial migration and reduction of plasma 16 concentration of markers of apoptosis, fas/apo-1. till date the treatment of sepsis and associated hepatotoxicity include specific antibiotics, fluid therapy, and use of supportive care including steroids and vasopressors. invention of newer treatment modalities and reevaluation of previous strategies is the dire need of time to reduce disease burden globally. this study was aimed to discover the combined dexamethasone and pentoxif ylline therapy efficiency and compare with individual agent therapy in treatment of lipopolysaccharide induced hepatotoxicity in white albino mice. materials and methods it was an experimental study in which majority of the ex traneous factors like age, diet, gender, environment, health status, lightening and housing 17 conditions were accounted for. this study was carried out in the department of pharmacology and therapeutics, army medical college, nust, rawalpindi over a period of 3 months from march 2015 to june 2015. all experimental protocols described in this study complied with “centre of research in experimental and applied medicine (cream)” army medical college ethics review committee for animal experimentation. thirty bal/b mice weighing 40-50 grams, aged 8 to 12 weeks were used throughout the study. all animals were placed in traditional wire topped, square shaped mouse cages at 20-22°c with humidity maintained at 40-70%. contamination free fresh water and nutritionally adequate rodent pellet diet (containing 4-7% fat and 11-15% protein) was 17 provided. lipopolysaccharides (lps) from escherichia coli o111:b4 lps, provided by sigma chemicals, usa had been extracted by phenol method containing 16 % rna and 1% protein. we selected 10mg/kg of body 18 weight, intraperitoneally as our study dose. dexamethasone was purchased locally and we selected 3mg/kg of body weight, intraperitoneally as 15,18 our study dose. pentoxifylline was purchased from sigma aldrich chemical usa. after a pilot study, 75 mg/kg of body weight, intraperitoneally was well tolerated by animals and hence was taken as our study dose. other reagents used in study includes phosphate buffered normal saline for preparation of lipopolysaccharide solution, absolute ethanol, and normal saline for preparation of melatonin and 10% formaldehyde for preserving tissues. again, a pilot study was carried out to determine the hepatotoxic dose of lps in balb/b mice. a dose of 10mg/kg of body weight, intraperitoneally and time dexamethasone and ptx in lps induced hepatoxicityjiimc 2021 vol. 16, no.2 80 interval of 17 hours between lps administration and terminal sampling of mice proved effectual for reproduction of hepatotoxic model. animals were segregated into control group receiving intraperitoneal normal saline (group 1), in toxic group receiving 10mg /kg of body weight, intraperitoneally lps (group 2) and into dexamethasone treatment group receiving 3mg/kg of body weight, intraperitoneally two hours after lps administration (group 3). in group 4, due to rapid elimination kinetics of pentoxifylline, it was administered twice, first 2 hours after lps injection at a dose 75mg/kg of body weight and secondly seven hours after lps administration at the same dose. animals of group 5 were co-treated with dexamethasone and two doses of pentoxifylline at mentioned protocol, two hours after lps injection. the first blood sample at the start of experiment (zero hours) was taken from lateral tail vein of mouse as per protocols approved by institutional animal 19 care and use committee (iacuc). drop jar method utilizing 20% v/v isoflurane in propylene glycol solution-soaked cotton gauze in bell jar was selected for terminal anesthesia followed by cardiac puncture sampling through closed ventral approach and midline laparotomy for liver removal. tissue was immediately fixed in 10 % formaldehyde and blood samples were stored at 4°c for latter chemical analysis. septicemia led to variable histopathological changes in liver as reported by several studies, we decided to use ishak modified histological activity index as 20 scoring system. score of one to four ranked as moderate inflammation and severe inflammatory changes due to sepsis produced score of fifteen to eighteen. also, serum elevations in alt and ast levels were measured for the determination of hepatic injury. data was entered in statistical package for social sciences (spss) version 20. the results of the serum analysis were expressed as means + standard error of means. the statistical significance of differences between means were analyzed with one way analysis of variance (anova) followed by post-hoc tukey test. statistical difference between serum marker at initial and final hours were found using paired t-test. independent / unpaired t-test was utilized to access difference of serum markers at 17 hours on lps group with another. the result of histopathology was analyzed using the “chi-square test”. all values were considered statistically significant if “p value” was equal or less than 0.05. results serum alt and ast levels did not rise statistically significantly after administration of normal saline in mice of group 1 (control group) (table i). animal of group 2 receiving intraperitoneal lps were prostrated and worn out during seventeen hours of experimentation with serum alt and ast levels rising to much higher values, a statistically significant difference when compared to levels at zero hour (table i). serum alt and ast levels did not increase significantly at 17 hours blood sampling of mice in group 3 (dexamethasone after lps) and group 4(pentoxifylline after lps) (table i). similar results were seen with co-administration of dexamethasone and pentoxifylline in animals of group 5. serum alt levels again failed to rise at 17 hours yielding an insignificant p value (0.316). same was the case with serum ast yielding a p value of 0.142. (table i). table i: comparison of means and ±sem of serum alt and ast levels at zero and 17 hours of each group anova was run to analyze the effect of our treatment on serum alt and ast levels (table ii &iii). there was a significant difference between groups in serum alt and ast levels at 17-hour terminal blood sampling. a post hoc comparison was carried out using tukey hsd test that showed that mean serum alt levels (345.2 ±76.5 iu/l) at 17 hours of group 2 (lps) were significantly different from group 3, group 4, and group 5 (table ii &iii). however, our re s u l t i n d i cate d t h at d exa m e t h a s o n e a n d pentoxifylline combined in group 5 treatment is no different from individual drug treatment in group 3 and 4 respectively (table ii &iii). dexamethasone and ptx in lps induced hepatoxicityjiimc 2021 vol. 16, no.2 81 p value ≤ 0.05 is considered significant. histopathological examination: liver slides were observed through light microscope at 10x, 20x and 40x magnification and were assorted according to criteria described (ishak/knoddels criteria). histopathological analysis of sections of liver of six animals of group 1 depicted the normal lobular organization of mouse liver that is hepatic triad and hepatocytes cord radiating from central venule and were graded as normal according to ishak's criteria (figure 1). in group 2(lps), marked inflammatory changes consisting of cellular infiltrates, loss of cellular organizations and periportal inflammation were evident (figure 1). whereas cross-section e x a m i n a t i o n o f l i v e r s l i d e s o f g r o u p 3(dexamethasone after lps), group 4(pentoxifylline after lps) and group 5 (dexamethasone + pentoxifylline after lps) exhibited negligible inflammatory cells aggregation in and around few portal areas (figure 1). they were graded as minimal inflammation in liver. as both variables are categorical and sample size is large, the chi-square test of association was employed to ascertain the statistical worth between the groups and histological grading. most eloquent change was when group 2 (lps group) was compared to control group (group 1) with p value ≤ 0. 007.comparison of group 2 (lps group) with group 3 (dexamethasone after lps), group 4 (pentoxifylline after lps) group 4 (dexamethasone + pentoxifylline after lps) all yielded a statistically compelling difference as p value of ≤ 0.05 in each group. table ii: anova comparisons of mean serum alt levels (iu/l) at 17 hours of each group table iii: anova comparisons of mean serum ast levels (iu/l) at 17 hours of each group fig 1: mouse liver histology at 20x of group 1,2,3 and 4 clockwise. pv-portal vein, cv centarl vein and ha hepatic arteriole discussion considering the immense immune mediated reaction in sepsis induced hepatic failure, this study was designed to evaluate the protective effects of dexamethasone and pentoxifylline as a combination therapy. we have shown in our study that dexamethasone and pentoxifylline alone and as a combination therapy offers protection against lps induced hepatic dysfunction. both the agents significantly abated the lps induced spike in serum alt and ast levels. the marked inflammation seen on liver tissue histology was decreased to minimal to moderate inflammation by dexamethasone and p e n t ox i f y l l i n e a l o n e a n d i n c o m b i n a t i o n . dexamethasone hepatoprotective role in our findings is in coherent with other studies. wang et al in 2009 certified that dexamethasone hundred percent protected wild-type mice injected with high dexamethasone and ptx in lps induced hepatoxicityjiimc 2021 vol. 16, no.2 82 dose of lps (20mg/kg of body weight) from 21 lethality. aytac in 2014 also demonstrated that same dose of dexamethasone improved survival and 10 lessened liver injury in septic mice. our second experimental agent ,pentoxifylline through suppression of tnf-α production and pde inhibition, has been investigated in many inflammatory disorders including sepsis and retains favorable 22,23 results like our study. although evidence-based treatment protocols have been implemented across the world, sepsis with organ failure is still a health hazard in developing countries like pakistan. lipopolysaccharide (lps) activates host innate response through lipopolysaccharide binding protein (lbp) and cd14 receptors resulting in activation of kinases cascade with phosphorylation of series of adaptor proteins. in liver, tnf-alpha and il-1 are antecedent inflammatory cytokines followed by production of il-6, il-8, il-10, adhesion molecules and no synthase. there's also activation of endothelial cells promoting fibrin deposition in 7 sinusoids. as a result there is hepatocytes dysfunction in counteraction to lps. dexamethasone has been shown to markedly decrease the inflammatory mediators, decline release of hydrogen peroxide from neutrophils, improves endothelial dysfunction, ameliorates coagulation disorder, and reduces the severity of organ failure including hepatotoxicity in septic 10-15 patients. several mechanisms have been explained for this hepato-protective role in lps induced septicemia. studies have shown that dexamethasone induces production of antii n f l a m m a t o r y p r o t e i n s ( a n n e x i n 1 , m a p k 10-15 phosphatase and inhibitors of nf-kβ). studies have also documented that direct and indirect o rga n i zat i o n o f g l u co co r t i co i d c y to p l a s m i c glucocorticoid receptor with pro-inflammatory gene transcription factor like activator protein 1 (ap-1) and nf-kβ inhibits their nuclear translocation and 10-15 transactivation function. our study also support this anti-inflammatory role of dexamethasone in animals of group 3 where in mice, injected with physiological and clinically applicable dose of 3mg/kg of body weight of dexamethasone after lps administration, were protected from hepatotoxicity. our study second experimental agent was pentoxifylline (ptx). it is a broad-spectrum phosphodiesterase inhibitor and adenosine receptor agonist/antagonist that has been utilized clinically for hemorheological disease. however, several studies have also proved its beneficial role through heterogeneous pathways for treatment of sepsis. pentoxif ylline (ptx) increases intracellular concentration of camp and cgmp in inflammatory cells line through inhibition of pde4 and pde7. this through activation of protein kinase a (pka) and camp response element binding protein (creb) down regulates nf-κb activity and diminishes tnf16,22 alpha production. these results support our study results wherein pentoxifylline lessened degree of hepatic dysfunction as evident by reduced serum alt and ast levels and minimal inflammation on histological examination of liver cross sections. we have adjudged the role of individual drugs in aversion of lps induced liver injury in our previous studies, however we were intrigued by the question whether these two drugs perform additively or not. for this purpose, we attested our animals of group 5 with dexamethasone 3mg/kg intraperitoneally along with two doses of pentoxifylline (75mg/kg i.p.) two hours after lps administration. the combination did restore serum amino transferases levels significantly (alt p≤ 0.01 & ast p value≤ 0.01) but essentially like individual dexamethasone and pentoxifylline effect in group.3 and group 4 respectively. hepatic inflammatory and necrotic changes annulment was also statistically significant (p≤0.05). study results of saez-llorens and fellows substantiated our findings. they revealed no s y n e r g i s m b e t w e e n d e x a m e t h a s o n e a n d pentoxif ylline in declination of meningeal inflammation produced by intra-cisternal injection 23 of endotoxin. hand and friends demonstrated that concomitant dexamethasone and pentoxifylline inhibited lps induced tnf synthesis to a greater level than either agent alone by acting on different points 24 in endotoxin evoked signaling pathway. due to unavailability of tnf-α levels measurement in our study we cannot firmly say their findings are noncompatible to ours, but we are undoubtedly of the view that combination therapy did not diminish tnfα downstream inflammation symbiotically. future work should be carried out on combination dexamethasone and ptx in lps induced hepatoxicityjiimc 2021 vol. 16, no.2 83 regimens via methodology alteration. conclusion dexamethasone and pentoxifylline both showed promising result in our study and significantly a m e l i o r a t e d l i p o p o l y s a c c h a r i d e i n d u c e d hepatotoxicity and hence. however, combination therapy has no superior role in treatment of lps/endotoxin induced hepatotoxicity when compared to individual agent alone. references 1. fleischmann c, scherag a, adhikari nk, hartog cs, tsaganos t, schlattmann p, et al. assessment of global incidence and mortality of hospital-treated sepsis. current estimates and limitations. american journal of 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corticosteroids for adult patients with septic shock: a systematic review with meta-analysis and trial sequential analysis. intensive care medicine. 2018 jul;44(7):1003-16. 9. lin ll, gu hy, luo j, wang l, zhang c, niu ym, zuo hx. impact and beneficial critical points of clinical outcome in corticosteroid management of adult patients with sepsis: meta-analysis and grade assessment. frontiers in pharmacology. 2019 sep 24; 10:1101. 10. aytac ho, iskit ab, sayek i. dexamethasone effects on vascular flow and organ injury in septic mice. journal of surgical research. 2014 may 15;188(2):496-502. 11. zhao y, ding c. effects of hydrocortisone on regulating inflammation, hemodynamic stability, and preventing shock in severe sepsis patients. medical science monitor: international medical journal of experimental and clinical research. 2018; 24:3612. 12. annane d. the role of acth and corticosteroids for sepsis and septic shock: an update. frontiers in endocrinology. 2016 jun 20; 7:70. 13. yazar e, er a, uney k, bulbul a, avci ge, elmas m, tras b. effects of drugs used in endotoxic shock on oxidative stress and organ damage markers. free radical research. 2010 jan 1;44(4):397-402. 14. araz o, demirci e, ucar ey, calik m, pulur d, karaman a, et al. comparison of reducing effect on lung injury of dexamethasone and bosentan in acute lung injury: an experimental study. european respiratory journal. 2014 sep 1;44(suppl 58): p3929. 15. wang zh, liang yb, tang h, chen zb, li zy, hu xc, et al. dexamethasone down-regulates the expression of microrna-155 in the livers of septic mice. plos one. 2013 nov 11;8(11): e80547. 16. brie d, sahebkar a, penson pe, dinca m, ursoniu s, serban mc, et al. effects of pentoxifylline on inflammatory markers and blood pressure: a systematic review and meta-analysis of randomized controlled trials. journal of hypertension. 2016 dec 1;34(12):2318-29. 17. carter rl, lipman ns. feed and bedding. inmanagement of animal care and use programs in research, education, and testing. 2nd edition 2018. crc press/taylor & francis. 18. wei sd, li jz, liu zj, chen q, chen y, chen m, et al. dexamethasone attenuates lipopolysaccharide-induced liver injury by downregulating glucocorticoid-induced tumor necrosis factor receptor ligand in kupffer cells. hepatology research. 2011 oct;41(10):989-99. 19. harikrishnan vs, hansen ak, abelson ks, sørensen db. a comparison of various methods of blood sampling in mice and rats: effects on animal welfare. laboratory animals. 2018 jun;52(3):253-64. 20. brunt em. grading and staging the histopathological lesions of chronic hepatitis: the knodell histology activity index and beyond. hepatology. 2000 jan;31(1):241-6. 21. wang x, nelin ld, kuhlman jr, meng x, welty se, liu y. the role of map kinase phosphatase-1 in the protective mechanism of dexamethasone against endotoxemia. life sciences. 2008 nov 7;83(19-20):671-80. 22. peng p, xia y. influency of pentoxifylline treatment for neonatal sepsis: a meta-analysis of randomized controlled studies. hong kong journal of emergency medicine. 2019 aug 9:1024907919864248. 23. saez-llorens x, ramilo o, mustafa mm, mertsola j, de alba c, hansen e, et al. pentoxifylline modulates meningeal inflammation in experimental bacterial meningitis. antimicrobial agents and chemotherapy. 1990 may 1;34(5):837-43. 24. hand wl, hand dl. influence of pentoxifylline and its derivatives on antibiotic uptake and superoxide generation by human phagocytic cells. antimicrobial agents and chemotherapy. 1995 jul 1;39(7):1574-77. dexamethasone and ptx in lps induced hepatoxicityjiimc 2021 vol. 16, no.2 84 original�article abstract objective: assessment of the functionality in patients with supracondylar fracture of femur managed with intermedullary tibial nails. study design: case series study. place and duration of study: we conducted a prospective cohort study for 6 months, from september 2021 to february 2022. materials and methods: 25 adult patients presented in the accidents and emergency department of railway general hospital, rawalpindi. they were managed using tibial nail and their functionalities after the operations were managed using the tegner-lysholm criteria measured at 2 weeks, 6 weeks, and 12 weeks till union achieved results: five of our patients were females and twenty males. average healing time was calculated at 15 weeks and 6 days approximately (2.646 sd) 24% (n=6) showed excellent healing, 48% (n=12) had good results and 28% (n=7) had fair results. we did not observe any complications. conclusion: tibial nails are convenient and effective to manage the patients with supracondylar fracture of femur and show good functional outcomes. key words: retrograde femoral nail, supracondylar femur fractures, tibial nail. majority of femoral fractures now achieve good 6 results. initially distal femur fractures were managed using dynamic condylar screws, condylar blade plates, distal femoral locking plates, and less 7 invasive stabilization system plates. the most significant disadvantages of these surgical options were deep tissue dissections, postoperative collection of hematomas, infection and a large surgical incision resulting in a scar on the lateral aspect of the thigh, except for less invasive 8 stabilization system technique. the application of blade plates requires great expertise and not many 9 orthopedic surgeons are skilled in it. furthermore, blade plates and dynamic condylar screws mechanically pull the distal fragment of the femur laterally which can result in mal-rotation and 10 consequently implant failure. recently retrograde intramedullary nailing for the management of supracondylar fracture of femur is being accepted owing to minimal blood loss, smaller surgical incisions, lower risks for infection, early 11 weight-bearing and decreased operative time. however, retrograde femoral nails designed especially for the fixation of supracondylar femoral fractures are expensive and not cost effective for 12,13 patients in developing countries. introduction distal femur fractures are very commonly seen in 1 patients suffering from high intensity trauma. they 2 contribute to 0.4% of all fractures. a unanimous mode of management for the different types of distal femur fractures; transverse, oblique, spiral, and comminuted, is still debated by orthopedic 3 surgeons. renowned surgeons like sir john charnley, initially managed, supracondylar fractures conservatively using manipulation and casting, skeletal traction, 4 external splints, and braces. unfortunately, these resulted in poorer outcomes and complications like non-union, mal-union and compartment syndrome 5 causing significant disability. with the advancements in surgical techniques functional outcome of intramedullary tibial nail in distal femur shaft fractures 1 2 3 4 5 6 raja adnan ashraf , kamran asghar , saba sohail , zara sohail , waleed bin waris , muhammad imran sohail , 7 qazi muhammad sibghatullah correspondence: dr. raja adnan ashraf assistant professor department of orthopedics pakistan railway hospital, rawalpindi e-mail: dr.addi79@yahoo.com 1,3,4,5,6,7 department of orthopaedics pakistan railway hospital, rawalpindi 2 department of orthopaedics fauji foundation hospital, rawalpindi received: may 20, 2022; revised: november 01, 2022 accepted: november 07, 2022 intramedullary tibial nail in distal femur fracturesjiimc 2022 vol. 17, no.4 256 doi: https://doi.org/10.57234/1348 use of tibial plates for fixation of supracondylar fractures of femur is being employed by a few surgeons due to cost effectiveness and analogous success rates as specially designed distal femoral 14 nails. we evaluated the functional outcomes of tibial locking nails in the supracondylar fractures of the femur. materials and methods we conducted a prospective study for 6 months, from september 2021 to february 2022. 25 adult patients presented in the accident and emergency department of railway general hospital, rawalpindi with supracondylar fracture of femur. the inclusion criteria were distal one-third femur fractures, linear type a extra-articular supracondylar femur fractures, and closed fractures. the exclusion criteria were all open fractures, b2, c2, b3, c3 fractures, and preoperative deformity. the study was commenced after getting approval from the ethical review board of the hospital. upon taking informed consents, all the patients were managed using tibial nail by an experienced consultant orthopedic surgeon team. a midline incision of 4cm was made from the inferior pole of the patella up to tibial tuberosity. the paratenon over the patellar tendon was incised sharply and the patellar tendon was split in the midline along with the direction of its fibers. a straight bone awl was used and inserted into the knee joint through the split tendon and positioned against the femoral inter-condylar notch. the position of awl was confirmed using the image intensifier as anteroposterior and lateral. a guide wire was passed after making an entry point and the awl removed. the fracture fragments were aligned under image intensifier and guide wire passed in the proximal fragment. the distal fragment was then reamed with flexible reamers and the predetermined tibial nail of appropriate diameter and length was then loaded over the jig. the nail was finally inserted over the guide wire and its position confirmed with the help of image intensifier. depending on the length of the nail, the proximal holes were locked. after inserting both proximal and distal locking screws, the jig was then disengaged, the joint washed thoroughly with normal saline to remove the debris, homeostasis achieved, and incision closed in layers. particular attention was paid to repair para-tenon of patellar tendon. postoperative x-rays were obtained, and patients were discharged on the 2nd postoperative day after non-weight bearing mobilization. follow-ups were done after 2 weeks, 6 weeks, and 12 weeks till union. the functional outcome was measured using tegnerlysholm criteria, which measures the functional outcome in terms of limping, pain, locking, stair climbing, support, instability, swelling and squatting. the follow up was ensured by taking phone numbers of the patients. spss 23 was used for statistical analysis. frequencies and percentages were calculated for the categorical variables while mean and standard deviations were calculated for the numerical variables. statistical significance was defined as a p value of 0.05. p value of 0.05 was considered statistically significant. results out of 25 patients 20(80%) were male and 5(20%) were female. the mean age in our study was 37. the average time of healing was between 12 and 21 weeks and mean time of healing was estimated near 15 weeks and 6 days with a standard deviation of 2.464 as shown in table i functionality assessed using tegner-lysholm scoring system showed excellent scores for 24% (n=6), good scores for 48% (n=12) and 28% (n=7) showed fair scores after management through tibial nail for supracondylar fractures of femur as assessed at 12 weeks interval (table ii). discussion in our study we treated 25 patients treated with tibial nail for supracondylar fracture of femur and documented 24% (n=6) showed excellent healing, 48% (n=12) had good results and 28% (n=7) had fair results. average healing time was calculated at 15 weeks and 6 days approximately (2.646 sd) retrograde nails for the management of femur fractures are a widely accepted and convenient option for most of extra articular supracondylar fractures of the femur. they are considered a preferred option compared to conventional blade plates, condylar screws and newer locking plates in terms of stability, surgical exposure and healing 15 time. nails have load sharing capability and provide better stability at the fracture site that promotes the intramedullary tibial nail in distal femur fracturesjiimc 2022 vol. 17, no.4 257 doi: https://doi.org/10.57234/1348 1 6 use of closed technique more commonly. retrograde nails have low complication rates compared to other methods when used for the 17 fixation of the supracondylar femur fractures. our study was conducted on 25 patients, and 20 were male and 5 females. the mean time of healing was 15 weeks and 6 days compared to 25 weeks in a study by gurkan et al. in which supracondylar femur fractures were fixed with standard retrograde 1 8 femoral nails. none of our patients had complications of nonunion or malunion. our results were comparable to gurkan et al. who reported excellent results in 29.4% (n=5), good in 35.3 (n=6), moderate in 31.2% (n=5), and poor results in 5.9% (n=1) of their patients. only 3 patients in our study developed coronal deformity. one patient developed valgus deformity and the other two patients developed varus deformity. this was also observed by gurkan et al in which postoperative radiographic examination showed varus angulation of 10° in 23.5% (n=4) and posterior angulation of 10-20° in another 23.5% (n=4) patients. 7 patients developed flexion contractures of 5 degrees while one patient developed extension contracture. contractures developed because of poor compliance of patients to physiotherapy. there were no nail ends protruding into the joint space. all nails were kept up to the level of lesser trochanter of the femur, to reduce the chances of stress fracture, 19 implant failure and rotational instability. all our cases were managed using a closed technique using a tibial nail compared to rao et al. who converted 25% of the cases to open technique for 20 reduction of the fracture fragment. rao et al. reported excellent results for 65% of their patients with the mean healing time of 16.2 weeks. average knee flexion was 108 degrees with an extensor lag of 4.15 degrees. simil sanders et al managed 18 patients of supracondylar femur fractures using ao universal tibial nail, 92% fractures healed within 12 weeks with no complications like infection, loss of 21 reduction, or nail failure knee flexion averaged at around 120 degrees, while only two knees had an extensor lag of more than 5 degrees. they reported the cost of retrograde smith and nephew femoral nails to be twice the price of zimmer tibial interlocking nails making it a more cost-effective method of fixation. our study had few limitations like in follow up of our study, we did not see postoperative complications like infection, nonunion, loss of reduction, stress fracture, or implant failure. further studies are recommended to confirm our results. conclusion it is concluded that the retrograde tibial locking nails for stabilization of extra articular supracondylar fractures of femur are convenient and result in good functional outcome in most of the patients. we recommend tibial nail, an implant of choice to treat supra condylar fracture femur. tibial nail has the added advantage of economic feasibility for the patients and easy learning curve for junior surgeons. however, more studies are required to support the evidence of our research. references 1. kim j-w, yoon y-c, oh c-w, han s-b, sim j-a, oh j-k. exchange nailing with enhanced distal fixation is effective for the treatment of infraisthmal femoral nonunions. arch orthop trauma surg. 2018 jan;138(1):27–34. 2. yoshino o, brady j, young k, hardy b, matthys r, buxton t, et al. reamed locked intramedullary nailing for studying femur fracture and its complications. eur cell mater. 2017 sep;34:99–107. 3. coon ms, best bj. distal femur fractures. in treasure island (fl); 2022. 4. xu z, zhang m, yin j, ren l, zeng y. redisplacement after reduction with intramedullary nails in surgery of intertrochanteric fracture: cause analysis and preventive m e a s u r e s . a r c h o r t h o p tr a u m a s u r g . 2 0 1 5 jun;135(6):751–8. 5. adams aj, mahmoud mah, wells l, flynn jm, arkader a. physeal fractures of the distal femur: does a lower threshold for surgery lead to better outcomes? j pediatr orthop b. 2020 jan;29(1):40–6. 6. abdelmonem ah, saber ay, el sagheir m, el-malky a. evaluation of the results of minimally invasive plate osteosynthesis using a locking plate in the treatment of distal femur fractures. cureus. 2022 mar;14(3):e23617. 7. du y-r, ma j-x, wang s, sun l, wang y, lu b, et al. comparison of less invasive stabilization system plate and retrograde intramedullary nail in the fixation of femoral supracondylar fractures in the elderly: a biomechanical study. orthop surg. 2019 apr;11(2):311–7. 8. kim j-w, kim t-y, ha y-c, lee y-k, koo k-h. outcome of intertrochanteric fractures treated by intramedullary nail with two integrated lag screws: a study in asian population. indian j orthop. 2015;49(4):436–41. intramedullary tibial nail in distal femur fracturesjiimc 2022 vol. 17, no.4 258 doi: https://doi.org/10.57234/1348 9. doshi hk, wenxian p, burgula mv, murphy dp. clinical outcomes of distal femoral fractures in the geriatric population using locking plates with a minimally invasive a p p r o a c h . g e r i a t r o r t h o p s u r g r e h a b i l . 2 0 1 3 mar;4(1):16–20. 10. kubiak en, fulkerson e, strauss e, egol ka. the evolution of locked plates. j bone joint surg am. 2006 dec;88 suppl 4:189–200. 11. charnley j. the closed treatment of common fractures. 4th ed. cambridge university press; 2003. 12. kumar n, kalra m. evaluation of valgus intertrochanteric osteotomy in neglected fracture neck femur in young adults. j clin orthop trauma. 2013 jun;4(2):53–7. 13. richards ja, berkay fb, davis cm, zamora ra. intra-articular fracture pattern in intercondylar distal femur fractures: an analysis of frequency and major fracture fragments. injury. 2021 apr;52(4):967–70. 14. yuan y, luo b, hao q, yuan j, qu g, hao p, et al. clinical outcomes of revision with retrograde intermedullary nailing for failed plating of distal femoral fractures: a r e t r o s p e c t i v e s t u d y. i n t o r t h o p [ i n t e r n e t ] . 2 0 2 0 ; 4 4 ( 1 1 ) : 2 4 3 7 – 4 2 . a v a i l a b l e f r o m : https://doi.org/10.1007/s00264-020-04621-x 15. yan r, wu y, qi y, li h, dong s, feng g. one-stage closed intramedullary nailing for delayed femoral fracture in mu ltip le in j u red patients . o rth o p su rg. 2022 mar;14(3):501–12. 16. papadokostakis g, papakostidis c, dimitriou r, giannoudis p v. the role and efficacy of retrograding nailing for the treatment of diaphyseal and distal femoral fractures: a systematic review of the literature. injury. 2005 jul;36(7):813–22. 17. el-kawy s, ansara s, moftah a, shalaby h, varughese v. retrograde femoral nailing in elderly patients with supracondylar fracture femur; is it the answer for a clinical problem? int orthop. 2007 feb;31(1):83–6. 18. gurkan v, orhun h, doganay m, salioğlu f, ercan t, dursun m, et al. retrograde intramedullary interlocking nailing in fractures of the distal femur. acta orthop traumatol turc. 2009;43(3):199–205. 19. alfurtas moftah, hassan khaled, marie mohsen, fahmy f. short term results of intramedullary fixation of supracondylar fracture of femur by retrograde intramedullary nail. zagazig univ med j. 2020;0(0):0–0. 20. wu c-c. retrograde locked intramedullary nailing for aseptic supracondylar femoral nonunion following failed locked plating. j orthop surg (hong kong). 2015 aug;23(2):155–9. 21. sanders r, koval kj, dipasquale t, helfet dl, frankle m. retrograde reamed femoral nailing. j orthop trauma. 1993;7(4):293–302. 22. pennock at, ellis hb, willimon sc, wyatt c, broida se, dennis mm, et al. intra-articular physeal fractures of the distal femur: a frequently missed diagnosis in adolescent a t h l e t e s . o r t h o p j s p o r t m e d . 2 0 1 7 oct;5(10):2325967117731567. intramedullary tibial nail in distal femur fracturesjiimc 2022 vol. 17, no.4 conflict of interest authors declared no conflicts of interest. grant support and financial disclosure authors have declared no specific grant for this research from any funding agency in public, commercial or nonprofit sector. data sharing statment the data that support the findings of this study are available from the corresponding author upon request. this is an open access article distributed under the terms of the creative commons attributionnoncommercial 2.0 generic license. 259 doi: https://doi.org/10.57234/1348 original�article abstract objective: to determine the effects of mcconnell taping combined with strengthening exercises on q angle and intensity of pain in females with patellofemoral pain syndrome. study design: randomized control trial place and duration of study: physical medicine & rehabilitation department of fauji foundation hospital st st rawalpindi from 1 jan to 31 june 2018. materials and methods: females with patellofemoral pain syndrome with age 25-45 years, having anterior knee pain, limited/painful knee range of motion and increased q angle>18 were included in the study through non-probability convenience sampling technique .numeric pain rating scale(nprs)and goniometry tools were used to measure the outcomes. a total of 70 approached cases only 48 met the inclusion criteria, out of which 40 subjects completed the treatment protocol. subjects were divided randomly in to experimental and control groups. both groups received standard treatment protocol including trans cutaneous electrical nerve (tens) and heating pad for 15 minutes while experimental group received mcconnell taping in addition. data was analyzed by using spss version 21. results: there was significant improvement in pain intensity and q angle in experimental group after mcconnell taping p value was <0.05 for pain. flexion rom was significantly improved in both groups p<0.05.while extension rom was in normal range pre and post treatment p<0.05. conclusion: results of this study shows that mcconnell taping reduces pain intensity and quadriceps angle in patients with patellofemoral pain syndrome. key words: patellofemoral pain syndrome, quadriceps angle, range of motion, taping technique, visual analogue scale. measurement which is taken in supine position 8,9 without the activation of quadriceps. clinically quadriceps angle, lateral hyper mobility of patella and j sign are mostly used for the evaluation of 8 patellar maltraking. structural rehabilitation programme is implemented for management of pfps including rest, patellar bracing and mcconnell taping is mostly used for the treatment of patellofemoral pain syndrome which improves quadriceps function, patellar alignment and 6, 10-12 decrease q angle. the available research evidence, however, would suggest that either taping change the quadriceps angle or not. in previous studies mcconnell taping enhanced the activity level of vastus medialis oblique relative to vastus lateralis, and decrease pain and improved function but the direction of tape and its effects on q angle were not targeted in this 9 study. some studies revealed that mcconnell taping shows positive results for patellofemoral pain syndrome, but the evidence is limited on the introduction the patellofemoral pain syndrome (pfs) is a possible cause of the anterior knee pain .it predominantly 1,2 affects the female patients. patellofemoral pain syndrome contributing to an estimated of 30-40% of 3, 4 all sports medicine visits in the united states 155 45% individual reports pfps. typical symptoms are knee pain on anterior aspect which is exacerbated by ascending and descending stairs, squatting as well as 6, 7 prolonged sitting. an increased in q angle >15 degree is considered the predisposing factor for patellofemoral pain syndrome. q angle is a static effects of mcconnell taping combined with strengthening exercises on quadriceps angle and intensity of pain in females with patellofemoral pain syndrome ruqia begum, furqan ahmed siddiqi, wardah ajaz qazi, kanwal zafar, arva naeem, nida kiani, samina javed correspondence: dr. ruqia begum lecturer foundation university college of physical therapy, foundation university school of health sciences, islamabad e-mail:rr.ruqia544@gmail.com foundation university college of physical therapy, foundation university school of health sciences, islamabad received: july 09, 2021; revised: may 30, 2022 accepted: june 13, 2022 mcconnell taping combined with strengthening exercisesjiimc 2022 vol. 17, no.2 114 13 outcome of the taping on q angle. a study was conducted by engy f et al in 2021,the result of their study significant difference between vas and lower extremity function after mcconnell tape with p value 14 was <0.05. another study was conducted by aminaka, and gribble examined the effects of mcconnell taping on knee pain and hip and knee kinematics in the sagittal plan during dynamic balance setting. the patients with patellofemoral pain syndrome group with mcconnell tape showed a reduction in knee pain and improvement in balance compared to non-tape condition. however there were no significant differences in hip and knee angle in the sagittal 15 plan. therefore this study was planned to investigate the effects of taping on the q angle and pain level in patients with patellofemoral pain syndrome. materials and methods this randomized control trial was conducted at physical medicine & rehabilitation department of st fauji foundation hospital rawalpindi from 1 jan st 2018 to 31 june 2018.study was approved by research ethical committee of riphah international university islamabad. the inclusion criteria of the study were known cases of patellofemoral pain syndrome, age 25-45, having anterior knee pain, limited/painful knee rom and q angle>18 were included in the study. participants having any history of knee surgery, systematic disease and other neuromuscular conditions were excluded from the study. after taking consent subjects who fulfilled the inclusion criteria were divided into group a (experimental) and group b (control) through convenience sampling technique. open epi tool was used for sample size calculation. sample size calculated was 40 and 20 patients were assigned in each group. study participants were assessed at base line and at the end of 2 weeks post intervention. in the control group treatment protocol was traditional exercises including quadriceps isometric and hamstring stretching 10 repetition with 3 sets for 4 days/week, trans cutaneous electrical nerve s t i m u l a t i o n ( t e n s ) w i t h f r e q u e n c y 5 0 100hz,continous cycle time and heating pad for 15 minutes. total duration of each session was 45 minutes for 2 weeks. while experimental group was given additional mcconnell taping. the patient was in supine position. total time for taping was 2 minutes in which a cover roll tape almost 15 cm in size was first applied directly over the skin. then 12 cm rigid tape leukotape p was applied by starting from lateral condyle of femur, anchor the patella and end on posterior aspect of the knee. for shifting of patella on medial side enough force was applied. at end of completion of taping procedure, a pouch of skin\crease almost 2 cm in width was visible on medial aspect of the knee. the participants were then instructed to remove the tape before going to bed. study outcomes i.e., pain and q angle were measured through numeric pain rating scale and by goniometry. quadriceps angle was statistically measured by using goniometer from three points i.e., anterior superior iliac spine, midpoint of patella and tibial tuberosity. data was analyzed by using spss 21. nonparametric test (mann whitney u) was applied for comparison between groups. results data of the study was stated as mean and standard deviation.comparasion of the two groups was done by using mann whitney u test while considering the p<0.05 as statistically significant. a total of 70 approached cases 48 patients met the inclusion criteria. only 40 subjects completed the treatment protocol 20 in each group. treatment protocol included the application of mcconnell taping with traditional exercise regimes for group a and group b received only traditional exercise. commonly affected population was workers (50%). mean of the age in the experimental group was 36.05 ±7.35 years while in the control group was 37.05±4.96. mean and sd of q angle of participants was 18.05±3.02. group a (experimental) showed significant decrease in q angle as compared to l group b (control) p<0.05.the intensity of the pain was significantly reduced in both the groups p<0.05. discussion patellofemoral pain syndrome is a common cause of anterior knee pain, it mainly affects females. the present study investigated the immediate effects of mcconnell taping on q angle and knee joint pain in females with patellofemoral pain syndrome. intensity of the pain was reduced in both groups, but its effects were noticed in experimental group as compared to control group with p value was <0.05. overall mean numeric pain rating scale decreased jiimc 2022 vol. 17, no.2 115 mcconnell taping combined with strengthening exercises significantly after taping from 8.28 to 2.9 in experimental group. a previous study reported that patients with patellofemoral pain syndrome who were provided mcconnell taping for two weeks re p o r te d s i g n i f i ca nt l y re d u c e d p a i n s co re immediately after treatment and for 12 month follow up. also 80% subjects achieved normal onset timing of vastus medialis oblique and vastus lateralis during squat and seated knee extension at 12 month follow 16,17 up. table i: comparison of q angle, intensity of pain and knee rom between experimental and control groups jiimc 2022 vol. 17, no.2 116 diagram mcconnell taping combined with strengthening exercises another study examined the emg activity between vl and vmo while the individual used the muscles for eccentric phase of descending stairs and concentric phase of ascending stairs. they found the peak emg ratio of vmo and vastus lateralis in descending stairs was lower than the ascending a stairs. double blinded randomized control trial was conducted on 30 patients with patellofemoral pain syndrome. they treated the patients for 12 sessions for a period of 2 weeks. significant improvement was 18 noticed in pain intensity in both groups. similarly, a study was conducted by a.m clifford in 2020 in which they used mcconnell taping as well as tibial internal rotation limitation taping for patellofemoral pain syndrome (pfps). the results of this study revealed that pain intensity were 19 decreased in both taping techniques. the results in current study also suggest that mcconnell taping is m o re e ffe c t i ve i n d e c re a s i n g q a n g l e i n patellofemoral pain syndrome. in this study the adjusted q angle values for laterally and neutral placed patella was very close to the centre of the reported ranges of q angle after adjustment of lateral patellar displacement in the experimental group as compared to the control group. the present study suggests that increasing knee flexion range of motion decrease the q angle and patellar lateral displacement p value <0.05.the results of this study are supported by tsung yu-lan in which they found the immediate effects of mcconnell taping on pain and q angle in patients with patellofemoral pain 3 syndrome p value0.05. a study was conducted by ajlan sac et al in which they found that higher q angle is associated with decreased knee strength and taping decrease pain and also q angle in patients 20 with pfps. conclusion the result of this study shows that mcconnell taping combined with strengthening exercises to decrease pain intensity and quadriceps angle in patients with patellofemoral pain syndrome. limitations prolonged effects of the study were not measured as time duration was limited. data was collected from single setting of physical medicine and rehabilitation department of fauji foundation hospital rawalpindi, so diversity was not achieved. disclaimer it was presented online in world conference on nd exercise medicine in malaysia on 2 nov 2021. references 1. kasitinon d, li w-x, wang exs, fredericson m. physical examination and patellofemoral pain syndrome: an updated review. current reviews in musculoskeletal medicine. 2021 oct 29(14):1-7. 2. fick cn, jiménez-silva r, sheehan ft, grant c. patellofemoral kinematics in patellofemoral pain syndrome: the influence of demographic factors. journal of biomechanics. 2022 jan (130):1-13. 3. rehman n, kashif m, sajjad a, hassan hmj, iram h. immediate effects of kinesio taping on pain in athletes with patellofemoral pain syndrome. physikalische medizin, rehabilitationsmedizin, kurortmedizin. 2020 dec; 30(06):344-349. 4. cho sh, moon hj. effects of kinesio-taping on balance abilities and proprioception sense. journal of international academy of physical therapy research. 2017;8(2):11631167. 5. smith be, selfe j, thacker d, hendrick p, bateman m, moffatt f, et al. incidence and prevalence of patellofemoral pain: a systematic review and meta-analysis. plos one. 2018 jan;13(1):0190892. 6. payne k, payne j, larkin ta. patellofemoral pain syndrome and pain severity is associated with asymmetry of gluteus medius muscle activation measured via ultrasound. american journal of physical medicine & rehabilitation. 2020;99(7):595-601. 7. javed s, riaz h, saeed a, begum r. effects of biodex balance training on symptomatic knee osteoarthritis in rawalpindi: a randomized control trial. jpma. 2021; 71(2):402-405. 8. sheehan ft, derasari a, fine km, brindle tj, alter ke. qangle and j-sign: indicative of maltracking subgroups in patellofemoral pain. clinical orthopaedics and related research®. 2010;468(1):266-275. 9. gaitonde dy, ericksen a, robbins rc. patellofemoral pain syndrome. american family physician. 2019 jan 15;99(2):88-94. 10. baheti nd, jamati mk. physical therapy: treatment of common orthopedic conditions: jp medical ltd; 2016 apr 10(1):1-9. 11. begum r, tassadaq n, ahmad s, qazi wa, javed s, murad s. effects of mcconnell taping combined with strengthening exercises of vastus medialis oblique in females with patellofemoral pain syndrome. jpma the journal of the pakistan medical association. 2020;70(4):728-730. 12. gulati a, mcelrath c, wadhwa v, shah jp, chhabra a. current clinical, radiological and treatment perspectives of patellofemoral pain syndrome. the british journal of radiology. 2018 jun; 91(1086):20170456. 13. g h o u r b a n p o u r a , ta l e b i g a , h o s s e i n z a d e h s , janmohammadi n, taghipour m. effects of patellar taping on knee pain, functional disability, and patellar alignments in patients with patellofemoral pain syndrome: a jiimc 2022 vol. 17, no.2 117 mcconnell taping combined with strengthening exercises randomized clinical trial. journal of bodywork and movement therapies. 2018;22(2):493-497. 14. syed s, bukhari b, afzal s, nasir m, ali s. comparison of effectiveness of mechanical hold versus kinesio taping in managing patellofemoral pain syndrome. pakistan biomedical journal. 2022 mar 31(5)(3):47-54. 15. aminaka n, gribble pa. patellar taping, patellofemoral pain syndrome, lower extremity kinematics, and dynamic postural control. journal of athletic training. 2008;43(1):2128. 16. paoloni m, fratocchi g, mangone m, murgia m, santilli v, cacchio a. long-term efficacy of a short period of taping followed by an exercise program in a cohort of patients with patellofemoral pain syndrome. clinical rheumatology. 2012;31(3):535-539. 17. jun h-p, chang e. the effect of mcconell tape on patients with patellofemoral pain. exercise science. 2019;28(4):324329. 18. pelletier a, sanzo p, kivi d, zerpa c. the effect of patellar taping on lower extremity running kinematics in individuals with patellofemoral pain syndrome. physiotherapy theory and practice. 2019;35(8):764-772. 19. clifford am, dillon s, hartigan k, o'leary h, constantinou m. the effects of mcconnell patellofemoral joint and tibial internal rotation limitation taping techniques in people with patello fem o ra l p a in sy n d ro m e. g a it & po st u re. 2020;82:266-272. 20. saç a, taşmektepligil my. correlation between the q angle and the isokinetic knee strength and muscle activity. turkish journal of physical medicine and rehabilitation. 2018 dec; 64(4):308-313. conflict of interest authors declared no conflicts of interest. grant support and financial disclosure authors have declared no specific grant for this research from any funding agency in public, commercial or nonprofit sector. data sharing statment the data that support the findings of this study are available from the corresponding author upon request. this is an open access article distributed under the terms of the creative commons attributionnoncommercial 2.0 generic license. jiimc 2022 vol. 17, no.2 118 mcconnell taping combined with strengthening exercises original�article abstract objective: to compare the effects of mulligan traction straight leg raise and passive straight leg raise in patients with lumbar radiculopathy. study design: randomized control trial. nd th place and duration of study: the study was conducted from 2 february 2017 to 30 june2017 at national institute of rehabilitation medicine, islamabad materials and methods: a total of 38 patients of either gender with age range of 40 to 60 years with low back pain and lumbar radiculopathy were recruited in the study and they were randomly allocated in to two groups through lottery method, traction straight leg raise, and passive straight leg raise group. patients with spinal surgeries and fractures were excluded from the study. conventional physiotherapy treatments including transcutaneous electrical nerve stimulation, hot pack, stretching and strengthening exercises were given to all patients. traction straight leg raise technique was performed on patients of experimental group and passive straight leg raise was performed on control group. patients were assessed on baseline and after 4 weeks through numeric pain rating scale, oswestry disability index, and goniometer. treatment duration was of 4 weeks with 2 sessions per week. results: mean age of all patients was 53.60 ± 3.82. experimental group showed much reduction in pain with pre median =6(1) and post median=2(1) as compared to control group pain with pre median= 6(1) and post median=4(1) on pain scale. traction straight leg raise also showed significant improvement in range of motion with pre median=50(10) and post median=70(10) of experimental group as compared to slr of control group with pre median= 50(15) and post median= 60(10). statistically both groups showed improvement, but experimental group improvement was more significant. conclusion: traction straight leg raise is more effective than passive straight leg raises in decreasing pain and improving range of motion in patients with lumbar radiculopathy key words: goniometer, oswestry disability index, passive straight leg raise, traction straight leg raise. lbp results in increasing levels of disability, activity restriction and lack of participation, such as an 3 inability to work. in general population, there is an estimation that yearly incidence of first ever episode of lbp is 6.3% to 15.4%.its prevalence increases in 60 4 to 65 years of age. in general population prevalence 5 of chronic lbp ranges from 15 to 45%. in lumbar radiculopathy, pain occurs in the lower back and radiates around hip region and down the posterior aspect of the thigh into the legs. symptoms are shooting pain, numbness and tingling in buttock and 6 leg. damage is caused by the nerve roots 7 compression that exit the spine from level l1 to s1. prevalence of lumbar radiculopathy been reported 8 up to 5%. prevalence of lumbar radiculopathy is reported to be 11% out of 12.9% in working 9 population. lumbosacral radiculopathy is up to 9.9% 10 to 25%. repetitive load on the spine is the common introduction low back pain is a common musculoskeletal discomfort, localized below the costal margin and above the inferior gluteal folds, with or without leg pain, affecting majority of adults and is the most 1 common cause of disability in developed countries. effects of mulligan traction straight leg raise versus passive straight leg raise in lumbar radiculopathy patients 1 2 3 4 asmar fatima , zoya mehmood , bintal wajeeh satti , shakeel ahmed correspondence: dr. asmar fatima hod rehabilitation sciences allied college of health sciences, multan e-mail: asmar.fatima@gmail.com 1 department of rehabilitation sciences allied college of health sciences, multan 2 department of rehabilitation sciences shifa tameer-e-millat university, islamabad 3 physiotherapist, central health clinic, (derby uk) 4 department of rehabilitation sciences jouf university sakkaka, saudi arabia received: september 14, 2021; revised: may 23, 2022 accepted: june 02, 2022 mulligan traction straight leg raise vs passive straight leg raisejiimc 2022 vol. 17, no.2 86 risk factor for radiculopathy. it is most found in 11 patients who are involved in heavy labour. there are numerous treatment options in literature for managing it. physical therapy treatment includes muscle stretching, traction, mckenzie exercise, 12 tens, ultrasound, interferential therapy, hot pack”. passive slr test is frequently used by clinicians to diagnose lumbar radiculopathy and check hamstring 13 tightness. techniques developed by brian mulligan are effective in treating radiculopathy i-e mobilization with movement (mwm) of extremities and spinal mobilization with limb movement (smwlm's). edmonton and singer emphasized for the use of sustained natural apophyseal glides that was first presented by mulligan to restore pain-free joint mobility. sustained natural apophyseal glides have been reported for their benefits in acute and 14 sub-acute thoracic spine conditions. tslr is a mwm technique of mulligan and is used in treating lumbar radiculopathy and hamstring tightness. it is reported in literature that mwms for managing lbp are used by many therapists as a part of their treatment approach. majority of therapists using these had several years of experience in the treating of lbp with mwms. many therapists reported improvement in active spinal rom and pain relief immediately after 8-9 the use of mwms the purpose of the study was to compare the effects of mulligan traction straight leg raise and passive straight leg raise in patients with lumbar radiculopathy. many patients with recurring low back pain have tight hamstrings, traction slr increase range of movement in few treatments. this study investigated whether mulligan's tslr is better treatment for the patients suffering with low back pain with radicular symptoms. materials and methods study design was randomized controlled trial and data was collected from physical therapy opd of national institute of rehabilitation medicine nd th islamabad from 2 january2017 to 30 june 2017.patients of both gender with 40 -60 years of age having low back pain and lumbar radiculopathy were included in the study. the study was approved from ethical review board of riphah international university with ref no. riphah/rcrs/rec/00201. patients with inflammatory conditions, spinal surgeries and fractures were excluded. a sample size 15 of 38 was calculated through open epitool. patients were randomly allocated in groups.18 patients were in experimental group (mulligan traction straight leg raise) and 20 patients were in control group (passive straight leg raise). 3 patients from experimental and 5 patients from control group were dropout and 30 patients completed the follow-up. 15 were from experimental group and 15 were in control group. passive straight leg raise (slr) group patients were treated with hot pack (10 min), high-rate tens for 15 16 min at 70hz frequency , stretching exercises (hamstring stretch, calf stretching), bridging exercise for back 3times per day with 10 repetitions and passive straight leg raise (3 sets of 10 repetitions). mulligan traction straight leg raise (tslr) group patients were treated with tslr technique (3 repetitions per session) and same conventional physical therapy treatment as control group were followed for this group. patients were educated regarding correct posture in standing, sitting, and weightlifting. home plan was given to patients that included stretching and strengthening exercises for back and leg. patients of both groups were asked to visit hospital twice a week. traction slr and passive slr techniques were performed on the patients of respective groups, and they were suggested to repeat the prescribed exercise home plan twice a day with 10 repetitions for 4 weeks. patients were assessed through numeric pain rating scale (nprs) for pain intensity, oswestry disability index (odi) for functional disability and goniometer for range of motion of hip joint. statistical analysis was done through spss version 21. parametric tests were applied for odi because p value was > 0.05 and nonparametric tests were applied for nprs, and straight leg raise because p value was < 0.05. results among 30 patients, 8 were male and 22 were female. mean age of all patients was 53.60 ± 3.82. majority of the patients affected with lumbar radiculopathy were housewives (83.3%).33.3% patients were having pain for more than 1 year,10% were having pain from less than 1 year. overall, 53.3 % participants presented with back pain radiating to right leg and 46.7 % came with pain radiation to left leg. frequency of nature and type of pain and other demographic variables are shown in table i. jiimc 2022 vol. 17, no.2 87 mulligan traction straight leg raise vs passive straight leg raise for inferential analysis, test variables including nprs, odi and slr were assessed by shapiro wilk test to identify the normality of data at baseline. lumbar oswestry disability index data was normally distributed with p-value> 0.05 therefore parametric tests (independent sample t-test and paired sample t-test) were applied. whereas non-parametric tests i.e. mann-whitney and wilcoxon signed rank tests for slr and nprs were applied as data was skewed for these variables with p-value < 0.05. nprs and slr post treatment showed improvement in terms of pain and range of motion in both groups with p value < 0.05 whereas more significant improvement in pain was observed in experimental group with pre-treatment mean 5.80 ± 0.86 and post treatment mean 1.80 ± 0.77 and range of motion was also more significantly increased in experimental group with pretreatment mean 49.66 ± 4.41 and post treatment mean 71.00 ± 5.73 as shown in tale #ii oswestry disability index post treatment showed improvement in control and experimental group with p value <0.05 (0.001). more significant improvement in traction slr group was observed, as shown in figure 1. table i: demographic data of patients table ii: mann whitney u test between control and experimental group comparison fig. 1: differences in odi between control and experimental group discussion the purpose of this study was to compare the effects of mulligan tslr and passive slr on patients with lumbar radiculopathy. the results of our study show that female experience low back pain with radiculopathy more than male. it is also observed in 17 the study conducted by aimin wu et al. traction straight leg raise (tslr) is effective in reducing low back pain caused by radiculopathy and improves slr range. the reduction in pain on nprs is more likely to the fact that tslr technique is more directed to specific functional movements of lumbar spine. it targets the joint restrictions. improved blood 18 circulation also reduce pain. the results of current study are similar to the results of study conducted by pooja kapadia et al on patients with hamstring tightness in which tslr technique improved slr range in patients with hamstring tightness and 19 lumbar radiculopathy. in this study it is also noted that tslr technique improves stretch tolerance of hamstring muscles as well. this technique is more effective in reducing low back pain and increasing extensibility of neural structure, low back extensors and posterior thigh musculature as compared to passive slr. this study correlates with the results of an rct, conducted by yıldırım, meric senduran, et al to compare the effectiveness of static stretching and mulligan tslr on hip flexion rom. the group in w h i c h ts l r wa s g i ve n s h owe d s i g n i f i ca nt improvement in hip flexion with p-value of 0.016 and 20 0.02 respectively after 4 weeks. riaz mu et al conducted another clinical trial in patients with jiimc 2022 vol. 17, no.2 88 mulligan traction straight leg raise vs passive straight leg raise lumbar radiculopathy and results of the study showed improvement in odi. this proves that mulligan's technique is more effective in improving 21 function. the current study also shows that mulligan's tslr is effective in improving activities of daily living and increasing back muscle and hamstring extensibility in patients with lumbar radiculopathy. mazumdar, j. et al conducted an rct to compare the effectiveness of mulligan tslr and muscle energy technique on hamstring tightness in male patients. results showed that both techniques 22 were effective reducing hamstring tightness. the current study also have similar results. a systemic review conducted by pourahmadi mr et al stated that mulligan's straight leg and bent leg raise techniques are effective in reducing pain and increasing hip flexion rom in patients with unilateral 23 lumbar radiculopathy. this study also has similar results in improving slr range with a p-value of 0.001. limitations this study has limitation of small sample size. limited sessions have been provided to patients and long term follow up could not be carried out. recommendation future studies should be conducted on larger sample size to determine the long-term effect of tslr on strength and flexibility of thigh musculature. emg studies can also be incorporated to assess the muscular activities during the application of different mulligan's techniques. conclusion this study concludes that mulligan traction straight l e g r a i s e c o m b i n e d w i t h c o n v e n t i o n a l physiotherapy treatment show more significant improvement in range of motion, pain reduction and improving function when compared with passive straight leg raise. references 1. clark s, horton r. low back pain: a major global challenge. the lancet. 2018 june 9; 391(10137):2302. 2. russo m, deckers k, eldabe s, kiesel k, gilligan c, vieceli j et al. muscle control and non-specific chronic low back pain. neuromodulation: technology at the neural interface. 2018 jan;21(1):1-9. 3. morris ld, daniels kj, ganguli b, louw qa. an update on the prevalence of low back pain in africa: a systematic review and meta-analyses. bmc musculoskeletal disorders. 2018 dec;19(1):1-5. 4. fatoye f, gebrye t, odeyemi i. real-world incidence, and prevalence of low back pain using routinely collected data. rheumatology international. 2019 apr;39(4):619-26. 5. akkarakittichoke n, janwantanakul p. seat pressure distribution characteristics for 1 hour sitting in office workers with and without chronic low back pain. safety and health at work. 2017 jun 1;8(2):212-9. 6. defrin r, brill s, goor-arieh i, wood i, devor m. “shooting pain” in lumbar radiculopathy and trigeminal neuralgia, and ideas concerning its neural substrates. pain. 2020 feb 1;161(2):308-18. 7. thompson j, merrill rk, qureshi sa, leven dm. compression of the s1 nerve root by an extradural vascular malformation: a case report and discussion of atypical causes of lumbar radiculopathy. international journal of spine surgery. 2020 feb 1;14(1):96-101. 8. berry ja, elia c, saini hs, miulli de. a review of lumbar radiculopathy, diagnosis, and treatment. cureus. 2019 oct;11(10). 9. durrani mm, malik a. decrease in pain one month after transforaminal lumbar steroid injection in patients with lumbosacral radiculopathy. life science journal. 2020;17(4). 10. shrestha p, subba l, agrawal p, lohani s. outcome of transforaminal epidural steroid injection for lumbar radiculopathy: initial three-year experience at upendra devkota memorial-national institute of neurological and allied sciences, nepal. chinese neurosurgical journal. 2020 dec;6(1):1-7. 11. rocha r. back injuries and management. handball sports medicine: basic science, injury management and return to sport. 2018 may 10:375 12. stochkendahl mj, kjaer p, hartvigsen j, kongsted a, aaboe j, andersen m, andersen mø, fournier g, højgaard b, jensen mb, jensen ld. national clinical guidelines for non-surgical treatment of patients with recent onset low back pain or lumbar radiculopathy. european spine journal. 2018 jan;27(1):60-75. 13. foo y, héroux me, chia l, diong j. involuntary hamstring muscle activity reduces passive hip range of motion during the straight leg raise test: a stimulation study in healthy people. bmc musculoskeletal disorders. 2019 dec;20(1):16. 14. das sm, dowle p, iyengar r. effect of spinal mobilization with leg movement as an adjunct to neural mobilization and c o n v e n t i o n a l t h e ra p y i n p a t i e n t s w i t h l u m b a r radiculopathy: randomized controlled trial. j med sci res. 2018;6(1):11-9. 15. tariq k, shoukat f, ahmed u. effectiveness of mulligan's bent leg raise technique versus muscle energy technique on pain intensity and hamstring flexibility in patients with knee osteoarthritis. rawal medical journal. 2020 apr;45(2):358-62. 16. rina sn. effectiveness of bent leg raise exercise along with conventional physiotherapy comparing with conventional physiotherapy alone for the patients with chronic radiating low back pain (doctoral dissertation, bangladesh health professions institute, faculty of medicine, the university of dhaka, bangladesh.). jiimc 2022 vol. 17, no.2 89 mulligan traction straight leg raise vs passive straight leg raise 17. wu a, march l, zheng x, huang j, wang x, zhao j, blyth fm, smith e, buchbinder r, hoy d. global low back pain prevalence and years lived with disability from 1990 to 2017: estimates from the global burden of disease study 2017. annals of translational medicine. 2020 mar;8(6). 18. irshad a, anwar n, ahmad m, khalid k, ilyas a, sohail m. effects of mulligan traction leg raise versus slump stretching on pain, and functional disability in lumbar radiculopathy. inmed. forum 2021 jun (vol. 32, no. 6, p. 71). 19. kapadia pd, meshram vk. a comparative study on immediate effects of traction straight leg and bent leg raises on hamstring muscle flexibility in normal individuals. ijar. 2019;5(4):274-8. 20. yıldırım ms, ozyurek s, tosun oç, uzer s, gelecek n. comparison of effects of static, proprioceptive neuromuscular facilitation and mulligan stretching on hip flexion range of motion: a randomized controlled trial. biology of sport. 2016 mar;33(1):89. 21. riaz mu, shah f, shah sm. comparison of spinal mobilization with leg movement and neurodynamic sliding technique for improving function in radicular leg pain: jrcrs. 2020; 8 (1): 33-36. journal riphah college of rehabilitation sciences. 2020 mar 30;8(1):33-6. 22. mazumdar j, shriwas jk, wani sk, deshpande n, dixit a, prakash s, et al. a comparison between mulligan traction straight leg raise technique vs muscle energy technique on hamstring tightness in asymptomatic male. int j physiother res. 2014;2(2):412-17. 23. pourahmadi mr, mohsenifar h, dariush m, aftabi a, amiri a. effectiveness of mobilization with movement (mulligan concept techniques) on low back pain: a systematic review. clinical rehabilitation. 2018 oct;32(10):1289-98. conflict of interest authors declared no conflicts of interest. grant support and financial disclosure authors have declared no specific grant for this research from any funding agency in public, commercial or nonprofit sector. data sharing statment the data that support the findings of this study are available from the corresponding author upon request. this is an open access article distributed under the terms of the creative commons attributionnoncommercial 2.0 generic license. jiimc 2022 vol. 17, no.2 90 mulligan traction straight leg raise vs passive straight leg raise case�report abstract with an upsurge interest in holistic view of physical and psychological disorders, bio psychosocial model has gained much attention. maternal depression is considered to manifold risks and vulnerabilities and early child developmental problems, including impaired cognitive, social and academic functioning. the present case study will highlight the intricacies linked with maternal depression in the infancy and early childhood of a 12 years old child, studying in a special education institute of city lahore. the history file revealed that low socioeconomic status and parental conflicts induced depression in the mother of the child, who showed carelessness to the extent of making child vulnerable of experiencing intellectual disability. key words: intellectual disability, maternal depression, maltreatment. the impact of maternal depression is not limited to mother only but its exposure is found to have multiple negative impacts on child's normal development in infancy and early development, including developmental delays, impaired cognitive, 4 emotional and behavioral functioning. infants of postpartum depressive mother have been reported to show patterns of dys-regulated attention and 5 arousal. the most solemn negative effects of postpartum depression are on the child's cognitive development, including language, iq, and piaget's object concept task. however, these effects are completely mingled and contextual influences. the studies on child behavior indorse the sound effects of postpartum depression on children's behavior, antisocial behaviors, and psychiatric disorders at home and at 6 school. among these cognitive impairments in children, one is intellectual disability (id). intellectual disability is a developmental disorder describing the condition in which individual's intellectual functioning level and adaptive skills are significantly below the average of his chronological age. as a result of id, individual's practical, social and conceptual functioning is 7 disturbed. family conflicts can cause maternal depression in postpartum period that is the significant predictors of child's emotional and behavioral behavior problems along with intellectual disability (id). the aim of the current study was to emphasize the importance of family conflicts, mental health of primary caregivers, specifically mothers who can have permanent negative impacts in child's development. introduction parents are the primary source of survival and development of children throughout their whole lives, but early childhood development puts a strong impact and determines the future of children. one of the disruptions in the healthy development of children is maternal depression that is a broad term for a spectrum of depressive conditions affecting women during pregnancy and up to one year 1 postpartum. studies have repeatedly revealed that maternal depression is associated with less optimal and insecure parenting. maternal mental health is more emphasized in postnatal period as compared to prenatal period as the postpartum depression (ppd) is associated with weak emotional involvement, neglect, lack of attention, and hostility 2 towards the child. warmness that is the charm of mother-child affiliation lacks in postpartum depression and is replaced by hostility towards child. there are pertinent associations between maternal depression and multiple disruptions in child including early child adjustment, developmental abnormalities, problematic parenting, family conflicts, parental negligence and other family 3 difficulties. maternal depression as a predictor of intellectual disability: bio psychosocial model speaks up rabia khadim, ayesha jabeen correspondence: ayesha jabeen assistant professor department of clinical psychology university of management and technology, lahore e-mail: ayesha.jabeen@umt.edu.pk department of clinical psychology university of management and technology, lahore funding source: nil; conflict of interest: nil received: november 19, 2019; revised: june 05, 2020 accepted: june 06, 2020 bio psycho-social model speaks upjiimc 2020 vol. 15, no.2 133 case study the present case study is about a 12 years old child who was referred by his teacher with the presenting complaints of speech difficulties, academics and behavioral problems of being hyper, aggressive and hitting others. the in-depth clinical interview with the father of child revealed that child's early developmental years made him vulnerable towards intellectual disability. apparently child's socioeconomic status was below-average. there were inter-parental conflicts and relationship difficulties. the mother of child also had poor mental health that made her vulnerable towards maternal depression. the child had a healthy normal birth and there was no sign of abnormality. he appropriately achieved the entire developmental milestone at 2 years except speech and toilet training. according to father, mother had no affiliation with her child and she used to physically abuse him. she had careless and neglected attitude towards child. in case of illness, mother used to pick those medicines for child that induced dizziness and sleepy effects as she used to give child extra doses of cough syrup. after the child got accidently burned, she misused the doctor's prescription for child which had the abnormal effect on child's development. the frequency of doses was unknown to father but he was suspicious about mother regarding child's condition. neglecting parenting and conflicts caused divorce of parents and child remained with his father. afterwards, child stopped speaking and showed inappropriate attention, aggression and hyperactivity as teasing and hitting others. the child started formal education at 4 years of age but had various unsuccessful experiences at normal schooling because of his speech and behavioral problems. so, at 7 years of age, he was admitted to a special education school where he was suspected with intellectual disability (id-moderate), affecting conceptual, social and practical domains of child. the developmental assessment tool, portage guide to early education (pgee) revealed the 9-10 years of overall discrepancy between chronological and functional age of child. he had 2-3 words speech, lack of socialization and cognitive impairment. bender gestalt test (bgt) was administered to find the developmental maturation of child that was up to 3 years. fig. 1: this figure is showing the func�onal level of the child on different areas of pgee fig. 2: this figure is showing the comparison of cogni�ve func�oning on pgee and bgt table i: conceptual, social and prac�cal domain of child according to his severity level bio psycho-social model speaks upjiimc 2020 vol. 15, no.2 134 discussion family provides the grounds for the upbringing of children where parents are the primary caregivers. parental factors contribute towards the bio-psycho and social developmental processes of children that have long lasting impact on future life. there are multiple factors in family processes that can influence the normal growth patterns of children including parental conflicts, poor mental health, negligence, lack of support and parental divorce. this case study brought all such factors into light that can have adverse effect on normal children throughout their whole life and make it worse for them. as in child's case, his parent's maltreatment made life full of negative challenges effecting his cognitions, emotions and behaviors. parental neglection, conflicts, financial worries and relationship difficulties can put negative impact of one of the spouse as mother's mental health (maternal depression) was affected badly in current case. maternal mental illness is associated with 4,8 child's cognitive, social and academic impairment. maternal depression is associated with multiple adverse outcomes for child. due to mental suffering of mother during postpartum depression (ppd), her hostile behavior towards child put into danger that lead towards overdose of medication. studies have revealed through the reports of overdose with promethazine (phenergan) can originate significant variations into the nervous system including 6 dizziness, restlessness, agitation, and confusion. these adverse effects put the psychology of child into danger that come out as hyperactivity, aggressiveness and hitting behavior. along with these behavioral issues, the overdose of promethazine plays a significant role towards the likelihood of intellectual disability (id). as a result, the child's intellectual and adaptive functioning was disrupted. studies have revealed that the social factors of parental conflicts, divorce and destructive home environment are those social factors that can lead towards maladjustment of children affecting their biological, psychological and social functioning. similarly, a disruptive home environment also has the profound effect on the wellbeing of children and 3 interferes with the healthy development. the key goal of this study was to understand all the parental factors including maternal depression which effect the healthy growth of children. table ii: case formula�on of child according to bio-psycho-social factors the intervention plan was developed according to the needs of child in which goals were taught in one setting. because of single parent, father couldn't give proper attention to child. family processes are accountable for child's development and intervention as both parents have their own specific roles to play. references 1. natasha k, sriraman, do-quyen p, reeti k. postpartum depression: what do pediatricians need to know? 2017; 38(12): 541-51. 2. heinisch c, galeris mg, gabler s, simen s, hoffmeister jj, fobel j et al. mothers with postpartum psychiatric disorders: proposal for an adapted method to assess maternal sensitivity in interaction with the child. 2019; 10:47. 3. slomain j, honvo g, emonts p, reginster jy, bruyere o. consequences of maternal postpartum depression: a systematic review of maternal and infant outcomes. 2019; 15: 174. 4. madlal ss, kassier sm. antenatal and postpartum depression: effects on infant and young child health and feeding practices. 2016; 31(1): 1-7. 5. abdollahi f, abhari fr, zarghami m. post-partum depression effect on child health and development. acta med iran 2017; 55(2):109-14. 6. mirhosseini h, moosavipoor sa, nazari ma, dehghan a, mirhosseini s, bidaki r et al. cognitive behavioral development in children following maternal postpartum depression: a review article. electron physician. 2015;7(8):1673-79. 7. american psychiatric association. diagnostic and statistical manual of mental disorders. 5th ed. washington; dc; 2013. 33 p. 8. abdollahi f, rezai abhari f, zarghami m. post-partum depression effect on child health and development 2017; 55(2): 109-14. bio psycho-social model speaks upjiimc 2020 vol. 15, no.2 135 original�article abstract objective: to study the teratogenic effects of bisphenol a on the testicular histogenesis of developing rat pups during prenatal and early postnatal life. study design: laboratory-based randomized control trial. place and duration of study: the present study was carried out at anatomy department of islamic international medical college rawalpindi in association with national institute of health (nih) islamabad from september 2018 to september 2019. materials and methods: eight weeks old 10 pregnant female rats were divided into 2 groups each containing 5 pregnant female rats. pups were delivered by spontaneous vaginal delivery. control group a was composed of 15 male rat pups from 5 pregnant female rats fed on the standard diet during pregnancy and lactation till day 21. experimental group b was composed of 15 male rat pups from 5 pregnant female rats which were given 250μg/kg/day bisphenol a subcutaneously during pregnancy and lactation till day 21. results: deterioration of histological parameters was significantly seen in group b. tubule differentiation index(tdi) in group b was 69.22%; significantly reduced as compared to control group a. the modified johnsen's criteria in group b was score 3 (in 33.3% rats ) and score 1 (in 26.6% rats) as compared to score 7 (in 100% rats) in control group a. 66.6% rats in group b showed severe (grade 4) and 26.6% rats showed moderate (grade 3) epithelial degeneration as compared to control group a. 46.6% rats in group b showed severe (grade 4) and 40% had moderate (grade3) congestion as compared to control group a.46.6% rats in group b showed severe (grade 4) vacuolization and 33.3% had moderate (grade3) vacuolization as compared to control group. conclusion: the teratogenic effect of bpa on developing rat testes is evident when given during prenatal and early postnatal life. the teratogenicity of bpa may adversely affect spermatogenesis and male fertility. key words: bisphenol a, developing rats, early postnatal testicular teratogen, prenatal. 5 bisphenol a. the european food safety authority (efsa) has determined the temporary tolerable daily 6 intake of bpa which is 4μg/kg/day. according to the data published by efsa in 2015; bpa exposure for 7 men and women is 1.01 to 1.06μg/kg/day. bisphenol a is a ubiquitous endocrine disrupting chemicals (edc) which is used in synthesis of epoxy resins and polycarbonate plastics, food cans, water pipes, receipt papers, baby feeding bottles and 3 currency notes. reproductive system is one of the 8 main systems targeted by this endocrine disruptor. exposure to such chemicals in humans is a probable 9 cause of male infertility. developing testis is fundamental component of male reproductive system which is susceptible to teratogens. bpa has deteriorating effects in pregnancy when exposed during critical period of embryonic testicular 10 development. animal studies revealed that bpa has 11 a potent teratogenic potential. in rats during prenatal testicular development (gestational days: introduction bisphenol a was manufactured first by a. p. dianin in 1891 and investigated in 1930s during the hunt for synthetic estrogens and is thus an important 1 2 endocrine disrupting chemical. ' bpa is a xenoestrogen which mimics estrogens and is able to 3 bind estrogen receptors. edward charles dodd first identified the estrogenic characteristics of bpa when 4 he was in search of an estrogen. a study on bpa reported that humans are exposed to 10μg/day of bisphenol a: a testicular teratogen in developing rats during prenatal and early postnatal life tooba khurshid, rehana rana, shabana ali, huma beenish, ali ahmed, syeda sara bano correspondence: dr. tooba khurshid senior lecturer department of anatomy islamic international medical college riphah international university, islamabad e-mail: khursheedtooba@gmail.com department of anatomy islamic international medical college riphah international university, islamabad funding source: nil; conflict of interest: nil received: october 30, 2019; revised: january 20, 2021 accepted: january 28, 2021 bisphenol a: a testicular teratogen in ratsjiimc 2021 vol. 16, no.1 19 13.5-16.5), there is migration of primordial germ cells towards genital ridge along with sertoli cells differentiation, formation of seminiferous cords and leydig cells differentiation. postnatal testicular development includes neonatal period (3–7 post natal days), early infantile period (8–14 days), late infantile period (15–20 days), juvenile period (21–32 12 days) and peri-pubertal period (32–55 days). oxidative stress induced by bpa during the testes development is the key factor in aetiology of male 11 infertility. exposure of preimplantation embryos to bpa impairs testes development and disrupts 6 testosterone synthesis. a study of bpa exposed rats reve a l e d a b n o r m a l s p e r m at i d s , i nte rst i t i a l congestion, scanty cellular components and empty tubular lumina with significant decrease in leydig cell count, germinal epithelium height and tubular 5 diameter. numerous phenol derivatives were detected in water bodies of river indus in pakistan. all samples we re a d u l te rate d w i t h p h e n o l , 2 , 4 b i s ( 1 , 1 13 dimethylethyl). to the best of researcher's knowledge, in pakistan where significant quantity of bpa is leached into water, such a study was needed to be conducted in pregnant rats to see teratogenic role of bpa during prenatal and early postnatal life. with exposure to bpa, this study could highlight the probable reason of increasing male infertility in pakistan by identifying the problem in progression of spermatogenesis in rat pups with the help of seminiferous tubule differentiation and histological scoring. materials and methods the experimental study was carried out by randomized control trial in animal house of national institute of health, islamabad (nih) from september 2018 to september 2019 after approval of ethics review committee. randomization was by simple random sampling. eight weeks old 10 female and 5 male albino sprague dawley rats were kept under standard temperature at 22 ± 0.5˚c in stainless steel cages in 12-hour light dark cycle with 50% humidity. adult female rats were caged with adult male rats (2 females/ male). they were given food and water ad libidum for 7-days to acclimatize. they mated under normal conditions in cage. female rats with presence of vaginal plugs were considered at day 0 of pregnancy. pregnant rats were divided into 2 groups. each group comprised of 5 pregnant rats. one group was fed on normal diet and other group was given bpa (table i). pups were delivered by spontaneous vaginal delivery at time of birth. male rat pups which were 21 days old were included in the study. male pups with obvious pathology or male pups older than 21 days old were rejected. delivered male pups were divided into two groups as in table i. this study constituted a sample size of 30 male rat pups. table i: grouping of animals (n=30) after 42 days of experiment, 21 days old male rat pups were euthanized and dissected. testes were fixed in bouin's fixative, stained with eosin and hematoxylin and examined under x10 and x40 power of light microscope and parametric data was collected by the principal researcher. microscopic parameters included tubule differentiation index (% of tubules with more than 3 layers of differentiated germinal epithelial cells) and assessment of spermatogenesis with modified johnsen's crirteria from 1-7 with 1 being the lowest (absence of germinal epithelium and cells) and 7 being the highest (presence of rounded spermatids). in between 7 and 1 spermatogonia, spermatocytes and 14 sertoli cells were seen . these two parameters were assessed by independent samples t test. the parameters of epithelial degeneration, congestion and vacuolization were classified according to international harmonization of toxicologic 15 pathology nomenclature. these three parameters were assessed by chi square test. the data was analysed by spss version 21. a p-value of less than 0.05 was considered significant. results tubule differentiation index (tdi) and modified johnsen's criteria were reduced in group b significantly as compared to control group a (figure 1, table ii). severe and moderate grades of epithelial bisphenol a: a testicular teratogen in ratsjiimc 2021 vol. 16, no.1 20 d e g e n e ra t i o n , i n t e r s t i t i a l c o n g e s t i o n a n d vacuolization were seen in rats of group b as compared to control group a. (figure 2, table iii, figure3, table iii, figure 4, table iii respectively). worldwide. almost half of these cases are attributed to male partner. a study by majid et al (2019) depicted that oxidative stress due to edcs is one of major mechanisms involved in causing male 16 infertility. programming of masculinization occurs during the gestation days 15–18 in laboratory albino discussion infertility is defined as failure to conceive after unprotected and frequent sexual intercourse for more than a year which affects 15% couples fig 1: figure 19 tdi and assessment of spermatogenesis with modified johnsen's criteria in testes of albino rat showing score 7 in control group a and score 3 in experimental group b. (a: control group a, b: experimental group b) (h&e, x40) table ii: group wise distribu�on of tubule differen�a�on index (anova) and assessment of spermatogenesis with modified johnsen's criteria (chi square test) of seminiferous tubules of testes among the control and the experimental groups in albino rats (n=30). p-value ≤ 0.05 fig 2: germinal epithelial degenera�on (severe) in testes of albino rat (arrow) shown in experimental group b. negligible degenera�on is seen in control group a (a: control group a, b: experimental group b) (h&e, x40) fig 3: inters��al conges�on (severe) in testes of albino rat (arrow) shown in experimental group b. negligible conges�on is seen in control group a (a: control group a, b: experimental group b) (h&e, x40) fig 4: vacuoliza�on of germinal epithelium (severe) in testes of albino rat (arrows) shown in experimental group b. negligible vacuoliza�on is seen in control group a (a: control group a, b: experimental group b) (h&e, x40) table iii: group wise distribu�on of tubular degenera�on, inters��al conges�on and germinal epithelial vacuoliza�on (chi square test) in testes of albino rats among the control and the experimental groups p-value ≤ 0.05 bisphenol a: a testicular teratogen in ratsjiimc 2021 vol. 16, no.1 21 rats and in humans between weeks 8–14 of 17 gestation. animal studies have shown that pregnant females are at risk from bpa exposure since 18 19 bpa is a known teratogen as well. ' in humans, bpa has been detected in maternal and fetal plasma, amniotic fluid, placental tissue and in milk of 20 lactating mothers. in present study, bpa was administered during pregnancy and 21 days after delivery during lactation. testicular histogenesis was assessed by quantitative and qualitative parameters. bpa adversely affected its development owing to its teratogenicity. tdi and modified johnsen's criteria have been evaluated in this study both prenatally and in early postnatal period to see teratogenic potential of bpa and its role in development of subsequent male infertility. differentiation of spermatogenic epithelium is indicated by tubule differentiation index. in present study, tdi in group b was significantly reduced as compared to control group which was due to disruption of germinal epithelial cells lipid membranes which occurred by generation of ros by bpa. a study on diabetic rat has shown reduction in 21 tdi in testes showing tubular damage. modified johnsen's criteria manifests progression of stages of spermatogenesis. the reduced score in this study with bpa indicated spermatogenic arrest due to leydig cells disruption which caused testosterone levels to fall. since testosterone is principally implicated in progression of spermatogenesis so the score fell. along with tubular degeneration there was loss of cells of spermatogenic lineage. this has been supported by a study in which bpa with dose of 22 100mg/kg/day was used. in a study, bpa has induced mitochondria-mediated apoptosis due to activation of caspases in cytosol of 23 hepatic cells. in present study group b, significant degeneration of germinal epithelium was seen. loss of normal cellular array and architecture of spermatogenic lineage was clearly evident in group b. as a result, sloughing of germinal epithelium from basement membranes occurred due to increased movement of smooth muscle cells as a result of ongoing inflammation by the released ros. this result is in line with a study in which bpa-induced oxidative damage is seen in kidney, testis and liver of 24 25 rats with degenerative changes. ' in present study, testicular interstitium showed significant congestion in bpa group. this was due to ongoing inflammation by free radicals which led to recruitment of inflammatory mediators in testicular blood vessels. this caused increased blood flow and hyperemia by focal dilation of blood vessels evident 26 as congestion. this result has been supported by 27 various studies on rat testes when exposed to bpa. vacuolization is due to disturbance of fluid balance in spermatogenic and sertoli cells. uncharged lipophilic bases and phospholipids enter cells by diffusion which become positively charged in organelles. accumulation of charged form of weak bases increases intraorganellar osmotic pressure which attracts water from extracellular 28 compartment and thus vacuoles appear. in present study, severe vacuolization of spermatogenic cells and sertoli cells was seen in group b rats as compared to control group. this result is in accordance with 29 other studies. being a rodent based developmental study it has offered constraints in inducing pregnancy in all the rats at the same time. lactation was an important event during the current study in which mothers and newborn pups showed individual variations. this study recommends future investigation into the imperative male infertility markers like s e m e n a n a l y s i s , s p e r m m o r p h o l o g y a n d immunohistochemistry. conclusion the present study indicates that bpa has detrimental effects on histology of developing testes owing to its teratogenic potential. thus, spermatogenesis and male fertility may be adversely affected by bpa especially when exposed to pregnant and nursing mothers. references 1. vandenberg ln, maffini m v., sonnenschein c, rubin bs, soto am. bisphenol-a and the great divide: a review of controversies in the field of endocrine disruption. endocr rev. 2009 feb 1;30(1):75–95. 2. liang f, huo x, wang w, li y, zhang j, feng y, et al. association of bisphenol a or bisphenol s exposure with oxidative stress and immune disturbance among unexplained recurrent spontaneous abortion women. chemosphere. 2020;257:127035. 3. xu a, li x, li k, zhang j, li y, gong d, et al. linoleic acid promotes testosterone production by activating leydig cell gpr120/ erk pathway and restores bpa-impaired testicular bisphenol a: a testicular teratogen in ratsjiimc 2021 vol. 16, no.1 22 toxicity. steroids. 2020;163. 4. caporossi l, papaleo b. exposure to bisphenol a and gender differences: from rodents to humans evidences and hypothesis about the health effects. j xenobiotics. 2015;5(1):15–9. 5. munir b, qadir a, tahir m. negative effects of bisphenol a on testicular functions in albino rats and their abolitions with tribulus terristeris l. brazilian j pharm sci. 2017;53(3):1–9. 6. tomza-marciniak a, stępkowska p, kuba j, pilarczyk b. effect of bisphenol a on reproductive processes: a review of in vitro, in vivo and epidemiological studies. j appl toxicol. 2018;38(1):51–80. 7. hass u, 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system. front endocrinol (lausanne). 2020;11(july):1–13. 12. picut ca, remick ak, de rijk epct, simons ml, stump dg, parker ga. postnatal development of the testis in the rat. toxicol pathol. 2015;43(3):326–42. 13. shaikh h, memon n, bhanger mi, nizamani sm. gc / ms based non-target screening of organic contaminants in river indus and its tributaries in sindh ( pakistan ). 2014;15(1):42–65. 14. kobyliak nm, falalyeyeva tm, kuryk og, beregova t v, bodnar pm, zholobak nm, et al. antioxidative effects of cerium dioxide nanoparticles ameliorate age-related male infertility : optimistic results in rats and the review of clinical clues for integrative concept of men health and fertility. epma j. 2015;(june). 15. mann pc, vahle j, keenan cm, baker jf, bradley ae, goodman dg, et al. international harmonization of toxicologic pathology nomenclature: an overview and review of basic principles. toxicol pathol. 2012;40(4):7s13s. 16. majid m, ijaz f, baig mw, nasir b, khan mr, haq iu. scientific validation of ethnomedicinal use of ipomoea batatas l. lam. as aphrodisiac and gonadoprotective agent against bisphenol a induced testicular toxicity in male sprague dawley rats. biomed res int. 2019;2019. 17. kita dh, meyer kb, venturelli ac, adams r, machado dlb, morais rn, et al. manipulation of pre and postnatal androgen environments and anogenital distance in rats. toxicology. 2016;368–369:152–61. 18. bakry s, sharf-el o, deen s, bakry w, ali a, shaeir f, et al. teratogenicity of bisphenol-a (bpa) in pregnant rat. am j toxicol sci. 2015;7(4):229–38. 19. moreman j, lee o, trznadel m, david a, kudoh t, tyler cr. acute toxicity, teratogenic, and estrogenic effects of bisphenol a and its alternative replacements bisphenol s, bisphenol f, and bisphenol af in zebrafish embryo-larvae. environ sci technol. 2017;51(21):12796–805. 20. sayıcı iu, simsek orhon f, topçu s, ulukol b, baskan s. preliminary study on bisphenol a levels and possible exposure history of mother and exclusively breastfed infant pairs. eur j pediatr. 2019 apr 1;178(4):541–50. 21. sanjeev s, murthy mk, devi ms, khushboo m, renthlei z, ibrahim ks, et al. isolation , characterization , and therapeutic activity of bergenin from marlberry ( ardisia colorata roxb .) leaf on diabetic testicular complications in wistar albino rats. 2019;7082–101. 22. yousaf b, amina, liu g, wang r, qadir a, ali mu, et al. bisphenol a exposure and healing effects of adiantum capillus-veneris l. plant extract (ape) in bisphenol ainduced reproductive toxicity in albino rats. environ sci pollut res. 2016;23(12):11645–57. 23. kamel ah, foaud ma, moussa hm. the adverse effects of bisphenol a on male albino rats. j basic appl zool vol. 2018;79(6):1–9. 24. acaroz u, ince s, arslan-acaroz d, gurler z, demirel hh, kucukkurt i, et al. bisphenol-a induced oxidative stress, inflammatory gene expression, and metabolic and histopathological changes in male wistar albino rats: p ro te c t i ve ro l e o f b o ro n . tox i c o l re s ( c a m b ) . 2019;8(2):262–9. 25. amjad s, rahman ms, pang mg. role of antioxidants in a l l e v i a t i n g b i s p h e n o l a t ox i c i t y. b i o m o l e c u l e s . 2020;10(8):1–26. 26. akintunde jk, farouk aa, mogbojuri o. metabolic treatment of syndrome linked with parkinson's disease and hypothalamus pituitary gonadal hormones by turmeric curcumin in bisphenol-a induced neuro-testicular dysfunction of wistar rat. biochem biophys reports. 2019;17(november 2018):97–107. 27. tolba am, mandour da. histological effects of bisphenol-a on the reproductive organs of the adult male albino rat. 2015;22:89–102. 28. sharma s, ahmad s, afjal ma, habib h, parvez s, raisuddin s. dichotomy of bisphenol a-induced expression of peroxisome proliferator-activated receptors in hepatic and testicular tissues in mice. chemosphere. 2019;236:124264. 29. marghani bh, ateya ai, saleh rm, halawa aa, eltaysh ra, awadin wf, et al. journal of veterinary healthcare issue no. : 2575 1212 p450 3 β hydroxysteroid dehydrogenase blood and tissue sampling. 2018;(3). bisphenol a: a testicular teratogen in ratsjiimc 2021 vol. 16, no.1 23 original�article abstract objective: the objective of this study was to determine the frequency of pathogens and their drug sensitivity pattern in children presenting with urinary tract infections. study design: it was a cross sectional study. place and duration of study: the study was conducted in 6 months from nov 01, 2013 to apr 30, 2014 at casualty and outpatient departments of pediatrics at benazir bhutto hospital, rawalpindi. materials and methods: all the children between 1‐12 years of age with one or more symptoms of uti were included in study. the collected urine samples of the patients were transported immediately to the laboratory for urinalysis, culture and sensitivity. cultures were done directly on cled agar medium and incubated for 48 0 hours at 37 c. sensitivities were checked for trimethoprim‐sulfamethoxazole, amoxycillin‐clavulanic acid, nalidixic acid and others. all data were entered and analyzed in spss version 16. results: out of 155 children, 72.26% (n=112) had e.coli, 14.84% (n=23) had klebsiella pneumoniae, 10.32% (n=16) had staphylococcus saprophyticus and 2.58% (n=4) had others. these bacterial pathogens were sensitive to amoxycillin‐clavulanic acid and trimethoprim‐sulfamethoxazole. conclusion: the results of the study revealed that escherichia coli followed by klebsiella and staphylococcus saprophyticus are the leading pathogens of urinary tract infection in children. out of three antimicrobials studied, amoxycillin‐clavulanic acid and trimethoprim‐sulfamethoxazole have been found to be superior in efficacy as compared to nalidixic acid. key words: urinary tract infection, children, pathogens, sensitivity. causes renal damage by renal scarring leading to end 4 stage renal disease. increasing resistance of bacterial pathogens is of worldwide concern that is varied in different regions 5 and even countries. most utis in developing countries are treated on an empirical basis; thus treatment should be based on available local data regarding the susceptibility of common pathogens to 6 antibiotics. there is increase of antibiotic‐resistant strains, which are created because of antibiotic abuse and inappropriate choice of antibiotics; however the recent development of new antibiotics has led to changes in the antibiotic susceptibilities of the 7 pathogens. different studies have shown study that the most commonly isolated organisms from urine culture were escherichia coli (66.3%), staphylococcus saprophyticus (14.9%), klebsiella pneumoniae (11%) and the highly active antibiotic against them was nalidixic acid (70%), and then amoxicillin‐clavulanic 1,8 acid (29.9%), co‐trimoxazole (16.4%). this study was designed to determine the microorganisms and the sensitivity patterns of these organisms to various drugs. the result of the study introduction the term urinary tract infection (uti) indicates the invasion by microorganisms of previously sterile urinary system. the worldwide incidence of urinary 1 tract infection in children is 30%. in usa the incidence of uti in children is 3‐7% in girls and 1‐2% 2 in boys. the prevalence ranges from 2‐8% 3 throughout childhood. however, in iran the incidence of uti is comparatively lower than the western world about 3% of girls and 1% of boys experience first episode before reaching 11 years of 1 age. childhood uti requires early diagnosis as it causative organisms and their sensitivity pattern of urinary tract infection in children 1 2 3 sidra tul muntaha, mutassim ismail, farhan hassan jiimc 2016 vol. 11, no.4 correspondence: dr. farhan hassan department of community medicine rawalpindi medical college holy family hospital, rawalpindi e‐mail: farhan.25hd@hotmail.com 1 department of pediatrics yusra medical & dental college, islamabad 2 department of pediatrics benazir bhutto hospital, rawalpindi 3 department of community medicine rawalpindi medical college holy family hospital, rawalpindi funding source: nil; conflict of interest: nil received: aug 01, 2016; revised: oct 15, 2016 accepted: nov 15, 2016 uti in children 145 jiimc 2016 vol. 11, no.4 uti in children would provide future guidelines for effective prescribing practices and management of utis for our population. the exact information about the infecting organism and pediatric utis in a region is usually not available, and if available it is outdated as antimicrobial sensitivity patterns are bound to change over a period of time. this study aims to facilitate the empiric treatment of patients with symptoms of utis. moreover, the data would also help authorities to formulate antibiotic prescription policies, at least for a region. materials and methods this was cross sectional descriptive study. duration of the study was six months from nov 01, 2013 to apr 30, 2014 and sampling technique was non‐ probability purposive. all children between 1‐12 years of age of either sex presented with one or more clinical symptoms of uti were included. all children who have already taken antibiotics in the past 24 hours, already catheterized, uncircumcised males or children with phimosis or paraphimosis were not included in study. basic demographic information including name, age, gender, weight, and height was collected. midstream urine samples of 155 patients were collected by aseptic measures for routine examination and culture sensitivity in children older than 2 years, by sterile adhesive pediatric urine bag in children up to 2 years and by suprapubic aspiration in children between 1 to 2 years of age, if necessary. t h e c o l l e c t e d s a m p l e s w e r e t ra n s p o r t e d immediately to the laboratory for urinalysis and culture and sensitivity. uti was defined by the presence of a pure growth of more than 105 colony forming units of bacteria per milliliter of urine. cultures were done directly on cled agar medium for 48 hours. antibiotics sensitivity was tested using disc diffusion technique by using various antibiotic discs as per guidelines of national committee for 9 clinical laboratory standards. sensitivities were checked for trimethoprim‐sulfamethoxazole, amoxycillin‐clavulanic acid, nalidixic acid and others. urine culture and sensitivity reports were evaluated and isolated microorganisms along with their sensitivities to the mentioned drugs were entered in already designed performa and all the reports were verified by the pathologist. all data were entered and analyzed by spss version 16. mean and standard deviation were calculated for age, weight and height. percentages and frequencies were calculated for gender, commonly isolated microorganisms (escherichia coli, klebsiella pneumoniae and staphylococcus saprophyticus) and their sensitivity patterns to various drugs (trimethoprim‐sulfamethoxazole, amoxycillin‐ clavulanic acid, nalidixic acid and others). results age distribution of the patients showed that 56.13% (n=87) were between 1‐6 years of age and 43.87% (n=68) were between 7‐12 years of age, mean +sd was calculated as 7.54+2.61 years. according to gender, 36.77% (n=57) children were males and 63.23% (n=98) were females. mean weight and height of the patients were recorded which came out to be 24.48+7.29 kg and 110.29+35.21 cm respectively. frequency of pathogens in children with uti was recorded as shown in table i. sensitivity pattern of various drugs for pathogens was recorded which showed escherichia coli (e. coli) most sensitive to trimethoprim‐sulfamethoxazole (66%), klebsiella pneumoniae to amoxycillin‐clavulanic acid (74%), and staphylococcus saprophyticus to amoxycillin‐ clavulanic acid (76%) as shown in table ii. table i: frequency of pathogens in children with uti (n=155) table ii: frequency of sensi�vity pa�ern of various drugs for pathogens in children with uti (n=155) 146 discussion in this study, out of 155 children, 36.77% (n=57) were male and 63.23% (n=98) were females with female to male ratio of 2.5:1.4. yolbas i et al. in their study analyzed age and gender‐wise data of the prevalence of uropathogens in community‐acquired urinary infections. they found that all the organisms were more common in females than males with ratio of 1 3.9:1.1 which is in agreement with our study. data from other international studies on pediatric patients also report that utis are more common in 10,11 females, which is similar to our finding. however unlike our study, kalantar et al. in his prospective study of 1696 children aged up to 5 years reported 12 male to female ratio of 1.07:1. jahanzeb et al. in their study included children up to 12 years of age and found that uti is more common in males with an overall male to female ratio of 1.2:1. during the first 13 year of life males were infected more than females. this was also reported by all other researchers, observed as 2.8‐5.4:1.0 in the first year of life and changing to 1:10 in the second year of life because in infancy more common in uncircumcised males and later in life more common in females due to shorter length of urethra in females which shortens the distance of travel for bacteria to reach the urinary 14 bladder. frequency of pathogens in children with uti was recorded, it showed that 72.26% (n=112) had e.coli, 14.84% (n=23) had klebsiella pneumoniae, 10.32% (n=16) had staphylococcus saprophyticus and 2.58% (n=4) had others. e. coli (72.26%) was the leading infecting organism of pediatric uti at our center. this is in consistent with studies reported by mashouf et 1 12 al. (57.4%) in iran, kalantar et al. (54.8%) in iran, 5 1 brad et al. (58%) in romania. data from the above 6 studies showed that e. coli are consistently found predominant uropathogen irrespective of country, community or hospital setting. our study demonstrated klebsiella pneumoniae in 10.32% subjects. yolbas i et al. in a study, showed similar data 1 with klebsiella spp. being detected in 20.7% cases 11 14 and in various parts of the world as 14.0%, 14.5% 13 and 21.0% cases. findings of study is in agreement with another study showing the most commonly isolated organisms from urine culture were e s c h e r i c h i a c o l i ( 6 6 . 3 % ) , s t a p h y l o c o c c u s saprophyticus (14.9%), klebsiella pneumoniae (11%) and the highly active antibiotic against them was nalidixic acid (70%), and then amoxicillin‐clavulanic 1,9 acid (29.9%), co‐trimoxazole (16.4%). in a study conducted by nayek k et al, author indicated a lower percentage of e.coli infections and a higher infection with proteus and klebsiella species. this could be explained on the basis of sampling technique and the different proportion of males to females in different 17,18 studies. on the other hand some have given a higher percentage of e.coli infection as compared to other organisms which is in agreement with our 19,20 study. we found a valuable laboratory data on antibiotic susceptibilities of uropathogens which allows comparison of the situation in our area with that in other countries and other regions of our country. amoxycillin‐clavulanic acid and trimethoprim‐ sulfamethoxazole were the most sensitive antibiotics in our study. these results are in 21,22 agreement with many other published articles. a study in turkey by rodríguez‐baño j et al. also reported that with amoxicillin‐clavulanate, cure rate of patients with cystitis was 93%, cure rates were 93% in children with susceptible isolates (mic < or =8 23 µ/ml). a study by çoban b et al showed sensitivity to trimethoprim‐sulfamethoxazole (56.9%), and to amoxycillin‐clavulanate (65.2%). they followed up patients for period of 5 years and observed the resistance of e. coli to amoxycillin‐clavulanate decreased from 40.3% to 31.3%, while the resistance to trimethoprim‐sulfamethoxazole decreased from 24 45.6% to 34.7%. a study by jackowska t et al. showed, 86% cases of urinary infection were caused by one of the isolated pathogens i.e. escherichia coli, klebsiella pneumoniae or proteus mirabilis. escherichia coli was the most common isolated pathogen (70‐74%). frequency of isolating of klebsiella pneumoniae grew from 6 to 10%. likewise, in the period of two years they observed the level of the susceptibility to trimethoprim‐sulfamethoxazole (90‐91%) remained same and a non‐statistically s i g n i f i c a n t l o w e r i n g o f s u s c e p t i b i l i t y t o aminopenicillins, and aminopenicillins combined with beta‐lactamase inhibitors from 92 to 74% 25 (p=0.2). 26 another study by mirsoleymani sr concluded from 19,223 collected samples that predominant agents of uti were successively e.coli (65.2%; 95%), jiimc 2016 vol. 11, no.4 uti in children 147 klebsiella pneumoniae (26%; 95%), pseudomonas aeruginosa (3.6%; 95%), staphylococcus coagulase positive (3.7%; 95%) and enterobacter species (0.4%; 95%), and our findings are consistent regarding the most common pathogen of the morbidity. conclusion escherichia coli followed by klebsiella pneumoniae and staphylococcus saprophyticus are the leading pathogens in children with uti. amoxycillin‐ clavulanic acid and trimethoprim‐sulfamethoxazole are superior in efficacy as compared to nalidixic acid. hence amoxycillin‐clavulanic acid or trimethoprim‐ sulfamethoxazole can be used safely when urine culture reports are awaited. references 1. yolbas i, tekin r, kelekci s, tekin a, okur mh, ece a, et al. community acquired urinary tract infection in children pathogens, antibiotic susceptibility and seasonal change. eur rev med pharmacol sci. 2013: 17; 971‐6. 2. roberts kb. urinary tract infection: clinical practice guideline for the diagnosis and management of the initial uti in febrile infants and children 2 to 24 months. pediatrics. 2011; 128: 595‐610. 3. pennesi m, l'erario i, travan l, ventura a. managing children under 36 months of age with febrile urinary tract infection: a new approach. pediatr nephrol. 2012; 274: 611‐ 5. 4. hamid f , md rafiqul islam, paul n, nusrat n , parveen r .urinary tract infection in children: a review .delta med col j. 2013; 1: 51‐7. 5. chakupurakal r, ahmed m, sobithadevi dn, chinnappan s, reynolds t. urinary tract pathogens and resistance pattern. j clin pathl. 2010 ; 63: 652‐4. 6. konca c, tekin m, uckardes f, akqun s, almis h, bucak h, et al. an overview of antibacterial resistance pattern of pediatric community acquired urinary tract infections. 2016; 20: 131‐9. 7. cellen im, maneksha rp, mccullagh e, ahmed s, o'kell f. an 11 year analysis of prevelant uropathogens and changing pattern of e. coli antibiotic resistance in 38,530 community uti. ir j med sci. 2013; 182: 81‐9. 8. paryani jp, memon sr, rajpar zh, shah sa. pattern and sensitivity of microorganisms causing urinary tract infection at teaching hospital. jlumhs. 2012; 11: 97‐100. 9. reller lb, weinstein m, jorgensen jh, ferraro mj. antimicrobial susceptibility testing: a review of general principles and contemporary practices. clin infect dis. 2009; 49: 1749‐55. 10. abdulhadi sk, yashua ah, uba a. organisms causing urinary tract infection in paediatric patients at murtala muhammad specialist hospital, kano, nigeria. int j biomed health sci. 2008; 4: 165–7. 11. brkic s, mustafic s, nuhbegovic s, ljuca f, gavran l. clinical and epidemiology characteristics of urinary tract infections in childhood. med arh. 2010; 64: 135–8. 12. kalantar e, motlagh me, lornejad h, reshadmanesh n. prevalence of urinary tract pathogens and antimicrobial susceptibility patterns in children at hospitals in iran. iran j clin infect dis. 2008; 3: 149–53. 13. jahanzeb khan afridi, mukhtiar ahmad afridi, rahida karim, arshia munir. causative organisms and their sensitivity pattern of urinary tract infection in children of tertiary care hospital. kjms. 2014; 7: 290‐94. 14. yoon je, kim wk, lee js, shin ks, ha ts. antibiotic susceptibility and imaging findings of the causative microorganisms responsible for acute urinary tract infection in children: a five‐year single center study. korean j pediatr. 2011; 54: 79‐85. 15. mashouf ry, babalhavaeji h, yousef j. urinary tract infections: bacteriology and antibiotic resistance patterns. indian pediatr. 2009; 46: 617–20. 16. brad gf, sabau i, marcovici t, maris i, daescu c, belei o, et al. antibiotic resistance in urinary tract infections in children. jurnalul pediatrului. 2010; 13: 73–7. 17. mortazavi f, shahin n. changing patterns in sensitivity of bacterial uropathogens to antibiotics in children. pak j med sci. 2009; 25: 801‐5. 18. nayek k, ghosh tn, chattopadhyay tk, ghosh n, banerjee a, saha i. clinicoetiological profile and drug sensitivity patterns of urinary tract infections in paediatric patients attending a rural tertiary care hospital. pak paed j. 2011; 35: 220‐5. 19. ghorashi z, ghorashi s, ahari hs, nezami n. demographic features and antibiotic resistance among children hospitalized for urinary tract infection in northwest iran. infect drug resist. 2011; 4: 171‐6. 20. bercion r, mossoro‐kpinde d, manirakiza a, le faou a. increasing prevalence of antimicrobial resistance among enterobacteriaceae uropathogens in bangul, central african republic. j infect dev ctries. 2009; 3: 187‐90. 21. habib s. highlights for management of a child with urinary tract infection. int j pediatr. 2012; 20: 943653. 22. saaedeh sa, mattoo tk. managing urinary tract infections. pediatr nephrol. 2011; 26: 1967‐76. 23. rodríguez‐baño j, alcalá jc, cisneros jm, grill f, oliver a, horcajada jp, et al. community infections caused by extended‐spectrum beta‐lactamase‐producing escherichia coli. turk pediatri ars. 2014; 49: 124‐9. 24. çoban b, ülkü n, kaplan h, topal b, erdoğan h, baskın e. five‐year assessment of causative agents and antibiotic resistances in urinary tract infections. turk pediatri ars. 2014; 49: 124‐9. 25. jackowska t, pawlik k, załeska‐ponganis j, kłyszewska m. etiology of urinary tract infections and antimicrobial susceptibility: a study conducted on a population of children hospitalized in the department of pediatrics at warsaw bielany hospital. med wieku rozwoj. 2008; 12: 705‐12. 26. mirsoleymani sr, salimi m, brojeni ms, ranjbar m, mehtarpoor m. bacterial pathogens and antimicrobial resistance patterns in pediatric urinary tract infections: a four‐year surveillance study (2009–2012).international journal of paediatrics. 2014; 2: 1‐6. jiimc 2016 vol. 11, no.4 uti in children 148 page 7 page 8 page 9 page 10 original�article abstract objective: to determine the risk factors, fetal outcome and maternal outcome of placental abruption. study design: retrospective observational study place and duration of study: january 2017 to june 2018, gynaecology department, bolan medical complex quetta. materials and methods: during the study, 189 patients with placental abruption data wes collected from records of labor room, obstetrical ward and neonatal intensive care unit. all diagnosed placental abruption cases were included in this study. the clinical data of the patients presented with placental abruption in our facility was reviewed and the fetomaternal outcome was analyzed. information collected from record included demographics, parity, gestational age, hb% at arrival and risk factors for placental abruption. data was analyzed using ms excel version 13 and results were presented as averages and percentages. results: during study period 189 cases of placental abruption were recorded. grandmultiparity (94.17%) and anemia (83.59%) were identified as major risk factors for placental abruption. the frequency of pih as a risk factor for placental abruption was recorded in (8.9%) cases and history of trauma was noted in [2.6%] cases. maternal deaths were found to be (2.11%) and the women undergone surgical intervention were (15.87%) with (14.28%) developed pph. only (28.57%) fetuses survived in this study population. intrauterine death was diagnosed at arrival in (60.84%) cases. early neonatal deaths were recorded in (13.22%) cases. conclusion: abruption is a frequent and major cause of maternal morbidity and perinatal mortality. anemia and grand multiparty are identified as major risk factors. the frequency of pih and trauma as a risk factor for placenta abruption is found lower than expectation. key words: anemia, maternal outcome, placental abruption, pih, fetal outcome. 4 -3.8 % in pakistan. the incidence appears to increasing in the usa, canada, and several nordic countries possibly due to increase in prevalence of 5 risk factor. it is one of the major causes of obstetric haemorrhage and common cause of maternal 6 morbidity and mortality. it is also a significant cause 7 of perinatal mortality. although etiology of abruptio placentae is not fully understood, its generally multifactorial, that is, abnormal placentation, placental insufficiency, vascular malformations and increased fragility of vessels predispose to hematoma formation resulting in separation of the 8 placenta. the risk factors for placental abruption are h y p e r t e n s i v e d i s o r d e r s o f p r e g n a n c y , polyhydramnios, advanced maternal age, maternal trauma, cigarette smoking, alcohol consumption, cocaine abuse, short umbilical cord, sudden decompression of the uterus, retro placental fibro myoma, amniocentesis, previous miscarriage, grand introduction placental abruption is defined as complete or partial separation of placenta prior to birth. placental abruption is an important cause of maternal and fetal morbidity and mortality. it occurs in around 1% 1 of all pregnancies. placental abruption is a major cause of maternal morbidity and perinatal mortality 1,2 globally and specially in the developing world. the rates of abruptio placentae as high as 4.4-4.5% have 2,3 been reported in developing countries. a study conducted by dar a et al reported an incidence of 3.5 a retrospective analysis of risk factors and fetomaternal outcome of placental abruption rakhshanda mushtaq, uzma afridi, fozia muhammad bakhsh correspondence: rakhshanda mushtaq senior registrar department of obstetrics & gynaecology bolan medical college, quetta e-mail: dr.rakhshinda.mushtaq@gmail.com department of obstetrics & gynaecology bolan medical college, quetta funding source: nil; conflict of interest: nil received: may 01, 2019; revised: november 08, 2019 accepted: december 08, 2019 placental abruption: risk factors and clinical outcomejiimc 2020 vol. 15, no.1 9 multiparity, preterm rupture of membranes (prom),low socioeconomic status and/or low pre 9,10,11,12 pregnancy body mass index. the clinical hallmarks of abruption include vaginal bleeding accompanied by tetanic uterine contractions, uterine hypertonicity, and a non-reassuring fetal 13 heart rate pattern. the signs and symptoms of abruptio placentae vary depending on the severity of bleeding and degree of separation of the 14 placenta. in two third of cases placental abruption is classified as sever due to associated fetomaternal 15 morbidity and mortality. the most common presentations include vaginal bleeding, uterine and abdominal pain and tenderness, abnormal uterine c o n t r a c t i o n s , p r e m a t u r e l a b o r, m a t e r n a l hemodynamic instability, fetal distress, and fetal 14 death. ultrasound examination is useful in diagnosis of placental abruption with reported 16 accuracy of 87.5% due to improved technology. the risk of recurrence of abruptio placentae is reported 17 as 4%-12%. receiving increasing number of women with this grave complication and non-availability of reliable data about baluchistan was the motivation to carry out this study. as bmch quetta is a tertiary care hospital and we receive patients referred from most of the peripheral hospital, so the results of study to some extent may reflect the situation in baluchistan. the objective to conduct this study was to determine the risk factors for abruptio placentae in women of baluchistan seen at bmch emergency ward with placental abruption and to describe the fetomaternal outcome for these patients. materials and methods this retrospective observational study was conducted to analyze all the cases of placental abruption seen at gynecological department of bmch quetta between january 2017 to june 2018.189 cases of placental abruption were included in this study. data was collected from records of labor room, obstetrical ward and neonatal intensive care unit (nicu) by authors. permission of ethical review board was obtained and all ethical issues were addressed. all diagnosed placental abruption cases were included in this study and other patients presented with antepartum haemorrhage due to other causes like placenta previa were excluded. we reviewed the clinical data of patients presented with placental abruption in our facility and analyzed the fetomaternal outcome. information collected from record included demographics, parity, gestational age, hb% at arrival, risk factors for placental abruption i.e. history of trauma, pih, prom, previous abruption, anemia, socioeconomic status, fetal outcome i.e. intrauterine death, early neonatal death, prematurity and maternal outcome i.e. shock, massive transfusion, operative intervention, pph and mortality. data was analyzed using ms excel version 13 and results were presented as averages and percentages. results during study period 189 cases of placental abruption were recorded. most of the cases were unbooked 165 (87%) table i. average gestational age at presentation was 35, 72 weeks (range, 28-41 weeks) table iv. grand multi parity 178 (94.17%) and anemia 158 (83.59%) were identified as major risk factors for placental abruption. 145 (76.71%) women belonged to poor socioeconomic strata. the frequency of pih as a risk factor for placental abruption was recorded in 17(8.9%) cases and history of trauma was noted in 5(2.6%) cases. 25(13.22%) women presented with history of prom and 4(2.1) had previous history of abruption.(table i). average maternal age was recorded as 36 years (range 22-45). table 4. placental abruption resulted in 4 (2.11%) maternal deaths during study period. 92 [48.67%] presented in labor room in the state of shock and 105(55.55%) required massive transfusion.30 (15, 87%) women needed surgical intervention and 27(14.28%) developed pph (table ii) only 54 (28.57%) fetuses survived in this study population. intrauterine death was diagnosed at arrival in 115 (60.84%) cases of placental abruption. early neonatal deaths were recorded in 25 (13.22%) cases.35 (18.51%) babies were delivered prematurely as a result of placental abruption. table iii. table i: risk factor for placental abrup�on placental abruption: risk factors and clinical outcomejiimc 2020 vol. 15, no.1 10 discussion abruptio placenta occurs in 0.8 1.0% of all pregnancies and 1.2% in twin pregnancies 8,19,20 worldwide. hossain et al reported an incidence 21 of 3.7% among pakistanis women. placental abruption is a major cause of obstetrical haemorrhage and perinatal deaths. increased maternal mortality and morbidity associated with 22 placental abruption is due to haemorrhage. during this study period 189 women presented to bmch emergency with placental abruption. 2.11% maternal deaths due to abruptio placentae were recorded. one mother was received dead in emergency with the diagnosis of placental abruption made by a general practioner. another woman developed dic after placental abruption and died. two women died as a result of irreversible shock and uncontrolled pph. like other developing countries, maternal deaths due to hemorrhage are common in our country due to either delay in reaching the health facility or non-availability of blood. 48.67% presented in labor room in the state of shock and received active resuscitation. 55.55% required massive transfusion both due to antepartum and postpartum haemorrhage.15, 87% women needed surgical intervention in the form of emergency caesarean section (24), application of b-lynch suture (7) and internal iliac artery ligation (3) for sever pph 27 women (14.28%) developed pph table ii. in the western world, maternal deaths due to placental abruption are rare; for instance a study done in finland found that, between 1972 and 2005 placental abruption had a maternal mortality rate of 0.4 per 1,000 cases (which means that 1 in 2500 women who had placental abruption died); this was similar to other western countries during that period. without any form of medical intervention, as often happens in many parts of the world, placental abruption has a high maternal mortality rate. the prognosis of this complication depends on whether treatment is received by the patient, on the quality of 23 treatment, and on the severity of the abruption. only 28.57% fetuses survived in this study population. intrauterine death was diagnosed at arrival in 60.84% cases of placental abruption. early neonatal deaths were recorded in 13.22% cases. 18.51% babies were delivered prematurely as a result of placental abruption. table iii poor perinatal outcome characterized by high intrauterine deaths observed in our study is consistent with other 2 4 , 2 5 reports from developing countries. the intrauterine death rate, maternal death rate, mean gestational age and pph rates reported by h. nazli et 25 el are consistent with results of our study. another study conducted by ohhashi m. et. al. reported that placental abruption accounts for 58% of perinatal 26 deaths and 26 % of cases involving brain damage. the fetal prognosis is mostly worse in case of placental abruption. currently, in the uk, about 15% 23 of fetuses die following this event. the maternal effect of abruption depends primarily on its severity, whereas its effect on the fetus is determined both by its severity and the gestational age at which it occurs. fetal morbidity is caused by the insult of the abruption itself and by issues related to prematurity when early delivery is required to alleviate maternal or fetal distress. delivery is required in cases of severe abruption or when significant fetal or maternal distress occurs, even in the setting of profound prematurity. in some cases, immediate delivery is the only option, even before the administration of corticosteroid therapy in this 27 premature infants. average gestational age at presentation was 35, weeks (range, 28-41 weeks). table iv grand multiparty (94.17%) and anemia (83.59%) are identified as major risk factors for placental abruption in our study. 83% women with placental abruption were found anemic (hb% less than 8) according to their blood samples drawn at arrival before the commencement of treatment. table ii: maternal outcome of placental abrup�on table iii: fetal outcome of placental abrup�on table iv: average maternal age and gesta�onal age of fetus at the time of presenta�on placental abruption: risk factors and clinical outcomejiimc 2020 vol. 15, no.1 11 knowing the fact that hb% will remain unchanged initially (as both plasma and rbcs are lost equally during haemorrhage, before the commencement of intravenous fluids, 4 women, though anemic were not included among these women as they had been received treatment outside and referred to bmch for management of placental abruption, in order to avoid the bias that whether the anemia is the cause or consequence of the placental abruption. most of the cases were unbooked 87% and 76.71% women belonged to poor socioeconomic strata. this seems that the lack of antenatal care and poor socioeconomic status are significant contributory factors. the frequency of pih as a risk factor for placental abruption was recorded in 8.9% cases and history of trauma was noted in 2.6% cases. the frequency of pih and trauma as a risk factor for placenta abruption are found lower than expectation. the 8.9% incidence of hypertensive disorder observed in our study may be an underestimate owing to masking of hypertensive disorder by lower blood pressures due to vaginal bleeding in patients with abruptio placentae. 13.22% women presented with history of prom and 2.1 had previous history of abruption. table i a review article by downes et el confirm our study results that placental abruption is associated with significant risk of maternal mortality, perinatal 2 8 mortality, pph and caesarean section. we acknowledge the limitations of our study that it doesn't describe the long term effects of placental abruption on fetus and mother as it is a retrospective study involving the record's analysis and most of these women are lost from follow up. the second limitation of this study was small sample size. a greater sample size is needed to better investigate the causal relationship between the risk factors of placental abruption. to conclude, abruptio placentae is a potentially serious obstetrical complication that tends to compromise maternal wellbeing and fetal viability. increased frequency of placental abruption is observed in women with low socioeconomic status, no antenatal checkup, and poor nutritional status. the results of our study provide important information to the obstetrician regarding the early identification of risk factors for placental abruption and developing individual antenatal care plans for women at risk of developing this complication. proper management of these risk factors may reduce the risk of placental abruption and associated adverse outcome for mother and fetus. furthermore, the results of our study highlighted the need for better equipped labor rooms and nicu to improve fetomaternal outcome in high risk pregnancies like placental abruption. poor socioeconomic status, lack of antenatal care and delay in getting medical help due to long distances were found to be the major contributory factors in bad outcome in our study. the results of this study reflect insufficiencies of our health care management system. as morbidity and mortality associated with placental abruption can be decreased by good antenatal care, correction of anemia, provision of contraceptive services and development of hospitals at far areas. the results of our study can be used to convince the policy makers to take in account the special circumstances of our province keeping in view the dynamics of this area. conclusion abruption is a frequent and major cause of maternal morbidity and perinatal mortality. anemia and grand multiparty are identified as major risk factors. the frequency of pih and trauma as a risk factor for placenta abruption is found lower than expectation. results of maternal and fetal outcome warrant the establishment of well-equipped labor rooms and nicu at tertiary care centers. references 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ø ±­ ° îððíå ìëò åí »®·¿´ ±²´·²»ã îððí ö«´§ å½·¬»¼ îððì ö«´§ïèãå ìëøí÷æ åï ­ ½ ®» » ² ã ߪ ¿ · ´ ¿ ¾ ´ » º ® ±³ æ ë î ô æ ¸ ¬ ¬ ° æñ ñ © © © ò ¾ ¸ ¶ ò ± ® ¹ ñ ¶ ± « ® ² ¿ ´ ñ î ð ð í ó ì ë ð í ó ¶«´§ñ¬¸»»º·½¿½§ óìîðò¸¬³ò ïîò ø«¼»½»µ îô ò¿¹§ öò츻 »ºº»½¬ ±º ­°¿­³±´§¬·½­ ±² ¼·´¿¬¿¬·±² ±º ¬¸» «¬»®·²» ½»®ª·¨ò ý»­µ¿ ù§²¿»µ±´ ïççéå êîæïïóìò ïíò í¸¿®³¿ öþô 𫲼·® ðô õ«³¿® ßô 󫮬¸§ òíò ü®±¬¿ª¿®·²» ¸§¼®±½¸´±® ·¼» ª­ò ª¿´»¬¸¿³¿¬» ¾®±³·¼» ·² ¿½½»´»®¿¬·±² ±º ´¿¾±®ò ײ¬ ö ù§²¿»½±´ ñ¾­¬»¬ îððïå éìæîëëóêðò ïìò í·²¹¸ õýô ö¿·² ðô ù±»´ òô í¿¨»²¿ ßò ü®±¬¿ª»®·²» ¸§¼®±½¸´±®·¼» º±® ¿«¹³»²¬¿¬·±² ±º ´¿¾±«®ò ײ¬ ö ù§²¿»½±´ ñ¾­¬»¬ îððìå èìæ ïéóîîò ìé original article abstract objective: to determine the effects of iron overload on height, body mass index (bmi), hemoglobin and serum ferritin levels in beta thalassemia major patients undergoing regular blood transfusion. study design: case control study. place and duration of study: it was carried out at quaid-e-azam university, islamabad in collaboration with jamila sultana foundation rawalpindi, thalassemia house rawalpindi and pakistan institute of medical th th sciences (pims), islamabad from 5 january 2010 to 5 december 2014. materials and methods: total 300 individuals were included in the study out of which 200 were beta thalassemia major patients and 100 were controlled matched for age and gender with the thalassemic group. they were further divided into 4 groups of <13 years female, ≥13 years female, <13 years male and ≥13 years male (each having 50 thalassemic and 25 control). height, bmi, hemoglobin and serum ferritin levels were determined. non parametric (spearman) co-relation co efficient was used to find the correlation between bmi and ferritin and hb levels. data was analyzed through graph pad prism 5.01. p<0.05 was considered statistically significant. results: all groups had reduced height, bmi, hb and high ferritin levels as compared to the control groups. significantly positive (p<0.001) correlation of bmi with hemoglobin and serum ferritin levels were observed in thalassemic females of ≥13. while <13 years thalassemic males had significant (p<0.01) negative correlation of bmi with hemoglobin. conclusion: our study revealed that beta thalassemic patients had reduced height and bmi, associated with high levels of serum ferritin and low hemoglobin. key words: body mass index, ferritin, height, hemoglobin, thalassemia major. these transfusions maintain a hemoglobin level higher than 9.5 gm/dl as anemia effects the normal 3,4 growth and development of these patients. despite the fact that blood transfusions are mandatory for the treatment of patients suffering from anemia, repeated transfusions lead to iron overload as human beings do not have the ability to 5 remove the extra accumulated iron. increased intestinal absorption of iron further worsens the 6 condition, due to iron overload. the iron gets deposited in various organs like liver, heart and endocrine glands which lead to various types of endocrinopathies like hypogonadism and diabetes m e l l i t u s w h i c h l e a d to reta rd e d p u b e r ta l 3 development in thalassemia major patients. underweight and under-nutrition may lead to loss of energy and susceptibility to injury and infection, under-function of multiple endocrine systems, as well as distorted body image and other psychological 7 problems. there is increased prevalence of bone disease in patients suffering from thalassemia major 8,9,10 as compared to normal individual. the bone growth depends on the sex steroids which regulate introduction thalassaemia major is a hereditary hemolytic disorder which is treated with repeated blood transfusions. about 240 million beta thalassemia 1 carriers are present all over the world. every year about 100,000 children are born with the disease of thalassemia. on diagnosis of a child with thalassemia homozygous there is a lifelong sequence of blood transfusion every three weeks along with chelation therapy and facing complications due to iron 2 overload and transfusion transmitted infections. growth failure in β-thalassemia major patients undergoing repeated transfusions 1 2 shazia ali , sarwat jahan jiimc 2016 vol. 11, no.3 correspondence: dr. shazia ali associate professor, physiology islamic international medical college riphah international university, islamabad e-mail: alishazia259@gmail.com 1 department of physiology islamic international medical college riphah international university, islamabad 2 department of animal sciences faculty of biological sciences quaid-i-azam university, islamabad funding source: nil ; conflict of interest: nil received: may 09, 2016; revised: july 15, 2016 accepted: aug 17, 2016 growth failure in β-thalassemia major patients 120 bone maturity. thalassemia major patients suffer from hypogonadism and fail to achieve their peak bone mass due to the bone disease which develops 9,11 during the course of their disease . serum ferritin levels above 1000 ng/ml are 12 considered as an iron overload. the levels of serum ferritin vary among patients getting multiple 13 transfusions. however, the cutting level at which iron toxicity and organ damage takes place is still not 14 identified. the biochemical screening such as serum ferritin and hemoglobin levels are of paramount importance in all beta thalassemia patients in pediatric and adolescent age groups. these levels should be detected and treated for preventing pubertal delay in such individuals which has not been recognized in our part of the world in view of their pubertal growth. therefore, present study was done to determine the effects of iron overload on height (cm), bmi (kg/m2), serum ferritin (ng/ml) and hemoglobin (gm/dl) levels along with exploration of the correlation of bmi with serum ferritin (ng/ml) and hemoglobin (gm/dl) levels of beta thalassemic patients of pubertal age group undergoing repeated blood transfusions with chelation therapy. materials and methods a case control study was carried out at quaid-e-azam university, islamabad in collaboration with jamila sultana foundation rawalpindi, thalassemia house rawalpindi and pakistan institute of medical th sciences (pims), islamabad from 5 january. 2010 to th 5 december 2014. the patients selected for the study were diagnosed as beta thalassemia major according to hemoglobin electrophoresis. these patients were on regular blood transfusions with chelation therapy (desferroxamine injections). patients suffering from any blood disorder other than beta thalassemia major or any other pathology besides spleen and liver enlargement or hepatitis b and c were not included. total 300 individuals out of which 200 were patients suffering from beta thalassemia major and 100 were control matched for age and gender. the age of thalassemic patients along with their corresponding control included in the study was between 8 to 22 years. informed consent and a detail proforma including history and clinical examination were filled on patients visit to the thalassemia center for blood transfusion with chelation therapy. height in centimeter and weight in kilogram were measured and bmi was calculated according to the 8 following formula. bmi= weight in kilogram height in meters² the blood samples from controlled individuals were collected in hospital and blood from thalassemic patients were collected when they came for their routine blood transfusions with chelation therapy. for collection of blood sample, the sampling area was cleaned with a spirit swab. blood sample of (3ml) was drawn from the right median cubital vein of both female and male patients and control individuals. blood was then collected in labeled serum separator tubes containing ethylene diamine tetra acetic acid (edta). the blood samples were centrifuged at 3000 rpm for 10 minutes, and serum separated was stored at 2 80c until analyzed. quantitative measurement of hemoglobin (gm/dl) was done by and serum ferritin was measured by using ferritin (ftl) elisa (enzyme-linked immunosorbent assay) technique. mean ± sem of data was calculated and analyzed through graph pad prism 5.01. comparison amongst bmi, hemoglobin and serum ferritin levels with the control group was done by using unpaired t-test. non parametric (spearman) co-relation co efficient was used to find the correlation between bmi and ferritin and hb levels. p<0.05 was considered statistically significant in both cases. results the results of present study for the following variables are: age mean ± sem of age in male and female patients of <13 years was 10.3± 0.20 years. male patients ≥13 years had mean ± sem of age 16.7 ± 0.42 years, whereas the female patients of ≥13 years had mean ± sem of age 17.8 ± 0.70 years. height (cm) all four groups of thalassemia patients showed significantly reduced (p<0.001) height in comparison with their corresponding control group. comparison of height (cm) of male and female thalassemic patients with their corresponding control of different age groups is represented in fig 1. bmi (kg/m2) comparison of body mass index (kg/m2), in control jiimc 2016 vol. 11, no.3 growth failure in β-thalassemia major patients 121 and thalassemic female and male patients of different age groups is shown in fig 2. all four groups of thalassemia patients showed significant reduction (p<0.001) in bmi on comparison with their corresponding control group. correlation of bmi (kg/m2) with hemoglobin (gm/dl) levels while thalassemic females of ≥ 13 years, bmi (kg/m2) had a significant (p<0.001) positive correlation with hemoglobin (gm/dl), (r=0.558). while thalassemic males of <13 years had a significant (p<0.001) negative correlation of bmi (kg/m2) with hemoglobin (gm/dl) levels (r=-0.374). on calculating correlation of bmi (kg/m2) with hemoglobin (gm/dl) in <13 years thalassemic males it was concluded that there was a significant (p<0.01) negative correlation of bmi (kg /m2) with hemoglobin (gm/dl) levels (r= -0.374). correlation of bmi (kg/m2) with hemoglobin (gm/dl) in control and thalassemic female and male patients in different age groups is represented in table i. correlation of bmi (kg/m2) with serum ferritin (ng/ml) levels correlation of bmi (kg/m2) with, serum ferritin (ng/ml) in control and thalassemic female and male fig 1: mean ± sem of height (cm) of female and male thalassemic pa�ents with their corresponding control of different age groups. ***=p<0.001(value vs corresponding control) fig 2: mean ± sem of bmi (kg/m2) of female and male thalassemic pa�ents with their corresponding control of different age groups. ***=p<0.001(value vs corresponding control) hemoglobin levels (gm/dl) all four groups of thalassemia patients showed significantly reduced (p<0.001) hemoglobin levels on comparison with their corresponding control group. comparison of hemoglobin (gm/dl) of female and male thalassemic patients with their corresponding control of different age groups are presented in fig 3. serum ferritin levels (ng/ml) comparison of serum ferritin (ng/ml) of female and male thalassemic patients with their corresponding control of different age groups are shown in fig 4. all four groups of thalassemia patients showed significantly raised (p<0.001) serum ferritin levels in comparison with their corresponding control group. fig 3: mean ± sem of hemoglobin (gm/dl) of female and male thalassemic pa�ents with their corresponding control of different age groups. ***=p<0.001, value vs corresponding control fig 4: mean ± sem of serum ferri�n (ng/ml) of female and male thalassemic pa�ents with their corresponding control of different age groups. ***=p<0.001, value vs corresponding control jiimc 2016 vol. 11, no.3 growth failure in β-thalassemia major patients 122 patients in different age groups is shown in table i. thalassemic females of ≥13 years had a significant (p<0.001) positive correlation with serum ferritin (ng/ml) levels ® 0.498). therapy can be chief contributing factors in 20 development of underweight thalassemic patients. deena et al. (2014) also showed similar results of 18 (30%) patients who had low bmi of more than 12 21 years of age. this finding is indicating that low bmi is highly dependent on disease progression and are in accordance with our present findings. viprakasit et al. (2001) explained that frequent blood transfusions normally reestablishes the normal 22 growth spurt. however, despite frequent blood transfusions the adolescent growth spurt is often delayed, except if rigorous iron chelation treatment 23 is commenced at an early age in life. previous studies on thalassemic patients revealed that average age of 12 ± 8 years occasionally suffered from growth failure as 77.4% of these patients had 24 normal bmi. although these results are contrary to our study findings where low bmi and reduced height was detected. shalitin et al. (2005) also observed that thalassemic patients receiving effective chelation therapy in prepubertal years still developed short stature with 25 significantly raised serum ferritin levels. but these finding were contrary to results obtained by de sanctis et al. (1994) who detected no significant difference in final height between patients who started chelation therapy during adolescence with high serum ferritin level and those who started chelation therapy during childhood with low serum 17 ferritin levels. hegazi et al. (2013) observed a significantly low hb levels and red blood cell count along with significant increase in the mean serum levels of iron and ferritin in thalassemic patients as compared with control 26 groups. these findings are in accordance with results obtained by charles and linker, (2005); who also reported that hb levels in thalassemic patients 27 are significantly lower than control. these results are similar to our study findings as all thalassemic groups had low hb levels as compared to the control groups. hegazi et al. (2013) carried out a study on thalassemic male and female patients of 4-18 years of age, where there was a significant increase in the mean serum levels of iron and ferritin in thalassemic 26 patients as compared to control groups. similarly, abdulzahra et al. (2011); work also revealed that iron indices were markedly increased in thalassemic table i: correla�on of bmi (kg/m2) with serum ferri�n (ng/ml) and hemoglobin (gm/dl) levels in thalassemic female and male pa�ents of different age groups **=p<0.01, ***=p<0.001, value are considered significant. discussion in our study we observed that patients suffering from thalassemia major presented with reduced height and weight which was associated with increased serum ferritin and low hemoglobin levels. najaf et al., (2008) research revealed that 70% of the males and 73% of female thalassemic patients of 10–27 15 years suffered from short stature. while li et al. (2002) observed short stature in 29.7% of patients. the iron overload leading to endocrinopathies, chronic anemia, zinc and folate deficiencies can lead 16 to short stature. these findings are in accordance to our study results in which we observed reduced height in all four groups of thalassemic males and females patients. therefore, close observation of growth in such individuals can lead to early detection of such findings can be managed to their full extent so, that the individual achieve their normal adult 17,18 height. patients with thalassemia major are exposed to many growth abnormalities as an outcome of the disease or due to the adverse effects of chelating therapy which they receive on regular basis as 19 described. work done by ali and hamdollah, (2004) on thalassemic patients revealed that reduced bmi was more apparent in greater than 10 years of age, 20 which are similar to our study results. thalassemic males of <13 and ≥ 13 years and thalassemic females of ≥13 years in our study had reduced bmi as compared to the control group. the explanation to these results can be that endocrinopathies which appear as a result of iron overload and development of side effects due to prolong use of chelation jiimc 2016 vol. 11, no.3 growth failure in β-thalassemia major patients 123 patients, and the mean serum level of ferritin were 28 also raised as compared to control group. similarly, in our study high serum ferritin levels were observed in all four thalassemic groups as compared to the control groups which was similar to the results reported by adil et al. 2012, suggesting that increased serum ferritin levels are related to short 24 stature and endocrinopathies. conclusion in beta thalassemic patients growth disturbance or delay is main clinical feature that affects the life and wellbeing of such individuals. our study has revealed that patients with beta thalassemia suffer from reduced height, bmi which is enhanced in patients having high levels of serum ferritin (ng/ml) and low hemoglobin (gm/dl). under-nutrition and complications of thalassemia such as tissue hypoxia and side effects of chelating therapy with desferrioxamine effect the patients with iron overload. therefore, lifelong care and management of such patients is mandatory which requires significant cost for proper treatment and ruling out other factors like various hormones that might play a role in development of short stature. references 1. argyropoulou mi, astrakas l. mri evaluation of tissue iron burden in patients with beta-thalassaemia major. pediatrradiol. 2007; 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24: 244–5. 14. olivieri nf, brittenham gm. iron-chelating therapy and the treatment of thalassemia. blood. 1997; 89: 739–61. 15. najaf ipour f, aliasgarzadeh a, aghamohamedzadeh n, bahrami a, mobasri m, niafar m, et al. a crosssectional study of metabolic and endocrine complications in betathalassemia major. ann saudi med. 2008; 28: 361–6. 16. li ck, luk cw, ling sc, chik kw, yuen hl, li ck, et al. morbidity and mortality patterns of thalassemia major patients in hong kong: retrospective study. hong kong med j. 2002; 8: 255–60. 17. de sanctis v, katz m, vullo c, bagni b, ughi m, wonke b. effect of different treatment regimes of linear growth and final height in beta thalassemia major. clinendocrinol. 1994; 40: 791–8. 18. arcasoy a, cavdar a, cin s, erten j, babacan e, gözdasoglu s, et al. effects of zinc supplementation in linear growth in bthalassemia (a new approach). am j hematol. 1987; 24: 127–36. 19. kattamis c, liakopoulou t, kattamis a. growth and development in children with thalassemia major. act paediatr scand. 1990; 1: 111-7. 20. ali akbar asadi pooya, hamdollah karamifar. body mass index in children with beta-thalassemia major. turk j haematol. 2004; 21: 177-80. 21. eissa ds, el gamal ra. iron overload in transfusiondependent b-thalassemia patients: defining parameters of comorbidities. egyptian j haematol. 2014 ; 39: 164–70. 22. viprakasit v, tanphaichitr vs, mahasandana c, assteerawatt a, suwantol l, veerakul g, et al. linear growth in homozygous beta-thalassemia and beta thalassemia/ hemoglobin e patients under different treatment regimens. j med assoc thai. 2001; 84: 929-41. 23. theodoridis c, ladis v, papatheodorou a, berdousi h, palamidou f, evagelopoulou c, et al. growth and management of short stature in thalassaemia major. j pediatr endocrinol metab. 1998; 11: 835-44. 24. adil a, sobani za, jabbar a, awan s. endocrine jiimc 2016 vol. 11, no.3 growth failure in β-thalassemia major patients 124 complications in patients of beta thalassemia major in a tertiary care hospital in pakistan. j pak med assoc. 2012; 62: 307-10. 25. shalitin s, carmi d, weintrob n, phillip m, miskin h, kornreich l, et al. serum ferritin level as a predictor of impaired growth and puberty in thalassemia major patients. eur j haematol. 2005; 74: 93–100. 26. hegazi, m a m, obada ma, elsheashaey. effect of iron overload on function of endocrine glands in egyptian beta thalassemia patients. journal of applied sciences research. 2013;9: 4656-62. 27. charles, a, linker m. current medical treatment and diagnosis. blood. 2005; 13: 482-8. 28. abdulzahra ms, al-hakeim hk, ridha mm. study of the effect of iron overload on the function of endocrine glands in male thalassemia patients. asian j transfus sci. 2011; 5: 127-31. jiimc 2016 vol. 11, no.3 growth failure in β-thalassemia major patients 125 page 33 page 34 page 35 page 36 page 37 page 38 1 editorial emerging physical therapy as an autonomous and specialized health care profession 1 2 syed shakil-ur-rehman , hossein karimi correspondence: dr. syed shakil-ur-rehman associate professor/ principal riphah college of rehabilitation sciences riphah international university, islamabad e-mail: shakil.urrehman@riphah.edu.pk received: feb 13, 2017; accepted: feb 25, 2017 according to the world confederation of physical therapy (wcpt) “physical therapy (pt) is an autonomous global health care profession and physical therapists (pts) serve the community to develop, maintain and restore the optimal movement and functional ability”. they can target the people from childhood to old age, where movement and functional abilities are threatened by ageing, injury, diseases, disorders, conditions or environmental factors. pts help their patients to enhance the quality of life, covering physical, psychological, social and emotional well being. they promote good health, play a preventive role, treat and manage patients suffering from diseases, rehabilitate the patients after injuries, and habilitate children born with disabilities, hence looking at the 1 clients’ health in a holistic approach. pts are skilled for comprehensive history taking, examination, evaluation of the findings from the examination, make clinical judgments, formulate diagnosis, prognosis, and plan the treatment. they are competent enough to independently give consultation to the patients, make referrals to other health care professionals, plan treatment, estimate the outcomes and advise self-management. the broad role of the pts in the health care system is to involve in public health strategies, health advocacy, supervision, delegation, leading the pt institutions, manage, teach, research, and develop and implement local, national and international health 2 policies. currently pt professional has a structured university level education including entry level doctor of physical therapy (dpt), master level programs in sub-specialties, and advanced research based doctoral (phd) and post-doctoral level programs. pt is a main stream health care profession and has e s t a b l i s h e d s u b s p e c i a l t i e s i n c l u d i n g ; musculoskeletal and manual physical therapy, neurological physical therapy, cardiovascular and pulmonary physical therapy, sports physical therapy, gynecological physical therapy, geriatric physical therapy, community based physical therapy, and pediatric physical therapy. currently some specialties have also developed their superspecialties like neurological physical therapy which is further subdivided into pediatric, adult and spinal cord injuries. being once used for polio epidemics and world war victims, it is now used for multiple purpose such as providing high quality evidence based patient care with strict adherence to the patients' safety, research, technological developments, education standards and professional ethics. pt profession in pakistan is trying tofulfill all the three parameters set by the commission on accreditation of physical therapy education (capte), usa. the first one is professional practice expectations by demonstration o f a c c o u n t a b i l i t y , a l t r u i s m , i n t e g r i t y , communication, clinical reasoning, and education. secondly it is used for the patient/client m a n a g e m e n t e x p e c t a t i o n s o f s c r e e n i n g , examination, evaluation, diagnosis, prognosis, planning of care, and outcome assessment. thirdly it is used for practice management expectations of prevention, health promotion, management of care delivery, practice consultation, social responsibility, 3 and advocacy. today pts are aware of the continuous professional development in academics, clinical expertise and research skills. they are updating competence along with lifelong learning to insure high quality evidence based health care services. clinical residency programs, clinical fellowship programs and clinical specialization programs are the integral part of pt education system globally, to achieve the objective of continuous professional development (cpd). furthermore there is licensure system for pts in developed countries and regulated through the government bodies with a view to establish the 4 competence of the pts. on the other hand there are professional bodies like world confederation of physical therapy representing 350,000 pts worldwide through 112 member organization/ 1 department of rehabilitation sciences riphah college of rehabilitation sciences riphah international university, islamabad 2 department of physical therapy university institute of physical therapy university of lahore, lahore 2 jiimc 2017 vol. 12, no.1 countries and they are striving to achieve high standard in pt education, research and practice. many other societies, organizations and associations are working for the same purpose at the country 5 level. as part of the global village this revolution of the pt profession also affected pakistan in the last decade. although pt education was introduced in fifties and there were only 4-5 pt institutions by 2007 but now there are approximately 80-90 institutions offering degree programs in pt. the first doctor of physical therapy program was started in 2007 along with post-professional doctor of physical therapy program for the existing practicing pts with 4 years bs degree. the higher education commission (hec) of pakistan developed a uniform curriculum for entry level doctor of physical therapy program in 2011 and it was revised in 2016 through the national curriculum revision committee which represented the key pt i n s t i t u t i o n s o f t h e c o u n t r y. a n o t h e r ke y development was the establishment of pakistan physical therapy association in 2008 and pts started struggling for the pakistan physical therapy council, which is in progress. national and international conferences were organized by the universities offering pt education and are now regular part of their academic calendar to develop research among the faculty members. pt journals were started and three research journals are regularly published to cover the pt research. ms and phd level programs were stated to educate the faculty through research based and clinical degree programs. the challenges we are currently facing in pakistan are regulation of the pt practice and education, lack of policies for job creation in government hospitals as per the community need, lack of specialized rehab centers, proper clinical service structure, advanced technology for patient care and research. references 1. world confederation for physical therapy. wcpt guideline for physical therapist professional entry level education. london, uk: wcpt; 2011. (access date 8th february, 2017). 2. world confederation for physical therapy. policy statement: education. london, uk: wcpt; 2011. (access date 8th february, 2017). 3. murphy w. through a glass darkly. in: healing the generations: a history of physical therapy and the american physical therapy association. lyme, ct: greenwich publishing group inc. 1995: 7-11. 4. american physical therapy association. today's physical therapist: a comprehensive review of a 21st-century health care profession. alexandria, va: american physical therapy association. 2011 jan. 5. world confederation of physical therapy. what is wcpt; london, uk: wcpt; 2011. (access date 8th february, 2017). jiimc december 2016 page 5 page 6 jiims final 25 original article abstract objective: to evaluate the community knowledge about diarrheal causes in children and use of ors as initial management tool study design. a descriptive cross sectional study. place and duration of study. the study was conducted in the outpatient department of railway hospital from july 15 to september 15, 2011. materials and methods: total 150 mothers were included in the study with inclusion criteria of having at least one child of less than five years of age. a pretested study questionnaire was admitted to the respondents duly filled by the researcher along with the in-depth interview .the result obtained through the study were then categorized into the causes related to digestive system, food contamination and use of hot and cold. results were analyzed on spss 13.0 results: out of 150 mothers included in the study, 30% believed contaminated food and water cause diarrhea where as 18% viewed infections such as bacterial or viral to be the cause. a large percentage i.e. 22% could not associate any cause to the occurrence of diarrhoea.69% continued the breast feeding and normal feeding during the disease but 31% discontinued the treatment and replaced it with rice water, yogurt ,juices and mineral water available in local markets conclusion: this study demonstrated that majority of mothers believed childhood diarrhea is caused by contamination of food and water with the bacterial and viral illness. key words prevalence , childhood diarrhea, sub urban population, breast feeding, contamination. introduction diarrheal diseases are major causes of childhood morbidity and mortality in developing countries. knowledge and practices of mothers or other care-takers of children are important determinants of the occurrence or outcome of diarrheal diseases. diarrheal diseases account for nearly 1.3 million deaths a year among children underfive years of age, making them the second most common cause of child deaths worldwide. over half of the deaths occur in j u s t f i v e c o u n t r i e s : i n d i a , n i g e r i a , 1afghanistan, pakistan and ethiopia. oral rehydration salts (ors) and oral rehydration therapy (ort), adopted by unicef and who in the late 1970s, have been successful in helping manage diarrhea among children. it is estimated that in the 1990s, more than 1 million deaths related to diarrhea may have been prevented each year, largely attributable to the promotion 2and use of these therapies. mull and mull (1988) emphasized the importance of incorporating mothers' perceptions of childhood diarrhea in ort programs (mull and mull, 1988; malik et al, 1992b; chavasse et al, 1996). improving the hygiene and maternal domestic practices is one of the most important means of reducing the 3prevalence of diarrheal disorder. kalsoom and saeed et al(1997) reported about maternal beliefs of bad breast milk, --------------------------------------------------------current maternal knowledge about diarrheal causes in children and role of oral rehydration salt mirza inam ulhaq, shahzad akhtar aziz, ayesha khan, ayesha jehan, anam farooq, feroz inayat correspondence: dr. mirza inam-ul-haque, department of community medicines islamic international medical college, rawalpindi. e-mail: mirza.inamulhaque@riphah.edu.pk 25 26 pregnancy, flies, food and utensils as the major causes of diarrhea. an observational study was conducted in an outpatient department of pakistan railway hospital, rawalpindi from july 15, 2011 to september 15, 2011. sampling technique was stratified random sampling .the sample size was 150 with the inclusion of all the mothers who had at least one child less than five year of age and educational status of at least matriculate. the data was collected through the distribution of pretested questionnaires filled by the final year students which included information about the common understanding of the term diarrhea, its causes, severity, complication, diet taken during diarrhea and management with ors. the questionnaire also includes different health education measures used for creating awareness about diarrhea prevention in people. the data was analyzed by using spss version 13.0. descriptive statistics were applied for all qualitative variables and presented in the forms of tables, frequencies and percentages. material and methods results the total 150 respondents were included in the study; of which 84% were mothers having at least secondary education and 16% belonged to graduate group: with 68% falling in the age up 15-20 years, 24% each in age groups 20-25 8 % in age group 25-35. a large percentage of 56% people perceived diarrhea to be watery or increased frequency of stools. 26% understood diarrhea is both, watery stools with vomiting. 12% believed watery stools with abdominal pain are characteristic of diarrhea. it was revealed that 30% believed contaminated food and water causes diarrhea where as 18% attribute infections such as bacterial or viral to be the cause. a large percentage i.e. 22% could not associate any cause to the occurrence of diarrhea. however, 6% reported other miscellaneous causes such as use of unsterilized feeders, teething, stress, weather changes, and drugs such as use of antibiotics, over-eating and consumption of junk food. table i: list of different beliefs about childhood diarrhea table ii: list of causes of childhood diarrhea table-iii shows 34 percent mothers had knowledge about ors preparation. 66 percent were totally unaware', 60% ofthe respondents treated diarrhea using self medication and 20% with ors and home 26 27 remedies and 20 % visited the outpatient department when the dehydration became severe. 69% continued the breast feeding and normal feeding during the disease but 31% discontinued the treatment and replaced it with rice water, yogurt, juices and mineral water available in local markets. the study also found out that 96% believed in creating mass awareness about diarrhea through television, radio and news paper specially during the summer season, as 98% knew it was a preventable disease which if not treated adequately can prove to be fatal. mothers in this part of pakistan have diverse and complex explanations about the causes of diarrhea based on individual experiences and personalities as well as educational status. a study conducted at institute of american academy of pediatrics about food absorption in infants showed majority of mothers held contaminated food as 4leading causes of diarrhoea. similar study done by(nielsen et al, 2001) indicates that its mandatory to target the wider range of people within the community including religious leaders ,elders, community health workers ,traditional workers .in other study published in south east asian journal of public health revealed various existing discussion table iii: knowledge about home made ors beliefs and practices as unbalanced diet of hot and cold food, contamination with flies ,worms in stomach ,soil eating ,passing of shadow. another study published in pediatric infectious diseases journal indicated that most of the mothers gave less food to children during diarrhea and medicine were given to child only when 5there is blood with stool. , while in our study, breast feeding and normal feeding were continued during diarrhea by majority this was important finding as there are fluid and electrolyte losses during diarrhea and if a child is in adequately fed, he may become dehydrated. the study also focused on the preventive measures for diarrhea control, almost all substantiated the correct method i.e. interrupting the mode of transmission (faeco-oral route) by using boiled water, m a i n t a i n i n g g e n e r a l h y g i e n e o f cooking/feeding utensils, washing hands before feeding the child, and improving the g e n e r a l s a n i t a t i o n c o n d i t i o n s . t h e integrated management of neonatal and childhood illness guidelines given by sante also recommended the interruption of transmission as most important control 6measure. water supply and sanitation are good predictors of diarrhea, in our study 9 out of every 10 respondents believed that keeping a clean house, washing fruits and vegetables, washing hands before cooking, washing kitchen utensils, supervising what children eat, and breast feeding were important ways to prevent diarrhea, same findings were also projected by murray and 7 , 8l o p e z . d i a r r h e a , e v e n t h o u g h a preventable disease has a high mortality 9index of 28% annually. therefore, ample emphasis should be laid on its prevention. in order to decrease high rates of morbidity 27 28 and mortality attributed to diarrhea, an en masse awareness campaign needs to be launched. there has been a reported decline in diarrheal mortality which is most likely d u e t o a d e q u a t e c a s e m a n a g e m e n t (introduced since 1980's). victoria and others' (2000) review provides oral rehydration therapy, has influenced the 10outcome of dehydrating diarrhoea. if the mixtures of ors is unavailable a simple homemade consisting of 5 gm table salt and 20 gm sugar dissolved in one liter of water can be easily prepared emphasis should be laid on homemade preparation as the cost is on the rise and cost effective measures are 11required . the study concluded mothers are important stake holders in children growth specially during breast feeding ,weaning and supplementary feeds ,all intervention must direct to enhance health education and similarly use of oral rehydration salt should be advocated at all levels of healthcare. 1. world health organization(2001),weekly epidemiological record,no.31,3 aug.2001 2. world health organization expert consultation. the optimal duration of exclusive breast conclusion references feeding,2001 3. govender t, barnes jm, pieper ch. contribution of water pollution from inadequate sanitation and housing quality to diarrheal disease in lowcost housing settlements of cape town, south africa. am j public health 2011;101:4-9 4. black r, cousens s, johnson hl, lawn je, rudan i, bassani dg, et al global, regional and national causes of child mortality in 2008: a systematic analysis the lancet 2010; 375:1969-87. 5. lifschitz ch carbohydrate absorption from fruit juices in infants,american academy of pediatrics 2000;105;4. 6. black re.persistent diarrhea in children in developing countries.pediatric infectious diseases journal 1993, 12:751-61 7. sante: the integrated management of neonatal and childhood illness: steps to prevent child mortality sante 2007; 13:1-8 8. murray cjl and lopez ad.the global burden of disease a comprehensive assessment of mortality and disability from diseases and risk factors in 1990 and projected to 2020 .geneva world health organization,1996 9. black r, cousens s, johnson hl, lawn je, rudan i, bassani dg, et al global, regional and national causes of child mortality in 2008: a systematic analysis the lancet. 2010; 375:1969-87. 10. victoria c.g., bryce j., fontaine o., monasch r. reducing deaths from diarrhoea through oral rehydration therapy. bulletin of the world health organization. 2000; 78:1246-55 11. who (2010) program for control of diarrheal diseases, scientific working group reports cdd/80.1, who geneva 28 original�article abstract objective: to appraise the preventive effect of turmeric on anti-mosquito coil smoke induced interstitial fibrosis in lungs of sprague dawley rats. study design: randomized control trial. st th place and duration of study: this study was completed in 10 months from 1 august 2014 to 28 may 2015; conducted at islamic international medical college, rawalpindi and national institute of health (nih), islamabad, pakistan. material and methods: three equal groups of 21 adult albino rats were made. control group x was retained in fresh air. experimental groups m & t inhaled mosquito coil smoke for 12 weeks. group t also had oral turmeric 300mg/kg body weight. after 12 weeks rats were dissected, and their lung tissues were studied microscopically for the presence of fibrosis. results: interstitial fibrosis was markedly present in the histological sections of lung tissues from experimental group m showing thickened fibrotic alveolar walls and inflammatory cell infiltrate with reduced air spaces in all animals (100%) in group m. fibrosis was present in 2 out of 7 rats in group t showing a significant protection with only 28.5% of animals with fibrotic lungs. no interstitial fibrosis (0%) was seen in the lung tissues of animals in control group x; all 7 rats showed well-formed alveoli. conclusions: interstitial lung fibrosis caused by anti-mosquito coil smoke can be protected with the use of turmeric. key words: covid-19, curcuma, mosquito coil, pulmonary fibrosis, turmeric. nutraceutical. turmeric has significant anti3 inflammatory and anti-oxidant properties. it has gained value as a digestive aid, treatment for fever, wounds, infections and blood disorders. data from animal and pharmacological studies also supports that active ingredients in turmeric play a protective role in various diseases like acute respiratory distress syndrome, chronic obstructive pulmonary disease and allergic asthma and also have proven antiviral properties against para-influenza type 3, respiratory 4,5,6 syncytial virus and herpes simplex virus, its therapeutic action is based on the inflection or prevention of oxidative stress and inflammation confirmed with the studies done at molecular & 7,8 cellular levels. the findings in these researches give substance to the possibility of testing turmeric for the prevention of pulmonary fibrosis caused by allethrins released from burning anti-mosquito coils. mosquitoes and the transmission of the mosquito borne diseases have been historically controlled by the use of chemical insecticides and mosquito repelling agents like anti-mosquito coil containing pyrethroids (allethrins), which play a central role in introduction modern medicine to a large extent has failed in its ambition to control both acute and chronic diseases. traditional herbal medicines have been found effective for the treatment and prevention of several 1 diseases. turmeric is a traditional herbal medicine. it's broad reaching mechanism of action and lack of systemic toxicity may make it best suited as an adjuvant therapy for various viral and other respiratory disorders like tobacco smoke induced epithelial damage and acute lung injury that are 2 resistant to currently available therapies. several diseases have been found to have inflammatory origin. turmeric is safe, affordable and efficacious preventive effect of turmeric against anti-mosquito smoke induced pulmonary fibrosis in laboratory rat saira jawed, wafa omer 1 2 correspondence: dr. saira jawed assistant professor department of anatomy hbs medical and dental college, islamabad e-mail: sairajawed371@gmail.com 1 2 department of anatomy /pathology hbs medical and dental college, islamabad funding source: nil; conflict of interest: nil received: february 11, 2020; revised: october 01, 2020 accepted: october 10, 2020 preventive effect of turmericjiimc 2020 vol. 15, no.4 222 9 mosquito control programs. more toxic products having higher concentration of allethrins are predominating the market due to the rapid spread of 10 resistance worldwide. the use of allethrins in higher concentrations and a complicated mixture of metallic vapors to tackle the resistant mosquitoes, 11 exposes the consumer to a severe health risk. it has already been addressed in the literature that exposure to mosquito coil smoke can have toxic effects on the lungs and can induce histopathological changes like severe emphysema, hyperplasia, chronic obstructive pulmonary disease, edema, hemorrhage & fibrosis, necrosis, hyperemia, connective tissue infiltration by inflammatory cells and obstruction by hyaline material within the lung 12,13 tissue. the objective of the current research was to demonstrate the efficacy of turmeric in preventing pulmonary fibrosis as there is insufficient literature on the preventive characteristics of turmeric against anti-mosquito allethrins present in coil smoke. material and methods this randomized control trial conducted at islamic international medical college, rawalpindi and national institute of health (nih), islamabad and was completed in 10 months. a total of 21 sprague dawley male rats weighing 250-300g were purchased from the animal house of national institute of health (nih) islamabad and were randomly divided into three groups; control group x and experimental groups m & t. the study was performed after an ethical approval from the institutional review committee of riphah international university. female rats and the rats having a weight of less than 250 g or having a physical disability were excluded from the study. groups m & t rats were placed in smoke exposure cabins at a temperature of 27±3ºc with a 12hr light/dark cycle along with standard laboratory diet and water. experimental groups were exposed to mosquito coil smoke for 7 hours per day for 12 weeks; group t received 300mg/kg body weight oral turmeric as well. all rats were sacrificed at the end of 12 weeks and left lungs of all were dissected out and preserved in 10% formalin. after tissue processing slides were prepared and stained with masson's trichrome to be studied microscopically first at low power, x10, and then at high power, x40 objective. the histological slides were interpreted by the pathologist. slides were studied for presence of interstitial fibrosis. masson's trichrome stained collagen fibers causing thickening of alveolar septa & alveolar spaces filled with proteinaceous fluid and inflammatory cell infiltrate causing reduction in alveolar spaces was taken as a criterion for interstitial fibrosis. results the lung tissue of all rats (100%) in group m (fig 2a) had a masson's trichrome stained dense fibrous connective tissue with collagen fibrils & thickening of alveolar walls with cellular infiltration, proliferation & airspaces filled with proteinaceous fluid. the interstitial infiltrate consisted of lymphocytes, plasma cells, mast cells and eosinophils resulting in interstitial fibrosis. interstitial pulmonary fibrosis was present in 2 out of 7 rats in group t; thus rats in group t showed a remarkable protection from pulmonary fibrosis with only 28.5% of animals developing fibrosis (fig 2b). the result is shown in table (fig 1). the masson's trichrome stained histological slides from the rats in control group x had normal honeycomb like alveolar structure with well-formed alveolar walls (fig 2c). table i: table represen�ng percentage of inters��al lung fibrosis in control and experimental groups jiimc 2020 vol. 15, no.4 223 preventive effect of turmeric discussion pulmonary fibrosis is a pattern of reaction to parenchymal damage in which lung has unusually high collagen fiber content per unit volume of 14 tissue. in the present study histological sections of the lungs of rats are stained with masson's trichrome in order to observe the fibrotic thickening of alveolar septa, reduced air spaces and presence of proteinaceous fluid. 100% of rats in group m showed thickened alveolar walls & proteinaceous fluid accumulated in interstitial space along with interstitial fibrosis. in group t, only 28.5% of rats showed the said histopathological parameters. inflammation is one of the etiological factor for the 14 development of fibrosis. as inflammatory reaction is observed in this case, it can be correlated to the development of fibrosis. fibrosis in the pulmonary interstitium is usually a result of alveolar damage due 14 to physical, chemical or microbial agents. allethrin in the coil smoke can be linked to the interstitial fibrosis observed in this study. the process of interstitial fibrosis is characterized by thickened alveolar walls that are fibrotic and contain an inflammatory cell infiltrate with reduced air spaces. macrophages are thought to be responsible for expressing fibroblast growth factor, resulting in the proliferation of fibroblasts and subsequent development of fibrosis. the excessive deposition of collagen fibers reflects reduced lung capacity leading to respiratory distress which is the main effect of air pollutant exposure. earlier study mentions that smoke induces lung destruction with inflammatory reaction, more fibroblasts are brought to the irritated area leading to more collagen fiber 15,16 deposition. in another study, fibrotic change was observed in lung parenchyma of rats after 6 weeks of exposure to mosquito coil smoke. similar histological appearance was seen in the lungs exposed to 17 asbestos and cigarette smoke. excessive deposition of collagen fiber has also been observed in the lungs 18 of rats in similar inhalational studies. turmeric is one of the herbal compounds that has been 19,20 investigated in fibrosis research. in the present research only 28.5 % of histological sections of rat lungs in the group t showed fibrous reaction. the result of this study is consistent with the previous studies. turmeric administration can inhibit 21 abnormal lung collagen formation. turmeric supplementation suppresses alveolar macrophages, expression of fibroblast growth factor by the macrophages and other inflammatory cells thereby ameliorating the inflammatory responses in the 22 lungs which prevents fibrosis in the lung tissue. the histopathological findings of the current research can further be utilized to test turmeric for the prophylaxis and treatment of covid-19 induced pulmonary fibrosis; which is considered to be the 23 most devastating outcome of this viral infection. conclusion interstitial lung fibrosis caused by anti-mosquito coil smoke can be protected with the use of turmeric. fig 2: (a) histological sec�on of a rat lung from group m showing thickened fibro�c alveolar septa (arrow), proteinaceous fluid (star) with reduced air space (double headed arrow) (b) histological sec�on of a rat lung from group t showing less thickened alveolar septa (arrow) with a few cellular infiltrates (star), well-formed alveoli and preserved air space (double headed arrow) (c) histological sec�on of a rat lung from group x showing normal alveolar septa (arrow) and alveoli showing honeycomb like pa�ern (double headed arrow) jiimc 2020 vol. 15, no.4 224 preventive effect of turmeric references 1. kant s, lohiya a, ahamed f, abdulkader rs, singh ak, silan v. comparative morbidity profile of patients attending an ayurveda clinic and a modern medicine clinic of a primary health center in rural haryana, india. j fam med prim care. 2018;7(2):374. 2. liang z, wu r, xie w, zhu m, xie c, li x, et al. curcumin reverses tobacco smoke-induced epithelial-mesenchymal transition by suppressing the mapk pathway in the lungs 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materials and methods: the study comprised fifty cases of oral squamous cell carcinoma randomly taken from the archives of sheikh zayed hospital and federal postgraduate medical institute, lahore as per the selection criteria agreed upon. the association of mucin-4 expression with different histological grades (based on the anneroth grading system) was analyzed in this study. data were entered into spss 20 for statistical analysis. age was represented as mean ± standard deviation while gender distribution and tumor grades were presented as frequencies and percentages. results: out of a total of fifty retrieved samples, thirty were analyzed (twenty were excluded based on the exclusion criteria). of these thirty samples, 16 (53.3%) were male and 14 (46.6%) were female. consistent with the anneroth grading method, grade i comprised 11 (36%), grade ii comprised 13 (43.3%), and grade iii comprised six cases (20%) respectively. overall positive expression of mucin-4 was found to be 73% and a significant relation was found to exist between the intensity score and the total score of muc-4 with anneroth grades of oral squamous cell carcinoma with a decrease in expression and an intensification in tumor grade. conclusion: a decrease in the expression of mucin-4 was noted with an increase in the tumor grade when the expression of mucin-4 was evaluated amongst separate histological categories of oral squamous cell carcinoma patients. key words: immunohistochemistry, muc4, mucin 4, oral squamous cell carcinoma, squamous cell carcinoma. epithelium of different organs is depicted and a modification in this expression is accompanied by c a n c e r ex p a n s i o n p ro m o t i n g c e l l g ro w t h , 3-5 differentiation, adhesion, and invasion. atypical expression of mucins in numerous cancers has been accepted and numerous mucins are recognized as therapeutic agents, diagnostic and prognostic markers, and appealing therapeutic 4-5 targets. muc4, one of the transmembrane mucins has lately emerged as an expedient biomarker. m o d if icat io n in ma n ifestat io n , a s well a s glycosylation, is documented concerning several epithelial malignancies for instance the esophagus, 6 breast, lung, pancreas, and cervix. in cancerous cells, biochemical alterations of muc4 in concert with changes in cell polarity permit its interaction with proteins that are otherwise 7 cytoarchitecturally segregated. muc4 enacts its function in tumor advancement secondarily through the anti-adhesion mechanism or directly through the 7 erbb2 signaling pathway. muc4 is furthermore localized in the oral squamous epithelium and its introduction m u c i n s a r e h i g h l e v e l m o l e c u l a r w e i g h t multifunctional glycoproteins expressed by innumerable epithelia of oculo-rhino-otolaryngeal tracts, respiratory tracts, reproductive tracts, and gastrointestinal tracts. being a foremost component of mucus, it aids to hydrate the epithelia, lubricates, 1-2 and shields them from injurious microbes. distinctive silhouette of mucin expression in the association of mucin-4 expression in anneroth grades of oral squamous cell carcinoma 1 2 3 4 5 naila umer , afifa ehsan , ali raza , rabia masood , saima chaudhry correspondence: dr. afifa ehsan, associate professor & hod oral biology, faryal dental college, lahore. e-mail: afifaehsan@gmail.com 1 department of oral pathology, faryal dental college, lahore 2 department of oral biology, faryal dental college, lahore 3,5 department of oral pathology, university of health sciences, lahore 4 department of oral pathology, islamic international dental college, islamabad received: june 06, 2022; revised: september 19, 2022 accepted: september 20, 2022 mucin-4 in oral squamous cell carcinomajiimc 2022 vol. 17, no.3 158 character in malignant alteration is under 8-12 research. the present study aimed to assess the countenance of mucin 4 in oral squamous cell carcinoma patients at a tertiary care hospital in pakistan as it can be a beneficial diagnostic and prognostic marker. materials and methods the present cross-sectional descriptive analysis was carried out at the department of oral pathology, university of health sciences, lahore from july 01, 2021, to december 31, 2021. ethical endorsement of the study was acquired through the ethical review board of the university of health sciences, lahore (letter#: uhs/education/126-16/039). a total of 50 cases of formalin-fixed paraffin blocks from diagnosed patients of oral squamous cell carcinoma (oscc) were recovered from the archives of sheikh zayed hospital, postgraduate medical institute, lahore. blocks with inadequate data and any sort of damage were excluded from the study. the h & e slides were prepared and graded using the multiparameter (anneroth's) grading system. also, 20 cases in which the stage of invasion was not found were excluded as anneroth grading couldn't be done on them. for immunohistochemistry with anti muc4 antibody, 4 µm dense tissue segments were chosen on poly-l-lysine covered. the segments were 0 dehydrated at 60 ċ for 50 minutes in warm air. following dewaxing, in xylene sections, they were positioned in scored alcohol. antigen repossession was done through placing slides in a coplin jar filled with antigen retrieval solutions. jars were then o positioned inside a warm water bath at 95 c for 30 minutes. then the slides were set aside to lower the temperature and evaporative damages were substituted by newly prepared phosphate-buffered saline (pbs). afterward, the slides were incubated for 15 minutes with 1-2 drops of h o additional 1-2 drops of protein 2 2. blocker were placed atop slides which were again incubated for another 10 minutes. subsequently, they were then washed 3 times with pbs using a washer bottle. primary antibody incubation was done for 2 hours with anti-muc 4 antibody (code ab52263; abcam, usa) reduced near the strength of 5µg/ml followed with biotinylated secondary antibody incubation for 30 minutes. following washing with pbs, slides remained i n c u b ate d fo r 1 0 m i n u te s w i t h s u b st rate c h r o m o g e n i c s o l u t i o n ( d a b ) a n d t h e n counterstained with hematoxylin. slides were then mounted employing dibutyl phthalate polystyrene xylene (dpx). human pancreatic cancer tissue was chosen as an affirmative control whereas excluding the principal antibody stage in the peroxidaselabeled streptavidin-biotin procedure delivered the negative control for muc4. 14 quantification: muc4 expression transpired to be appraised based upon the extent and intensity of immunolabelling in the tumor's cell membrane as well as cytoplasm. the complete score for every single case was determined by the accumulation of the proportion score (ps) along with the intensity score (is) of that case. 14 scoring criteria are given in table i. data were entered into spss 20 for statistical analysis. age was represented as mean ± standard deviation (sd) and the significance level remained at p ≤ 0.05. gender distribution and tumor grades were presented as frequencies and percentages. table i: scoring criteria of muc4 expression results our study comprised 50 cases of oscc out of which 20 were excluded based on the exclusion criteria and the rest were analyzed. in the 30 cases that underwent analysis, the average age range of the patients was found to be 53 ± 3.77 years with the majority of them being male (53.3%) while only 46.6% were observed to be females. the most common site of involvement in this study was found to be the tongue and buccal mucosa while gingiva, lower lip, palate, and tonsil were less common. grade 2 comprised a total of 43.3% cases which were recorded to be the maximum followed by grade 1 jiimc 2022 vol. 17, no.3 159 mucin-4 in oral squamous cell carcinoma (36%) and grade 3 (20%) (table ii). out of the total, 73% of cases were found to be positive for muc-4 expression while the rest were negative (figure 1). most of the tumors showed moderate intensity highlighting 33 66% of tumors. a significant relation (p ≤ 0.05) was established between intensity and total score of muc-4 with anneroth grades of oscc with a decrease in expression and an intensification in tumor grade (table iii). table ii: demographic data & anneroth tumor grades of oscc fig. 1: mucin-4 expression in oral squamous cell carcinoma (oscc) table iiiintensity, proportion & total score of mucin-4 fig. 2: well differentiated oral squamous cell carcinoma (grade1) (h&e; 10x10 x) fig. 3: strong cytoplasmic expression in welldifferentiated oscc (grade 1) (muc4 ihc; 10 x 10 x) fig. 4: moderately differentiated oscc (grade 2) (h&e; 10 x 10 x) jiimc 2022 vol. 17, no.3 160 mucin-4 in oral squamous cell carcinoma discussion oral squamous cell carcinoma remains nevertheless one of the greatest widespread tumors globally and 15-19 the second most common tumor in pakistan. it is of immense significance to be a consistent diagnostic and prognostic biomarker for cancer patients to be able to make available indispensable information for attaining a clinical conclusion. lately, mucins have been contemplated as prospective biomarkers in cancer diagnosis attributable to their distinctive representation in cancer patients as contrasted to the normal one. among them, muc4 is considered a 15-18 promising one. in the current study expression of muc-4 was observed in 73% of oral squamous cell carcinoma cases with the majority of tumors presenting a moderate intensity of the marker staining 33 66% of tumor cells. this positive ratio was analogous to the investigations carried out by narashiman et al. and kohli et al. while variance was found in one study performed in the population of japan where the proportion of positive expression was found to be 40 1 0 1 1 %. this variance can be attributed to dissimilarities in the population targeted where the incidence of oscc is low. the rest of the studies have targeted the south asian population with an elevated incidence rate of oral squamous cell 12-14 carcinoma. studies conducted by hamada et al, narashiman et al., and kohli et al. have categorized oscc only based o n t h e d e g r e e o f t u m o r d i f fe r e n t i a t i o n / keratinization and did not take into consideration any other parameters contemplated in anneroth's 8,10-11 grading systems. no study has so far compared anneroth's tumor grading system for oscc regarding muc4 expression. in the current study, the anneroth grade of oscc when associated with muc4 expression revealed statistically significant results. a reduction in expression in conjunction with an intensification in tumor ranking was observed. allred scoring system was utilized in our study encompassing both intensity (is) and proposition score (ps) as contrasted to the rest of the studies which only considered ps. when the association of muc4 expression was equated with a grade of tumors a strong to moderate expression was observed in grade 1 tumors, mild to moderate in grade 2 while grade 3 tumors revealed weak/mild expression only. a noteworthy relationship was established concerning the expression of muc4 and intensity in addition to total score (is + ps). when tumor grade correlation in conjunction with positive and negative expression of muc 4 was assessed, no substantial relation was obtained. this finding was analogous to the results of studies carried out by hamada et al. they correlated various grades of scc with positive and negative muc4 expression instead of a difference in the positivity that is from weak to strongly positive, while our findings were significant 8 as regards this aspect. a lessening in muc 4 expression in moderately as well as poorly differentiated scc could possibly be accredited to the deficit of differentiation of squamous cells as contrasted to well-differentiated scc. formerly many investigations carried out upon the function of muc4 in scc have revealed the aforementioned's association in conjunction with tumor differentiation. philipe guillem in 2000 reported the association of muc4 gene expression with squamous differentiation, as he discerned the strongest hybridization signals in well-differentiated 20 esophageal scc. correspondingly, a study done by kathpalia to determine cellular pathways in cutaneous scc found muc 4 m rna upregulation 20-23 nearly threefold in well-differentiated scc. conclusion in conclusion, a decrease in the expression of mucin4 was seen with an increase in the tumor grade when the expression of mucin-4 was assessed amongst separate histological categories of oral squamous cell carcinoma patients. the findings of our study also reveal upregulation (73%) of muc4 appearing in fig. 5: moderately strong cytoplasmic expression in moderately differentiated oscc (grade 2) (muc4 ihc; 10 x 10 x) jiimc 2022 vol. 17, no.3 161 mucin-4 in oral squamous cell carcinoma tumor tissue alongside negative expression in the regular epithelium. loss of muc4 expression along with an intensification in tumor scoring is observed. given that the differential expression of muc4 is observed with higher expression in grade 1 tumors in contrast to grade 3, so it provides supportive evidence to incorporate it as a marker for tumor cell differentiation. strength of study given the differential expression of muc4, it provides supportive evidence to incorporate it as a marker for tumor cell differentiation. limitations of study the study was conducted on a smaller scale with less sample size. further studies should be conducted with larger sample sizes including a larger number and a wider spectrum of participants from different hospitals in various areas of the country. future recommendations muc4 can demonstrate to be a beneficial diagnostic and prognostic marker. furthermore, additional epidemiological studies should be carried out in the future on a greater scale to extend these discoveries and find a correlation between muc4 expression with tumor stage, treatment modalities, and patient outcome. references 1. bansil r, turner bs. mucin structure, aggregation, physiological functions and biomedical applications. current opinion in colloid & interface science. 2006 jun 1;11(2-3):164-70. 2. pinzón martín s, seeberger ph, varón silva d. mucins and pathogenic mucin-like molecules are immunomodulators during infection and targets for diagnostics and vaccines. frontiers in chemistry. 2019 oct 22;7:710. 3. k r i s h n s r . 2 0 1 6 . s e c r e t o r y m u c i n m u c 5 a c i n g a s t r o i n t e s t i n a l m a l i g n a n c i e s . d o c t o r a l dissertations.university of nebraska medical center.digtal commons database. 4. kufe dw. mucins in cancer: function, prognosis and therapy. nature reviews cancer. 2009 dec;9(12):874-85. 5. hollingsworth ma, swanson bj. mucins in cancer: protection and control of the cell surface. nature reviews cancer. 2004 jan;4(1):45-60. 6. chakraborty s, jain m, sasson ar, batra sk. muc4 as a diagnostic marker in cancer. expert opinion on medical diagnostics. 2008 aug 1;2(8):891-910. 7. singh ap, chaturvedi p, batra sk. emerging roles of muc4 in cancer: a novel target for diagnosis and therapy. cancer research. 2007 jan 15;67(2):433-6. 8. hamada t, wakamatsu t, miyahara m, nagata s, nomura m, kamikawa y, yamada n, batra sk, yonezawa s, sugihara k. muc4: a novel prognostic factor of oral squamous cell carcinoma. international journal of cancer. 2012 apr 15;130(8):1768-76. 9. macha ma, rachagani s, pai p, gupta s, lydiatt wm, smith rb, johansson sl, lele sm, kakar ss, lee jh, meza j. muc4 regulates cellular senescence in head and neck squamous cell carcinoma through p16/rb pathway. oncogene. 2015 mar;34(13):1698-708. 10. narashiman s, narasimhan m, venkatraman g. expression of mucin 4 in leukoplakia and oral squamous cell carcinoma: an immunohistochemical study. journal of oral and maxillofacial pathology: jomfp. 2014 jan;18(1):25. 11. kohli m, shivam ak, ahuja p, dutta j. mucin-4: a novel marker for oral cancer. journal of oral and maxillofacial pathology: jomfp. 2019 jan;23(1):49. 12. rathee r, devi a, narwal a, kamboj m, singh s. immunohistochemical coexpression of muc1 and muc4 in oral leukoplakia and oral squamous cell carcinoma. head and neck pathology. 2021 sep;15(3):831-42. 13. almangush a, mäkitie aa, triantafyllou a, de bree r, strojan p, rinaldo a, hernandez-prera jc, suárez c, kowalski lp, ferlito a, leivo i. staging and grading of oral squamous cell carcinoma: an update. oral oncology. 2020 aug 1;107:104799. 14. kwon ky, ro jy, singhal n, killen de, sienko a, allen tc, zander ds, barrios r, haque a, cagle pt. muc4 expression in non–small cell lung carcinomas: relationship to tumor histology and patient survival. archives of pathology & laboratory medicine. 2007 apr;131(4):593-8. 15. bray f, ferlay j, soerjomataram i, siegel rl, torre la, jemal a. global cancer statistics 2018: globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries. ca: a cancer journal for clinicians. 2018 nov;68(6):394-424. 16. anwar n, pervez s, chundriger q, awan s, moatter t, ali ts. oral cancer: clinicopathological features and associated risk factors in a high risk population presenting to a major tertiary care center in pakistan. plos one. 2020 aug 6;15(8):e0236359. 17. qureshi ma, syed sa, sharafat s. lip and oral cavity cancers (c00-c06) from a mega city of pakistan: ten-year data from the dow cancer registry. journal of taibah university medical sciences. 2021 aug 1;16(4):624-7. 18. malkani n, kazmi s, rashid mu. epidemiological assessment of oral cancer burden in pakistan. cancer investigation. 2021 nov 26;39(10):842-53. 19. khaleel me, raza a, ehsan a, masood r, javed m. clinicopathological spectrum of oral squamous cell carcinoma at a public sector health facility. biomedica. 2015;31(1):21-6. 20. guillem p, billeret v, buisine mp, flejou jf, lecomte-houcke m, degand p, aubert jp, triboulet jp, porchet n. mucin gene expression and cell differentiation in human normal, premalignant and malignant esophagus. international journal of cancer. 2000 dec 15;88(6):856-61. 21. kaur s, momi n, chakraborty s, wagner dg, horn aj, lele sm, theodorescu d, batra sk. altered expression of transmembrane mucins, muc1 and muc4, in bladder cancer: pathological implications in diagnosis. plos one. jiimc 2022 vol. 17, no.3 162 mucin-4 in oral squamous cell carcinoma 2014 mar 26;9(3):e92742. 22. kathpalia vp, mussak en, chow ss, lam ph, skelley n, time m, markelewicz jr rj, kanduc d, lomas l, xiang z, sinha aa. genome-wide transcriptional profiling in human squamous c e l l c a r c i n o m a o f t h e s k i n i d e n t i f i e s u n i q u e tumor-associated signatures. the journal of dermatology. 2006 may;33(5):309-18. 23. macha ma, rachagani s, pai p, gupta s, lydiatt wm, smith rb, johansson sl, lele sm, kakar ss, lee jh, meza j. muc4 regulates cellular senescence in head and neck squamous cell carcinoma through p16/rb pathway. oncogene. 2015 mar;34(13):1698-708. conflict of interest authors declared no conflicts of interest. grant support and financial disclosure authors have declared no specific grant for this research from any funding agency in public, commercial or nonprofit sector. data sharing statment the data that support the findings of this study are available from the corresponding author upon request. this is an open access article distributed under the terms of the creative commons attributionnoncommercial 2.0 generic license. jiimc 2022 vol. 17, no.3 163 mucin-4 in oral squamous cell carcinoma original�article abstract objective: to determine the frequencies of different types of granulomas in patients suffering from cutaneous leishmaniasis. study design: descriptive cross-sectional study. place and duration of study: armed forces institute of pathology, combined military hospital, rawalpindi, dec 2021 to oct 2022. materials and methods: this study was conducted on 290 patients suffering from cutaneous leishmaniasis. patients aged between 18 and 70 years of both genders were included, while those who had already received treatment for leishmaniasis, or suffered from mucocutaneous or visceral leishmaniasis were excluded. all patients underwent a punch biopsy, tissue which was stained with hematoxylin and eosin, and then studied for the presence of granulomas and parasitic index. pcr was done to confirm species of leishmania causing disease. data was analyzed using spss 26.0. results: our study population had a median age of 38.00 (16 63) years, with a male majority: 185 (63.8%). granuloma formation was seen in 185 (63.8%) patients: 121 (41.7%) had a tuberculoid granuloma and 13 (4.5%) had suppurative granulomas, while 51 (17.6%) had caseating ones. l. tropica was the most seen organism accounting for 255 (87.9%) cases, l. major was the infective organism in 26 (9.0%) patients, while l. infantum was found in 9 (3.1%) cases. factors such as gender (p=0.273), age of the patient (p=0.901), disease duration (p=0.366), site of lesion (p=0.669), type of skin lesion (p=0.490), parasite index (p=0.297) and species of leishmania (p=0.870) did not have any significant association with the development of non-caseating granulomas. conclusion: chronic granulomatous inflammation is a common finding on histopathology in cutaneous leishmaniasis and vigilance is required to avoid confusion with other endemic granulomatous skin conditions. key words: cutaneous leishmaniasis, mycobacterium tuberculosis, non caseating granulomas, polymerase chain reaction, ridley modified parasitic index. with just the cutaneous form having an estimated 1,2 incidence of one million new cases per annum. pakistan accounts for approximately 10% of the global disease burden for all forms of leishmaniasis 3 which amounts to an estimated half a million cases. leishmania is diagnosed using a wide variety of tests such as direct visualization of the parasite in a tissue specimen, skin hypersensitivity testing, antibody detection and molecular methods such as polymerase chain reaction, however, such definitive but expensive methods are not readily available in resource-poor countries, and diagnosis is based on 4,5 clinical and tissue examination. however, this diagnostic approach is not without risk: leishmania is known for its ability to imitate different skin conditions not only macroscopically, 6 but microscopically as well. histologically, the disease may present in wide variety of ways including introduction leishmaniasis is a common tropical disorder attributed to an obligate intracellular protozoan which is transmitted to humans by the bite of the phlebotomus or lutzomyia sand-fly and causes manifestations by which it is classified into the cutaneous, mucocutaneous, and visceral disease, non-caseating granulomas in skin biopsies of leishmania cases 1 2 3 4 5 siyab ahmad , nadeem zafar , muhammad owais qurni , shabir ahmad orakzai , muhammad atif khalil , wajahat ahmad 6 khan correspondence: dr. siyab ahmad department of histopathology armed forces institute of pathology, rawalpindi e-mail: siyabamc@gmail.com 1,2,5,6 department of histopathology armed forces institute of pathology, rawalpindi department of histopathology 3 combined military hospital, multan 4 department of pathology swat medical college, swat received: november 19, 2022; revised: january 10, 2023 accepted: january 31, 2023 non-caseating granulomas in cutaneous leishmaniasis.jiimc 2023 vol. 18, no.1 15https://doi.org/10.57234/jiimc.march23.1574 parasitized macrophages with lymphocy tic 7 infiltration or non-specific chronic inflammation. it is also associated with the formation of granulomas: these can vary from non-specific ill-defined 7,8 granulomas to epithelioid granulomas. cases of cutaneous leishmaniasis have been demonstrated to show caseous necrosis as well, and have the 9 potential to be misdiagnosed as tuberculosis, or may be mischaracterized as a non-infectious disease 10 such as pyoderma gangrenosum. we conducted this study with the aim of determining frequencies of different types of granulomatous inflammation in patients suffering from cutaneous leishmaniasis. understanding the nature of the myriad types of histological pictures that leishmaniasis can present with is an important concept to understand, the lack of which can result in the misdiagnosis of the disease, and the institution of inappropriate management, with potentially dire consequences for the patient and the treating team. recognition that leishmaniasis can mimic the histological picture of other diseases and remaining sentient to the possibility of the presence of this endemic parasite will go a long way towards reducing the morbidity associated with it. materials and methods we conducted this descriptive cross-sectional study st st between 1 dec 2021 and 31 oct 2022 in armed forces institute of pathology, combined military hospital, rawalpindi, on 290 patients suffering from cutaneous leishmaniasis, after obtaining informed consent. approval from the institutional review board of the hospital was obtained. sample selection was carried out via non-probability, consecutive sampling. the who sample size calculator was used to calculate the sample size keeping a confidence level of (1-α) of 95%, an absolute precision (d) of 0.05 and an anticipated population proportion (p) of 0.748, which was the percentage of patients with cutaneous leishmaniasis suffering from non11 caseating granulomas, from aoun et al. . for convenient sampling patients aged between 15 and 70 years of both genders were included in the study. patients who had received previous treatment for leishmaniasis, or suffered from mucocutaneous or visceral leishmaniasis, or those who were suffering from malignancies, immunosuppressed states, drugs that caused immunosuppression, or patients who had a positive pcr for mycobacterium tuberculosis were excluded. all patients' details were documented for demographic data such as age and gender on enrollment, as well as for duration of disease, site of lesion and type of skin eruption. each patient underwent a punch biopsy of about 5 mm, which was processed and preserved as tissue blocks. subsequent slides were prepared using hematoxylin and eosin stain. at this point, patients were documented for type of granuloma, if any. diagnosis of leishmaniasis as well as confirmation of species was done by polymerase chain reaction (pcr) targeting kinetoplast dna. in a brief, the formalin-fixed, paraffin-embedded tissue blocks were used to extract dna. leishmania ribosomal internal transcribed spacer 1 (its1) was amplified using primers. this was done in a 50 ml amplification reaction. the following stages and conditions were employed for amplification on the px2 thermal cycler: 95 c for 2 min, 35 cycles of (95 c for 20 sec, 53 c for 30 sec, 72 c for 1 min), and 72 c for 11 6 min. furthermore, ridley modified parasitic index quantifies the parasitic load of amastigotes in cutaneous lesions and has a numerical score from 1 11 to 6 as displayed in table i. table i : ridley modified parasitic index data was analyzed using the statistical package for the social sciences (ibm spss statistics for windows version 26, ibm corp; armonk, usa). mean and standard deviation was calculated for quantitative variables specifically patient age and duration of disease. qualitative variables like gender, site of skin lesion, type of eruption, parasitic index, species of leishmania, presence and type of granuloma were recorded in terms of frequency and percentage. patients were divided into three groups: one with caseating granulomas, one without and one with no jiimc 2023 vol. 18, no.1 16 non-caseating granulomas in cutaneous leishmaniasis. https://doi.org/10.57234/jiimc.march23.1574 granuloma formation. quantitative variables were compared across groups using the independent samples t-test / one-way anova test while the chi square test / fischer exact test was used for qualitative variables and a p-value of ≤ 0.05 was considered significant. results this study was conducted on a total of 290 patients with a median age of 38.00 (16 63) years. most of the patients were male i.e., 185 (63.8%), while the median duration from onset of skin lesion to presentation was 27.00 (6 49) weeks. a total of 112 (38.6%) had a lesion present on the upper limbs, the lower limbs were affected in 89 (30.7%), while the head and neck region and the trunk were involved in 80 (27.6%) and 9 (3.1%) cases, respectively. nodules were seen in 159 (54.8%) i.e., most of our cases, followed by ulcers: 97 (33.4%) and 34 (11.7%) had papular lesions at presentation. table-ii shows the patient characteristics distributed according to gender at the time of presentation. (87.9%) cases, while leishmania major (l. major) was the infective organism in 26 (9.0%) patients, while leishmania infantum (l. infantum) were found in the least number of patients i.e., 9 (3.1%). granuloma formation was seen in 185 (63.8%) patients: 121 (41.7%) had a tuberculoid granuloma while 51 (17.6%) and 13 (4.5%) had caseating and suppurative granulomas, respectively. thus, a total of 134 (46.2%) patients had non-caseating granulomas while and 105 (36.2%) had no evidence of any granuloma on histology. table ii: patients characteristics according to gender table-iii displays the histological characteristics of the leishmaniasis for the sample according to gender. a parasite index of one was seen in 27 (9.3%) patients, cases with an index of two were 45 (15.5%), those with a parasite index of three accounted for 59 (20.3%) cases, while an index of four, five and six were seen in 67 (23.1%), 63 (21.7%), and 29 (10.0%) cases, respectively. leishmania tropica (l. tropica) was the most seen organism accounting for 255 table iii: histological characteristics according to gender table-iv shows the comparison between patients with non-caseating granulomas, those without and those patients who did not have granulomas. factors such as gender, age of the patient, disease duration, site of lesion, type of skin lesion, parasite index and species of leishmania were not associated with the development of non-caseating granulomas. discussion granuloma formation occurs in response to persistent inflammatory stimulation which results in the aggregation of inflammatory cells (primarily macrophages): an immune protective mechanism which neutralizes foreign/pathogenic matter by 12 encapsulation and neutralization. cutaneous leishmaniasis, in its limited form, is usually cleared spontaneously by the immune system without jiimc 2023 vol. 18, no.1 17 non-caseating granulomas in cutaneous leishmaniasis. https://doi.org/10.57234/jiimc.march23.1574 table iv: comparison of different variables with and without chronic granulomatous inflammation caseating, 17.6% caseating), while 36.2% did not appear to have any granulomas on histological examination in our study. most of the non-caseating granulomas were tuberculoid, while a minority were suppurative. cardozo et al reported that 84.0% of their cases had granuloma formation, with the majority of these having non-caseating granulomas, 15 while less than 1.0% had caseating ones. most of their patients had ill-defined histiocytic aggregates rather than the well-formed granulomas seen in our 15 study. aoun et al reported granuloma formation in 61.5% of their study, of which 46.1% were non11 caseating, while 15.4% demonstrated caseation, while andrade-narvaez et reported that 43.8% had granulomas in their study, none of whom 16 demonstrated caseation. the variability in results may be attributable to a number of reasons: granuloma formation may be dependent on a number of host and disease factors which were not homogenous across the studies mentioned above, which may account for the differences in histological patterns seen. our study had a median age of 38.00 (16 63) years, age did not appear to have any association with the visualization of non-caseating granulomas, (p=0.901). this figure is in keeping with existing studies on the subject such as debash et al who reported that the maximum number of cases of cutaneous leishmaniasis were seen in the range of 15 to 49 years in their study, while bisetegn et al reported a mean age of 31.9 ± 14.29 years for their 17,18 sample. moreover, aoun et al also reported that there was no association between the development 11 of different types of granulomas and age. the most of our study sample was male i.e., 185 (63.8%). gender did not appear to have an association with the formation of non-caseating granulomas, (p=0.273). wijesinghe et al and solomon et al both noted that cutaneous leishmaniasis was more likely to be present in males, which is likely due to increase outdoor activities and differences in clothing when compared to 19,20 females. in addition, aoun et al also concluded that gender did not appear to be associated with the 11 development and type of granuloma. most patients i.e., 38.6% had a lesion on the upper limbs, while the lower limbs had lesions in 30.7% cases. the head and neck region were affected in intervention in about a month, however, that is not always necessarily the case and the disease may take as long as six years to clear, necessitating confirmation of diagnosis and institution of 13 appropriate treatment. however, the process of diagnosis may be difficult in areas without molecular methods of disease confirmation i.e., reliant on histology for establishing presence of the disease: cutaneous leishmaniasis is known as the great imitator and it has the ability to mimic almost any 14 dermatosis, hence the requirement for this study. granulomas were seen in 63.8% (46.2% nonjiimc 2023 vol. 18, no.1 18 non-caseating granulomas in cutaneous leishmaniasis. https://doi.org/10.57234/jiimc.march23.1574 27.6% patients while the trunk was least affected: 3.1% cases, in our study. anatomical location of the lesion did not appear to have an association with the development of non-caseating granulomas, (p=0.669). rather et al noted in their study that lesions tended to occur on exposed areas, while aoun et al also confirmed that the bites were most commonly found on the extremities and the head and neck region as in our study, and that location did not have any effect on the development of noncaseating granulomas, a fact that was also concurred 11,22 with by aguado et al. the principle macroscopic skin manifestation of disease were nodules in our study which accounted for 54.8% cases. ulcers were seen in 33.4% patients while papular lesions were the least common and occurred in 11.7%. the type of macroscopic skin lesion did not appear to have a significant association with the development of non-caseating granulomas, (p=0.490). our results were in contrast to wijesinghe et al who noted that the occurrence of papules, nodules and ulcers occurred at the roughly same f re q u e n c i e s o f 3 4 . 7 % , 3 2 . 7 % a n d 3 0 . 6 % , 19 respectively, while aoun et al reported that the majority of patients had nodular lesions (49.2%), while ulcerative lesions were also common (49.2%), 11 which was in agreement with our results. variability in results between our study and wijesinghe may be due to the delayed presentation seen in the latter study which may lead to worsening of the skin lesion. aoun et al, like our study, also noted that the type of macroscopic lesion was not associated with the 11 development of non-caseating granulomas. the parasitic index did not appear to have a relationship with the development of non-caseating granulomas, (p=0.297), in our study, which was 11 concurred with by aoun et al (p=0.09), however, wijesinghe et al reported that having a higher parasitic index was associated with a higher risk of developing granulomas, (p=0.027), which was at 19 odds with our study. this aspect of research requires further study before concrete conclusions can be drawn, but studies have shown that the number of organisms reduce as the cutaneous leishmaniasis becomes chronic but the granulomas 23 form regardless. lastly, l. tropica was the most seen species in our study, accounting for 87.9% of our sample, followed by l. major, which affected 9.0% patients, while l. infantum was isolated in 3.1% cases. none of the s p e c i e s h a d a ny p ro p e n s i t y t o w a r d s t h e development of non-caseating granulomas, (p=0.870). previous studies have shown the most common organism in pakistan is l.tropica in patients with cutaneous leishmaniasis which forms the bulk of cases, while l. major accounts for a minor 24 percentage, and l. infantum is rarely seen. studies have also previously demonstrated that no species is associated with the development of non-caseating 11 granulomas. study limitations this research protocol was conducted as a singlecenter study and was limited by its small sample size. secondly, this study was performed on military personnel and their wards which has robust screening programs which may have resulted in early detection of disease which may or may not have affected the frequency of granuloma formation. lastly, a case-control study would give a better idea of the association of different disease and patient factors with the formation of different types of granulomas and should be the subject of future research. conclusion c u t a n e o u s l e i s h m a n i a s i s i s a c o m m o n l y encountered disease that may present as a diagnostic dilemma in our part of the world due to its ability to mimic other common skin conditions such as tuberculosis and leprosy in terms of histological features. recognition that the disease can commonly cause manifestations such as non-caseating and caseating 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glazer y, schwartz e. gender and cutaneous leishmaniasis in israel. trop med infect dis. 2022 aug 12;7(8):179. doi: 10.3390/tropicalmed7080179. 21 rather s, wani m, shah fy, bashir s, yaseen a, giri fa, et al. clinical and epidemiological study of cutaneous leishmaniasis in two tertiary care hospitals of jammu and kashmir: an emerging disease in north india. int j infect dis. 2021 feb;103(1):138-145. doi: 10.1016/j.ijid.2020.11.002. 22 aguado m, espinosa p, romero-maté a, tardío jc, córdoba s, borbujo j. outbreak of cutaneous leishmaniasis in fuenlabrada, madrid. actas dermosifiliogr. 2013 may;104(4):334-42. doi: 10.1016/j.adengl.2013.03.005. 23 çulha g, doğramaci aç, hakverdi̇ s, seçi̇nti̇ i̇e, aslantaş ö, çeli̇k e, et al. the investigation of the association of cutaneous leishmaniasis in biopsy specimens of the patients with granulomatous disease and skin cancer using the molecular method. iran j parasitol. 2020 julsep;15(3):307-314. doi: 10.18502/ijpa.v15i3.4194. 24 ahmad s, obaid mk, taimur m, shaheen h, khan sn, niaz s, et al. knowledge, attitude, and practices towards cutaneous leishmaniasis in referral cases with cutaneous lesions: a cross-sectional survey in remote districts of southern khyber pakhtunkhwa, pakistan. plos one. 2022 may 26;17(5):e0268801. doi: 10.1371/journal.pone.0268801. jiimc 2023 vol. 18, no.1 20 non-caseating granulomas in cutaneous leishmaniasis. https://doi.org/10.57234/jiimc.march23.1574 conflict of interest authors declared no conflicts of interest. grant support and financial disclosure authors have declared no specific grant for this research from any funding agency in public, commercial or nonprofit sector. data sharing statment the data that support the findings of this study are available from the corresponding author upon request. this is an open access article distributed under the terms of the creative commons attributionnoncommercial 2.0 generic license. jiimc 2023 vol. 18, no.1 21 non-caseating granulomas in cutaneous leishmaniasis. https://doi.org/10.57234/jiimc.march23.1574 original�article abstract objective: this study was conducted to determine awareness about signs, symptoms and the risk factors of breast cancer and its screening methods amongst female teenage students in the federal territory of pakistan. study design: descriptive cross sectional study. place and duration of study: rawalpindi medical university, rawalpindi from 1st march 2018 to 15th june 2018. materials and methods: using descriptive research design, quantitative data was collected using a close ended questionnaire derived from literature which was distributed amongst 450 females studying in various institutions of islamabad, pakistan. the awareness levels were categorized on a numerical scale of 0 to16; (05=unaware), (6-10=moderately aware), (11-16= well-aware). analysis was done using statistical package for social sciences version 23. three groups were compared by applying chi square test and significance was set at p<0.05. results: the percentage of the minimally aware teenagers was 40.89%, of moderately aware ones 53.11%, while only 6% females were maximally aware. there was a significant relationship between age of the individuals and awareness levels (p=0.00). the total awareness score and information regarding all risk factors of breast cancer was significantly related to education level of individuals, (p=0.00). conclusion: our study's results show moderately sufficient awareness about breast cancer symptoms, risk factors and screening methods amongst female teenagers studying in the federal territory of pakistan. key words: awareness, breast cancer, female teenagers, pakistan. rate of breast cancer among the females in pakistan is significantly higher (50/100,000) than that of 4 indian women (19/100,000). information regarding infirmity and fatality of breast cancer in pakistan's general population is insufficient due to the lack of a 5 cancer report cataloguing system at national level. adolescence is a period of rapid change and proper health education during this time is essential to instill good health behaviors amongst young adults. promotion of health care and attitude towards it, if 4 fostered early in life can yield long lasting results. breast self-examination (bse) is deemed to be the best general pre-clinical approach to improve breast health awareness and allows timely detection of any 6 peculiarities. the awareness of young women regarding breast cancer is of utmost relevance because it will serve to transfer the knowledge to their families and social circles and help in timely detection, which will hopefully lead to better 5 treatment outcomes. lack of awareness amongst the general public often ensues a late diagnosis of breast cancer, diminishing chances of disease-free 5 survival leading to poor treatment prognosis. healthy survival is significantly influenced by the introduction breast cancer is currently the most commonly diagnosed and fatal cancer amongst women in the world. there were approximately 8.8 million deaths due to it in 2015. breast cancer is the most prevalent cancer in women in 140 countries and the most frequent cause of cancer death in 101 countries. the age standardized incidence rate (asir) of breast cancer is highest in pakistan in asia as stated by begum et al. due to high mortality rate, it presents a 1,2 major global health problem. as stated above the frequency of breast cancer occurrence in pakistan is maximum amongst asian 3 countries. despite pakistan and india having a similar socio-cultural environment, the incidence breast cancer awareness amongst teenage females: need of the hour 1 2 3 4 5 hamna atique , hurmat fatima azeem , sidra hamid , tahmina yousaf , yusra binte hafeez correspondence: dr. sidra hamid assistant professor rawalpindi medical university, rawalpindi e-mail: drsidraqaiser@gmail.com 1,2,5 3 mbbs student/department of physiology rawalpindi medical university, rawalpindi 4 department of gynecology national institute of health, islamabad funding source: nil; conflict of interest: nil received: january 18, 2019; revised: november 30, 2020 accepted: december 01, 2020 breast cancer awareness jiimc 2021 vol. 16, no.2 85 time at which breast cancer is diagnosed and treated. the 5 years disease-free survival for breast cancer diagnosed at stage i and ii is 85%, whereas it is 7 only 10% at later stage of diagnosis i.e. stage iv. commonly pakistani women develop breast cancer at a younger age and are diagnosed when cancer has progressed to a more severe stage as compared to 6 women of the western world , because they tend to overlook the early warning signs and consequently medical check-up and treatment is delayed. according to a cancer registry report of pakistan in 2016, with patients being registered in shaukat khanum memorial cancer hospital and research center (skmch&rc) located in lahore and peshawar and the karachi diagnostic center (kdc); out of a sheer 6,587 malignancies reported, breast cancer was the predominant malignancy among adults (age=>18) with 1,441 cases registered from january 8 to december 2016. breast cancer awareness amongst pakistani people is limited owing to low literacy rates and the general taboo associated with discussion of human body 9 parts specific to one gender. a very important but rarely known fact is that breast cancer development at a younger age (lesser than 35 years) is liable to be more destructive with 10 comparatively poor progress , that is why it is much more important to educate the adolescents about it. as yet, no such educational investigation has been undertaken to judge the awareness levels of this disease among the young adult female population in this territory. hence, this study was carried out to assess the awareness corresponding with the risk factors, symptoms and diagnosis methods of breast cancer amongst teenage female students in islamabad, pakistan. materials and methods this descriptive cross-sectional study was carried out amongst teenage females studying in various st institutions across islamabad, from 1 march 2018 to th 15 june 2018. the ethical approval for the study was obtained from institutional research forum of rawalpindi medical university. the study population consisted of consenting females aged 13-19 years (n = 450) with no prior history of breast cancer and excluding students getting medical education or the like. the sample size was calculated using the who calculator. data, being parametric in nature, was gathered using a close-ended questionnaire derived from literature. those unwilling to participate were not given the questionnaire. the study population was divided into three groups based on education: matric/ o levels, fsc/a levels and undergraduate. the questionnaire consisted of 26 questions regarding breast cancer, under 4 sub-headings: socio-demographic characteristics such as name, age and educational level of the participant; general knowledge regarding breast cancer; knowledge of its risk factors and information about its screening (including knowledge of breast self-exam (bse) and clinical breast exam (cbe) and family history of incidence of breast cancer). amongst the first questions asked after the socio-demographic section were: whether the person had heard of breast cancer and its incidence rate, along with their source of information. knowledge regarding risk factors was reviewed by requesting the respondents to determine which of the following were potential symptoms or hazards for breast cancer – presence of a lump or nodule in the breast, pain/redness/swelling etc.(table i) comprehension of bse was assessed with three questions including knowledge about frequency of bse, information in regard to the appropriate time for bse and information by whom bse should be carried out by. furthermore, they were asked if anyone they knew had undergone cbe (clinical breast-exam) or been diagnosed with breast cancer. each accurate response scored one point and each inaccurate response scored zero. the awareness levels were categorized on a numerical scale of 0 to 16; 0 5: unaware, 5 10: moderately aware, 10 16: well aware. p<0.05 was fixed as the significance demarcation. the participants were also requested to search about breast cancer and its risk factors if they were unaware of it, at the end of the study. data analysis was done using social package for statistical sciences (spss) version 23. descriptive results were computed with frequencies while the inferential statistics were determined by chi-square tests along with their p values. results our study enrolled 450 female participants aged 1319 years (mean 16.46 + 1.65 years). only 47.6% of the participants were familiar with the incidence rate of breast cancer awareness jiimc 2021 vol. 16, no.2 86 breast cancer in pakistan, and of it being the most prevalent cancer in the country. media (35.3%) and books (15.6%) were the most popular information sources about breast cancer amongst the study participants. presence of redness and swelling were the most commonly known symptoms regarding breast cancer (54.4%). 34.2% of the students knew that breast cancer is hereditary and 54.2% regarded a breast lump or nodule as a symptom. around 30% considered obesity and physical inactivity to be risk factors. moreover, 44.7% of the respondents were aware that breast feeding does not cause breast cancer. performed it. moreover, out of the 28% who knew about breast self-exam, 60% did not perform it. only 11% of the total participants actually practiced the examination. one factor that was found to positively increase the knowledge regarding breast cancer was having a near relation who had suffered from it (n=109). it did not however appear that those with previous family history of breast cancer had necessarily good awareness (good score) of all aspects of it. but still, most of the participants (68%), with a previous familial breast cancer diagnosis were moderately aware (n=74). whereas, only 0.06% (n=7) of the respondents with a previous family history of breast cancer were fully aware of its symptoms and risk factors while 26% (n=28) were unaware. only 30.9% of the participants were appreciative of the fact that men could develop breast cancer too, highlighting lack of good knowledge. the results were analyzed based on the three education groups: fsc/a levels (n=209), matric/o levels (n=179), undergraduate (non-medical students) (n=62).education was compared against age, marital status, source of information of breast cancer, previous breast cancer diagnosis in the family and the information about incidence of breast cancer and its possible risk factors (presence of lump nodule in breast, redness/swelling/, hereditary factors, advancing age, breast-feeding, primiparous age more than 30, contraceptive pills, physical inactivity, obesity). further on, education level was compared with the knowledge of bse, its practice and attitudes towards the development of any risk factors. discussion this study involves a population with an outlook on the incidence rate of breast cancer in pakistan table i: perception of participants about the manifestations and risk factors of breast cancer and its relationship with total awareness levels the percentage of the minimally aware teenagers, (cut-off value=0) was 40.89%, of moderately aware ones (cut off value=10) 53.11%, while only 6% females (cut-off value=15) were maximally aware. older respondents (17-19 years) had better understanding of the specificities of breast cancer than younger respondents. majority of the respondents received a score of 6 (13.3%) and 8 (13.1%) out of 16 and were regarded as moderately aware. the total awareness score and knowledge pertaining to all risk factors of breast cancer was significantly related to education level of individuals, (p=0.00 each). there was convincing relationship between age of the individuals and awareness levels (p=0.00). regarding breast self-exam (bse), an important finding was that three quarters of the students did not know about it and its importance as an efficient diagnostic tool of breast cancer and neither fig 1: status of breast cancer awareness in study population breast cancer awareness jiimc 2021 vol. 16, no.2 87 (47.6%) with a relationship between age of the individuals and awareness levels (p=0.00). more than half the teenage females had moderate awareness (53.11%) along with a portion of the partakers who knew about breast self-exam (28%). it is relatable to a study regarding awareness levels of breast cancer among students of southern punjab, 11 pakistan , in which the most favored sources of information regarding breast cancer were common with our study: television and school/college education in relation to media (35.3%) and books (15.6%). in another study on the population of bahawalpur, no significant association was found between education level and the knowledge of 12 breast cancer (p=0.100). our results were consistent with a nigerian study in which 55% of the study population had poor 1 knowledge of symptoms and risk factors. the awareness scores of our female participants are 11,13 similar to previous studies carried out in pakistan and comparable with an indian study in which 57% participants showed moderate awareness score in correlation to our 53%. breast self examination is an easy examination that can be performed by the women themselves. its regular practice can help in the early detection of the 14 disease, improving survival prospects. in our study, only 1/5th of the females aware of bse actually performed it. this was in correspondence with a jordanian study which had a small population having bse awareness (34.9%) and only 61.1% of those had affirmative performance response as compared to 15 our 40% of the 28% group. owing to a small sample size, the statistics of our study cannot be generalized on all the pakistani population. this exploratory study is the first of its kind to be carried out on teenage females in pakistan as opposed to the previous studies that have been carried out mostly on older age groups of the health profession. it was conducted to appraise the breast cancer awareness in adolescent population as a benchmark to designing a target-specific awarenessbased breast cancer early detection program. conclusion our study's results show moderately sufficient awareness about breast cancer symptoms, irs risk factors and screening methods amongst female teenagers studying in the federal territory of pakistan. acknowledgements we are extremely grateful to the participants from punjab college, beaconhouse agal, beaconhouse margalla campus, imcg i-8/4, imsg i-8/1, pbf college, opf girls college, benchmark school system, pakturk school and college, skans school of accountancy, hitec, foundation university and nust for participating in this study. we would also like to thank the rawalians students research society (rsrs) and the physiology department of rawalpindi medical university for all the help they provided in this study. references 1. world health organization cancer key facts [internet]. [cited 2020]. available from: http://pinkoak.org/wpcontent/uploads/2018/03/who-cancer-fact-sheet-2017. 2. begum n. breast cancer in pakistan: a looming epidemic. j coll physicians surg pak. 2018;28(2):87-88. 3. rizvi f, rajput m, afzal m (2013). knowledge and practice of breast self-examination. jrmc. 17(1), 88-90. 4. ginsberg gm, lauer ja, zelle s, baeten s, baltussan r. cost effectiveness of strategies to combat breast, cervical, and colorectal cancer in sub-saharan africa and south east asia: mathematical modelling study. bmj (clinical research ed). 2012;344:e614. 5. omotara b, yahya s, amodu m, bimba j. awareness, attitude and practice of rural women regarding breast cancer in northeast nigeria. j community med health educ. 2012; 2:148. 6. bhurgri y, bhurgri a, hassan sh, et al (2000). cancer incidence in karachi, pakistan: first results from karachi cancer registry. int j cancer. 2000 ;85(3):325-9. 7. rasheed r. breast cancer. j coll physicians surg pak. 2013;23(10):766-7. 8. madubogwu ci, egwuonwu ao, madubogwu nu, njelita ia. breast cancer screening practices amongst female tertiary health worker in nnewi. j can res ther 2017;13:268-75. 9. shahzad a. in conservative pakistan, women challenging taboos that are hiding the rise of breast cancer. 2014. available from url: http://news.nationalpost.com/ news/in-conservative-pakistan-women-challengingtaboos-that-are-hiding-the-rise-of-breast-cancer. 10. erbil n, bolukbas n. health beliefs and breast selfexamination among female university nursing students in turkey. asian pac j cancer prev. 2014;15(16):6525-9. 11. noreen m, murad s, furqan m, sultan a, blood sworth p. knowledge and awareness about breast cancer and its early symptoms among medical and non-medical students of southern punjab, pakistan. asian pac j cancer prev. 2015;16(3):979-84. 12. masood i, saleem a, hassan a, sadeeqa s, akbar j. a quantitative study to assess breast cancer awareness among females in bahawalpur pakistan. cogent medicine. breast cancer awareness jiimc 2021 vol. 16, no.2 88 2016; 3:1236479. 13. gilani gm, kamal s, akhter as. a differential study of breast cancer patients in punjab, pakistan. journal of pakistan medical association. 2003; 53(10), 478-81 j pak med assoc. 2003;53(10):478-81. 14. gadgil a, sauvaget c, roy n, frie k, chakraborty a, lucas e et al. breast cancer awareness among middle class urban women a community-based study from mumbai. india asian pac j cancer prev.2015;16(15):6249-6254. 15. suleiman a. awareness and attitudes regarding breast cancer and breast self-examination among female jordanian students. j basic clin pharm. 2014;5(3):74-78. breast cancer awareness jiimc 2021 vol. 16, no.2 89 original�article abstract objective: the purpose of this study was to assess and correlate the personality traits with job satisfaction level of surgeons in pakistan. study design: quantitative, correlational study place and duration of study: the study was conducted at 8 teaching hospitals of rawalpindi and islamabad th th from 17 january to 17 june 2017. materials and methods: a total of 132 surgeons were selected by convenient sampling. big five inventory (bfi) for personality assessment and minnesota satisfaction questionnaire (msq) for job satisfaction were used. data collected from 105 surgeons was analyzed on spss version 21. correlation coefficient for each personality factor with job satisfaction was calculated using pearson's test. results: the mean job satisfaction level of surgeons included in our study was 73.828 ± 11.68. the mean likert score for personality using bfi was highest for agreeableness (4.00) followed by conscientiousness (3.75), openness (3.54) and extraversion (3.37) and was lowest for neuroticism (2.52). pearson's test showed a positive correlation of agreeableness, extraversion and conscientiousness and a negative correlation of openness and neuroticism with job satisfaction level of surgeons in pakistan. among these the positive correlation of agreeableness (r=0.32, p-value=0.001) and a negative correlation of neuroticism (r= -0.21, pvalue=0.027) was statistically significant. conclusion: the overall job satisfaction level of surgeons in pakistan is towards the positive side. the surgeons assessed in our study had a balance of different personality traits with the value being highest for agreeableness and lowest for neuroticism. the personality traits of agreeableness and neuroticism strongly correlate with job satisfaction. key words: job satisfaction, personality, surgeons. satisfaction and both of these factors are also 2 influenced by personality. surgery is a demanding field with long working hours and a variety of stresses that requires dedication, devotion and a 3 strong personality. it is anticipated that people who cannot sustain this stress will be dissatisfied in this profession. research shows that the job satisfaction level of surgeons is on the decline and many 4 surgeons complain of fatigue and burn out. selecting and training only those, who have the right 5 aptitude for a specialty is a novel idea. although studies have been conducted internationally on the personality traits of surgeons and as well as on their job satisfaction. limited literature is available that correlates these two aspects. this aspect needs exploration and a relationship needs to be established. differences in social upbringing, training, inhospitable and sometimes hostile hospital environment and ill developed service structure of the surgeons working in pakistan means introduction: personality is defined as the characteristics and behaviors that define a person. it is made up of a combination of different elements and is influenced by a variety of factors which include early childhood experiences, relationships, life events, education, 1 society, culture and genetic factors. job satisfaction is a measure of how happy or satisfied an employee is while working in an organization. studies show that a doctor's performance is linked to his job assessment of personality traits and job satisfaction in surgeons: a correlational study 1 2 3 muhammad wajih uddin butt , rahila yasmeen , manya tahir correspondence: muhammad wajih uddin butt combined military hospital, rawalpindi e-mail: wajih_50@hotmail.com 1 department of surgery combined military hospital, rawalpindi, 2 riphah academy of research and education 3 department of medical education islamic international medical college riphah international university, islamabad personality traits and job satisfaction among the surgeonsjiimc 2020 vol. 15, no.3 funding source: nil; conflict of interest: nil received: december 06, 2017; revised: july 04, 2020 accepted: july 04, 2020 192 forms that were incompletely filled were excluded from the study. 20 of the participants did not return the questionnaire so the final data of 105 surgeons (93 males, 12 females) was entered in spss version 21 for analysis. the personality assessment was made using the 44 11 item big five inventory. the job satisfaction level of the surgeons was assessed using the 20 item short form version of minnesota satisfaction 16 questionnaire. both the instruments are widely used, reliable and valid tools. the surgeons rated themselves for each item on a likert scale of 1 to 5 in both the questionnaires. the mean likert score and sd of each item and the mean of each scale were calculated. all the 5 factors of personality acted as independent variables whereas the job satisfaction was the dependent variable. correlation coefficient for each personality factor with the job satisfaction was calculated using pearson's test. significance for each correlation was calculated. a p value of less than 0.05 was considered significant. results the filled questionnaires from 105 surgeons were analyzed having 93 males and 12 females (table i). the study included both general surgeons and subspecialists (table ii). the mean age of the surgeons was 40.38 (std. deviation 7.369) with a minimum age of 30 years and a maximum age of 59 years (table iii). the mean working hours per day were 11 hours with a minimum of 6 and a maximum of 18 hours per day (table iii). mean experience in year's post fcps was 9.50 years with a minimum of 1 and a maximum of 31 years (table iii). table iv gives the number of surgeons included from each hospital. that the results of our study could be different from 6 studies carried out internationally. the study will guide us about the suitability of different personality traits for surgical specialty. this will in turn help in career counselling of future specialists and in making 7 placement decisions. incorporating personality testing into the selection and recruitment process will help in choosing 'the right person for the right job'. this would result in better performance and better job satisfaction of our surgeons and will 8,9,10 directly affect patient outcomes. materials and methods a quantitative, correlational study was carried out among the fcps qualified general surgeons and subspecialists (urologists, thoracic, vascular, orthopedic, pediatric, plastic, cardiac and neuro surgeons) working at eight public, private and military hospitals of rawalpindi and islamabad (combined military hospital, military hospital, armed forces institute of urology, armed forces institute of cardiology, pakistan institute of medical sciences, pakistan railway hospital, fauji foundation th hospital and benazir bhutto hospital) from 17 th january to 17 jun 2017. the ethical approval was obtained from the “ethics review committee (erc) riphah university”. informed written consent was taken from each of the participant on a pre designed proforma. permission to carry out the study among the surgeons working at the hospital was also obtained from the ms/commandants of the respective hospitals/ institutes. confidentiality and anonymity was strictly maintained and guaranteed to all of the participants. the sample size was calculated using the sample size calculator. the accessible number of surgeons in hospitals of rawalpindi and islamabad was 200. keeping the confidence interval at 95% and a 5% margin of error the recommended sample size was calculated as 132. convenient sampling was done to select 132 fcps qualified male and female general surgeons and sub specialists. the fcps part 2 trainees, non fcps qualified surgeons, retired and non-practicing surgeons were excluded from the study. the participants were contacted via personal visits, phone call or email and were briefed about the purpose and nature of the study followed by distribution of questionnaires via email or hard copies. after collecting the filled questionnaires 7 table i: gender distribu�on among the sample popula�on the mean job satisfaction level was 3.691/ 5 ± 0.584. the mean overall score of the job satisfaction in msq was 73.828/100 with a std. deviation of 11.686. the minimum score obtained was 43/100 while the maximum was 99/100. the mean likert score was highest for agreeableness relate personality traits with job satisfaction of surgeonsjiimc 2020 vol. 15, no.3 193 frequency percent the correlation coefficient calculated by the pearson's test showed an r value that is positive for agreeableness (r= 0.327), extraversion (r= 0.054) and conscientiousness (r= 0.035); and is negative for openness (r= -0.144) and neuroticism (r= -0.217). t h i s s h o w s t h a t t h e r e i s a po s i t i v e correlation between three of the personality factors (agreeableness, extraversion and conscientiousness) and job satisfaction; and there is a negative correlation between two personality factors (openness, neuroticism) and job satisfaction level of surgeons in pakistan (figure ii). the r value for agreeableness (r=0.327) was more than 0.3 which indicates a strongly positive correlation. the pvalue for agreeableness (0.001) and neuroticism (0.027) was �0.05 which shows a statistically significant relationship. (4.00) followed by conscientiousness (3.75), openness (3.54) and extraversion (3.37) and was lowest for neuroticism (2.52) (figure i). table ii: frequency of general surgeons and subspecialists in the sample popula�on table iii: age, working hours per day and years of experience post fcps of the sample popula�on table iv: hospital se�ng of the surgeons fig 1: graph showing the mean likert scores of independent variables (personality factors) fig 2: graph showing the correla�on coefficient of personality traits with job sa�sfac�on level discussion the results of our study support the relationship of personality with the job satisfaction level of surgeons 12 in pakistan. the mean job satisfaction was 73.828/100 ± 11.68 implying that the surgeons included in our study had an 'average degree of job satisfaction' as measured by the msq (�75=high, 2574=average, �25=low) showing thereby that the job satisfaction level of surgeons in pakistan is towards the positive side and is better as compared to studies 4,8 carried out elsewhere. the means of the likert score for the five personality variables using the bfi showed that the surgeons included in our study had a balance of different personality traits with the value being highest for agreeableness and lowest for neuroticism. the values are comparable to a study that compared the personality traits of surgeons and non-surgeons at relate personality traits with job satisfaction of surgeonsjiimc 2020 vol. 15, no.3 194 frequency percent n minimum maximum mean std. devia�on correlation of openness with job satisfaction. this can probably be due to the influence of departmental or administrative restraints and a lack of research and discovery culture in our hospitals and society. openness involves six facets including active imagination, aesthetic sensitivity, awareness about own feelings, preference for variety, experience seeking and intellectual curiosity. people who score low on openness are considered conventional, 6 traditional and closed to experience . they prefer routine to new experiences and have a narrower range of interests. surgeons who like to introduce new techniques or procedures, want to bring change to the existing systems, introduce new and evidence based teachings and have an innovative nature are always met with resistance and are seldom supported by the administration or seniors. this causes frustration and makes them disillusioned. this fact has been highlighted in our study. people who are high on the score of openness are dissatisfied and those low on the score of openness limitations of our study can be the bias caused by the element of faking by the participants. they are 15 satisfied with their profession. this means that surgeons having conventional ideas and those that stick to the routine without taking risks will generally remain satisfied with their jobs. the results of job satisfaction can be affected by mood and problems faced by the surgeons at that point of time, both at personal and professional level. similarly the results can differ among the surgeons working in public, private and military hospitals as the workload, clientele, service structure, perks, privileges, security and professional development opportunities are different among these setups and 16,17,18 this aspect needs further exploration. conclusion we can conclude by saying that personality plays a significant role in the job satisfaction of surgeons in practice. the results of our study show that the overall job satisfaction level of surgeons in pakistan is towards the positive side. the surgeons assessed in our study had a balance of different personality traits with the value being highest for agreeableness and lowest for neuroticism and these two personality traits strongly correlate with job satisfaction level. our study shows that the personality traits of agreeableness, extraversion and conscientiousness d i f fe re n t c a re e r p o i n t s w h i c h w e re ; conscientiousness 4.30, agreeableness 3.76, openness 3.75, extraversion 3.74 and neuroticism 3 2.46. the results of our study show a positive correlation between the personality traits of agreeableness, extraversion and conscientiousness and a negative correlation between openness and neuroticism with the job satisfaction level. agreeableness and neuroticism strongly correlate with job satisfaction as per our results. this implies that surgeons who are high on the scale of neuroticism are dissatisfied with their job and those who are low on the scale of neuroticism are more satisfied. conversely, the higher someone is on the scale of agreeableness the more satisfied he is. this can be compared with the results of a meta-analysis relating the big five traits to job satisfaction which showed that neuroticism correlates strongly with j o b s at i sfa c t i o n , fo l l owe d c l o s e l y by conscientiousness and extraversion. agreeableness and openness to experience showed a weak 12 correlation with job satisfaction. our result for agreeableness show a fairly strong and statistically significant correlation which is different from studies carried out elsewhere according to which conscientiousness and extraversion are the 8 strongest predictors of job satisfaction in surgeons. the facets grouped under agreeableness are; trust, altruism, compliance, modesty, kindness, cooperation, empathy helpfulness and tendermindedness compliance. they get along well with others and are more likely to control negative emotions like anger in conflict situations. this can be explained on the basis of our social and cultural structure. family values, relationships and traditions are given a high place in our society. surgeons possessing such attributes will most likely be 13 satisfied in their jobs. however those lacking these traits can face adjustment issues and decreased 14 satisfaction level. our results also showed a weakly positive correlation between conscientiousness, extraversion and job satisfaction. this aspect needs further exploration as according to many international studies including one on trauma surgeons; the personality trait of extraversion strongly correlates with academic/profession 8 performance and job satisfaction. the other surprising finding in our study is the negative relate personality traits with job satisfaction of surgeonsjiimc 2020 vol. 15, no.3 195 8. foulkrod kh, field c, brown cvr. trauma surgeon personality and job satisfaction: results from a national survey. am surg. 2010;76(4):422–7. 9. preece ra, cope ac. are surgeons born or made? a comparison of personality traits and learning styles between surgical trainees and medical students. j surg educ. elsevier; 2016;73(5):768–73. 10. gates r, workman a, collier b. job satisfaction and workplace stressors among surgical providers at a single institution. j am acad physician assist. 2019;32(11):42–7. 11. john r, big-five t, pervin la. big five inventory ( bfi ). 1999;2. 12. judge ta, heller d, mount mk. five-factor model of personality and job satisfaction: a meta-analysis. j appl psychol. 2002;87(3):530–41. 13. sievert m, zwir i, cloninger km, lester n, rozsa s, cloninger cr. the influence of temperament and character profiles on specialty choice and well-being in medical residents. peerj. 2016;4:e2319. 14. doherty em, nugent e. personality factors and medical training: a review of the literature. med educ. 2011;45(2):132–40. 15. azeem mf, paracha at, shakeel w, saboor mj. international transaction journal of engineering , management , & applied sciences & technologies five-factor personality model�: a comparative study of public and private hospitals sector. 2020;11(2):1–14. 16. weiss dj, dawis r, england g, lofquist l. manual for the minnesota satisfaction questionnaire. manual for the minnesota satisfaction survey. 1967. p. 125. 17. kumar r, ahmed j, shaikh bt, hafeez r, hafeez a. job satisfaction among public health professionals working in public sector�: a cross sectional study from pakistan. 2013;1–5. 18. khan hs, khan ra, azhar j. personal qualities of brilliant surgeons: a myth or reality. pak armed forces med j. 2018;68(5):1126–58. are more suited for surgical practice as these factors correlate positively while neuroticism and openness correlate negatively with job satisfaction of surgeons in pakistan. we recommend that the assessment of personality should be incorporated in the selection process and for career counseling of aspiring surgeons. educational programs should be developed that can help to enhance the personality attributes that are necessary for success in the surgical practice. references 1. komarraju m, karau sj, schmeck rr, avdic a. the big five personality traits, learning styles, and academic achievement. pers individ dif. elsevier ltd; 2011;51(4):472–7. 2. judge ta, heller d, mount mk. five-factor model of personality and job satisfaction: a meta-analysis. j appl psychol. 2002;87(3):530–41. 3. drosdeck jm, osayi sn, peterson la, yu l, ellison ec, muscarella p. surgeon and nonsurgeon personalities at different career points. j surg res. 2015 jun;196(1):60–6. 4. chen ky, yang cm, lien ch, chiou hy, lin mr, chang hr, et al. burnout, job satisfaction, and medical malpractice among physicians. int j med sci. 2013;10(11):1471–8. 5. lovejoy c, nashef s. surgeons' personalities and surgical outcomes. bull r coll surg engl. 2018;100(6):259–63. 6. hojat m, erdmann jb, gonnella js. personality assessments and outcomes in medical education and the practice of medicine: amee guide no. 79. med teach. 2013;35(7):e1267-301. 7. kwon oy, park sy. specialty choice preference of medical students according to personality traits by five-factor model. korean j med educ. 2016;28(1):95–102. relate personality traits with job satisfaction of surgeonsjiimc 2020 vol. 15, no.3 196 jiims final.cdr 1 the art and science of dentistry has p ro g re s s e d v e r y r a p i d l y s i n c e t h e introduction of the high-speed handpiece in 1the 1950s. there has been a paradigm shift from paternalistic management of obvious problems to a medical model of dental care, w h i c h i n c l u d e s p r e v e n t i o n a n d management of dental disease and prosthetic rehabilitation to restore normal oral function. discovery of the relationship between oral health and systemic disease has raised awareness concerning the importance of oral health. advancements in technology offer a variety of solutions for managing similar dental situations and it is incumbent upon each practitioner, as a member of an ethical profession, to educate patients about their appropriate treatment o p t i o n s , a l l o w i n g t h e m t o m a k e autonomous treatment choices that are in their best interest. it generally is understood that many treatment options are available 2for any given dental condition. a definite decision-making process helps to determine the appropriateness of each treatment modality. dentistry is a moral profession, guided by normative principles. as a result; dentists are obligated to choose a course of treatment that allows them to be “caring and fair in 3their contact with patients.” although increased commercialism may be difficult to avoid, patient autonomy should be the overwhelming decision. members of the dental profession and the community at large expect dentists to act ethically, according to a balance of certain norms: nonmalfeasance, beneficence, justice, veracity, 4and respect for patient autonomy. the personal virtues of the dentist and the intrinsic values of the profession, the patient, and society must be considered when choosing appropriate treatment for any given situation. it is pertinent to explore the elements of decision making in dental care, as patient participation is a field which has both ethical and legal implications in an increasingly user-focused, 'consumerist' health service, given that most dental care is paid for, in part or whole, by the patient. more importantly, b y i d e n t i f y i n g t h e p a t i e n t ' s d e n t a l preferences as active, passive or somewhere in-between, clinicians would obtain an insight not only into the outcome the patients has perceived but also in deciphering between different patient personalities. dentists need to help patient participation in the decision making by explaining the nature of the disease, treatment options, benefits of the options, time required in completing the treatment and most importantly the cost incurred in achieving the desired treatment. 1. a millennium of dentistrya look into the past, present and future of dentistry. available at: http://www.agd.org/public/oralhealth/defa references editorial ------------------------------------------------ulfat bashir decision making in dental health seeking behaviors correspondence: prof. ulfat bashir hod orthodontics department islamic international dental college islamabad 1 2 ult.asp?issid=305&topic=h&artid=1255. accessed july 20, 2007. 2. healthy people 2010, vol. 2. washington, dc: department of health and human services; 2000. 3. american dental association. principles of ethics and code of professional conduct. available at: http://www.ada.org/prof/prac/ law/ code/ada_code.pdf. accessed june 2007. 4. windholrn r, cuenin m. an implant versus a conventional fixed prosthesis: a case report. gen dent 2007; 55:44-47. 2 jiims final.cdr 35 original article abstract objective: to determine the frequency of wound infection with skin closure by removable subcuticular sutures in non complicated open appendectomy wound. study design: descriptive case series place and duration of study: department of surgery railway hospital rawalpindi, seven months and ten st th days, from 1 nov, 2009 to 10 june, 2010. materials and methods: the study was carried out after taking approval from the hospital ethics committee. seventy three adult patients of either sex admitted in department of surgery with diagnosis of acute appendicitis were included in the study by non probability consecutive sampling. all the patients were explained about the procedure and an informed written consent was obtained. right grid iron abdominal incision centred over the mc burney's point was used to open the abdomen. appendicectomy was done. in all patients subcuticular stitches rd th by using polypropylene 2/0 were applied to close the skin. all the patients were followed on 3 , 7th and 30 post operative day for examination of wound . data was entered in the predesigned proforma (annexed) for analysis. results: out of 73 patients 6(8.2%) suffered from wound infection. successful open management of the infected wounds was done. rest of the patients had uneventful recovery. conclusion: frequency of wound infection is negligible with removable subcuticular skin suture in non complicated open appendicectomy wound. key words: appendicitis, open appendicectomy, subcuticular skin closure, wound infection. introduction the vermiform appendix is a blind ended long, narrow, muscular tube arising from the posteromedial aspect of the caecum, about 1 inch (2.5 cm) inferior to the ileocaecal 1,2valve. acute appendicitis is one of the most common abdominal emergencies for which patients attend the emergency 3department. appendicectomy is the most commonly performed surgical operation all 1,4,5over the world. different etiological and pathological factors are considered in acute appendicitis ranging from infection of appendix to occlusion of the appendicular l u m e n d u e t o f e c o l i t h , l y m p h o i d h y p e r p l a s i a , p a r a s i t e s a n d 6t u m o r. appendicitis can be divided into acute non perforated appendicitis and perforated appendicitis. non perforated appendicitis can be further classified into non gangrenous and gangrenous. typically the patient of acute appendicitis presents with complaint of migratory pain to right iliac fossa, which means the pain initially starts in the 7,8 epigastrium or pararumbilcal region. most of the times this pain is associated with anorexia, nausea and vomiting with gaurding, rigidity and rebound tenderness 5 , 9 , 1 0on palpation. diagnosis of acute appendicitis is basically done on clinical grounds. however different laboratory and r a d i o l o g i c a l i n v e s t i g a t i o n s h e l p i n 11,12supporting the diagnosis. the surgical management of acute appendicitis is 13appendicectomy. this can be done as traditional open appendicectomy, mini appendicectomy or by laparoscopic approach. in cases of non complicated --------------------------------------------------------removable subcuticular skin sutures in open appendicectomy; surgeons fear hamid rasheed goreja, salman najam sheen, khalid farooq danish, salma naz correspondence: dr. hamid rasheed goreja senior registrar surgery department islamic international medical college & trust pakistan railway hospital, rawalpindi e-mail: hamidgoreja@yahoo.com 35 36 appendicitis, after open appendicectomy the skin can be closed by silk,which is 14applied in interrupted fashion. conversely prolene or vicryl can be used to close the skin 15as subcuticular running suture. choice of suture material depends upon a lot of factors including the patient, tissue, anatomical area, surgeon, and economic factors. in this new era a lot of new materials have been invented which make a surgeon's job 17difficult to choose any material for closure. skin can be closed using sutures in interrupted, subcuticular or mattress fashion using absorbable or non absorbable 18materials. although the outcomes of surgical skin closure may be influenced by the indication for the procedure, the location of the surgical site, and associated i n t r a o p e r a t i v e a n d p o s t o p e r a t i v e complications, the goal of any skin closure technique is to produce appropriate skin approximation and adequate healing with minimal wound complications, scarring, 16,17pain, and cost. infections occurring in surgical incisions were initially called wound infections, but 7now called as surgical site infection. multiple etiological factors are involved in the development of ssi. efforts should be made to adjust the modifiable risk factors. cigarette smoking, old age and obesity, choice of suture material and suturing technique are known etiological factors for 20ssi along with the bacteria. t h e m o s t c o m m o n o r g a n i s m i s 21staphylococcus aureus. surgical site infection is a serious issue which needs to be addressed and efforts should be made at every level starting from the ward, hospital 19,20policy and national level to prevent them. since appendicectomy is considered as a clean contaminated surgery, therefore most surgeons have a fear of closing the wound in a subcuticular fashion due to high risk of wound infection. this study is planned to alleviate this fear of increased risk of wound i n f e c t i o n i n n o n c o m p l i c a t e d o p e n appendicectomy wound having skin closure with removable subcuticular stitches. a descriptive study was conducted in the department of surgery at pakistan railway hospital from 1st nov, 2009 to 10th june, 2010. seventy three adult patients of either sex admitted with the diagnosis of non complicated appendicitis were included in the study with convenient sampling technique. sample size was calculated by using who sample size calculator taking confidence level of 95%, population proportion 5% and absolute precision 5%. all male and female adult patients admitted in surgical department who had undergone o p e n a p p e n d i c e c t o m y f o r a c u t e appendicitis and their appendix was non gangrenous and non perforated were included in the study. exclusion criteria known diabetic patients, patients with malignant disease. patients with chronic liver disease. patients with chronic renal failure. patients on steroids. data collection all patients were explained about the procedure and an informed written consent was obtained. right grid iron abdominal materials and methods � � � � � incision was used to open the abdomen. appendicectomy was done. peritoneum was closed by vicryl 2/0.interrupted and continuous sutures by vicryl 1 were applied 36 37 to the internal oblique muscle and external oblique appaneurosis respectively. sub cutaneous tissue was closed by vicryl 2/0 interrupted stitches. in all patients s u b c u t i c u l a r s t i t c h e s b y u s i n g polypropylene 2/0 were applied to close the skin. all the patients received 3 doses of antibiotics (ceftriaxone and metronidazole), 1 at the time of induction of anesthesia and 2 doses post operatively at 12 hour interval. p a t i e n t s w e r e d i s c h a r g e d o n 3 r d postoperative day after examination of the wound. stitches were removed at 7th post operative day. all the patients were followed on 7th and 30th post operative day for examination. data was entered in the preformed proforma (annexed) for analysis. data was analyzed by using spss version 10. frequency and percentage was used for qualitative variables i.e. wound infection, pain or tenderness, swelling, redness or heat and pus discharge from the incision on 3rd, 7th, and 30th post operative day. out of 73 patients 6(8.2%) suffered from w o u n d i n f e c t i o n . s u c c e s s f u l o p e n management of the infected wounds was done. rest of the patients had uneventful recovery. appendicectomy is considered as a clean contaminated surgery, therefore most surgeons have a fear of closing the wound in results discussion a subcuticular fashion due to high risk of wound infection. this study was planned to alleviate this fear of increased risk of wound i n f e c t i o n i n n o n c o m p l i c a t e d o p e n appendicectomy wound having skin closure with removable subcuticular stitches.our study supports that the wound a f t e r o p e n a p p e n d i c e c t o m y i n n o n perforated non gangrenous appendix can be closed by subcuticular removable sutures by prolene. in our study wound infection occurred in 6 patients (8.2%) only. a randomized controlled trial was conducted by hamid ghaderi et al in imam khomeini hospital tehran in 2010 to compare the wound infection rate after open appendicectomy in non complicated appendicitis. they took 278 patients admitted via emergency department and divided them in two groups. in one group the wound was closed by interrupted method and second group wound was closed by subcuticular prolene stitch. they did not find any gross difference in wound infection, 08 patients in interrupted group and 05 patients in subcuticular group with a p value of 0.415. so they concluded that frequency of wound infection doesn't increase with application of non absorbable suture in non open appendicectomy 15wounds. fashina ib, and associates in 2009 conducted a prospective study in 250 cases of appendicitis in department of surgery, college of medicine, university of lagos and lagos university teaching hospital, idi-araba, lagos, nigeria. they analyzed the w a y o f p re s e n t a t i o n , m a n a g e m e n t , operative findings and management figure 1: frequency of wound infection in study group (n= 73). wound infection 37 38 outcome in patients of acute appendicitis. they found that 08 % of the patients had 22wound infection. it was controlled clinical trial in which they divided the patients in two groups. in one group the wound was closed interrupted method and other by subcuticular method. they concluded that there is no significant increase in the wound infection rate when wound is closed with 22subcuticular technique. another study done by a. hussain and associates to evaluate the wound infection incidence in patients with acute non complicated appendicitis and perforated and gangrenous appendicitis. this was an observational study which was carried out on 400 patients with gangrenous or perforated (50%) and simple appendicitis (50%). both groups underwent primary wound closure. wound infections were observed in 15 patients (3.7%), including 6 cases of simple and 9 cases of gangrenous appendicitis which was not statistically 14significant. frequency of wound infection is 8.2% with removable subcuticular skin suture in non complicated open appendicectomy wound. the result of this study is comparable to studies conducted elsewhere in clean c o n t a m i n a t e d s u r g e r i e s l i k e appendicectomys the wound nfection is 5 10 %. so it is concluded that by using prolene in subcuticular fashion the rate of wound infection does not rise. it implies that the fear of surgeons to close the appendicectomy wounds by subcuticular closure is baseless. it is recommended that the skin should be closed with removable subcuticular sutures in non complicated open appendicectomy conclusion recommendations wound as it does not increase the rate of wound infection. references 1. humes d, simpson j. acute appendicitis. bmj 2006; 333: 530-4. 2. o g u n t o l a a , a d e o t i m , o y e m o l a d e t. appendicitis: trends in incidence, age, sex, and seasonal variations in south-western nigeria. ann afr med 2010; 9: 213-7. 3. evans srt. appendicitis 2006. ann surg 2006; 244: 661-2. 4. lansdown mrj, gray ajg, treasure t, layer gt. appendicectomy: who performs it, when and how? ann r coll surg engl 2006; 88: 530-4. 5. chamisa i. a clinicopathological review of 324 appendices removed for acute appendicitis in durban, south africa: a retrospective analysis. ann r coll surg engl 2009; 91: 688-92. 6. akbulut s, tas m, sogutcu n, arikanoglu z, b a s b u g m , u l k u a , e t a l . u n u s u a l histopathological findings in appendectomy specimens: a retrospective analysis and literature review. world j gastroenterol 2011; 17: 1961-70. 7. adisa a, omonisi a, osasan s, alatise o. c l i n i c o p a t h o l o g i c a l r e v i e w o f schistosomalappendicitis in south western nigeria. trop gastroenterol 2010; 30: 230-2. 8. lin ch, chen jh, li tc, ho yj, lin wc. c h i l d re n p re s e n t i n g a t t h e e m e rg e n c y department with right lower quadrant pain. kaohsiung j med sci 2009; 25: 1-9. 9. hansson le, laurell h, gunnarsson u. impact of time in the development of acute appendicitis. digestive surgery 2008; 25: 394-9. 10. morishita k, gushimiyagi m, hashiguchi m, stein gh, tokuda y. clinical prediction rule to distinguish pelvic inflammatory disease from acute appendicitis in women of childbearing age. am j emerg med 2007; 25: 152-7. 11. jamal s, amin m, salim m, mehmood a. c l i n i c o p a t h o l o g i c a l d i a g n o s i s o f a c u t e appendicitis after emergency appendicectomy rawal med j 2005; 30: 56-8. 12. salari aa, binesh f. diagnostic value of anorexia in acute appendicitis. pak j med sci 2007; 23: 68-70. 38 39 13. m o h a m e d f , k h o o k k . a c u t e a p p e n d i c i t i s : l e a v i n g n o r m a l l o o k i n g appendices. bmj 2006; 333: 652. 14. hussain a, mahmood h, geddoa e, james a.three none: a a new technique for open appendectomy. prospective non-randomized comparative study. european surgery 2008; 40: 125-9. 15. ghaderi h, shamimi k, moazzami f, aminian a, jalali sm, afghani r, et al. a new look at an old dogma: wound complications in two methods of skin closure in uncomplicated appendicitis. tumj 2010; 68: 54-8. 16. tajirian al, goldberg dj. a review of sutures and other skin closure materials. j cosmet laser ther 2010; 12: 296-302. 17. hochberg j, meyer km, marion md. suture choice and other methods of skin closure. surg clin north am 2009; 89: 627-41. 18. gaertner i, burkhardt t, beinder e. scar appearance of different skin and subcutaneous tissue closure techniques in caesarean section: a randomized study. eur j obstet gynecol reprod biol 2008; 138: 29-33. 19. wenzel rp. minimizing surgical-site infections. n engl j med 2010; 362: 75-7. 20. woodfield jc, beshay nmy, pettigrew ra, plank ld, van rij am. american society of anesthesiologists classification of physical status as a predictor of wound infection. anz j surg 2007; 77: 738-41. 21. anderson dj, kaye ks. staphylococcal surgical site infections. infect dis clin north am 2009; 23: 53-72. 22. fashina i, adesanya a, atoyebi o, osinowo o, atimomo c. acute appendicitis in lagos: a review of 250 cases. postgrad med j 2009; 16: 26873. 39 original�article abstract objective: to analyze the impact of dental erosion among preschool children in peshawar. st place and duration of study: study was conducted in peshawar, kpk pakistan over a period of 8 months from 1 rd december 2019 – 3 july 2020. study design: this was a descriptive cross-sectional study. materials and methods: this study was conducted among preschool children in private schools of hayatabad peshawar on 1021 children with age range of 3-5 years. parents of the invited children were asked to complete a questionnaire and consent form at home, distributed forehand. examination was done according to basic erosive wear examination (bewe) criteria. clinical examination of the children was performed in their classrooms using disposable dental mirror and a ball-ended who cpitin probe on all the surfaces of the deciduous teeth. status of the dental erosion of the entire sextant was represented by the tooth surface with the highest noted bewe score in that sextant. the association of erosive tooth wear with children's socioeconomic status, dental and oral hygiene habits was calculated using multiple logistic regression. results: total of 1021 preschool children assessed in this study revealed prevalence of dental erosion (bewe score>0) to be 12.2%. among these 92(9.01%) children had initial tooth wear,27(2.6%) had distinct tooth loss, and 6(0.58%) showed severe tooth loss. prevalence of erosive tooth wear was recorded to be 1.9%, 4.8% and 27.1% among 3, 4 and 5-year-old children respectively. conclusion: prevalence of dental erosion among preschool children in peshawar is low. however, increasing age, parental education as well as poor dietary and oral hygiene habits were the factors deemed to contribute towards increasing prevalence. key words: erosive tooth wear, oral hygiene, preschool children, parental education. the enamel of deciduous teeth is thinner when compared to permanent tooth surface and morphological difference between the two 4 dentitions exists. this clarifies the fast and rapidly progressing erosive process in primary teeth. even short-term exposure to acids may lead to advanced lesion extending to dentine in deciduous teeth. to o t h w e a r m ay e n t a i l t o o t h s e n s i t i v i t y, compromised esthetics, altered occlusion and even 4 pulpal exposure in severe cases. moreover, child may face a compromise in the entire dentition for his lifetime due to early damage to the teeth from dental 5 erosion. tooth wear in deciduous dentition is considered as the prognosticator of the augmented 6,7 risk of the tooth wear in permanent dentition. early diagnosis of tooth wear and prevention is the need of time as treatment in such cases might be 8 complex, expensive and challenging . the evidence available on the prevalence of dental erosive wear in preschool children in peshawar is not sufficient. therefore, the study aims to concentrate on the prevalence of dental erosion among preschool introduction dental erosion and the subsequent tooth wear are the irreversible loss of tooth enamel by acids from a non-bacterial source and are not directly related to mechanical or traumatic factors or dental caries. they are both documented as a major progressive 1 problem in preschool children. on the basis of literature review, acidic beverages 2 and food increase the potential for dental erosion, which can lead to consequences like hypersensitivity, 3 bad aesthetics, pulp exposure and malocclusion. prevalence and severity of dental erosion among preschool children in peshawar 1 2 3 4 5 6 gulandama alam khan , laila mustafa , madeeha bangash , ammara sami , fatimah shiraz , zarsanga haider correspondence: dr. madeeha bangash hod paediatric dentistry rehman college of dentistry, peshawar e-mail: madeeha.bangash@rmi.edu.pk 1,3,4 5 department of paediatric dentistry/physiology / 6 operative dentistry rehman college of dentistry, peshawar 2 department of paediatric dentistry shifa college of dentistry, islamabad received: march 21, 2021; revised: december 10, 2021 accepted: january 11, 2022 dental erosion in preschool children jiimc 2022 vol. 17, no.2 91 children in hayatabad peshawar, pakistan. materials and methods this was a descriptive cross-sectional study and included 1021 kindergartens. children from private schools of hayatabad, peshawar were included in the study using stratified random sampling technique over an interval of 8 months (december 2019 – july 2020). sample size was calculated using g-power with effect size 0.42, α-error 0.05 and power of 0.95. consent was obtained from the ethical review board of rehman college of dentistry (ec ref. no. rcd-2003-009). the dental examination was performed according to basic erosive wear examination (bewe) criteria. out of 121 children, 534 were girls and 487 were boys. age range was 3 to 5years. according to bewe criteria tooth erosion is divided into 4 levels. score 0 = no tooth surface loss, score 1 = initial enamel loss, score 2 = distinct defect spanning less than 50% of the tooth and score 3 = hard tissue loss 9 of more than 50%. healthy kindergarten 3 to 5 years old children in the selected schools were included in the study population upon their parental consent. children having special needs and those suffering from severe chronic diseases were excluded from the study. a questionnaire and consent form were distributed to parents of the invited children forehand, prior to conducting the survey and were asked to complete it at home within a week. the questionnaire contained t w o f r a g m e n t s i n c l u d i n g d e m o g r a p h i c characteristics (sex, age parental education, place of birth and family income) and oral hygiene behaviors (tooth brushing and snacking frequency and history of previous dental visit). a research subordinate r e q u e s t e d t h e p a r e n t s t o c o m p l e t e t h e questionnaire in case of missing data in the returned questionnaires via a phone call. all three dentists were trained in bewe assessment. instrument used in classroom were disposable dental mirror, head lamp (illumination in 100 mm working distance: = 40000 lux, adjustable rang fluctuation distance: 12.5 mm, direction of illumination: vertical 45 degree adjustable) for vision, cotton to dry the tooth surface, face mask, gloves and who cpitn ball end probe. after examining all the surfaces of the primary teeth, status of dental erosion of the entire sextant was represented by the tooth surface with the highest noted bewe score in that sextant. in addition, following the diagnostic criteria of the who, the decayed, missing and filled tooth index (dmft) was 10,11 adopted. caries experience was measured to be “yes” if dmft score was greater than 0, and “no” if dmft score was = 0. statistical analysis was performed using spss version 20. significance level was set at p≤0.005. descriptive statistics were used to calculate counts, means and standard deviations. fisher exact test was used to calculate significance among both genders, chi square test was preformed to test relationship between categorical variables while significance level of dental erosion in various age groups was calculated using independent t test. results among 1021 children examined, 6(0.58%) were scored 3, 27(2.6) were scored 2, 92(9.01%) were scored 1 and 896(87.7%) were scored 0 according to bewe criteria. out of 487 male children 0.41% and out of 534 females 0.74% had severe erosive loss as shown in table i. in sextant assessment, upper anterior teeth were the most damaged teeth and, lower right and left posterior teeth were least damaged teeth. children of age 5 years were mostly prone to dental erosion according to our study. the prevalence and severity of dental erosion are labelled in table i in the context of gender and age, showing erosive tooth wear increased with increasing age among the study population. male children were more effected with dental erosive wear (fisher's exact test p=0.028). values for birthplace according to chi square= 1.146 and p= 0.766 were not significant, which showed that birthplace had no effect to cause or increase dental erosive wear (table iii). table ii presents the severity and prevalence of dental erosion in all the sextants. the anterior maxillary primary teeth were ranked as teeth showing highest prevalence and more severe dental erosion as compared to other sextants, whereas the lower mandibular molars as the lowest in terms of prevalence of tooth erosive wear. sociodemographic characteristics linked to erosive tooth wear are described in table iii. child's age, parental education level and frequency of daily snacking were the factors that showed associated dental erosion in preschool children jiimc 2022 vol. 17, no.2 92 table i: prevalence and severity of erosive tooth wear among 3-5 years old children in peshawar table ii: distribution of severity of bewe scores in each sextant table iii: sociodemographic characteristics linked to tooth erosive wear dental erosion in preschool children jiimc 2022 vol. 17, no.2 93 with the prevalence of dental erosion statistically (bewe>0) (p<0.05). male children who had bewe score >0% were 14.9% and female children who had bewe score >0% were 9.7%. this displayed that male children are more prone to dental erosive wear as compared to girls. bewe score >0% in 3, 4 and 5year-old children were recorded as 1.9%, 4.8% 21.7% respectively indicating increase in erosive tooth wear with increase in age (shown in figure-i). parental education levels (primary, secondary and tertiary), snacking frequency, tooth brushing snaking frequency. carbonated drinks and fruit juices have acidic ph. therefore, been implicated in the growing incidence of erosion. dental wear is a general term used to describe a non-carious surface loss of the dental hard tissues that can be caused by abrasion, de-mastication, attrition, abfraction, resorption and erosion or a combination of any of 12 these. there is currently a growing interest among dentists and researchers about dental erosion although the reports have appeared frequently in literature. reformed lifestyle and eating patterns, with bigger consumption of acidic foods and beverages are considered probable risk factors for 13 dental erosion. 14 moss sj et al reported that erosive loss of tooth enamel occurs only in susceptible individuals irrespective of patterns of food and beverage consumption, concluding the fact that consumption of an acidic drink or food alone is highly questionable to cause erosion. the ability of a drink to resist buffering by saliva may 15 play an important part in the process of erosion. cough syrups are also associated with a significant decline in ph of the saliva with an increased risk of 7 development of caries in children. one of the studies among preschool children in hong 16 kong states that there is a decline in dental erosion with increasing parental education. in contrast to this, our study revealed that children of those parents who had a higher education status suffered from erosive tooth wear more easily. one possible reason to explain this could be the fact that parents with higher education have high socioeconomical status due to which their children can easily afford acidic(carbonated) drinks and food as compared to 16 poor families. 17 dental erosive wear increases with increasing age. as age increases exposure for dental erosion wear 18 also increase. this is in accordance with our results where children with age 5 years old have more dental erosive wear as compared to 3and 4-years old children. upper anterior teeth are more damaged sextant as 19 compared to other due to dental erosive wear. in our study 3% of upper anterior teeth had bewe score=3, which demonstrates that upper anterior teeth are more prone to dental erosive wear and lower posterior teeth are least prone to the dental fig. 1: showing association of age with bewe scores frequency, dental caries experience, place of birth and income, were some of the predominant features affecting the rate of dental erosive wear in children. discussion dental erosion is multifactorial. our results illustrate that many factors are involved in tooth erosion like acidic food, acidic drinks, parental education, family income, gender, tooth brushing frequency and dental erosion in preschool children jiimc 2022 vol. 17, no.2 94 frequency brushing caries erosion wear. various factors strengthening our results were a high sample size, a good inter examiner reliability (kappa value=0.76), and stratified random sampling technique for study population. however, certain limitations of this study must be investigated as the basic potential risk factors for erosive tooth wear including the types of acidic foods consumed and gastroesophageal reflux were not taken in account which might possibly lead to a bias during multivariate analysis. this demands for further research projects focusing on depth over the interplay between the medical conditions and the nutritional factors. nevertheless, the useful evidence provided by this study regarding the burden of erosive dental wear as well as its correlation with sociodemographic factors can provide a baseline data to serve as a convenient tool for designing community-based preventive programs. conclusion there is a low prevalence of dental erosion among preschool children in peshawar. however, increasing age, parental education as well as poor dietary and oral hygiene habits were the factors deemed to contribute towards increasing prevalence. references 1. el aidi h, bronkhorst em, truin gj. a longitudinal study of tooth erosion in adolescents. journal of dental research. 2008;87(8):731-5. 2. ehlen la, marshall ta, qian f, wefel js, warren jj. acidic beverages increase the risk of in vitro tooth erosion. nutrition research. 2008;28(5):299-303. 3. de oliveira pt, somacal dc, júnior lh, spohr am. aesthetic rehabilitation in teeth with wear from bruxism and acid erosion. the open dentistry journals. 2018; 12:486. 4. principles of regenerative medicine (third edition),2019. https://www.sciencedirect.com/topics/medicine-andd e n t i s t r y / d e c i d u o u s t e e t h # : ~ : t e x t = p r i m a r y %20teeth%20have%20thinner%20enamel,crown%20size %20than%20permanent%20pulps. 5. lussi a. erosive tooth wear–a multifactorial condition of growing concern and increasing knowledge. in dental erosion 2006 (vol. 20, pp. 1-8). karger publishers. 6. zhao d, tsoi jk, wong hm, chu ch, matinlinna jp. paediatric over the counter (otc) oral liquids can soften and erode enamel. dentistry journal. 2017;5(2):17. 7. dave ph, gurunathan d, vasantharajan ms. comparison of ph levels of the saliva before and after the consumption of cough syrups in children. biomedical and pharmacology journal. 2018;11(3):1443-8. 8. lussi a. erosive tooth wear–a multifactorial condition of growing concern and increasing knowledge. in dental erosion 2006 (vol. 20, pp. 1-8). karger publishers. 9. bartlett d, ganss c, lussi a. basic erosive wear examination (bewe): a new scoring system for scientific and clinical needs. clinical oral investigations. 2008;12(1):65-8. 10. dentalcare.co m. https://w w w. d entalcare.co m/en u s / p r o f e s s i o n a l e d u c a t i o n / c e c o u r s e s / c e 3 6 8 / e p i d e m i o l o g y t h e d m f index#:~:text=the%20dmft%20index%20expresses%20the ,of%200%20to%2088%20surfaces. 11. silveira jl, oliveira vd, padilha ww. evaluation of the reduction of the visible plaque index and of the gum bleeding index in a program of oral health promotion for children. pesquisa odontológica brasileira. 2002 ;16(2):16974. 12. imfeld t. dental erosion. definition, classification, and links. european journal of oral sciences. 1996;104(2):151-5. 13. ten gate jm, imfeld t. dental erosion, summary. european journal of oral sciences. 1996;104(2):241-4. 14. moss sj. dental erosion. international dental journal. 1998;48(6):529-39. 15. edwards m, creanor sl, foye rh, gilmour wh. buffering capacities of soft drinks: the potential influence on dental erosion. journal of oral rehabilitation. 1999;26(12):923-7. 16. duangthip d, chen kj, gao ss, lussi a, lo ec, chu ch. erosive tooth wear among preschool children in hong kong. i n t e r n a t i o n a l j o u r n a l o f p a e d i a t r i c d e n t i s t r y. 2019;29(2):185-92. 17. arnadottir ib, holbrook wp, eggertsson h, gudmundsdottir h, jonsson sh, gudlaugsson jo, saemundsson sr, eliasson st, agustsdottir h. prevalence of dental erosion in children: a national survey. community dentistry and oral epidemiology. 2010;38(6):521-6. 18. duangthip d, chen kj, gao ss, lussi a, lo ec, chu ch. erosive tooth wear among preschool children in hong kong. i n t e r n a t i o n a l j o u r n a l o f p a e d i a t r i c d e n t i s t r y. 2019;29(2):185-92. 19. duangthip d, chen kj, gao ss, lussi a, lo ec, chu ch. erosive tooth wear among preschool children in hong kong. i n t e r n a t i o n a l j o u r n a l o f p a e d i a t r i c d e n t i s t r y. 2019;29(2):185-92. dental erosion in preschool children jiimc 2022 vol. 17, no.2 95 conflict of interest authors declared no conflicts of interest. grant support and financial disclosure authors have declared no specific grant for this research from any funding agency in public, commercial or nonprofit sector. data sharing statment the data that support the findings of this study are available from the corresponding author upon request. this is an open access article distributed under the terms of the creative commons attributionnoncommercial 2.0 generic license. dental erosion in preschool children jiimc 2022 vol. 17, no.2 96 original�article abstract objective: to explore the hepatoprotective effect of n‐acetylcysteine on methimazole induced hepatic damage in mice. study design: randomized control trial. place and duration of study: the study was carried out from nov 2014 to oct 2015 at the animal house of army medical college, rawalpindi. materials and methods: thirty male balb/c mice were randomly divided into three groups of ten animals each. group i: control group (c), group ii: methimazole treated group (m), group iii: pretreated n‐acetylcysteine (nac) group. single dose of methimazole (mmi) (1000mg/kg, i.p) was injected for induction of hepatotoxicity. n‐acetylcysteine (nac) (300mg/kg, i.p) was given pre methimazole (mmi) administration. the extent of hepatic injury was determined by evaluation of serum alanine transaminase (alt) and alkaline phosphatase (alp) along with liver histopathology. results: methimazole (mmi) produced liver damage as evident by markedly raised liver enzymes along with necrosis and inflammatory cell infiltration. n‐acetylcysteine (nac) treated group resulted in reduction in elevation of serum biomarkers and improvement of histological picture. conclusion: n‐acetylcysteine (nac) holds significant hepatoprotective effect against methimazole (mmi) induced hepatotoxicity. key words: methimazole, hepatotoxicity, n‐acetylcysteine. intermediates cause oxidative and carbonyl stress, 4 mitochondrial impairment and immune reactions. previous studies have also identified cellular glutathione as an important susceptibility factor in 5 mmi induced cytotoxicity. despite reports of mmi induced liver damage, no specific protective has been developed against it. however, an indisputable area of medicinal benefit involves attenuation of oxidative hepatic damage. researches have recognized the role of antioxidants 6 in various types of drug induced liver injuries. n‐ acetylcysteine; the acetylated non enzymatic a n t i o x i d a n t h a s b e e n t h e a n t i d o t e f o r acetaminophen poisoning since 1974. however, its safety and efficacy has been proven outside acetaminophen overdose in liver transplant related damage, fibrosis, hepatitis, alcoholism, heavy metal toxicity and wide range of glutathione deficient 7 genetic and metabolic disorders. nac exerts its beneficial effects in these clinical settings through g l u t a t h i o n e d e p e n d e n t a n d i n d e p e n d e n t 8 mechanisms. the aim of the conducted study was to explore the protective effect of nac against mmi induced hepatotoxicity in mice. materials and methods introduction methimazole (mmi) is the most frequently 1 prescribed antithyroid drug worldwide. the preferred use of mmi for hyperthyroidism can be attributed to its better compliance and superior safety profile. however, its clinical use is associated with many extra thyroidal toxicities including hepatotoxicity which limit its usefulness. mmi induced hepatic injury has an incidence of 6.6% in adults presenting as hepatitis, cholestasis and acute 2,3 liver failure. liver injury produced by mmi is dependent upon bio activation to its reactive metabolites i‐e n‐ methylthiourea and glyoxal. these hepatoprotective effect of acetylated amino acid on methimazole induced hepatotoxicity in mice 1 2 3 4 zunera hakim , akbar waheed , aroosa ishtiaq , wardha mazhar jiimc 2016 vol. 11, no.4 correspondence: dr. zunera hakim department of pharmacology islamic international medical college riphah international university, islamabad e‐mail: zunerahakim@gmail.com 1,2 department of pharmacology islamic international medical college riphah international university, islamabad 3 department of pharmacology fazaia medical college, islamabad 4 department of pharmacology foundation university medical college, rawalpindi funding source: nil; conflict of interest: nil received: apr 10, 2016; revised: jun 07, 2016 accepted: oct 15, 2016 hepatoprotective effect of acetylated amino acid 167 an experimental study was carried out at the animal house of army medical college, rawalpindi from nov 2014 to oct 2015. the conducted trial was a joint venture of department of pharmacology and therapeutics and department of pathology, army medical college. thirty male 8‐10 weeks old balb/c mice, weighing 30‐40 gram were provided by national institute of health, islamabad. mice were housed under standard husbandry conditions 0 (temperature 20 ± 2 c, humidity 40‐60% and 12 hour light/dark cycle) with diet, water and libitum. animal care and research was carried out in accordance with protocols of ethical committee of “centre of research in experimental and applied medicine (cream)”. mmi of analytical grade was purchased from sigma chemicals usa through a licensed dealer. nac injections of aumur pharmaceuticals were purchased from karachi based pharmacy. only adult healthy male mice weighing > 30 grams and < 40 grams with normal lfts and no obvious abnormality were included in the study. after one week of acclimatization mice were randomly divided into three groups with ten animals each. group i (n=10) served as the control group (c) and was given normal saline intraperitoneally (i.p). group ii was mmi treated group (m) and given mmi dissolved in normal saline (1000mg/kg i.p). 1000 mg/kg i.p of mmi was taken as the appropriate toxic dose after conduction of pilot study with various previously 9,10 mentioned experimental doses. group iii; nac pretreatment (nac ‐pre) group was intervened with 11 nac (300 mg/kg i.p) one hour before mmi. baseline sampling of all animals was done through 12, 13 tail vein obtaining at the start of research. after 14 recommended recovery period , intervention was carried out and blood samples were collected by performing cardiac puncture five hours after mmi 10 administration. serum obtained from clotted blood by centrifugation at 3000 revolution/min was used for analysis of alt and alp by commercially available kits of cormay and linear. alt was estimated by ifcc method while calorimetric method (dgkc method) was applied for alp. at the end of experimental period, liver was removed and fixed in 10% formalin. hematoxylin and eosin (h&e) stained slides were prepared and studied under microscope for histopathological findings. data was analyzed using spss 21. all data was expressed as mean ± s.e.m. statistical difference between serum markers at initial and final hours was calculated using students t‐ test. one way anova followed by post hoc turkey was applied for multiple comparisons between groups. p <0.05 was considered significant. results effect of n‐acetylcysteine on serum alt levels baseline and final values of alt of g‐i (control group) and g‐iii (nac pretreated group) remained within normal range during the experimental period (fig 1). an insignificant p value was obtained when g‐i was compared with g‐iii (table ii). mmi significantly raised alt levels (261.33±20.30) as compared to initial values (45.33± 9.84) (fig 1) and control group i. (table i). nac affords protection against mmi induced hepatic insult by mitigating the rise in alt as evident by significant difference between g‐ii and g‐ iii (table iii). effect of n‐acetylcysteine on serum alp levels results revealed an insignificant difference between initial and final levels of alp of g‐i and g‐iii (fig 2) which was also reflected in their intergroup comparison (table ii). a significant increment was observed in final serum alp levels (251 ±17.61) of drug treated group ii (fig 2). comparison of g‐ii (m) with control group g‐i revealed statistically significant difference (table i). a trend of lowering of alp levels was displayed by nac pretreatment as fig 1: ini�al and final values of alt (u/l) of g‐i, g‐ii and g‐iii *p < 0.05 =significant jiimc 2016 vol. 11, no.4 168 hepatoprotective effect of acetylated amino acid evident by p value < 0.05 when compared with g‐ii (m) (table iii). histopathological findings light microscopy of h & e stained slides of control group showed normal lobular appearance with central vein, portal triad and radiating hepatocyte cords (fig 3). mmi administration caused cellular discontinuity, vascular congestion, loss of hepatocyte radial distribution and inflammatory cell infiltration (fig 4 and 5). nac pretreatment resulted fig 2: ini�al and final values of alp (u/l) of g‐i, g‐ii and g‐iii *p < 0.05= significant table i: comparison of alt and alp between g‐i and g‐iii *p value < 0.05 = significant table ii: comparison of alt and alp between g‐i and g‐iii *p value < 0.05 = significant table iii: comparison of alt and alp between g‐ii and g‐iii *p value < 0.05 = significant fig 3: pictograph of h & e stained liver specimen of control group at 40x showing central vein (cv), hepatocyte (h) and sinusoid space (s) fig 4: pictograph of mmi treated group (m) at 40x revealing cellular discon�nuity and loss of radial distribu�on of hepatocytes. fig 5: pictograph of mmi treated group (m) at 40x revealing portal inflamma�on jiimc 2016 vol. 11, no.4 169 hepatoprotective effect of acetylated amino acid in preservation of liver architecture with minimal portal and lobular inflammation (fig 6). discussion drug induced liver injury (dili) is an unresolved health problem with an impact well beyond the number of cases occurring annually. it has become the most common reason for termination of drug development and withdrawal of approved products from market. antithyroid medicines are included among the thousand (1000) drugs known to cause 15 hepatic damage. although the precise mechanism of mmi induced hepatotoxicity requires further exploration, however the role of reactive metabolite, oxidative and carbonyl stress, intracellular target dysfunction and immunological reaction has been implicated. the hepatotoxic metabolites produced as a result of biotransformation are capable of reacting with enzymatic and non‐enzymatic antioxidants (gsh) rendering them ineffective and 16 ensuing toxicity. liver is central to all detoxification processes and adversely targeted by mmi during its administration. our results showed that mmi produced an abnormal increase in alt and alp (p < 0.05) which was reflected as cellular discontinuity, necrosis and portal inflammation on microscopy. the significant rise in biochemical markers and histopathological findings were in accordance with the research of 1 7 tashkandi and his fellows in 2014. they demonstrated that administration of mmi produced a percentage increase of 202 and 191 in alt and alp along with 61% decrease in antioxidant enzymes. coherent with our findings, heidari and mates reve a l e d e l evat i o n o f l i ve r e n zy m e s w i t h concomitant decrease in gsh levels as a 18 consequence of mmi induced hepatic insult. this h i g h l i g ht s t h e ro l e o f ox i d at i ve st re s s i n pathophysiology of mmi induced hepatic insult and the function of gsh in detoxification of its toxic intermediates. thus gsh depleted hepatocytes are more susceptible to mmi induced injury producing remarkable damage at one thirtieth the normal toxic 9 dose. antioxidants have been documented to play their protective role in conditions set in the background of oxidative stress and impede progression of these d i s e a s e s . s t u d i e s h a v e r e v e a l e d t h e hepatoprotective potential of many amino acids against drug induced liver injuries due to their 6 antioxidant effects. present study evaluated the protective capacity of n‐acetylcysteine (nac) in mmi induced hepatotoxicity. pretreatment with acetylated cysteine in g‐iii (n‐group) prevented the elevation of alt and alp observed in mmi treated group –ii (p < 0.00). injection of nac one hour before mmi also managed to preserve the hepatic architecture with minimal inflammatory changes on histopathology. insignificant difference (p > 0.05) between alt and alp of control group (c) and nac pretreated group‐iii also adds weight to the hepatoprotective effect of nac. heidari and colleagues demonstrated that administration of organosulfur compounds attenuated cell death and prevented ros formation, mitochondrial damage 19 and lipid peroxidation caused by mmi. since many studies has recognized oxidative stress as a major causative factor of mmi induced cellular 4,16 damage , nac's beneficial effects can be attributed to its direct and indirect antioxidant properties. acting as membrane permeable source of l‐cysteine for endogenous gsh, it can facilitate neutralization of cytotoxic metabolites before they can initiate 20,21 damage. this acetylated amino acid can also defend against liver damage by scavenging free 22 radicals and toxic aldehydes. this attenuation of oxidative stress through prevention of gsh depletion and glyoxal trapping by nac was also reported by 23 heidari and mates. the results affirmed the notion that nac extends its protective effects against mmi induced liver damage evident by prevention of rise of serum alt and alp fig 6: pictograph of nac treated group showing preserved architecture of hepa�c parenchyma and portal triad with minimal inflamma�on jiimc 2016 vol. 11, no.4 170 hepatoprotective effect of acetylated amino acid along with preservation of hepatic lobular organization. conclusion n‐acetylcysteine holds hepatoprotective potential against mmi induced liver injury due to broad spectrum of physiological activities, however further investigation is required to endorse the prophylactic role of nac in thionamide induced hepatotoxicity. references 1. emiliano ab, governale l, parks m, cooper ds. shifts in propylthiouracil and methimazole prescribing practices: antithyroid drug use in the united states from 1991 to 2008. the journal of clinical endocrinology & metabolism. 2010; 95: 2227‐33. 2. nakamura h, noh jy, itoh k, fukata s, miyauchi a, hamada n. comparison of methimazole and propylthiouracil in patients with hyperthyroidism caused by graves’ disease. the journal of clinical endocrinology & metabolism. 2007; 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protective agents against methimazole‐induced liver injury. journal of biochemical and molecular toxicology. 2015; 29: 173‐81. jiimc 2016 vol. 11, no.4 171 hepatoprotective effect of acetylated amino acid page 29 page 30 page 31 page 32 page 33 july 2013.pdf ßþíìîßýì ñ¾¶»½¬·ª»æ ì± ¼»¬»®³·²» ¿­­±½·¿¬·±² ±º ®·­µ º¿½¬±®­ ©·¬¸ ¸»°¿¬·¬·­ þ ­«®º¿½» ¿²¬·¹»² °±­·¬·ª·¬§ ·² °®»¹²¿²¬ ©±³»²ò í¬«¼§ ü»­·¹²æ ý¿­» ½±²¬®±´ ­¬«¼§ò ð´¿½» ¿²¼ü«®¿¬·±² ±º í¬«¼§æ 쩱 §»¿®­ º®±³ îððì ¬± îððê ¿¬ ß¹¸¿ õ¸¿² ë²·ª»®­·¬§ ø±­°·¬¿´ò 󿬻®·¿´­ ¿²¼ 󻬸±¼­æ ß ¬±¬¿´ ±º îïð ­«¾¶»½¬­ ·²½´«¼·²¹ íë ½¿­»­ ¿²¼ ïéë ½±²¬®±´­ ©»®» »²®±´´»¼ ·²¬± ­¬«¼§ò ß ¼»¬¿·´»¼ ¸·­¬±®§ º®±³ ­¬«¼§ ­«¾¶»½¬­ ©¿­ ®»½±®¼»¼ ±² ¿ °»®º±®³¿ ¼«®·²¹ ¿²¬»²¿¬¿´ ª·­·¬­ò ë²·ª¿®·¿¬» ¿²¼ ³«´¬·ª¿®·¿¬» ¿²¿´§­·­ ©¿­ ¼±²» «­·²¹ íðíí °¿½µ¿¹»ò î»­«´¬­æ ß ­·¹²·º·½¿²¬ ¿­­±½·¿¬·±² ©¿­ ±¾­»®ª»¼ º±® ¬¸» ¸·­¬±®§ ±º ¿¬ ´»¿­¬ º±«® ·²¶»½¬·±²­ º±® ³·²±® ·´´²»­­»­ ·² °¿­¬ ±²» §»¿® ø¿¼¶«­¬»¼ ±¼¼­ ®¿¬·± øßñî÷ ã ëòëå çëû ½±²º·¼»²½» ·²¬»®ª¿´ øý×÷æ ïòêô ïèòï÷ ¿²¼ ¸·­¬±®§ ±º ¾´±±¼ 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descriptive cross-sectional study. place and duration of study: the department of gynecology and obstetrics, fauji foundation hospital, rawalpindi, over a period of six months from may 2019 to october 2019. materials and methods: study participants were 159 pregnant women presented to antenatal clinics. the inclusion criteria were gestational age more than 30 weeks with singleton pregnancies, sure last menstrual period, period of gestation confirmed by dating ultrasonography, small for dates or clinical suspicious of intrauterine growth restriction, and women who provided informed consent. doppler scan was performed in all those women. results: mean age of all the enrolled women was 26.8 (± 6.6) years. out of 159 women, 32 (20 percent) were nulliparous. on doppler scan, 29 (18.2 percent) women had intrauterine growth restriction. the mean gestational age at the time of delivery was 35.3 (± 0.95) weeks. caesarean section was performed in 131 (82.5 percent) of the deliveries. at birth, 24 (15.1 percent) had intrauterine growth restriction. the sensitivity, specificity, positive and negative predictive values of doppler scan to detect intrauterine growth restriction were 83.3 percent, 93.3 percent, 69.0 percent, and 96.9 percent respectively. the diagnostic accuracy of doppler scan was 91.8 percent. conclusion: our study shows a high sensitivity and specificity of doppler scan in detecting intrauterine growth restriction. key words: intrauterine growth restriction, middle cerebral artery, pulsatilityindex, pregnant women, resistive index, umbilical artery. 3 organization criteria for taking public health action. iugr may be caused by maternal, fetal, placental, 4 and external factors. early detection of compromised iugr fetuses and timely intervention is among the major objectives of 5 current prenatal care services. abnormal findings of fetal size, weight and symmetry ultrasound leads to suspicion of iugr. various methods used to determine iugr comprise of abdominal palpation to measure symphysis-fundal height, fetal ultrasound 6 biometry and ultrasound doppler flow velocimetry. however, symphysis-fundal height measurements have inadequate accuracy to diagnose an iugr fetus. however, abdominal circumference and estimated fetal weight are the more accurate sonographic 7 diagnostic measurements to predict iugr. nevertheless, recent research has shown that ultrasound doppler flow velocimetry is the best tool 8 to detect iugr. however, variations in sensitivity and specificity of doppler ultrasonography in detecting iugr have introduction intrauterine growth restriction (iugr) is a condition in which a fetus is unable to attain its genetically 1 predetermined growth potential. fetuses with intrauterine growth restriction are at higher risk of perinatal mortality, neurological abnormalities, and 2 poor performance at school. it is also one of the major problems in developing countries like pakistan with incidence of 25%, more than world health diagnostic accuracy of umbilical artery and middle cereberal artery doppler in detection of intrauterine growth restriction 1 2 3 4 5 6 asia raza , azra saeed awan , seema gul , nadia ahmed bokhari , hina tabassum , samina irshaad correspondence: dr. nadia ahmed bokhari assistant professor department of obstetrics & gynecology foundation university medical college, foundation university, islamabad e-mail: nadia67bukhari@hotmail.co.uk 1,2,4,5,6 department of obstetrics & gynecology foundation university medical college, foundation university, islamabad 3 department of obstetrics & gynecology watim medical and dental college, islamabad funding source: nil; conflict of interest: nil received: january 12, 2021; revised: september 17, 2021 accepted: september 21, 2021 accuracy of umbilical artery and middle cerebral artery doppler in iugrjiimc 2021 vol. 16, no.4 219 9 been reported worldwide. therefore, use of doppler ultrasonography as a predictive test to detect iugr in our clinical settings is questionable. hence, the aim of the present study was to determine the diagnostic value of doppler in detecting the iugr among the pregnant women in our clinical settings. this study would help to determine the diagnostic value of doppler ultrasonography in detecting intrauterine growth restriction in our setup for better management of i u g r fet u s e s . ea r l y d i a g n o s i s a n d t i m e l y management will help in reduction of perinatal mortality in these fetuses. materials and methods a descriptive cross-sectional study was conducted in obstetrics and gynecology department, fauji foundation hospital, rawalpindi, over a period of six months from may 2019 to october 2019. a total of 159 pregnant women were selected using nonprobability purposive sampling technique. women having gestational age more than 30 weeks, visiting antenatal clinics were included in the study. the sample size was estimated by using the world health organization (who) sample size calculations. the confidence interval level was considered at 95 percent and absolute precision was taken as 10 9 percent. by choosing the sensitivity of 89 percent , 9 specificity of 92 percent and prevalence of 24 10 percent , the required sample size was 159 pregnant women who underwent doppler scan to detect iugr. women having singleton pregnancies beyond 30 weeks of gestation, sure about last menstrual p e r i o d ( l m p ) a n d d a t e s c o n f i r m e d b y ultrasonography in second trimester (before 22 weeks of gestation) and small for date or clinical suspicious of iugr (more than 2 weeks difference b e t w e e n g e s t a t i o n a l a g e a n d u l t ra s o u n d parameters) were included in the study. women having multiple pregnancies, presence of fetal congenital anomalies, unsure about last menstrual period or no dating scan available were excluded. data was collecting on a predesigned proforma after taking informed verbal consent from the study participants. a brief demographic and clinical history including age, parity, socio-economic status and about the previous obstetric details, and duration of gestation were asked to every enrolled woman. doppler scan was performed in all women who were diagnosed to have iugr based on ultrasonography findings. an umbilical artery doppler abnormality was defined th when the resistive index (ri) was above the 95 centile for gestational age or the presence of an absent end-diastolic flow (aedf) or reversed enddiastolic flow (redf). middle section of the mca and free loop of umbilical artery were chosen for measurement during periods of fetal apnea. the values of pulsatility indexes (pi) of the mca and umbilical artery doppler were calculated. the measurements were taken on weekly basis when doppler values were not normal or fortnightly with growth scan. the measurement before delivery was taken for the analysis. at a minimum, three measurements were obtained, and the mean values were used. all the enrolled women whether with normal or abnormal doppler findings were followed till the time of delivery to observe the neonatal outcomes for the diagnosis of iugr based on birth th weight (below the 10 percentile for its gestational age and a term neonate with birth weight less than 2,500 grams). all this information was collected on pre-designed proforma. data was analyzed using statistical tests for social sciences (spss) version 21. means and standard deviations were calculated for continuous variables while proportions and frequencies were calculated for categorical variables. results were presented in the form of tables. to examine the accuracy of doppler scan in detection of iugr, we calculated the values of sensitivity, specificity, positive predictive value (ppv), negative predictive value (npv) and diagnostic accuracy (da) by using the following 2x2 11 table (table-i). table i: calculation of diagnostic accuracy of doppler scan in detecting iugr · sensitivity = a/ a+c x 100 · specificity = d/ b+d x 100 · positive predictive value = a/ a+b x 100 · negative predictive value = d/ c+d x 100 results this study was conducted on 159 participants. mean (sd) age of all the enrolled women in our study was jiimc 2021 vol. 16, no.4 accuracy of umbilical artery and middle cerebral artery doppler in iugr neonatal birth weight 220 26.8 (sd = ± 6.6) years. on doppler ultrasound and had low birth weight on delivery. the sensitivity, specificity, positive and negative predictive values of doppler scan to detect intrauterine growth restriction were 83.3 percent, 93.3 %, 69.0 % and 96.9 % respectively. the diagnostic accuracy of doppler scan was 91.8 % (table-v). table ii: age distribution of enrolled women (n=159) out of 159 women, 32 (20 %) were nulliparous and 127 (80%) were parous (table-iii). the mean (sd) gestational age at the time of delivery was 35.3 (± 0.95) weeks, 18 (11.3 %) women were delivered by normal vaginal whereas a great majority, 131 (82.5 %) women were delivered by c-section. in 10 (6.2 %) women, forceps were applied during the delivery time. values of normal, absent, and reverse diastolic flow in middle cerebral artery are given in table iii. table iii: descriptive statistics (n=159) doppler findings (umbilical artery and mca) of all the enrolled women (n=159) are given in table iv. table iv: doppler findings (umbilical artery and mca) of all the enrolled women (n=159) note: ua, umbilical artery; mca, middle cerebral artery, ri, resistance index; pi, pulsatility index; s/d, systolic to diastolic ratio. on doppler ultrasound, iugr was present in 29 (18.2 %) pregnant women whereas in 130 (81.8 %) pregnant women iugr was not detected (table-v). at birth, 24 (15.1 %) babies were low birth weight whereas in 135 (84.1 %) babies had normal birth weight (no iugr). so, 20 (12.5%) women had iugr table-v: diagnostic value of doppler scan to detect iugr among all the enrolled women (n=159 discussion every fetus has a specific growth potential that is inherited from parents. intrauterine growth restriction (iugr) may be due to abnormal genetic makeup of the fetus or placental development, maternal medical disorders and environmental 12 factors like toxins and viral infections . iugr is linked with substantial perinatal morbidity and mortality. its long-term complications in childhood include cerebral palsy due to permanent brain damage, while in adult life it is found to be associated with noninsulin-dependent diabetes mellitus and hypertension. diagnosis of intrauterine growth restriction becomes 13 problematic sometimes . most sga fetuses are normal, but much unnecessary intervention can be done if they are mistaken as cases of iugr. on the other hand, growth retarded fetuses may not be 14 sga . doppler velocity measurement has been widely used in antenatal diagnosis of iugr for more than twenty years. fetal wellbeing is predicted through blood flow in many vessels, particularly in 15 the umbilical artery. in our study, 159 pregnant women with mean age of 26.8 years were enrolled. out of 159 pregnant women, iugr was detected in 29 (18.2 %) pregnant jiimc 2021 vol. 16, no.4 accuracy of umbilical artery and middle cerebral artery doppler in iugr 221 women on doppler scan, while based on birth weight 24 (15.1 %) babies were declared as iugr. the results are like another study where color doppler ultrasonography showed the iugr in 73 (56.59%) patients and birth confirmed iugr in 71 (55.04%) cases where as 58 (44.96%) patients revealed no 16 iugr . in our study, the sensitivity, specificity, positive and negative predictive values of doppler scan to diagnose iugr were 83.3 percent, 93.3 percent, 69.0 percent, and 96.9 percent respectively. the diagnostic accuracy of doppler scan was 91.8 percent. in another study, umbilical artery doppler ultrasound had sensitivity 85.3%, specificity 72.5%, positive predictive value 84.1%, negative predictive value 74.4% and diagnostic accuracy of 80.1%. our study showed a substantially high sensitivity and specificity of doppler scan in detection of iugr in our clinical settings and our findings are comparable with other similar studies around the world. similar to our study, a recent study has been carried out in our neighboring country, india, where the diagnostic accuracy of ua and mca doppler scan was used in detecting iugr in their study population. the investigators enrolled 90 pregnant women between gestational ages of 30 weeks and above having fetuses with intrauterine growth restriction, similar to our study population. the diagnostic accuracy of doppler scan in detecting iugr in their study population was lower than what we have found in 17 our study. quite similar to our findings, in united kingdom, a study enrolled 52 women for doppler studies of iugr fetuses, the authors reported a sensitivity and specificity of 96 percent and 84 18 percent respectively. there are several reasons that our study found a higher sensitivity and specificity than what they found. however, the most common reason is that in our study we conducted doppler scan after 30 weeks of gestation while many studies reported have conducted doppler in first or second trimester of pregnancy. in a recent study, doppler studies have been used to detect early onset iugr in first two trimesters, with detection rates of about 50 percent with false positive rate of 7 percent. however, its use as an isolated screening tool had low sensitivity and positive predictive value if used alone as a screening 19 tool to detect iugr in first and second trimesters. in fetuses with iugr, blood flow is redistributed from periphery towards the brain. umbilical artery (ua) middle cerebral artery (mca) is the most studied fetal arteries for doppler studies due to its easy 20 accessibility. conclusion findings of our study suggest high sensitivity and specificity of doppler scan in detecting iugr in our study population. however, there is a need to conduct large scale, multicenter randomized controlled trials to determine the diagnostic accuracy of fetal doppler ultrasonographies in detecting iugr in our local population. references 1. ross mg, zion mansano r. fetal growth restriction: practice essentials, causes of intrauterine growth restriction, perinatal implications [internet]. emedscape. 2020. available from: https://emedicine.medscape. com/article/261226-overview. 2. malhotra a, allison bj, castillo-melendez m, jenkin g, polglase gr, miller sl. neonatal morbidities of fetal growth restriction: pathophysiology and impact. vol. 10, frontiers in endocrinology. 2019. 3. mohammad n, sohaila a, rabbani u, ahmed s, ahmed s, ali sr. maternal predictors of intrauterine growth retardation. j coll physicians surg pakistan. 2018;28(9):681–5. 4. sharma d, shastri s, sharma p. intrauterine growth restriction: antenatal and postnatal aspects. vol. 10, c l i n i ca l m e d i c i n e i n s i g ht s : pe d i at r i c s . 2 0 1 6 . p . cmped.s40070. 5. tambat ar, chauhan a. relationship of the findings of colour doppler and non-stress test with the perinatal outcome among the cases of intra-uterine growth restriction. mvp j med sci. 2016;3(2):115. 6. cherian, g a. diagnosis of intrauterine growth restriction cherian ag curr med issues. curr med issues. 2017;15(4):267–70. 7. gutaj p, wender-ozegowska e. diagnosis and management of iugr in pregnancy complicated by type 1 diabetes mellitus. vol. 16, current diabetes reports. 2016. 8. khadija s, amir gilani s, butt s, yousaf m, bacha r, hassan gilani sz ul. the efficacy of doppler indices in third trimester of iugr pregnancies. obstet gynecol res. 2019;03(01):1–9. 9. cnossen js, morris rk, ter riet g, mol bwj, van der post jam, coomarasamy a, et al. use of uterine artery doppler ultrasonography to predict pre-eclampsia and intrauterine growth restriction: a systematic review and bivariable meta-analysis. vol. 178, cmaj. 2008. p. 701–11. 10. malik a, ashraf r, hanson la. cytokines in the placenta of pakistani newborns with and without intrauterine growth retardation. vol. 3, pakistan journal of medical and health sciences. 2009. p. 279. 11. stojanović m, apostolović m, stojanović d, milošević z, jiimc 2021 vol. 16, no.4 accuracy of umbilical artery and middle cerebral artery doppler in iugr 222 toplaović a, lakušić vm, et al. understanding sensitivity, specificity and predictive values. vojnosanit pregl. 2014;71(11):1062–5. 12. manandhar t, prashad b, nath pal m. risk factors for intrauterine growth restriction and its neonatal outcome. gynecol obstet. 2018;08(02). 13. sharma d, sharma p, shastri s. postnatal complications of intrauterine growth restriction. j neonatal biol. 2016;05(04). 14. kesavan k, devaskar su. intrauterine growth restriction: postnatal monitoring and outcomes. pediatr clin north am [ i n t e r n e t ] . 2 0 1 9 ; 6 6 ( 2 ) : 4 0 3 – 2 3 . av a i l a b l e f r o m : https://doi.org/10.1016/j.pcl.2018.12.009. 15. figueras f, gratacós e. update on the diagnosis and classification of fetal growth restriction and proposal of a stage-based management protocol. fetal diagn ther. 2014;36(2):86–98. 16. mehdi sa, bukhari h, dogar ih, shabbir i. diagnostic accuracy of color doppler of cerebral and umbilical pulsatality in diagnosing iugr, taking birth weight as gold standard. prof med j. 2020;27(03):651–9. 17. bano s, chaudhary v, pande s, mehta vl, sharma ak. color doppler evaluation of cerebral-umbilical pulsatility ratio and its usefulness in the diagnosis of intrauterine growth retardation and prediction of adverse perinatal outcome. indian j radiol imaging. 2010;20(1):20–5. 18. bamfo jeak, kametas na, chambers jb, nicolaides kh. maternal cardiac function in fetal growth-restricted and n o n g ro w t h re s t r i c t e d s m a l l fo r g e s ta t i o n a l a g e pregnancies. ultrasound obstet gynecol. 2007;29(1):51–7. 19. pedroso ma, palmer kr, hodges rj, costa f da s, rolnik dl. uterine artery doppler in screening for preeclampsia and fetal growth restriction. vol. 40, revista brasileira de ginecologia e obstetricia. 2018. p. 287–93. 20. mari g, hanif f, kruger m, cosmi e, santolaya-forgas j, treadwell mc. middle cerebral artery peak systolic velocity: a new doppler parameter in the assessment of growthre st r i c te d fe t u s e s . u l t ra s o u n d o b ste t gy n e co l . 2007;29(3):310–6. jiimc 2021 vol. 16, no.4 accuracy of umbilical artery and middle cerebral artery doppler in iugr 223 original�article abstract objective: to compare the mean interappointment pain using ledermix paste and no intracanal medicament in patients with acute apical periodontitis. study design: randomized controlled trial. st place and duration of study: operative dentistry department, watim dental college, rawalpindi, from 1 st march to 31 august 2018. materials and methods: sixty patients who were fulfilling the inclusion criteria were selected. two groups were made group 1 and group 2. the patients were divided into these groups based on table of random numbers. single blind technique was followed while dividing the patients. group 1 patients had ledermix placed into the tooth and group 2 patients had no intracanal medicament placed into the tooth. patient pain score was recorded after 48 hrs using visual analogue scale. spss version 23 was used to analyze the data. results: mean inter-appointment pain was 3.23±1.43 for ledermix (group-1) and for no intracanal medicament (group 2); the mean inter-appointment pain was 5.87±1.30. a statistically significant difference was recorded with a p-value of 0.005. conclusion: patients in which ledermix was placed as an intracanal medicament experienced significantly less inter-appointment pain as compared to patients having no intracanal medicament (p=0.005) at 48 hours. hence, ledermix can be effectively used as an intracanal medicament to reduce inter-appointment pain for patients seeking endodontic treatment for acute periapical periodontitis in routine clinical settings. key words: acute apical periodontitis, intracanal medicament, inter-appointment pain, ledermix, root canal therapy. tooth, condition of periapical tissues and 3 preoperative severity of disease. microbial injury is 4 the most common cause of inter-appointment pain. frequency of interappointment pain is greater in teeth with necrotic pulp having periapical lesionsas compared to teeth with vital pulps. cleaning and shaping holds greater importance in comparison to the placement of intracanal medicaments in 6 disinfecting the root canal system. obturation effectively entombs and seals the microorganisms remaining within the root canal system. thus, placement of an intracanal medicament may not be 7,8 required. infection of root canal and surrounding tissues may occur from the microorganisms remaining in 9 dentinal tubules after shaping and cleaning. the placement of intracanal medicaments would 10,11 enhance the disinfection of root canal. antiinflammatory agents have been incorporated in these intracanal medicaments. the antibiotics have been shown to be effective in necrotic teeth and for the periradicular tissues. the local administration of introduction infection of the root canal can result in apical 1 periodontitis. the objective of root canal treatment is to reduce the bacterial load from the root canal. the prevalence of inter-appointment pain was 2 reported to be 2.3%. the occurrence of interappointment pain is influenced by various factors. these include age of patient, gender, type of comparison of the effect of ledermix paste and no intracanal medicament on interappointment pain during root canal therapy 1 2 3 4 5 6 ammarah afreen , zarah afreen , sadia daaniyal , shoaib rahim , aamna khalil , umer javed correspondence: dr. ammarah afreen assistant professor department of operative dentistry watim dental college, islamabad e-mail: ammarahafreen@gmail.com 1 2,3 department of operative dentistry/ prosthodontics watim dental college, rawalpindi 4 department of prosthodontic foundation university college of dentistry, foundation university islamabad 5 department of prosthodontics multan medical and dental college, multan 6 department of prosthodontics poly clinic hospital, islamabad funding source: nil; conflict of interest: nil received: july 17, 2020; revised: june 20, 2021 accepted: july 06, 2021 comparison of ledermix paste and no intracanal medicament on inter appointment pain during rctjiimc 2021 vol. 16, no.3 156 antibiotics is a more effective method for reduction 12 of pain during endondontic treatment. the combination of antibiotics and corticosteroids in medicaments such as ledermix are highly effective in acute apical periodontitis. the objective of our study was to compare the mean inter-appointment pain using ledermix paste and no intracanal medicament in patients with acute apical periodontitis. materials and methods study was conducted after approval of institutional ethic review committee. the study design was randomized controlled trial. sampling technique was non-probability consecutive sampling. inclusion criteria consisted of both male and female patients with age ranging from 18-50 years, with symptomatic mandibular posterior teeth with a diagnosis of acute apical periodontitis and those willing to undergo endodontic treatment. exclusion criteria included patients with teeth that were malposed, with a fluctuant facial swelling, immature root apices, root fractures, mentally handicapped patients, terminally ill patients and non-cooperative patients. study was conducted from march to august 2018 at operative department, watim dental college, rawalpindi. sixty patients who were fulfilling the inclusion criteria were invited by the principal investigator to participate in the study. informed consent was taken from all the patients. the patients were divided into two groups based on table of random numbers. single blind technique was followed while dividing the patients. the principal investigator performed all endodontic treatment. local anaesthetic was used to anesthetize the tooth. rubber dam was used to achieve the isolation. access cavity was prepared with a round bur. pulpectomy was done and working length confirmed by taking a periapical radiograph. step back technique was used to prepare the canals till 35k file. during the treatment, the irrigation of the canals was done using miton's technique in which 1% naocl was used alternating with 15% edta. paper points were used to dry the canals. lentulo-spiral was used to place the following medicaments into canals in the groups. group 1: ledermix paste group 2: no intracanal medicament access cavity was sealed with sterile cotton and cavit. patient was recalled after 48 hours. visual analogue scale was used to record the degree of pain on a scale of 0 to 10 with 0 indicating no pain and 10 indicating worst pain. followup was ensured by keeping contact number and address of the patients. spss version 23 was used to analyze the data. for both qualitative and quantitative variables, descriptive statistics were calculated. for age and pain scores (quantitative variables) mean+sd was calculated. for gender (qualitative variable) frequency and percentage was calculated. comparison of the mean pain score in the two groups was done using paired sample t-test. p-value< 0.05 was considered significant. results a total of 60 patients with acute apical periodontitis were included in this study for root canal treatment. the patients were equally divided into two groups. in-group 1, patients were treated with ledermix as intracanal medicament and group 2 served as control (no intracanal medicament). average age of the patients was 28.32±8.95 years. similarly, overall average inter-appointment pain score was 4.55±1.89 as shown in table i. out of 60 patients, 35(58.3%) were females and 25(41.7%) were males. mean inter-appointment pain was 3.23±1.43 for ledermix and for no intracanal medicament; the mean inter-appointment pain was 5.87±1.30 as presented in table ii. mean difference was 2.64±1.93. average score for intracanal medicament i.e ledermix on visual analog scale for pain was 3 as shown in table iii whereas average score was 6 or 7 for patients in which no intracanal medicament was placed as shown in table iii. according to independent sample t-testthe null hypothesis is rejected implicating that ledermix is effective in reducing pain in patients with acute apical periodontitis. c o m p a r i s o n o f m e a n d i ffe re n c e o f i nte r appointment pain between groups with respect to male and female was also calculated as shown in table iv. for males in whom ledermix intracanal medicament was used, the mean inter-appointment pain was 3.00±1.55 and in whom no intracanal medicament was used, the mean pain score was 5.67±1.44. in males, significant difference was not observed between groups (difference 2.67±1.85). comparison of ledermix paste and no intracanal medicament on inter appointment pain during rctjiimc 2021 vol. 16, no.3 157 for females, the mean inter-appointment pain for ledermix and no intracanal medicament was 3.35±1.56 and 6.07±1.16 respectively. in females' significant difference was not observed between groups (difference 2.72±1.95). independent sample t-test for gender for both no intracanal medicament as well as for medication (i.e., ledermix) are insignificant as p>0.05. for no intracanal medicament p=0.242 and for medication p=0.141. both the p values are greater> than 0.05 showing that the variable tested here i.e., gender is not significant. clinical researchers have shown that interappointment pain is not relieved nor it can be 13 prevented by the use of intracanal medicaments. patil et al, concluded in his study that interappointment dressing with calcium hydroxide does not relieve pain in all cases and therefore use of i n t r a c a n a l m e d i c a m e n t i s n o t a l w a y s 14 recommended. the results of study conducted by ehrmann et al., were similar to those with our study. in this study, patients in which ledermix dressing was used as intracanal medicament experienced significantly less 9.5±14.6 post operative pain than those patients in which no intracanal medicament 15 16.3±20.8 was placed at 48 hours. the frequency of interappointment pain was studied by same group of researchers. in this study three treatment modalities were used that included use of no intracanal medicament, calcium hydroxide and ledermix medicament. pain incidence was found to be 6.9% with ledermix while it was 12.3% with calcium hydroxide and it was 16.7% with no intracanal 16.17 medicament at 4 hours. negm reported in his study that in 85% of the cases pain was completely relieved after 1 hour whereas more than 93% of the 18 cases were pain free after 24 hours. in majority of patients when ledermix is placed in the root canal system reduction of pain occurs within an hour. the study conducted by schneider supports this results in which it is stated that when a steroid antibiotic combination such as ledermix is placed in the root canals, pain of the patient subsides before he even leaves the dental office. many studies have confirmed that ledermix is an effective intracanal medicament. it is perfect for use between the appointments and in root canal therapy. the intra canal use is not associated with any systemic side effects. it can be removed easily removed from the 19 canal as it is water soluble. in the current study no adverse effects were found with the use of ledermix paste as well. smith et al, has demonstrated that the periapical inflammation is significantly reduced by the preparation that contain corticosteroid following 20 the canal preparation. in contrast to this, seltzer strongly criticized the use of corticosteroids. in his study he has stated that the major drawback of using corticosteroids is their effect on inflammatory cells. he also stated that repair process is adversely 21 affected by the use corticosteroids. steroids are not table i: descriptive statistics of age and pain table ii: inter-appointment pain according to use of intracanal medicament table iii: average score on vas table iv: pain on visual analogue score for patients grouped on the basis of gender discussion placement of intracanal medicaments results in the reduction of microbial factors. it was concluded from the present study that pain associated with necrotic teeth having acute apical periodontitis in which ledermix dressing was placed experienced less pain as compared to those patients in which no intracanal medicament was placed after first 48hrs. contrary to our findings on the use of intracanal medicaments, in which mean pain score for ledermix (3.23±1.43) on vas was less in contrast to no intracanal medicament (5.87±1.30), number of comparison of ledermix paste and no intracanal medicament on inter appointment pain during rctjiimc 2021 vol. 16, no.3 158 widely used due to their immunosuppressive effects in endodontics. to prevent the potential invasion of bacteria, antibiotics should be added to the steroids 22 in topical formulations. both the components used in ledermix paste have the ability to diffuse through the cementum and dentinal tubules. in this way they reach the 11 periapical tissue as well as the periodontium. the demeclocycline component of the ledermix paste has the ability to diffuses through the dentine over a period of time. during the first few days, the concentration of demeclocycline is very high. it is high enough to inhibit most of the known bacteria causing endodontic infection in the dentine. 23 however its concentration decreases over time. the diffusion of corticosteroid component of ledermix paste (triamcinolone) is found to be much higher than the antibiotic component (demeclocycline). during the first 3-8 hours, the rate of diffusion of triamcinolone is highest with 30% of the 6 triamcinolone released during the first 24 hrs. it can be inferred from this that triamcinolone component of ledermix is effective in initial acute phase whereas the antibiotic component of ledermix i.e. demeclocycline provides antimicrobial substantivity. we observed that there is no significant difference between groups for gender. our results match with the findings of absi et al. they also observed that there was no association between patient's gender 24 and inter-appointment pain. contrary to our findings, study by nair et al., observed that there is greater incidence of inter-appointment pain in females as compared to males. levels of nor adrenaline and serotonin can be altered in females due to changes in female hormone levels during menstruation, use of oral contraceptives and hormone replacement therapy, therefore leading to 25 decreased pain threshold in females. limitations of the study our study was not multi-centered and was not double blinded. therefore, exceptional level of accuracy could not be achieved. more longitudinal studies need to be carried out or planned in order to evaluate the demerits and side effects of local application of the antibiotic as well as corticosteroid that might include development of bacterial resistant strains and suppression of immune cells. conclusion less inter-appointment pain was experienced by the patients in with ledermix was used as an intracanal medicament as compared to patients having no intracanal medicament (p=0.005) at 48 hours. hence, ledermix can be effectively used as an intracanal medicament to reduce inter-appointment pain for patients seeking endodontic treatment for acute periapical periodontitis in routine clinical settings. references 1. gomes bpfa, herrera dr.etiologic role of root canal infection in apical periodontitis and its relationship with clinical symptomatology.braz oral res. 2018 oct 18;32(suppl 1):e69. 2. azim aa,azim ka, abbott pv.prevalence of interappointment endodontic flare-ups and host-related factors.clin oral investig. 2017 apr;21(3):889-894. 3. nair m, rahul j, devadathana incidence of endodontic . flare-ups and its related factors: a retrospective study.j int soc prev community dent. 2017 jul-aug; 7(4): 175–179. 4. shikas.interappointment pain & flare up during endodontic treatment procedures: an update. international journal of applied dental sciences 2017; 3(4): 348-351. 5. onay eo, ungor m, yazici ac.the evaluation of endodontic flare-ups and their relationship to various risk factors. bmc oral health. 2015 nov 14;15(1):142. 6. kumar a, tamanna s, iftekhar h.intracanal medicaments – their use in modern endodontics: a narrative review. journal of oral research and review. 2019;11(2):94-99. 7. kim d, kim e.antimicrobial effect of calcium hydroxide as an intracanal medicament in root canal treatment: a literature review part ii. in vivo studies.restor dent endod. 2015 may;40(2):97-103. 8. riaz a1, maxood a1, abdullah s. comparison of frequency of post-obturation pain of single versus multiple visit root canal treatment of necrotic teeth with infected root canals. a randomized controlled trial.j pak med assoc. 2018 oct;68(10):1429-1433. 9. kundabala m, jagadishs, ramya s.efficacy of ledermix as a root canal medicament in symptomatic teeth: a clinical study. journal of interdisciplinary dentistry. 2014; 4(2): 8588. 10. attia da, farag am, afifi ik, darrag am. antimicrobial effect o f d i ffe re nt i nt ra ca n a l m e d i cat i o n s o n va r i o u s microorganisms. tanta dent j. 2015;12(1):41-7. 11. dall aq, jouhar r, ahmed n. comparison of interappointment pain between ledermix and no intracanal medicament in acute apical periodontitis. j liaquat med uni health sci.2011; 10:3. 12. segura-egea jj, gould k, şen bh.antibiotics in endodontics: a review.int endod j. 2017 dec;50(12):1169-1184. 13. quadir f, amin f, shahbaz u. comparison of intracanal medications for assessment of pain after root canal treatment. pakistan oral and dental journal. 2015;35(2): 286-289. comparison of ledermix paste and no intracanal medicament on inter appointment pain during rctjiimc 2021 vol. 16, no.3 159 14. patil aa, joshi sb, bhagwat sv.incidence of postoperative pain after single visit and two visit root canal therapy: a randomized controlled trial. j clin diagn res. 2016 may;10(5): zc09-12. 15. ehrmann eh, messer hh, adams gg. the relationship of intracanal medicaments to postoperative pain in endodontics. int endod j. 2003;36(12): 868-75. 16. ehrmann eh, messer hh, clark rm. flare ups in e n d o d o n t i c s a n d t h e i r re l a t i o n s h i p t o va r i o u s medicaments. austendod j. 2007;33(3): 119-30. 17. manohar mp1, sharma s.a survey of the knowledge, attitude, and awareness about the principal choice of intracanal medicaments among the general dental practitioners and nonendodontic specialists.indian j dent res. 2018 nov-dec;29(6):716-720. 18. negm mm. intracanal use of a corticosteroid-antibiotic compound for the management of post-treatment endodontic pain. oral surg oral med oral pathol oral radiolendod. 2001;92(4): 435-9. 19. bansal r, jain a overview on the current antibiotic . containing agents used in endodontics.n am j med sci. 2014 aug;6(8):351-8. 20. smith rg, patterson ss, el-kafrawy ah. histologic study of the effects of hydrocortisone on the apical periodontium of dogs. j endod. 1976;2(12): 376-80. 21. seltzer s, naidorf ij. flare-ups in endodontics: i. etiological factors. j endod 1985;11(11): 472–478. 22. sivakumar nr. steroids in root canal treatment.int j pharm pharm sci. 2014;6(3),17-19. 23. abbott pv, hume wr, heithersay gs. barriers to diffusion of ledermix paste in radicular dentine. endod dent traumatol. 1989;5(2): 98–104. 24. absi ma, niazi fh, naseem m. interappointment pain during root canal treatment by comparing the crowndown and apical step back techniques. j pak dent assoc 2014; 23(3):100-105. 25. nair m, rahul j, devadathan a.incidence of endodontic flare-ups and its related factors: a retrospective study. j int soc prev community dent. 2017 jul-aug;7(4):175-179. comparison of ledermix paste and no intracanal medicament on inter appointment pain during rctjiimc 2021 vol. 16, no.3 160 original�article abstract objective: to compare the effectiveness of sustained-stretch-mobilization against oscillatory-mobilization in the management of adhesive capsulitis. study design: it was randomized control trial. place and duration of study: the study was conducted at physiotherapy department of national institute of rehabilitation medicine islamabad from september 2015 to february 2016. materials and methods: thirty seven patients were included in the study and convenient sampling technique was used for randomization. nineteen patients were treated with sustained-stretch-mobilization technique and 18 patients were treated with oscillatory-mobilization. patients with the capsular pattern in frozen and thawing stage with apley's scratch test positive, age between 3060 were included in the study. patients with limited range of motion due to secondary cause i.e. followed by cervical spondylosis, rotator cuff tendinitis or trauma etc were excluded. pre-treatment and post-treatment values of range of motion, numeric pain rating scale and shoulder pain and disability index were analyzed by spss 21. results: both manual therapy techniques are equally effective for external rotation, internal rotation, numeric pain rating scale and shoulder pain disability index but abduction showed that oscillatory-mobilization was more effective. conclusion: sustained-stretch-mobilization and oscillatory-mobilization are equally effective for patients with adhesive capsulitis to relieve pain and restore range of motion. key words: adhesive capsulitis, oscillatory-mobilization, sustain-stretch-mobilization. years, and after the first has recovered. the nondominant shoulder is more likely to be affected. an increased prevalence of adhesive capsulitis was confirmed in female patients as well as those who 3 had a longer duration of diabetes mellitus. adhesive capsulitis of the shoulder is clinically described as having three phases: freezing or painful phase that usually lasts from 2 to 9 months, frozen or progressive stiffness phase that lasts for 10-36 weeks, thawing or resolution phase that typically lasts for 15-24 months in nonoperative cases. the symptoms may persist for as 4 long as 6-10 years from onset. adhesive capsulitis can be of two type's primary in which patients have symptoms but the etiology is unknown and secondary type in which symptoms are due to definite cause like after surgery, post traumatic, joint or soft tissues injuries. the pathology of adhesive capsulitis remains unclear. arthroscopy and open exploration of the capsule shows that the condition affects the glenohumeral capsular tissue and is particularly 5 localized to the coracohumeral ligament. sign and symptoms of adhesive capsulitis are pain which starts slowly and is felt at the insertion of the deltoid, inability to sleep on the affected side, little introduction adhesive capsulitis is a condition of unknown etiology affecting shoulder mobility and function including stiff and painful shoulder with decrease range of motion in every direction. duplay (1896) was first investigator who recognized this extra articular disorder and designated the clinical term 1 “scapulo-humeral periarthritis”. codman (1934) described the unknown etiology and termed this 2 condition as "frozen shoulder". later naviesar (1945) used the term “adhesive capsulitis. adhesive capsulitis is common among patients in sixth decade of life, and onset before the age of 40 is rare and more common in women than men. the uninvolved shoulder also becomes affected, usually within five comparison of manual therapy techniques in adhesive capsulitis 1 2 3 4 5 sumera amanat , abdul ghafoor sajjad , fareeha kausar , qamar mehmood , syed ali hussain correspondence: dr. abdul ghafoor sajjad assistant professor, rehabilitation sciences riphah college of rehabilitation sciences riphah international university, islamabad e-mail: abdul.gahfoor@riphah.edu.pk 1,3,4 department of clinical physical therapy national institute of rehabilitation medicine, islamabad 2,5 department of physical therapy and rehabilitation sciences riphah college of rehabilitation sciences riphah international university, islamabad funding source: nil; conflict of interest: nil received: jan 20, 2017; revised: apr 15, 2017 accepted: nov 4, 2017 sustained vs oscillatory mobilization in adhesive capsulitisjiimc 2017 vol. 12, no.4 173 local tenderness, restriction of both arom and prom in a specific capsular pattern with external rotation limited more than abduction and abduction more than internal rotation. radiographs are usually normal. many treatment modalities are used for this condition and the fundamental goal of treatment is 6 to restore and maintain function. treatment strategies include physical therapy, non-steroidal anti-inflammatory drugs, corticosteroid injections, suprascapular nerve block, manipulation under anesthesia, arthroscopy and open surgery, or combination of these modalities. in physical therapy pain is relieved by electrotherapy, hot pack and range of motion is gained by joint mobilization. there are different schools of thoughts about joint mobilization. systemic reviews done by matthew j page (2014) conclude that a combination of manual therapy and exercise are not so effective when compare with intra articular injections in short term relief. for long term result we need high-quality rcts to establish the benefits and harms of manual therapy and 7 exercise interventions that reflect actual practice. kaltenborn technique of manual therapy gives sustained glides in three grades (i, ii, iii).grade i and ii are used for pain management and grade iii is more effective in improving range of motion, choi w-sp et 8 al interpreted the effectiveness of kaltenborn mobilization by measuring the acromion-humeral distance (ahd) whereas inferior glide is applied in grade ii and grade iii to increase the abduction range of motion. results showed that grade iii mobilization was more effective in improving range of motion in maitland-mobilization oscillatory glides are given in five grades. grade i and ii of maitland mobilization techniques are primarily used for treating joints limited by pain. grades iii and iv are primarily used as stretching maneuvers. shrivastava ankit et al conducted a randomized control trail to compare the effe c t i ve n e s s o f m u l l i ga n a n d m a i t l a n d mobilization. results showed that extension improved more with mulligan technique while all other ranges showed equal improvement with both techniques. both techniques were also effective for 9 pain relief but mulligan gave slightly better result. adhesive capsulitis is challenging condition therefore it is difficult to decide which treatment technique is more effective. many treatment strategies are available now a days but the purpose of the current study was to compare the effectiveness of sustained-stretch-mobilization against oscillatory-mobilization in the management of adhesive capsulitis. materials and methods a randomized controlled trial was conducted at the department of physiotherapy, national institute of rehabilitation medicine islamabad from september 2015 to february 2016. the inclusion criteria of study were patient following the capsular pattern of adhesive capsulitis, frozen and thawing stage, apley's scratch test positive, age 3060 and 50% limited rom. all patients had restriction of movements in all directions. patients were excluded if they had adhesive capsulitis followed by cervical spondylosis, limited rom other than adhesive capsulitis and patients with rotator cuff tendinitis. thirty seven diagnosed adhesive capsulitis patients with age between 30 and 60 were taken. convenient sampling technique was used to collect the data. after the initial assessment, written informed consent forms were obtained from the participants who met the inclusion criteria. the selected subjects were randomly allocated to two different groups: kaltenborn mobilization group having 19 patients and maitland mobilization group having 18 patients. variables include numeric pain rating scale (nprs) for pain and shoulder pain and disability index (spadi) for functional outcome measurement and shoulder rom including external rotation, abduction and internal rotation. rom was measured by goniometer. after the assessment and the data collection, participants were given the therapeutic intervention according to their groups. st th patients were assessed at the 1 and the 10 visit. in order to compare the effects of two treatment techniques, patients are treated with mobilization and home exercise plan. glides given included anterior, posterior and caudal glides in grade iii with 10 seconds hold, 10 reps, and 3 sets 5 days a week in mid-range position for 10 days. before giving glides distraction with 10 seconds hold, 10 repetitions were given and scapular glides (superior, inferior and medial, lateral) were also included. maitland mobilization group (n=19) were treated with maitland mobilization and home exercise plan. jiimc 2017 vol. 12, no.4 174 sustained vs oscillatory mobilization in adhesive capsulitis this group received oscillatory glides at the rate 2oscillation per sec for 1 minute with 3 sets for 5 days a week. direction of glides was anterior, posterior and inferior. total numbers of sessions were 10. using spss 21 paired sample t-test was used to analyze within-group variables and independent sample t-test was done to analyze between-groups variables. results the mean age of the study participants was 50.65± 6.413. the onset of pain was gradual in 89.19% patients while 10.81% had sudden onset, 94.59% patients had diurnal variation of symptoms worsening at night. table no i shows the pre-treatment and posttreatment values of sustained mobilization group while that for the oscillatory-mobilization group is shown in the table no ii and both of which show significant differences. table no iii shows the comparison of abduction, internal rotation, external rotation, nprs and spadi mean values for both sustained mobilization group and oscillatory-mobilization group which shows statistically no significant difference except for abduction where oscillatory-mobilization is considered far better. discussion the result of current study shows that sustainedstretch-mobilization and oscillatory-mobilization are equally effective in terms of spadi, nprs, external rotation and internal rotation in patients with adhesive capsulitis except abduction which responds better to oscillatory-mobilization. in a previous review on adhesive capsulitis conducted about phases of adhesive capsulitis ( f re ez i n g , f roze n a n d t h a w i n g ) a n d t h e i r recommended treatment, it is concluded that pain reducing medications and steroid injections must be used in freezing phase and manual therapy along with exercise in frozen and thawing phases. in resistant cases which show no improvement other surgical treatments are recommended. in current study patients in frozen and thawing phases were divided into two groups and given different manual mobilization therapies and significant improvement 10 has been noticed. an rct done by shruti naik et al (2015) to compare the two different manual therapy techniques in adhesive capsulitis concluded that mdt and maitland mobilization were equally effective in reducing pain, improving the range of motion and also the functional scores in individuals with stage ii 11 adhesive capsulitis. in this study we also observe the improvement in both groups. a randomized multiple treatment trials were organized by jing-lan yang et al for the comparison of different mobilization techniques such as midrange mobilization, end-range mobilization, and mulligan's mobilization. results of the study showedthat end-range mobilization and mulligan mobilization were more effective than mid-range m o b i l i za t i o n . i n c u r r e n t s t u d y m i d ra n g e table i: pre-treatment and post-treatment mean and standard devia�on values for sustained mobiliza�on group with p values table ii: pre-treatment and post-treatment mean and standard devia�on values for oscillatory-mobiliza�on group with p values table iii: comparison of sustained-stretch-mobiliza�on and oscillatory-mobiliza�on groups jiimc 2017 vol. 12, no.4 175 sustained vs oscillatory mobilization in adhesive capsulitis mobilization was used in control group and significant improvement was observed in nprs 12 (p=.00). syed shakil-ur-rehman et al conducted an rct to m a ke a c o m p a r i s o n b e t w e e n k a l t e n b o r n mobilization and scapular mobilization in patients of adhesive capsulitis with abduction range of motion above 90o. the results of this study show that sustained-stretch-mobilization is more effective than scapular mobilization. in current study patients have been given sustained stretch glides and significant (p=.00) improvement was observed in 13 nprs and spadi scale. gokhan doner pet al conducted a study assessing the effe c t i ve n e s s o f m a i t l a n d m o b i l i zat i o n i n comparison to exercise. it is concluded that exercise with maitland mobilization is far better than exercise alone. in current study oscillatory-mobilization has been used and found significant improvements in 14 nprs (p=.00) and spadi (p=.00) has been observed. conclusion the result of current study concluded that both sustained-stretch-mobilization and oscillatorymobilization are equally effective. the spadi, nprs, external rotation and internal rotation responds better thanoscillatory-mobilization. references 1. depalma a. loss of scapulohumeral motion (frozen shoulder). annals of surgery. 1952; 135: 193-204. 2. bunker t. frozen shoulder: unravelling the enigma. annals of the royal college of surgeons of england. 1997; 79: 2103. 3. chiaia ta, hannafin ja. adhesive capsulitis. techniques in shoulder & elbow surgery. 2014; 15: 2-7. 4. pearsall aw, holovacs tf, speer kp. the intra-articular component of the subscapularistendon: anatomic and histological correlation in reference to surgical release in patients with frozenshouldersyndrome. arthroscopy: . the journal of arthroscopic & related surgery. 2000; 16: 23642. 5. hand g, athanasou n, matthews t, carr a. the pathology of frozen shoulder. bone & joint journal. 2007; 89: 928-32. 6. baltsezak s. sat0511 management of adhesive capsulitis with landmark guided high volume steroid injections in the community based musculoskeletal clinic. bmj publishing group ltd. 2016. 7. page m, green s, kramer s, johnston r, mcbain b, chau m, et al. manual therapy and exercise for adhesive capsulitis (frozen shoulder). 2014; 26: 11275. 8. choi ws, park jh, jung bj, moon ok, min ko, an hj. a study on shoulder joint motions in the caudal gliding of kaltenborn-evjenth concept®. journal of the korean society of radiology. 2012; 6: 427-33. 9. shrivastava a, shyam ak, sabnis s, sancheti p. randomised controlled study of mulligan's vs. maitland's mobilization technique in adhesive capsulitis of shoulder joint. indian j physiother occup ther int j. 2011; 5: 12-5. 10. schleip r, findley tw, chaitow l, huijing p. fascia: the tensional network of the human body-e-book: the science and clinical applications in manual and movement therapy: elsevier health sciences. 2013; 2: 199-201. 11. reddy bc, metgud sa. randomized controlled trial to investigate the effect of mulligan’s mwm and conventional therapy in stage ii adhesive capsulitis. indian journal of physical therapy. 2015; 3: 549-55. 12. yang jl, chang cw, chen sy, wang sf, lin jj. mobilization techniques in subjects with frozen shoulder syndrome: randomized multiple-treatment trial. physical therapy. 2007; 87: 130715. 13. rehman ss, danish kf, khan a, sheikh si, sibtain f. comparison between kaltenborn and general scapular mobilization in adhesive capsulitis patients. journal of rawalpindi medical college (jrmc). 2012; 16: 121-2. 14. doner g, guven z, atalay a, celiker r. evaluation of mulligan's technique for adhesive capsulitis of the shoulder. journal of rehabilitation medicine. 2013; 45: 87-91. jiimc 2017 vol. 12, no.4 176 sustained vs oscillatory mobilization in adhesive capsulitis page 13 page 14 page 15 page 16 original�article abstract objective: to determine the frequency of different operative morbidities among patients with previous one and previous two caesarean sections. study design: cross sectional study. place and duration of study: study was carried out in department of obstetrics and gynecology of nishtar th th hospital multan, from 13 january 2016 to 12 june 2016. materials and methods: three hundred and thirty-six women of reproductive age group having previous one or two cesarean sections undergoing emergency or elective cesarean section with gestational amenorrhea of >30 weeks were included. women with medical illness e.g. cardiac, hypertension, renal, diabetes, uterine anomalies e.g. sub septate or bicornuate uterus were excluded. in all these women, type of maternal morbidities was noted in term of presence or absence of thick intraoperative adhesions, extremely weakened lower uterine segment and wound dehiscence. results: age of women ranged between 18 to 45 years with 33.279± 5.33 years mean age. mainstream of the women were between 26 to 35 years. parity range of this study was from 1 4. mean gestational age was 37.122 ±1.48 weeks, while mean number of previous c section was 1.610±0.48. dense intraoperative adhesions found in 56.5%, extremely thinned out lower uterine part found in 23.5% and scar dehiscence was found in 13.7% of the total patients. when comparing outcomes in ladies with previous one and previous two cesarean sections, dense intraoperative adhesions was 23.7% versus 77.6% (p=0.000), extremely thinned out lower uterine segment was 31.3% versus 18.5% and scar dehiscence was 29% versus 3.9% respectively. conclusion: females with history of recurrent cesarean section have possibility of having several intraoperative morbidities, which could escalate the frequency of maternal illness and deaths. key words: cesarean section dense intraoperative adhesions scar dehiscence., , the fetus from mother in an effort to protect the fetus of a moribund woman but now a days it has 2 become another mode of delivery. since 1980s, worldwide rate of caesarean section has risen extensively in all developing and developed 3 countries. rendering to the world health organization (who) recommendations, nationwide rates of c-sections should not surpass 5 to 15 per 100 1,4 live births. the rate of cesarean deliveries recommended by the who has exceeded by various countries like india, brazil, usa , australia, china etc., 1 similarly it has also increased in pakistan. there are numerous indications of cesarean deliveries, but cesarean delivery due to previous cesarean sections is a main indication. the parallel rise in rate of cesarean section has caused scarred uterus in a number of patients and resulted in a gradual increase of maternal mortality and morbidity. though, the procedure is now more protected because of advancements in antibiotics, anesthesia technology and blood transfusion facilities but as compared to normal vaginal introduction caesarean section is the delivery of baby done by an operative incision made through the abdomen and 1 the uterus, in order to save maternal and fetal life. initially cesarean sections were executed to deliver operative morbidities among patients with previous caesarean sections 1 2 3 4 5 6 samia ghaffar , tabassum shaheen , bushra ghaffar , sunia ghaffar , hala haq , fatima khawar correspondence: dr. sunia ghaffar assistant professor pathology department of pathology hitec-ims dental college, taxila e-mail: sghaffar25@gmail.com 1 department of gynecology district head quarter hospital, vehari 2 department of gynecology nishtar hospital, multan 3 department of medicine basic health unit 55gb, jaranwala 4 department of pathology hitec-ims dental college, taxila 5 department of pathology fazaia medical college, islamabad 6 department of medicine district head quarter hospital, sargodha funding source: nil; conflict of interest: nil received: march 03, 2020; revised: november 04, 2020 accepted: november 19, 2020 operative morbidities with previous c/sectionsjiimc 2021 vol. 16, no.3 176 deliveries, cesarean section still have substantial 5 risks to the women. as compared to vaginal deliveries, a mother delivered by caesarean is at greater risk of injury and that risk rises with increased rate of surgical deliveries. though, several problems 6 are linked to emergency abdominal deliveries. there are numerous maternal health issues occurring due to repeated cesarean sections such as thinned out lower uterine segment , dense intraoperative adhesions, injury to neighboring structures, scar dehiscence, hemorrhage and 7 , 8 infections etc. to control life threatening hemorrhages, obstetrical hysterectomy has to be done as a last option which is usually caused by morbid adherence of placenta, placenta previa, , 9,10 uterine atony or rupture of uterus. the objective of this study was to determine the frequency of different operative morbidities among patients with previous one and previous two cesarean sections. materials and methods it was cross sectional study, carried out in the department of obstetrics and gynecology of nishtar hospital, multan th conducted from 13 january 2016 th to 12 june 2016. permission from ethical review board of cpsp was taken for the study. sample size n=336 calculated by who calculator. sample collection was done by non-probability consecutive sampling technique keeping 95% confidence level. all women of reproductive age group (18-45yrs) having previous one or two cesarean sections, women undergoing emergency or elective cesarean section and women with gestational amenorrhea of >30 weeks were included in the study. while women with medical illness e.g., cardiac, htn, renal, diabetes, women having uterine anomalies e.g., sub septate or bicornuate uterus, women having uterine scar other than cesarean section e.g., myomectomy and women having previous classical cesarean sections were not included in the study. history was taken from women involved in study using to structured questionnaire. conversant permission was taken from all the women. confidentiality of data maintained and was strictly used for research purpose. in all these women, types of maternal morbidities were noted in term of presence or absence of thick intraoperative adhesions, extremely thinned out lower uterine part, injury to neighboring structures, excessive hemorrhage, scar dehiscence or rupture and obstetrical hysterectomy and were noted in the performa. statistics analysis done by spss software version 20. frequencies and percentages were commuted for categorical statistics such as age groups, parity, dense intraoperative adhesions, enormously thinned out lower uterine segment, scar dehiscence. m e a n ± s t a n d a rd d e v i a t i o n d i s p e n s e d fo r quantitative variables like age, gestational age, and no. of previous cesarean sections. effect modifiers like age, no of previous cesareans and parity were controlled by stratification and effects of these were seen on outcome through chi-square test. p value ≤0.05 was deliberated significant. results the participant's age of the study ranged from 18 to 45 years with mean age 33.279± 5.33 years. majority of the women were in the age group of 26 to 35 years. while parity ranged from 1-4. mean gestational age was 37.122 ±1.48 weeks, while mean number of previous c section was 1.610±0.48. dense intraoperative adhesions were found in 56.5% of the patients. extremely thinned out lower uterine segment seen in 23.5% of the patients. scar dehiscence was found in 13.7% of the patients. association of dense intraoperative adhesions, lower uterine segments and scar dehiscence with age, parity and number of previous c/sections is shown in table i, ii and iii, respectively. table i: association of dense intraoperative adhesions with age, parity and previous sections operative morbidities with previous c/sectionsjiimc 2021 vol. 16, no.3 177 discussion our study shows that dense intraoperative adhesions and scar dehiscence is highly associated with age, parity, and previous c-sections. while the extremely thinned out lower uterine segment was found to be nonsignificant with age and parity but highly significant with multiple c sections. literature also shows strong association of the operative morbidities with age parity and increased number of caesarian sections. maternal morbidity escalates with increased number of abdominal deliveries. spontaneous vaginal deliveries have progressively decreased due to increased rate of cesarean deliveries especially in 6 industrial countries throughout the world. there are many maternal morbidities of repeat caesarean sections such as dense intraoperative adhesions, weakened out lower uterine segment, scar dehiscence and injury to neighboring 7, 8 structures. obstetrical hysterectomy is done as a last option to control critical hemorrhages that is generally caused by placenta previa, morbidly adherent placenta, uterine atony or uterine 9,10 rupture. however some studies found no significant variance in the risk of uterine rupture or dehiscence between those with more than one caesarean and the other group of previous one 11,12 caesarean. in our study dense intraoperative adhesions were seen in 56.5%, extremely thinned out lower uterine segment was found in 23.5% and scar dehiscence was found in 13.7% of the patients. frequency of dense adhesions were 23.7% in women with previous one cesarean while thinned out lower uterine segment were 15.6% in women with previous two cesarean. results of our study are also well-matched with a study conducted at liaqat university of medical & health sciences, sindh which showed 22.8% frequency of dense adhesions with previous one caesarean sections versus 35.5% in females with previous two caesareans, whereas frequency of thinned out lower uterus was 8.7% among women with previous one caesarean versus 7, 13 15.6% women with previous two caesareans. in our study we observed increased frequency of scar dehiscence in cases having previous 2 cesarean sections while in other studies, frequency of scar dehiscence and rupture of previous uterine scar increased with the increased no. of caesarean 1 4 , 1 5 sections. our study showed more dense adhesions in women with previous two cesareans in contrast to previous one caesarean. that was because record of prior surgeries was not available in majority of cases which also has a link with formation of adhesions. our study showed increase in risk of dense adhesion with subsequent cesarean sections. considerably more adhesions were observed in ladies having two surgical deliveries as compared to patients with one surgical delivery. various studies show different tolls of adhesions and their consequences. they are 14 16 17 reported to be 12% , 48% and 73%. . as compared to primary cesarean section, second cesarean takes more time duration and urinary bladder damages are considerably common in the e x i s t e n c e o f a d h e s i o n s a n d a t r e p e a t e d 6,18,19 cesareans. mothers with several abdominal deliveries are significantly liable to to have ruptured uterus, scar dehiscence, placental adherence and 6, 20 placenta previa. it is also found compatible with studies which suggested that a single c/section is sufficient in restricting the physiological stretching of lower uterus in succeeding gestations, so averting movement of placenta away to the upper uterine segment with consequences of enlarged numbers of table ii: association of scar dehiscence with age, parity and previous sections table iii: association of extremely thinned out lower uterine segment with age, parity and previous sections. operative morbidities with previous c/sectionsjiimc 2021 vol. 16, no.3 178 21,22 placenta previa with uterus having scars. it was a single centered study with small sample size within a limited time frame. so, it may not be applied on whole population. also record of previous surgeries related or unrelated to gynae/obs was not available in majority of cases which also has a link with formation of adhesions. this study shows increased frequency of operative morbidities with increasing caesarean sections in our regions, so it is necessary to keep our number of cesarean sections to a reasonable limit and vaginal birth should be preferred approach of delivery. however, a study with large sample size involving different ethnic backgrounds should be done. conclusion concluded that women with successive caesareans, age advancement and increasing parity are at danger of having numerous intraoperative morbidities. there are increased chances of development of abdominal adhesions, scar dehiscence and uterine rupture which may enhance the rate of maternal indisposition and death. references 1. 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;31(8):1058-69. 2. okabayashi k, ashrafian h, zacharakis e, hasegawa h, kitagawa y, athanasiou t, et al. adhesions after abdominal surgery: a systematic review of the incidence, distribution and severity. surg today. 2014;44(3):405-20. 3. ye j, betrán ap, guerrero vela m, souza jp, zhang j. searching for the optimal rate of medically necessary cesarean delivery. birth. 2014;41(3):237-44. 4. molina g, weiser tg, lipsitz sr, esquivel mm, uribe-leitz t, azad t, et al. relationship between cesarean delivery rate a n d m a t e r n a l a n d n e o n a t a l m o r t a l i t y. j a m a . 2015;314(21):2263-70. 5. jolly j, walker j, bhabra k. subsequent obstetric performance related to primary mode of delivery. bjog. 1999;106(3):227-32. 6. zia s, rafique m. intra-operative complications increase with successive number of cesarean sections: myth or fact? obstetrics & gynecology science. 2014;57(3):187-92. 7. khursheed f, sirichand p, jatoi n. intraoperative complications encountered in patients with repeat cesarean section. jlumhs. 2009;8(01):76. 8. somani ss, sudhir s, somani sg. a study of intra-operative maternal morbidity after repeating caesarean section. international journal of reproduction, contraception, obstetrics and gynecology. 2017;7(1):291-6. 9. shellhaas cs, gilbert s, landon mb, varner mw, leveno kj, hauth jc, et al. the frequency and complication rates of hysterectomy accompanying cesarean delivery. obstet gynecol. 2009;114(2 pt 1):224. 10. creanga aa, bateman bt, butwick aj, raleigh l, maeda a, kuklina e, et al. morbidity associated with cesarean delivery in the united states: is placenta accreta an increasingly i m p o r t a n t c o n t r i b u t o r ? a m j o b s t e t g y n e c o l . 2015;213(3):384. e1-. e11. 11. asakura h, myers sa. more than one previous cesarean delivery: a 5-year experience with 435 patients. obstet gynecol. 1995;85(6):924-9. 12. reif p, brezinka c, fischer t, husslein p, lang u, ramoni a, et al. labour and childbirth after previous caesarean section: recommendations of the austrian society of obstetrics and gynaecology (oeggg). geburtshilfe frauenheilkd. 2016;76(12):1279. 13. zafar b, shehzad f, naseem a, safdar ca. exteriorization or in-situ repair, comparison of options for uterine repair at cesarean delivery. pakistan armed forces medical journal. 2016(4):570. 14. weerawetwat w, buranawanich s, kanawong m. closure vs non-closure of the visceral and parietal peritoneum at cesarean delivery: 16 years study. journal-medical association of thailand. 2004;87(9):1007-11. 15. bamigboye aa, hofmeyr gj. closure versus non-closure of the peritoneum at caesarean section: short-and long-term outcomes. the cochrane database of systematic reviews. 2014(8):1. 16. bahmanyar er, boulvain m, irion o. 161 non-closure of the peritoneum during cesarean section: long-term follow-up of a randomized controlled trial. am j obstet gynecol. 2001;185(6):s125. 17. lyell dj, caughey ab, hu e, daniels k. peritoneal closure at primary cesarean delivery and adhesions. obstet gynecol. 2005;106(2):275-80. 18. ray nf, larsen jj, stillman rj, jacobs rj. economic impact of hospitalizations for lower abdominal adhesiolysis in the u n i t e d s t a t e s i n 1 9 8 8 . s u r g g y n e c o l o b s t e t . 1993;176(3):271-6. 19. cim n, elçi e, elçi gg, almalı n, yıldızhan r. are the skin scar characteristics and closure of the parietal peritoneum associated with pelvic adhesions? turkish journal of obstetrics and gynecology. 2018;15(1):28. 20. qublan hs, tahat y. multiple cesarean section. the impact on maternal and fetal outcome. saudi med j. 2006;27(2):210-4. 21. hendricks ms, chow y, bhagavath b, singh k. previous cesarean section and abortion as risk factors for developing placenta previa. j obstet gynaecol res. 1999;25(2):137-42. 22. mohamed i, ali qm, kamaleldin b. association of placenta previa with repeat cesarean section in sudan and saudi arabia2014-2015. journal of medical and dental science research. 2016;3(2):07-11. operative morbidities with previous c/sectionsjiimc 2021 vol. 16, no.3 179 original�article abstract objective: to compare the effects of silymarin and coffee on liver enzymes in acetaminophen-induced hepatotoxicity in rats. study design: experimental-randomized control study. place and duration of study: the research was conducted from october 2018 to october 2019 in pharmacology department at iimct in mutual collaboration with national institute of health (nih) islamabad. material and methods: at day 0 after initial blood sampling, acetaminophen (300 mg/kg) by intraperitoneal route was given to 30 rats to induce hepatotoxicity. these rats were further divided into three experimental groups on day 8. group 2 was a disease control group, silymarin (100mg/kg) was given to group 3 rats and group 4 rats were treated with coffee (200 mg/kg) through intragastric gavage for fourteen days. terminal blood sampling was done at day 21 through cardiac puncture for biochemical estimation on same day. mean± sem was calculated and analyzed through spss 20. p value less than 0.05 was considered statistically significant. results: our results showed major elevation (p<0.05) in alanine aminotransferase and aspartate aminotransferase levels in group 2 when compared to normal control -group. the rats treated with silymarin & coffee considerably (p <0.05) lowered biomarker enzymes in comparison to disease control group 2 respectively. conclusion: coffee lowers alt and ast levels as compared to silymarin in acetaminophen induced hepatotoxicity in rats. key words: acetaminophen, alanine transaminase, aspartate aminotransferases, coffee, silymarin. treating liver ailments, when administered chronically or sub-chronically have been found to 5,6 have adverse effects. therefore in recent years exploration of antioxidants of plant source and their hepatoprotective potential is being under solemn consideration. so that people may consume them because the use of natural medication and nutritional habits is appreciated by general public 7 usually. flavonoids are considered good antioxidant compounds generally due to their phenolic structures and inhibition of free radical mediated 8 processes. one of the flavonolignane extracted from milk thistle, “silymarin” has been utilized for the treatment of various liver disorders that portray functional impairment or degenerative necrosis. it is familiar for its antioxidant, anti-inflammatory and anti-fibrotic properties and exhibits protective effects in different liver issues. it acts as a free radical scavenger which consequently prevents lipid peroxidation and its related cell injury by stabilizing 9 the membrane. among the most commonly consumed beverages worldwide prepared from plants, coffee holds a significant position specifically nd among working people. it is the 2 most traded commodity in the world having lots of diversities in introduction liver injury has a diffused pathology and if not controlled effectively then may lead to fibrosis, 1,2 cirrhosis and hepatocellular carcinoma. there is high prevalence of all sorts of hepatitis in pakistan. also, pakistan has been named as “cirrhotic state” because both hbv and hcv are responsible for more than 75% of cirrhosis which further leads to 3,4 hepatocellular carcinoma. these all challenging diseases with high prevalence around the globe have less effective long term treatment which make 2 them financial burden and cause of death. steroids, vaccines, interferons, antiviral drugs and many other conventional drugs, which are usually used for hepato-protective effects of silymarin and coffee in rats 3 4 5 6 sidra mumal, akbar waheed, abdul azeem, hira waqas cheema, fakhra noureen, abeera zainab 1 2 correspondence: dr. sidra mumal department of pharmacology islamic international medical college riphah international university, islamabad e-mail: sidramumal2@gmail.com 1,2,3 4 5 department of pharmacology/anatomy /pathology / 6 biochemistry islamic international medical college riphah international university, islamabad funding source: nil; conflict of interest: nil received: november 19, 2019; revised: october 08, 2020 accepted: october 13, 2020 jiimc 2020 vol. 15, no.4 241 hepato-protective effects of silymarin & coffee types and ways of preparation from seeds. over the last period of years immediate development has been seen in the pakistan's beverage industry. there is growing market and prompt opening of different 10 coffee shops for the people to approach it easily. coffee is not only an aromatic flavored drink but is 7 also a rich source of dietary antioxidants. it is a multiplex mixture of varying compounds including caffeine (1, 3, 7trimethylxanthine) and up to 1000 described phytochemicals which help in combating 11 reactive oxygen species. epidemiological data over the last years shows the inverse relationship of 7 coffee and the risk of several liver diseases. large amount of chlorogenic acid present in coffee reduce the risk of glucose intolerance and non-alcoholic 12 fatty liver disease. redox equilibrium is restored as well as expression of pro-inflammatory cytokines is reduced. specifically nicotinic acid present in coffee is a potent anti-fibrotic agent while caffeine blocks tgf-b as well as suppression of dna synthesis and enhances apoptosis of hepatic stellate cell (hsc). all these processes account for hepatoprotection. thus it is proposed that two or more cups of coffee in a day protects the liver and ameliorates almost all liver 7,13,14,15 ailments. so the present study was performed to compare the efficacy between silymarin and coffee in terms of reversal of hepatic damage. material and methods this randomized-control trial done by balloting method was conducted at the pharmacology department with multidisciplinary -research -lab at iimct in mutual collaboration of animal -house in nih, islamabad from ctober 2018-oct 2019. accredited ethical review committee of the institute approved the research proposal before starting the study. research grade acetaminophen and silymarin were obtained from sigma aldrich. coffee beans were procured from al-fatah super store in centaurus mall, islamabad and sent to herbarium section of national agriculture research centre (narc) for identification and validation through proper taxonomic rules. coffee beans were then grinded, powdered and kept airtight in cool and dry place. the present study included forty adult healthy male albino rats weighing 300-350 grams with normal baseline liver function tests. exclusion criteria was female rats and abnormal liver function tests. rats were kept under controlled environment with temperature of 20-25 degree celsius and constant twelve hour dark and light cycle. no mortality or morbidity was observed during the whole period of experiment. division was done into four groups having ten rats in each cage. blood samples were drawn from two rats of every group at day 0 by intracardiac blood sampling method. group 1 was a control group which received normal diet and tap water. rats in other three groups were given acetaminophen 300 mg/kg injection through intraperitoneal route (just once at day 0) for the induction of hepatotoxicity. to assess the advancement of study, second blood sampling of th two rats from three groups was done on 8 day. after the confirmation, no treatment was given to group 2 (disease control) rats. rats in group 3 received 16 silymarin 100 mg/kg through intragastric gavage once daily and group 4 was treated with coffee once daily in the morning. preparation of coffee involved mixing of coffee powder in boiling water and then 17 filtering it on paper. 200mg/kg dose was given to the rats through gavage method. on day 21 after giving anesthesia with chloroform, blood samples from all the rats which were not in the fasting state, were drawn through cardiac puncture by 3 cc syringe. after clot formation, blood samples were 18 centrifuged at 3500 rpm for 5 min by bench top centrifuge. in tubes serum was separated for final biochemical estimation which was done on same day by using alt kit (merck) and ast kit (merck) on chemistry analyzer. mean± sem of all four groups was calculated and for comparison post-hoc tukey test was done. all this was analyzed statistically by using spss 20. p value less than 0.05 was chosen significant for the results obtained. results transaminase levels were increased significantly (p<0.05) in rats of group 2 (disease control) due to treatment with acetaminophen as compared to group a (normal control). results obtained in group 4 (coffee treated) showed significant reduction in serum biomarkers as compared to group 3 rats who were treated with silymarin. summary of results is as followed: discussion raised levels of transaminases i.e. alt and ast makes them important for diagnosis, confirmation as jiimc 2020 vol. 15, no.4 242 hepato-protective effects of silymarin & coffee well as for determining the extent of liver damage clinically and experimentally. the present study showed reduction in transaminase levels of group 3 and group 4 rats which were given silymarin and coffee. but coffee ameliorated the hepatic damage more significantly as compared to silymarin. in this study, single intraperitoneal injection of acetaminophen 300mg/kg is used to induce acute liver injury in rats of experimental groups (group 2 to group 4) which resulted in significant increase in serum alt and ast levels as compared to normal control group 1. and then group 2 is taken as disease control group. this study is supported by the study done by jersiah and colleagues who used 300 mg/kg dose of acetaminophen intraperitoneal injection in rats to cause the acute hepatotoxicity and increased 19 “alt” and “ast” levels in rats. 9 20 silymarin and coffee , both are derived from plants and each one has hepatoprotective activity owing to their antioxidant potential. special attention has been given to coffee in the present study as it is also commonly consumed beverage by 10 the people. comparison has been done with silymarin, a standard drug that is not something new for liver patients but its bad taste and low bioavailability are the limitations of its usage. according to results, reversal of hepatic damage in the rats was seen with the usage of silymarin 100mg/kg in group 3. the reversal is due to its membrane stabilizing activity which prevents leakage of intracellular enzymes. this is supported by the study of godswill j.udom who investigated the hepatoprotective properties of ethanol seed extract of citrus paradisi macfad (grape fruit) against 21 paracetamol-induced hepatotoxicity in wistar rats. our results of alt and ast of group 3 are also in concordance with the study of bektur and colleagues who studied the protective effects of s i l y m a r i n a ga i n s t a c e t a m i n o p h e n i n d u c e d 8 hepatotoxicity and nephrotoxicity in mice. significant difference in the means of biochemical parameters of group 4 (coffee 200mg/kg) as compared to the means of group 2 showed that coffee improved the signs of liver damage and s h o w e d r e v e r s a l o f i n f l a m m a t o r y s i g n s . hepatoprotective activity is due to the phenolic content in the coffee that prevents lipid peroxidation against free radicals. moreover caffeine and na block tgf-b and enhance apoptosis of hepatic 22 stellate cells. these results are in accordance with ibrahim halil bahcecioglu who studied serum marker levels and histopathology in pistacia terebinthus coffee protects against thioacetamide-induced liver injury in rats which showed the preventive effect 23 against experimental hepatotoxicity. jonathan arauz studied coffee consumption prevents fibrosis in a rat model that mimics secondary biliary cirrhosis in humans and concluded that increase in liver function tests was completely mitigated by coffee in 24 accordance with results of this research. federico salomone studied that coffee enhances the expression of chaperones and antioxidant proteins in rats with non-alcoholic fatty liver disease and concluded that there was a reduction in serum markers in the rats fed on high fat diet plus coffee to 25 healthy control levels. there was also a significant difference of results between group 3 and group 4 which showed that both agents used for the reversal of apap induced hepatotoxicity showed improvement in the biochemical parameters but coffee was better than silymarin in improving the lfts. table i: mean ± sem of alt and ast values among all groups *= sig value alt = alanine aminotransferase, ast= aspartate aminotransferase table ii: post -hoc -comparison of “alt” and “ast” b/w groups *= significant alt= alanine –amino -transferase, ast= aspartate –amino –transferase jiimc 2020 vol. 15, no.4 243 hepato-protective effects of silymarin & coffee conclusion silymarin and coffee individually ameliorate the hepatotoxic effects but coffee has more beneficial hepatoprotective effects than silymarin in acetaminophen induced hepatotoxicity in rats. for future, histopathology aspect can be explored .further, individual constituents of coffee can be explored for hepatoprotection. references 1. ali saber sarg n. the role of cymbopogon citratus extract in protecting the liver against injurious effect of dimethylnitrosamine in rats. int j clin dev anat. 2015;1(4):89. 2. furtado ks, prado mg, aguiar e silva ma, dias mc, rivelli dp, rodrigues mam, et al. coffee and caffeine protect against liver injury induced by thioacetamide in male wistar rats. basic clin pharmacol toxicol. 2012;111(5):339–47. 3. butt as. epidemiology of viral hepatitis and liver diseases in pakistan. euroasian j hepato-gastroenterology. 2015;5:43–8. 4. parkash o, hamid s. next big threat for pakistan hepatocellular carcinoma ( hcc ). 2016;66:735–9. 5. koh ph, mokhtar ram, iqbal m. antioxidant potential of cymbopogon citratus extract: alleviation of carbon tetrachloride-induced hepatic oxidative stress and toxicity. hum exp toxicol. 2012;31(1):81–91. 6. freitag af, cardia gfe, da rocha ba, aguiar rp, silva-comar fm de s, spironello ra, et al. hepatoprotective effect of silymarin ( silybum marianum ) on hepatotoxicity induced by acetaminophen in spontaneously hypertensive rats. evidence-based complement altern med. 2015;2015:1–8. 7. xiong f, guan ys. cautiously using natural medicine to treat l i v e r p r o b l e m s . w o r l d j g a s t r o e n t e r o l . 2017;23(19):3388–95. 8. bektur ne, sahin e, baycu c, unver g. protective effects of silymarin against acetaminophen-induced hepatotoxicity and nephrotoxicity in mice. toxicol ind health. 2013;32(4):589–600. 9. jalali sm, najafzadeh h, bahmei s. protective role of silymarin and d-penicillamine against lead-induced liver toxicity and oxidative stress. toxicol ind health. 2017;33(6):512–8. 10. manan a, shahid b, sultan a, ahmed ui. consumer demand for beverages in pakistan. cercet agron mold. 2017;50(2):109–20. 11. rybakowska im, milczarek r, slominska em, smolenski rt. effect of decaffeinated coffee on function and nucleotide metabolism in kidney. mol cell biochem. 2018;439:11–8. 12. katayama m, donai k, sakakibara h, ohtomo y, miyagawa m, kuroda k, et al. coffee consumption delays the hepatitis and suppresses the inflammation related gene expression in the long-evans cinnamon rat. clin nutr [internet]. 2014;33(2):302–10. 13. saleem m, latif a. multiple beneficial effects associated with coffee consumption on human liver. j hepatol gastrointest disord. 2017;03(02):1–7. 14. arauz j, ramos-tovar e, muriel p. coffee and the liver. liver pathophysiology: therapies and antioxidants. elsevier inc.; 2017. 675–685. 15. dranoff ja. coffee consumption and prevention of cirrhosis: in support of the caffeine hypothesis. gene expr. 2018;18(1):1–3. 16. das s. hepatoprotective activity of methanol extract of fenugreek seeds on rats. int j pharm sci res. 2014;5(4):1506–13. 17. arauz j, zarco n, hernández-aquino e, galicia-moreno m, favari l, segovia j, et al. coffee consumption prevents fibrosis in a rat model that mimics secondary biliary cirrhosis in humans. nutr res [internet]. 2017;40:65–74. 18. ebrahimi e, shirali s, talaei r. the protective effect of marigold hydroalcoholic extract in stz-induced diabetic rats: evaluation of cardiac and pancreatic biomarkers in the serum. j bot. 2016;2016:1–6. 19. jarsiah p, nosrati a, alizadeh a, hashemi-soteh mb. hepatotoxicity and alt/ast enzymes activities change in t h e r a p e u t i c a n d t o x i c d o s e s c o n s u m p t i o n o f acetaminophen in rats. int biol biomed j. 2017;3(3):118–24. 20. aleksandrova k, bamia c, drogan d, lagiou p, trichopoulou a, jenab m, et al. the association of coffee intake with liver cancer risk is mediated by biomarkers of inflammation and hepatocellular injury: data from the european prospective investigation into cancer and nutrition. am j clin nutr. 2015;102(6):1498–508. 21. udom gj, yemitan ok, umoh ee, mbagwu hoc, ukpe e, thomas ps. journal of herbal drug. 2018;8(4):219–25. 22. katayama m, donai k, sakakibara h, ohtomo y, miyagawa m, kuroda k, et al. coffee consumption delays the hepatitis and suppresses the inflammation related gene expression i n t h e l o n g e v a n s c i n n a m o n r a t . c l i n n u t r. 2014;33(2):302–10. 23. bahcecioglu ih ali., ispiroglu m, tuzcu m, orhan c, ulas m, demirel u, et al. pistacia terebinthus coffee protects against thioacetamide-induced liver injury in rats. acta medica (hradec kralove). 2015;58(2):56–61. 24. arauz j, zarco n, hernández-aquino e, galicia-moreno m, favari l, segovia j, et al. coffee consumption prevents fibrosis in a rat model that mimics secondary biliary cirrhosis in humans. nutr res. 2017;40:65–74. 25. salomone f, li volti g, vitaglione p, morisco f, fogliano v, zappalà a, et al. coffee enhances the expression of chaperones and antioxidant proteins in rats with n o n a l c o h o l i c f a t t y l i v e r d i s e a s e . tr a n s l r e s . 2014;163(6):593–602. jiimc 2020 vol. 15, no.4 244 hepato-protective effects of silymarin & coffee original�article abstract objective: to compare nebivolol versus metoprolol therapy in controlling heart rate and improvement in left ventricular ejection fraction in patients with congestive cardiac failure. study design: randomized controlled trial. place and duration of study: out-patient department of cardiology, pakistan institute of medical sciences st th (pims), islamabad from 1 march 2016 to 28 february 2017. materials and methods: a total of 262 cases were included. a detailed clinical examination, electrocardiography and echocardiography were done by blinded operators. randomization of patients into group a and group b via random number table was done. group a received nebivolol and group b received metoprolol tartrate for six months. patients of all age groups, of either gender or all socioeconomic strata, with the clinical diagnosis of cardiac failure were included in this study. decompensation of heart failure requiring hospitalization and bradycardia or atrioventricular blocks developing during the study was taken as a criterion for drop out. history of diabetes, hypertension, and smoking was recorded. left ventricular ejection fraction and heart rate were documented and compared amongst the two groups. chi square test was applied for comparison between qualitative variables while the independent samples t-test was used to compare quantitative variables between groups. analysis of data was done using spss version 21. a p-value of ≤ 0.05 was considered significant. results: our study population was 262 patients with a mean age of 49.25 + 31.74 years, range between 18 and 80 years. patients in group a, on nebivolol demonstrated a significant improvement in left ventricular ejection fraction (p=0.00031) and heart rate (p=0.00163) when compared to patients in group b, on metoprolol. conclusion: nebivolol was found to more effective in improving left ventricular ejection fraction and heart rate in patients with congestive cardiac failure. key words: congestive cardiac failure, heart rate, left ventricular ejection fraction, metoprolol, nebivolol. 1,2 or functional abnormality. in diastolic cardiac failure, more than 50% of the ejection fraction is preserved despite signs and symptoms of failure. diminished left ventricular ejection fraction (lvef) with clinical features is usually associated with 3,4 systolic cardiac dysfunction. tachycardia associated with cardiac failure carries a grim prognosis. an elevated heart rate serves as a trigger for the development of cardiac complications in various ailments including cardiac failure, myocardial infarction, and hypertension. patients with poorly controlled tachycardia have increased 5,6 cardiovascular morbidity and mortality. the risk of cardiac failure development in the general 7 population is 1 in 5 at the age of 40 years. data regarding the pattern and outcome of heart failure from developing countries is sparse. cardiac failure affected approximately 6.6 million population in america in 2010 with a total expenditure in introduction congestive cardiac failure (ccf) is a disease in which patients have breathlessness at rest or during exercise, easy fatiguability, or signs of fluid accumulation, which are associated with an objective dysfunction of the heart due to a structural comparison of nebivolol with metoprolol in controlling heart rate and improving left ventricular ejection fraction in patients with congestive cardiac failure 1 2 3 4 5 6 amjad ali shah , asma rauf , siyab ahmad , mahboob ur rehman , niaz ali , bilal ahmad correspondence: dr. siyab ahmad assistant professor department of pathology swat medical college, swat e-mail: siyabamc@gmail.com 1,6 5 department of cardiology/surgical saidu group of teaching hospital, swat 2 department of cardiology bilal hospital, rawalpindi 3 department of pathology swat medical college, swat 4 department of cardiology pakistan institute of medical sciences, islamabad received: october 09, 2020; revised: september 15, 2022 accepted: september 19, 2022h comparison of nebivolol with metoprolol in ccfjiimc 2022 vol. 17, no.3 181 healthcare services on the disorder of 34.4 billion 8 dollars. there are three types of receptors controlling cardiac functions: β & β adrenergic receptors produce a 1 2 positive chronotropic and inotropic effect as opposed to β adrenergic receptor producing a 3 negative inotropic effect via nitric oxide synthesis 9,10 pathway. in cardiac failure, β blockers have been recommended as the main treatment modality as it has both prognostic and symptomatic benefits. β blockers have been proven to be effective in decreasing the number of death and improving 11 morbidity. moreover, the β blockers which cause vasodilatation may be better in treating cardiac failure because it results in a decrease in after-load when compared to drugs of the same class that do 12 not have this function. nebivolol is on the latest β blockers developed and has a significant arteriolar dilatory effect. it lacks sympathomimetic activity and is a highly selective β -adrenergic blocker as 1 13 compared to other drugs in this class. this study was conducted to compare nebivolol versus metoprolol therapy in controlling heart rate and improvement in left ventricular ejection fraction in patients with congestive cardiac failure materials and methods this randomized controlled trial was conducted from th 1 march 2016 to 28 february 2017 at the outpatient cardiology department of pakistan institute of medical sciences (pims), islamabad. the sample size was calculated using the world health organization (who) sample size calculator using the formulae for hypothesis test for two population proportions (one-sided), keeping a level of significance of 22.1%, a power of the test of 80.5%, a population portion 1 of 26.4%, and a population proportion 2 of 35.7%, giving us a sample size of 131 14 patients in each group or 262 total patients. approval from the ethical committee of the hospital was obtained (letter no hec 2240, 05/05/2014). the study population included those patients who had congestive cardiac failure based on the clinical history and confirmed on echocardiography as having either systolic or diastolic dysfunction, having sinus rhythm. adults of 18 years or above and of both genders were included. the patients with comorbidities like asthma, chronic obstructive airway disease (copd), peripheral arterial disease, heart blocks, and acute decompensated cardiac failure were not included in the study. a detailed history was taken. history of diabetes, hypertension, and smoking were recorded. the new york heart association classification was used to stratify patients according to the severity of dyspnoea at the index visit and subsequently thereafter. clinical examination was done after five minutes of rest to record heart rate, and blood p r e s s u r e w a s r e c o r d e d u s i n g m e r c u r y sphygmomanometers. detailed echocardiography was done by a blinded operator. other medications being taken according to guideline-directed medical treatment (including angiotensin converting enzyme (ace) inhibitors, angiotensin receptor blockers, diuretics, digoxin, nitrates) by the patients were noted. left ventricular end-diastolic and end-systolic dimensions, volumes and ejection fraction were recorded with the mmode and simpson's method and a mean of three values was taken on echocardiography. diastolic function was recorded with echocardiography by measuring e and a mitral inflow waves with pulsed wave doppler. e prime was recorded with tissue doppler from the lateral mitral annulus. isovolumic relaxation time (ivrt) and deceleration times were recorded with doppler echocardiography. randomization was done, with the patients being sorted into two groups to get either metoprolol tartrate (group b) or nebivolol (group a) according to a random number table. the procedures were reconducted at one-, threeand six-months after drug administration by blinded operators. at each visit, an electrocardiogram (ecg) was performed to note the pr interval and history and physical examination was done. dose titration of β blockers was done at two weekly intervals keeping in view the symptoms, heart rate and pr interval with a target of 60 to 70 bpm. after entering data, analysis was done with spss software version 21.0. the categorical variables like gender, diabetes, hypertension, smoking, and efficacy were analysed as frequencies and percentages. the mean baseline lvef and heart rate values were compared with post-intervention values after 6 months using the independent samples t-test. independent sample t-test was also used to compare mean change in heart rate and lvef between two jiimc 2022 vol. 17, no.3 182 comparison of nebivolol with metoprolol in ccf groups. a p-value< .05 was considered significant. results a total of 262 patients were included in the study. the mean age of the patients was 49.25 ± 31.74 years that ranged from 18 to 80 years. most of the patients in group a i.e., 46 (35.2%) were aged between 61-70 years, while in group b, 35 (26.7%) were also in the same age group. a total of 78 (60%) of patients in group a were male, while this number was 73 (56%) in group b. patient distribution according to age group and the presence of risk factors is exhibited in table i. in group a, the mean and standard deviation of prelvef increase was increased to a greater degree in the nebivolol group as compared to metoprolol group. in group a, heart rate deceleration was more after the 6 months of nebivolol therapy than when compared with the metoprolol group with the same duration of therapy. heart rate deceleration was more in patients having ages less than 60 years in both groups. data for this variable is displayed in table ii. in group a, the average deceleration of heart rate table i: distribution of patients according to age and risk factors treatment lvef in our study was 45.23 ± 24.77% with a range of 20-70%. the mean and standard deviation of pre-treatment heart rate in our study was 50.13 ± 34.86 bpm with a range of 50-120 bpm, while in group b, the mean and standard deviation of pretreatment lvef in our study was 43.13 ±17.07% with a range of 24-62%. the mean and standard deviation of pre-treatment heart rate in our study was 85.10± 25.16 bpm with a range of 60-110 bpm. in group a, lvef increased after the 6 months nebivolol therapy in patients up to the age of 60 years while it decreased after the age of 60 years while in group b, lvef increased after 6 months metoprolol therapy in patients up to the age of 60 years while it is decreased after the age of 60 years. table ii: age-wise distribution of patients having according to lvef and heart rate was more in patients having diabetes, hypertension, and smokers, while in group b, the average deceleration of heart rate was more in smokers and those who had diabetes and hypertension. the data for these variables is displayed in table iii. in group a, the average improvement in lvef was more in hypertensive and diabetics, while in group b the average improvement in lvef was 9% in hypertensive. the average improvement of lvef was higher with nebivolol in each age group when jiimc 2022 vol. 17, no.3 183 comparison of nebivolol with metoprolol in ccf table iii: average heart rate improvement in patients having ccf in according to different risk factors. tolerability were noted at initiation and after 3 months of administration of nebivolol (2.5 and 5 mg, 15 n = 6) or placebo (n = 6). in 4 patients nebivolol was better tolerated resulting in improvement of dyspnoea. heart rate decreased while the maximum exercise duration and performance remained stable. lvef increased (ejection fraction 31.5 ± 10.11 to 42.0 15 ± 10.99%, p ≤ 0.01) after treatment with nebivolol. the left ventricular end-systolic diameter decreased in the nebivolol-group from 56.5 ± 9.40 to 50.2 ± 9.43 mm (p ≤ 0.02). this show that with nebivolol 15 treatment lvef may improve. the eneca (efficacy of nebivolol in the treatment of elderly patients with chronic heart failure as add-on therapy to ace inhibitors or angiotensin ii receptor blockers, diuretics, and/or digitalis) study showed that nebivolol treatment had markedly increased lvef in comparison to placebo in all subgroups of 14 population under study. in a double blinded randomized control study by shibata et al wherein they studied the benefits of nebivolol and compared it with placebo. it was inferred that the nebivolol group demonstrated a greater improvement despite the poor conditions like age, gender, ejection fraction, diabetes, or prior ischemic cardiac insult. moreover, it was shown that to prevent death and hospital admission, nebivolol should be continued 16 for 2 years. there are very few comparative studies in treating 17 cardiac failure with β-adrenergic blockers. in two small clinical trial where in nebivolol was compared with carvedilol in terms of exercise tolerance, both the drugs had beneficial effect in improving exercise tolerance after twelve months of treatment. conversely, in a trial by patrianakos et al, there was no difference in improvement in lvef and left 17 ventricular end systolic volume. both carvedilol and nebivolol had beneficial effect on exercise tolerance and neither drug had declined exercise tolerance at earlier assessment. the drawback of this study was its low power, more over patrianakos and colleagues conducted their study in patients with non-ischemic dilated cardiomyopathy so extrapolating it to other cardiac failure patient due ischemic disease is 18 inappropriate. in order to establish the benefit of one β blocker over the other in treatment of cardiac failure more head-to-head comparative studies should be done. moreover, these should be high compared to metoprolol. this data is displayed in table iv. table iv: average lvef (%) of patients having ccf in different risk factors. discussion in our study, the mean and standard deviation of lvef was 45.23 ± 24.77% with a range of 20-70%. the mean and standard deviation of heart rate in our study was 50.13 ± 34.86 bpm with a range of 50-120 bpm. there were 2 (0.8%) patients of the age range of 18-20 year, in whom the lvef decreased to 3% after the 6 months nebivolol therapy. a total of 9 (3.5%) patients belonged to the age range of 21-30 years and lvef increased in them to 06% after the 6 months nebivolol therapy. 19 (7.2%) patients of the age range of 31-40 years had an lvef increased to 04% after the 6 months nebivolol therapy, 42 (16%) patients of the age range of 41-50 years had an increase in lvef of 7% after the 6 months nebivolol therapy, while 72 (27.5%) patients of the age range of 51-60 years saw lvef increased to 5% after the 6 months nebivolol therapy. lastly, 64 (24.4%) patients of the age range of 61-70 years developed an lvef decrease of 9% after the 6 months nebivolol therapy. in a study brehm et al, the average improvement of cardiac rate was noted in 63% study population having ef of 13-39% in a double-blinded randomized controlled trial. exertion time, cardiac rate, lvef and jiimc 2022 vol. 17, no.3 184 comparison of nebivolol with metoprolol in ccf power studies before jumping to any concrete conclusions. furthermore, sim et al have noted that nebivolol is beneficial even in low doses, providing benefits at the roughly the same degree as higher 19 doses without the added risk of side effects. lastly, seleme et al noted that nebivolol was of great use in the management of hypertension that was comparable in its effectiveness to more established drug classes such as ace inhibitors and calcium 20 channel blockers. limitations our study was limited by the duration of follow-up i.e., up to six months: heart failure is a chronic condition and, the effects of nebivolol need to be observed for a longer duration against standard treatment, to determine whether short-term benefits translate into long-term ones. secondly, our study did not look at the side-effects of both studyarms in detail, which is another aspect that should be adequately reviewed before changing established clinical practices. lastly, this was a single-center study, with patients being drawn from ethnic groups, so the results may not be generalizable to the rest of the country. conclusion nebivolol was found to improve lvef and cardiac rate in this cohort of patients presenting with heart failure and further collective studies at a larger scale are required to establish its non-inferiority and subsequently, its superiority over other betablockers so that such prescribing may be inculcated into local and international practice guidelines. references 1. malik a, brito d, vaqar s, chahbra l. congestive heart failure. in: statpearls [internet]. treasure island (fl): statpearls publishing; 2022 jan-. available from: https://www.ncbi.nlm.nih.gov/books/nbk430873/. 2. hajouli s, ludhwani d. heart failure and ejection fraction. in: statpearls [internet]. treasure island (fl): statpearls p u b l i s h i n g ; 2 0 2 2 . a v a i l a b l e f r o m : https://www.ncbi.nlm.nih.gov/books/nbk553115/. 3. sarwar m, majeed sm, khan ma. types and frequency of cardiac arrhythmias in patients with heart failure. j pak armed forces med j 2014;1(1):s109-13. 4. sanhoury m, mohamed f, sadaka m, abdel-hay ma, sobhy m, elwany m. the impact of asymptomatic ventricular arrhythmias on the outcome of heart failure patients with reduced ejection fraction. egypt heart j. 2022 16;74(1):11. 5. khan ma, majeed sm, sarwar m. screening of high risk patients with mitral valve prolapse – role of heart rate variability. j islam int med coll. 2013;9(3):59-62. 6. zhao w, zhao j, rong j. pharmacological modulation of cardiac remodeling after myocardial infarction. oxid med cell longev. 2020 ;2020(1):8815349. 7. savarese g, lund lh. global public health burden of heart failure. card fail rev. 2017 apr;3(1):7-11 8. seemi s, iffat s, ahmed sana js. diagnostic accuracy of electrocardiography in diagnosis of left ventricular hypertrophy. j islam int med coll. 2014;9(3):63–8. 9. ali dc, naveed m, gordon a, majeed f, saeed m, ogbuke mi, et al. β-adrenergic receptor, an essential target in cardiovascular diseases. heart fail rev. 2020 ;25(2):343354. 10. raja gs, khan hf, siddiqui a. cardiac autonomic modulation in psychologically stressed subjects as reflected by heart rate variability. j islam int med coll. 2015;10(3):199–203. 11. silverman dn, de lavallaz jd, plante tb, infeld mm, goyal p, juraschek sp, et al. beta-blocker use in hypertension and heart failure (a secondary analysis of the systolic blood pressure intervention trial). am j cardiol. 2022 ;165(1):5864. 12. alvi aa, khan ma, ali w. control of oral anticoagulant therapy using inr in patients with artificial heart valves. j islam int med coll. 2014;9(2):3–6. 13. priyadarshni s, curry bh. nebivolol. in: statpearls [internet]. treasure island (fl): statpearls publishing; 2022. available from: https://www.ncbi.nlm.nih.gov/books/nbk551582/. 14. edes i, gasior z, wita k. effects of nebivolol on left ventricular function in elderly patients with chronic heart failure: results of the eneca study. eur j heart fail [internet]. 2005;7(4):631–9. 15. brehm br, wolf sc, gorner s, buck-muller n. effect of nebivolol on left ventricular function in patients with chronic heart failure : a pilot study. 2002;4(5):757–763. 16. shibata mc, flather md, wang d. systematic review of the impact of beta blockers on mortality and hospital admissions in heart failure. eur j heart fail [internet]. 2011;3(3):351–7. 17. veverka a. nebivolol in the treatment of chronic heart failure. 2017;3(5):647–54. 18. patrianakos ap, parthenakis fi, mavrakis he, diakakis gf, chlouverakis gi, vardas pe. comparative efficacy of nebivolol versus carvedilol on left ventricular function and exercise capacity in patients with nonischemic dilated cardiomyopathy. a 12-month study. am heart j. 2015;150(5):985-985. 19. sim ds, hyun dy, jeong mh, kim hs, chang k, choi dj, et al. effect of low-dose nebivolol in patients with acute myocardial infarction: a multi-center observational study. chonnam med j. 2020 ;56(1):55-61. 20. seleme vb, marques gl, mendes ae, rotta i, pereira m, júnior el, et al. nebivolol for the treatment of essential systemic arterial hypertension: a systematic review and meta-analysis. am j cardiovasc drugs. 2021;21(2):165-180. jiimc 2022 vol. 17, no.3 185 comparison of nebivolol with metoprolol in ccf conflict of interest authors declared no conflicts of interest. grant support and financial disclosure authors have declared no specific grant for this research from any funding agency in public, commercial or nonprofit sector. data sharing statment the data that support the findings of this study are available from the corresponding author upon request. this is an open access article distributed under the terms of the creative commons attributionnoncommercial 2.0 generic license. jiimc 2022 vol. 17, no.3 186 comparison of nebivolol with metoprolol in ccf untitled-1 1 editorial medical documentationan ignored aspect in patient care ishtiaq ahmed correspondence: prof dr. ishtiaq ahmed consultant & hod, surgery al-nafees medical college & hospital, islamabad e-mail: surgish2000@yahoo.com received: feb 19, 2018; accepted: feb 22, 2018 the medical record is the wellspring of data for countless decisions regarding patient care from doctors, paramedical and administrative staff. even though, during recent years the ancillary activities like audit, research, legal etc which depend on the medical record have received most of the attention. the most frequent problem encountered by administrative and medical authorities is probably as old as the concept of the medical records itself i.e. its completion in time and in accurate manner. an inaccurate or incomplete medical record reflects that the patient care was incomplete. medical record which contains gaps depicts poor clinical care, demonstrate non-compliance with institutional policies and can be used to support allegations of negligence or fraud. moreover, an incomplete patients clinical documentation can leads to legal actions, can results in loosing job, contribute to imprecise quality and care information, leading to lost revenue/reimbursement to institution or physician, inappropriate billing and leading to charges of fraud. in addition, incomplete or improper documentation interfere with research, data analysis, patient-related studies and most likely compromises 1,2 safe patient care. that's why every health care provider institution should ensure timely, precise and complete clinical documentation of all patients at any cost. keeping in view all this, the proper documentation has become an integral part of patient management and it has evolved into a science of itself. this is the only mode for clinician to prove that a proper treatment was carried out. there is a strong consensus that properly maintained medical record is of immense help in the scientific evaluation and analysis in patient management issues. its s i g n i f i c a n c e f o r c l i n i c i a n s a n d m e d i c a l establishments is for three important reasons. firstly, it will help them in the scientific evaluation of patient's profile, treatment outcome analysis, and in planning the treatment protocols. secondly, it is also helpful in planning institutional or governmental strategies for future medical care. in addition, it is also used to inquire the issue of alleged medical negligence during treatment because the legal system relies mainly on documentary evidence. in these scenarios, the documentation is the most important evidence which decide the sentencing or 2,3,4,5 acquittal of the doctor. it is disheartening to observe that in spite of knowing the significance of proper medical record keeping, this matter is still in a nascent phase in our country. it is wise to remember that “poor records mean poor 3 defense, no records mean no defense”. abernethy et al after reviewing the documents has observed that insufficient data availability has hindered the quality assessment. of the all eligible patients for analysis, only 12.22% patients can be included in the full analysis. they observed that the sex was un identified in 17%, missing data on race or ethnicity in 26%, confirmed diagnosis in 86%, only 38% provided tnm stage, missing histo-pathology in 34% and up to 10% of records did not revealed dates of administration of chemotherapy to the patients. after switching to electronic medical record keeping the reporting has improved significantly but documentation problems persisted. overall, they concluded that the records containing data sufficient to evaluate conformance to the colorectal cancer 6 metrics, conformance was low as 50% to 70%. medical records comprises of a variety of information's from patient's history, clinical findings, investigations, treatment planned, pre and postoperative care, operation notes, daily progress notes of a patient, diagnosis, discharge summary and follow up plan etc which can be used for varied evaluations. for example, in case of a surgery, a properly obtained consent will go a long way in proving that the surgical procedures were carried out with the patient's concurrence. similarly, meticulous or properly endorsed operation notes can protect a surgeon in case of alleged negligence claims. it needs to be the concerted effort of all department of surgery alnafees medical college & hospital, islamabad 2 jiimc 2018 vol. 13, no.1 members of team who are involved in patient care in keeping the proper medical record. in this regard, the doctor is the prime person to oversee this documentation process and is primarily responsible for patient's histor y, clinical examination, investigation plan, treatment prescribed, operation details, consent forms, referral notes, discharge summary and medical certificates. other than this, proper recording of nursing care, laboratory data, diagnostic evaluations reports, record of pharmacy and billing processes is also crucial which needs to be maintained by paramedical or administrative staff. in order to maintain proper hospital record, doctor, paramedical and nursing staff should be trained 2 properly. the medical facilities in pakistan range from smaller clinics to large hospitals and from private sector to public sector medical facilities. proper medical record keeping is a separate and specialized domain in some of the public sector, teaching and corporate hospitals of urban setup which are having dedicated medical records officers capable of handling these documents. however, it is yet to develop into a proper record keeping process in majority of hospitals and clinics that provide medical facilities to a large section of the people in pakistan. to conclude, when documentation is complete and accurate in all domains, it works wonders at telling a patient's story and can even improve patient care. to achieve this, the documentation in the medical record needs to be complete and accurate to facilitate effective continuum of care.” references 1. po o r d o c u m e n t a t i o n : t h e c o n s e q u e n c e s . s t a f f development weekly: insight on evidence-based practice i n e d u c a t i o n , j a n u a r y 3 1 , 2 0 0 8 . w e b s i t e : [ www.hcprofessor.com]. 2. schaeffer j. poor documentation: why it happens and how to fix it. for the record . 2016; 28: 12-6. 3. thomas j. medical records and issues in negligence. indian j urol. 2009; 25: 384–8. 4. griffiths p, debbage s, smith a. a comprehensive audit of nursing record keeping practice. br j nurs. 2007; 16: 132427. 5. prideaux a. issues in nursing documentation and recordkeeping practice. br j nurs. 2011; 20: 1450-4. 6. abernethy ap, herndon je, wheeler jl, rowe k, marcello j, patwardhan m. poor documentation prevents adequate assessment of quality metrics in colorectal cancer. j oncology practice. 2017; 12: 234-9. page 6 page 7 original�article abstract objective: to determine the seroprevalence of dengue virus infection by detecting igg antibodies in a tertiary care hospital in rawalpindi. study design: cross sectional study. place and duration of study: virology department, armed forces institute of pathology rawalpindi, july 2021 to december 2021. materials and methods: a total of one hundred and fifty healthy general population of rawalpindi aged 15 – 45 years were included in this study. enzyme linked immunosorbent assay (elisa) was performed for the detection of dengue immunoglobulin g (igg) antibody in serum samples of patients. statistical package for social sciences (spss) version 25 was used to analyze the data. results: among 150 patients, 71 (47.3%) were males and 79 (52.7%) were females. out of total patients, 50 (33.3%) were positive and 100 (67.7%) were negative for dengue igg antibodies. majority of dengue igg positive patients were 25-40 years of age. acute febrile illness was present among 37 (24.6%) patients and was absent in 113 (75.3%) patients. participants provided history of presence of waste points and stagnant water in surrounding areas of 84 (56%) patients. conclusion: this study shows that there was a high exposure of dengue virus in rawalpindi population. this can be problematic from public health point of view in future as sensitized population against dengue virus is more prone to dengue fever and serious effects of dengue virus reinfection. key words: dengue fever, dengue virus, enzyme linked immunosorbent assay, immunoglobulin g, seroprevalence. 350,000 people have been admitted to hospitals across asia since 1956, with nearly 12000 reported 5 deaths. after 2006, epidemics of dengue occurred each year which has increased populations of infected people with this virus in different cities of pakistan. in upcoming years, it is expected to become 6 a health concern in asia including pakistan. df spreads by mosquitos mainly in tropical and sub tropical regions because of its peri-domestic breeding. dengue virus is caused by the aedes aegypti, which also causes yellow fever. the growth and reproduction of this vector is associated with freshwater reservoirs. international travelers were one of the main facilitators in the global spread of 7 this disease. dengue cases have increased up to 30 folds in past 50 years and approximately half of the world's population in over 100 countries is affected by this disease. the first confirmed and reported cases of dengue fever took place in asia, north america, and africa consecutively in 1779-1780. according to who, an expected 1.3 billion number of cases df 8 were reported between 1996 to 2005. global travel was mainly responsible for rapid spread of this introduction dengue fever (df) is a significant public health issue worldwide, affecting millions of individuals annually 1 including pakistan. in pakistan last major outbreak occurred in 2019, resulting in 53000 cases and 95 1 reported deaths. outbreaks of df in rawalpindi 2 region became more frequent after 2011 outbreak. the world health organization (who) classified df in 1997 and revision of this classification was done in 2009 to make it more inclusive. df was divided into three categories in 1997 as df, undifferentiated 3 fever, and dengue hemorrhagic fever (dhf). dengue was categorized later in 2009 as with warning signs or without warning signs and severe dengue. fever and at least two clinical symptoms or any warning 4 signs are required for dengue diagnosis. more than seroprevalence of dengue virus by detection of igg antibodies: a tertiary care hospital study in rawalpindi muhammad ali rathore, memoona arif, eijaz ghani, saifullah khan niazi, faraz ahmed, hammad hussain correspondence: dr. faraz ahmed registrar department of virology armed forces institute of pathology, rawalpindi e-mail: farazahmed88@live.com department of virology armed forces institute of pathology, rawalpindi received: january 18, 2023; revised: may 01, 2023 accepted: may 15, 2023 jiimc 2023 vol. 18, no. 2 seroprevalence of dengue virus 116 https://doi.org/10.57234/jiimc.june23.1644 disease. the total number of cases of dengue virus infection according to who gradually increased from 505,430 in 2000 to more than 2.4 million in 2010 and 5.2 million in 2019. this increase occurred during the previous 20 years and 960 fewer deaths were 9 reported in 2000 as compared to 4032 in 2015. the basis for the laboratory diagnosis of dengue infection is by detection of glycoprotein dengue ns1 antigen, dengue anti-igm, anti-igg, and polymerase chain reaction (pcr) for the detection of denv. the production of antibody against denv infection depends on the immune status of the host. patients with early-stage dengue infection have significant amounts of the nonstructural protein (ns1) in their sera, and this presence is persistent from day 1 to day 9 after the onset of symptoms. in cases of dengue infection, igm may become detectable on days 4–5 of illness and last for 12 weeks, but igg develops by day 14 and may last a lifetime. the igg rises within 1 to 2 days following the development of symptoms in secondary dengue infection, along with the igm 10 antibodies. the four denv serotypes are 1, 2, 3, and 4. secondary infection caused by another serotype leads to increased chances of severe dengue due to antibody dependent enhancement. several studies have been conducted on dengue virus seroprevalence globally and locally, there is still a lack of data on the prevalence of the virus in the rawalpindi region of pakistan. this article aims to fill this research gap by conducting a study on the seroprevalence of dengue virus by detection of igg antibodies in a tertiary care hospital in rawalpindi. therefore, this study was conducted to establish the exposure of rawalpindi population to previous dengue infection by detecting igg. previous exposure of dengue infection determines the seroprevalence and burden of the disease. individual with positive igg is more vulnerable for severe dengue reinfection due to antibody dependent enhancement. reinfection with dengue should be prevented by prompt management. materials and methods this cross-sectional study was carried out in the virology department of the armed forces institute of pathology rawalpindi, rawalpindi, from july 2021 to december 2021. approval from institutional review board (irb) (bs ahs/vir-2/read-irb/21/625) was jiimc 2023 vol. 18, no. 2 seroprevalence of dengue virus taken. the sampling technique was non-probability consecutive sampling. sample size was calculated by confidence interval of 95%, a margin of error of 5%, and a reported prevalence of dengue igg of 18% 11 from a prior local study of pakistan. the sample size of 150 was estimated by the who sample size calculator. patients of either gender, aged between 15 to 45 years and resident of rawalpindi were included in this study. patients with autoimmune diseases, acute febrile illness or those who were not willing were excluded. patients were informed about the study's purpose and written consent was taken. the demographics information of the participants included age, gender, and history of febrile illness during last one-year, previous history of dengue virus infection and environmental surroundings such as presence of waste points and stagnant water were recorded. participants were selected from general population of rawalpindi. blood specimen of participants was drawn at armed forces institute of pathology, rawalpindi and was transported to virology department. specimen was centrifuged at 3500 rpm for 4 minutes to separate serum. indirect manual elisa with dengue elisa igg kit of vircell spain was used for the detection of igg antibody against dengue virus and optical density 12 was analyzed by elisa plate reader. the statistical package for the social sciences (spss) version 25.00 was used to analyze the data. for co nt i n u o u s va r i a b l e s , m e a n a n d s d we re determined. categorical variables were calculated by using frequency and percentages. p-value of ≤ 0.05 considered statistically significant. results among total 150 patients, 71 (47.3%) were males and 79 (52.7%) females. dengue igg antibodies were detected in 50 (33.3%) patients. patients of different age groups showed positive seroprevalence, however middle age group showed higher frequency of dengue igg detection as shown in figure 1. age group (26-35 years) showed the highest prevalence of 25 (59.5%) cases whereas age group (15-25 years) showed the least prevalence of 10 cases (37%). about 37 (24.7%) patients had a history of acute febrile illness during the last 1 year, whereas 113 (75.3%) had no such history. the presence of waste points and stagnant water within 400 meters among 117https://doi.org/10.57234/jiimc.june23.1644 seropositive individuals was observed in 84 (56%). positive for ns1, 11.3% were positive for dengue igm, and 4.9% cases were positive for dengue igg. this study shows low seroprevalence of dengue igg in comparison with our study. a study was conducted by eshetu d et al in 2016, in ethiopia on dengue seropositivity and related risk 14 factors. in this study, risk factors associated with prevalence of denv were evaluated. a total of 529 samples of patients having acute febrile illness were taken in 2016 and tested for dengue igg and igm antibodies. the prevalence of igg and igm antibody was 25.1% and 8.1% respectively which is lower in comparison with our study. overall, people of age group 15-35 years accounted for 47.45 % of cases whereas 19.86% of cases were seen in age group 3145 years. this showed that age group of young adults was more frequently infected by this virus as compared to other age groups. a study conducted in multan, pakistan by mukhtar et al, shows that out of 689 dengue suspected cases, 54.1% were positive for dengue igg (27.6%) and igm (54.7%). these results show high seroprevalence of 15 dengue infection in comparison with our study. a study conducted in lahore, found that seroprevalence of dengue igg was 55.8% in the general population. this study also found that the prevalence was higher in males 62.2% than in f e m a l e s 4 9 . 3 % . t h i s s t u d y s h o w s h i g h seroprevalence of dengue igg in comparison with 16 our study. in a study conducted in the district of mardan in khyber pakhtunkhwa in 2017, a total number of 1978 patients were studied who were infected with 17 denv. a total of 302 were positive (208 males and 94 females) for antibodies against denv. number of cases of dengue virus infection was higher in males 10.5% than in females 4.75%. the low prevalence in comparison with our study was found in this study of igg and igm antibodies was 23.84% and 53.9% respectively. the maximum amount of positivity of 47 % was in patients of age group 15 to 35 years. there has been a variation in seroprevalence of dengue among different age groups and gender in 18 previous studies. dengue viral infection prevalence is not similar but is different in various cities across 19 pakistan. our study showed that a considerable proportion of population of rawalpindi might be exposed to denv in the past which was detected by fig. 1: igg seropositivity in relation with different age groups discussion dengue fever is a major public health concern worldwide, and seroprevalence studies are essential in understanding the spread and impact of the diseases. pakistan is one the countries with highest incidence of dengue fever according to who. our study determined seroprevalence of dengue igg in rawalpindi. dengue seroprevalence determine the percentage of individuals in population who have been infected with a dengue virus. in our study, 150 samples were collected to determine the seroprevalence of dengue virus. there were 47.3% males and 52.7% females. the igg antibody was detected using enzyme linked immunosorbent assay. dengue igg antibody was found in 33.3% patients. according to our results, out of 50 positive samples, 35.2% were males and 31.6% were females. this showed that prevalence of infection among males was approximately equal to females. age group (26-35 years) showed the highest prevalence and 59.5% were positive for igg antibodies against dengue virus. the age group (1525 year) showed the least prevalence of 37%. in majority of cases waste points and stagnant water was present near the homes of people which also indicate to the problem of df in urban and semi urban regions. these waste and stagnant water help in the propagation of mosquitoes which in turn help in spreading denv. a study was conducted by jyothi 13 et al in india. five hundred and twenty serum samples were collected from clinically suspected dengue fever cases. a total of 11.9 % of the total tested serum samples were positive for one or more of the three serological markers (ns1, igm, and igg). among 62 positive serum samples, 62.9% were jiimc 2023 vol. 18, no. 2 seroprevalence of dengue virus 118 https://doi.org/10.57234/jiimc.june23.1644 igg antibodies. the population is especially at risk in future but to an outbreak by a different serotype of denv. it is crucial to carry out extensive seroprevalence studies to ascertain the true scale of the issue. timely identification can aid in reducing the morbidity and mortality rates. neglecting the matter could result in significant dengue-related complications. limitations the study was based on single center data in virology department of the armed forces institute of pathology rawalpindi. sample size was small, and the duration of study was short which could have affected the results. conclusion in this study it is concluded that there is a high exposure of denv in rawalpindi population. this can be problematic from public health point of view in future as sensitized population against dengue virus is more prone to serious effects of dengue virus reinfection with a different serotype. recommendations both large-scale epidemiological studies and vector control initiatives are urgently required. it is a concerning scenario, and if it is not handled by taking precautions, dengue will probably become a much bigger health issue in the years to come. references 1. ali l, gul z, ijaz a, khalid n, zeb f, afzal s, et al. an overview of dengue viral infection circulating in pakistan. j vector borne dis 2022; 59:109-14. 2. hussain ab, muhammad ali rathore ma, khan fa. seasonal and demographic aspects of dengue outbreak of 2012 in northern pakistan. pakistan journal of pathology 2011;22(3):112-117 3. world health organization. dengue hemorrhagic fever: diagnosis, treatment, prevention and control, 2nd edition. who, geneva 1997. http://apps.who.int/iris/bitstream/ 10665/41988/1/9241545003_eng.pdf 4. world health organization. dengue: guidelines for diagnosis, treatment, prevention and control, new edition. who: geneva 2009. http://www.who.int/tdr/publications/ documents/dengue-diagnosis.pdf?ua=1. 5. gubler dj. dengue and dengue hemorrhagic fever: its history and resurgence as a global public health problem. in: gubler dj, kuno g, editors. dengue and dengue hemorrhagic fever. oxford: cab international; 1997. p. 122. 6. 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 jun 15;18(1):745. doi: 10.1186/s12889-018-5676-2. pmid: 29907109; pmcid: pmc6003098. 7. liebig j, jansen c, paini d, gardner l, jurdak r. a global model for predicting the arrival of imported dengue i n f e c t i o n s . p l o s o n e 2 0 1 9 ; 1 4 ( 1 2 ) : e 0 2 2 5 1 9 3 . https://doi.org/10.1371/journal.pone.0225193. 8. zeng z, zhan j, chen l, chen h, cheng s. global, regional, and national dengue burden from 1990 to 2017: a systematic analysis based on the global burden of disease study 2017. e clinical medicine. 2021 jan 6; 32:100712. doi: 10.1016/j.eclinm.2020.100712. 9. world health organization. dengue and severe dengue. h t t p s : / / w w w . w h o . i n t / n e w s r o o m / f a c t sheets/detail/dengue-and-severe-dengue 10. raafat n, blacksell sd, maude rj. a review of dengue diagnostics 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southern ethiopia. bmc infectious diseases. 2020 aug 31;20(1). 15. mukhtar, m.u., mukhtar, m. and iqbal, n. (2018), dengue fever is an emerging public health concern in the city of multan, pakistan: its seroprevalence and associated risk factors. microbiol immunol, 62: 729-731. 16. mahmood, shahid, et al. “seroprevalence of dengue igg antibodies among healthy adult population in lahore, pakistan.” international scholarly research notices, hindawi, 12 sept. 2013, 17. anwar f, ahmad s,haroon m, haq iu,khan hu, khan j et al. dengue virus epidemics: a recent report of 2017 from district mardan, khyber pakhtunkhwa province, pakistan. international journal of mosquito research 2019; 6(1): 4649. 18. prattay kmr, sarkar mr, shafiullah azm, islam ms, raihan sz, sharmin n. a retrospective study on the sociodemographic factors and clinical parameters of dengue disease and their effects on the clinical course and recovery of the patients in a tertiary care hospital of bangladesh. ngondi jm, editor. plos neglected tropical diseases. 2022 apr 4;16(4):e0010297. 19. khan j, adil m, wang g, tsheten t, zhang d, pan w, et al. a jiimc 2023 vol. 18, no. 2 seroprevalence of dengue virus 119https://doi.org/10.57234/jiimc.june23.1644 cross-sectional study to assess the epidemiological situation and associated risk factors of dengue fever, knowledge, attitudes, and practices about dengue prevention in khyber pakhtunkhwa province, pakistan. frontiers in public health. 2022 jul 29;10. conflict of interest authors declared no conflicts of interest. grant support and financial disclosure authors have declared no specific grant for this research from any funding agency in public, commercial or nonprofit sector. data sharing statment the data that support the findings of this study are available from the corresponding author upon request. this is an open access article distributed under the terms of the creative commons attributionnoncommercial 2.0 generic license. jiimc 2023 vol. 18, no. 2 seroprevalence of dengue virus 120 https://doi.org/10.57234/jiimc.june23.1644 original article abstract objective: to determine the knowledge, attitude and practices of barbers about hepatitis b&c transmission in islamabad. study design: a descriptive cross-sectional survey. place and duration of study: study was conducted on barbers (street barbers and shop owner barbers) placed in different sectors of urban areas of islamabad from september 2012 to march 2013. materials and methods: a kap survey (knowledge, attitude and practice survey) was done. one hundred and twenty six barbers were selected through non-probability sampling technique. a pre-tested structured questionnaire was used to collect the data. the data was analysed through spss version 17. descriptive statistical analysis was carried out in order to document frequencies and percentages. results: it was found that only 39% of the barbers had knowledge about different aspects of hepatitis b&c (sterilization of instruments before using on next client ,mode of transmission, sign and symptoms, treatment, vaccination and which organ is effected most ). conclusion: there is a huge gap in knowledge about hepatitis b&c transmission amongst barbers which highlights the importance of health education and different awareness raising campaigns to target this issue and bridge the gap. key words: barbers, hepatitis b, hepatitis c, kap survey. contaminated needles, vertical transmission, unsafe 4 sex and reuse of razors by barbers. the prevalence of hepatitis b & c infection worldwide in general population is around 10–15%, and majority of the cases are seen in rural population as compared to the 5 , 6 urban. unfortunately, pakistan has a high prevalence rate of hepatitis b and c with a constant 7,8 rise in the number of cases. some of the major reasons for the constant rise in number of infected cases may be because of lack of health care facilities, low socio economic class, poor political commitment and most important among them is the lack of education and awareness about the transmission of 9 these infectious diseases. there are many risk factors of hepatitis b&c. any person who has an exposure and not been vaccinated can become infected. risk factors include sharing infected needles in drug users, sharing razors/blades, transmission of infection from mother to her child, unprotected sexual contact with infected person, tattooing or body piercing, equipment not properly sterilized, transfusions of infected blood and individuals subjected to medical or dental interventions if equipment is not properly 10 sterilized. mostly cases of hepatitis remain u n d i a g n o s e d , b e c a u s e o f n o n s p e c i f i c symptomatology. the common symptoms of introduction developing world is facing a burden of epidemics of blood borne diseases. these diseases increase the morbidity and mortality, ultimately resulting in heavy burden on national economics and individual 1,2 level. globally, each year around 2 billion people are infected with the hepatitis b virus (hbv), of which 1,2 more than 350 million have chronic hbv infections. an estimated, more than 180 million people worldwide are infected with hepatitis c virus (hcv) 3 and 3–4 million are newly infected each year. it is a blood borne infection transmitted by infected blood and blood products through transfusions, knowledge, attitude and practices of barbers about hepatitis b&c transmission in islamabad 1 2 3 4 shahid aziz , iffat atif , tahira sadiq , farah rashid jiimc 2016 vol. 11, no.3 correspondence: dr. tahira sadiq assistant professor, community medicine islamic international medical college riphah international university, islamabad e-mail: tahira_sadiq@hotmail.com 1 department of social sciences szabist, islamabad 2,4 department of community medicine yusra medical & dental college, islamabad 3 department of community medicine islamic international medical college riphah international university, islamabad funding source: nil ; conflict of interest: nil received: apr 02, 2016; revised: jun 18, 2016 accepted: aug 22, 2016 hepatitis b & c transmission 103 hepatitis are loss of appetite, weakness, low grade fever, muscle aches or joint pains, vomiting and 11 abdominal pain. the “barber” profession has a very old history. the historical records of barbers indicate that they have 12 important role in the community. barbers at that times were considered as the medicine men and the scholars of their religion, they belonged to the groups who offer their services for bloodletting, circumcision, extraction of teeth and different types of minor operations. with the development of health sector, their role has been limited to hair 13, 14 cutting and shaving only. control of chronic diseases like hepatitis b&c are very difficult in countries where health facilities are expensive and not easily accessible, especially for low socio economic group. on average the cost of treatment for these diseases is beyond the affordability of an average earning citizen of 14 pakistan. almost everyone is utilizing the barber’ services in our society. this may be a potential source of infectious diseases like hepatitis b & c. taking into consideration this threat of viral infections particularly hepatitis and aids, linked to this occupation; awareness amongst barbers holds a significant importance. positive attitude and right practices of the barbers would significantly decrease 6,13 the prevalence of these infections. main theme of the current study is to assess the knowledge about the role of barbers in spreading hepatitis b&c infection. the outcome of this current study will motivate the health educators, community developers and non-governmental organization to identify gaps and barriers in knowledge, attitude & practices of barbers with the impacts on disease transmission. the novelty of this research is the inclusion of street barbers who, so far neglected in different studies. materials and methods a descriptive kap (knowledge, attitude and practice) survey was carried out among barbers in urban areas st th of islamabad from 1 september, 2012 to 30 march 2013. the calculated sample size was 126 using who sample size calculator by keeping 95% confidence interval, proportion (p) 9% and precision (d) 0.05 (5%) using non-probability purposive sampling technique. the data was collected by the researcher assisted by capital development authority. this study was carried out in different sectors of islamabad. the barbers selected for this study were both shop owners and street barbers. the purpose of selecting these both types of barber was to represent the different socio-economic group of the community. the data was collected after informed consent from the barber's shops and street barbers and all those barbers /shop owners were excluded who did not give the consent. the purpose and importance of the study was e x p l a i n e d t o e a c h r e s p o n d e n t a n d d a t a confidentiality was assured. the data was collected using a structured closed ended questionnaire in urdu language to avoid language barrier. at the completion of the questionnaire, health education session was given to barbers regarding their own protection as well as the protection of their customers. the data was analyzed using spss version 17.0. results there were two types of barbers selected for the study, 104 (82.5%) of them were shop barbers whereas 22 (17.5) were street barbers working in green belt areas sitting at places adjacent to different markets. the mean age of the barbers was 34.4 years + 12.2. out of the total 34 (27.0%) did not acquire any school education while 1 (.8%) can read and write, 43 (34.1%) got primary education, 33 (26.2%) middle, 13(10.3%) till matric and only 2(1.6%) were educated to intermediate and above. it was found that 50(39%) of barbers had knowledge of hepatitis b & c as a major disease, 17(13.5%) had some knowledge and 59(46.8%) were totally unaware of the disease. discussion the present study carried out to assess the knowledge of barbers regarding hepatitis b & c and their current practices. the study revealed that there is a huge gap in knowledge about hepatitis b & c among barbers, showing more than 85% were not aware of the signs and symptoms of this disease, and almost 80% did not know that they are vulnerable to 6 the infections. the prevalence of hbv and hcv has been widely investigated in many occupational groups, but relatively few data are available on the prevalence in barbers who are involved in the transmission of these infections and are at elevated risk of exposure jiimc 2016 vol. 11, no.3 hepatitis b & c transmission 104 to blood borne pathogens. in our study, 17.5% of mobile barbers and 82.5% shop barbers had evidence of current or past hbv infection (all were unvaccinated against hbv), similar to a previous study in rabat region of morocco, in 2007, which showed that traditional barbers 1.9% and 1.7% respectively had active hbv and 1.1% of barbers and 1.3% of clients had chronic hcv. in casablanca region same type of study conducted in 2001 among barbers showed that they did not have the knowledge about the concept of infectious risk linked with blood, particularly of hepatitis b and c and hiv; majority of them had not been vaccinated. in this survey different tests were applied in which syphilis serology found positive in 7%. hepatitis b virus found positive in 2% and hepatitis c virus found positive in 5% barbers. in islamabad and allied cities, a study was carried out by private university students which showed that barbers knowledge about hepatitis b & c was very poor which is one of the key health issues of any developing country endorse the findings of current 12,13 study. the study found out that 13% of barbers had knowledge about hepatitis b&c affects liver and transmitted through infected razors. 14-15 some studies showed that barbers who are relatively young had better knowledge about the hazards of using old blade which was not the case in our study. similarly, in our study no relationship was seen between the working experience of the barbers 16 and increased knowledge about hepatitis b & c. the findings of current study obviously indicate that more efforts are required for the awareness regarding health issues for both barbers and their customers to decrease the prevalence of these infections. there are several studies showing that barber shops are important places for spreading of 6 infectious diseases like hepatitis b&c and hiv/aids. a study conducted in italy showed strongest association with barber shop shaving for hbv and table i: knowledge of barbers about hepa��s b & c about 51% of respondents knew that hepa��s b & c are treatable diseases and there main source of informa�on was television. table ii: a�tudes of barbers about hepa��s b & c table iii: prac�ces of barbers about hepa��s b & c jiimc 2016 vol. 11, no.3 hepatitis b & c transmission 105 17 with tattooing for hcv cases. while researching on 16 the knowledge and practices of barbers in india , it was found that large proportion of mobile barbers working in green belt areas are totally ignored. these mobile barbers are more unaware about the transmission of infectious diseases particularly through different instruments used by them. similar findings were depicted in our study too, only 19% barbers were aware that infectious diseases spread through their instruments and 62% had no knowledge altogether. in a related study conducted in italy noted that 90% of barbers washed hands after each customer handling, 66% did not change the towel after each customer. in addition, this study indicated that circumcision or minor surgeries also conducted by these barbers in rural areas. a study conducted in sivas region of turkey “prevalence of hepatitis b and c virus infection” explained that hepatitis b&c infection can be spread through razors, different type of barber's instruments and other related possessions, the findings consistent with the current research. it is important to realize that more efforts are required to raise awareness amongst barbers by launching different types of awareness programs. for better planning and implementation of adequate health promotion and intervention measures for controlling hepatitis b, it is important for both health care providers and policy makers to know the real burden of chronic hepatitis b in region and 18 population specific groups. the health officials and authorities must develop appropriate strategies and monitor systems to restrict the barbers not fulfilling the pre-requisites for registration. large scale efforts and resources are considered necessary to meet these goals. this information is comparable to our study in order to complement the conclusion and recommendations drawn from this study. conclusion the current study highlighted the gap between knowledge & practices of barbers regarding hbv & hcv working in various sectors of islamabad. majority of barbers did not know the extent of risk to themselves and their customers are facing due to their lack of awareness about infectious disease spread through their casual attitude and practices. various awareness raising programs and campaigns are required involving mass media at national level. the competent authorities must be involved through which all barbers of islamabad region should be registered, properly vaccinated and tested for hepatitis b & c on annual basis cost-effectively. references 1. world health organization. hepatitis b. fact sheet who/204.geneva: who 2000. 2. world health organization fact sheet. 164: hepatitis c. geneva who 2000. 3. shepard cw, finelli l, alter mj. global epidemiology of hepatitis c virus infection. lancet infec dis. 2005; 5: 558–67. 4. lopez ad, mathers cd, ezzati md, jamison t, murray cj. changes in individual behavior could limit the spread of infectious diseases. london: oxford university press, 2006. 5. shalaby s, kabbash ia, el saleet g, mansour n, omar a, el nawawy a. hepatitis b and c viral infection: prevalence, knowledge, attitude and practice among barbers and clients in gharbia governorate, egypt, east mediterr health j. 2010; 16: 10–7. 6. waheed y, shafi t, safi sz, qadri i. hepatitis c virus in pakistan: a systematic review of prevalence, genotypes and risk factors. world j gastroenterol. 2009; 15: 5647–53. 7. hamid s, umar m, alam a, siddiqui a, qureshi h, butt j. psg consensus statement on management of hepatitis c virus infection-2003. j pak med assoc. 2004; 54: 146–50. 8. alam mm, zaidi sz, malik sa, naeem a, shaukat s, sharif s, et al. serology based disease status of pakistani population infected with hepatitis b virus. bmc infect dis 2007; 7: 64. 9. gibb dm, goodall rl, dunn dt, healy m, neave p, cafferkey m, et al. mother-to-child transmission of hepatitis c virus: evidence for preventable peripartum transmission. lancet. 2000; 356: 904–7. 10. mele a, corona r, tosti me, palumbo f, moiraghi a, novaco f, et al. beauty treatment and risk of parenterally transmitted hepatitis: results from the hepatitis surveillance system in italy. scand j infect dis 1995; 27: 441–4. 11. bari a, akhtar s, rahbar mh, luby sp. risk factors of hepatitis c virus infection in male adults in rawalpindi islamabad. pakistan. trop med int health. 2001; 6: 732–8. 12. syed aa, rafe mj, huma q, sten hv. hepatitis b and c in pakistan: prevalence and risk factors. international journal of infectious diseases. 2009: 13: 9-19. 13. janjua nz, nizamy ma. knowledge and practices of barbers about hepatitis b and c transmission in rawalpindi and islamabad. j pak med assoc. 2006; 54: 116–9. 14. wazir ms, mehmood s, ahmed a, jadoon hr. awareness among barbers about health hazards associated with their profession. j ayub med coll abbottabad 2008; 20: 35–8. 15. quddus a, luby sp, jamal z, jafar t. prevalence of hepatitis b among afghan refugees living in balochistan, pakistan. int j infect dis. 2006; 10: 242—7. 16. khandait dw, ambadekar nn, vasudeo nd. “knowledge and practices about hiv transmission among barbers” indian journal of medical sciences, april, 2009; 53 : 167-71. 17. mariano a, mele a, tosti me, parlato a, gallo g, ragni p, et jiimc 2016 vol. 11, no.3 hepatitis b & c transmission 106 al. “role of beauty treatment in the spread of parenterally transmitted hepatitis viruses in italy, journal of medical virology. 2004; 74: 216-20. 18. candan f, alagözlü h, poyraz o, sümer h. “prevalence of hepatitis b and c virus infection in barbers”, sivas region of turkey, oxford journals 2001. jiimc 2016 vol. 11, no.3 hepatitis b & c transmission 107 page 16 page 17 page 18 page 19 page 20 1 editorial liquid biopsy: opportunities and expectations rizwan hashim introduction tumors have an abnormal rate of cell growth and cell division. tumor cells release circulating tumor dna (ctdna), cell free dna (cfdna), mrna and 1 microrna, in the blood and body fluids which are 2 the by-product of tumor cell lysis. both ctdna and cfdna provide valuable information regarding the cancer related mutations, genetic aberrations and 3 presence of cell free nucleic acid (cfna). the ctdna provides information about the primary tumor and its secondaries / metastases. it is these ctdna that anchor into novel locations and start dividing to 2 develop secondaries of the tumours. tumor biopsy is an invasive procedure in which tissue is excised from a growth and examined under a microscope. however, “liquid biopsy” is a relatively newer technique to find and evaluate cancer cells or their products in blood and body fluids that circulate after tumor cell lysis. historical aspect for the use of liquid biopsy: the basis of liquid biopsy was the observation made 4 by ashworth in 1869, where the circulating tumor cells were detected in a patient with tumor secondaries. the metastatic sites also shed tumor cells in the blood stream that could be detected and analyzed. it was after a long gap when scientists realized that the cell free dna (cf dna) could be detected, analyzed, and quantified. it was in 1948 when cell free dna and free rna was first detected 5 and quantified. this was done both in healthy individuals and those who had cancer. progressing forward, it was in 1966 the researchers detected large volumes of cell free dna in patients who had lupus. by 1980 the cell free dna was also detected among oncology patients. in 1994 the scientists started detecting specific mutations from the cell free dna present in the blood of oncology patients ® and by 2000 veridex introduced cell search ctc test, for liquid biopsy assay as a first commercially available test for liquid biopsy, however capp seq: cancer personalized profiling by deep sequencing is another method for quantifying ctdna analysis that 6 ® is being used. the cobas egfr was the first liquid biopsy test that was approved by fda in 2016. this test was for egfr gene mutation to be detected in 7 blood drawn from cancer patients. nowadays, ctdna and cfdna can be analyzed commercially by mag max cell free dna isolation kits and cell free nucleic acid isolation kits used for liquid biopsy 1 specimens. applications and advantages of the liquid biopsy technique: when blood/body fluids are drawn as liquid biopsy for ctdna and cfdna, they also contain membrane 8, 9 bound lipid globules called exosomes. they contain tumor proteins, lipids, dna fragments and micro rna. the tumor related material in the exosomes can be analyzed to provide information about the mechanism involved in signals between the tumor cells, especially between primary tumors and metastatic sites. this is one of the many novel features of liquid biopsy and is not achieved by conventional tissue biopsy. liquid biopsy provides a window of opportunity to understand tumor cell signaling that can be manipulated by various treatment modalities for cancer management. as cancer is a complex problem with systemic effects, liquid biopsy with frequent sampling provides a unique chance for mutation characterization and 10,11,12,13 exosomal analysis. together, these analytes have the strength to give the details of the tumors genetics, its metastasis and 14,15 various stages of tumor progression. the information provided is used for: genomics, e p i ge n o m i c s , t ra n s c r i p to m i c s , p ro te o m i c s , metabolomics and information regarding minimal 16 residual disease. the major oncology domains where liquid biopsies have been successfully used 17 are: colorectal, breast and lung cancers, mainly to predict therapy responses and to monitor the correspondence: prof. dr. rizwan hashim fazaia medical college, air university islamabad e-mail: riznajmi20011@hotmail.com received: july 16, 2020; accepted: november 11, 2020 department of pathology fazaia medical college, air university islamabad acknowledgement 1. no conflict of interest is declared. 2. no financial assistant or grant was provided. 3. no endorsement of any device / kit / manufacturer or technology is implied. references 1. schwarzenbach h, hoon dsb and pantel k. cell-free nucleic acids as biomarkers in cancer patients. nat rev cancer 2011; 11: 426–437. 2. haber da and velculescu ve. blood-based analyses of cancer: circulating tumor cells and circulating tumor dna. cancer discov 2014; 4: 650–661. 3. diehl f, li m, dressman d, et al. detection and quantification of mutations in the plasma of patients with colorectal tumors. proc natl acad sci usa 2005; 102: 16368–16373. 4. ashworth tr. a case of cancer in which cells similar to those in the tumors were seen in the blood after death. aust med j 1869; 14: 146–149. 5. dominguez-vigil ig, moreno-martinez ak, wang jy, et al. the dawn of the liquid biopsy in the fight against cancer. oncotarget 2018; 9: 2912–2922. 6. newman am, bratman sv, to j, et al. an ultrasensitive method for quantitating circulating tumor dna with broad patient coverage. nat med 2014; 20: 548–554. 7. malapelle u, sirera r, jantus-lewintre e, et al. profile of the roche cobasvr egfr mutation test v2 for non-small cell lung cancer. expert rev mol diagn 2017; 17: 209–215. 8. wan jcm, massie c, garcia-corbacho j, et al. liquid biopsies come of age: towards implementation of circulating tumour dna. nat rev cancer2017; 17: 223–238. 9. zhang w, xia w, lv z, ni c, xin y, yang l. liquid biopsy for cancer: circulating tumor cells, circulating free dna or exosomes? cell physiol biochem. 2017 may 1;41(2):755–68. 10. konig l, kasimir-bauer s, bittner ak, et al. elevated levels of extracellular vesicles are associated with therapy failure and disease progression in breast cancer patients undergoing neoadjuvant chemotherapy. oncoimmunology 2017; 7: e1376153. 11. sadovska l, eglitis j and line a. extracellular vesicles as biomarkers and therapeutic targets in breast cancer. anticancer res 2015; 35: 6379–6390. 12. valadi h, ekstro€m k, bossios a, et al. exosome-mediated transfer of mrnas and micrornas is a novel mechanism of genetic exchange between cells. nat cell biol 2007; 9: 654–659. 13. bettegowda c, sausen m, leary rj, et al. detection of circulating tumor dna in early and late stage human patients for relapse. the developed assays are 18,19 sensitive to detect these organ related mutations. among other promising capabilities of liquid biopsy are the analysis of heterogeneity of tumor genetics, detection of very early treatment related resistance, detection of residual disease affecting prognosis, 17, 20, 21, 22 recurrence and follow up. among the common applications for use of liquid biopsy technique is, early detection of cancer related dna. this would help to plan the treatment, to review how well the patient is responding to treatment and to detect the recurrence of cancer. as liquid biopsy usually involves detection of cancer cells/dna by drawing of blood, the same can be done multiple times. this helps the oncologists to monitor the molecular changes taking place in the tumor 23 during treatment. liquid biopsies also provide a method to trace the tumor genetic variations sequentially that is not possible by using traditional 22 tissue biopsy. hence, liquid biopsy provides a non-invasive 25 substitute for traditional tissue biopsies and has become a popular field, with features for improved diagnoses for oncology and other types of diseases like down syndrome screening and detection of fetal 2, 25, 26 dna in maternal circulation. recently, liquid biopsy has made a place in precision medicine that manages patient with targeted therapies with 27 improved detection of various genetic aberrations. limitations of liquid biopsy technique: despite many advantages there remain many 28, 29 30, 31 challenges; from timing of sample, collection 32, 33, 34 with relation to the stage of disease adequate volume of sample collected, proper storage of sample, dna isolation, sequencing and detection of relevant mutation, careful analysis with clinical 35 validation of mutation analysis procedures. summary and conclusion: it appears that the future of liquid biopsy is an ambitious endeavor and entails technological advancements but this procedure is gaining worldwide acceptance for early cancer detection, genetic evolution and monitoring of treatment 36 resistance. moreover, with quantum leaps in technology and computation of data we can achieve much with the use of liquid biopsy and also save many precious lives through early revelation and 37, 38, 39, 40 analysis. 2 jiimc 2021 vol. 16, no.1 27. abbosh c, birkbak nj, wilson ga, et al. phylogenetic ctdna analysis depicts early stage lung cancer evolution. nature 2017; 545: 446–451. 28. mandel p and metais p. les acides nucle´ iques du plasma sanguin chez l'homme. c r seances soc biol fil 1948; 142: 241–243. 29. kammesheidt a, tonozzi tr, lim sw, et al. mutation detection using plasma circulating tumor dna (ctdna) in a cohort of asymptomatic adults at increased risk for cancer. int j mol epidemiol genet 2018; 9: 1–12. 30. aravanis am, lee m and klausner rd. next-generation sequencing of circulating tumor dna for early cancer detection. cell 2017; 168: 571–574. 31. lv q, gong l, zhang t, et al. prognostic value of circulating tumor cells in metastatic breast cancer: a systemic review and meta-analysis. clin transl oncol 2016; 18: 322–330. 32. mitchell ps, parkin rk, kroh em, et al. circulating micrornas as stable blood-based markers for cancer detection. proc natl acad sci usa 2008; 105: 10513–10518. 33. gerlinger m, rowan aj, horswell s, et al. intratumor heterogeneity and branched evolution revealed by multiregion sequencing. n engl j med 2012; 366: 883–892. 34. de bruin ec, mcgranahan n, mitter r, et al. spatial and temporal diversity in genomic instability processes defines lung cancer evolution. science 2014; 346: 251–256. 35. torga g and pienta kj. patient-paired sample congruence between 2 commercial liquid biopsy tests. jama oncol 2018; 4: 868. 36. vansant g, wang y, hom b, et al. analysis of circulating tumor cells (ctcs) in patients across multiple metastatic breast cancer (mbca) cohorts identifies marked inter and intra patient heterogeneity in ctc size, shape, and overall morphology. j clin oncol 2018; 36: 1084. 37. cuzick j, thorat ma, andriole g, et al. prevention and early detection of prostate cancer. lancet oncol 2014; 15: e484–e492. 38. cohen jd, li l, wang y, et al. detection and localization of surgically resectable cancers with a multi analyte blood test. science 2018; 359: 926–930. 39. strickler jh, loree jm, ahronian lg, et al. genomic landscape of cell free dna in patients with colorectal cancer. cancer discov 2018; 8: 164–173. 40. shain ah, yeh i, kovalyshyn i, et al. the genetic evolution of melanoma from precursor lesions. n engl j med 2015; 373: 1926–1936. malignancies. sci transl med 2014; 6: 224ra24. 14. dittamore r, wang y, daignault-newton s, et al. phenotypic and genomic characterization of ctcs as a biomarker for prediction of veliparib therapy benefit in mcrpc. j clin oncol 2018; 36: 5012. 15. scher hi, jendrisak a, graf r, et al. ctc phenotype classifier to identify mcrpc patients with high genomic instability ctcs and to predict failure of androgen receptor signaling (ar tx) and taxane (t) systemic therapies. j clin oncol 2016; 34: 5044. 16. pantel k, alix-panabières c. liquid biopsy and minimal residual disease — latest advances and implications for cure. nat rev clin oncol. 2019 jul 1;16(7):409–24. 17. garcia-murillas i, schiavon g, weigelt b, et al. mutation tracking in circulating tumor dna predicts relapse in early breast cancer. sci transl med 2015; 7: 302ra133–302ra133. 18. diehl f, li m, dressman d, et al. detection and quantification of mutations in the plasma of patients with colorectal tumors. proc natl acad sci usa 2005; 102: 16368–16373. 19. elazezy m, joosse sa. techniques of using circulating tumor dna as a liquid biopsy component in cancer management. comput struct biotechnol j. 2018 jan 1;16:370–8. 20. beaver ja, jelovac d, balukrishna s, et al. detection of cancer dna in plasma of patients with early stage breast cancer. clin cancer res 2014; 20: 2643–2650. 21. olsson e, winter c, george a, et al. serial monitoring of circulating tumor dna in patients with primary breast cancer for detection of occult metastatic disease. embo mol med 2015; 7: 1034–1047. 22. shaw ja, page k, blighe k, et al. genomic analysis of circulating cell-free dna infers breast cancer dormancy. genome res 2012; 22: 220–231. 23. siravegna g, marsoni s, siena s, et al. integrating liquid biopsies into the management of cancer. nat rev clin oncol 2017; 14: 531–548. 24. schrock ab, pavlick d, klempner sj, et al. hybrid capture based genomic profiling of circulating tumor dna from patients with advanced cancers of the gastrointestinal tract or anus. clin cancer res 2018; 24: 1881–1890. 25. gray kj and wilkins-haug le. have we done our last amniocentesis? updates on cell free dna for down syndrome screening. pediatr radiol 2018; 48: 461–470. 26. fan hc, blumenfeld yj, chitkara u, et al. analysis of the size distributions of fetal and maternal cell free dna by paired end sequencing. clin chem 2010; 56: 1279–1286. jiimc 2021 vol. 16, no.1 3 original�article abstract objective: the study was done to compare the effectiveness of platelet rich plasma (prp) vs steroid injections in the management of planter fasciitis. study design: it was a comparative study. place and duration of study: this study was conducted for the duration of one year from october 2021 to september 2022 in pakistan railway general hospital, rawalpindi. materials and methods: the study was conducted on 500 patients that visited tertiary care unit for a period of one year. two groups were made based on random sampling technique and type of treatment given for plantar fasciitis (platelet rich plasma and steroid). after the preparation of platelet rich plasma by centrifugation method that separates the red blood cells from plasma and obtain the final volume of plasma with high concentration of platelets. a total of 3ml of platelet rich plasma was injected after all aseptic measures around the area of maximal tenderness in group a patients. 40 mg injection of triamcinolone acetonide was given to the all the participants in group b patients after doing all aseptic measures around the area of maximal tenderness after clinical examination results: there were 250 patients in each group including both male and females. the average age of patients in our study was 45.9 ± 5.6 years and 45.9±4.5 years in both groups respectively. patient in group a had more effective pain relief in long term follow up than patients in group b. the visual analog scale (vas) score values gradually decreased as the duration of treatment increased with the lowest value obtained as 0.68 ± 0.65* and 0.60 ± 0.69* for steroid and prp group respectively. there was no post injection problem in either group. conclusion: our study concludes that prp administration for the treatment of plantar fasciitis can be more effective as compared to steroid as it gives positive results even after 12 months of follow-up. key words: plantar fasciitis, steroid injections, and platelet-rich plasma (prp), foot function index (ffi), visual analog pain scale. orthopedic condition characterized by pain and tenderness in the heel and bottom of the foot. it results from the inflammation and micro tears in the plantar fascia. this condition affects daily activities such as walking and standing and can be paralyzing. there are several treatment options available for plantar fasciitis, including rest, medications, shockwave therapy, tapping and injections. two highly known injection therapies used for plantar fasciitis are platelet-rich plasma (prp) and steroid injections. in prp therapy, the affected area is 1-2 injected with a concentrated solution of platelets and growth factors from the patient's own blood. this solution is believed to promote healing and reduce inflammation with no adverse effect on the plantar fasciitis. steroid injections, on the other hand, involve the injection of a corticosteroid into the affected area to reduce inflammation. recent introduction plantar fasciitis also known as plantar fasciosis is an to compare the effectiveness of platelet rich plasma vs steroid injection in the management of planter fasciitis 1 2 3 4 5 raja adnan ashraf , muhammad munir haider , faizan rauf , syed abrar hussain sherazi , muhammad nadeem kashmiri , 6 ayesha amin correspondence: dr. raja adnan ashraf assistant professor department of orthopedic pakistan railway general hospital, rawalpindi e-mail: dr.addi79@yahoo.com 1 department of orthopedic pakistan railway general hospital, rawalpindi 2,4 department of orthopedic dhq hospital sargoda medical college, sargoda 3 department of orthopedic hitec institute taxilla 5 department of orthopedic watim medical college, islamabad 6 department of radiology benazir butto hospital, rawalpindi received: april 10, 2023; revised: may 20, 2023 accepted: may 25, 2023 jiimc 2023 vol. 18, no. 2 prp vs steroid injections in planter fasciitis 128 https://doi.org/10.57234/jiimc.june23.1686 studies suggest the use of steroid injection if the pain is persistent for more than 6 weeks despite use of 3. noninvasive modalities there is ongoing debate a m o n g m e d i c a l p r o f e s s i o n a l s a b o u t t h e effectiveness of these two treatments for plantar fasciitis. some studies suggest that prp may be more effective than steroid while others suggest the 4-6 opposite. a meta-analysis found that prp was more potent than placebo injections in reducing pain, the effect was not statistically significant. several studies have investigated the effectiveness of steroid injections for the therapy of plantar fasciitis. in addition to the meta-analysis, several other studies have also provided evidence for the effectiveness of prp. the purpose of the following study was to d e t e r m i n e t h e d i f f e r e n c e s b e t w e e n t h e 7 8 effectiveness of platelet-rich plasma (prp) injection and steroid injection in the management of plantar fasciitis. plantar fasciitis is most seen in people between the ages of 40 and 60 and is more common in women than men. prp is a relatively new treatment for plantar fasciitis and more research is needed to determine its long-term effectiveness. it is important to note that prp is not suitable for everyone and should be avoided in cases of platelet dysfunction or bleeding disorders. steroid injections have been used for decades to treat a variety of conditions, including plantar fasciitis. they are wellestablished treatment option and are effective in 9. reducing pain and inflammation. they can have side effects, such as thinning of the skin or changes in skin color, especially if used repeatedly. they should not be used in patients who have an infection or skin 10 condition at the injection site . they should also be avoided in patients who are diabetic or have poor circulation to the feet. the study aimed to evaluate the safety and tolerability of both treatments, as well as their impact on quality of life. materials and methods the aim of this comparative study was to evaluate the effectiveness of platelet rich plasma vs steroid in patients with planter fasciitis. this study was conducted in the department of orthopedics, pakistan railway general hospital, rawalpindi from october 2021 to september 2022 on 500 patients who visited tertiary care unit for a period of one year. methodology was designed after permission from ethical review board. two groups were made based on type of treatment given for plantar fasciitis (prp and steroids). participants were equally and randomly divided into 2 groups by lottery method and after recruitment of the participants, the nature of the research, as well as its goals, was explained to each participant and written informed permission was acquired from patients or their families. there were 250 patients in each groups. the average age of patients in our study was 45.9 ± 5.6 years and 45.9±4.5 years in both groups respectively. patients with age 18 to 65 years old, diagnosed with the planter fasciitis and pain of more than 4 on a visual analog scale who failed to respond for conservative management were included in the study. exclusion criteria included previous trauma/surgery on the affected heel, pregnancy, active infection, previous injections, and bleeding disorders. all participants had heel pain for at least 6 months and had failed previous conservative treatment. the injection of triamcinolone acetonide (40mg) was given to the all the participants in the steroid group. the injection of autologous plateletrich plasma (3ml) was given to all the patients in the prp group. for preparation of prp, an initial method of centrifugation that separated the red blood cells from plasma followed by second centrifugation to concentrate platelets and ultimately obtain the final smallest volume of plasma with high concentration of platelets .the statistical package for the social sciences (spss) version 23 was used throughout the data analysis process. descriptive statistics was used to o u t l i n e t h e d e m o g ra p h i c a n d a n a l y t i c characteristics of the participants. the primary outcome measured the change in pain score measured on a vas after the injection. secondary outcome measured functional improvement measured by the foot function index (ffi), patient satisfaction, and adverse effects. results there were 100 males and 150 females in prp group and 118 males and 132 females in the steroid group. in the prp group there were 130 patients whose right foot was affected, and 120 patients had left foot affected. in the steroid group there were 120 patients with right and 130 with left foot affected as shown in table no. i. visual analogue scale score was compared for patients. the data was collected after 1, 6 and 12 jiimc 2023 vol. 18, no. 2 129 prp vs steroid injections in planter fasciitis https://doi.org/10.57234/jiimc.june23.1686 table i: characteristic features of patients procedure and there is utmost need to do the long term follow up of patients to determine the single modality that is efficient, cost effective with less complication compared to different surgical techniques that put more burden on patients and associated with higher complications. recently the prp use has gained attention for the treatment of 11 foot and ankle pathologies . the corticosteroid injection help to relieve inflammation, promote fibrosis that ease pain and rapid healing with less 12 complexity. this study was designed for the comparison of the results of steroid injection and prp for the plantar fasciitis treatment. our study has suggested that during the initial stages of treatment and after 1, 6 months of treatment the steroid injection had more functional outcomes than single dose of prp for plantar fasciitis but after a follow-up of 12 months the mean vas score was less for prp as compared to steroid injection which suggest that long term effectiveness can be obtained by using prp. studies have shown that because of mechanical loading plantar fasciitis is caused by the 12 inflammatory reaction to micro tears . steroid injections are in use for treatment of plantar fasciitis, 13 but it only gives short term positive results . in our study we compared the visual analogue scale scores for patients before treatment and after 1, 6 and 12 months of treatment for both groups. it was found as per vas scores that there was a significantly noticeable improvement in pain after 1, 6 and 12 months of treatment in case of both prp and steroid groups. our study is in accordance with the previous reports where there was gradual reduction in vas score after steroid and prp treatment. table ii shows the vas score values that gradually decreases as the duration of treatment increases with the lowest value obtained as 91.05%(0.68 ± 0.65)* and 92.27%(0.60 ± 0.69*) for steroid and prp group respectively. the average pain reduction for steroid group is lower than prp group after 1 and 6 months of treatment but after 12 months the values were calculated, and data revealed that the mean vas score of prp was less than the mean vas score of steroid group which suggest that steroid injection can give better results for short term pain relief, but prp dose can be used as a long-term treatment. steroid injections have been used for decades to treat a variety of conditions, including plantar months of treatment. it was found as per vas scores that the statistically significant improvement was observed in pain after 1, 6 and 12 months of treatment in case of both prp and steroid groups. table ii shows the vas score values gradually decreases as the duration of treatment increases with the lowest value obtained as 0.68 ± 0.65* and 0.60 ± 0.69* for steroid and prp group respectively. the vas scores for steroid group are lower than prp group in the initial duration of treatment but after a follow-up of 12 months. the mean vas score of steroid group and prp group was compared. the prp vas scored was better than steroid group. table ii: vas scores comparison of both treatment groups for pretreatment and post treatment at 1, 6 and 12 months the statistical analysis was conducted. for equality of mean the t test, for equality of variance the levene's test and degree of freedom was calculated. it was found that the data was significant statistically. table iii: statistical analysis of the results discussion despite the introduction of multiple non-surgical methods for the effective treatment of plantar fasciitis, there is still needed to determine the ideal jiimc 2023 vol. 18, no. 2 130 prp vs steroid injections in planter fasciitis https://doi.org/10.57234/jiimc.june23.1686 13 fasciitis . they are well-established treatment option and are effective in reducing pain and inflammation. they act quickly and the relief of pain 14 is usually noticed within a few days . another study also explains the anti-inflammatory activity of 15 steroid injections and prp dose . as per studies growth factors and proteins like vitronectin, fibronectin and thrombospondin found in prp play an important role in the healing of tissue and for the 16 regeneration of bones . prp with the assistance of growth factors stimulates stem cells to fasten the 17 repair of cells and improves the circulation of blood. as per studies it was found that prp also enhances the tenocyte proliferation for the fast recovery of tendon as it has growth factors that provides revascularization thereby increasing the expression 18-20 of collagen in the tenocytes. the statistical analysis was conducted. for equality of mean the t test, for equality of variance the levene's test and degree of freedom was calculated. it was found that the data was significant statistically. our study shows the anti-inflammatory response of prp dose after 1, 6 and 12 months and the long-term results were significantly better than steroids. in our study before treatment the vas score in steroid group was 7.60 ± 0.82 and after treatment an average pain reduction was found to be 47.36%(4.00 ± 1.00)*, 36.48%(2.80 ± 1.00)* and 91.05%(0.68 ± 0.65)* for 1, 6 and 12 months respectively. meanwhile the vas score for prp before treatment was 7.72 ± 0.84 and after 1,6 and 12 months of treatment by prp dosage the average pain reduction was found to be 16.58%(6.44 ± 0.92)*,49.22% (3.92 ± 0.91)* and 92.27%(0.60 ± 0.69)* respectively. that explains the gradual decrease in vas score and slight difference in the vas scores for prp and steroid groups. previous studies have reported that prp has better outcomes than steroid for plantar fasciitis, our results showed that despite low vas score in steroid group, prp is better 20-21 option as it gives long term results . it is important to note that prp is not suitable for everyone and should be avoided in cases of platelet dysfunction or bleeding disorders. conclusion being an elective procedure, patient satisfaction following injection remains an important factor for the surgeon when recommending this procedure for treatment. our study concludes that prp administration for the treatment of plantar fasciitis can be more effective as compared to steroid as it gives positive results even after 12 months of followup, therefore it can be considered as a long-term treatment as compared to steroid injections. however, more studies need to be done by using larger sample size and longer follow-up period so that a more elaborate and precise result can be made to better understand the efficacy of prp. references 1. seth i, bulloch g, seth n, lower k, rodwell a, rastogi a, gibson d, bedi h. the role of corticosteroid injections in treating plantar fasciitis: a systematic review and metaanalysis. the foot. doi: 10.1016/j.foot.2023.101970. 2. ahadi t, cham mb, mirmoghtadaei m, raissi gr, janbazi l, zoghi 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the efficacy and safety of extracorporeal shock wave therapy on plantar fasciitis in patients with axial spondyloarthritis: a double-blind, randomized controlled trial. rheumatology i n t e r n a t i o n a l . 2 0 2 2 a p r ; 4 2 ( 4 ) : 5 8 1 5 8 9 . d o i : 10.1007/s00296-022-05098-0. jiimc 2023 vol. 18, no. 2 conflict of interest authors declared no conflicts of interest. grant support and financial disclosure authors have declared no specific grant for this research from any funding agency in public, commercial or nonprofit sector. data sharing statment the data that support the findings of this study are available from the corresponding author upon request. this is an open access article distributed under the terms of the creative commons attributionnoncommercial 2.0 generic license. 132 prp vs steroid injections in planter fasciitis https://doi.org/10.57234/jiimc.june23.1686 original�article abstract objective: to determine the significance of cord blood albumin estimation as a predictor of neonatal jaundice. study design: it was a prospective observational study. place and duration of study: this study was carried out in gynae/obs department, neonatal intensive care unit and pathology laboratory at railway hospital rawalpindi in collaboration with the biochemistry department of islamic international medical college from june 2015 to march 2016. materials and methods: ninety full term neonates were divided into three groups based on their cord blood albumin concentration. group i, with albumin less than 2.8 gm/dl, group ii with albumin between 2.8 ‐ 3.3 gm/dl and group iii greater than 3.3 gm/dl. serum bilirubin level more than 1mg/dl was taken as standard for all the groups. follow up was done for those neonates who had albumin less than 3 gm / dl and bilirubin more than th th 1 mg/dl. the babies were followed up on 7 and 15 day for the appearance of jaundice. depending upon the extent, and delayed recovery from jaundice they were followed up to 20th post delivery day. results: it was found that all neonates of group i and ii who had albumin levels less than 3.3gm/dl, developed jaundice. out of these 16.75% from group i received phototherapy and only 3% needed exchange transfusion. whereas 10% jaundice neonates from group ii received phototherapy. out of 30 neonates in group iii, 60% neonates developed jaundice but none required phototherapy or exchange transfusion. conclusion: it is concluded that low albumin levels in the cord blood taken after birth is a good predictors of neonatal jaundice. key words: albumin, bilirubin, cord blood, neonatal jaundice, predictor. 3 and a larger bilirubin peak. bilirubin is a yellow co l o re d p i g m e nt w h i c h i s p ro d u c e d f ro m hemoglobin during destruction of erythrocyte. so increased production, impaired uptake of bilirubin by liver and in‐effective conjugation causes increase level of unconjugated bilirubin leading to 4 hyperbilirubinemia. for the detection of potential severity of neonatal hyperbilirubinemia the main criterion is the serum concentration of free bilirubin, or if it cannot be determined, the bilirubin/albumin 5 ratio is taken. bilirubin is normally glucuronidated and excreted by the liver into bile. failure of this system can lead to a buildup of conjugated bilirubin 6 in the blood, resulting in jaundice. there are several neurotoxic effects attributed to jaundice like sensorineural deafness, neonatal seizures, auditory 7 neuropathy, cerebral palsy and apnoea. it has been observed that during the first week of life unconjugated serum bilirubin level is more than 1 8 mg/dl (17 mol/l), in almost all neonates. albumin is the major protein present in abundant amount in the blood and has the property of binding to many 9 hormones and nutrients. albumin has a specific site for binding with bilirubin and is responsible for transporting it to the liver, its flexible structure of the helps it to adapt readily to ligands, and it has three introduction neonatal jaundice is one of the most common conditions requiring medical attention in newborn babies. about 60% of neonates born at term and 80% of neonate born before term (preterm) develop, 1 jaundice in the first week of life. it is also known as icterus neonatorum and in the first postnatal week, approximately two thirds of all newborns develops icterus neonatorum in which bilirubin deposition occurs in the skin and mucous membrane. in majority of neonates such deposition is of little 2 consequence. it is mostly physiological since liver is not mature enough to handle the bilirubin load and this increased load is due to a higher circulating erythrocyte volume, a shorter erythrocyte life span, decreased cord blood albumin: a predictor of neonatal jaundice 1 2 3 4 erum rashid chaudhry , abdul khaliq naveed , amena rahim , zunnera rashid chaudhry jiimc 2016 vol. 11, no.4 correspondence: dr. erum rashid chaudhry department of biochemistry islamic international medical college riphah international university, islamabad e‐mail: mhareeb.nabiha@gmail.com 1,2,3 department of biochemistry islamic international medical college riphah international university, islamabad 4 department of pharmacology rawal institute of health sciences, islamabad funding source: nil; conflict of interest: nil received: jun 17, 2016; revised: sep 16, 2016 accepted: oct 28, 2016 cord blood albumin as predictor of jaudice 149 domain in its structure which offers a different kinds 9 of binding sites. in liver glucrounyltransferase an enzyme binds this unconjugated bilirubin with glucuronic acid. this conjugated bilirubin (water 10 soluble) can now be readily excreted in bile. in the term babies the normal lower limit of the serum 11 albumin at the time of birth is 2.8gm/ dl. in the developing countries like, sub‐saharan africa, asia and latin america, there is increased incidence of neonatal morbidity and mortality, attributed to neonatal jaundice (nnj). increase level of unconjugated bilirubin causes brain damage, kernicterus is a term for nnj when it involves brain leading to neurological handicap and early death of 12 affected infants. kernicterus occurs when the molar 13 bilirubin‐ to‐ albumin (b: a) ratio is >0.8. however, this can be avoided by the appropriate use of phototherapy and exchange blood transfusion to 12 control serum bilirubin levels. most of the healthy term infants are discharged earlier because of medical, social and economic reasons. it has been observed that commonest cause for readmission d u r i n g t h e e a r l y n e o n a t a l p e r i o d i s hyperbilirubinemia. such readmissions are exposes a healthy newborn to the hospital environment, causing emotional problems that involves extra expenses for both family and the institution along 14 with the risks of poor breast‐feeding. hence early prediction of level of albumin in cord blood can not only be used for early detection of neonatal jaundice but can be helpful to prevent re‐hospitalization of babies. it will also reduce the economic burden of re‐ hospitalization on family. materials and methods this study was carried out in gynae/obs department, neonatal intensive care unit , pathology laboratory at railway hospital rawalpindi in collaboration with the biochemistry department of islamic international medical college from june 2015 to march 2016. ninety term neonates were selected and randomly divided in 3 groups with thirty neonates in each group. term babies of both genders with any mode of delivery, birth weight above 2000 gm, apgar score over 7 and absence of significant illness or major congenital malformation were included in our study. babies having significant illness (sepsis, rds, asphyxia, idm that could aggravate hyper bilirubineia) gestational age <37 weeks birth weight below 2000 gm, rh incompatibility were excluded from the study. after the informed consent of the parents 2 ml of blood was collected from the cord vein and serum was separated in the lab. quantitative in vitro estimation of serum albumin was done by calorimetric biuret method. total bilirubin was estimated with jendrassik grof method on photometric system ‐ micro lab 300. 2 ml of cord blood was taken from the neoente with 5ml syringes and tranferred to gel tubes. all neonates were assessed for the appearnce of jaundice at time of discharge, and neonates who had serum albumins less than 3gm/dl amd bilirubin more than 1mg/dl th th were followed up from7 till 20 post delivery day. those babies who were physically jaundiced were re‐admitted and their total serum bilirubin levels were repeated. depending upon their bilirubin levels all neonates in group i with serum albumin less than 2.8 gm/dl, group ii with albumin between 2.8 ‐ 3.3 gm/dl and group iii greater than 3.3 gm/dl were managed accordingly. all of our data was tested for normality. kruskal –wallis test was performed to compare the parameters in between the groups, mannwhitney‐u test was applied to compare the parameters within the groups. a p‐value of < 0 .05 was considered significant. correlation analysis was carried out using spaermans corelation test. results in whole study group 86.7% neonates suffered from neonatal jaundice in group i and ii 100% of neonates suffered from jaundice and in group iii 60% had jaundice. table i: median iqr of study groups on the basis of cord blood albumin and bilirubin concentra�on (n=90) when compared by kruskalwallis a statistically significant difference of (p=0.00) was found, between all groups. when compared by using mann‐whitney u test a statistically significant difference of (p=0.00) was seen between group i and ii and between group i and iii. p value of (0.02) was found between group ii and iii. jiimc 2016 vol. 11, no.4 150 cord blood albumin as predictor of jaudice discussion this study was commenced to distinguish the relation of serum albumin and bilirubin with neonatal jaundice. cord blood albumin and bilirubin was measured after the delivery of neonates. a total of 90 neonates of both genders with weight ranging between 2 ‐ 4 kg were selected. it was found out that all the neonates with low albumin and high bilirubin developed jaundice and 16.7% in group i and 10% in the group ii received phototherapy and one neonate required exchange transfusion. in this study it was found that neonate of group i with albumin less than 2.8 mg/dl developed jaundice within 72 hrs after birth and 16.7% required 3 phototherapy in hospital. sahu, et.al (2011) conducted a study on neonates and suggested that infants with low levels of albumin showed high bilirubin level and needed intensive phototherapy than those with high albumin level. only one neonate from this group needed exchange transfusion and 83.3 % did not require any intervention like phototherapy or exchange transfusion. none of the baby from group iii with cord blood a l b u m i n g re ate r t h a n 3 . 3 g m / d l re q u i re d phototherapy or exchange transfusion. sahu et al, in his study suggested that neonates with cord blood albumin level greater than 3 gm/dl require any 3 interventional therapy or exchange transfusion. our study showed that decreased serum albumin level leads to increased serum bilirubin level. this can be due to decreased availability of serum albumin to bind with bilirubin and transport it to excretory organs. bairagi et al 2015, suggested that albumin has binding sites for bilirubin in subdomain 15 2a. phototherapy has a standard role in treating neonatal hyperbilirubinemia. it lowers the serum bilirubin level as it uses light energy from the light source in altering the structure and the shape of bilirubin, converting bilirubin into isomers that are water‐soluble and are not dependent on the process of conjugation for their elimination from the body. even when normal conjugation is deficient it converts bilirubin to molecules that can be easily excreted. bernaldo and serge in one of their study stated that the neonates having bilirubin levels in the serum that are above 2 mg / dl have 53% of 14 probability of receiving phototherapy. in our study, in group i about 16.7% neonates received phototherapy. in group ii, a total of 10% received phototherapy. these results are in accordance with the results of the study done by 14 bernaldo and serge. in group iii, none received phototherapy. this is supported by study done 3 bysahu et al. in addition to phototherapy, exchange transfusion are extensively used world‐wide for treating hyperbilirubinemia. it is considered as gold 16 standard treatment for neonatal jaundice. in our study only one child required exchange transfusion due to raised bilirubin levels upto 20 gm/dl. m. rahman in 2015 in one of his study suggested that neonates require exchange transfusion due to 17 hyperbilirubinemia, septicemia or g6pd deficiency. conclusion the result of the present study revealed that the albumin taken from the cord blood immediately after the birth of the neonates can be used for the prediction of neonatal jaundice.it is further concluded that low albumin levels less than 2.8 gm/dl is not sufficient to bind with high level of bilirubin produced in neonates,leading to hyperbilirubinemia causing neonatal jaundice. table ii: comparison of cord bilirubin in all groups by mann‐whitneyu test phototherapy was to be given to 26.7% of the whole study population. in group i, 16.7 % received conventional phototherapy for the treatment of jaundice. in group ii, 10.0 % received phototherapy. in group iii, none of the neonate needed hospital intervention like phototherapy. table no iii: frequency distribu�on of phototherapy in all age groups jiimc 2016 vol. 11, no.4 151 cord blood albumin as predictor of jaudice further well designed research with large sample size is recommended for more clarification and assesment of relation of low level of albumin with neonatal jauindice. references 1. rennie j, burman roy s, murphy ms. guideline development group. neonatal jaundice: summary of nice guidance. bmj. 2010; 340: 1190‐6. 2. lauer bj, spector nd. hyperbilirubinemia in the newborn. pediatrics in review‐elk grove. 2011; 32: 341‐6. 3. sahu s, abraham r, john j, mathew aa, george as. cord blood albumin as a predictor of neonatal jaundice: int j biol med. 2011: 2: 436‐8. 4. nazer h, katz j. unconjugated hyperbilirubinemia. 2013; emedicine. medscape.com/article/178841. 5. petit fm, gajdos v, parisot f, capel l, aboura a, lachaux a, et al. paternal isodisomy for chromosome 2 as the cause of crigler–najjar type i syndrome. european journal of human genetics. 2005; 13: 278‐82. 6. van de steeg e, stránecký v, hartmannová h, noskovál, hřebíček m, wagenaar e, et al. complete oatp1b1 and oatp 1b3 deficiency causes human rotor syndrome by interrupting conjugated bilirubin reuptake into the liver. the journal of clinical investigation. 2012; 122: 519‐28. 7. amin sb, lamola aa. semin perinatol new born jaundice technologies: unbound bilirubin and bilirubin binding capacity in neonates. pubmed ‐ indexed for medline‐– 2011; 35: 13440. 8. maisels mj. what's in a name? physiologic and pathologic jaundice: the conundrum of defining normal bilirubin levels in the newborn. pediatrics. 2006; 118: 805‐7. 9. roche m, rondeau p, singh nr, tarnus e, bourdon e. the antioxidant properties of serum albumin. febs letters. 2008 ; 582: 1783‐7. 10. nikolaev av, rozhilo ya, starozhilova tk, sarnatskaya vv, yushko la, mikhail ovskii sv, etal. mathematical model of binding of albumin‐bilirubin complex to the surface of carbon pyropolymer. bulletin of experimental biology and medicine. 2005; 140: 365‐9. 11. burtis ca, ashwood ar, bruns de. tietz textbook of clinical chemistry and molecular diagnostics. elsevier health sciences; 4th ed. 2008. 12. ogunfowora ob, daniel oj. neonatal jaundice and its management: knowledge, attitude and practice of community health workers in nigeria. bmc public health. 2006: 6; 1‐5. 13. bunt je, rietveld t, schierbeek h, wattimena jd, zimmermann lj, van goudoever jb. albumin synthesis in preterm infants on the first day of life studied with [1‐13c] leucine. american journal of physiology‐gastrointestinal and liver physiology. 2007; 292: 1157‐61. 14. bernaldo aj, segre ca. bilirubin dosage in cord blood: could it predict neonatal hyperbilirubinemia. sao paulo med. 2004; 122: 99‐103. 15. bairagi u, mittal p, mishra b. albumin: a versatile drug carrier. austin therapeutics. 2015; 2: 1021‐6. 16. b a d i e e z . e x c h a n g e t r a n s f u s i o n i n n e o n a t a l hyperbilirubinaemia: experience in isfahan, iran. singapore medical journal. 2007: 48: 421‐3. 17. rahman m, sarkar pk, nazrin t, chowdhury k, jahan ra, islam ms, et al. study on neonates who received exchange transfusion at dhaka shishu hospital. northern international medical college journal. 2015; 6: 70‐2. jiimc 2016 vol. 11, no.4 152 cord blood albumin as predictor of jaudice page 11 page 12 page 13 page 14 original�article study design: observational descriptive study. place and duration of study: this study was conducted at shaikh khalifabin zahed al-nahyan hospital st th rawalakot from 1 january 2019 to 30 june 2019. materials and methods: children less than age 05 years, brought to the pediatric outpatient department were included in the study by consecutive sampling. the vaccination status of these subjects was noted and confirmed by vaccination card issued to them by the local health authority. a self-designed performa was filled by interviewing the mothers; which included detail about mother's and child age, address, socioeconomic status, education of mother, awareness of mothers regarding preventive role of vaccination and status of vaccination of child.data was entered on spss version 20 and statistical analysis was done. results: a total of 397 mothers responded. out of these 82.9% mothers were educated and 17.1% were uneducated, 67.2% were aware about the preventive role of vaccination and 32.8% were unaware. study showed that 79.3 % children were fully and 1.5% were partially vaccinated, whereas 19.1 % were unvaccinated. vaccination rate was 85% among children where mothers were aware about the preventive role of vaccination, as compared to 67.7% children of unaware mothers (p<0.0001). statistically no significant association was found between maternal education and status of vaccination (p=0.072). abstract objective: to know the status of vaccination among children via expanded program of immunization and its relation with maternal education and awareness of mothers about vaccination. conclusion: vaccination status of children is not satisfactory in azad kashmir. the status of vaccination among the children is directly related to the awareness of mothers about the preventive role of vaccination. key words: awareness, education, immunization, mothers. 5 globally since 2005 and vaccination was one reason. a complete course of vaccination leads to prevention of diphtheria, pertussis and tetanus not only in 6 children but also in adults. some vaccines used during pregnancy result in prevention of neonatal diseases. tdap is used during pregnancy, which 7 includes tetanus, diphtheria and pertussis vaccine. to vaccinate the children, the vaccines are provided by the government free of cost via expanded program of immunization (epi) in pakistan. expanded program of immunization was started in 1978 against six common diseases; tuberculosis, poliomyelitis, measles, tetanus, pertussis and diphtheria. later on hepatitis b vaccine, hib and pneumococcal vaccine were included in epi in 2002 and 2009 respectively. 8 inactivated polio vaccine was added in 2015 rota 9 virus vaccine also has been added to in 2017. pakistan is among those countries where progress of vaccination is not according to the international standards, although vaccination has increased from 10 54% in 2012-2013 to 66% in 2017-2018. coverage is introduction in pakistan the infant mortality rate is about 60/1000 live births and neonatal mortality is 40/1000 live 1 births. however, as compared to pakistan the infant 2 mortality rate in azad kashmir is 58/1000 live births. many deaths under 05 years of age can be prevented 3 by effective vaccination. there is significant reduction in mortality worldwide among children less than 5 year of age, from 69·4 per 1000 live births to 38·4 per 1000 live births between 2000 and 2016. one of the factors causing this reduction in child 4 mortality is vaccination of children. about 3.6% reduction per year was found in child mortality immunization status of children: a study at shaikh khalifa bin zayed al-nahyan hospital rawalakot azad kashmir sadiq hussain, muhammad farooq, muhammad nadeem, shazia siddiq, raja imtiaz ahmed, irum javed correspondence: dr. muhammad nadeem department of medicine poonch medical college, rawalakot e-mail: docnadeem78@gmail.com department of pediatrics poonch medical college, rawalakot funding source: nil; conflict of interest: nil received: april 28, 2020; revised: august 16, 2020 accepted: august16, 2020 immunization status of children in azad kashmirjiimc 2020 vol. 15, no.3 159 done in spss for windows, version 20. means and standard deviations were calculated for quantitative variables like age of children. frequencies were calculated for qualitative variables like gender, education, awareness of mothers, socio economic status and vaccination status. chi square test was applied to see the relation between different factors and status of immunization. p value ≤ 0.05 was considered as significant. results total 397 mothers responded to our questionnaire. out of these 83% (n=329) were educated and 17% (n=68) were uneducated, 67.2% (n=267) were aware about the preventive role of vaccination and 32.8% (n=130) were unaware, 56.4% (n=224) were from rural background and 43.6% (n=173) belonged to urban areas. as for as socioeconomic status was concerned, 62.7% (n=249) were from lower class, 36.8% (n=146) from middle class and only 0.5% (n=2) from upper class. out of 397 children, 56.2% (n=223) were male and 43.8% (n=178) were female. average age of children was 26 + 6.17 months. vaccination status of children is shown in table i. association of maternal education and awareness of mothers about the preventive role of vaccination with the status of vaccination is shown in table ii. we do not have enough data from azad kashmir about the exact status of vaccination in children and role of maternal education and information in vaccination. therefore we conducted this study to know the status of vaccination among children visiting the sheikh khalifa bin zayed hospital rawalakot azad kashmir and its association with maternal education and awareness of mothers regarding role of vaccination in prevention of diseases. materials and methods this observational descriptive study was conducted at department of pediatrics, shaikh khalifa bin zayed st al-nahyan hospital rawalakot from 1 january 2019 th to 30 june 2019. in this study 397 subjects were included by consecutive sampling. informed verbal consent was taken from the mothers before enrollment. ethical approval was taken from the hospital ethics committee before the start of study. vaccination status of children less than age 05 years, brought to the pediatric outpatient department of shaikh khalifa bin zayad al-nahyan teaching hospital with different complaints was noted. the vaccination status of these subjects was confirmed by vaccination card issued to them by the local health authority. mothers who were not sure about the status of vaccination of child were excluded from the study. a performa was designed which included mother's and child age, address, socioeconomic status, education of mother, awareness of mother about preventive role of vaccination and status of vaccination of child. the performa was filled by interviewing the mothers by the authors from pediatric department. data was entered on spss and statistical analysis was not uniform throughout the country and for all diseases. studies have shown that coverage is better in some areas as compared to others, same is true for 11,12,13,14 different diseases. many children are still either unvaccinated or under vaccinated in 11 pakistan. the vaccine coverage in azad jammu and kashmir is claimed 94 % by government of azad 2 kashmir but no studies are available to confirm these statistics. many factors affect vaccination, including maternal education and information about 14,15 preventive role of vaccination. in many countries formal maternal education has shown a positive 15 correlation in promoting immunization in children. table i: vaccina�on status of children (n=397) table ii: associa�on of maternal educa�on and awareness of mothers with the vaccina�on status of children (n=397) our study showed that only 79.3 % children were fully vaccinated. vaccination coverage is less than discussion immunization status of children in azad kashmirjiimc 2020 vol. 15, no.3 160 va va 1. anwar j, torvaldsen s, sheikh m, and taylor r. underestimation of maternal and perinatal mortality revealed by an enhanced surveillance system: enumerating all births and deaths in pakistan. bmc public health 2018; 18:428. 2. hussain a. [internet]. pndajk.gov.pk. 2020. available from: https://www.pndajk.gov.pk/uploadfiles/downloads/final %20ajk%20at%20a%20glan. 3. children: reducing mortality [internet]. who.int. 2020. available from: https://www.who.int/news-room/factsheets/detail/children-reducing-mortality. 4. global, regional, and national under-5 mortality, adult mortality, age-specific mortality, and life expectancy, 19702016: a systematic analysis for the global burden of disease study 2016. lancet. 2017; 39:1084-1150. shown a positive correlation in increasing vaccination in our study. these results are 21 comparable with studies done earlier. this study shows that mere education is not the only tool that will increase vaccination in children; it is the information regarding the preventive role of vaccination that helps. mothers have leading role in increasing vaccination of their children. it will be more rewarding if mothers are educated about the disease preventing role of vaccines and 22 consequences of not vaccinating their children. all available means of educating the mothers about the life saving and health promoting role of vaccines should be utilized. these include community, political and religious leader's involvement. print, electronic and social media also should be used to achieve the target. these community and media campaigns should mobilize the society so that the vaccination of children becomes the mouth word of 23,24 the society. our study had few limitations. it was single center study including children less than 5 year of age only. it was a hospital based study not community based. we also studied only two factors associated with vaccination status. community based studies considering more factors are required in future. 5. wang h , liddell ca, coates mm, mooney md, levitz ce, schumacher ae et al. global, regional, and national levels of neonatal, infant, and under-5 mortality during 1990–2013: a systematic analysis for the global burden of disease study conclusion vaccination status of children is not satisfactory in azad kashmir. the status of vaccination among the children is directly related to the awareness of mothers about the preventive role of vaccination. references international standards. who recommends at least 90% national vaccination coverage and 80% in every 13 district. we also concluded that awareness of mothers regarding the preventive role of vaccination is significantly associated with status of vaccination. no association was found between maternal education and vaccination status. our study showed that 79.3% (n=315) children were completely vaccinated, whereas 19.1% (n=76) were unvaccinated. our result does not match the results of 2017 census; it is shown that coverage is 94% in 2 azad kashmir. however it is close to immunization 10 coverage in pakistan which is 80 %. this vaccination coverage is less than the global targets of vaccination 13 which should be > 90%. many studies from pakistan has shown much lower vaccination coverage as 11,12,13,14 compared to our results. vaccination coverage in azad kashmir is lower than other countries of 16 south asia. comparing with developed world we are far behind, a study from china shows full 17 immunization in 93% children. there are many factors which affect vaccination in children. these factors are maternal education and awareness of mothers about vaccination, political commitments of governments, socioeconomic setup, availability of vaccines, outreach population, low salaries of health workers, health workers home visits, lack of information about vaccines benefits 15,18 and side effects of vaccine. among these factors, maternal education is considered an important factor in promoting vaccination in children. the impact of education is highlighted in various studies in different parts of the world. in these studies education has shown a positive correlation in 19 promoting vaccination. education also increases vaccination indirectly by improving socioeconomic 20 status. although 28% children of uneducated mothers were found unvaccinated as compared to 19% and 16.7% children of mothers having education below matric and above matric respectively in our study but statistical difference was not significant (p value= .072). this is in contrast with the above mentioned studies. this contrast may be due to difference in education standards, different geographical distribution and sampling technique. however, information received through different sources leading to awareness of mothers about the preventive role of vaccination from infections has immunization status of children in azad kashmirjiimc 2020 vol. 15, no.3 161 84-91. 15. freedman ag, nicholas k. the effect of social determinants on immunization programs. . hum vaccinimmunother 2012; 3: 293-301. 16. hasman a, noble dj. childhood immunization in south asia – overcoming the hurdles to progress. perspect public health. 2016; 136: 273-77. 17. cao l, zheng js, cao ls, cui j, duan mj, xiao qy. factors influencing the routine immunization status of children aged 2-3 years in china. plos one. 2018; 13: e0206566. 18. mukungwa t. factors associated with full immunization coverage amongst children aged 12–23 months in zimbabwe. african population studies. 2015; 29: 1761-74. 19. balogun sa, yusuff ha, yusuf kq, al-shenqiti am, balogun mt, tettey p. maternal education and child immunization: the mediating roles of maternal literacy and socioeconomic status. pan afr med j. 2017; 26: 217. 20. streatfield k, singarimbun m, diamond i. maternal education and child immunization. demography. 1990; 27:447-55. 21. owais a, hanif b, siddiqui ar, agha a, zaidi ak. does improving maternal knowledge of vaccines impact infant immunization rates? a community-based randomizedcontrolled trial in karachi, pakistan. bmc public health. 2011; 11:239. 22. handy lk, maroudi s, powell m, nfila b, moser c, japa i, et al. the impact of access to immunization information on vaccine acceptance in three countries. plos one. 2017; 12.0180759. 23. sheikh a, iqbal b, ehtamam a, rahim m, shaikh ha, usmani ha, et al. reasons for non-vaccination in pediatric patients visiting tertiary care centers in a polio-prone country. arch public health. 2013; 71:19. 24. jones am, omer sb, bednarczyk ra, halsey na, moulton lh, and salmon da. parents' source of vaccine information and impact on vaccine attitudes, beliefs, and nonmedical exemptions. advprev med. 2012; 2012. 2013. lancet 2014; 384:957–79. 6. trucchi c, zoppi g. decennial diphtheria-tetanus adult boosters: are they really necessary? j prev med hyg. 2015; 56: e44–e48. 7. mehta b, chawla s, kumar dharma v, jindal h, bhatt b. adult immunization: the need to address. hum vaccinimmunother. 2014; 10:306-9. 8. waheed m. who emro | pakistan second endemic country to introduce ipv into routine immunization schedule | pakistan-infocus | pakistan [internet]. e m r o . w h o . i n t . 2 0 2 0 . a v a i l a b l e f r o m : h t t p : / / w w w. e m r o . w h o . i n t / p a k / p a k i s t a n infocus/introduces-ipv-in-routine-immunization.html 9. waheed m. who emro | expanded programme on immunization | programmes | pakistan [internet]. e m r o . w h o . i n t . 2 0 2 0 . a v a i l a b l e f r o m : http://www.emro.who.int/pak/programmes/expandedprogramme-on-immunization.html 10. arfan w. pakistan demographic and health survey 20172018 key indicators report [internet]. nips.org.pk. 2020. available from: https://nips.org.pk/study_detail. php?detail=mtc5. 11. shaikh bt, ulhaq z, tran n, hafeez a. health system barriers and levers in implementation of the expanded program on immunization (epi) in pakistan: an evidence informed situation analysis. public health rev. 2018; 39: 24. 12. rasheed m, akram u, asif n, ahmed k, zafar s, mumtaz s. expanded programme of immunization (epi) status among children of factory workers. jimdc. 2014;2:62–66. 13. butt m, mohammed r, butt e, butt s, xiang j. why have immunization efforts in pakistan failed to achieve global standards of vaccination uptake and infectious disease control? risk managhealthc policy. 2020; 13: 111-24. 14. imran h, raja d, grassly nc, wadood mz, and safdar rm, o'reilly km. routine immunization in pakistan: comparison of multiple data sources and identification of factors associated with vaccination. international health. 2018; 10: immunization status of children in azad kashmirjiimc 2020 vol. 15, no.3 162 original�article abstract objective: the objective of this study was to determine the frequency of red cell alloantibodies in pregnant women of north west pakistan. study design: it was a descriptive study. place and duration of study. this study was conducted in one year november 2012 to october 2013 at the haematology department, army medical college, national university of sciences and technology (nust) in collaboration with department of gynaecology and obstetrics, military hospital, rawalpindi. materials and methods: a total of 600 samples were studied and it was a non probability convenience sampling. pregnant females of any age, parity and gestational age were included in the study and women with known autoimmune diseases (sle, rheumatoid arthritis) were excluded. data was collected through specifically designed proforma and was analysed by using spss version 20. descriptive statistics were used to describe the data. frequency and percentages were calculated for qualitative variables like blood group and alloantibodies. mean and standard deviation were calculated for quantitative variables like age, gestational age and parity. chi-square test was applied to find an association between all categorical variables. p-value <0.05 was considered significant. results: the frequency of alloantibodies in pregnant women in this study was 0.5% (3/600). prevalence of alloimmunization specifically in rhnegative blood group was 5.5% (3/54). all the antibodies detected were anti-d antibodies. conclusion: rh d antibodies are the only frequent antibodies in majority of pregnant women with rh negative blood group. so the practice of routine antenatal antibody screening for every pregnant woman should be avoided. key words: antibody formation, blood group antigens, pregnancy, pakistan. 3 newborn. antibody screening is done in pregnancy to identify these pregnancies which are at risk of fetal and neonatal hemolytic disease resulting from clinically 4 significant maternal alloantibodies. despite the introduction of rh ig this abo and rh incompatibility is still the major cause of haemolytic disease of the newborn in developing countries raising the importance of antibody screening in all antenatal 5 women irrespective of their blood phenotype. studies have shown variation in frequency of 6,7 alloantibodies among different countries. in asia although anti-d antibodies are the most frequent but the difference lies in the frequency of rest of the 8,9 clinically significant antibodies. developed countries like uk and netherlands do have their own guidelines for the antibody screening 10,11 in pregnant women. in pakistan only few case reports and prospective studies reveal the presence of some rare alloantibodies like anti-rh17, anti12,13,14 rhnull and anti-kell antbodies. these cases do raise the importance of such studies in order to know the prevalence of alloantibodies among pakistani introduction red blood cell alloantibodies are the unexpected immuneantibodies found other than the naturally occurring antibodies in the body, produced in response to the introduction of red cells possessing antigens that the subject lacks, as in cases of pregnancy, transfusion, transplantation or injection 1,2 of any immunogenic material. in pregnancy alloantibodies appear when fetal rbcs carrying a paternal antigen that is foreign to the mother, enters the maternal circulation and this incompatibility of blood groups between the mother and fetus can lead to alloimmune haemolytic disease of the frequency of red cell alloantibodies in pregnant women of north west pakistan 1 2 3 maria shafiq , ayesha noor , amer siddiq correspondence: dr. maria shafiq department of haematology army medical college, rawalpindi e-mail: khanmariashafiq@gmail.com 1 department of haematology army medical college, rawalpindi 2 3 department of haematology/ chemical pathology hbs medical college islamabad funding source: nil; conflict of interest: nil received: june 19, 2017; revised: aug 28, 2017 accepted: nov 30, 2017 red cell alloantibodies in pregnancyjiimc 2017 vol. 12, no.4 185 women which can enable us to set our own guidelines for the antenatal antibody screening. materials and methods it was a descriptive study and was conducted in the hematology department, army medical college, national university of sciences and technology (nust) in collaboration with department of gynaecology and obstetrics, military hospital, rawalpindi. it was completed in one year from nov 2012 to oct 2013. it was a non probability convenience sampling. a total of 600 pregant females were recruited from the out-patient department of gynaecology and obstetrics who came for routine antenatal checkups and were advised routine blood tests. all pregnant women were included irrespective of their age, parity and gestational age. women with known autoimmune diseases were excluded. history was taken from the females according to the structured questionnaire. their age ranged from 19 to 40 years. majority of females were in their third trimester and were primigravida. they were asked about their gravida status, transfusion experience and especially the blood group of their husbands. out of 600 women only 321(53.5%) were aware of their husband's blood group. obstetric history was also taken and those who gave history of one or more abortions were considered to have bad obstetric history. permission from the hospital ethical committee was taken. informed consents were obtained from all the patients. 5.5 ml of venous blood was withdrawn from antecubital vein using 10 ml syringe and was collected in two separate tubes. 2.5 ml blood was for the tube containing edta for abo and rh grouping and the other 3 ml blood was left to clot in the plain tube for antibody screening and identification. sample of each patient was given a laboratory number and record was maintained. each sample was then analysed. blood group was determined by forward and reverse blood grouping technique using commercially prepared blood grouping reagents (biotec) and freshly prepared pooled red cells. during rh blood typing, indirect antiglobulin test was performed on all negative results in order to confirm the weak d phenotype before reporting the sample as rh positive or negative. but we were not able to notice the presence of any weak d antigen among 54 rh negative blood samples. all samples irrespective of their blood group were screened for antibodies using 3 cell panel (diamed) by performing indirect antiglobulin test (iat). the samples which showed positive results on screening were identified using 11 cell panel (diacell). microscopy was done on all negative samples in all stages of iat. data was entered on a specifically designed proforma and was analysed using spss version 20. descriptive statistics were used to describe the data. frequency and percentages were calculated for qualitative variables like blood group, alloantibodies. mean and standard deviation (sd) were calculated for quantitative variables like age, gestational age, parity. chi-square test was applied to find an association between all categorical variables. pvalue <0.05 was considered significant. results a total of 600 women were screened for red cell alloantibodies. age range of patients included in the study was 19 years to 40 years. maximum number of patients 351(58.5%) presented in their third trimester. (fig i). fig 1: presenta�on of study group in various trimesters previous transfusion history was given by 123(20.5%) women. regarding the major blood group systems, figure ii shows the frequency of major blood group systems there were 546 (91%) d antigen positive and 54(9%) d antigen negative women in the study group. among the study group there were 348(58%) primigravida and 252(42%) multigravida females. jiimc 2017 vol. 12, no.4 186 red cell alloantibodies in pregnancy out of 348 primigravida 37(10.6%) were found to be d antigen-negative and the rest of 17 d antigen negative were multigravida (table i). obstetric history and in 0% (0/485) of antenatal women without an adverse obstetric history hence this study also shows a statistically significant association between adverse obstetric history and alloimmunisation rate (p<0.001) (table ii). fig 2: frequency of different blood groups among study group table i: rh phenotypes of primigravida and mul�gravida females a total of 3 irregular antibodies were identified in their blood samples, showing an overall frequency of alloantibodies as 0.5% (3/600). within the whole study group (n=600), anti-d was the only detected antibody, accounting for 100% of all the allantibodies. the husband's blood group was found to be d antigen-positive in all. among the 54 women in the d antigen-negative group, 3 developed antibodies, so the prevalence of alloimmunization in this group was 5.5% (3/54). no antibody was detected among the d antigen-positive group, showing an association of rh d antigen with antibody formation (p<0.001). an association is seen between antibody formation and the blood phenotype, as all the three women who were anti-d antibody positive belong to a negative blood phenotype. in this study, alloantibodies were found in 1.2% (3/249) of multigravida females and in 0% (0/348) of antenatal women who were primigravida showing statistically significant association between multigravida status and alloimmunization rate (p<0.041). as alloantibodies were found in 2.7% (3/112) of antenatal females with an adverse table ii: associa�on between an�body forma�on and rh phenotype (p<0.001), gravida status (p<0.041), adverse obstetric history (p<0.001) discussion this study with 0.5% frequency of red cell alloantibodies shows that throughout the world this frequency varies. a comparison of different study results are shown in table iii. in this study frequency is less as compared to the study carried out in iran(4.5%) and southern 15,16 pakistan(1.8%). reason behind it is that firstly the sample size in this study is smaller which increases the chances of missing rare antibodies which are reported in different case reports and secondly majority of females are primigravida in this study. it is also evident from this study that multigravida status, bad obstetric history and rh-negative phenotype are main risk factors for antibody formation which supports the studies carried out in 9,17 india and malaysia. in contrast to these studies, a nigerian study reveals comparatively higher alloimmunization rate of rh positive phenotype when compared to rh negative phenotype as 13 out of 17 detected antibodies were found in sera of rh 4 positive females. anti d antibodies are the most frequently seen in this study like europe, arab and asia with china as an exception showing anti e and anti mi antibodies 8,18 more common than anti d antibodies. recent studies carried out in america and australia also show anti e antibody more prevalent than anti d 19,20 antibodies. so these antibodies other than anti-d antibodies are the reason behind persistence of this hemolytic disease even after the introduction of rhig. the different red cell alloantibodies reported to jiimc 2017 vol. 12, no.4 187 red cell alloantibodies in pregnancy cause haemolytic disease worldwide are anti co (a), anti rh 17, anti diego, anti kell , anti c, anti cw, anti 21-,29 jk(b) and anti kpa. keeping in view the evidence of presence of these rare alloantibodies in pakistani women each and every blood group was screened for red cell alloantibody but none of these were found. many developed countries have formulated their own antenatal antibody screening guidelines in order to decrease the disease incidence. these countries include uk, netherlands, sweden, 10,11,30,31 australia and newzealand. studies conducted in china suggested that routine antenatal antibody screening of every chinese pregnant woman is not beneficial except those who are d antigen-negative or those having a previous history of haemolytic 8,18 disease of the newborn. guidelines for screening have also been laid down by the drug controller general, india (drugs and cosmetics act., 1989). in 2007, a case was reported in india wherein two women of rh (d) positive phenotype were found to be positive for alloantibodies has promulgated the need for antibody screening in rh (d) positive 32 women as well. unlike these countries, pakistan lacks the availability of proper antenatal antibody screening guidelines. this study can be helpful in formulating these guidelines by suggesting that regular antibody screening of each and every pregnant woman is not necessary and can be a burden on economy so it should remain limited to females with rh negative phenotype. females who have bad obstetric history, are multigravida should also be considered important candidates for antibody screening. there is a need of carrying this study in all regions of pakistan with large sample size so that we could be able to identify population which is at increased risk of developing haemolytic disease of newborn. conclusion rh d antibodies are the only frequent antibodies in majority of pregnant women with rh negative blood group. however, keeping in view the absence of nonrh d antibody in our setup, a guideline can be formulated about introduction of routine antenatal red cell alloantibody screening for just the women having rh-negative phenotype. however in order to lower the risk of haemolytic disease of the newborn, rh – positive women with bad obstetric history and table iii: frequency of red cell alloimmuniza�on jiimc 2017 vol. 12, no.4 188 red cell alloantibodies in pregnancy increased gravida status can also be selected for alloantibody screening test. references 1. hoff brand av. blood transfusion. in: essential haematology. 6th ed. uk: black well publishing limited, oxford. 2011; pp. 397-412. 2. jeremiah za, mordi a. evaluation of the clinical utility of maternal alloantibody screening as a surrogate to antiglobulin crossmatch procedures in resource limited settings. international journal of blood transfusion and immunohematology. 2011; 1: 1-6. 3. cohen dw. hemolytic disease of the newborn: rbc alloantibodies in pregnancy and associated serologic issues. 2012. 4. jeremiah za, mordi a, buser fi, adias tc. frequencies of maternal red blood cell alloantibodies in port harcourt, nigeria. asian j 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med. 2013; 23: 254-9. jiimc 2017 vol. 12, no.4 190 red cell alloantibodies in pregnancy page 25 page 26 page 27 page 28 page 29 page 30 original�article abstract objective: to assess the knowledge and attitude of healthcare workers about covid-19 in the department of pathology. study design: a cross sectional study. place and duration of study: pathology department of fauji foundation medical hospital and pakistan rd rd institute of medical sciences from 3 march 2020 to 3 may 2020. materials and methods: out of 210 health care workers,183 responded to the questionnaire. sampling technique was consecutive and non-probable. data was collected through a pretested questionnaire comprising of 3 parts including demographic data, questions to assess the knowledge and attitude. t-test and anova was used to analyze the relationship between the dependent variables (knowledge and attitude), and the independent variables (demographic characteristics). pearson correlation was used to assess the relationship between the knowledge and attitude (mean). the level of significance was taken as p <0.05. results: overall the survey had a good response of 77%. males 58% were with highest percentage of hcws being post graduate trainee (50%). out of 183, 94% had heard about the covid-19 outbreak. having knowledge that fever, cough, sore throats and shortness breath are symptoms of covid-19 (97%, 98%, and 100%, respectively). however, there were some negative attitudes; only 58% participants thought that they would accept isolation in a health care facility if infected with covid-19 and less than 60% of the participants were of the view that 'transmission of covid19 can be prevented by frequent hand washing. overall, the study participants possessed negative attitude of 31%. conclusion: it is concluded from our study that the overall knowledge of hcws about covid-19 pandemic is good but there is lack of knowledge on its management, a negative attitude is detected among hcws. additional educational campaigns and workshops are needed for hcws in the setting of laboratory to improve their knowledge and attitude towards this pandemic. key words: attitude, covid-19, healthcare worker, knowledge, pakistan. th data by who [6 march 2020] there were 98,192 1 confirmed cases and 3,380 deaths worldwide. first outbreak of covid-19 was reported in wuhan, china in december 2019 and now has become an 1 u n p r e c e d e n t e d p u b l i c h e a l t h c o n c e r n . coronaviruses are a huge group of enveloped viruses. they are named so because of their outer 2 protein envelope resembling a crown. their primary target is the human respiratory tract. symptoms appear after the incubation period of 2-14 days with 2 death occurring within 6-41 days of symptoms . most common symptoms are cough, fatigue, and fever with clinical presentation of pneumonia. virus spreads to human through feco-oral, air droplet and 4 personal contact . various outbreaks occurred in the past such as severe acute respiratory syndromecoronavirus (sars), with reported 8096 confirmed cases 774 deaths in 2003 and middle east introduction who declared covid-19 as a public health th emergency of international concern (pheic) on 30 1 january 2020. surprisingly, an alarming number of cases were reported in march globally making covid19 an emerging pandemic? according to the updated knowledge and attitude of health care workers (hcw) about covid-19 pandemic in the department of pathology 1 2 3 4 5 6 mariam khan qamar , armaghana qamar khan , aamir afzal , shahid ahmad abbasi , atif abbas , fauzia khan correspondence: dr. mariam khan qamar final year post graduate trainee department of pathology fauji foundation hospital, islamabad e-mail: mariamkhanqamar@gmail.com 1,3,4 5 department of pathology/medicine fauji foundation hospital, islamabad 2 department of histopathology pakistan institute of medical sciences, islamabad 6 department of hematology district head quarter hospital, mirpur azad kashmir funding source: nil; conflict of interest: nil received: december 29, 2020; revised: april 22, 2021 accepted: april 27, 2021 health care workers (hcw) and covid-19 pandemic jiimc 2021 vol. 16, no.2 68 respiratory syndrome (mers-cov) in 2012 with 5 2494 confirmed cases 858 deaths. these two viruses had an 80% (sars) 50% (mers-cov) genomic and 5 transmission similarity with covid-19. be it a medical emergency or a situation like pandemic the hcws are on the front-line of cover against any disease or 6 an infection. in order to treat these patients, they are in close proximity with the patients making them vulnerable of contracting the disease and extremely 6 difficult to protect them. although vaccine is now available still the most critical intervention is the application of preventive measures for the 7 containment of this disease. in the past during an epidemic of sars and mers-cov many hcws were 7 contracted with this disease. a study showed that an astounding 9,400 number of hcws got covid-19 in 8 spain with fear of collapsing the health care system. the situation in pakistan is rather grim with scarcity of resources and unpreparedness for this pandemic. despite various national guidelines on prevention of emerging covid-19, the knowledge and attitude of hcws are still uncertain. to our knowledge, there is paucity of research that evaluated the knowledge and attitude of health care workers in the setting of pathology laboratory in pakistan. laboratory personnel are the ones handling specimen of suspected cases of covid-19. it is crucial they have sound knowledge of this disease for their personal safety as well as the coworkers. the aim of this prospective cross-sectional study was to identify the gaps in their perceived knowledge about the pandemic and their attitude regarding it with the purpose to fill in those gaps by providing adequate training and imparting knowledge to ensure they are well educated and informed to reinforce good practices. therefore, a study was planned to assess the knowledge and attitude of healthcare workers (hcw), including the doctors and laboratory technicians about covid-19 pandemic in the setting of pathology. materials and methods it was a cross sectional study. this study was conducted among healthcare workers (hcws) in pathology department (including microbiology, h e m ato l o g y, h i sto p at h o l o g y, a n d c h e m i ca l pathology) of two tertiary hospitals named as pakistan institute of medical sciences and fauji foundation medical hospital. duration of study was rd rd 03 months i.e from 3 march 2020 to 3 may 2020. sample size was 210 healthcare workers. it was a consecutive and non-probable sampling technique. the ethical approval was taken from the ethical review committee of the hospitals. all healthcare workers (assistant professor, post graduate trainee, medical technologist, lab technologists) were included in this study. the sanitary workers and other staff were excluded from this study. the data was 2 collected through pretested questionnaire. therefore; it was a “pilot study”. it was assured to the participants that their information would remain anonymous. this questionnaire comprised of three parts. the first section included the demographic characteristics of the participants (age, gender, occupation, years of experience, and source of information on covid-19). the second part had 10 questions concerning the knowledge on covid-19, and the last part included the attitude towards covid-19 comprising of total 8 questions. in this section the answers were assessed through a 5points likert scale of agreement. one point was given to each correct answer in relation to knowledge. a cut off level of <7 was taken d as poor knowledge, and< 7 meant good knowledge. the total knowledge scores for the healthcare workers (pathology department) were between 0 (given no right/correct answer) and 10 (for giving all right/correct answers). based on the 5-points likert scale attitude was given from 1-5 on strongly agree to strongly disagree. a mean score of < 2 (strongly agree or agree) was taken as a positive attitude. a score of 3 to 5 as a taken negative attitude (strongly disagree or disagree or undecided). therefore, lower the attitude scores gives greater the probability of positive attitudes and the reverse was applied for a high score. data was entered and analyzed in spss 21.0 software. the descriptive analysis as was reported as frequency, 2 percentage and mean. t-test and anova were used for analyzing the relationship between the dependent (knowledge and attitude), and i n d e p e n d e n t v a r i a b l e s ( d e m o g r a p h i c characteristics) of the participants. pearson correlation was used to assess the relationship 2 between mean of knowledge and attitude scores. the level of significance was taken as p<0.05. results out of 210 hcws, 183 (87%) of participants health care workers (hcw) and covid-19 pandemic jiimc 2021 vol. 16, no.2 69 completed and returned the questionnaire. mean age of the participants was (37.79±11.19) years, most of them being male participants (58%), the highest percentage of hcws were post graduate trainees (28%) & lab technicians (50%) and most of the staff had more than 10 years' experience (74%). there were 94% of participants had knowledge of covid-19 outbreak. social media and television (78% and 51% respectively) was the main sources of covid-19 information [table i]. most of the participants had the knowledge that covid-19 is a virus and is transmitted by being in close contact with the infected person. having knowledge that fever, cough, sore throats and shortness of breath are symptoms of covid-19 (97%, 98%, and 100%, respectively). ninety percent participants were of the view that healthcare workers (hcws) have a greater risk of infection, whereas only 25% of the participants were of the view about the 'availability of covid-19 vaccine in markets. this survey had an overall good response with 77% of the participants had sufficient knowledge [table ii]. however, about two-third of participants knew that 'participants were concerned for their family members might get infected' and 'participants think that 'they too would probably get illnesses (75% and 65% respectively). however, there were some negative attitudes; only 58% participants thought that they would accept any isolation in health facilities if getting covid-19. another negative attitude finding showed that less than 60% of the participants were of the view that 'transmission of covid19 can be prevented by frequent hand washing. overall, study participants possessing less sufficient attitude 31% recorded as in [table iii]. the a s s o c i a t i o n b e t w e e n t h e d e m o g r a p h i c characteristics and knowledge and attitude of hcws is shown in [table iv]. occupation was correlated with the knowledge and attitude scores. according to which assistant professor, post graduate trainees showed who had greater levels of knowledge were also found to have a higher level of a positive attitude towards covid-19 in contrast to the lab technologist (lab technician & lab attendants) (9.75 vs. 10.36, 9.78 vs. 10.84, 7.00 vs. 12.67), and (7.17 vs.12.11, 9.75 vs. 11.57, p < 0.05). besides, pearson's correlation analysis showed a significant positive correlation between the scores of mean knowledge and attitude among healthcare workers towards covid-19 (r=0.249, p<0.05). the higher the attitude scores, the higher the probability of positive attitudes; while the greater the knowledge scores, higher is the probability of good knowledge. hence having a good knowledge on covid-19 was associated with a positive attitude. table i: demographic characteristics of healthcare workers (n=183) table ii: knowledge of health care worker on covid-19 health care workers (hcw) and covid-19 pandemic jiimc 2021 vol. 16, no.2 70 discussion by looking at the worldwide trend it can be clearly stated that health workers are increasingly being infected with covid-19. the situation in pakistan is no different. according to the latest who report until 8 now 509 hcws got tested positive for covid-19. our study showed good knowledge of hcws towards covid-19. there were [94%] hcws who knew that covid-19 is a pandemic and for majority [78.1%] this source of information was social media. in contrast to this a study conducted in vietnam showed the major source to gather information on covid-19 was media such as television [79.2%] and social media 9 [91.1%] in our study only a minority [23%] got this information from the website of health ministry and hospitals with the other study showing good response rate [82.6%] of gathering this information 10 from the website of hospital/health ministry. this is also another concern for the government of pakistan as it is imperative to consider specialized channels to update correct knowledge to the hcws. social media being the major source [91.1%] of information can 11 either support or hinder the efforts of public health. a study coined the term 'infodemic' to social media platform to outline the peril of misinformation through social media aggravating the psychological 11 impact of covid-19. in our study hcws had a sound knowledge of disease transmission and symptoms. there were 97.3% of hcws that knew it is a virus with 98.4% -100% had knowledge of its correct mode of disease transmission and symptoms. they [93.4%] knew that the incubation period of the disease was 2-17 days. however, our results were not in agreement with other studies conducted on hcws. a study was conducted in jordan showed poor knowledge of hcws with only 34.1% knew the table iii: attitude of healthcare workers toward covid-19 in pathology department table iv: knowledge and attitude scores of health care workers in pathology department p value < 0.05 is significant* health care workers (hcw) and covid-19 pandemic jiimc 2021 vol. 16, no.2 71 12 correct incubation period of covid-19. a similar study was conducted on hcws which also showed poor knowledge. it was found that only 39% and 36.4% knew the source of transmission and the 13 incubation period of covid-19. having correct knowledge of its transmission and the incubation period are crucial to hcws for the prevention of this disease. as prevention is the most critical intervention for the containment of this disease since no vaccination is currently available to treat 14 this disease. according to the results 58% of hcws thought that washing hands with soaps and detergent and wearing of mask can prevent this disease. these results were not same as the above study where 97% had the same finding and another study on mers showing 94% knowing the prevention 15 of the infectious disease. our study showed meager knowledge of hcws in the management of covid-19. only 10.9% thought that the first line treatment was antibiotics and with 25% stating that the vaccine for covid-19 is available. this result is same as of other studies conducted on mers and sars where the respondents did not have knowledge of its 16 management. in our study 75% of hcws raised their concern for contracting the disease with 67% feared for their families of getting the disease from them. the results were in accordance with another study where 67% of hcws feared that their family 17 members might get the disease. this perceived anxiety for getting the disease by hcws is common in any pandemic. feared that their family members might harbor the disease is contributed to the resource scarcity of ventilators and treatment modalities in under resourced country like pakistan. we feel the need to address the significant fear of hcws for spreading the disease to the family members. this can be achieved by implementing stringent infection control measures in the hospital through making local sops based on the national guidelines and through provision of psychological support by proper counseling. our study did not show an optimal attitude of hcws towards the pandemic. majority [91%] thought that the transmission of this disease could be prevented by active contribution of hcws in the infection control program in the hospitals through participation but only 78% of the medical staff was willing to take part in an anti-epidemic activity. our findings showed that only 58% of the respondents agreed for isolation in case of symptoms. these findings were not like other studies where 96% of the participants agreed 17 to isolate themselves. we feel the need to further probe into the cause of this lack of positive response. our study had certain limitations. it is a cross sectional study on hcws in the pathology department therefore it cannot be generalized to all the health care professionals. additional studies need to be done at a larger scale on all hcws to assess the need to educational interventions at a national level. despite these limitations we feel our study provides valuable and genuine information of the knowledge and attitude of healthcare workers of pathology department during the peak time of covid-19 pandemic. conclusion it is concluded from our study that the overall knowledge level is good among hcws but there is lack of knowledge on the management of covid-19. however, a negative attitude is detected among hcws. additional educational campaigns and workshops are needed for hcws in the setting of laboratory to improve their knowledge and attitude towards this pandemic. references 1. aiello f, afflitto gg, mancino r, li jp, cesareo m, giannini c, nucci c. coronavirus disease 2019 (sars-cov-2) and colonization of ocular tissues and secretions: a systematic review. eye. 2020;34(7):1206-11. 2. huynh g, nguyen tn, vo kn, pham la. knowledge, and attitude toward covid-19 among healthcare workers at district 2 hospital, ho chi minh city. asian pacific journal of tropical medicine. 2020;13(6):260. 3. chen n, zhou m, dong x, qu j, gong f, han y, qiu y, wang j, liu y, wei y, yu t. 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and attitude among healthcare workers towards covid-19: a cross sectional study from jeddah city, saudi arabia. the journal of infection in developing countries. 2020;14(10):1090-7. health care workers (hcw) and covid-19 pandemic jiimc 2021 vol. 16, no.2 73 143 editorial changing patterns of anti‐microbial resistance and their financial impact on patient care abdul bari khan, shahina yasmin correspondence: prof. col (r) dr. abdul bari khan si (m) professor of microbiology & hod pathology islamic international medical college riphah international university, islamabad e‐mail: abdul.barikhan@riphah.edu.pk received: dec 10, 2016; accepted: dec 12, 2016 as defined by world health organization (who), “antimicrobial resistance (amr) occurs when microorganisms such as bacteria, viruses, fungi and parasites change in ways that render the medications used to cure the infections they cause 1 ineffective. amr is a very serious threat of present time to the human health security all over the world. it has been reported against almost every anti microbial discovered so far and in every country or community on the surface of the globe. the antibiotic resistance (abr) shown by bacteria is more prevalent globally and specially in low and middle income countries resulting in devastating results. the who, in one of the latest reports has described that globally 3.6% of all new cases and 20.2 % of previously treated cases of tuberculosis (tb) are estimated to have multi drug resistant tb (mdr‐tb) and on the average 9.7% of these mdr‐tb cases are found to be extensively drug resistant (xdr‐tb). great concern has been aroused by antibiotic resistance shown by particular bacteria against specific antibiotic groups like methicillin resistant staphylococcus aureus (mrsa), the extended spectrum beta lactamase (esbl) producing gram negative bacilli and cocci leading to resistance against fluoroquinolones and 3rd generation c e p h a l o s p o r i n s , ca r b a p e n e m a s e p ro d u c i n g members of bacterial family enterobacteriaceae becoming resistant to almost all antibiotics including carbapenems, the last resort antibiotics for these and ndm‐1 producing bacteria resistant to most antibiotics except polymyxin. the other emerging threatening pathogens include 3rd generation cephalosporin resistant neisseria gonorrhoeae, vancomycin resistant enterococci and staphylococci, multidrug resistant salmonellae and haemophilus 2influenzae. about 10‐17% of all new patients of hiv infection in australia, europe japan and usa are infected by virus resistant to at least one antiretroviral drug. emergence of plasmodium falciparum resistant to almost the last resort antimalarial named artemisinin is another dreadful threat. similarly antimicrobial resistance against antivirals like adamantanes by influenza virus type a, and against anti‐fungals like fluconazoles by candida is among all 2 types of antimicrobial resistances. out of the above mentioned list, almost every type of antimicrobial resistance is present in pakistan. but the most devastating and alarming are mdr and xdr mycobacterium tuberculosis, chloroquin and multi resistant plasmodia, esbl and carbapenemase producing enterobacteriaceae, mrsa, vancomycin resistant enterococci and staphylococci and 3,4,5,6 multidrug resistant typhoid salmonellae. although sufficient numbers of comprehensive studies covering all aspects of the additional financial burden faced with infections by multi‐ resistant microbes are not found in medical literature, yet the longer hospital stay, increased hospital cost, and higher mortality have been 2,7 reported in various studies. however it is confirmed that the increasing microbial resistance has got great economic impact on the patient care because 2nd and 3rd line regimens have been reported to be 3 times and 18 times more expensive 8 respectively than the first‐line drugs. more importantly, we are facing a global scenario where sporadic antimicrobial resistance has been found 9 even to the last resort antimicrobials. in 2009 a joint technical report presented a data of financial impact of infections with multi resistant bacteria and reported death of 25 thousand patients who died in a year from infection by multi resistant bacteria in european union (eu), iceland, & norway. in addition there were approximately 2.5 million extra hospital days due to infection by these organisms. the estimated financial burden both direct and indirect due to antibiotic resistant bacteria was found to be €1.5 billion (euro) each 10 year in eu. centre for disease control and prevention (cdc) usa has cited a study of 2009 showing an estimate of as high as $20 billion in excess as direct healthcare costs, and additional cost to society for lost productivity as high as $35 billion a year in usa as a result of infections by multi resistant departmetn of microbiology islamic international medical college riphah international university, islamabad 144 jiimc 2016 vol. 11, no.4 11 bacteria. a recent study chaired by an economist have estimated that if the ever increasing bacterial resistance is not checked at this stage there would be 300 million deaths prematurely in the next 35 years leading to economic loss of 60 to 100 trillion usd by 12 the year 2050. pakistan is one of the top 10 countries in the world with high burden of tuberculosis. with an average of 510,000 new cases of tuberculosis including 26,000 cases of mdr tb and about 2,500 estimated cases of xdr tb puts a huge economic burden for its management and treatment in view of the estimated per person treatment cost for tb ranges from 100 to 1,000 us dollars in susceptible infection and 2,000 to 20,000 dollars for mdr tb. moreover the success rate of tb treatment is up to 83% in susceptible 13 patients, 52% for mdr tb and 28% for xdr tb. this shows that a very comprehensive infrastructure and huge funds other than current international donations are required to cope with the situation. similarly addition of 1.5 million cases of malaria every year with about 12% of these caused by plasmodium falciparum and rest by p. vivax is a big figure for consideration. the current eruption of chloroquin resistance in p. vivax can lead to a huge 6 burden on health care budget of the country. a research report showing the total costs per malaria episode (including direct and indirect household costs and health system costs) based on disease severity and the presence of complications and co‐ morbidities ranged from us$ 7.99 to $ 229.24 in ghana, from us$ 5.2 to $ 137.74 in tanzania, and 14 from us$ 11.24 to $ 287.81 in kenya. due to non availability of a comprehensive data the financial burden due to infections by mrsa, esbl and carbapenemase producing organisms for our country is difficult to calculate. we have compared the cost of the antibiotics only for 10 days treatment of a patient suffering from some systemic disease caused by escherichia coli sensitive to 3rd generation cephalosporins and resistant to that and treated with meropenem. the cost of antibiotics comes to rs 7,500 ‐15,000 and 30,000 ‐60,000 respectively. this example can show us how multi resistant organisms can influence the health care budget of a hospital, 15 family and a country. in view of above, there is an utmost requirement of having serious considerations is planning and execution of preventive measures against rapid development & spread of amr at individual, hospital, community, national and international level. reference 1. w h o o n l i n e q & a o c t , 2 0 1 6 . a v a i l a b l e a t www.who.int/features/qa/75/en/. 2. world health organization. antimicrobial resistance: global report on surveillance. 2014: x ‐xiii. 3. hussain t. pakistan at the verge of potential epidemics by multi‐drug resistant bacteria. adv. life sci. 2015; 2: 46‐7. 4. ali i, rafique z, ahmad s. prevalence of multi‐drug resistant uropathogenic escherichia coli in potohar regions of pakistan. asian pac j trop biomed. 2016; 6: 60‐6. 5. qamar fn, azmatullah a, kazi am, khan e, zaidi ak. a three year review of antimicrobial resistance of salmonella enterica serovar typhi and paratyphi a in pakistan. [abstract] j inf dev ctries. 2014; 8: 981‐6. 6. khan a, godil fj, naseem r. chloroquin‐resistant plasmodium vivax in pakistan: an emerging threat [correspondence] nov,2016 lancetgh (4): available at http://www.thelancet.com/pdfs/journals/langlo/piis2214 ‐109x(16)30251‐0.pdf assessed on 05 dec, 2016. 7. christian g. giske, dominique l. monnet, otto cars. mini review clinical and economic impact of common multidrug‐ resistant gram‐negative bacilli. antimicrob agents chemother. 2008; 52: 813–21. 8. w h o f a c t s h e e t 2 0 1 6 . a v a i l a b l e a t http://www.who.int/mediacentre/factsheets/fs194/en/ (accessed on 7 dec 2016). 9. michael ca, dominey howes d, labbate m. the antibiotic resistance crisis: causes, consequences, and management. front public health. 2014; 2:145. [pmc free article] pubmed accessed on 2 dec,2016. 10. ecdc/emea. joint technical report 2009. the bacterial challenge: time to react (accessed on 6 dec, 2016) available at http://ecdc.europa.eu/en/publications/publications/ 0909_ter_the_bacterial_challenge_time_to_react.pdf. 11. cdc 2013 antibiotic resistance threats in the united states, (accessed on 6 dec, 2016) available at h t t p : / / w w w. c d c . g o v / 2 c 2 f 2 4 3 7 ‐ 8 c 1 2 ‐ 4 0 7 3 ‐ a 6 7 1 ‐ 58641becc9d8/finaldownload/downloadid11d0b72ce9 840af4eb2fef6b3a6b737d/2c2f2437‐8c12‐4073‐a671‐ 58641becc9d8/drugresistance/pdf/ar‐threats‐2013‐ 508.pdf. 12. jim o'neill. antimicrobial resistance: tackling a crisis for the health and wealth of nations december 2014(accessed on 6 d e c , 2 0 1 6 ) a v a i l a b l e a t h t t p s : / / a m r ‐ review.org/sites/default/files/amr%20review%20paper% 20%20tackling%20a%20crisis%20for%20the%20health%2 0and%20wealth%20of%20nations_1.pdf. 13. world health organization 2016. global tuberculosis report 2016‐p152[accessed on 5 dec, 2016] available at http://www.who.int/tb/publications/global_report/en/. 14. sicuri e, vieta a, linder l, constenla d, sauboin c. the economic costs of malaria in children in three sub‐saharan countries: ghana, tanzania and kenya. malaria journal 2013; 12:307. available at https://malariajournal. biomedcentral.com/articles/10.1186/1475‐2875‐12‐307 (accessed on 8 dec, 2016). 15. neeshat mq, (editor) pharma guide 24 edition 2016; 636‐ 838. pharma guide publishing company pakistan. page 5 page 6 jiims final 29 original article abstract objective: to find out the effects of heparin added to the irrigating solution on anterior chamber reaction in pediatric cataract surgery. study design: a quasi experimental study. place and duration of study: this study was conducted in a tertiary eye care hospital from jan 2008 to july 2010. materials and methods: twenty eyes of fifteen patients aging 4 years to 10 years with uncomplicated pediatric cataract were selected in the study. all children underwent cataract extraction under general anesthesia and received anterior chamber irrigation with heparin sodium (5 iu/cc) during operation added to the irrigating solution of balanced salt solution (bss plus). all patients received standardized postoperative treatment. all patients were followed on the first post operative day, after one week, after one month and were advised follow up at the 3rd and 6th months and postoperative anterior chamber reaction was documented according to modified hogan's classification on each visit. results: mild anterior chamber reaction was observed in 10 patients (50%) and moderate anterior reaction was th observed in only (15%) three patients on first follow up. anterior chamber reaction disappeared on 7 post operative day in all patients. fibrin formation, anterior and posterior synechia, cyclitic and pupillary membrane formation was not observed in any patient. there was also no intraocular lens deposits or posterior capsular th opacification (pco) in any of the cases after the follow up of 6 months. conclusion: heparin sodium in the irrigating solution is safe, effective, and promising method to prevent early postoperative inflammatory reaction in pediatric cataract surgery. key words: heparin, cataract, anterior chamber reaction, anticoagulation, antiproliferative. reactions are associated with younger age and may be affected by surgical technique, intraoperative injury to adjacent structures such as iris, presence of antecedent ocular infection, and remnants of retained cortical 5material . heparin has anti-inflammatory and antiproliferative effects in addition to its anticoagulant function, inhibits fibrin formation after intraocular surgery, and has also been shown to inhibit fibroblast 6activity. we present a prospective study to determine the influence of heparin in irrigating solution on the post operative cellular reaction in pediatric cataract surgery. it was a prospective non-randomized clinical interventional study conducted materials and methods introduction pediatric cataract presents the major preventable cause of visual impairment and 1blindness in childhood. the estimated number of children who are blind because of 2cataract is as high as 200,000. cataract surgery with intraocular lens (iol) implantation has been fully accepted in children over the age of 12 years since 3,4several years. cataract surgery and other intraocular procedures have a higher i n c i d e n c e a n d m o r e p r o n o u n c e d postoperative inflammatory reactions in 5children compared with adults. these ------------------------------------------------the effect of heparin on anterior chamber reaction in pediatric cataract surgery yasir iqbal, sohail zia, aneeq mirza correspondence: dr. yasir iqbal senior registrar, eye department islamic international medical college pakistan railway hospital, rawalpindi e-mail: yazeriqbal@yahoo.com 29 30 during the period of jan 2008 to july 2010. all the children with uncomplicated cataract were selected. they were allotted hospital number and were prepared for general anesthesia with all the systemic review and investigations. the parents were asked to sign an informed consent for the procedure. all children underwent cataract extraction under general anesthesia by an experienced surgeon. the patients received anterior chamber irrigation with heparin sodium (5 iu/cc) during operation added to the irrigating solution of balanced salt solution (bss plus).a conjunctival flap was made at superotemporal part of the limbus. scleral tunnel was constructed using a crescent knife and extended up to 1.0 mm into clear cornea. a 3.2mm keratome was used to access the anterior chamber and the internal corneal incision was extended for about 0.5mm more than the external scleral incision. the anterior chamber was d e e p e n e d u s i n g a v i s c o e l a s t i c a n d continuous curvilinear capsulorrehexis of 5 6 mm was done using a bent 27-gauge needle mounted on the irrigating infusion. the nucleus was aspirated and the cortex was washed using a simcoe cannula. a 6.5 mm optic pmma pciol was implanted in the capsular bag inflated by viscoelastic. the viscoelastic material was replaced by bss solution containing heparin sodium (5 iu/cc). the integrity of the self-sealing scleral incision was ensured and the cut conjunctival flap was apposed using a forceps fitted to bipolar diathermy. subconjunctival injection containing gentacin and dexamethasone were given in the end. standardized postoperative treatment comprised of prednisolone acetate 1% (pred forte by allergan) one hourly for one week followed by five times a day for the second week and tapered over six weeks and moxifloxacin (vigamox by alcon) four times a day for one month. no oral steroids or topical mydriatic treatment was given. all patients were followed on the first post operative day, after one week, after one month and were advised follow up at the 3rd and 6th months. at all visits, postoperative intraocular complications, including cellular reaction based upon modified hogan's classification, fibrin formation, anterior and posterior synechia, cyclitic and pupillary membrane formation, intraocular lens deposits and posterior c a p s u l a r o p a c i f i c a t i o n ( p c o ) , w e r e recorded. twenty eyes of fifteen patients aging 4 years to 10 (mean +.05) years consisting of 45% males and 55% females were included in the study. mild anterior reaction was seen in 10 cases (50%) and moderate anterior chamber reaction was observed in only (15%) three patients (table. i). it was observed that anterior chamber reaction disappeared in all cases on the 7th post operative day. pupillary irregularity was not reported in any of these cases. there was no fibrin formation, anterior and posterior synechia, cyclitic and pupillary membrane formation. there were no intraocular lens deposits or posterior capsular opacification (pco) in any of the cases after the follow up of 6th m o n t h . h y p h e m a o r i n t r a o c u l a r hemorrhage due to heparin was not reported in any of the cases. a t e n d e n c y t o w a r d s i n c r e a s e d results discussion 30 31 postoperative inflammation in children is 7well recognized. to control post op inflammation in pediatric cataract surgery is always a challenge for eye surgeon. intraocular inflammation manifests itself as increased cells and flare, inflammatory p r e c i p i t a t e s o n t h e i o l a n d t h e endothelium, formation of synechia, and 7inflammatory cyclitic membranes. the pathogenesis of postoperative fibrinoid inflammation is unknown. the fibrinoid reaction after pediatric cataract surgery is may be caused by the breakdown of the immature blood aqueous barrier (bab) and insufficient trabecular 8meshwork fibrinolytic activity. secondary complications of severe fibrinoid reaction i n c l u d e p u p i l l a r y m e m b r a n e a n d 9opacification of the anterior hyaloid face. therefore, measures that may prevent or decrease inflammation in these eyes deserve consideration. in addition to its well-known anticoagulant activity, heparin has antii n f l a m m a t o r y a n d a n t i p r o l i f e r a t i v e p r o p e r t i e s . h e p a r i n i n h i b i t s f i b r i n formation after intraocular surgery and has also been shown to inhibit fibroblast 10 10,11activity. studies. elucidate several mechanisms through which heparin may inhibit inflammation including induction of apoptosis in human peripheral blood neutrophils, inhibition of the complement activation and lymphocyte migration, land p-selectin, adhesion-molecule support of the initial attachment of leukocytes to the vessel wall at the inflammation site, neutrophil chemotaxis, and generation of refractive oxygen species by mononuclear and polymorphonuclear leukocytes. in our study of pediatric cataract surgery, addition of heparin to the irrigating bss prevented postoperative inflammatory complications. in this study it was shown that early postoperative inflammatory reactions were 13rare. bayramlar and colleagues. also concluded that the addition of heparin to the irrigating solution during surgery decreases postoperative fibrinoid reaction and late inflammatory complications. the same was 14concluded by iverson and colleagues. in their study.hyphema, which can be thought of have occurred during surgery due to heparin irrigation, was not seen in our study. however, this risk can also be diminished by using low molecular weight 14heparin. iverson and colleagues. suggest that fragmin, at a concentration of 5 iu/ml, lowers the risk of hemorrhage during vitreoretinal and lensectomy surgeries. our results suggest that adding heparin sodium to the irrigating solution seems to be a safe, effective, and promising method to prevent early postoperative inflammatory reaction in pediatric cataract surgery. 1. taylor d. the doyne lecture. congenital cataract: the history, the nature and the practice. eye. 1998; 12:9-36. 2. lloyd i c, ashworth j, biswas s, abadi r v. advances in the management of congenital and infantile cataract .eye 2007; 21, 1301-9. conclusion references table-i: anterior chamber reaction in post operation cataract children (n=20) 31 32 3. simons bd, siatkowski rm, schiffman jc, surgical technique, visual outcome, and complications of pediatric intraocular lens implantation. j pediatr ophthalmol strabismus 1999; 36:118-24. 4. mazhar u h, umair a q, aziz u r , nasir b, rashid h a. complication and visual outcome after peadiatric cataract surgery with or without intra ocular lens implantation. pak j ophthalmol 2011; 27 30-4. 5. rumelt s, stolovich c, segal zi, rehany u. i n t r a o p e r a t i v e e n o x a p a r i n m i n i m i z e s inflammatory reaction after pediatric cataract sutgery. am j ophthalmol. 2006; 141:433-7. 6. kruger a, amon m, formanek ca, schild g, kolodjaschna j, schauersberger j. effect of h e p a r i n i n t h e i r r i g a t i o n s o l u t i o n o n postoperative inflammation and cellular reaction on the intraocular lens surface. j cataract refract surg. 2002; 28:87-92. 7. dada t. intracameral heparin in pediatric cataract surgery. j cataract refract surg. 2003; 29:1056. 8. mehta js, adams gg. r-tpa following pediatric cataract surgery. br j ophthalmol, 2000; 84:983-6. 9. charlotta z , maria k. paediatric cataract surgery .acta ophthalmol scand, 2007;85: 698-710 10. wilson me, trivedi rh. low molecular-weight heparin in the intraocular irrigating solution in pediatric cataract and intraocular lens surgery. am j opthalmol, 2006; 141:537-8. 11. yelda b ö, arzu t, nadire e, baran k, ömer k d. effect of heparin in the intraocular irrigating solution on postoperative inflammation in the pediatric cataract surgery. clin ophthalmol. 2009; 3: 363-5. 12. knight-nanan d, o'keefe m, bowell r. outcome and complications of intraocular lenses in children with cataract. j cataract refract surg, 1996; 22:730-6. 13. bayramlar h, totan y, borazan m. heparin in the intraocular irrigating solution in pediatric cataract surgery. j cataract refract surg. 2004; 30:2163-9. 14. iverson d, katsura h, hartzer mk. inhibition of intraocular fibrin formation following infusion of low-molecular-weight heparin during vitrectomy. arch ophthalmol,1991; 104:405-9. 32 original�article abstract objective: to determine the frequency of depression, anxiety, and stress during covid-19 among frontline healthcare workers (doctors vs. rescuers) in pakistan. study design: cross-sectional online questionnaire survey. place and duration of study: centre for islamic psychology, riphah international university, lahore campus th th from 25 april 2020 to 20 june 2020. materials and methods: a total of 364 frontline healthcare workers (n=182 doctors and n=182 rescuers) were included in the final analysis. the depression, anxiety, stress scale (dass-21) was used to collect online data via google form through convenience sampling. statistical data analysis was done using the statistical packages for social sciences (spss-23), and the frequencies, percentages, mean, and standard deviation were calculated. independent samples-t test was employed to identify differences between doctors and rescuers on depression, anxiety, and stress scale. results: the mean age of the participants was 28.79 + 5.46 years. the study identified highly significant difference in depression (t (363) = 11.10, p<.01), anxiety (t (363) = 7.30, p<.01), and stress (t (363) = 10.21, p<.01) between doctors and rescue workers during covid-19. the majority of doctors reported a moderate level of depression (41%), extremely severe anxiety (30%), and a moderate level of stress (22%), while the majority of rescue workers reported a moderate level of depression (21%), moderate anxiety (14%) and extremely severe stress (10%). conclusion: the frequency of depression, anxiety, and stress is higher among doctors as compared to rescuers. the study has manifold implications for healthcare workers and psychological health professionals to implement preventive and intervention programs to combat psychological problems. key words: anxiety, covid-19, depression, frontline workers, stress. world health organization (who) declared covid19 as a fatal respiratory disease with a public health emergency of global concern. who provided some guidelines to manage this novel virus at the primary level covid-19 is the third pandemic after sars and 2 mers. evidence from these epidemics also indicates that the sudden onset and life-threatening disease exposed healthcare professionals to long-lasting 3 mental health problems. to prevent the rapid transmission rate of this disease, one of the major guidelines is social distancing. however, doctors and rescuers were the only volunteers who instead of distancing themselves provided first-hand treatment to the sufferers. doctors are front-line workers treating patients with a transmittable pathogen, covid-19 positive, and those who are suspected cases. dealing with the mass quarantine of patients is also a causal factor of stress and anxiety among healthcare workers. during the outbreak of severe acute respiratory syndrome, introduction a constant threat of confronting both natural and man-made disasters is faced by healthcare workers. from swine flu pandemics in 2009 to the earthquake, tsunami in northern japan, and the recent corona virus cases initially reported in wuhan have changed healthcare workers, especially doctors and rescue workers perception of disaster preparedness. from wuhan, china a fatal respiratory disease (covid-19) started and became a major physical and mental 1 health threat for almost 160 countries. in 2020, the depression, anxiety, and stress among frontline healthcare workers during covid19 goolam hussein rassool, kalsoom nawaz, sara latif, umair mudassar correspondence: sara latif lecturer higher education department, islamabad e-mail: saralatif31@yahoo.com department of psychology riphah institute of clinical & professional psychology riphah international university, lahore, pakistan received: june 21, 2021; revised: november 28, 2022 accepted: may 06, 2023 jiimc 2023 vol. 18, no. 2 depression, anxiety & stress among healthcare workers 121https://doi.org/10.57234/jiimc.june23.633 it was identified that healthcare workers experienced anxiety, fear, depression, and 4,5 frustration. all healthcare professionals were involved, directly and indirectly, in working with patients during the covid-19 epidemic. the rescue 1122 team was formulated specially to work as a rapid-response crisis management team to combat the crisis and traumatic events. providing prehospital services during the pandemic eventually increases their vulnerability to stress and other psychological or emotional problems among 6 healthcare professionals. many studies found that without safeguarding their mental health and receiving adequate training in the medical and psychosocial management of this pandemic, healthcare workers experienced many mental health 7 problems. to the patients, the quality of healthcare services may be affected by the psychological problems faced by healthcare workers because of a prolonged and high level of work-related stress. for healthcare workers to ensure psychological well-being, a planned strategy is thus required. mental health problems and the risk of infections are highest for the 8 people working in hospitals . globally, the pervasiveness of depression, anxiety, and stress during the pandemic varied among various frontline workers. the reason may be an active number of cases and available resources to combat the covid9 19 pandemic. a chinese study reported almost half of the health care workers experienced depression 50.4%, anxiety 44.6%, insomnia 34% and 71.5% 10 reported distress. the healthcare workers are life saviors for their nation to care for and manage the pandemic covid-19. frontline healthcare workers who ultimately save human lives, their own physical 11 and psychological health is most important. there is limited literature available in pakistan on psychological issues faced by frontline health care workers (doctors vs. rescuers) and likewise, there is the unavailability of any evidence-based training manual/ guide for disaster preparedness of health care workers and their psychological well-being. therefore, there is a need to assess the psychological health of workers (doctors vs. rescuers) who were serving at their official locations during an epidemic situation in pakistan. the present study was conducted to examine the incidence of psychological disorders i.e., depression, anxiety, and stress among frontline healthcare workers and rescuers in the peak times of covid-19 in pakistan. for this purpose, the two groups, doctors and rescuers, were selected to measure the levels of depression, anxiety, and stress. this study has manifold implications such as it will guide the importance of the development of a manual for disaster preparedness for healthcare workers and psychological intervention at the primary level. the objective of this present study was to determine the incidence of depression, anxiety, and stress among frontline healthcare workers and rescuers in pakistan during covid-19. materials and methods in the present study, a cross-sectional online questionnaire survey design was employed. it was th th conducted between 25 april 2020 to 20 june 2020, in different sectors such as services hospital, jinnah hospital, lahore; district health authority, sialkot, coronavirus field hospital hockey stadium, sialkot to collect data from doctors. whereas the different rescue stations from lahore, sheikupura, kasur, sialkot, gujranwala, and gujrat were targeted to collect data from rescuers during the strict lockdown due to covid-19 in pakistan. the 364-sample size of both groups doctors and rescuers were gathered online on google software form through whatsapp and emails by using convenience sampling and 360 valid responses were gathered (response rate = 72%). the present research was conducted by following all ethical principles. foremost, ethical committee approval was sought from the departmental academic & research committee (darc) which works as an institutional review board (irb). after that, informed consent was taken from every participant by adding it at the beginning of the google software form. the aim and nature of the research were clarified to them. further, a demographic sheet was attached along with the depression, anxiety, and stress scale after the informed consent. participants were assured of the provision of secrecy and confidentiality of data, and the significance of the current study. the participants' anonymity was reserved by giving the code to every response sheet. the participants included in the study were medical doctors who were providing tertiary care to patients jiimc 2023 vol. 18, no. 2 122 depression, anxiety & stress among healthcare workers https://doi.org/10.57234/jiimc.june23.633 diagnosed with covid-19 in coronavirus wards and emergencies. in addition, some rescuers work to bring people out of harm after a disaster, such as receiving the patients from their doors, giving emergency treatments, and caring for them on their way to treatment centers and hospitals. the exclusion criteria of this study participants were doctors and rescuers not directly dealing with the patients diagnosed with covid-19 and not available round the clock in emergency settings. besides the demographic sheet, to measure depression, anxiety, and stress levels, dass questionnaire was used. it is developed by loviband 12 and it consists of 21 items. it includes three selfreported subscales i.e., depression, anxiety, and stress. every subscale comprised of 7 items with a 0 to 4-point likert scale from (0) did not apply to me, (3) applied to me very much to rate the level of severity that an individual experienced in every state from the past week. the reliability coefficient is 92. the subscale depression measures the dysphoric mood, depreciation of life, desperation, selfcriticism, anhedonia, and inertia while the subscale anxiety evaluates autonomic stimulation, muscular effects, a feeling of anxiousness, and anxiety from situations. the subscale stress assesses chronic unspecified arousal, being disturbed, perplexed, nervousness, impulsiveness, irritability, being spontaneous, and impatient. the cumulative score can be obtained by the sum of each subscale. a high score showed a high level of respective construct and vice versa. this measure provides the range of scorers from normal to mild, moderate to severe, and extremely severe. subsequently, data entry, data analysis, and data reporting were accomplished fairly. the data was analyzed on statistical packages for social sciences (spss-23). the frequency of depression, anxiety, and stress were measured through descriptive statics including frequencies, percentages, mean and standard deviation of demographic variables represented in tabular as well as graphical form. further, t-test analysis was used to see the differences among doctors and rescue workers on depression, anxiety, and stress. results the mean age of the participants in this study was 28.79 + 5.46 years. a total of 254 (69.8%) participants were less than 30 years, 95 (26%) were of age range 30 – 40 years and 15 (4%) were above 40 years. a total of 250 (68.7%) participants were male and 114 (31%) were female and majority of the participants 153 (42%) reported the major source of information regarding covid-19 to be tv news. furthermore, t test revealed highly significant difference in depression (t (363) = 11.10, p<.01), anxiety (t (363) = 7.30, p<.01), and stress (t (363) = 10.21, p<.01) between doctors and rescue workers during covid19. as also illustrated in figure 1, the majority of doctors' responses depict that they experience different levels of depression, anxiety, and stress during covid-19. the responses of doctors showed that the average level of depression, anxiety, and stress experienced was (10.4%: 14.8%: and 28.6% respectively). furthermore, the mild level of depression, anxiety, and stress was (15.9%: 15.4%: 15.9% respectively) and the moderate level of depression, anxiety, and stress was reported to be (40.7%: 18.1%: 26.4% respectively). severe levels of depression, anxiety, and stress experienced by the doctors emerged to be (12.1%: 22.0%: and 15.4% respectively). the participant responses indicate that the extremely severe level of depression, anxiety, and stress was (20.9%: 29.7%: and 13.7% respectively). the responses of the doctors indicated that participants could manage stress during covid19, and the results of the participants show a greater degree of depression and anxiety over covid-19. figure 2 illustrates the number of rescue workers experiencing different levels of depression, anxiety, and stress during covid-19. the majority of participants' rescue worker's responses showed that the average level of depression, anxiety, and stress was (50.5%: 42.9%: and 75.3% respectively). the results of the participants showed that mild level of depression, anxiety, and stress was (21.5%: 19.8%: and 5.5% respectively). the result of moderate depression anxiety and stress was (21.5%: 13.7%: and 7.7% respectively). the participants' responses indicate that the levels of severe depression, anxiety, a n d st re s s we re ( 2 . 7 % : 1 3 . 2 % : a n d 7 . 1 % respectively). the ratio of extremely severe depression, anxiety, and stress was (3.8%: 10.4%: and 4.4% respectively). the results of rescue workers showed that participants manage their depression, jiimc 2023 vol. 18, no. 2 123 depression, anxiety & stress among healthcare workers https://doi.org/10.57234/jiimc.june23.633 anxiety, and stress in a better way during covid-19. the psychometric properties of the questionnaire revealed cronbach's alpha reliability coefficient r= .88 for the depression subscale, anxiety r=.78, and stress r=.88. doctors and rescue workers emerged which further indicates that doctors are more likely to experience it comparatively. the results of the present study are in congruence with the studies that highlight differences between frontline health care workers i.e. doctors vs. rescue workers experiencing psychological problems. the findings of the study by elbay et al. (2020) indicate that the frontline workers are more prone to mental health problems due to increased working hours, and increased no of covid19 patients cared for. it was found that 64.7% of doctors reported depressive symptoms, anxiety 13, 14 51.6%, and 41.2% stress-related symptoms. in another study that was conducted by vagni, maiorano, giostra, and pajardi (2020), the findings showed that healthcare workers were more prone to stress and arousal than other workers in emergency settings. furthermore, the medical professionals dealing directly with the patients of covid-19 and are involved in their treatment were experiencing more levels of stress and were more susceptible to 15 developing secondary trauma. the findings of the study also revealed that the majority of the doctors experienced moderate levels of depression. whereas few doctors also reported table i: descriptive statistics of demographic variables of the sample (n=364) note. f = frequency, % = percentage, m = mean table ii: differences between doctors and rescuers in the study variables (n = 364). note. ***p<.001, ll = lower limit, ul = upper limit ci = confidence interval fig. 1 doctors experiencing depression, anxiety, and : stress during covid-19 (n=182). fig. 2: rescue workers experiencing depression, anxiety, and stress during covid-19 (n= 182) discussion the findings of the current study depict that frontline health care workers (both doctors and rescue workers) experienced depression, anxiety and stress during covid-19 outbreak. highly significant difference in depression, anxiety, and stress between jiimc 2023 vol. 18, no. 2 124 depression, anxiety & stress among healthcare workers https://doi.org/10.57234/jiimc.june23.633 severe anxiety and an extremely severe form of stress. the results are consistent with the findings by amin et al. (2022) in which the prevalence rate of depression/anxiety was (43%) reported among 16,17 frontline physicians in pakistan. ullah et al. (2022) reported one-third of healthcare workers had depression while half had anxiety during this 18 outbreak of covid-19. also salman et al. (2022) supported the current study by reporting the higher level of depression in frontline healthcare workers 19 including doctors, nurses, and pharmacists. its evident from the literature also that major threat to covid-19 were the speculations regarding rapid transmission and unavailability of prevention protocols and vaccination and subsequently the 16 development of psychological problems. in the current study majority of the rescuers also reported moderate level of depression. few rescuers also had reported severe anxiety and extremely severe stress. the findings of the existing study are in line with the findings by ahmad et al. (2015), the rescue workers experienced severe and extreme severe levels of depression and anxiety symptoms 20 during their daily life. a study conducted by sandesh et al. (2020) provides similar findings such as the highest levels of depression, anxiety and stress levels of healthcare employees emerge from the pandemic 21 and in emergencies. the findings showed 32.6 and 45.7 percent of the participants were experiencing severe and extremely severe levels of depressive and anxiety symptoms respectively. moreover, the source of information regarding covid-19 was requested from respondents. the majority of the sample (42%) relied on television news and others take an update from social media networks including whatsapp, facebook, twitter, and also from newspapers, tv programs, and friends. the media coverage created more distressing consequences during the outbreak of 15, 22 sars. hence, the intensity of depression, anxiety, and stress may increase because of consistent exposure to media. limitations firstly, a total of 182 doctors and 182 rescue workers' data was retained (response rate = 72%). the dropout rate was high due to doctors' and rescuers' hectic routines, responsibilities, and time constraints. secondly, the research was based on a self-administered questionnaire and thus, could not confidently depend on self-reported data on depression, anxiety, and stress. also, the p a r t i c i p a nt ' s e n ga ge m e nt i n d e a l i n g w i t h coronavirus was not directly observed and assessed. thirdly, this study couldn't differentiate the specialization among doctors that work with joint hands in this pandemic phase. fourthly, it doesn't include the other health care workers such as nurses, and paramedical staff. recommendations during pandemics and emergency settings, h e a l t h ca re wo r ke rs ( d o c to rs , n u rs e s , a n d paramedical staff) and rescuers are the frontline employees that provide essential services to the general public. therefore, it was a dire need to design a study that targets the assessment of mental health risks among these groups. thus in addition to this study, qualitative research (interviews and case studies) can generate more rich data that would further guide the need of developing crisis 16 intervention strategies at the national level. it is further recommended that outcome-based studies should be designed that investigate the efficacy of p syc h o l o g i c a l t re a t m e n t p ro g ra m s a m o n g healthcare workers. conclusion both doctors and rescuers are always on the front line in face of any calamity. both professions are associated with a risk of mental health problems. however, doctors are more prone to experience depression, anxiety, and stress as compared to rescuers. almost half of the doctors experienced moderate levels of depression, one-third had anxiety th and stress whereas the 1/4 of rescuers experienced moderate levels of depression and only few had experienced severe anxiety and severe stress. references 1. li q, guan x, wu p, wang x, zhou l, tong y, et al. early transmission dynamics in wuhan, china, of novel coronavirus–infected pneumonia. new england journal of medicine. 2020 jan 29; 382(13):1199-207. doi: 10.1056/nejmoa2001316 2. jiloha rc. covid-19 and mental health. epidemiology international (e-issn: 2455-7048). 2020 mar 25; 5(1):7-9. doi: 10.24321/2455.7048.202002 3. liua x, kakadeb m, fullerb cj, fanb b, fangc y, and kongc j, jiimc 2023 vol. 18, no. 2 125 depression, anxiety & stress among healthcare workers https://doi.org/10.57234/jiimc.june23.633 et al. depression after exposure to stressful events: lessons learned from the sars epidemic. compr psychiatry. 2012 jan; 53(1):15-23. doi: 10.1016/j.comppsych.2011.02.003 4. chong my, wang wc, hsieh wc, lee cy, chiu nm, yeh wc, et al. psychological impact of severe acute respiratory syndrome on health workers in a tertiary hospital. the british journal of psychiatry. 2004 aug; 185(2):127-33. doi: 10.1192/bjp.185.2.127. 5. goulia p, mantas c, dimitroula d, mantis d, hyphantis t. general hospital staff worries, perceived sufficiency of information and associated psychological distress during the a/h1n1 influenza pandemic. bmc infectious diseases. 2010 dec; 10(1):1-1. doi: 10.1186/1471-2334-10-322. 6. drapeau a, marchand a, beaulieu-prévost d. epidemiology of psychological distress. mental illnesses-understanding, prediction, and control. 2012 jan 5; 69:105-6. doi:10.5772/30872 7. greene t, harju-seppänen j, adeniji m, steel c, grey n, brewin cr, et al. predictors and rates of ptsd, depression and anxiety in uk frontline health and social care workers d u r i n g c o v i d 1 9 . e u r o p e a n j o u r n a l o f psychotraumatology. 2021 jan 1; 12(1):1882781. doi: 10.1080/20008198.2021.1882781 8. xing lq, xu ml, sun j, wang qx, ge dd, jiang mm, et al. anxiety and depression in frontline health care workers during the outbreak of covid-19. international journal of social psychiatr y. 2021 sep; 67(6):656-63. doi: 10.1016/j.heliyon.2021.e08570 9. rana w, mukhtar s, mukhtar s. mental health of medical workers in pakistan during the pandemic covid-19 outbreak. asian journal of psychiatry. 2020 jun; 51:102080. doi: 10.1016/j.ajp.2020.102080 10. lai j, ma s, wang y, cai z, hu j, wei n, et al. factors associated with mental health outcomes among health care workers exposed to coronavirus disease 2019. jama network open. 2020 mar 2; 3(3):e203976. doi: 10.1001/jamanetworkopen.2020.3976 11. chen q, liang m, li y, guo j, fei d, wang l, et al. “mental health care for medical staff in china during the covid-19 o u t b r e a k ” : c o r r e c t i o n . d o i : 1 0 . 1 0 1 6 / s 2 2 1 5 0366(20)30078-x. 12. lovibond pf, lovibond sh. the structure of negative emotional states: comparison of the depression anxiety stress scales (dass) with the beck depression and anxiety inventories. behaviour research and therapy. 1995 mar 1; 33(3):335-43. doi: 10.1016/0005-7967(94)00075-u. 13. elbay ry, kurtulmuş a, arpacıoğlu s, karadere e. depression, anxiety, stress levels of physicians and associated factors in covid-19 pandemics. psychiatry r e s e a r c h . 2 0 2 0 m a y 2 7 : 1 1 3 1 3 0 . d o i : 10.1016/j.psychres.2020.113130. 14. tang l, bie b, park se, zhi d. social media, and outbreaks of emerging infectious diseases: a systematic review of literature. american journal of infection control. 2018 sep 1; 46(9):962-72. doi: 10.1016/j.ajic.2018.02.010. 15. vagni m, maiorano t, giostra v, pajardi d. hardiness, stress and secondary trauma in italian healthcare and emergency workers during the covid-19 pandemic. sustainability. 2020; 12(14):5592. doi: 10.3390/su12145592. 16. li s, wang y, xue j, zhao n, zhu t. the impact of covid-19 epidemic declaration on psychological consequences: a study on active weibo users. international journal of environmental research and public health. 2020 jan; 17(6):2032. doi: 10.3390/ijerph17062032. 17. amin f, sharif s, saeed r, durrani n, jilani d. covid-19 pandemic-knowledge, perception, anxiety and depression among frontline doctors of pakistan. bmc psychiatry. 2020 dec; 20(1):1-9. doi: 10.1186/s12888-020-02864-x. 18. ullah i, khan ks, ali i, ullah ar, mukhtar s, de filippis r, et al. depression and anxiety among pakistani healthcare workers amid covid-19 pandemic: a qualitative study. annals of medicine and surgery. 2022 jun 1; 78:103863. doi: 10.1016/j.amsu.2022.103863. 19. salman m, mustafa zu, raza mh, khan tm, asif n, tahir h, et al. psychological effects of covid-19 among health care workers, and how they are coping: a web-based, crosssectional study during the first wave of covid-19 in pa k i sta n . d i s a ste r m e d i c i n e a n d p u b l i c h e a l t h preparedness. 2023; 17:e104. doi: 10.1017/dmp.2022.4 20. ahmad s, arshad t, kausar r. psychological correlates of distress in rescue 1122 workers in pakistan. international journal of emergency mental health and human r e s i l i e n c e . 2 0 1 5 ; 1 7 ( 2 ) : 4 8 6 9 4 . d o i : 10.15537/smj.2016.7.15004 21. sandesh r, shahid w, dev k, mandhan n, shankar p, shaikh a, et al. impact of covid-19 on the mental health of healthcare professionals in pakistan. cureus. 2020 jul; 12(7). doi: 10.7759/cureus.8974. 22. ho cs, chee cy, ho rc. mental health strategies to combat the psychological impact of covid-19 beyond paranoia and panic. ann acad med singapore. 2020 jan 1; 49(1):1-3. https://pubmed.ncbi.nlm.nih.gov/32200399/. jiimc 2023 vol. 18, no. 2 126 depression, anxiety & stress among healthcare workers https://doi.org/10.57234/jiimc.june23.633 conflict of interest authors declared no conflicts of interest. grant support and financial disclosure authors have declared no specific grant for this research from any funding agency in public, commercial or nonprofit sector. data sharing statment the data that support the findings of this study are available from the corresponding author upon request. this is an open access article distributed under the terms of the creative commons attributionnoncommercial 2.0 generic license. jiimc 2023 vol. 18, no. 2 127 depression, anxiety & stress among healthcare workers https://doi.org/10.57234/jiimc.june23.633 case�report abstract any rotation of uterus along its long axis which is more than 45 degrees at the junction between corpus and 1,2 cervix [figure 1] is called uterine torsion. torsion of uterus is a rare phenomenon, and the true pathogenesis 3 of the condition is still not clear. here we present a case of complete uterine torsion in a 37-year-old lady who underwent cesarean section at 39 weeks of gestation due to oblique lie. this patient had two small uterine fibroids and, in the past, she had right salpingectomy for right tubal pregnancy. intra-operatively, due to complete torsion of uterus, inadvertently incision was given in the posterior wall of uterus considering it as anterior wall, but hemostasis was successfully secured and post operatively patient recovered well. this case illustrates that while doing cesarean section on gravid uterus especially in the background of previous pelvic surgery and in the presence of fibroids, obstetricians must exercise caution to identify torsion of uterus which is through a rare but significant uterine pathology that can cause incorrect posterior uterine wall incision. key words: uterine torsion, fibroids, posterior wall incision. with good apgar scores, placenta and membranes were removed completely and then uterus was exteriorized after adhesionolysis. only on exteriorization of uterus it could be identified that uterus had complete torsion of 180 degrees along its long axis and seemingly anterior wall of uterus was in fact its posterior wall. uterus was closed in layers and then interiorized. hemostasis was successfully secured, and an intraperitoneal drain was left in situ in pouch of douglas and abdomen was closed in layers. estimated blood loss was about 1.0 liter and patient received two units of blood. postoperatively she was kept under observation in high dependency area. drain was removed after 24 hours of surgery. postoperatively her hemoglobin was 8 g/dl while her pre-op hemoglobin was 10.1g/dl. patient was discharged from hospital on third postoperative day along with her baby. she was also well on her postoperative follow-up in opd. case a pregnant lady in her fifth pregnancy presented in gynecology opd at 39 weeks of gestation with oblique lie. previously she had three vaginal births and also had right salpingectomy for tubal pregnancy. after laparotomy she had conceived after a significant period of infertility. course of her index pregnancy had remained unremarkable till her last visit in opd. her obstetrical ultrasound revealed a single live fetus in oblique lie with adequate liquor and lower edge of placenta was away from cervical os. ultrasound also revealed a small 4 ×4 cm fibroid in the anterior uterine wall. she was booked from opd for elective cesarean section. after preoperative preparation, cesarean section was performed. intra operatively, bowel was found adherent with both uterus and anterior abdominal wall especially on left side. right adnexa appeared as a totted band of peritoneum that after crossing in front of the uterus became adherent with the left side of uterus. it was pushed aside, and uterine incision was made. a small fibroid about 3 ×4 cm in the course of uterine incision got separated. a female baby was delivered uterine torsion, leading to posterior uterine wall incision at cesarean section ayman khalil othman al-tarifi, nafees akhtar, aladin alhadi alamri correspondence: dr. nafees akhtar department of obstetrics & gynecology maternal and children hospital, arar, kingdom of saudi arabia e-mail: akhtarnafees29@gmail.com department of obstetrics & gynecology maternal and children hospital, arar, kingdom of saudi arabia funding source: nil; conflict of interest: nil received: august 01, 2021; revised: september 01, 2021 accepted: september 05, 2021 uterine torsion in pregnancyjiimc 2021 vol. 16, no.3 fig. 1: torsion of uterus caused by rotation of uterus along its long axis at the junction between corpus uteri and cervix 200 discussion though the true etiology of uterine torsion is still unknown, but a number of conditions have been proposed causing this pathology which include adhesions due to previous surgeries, fibroid uterus, ovarian tumors, uterine malformations and fetal 1-3 malpresentation. in our case patient has pelvic adhesions due to previous surgery for right salpingectomy, two uterine fibroids in the anterior uterine wall and fundal region, and also the lie of baby was oblique. in accordance with previous literature all these factors may have caused uterine torsion in our case. uterine torsion can develop at any maternal age, parity, or gestational age. as presentation can be non-specific with or without any 4,5 symptoms, in our case due to the absence of any symptoms as well as due to the rarity of the condition, uterine torsion was diagnosed only at the time of cesarean section. the degree of uterine torsion may vary from 45 degrees to 180 degrees and in literature cases with even 720-degree torsion have 4-6 been reported. in our case as the right adnexal structures became adherent with adnexal structures on left side, apparently this may have caused a large 3 torsion in uterus of about 180 degrees. theoretically, pelvic anatomical misalignment caused by uterine torsion may be one of the elements for secondary subfertility after laparotomy, in this case. besides uterine torsion separation of small myoma across the uterine incision was managed without much trouble and also previously cases of unplanned but inevitable myomectomies at the time of cesarean 7 sections have been reported without complications. in our case despite the undiagnosed uterine torsion the good handling of cesarean section by the expert operator ensured good maternal and fetal outcome but in the literature a 12-15% perinatal mortality rate 4,8 has been reported in such cases. this case emphasizes that in the presence of risk factors of uterine torsion obstetricians should be cautious to recognize the pelvic anatomical alignment completely in order to avoid incorrect uterine incision and the resulting increased maternal and fetal morbidity. conflict of interest: there is no conflict of interest among authors related to this manuscript. patient consent: informed consent for cesarean section was taken. references 1. dua a, fishwick k, deverashetty b. uterine torsion in pregnancy: a review. the internet j gynecol obstet. 2005; 6(1): 1-3. 2. bukar m, moruppa jy, ehalaiye b, ndonya dn. uterine torsion in pregnancy. j obstet gynecol. 2012 nov; 32(8):805–6. 3. hoffmann s, jayaratnam s. uterine torsion–a case report and literature review. glob j reprod med. 2018; 5(2): 555664. doi: 10.19080/gjorm.2018.05.555664. 4. choiy h, guisera l. uterine torsion in third trimester pregnancy. korean j perinatol. 2016; 27(1): 67-69. 5. farhadifar f, bahram n, shahgheibi s, soofizadeh n, rezaie m. asymptomatic uterine torsion in a pregnant woman. indian j surg 2014; 76:321-2. 6. sachan r, patel ml, sachan p, arora a. complete axial torsion of pregnant uterus with leiomyoma. bmj case report published online: [2015 sep 5]. available from: http://dx.doi.org/10.1136/bcr-2014-205558 [cited on 10 december 2020]. 7. rich da, stokes im. uterine torsion due to a fibroid, emergency myomectomy and transverse upper segment cesarean section. bjog: an international journal of obstetrics and gynecology. 2002; 109: 105-106. 8. wilson d, mahalingham a, ross s. third trimester uterine torsion: case report. j obstet gynecol canada. 2006; 28:531-5. uterine torsion in pregnancyjiimc 2021 vol. 16, no.3 201 original�article abstract objective: this study was aimed to assess parental perception and attitudes regarding dietary and oral hygiene habits of their children. study design: questionnaire based survey place and duration of study: parents of children who visited a tertiary care dental hospital in peshawar over a period of 1 year (july 2019 to june 2020) were encompassed in this study. materials and methods: parents of 352 children aged 1-6 years visiting a tertiary care hospital were asked to fill a questionnaire with ajzen's theory of planned behavior consisting of standard questions about intention, attitude, subjective norms, perceived behavioral control, indulgence, maternal oral health behavior and dietary habits and scored on likert's scale. results: out of 352 interviewed, parents showed average attitudes, subjective norms, and perceived behavioral control (pcb) with mean scores of 4.61, 5.54,7.89 respectively.72.44% of the study sample confirmed weak intentions towards brushing their child's teeth. general multivariate regression model analysis revealed a significant correlation of attitudes, subjective norms, and pcb towards intention. however, strong intenders showed weak indulgence (mean 5.05). 87% of the parents were not accustomed with the fact that nighttime breastfeeding can cause caries. conclusion: parents showed weak perception and intentions towards brushing their children's teeth twice daily which might endure a negative impact on their child's oral health and should be addressed while designing policies concerning oral health. key words: caries, intention, indulgence, perception, subjective norms. perceptions serving as major contributing factors 2,3,4 towards the origin of this disease . in general ecc is m o r e p r e v a l e n t i n c h i l d r e n w i t h l o w e r 5,6 socioeconomic status in developed countries . 6 however, the reverse was reported in pakistan . being multifactorial, ecc for instance is influenced by a variety of parental factors including parental own oral hygiene habits, parental distress, dysfunctional parental behaviors and especially an association between maternal and toddler's tooth brushing 7,8 habits is reported . a study reported that parental own oral heath related knowledge, attitudes and being proactive towards dental treatment of their children had a greater impact on caries score of the 9 children then their own behaviors . theory of planned behavior (tpb) has successfully explained a wide divergence in several healthrelated behaviors including behaviors related to oral 10 hygiene care . according to tbp, the very intention to perform a behavior is the actual predecessor of performing that very behavior for instance, tooth brushing. this intention to brush is then influenced by their attitudes toward brushing, subjective norms about brushing and perceived behavioral control introduction early childhood caries (ecc) is a multifactorial disease in primary teeth of children aged 6 years or less presenting with any caries, cavitated or filled 1 tooth surface in one or many teeth . conferring to various theoretical models at multilevel, the burden of ecc is multifactorial in origin and involves influences at individual, family and community levels and provides empirical evidence of social, cultural, ethnic, parental attitudes and knowledge of parent's perception and attitudes towards brushing their children's teeth 1 2 3 4 5 madeeha bangash , laila mustafa , shakeel kazmi , qaiser omer , ifra sana khattak correspondence: dr. madeeha bangash hod paediatric dentistry rehman college of dentistry, peshawar e-mail: madeeha.bangash@rmi.edu.pk 1,5 department of paediatric dentistry rehman college of dentistry, peshawar 2 department of paediatric dentistry shifa college of dentistry, islamabad 3 department of dentistry school of dentistry, shaheed zulfiqar ali bhutto medical university, islamabad 4 department of special care dentistry associates dental practice, islamabad funding source: nil; conflict of interest: nil received: february 08, 2021; revised: october 12, 2021 accepted: october 15, 2021 parental perception towards brushing teethjiimc 2022 vol. 17, no.1 36 11 towards tooth brushing. this study focuses on the objective of assessment of perception and attitude in the direction of brushing their children's teeth among parents visiting a tertiary care hospital in peshawar. materials and methods this baseline survey constituted parents of 352 children, aged 1-6 years who attended a tertiary care hospital in peshawar over a period of 1 year (july 2019 to june 2020). patients above 6 years were excluded from the study. sample size was calculated using g-power with effect size of 0.03 and α-error of 0.05 using convenience sampling technique. ethical ratification was obtained from the ethical committee of rehman college of dentistry (ref. no. 19-11-032). parents of the children attending paediatric dentistry were briefed about the purpose of the study and an informed consent was taken from all who volunteered for participation. a questionnaire was designed after a few revisions in an already validated interview in accordance to our 9 study population . all the questions were in accordance with the components of ajzen's theory of planned behavior highlighting their intention, attitude, subjective norms, perceived behavioral control, indulgence, maternal oral health behavior and dietary habits. each component consisted of standard questions marked on likert's scale from 15, with 1 highlighting a strong and highest number and 2-5 scores labelled as weak intentions. data analysis was done using spss version 22. to tabulate means, standard deviation and percentages of all the continuous variables, descriptive statistics were performed. eta square was used to highlight the amount of dispersion and associations. independent sample t test for parametric analysis and significance level was set at p ≤ 0.001. 95% confidence interval was used for estimating a proposed range of values. results out of 352 parents who responded, about 46% believed that children are prone to caries and the majority of parents (91%) agreed to the fact that high intake of sugar can cause caries, while 60% highlighted fizzy drinks as one source of caries. surprisingly, about 87% didn't know that caries can be caused by breastfeeding at night. ambivalence was recorded regarding the idea of introducing sugary food to their children at meals time or between meals. majority of the parents (69%) assumed that tooth brushing is only necessary after the eruption of all teeth in the mouth and in contrast to a minority of only 11% who considered tooth brushing important soon after the eruption of the first tooth in the mouth. while notably a high percentage (81.8%) was cognizant of useful effects of fluoride in the toothpaste as shown in table i. table i: frequency distribution of parent's oral hygiene knowledge parents showed favorable attitudes (mean 4.61) and subjective norms for child's brushing (mean 5.54) and a strong perceived behavioral control for tooth brushing (mean 7.89). parental indulgence for brushing showed an average mean of 5.05. while a mean of 12.03 for frequent maternal oral hygiene performance. 72.44% of the study sample confirmed weak intentions towards tooth brushing of their children's teeth as shown in table ii. 37 jiimc 2022 vol. 17, no.1 parental perception towards brushing teeth table ii: range, means and standard deviation (sd) for sum of scores for attitude, subjective norms, perception, indulgence and maternal oral hygiene behavior while keeping intention to brush their child's teeth as a fixed factor a multivariate glm (general linear model) analysis was performed as shown in table iv. the mean values provide evidence that intenders showed a more frequent attitude, subjective norms and perceived behavioral control. in contrast strong intenders showed weak indulgence and vice versa. all the components of tbp showed a significant discrimination between the two groups with partial eta squared apart from maternal oral hygiene behavior which failed to maintain a significant relationship in multivariate glm analysis. note: frequency(n) of parent's intention to brush their child's teeth twice daily n (%) table iii shows associations between intention and parental attitude and subjective norms were highly significant as revealed by independent sample t test (p<0.001) and mild significance with perceived behavioral control (p=0.006). in contrast there was no significant association found between indulgence and maternal oral hygiene behavior. table iii: independent sample t test for parent's attitude, maternal oral hygiene behavior and perception by intention to brush their child's teeth p=<0.001** table iv: effect size (partial eta squared) for parent's attitude, perception and maternal oral hygiene behavior by intention to brush their child's teeth note: intention kept as fixed factor in multivariate general linear model. p<0.001** discussion to our acquaintance this study is the first to assess intentions of tooth brushing and its covariates amongst parents of children aged 1-6 years visiting tertiary care hospital in peshawar. the results are consistent with previous studies showing that the tpb components, attitudes, subjective norms, and perceived behavioral control, were independent significant control variables of parental intention to 38 jiimc 2022 vol. 17, no.1 parental perception towards brushing teeth brush their children's teeth and supports tbp for prediction of oral health related behaviors as well as intention of the parents to superintend their child's 12,13 oral health . the appropriateness of the tpb model detected in this study harmonies with that of a metaanalysis of tbp concerning several health-related behaviors, which accounted for 44% of the 14 contradiction in behavioral intentions. this study discovered that parents with strong intention to brush their children's teeth performed their own oral hygiene habits more frequently. however, these results were not significant in multivariate regression analysis concluding that parents' own oral hygiene performance was influenced by caudal perceptions and attitudes. 15 according to theory of socialization , parental in specific mother's overt behavior has a significant influence on child's oral health behaviors implying this as a modelling process particularly in pre-school 16 children. results revealed that the parent's intention for brushing their child's teeth was motivated by their attitudes, perceived behavioral control and subjective norms in descending order. strong intentions were thus owned by those parents who perceived promising consequences following regular tooth brushing in their children (good attitude) as well as parents who felt that they were capable of managing their children's teeth twice daily (strong perceived behavioral control) and who felt prescriptive pressure from family and people they knew regarding importance of tooth brushing (favorable subjective norms).these results were consistent with previous studies in which contribution of attitudes, subjective norms and perceived behavioral control towards parental 12,17 intention was analyzed in the context of tbp . in contrast, strong indulgent parents who believed that it is not worth a quarrel to force a child to brush when he doesn't want to brush reported weak intentions to tooth brushing. therefore, an increased tendency of parental indulgence had a negative impact on their intention to brush their child's teeth twice daily. marshman z reported that despite parents being aware of the importance of tooth brushing in children in the united kingdom, child's behavioral problems as well as parent's own stress regarding their whining and timid behavior are the actual barriers towards implementation of tooth brushing 18 habits in their children. the behavioral mediators identified in this study can serve as substantial tools for designing communitybased caries prevention programs. the level of the associations and the synchronization of the findings with tbp is an indicator of the reliability and validity of the results. however, when it comes to face-toface interviews, social desirability, which is the tendency of survey respondents to answer questions in manner that is deemed to be more socially favorable than their true answers to escape negative evaluation, is one of the major documented 19 problems . it can take the form of “overreporting” a good behavior or “under-reporting” a bad behavior. therefore, the major limitation of this study was an inclination towards socially desirable which may be accredited to the very datum that p a re n t s w e re g e n e ra l l y c o nv e rs a n t a b o u t precautionary measures for caries anticipation. vagueness about the timing of giving sugary snacks to their kids was recognized as an area of ambiguity. 20 in accordance with previous study , the majority of mothers did not recognize nighttime breastfeeding as a contributory factor for caries. parental ignorance in this matter must be catered with awareness programs regarding this rehearsal, nevertheless, cultural as well as religious traditions that cheers breastfeeding till 2 years must be well-thought21,22 out. conclusion overall parents reported weak perception and intention for regular tooth brushing behaviors. to motivate parents about their child's dietary and oral health related practices, their attitudes, subjective norms, and perceived behavioral control seems to be more important than their accurate oral health related information and should be addressed while designing oral health policies. references 1. seow wk. biological mechanisms of early childhood caries. community dentistry and oral epidemiology. 1998 oct;26(s1):8-27. 2. reisine st, psoter w. socioeconomic status and selected behavioral determinants as risk factors for dental caries. journal of dental education. 2001 oct;65(10):1009-16. 3. petersen pe. sociobehavioural risk factors in dental caries–international perspectives. community dentistry 39 jiimc 2022 vol. 17, no.1 parental perception towards brushing teeth and oral epidemiology. 2005 aug;33(4):274-9. 4. hooley m, skouteris h, boganin c, satur j, kilpatrick n. parental influence and the development of dental caries in children aged 0–6 years: a systematic review of the literature. journal of dentistry. 2012 nov 1;40(11):873-85. 5. knoblauch u, ritschel g, weidner k, mogwitz s, hannig c, v i e rg u t z g , l e n k m . t h e a s s o c i at i o n b e t we e n socioeconomic status, psychopathological symptom burden in mothers, and early childhood caries of their children. plos one. 2019 oct 28;14(10):e0224509. 6. sami a, bangash m, mustafa l, shiraz f, khan ga, nazir u. “influence of socioeconomic status on caries score among primary school children of peshawar”. the professional medical journal. 2019 oct 10;26(10):1738-41. 7. rai nk, tiwari t. parental factors influencing the development of early childhood caries in developing nations: a systematic review. frontiers in public health. 2018 mar 16;6:64. 8. kim seow w. environmental, maternal, and child factors which contribute to early childhood caries: a unifying conceptual model. international journal of paediatric dentistry. 2012 may;22(3):157-68. 9. skeie ms, klock ks, haugejorden o, riordan pj, espelid i. tracking of parents' attitudes to their children's oral healthre l ate d b e h av i o r – o s l o, n o r way, 2 0 0 2 – 0 4 . a c ta odontologica scandinavica. 2010 jan 1;68(1):49-56. 10. ajzen i. the theory of planned behaviour: reactions and reflections. 11. beale da, manstead as. predicting mothers' intentions to limit frequency of infants' sugar intake: testing the theory of planned behavior 1. journal of applied social psychology. 1991 mar;21(5):409-31. 12. soltani r, sharifirad g, mahaki b, eslami aa. determinants of oral health behavior among preschool children: application of the theory of planned behavior. journal of dentistry. 2018 dec;19(4):273. 13. kasmaei p, bitama f, mehrabian f, ashouri a, abbasi kakrodi m, karimy m. predicting tooth brushing behavior among students in guilan, north of iran: an application of the theory of planned behavior. international journal of pediatrics. 2020 jun 1;8(6):11473-83. 14. mceachan rr, conner m, taylor nj, lawton rj. prospective prediction of health-related behaviours with the theory of planned behaviour: a meta-analysis. health psychology review. 2011 sep 1;5(2):97-144 15. heffernan cj. social foundations of thought and action: a social cognitive theory, albert bandura englewood cliffs, new jersey: prentice hall, 1986, xiii+ 617 pp. hardback. us $39.50. behaviour change. 1988 mar;5(1):37-8. 16. mattos mg, fernandez ca, masterson d, maia lc, de almeida neves a. is the caregivers' oral health related to dental caries in children or adolescents? a systematic review. clinical oral investigations. 2019 oct;23(10):384354. 17. van den branden s, van den broucke s, leroy r, declerck d, hoppenbrouwers k. predicting oral health-related behaviour in the parents of preschool children: an application of the theory of planned behaviour. health education journal. 2015 mar;74(2):221-30. 18. marshman z, ahern sm, mceachan rr, rogers hj, grayburrows ka, day pf. parents' experiences of toothbrushing with children: a qualitative study. jdr clinical & translational research. 2016 jul;1(2):122-30. 19. mcdowell i. measuring health: a guide to rating scales and questionnaires. oxford university press, usa; 2006. 20. dhull ks, dutta b, devraj im, samir pv. knowledge, attitude, and practice of mothers towards infant oral healthcare. international journal of clinical pediatric dentistry. 2018 sep;11(5):435. 21. hartwig ad, romano ar, azevedo ms. prolonged breastfeeding, and dental caries in children in the third year of life. journal of clinical pediatric dentistry. 2019;43(2):916. 22. santos bz, dotto pp, guedes rs. breastfeeding and risk of dental caries. epidemiologia e servicos de saúde. 2016; 25:633-5. 40 jiimc 2022 vol. 17, no.1 conflict of interest authors declared no conflicts of interest. grant support and financial disclosure authors have declared no specific grant for this research from any funding agency in public, commercial or nonprofit sector. data sharing statment the data that support the findings of this study are available from the corresponding author upon request. this is an open access article distributed under the terms of the creative commons attributionnoncommercial 2.0 generic license. parental perception towards brushing teeth original�article abstract conclusion: ropivacaine was more effective in reducing post episiotomy perineal pain as compared to lignocaine. study design: randomized controlled trial. materials and methods: in this study 100 patients with singleton pregnancy and vertex presentation undergoing vaginal deliveries were randomly divided into either 2% lignocaine group or 0.75% ropivacaine group on the basis of subcutaneous infiltration of the corresponding local anesthetic before perineal repair. main outcomes studied between the 2 groups include mean pain scores assessed by visual analogue scoring system (vas) at the time of suturing and then at 30 mins, 3 hours and 6 hours post partum. the need for additional local anesthetic, on-demand analgesia and side effects were also noted. the outcomes between the two groups were compared and analyzed by spss version 23. key words: analgesia, lignocaine, ropivacaine. place and duration of study: this prospective trial was conducted in gynecology and obstetrics department of kahuta research laboratories (krl) hospital, islamabad over the period of 3 months from may 2018 to august 2018. results: a total of 100 women were randomized and equally allocated into one of the two groups. mean pain score of ropivacaine was compared with lignocaine and was found to be significantly reduced at the time of suturing (p=0.005), 3 hours (p=0.00) and 6 hours (p=0.001) post partum. but no statistical difference was found in pain score at 30 minutes post partum (p=0.713). the need for additional local anesthetic at suturing (p=0.004) and need for on-demand analgesia (p=0.001) was higher in lignocaine group. no side effects were noted in both groups. objective: to compare the analgesic efficacy of ropivacaine (0.75%) with lignocaine (2%) in reducing the pain of perineal tears during suturing and postpartum. the common problem that affects almost 85–95 % of females includes the post-partum perineal pain for the initial 24 hours. the intensity of pain varies with 6 the degree of the tear/injury. this pain is so arduous that it has negative impact on the mother child bonding like delay in initiating breastfeeding and almost 42 % of these females are not able to carry out the basic activities like sitting, walking, micturition or 6 sleep. about 91% of those with third or fourth th degree tears would complain of pain up to 7 post7 partum day. common surgical procedure performed worldwide 3 during spontaneous or assisted vaginal deliveries. the worldwide rates of episiotomies vary due to selective episiotomy recommendation and was found to be 27% overall in who report , about 54% 4 for nullipara and 6% for multipara. some countries are having as low rates as 9.70% such as sweden 5 whereas others have as high as 100% like taiwan. introduction spontaneous vaginal birth is associated with trauma to the vagina and perineum. this trauma may be in the form of minor/major lacerations or tears occurring spontaneously during vaginal birth or are iatrogenic. the latter term, which includes episiotomy, is defined as a surgical incision or a cut given by the trained mid-wives or obstetrician into the perineum in order to enlarge the vaginal outlet to 1,2 facilitate the birth of baby. episiotomy is one of the analgesic efficacy of ropivacaine versus lignocaine in perineal tears: a randomized controlled trial hasina sadiq, irum sohail, maria habib correspondence: dr. hasina sadiq post graduate trainee department of gynecology and obstetrics krl hospital islamabad e-mail:humbleschlr3@gmail.com department of gynecology and obstetrics krl hospital islamabad funding source: nil; conflict of interest: nil received: march 19, 2019; revised: september 09, 2019 accepted: october 30, 2019 analgesic efficacy of ropivacaine in perineal repairjiimc 2019 vol. 14, no.4 179 degrees) were included. while women with fourth degree perineal tear, midline episiotomy, allergy to local anesthetic agent, local infection, and chronic analgesic use before and during pregnancy, drug dependence, major postpartum complications, epidural analgesia, chronic pain syndrome/ neuropathic pain, any comorbid i.e., diabetes mellitus and heart disease were excluded. the data was analyzed on the spss 23 by using chi square test. mean pain scores, age and weight were calculated (mean±s.d) and then independent student t-test applied to compare the two groups. the categorical data was analyzed by applying chi square test and the results were expressed as number or percentages. a p-value < 0.05 was considered statistically significant. the need for on-demand systemic analgesia was also noted in both groups. all the patients were observed for side effects and complications. all the data was entered in a performa. the patients were randomly allocated into one of the interventional group after explaining the procedure and taking verbal informed consent. group a was assigned to those receiving 10 ml of 2% lignocaine and group b to those receiving 10 ml of 0.75% ropivacaine. after negative aspiration, the local anesthetic agent was infiltrated into the vaginal and perineal skin for repairs of mediolateral episiotomy or tears. after infiltration of 5 minutes, the episiotomy or tear was stitched by post-graduate resident using a continuous suture technique for the vaginal mucosa and interrupted suture for the muscle and perineal skin. the patients were familiarized with the visual analogue scoring system. visual analogue scoring scale is a type of numerical rating scale ranging from 1 to 10 with 1 indicating no pain and 10, the severe pain, as shown in figure 1. the pain assessment was made at the time of suturing and the need for additional local anesthetic agent was noted. in both groups, lignocaine was given as additional analgesia if needed. all the patients were shifted to postnatal ward, and further pain assessments were made via vas scoring at 30 minutes, 3 hours and 6 hours post-delivery by the same resident. vas scoring less than 4 was considered efficacious. patients with no formal education were assessed for pain by the pictorial presentation of the numerical rating scale. the objective of this study was to compare the effectiveness of 2% lignocaine with the ropivacaine 0.75% in reducing the post episiotomy perineal pain. a total of 100 patients with singleton pregnancy undergoing spontaneous vertex delivery were included on the basis of specific criteria. women st nd rd with episiotomy and perineal injury (1 , 2 and 3 ropivacaine is safer and less cardiotoxic among the three. it has prolonged duration of action and is effective up to 10 hours that can be attributed to its 6 slow reabsorption. also reduces the peripheral 8 hyperalgesia due to its anti-inflammatory effects. ropivacaine is generally used for skin infiltration in hemorrhoidectomy and inguinal hernia repair, and 9 has better analgesic effects. different modalities have been practiced under domain of obstetric analgesia to provide pain relief to laboring females such as epidural analgesia, intra dermal injections of different substances and inhalational agents. least attention has been given to the post-delivery perineal pain explicitly. local anesthetic agents have been widely used to alleviate the pain while suturing the perineal tears. these agents differ on the basis of their chemical structure that in turn affects its efficacy and duration of 6 action. they share same mechanism of action and block the nerve impulse conduction by blocking the sodium channels at the distal nerve free endings 6 and along axon. traditionally lignocaine, an intermediate acting agent has been used in either 1% or 2% concentration forms. it acts within 1 to 5 minutes after administration and analgesic effect 8 persists for 2 hours. whereas, long acting anesthetic a g e n t s l i ke ro p i va c a i n e , b u p i va c a i n e a n d 7 levobupivacaine are now preferred. this was a prospective single blinded randomized control trial conducted over a period of 3 months from may, 2018 to august, 2018. the study participants were consecutively recruited from the labor ward of krl hospital islamabad. ethical approval was taken from the ethical review committee of the hospital. the sample size was calculated on the basis of who sample size criteria by statistician and it came out about 38 patients in 6 each group for statistically significant results. but for better results we have included more patients in both groups. materials and methods analgesic efficacy of ropivacaine in perineal repairjiimc 2019 vol. 14, no.4 180 the pain is now considered as a fifth vital sign and it is associated with adverse effects like poor wound healing, wound infection, hypertension, deep venous thrombosis, delayed discharge from hospital 10 and depression. however, persistent perineal pain is most commonly associated with the instrumental delivery. the incidence of persistent perineal pain is documented up to 7% at 6 weeks post partum and 11 4% at 6 month post partum. the main aim of the current study is to alleviate the post episiotomy perineal pain without further increasing use of systemic analgesics. discussion based on the results shown in table ii and figure 2, mean pain scores were significantly reduced in the ropivacaine group at the time of suturing, 3 hours and 6 hours post partum. but no significant difference was found at the pain scores at 30 minutes post perineal repair. additional analgesic requirement at the time of suturing was greater in lignocaine groups. most of the patients in lignocaine group complained of pain after 3 hours post delivery. they had greater vas scores and demanded for oral analgesics as compared to ropivacaine, as shown in table iii. results baseline characteristics of 100 study participants are shown in table i which shows no statistical significant difference in the age, weight, parity, types of delivery and the degree of tear among the two groups. no side effects were noted in any of the patients in either group. all the patients remained vitally stable post natally, were mobilized, and encouraged to void urine. as per hospital protocol, due to heavy workload the uncomplicated vaginal deliveries were discharged after 6 to 8 hours of delivery therefore, the maternal satisfaction to carry out basic activities could not be assessed. fig 1: visual analogue scale table i: baseline characteris�cs of study par�cipants table ii: mean vas pain scores fig 2: comparison of vas scores between two groups table iii: need for addi�onal local analgesia at suturing and on demand systemic analgesia in both groups analgesic efficacy of ropivacaine in perineal repairjiimc 2019 vol. 14, no.4 181 conclusion there were no adverse effects noted in our study participants of either group similar to the other 8 6 studies by gutton et al and nagraj et al. maternal satisfaction was not assessed in our study due to the early discharge of uncomplicated patients as per hospital protocol. the need for additional analgesia at the time of suturing was not studied in any of the previous studies but it was taken into account in this study. ropivacaine is more effective in reducing post episiotomy perineal pain as compared to lignocaine. it can be safely used by the obstetricians as has least side effects and therefore, can replace lignocaine. 2. management of the second stage of labor. international journal of gynecology & obstetrics. 2012; 119(2):111-6. and insignificant among three groups (p=0.09). whereas about 35% of patients in ropivacaine group did not require analgesia as compared to 90% of patients in our study. this can be explained by the simultaneous epidural infusion and the total 24 hour p e r i o d t a ke n i n t o a c c o u n t f o r a n a l g e s i c consumption. in clinical use, other drugs have also been compared to lignocaine. clonidine has been used as an adjuvant to lignocaine and when compared to lignocaine alone, the combined group was significantly lowering the pain intensity and helped the patients to carry out routine activities with ease like 14 squatting, walking, sitting. similarly another study compared the lignocaine alone with combination of metaclopramide and lignocaine for third degree perineal repairs, and it found significant decrease in 15 mean pain scores after episiotomy for 24 hours. hypotension and bradycardia were the main side effects noted in the metaclopromide and lignocaine combined group. the limitation of this study is that the mean pain scores were noted only up to 6 hours due to the early discharge of uncomplicated vaginal deliveries. blinding of professionals and medical staff was not done. references 1. jiang h, qian x, carroli g, garner p. selective versus routine use of episiotomy for vaginal birth. cochrane database of systematic reviews. 2017(2). 3. hartmann k, viswanathan m, palmieri r, gartlehner g, thorp j, lohr kn. outcomes of routine episiotomy: a about 40% of patients in the lignocaine group required oral analgesics after 3 hours as compared to that of ropivacaine group in our study. in a study by 6 nagraj et al concluded that the ropivacaine group did not require oral analgesics for 24 hours but the lignocaine group requires analgesics after 4 hours. 12 similarly, study by deshpande et al concluded that the time for first analgesic demand was prolonged in ropivacaine group after about average 10.2 hours as compared to 2.2 hours in lignocaine group. prolonged analgesic effect of ropivacaine for skin surgeries after skin infiltration has also been proven 13 by moffitt et al which is about 10 hours and for lignocaine it is up to 2 hours. these were similar to our study in which the lignocaine group needed rescue analgesia after 3 hours and can be justified by the shorter half-life of lignocaine. in our study the mean pain scores were significantly lowered at the time of suturing, 3 hours and 6 hours post-partum in the ropivacaine group but nonsignificant among two groups after 30 minutes of 8 repair. study by gutton et al in 2013 showed effective reduction in pain scores at 2, 24 and 48 hours post episiotomy repair in ropivacaine group and higher maternal satisfaction at 48 hours. the mean pain score was below 4 in ropivacaine group as compared to lignocaine group. similarly, a study 6 conducted by nagraj et al highlighted that analgesic efficacy of lignocaine and ropivacaine was equal till 4 hours of perineal repair that was in contrast to our study. however, pain scores were higher in lignocaine group after 4 hours that was attributed to the decreased half-life of lignocaine. it was also noted that mean vas score was less than 1 after 4 hours in ropivacaine group and hence highlighting the greater efficacy of ropivacaine. when compared to our study the pain scores were assessed up to 6 hours, and they were significantly lowered in ropivacaine group, but maternal satisfaction could not be assessed due to early discharge. in our study, about 90% of patients in ropivacaine group and 60% in lignocaine group did not require 9 oral analgesia. contrary to our results, schinkel et al in france compared ropivacaine, lignocaine and saline use for perineal infiltration for first 24 hours in patients given epidural analgesia. they concluded that the proportion of patients not demanding oral analgesia were more in lignocaine group about 53% analgesic efficacy of ropivacaine in perineal repairjiimc 2019 vol. 14, no.4 182 obstetric anesthesia. 2010; 19(3):293-7. 12. d e s h p a n d e j p, s a u n d a t t i k a r g y. l i g n o c a i n e versusropivacaine infiltration for postpartum perineal pain. anesth essays res. 2017; 11(2):300–3. 13. moffitt dl, de berker da, kennedy ct, shutt le. assessment of ropivacaine as a local anesthetic for skin infiltration in skin surgery. dermatologic surgery. 2001; 27(5):437-40. 10. khan zh, karvandian k, maghsoudloo m, albareh h. the role of opioids and non-opioids in postoperative pain relief; a narrative review. arch anesth&crit care. 2018; 4(1):430-5. 14. bhatia u, soni p, khilji u, trivedi yn. clonidine as an adjuvant to lignocaine infiltration for prolongation of analgesia after episiotomy. anesth essays res. 2017; 11(3):651–5. 15. shabanian s, kalbasi s, shabanian g, khoram b, ganji f. the effect of metoclopramide addition to lidocaine on pain of patients with grades ii and iii post-episiotomy repair. j clindiagn res. 2017; 11(4):11–4. 11. kainu j, sarvela j, tiippana e, halmesmäki e, korttila k. persistent pain after caesarean section and vaginal birth: a cohort study. international journal of obstetric anesthesia. 2010; 19(1):4-9. systematic review. jama. 2005; 293(17):2141-8. 4. liljestrand j. episiotomy for vaginal birth: rhl commentary. the who reproductive health library. 2003. 5. graham id, carroli g, davies c, medves jm. episiotomy rates around the world: an update. birth. 2005; 32(3):21923. 7. carbonnel m, cocquet p, and weber m, constant j, beldi s, abbou h et al. perineal infiltration with levobupivacaine or placebo for episiotomies or second-degree tears: a double-blind randomized study. glob surg. 2017; 3(4). 9. schinkel n, colbus l, soltner c, parot-schinkel e, naar l, fournié a et al. perineal infiltration with lidocaine 1%, ropivacaine 0.75%, or placebo for episiotomy repair in parturients who received epidural labor analgesia: a double-blind randomized study. international journal of 6. nagaraj p, thalamkandathil n, sadique h. ropivacaine versus lidocaine for episiotomya randomised double blind study. j evid based med healthc. 2017; 4(33):1954-9. 8. gutton c, bellefleur j, puppo s, brunet j, antonini f, leone m et al. lidocaine versus ropivacaine for perineal infiltration post-episiotomy. international journal of gynecology & obstetrics. 2013; 122(1):33-6. analgesic efficacy of ropivacaine in perineal repairjiimc 2019 vol. 14, no.4 183 original�article abstract objective: to compare the toxic effects of cigarette and water pipe/shisha smoking on hematological parameters such as hemoglobin (hb) and total leukocyte count (tlc) and also on serum triglycerides levels (tag) in balb/c mice. study design: experimental randomized controlled study. place and duration of study: the study was carried out at islamic international medical college, department of anatomy in collaboration with national institute of health. duration of the study was six months, from october st th 1 2013 till march 30 2014. materials and methods: forty adult male mice of strain balb/c were obtained from national institute of health and were randomly divided into three groups. they were kept in whole body smoke exposure chamber. control group c was exposed to fresh air. cigarette smoke group cs and shisha/water pipe smoke group ss were exposed to cigarette and water pipe smoke respectively in separate chambers for 8 weeks. after 8 weeks, blood samples were collected by cardiac puncture in separately labeled test tubes. blood was analyzed for hematological parameters including hemoglobin and total leucocyte count and also triglycerides and results were compared among three experimental groups. data was analyzed using spss version 20.0. mean ± s.d was used for quantitative hematological and biochemical parameters. a p-value of ≤ 0.05 was considered as statistically significant. results: average hemoglobin was 11.95 ± 0.792 g/dl in control group c, 13.80 ± 1.095 g/dl in group cs and 13.66 ± 1.349 g/dl in group ss. control group had significantly lower average hemoglobin as compared to group cs (p<0.05) and group ss (p<0.05). average serum triglyceride level was 102.50 ± 31.785 mg/dl in control group, 127.80 ± 13.487 mg/dl in group cs and 147.00 ± 18.326 mg/dl in group ss. all the groups were significantly different from each other (p<0.05). median total leukocyte count was 5900/µl (iqr: 5150-6875 /µl) in control group, 5200/ µl (iqr: 4200 – 7200/µl) in group cs and 9900/µl (5300 – 13300/µl) in group ss. difference among three groups was significant (p<0.001). conclusion: water pipe smoking is more toxic than cigarette smoking in terms of its adverse effects on hemoglobin, total leukocyte count and serum triglycerides levels. key words: cigarette smoking, hemoglobin, total leukocyte count, triglycerides, water pipe smoking. carboxy hemoglobin is formed when carbon multiple ways of tobacco smoking with cultural differences around the globe. common ways of smoking include cigar, cigarettes, hookah, water 1 pipe, vaporizers and kretek. tobacco, smoked by any means, contains more than 4000 compounds and free radicals among which, nicotine and carbon monoxide are responsible for most of the deleterious effects associated with long term smoking. in addition to many known cardiovascular, respiratory and neurological disorders, these free radicals are believed to cause derangements in hematological parameters like hemoglobin, white 2 cells count and triglycerides levels. introduction researches show that life span of a tobacco smoker, on an average, is reduced by approximately ten years 1 as compared to people who do not smoke. there are water pipe a safe alternative to cigarette? a comparative study on hematological and biochemical parameters in mice exposed to cigarette and water pipe smoke 1 2 3 shazia imran , rubina shafi , tahira sadiq correspondence: dr. shazia imran department of anatomy islamabad medical and dental college, islamabad e-mail: drshaziahassan@gmail.com 1 department of anatomy islamabad medical and dental college, islamabad 2 3 department of pathology/community medicine islamic international medical college riphah international university, islamabad is water pipe a safe alternative to cigarette smokingjiimc 2020 vol. 15, no.3 funding source: nil; conflict of interest: nil received: july 22, 2020; revised: september 04, 2020 september 06, 2020 177 monoxide, ammonia, polycyclic aromatic hydrocarbons (pahs), aldehydes, phenolic 9 compounds and heavy metals, to name a few. the difference in heating process and charcoal combustion might lead to more toxicants in water pipe smoke. a complete session of water pipe smoking usually lasts 60 minutes, with smokers taking up to two hundred puffs. on the other hand, cigarette smoking takes about 7 minutes with 8-12 puffs/cigarette. there is thus possibility of inhaling higher levels of toxicants in water pipe smoking than 10 cigarette smoking. this study was thus done with an objective to compare the toxic effects of cigarette and shisha/water pipe smoking on hematological parameters such as hemoglobin (hb) and total leukocyte count and on biochemical parameter serum triglycerides levels (tag) in balb/c mice. materials and methods this randomized controlled trial was conducted at islamic international medical college, rawalpindi, in the department of anatomy in collaboration with 10,11 national institute of health islamabad. the institutional review committee of riphah international university approved the study design and duration of the study was six months, from st th october 1 2013 till march 30 2014.sample size consisted of forty male balb/c mice, weighing 3545g which were obtained from animal house of nih, islamabad and were kept in separate cages. mice with any pathology and less than 3 months old, weighing less than 35g or more than 45g were not included. female mice were not used because of risk 0 of pregnancy. all mice were kept in a room at 24 c with 12 hours light and dark cycle and were given palleted diet. they were acclimatized for one week before smoke exposure. they were randomly divided into 3 groups; control group c n =10, shisha smoke (ss) group n =15 and cigarette smoke (cs) group n =15. simple randomization was done using random allocation cards through computer-generated random numbers. for water pipe smoke commercial ma'assel was used that contains 30% tobacco and 70% honey or 11 molasses. nonfiltered cigarettes of a local brand with known percentage of nicotine content were used for cigarette smoke. locally made plastic chamber were used for whole body inhalational monoxide binds with hemoglobin resulting in left sided shift of the oxygen-hemoglobin dissociation curve. this results in reduced ability of the hemoglobin to carry and deliver oxygen to the tissue leading to compensatory high levels of hemoglobin 2,3 in smokers. total leucocyte cell count is a useful, relatively inexpensive biomarker used to assess endothelial damage and is also an important predictor of atherosclerosis and cardiovascular disease. nicotine in tobacco smoke induces an inflammatory response in the tracheobronchial tree along with an increase in the inflammatory markers in the blood. smokers with high tlc count might be at greater risk for developing atherosclerosis and cardiovascular 3 diseases as compared to non-smokers. similarly, a proatherogenic lipid profile is also related to an increased incidence of coronary artery disease in smokers. studies have shown high levels of triglycerides in smokers posing a greater rick of 4 atherosclerotic changes in cardiovascular system. nicotine stimulates adrenal-sympathetic system which releases catecholamine. this surge in catecholamines induces lipolysis, thus increasing levels of serum free fatty acid, promoting cholesterol 5 synthesis, and secretion in the liver. recently, water pipe smoking has regained popularity especially in young population. when compared to a cigarette, water pipe tobacco smoking is associated with almost four-fold more carboxy hemoglobin, and more than 50-fold inhaled volume of smoke. thus, water pipe smoking is associated 6 with more risk of dependence, disease, and death. it is a common misconception that water pipe smoke is comparatively less harmful than cigarette smoke because the smoke first passes through water before being inhaled through the mouth piece. thus, it filters the smoke from tar, nicotine and other carcinogenic substances. on the contrary, the water 3 only cools down the smoke and this leads to deeper inhalation by the smoker. this causes deep penetration of smoke into the lungs leading to 7 adverse health effects. in fact, water pipe smoking has been suspected to be a risk factor for a number of diseases such as lung and esophageal cancer, cardiovascular disease and adverse pregnancy 8 outcomes. mainstream hookah smoke contains several toxicants including tar, nicotine, carbon jiimc 2020 vol. 15, no.3 178 is water pipe a safe alternative to cigarette smoking statistically significant. 12 exposure. these chambers were designed 13,14 according to the who specifications. approximately 10g of water pipe flavor was placed in the plate on the top of water pipe apparatus and covered with aluminum foil. hot coal biscuit was placed over it and smoke was introduced as puffs into the chamber using a manual vacuum pump. twenty commercial non-filtered cigarettes were ignited and placed in a plastic stand and placed in the chamber of cs group. the smoke-exposure group cs was exposed to nicotine concentrations equivalent to shisha/water pipe smoke group. the flavor used in shisha/water pipe contains approximately 2.5 mg of 15 nicotine. the nicotine content in side stream smoke of one cigarette is 0.12 mg. so, nicotine content in 20 16 cigarettes is 2.4 mg. the mice in experimental groups were exposed to smoke until all water pipe flavor and cigarettes were consumed, which took approximately two hours. mice were exposed to water pipe and cigarette smoke in morning and evening for two months. all nd mice were sacrificed at the end of 2 month. they were anaesthetized 24 hours after the last dose of smoke by placing them in a closed glass container with cotton balls soaked in chloroform, until they lose consciousness. blood samples were collected by cardiac puncture in separately labeled test tubes. the blood for hemoglobin and total leucocyte counts was collected in test tubes with anticoagulants while the blood for triglycerides was collected in plain test tubes and serum was extracted after centrifugation. the values were obtained by using commercially available kits. (hemoglobin meter hb-101 certeza germany for hb and coulter® dxh 800 analyzer for tlc). statistical analysis was done using spss version 20.0. mean ± s.d was used for quantitative biochemical parameters. the quantitative variables hb, tlc count and tag were checked for normal distribution by applying kolmogorov-smirnov test that showed that hb and tag were normally distributed variables. one way analysis of variance (anova) was used to compare the mean differences of normally distributed data of hb and tag levels among three groups. post-hoc tukey test was applied to compare which group mean differs individually from other two groups. a p-value of ≤ 0.05 was considered as a b c fig 1 (a) photograph showing genera�on of water pipe 11,12 smoke with manual vacuum pump , (b) whole body cigare�e smoke exposure chamber showing burnt cigare�es and (c) blood collec�on through cardiac puncture. results the average hemoglobin was 11.95 ± 0.792 g/dl in control group c, 13.80 ± 1.095 g/dl in group cs and 13.66 ± 1.349 g/dl in group ss. anova test showed a significant p value and post hoc test was then applied to compare all the three groups individually with each other. the cs and ss groups were jiimc 2020 vol. 15, no.3 179 is water pipe a safe alternative to cigarette smoking discussion the tobacco smoke is known to cause many biochemical changes in the body including alterations in hemoglobin, white cell counts and triglycerides levels. free radicals and peroxides generated during smoking are reportedly linked with physiological changes in the body such as increased synthesis of prostaglandins and thromboxane and advanced pathological changes like atherosclerosis, inflammation and metastatic changes. effects of smoking on antioxidant status and hematological parameters have been extensively studied but results on comparative effects of cigarette and water pipe smoking are inconsistent. in this study, hematological parameters were used for comparative analysis among study groups. the hemoglobin levels showed significant differences between control and experimental groups. while it was normal in control group c, the value was higher in both experimental groups ss and 3 cs. similar results have been shown by asif , shah 16 17 bk , and kumar in their studies done on effects of cigarette smoke on hemoglobin levels. according to 18 rabbe normal value of hemoglobin in male mice is 13.3-16.1g/dl. carboxyhemoglobin, formed after binding of carbon monoxide with oxygen, is an inactive compound that shifts the dissociation curve of hemoglobin to the left side. this reduces the ability of hemoglobin to deliver oxygen to the tissue. tissue hypoxia leads to an increased secretion of erythropoietin causing enhanced erythropoiesis. smokers, thus, maintain a 2,3 higher hemoglobin level than non-smokers to compensate the tissue hypoxia. the difference between the values of group cs and ss was highly significant. a single water pipe session significantly (p<0.05) different from control group c. control group had significantly lower average hemoglobin as compared to group cs (p<0.05) and group ss (p<0.05). while the difference in hemoglobin between experimental group cs and experimental group ss was not significantly (p > 0.05) different. group cs although had higher average hemoglobin level than group ss but this difference was insignificant statistically (table-i). the average serum triglyceride level was 102.50 ± 31.785 mg/dl in control group, 127.80 ± 13.487 mg/dl in group cs and 147.00 ± 18.326 mg/dl in group ss. all the groups were significantly different from each other (p<0.05). control group had significantly lower average serum triglyceride level as compared to group cs (p<0.05) and group ss (p<0.05) while the group ss had significantly (p<0.05) higher level of tg as compare to cs group (table-i). the total leukocyte count (tlc) was normal in the control group c (normal range: 5500-11,000/µl). the data of tlc count did not follow the normal distribution based upon kolmogorov smirnov test of normality so interquartile range (iqr) was calculated for this data. median tlc count was 5900/µl (iqr: 5150-6875 /µl) in control group, 5200/ µl (iqr: 4200 – 7200/µl) in group cs and 9900/µl (5300 – 13300/µl) in group ss. difference among three groups was significant (p<0.001) (table-ii). table i: post hoc comparison of hemoglobin (g/dl) and serum triglycerides (mg/dl) between the groups. * difference is significant at 5% level of confidence ¥ difference is not significant at 5% level of confidence table ii: comparison of white cell count between the group cs and ss * p-value by kruskal-wallis test is significant at 5% confidence level jiimc 2020 vol. 15, no.3 180 is water pipe a safe alternative to cigarette smoking elevated tag levels with no significant difference between the two groups. this supports the finding in this research in which the difference between group cs and ss was statistically insignificant (p=0.078). 26 according to rashidi , smokers are susceptible to metabolic disorders characterized by insulin resistance, which increases postprandial triglyceride and low density lipoprotein. similar results are 30 reported by mc govern who observed that high doses of nicotine lead to resistance to insulin. this causes rapid surge in the levels of catecholamines. smokers have low levels of adiponectin, an adiposederived protein which modulates insulin sensitivity and has anti-inflammatory effects. the insulin resistance alters body composition leading to an increased fat in viscera. conclusion water pipe/shisha smoke contains higher levels of chemical irritants that cause respiratory tract inflammation as well as derangements in many hematological and biochemical parameters that are indicators of several systemic disorders. the damage is more as compared to cigarette smoke given in same quantity and for same duration. thus, water pipe smoking is not a safe alternative to cigarette smoking. limitation of the study baseline values of hematological and biochemical parameters could not be recorded in experimental animals because of their small age and size. thus, values were compared with those of control group. future recommendations further experimental studies can be carried out on rabbits or even humans comparing effects of cigarette and water pipe smoke with baseline parameters. references 1. soflaei ss, darroudi s, tayefi m, tirkani an, moohebati m, ebrahimi m et al. hookah smoking is strongly associated with diabetes mellitus, metabolic syndrome and obesity: a population-based study. diabetology & metabolic syndrome. 2018 dec 1; 10(1):33-38. 2. malenica m, prnjavorac b, bego t, dujic t, semiz s, skrbo s et al. effect of cigarette smoking on haematological parameters in healthy population. medical archives. 2017 apr; 71(2):132-136. 3. asif m, karim s, umar z, malik a, ismail t, chaudhary a et al. effect of cigarette smoking based on hematological parameters: comparison between male smokers and nonsmokers. turkish journal of biochemistry. 2013 jan 1; 38(1); 7 delivers higher levels of co than a single cigarette , which explains the higher levels of hemoglobin in group ss as compared to group cs in this research. in 19 a comparative study by eissenberg , the first five minutes of water pipe smoking produced more than four times more carboxyhemoglobin as compared to an entire cigarette. the normal range of tlc count in mice is 500020 12,000/µl. tlc count was increased in smoke exposure groups as compared to the control. an increase in tlc count in smokers has been reported 16, 21 22 3 previously by kume , shenwai, asif and 23 malenica. all of them have observed an increased total leukocyte count in smokers as compared to 22 nonsmokers. according to shenwai, toxicants in smoke cause marked release of inflammatory cytokines from the epithelial cells which influence the growth, differentiation and activation of leucocytes. inflammation also cause endothelium damage and increased aggregation of leukocytes that further predispose to microcirculatory occlusion and vascular damage. this can be the underlying mechanism of leukocytosis in smokers. nicotine also causes a surge in circulating catecholamine which 22 can increase the total white cell count. the difference between group cs and ss was statistically significant. this could be possible due to large volume of smoke per puff in shisha/water pipe smoking as compared to cigarettes. according to 15 chaouachi ,cigarette smokers on an average take 710 puffs, inhaling a total of 550 ml of smoke. in contrast, complete water pipe session usually encompasses 60 minutes with around 150 puffs. the 11,12 smoker inhales 500 ml of smoke in each puff. thus one complete session of water pipe smoking 15 produces 50,000ml of smoke causing much higher degree of systemic inflammation and leucocytosis. the comparative analysis of serum triglycerides (tag) also showed differences among study groups. the normal range of serum triglyceride in mice is 24 102-188mg/dl. the control group c showed a normal average level of 126mg/dl while group cs and ss showed an increase in triglyceride levels. this has been reported earlier in cigarette smokers by 25 26 27 4 28 yan-ling , rashidi , alharbi and lietz. shafique observed a significantly increased levels of tag in 29 water pipe smokers. sahnoun in his comparative research on water pipe and cigarette observed an jiimc 2020 vol. 15, no.3 181 is water pipe a safe alternative to cigarette smoking effect of smoking on the blood parameters of young adults. journal of clinical & diagnostic research. 2012; 6(7); 361364. 18. raabe bm, artwohl je, purcell je, lovaglio j, fortman jd. effects of weekly blood collection in c57bl/6 mice. journal of the american association for laboratory animal science: jaalas. 2011; 50(5):680-685. 19. eissenberg t, shihadeh a. waterpipe tobacco and cigarette smoking: direct comparison of toxicant exposure. american journal of preventive medicine. 2009;37(6):518-23. 20. mcgarry mp, lee jj, protheroe ca. mouse hematology: a laboratory manual: cold spring harbor laboratory press; 2010. 21. fernández jaf, prats jm, artero jvm, mora ac, fariñas av, espinal a, et al. systemic inflammation in 222.841 healthy employed smokers and nonsmokers: white blood cell count and relationship to spirometry. tobacco induced diseases. 2012;10(1):1-8. 22. shenwai m, aundhakar n. effect of cigarette smoking on various haematological parameters in young male smokers. indian journal of basic and applied medical research. 2012;2(5):386-92. 23. malenica m, prnjavorac b, bego t, dujic t, semiz s, skrbo s et al. effect of cigarette smoking on haematological parameters in healthy population. medical archives. 2017 apr;71(2):132-136. 24. wirth-dzięciołowska e, karaszewska ts, pyśniak mg. selected blood serum biochemical indicators in twelve inbred strains of laboratory mice. animal science papers and reports. 2009;27(2):159-67. 25. yan-ling z, dong-qing z, chang-quan h, bi-rong d. cigarette smoking and its association with serum l i p i d / l i p o p r o t e i n a m o n g c h i n e s e nonagenarians/centenarians. lipids in health and disease. 2012;11(1):94-99. 26. rashidi h, salesi m, fatahi f. effects of cigarette smoking on postprandial triglyceride in healthy smokers. iranian journal of diabetes and lipid disorders. 2010;9:1-4. 27. alharbi wd. influence of cigarette smoking on lipid profile in male university students. pak j pharma. 2011;28(2):4549. 28. shafique k, mirza ss, mughal mk, arain zi, khan na, tareen mf, et al. water-pipe smoking and metabolic syndrome: a population-based study. plos one. 2012;7(7). 29. sahnoun z, zeghal km, hakim a. water pipe tobacco smoking and cigarette smoking: comparative analysis of the smoking effects on antioxidant status, lipid profile and cardiopulmonary quality in sedentary smokers tunisian. international journal of pharmaceutical science invention. april 2013;2(4):51-57. 30. audrain-mcgovern j, benowitz n. cigarette smoking, nicotine, and body weight. clinical pharmacology and therapeutics. 2011;90(1):164-68. 75-80. 4. lietz m, berges a, lebrun s, meurrens k, steffen y, stolle k et al. cigarette-smoke-induced atherogenic lipid profiles in plasma and vascular tissue of apolipoprotein e-deficient mice are attenuated by smoking cessation. atherosclerosis. 2013 jul 1; 229(1):86-93. 5. chwyeed s h. a comparison between the effect of shisha and cigarette smoking on serum lipid profile of males in nasiriyah city. medical journal of babylon. 2018 jan 1; 15(1):39-42. 6. cobb co, shihadeh a, weaver mf, eissenberg t. waterpipe tobacco smoking and cigarette smoking: a direct comparison of toxicant exposure and subjective effects. nicotine & tobacco research. 2011 feb 1; 13(2):78-87. 7. jukema jb, bagnasco de, jukema ra. waterpipe smoking: not necessarily less hazardous than cigarette smoking. netherlands heart journal. 2014 mar 1; 22(3):91-99. 8. akl ea, gaddam s, gunukula sk, honeine r, jaoude pa, irani j. the effects of waterpipe tobacco smoking on health outcomes: a systematic review. international journal of epidemiology. 2010 jun 1; 39(3):834-57. 9. qasim h, alarabi ab, alzoubi kh, karim za, alshbool fz, khasawneh ft. the effects of hookah/waterpipe smoking on general health and the cardiovascular system. environmental health and preventive medicine. 2019 dec; 24(1):1-7. 10. husain h, al-fadhli f, al-olaimi f, al-duraie a, qureshi a, alkandari w et al. is smoking shisha safer than cigarettes: comparison of health effects of shisha and cigarette smoking among young adults in kuwait. medical principles and practice. 2016; 25(2):117-22. 11. imran s, shan m, nisar m, muazam s. submucosal gland hypertrophy in trachea of mice exposed to shisha smoke journal of islamabad medical & dental college (jimdc); 2015:4(2):55-59. 12. imran s, shan m, muazam s. a comparative histological study of submucosal gland hypertrophy in trachea of mice exposed to cigarette and shisha smoke. j coll physicians surg pak. 2018; 28(3):192-195. 13. principles w. methods for evaluating the toxicity of chemicals. part 1. environ health criteria. 1978; 6:128. 14. hinners r, burkart j, contner g. animal exposure chambers in air pollution studies. archives of environmental health: an international journal. 1966; 13(5):609-15. 15. chaouachi k. hookah (shisha, narghile) smoking and environmental tobacco smoke (ets). a critical review of the relevant literature and the public health consequences. int j environ res public health 2009; 6:798-843. 16. shah b, nepal a, agrawal m, sinha a. the effects of cigarette smoking on hemoglobin levels compared between smokers and non-smokers. sunsari technical college journal. 2013; 1(1):42-4. 17. kumar j, kumar g, sharma a, ahmed khan, sharma s. the jiimc 2020 vol. 15, no.3 182 is water pipe a safe alternative to cigarette smoking case�report abstract tumors of parotid glands are majority benign and commonest of them is pleomorphic adenoma. patients commonly presents with a painless swelling in face. parotid oncocytoma is a rare parotid tumor with incidence th of 0.1-1.5% (rarest of salivary tumor type) of all parotid tumors, and it occurs in 6-8 decade of life. in this case report we will present a case of 75 years old male with painless swelling in parotid gland and diagnosis of oncocytoma was made. key words: benign tumors, oncocytoma, parotid gland. vascularity on doppler ultrasound. it was predominantly in superficial lobe with mild extensions into deep lobe, and possibility of pleomorphic adenoma was arisen. we then proceeded for fine needle aspiration cytology (fnac) which showed moderate cellular smear composed of cluster and sheets of oncocytic cells with bland central nuclei, no mitosis was seen. these features were favoring oncocytic neoplasm. patient was counselled in detail about surgery and possible complications, and he was admitted in the hospital for superficial parotidectomy. nerve stimulator was used for the identification of facial nerve. we performed superficial parotidectomy and extension of tumor into deep lobe was also excised preserving facial nerve (shown in figure 1). a drain was placed, and wound was closed. postoperatively he had drooping of the angle of mandible, but there was no significant saliva leak. patient was discharged on postoperative day 2. currently he only has minimal droop which is not visible. his final histopathology report showed that superficial lobe had focal chronic inflammation and deep lobe was oncocytic neoplasm favoring oncocytoma was partially circumscribed, had monomorphic large polygonal cells, which had abundant eosinophilic granular cytoplasm, nuclei were small, centrally placed, round to oval with prominent nucleoli, there was mild hyperchromasia but no nuclear atypia or pleomorphism and mitosis was present, stroma was vascular. immunohistochemistry showed p63 focal present ck5/6 was patchy positive. introduction parotid gland is bilateral and one of the major salivary glands. tumors of salivary gland are uncommon and represent 1% of head and neck case a 75-year-old male presented to us in surgical opd of shifa international hospital on dec 06, 2020, with complaints of swelling left angle of mandible and preauricular region. he noticed this swelling 2 months ago as a small pea size nodule and it progressively increased in size. swelling was painless and there was no associated fever, dry mouth or pain while chewing. he did not notice any change in salivation. patient had no co-morbid and no prior exposure to radiations. there was no past surgical history, and he wasn't on any routine medications. upon examination patient was vitally stable. there was a swelling in left preauricular region extending till the angle of mandible and had size of ~2x2cm. swelling was soft, nontender, mobile and nonfluctuant. surface of swelling was smooth and had regular margins. bimanual palpation was done which showed no attachment to muscles and mobile mass. no lymph nodes were palpable. facial nerve was intact. his laboratory workup was normal. ultrasonography of swelling showed a well-defined lesion with macro lobular margins and hypo echoic appearance in left parotid gland which measured approximately 17.4*13. 5mm. swelling showed mild internal parotid gland oncocytoma-a case report 1 muhammad amir , 2 3 4 5 6 sibgha aimon , sehrish latif , fareeha farooqui , memoona zartash , humera naz altaaf correspondence: dr. sehrish latif assistant professor surgery shifa college of medicine shifa temeeremillat university, islamabad e-mail: sehrish64@live.com 1,2,3,4,6 department of surgery shifa college of medicine shifa temeeremillat university, islamabad 5 department of radiology shifa international hospital, islamabad received: june 30, 2022; revised: december 02, 2022 accepted: december 11, 2022 parotid gland oncocytoma a rare entityjiimc 2022 vol. 17, no.4 292 doi: https://doi.org/10.57234/1387 1 tumors . most common site of tumor in salivary gland is parotid gland which accounts for 85% of all. out of this 85%, majority of it are benign and commonest benign tumor is pleomorphic adenoma, w h e r e a s c o m m o n e s t m a l i g n a n t t u m o r i s 1 mucoepidermoid . rarely an entity is parotid oncocytoma, as it occurs in less than 1 percent of all salivary tumor types. its clinical presentation is often misdiagnosed as pleomorphic adenoma or other 2 types. majority tumors of parotid glands are benign whereas tumors of minor salivary glands are predominantly malignant. salivary gland tumors are slow growing and are well circumscribed. lesion which are rapidly growing, have pain, paresthesia, and facial nerve weakness have increase potential of being malignant and needs further workup and are 2 managed aggresively. recent publications showed that multiphase contrast enhanced ct is potentially helpful, as few of the parotid tumors are invisible on ct scan resulting in reducing effectiveness of the scan.3 however, cytological analysis (fnab) is excellent tool to exactly 3 diagnose the oncocytoma as an entity. mri is an improved study showing enough information of soft tissues, providing characterized 4 parotid masses. in this case report we are presenting a case of 75 years old male with painless swelling of left parotid gland, which on workup was diagnosed with oncocytoma, a rare benign parotid gland tumor. discussion parotid gland is the most common site of tumor in all salivary glands, and majority of tumors in parotid gland are benign. most common benign tumor in parotid gland is pleomorphic adenoma, whereas most common malignant tumor is mucoepidermoid 2 tumor. oncocytoma is a rare benign parotid tumor with 5 incidence of 0.5-1.5% in salivary gland . commonest location of oncocytoma is parotid, however they can be found in other areas including but not limiting to 5 sublingual gland, soft palate, and hard palate . the word oncocyte is derived from greek word “onkousthai” meaning enlarge/swollen and this was first recognized in 1897 by schaffer who observed presence of eosinophilic cells in salivary glands, later hamperl in 1931 fully characterized the term 12-13 oncocyte. oncocytes are epithelial cells with a b u n d a n t e o s i n o p h i l i c c y t o p l a s m a n d 7 mitochondria , due to characteristic eosinophilic 11 cytoplasm oncocytes are also called oxyphilic cells. the term oncocytoma was first described by jaffe in 1932 who called tumors of salivary glands with 9, 11 abundant oncocytes as oncocytoma. th incidence of oncocytoma is most common in 6-8 8 decade of life with relative female predisposition. in 2005 world health organization (who) classified oncocytic neoplasm in three distinct types and these are oncocytosis, oncocytoma and oncocytic carcinoma. oncocytosis has only hyperplastic change and it present with generalized enlargement of salivary gland, oncocytoma is a benign wellcircumscribed and encapsulated lesion whereas oncocytic carcinoma is infiltrative with mitosis and 10.13 pleomorphic cells. oncocytes are normally present in limited number in normal tissue like in thyroid, parotid, pancreas, with advancing age their number increases and transformation into tumor occur which is thought to be because of exhaustion of cell and mitochondrial hyperplasia, this leads to metaplastic transformation 9 of normal cells. presentation of oncocytoma is as a painless swelling. risk factors are unknown although in 20% of cases, figure 1 parotid gland oncocytoma a rare entityjiimc 2022 vol. 17, no.4 293 doi: https://doi.org/10.57234/1387 prolonged radiation exposure is found to be the cause. mri and ct are investigation of choice but diagnosis of oncocytoma is usually made by use of 7 fnac, with accurate diagnosis in 29% cases. histopathological, oncocytoma has low mitotic rate and less pleomorphism as compared to oncocytic carcinoma which has high rate of mitotic activity and 5 pleomorphism. management involves surgical excision of tumor w i t h p r e s e r v a t i o n o f f a c i a l n e r v e , f i n a l histopathology confirms the diagnosis. recurrence is reported in 20-30% of patients, so follow-up is 12 advised with mri after 1 and 2 years. conclusion oncocytoma of parotid gland is a rare benign tumor, with limited reporting. definitive treatment so far is with surgical excision. though rare but proper imaging includes ct and mri followed by fnab would help in proper surgical approach. its recurrence has been documented so follow-up is advised in all patients with mri. references 1. sharma v, kumar s, sethi a. oncocytoma parotid gland. ann maxillofac surg. 2018 jul-dec;8(2):330-332. doi: 10.4103/ams.ams_154_17. pmid: 30693257; pmcid: pmc6327801. 2. laurie s a. salivary gland tumors: epidemiology, diagnosis, evaluation, and staging. up-to-date. oct 2021 3. kei pl, tan ty. ct “invisible” lesion of the major salivary glands a diagnostic pitfall of contrast-enhanced ct. clin radiol 2009; 64: 744–46. 4. alps hh, eisele dw, westra wh. the role of fine needle aspiration in the evaluation of parotid masses. curr opin otolaryngol head neck surg 2006; 14: 62–66 5. sharma v, kumar s, sethi a. oncocytoma parotid gland. ann maxillofac surg. 2018; 8(2): 330–332. 6. elias n, katherine p, maria g. a rare case of oncocytoma of the parotid gland with aggresssive features and malignant potential: a case report. j otolaryngol ent res. 2018;10(2):114-116. 7. hamada s, fujiwara k, hatakeyama h, homma a. oncocytoma of the parotid gland with facial nerve p a r a l y s i s . c a s e r e p o t o l a r y n g o l . 2 0 1 8 j u n 21;2018:7687951. doi: 10.1155/2018/7687951. pmid: 30034902; pmcid: pmc6032967. 8. imran s, allen a, shokouh-amiri m, garzon s, saran n. parotid oncocytoma: ct and pathologic correlation of a rare benign parotid tumor. radiol case rep. 2019 nov 9;15(1):31-34. doi: 10.1016/j.radcr.2019.10.003. pmid: 31737142; pmcid: pmc6849430. 9. korbia a e, jellalia s, njimaa m, harrathia k, bouataya r, ferjaouia m, et al .parotid gland oncocytoma: a rare case and literature review. journal of medical cases. 2019;5: 10(5),146-149. 10. chakrabarti i, basu a, ghosh n. oncocytic lesion of parotid gland: a dilemma for cytopathologists. j cytol. 2012;29(1):80-82. doi:10.4103/0970-9371.93236 11. araya j, martinez r, niklander s, marshall m, esguep a. incidence, and prevalence of salivary gland tumours in valparaiso, chile. med oral patol oral cir bucal. 2015 sep 1;20(5):e532-9. doi: 10.4317/medoral.20337. pmid: 26034925; pmcid: pmc4598920. 12. kinoshita y, harada h, kobayashi tk. multifocal adenomatous oncocytic hyperplasia of the parotid gland. case rep oncol. 2014;7(3):819-824. doi:10.1159/ 000370146. 13. kumar r, natarajan s, sneha ks, chitra ns, boaz k, manaktala n. oncocytes in mucoepidermoid carcinoma of the palate: diagnostic challenges. case rep dent. 2017;2017:5741821. doi: 10.1155/2017/5741821. epub 2017 dec 28. pmid: 29445552; pmcid: pmc5763101. conflict of interest authors declared no conflicts of interest. grant support and financial disclosure authors have declared no specific grant for this research from any funding agency in public, commercial or nonprofit sector. data sharing statment the data that support the findings of this study are available from the corresponding author upon request. this is an open access article distributed under the terms of the creative commons attributionnoncommercial 2.0 generic license. parotid gland oncocytoma a rare entityjiimc 2022 vol. 17, no.4 294 doi: https://doi.org/10.57234/1387 community�report abstract “more than 90 percent of all systemic diseases have oral manifestations, meaning that your dentist could be the first health care provider to diagnose a health problem” (raymond martin, academy of general 1 dentistry). 2 oral health is widely recognized as a significant determinant of general health. the burden of poor oral health 3 has crucial social and economic implications, especially in the developing world. low bmi, poor pregnancy outcomes, low birth weight, diabetes mellitus and cardiovascular diseases are some of the conditions 4 associated with compromised oral health. in third world countries, other risk factors such as poor socioeconomic status, lack of dental health education and awareness and inappropriate health policies further 5 contributes to the oral ill health of the general population. islamic republic of pakistan ever since her embodiment has been paving roads to become a welfare state. on one hand it is the only muslim nuclear power, while on other hand the country has been a victim of political instability and inaptness of beneficial policies. pakistan has a total population of 180 million, majority of which 6 resides in rural areas. pakistan ranks at 146 out of 187 countries in human development index and spends only 7 0.5% of gdp on the health sector which includes oral health services. the challenges to oral health care system in pakistan are substantial. with scarce resources it is difficult to contend with procurement of dental treatment; the prevention of oral diseases and the promotion of oral health. there lies a paucity of dental workforce in pakistan, especially in rural areas. according to who recommendations, dentist to population 8 ratio in developing countries should be 1:7500. as of december 2016, the total number of registered dentists 9 by pm&dc is 17,125. this makes the dentist to population ratio of 1: 130,581 – this ratio drops to more than 1: 200,000 in rural areas of the country. mission 2017' (pdm 17) was jointly planned by the team of experts from imana and riphah. the project was set up as a three step process. the first step of the project was to set up fully operational dental camps, providing free oral health services to the population who could not afford the dental treatment. secondly, the mission set out to educate the masses with respect to oral health hygiene and its maintenance. thirdly, an important objective with abiding aftermath was to conduct an oral health needs assessment of this population. these assessments, would in turn serve as a guideline for similar field projects directing towards the areas to be focused in the future. also, this would be beneficial with respect to informing local health bodies to help build better oral health care policies. after eight months of detailed planning, the first leg of the pdm 17 was initiated in august, 17. in this mission imana's 16-member team of dentists, dental hygienists and dental students from howard university, washington d.c, headed by dr. sultan chauhdary took part along with a 26-member team from riphah, islamic international dental college, inclusive of dentists, dental hygienists and dental oral health is still considered an amenity rather than a need among the masses in pakistan. the population is burdened with many oral diseases because of the combination of limited resources and mismanagement of the available resources to address the oral health situation in pakistan, riphah international university, in collaboration with the islamic medical association of north america (imana), started a relief project focusing on the oral health needs of the socioeconomically deprived population in the rural areas of northern punjab. imana, founded in 1967, is the largest muslim medical organization in north america carrying out 10 medical relief programs all over the world. this outreach project named 'pakistan dental reorienting primary oral healthcare – pakistan dental mission 2017, an imana-riphah collaboration hajra mustasim, muhammad humza bin saeed correspondence: dr. humza bin saeed assistant professor, community dentistry islamic international dental college riphah international university, islamabad e-mail: humza.saeed@riphah.edu.pk department of community dentistry islamic international dental college riphah international university, islamabad received: aug 15, 2017; accepted: aug 25, 2017 effects of stem cells and exercise on rheumatoid arthritisjiimc 2017 vol. 12, no.3 160 assistants. riphah's team was led by dr. muhammad humza bin saeed. th this field mission lasted a week starting from 7 aug th till 11 aug, 2017. the teams visited the districts of doltala, village missa kaswal, dharyala kahun kalarkahar, khora khel attock and lastly pakistan sweet homes orphanage, islamabad. every day the camps were setup into mini dental hospitals around 9:00 am and operated unfalteringly till the treatment of last person. the camp treated patients with all kinds of dental problems, many counseled and medicated with free medicines. respecting the cultural limitations and to provide comfort to the locals, male and female patients were treated separately. a total of about 1500 patients were treated over the period of these camps. the data collected during these dental camps suggested that the prevalence of dental caries among this population was quite high. traditional treatment of oral disease is extremely costly, the fourth most expensive disease to treat in most industrialized countries. the camp was equipped enough to manage all kinds of basic dental treatments and provide immediate relief to patients. at the end of the camps, dr sultan commented that this was his first experience of working in pakistan and most definitely, a memorable one. on the behalf of his team, he commended the efforts of the riphah dental team and local authorities involved in arranging these camps. a particular observation that dr sultan was found to be highly impressive was the large number of female dentists who volunteered to participate in this camp. when this project was being planned, it was expected that the total number of patients to be treated, would be around 4000. however, during the dental camps the patients' attendance was around 1500. even though extensive efforts had been made by the organizers to spread the information regarding the dental cams, a relatively low attendance was observed. the low turnout proposes the possibility that the local population does not value their oral health as much as general health. this observation was supported by the clinical evidence, as many of the patients who came for the treatment had severely progressed caries and the only treatment that could be offered to them was extraction. this alarming lack of concern for oral health must be tackled with an upstream approach by focusing on increasing oral health education among the masses. engaging the lady health workers (lhws) in the different basic health units for oral health promotion would be a good place to start. this would require lobbying and advocacy at the government level to approve oral health education programs for the lhws and mothers in rural areas. dental camps supporting the effort of the oral health educators would prove to be highly effective adjuncts to the whole process. this education must reach the commoners. a healthy community will not only be able to perform better but will also impress less financial burden on the society. this imana-riphah camp is a step forward to public welfare of the country but the journey must not end here. this great initiative must continue so that the general public can benefit and be more active members of the society, each individual contributing in their own capacity. this would have an impact on lowering poverty and increasing the overall health of the society. furthermore, it will improve maternal and child health and reduce geriatric health issues. at the government level, acceptable and practical time-defined health related goals and standards of oral health should be decided and documented. barriers to oral health promotion need to be overcome through co-operation between various sectors. local and federal policies must focus on reducing such health inequalities. advocacy of oral health education initiatives through collaborations such as the imana-riphah pdm project must be supported and promoted equally by local health bodies and the government. together a difference could be made, lives could be changed and the quality of life could in turn be improved. “only through improved dental awareness and education can we make an impact on dental health and ultimately the cost of providing care” (sharon 11 zelkind, vice president, healthplx). references 1. martin r. dental quotations 2017 [cited 2017 20-8-2017]. available from: http://www.homesteaddentalco.com/blog /take-control-of-your-oral-health/. 2. sheiham a. oral health, general health and quality of life. bulletin of the world health organization. 2005; 83: 644. 3. tapsoba h, deschamps jp. promotion of orodental health in effects of stem cells and exercise on rheumatoid arthritisjiimc 2017 vol. 12, no.3 161 adolescents in africa. promot educ.1997; 4: 26-8. 4. destefano f, anda rf, kahn hs, williamson df, russell cm. dental disease and risk of coronary heart disease and mortality. bmj. 1993; 306: 688-91. 5. pack ar. dental services and needs in developing countries. international dental journal. 1998;48: 239-47. 6. naseem m. an outline of the oral health challenges in “pakistani” pop-ulation and a discussion of approaches to these challenges. jpda. 2013; 22 7. [ c i t e d 2 0 1 7 2 1 8 2 0 1 7 ] . a v a i l a b l e f r o m : http://www.emro.who.int/pak/prgrammes/healthsystemstrenghtening-hss.html. 8. sandesh n, mohapatra ak. street dentistry: time to tackle quackery. indian journal of dental research. 2009; 20: 1. 9. pmdc. pakistan medical and dental council medical statistics islamabad: pmdc; 2017 [cited 2017 21-8-2017]. a v a i l a b l e f r o m : h t t p : / / w w w . p m d c . o r g . p k /statistics/tabid/103/default.aspx. 10. imana. islamic medical association of north america 2017 [cited 2017 21-8-2017]. available from: https://imana.org. 11. zelkind s. dental quotations 2017 [cited 2017 20-8-2017]. a v a i l a b l e f r o m : h t t p : / / w w w. m y s m i l e g u i d e . c o m /testimonials.asp. effects of stem cells and exercise on rheumatoid arthritisjiimc 2017 vol. 12, no.3 162 page 43 page 44 page 45 original�article abstract objective: the aim of this was to compare the effects of constraint movement therapy and conventional therapy for improving motor function of upper limb in patients with sub-acute stroke. study design: a randomized controlled trial. place and duration of study: the study was carried out from january 2016 to december 2016 in rafsan neuro rehabilitation centre, peshawar. materials and methods: a total of 60 patients with sub-acute stage of stroke were randomly allocated into constraint induced movement therapy and conventional therapy groups. patients in conventional therapy group followed conventional physical therapy rehabilitation activities while patients in the constraint induced movement therapy group were guided to perform the same activities while constraining their less effected limb. patients in both groups were assessed just before and six weeks after the start of these therapies. mann whitney u test was used to compare the results of both treatment. results: the patients in constraint induced movement therapy group showed better results on upper arm function, hand movement and advanced hand activities of motor assessment scale as compared to the patients in conventional therapy group. the mean rank for upper arm function of constraint induced movement therapy and conventional therapy group were 40 and 20, respectively (p=0.001), hand movement for cimt and ct were 40 and 20 (p=0.001) and advanced hand activities for cimt and ct group were 43 and 17 (p=0.001), respectively. the patients in induced movement therapy group showed 20% better result on upper arm function, 21% on hand movements and 26% on advanced hand activities of motor assessment scale. conclusion: it is concluded that constraint induced movement therapy provides improved upper arm function, hand movement and advanced hand activities as compared to the conventional therapy for the patients with sub-acute stroke. key words: constraint induced movement therapy, paretic upper limb, upper limb motor function, sub-acute stroke. surprising that no large scale epidemiological surveys have been carried out in pakistan regarding stroke and therefore, the true incidence of stroke remained unclear from the available literature. however, still an estimated annual incidence of 200/100,000 population may be found in the 4 literature in some trial with limited scope. the increasing number of patients with stroke in low and middle income countries is alarming and it accounts 5 for significant number of the stroke mortality. the consequences of stroke are not limited to either of the limbs and it can significantly affects both upper 6 and lower limbs. upper limb dysfunction amongst patients with stroke population reduces patient's independence and has a significant adverse impact 7 on quality of life. the common problems associated with stroke in upper limb are muscle spasticity and loss of dexterity which hinders their activities of daily 8 living. it has been reported that 55% to 75% of patients suffering from stroke have difficulty in 9 grasping, holding and manipulating objects. introduction stroke or cerebrovascular accident affects a big 1 proportion of population every year. globally, it is the third most common cause of death and has been reported to be one of the commonest causes for long 2 term disability. it has been reported that patients 3 with stroke cost almost 9.0 billion pounds in uk. it is the effects of constraint induced movement therapy in improving functions of upper limb in patients with stroke 1 2 3 gouhar rahman , haider darain , salman farooqi correspondence: dr. haider darain assistant professor/director khyber medical university institute of physical medicine and rehabilitation peshawar e-mail: haider.kmu@hotmail.com 1 department of physical therapy rafsan center of neurological rehabilitation peshawar 2,3 department of physical therapy khyber medical university institute of physical medicine and rehabilitation peshawar funding source: nil; conflict of interest: nil received: aug 27, 2016; revised: feb 17, 2017 accepted: feb 18, 2017 constraint induced movement therapy in stroke patients jiimc 2017 vol. 12, no.1 3 jiimc 2017 vol. 12, no.1 therefore, strategies to improve upper extremity function amongst stroke population are important to 10 ameliorate motor recovery in upper limb. traditionally, neurophysiological approaches developed by bobath, brunstrom, rood & kabat are u s e d f o r e n h a n c i n g r e c o v e r y i n s t r o k e 11 rehabilitation. however, new and convincing evidence techniques which have been reported to facilitate neuroplasticity included movement therapy protocols, task oriented approach, constraint induced movement therapy and mental 12,13 imagery. movement therapy protocols are based on motor learning principles and are capable of 14 facilitating neural reorganization following stroke. while motor learning refers to permanent changes in behavior that occurs due to practices and 15 experiences of individuals. movement therapy protocols target deficits in neuromuscular system and use repetition or an experience for improving 16 skilled motor activity. repetitive practice for reaching to a glass of water improves the elbow extension, causes structural and functional changes in the motor cortex and cerebellum. these changes due to functional activities are resulted due to motor 17 recovery and remain permanent. on the other hand, changes resulted from doing simple exercises like performing elbow flexion-extension without any task remain may not achieve the proposed goals of 18 treatments in patients having stroke. similar findings have resulted in the development of task oriented goals for improving function of upper 19,20 extremity in patients with stroke. it has been reported that task-specific training with or without constraining the less affected limb had resulted in improving performance of the involved limb in both 21 chronic and sub-acute stroke survivors. the physiology behind the latter fact involves an increase in signals from higher center to the affected limb resulting constraining the unaffected limb and 22 enforcing it to significantly participate. the rationale behind constraint induced movement therapy is to overcome learned non-use movements and bring about functional reorganization of primary motor cortex. studies on the this model of constraint induced movement therapy have shown achieving 23 better functional outcomes in patients with stroke. however, the trials carried out on the effectiveness of constraint induced movement therapy are limited in proposing a minimum dose of constrained induced movement therapy for the treatment applied. moreover, to the authors’ knowledge no published data was found on the topic in the whole country. therefore, this clinical trial was designed to compare the effectiveness of the distributed model of constraint induced movement therapy and conventional physical therapy in improving function of upper limb in patients with stroke. materials and methods this was randomized controlled trial carried out at rafsan neuro rehabilitation centre, peshawar from january 2016 to december 2016. the inclusion criteria for the patients in this trial was limited to subacute stroke patients who were able to score 19 or more on mini mental state questionnaire, 20° of wrist extension and 10° of finger extension in the affected upper limb, a minimum of 2 score in the ‘upper arm function’ section on the motor assessment scale. subjects were excluded if they exhibited; excessive spasticity > 3 on the modified ashworth scale, excessive pain in the affected upper limb, as measured by a score of > 4 on a 10 point visual analog scale. a total of 60 patients having stroke were randomly allocated into constraint induced movement therapy and conventional therapy groups. random numbers were generated through an excel sheet and 60 pre-labeled envelopes (30 labeled as constrained induced movement therapy and 30 labeled as conventional therapy) were placed in a container. each willing patients was asked to pick an envelope for group allocations. the study was approved by the ethical committee of khyber medical university, peshawar. informed consents were obtained from all the participants. all patients received routine 2 hours physiotherapy sessions for 5 days a week. however, the patients in constraint movement induced therapy group wore the constraint during the routine physiotherapy sessions. constraint is a cotton upper arm sling, with a strap around the neck for support. participants were not asked to wear the constraint in unstable environments and during bilateral hand activities (e.g. opening bottles, lifting jars). participants were encouraged to wear the constraint independently; subjects who could not wear it independently were assisted for it. the subjects were provided with a log book to enlist all activities performed during the 4 constraint induced movement therapy in stroke patients jiimc 2017 vol. 12, no.1 constraint wear period. this log book was reviewed and discussed with the patients or their caregivers on regular basis before starting a new therapy session. the functional task practice includes: picking up glass of water and drinking it, reaching for an item and putting into mouth, opening lid of bottles, arranging puzzles, peg boards and in real environment the activities encouraged were turning handles of doors, turning pages of newspapers and magazines. the complex tasks were broken down into simple components for the individuals who were not able to perform those steps. the levels of the tasks were adjusted according individuals' needs and capacities. all participants were tested at baseline and after six weeks following the treatment. participants were kept blinded to the group allocation. moreover, the testing teams were also blinded to the patients’ allocation, making the study a double blinded randomized controlled trial. the assessment tool used for evaluation of the participants was motor assessment scale (upper arm functions, hand movements and advanced hand activities). it is 6point ordinal scale, measuring the activity level of upper limb. the test-retest reliability and inter-rater reliability of the scale have been reported r = 0.98 and 0.95, respectively. motor assessment scale responses are similar to the responses of action reach arm test which is one of the commonest outcome measures used in clinical trials carried out on evaluation of constraint induced movement therapy for upper extremity functions in patient with 24 stroke. spss version 23 was used to analyze data. a non-parametric test mann whitney u test was used to assess the difference between the outcomes of both treatments. results both the groups consisted of equal number of participants (30 participants in each group). the mean age for the participants in constraint induced movement therapy group and conventional therapy group was age 54.4 ± 9.7 years and 56.4 ± 7.3 years, respectively. the average duration from the onset of stroke to the recruitment was between 3 and 9 months in the patients in both groups. baseline physical and clinical characteristics indicated no significant differences amongst the mean scores of the participants in both groups (table i). significant differences on upper arm function, hand movement and advanced hand activities were observed amongst the patients in constraint induced movement therapy and conventional therapy groups. the patients in cimt group showed 20% more improvement on upper arm function of motor assessment scale when compared with the outcomes of the patients in conventional therapy group (table ii). moreover, the patients in cimt group showed better outcomes on hand movements and advanced hand activities compared to the patients in conventional therapy group (21% and 26% more improvement, respectively) (table ii). table i: baseline test sta�s�c and ranks for the pa�ents in both groups cimt: constraint induced movement therapy ct: conven�onal therapy table ii: post treatment test sta�s�c and ranks discussion the aim of this randomized controlled trial was to compare the effectiveness of constraint induced movement therapy and conventional therapy for improving function of upper limb in patients with stroke. in conventional therapy patients are engaged for around 60 hours of therapy during a six week rehabilitation program in a specialized rehabilitation center designed for patient in sub-acute phase of stroke. patients in this program attended 2-hours 5 constraint induced movement therapy in stroke patients jiimc 2017 vol. 12, no.1 physiotherapy session for 5 days for the mentioned duration. patients in the constraint therapy group followed the same pattern of rehabilitation along with restricting their less affected limb during performing the suggested activities. the use of constraint induce movement therapy has been suggested to the patients who are in their sub-acute 25 or chronic phase of stroke rehabilitation. the latter technique involved constraining less affected limb of stroke patients for 5 hours each day for 10 weeks. however, the same technique is not well developed in majority of the asian countries including pakistan. therefore, with slight modification the duration was decreased to 2 hours each for six weeks. one of the other reasons for allowing this modification was exiting protocols of the rehabilitation center where this clinical trial was deployed. the center is one the few centers in the country working specifically on rehabilitation of stroke. the present study results indicated that constraint induced movement therapy for 6-weeks duration promoted significant improvement in upper limb function in patients who were in sub-acute phase of stroke. these findings are consistence with the findings reported by wolf et al. 2006 in a randomized controlled trial comparing the effectiveness of constraint induced movement 26 therapy and conventional therapy. in the latter clinical trial, a total of 222 patients in a single center were randomly allocated to either of the groups and were assessed for functional abilities in upper arm. in the latter trails, patients in both experimental and control group were able to maintain activities of daily living with significant differences amongst the mean scores of the patients when assessed on functional outcomes. in this clinical trial upper arm function, hand movement and advance hand activities of motor assessment scale were used for comparing the effectiveness of constraint induced movement therapy and conventional therapy for rehabilitation of stroke patients who were in sub-acute phase. this scale has been reported to be sensitive, valid and reliable measure for the assessment of upper limb 27 function in patients who had stroke. the same scale has been used in clinical trials assessing the acute effects of additional task for improving mobility and 28 function in upper limbs of patients with stroke. moreover, the use of the same scale for assessing bilateral and unilateral functions of upper arm for 29 patients with chronic has been reported. this suggests that the scale may be used for assessing function of upper limb in stroke patients during different phases of rehabilitation. one of the limitations of this clinical trial was performing assessment of the patients with only a patient-reported outcome measure (motor assessment scale). use of functional tests for assessing the gains in upper limb of the patients in both the constraint induced movement therapy and conventional therapy were not included in the trial. still, the used of a sensitive, reliable and valid scale during the assessment provide findings that can be generalized. another limitation of this clinical trial was lack of an objective assessment tools that would have been used for assessing compliance of patients to the proposed treatment protocols in both the constraint induced movement therapy and conventional therapy groups. conclusion the findings of this clinical trial suggest that despite some modification in the techniques of constraint induced movement therapy, still the patients in the group are superior and the modified techniques can be used for enhancing functional activities in the patients with stroke. references 1. norrving b, kissela b. the global burden of stroke and need for a continuum of care. neurology. 2013; 80: 512. 2. adamson j, beswick a, ebrahim s. is stroke the most common cause of disability? journal of stroke and cerebrovascular diseases. 2004; 13: 171-7. 3. saka o, mcguire a, wolfe c. cost of stroke in the united kingdom. age and ageing. 2009; 38: 27-32. 4. khealani ba, hameed b, mapari uu. stroke in pakistan. journal of the pakistan medical association. 2008; 58: 400. 5. feigin vl. stroke epidemiology in the developing world. the lancet. 2005; 365: 2160-1. 6. neckel n, pelliccio m, nichols d, hidler j. quantification of functional weakness and abnormal synergy patterns in the lower limb of individuals with chronic stroke. journal of neuroengineering and rehabilitation. 2006; 3: 1. 7. page sj ,sisto s, levine p, mcgrath re. efficacy of modified constraint-induced movement therapy in chronic stroke: a single-blinded randomized controlled trial. 2004; 85: 8-14. 8. bakheit amo , ward ab, poewe w, wissel j. muller r, benecke et al. a randomized, double-blind, placebocontrolled, dose-ranging study to compare the efficacy and safety of three doses of botulinum toxin type a (dysport) with placebo in upper limb spasticity after stroke. 2000; 31 :2402-6. 6 constraint induced movement therapy in stroke patients jiimc 2017 vol. 12, no.1 9. gad alon, alan f, levitt, patricia a. functional electrical stimulation enhancement of upper extremity functional recovery during stroke rehabilitation: a pilot study. 2007; 21: 207-15. 10. jorgensen hs, nakayama h, raaschou ho, vive larsen j, stoier m, olsen ts. outcome and time course of recovery in stroke, part ii: time course of recovery. the copenhangen stroke study. 1995; 76: 406-12. 11. paci m. physiotherapy based on the bobath concept for adults with post-stroke hemiplegia: a review of effectiveness studies. 2003; 35: 2-7. 12. gauthier lv, taub e, perkins c, ortmann m, mark vw, uswatte g. remodeling the brain: plastic structural brain changes produced by different motor therapies after stroke. 2008; 39: 1520-5. 13. jonsdottir j, cattaneo d, recalcati m, regola a, rabuffetti m, ferrarin m, et al. task-oriented biofeedback to improve gait in individuals with chronic stroke: motor learning approach. neurorehabilitation and neural repair. 2010; 24: 478-85. 14. krakaver dw. motor learning: its relevance to stroke recovery and neurorehabilitation. current opinion neurology. 2006; 19: 84-90. 15. schnidt ra, lee td. motor control and learning: a behavioral emphasis, human kinetics. 2005. 16. jette du, lathan nk, smout rj, gassaway j, slavin md, horn sd. physical therapy interventions for patients with stroke in inpatient rehabilitation facilities. 2005; 85: 238-48. 17. kleim ja, jones ta. principles of experience-dependent neural plasticity: implications for rehabilitation after brain damage. 2008; 51: 225-39. 18. nudo rj, plautz ed, frost sb. role of adaptive plasticity in recovery of function after damage to motor cortex. 2001; 24: 1000-19. 19. feys h, verbeke g. early and repetitive stimulation of the arm can substantially improve the long-term outcome after stroke: a 5-year follow-up study of a randomized trial. 2004; 35: 924-9. 20. winstein cj, rose dk, tan sm, lewthwaite r, chui hc, azen sp. a randomized controlled comparison of upperextremity rehabilitation strategies in acute stroke: a pilot study of immediate and longterm outcomes. 2004; 85: 6208. 21. kwakkel g. impact of intensity of practice after stroke: issues for consideration. 2006; 28: 823-30. 22. taub e, uswatte g, mark vm, morris dm. the learned nonuse phenomenon: implications for rehabilitation. 2006; 42: 241-50. 23. page sj, sisto s, johnston mv, levine p. modified constraint induced therapy: a randomized, feasibility and efficacy study. 2001; 16: 180-4. 24. taub e, uswatte g, pidikiti r. constraint-induced movement therapy: a new family of techniques with broad application to physical rehabilitation – a clinical review. 1999; 36: 23751. 25. wolf sl, winstein cj, miller jp, thompson pa, taub e, uswatte g, et al. retention of upper limb function in stroke survivors who have received constraint-induced movement therapy: the excite randomised trial. the lancet neurology. 2008; 7: 33-40. 26. wolf sl, winstein cj, miller jp, taub e, uswatte g, morris d, et al. effect of constraint-induced movement therapy on upper extremity function 3 to 9 months after stroke: the excite randomized clinical trial. jama. 2006; 296: 2095104. 27. lannin na. reliability, validity and factor structure of the upper limb subscale of the motor assessment scale (ulmas) in adults following stroke. disability and rehabilitation. 2004; 26: 109-16. 28. blennerhassett j, dite w. additional task-related practice improves mobility and upper limb function early after stroke: a randomised controlled trial. australian journal of physiotherapy. 2004; 50: 219-24. 29. summers jj, kagerer fa, garry mi, hiraga cy, loftus a, cauraugh jh. bilateral and unilateral movement training on upper limb function in chronic stroke patients: a tms study. journal of the neurological sciences. 2007; 252: 76-82. 7 constraint induced movement therapy in stroke patients jiimc december 2016 page 7 page 8 page 9 page 10 page 11 67 dengue fever is a very hot topic nowadays, not only among health professionals but among politicians as well. and it is rightly so because since 2010, pakistan has been experiencing an epidemic of dengue fever that has caused 16 580 confirmed cases and 257 deaths in lahore and nearly 5000 cases and 60 deaths reported from the rest of the country. the three provinces facing the epidemic are khyber pakhtunkhwa, punjab and sindh. this year punjab has reported 2300 cases, of which 50% alone are from rawalpindi district. in spite of allocation of additional funds it has resulted in draining much of the already meager health resources. while handling the epidemic a lot of emphasis was on providing indoor treatment facilities including platelet transfusions to as many patients as possible. while doing so important principals of community medicine for dealing with epidemics were largely ignored because of the political pressure on the hospital administrators and doctors. it is not only pakistan facing this menace, it is estimated that about 2.5 billion people (over 40% of the world population) are at risk. there are about 50-100 million cases occurring in the population at risk every year. dengue is transmitted by an arthropod (mosquito aedes aegypti ) and caused by a flavivirus infection, the primary host of which are human. therefore the emphasis for controlling the disease should be on the vector control (mainly aedes aegypti mosquito) and protection from mosquito bite. this is what the who recommends. obviously the responsibility for vector control rests on civic bodies and the society itself. in a country where leaking fresh water pipes, broken roads and ditches holding rain water, tyres and pottery shops are abundant with no sense of responsibility for regular garbage disposal and mosquito control, there is abundant space for breading of vector. this is added by underground fresh water tanks, most favorite site for aedes to breed is in almost every house. the money which is spent upon providing treatment facilities, which are expensive, should be diverted towards improving civic services and creating awareness about the preventive measures, which are far less expensive. prevention is better than treatment as it also reduces morbidity whereas treatment will only reduce mortality. t h e wo r l d h e a l t h o r g a n i z a t i o n recommends an integrated vector control program consisting of five elements. if these are practiced in an integrated manner, the disease can be prevented. these are: 1. advocacy, social mobilization and legislation to ensure that public health b o d i e s a n d c o m m u n i t i e s a r e strengthened; 2. collaboration between the health and other sectors (public and private); 3. an integrated approach to disease control to maximize use of resources; 4. evidence-based decision making to ensure any interventions are targeted editorial ------------------------------------------------masood anwar correspondence: prof. masood anwar dean faculty of health and medical sciences riphah international university islamabad dengue fever: a drain on health resources 68 appropriately; and 5. c a p a c i t y b u i l d i n g t o e n s u re a n adequate response to the local situation. this should also be remembered that not every person suffering from fever, body aches and thrombocytopenia is suffering f r o m d e n g u e . m a l a r i a , e s p e c i a l l y falciparum malaria which is also caused by mosquito bite and which also occurs in about the same season has similar signs and symptoms. it is essential that all blood slides from suspected patient must be seen by a well-trained technician, if not by a haematologist. i have yet to see a case of falciparum malaria which does not have some degree of thrombocytopenia. another i m p o r t a n t d i ff e re n t i a l d i a g n o s i s i s chickengunya virus infection. it is also caused by bite of aedes mosquito and has sign and symptoms very similar to dengue. therefore appropriate laboratory diagnosis is also important to establish the diagnosis of dengue fever. even if the diagnosis is confirmed, patient needs not to be admitted in the hospital and if admitted he needs not to be in an isolation ward. patients of dengue are best isolated under a mosquito net in the same ward. who in 2009 gave new dengue case definition to facilitate decision regarding indoor management of patients. these are: a. d e n g u e w i t h o u t wa r n i n g s i g n s expanded: when there is fever and two of the following: ! nausea, vomiting ! rash ! aches and pains ! leukopenia ! positive tourniquet test b. dengue with warning signs expanded: dengue as defined above with any of the following: ! abdominal pain or tenderness ! persistent vomiting ! clinical fluid accumulation (ascites, pleural effusion) ! mucosal bleeding ! lethargy, restlessness ! liver enlargement >2 cm ! l a b o r a t o r y : i n c r e a s e i n h c t concurrent with rapid decrease in platelet count c. severe dengue expanded: dengue with at least one of the following criteria: ! severe plasma leakage leading to: – shock (dss) – f l u i d a c c u m u l a t i o n w i t h respiratory distress ! severe bleeding as evaluated by clinician ! severe organ involvement – liver: ast or alt ≡ 1000 – cns: impaired consciousness – failure of heart and other organs in (a) hospital admission is not required. second stage requires close supervision and medical intervention but admission and vigorous treatment is essential in third case. following who guidelines, both for prevention and treatment with strict monitoring and audit will not only substantially reduce the cost of dengue control but may completely eliminate the disease. page 4 page 5 jiims final.cdr 15 original article abstract objective: dna analysis for the genetic mapping of candidates of deafness genes in pakistani families. study design:it was a cross sectional study. place and duration of the study: department of biochemistry/molecular biology, quaid i azam university, islamabad pakistan. the clinical examination, biochemical tests, interpretation of results and preparation of results completed in approximately one year, 2006 2007. materials and methods: study was conducted on two pakistani families. subjects (families) selected for the study: two pakistani families labeled as family a and b were selected for the study. family a comprises of three normal and three affected (deaf) individuals. family b comprises of two normal and four affected (deaf) individuals. the blood samples were immediately dispatched to molecular genetic laboratory, quaid i azam university, islamabad for analysis 2006 2007. results: in family a, linkage was established to dfnb47 locus on the chromosome 2p25.1-p24.3. in family b, linkage to dfnb1 locus was excluded first by genotyping polymorphic microsatellite markers linked to the candidate region and then by sequencing gjb2 gene conclusion: the genetic mapping of candidates of deafness genes brings greater understanding of molecular basis of deafness and would modify the preventive and curative methods. key words: dnf, dna, gjb, pcr and electrophoresis x-chromosomal recessive, or maternal 7trait. x-chromosomal dominant and y linked transmission are rare. syndromic hearing impairment is associated with malformation of the external ear or other organs with medical problems involving other organ systems. more than 70% of the hereditary 8hearing loss is non syndromic. of the 30,000 50,000 human genes, 1% i.e. 300 500 genes, are estimated to be necessary 9for hearing. gap junctions are clusters of intercellular channels, vital of intercellular communication. the following connexins expressed in the auditory system have been implicated in hereditary deafness, gjb2, 11, 14, 16gjb3, gjb6 and gja1. mutation in the alpha tectorin gene on chromosome 11q has been found in families with both autosomal dominant and autosomal recessive having 15prelingual hearing loss. mutations in the trans membrane inner ear (tmie), trans membrane channel like 1 (tmc1), my06 introduction hearing impairment is the most common 1sensory disorder worldwide. it is clinically and genetically very heterogeneous and auditory genes are discovered at very rapid p a c e . g e n e t i c f a c t o r s a re p ro b a b l y responsible for more than 50% of the cases of 2early onset h1. where as in most of the late onset h1 a combination of genetic as well as 3environmental factors is involved. studies of the epidemiology of hearing impairment have suggested that approximately 1 in 1000 to 1 in 2000 children show a profound 4, 6hearing loss at birth or in early childhood. most frequently hearing impairment, is classified as syndromic or non syndromic, or according to its transmission via as autosomal dominant, autosomal recessive, ------------------------------------------------genetic mapping of candidates of deafness genes in pakistani families irum afshan, mubin mustafa, nasim ilyas, usman nawaz, kashif rahim, saleem murtaza correspondence: dr. irum afshan m.sc, m.phil biochemistry qau ph.d scholar, biochemistry nust, islamabad 15 16 gene, my015 gene, transcription regulators, pou3f4, pou4f3, icere-1, coch, kcnq4, col11a2 and mitochondrial genes (12 srrna gene) have been found to be involved in different types of deafness in 17, 30many studies. a cross sectional study was conducted on two pakistani families at department of biochemistry/molecular biology, quaid i azam university, islamabad pakistan. the clinical examination, biochemical tests, interpretation of results and preparation of thesis completed in approximately one year 2006-2007. families studied two families labeled as family a and b were selected for the study. family a comprises of three normal and three affected (deaf) individuals. family b comprises of two normal and four affected (deaf) individuals. after detailed discussion with the elders of these families, genetic pedigrees were 37drawn by following standard method. mode of inheritance was inferred through pedigree analysis. blood sampling blood samples from both normal as well as affected individuals including their parents were collected by 10 cc syringes (08×38 mm 21g×11/2) in standard potassium edta tubes. the blood samples were immediately dispatched to molecular genetic laboratory, quaid i azam university, islamabad for analysis 2006-2007. extraction and purification of genomic dna from blood genomic dna was extracted from blood by phenol / chloroform method. dna dilution and micro pipetting polymerase chain reaction (pcr) materials and methods pcr was performed using gene amp pcr system 2400 and 9600 thermo cycler (perkin elimer usa). agarose gel electrophoresis agarose gel electrophoresis was carried out to analyze the amplified dna samples. after electrophoresis amplified product was detected by placing the gel on uv trans illuminators (life technology, usa). polyacrylamide gel electrophoresis gel was photographed by using digital camera dc 120 (kodak, usa). genotyping and primer database analysis m i c ro s a t e l l i t e m a r k e r s m a p p e d b y cooperative human linkage centre (chlc), were obtained from research genetics, inc. (usa). the cytogenetic location of these markers as well as the length of the amplified product was obtained from genome data base homepage (www.gdb.org) and marshfield medical center(www.marshmed.org.gov/genetics) linkage studies l i n k a g e s t u d i e s w e r e p e r f o r m e d , automated genetic analyzer abi prism 310 (applied bio system, usa). in the present study family a was first tested for mapping to several known loci by using polymorphic microsatellite markers from their candidate linkage intervals. the family a was found to be linked to dfnb47 locus on chromosomal region 2p25.1-p24.3. two loci for arnsh1 have previously been 2localized to chromosome. in family bdnfb1 and several other loci were tested for linkage. electropherograms obtained by genotyping the microsatellite linked to the candidate linkage gene interval revealed that the affected individuals were heterozygous for different combinations of results 16 17 parental alleles, thus indicating exclusion of family b from linkage to dfnb1 and several other known autosomal recessive non syndromic hearing loss loci. linkages to dfnb1 locus were also excluded by sequencing the coding region of exon 2 of gjb2 gene. the novel locus harboring the disease gene in family b can be located by a genome wide search by using polymorphic markers spaced at 10 cm apart on all the autosomes. to date 23 known genes lie in the 5.3 mbregion that contains dfnb 47. one of the genes in this region, kcnfi, is a strong candidate for dfnb47. this gene codes for p o t a s s i u m v o l t a g e g a t e d c h a n n e l . potassium ion channels are a diverse family of plasma member's proteins that play an essential role in various cellular processes, including maintenance of membrane 31potential and cell signaling. kcnq4 is a voltage gated k+ channel gene expressed in the cochlea. voltage-gated k+ channel genes have been shown to be responsible for various hereditary diseases. for instance, mutation in the kvlqti gene (a voltagegated k+ channel gene) result in jervell and lange-nielsen syndrome (jlns) and long qt syndrome, which are inherited ar disease, with congenital hi being one of 32their characteristics. jlns can also result from mutations in another voltage-gated k+ channel gene, kcnei. another good candidate gene is inhibitor of dna binding 2 (id2), which is a member of the id family genes that promotes cell proliferation. in embryonic mouse, id2 expression was detected in the vestibular and acoustic ganglia, and also in the epithelium of the otic vesicle and discussion 33surrounding mesenchyme . other genes that are expressed in the inner ear include: (1) cleavage and polyadenylation specific factor 3 2004); (2) tyrosine 3/ tryptophan 5monooxygenase (ywhaq), which is also expressed in the spinal cord of patients with 3 5amyotrophic lateral sclerosis. and ornithine decarboxylase 1 (odci), the rate limiting enzyme in polyamine synthesis. the recent identification of several deafness genes by molecular genetic studies has enabled the molecular basis of normal and pathological auditory function. in the coming years, further deafness genes are sure to be identified and mouse models for the human disease will be constructed as start in the long process of understanding the pathological processes involved in deafness. the rate of discovery of deafness genes by positional cloning in human will be accelerated by the freely available human genome sequence and by a catalogue of expressed sequence tags (ests) within genetic intervals known to contain locus for human hereditary hearing loss. to assist in the identification of deafness genes cdna library has been synthesized, partially sequenced and many ests assigned map 36position. the genetic mapping of candidates of d e a f n e s s g e n e s b r i n g s g r e a t e r understanding of molecular basis of d e a f n e s s a n d w o u l d m o d i f y t h e preventive and curative methods. 1. berlin-glindzicz m. hereditary deafness and pheno-typing in humans. br med bull 2002;63 :73-94. 2. marzita ml, rawlings b, remington b, amos ks, nance we. genetic epidemiological studies of conclusion references 17 18 early-early on set deafness in the u.s schoolage population. am j hum genet 1993;57:62935. 3. cohen mm, gorlin rj. epidemiology, etiology, and genetic patterns; in gorlin rj toriello hv, cohenmm (ed). hereditary hearing loss and its syndromes. oxford monographs on medical genetics. 1995; p: 9-21. 4. parving a. epidemiology of hearing loss and etiological diagnosis of hearing impairment in childhood. int j ped otorhined 1983; 7:29-38. 5. newton ve. etiology of bilateral sensorineural hearing loss in young children. j laryngol otology 1985; 10:1-57. 6. fortnum h, davis a. epidemiology of permanent childhood hearing impairment in trent region. brit j aud 1997;31:409-46. 7. smith an, brothwick kj. molecular cloning and characterization of novel tissue specific isoforms of the human vacuolar h (+) atpase c, g and d subunits, and their evaluation in autosomal recessive distal renal tubular acidosis. gene 2002; 297: 169-77. 8. van camp g, coucke p, nalenans w. localization of gene for non syndromic hearing loss to chromosome 7p15. mol genet 1995; 4: 2159.63 9. friedman bt, griffith ja. human non syndromic sensorineural deafness. ann rev hum genet. 2003; 4:341-402. 10. kikuchi t, kimura rs, paul dl, adams jc. gap junctions in the rat cochlea: immuno histochemical and ultra structural analysis. anat embryo 1995; 191:101-18. 11. scott da, kraft ml. conexant mutations and hearing loss. nature 1998; 391: 32. 12. carrasquillo mm, zlotogora j, barges s, chakravarti a. two different connexin 26 mutations in an inbred kindred segregating n o n s y n d r o m i c r e c e s s i v e d e a f n e s s : implications for genetic studies in isolated populations. hum mol genet 1997; 6:2163-72. 13. richard g, white tw. functional defect of c*26 resulting form a heterozygous missense mutation in a family with dominant deaf mutes and palm planter kerato derma. hum genet 1998; 103: 393-9. 14. teubner b, michel v. connexin 30 (gjb6) deficiency causes severe hearing impairment and lack of end cochlear potential. hum mol genet 2003;12: 13-21 15. verhoeven k, van laer l, kirschlofer k. mutation in human alpha tectorin gene cause autosomal dopminant non syndromic hearing impairment. nat genet 1998;19: 60-2. 16. liu xz, xia x adams j, chen zy. mutation in gja (connexin 43) are associated with non syndromic autosomal recessive deafness. hum mol genet 2001; 10: 2945 51 17. mitchem kl, hibbard e beyer la bosom k dootz ga. mutation of the novel gene tmie results in sensory cell defects in the inner ear of sponner, a mouse model of human hearing loss dfnb6. hum mol genet 2002; 11:1887-98. 18. kurima k, peters lm, yang y, reazuddin s ahmed zm. dominant and recessive deafness caused by mutation of a novel gene, tmci, required for cochlear hair-cell function. nat genet 2002; 30:277-84. 19. petersen mb. non syndromic, autosomal dominant deafness. clin genet 2002; 62: 1-13. 20. wang a, liang y, friedell ra. association of unconventional myosin myo15 mutations with human non syndromic deafness dfnb3. science 1998; 280: 1447-51. 21. cantos r, cole lk, acampora d, simeone a, wu dk. patterning of the mammalian cochlea. proc natl acad sci usa 2000; 97:1707-13. 22. anagnostopoulos av. a compendium of mouse knockouts with inner ear defects. trends genet 2002;18:21-38. 23. de kok yj, van der maarel sm, biterglindziez m, huber i, monaco ap, malcolm s et.al. association between xlinked mixed deafness and mutations in the pou domain gene pou3f4. science. 1995;267: 685-8. 24. vahava o, morell r, lynch ed. mutation in transcription factor pou4f3 associated with inherited progressive hearing loss in humans. science 1998;27: 1950-4. 25. van camp g, willens pj, smith rj. non syndromic hearing impairment unparalleled heterogeneticity. am j hum genet 1997;60: 75864. 26. khetarpal u, schuknecht hf, gacek rr, holmes lb. autosomal dominant sensorineural hearing loss, pedigrees, audiologic finding, and temporal bone findings two kindreds. arch otolaryngol head neck surg. 1991; 117: 1032-42. 18 19 27. kubisch c, schroeder bc, friedrich t, lutjohann b, e1amraoui a. kcnq4, a novel potassium channel expressed in sensory outer hair cells, is mutated in dominant deafness. cell 1999;96:437-46. 28. vikkula m, mariman ec, liu vc. autosomal dominant and recessive osteochondrodysplasias associated with the col11a2 locus. cell 1995;80: 431-7. 29. fischel ghodsian n. mitochondrial deafness mutations reviewed. hum mutat 1999;13:26170. 30. zhoa h, li r, wang q. maternally inherited aminoglycoside induced and non syndromic deafness is associated with novel c149t mutation in the mitochondrial 12s rrna gene in large chinese family. am j hum genet 2004; 75: 139-52. 31. s u k , k y a w h , f a n p. i s o l a t i o n a n d characterization, and mapping of two human potassium channels. biochem biophys res commun 1997; 24: 675-81. 32. ilhan a, tuncer c komsuoglu ss, kali s. jervell and lange-nielsen syndrome: neurologic and cardiologic evaluation. pediatr neurol 1999;21:809-13. 33. jen y, manova k, benezra r. each member of t h e i d g e n e f a m i l y e x h i b i t s a u n i q u e expression pattern in mouse gastrulation and neurogenesis. dev dyn 1997;208:92-106. 34. calzado ma, sancho r, munoz e. human immunodefiency virus type 1 that increases the expression of cleavage and polyadenylation specificity factor 73kilodalton subunit modulating cellular and viral expression. j viral 2004; 78:6846-54. 35. malaspina a, kaushik n de bellerouche j. a 143.3 m rnais upregulated in amyotropic lateral sclerosis spinal cord. j neurochem 2000;75:2511-20. 36. skvorak ab, weng z. human cochlear expressed sequence tags provide inside into cochlear gene expression and identify candidate gene for deafness. hum mol genet 1999; 8: 439-52. 37. b e n n e t t r l , s t e l n h a u s k a , u h r i c h . recommendations for standardized human pedigree nomenclature. am j hum genet 1995; 56: 745-52. 38. ma tabatabaiefar, f alasti, zohour m. genetic linkage analysis of 15 dfnb loci in a group of iranian families with autosomal recessive hearing loss. iranian journal of public health 2011;40 : 34-8. 39. kelsell dp, dunlop j, stevens hp, lench nj, liang jn, et al. connexin 26 mutations in hereditary non-syndromic sensorineural deafness. nature 2009; 387: 80-3. 40. h e r e d i t a r y h e a r i n g l o s s h o m e p a g e . available:http://herditaryhearingloss.org/.ac ces-sed april 2010. 41. b sagong, r park, kim y. .two novel missense mutations in the tecta gene in korean f a m i l i e s w i t h a u t o s o m a l d o m i n a n t nonsyndromic hearing loss ann clin lab sci autumn 2010;40: 380-5. 19 original�article abstract objective: to determine and compare the levels of ischemia modified albumin (ima) in healthy individuals , diabetes without retinopathy, and diabetic having no proliferative and proliferative retinopathy. study design: cross sectional comparative study. place and duration of study: diabetic clinic, lahore general hospital from september 2104 to may 2015. materials and methods: sixty subjects were divided into three groups with 20 subjects in each. group i was control group, included healthy subject, group ii included diabetics without retinopathy and group iii included diabetics with retinopathy which comprised of both diabetics with proliferative and non-proliferative diabetic retinopathy. indirect method using a 90 % d lens was used to diagnose diabetic retinopathy by a consultant ophthalmologist. the levels of ima were measured by a colorimetric albumin cobalt binding assay and the values were presented as absorbance units. data was analyzed using ibm spss version 23. results: out of 66 % of diabetics individuals 33% were diabetics without retinopathy and 33 % were diabetics with retinopathy out of which 55% had proliferative diabetic retinopathy (pdr) and 45% had non proliferative diabetic retinopathy (npdr). low levels of ima were seen in 33% of diabetics without retinopathy and significantly higher levels of ima were seen in 27 % of diabetics with proliferative diabetic retinopathy. conclusion: we conclude from our study that the levels of ima raise with the progression of the disease, higher levels of ima are seen in diabetics with proliferative as compared to non proliferative diabetic retinopathy and as compared to diabetic without retinopathy. key words: albumin,diabetes mellitus,diabetic retinopathy,ischemia,oxidative stress. early treatment diabetic retinopathy study (etdrsthe modified airlie house classification). diabetic retinopathy advances from very mild retinopathy, to non proliferative diabetic retinopathy (npdr ) to proliferative diabetic retinopathy (pdr) in which proliferation of the new blood vessels, in the retina 4,5,6, and vitreous gel occurs, thus filling the eye . human serum albumin has n –terminal which has a tendency to cohere metal ions such as nickel, iron and cobalt. exposure of human serum albumin to ischemia or oxidative stress leads to biochemical degradation of n terminal thus decreasing its affinity for the metal ions. this human serum albumin having reduced ability to cohere to metal ions is called as ischemia modified albumin. 7 initially serum ima was well thought-out as a valuable indicator for acute coronary syndrome and 8 cardiac ischemia. however, now ima is also known 9 as an indicator of oxidative stress. study in the patients of diabetes have shown higher levels of ima as compared to controls , which result due to uninhibited oxidative stress, on the endothelial cell because of hyperglycemia and subsequently introduction diabetes mellitus is globally a major public health 1 priority. the complications of the disease are broadly classified as acute and late complications. which are further classified as microvascular and 2 m a c ro va s c u l a r co m p l i cat i o n s . a m o n g t h e commonest microvascular complications is diabetic retinopathy, which eventually leads to blindness in 3 most cases. the diabetic retinopathy is classified according to ischemia modified albumin levels in diabetes mellitus patients with and without diabetic retinopathy 1 2 3 4 5 6 sana rasheed chaudhry , muniza saeed , zunnera rashid chaudhry , komal iqbal , erum rashid , faiza rasheed correspondence: dr. sana rasheed chaudhry assistant professor physiology ameer-uddin medical college, lahore e-mail: sanajawad53.sj@gmail.com 1,2,4 department of physiology ameer-uddin medical college, lahore 3 department of pharmacology rawal institute of health sciences, islamabad 5 department of biochemistry quetta institute of medical sciences, quetta 6 department of ophthalmology mughal eye hospital, lahore funding source: nil; conflict of interest: nil received: september 16, 2020; revised: june 10, 2021 accepted: july 06, 2021 ischemia modified albumin in diabetic retinopathy jiimc 2021 vol. 16, no.3 161 released reactive oxygen species modifies the 10 albumin. increased levels of ima have been seen in patients with diabetic retinopathy as compared to diabetics without retinopathy however very limited literature is available for the levels of ima in different stages of diabetic retinopathy. a study done by reddy et al, showed increased levels of ima in diabetics suffering from pdr when compared with diabetics with npdr. the succession of the disease from npdr to pdr results in increased production of reactive oxygen species thereby increasing the levels 11 of serum ima in diabetics with pdr. a study done by gulpamuk et al, suggested that levels of ima can be used as a biomarker to determine the damage due to tissue ischemia in dm and to classify the different stages of dr, in the 12 future. diabetes and its complications considerably influence the life of the patient. till now no economical marker is available for the early detection of the progression of diabetic retinopathy to proliferative diabetic retinopathy. so, the aim of the study was to determine and compare levels of ima in healthy individuals, diabetics without retinopathy and diabetics with npdr and pdr. materials and methods this comparative and cross-sectional study was carried in diabetic clinic of lahore general hospital on 60 subjects including both males and females from september 2014 to may 2015. sample size came out to be 20 in each group with the power of study=90. subjects were selected by nonprobability, purposive sampling. the protocol of this research was accepted by the members of ethical review committee of the post graduate medical institute of lahore. the subjects of the study were split into three groups. the control group 1 consisted of 20 normal healthy adults, group 2 was of 20 diabetic patients without retinopathy and group 3 had 20 diabetic patients with retinopathy out of which 11 had proliferative diabetic retinopathy and 9 had no proliferative diabetic retinopathy. presence or absence of diabetic retinopathy was diagnosed by an ophthalmologist on slit lamp through an indirect method using a 90d lens. subjects with history of smoking, hypertension, end stage renal disease, diabetic foot, autonomic neuropathy, liver cirrhosis, acute coronary syndrome, and cerebrovascular occlusion were excluded from the study based on history and clinical examination. each participant was briefed about the study and then written informed consent was taken. 4 ml of blood sample was collected from antecubital vein under aseptic conditions and was put in gel vial (yellow top) for measurement of ima. sample was then routinely centrifuged within 1 hour of collection for 15 minutes at 3000 revolutions per minutes and aliquots of serum samples were stored at -20 °c for a maximum of one week before ima measurement. serum levels of ima were measured by colorimetric method explained by bar-or et al and results were reported in absorbanse units, data was analyzed using spss version 23 and was explored for normality by shapirowilk's statistics test of normality. data came out to be nonparametric. kruskal wallis test and mann whitney u test was applied to compare the parameters among the groups and two groups respectively, and the value of p< 0 .05 was taken as statistically significant results comparison of the levels of ima in the three groups showed a significant difference of p<0.00 respectively. fifty five percent of the population of diabetic retinopathy group had pdr and 45 percent had npdr (table i). comparison of serum ima levels in group i and diabetics with proliferative retinopathy and no proliferative diabetic retinopathy revealed a significant difference as shown in table ii. comparison of serum ima between the diabetics without retinopathy and diabetics with pdr revealed a significant difference however, when ima of . diabetics without retinopathy was compared with npdr a nonsignificant difference was seen as shown in table iii. when the levels of ima were compared between diabetics with no proliferative and proliferative diabetic retinopathy a significant difference was revealed as shown in table iv. table i: frequency distribution of study population ischemia modified albumin in diabetic retinopathy jiimc 2021 vol. 16, no.3 percentage % 162 compared to any other tissue in the body, which 14 renders retina susceptible to oxidative stress. in our study there was non-significant difference in the level of ima in patients without diabetic retinopathy with non proliferative diabetic retinopathy. our result is in correlation with the result shown by bozkurl et al in 2019 on a group of diabetics without retinopathy and diabetics with non-proliferative diabetic retinopathy in which that the concentration of an oxidative stress marker rises in proportion to the severity of the dr, but the 15 comparison did not show the significant difference. gulpamuk et al, 2018 in one of his research concluded that increase in oxidative stress in diabetics leads to increase levels of oxidative stress markers such as ima in diabetics having proliferative retinopathy when compared to diabetics without 12 retinopathy. the progression of the disease from npdr to pdr causes a noteworthy rise in the levels of oxidative stress which is reflected by high levels of ima in our study in diabetics with proliferative diabetic retinopathy as compared to diabetics with nonproliferative diabetic retinopathy. this result is similar to the results seen by gulpamuk et al in 2018 in which increase in levels of serum ima were seen in pdr patients as compared to those having npdr thus indicating underlying ischemia and subclinical 12 inflammation. thus, we can say as there is progression of disease from non-proliferative to proliferative diabetic retinopathy there is more oxidative stress leading to underlying ischemia and subclinical inflammation. so, increased level of ischemia modified albumin can be taken as a marker of proliferative diabetic retinopathy patients as compared to those with non proliferative diabetic retinopathy limitations and recommendations follow-up of the patients with npdr should have been done in order to see the alteration in the levels of ima so that the disease may not progress to pdr. in further studies antioxidants levels and lipid profile should be estimated to evaluate the oxidative status of the body. conclusion we conclude from our study that the levels of ima raise with the progression of the disease, higher levels of ima are seen in diabetics with proliferative discussion oxidative stress induced by high blood glucose level in diabetic patients is a leading cause of many ocular degenerative changes, to reduce the hazardous effects of diabetes mellitus on vision an effective screening marker should be introduced to assess the progression of diseases to the proliferative diabetic retinopathy which is a leading cause of blindness. our study shows high levels of ima in diabetics with npdr, and pdr are seen as compared to controls group. reddy vs et al, 2016 in one of his study concluded that the levels of ischemia modified albumin were higher in patients with npdr as compared to control group, this supports the idea that there is a role of oxidative stress in the 11 development of diabetic retinopathy. gaonkar b et. al 2020 in his study concluded that the concentration of oxidative stress markers are higher in patients with proliferative diabetic retinopathy as compared to controls, the results of his study support our study as there is high level of ima in diabetic with pdr as 13 compared to controls. retina has a large amount of polyunsaturated fatty acid, and also has maximum capacity of oxygen uptake and glucose utilization as table ii: comparison of ima levels between healthy controls, diabetic with pdr and npdr table iii: comparison of ima levels between diabetics without retinopathy and diabetic with pdr and npdr table iv: comparison of ischemia modified albumin levels in diabetics with pdr and npdr ischemia modified albumin in diabetic retinopathy jiimc 2021 vol. 16, no.3 163 as compared to non proliferative diabetic retinopathy and as compared to diabetic without retinopathy. references 1. forouhi ng, wareham nj. epidemiology of diabetes. medicine: 2010; 38(11):602-6. 2. alaboud af, tourkmani am, alharbi tj, alobikan. ah, abdelhay o, al batal sm, et al. microvascular and macrovascular complications of type 2 diabetic mellitus in central, kingdom of saudi arabia. saudi med j. 2016; 37(12):1408-11. 3. nentwich mm, ulbig, mw. diabetic retinopathy-ocular complications of diabetes mellitus. world j. diabetes. 2015; 6(3):489-99. 4. salmon jf, kanski's jj. clinical ophthalmology asystemic th approach. 9 edition: elsevier;2020;498. 5. singh rp, elman mj, singh sk, fung ae, stoilov i. advances in the treatment of diabetic retinopathy. journal of diabetes and its complications. 2019 dec 1;33(12):107417. 6. loukovaara s, piippo, n, kinnunen,k, hytti, m, kaarniranta, k, kauppinen, a. nlrp3 inflammasome activation is associated with proliferative diabetic retinopathy. acta ophthalmol. 2017; 95(8):803-8. 7. oran, i, oran, b. ischemia-modified albumin as a marker of acute coronary syndrome: the case for revising the concept of “n-terminal modification” to “fatty acid occupation” of albumin. dis markers. 2017;2017(2):1-8. 8. coverdale, jp, katundu, kg, sobczak, ai, arya, s, blindauer, ca, stewart, aj. ischemia-modified albumin: crosstalk between fatty acid and cobalt binding. prostagleukotress. 2018; 135:147-57. 9. bahinipati, j, mohapatra, pc. ischemia modified albumin as a marker of oxidative stress in normal pregnancy. jcdr. 2016;10(9):15-17. 10. turk, a, nuhoglu, i, mentese, a, karahan, sc, erdol, h, erem, c. the relationship between diabetic retinopathy and serum levels of ischemia-modified albumin and malondialdehyde. retina. 2011;31(3):602-8. 11. reddy vs, sethi s, gupta n, agrawal p, siwach rc. significance of ischemia-modified albumin as a simple measure of oxidative stress and its discriminatory ability in diabetic retinopathy: literature review and meta-analysis. retina. 2016;36(6):1049-57. 12. gulpamuk b, tekin k, sonmez k, inanc m, neselioglu s, erel o, yilmazbas p. the significance of thiol/disulfide homeostasis and ischemia-modified albumin levels to assess the oxidative stress in patients with different stages of diabetes mellitus. scandinavian journal of clinical and laboratory investigation. 2018 feb 17;78(1-2):136-42. 13. gaonkar, b, prabhu, k, rao, p, kamat, a, rao addoor k, varma, m. plasma angiogenesis and oxidative stress markers in patients with diabetic retinopathy. biomarkers. 2020; 11:1-5. 14. saccà, sc, cutolo, ca, ferrari, d, corazza, p, traverso, ce. the eye, oxidative damage and polyunsaturated fatty acids. nutrients. 2018;10(6):668-82. 15. bozkurt e, çakır, b, çelik, e, doğan, e, uçak, t, alagöz, g. correlation of the aqueous humor total antioxidant capacity, total oxidant status, and levels of il-6 and vegf with diabetic retinopathy status. arquivosbrasileiros de oftalmologia. 2019; 82(2):136-40. ischemia modified albumin in diabetic retinopathy jiimc 2021 vol. 16, no.3 164 jiims final 8 original article abstract objective: the objective of this study was to observe changes in spermatogenesis testes of albino rats exposed to intraperitoneal lead acetate and to look for the reversibility of these changes after cessation of lead acetate and subsequent oral administration of honey. study design: experimental animal study. place and duration of study: national institute of health islamabad from january to june, 2009. materials and methods: animals were obtained from the animal house of n.i.h and were divided into three groups a, b and c. group a was subdivided into two groups a-i and a-ii. group b was also subdivided into two sub groups; b-i & b-ii. group c was not subdivided into subgroups. the animals in group a were used as control, while those of groups b and c were treated with lead acetate that was given intraperitonially in the dose of 4mg/kg body weight, 5 days a week for 6 weeks. the animals in group b-i were sacrificed at the end of six week to observe the toxic changes while animas in group b-ii were kept alive for another 6 weeks on normal diet. the animals in group c were given honey in dosage of 10ml/100ml water with normal diet for further 6weeks. these groups (b-ii and c) were then sacrificed after 12 weeks to observe the effects of honey on spermatogenesis. results: the histological comparison of testes of both groups of animals showed that after six weeks, the width of germinal epithelium and the number of spermatogenic cells had decreased in lead toxic groups as compared to the control rats (p<0.05) and in majority of the seminiferous tubules, the basement membrane was disrupted. the width of germinal epithelium, and the number of spermatogenic cells were improved after oral administration of honey. conclusion: this study provides evidence that lead has toxic effects on testis which are partially reversible on oral intake of honey. key words: lead, testes, rat, honey. 2. workers exposed to high levels of lead in refineries and smelters. they also come in contact while manufacturing of lead batteries and cables, rubber and (pvc) 5plastic products. 3. the center for disease control (cdc) discovered that there is no toxic threshold for lead. this means that there is no measurable level of lead in the body 6below which no harm can occur. lead toxicity has shown to disrupt both spermatogenesis and 7steoidogenesis. thus; it becomes imperative to find out measures, by which our body can maintain and regulate healthy living and homeostasis even if exposed to high levels of lead toxicity. the standard treatment of lead toxicity is chelation therapy which has many 8side effects. honey is a sweet, golden introduction in pakistan people are specially exposed to lead pollution through three main sources 1i.e., air, soil, and water. lead toxicity induces rupture of nuclear membrane accompanied by fragmentation of nucleus 2in testis (karyorrhexis). in the females, lead toxicity results in irregular menstrual periods, decreased ovarian weight, 3decreased corpora leutea. the common sources of lead are: 1. when the lead rich gasoline comes in c o n t a c t w i t h t h e s o i l , i t g e t s 4contaminated. --------------------------------------------------effects of honey on lead induced changes in spermatogenesis saffia shaukat, imran qureshi, rehmah sarfraz correspondence: dr. saffia shaukat assistant prof. of anatomy islamabad medical & dental college, islamabad bahria university e-mail: saffiailyas@yahoo.com 8 9 coloured, viscous liquid food produced in the honey sac sofvarious honey bees. its value in treating burns, infected surgical wounds and ulcers is established. its viscosity enables it to absorb water from surrounding inflamed tissue. honey is remedial in cases of persistent coughs and 9sore throat. it provides an important part of energy needed by the body to combat 10infections, and for blood formation. honey is cheap, easily available, that's why i have use honey for my research project. a total of 50, eight weeks old healthy adult male albino rats of sprague dawley strain, weighing 200±10 gm were used in the study. these animals were randomly divided into three groups; one was labeled as control (a), while the other was labeled as experimental (b and c) group. these animals were randomly divided into three groups. day 0 was considered to be the starting day of experiment. 1. group a was further subdivided into two subgroups; a-i &a-ii (each group having 10 animals) 2. group b was also subdivided into two sub groups; b-i & b-ii (each group having 10 animals) 3. group c with 10 animals was not subdivided into subgroups. 4. a-i group was control group for lead toxic group b-i. both groups were sacrificed at six weeks. 5. a-ii group was control group for b-ii and c. both groups were sacrificed at twelve weeks. all animals were kept in the animal house under standard conditions at a room temperature r a n g i n g between18o c to 26o c for six weeks. they materials and methods were maintained on 12 hours light and dark cycle. the rats were fed ad libitum. day 0 was considered to be the starting day of experiment. the animals in group b-i, b-ii and c were treated with intraperitoneal lead acetate in the dosage of 4mg / kg body weight / day, 5 days a week for a period of 6 weeks. the animals in group b-i were sacrificed at the end of six week to observe the toxic changes while animals in group bii were kept alive for another 6 weeks on normal diet. the animals in group c were given honey in dosage of 10ml/100ml water with normal diet for further 6weeks. these groups (b-ii and c) were then sacrificed after 12 weeks to observe the effects of honey on spermatogenesis. after sacrifice, each animal was taken out of the jar and placed on the dissecting board. the scrotal sac was then opened with the help of forceps and scissors. testes were examined with the help of hand lens and their colour, consistency and gross appearance was noted. the testes were fixed in formalin and then processed for paraffin embedding. five micrometer thick section were cut, stained with hematoxylin & eosin, and observed microscopically for germinal epithelium thickness and to study the cells of spermatogenic series. statistical analysis the data was entered into spss version 13.0. analysis of variance (anova) was used to compare the change in variables between the groups. mean and standard deviation of the parameters were calculated and results of different study groups were compared. pvalue of < 0.05 was considered significant. all the rats in control group a remained results 9 10 active and healthy with normal feeding behavior. after six weeks, the animals in group c were relatively more active than group b-ii animals. the testes of rats exposed to toxic dose of lead (group b-i & bii) showed reduction in size; they were pale looking, tough in consistency and showed resistance on cutting. it was difficult to pluck out any tubule from the testes and stringing out phenomenon was absent. the testes of the rat in group c were light pink in color and firm in consistency. their blood vessels were visible under magnifying glass and showed mild resistance on cutting. the animals in this group gained significant weight increase in the testes i.e. 1.27 gm. (sd ± 0.040) in comparison with group b-ii. germ cell count / cross section of seminiferous tubule: the average germ cell count in group a-i w a s 3 0 4 . 5 3 c e l l s / c r o s s s e c t i o n o f seminiferous tubule (sd + 28.46), in group a-ii it was 323.53 cells/unit (sd = 28.46), in group b-i it was 116.91 cells/unit (sd + 32.66), in group b-ii it was 136.24 cells/unit (sd + 33.51) and in group c it was 214.58 cells/unit (sd + 33.51). the difference between all the groups was significant (p < 0.001). the germ cell count was significantly higher in group a-i as compared to groups b-i, b-ii and c (p < 0.001) (figure 1). the difference between groups a-i and a-ii was insignificant (p > 0.467). in group a-ii, the germ cell count was significantly higher as compared to groups b-i, b-ii and c (p < 0.001) but the difference from group a-i was insignificant (p > 0.467). the germ cell count was significantly lower in group b-i as compared to groups a-i, a-ii and c (p < 0.001) but the difference from group b-ii was insignificant (p > 0.449) figure 2. in group bii, the germ cell count was significantly lower as compared to groups a-i, a-ii and c (p < 0.001) but insignificant from group b-i (p > 0.449). the germ cell count in group c was significantly lower as compared to groups a-i and a-ii but significantly higher as compared to groups b-i and b-ii, (p < 0.001). (figure .3) & table no.ii the testes of rats in the control group a were easily pushed out of the scrotal sac, well vascularized and were soft in consistency. they were pink in colour and on cutting, gave little resistance. the seminiferous tubules had normal plucking and stringing figure-1: photomicrograph; testis cross section, seminiferous tubule of control group ai, animal1 number 1. h & e x 400 out phenomenon of the tubules. the mean weight of pairedtestes was 1.28 gm (sd + 0.04).the testes of rats exposed to toxic dose of lead (group b) showed reduction in size; t h e y w e r e p a l e l o o k i n g , t o u g h i n consistency. it was difficult to pluck out any tubule from the testes. the mean weight of paired testes was 1.16 gm (sd ± 0.029) in group b . the epithelial height was significantly 10 11 higher in group a as compared to groups b, (p < 0.001) figure 1. figure-2: photomicrograph-section of testis of experimental group (group b-i) animal number 10, showing reduced germ cell count and reduced height of germinal epithelium. h&e stain. x 420. figure 3: photomicrograph; cross section of testis; honey treated group c, animal number 10, seminiferous tubule showing basement membrane and spermatogenesis h&e stain x 400 figure 4: bar chart showing description of germ cell count (cells/ cross section of seminiferous tubule) in all the study groups (error bars ± sd table no-i: table showing description of germ cell count (cells/ cross section of seminiferous tubule) in all the study groups (error bars ± s discussion the present study was conducted to evaluate the protective role of honey on lead induced histological changes in the rat's testes. lancranjan et. al, (1975) and cullen et al., (1983)conducted a study on men exposed to lead at their workplace. they s h o w e d a b n o r m a l i t i e s o f 11,12spermatogenesis. roshandel (2006) found that after 8 weeks of lead exposure, there was decrease in the height of germinal 11 12 epithelium and the number of sertoli cells in test group, whereas spermatogonia and p r i m a r y s p e r m a t o c y t e s r e m a i n e d unchanged . this study showed that lead intoxication induced some changes in the adult testes which were irreversible even after d-penicillamine treatment which is contrary to our results, which showed that honey caused partial reversible changes in 13the testes. another study conducted by 14sokol (1985). revealed that lead acetate exposure in 52 days old male wistar rats is toxic to the reproductive axis and caused abnormalities of spermatogenesis which is in accordance to the present study. there was no testicular weight change found in that study as 0.3% lead acetate was given in distilled water. however rats lost overall 14weight. manlay (1995) administered lead acetate to rats in the dose of 8mg/kg body 15weight, 5 days a week for 35 days. the study concluded that the germ cells and sertoli cells were not affected by such a high dose of lead and this is in contrary to the present study but it did affect accessory sex glands by reducing the intertubular tissue volume in testes which indicate leydig cell 15function impairment. during past three decades, the decline in male reproductive health and fertility has been linked with 16environmental toxicants and xenobiotics. a study conducted by mohammed (2011) showed that honey could improve the toxic effect of lead on testicular function partly by improving testicular blood flow and spermatogenesis via the oestrogenic activity 17of its phenolic compounds. my present study validated the previous studies results and further added a new dimension to the existing literature by investigating the effect of honey on lead-induced toxicity in the testes of sprague dawley rats. this study provides evidence that lead has toxic effects on testis which are partially reversible on oral intake of honey. 1. rajendra ramlogan. environment and human h e a l t h : a t h r e a t t o a l l . e n v i r o n m e n t a l management and health 1997; 8: 51-66. 2. benoff s, jacob a, hurley ir. male infertility and environmental exposure to lead and cadmium. hum reprod 2000; 6: 107-21. 3. srivastava v, robert k. dearth, jill k. hiney,lisa m. ramirez, gerald r. bratton and w. les dees. the effects of low-level pb on steroidogenic acute regulatory protein (star) in the prepubertal rat ovary. toxicological sciences 2004; 77: 35-40. 4. farooq y, hussain mm, aleem sb, frooq ma. lead intoxication. the extent of lead problem and its management. pak j physiol 2008; 4(2). 5. n. shobha, ab. taly, s sinha and t. venkatesh. radial neuropathy due to occupational lead exposure; phenotypic and electrophysiological characteristies of five patients. ann. india acadamy neurol 2009; 1-11. 6. p a t r i c k l . l e a d t o x i c i t y , a r e v i e w o f literature.part 1;expoure, evaluation and treatment. alternative medicine review,a journal of clinical therapeutic. november 2006; 11; 2-22. 7. ahmed e. abdel moniem, mohamed a. dkhil, and saleh al-quraishy. protective role of flaxseed oil against lead acetate induced oxidative stress in testes of adult rats. african journal of biotechnology 2010;9:7216-23 8. swaran j.s. flora s, pande m and mehta a. beneficial effect of combined administration of s o m e n a t u r a l l y o c c u r r i n g a n t i o x i d a n t s (vitamins) and thiol chelators in the treatment of chronic lead intoxication. chemico-biological interactions 2003; 2:67-80. 9. ndayisaba g, bazira l, habonimana e, muteganya d. clinical and bacteriological outcome of wounds treated with honey. j orthop surg 1993; 7:202-4. conclusion references 12 13 10. noori s. effects of daily consumption of honey solution on hematological indices and blood levels of minerals and enzymes in normal individual. journal of medicinal food 2003;6: 135-40. 11. l n a c r a n j a n , p o p e s c u j l , g a v e n s c u o reproductive ability of workmen occupationally exposed to lead. arch. environ health, 1975; 30:396-401. 12. c u l l e n . a d u l t i n o r g a n i c i n t o x i c a t i o n : presentation of 31 new cases and review of recent advantages in the literature. medicine 1983;62: 221. 13. chapin, robert e, long term low dose exposure alters the gonadotrpin-releasing hormone system in the male rat, environ health pesrpect, 2002;110: 871-74. 14. roshandel d., roshandel g., golalipour j m. morphometric changes of rat testis of sub chronic oral lead intoxication and d penicillamin treatment, pakistan journal of biological seinces 2006; 9:1310-14. 15. sikka s c, wang,r. endocrine disruptors and estrogenic effects on male reproductive axis. asian journal of andrology 2008;10:134-45. 16. mohamed m, siti a.s., hasnan j, kuttulebbai n.s.s., zul i.m.i., and mohammed n.i., effect of honey on testicular functions in rats exposed to cigarette smoke. journal of apiproduct and apimedical science 2011; 3:12-17. 13 207 editorial new and emerging therapeutic agents for the management of sars-cov-2 coronavirus infection covid-19 sayed subhan bukhari, shaun h livsey covid-19 emerged as a new severe acute respiratory illness in wuhan, china in december 2019 and rapidly spread worldwide to become a global 1 pandemic. although the figures keep changing on daily basis, by the end of october 2020, over 44 million people have been diagnosed with covid-19 worldwide, according to world health organization. the pandemic has claimed more than a million human lives so far and resurgence in the number of new cases and continued growth in some countries has threatened both high and low-resource countries alike. in january 2020, the virus responsible for the coronavirus infectious disease 2019 (abbreviated as covid19) was isolated and its rna genome 2,3 sequenced and shared globally online. from complete genome sequencing it transpired that the cause of the severe acute respiratory illness that became known as covid-19 is in fact a novel coronavirus, named sars-cov-2. since then every so often new information about the virus and the new infection is emerging and history is constantly being rewritten. subsequent phylogenetic analysis of the viral genome sequence suggests that sars-cov-2 originated in animals, probably bats, and was transmitted to other animals before crossing the human species barrier at the huanan wet market in 4,5,6 wuhan city. the search for specific therapeutic drugs to effectively treat covid-19 commenced as early as the discovery of the virus itself. however, with many studies carried out independently in small numbers of patients, there is a risk that such trials may lack s u f f i c i e n t s t a t i s t i c a l p o w e r f o r c l i n i c a l recommendations. in this editorial, we will describe selected agents which are under investigation in large scale studies and which are more likely to produce robust outcome data for the efficacy and safety of these agents in the management of covid19. these studies include the world health organisation (who) solidarity study and the 7,8 french discovery study. who study, “solidarity” this is an international clinical trial to help find out an effective treatment for covid-19 which was launched by the world health organization (who) and partners. it is one of the largest international randomised trials for covid-19 treatments, enrolling almost 12, 000 patients in 500 hospital sites in over 30 countries. this study is evaluating the effect of drugs on 3 important outcomes in covid-19 patients: mortality, need for assisted ventilation and 7,8 duration of hospital stay. the study compares treatment options against standard of care to assess their relative effectiveness against covid-19. by enrolling patients in multiple countries, the solidarity trial aims to evaluate whether any of the drugs improve survival or reduce the need for ventilation or reduce the duration of hospital stay. the trial is open to adding other drugs based on emerging new evidence. however, until such time as there is sufficient evidence, who cautions physicians and medical associations against re co m m e n d i n g o r a d m i n i ste r i n g u n p rove n treatments to patients with covid-19 or people selfmedicating with such agents. who guidance on compassionate use can be found on the following l i n k : h t t p s : / / w w w . w h o . i n t / n e w s ro o m /co m m e nta r i e s / d eta i l /o ff l a b e l u s e o f medicines-for-covid-19. the solidarity trial published interim results in october 2020 which indicate that all four treatments evaluated (remdesivir, hydroxychloroquine, lopinavir/ritonavir and interferon) had little or no effect on overall mortality, initiation of ventilation and duration of hospital stay in hospitalised patients. this study is considering evaluating other correspondence: prof. sayed subhan bukhari consultant in infection medicine training programme director, honorary clinical professor university hospitals of leicester nhs trust, leicester, united kingdom e-mail: sayed.bukhari@uhl-tr.nhs.uk received: october 30, 2020; accepted: november 16, 2020 university hospitals of leicester nhs trust, leicester, united kingdom h as b een ceased sin ce ju n e 29, 2020) + lopinavir/ritonavir plus interferon ß-1a versus soc (this treatment arm has been ceased since june 29, 2020) + hydroxychloroquine (this treatment arm has been ceased since may 24, 2020). the primary objective of the study is to evaluate the clinical efficacy and safety of different investigational therapeutic options relative to the control arm in patients hospitalised with covid-19, the primary endpoint is subject clinical status (on a 7-point ordinal scale) at day 15. the secondary objectives of the study are to evaluate: 1) the clinical efficacy of different investigational therapeutic agents through 28 days of follow-up as compared to the control arm as assessed by clinical severity (7-point ordinal scale, national early warning score, oxygenation, mechanical ventilation), hospitalisation, mortality through 28 days of follow-up, in-hospital mortality and 90-day mortality, 2) the safety of different investigational therapeutic options through 28 days of follow-up as compared to the control arm as assessed by the cumulative incidence of serious adverse events (saes), the cumulative incidence of grade 3 and 4 adverse events (aes), the discontinuation or temporary suspension of antiviral drugs for any reason, and the changes in white blood cell count, haemoglobin, platelets, creatinine, blood electrolytes, prothrombin time and international normalised ratio (inr), glucose, total bilirubin, alanine aminotransferase (alt), and aspartate 7,8 aminotransferase (ast) over time. other agents that have shown potential for the treatment of earlier coronavirus infections sars and mers are also being evaluated on the basis that the viruses share structural similarities with sars-cov-2. these include novel agents in development and antivirals currently in use for other indications. in addition, several studies have evaluated potential 9,10,11 treatments in vitro. a number of these therapies appear to have been introduced in china but are not well reported in english language scientific literature. china, as the country with the longest experience of managing covid-19, is likely to have valuable expertise to share with the rest of the world. following is a summary of various agents under investigation for the treatment of covid-19 that 7,8 have shown some promise. 1. chloroquine/hydroxychloroquine: this drug treatments, to continue the search for effective covid-19 therapies. so far, only corticosteroids have been proven effective against severe and 7,8 critical covid-19 infection. in july 2020, who accepted the recommendation from the solidarity trial's international steering committee to discontinue the trial's hydroxychloroquine and lopinavir/ritonavir arms. the international steering committee formulated the recommendation in light of the evidence for hydroxychloroquine vs standard-of-care and for lopinavir/ritonavir vs standard-of-care from the solidarity trial interim results, and from a review of the evidence from all trials presented at the 1-2 july 2020 who summit on covid-19 research and innovation. these interim trial results demonstrated that hydroxychloroquine and lopinavir/ritonavir produce little or no reduction in the mortality of hospitalised covid-19 patients when compared to standard of care. consequently, solidarity trial investigators interrupted the trials with immediate effect. it is noteworthy that this decision applies only to the conduct of the solidarity trial in hospitalised patients and does not affect the possible evaluation in other studies of hydroxychloroquine or lopinavir/ritonavir in non-hospitalised patients or as preor postexposure prophylaxis for covid-19. french study, “discovery” france is co-ordinating the discovery trial to compare the same drugs with standard care in a network of 3,200 patients in belgium, france, germany, luxembourg, the netherlands, spain, sweden and the uk. this will be randomised but 7,8 non-blinded and will assess outcomes at 15 days. this study is a multi-centre, adaptive, randomised, open clinical trial of the safety and efficacy of treatments of covid-19 in hospitalised adults. the study is a multi-centre and multi-country trial that will be conducted in various sites in europe. adult patient (≥18 year-old) hospitalised for covid-19 with spo2 ≤ 94% on room air or acute respiratory failure requiring supplemental oxygen or ventilatory support are randomised between 4 treatment arms, each to be given in addition to the usual standard of care (soc) in the participating hospital: soc alone v e r s u s s o c + r e m d e s i v i r v e r s u s s o c + lopinavir/ritonavir versus soc (this treatment arm 208 jiimc 2020 vol. 15, no.4 8 and cytokine storm. 6. fav i p i rav i r + i nte r fe ro n a l p h a : i n t h i s combination, favipiravir blocks viral rna synthesis and interferon alpha stimulates innate antiviral response. this combination is being 10 studied in a number of trials in china. 7. fa v i p i r a v i r + b a l o x a v i r m a r b o x i l : t h i s combination of two antiviral agents blocks viral rna synthesis. the u.s. food and drug administration has approved baloxavir marboxil for the treatment of acute uncomplicated influenza (flu) in patients 12 years of age and older who have been symptomatic for no more than 48 hours. now it is being studied against 11 covid19 in combination with favipiravir. 8. ribavirin + interferon alpha+ lopinavir/ritonavir: this is a triple therapy combination of antiviral agents. ribavirin inhibits the activity of the enzyme rna dependent rna polymerase, due to its resemblance to building blocks of the rna molecules. it may inhibit replication of sarscov-2. lopinavir/ritonavir combination is viral protease inhibitors which may also inhibit sars-cov-2 virus and thus reduce adverse outcomes of covid-19 infection. interferon alpha stimulates innate antiviral response. triple therapy is recommended by national health commission of the people's republic of china as per guidelines for diagnosis and treatment of novel coronavirus pneumonia 2020 (trial version 17 5). a trial claiming to show efficacy with hydroxychloroquine plus azithromycin received wide 12 coverage in the lay media. this study had important methodological deficiencies and its conclusions have 18 been disputed by expert reviewers. in addition, this combination is associated with an increased risk of qt interval prolongation which may turn out to be fatal in some high risk patients. another controlled trial indicated that the combined viral protease inhibitor formulation of lopinavir/ritonavir is 13 ineffective. however, an uncontrolled trial of remdesivir which has in vitro activity against sars-cov-2, demonstrated improvement in 36 of 53 (68%) covid-19 patients who were severely ill and who had oxygen saturation at ≤94% or were receiving 14 oxygen support. more recently, a randomised impairs release of virus after cell entry and blocks virus binding to cell receptor. it modulates immune response. the food and drug administration (fda) has given emergency use authorisation in the usa, however, the uk medicine and healthcare products regulatory agency (mhra) states that it should only be used within a clinical trial. it is being investigated in t h e w h o s o l i da r i t y s t u d y. h yd rox y chloroquine is the preferred choice as it is associated with fewer adverse effects than chloroquine. 2. h y d r o x y c h l o r o q u i n e + a z i t h r o m y c i n : hydroxychloroquine impairs release of virus after cell entry and block virus binding to cell receptor. it modulates immune response. a z i t h ro my c i n p o s s e s s e s p o s s i b l e a n t i inflammatory action and it prevents secondary bacterial infection. one trial suggests reduction in viral nasopharyngeal carriage at 6 days in 20 patients as compared with unmatched untreated cohort, with azithromycin reinforcing 12 the effect of hydroxychloroquine. 3. lopinavir/ritonavir: these agents are viral protease inhibitors. the use of this combination may inhibit sars-cov-2 virus and thus reduce adverse outcomes of infection. a randomised controlled trial including 200 patients, suggested 13 no benefit so far. another trial is now underway in combination with a steroid, dexamethasone. lopinavir/ritonavir combination is also being investigated in the who solidarity study. 4. remdesivir: this drug blocks viral rna synthesis. it has a broad-spectrum of activity against many coronaviruses. it was given emergency use authorisation by the fda in the usa. clinical 14,15,16 trials have reported preliminary results. data from a study called adaptive covid-19 treatment trial (actt) indicates beneficial effect on reduction of time to recovery. remdesivir is included in the who solidarity study. 5. tocilizumab: this agent blocks interleukin-6 signalling which may inhibit the cytokine release in cytokine storm during severe covid-19 infection. covacta trial supported by the us fda is currently studying the role of tocilizumab in patients with severe covid-19 pneumonia jiimc 2020 vol. 15, no.4 209 references 1. wang c, horby pw, hayden fg, gao gf. a novel coronavirus outbreak of global health concern. the lancet. 2020; 395(10223):470-3. doi: 10.1016/s0140-6736(20)30185-9. 2. world health organization. novel coronavirus (2019-ncov). s i t u a t i o n r e p o r t – 1 . 2 0 2 0 . a v a i l a b l e f r o m : https://www.who.int/docs/default-source/coronaviruse/si tuation-reports/20200121-sitrep-1-2019-ncov.pdf?sfvrsn= 20a99c10_4 3. world health organization. coronavirus disease 2019 (covid-19). situation report – 113. 2020. available from: https://www.who.int/emergencies/diseases/novel-corona virus-2019/situation-reports 4. lu r, zhao x, li j, niu p, yang b, wu h et al. genomic characterisation and epidemiology of 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et al. compassionate use of remdesivir for patients with severe covid-19. n engl j med. 2020; 382(24):23272336. doi: 10.1056/nejmoa2007016. 15. wang y, zhang d, du g, du r, zhao j, jin y, et al. remdesivir in adults with severe covid-19: a randomised, double-blind, control study has been published from china 15 including 237 patients, and headline results released from a global phase 3 trial named adaptive covid-19 treatment trial (actt) including 1063 16 patients. both of these studies included significant numbers of hospitalised patients with covid-19 pneumonia. in the study from china, remdesivir did not reduce time to clinical improvement, however, there was a trend towards faster improvement in patients who had a duration of symptoms of 10 days or less. by contrast, the actt study suggested that treatment with remdesivir was associated with a more rapid 16 recovery as compared with placebo. median time to recovery was 11 vs 15 days, p<0.001, and there was an overall trend towards improved mortality (8.0% vs 11.6%; p=0.059). more data is required to provide a clearer picture on the benefits of remdesivir in rapid recovery and improved mortality from covid-19. the role of adjunctive agents such aspirin in severe covid-19 infection with pneumonia has also been evaluated. a recent study indicated that hospitalised patients with covid-19 who received aspirin prior to hospital admission or within 24 hours of hospital admission had a significantly lower risk of complications and death compared with patients 19 who did not receive aspirin. aspirin use had a crude association with less mechanical ventilation (35.7% vs 48.4%; p = .03) and reduced intensive care unit admission (38.8% vs 51.0%; p = .04), but no crude association with in-hospital mortality (26.5% vs 23.2%; p = .51). two of the most significant events in the pathophysiology of sars-cov-2 virus infection are cytokine storm and micro clot formation. the beneficial effects of aspirin in severe covid-19 infection are believed to be blood thinning action and prevention of micro clot formation. the conclusion of this study was that aspirin use may be associated with improved outcomes in hospitalised 19 covid-19 patients. however, sufficiently powered randomised controlled trials are required to elucidate the causal relationship between aspirin use and reduced lung injury and mortality in covid19 patients. conflict of interest the authors confirm that they have no conflict of interest. jiimc 2020 vol. 15, no.4 210 p n e u m o n i a . c h i n m e d j . 2 0 2 0 ; d o i : 1 0 . 1 0 9 7 / cm9.0000000000000790. 18. kim ahj, sparks ja, liew jw, putman ms, berenbaum f, duarte-garcía a, et al. a rush to judgment? rapid reporting and dissemination of results and its consequences regarding the use of hydroxychloroquine for covid-19. ann i n t e r n m e d . 2 0 2 0 ; 1 7 2 ( 1 2 ) : 8 1 9 8 2 1 . d o i : 10.7326/m20-1223 19. chow, jonathan h, khanna, ashish k, kethireddy, shravan, et al. aspirin use is associated with decreased mechanical ventilation, icu admission, and in-hospital mortality in hospitalized patients with covid-19. anesthesia & analgesia. doi: 10.1213/ane.0000000000005292. placebo-controlled, multicentre trial. lancet 2020; 3 9 5 ( 1 0 2 3 6 ) : 1 5 6 9 1 5 7 8 . d o i : h t t p s : / / d o i . o r g / 10.1016/s0140-6736 (20)31022-9. 16. institutes of health. nih clinical trial shows remdesivir accelerates recovery from advanced covid-19. 2020. available from: https://www.nih.gov/news-events/ news-releases/nih-clinical-trial-shows-remdesivir-accelera tes-recovery-advanced-covid-19 17. zeng ym, xu xl, he xq, tang sq, li y, huang yq, et al. comparative effectiveness and safety of ribavirin plus interferon-alpha, lopinavir/ritonavir plus interferon-alpha and ribavirin plus lopinavir/ritonavir plus interferon-alpha in in patients with mild to moderate novel coronavirus jiimc 2020 vol. 15, no.4 211 original article abstract background: transition from traditional to integrated curriculum has been very slow in pakistan. however in the last few years there has been tremendous increase in the number of medical schools. early clinical and community exposure is one of the key factors in generating interest of medical students in learning the clinical aspect of the basic sciences. for this purpose 'dch module' was incorporated in the first 3 years of the medical curriculum at islamic international medical college. objective: to develop and implement dch module for early clinical exposure of mbbs students. to determine teachers' and students' perceptions of about its influence on the overall learning of medicine. study design: action research. place and duration of study: islamic international medical college from jan 2011 to jan 2014. materials and methods: initially wise man approach was used to develop the module. however modifications were brought into the module applying the united nations approach of designing a curriculum. the module has been incorporated in the curriculum, aligning it with the last 2 years of intensive clerkship of a five year mbbs program. results: significant improvement has been observed by the faculty, in students' approach about dealing with the clinical context of the basic sciences. it has also resulted in better communication skills and their reasoning approach in pbl sessions. conclusion: early clinical exposure enhances the interest and understanding of medical students of the basic sciences. it lays the foundation of the students towards a professional and clinical approach in dealing with patients, which is in addition to better integration of basic sciences with clinical sciences. key words: students' perceptions, learning, community exposure. commission was set up to study the problem recommended mobilization of knowledge for health professionals of all countries so that they are not only locally responsive but also globally connected with ultimate purpose of providing high quality health 3 care to all. now the developing countries are faced with the uphill task of reforms in few years which was completed by developed countries in 100 years.the process is both human and material resource intensive, making it further difficult for developing countries. it is therefore imperative the each country shall accomplish this goal in its “local context”, 4 making best use of available resources. in pakistan, process of reforming medical curriculum was initiated in 2009 when a selected cohort of medical schools, considered to be better equipped with required knowhow were allowed by pakistan medical and dental council to develop and 5 implement new curricula. islamic international medical college is one of these medical schools. over the last five years, an integrated curriculum with emphasis on learning and is student centered has been developed and implemented. one of the key introduction 1 ever since the publication of flexner's report a major paradigm shift has occurred in medical education. the emphasis has shifted from “teaching by teachers” to “learning by students”. this obviously could not be achieved without reforming the curricula from traditionally “teacher centered” to 2 modern “student or learner centered”. the process of shifting has been rapid in north america and europe with almost 100% medical schools having implemented the shift. but unfortunately, developing countries have lagged miles behind. while there are no geographical boundaries between diseases and health care, there are marked differences in standards of health professional's education and health care standards. lancet ------------------------------------------------early community and hospital contact of undergraduate medical students; innovating the mbbs curriculum through dch (doctor, community and hospital) module masood anwar, rehan ahmed khan correspondence: prof. masood anwar professor of hematology dean faculty of health & medical sciences principal islamic international medical college riphah international university, islamabad e-mail: masood.anwar@riphah.edu.pk jiimc 2014 vol. 9, no. 3 early community and hospital contact of mbbs students 103 directional elements in its development was the postulate that early clinical and community exposure is one of the key factors in generating interest of medical students in learning the clinical aspect of the 6 basic sciences. the rationale of exposing the beginner to healthcare delivery system(s) at the start of their medical career is that this early exposure to patients and community will stimulate among students critical thinking of health issues in general and common diseases in particular leading to a c q u i s i t i o n o f m u l t i d i s c i p l i n a r y i nte g rate d knowledge of these issues and diseases. learning in an urban, suburban or rural community designed to enable the student to gain an understanding of the relationship of the health and disease, multi sectorial e n g a g e m e n t i n c o m m u n i t y d e v e l o p m e n t , community health problems and their solution under a primary health care program will help the student to overcome his/her own feeling of 7 hesitance from patients and hospital environment. this adaptation will contribute to develop a strong desire in the students to solve the problems of the patients and to learn medicine. for this purpose 'disease community and health (dch) module' was incorporated in first three and a half years aligning first two spirals with last one year of intensive clerkship. materials and methods for the purposes of this module a community-based learning activity is defined as an activity that takes place within a community or in any of a variety of health service settings at the primary or secondary health care level, where community is observed and followed up over a period of time. initially the wisemen approach was used to develop the 8 m o d u l e . a g ro u p o f 3 q u a l i f i e d m e d i ca l educationists, under the guidance of dean faculty of health and medical sciences, developed the draft of c o n t e n t s , l e a r n i n g m e t h o d o l o g y a n d implementation plan. the main emphasis was laid on student's early exposure to community and hospital patients and teaching communication skills. using united nations approach8, it was then presented to all heads of clinical departments to provide their input. they were advised that while suggesting modifications, they shall take into consideration the 9 u n i c e f d o c u m e n t , l a n c e t c o m m i s s i o n recommendations3 and competencies described in 10 11 tomorrow's doctor and scottish doctor. the document was then discussed in faculty board. the module was then finalized by the same group of medical educationalist but this time they were assisted by senior faculty of community medicine department. the content, learning outcomes, assessment methodology was decided in several meetings. the final draft was then presented to the c u r r i c u l u m c o m m i t t e e a n d a p p r o v e d f o r implementation. the module has been incorporated in first three years of the curriculum, aligning it with the last 2 years of intensive clerkship of a five year mbbs program. the initial impact of module was assessed after one year. results the module the dch module developed has the following main features (competencies). knowledge  student will be able to know the structure of primary, secondary and tertiary health care systems.  student will be able to know the common complaints with which the patients present in various departments of the hospital.  students will be able to understand the basic components of history taking and examination and their importance diagnosing a clinical problem.  s t u d e n t s w i l l b e a b l e t o u n d e r s t a n d environmental and behavioral aspects of common medical problems in the community.  students will be able to search for and implement measures to modify the population habits and environment responsible for common diseases in the community. skills  students will be able to take history in a proper sequence that is relevant to patients attending a specific clinical department.  students will be able to demonstrate steps in clinical examination of patients attending a specific clinical department.  students will be able to identify population behavior and environmental factors responsible for common diseases in the community.  students will be able implement preventive measures in the population to reduce the jiimc 2014 vol. 9, no. 3 104 early community and hospital contact of mbbs students burden of common diseases and record the outcome. attitude  s t u d e nt s w i l l b e a b l e to d e m o n st rate communication skills while taking history from the patients.  students will be able to demonstrate bed side manners while examining patients.  student will be able to communicate with the population and persuade to implement proposed measures for decreasing the disease burden. module implementation each entry in our medical school comprises 100 students. the class was divided into 6 batches with equal number (16) of students in each batch. initially each batch was rotated in each of the major clinical departments to acquire skills in history taking and basic clinical examination. both skill lab and actual patients were utilized for this purpose. they were then rotated to community settings, basic health units (bhu) and lady health worker's centers. the sessions are planned one full day in each fortnight. the batch 2013 has completed its first year. in second year, the students groups will be allotted a set of households in identified suburban and rural communities to study their health issues/habits, suggest and implement modifications. towards the end of third year they will study the outcome of interventions and submit a written report. faculty's observations to assess the impact of this innovation of the curriculum, a focus group of clinical teachers were invited to discuss their observations regarding the module itself, its implementation and impact on student's learning. summary is as under: a. they were unanimous in expressing satisfaction about the contents and design of the module. b. majority suggested increasing the skill lab component and simulated patient introduction to improve communication and clinical skills. c. they were unanimously satisfied in effective ness of the module. d. majority was of the opinion to increase the duration of the module. students' perception a questionnaire was distributed to the second year students (who have completed one year of this module) to know their perception of this module. the results are reported in table i. table i: students' perception discussion a curriculum, in fact, is systematic packaging of competencies that are to be acquired by a learner 9 through organized learning activities. these competencies may vary from place to place depending upon social, cultural, ethnic and economic status of the population. ideally a curriculum should include what the society envisages as important for teaching and learning. this vision of the society is developed usually by professional bodies constituted for this purpose taking in consideration local requirements, available resources (including human resource) and health s t r u c t u r e . t h e s e b o d i e s c o u l d b e l o c a l (governments), regional or global e.g. who, unesco etc. is vision in the light of research, need analyses, available resources and gap analyses. obviously these are going to differ from one to other society. in case of medical education, as there are neither geographical boundaries for health professionals to work nor for the disease to travel, there is also a requirement for curriculum to be 3,7 holistic and global in its contents. the dch module of our curriculum was developed keeping above factors in mind. in pakistan the curricular change is still in its infancy therefore there is not only dearth of trained and motivated faculty to implement the reforms but there is also a fair amount of resistance from senior faculty members and officials. this resulted in some gaps in module designing and implementation as evident from faculty select group review discussion. this is not unusual and has been 4 subject of several expert reviews. it only requires constant monitoring and modifications as suggested 12 by experts. like any other developing country there are two extremes in health care delivery. on the one side are state of the art tertiary care hospitals which jiimc 2014 vol. 9, no. 3 105 early community and hospital contact of mbbs students are well equipped and have well educated and well trained faculty, while on the other side extremely basic health units often lacking in essential equipment, man power and finances. the irony of the fact is that only a very small number of patients benefit from hospitals, which are also teaching hospitals for medical schools while majority looms with basic health unit or private practitioners. moreover the students do not get opportunity of seeing many patients and diseases in their actual environment.7 introduction of this module has certainly stimulated students learning as expected and is evident from their critical responses. student's perceptions were elicited only in three areas, considered to be the key elements of this module. these are community exposure, patient exposure and communication skills. in all 60-75% students have shown satisfaction (good or adequate). however there are 25-40% students who are not satisfied. this is primarily because for almost all nonfaculty mentors involved it was the first experience. this difficulty is also recorded in literature.4 we expect that with some training and experience they will be able to make these exposures more fruitful learning activity for the students. conclusion dch module has been able to achieve its objectives but there is still room for its improvement in the light of faculty and student's comments. non-faculty mentors involved in its implementation also require some training. true impact of the module can only be assessed on its completion. references 1. flexner a. medical education in united states and canada: a report to carnegie foundation for the advancement of teaching. bulletin no. 4, 1972 (revised), the carnegie foundation for the advancement of education, new york 2010. 2. gibbs t, mclean m. twelve tips to designing and implementing a learner centered curriculum: prevention is better than cure. medical teacher. 2010; 32:225-30. 3. frenk j, chen l, bhutta za, cohen j, crisp n, evans t, et al. health professionals for a new century: transforming e d u cat i o n to st re n gt h e n h e a l t h syste m s i n a n interdependent world. the lancet 2010; 376 (9756):192358. 4. dauphinee d. forgetting lessons past: failure to consider context and resources in curricular change. medical education. 2009; 43:502-4. 5. p a k i s t a n m e d i c a l & d e n t a l c o u n c i l . p e r s o n a l communication. 6. esphahani rj, yazdi mj. effect of early clinical exposure on learning motivation of medical students. future of medical education. 2012; 2(2):3-7. 7. mennin s, petroni-mennin r. community based medical education. the clinical teacher. 2006; 3: 90-6. 8. harden rm. ten questions to ask when planning a course or curriculum. medical education. 1986; 20:356-65. 9. http://www.unesco.org /new/en/education/themes / s t r e n g t h e n i n g e d u c a t i o n s y s t e m s / q u a l i t y framework/core-resources/curriculum/ accessed on 0405-2014. 10. tomorrow's doctors (2009). general medical council, uk. h t t p : / / w w w . g m c u k . o r g / p u b l i c a t i o n s / undergraduate_education_publications.asp#1accessed on 04-05-2014. 11. http://www.scottishdoctor.org/accessed on 04-05-2014. 12. van der vleuten c, schuwirth lwt. assessing professional competence: from methods to programs. med educ. 2005; 39:309-17. jiimc 2014 vol. 9, no. 3 106 early community and hospital contact of mbbs students original�article abstract objective: to compare the cytomorphometric changes in buccal mucosal cells of cigarette smokers, naswar users and non-users/smokers. study design: cross sectional comparative. place and duration of study: pgmi, lahore & islamic international dental college, islamabad: between july 2013-january 2014. materials and methods: cellular diameter cd, nuclear diameter nd and nuclear to cytoplasmic ratio n/c ratio were assessed in buccal smears taken with wooden spatula from clinically normal mucosa of smokers, naswar users and control group. the sample size was 99 male subjects of ages 15yrs-60yrs, divided into three groups (33 each group) i.e., m as control group, s as smoker group and n as naswar users' group. slides were stained with three stains hematoxylin and eosin stain, giemsa stain and papanicolaou stain. the data was collected through random sampling. the cytomorphometric variables were measured by using stage and ocular micrometers. the cytopathological variables as inflammatory cells, mitotic figures, pleomorphism and hyperchromatism were also studied. the results were then statistically analyzed using spss version 18. results: the mean cellular diameter of group m, s and n was 43.8µm, 54.3µm and 42.7µm respectively. the mean nuclear diameter of m, s and n was 9.97µm, 12.6µm and 11.8µm respectively. and the mean n/c ratio of group m, s and n was 1:4.4, 1:4.3and 1:3.5 respectively. conclusion: the comparative changes assessed by this study depicts cause effect relationship with smoking and naswar use. association of these changes with dysplasia or pre-malignancy needs further verification with the help of specific immune markers. key words: cytomorphometry, tobacco, naswar, oral neoplasms, smokers. common malignant alteration of squamous epithelium encountered in oral cavity. it is one of the sixth most common malignant tumors in world and 1 third most common in pakistan. there are multiple causative factors for oscc among which smoking, use of areca nut, betel quid or pan and tobacco chewing, naswar, pan masala, gutka are considered 2 to be major risk factors among pakistani population. although visibly detectable due to the accessibility of the oral cavity, oral cancer has a high morbidity and mortality because it is diagnosed typically at an advanced stage when it is finally clinically visible. 3 early diagnosis is crucial for better prognosis. exfoliative cytology is used to investigate the effect 4 of tobacco on the oral epithelial cells. it is one of simple non-invasive investigative tool for early 5 diagnosis of dysplastic changes in oral lesions. quantifiable methods based on the measurement of variables as nuclear diameter nd, cellular diameter cd and nuclear to cytoplasmic ratio n/c ratio can accelerate the sensitivity of exfoliative cytology for introduction oral squamous cell carcinoma (oscc) is one the most a comparative cytomorphometric analysis of buccal mucosal smears of cigarette smokers and naswar (nicotiana tabaccum) users 1 2 3 4 5 6 7 rabia masood , rozinah jaffar , nadia zaib , naila umer , sara haq , munnazza javed , ali raza correspondence: dr. rabia masood associate professor department of oral pathology islamic international dental college, riphah international university, islamabad e-mail: rabia.masood@riphah.edu.pk 1 department of oral pathology islamic international dental college, riphah international university, islamabad 2 department of pathology services institute of medical sciences, islamabad 3 depatment of oral pathology, foundation college of medicine and dentistry, foundation university, rawalpindi. 4,7 department of oral pathology faryal dental college, lahore 5 department of community and preventive dentistry saidu college of dentistry, swat 6 department of dentistry, rural health center, bahawalpur received: january 09, 2020; revised: september 22, 2021 accepted: october 21, 2021 cytomorphometry of tobacco usersjiimc 2022 vol. 17, no.2 97 the early diagnosis of oral premalignant and malignant lesions, because these methods are 4 precise, objective and reproducible. simple noninvasive techniques like exfoliative cytology can be employed as a chairside technique and in mass screening programs for identification of cellular changes in oral mucosa of individuals with tobacco habits. various studies have been conducted among different population across the globe to see the effect of tobacco and its products on oral mucosal 6-9 cells using this noninvasive tool. the purpose of present study was to compare the cytomorphometric changes in buccal mucosal cells of cigarette smokers, naswar users and nonusers/smokers among pakistani population and to analyze the cause–effect relationship between tobacco uses and quantitative alterations made. materials and methods this was cross-sectional comparative study which was carried out at post graduate medical institute, lahore and islamic international dental college, riphah international university, islamabad. the duration of the study was six months. the sample size was 99 in total, calculated by who calculator; divided into three groups of 33 each as m (control group), n (naswar users) and s (smoker group). nonprobability convenient sampling technique was used. a written consent proforma was filled and submitted by all the subjects included in the study, as per the requirements of the ethical review committee. the study was approved by the institution's ethical review board. the letter number was: iidc/irc/2017/02/001. male subjects above 15 years of age were included in all the 3 groups. among the naswar users, subjects using naswar for atleast three years or more and 3-4 times /day were included; as for the smoker groups individuals smoking 1 pack/day (20 cigarettes) for at least 3 years or more were included. while control group included the subjects with no history of tobacco use in any form. subjects with poor oral hygiene, any pre-existing premalignant or malignant lesion, denture wearers, tobacco users of any form were excluded. also, individuals suffering from chronic debilitating diseases or undergoing any drug therapies that may cause oral mucosal changes were also excluded. data was collected from the subjects by requesting them initially to rinse their mouth with water. then smears were taken using a moistened wooden spatula from the buccal mucosa of all the subjects. three glass slides per each subject were marked with their reference number and alphabet of their particular group. the smears were taken and immediately fixed in using cyto-fixi spray (95 % 10 alcohol). slides of each subject were stained hematoxylin and eosin stain, papanicolaou stain and giemsa stain respectively. cellular diameter (cd) and nuclear diameter (nd) of the 100 cells in each smear were measured by using pre calibrated ocular micrometer fixed in eye piece of microscope on 40 x. the ocular micrometer was pre-calibrated with the help of stage 11 micrometer. the following equation shows the calibration. 100 div on ocular micrometer = 30 divisions on stage micrometer (one div =10µm) = 30×10 100 div on ocular micrometer = 300 um 1 div on ocular micrometer = x x =3 µm in each case 100 clearly defined cells, from left to right in n direction were analysed for variables cd, nd and n/c ratio using ocular micrometer. cytopathological variables i.e., inflammatory cells, presence of mitotic figures, pleomorphism, hyperchromatism were also studied under microscope. data analysis was carried out using statistical package for social sciences (spss) version 18. one way anova, post hoc tukeys test was used to compare means of cd, nd and n/c among the three groups. p value of 0.05 or less was taken as statistically significant. results after completing the performas the readings were compared in all three groups and all three stains. for each variable i.e. cd, nd and n/c ration mean was calculated in every group and then was compared and statistically analysed. summarizing the cytomorphometric results in table i, the cellular diameter is highest in smokers on pap stain. nuclear diameter nd shows a significant increase in smokers and naswar users on all three stains as compared to the control group. the highest cellular diameter (55.22µm±3.36) cytomorphometry of tobacco usersjiimc 2022 vol. 17, no.2 98 among all three stains was found to be in the smokers who smoked for more than 10 years. likewise, in naswar users the highest cellular diameter was recorded as 45.46 µm±1.65 in those subjects who had been using naswar for more than 10 years. moreover, among all three stains cd was highest in smokers who consumed 2packs/day showed a value of 54.58 µm±2.95 as compared to others who smoked less cigarettes. similarly, for naswar users, cd was found to be highest in those consuming naswar for 5-6 times per day i.e., 44.09 µm±2.02. o n e way a n o va wa s a p p l i e d to co m p a re cytomorphometric findings among groups with respect to frequency of smoking or naswar use /day and duration of use, however in both cases results were statistically insignificant with p-value more than 0.05. when variance analysis was conducted to analyse any difference in the nuclear diameter between the three groups, a statistically significant difference was found (p = 0.000). the intergroup post-hoc tukey analysis revealed that the difference in the nuclear diameter between the smoker's group (12.68 µm± 0.91) and the control group (9.97 µm± 0.80) was significant. however, the difference in the nuclear diameter between the naswar users (11.80 µm± 2.23) and the smoker group (12.68 µm± 0.91) was not significant (p > 0.005). while the difference in the nd between the naswar users' group (11.80 µm± 2.23) and the control group (9.97 µm± 0.80) was significant (p=0.001). the mean difference between cd, nd, and n/c ratio in all three stains, among the three groups, s, n and m was found to be statistically highly significant i.e., p=0.001 on one way anova. while on post hoc tuckey test between s and n, cd and n/c ratio were highly significant p=0.000 while nd was not significant. while between s and m, cd and nd both were significant and showed p=0.000 while n/c ratio was not significant. in comparison between n and m, nd and n/c ratio were found to be significant while cd was not significant. the cytopathological variables such as presence or absence of inflammatory cells, pleomorphism, hyperchromatism and mitotic figures were also studied on all three stains. although all the variables were studied on all three stains but the results were same for each one of them with a very negligible difference, thus for convenience of understanding the results observed on h&e stain only, are presented here. out of 33 cases of each group, inflammatory cells were present in 23 (70%), 17 (51%) and 7 (21%) cases of naswar users, smokers and control group respectively. chi square test was used, and statistically significant results were found between the groups with a p value of <0.05 with regard to pleomorphism, hyperchromatism and mitotic figures, none was found in any of the studied groups. discussion oral squamous cell carcinoma is caused by use of 3 different forms of tobacco. commonly oral cancers are diagnosed at advanced stages, which results in its poor prognosis decreasing the survival rates among the patients. oral exfoliative cytology has been proven to detect early changes in the cells even before the onset of the clinical lesion, and this technique is inexpensive and easy with high 4,5 sensitivity rates and diagnostic values. in the p r e s e n t s t u d y , c y t o m o r p h o m e t r i c a n d cytopathological variables were studied on buccal cells using exfoliative cytology and compared among three groups i.e. naswar users, cigarette smokers and control group. with regard to cellular diameter, variable results are shown by various studies conducted worldwide, like hande and chaudhary in 2010 conducted a study using cytomorphometry and showed that systemic and external factors affect the cytomorphometric variables such as nd, cd and n/c ratio. as the cd is increased in smokers in the present study, it may be due to any factor which is caused by smoking cigarettes. the results of the present study, i.e, increase in the cd of smokers as compared to the control group, contrasts with the other studies carried out like in case of sumit babuta (2014) and 3,6 goregen, (2011). whereby in a study conducted by ramesh et al. (1999) cd was decreased in cigarette 7 smokers. similarly, a study conducted by ogden et al. (1997) also showed a decrease in cd of tobacco 1 users. however, the results of buccal mucosal smears of naswar users showed strikingly similar results with study conducted by hande and chaudhary in 2010 8 showing decrease in cd. ramaesh et al in 1998 and ogden et al in 1997 also showed a decrease in cd of 1,8 tobacco chewers in their respective studies. the decrease in the cd in the present study can be an cytomorphometry of tobacco usersjiimc 2022 vol. 17, no.2 99 9 early detection of dysplastic or malignant change. the next variable studied in this study was nuclear diameter, both smokers and naswar users group showed an increase in nd in comparison with the control group. this may be due to various reasons including use of tobacco or increase in dna content 8 as stated by hande and chaudhary in 2010. other studies which have been conducted in the past on the same subject showed the similar results which are consistent with the findings of the present study i.e; increase in nuclear diameter of tobacco users, be 3,4,10,11 they smokers or naswar users. ogden et al observed in 1997 that 5 % average increased in nuclear diameter of smokers when 1 compared with those of the non-smokers. while a study conducted by goregen in 2011 showed an increase of 16.5 % increase in nd of smokers as compared to non-smokers which was attributed to 8 smoking. none of the groups showed significant relationship between nd and duration or frequency of smoking or naswar use. this finding contrasts with the results of a studies which were carried out by 3,12,13 saranya, 2014 and goregen, 2011. the third cytomorphometric variable studied in the study was n/c ratio, highest n/c ratio was observed in the naswar user group. this finding is due to the fact the nd in naswar user group was higher than the control group while their cd was smallest among the three groups (smokers, naswar users and control group) due to which the n/c ratio has automatically increased. carried out a study which showed that n/c ratio helps us to show the precise relationship in 14 the altered cellular and nuclear diameter. n/c ratio in the smokers was also higher when compared with the control group which could be because of increased cd and nd in the respective group. increase in the n/c ratio can be indicative of an early dysplastic change because in squamous cell 14 carcinoma the n/c ratio is increased to 1:1 from 1:4. this result of the present study is also consistent with the results of previous studies conducted by multiple 6,12,13 authors in the past decade. conclusion changes in cellular diameter, nuclear diameter and n/c ratio was observed among smokers and naswar chewers when compared to control group which might indicate a cause affect relationship. the results seen in this study are limited to a reactionary change with smoking and naswar use. the relationship of these changes with pre-malignancy or malignancy needs further research with the help of more accurate methods as immuno-markers table i: comparison of cytomorphometric readings in three stains h & e, pap, giemsa, in smokers, naswar users and control group. s= smoker, n= naswar user, m =control group. cd= cellular diameter, nd= nuclear diameter, n/c= nuclear /cytoplasmic ratio table ii: result of post hoc tukey test among groups on h & e, pap, and giemsa stain s= smoker, n= naswar user, m =control group. cytomorphometry of tobacco usersjiimc 2022 vol. 17, no.2 100 references 1. ogden g, cowpe j, wight a. oral exfoliative cytology: review of methods of assessment. journal of oral pathology & medicine. 1997;26(5):201-5. 2. gupta n, gupta r, acharya ak, patthi b, goud v, reddy s, et al. changing trends in oral cancer-a global scenario. nepal journal of epidemiology. 2016;6(4):613. 3. g ö r e g e n m , a k g ü l h m , g ü n d o ğ d u c . t h e cytomorphological analysis of buccal mucosa cells in s m o ke rs . tu r k i s h j o u r n a l o f m e d i c a l s c i e n c e s . 2011;41(2):205-10. 4. hashemipour ma, aghababaie m, mirshekari tr, asadishekaari m, tahmasbi-arashlow m, tahmasbi-arashlow f, et al. exfoliative cytology of oral mucosa among smokers, opium addicts and non-smokers: a cytomorphometric study. archives of iranian medicine. 2013;16(12):0-. 5. anwar n, pervez s, chundriger q, awan s, moatter t, ali ts. oral cancer: clinicopathological features and associated risk factors in a high risk population presenting to a major t e r t i a r y c a r e c e n t e r i n p a k i s t a n . p l o s o n e . 2020;15(8):e0236359. 6. babuta s, garg r, mogra k, dagal n. cytomorphometrical analysis of exfoliated buccal mucosal cells: effect of smoking. acta medica international. 2014;1(1):22. 7. ramaesh t, mendis b, ratnatunga n, thattil r. diagnosis of o ra l p re m a l i g n a nt a n d m a l i g n a nt l e s i o n s u s i n g cytomorphometry. tropical dental journal. 1999:23-8. 8. hande ah, chaudhary ms. cytomorphometric analysis of buccal mucosa of tobacco chewers. rom j morphol embryol. 2010;51(3):527-32. 9. palaskar s, jindal c. evaluation of micronuclei using papanicolaou and may grunwald giemsa stain in individuals with different tobacco habits–a comparative study. j clin diagn res. 2010;4:3607-13. 10. zahid t, hussain si, siddiqui ah, junaid st, ahmed z, noorani mm. health seeking behavior of oral cancer patients of low socioeconomic status: a cross sectional study in a tertiary care hospital of karachi. journal of the dow university of health sciences (jduhs). 2014;8(2):72-9. fig. 1: inflammatory cells in naswar users at 40x fig. 2: cells stained with pap stain in naswar users with ocular micrometer at 40x fig. 3: cells stained with geimsa stain in naswar users with ocular micrometer 40x fig. 4: cells stained with h&e stain in naswar users with ocular micrometer at 40x cytomorphometry of tobacco usersjiimc 2022 vol. 17, no.2 101 11. bile k, shaikh j, afridi h, khan y. smokeless tobacco use in pakistan and its association with oropharyngeal cancer. emhj-eastern mediterranean health journal, 16 (supp), 24-30, 2010. 2010. 12. masood r, zaib n, jaffar r, khan ka, javed m, raza a, et al. cytomorphometry of buccal smears of nicotiana tabacum (naswar) users: a pilot study. pakistan oral and dental journal. 2014;34(3):445-8. 13. mohanta a, mohanty p. cytomorphometric analysis of nonkeratinized malignant squamous cells in exfoliated cytosmears of human oral neoplasm. j carcinog mutagene. 2016;7(1):1-8. 14. al-jaber a, al-nasser l, el-metwally a. epidemiology of oral cancer in arab countries. saudi medical journal. 2016;37(3):249. cytomorphometry of tobacco usersjiimc 2022 vol. 17, no.2 conflict of interest authors declared no conflicts of interest. grant support and financial disclosure authors have declared no specific grant for this research from any funding agency in public, commercial or nonprofit sector. data sharing statment the data that support the findings of this study are available from the corresponding author upon request. this is an open access article distributed under the terms of the creative commons attributionnoncommercial 2.0 generic license. 102 original�article abstract objective: purpose of this study was to determine association between nerve conduction studies and neurological examination scores in patients with diabetes who had known detectable sensorimotor neuropathy. study design: cross sectional descriptive study. place and duration of study: this study was conducted at the islamic international medical college, combined military hospital and armed forces institute of rehabilitative medicine in rawalpindi, pakistan, from january 2006 to january 2015. materials and methods: patients with confirmed diabetes (n=30) and clinically detectable sensorimotor polyneuropathy according to clinical scores were selected for inclusion. the type of fiber involved was determined on the basis of the modified diabetic neuropathy symptom (dns) score and modified diabetic neuropathy examination (dne) score. results: neuropathy disability score results showed a significant positive correlation with the results of nerve conduction studies in both large and small types of fiber. conclusion: in patients with type 2 diabetes and advanced neuropathy, association among the results of neuropathy disability scores and nerve conduction studies indicates the impaired functioning of both small and large nerve fiber. key words: diabetes, diabetic neuropathy, diabetes mellitus. this results in abnormal flow in ion channels such as sodium potassium pumps, sodium channels or calcium channels, and these disruptions can cause 5,6,7 abnormal nerve conduction. the diabetic neuropathy symptom (dns) and diabetic neuropathy examination (dne) scores can 5 be used to detect diabetic polyneuropathy. the clinical diagnosis can be confirmed by scoring systems such as the neuropathy disability score (nds) and neuropathy symptom score (nss). hence, for our study dns and dne scores are used whereas, clinical diagnosis is confirmed by nds and nss. clinically, large‐fiber neuropathies can be distinguished from small‐fiber neuropathies during neurologic testing. if tendon reflexes or vibration 6 sense are impaired, aa or ab fibers are involved, whereas if pain or thermal sensation are impaired, ad or c fibers are involved. the american academy of neurology has suggested that a combination of clinical symptoms and signs with electrodiagnostic findings provides the most accurate diagnosis of 7 distal symmetric polyneuropathy. in previous studies, a significant correlation was introduction in 2014, the nationwide prevalence of diabetes 1 mellitus was estimated at 6.8% in pakistan. uncontrolled diabetes mellitus may lead to neuropathy, retinopathy and macrovascular disease. if these complications are left unchecked, then they 2 3 may lead to blindness, foot ulcers and sexual 4 dysfunction. diabetic neuropathy, one of the c o m p l i c a t i o n s o f d i a b e te s , a r i s e s d u e t o derangements in the levels of insulin and glucose. correlation between nerve conduction studies and neurological scores according to fibre type in patients with diabetic sensorimotor polyneuropathy 1 2 3 4 5 zulfiqar ali amin , sidra jahangir , ambreen asad , muhammad umer nisar , mohammad asad qureshi , 6 7 8 nadeem ahmed , mujeeb ur rehman abid butt , junaid haris farooq jiimc 2016 vol. 11, no.4 correspondence: dr. sidra jahangir yusra medical and dental college, islamabad e‐mail: sidrajahangir20@yahoo.com 1 department of medicine combined military hospital, lahore 2,3,4,8 department of physiology yusra medical and dental college, islamabad 5 department of spine combined military hospital, rawalpindi 6 department of physical therapy (afirm) combined military hospital, abbottabad 7 department of medicine shalimar medical and dental college, lahore funding source: nil; conflict of interest: nil received: july 01, 2016; revised: sep 07, 2016 accepted: oct 25, 2016 nerve conduction studies and neurological examination scores 172 f o u n d b e t w e e n c l i n i c a l f i n d i n g s a n d neurophysiological test results depending on the fiber type. unlike earlier studies, however, our approach included four known neurological scoring systems and compared their scores according to fiber type. the objective of this study was to search for correlations between the results of nerve conduction studies and neurological examination scores in clinically detectable sensorimotor neuropathy in patients with type 2 diabetes, according to the type of fibre involved. materials and methods this cross‐sectional descriptive study was conducted from january 2006 to january 2015. purposive sampling was used to select 30 patients diagnosed as having type 2 diabetes from outpatients who had clinically detectable peripheral neuropathy (n=30) on the basis of diabetic neuropathy symptom (dns) and diabetic neuropathy examination (dne) scores. the inclusion criteria were age between 25 and 61 years (male or female) and duration of known diabetes greater than 1 year. patients with any other type of neuropathy or musculoskeletal disorder, and patients, who were taking medications that could affect the course of neuropathy, were excluded from the study. diabetic neuropathy was confirmed by history and by dns and dne scores. neuropathy was graded on the basis of the modified neuropathy disability score (nds) and neuropathy symptom score (nss) results. physical examination was done, including tendon reflexes and vibration sense. if tendon reflexes or vibration sense was impaired, the patient was considered to have large‐fiber neuropathy; if pain or thermal sensation was impaired, the patient was considered to have small‐fiber involvement. if both types of impairment were observed, the patient was considered to have both large‐ and small‐fiber neuropathy. a simplified protocol for nerve conduction studies was used to record amplitudes, velocities and latencies from a minimum of two and a maximum of six nerves. amplitudes, velocities and latencies were measured individually, and were assigned numerical grades of severity according to their values. then a net score was assigned to each variable, and each value was labeled as normal, mild, moderate, or severe neuropathy based on the average value recorded from two to six nerves. the presence or absence of neuropathy was recorded as an outcome. an overall score (grade) of normal, mild, moderate or severe neuropathy was assigned to the results of nerve conduction studies on the basis of the recorded amplitudes, velocities and latencies. f wave and h reflex were tested only if needed distinguish between types of neuropathy. fasting and random blood glucose were measured by glucometer. hemoglobin (hba1c) was measured using high performance liquid chromatography (hplc) in afip laboratory to check long‐term blood glucose control. means and standard deviations of fasting blood glucose, random blood glucose and hba1c were calculated. spearman's rho test was used to estimate the correlation between nerve conduction measures and neurological examination scores according to the fiber type. the data were analyzed with spss v.20.0 software. results each neurological score was compared to different components of nerve conduction studies in all 30 patients. the laboratory profile of the patients was fasting blood glucose (mmol/l) 9.05±3.8 (mean ± sd), random blood glucose (mmol/l) 13.49±4.65 (mean ± sd), and hb a1c (%) 6.82±1.36 (mean ± sd). correlations were calculated for neuropathies involving large fibers and both fiber types, but could not be calculated for small–fiber neuropathies because none of the patients in this study had exclusively small‐fiber involvement. among the 30 patients, both fiber types were involved in 12 (40%), large‐fiber neuropathy was identified in 17 (56.7%), and the fiber type in 1 patient (3.3%) could not be determined. regardless of the type of fiber involved, nds correlated with the findings of nerve conduction studies. the other scores, i.e. dns, dne and nss, did not correlate significantly with components of nerve conduction studies regardless of whether small, large or both types of fiber were involved. details of these results are shown in table i. the positive correlations between nds scores and different components of nerve conduction studies are shown in figures 1‐4. jiimc 2016 vol. 11, no.4 nerve conduction studies and neurological examination scores 173 in patients with disorders affecting only large fiber, dns, dne, nss and nds results showed correlations with components of nerve conduction studies. these results are summarized in table ii. table i: correla�on between neurological scores and nerve conduc�on studies according to type of fiber *correla�on significant at the 0.05 level (2‐tailed) **correla�on significant at the 0.01level (2‐tailed) dns: diabe�c neuropathy symptom score. dne: diabe�c neuropathy examina�on score. nss: neuropathy symptom score. nds: neuropathy disability score fig 1: correla�on between neuropathy disability score and net score of latencies found in nerve conduc�on studies (n=30) in persons with type 2 diabetes. sca�er plot showing significant posi�ve correla�on between neuropathy disability score and latencies in nerve conduc�on studies in both types of fiber. fig 2: correla�on between neuropathy disability score and net score of amplitudes found in nerve conduc�on studies (n=30) in persons with type 2 diabetes. sca�er plot showing significant posi�ve correla�on between neuropathy disability score and amplitudes in nerve onduc�on studies in both types of fiber fig 3: correla�on between neuropathy disability score and net score of veloci�es found in nerve conduc�on studies (n=30) in persons with type 2 diabetes. sca�er plot showing nonsignificant posi�ve correla�on between neuropathy disability score and veloci�es found in nerve conduc�on studies in both types of fiber. fig 4: the correla�on between neuropathy disability score and score of nerve conduc�on studies (n=30) in persons with type 2 diabetes. sca�er plot showing significant posi�ve correla�on between neuropathy disability score and in nerve conduc�on studies in both types of fiber jiimc 2016 vol. 11, no.4 nerve conduction studies and neurological examination scores 174 12 out of 30 nerve conduc�on study variables value dns nss nds dne nerve conduc�on study scores r p ‐0.058 0.857 ‐0.323 0.306 0.727 0.007** ‐0.046 0.886 nerve score amplitudes r p ‐0.058 0.857 ‐0.323 0.306 0.727 0.007** 0.093 0.775 nerve score veloci�es r p 0.266 0.404 ‐0.023 0.942 0.551 0.063 ‐0.018 0.957 nerve score latencies r p 0.122 0.706 ‐0.313 0.321 0.697 0.012* ‐0.048 0.881 17 out of 30 nerve conduc�on study variables value dns nss nds dne nerve conduc�on study scores r p ‐0.225 0.385 0.085 0.745 0.229 0.377 0.169 0.518 nerve score amplitudes r p ‐0.168 0.519 0.185 0.476 0.303 0.237 0.444 0.074 nerve score veloci�es r p ‐0.139 0.594 0.146 0.577 0.147 0.572 0.050 0.849 nerve score latencies r p ‐0.079 0.763 0.068 0.796 0.071 0.785 ‐0.051 0.845 table ii: correla�on between neurological scores and nerve conduc�on studies for large fiber type correla�ons were not significant. dns: diabe�c neuropathy symptom score. dne: diabe�c neuropathy examina�on score nss: neuropathy symptom score nds: neuropathy disability score discussion our study shows a significant positive correlation between nds and components of nerve conduction studies in patients with large‐ and small‐fiber impairment. the clinical examination scoring systems we used ware carefully selected to identify the type of fiber involved, and to allow the major components of neuropathy to be studied with 8 straightforward clinical examination. franssen et al. showed that amplitude in nerve conduction studies correlates with axonal neuropathy, which is highly predominant in our 9 patients. latency can also show significant correlation with axonal neuropathies, especially in advanced cases. velocity, in contrast, was not affected much – an unsurprising lack of association with axonal neuropathies, as pointed out by malik, et 10 al. although we found correlations between nds scores and velocity in nerve conduction studies regardless of fiber type, this result may be due to advanced neuropathy in which demyelination has started in addition to axonal loss. feki et al. found a significant correlation between nds results and nerve conduction findings, as well as between nss and nerve conduction results, but they also found, as we did, that the former correlation was 11 more significant. although 12 of our patients had deranged nerve conduction findings consistent with small‐fiber disorders, their clinical scores reflected signs of both small‐ and large‐fiber neuropathy; therefore, these patients were considered to have impairments in both types of fiber. lefaucheur et al. found a significant correlation between clinical findings and neurophysiological test results according to fiber type. these authors first determined the type of fiber involved on the basis of nerve conduction studies and clinical examination 12 independently, and then looked for correlations. we determined which type of fiber was involved by clinical examination and then looked for correlations between the clinical examination results and nerve conduction studies according to fiber type. unlike earlier studies, however, our approach included four known neurological scoring systems and compared their scores according to fiber type. regarding nds, we found that the scores correlated with nerve conduction findings, although this correlation was confirmed only in patients with neuropathy that affected both types of fiber. liu et al. showed that the most common clinical and electrophysiological manifestation of diabetic neuropathy is a sensory disturbance, which is more 13 severe in the lower limbs. however, when sensory symptoms are considered, electrophysiological changes are not always consistent with clinical 14 manifestations. symptom scores are not always reliable because they focus on symptoms alone. the exploration of symptoms is always patient‐dependent and is affected by many confounding factors such as the patient's mental state, literacy level and attitude toward being labeled neuropathic or not. symptom scores are thus unreliable when used alone to assess neuropathy, at least in the examination protocols currently in use. in many neuropathies, the pathophysiological and clinical profiles may be 15 heterogeneous across patients. this variability may be responsible for the differences in results when patients are examined with two or more different techniques, as each technique focuses on a specific aspect of the patient's illness. our impression is that if a more comprehensive battery of symptoms were used to assess neuropathy, the results may be more reliable. searching for correlations between the findings from neurological examination and nerve conduction studies is a way to explore two different aspects of neuropathy. nerve conduction studies measure the strength of local signal transport, whereas neurological examination assesses the overall function of the nerve as well as the muscles involved. however, abnormal findings in nerve conduction studies also eventually point to impaired overall nerve functioning. we found that in patients with both small and large fiber involvement, the correlation between these two sources of information was indicative of more advanced neuropathy. if carefully examined and investigated, many idiopathic neuropathies can be assigned to known 16 causes of neuropathy after appropriate testing. the findings of patient assessment by clinical examination also depend on normal receptor functioning, which is not the case with nerve conduction studies. rota et al. correlated clinical neuropathy with the jiimc 2016 vol. 11, no.4 nerve conduction studies and neurological examination scores 175 results of electrophysiological tests, but did not 17 categorize patients according to severity. they investigated only persons with impaired neurological scores according to the nds and nss, and who also had impaired nerve conduction. their results are consistent with our findings. in the present study we also recorded nerve conduction in those patients who did not have positive findings on clinical examination, and found neuropathy in many of these patients. this aspect of our study is important in establishing the value of nerve conduction studies in patients like the ones enrolled in our study. an important difference between our study and others is that usually a full battery of nds and nss is claimed to have been tested, which is rather impractical in daily clinical practice both for the physician and for outpatients, especially in settings 18,19 with a heavy patient turnover. a complete battery of scoring systems assesses many components which are not related to peripheral neuropathy, and so are not relevant to the aims of the present study. we have, however, included modified forms of both examination systems, with the aim of testing related components of nerve functioning in an effort to search for an approach to clinical diagnosis that would be practical for the physician. in pakistan it is common practice to perform neurological examination and nerve conduction studies in centers where both facilities are available. to date, however, the correlations between these two methods have not been analyzed either directly (in comparison to clinical examination findings) or according to the type of fiber involved. in our sample we are unable to confirm significant correlations between clinical signs of neuropathy documented with different scoring systems and evidence of impaired nerve functioning obtained with nerve conduction studies in patients with small‐ fiber dysfunction, but the correlations are significant in those with large‐fiber or mixed large‐ and small‐ fiber dysfunction. our findings give us insight into the reasons for differences in the performance of various scoring systems used to detect neuropathy. however, the influence of confounding factors such as the subjectivity of clinical assessments needs to be taken into account. future studies should include more specific variables. moreover, many patients do not recognize their symptoms unless asked about them through direct questioning. this aspect may also contribute to discrepancies between the results of sensory clinical scoring systems and nerve conduction studies among patients with diabetic sensorimotor polyneuropathy involving different types of nerve fibers. according to our results, more patients had large‐ or mixed‐fiber impairment rather than only small‐fiber impairment. this finding needs to be investigated further in patients with newly‐diagnosed diabetes to determine whether small or large fibers are initially affected, and follow‐up studies will be needed to determine whether impairment in one type of fiber evolves toward impairment in the other type. it is also possible that small fibers, if affected early, may recover earlier during treatment for hyperglycemia, whereas mainly large fiber impairment appears later, or remains detectable for longer during the course of diabetes. conclusion in patients with type 2 diabetes and advanced neuropathy, our use of more objective examination tools showed that the correlation between the findings of ner ve conduction studies and neurological examination scores indicative of sensorimotor neuropathy reflects the involvement of a specific type of nerve fiber. for patients with both small‐ and large‐fiber neuropathy, objective tests such as the nds also correlate with nerve conduction study results. acknowledgment we thank k. shashok (author aid in the eastern mediterranean) for improving the use of english in the manuscript. references 1. international diabetes federation. idf diabetes atlas. (2014). accessed: july 29, 2015: http://www.idf.org/ diabetesatlas. 2. basit a, hydrie mzi, hakeem r, ahmedani m, masood q: frequency of chronic complications of type ii diabetes. journal of college of physicians and surgeons pakistan. 2004; 14: 79–83. 3. mahmood k, akhtar st, talib a, abbasi b , salekeen su, naqvi if: clinical profile and management, outcome of diabetic foot ulcers in a tertiary care hospital. journal of college of physicians and surgeons pakistan. 2008; 18: 408‐ 12. 4. dipreta ja. outpatient assessment and management of the diabetic foot. medical clinics of north america. 2014; 98: jiimc 2016 vol. 11, no.4 nerve conduction studies and neurological examination scores 176 353–73. 5. meijer jw, bosma e, lefrandt jd, links tp, smit aj, stewart re, et al. clinical diagnosis of diabetic polyneuropathy with the diabetic neuropathy symptom and diabetic neuropathy examination scores. diabetes care. 2003; 26: 697‐701. 6. guyton ac, hall je. guyton and hall textbook of medical 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of internal medicine. 2004; 164: 1021–5. 17. rota e, quadri r, fanti e, isoardo g, poglio f, tavella a, et al. electrophysiological findings of peripheral neuropathy in newly diagnosed type ii diabetes mellitus. journal of peripheral nervous system. 2005; 10: 348–53. 18. alport ar, sander hw. clinical approach to peripheral neuropathy: anatomic localization and diagnostic testing. continuum (minneap minn). 2012; 18: 13–38. 19. calvet jh, dupin j, winiecki h, schwarz peh : assessment of small fiber neuropathy through a quick, simple and non invasive method in a german diabetes outpatient clinic. experimental and clinical endocrinology and metabolism. 2012; 121: 80‐3. jiimc 2016 vol. 11, no.4 nerve conduction studies and neurological examination scores 177 page 34 page 35 page 36 page 37 page 38 page 39 original�article abstract objective: to compare the efficacy of 30ml/kg/hr ringer's lactate with 10ml/kg/hr to prevent postoperative vomiting (pov) in children undergoing tonsillectomy in general anesthesia. study design: a randomized control trial. th th place and duration of study: the study was conducted for a period of 06 months from 15 may 2017 to 16 november 2017 at holy family hospital, rawalpindi. materials and methods: this study was conducted in the department of anesthesia at holy family hospital after approving it from the hospital ethical board. informed consent (written) was taken from 130 patients. included patients were between 6 -12 years of age and belonged to american society of anesthesia physical status (asa class) i or ii. they were divided randomly into 2 equal groups by using computer generated numbers. group a got 10 ml/kg ringer's lactate and group b got 30 ml/kg ringer's lactate as perioperative fluid from the time of induction till the surgery ended. postoperative vomiting (pov) was recorded at 0, 4 , 8 , 12, 16 , 20 and 24 hours of surgery. therapy was found to be effective if no episode of postoperative vomiting was observed in 24 hours. data was analyzed using spss 17. results: 30 ml/kg ringer's lactate was found effective in preventing postoperative vomiting in 69% cases and 10 ml/kg ringer's lactate prevented it in 15% cases. post operative vomiting occurred in 85% cases in group a in comparison with 31% cases in b group. the difference between two groups was statistically significant (p<0.05). conclusion: super hydration with 30 ml/kg ringer's lactate is an effective way to reduce the frequency of pov in children undergoing tonsillectomy in general anaesthesia. key words: general anesthesia, nausea, postoperative vomiting, super hydration, tonsillectomy. tonsillectomy is one of the most common surgeries 7 done in children across the world. the pov incidence is up to 73% without any antiemetic medications (prophylactic) in children undergoing 8 tonsillectomy. pov may result in increased rate of aspiration, patient dissatisfaction, delayed discharge 9,10,11 and unanticipated hospital admission. p reve nt i o n o f p ov i s ve r y i m p o r ta nt fo r improvement of patient satisfaction and to enhance medical outcome. nowadays, in the era of ambulatory surgery, it is necessary to prevent pov to 12 speed up recovery. there are various strategies used to decrease the incidence of pov in patients undergoing ga. local anesthetic infiltration in addition to nsaids and paracetamol could serve as multimodal analgesia and thus decrease the incidence of pov attributed to postoperative pain. pharmacological antiemetic includes benzamides ( e . g m e t o c l o p ra m i d e ) , p h e n o t h i a z i n e s ( e . g perphenazine), antihistamines(e.g dimenhydrinate), midazolam, steroids(e.g dexamethasone) and 8 serotonin receptors antagonists (e.g ondansetron). introduction postoperative vomiting (pov) is one of the major concerns for patients undergoing general anesthesia 1,2 (ga). incidence of pov is 30% in patients having surgeries in ga and may rise to 80% in high risk 2,3 patients. pov is the ejection of stomach contents through the mouth in the postoperative period. risk factors for pov may include ga, female sex, use of 4 intra-operative opioids , history of pov, duration of anesthesia and surgery, type of surgery (upper airway surgeries, abdominal or pelvic surgeries, breast surgery), smoking (decreased risk of pov with 5,6 the use of tobacco) and age < 40 years. effect of intravenous fluid therapy on postoperative vomiting in children undergoing tonsillectomy 1 2 3 4 5 6 qudsia rasool , ayesha nazir , fizza batool , jawad zahir , anum malik , tabassum aziz correspondence: dr. ayesha nazir senior registrar department of anaesthesia holy family hospital, rawalpindi e-mail: dr.ayeshanazir@gmail.com 1,2,3,4,5 6 department of anaesthesia/ent holy family hospital, rawalpindi funding source: nil; conflict of interest: nil received: june 10, 2021; revised: march 08, 2022 accepted: march 09, 2022 super hydration and post operative vomiting jiimc 2022 vol. 17, no.1 19 pharmacological prophylaxis for pov might not be cost effective and may also result in various side effects like agitation, bradycardia, dizziness, 13 sedation, and extra pyramidal symptoms etc. intravenous fluid therapy has shown a major role in 14 decreasing the incidence of pov. lactated ringer's solution is a crystalloid used in routine as peroperative fluid. a study conducted by elgueta and colleagues have shown a decrease in pov using 30ml/kg as compared to 10ml/kg from 82% to 62% 13 (relative reduction of 24%, p=0.026). studies on decreasing the incidence of pov in the pediatric population scheduled for tonsillectomy using super-hydration (30ml/kg/hr) have been conducted internationally but no such study has been done in pakistan yet. aim of this study was to observe the antiemetic effect of super-hydration on prevention of pov in children undergoing surgical removal of tonsils (tonsillectomy), so that a costeffective antiemetic strategy could be established and implemented in resource-stricken countries such as ours. materials and methods this rct was conducted in the operation theatres of holy family hospital, from 15-05-2017 to 16-112017. sample size of 65 was calculated in each group with the help of who sample size calculator with the level of significance set at 5%. the patents included were children between the ages of 6-12 years belonging to either asa class i/ ii undergoing planned surgery (tonsillectomy with or without adenoidectomy). whereas patients with comorbidities such as diabetes mellitus, obesity (bmi > 95th percentile for age and sex), mental retardation, known gerd and those with history of antiemetic intake within 24 hours before surgery were not included. after getting approval of the ethical committee of the hospital, an informed consent was received from all the parents, 130 patients were selected based on the above-mentioned criteria. all patients u n d er went p reo p erat ive eva lu at io n by a n anaesthetist before surgery. patients were instructed to observe fasting according to the asa guidelines. they were then randomly sorted into two equal groups by the computerized system. group a received 10ml/kg/hr ringer's lactate during surgery. group b received 30ml/kg/hr ringer's lactate during surgery. no premedication was given. on reaching the operation theatre, standard asa monitors such as pulse oximeter, ecg leads, and nibp cuff were applied. general anesthesia induction was done with sevoflurane at 4mac in oxygen 100% as carrier gas at fresh gas flow rate of 6 l/min via a facemask. after gaining an intravenous access, atracurium 0.5 mg/kg and nalbuphine 0.2 mg/kg were given intravenously. tracheal intubation was done 3 m i n u te s af te r g i v i n g m u s c l e re l axa nt a n d maintenance of anesthesia was done with sevoflurane at 1 mac with fio2 set at 0.5%. interventional therapy was started after induction. patients as well as the anesthesiologists were blinded to the group assignment. ringer's lactate was continuously given with the help of a pump with screen and solution bag hidden with a cover for maintaining blinding. on completion of surgery, all inhalational agents were turned off and fio2 turned to 1. reversal agent neostigmine and glycopyrrolate 0.05 mg/kg and 0.001 mg/kg respectively, were given upon return of some degree of airway reflexes. patient was extubated when criteria of tidal volume was fulfilled. after tracheal extubation, ringer's lactate was stopped. when patients were sufficiently awake to maintain the airway without needing any assistance, they were shifted to the post-anaesthesia care unit (pacu). one parent was allowed to stay in pacu. in pacu patients were observed by a post graduate trainee, who was blinded to group allocation, for any episode of vomiting in postoperative period every four hours up till 24 hours. the episode of vomiting was recorded in the proforma specifically designed for the study. the frequency was recorded as 0 in case of no pov in 24hours, as 1 if one episode of pov occurred in 24hours and 2 if more than 1 episode of pov occurred in 24hours. the time span of hospital stay was also noted. in pacu no additional i.v. fluid was given and the patient was allowed to drink liquid after 3-4 hours. if severe vomiting occurred, it was treated with first line drug ondansetron 0.15mg/kg i.v. if vomiting persisted, a 2nd rescue antiemetic diphenhydramine 0.015mg/kg i.v. was administered. patient was discharged a day after surgery. data collection was 20 jiimc 2022 vol. 17, no.1 super hydration and post operative vomiting done on a structured proforma and spss (version 17) was used for the analysis. mean with s.d was calculated for quantitative variables such as weight, height, and age in both study groups. frequency & percentages were presented for qualitative variables such as gender and effectiveness of both groups. the chi-square test was used to compare the proportion of vomiting between the two groups. a p-value of less than 0.05 was regarded to be statistically significant. effect modifiers such as age and gender were controlled with stratification and following stratification chi square test was also applied. results in this study an aggregate of 130 patients were enrolled and divided into 2 equal groups of 65 each, randomly with the help of computer-generated numbers. there was no notable contrast among the two groups in terms of mean age, weight, height, bmi, and gender distribution as shown in [tables i and ii]. fluid therapy with 30ml/kg/hr i.e the superhydration group or group b was effective 69% in preventing pov whereas fluid therapy with 10ml/kg/hr i.e group a was found to be only 15% effective. after application of the chi square test, with a p value of less than 0.05 regarded as significant, the difference between the two groups was statistically significant as shown in [table iii]. pov occurred in 85% patients in a group as compared to 31% in group b. the data was again analyzed post-stratification for age and gender and the difference in frequency of pov was found to be statistically significant between the two groups [tables iv and v]. therefore, the data strongly indicates super-hydration to be an effective remedy against pov in young children. frequency of pov* 0= no pov in 24 hours 1= 1 episode in 24 hours 2=>1 episode in 24hours table iv: comparison of frequency pov between the two groups; stratified according to age (n= 130) table i: comparison of age, weight, height and bmi between the two groups (n= 130) table ii: comparison of gender distribution between the two groups table iii: comparison of frequency of pov between the two groups (n= 130) p value < 0.05 is significant discussion tonsillectomy is one of the commonest procedures 15 in the paediatric age group that is done under 13 general anesthesia . pov is the most frequent 16 complication occurring post operatively, which not only is troublesome for patients but may result in longer hospital stay. the average frequency of pov is about 40% or higher in children aged three years and 21. above in our study, we observed a substantial reduction in pov with superhydration, 31% of the patients 21 jiimc 2022 vol. 17, no.1 super hydration and post operative vomiting experienced no episode of pov in the first 24 hours by use of 30ml/kg perioperative fluids as compared to 85% in the group with 10 ml/kg perioperative fluids. the use of antiemetic for treatment of pov was also much less in group with superhydration, 64% of the patients in the group with 10ml/kg perioperative fluid experienced one episode of pov and had to be given rescue antiemetics while 29% of the patients in the superhydration group experienced 1 episode of pov and required rescue antiemetics, similarly 20% of the patients in the group with 10ml/kg perioperative fluid experienced more than one episode of pov while only 1% of the patients in the superhydration group experienced more than 1 episode of pov. similar results were generated after stratification for age, gender and bmi, thus the superiority of superhydration as antiemetic therapy was repeatedly established. the reason behind the antiemetic effect of fluid therapy is not clear yet but it is hypothesized that supplemental intraoperative fluids reduce any preexisting deficit of intravascular volume due to compulsory fasting prior to surgery, so by maintaining fluid balance, it helps prevent vasoconstriction of the splanchnic vessels and p o s s i b l e m e s e nte r i c i s c h e m i a re s u l t i n g i n suppression of serotonin production -a strong 17,18, 21.. mediator of both nausea and vomiting another mechanism through mediation by antidiuretic hormone (adh) has also been 2 1 sug gested . anesthesia drugs bring about vasodilation resulting in hypovolemia (relative). the decreased negative feedback of stretch receptors located in the right atrium causes an increase in the levels of adh which then results in higher frequency 21 of pov. superhydration not only serves a purpose to replenish the depleted stores of body water but also helps in keeping the body tissues well hydrated in the postoperative period. as they say, 'a dry throat is a sore throat'. the doctrine of superhydration dictates that an adequate number of fluids is required to keep the saliva flowing. this makes swallowing easier and washes the throat and reduces the risk of infection and bleeding. for this purpose, it is mandatory to encourage oral intake of fluids as soon as the child is able to take oral feeds. this is only possible if there is minimal to none vomiting in the postoperative period. in an earlier study, elgueta et al. found a decrease of 82% to 62% in pov (p=0.02) in children receiving 13 superhydration as compared to children with restricted fluid undergoing tonsillectomy. 17 in another study, magner et al observed decreased incidence of pov in the group receiving 30ml/kg fluid as compared to the group receiving 10ml/kg (8.6% vs 25.7% p=0.01) in patients undergoing gynecological laparoscopic surgeries. they also observed a substantial fall in incidence of severe nausea in the group with 30ml/kg. antiemetic use was alsoa decreased. 18 schuster et al also found decrease in frequency in pov by larger intra operative fluids used in adult patients undergoing laparoscopic gastric bypass 19 surgeries. goodarzi et al also found intraoperative superhydration effective in reducing pov (in children undergoing strabismus surgeries). there was a reduction from 54% to 22% (p0.001) in the 20 superhydration group. however, dagher et al observed no difference in reduction of ponv using 30 ml/kg or 10 ml/kg perioperative fluids in patients undergoing thyroidectomy. 21 recently ashok et al found use of intra operative liberal fluid therapy to be effective in reduction of pov in children undergoing abdominal (lower) 21 surgeries. the incidence was markedly low in liberal group patients in comparison to the restricted group; 21 45.8% vs 27.4% (p=0.021). the parents of liberal group were more satisfied in comparison to the 21 restricted group (p=0.04). hthe jjp-value < 0.05 is significant* 22 jiimc 2022 vol. 17, no.1 table v: comparison of frequency of pov between the two groups; stratified according to gender (n=130) super hydration and post operative vomiting some limitations of our study are worth mentioning. we did not use any prophylactic antiemetic for these p a t i e n t s . t o n s i l l e c t o m i e s a n d o t h e r otolaryngological surgeries have a higher incidence of pov, so relying alone on fluid therapy might have led to somewhat increased incidence of pov as opposed to the incidence with the use of combination of prophylactic antiemetic and superhydration. however, these patients` parents agreed to this study protocol and had no objections. these patients were monitored for 24 hours and any episode of pov was treated as soon as possible. based on our results, however, we consider that for this type of surgery, super-hydration on its own is not sufficient as the only antiemetic prophylactic strategy. our last limitation is that we did not administer steroids which has a proven analgesic and antiemetic effect. considering fluid therapy as an antiemetic routine in combination with other strategies in future will be quite helpful especially in our settings where cost effectiveness matters a great deal. also, it will lead to decreased use of other pharmacological agents and will help to avoid their side effects as well. this will also increase the level of satisfaction of patients and will help to decrease duration of hospital stay. conclusion super hydration with 30 ml/kg ringer's lactate is an effective way to reduce the frequency of pov in children undergoing tonsillectomy in general anesthesia. references 1. echevarría gc, altermatt fr, paredes s, puga v, auad h, veloso am, elgueta mf. intraoperative lidocaine in the prevention of vomiting after elective tonsillectomy in children: a randomised controlled trial. eur j anaesthesiol. 2018 may;35(5):343-8. 2. jin z, gan tj, bergese sd .prevention and treatment of postoperative nausea and vomiting (ponv): a review of current recommendations and emerging therapies. ther clin risk manag. 2020 dec 31;16:1305-17. 3. weibel s, rücker g, eberhart lh, pace nl, hartl hm, jordan ol et al. drugs for preventing postoperative nausea and vomiting in adults after general anaesthesia: a network meta-analysis. cochrane database syst rev. 2020 oct 19;10(10):cd012859. 4. elvir-lazo ol, white pf, yumul r, eng hc. management strategies for the treatment and prevention of postoperative/post discharge nausea and vomiting: an updated review. f1000 res. 2020 aug 13;9: f1000 faculty rev-983. 5. gupta r; soto r. prophylaxis and management of postoperative nausea and vomiting in enhanced recovery protocols. perioper med. 2016; 5: 4. 6. stoicea n; gan tj; joseph n; uribe a; pandya j; dalal r; bergese sd. alternative therapies for the prevention of postoperative nausea and vomiting. front med (lausanne). 2015; 2: 87. 7. cullen ka; hall mj; golosinskiy a. ambulatory surgery in the united states. natl health stat report. 2009 jan 28;(11):1 25. 8. fujii y. current management of vomiting after tonsillectomy in children. curr drug saf. 2009; 4:62-73. 9. kovac al. postoperative nausea and vomiting in pediatric patients. paediatr drugs.2021 jan;23(1):11-37. 10. jewer jk, wong mj, bird sj, habib as, parker r, george rb. supplemental perioperative intravenous crystalloids for postoperative nausea and vomiting. cochrane database syst rev. 2019 mar 29;3(3):cd012212 11. cao x, white pf, ma h. an update on the management of postoperative nausea and vomiting j anesth. 2017 aug;31(4):617-626. 12. gan tj, belani kg, bergese s, chung f , diemunsch p, habib as et al. fourth consensus guidelines for the management of postoperative nausea and vomiting. anesth analg. 2020 aug;131(2):411-48. 13. elgueta mf, echevarría gc ; de la fuente n; cabrera f; valderrama a; cabezón r; muñoz hr; cortinez li. effect of intravenous fluid therapy on postoperative vomiting in children undergoing tonsillectomy. br j anaesth. 2013 apr;110(4):607-14 14. apfel cc; meyer a; orhan-sungur m; jalota l; whelan rp; jukar-rao s. supplemental intravenous crystalloids for the prevention of postoperative nausea and vomiting: quantitative review. br j anaesth. 2012 jun;108(6):893-902. 15. bartolek d, jakobović j, bartolek f, finci d, munjiza a. reduced-dose rocuronium for day-case tonsillectomy in children where volatile anaesthetics are not used: operating room time saving. paediatr anaesth. 2010 jan;20(1):47-55. 16. pierre s and whelan r. nausea and vomiting after surgery. bja educ. 2013: 13(1): 28–32. 17. magner jj, mccaul c, carton e, gardiner j, buggy d. effect of intraoperative intravenous crystalloid infusion on postoperative nausea and vomiting after gynaecological laparoscopy: comparison of 30 and 10 ml kg−1. br j anaesth. 2004 ;93(3) :381–385. ; 18. schuster r alami rs; curet ms; paulraj n; morton jm; brodsky jb; brock-utne jg; lemmens hjm . intraoperative fluid volume influences postoperative nausea and vomiting after laparoscopic gastric bypass surgery. obes surg. 2006 jul;16(7):848-51. 19. goodarzi m, matar mm, shafa m, townsend je, gonzalez i .a prospective randomized blinded study of the effect of intravenous fluid therapy on postoperative nausea and vomiting in children undergoing strabismus surgery. j clin anesth. 2016 nov; 34:136-42. 20. dagher cf, abboud b, richa f, abouzeid h, el-khoury c, doumit c, yaghi c, yazbeck effect of intravenous .p. crystalloid infusion on postoperative nausea and vomiting 23 jiimc 2022 vol. 17, no.1 super hydration and post operative vomiting after thyroidectomy: a prospective, randomized, controlled study. eur j anaesthesiol. 2009 mar;26(3):188-91. 21. ashok v, bala i, bharti n, jain d, samujh r. effects of intraoperative liberal fluid therapy on postoperative nausea and vomiting in children-a randomized controlled trial. paediatr anaesth. 2017 aug;27(8):810-815. 24 jiimc 2022 vol. 17, no.1 conflict of interest authors declared no conflicts of interest. grant support and financial disclosure authors have declared no specific grant for this research from any funding agency in public, commercial or nonprofit sector. data sharing statment the data that support the findings of this study are available from the corresponding author upon request. this is an open access article distributed under the terms of the creative commons attributionnoncommercial 2.0 generic license. super hydration and post operative vomiting original�article abstract objective: to study the risk of psychosis in south asian communities in bradford and investigate the role of cannabis as a contributory factor. study design: naturalistic studies based on electronic summary records. place and duration of study: the studies were conducted at the becklin centre, st james's university hospital, leeds and the university of leeds, school of medicine from 2018 to 2020. material and method: a service evaluation and research project looking into the role of cannabis included 194 st th patients admitted to acute psychiatry wards at the becklin centre between 1 january 2016 and 30 november 2018. epidemiological study used electronic summary records provided by the bradford early intervention for psychosis service of 15-35-year old newly diagnosed cases with first episode psychosis in 2013-15 and local census data to calculate the risks ratios. results: compared with indigenous white population, pakistanis in bradford had significantly higher risk of psychosis (rr: 1.41, 95% ci 1.07, 1.85*). this trend was also seen in bangladeshi community (rr 1.72, 95% ci 0.91, 3.28*). indian community, on the other hand, experienced lower risk (rr 0.54, 95% ci 0.20, 1.27). conclusion: we found increased risk of psychosis in pakistani and bangladeshi communities but not in indian community. key words: bradford, ethnic, psychosis, risk ratio. caribbean in the uk. these studies found that the incidence of schizophrenia was 4-6 times higher than the indigenous white population and was more 5 marked in the second generation. whilst an increased incidence of schizophrenia has been consistently reported in people of african caribbean origin who are resident in the uk, the results are less consistent for those of south asian 6 origin. in the æsop study, the incidence of psychosis, although increased, was raised to a much lesser extent in asian and non-indigenous white populations. another study in east london, had found the incidence to be raised in most migrant and minority ethnic groups, however, in pakistani and bangladeshi populations, this trend appeared to be 7 evident only in women. bradford (population 530,000), a yorkshire city with a rich industrial history of cotton and woollen mills, is home to a number of immigrant communities from the subcontinent including pakistanis, bangladeshis and indians. pakistanis from kashmir in the north of pakistan are the largest ethnic group (110,000) and there are sizeable indian and bangladeshi populations. anecdotally, the prevalence of schizophrenia among pakistanis in bradford was said to be 2-5 times higher and since the district has the largest proportion introduction the association between migrant status and schizophrenia was reported in 1930s among 1 , 2 norwegian immigrants in new york which suggested that stressful life experiences played a role in the causation of psychosis. an influential paper, 3 in which the norwegian psychiatrist odegaard reported the findings of his study in wisconsin, argued that the increased incidence could be attributed to selective migration of people who were genetically at a higher risk. this was handy munition for anti-immigration politicians of that time and 4 although later studies did not support this claim it stymied further investigations in the field. interest in the topic was rekindled in the 1980s by findings concerning first and second generation african migration and psychosis: evidence from south asian communities in bradford cara beattie , fraser ritchie, alastair cardno, tariq mahmood correspondence: dr. tariq mahmood consultant psychiatrist & honorary senior lecturer becklin centre, st james's university hospital leeds, united kingdom e-mail: tariq.mahmood5@nhs.net department of psychiatry becklin centre, st james's university hospital leeds, united kingdom funding source: leeds & york partnership nhs foundation trust; conflict of interest: nil received: july 18, 2020; revised: october 01, 2020 accepted: october 05, 2020 migration and psychosisjiimc 2020 vol. 15, no.4 226 (20.3%) of people of pakistani origin in england, there was an opportunity to study these reports in a 8,9 systematic manner. this was made easier by the existence of an early intervention service (eips) in bradford since 2005, which up until 2016 accepted cases in 15-35 age band and had gathered a substantial case load. according to unpublished eips data 29.5% of bradford eips referrals were of pakistani ethnicity. migrant status is now a well-recognised risk factor for the development of psychosis; however, its antecedents have not been that well elucidated. social disadvantage, unemployment and residence in densely populated innercity areas are applicable 10 to new immigrants however, it is the use of illicit substances which is often under the spotlight. there are reports to suggest that cannabis use has a greater 11 effect in inducing psychosis in urban environments. the evidence, however, is sketchy as there are no systematic studies of migrant populations such as community surveys, possibly due to the difficulty, which any attempt to gather such stigmatising information will encounter. we, therefore, addressed this question indirectly by looking into the drug use histories of patients (icd-10, f20-29) of various ethnic backgrounds admitted to an acute psychiatry unit in leeds, a neighbouring yorkshire city (population 800,000) with sizeable populations of south asian origin. the findings of this extended study research project (esrep) undertaken by two th university of leeds 4 year medical students are reported in this paper. material and methods 8 as reported in an earlier paper by saleem et al in 2019, eips bradford provided anonymous summary data on the number of 15-35 year old newly diagnosed with first episode psychosis in 2013, 2014 and 2015, grouped by ethnicity, gender and 10-year age bands. permission to use these data for the current study was granted by the medical director of bradford district care nhs foundation trust. eips bradford uses comprehensive assessment of at risk mental state (caarms) interviews to establish the 12 diagnoses according to icd-10 criteria. only cases with non-affective first episode psychoses were 13 included. the revman 5.3 program was used for analysis and data from the three years 2013-15 were combined. risk ratios (rrs) with 95% confidence intervals were calculated and rrs with 95% confidence intervals that did not include 1 were regarded as statistically significant at p<0.05, twotailed. population data were obtained from 2011 census figures published on the website of the office of national statistics. table i shows the basic demographic data derived from census 2011, which provides the denominators for relative risk (rr) calculations. compared with british white in bradford (23% in 15-35 age band), the three south asian communities are youthful, as 36 – 48% of their members fall in this age band. another noteworthy observation is female preponderance in british white, pakistani and bangladeshi communities. indian community, on the other hand, has fewer females. extended study research project (esrep) obtained the ethnicity and drug use data from the electronic records of 194 patients admitted with icd10 (f2029) diagnosis of psychosis to four acute adult wards st at the becklin centre between 1 january 2016 and th 30 november 2018. fifteen patients were excluded as no data on cannabis use was available in their electronic case notes. patients were categorised as either “white british” (n=101, male 72, female 29) or “non-white british” (n=78, male 52, female 26). parametric and non-parametric tests were used to analyse the data. research approval was granted by the leeds & york partnership trust research & development and esrep board of the university of leeds, school of medicine (r&d 2018-673-se). table i: census 2011 data for bradford† 8 †adapted from saleem et al results table ii shows the risk of first episode psychosis for each ethnic group. compared with uk white population, pakistanis, and bangladeshis had higher jiimc 2020 vol. 15, no.4 227 migration and psychosis incidence rates (50, 71, 87/100000 respectively in 15-35 age band). people of indian origin, on the other hand, had a lower incidence rate (27/100000). the esrep carried out by medical students cb and fr found a high rate (53.70%) of cannabis use in all acute patients admitted with a diagnosis of icd-10 psychosis. table v compares the rates of cannabis use in white british (47.52%) and non-white british (60.26%) patients and shows a trend towards greater 2 use in non-white british (x =2.864, p 0.091; or 1.554, 95% ci 0.824,2.933). table ii: incidence of psychosis and risk ra�o *sta�s�cally significant at p<0.05 ‡ trend towards 8 significance †adapted from saleem et al table iii shows the risk of psychosis in 10-year age bands for each ethnic group. the risk compared to whites is significantly higher in 25-35 old pakistanis (rr 1.92, 95% ci 1.29, 2.87) and bangladeshis (rr 2.64, 95% ci 1.13, 6.19). in contrast to the british white, british-indian population appears to show a lower risk for this age group. table iii: risk of psychosis by ethnic group and 10-year age bands *sta�s�cally significant at p<0.05 8 †adapted from saleem et al table iv shows gender analysis of risk in the four ethnic groups. we see significantly increased risk for pakistani and bangladeshi males (rr 1.46, 95% ci 1.16, 1.83; 2.42, 95% ci 1.17, 5.02)) whereas indian males showed a non-significant lower risk (rr 0.65, 95% ci 0.21, 2.07). table iv: risk of psychosis by ethnic group and gender *sta�s�cally significant at p<0.05 8 †adapted from saleem et al table v: history of cannabis use in acute psychiatric admissions ‡ p 0.091 discussion higher risk of psychosis in immigrant communities this naturalistic study confirmed the anecdotal reports of higher incidence of psychosis in bradford south asian ethnic groups and found that it is true in the case of british pakistani and british bangladeshi communities (rrs 1.41 and 1.72). however, the risk for british indians is lower (rr 0.54), which is surprising but not unique as it has been reported 14 before. stillman and mckenzie (2009) report the findings of a study of tongans, who were selected through a ballot and accepted for migration to new zealand. compared with those who were unsuccessful in the ballot, the mental health of migrants, particularly women, was significantly jiimc 2020 vol. 15, no.4 228 migration and psychosis better. this study, however, was carried out only 11 months after resettlement in new zealand and it will be interesting to see if the tongans in new zealand continue to enjoy the positive effect of migration, which indian migrants in bradford have experienced over 50 years. duration of untreated psychosis this is a noteworthy finding that pakistani and bangladeshi group has a significantly higher risk in the age band 25-35 years, which suggests late presentation for treatment and is consistent with anecdotal reports that patients are first taken to 15 traditional healers , a practice brought over from their homelands. this practice, unfortunately, 16 prolongs the duration of untreated psychosis which 17 is well known to have an adverse effect on outcome. it may, therefore, pay to promote mental health education amongst ethnic communities and their traditional healers. gender differential 7 in their east london study coid et al had found a small increase in the risk of psychosis in pakistani and bengali women. we found a higher risk of psychosis in pakistani and bengali men, which is more consistent with observations of local mental health practitioners and psychiatrists practising on the subcontinent. underlying factors schizophrenia is a serious and enduring illness which causes great suffering to affected individuals and their families and generates a huge societal burden. it is imperative, therefore, that we try to find the causes of increased risk of psychosis in ethnic populations. one factor which distinguishes bradford pakistanis from other populations is a high rate of first cousin marriages which is reported to be 18 as high as 70% and has increased from 55% found 19 by darr & model in 1988, which was an increase on 33% among the mothers of women included in that 20 study. dobrussin and colleagues have shown that the risk of developing schizophrenia is elevated in populations with high consanguinity. therefore, it may be that the higher incidence of schizophrenia among bradford pakistani and bangladeshi communities is partly due to elevated genetic loading associated with cousin marriages. based on the observation that cannabis use can increase the risk of developing schizophrenia, 21 hickman et al quantified the theoretical increase in the incidence and prevalence of schizophrenia that may follow a population wide increase in the use of cannabis. their models predicted that by 2010, cannabis use will lead to 29% increase in incidence of schizophrenia among men. the esrep project undertaken by leeds university medical students cb and fr under the supervision of tm and ac addressed this question as to whether cannabis use is a modifiable risk factor for increased psychosis in ethnic populations. they found a trend towards greater cannabis use in non-white british patients, which suggests that a larger study such as a community survey is needed to find a definitive answer to this question. the naturalistic design of these studies has some limitations such as reliance on electronic summary data precludes analysis of individual variations. however, this is offset by the fact that research on populations and themes, which tend not to attract the attention of grant giving bodies, can be carried out by workers such as enthusiastic medical students and junior doctors, who are prepared to give their time out of goodwill to the cause of science. conclusions compared with indigenous whites in bradford, south asians of pakistani and bangladeshi origin are experiencing a higher risk of psychosis, though, the incidence rates do not appear to be as elevated as in those of african and caribbean origin. however, this does not completely disprove the anecdotal reports of increased prevalence among some ethnic groups which may be due to delayed recognition suggested by elevated incidence rates in 25-35 age band, thus increasing the duration of untreated psychosis and decreasing the chances of better outcome. in view of the above, it will not be out of place to make the customary call for more research to find the definitive answers. however, the fundamental questions such as genetics of schizophrenia may take more time to be answered or they may be unanswerable as they are integral to human condition. in the meantime there is cause for optimism in that some of the underlying factors such as cannabis use are modifiable with health education and adoption of preventive strategies. acknowledgements we are grateful to the medical directors of bradford jiimc 2020 vol. 15, no.4 229 migration and psychosis and leeds mental health trusts for allowing us to carry out these studies; to dr julie robinson for accommodating the esrep students in her department; and to catherine ding (bdct) and tom 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bedouin population in southern israel. world journal of biological psychiatry 2009; 10(4):334-336. 21. hickman m, vickerman p, macleod j, kirkbride j, jones p. cannabis and schizophrenia: model projections of the impact of the rise in cannabis use on historical and future trends in schizophrenia in england and wales. addiction 2007; 102:597–606. jiimc 2020 vol. 15, no.4 230 migration and psychosis original�article abstract objective: to evaluate the neuroprotective potential of curcumin against tartrazine made nissl rim changes in neurons of the motor cortex in cerebrum of rats. study design. laboratory based experimental research. place and duration of study: department of anatomy, islamic international medical college, rawalpindi from th th 30 sep 2019 to 30 july 2020. materials and methods: forty-five adult male albino rats (250-300gm) were divided randomly into three groups. (n=15). group a, rats were given standard rat diet. group b, rats were given tartrazine orally by dissolving in tap water with dose of 7.5 mg/kg body weight. group c, rats were given 200mg/kg of curcumin along with tartrazine orally by dissolving in tap water, daily for 28 consecutive days. at the end, animals were euthanized and dissected to remove the brain. coronal section of 5mm thickness of rat motor (frontal) cortices in the precentral areas were taken for further processing. after embedding,5μm thick coronal sections were obtained and stained with toluidine blue to visualize the nissl substance. results were analyzed using spss version 21. results: the curcumin administration significantly improved the nissl rim thickness (p-value < 0.001 on intergroup comparison). nissl's rim thickness was found to be 1.77 ±0.284µm, 1.01±0.974 µm and 1.92±0.193 µm in groups a, b and c respectively. conclusion: the curcumin significantly restores the nissl rim thickness and alleviate the tartrazine induced neurotoxic changes in gray matter of motor cortex. key words: curcumin, food azo compounds, nissl bodies, oxidative stress, tartrazine. sulfanilic acid which act as precursor of reactive oxygen species (ros). this metabolite can cross the blood brain barrier (bbb) and results in oxidative 2,3 stress mediated nervous tissue injury. it is reported that its consumption even at adi level can result in antagonistic health effects like genotoxicity, embryo 4 toxicity and carcinogenicity. tartrazine induced neurotoxicity has been reported in various brain sub regions including frontal cortex, hippocampus and 5 cerebellum .an immunohistochemical recoloring with the anti-ssdna counteracting agent (apoptotic cell marker) detailed plenteous apoptotic cells in the 6 brain cortex. tartrazine could be source of behavioral alterations in human children similar to 7,8 rat progeny. the brain is exceedingly helpless to the harm caused by free radicals since of its quick oxidative metabolic action, high polyunsaturated fatty acids content, quite low antioxidant levels. various tartrazine induced histopathological changes in nervous tissue have been reported including neuronal degeneration, vacuolation in gray 9 and in white matter. increasing research suggests that nutritional antioxidant supplementation can introduction food dyes are commonly used to enhance the food fascination among the consumers around the globe. with the rapid industrialization and color revolution a large variety of artificial food colors have been added into our diet. tartrazine is one of most widely used food dye amongst all. it is extensively used in various daily edible food items as well as in non-food products. for human utilization, worthy every day 1 (adi) of this color is 0-7.5 mg/ kg.bw/day. orally ingested tartrazine undergoes azoreduction in gut and liver lead to production of aromatic amine curcumin's neuroprotective efficacy against tartrazine-induced nissl rim alterations in adult male rats' motor cortex 1 2 3 4 5 6 maleeha zafar , shabana ali , huma beenish , tooba khursheed , nabeeha hussain , iram zakria correspondence: dr. maleeha zafar senior lecturer department of anatomy hitec institute of medical sciences, taxila e-mail: maleeha.wcpk@gmail.com 1,6 department of anatomy hitec institute of medical sciences, taxila 2,3,4,5 department of anatomy iimc, rawalpindi funding source: nil; conflict of interest: nil received: march 22, 2021; revised: august 18, 2021 accepted: august 20, 2021 neuroprotective role of curcumin jiimc 2021 vol. 16, no.3 180 reduce oxidative stress, minimize brain damage, and 10 improve behavioral functioning. curcumin a compelling antioxidant and a naturally available food color. it is the main constituent of turmeric. it has anti-tumor, anti-inflammatory, and a n t i ox i d a n t p r o p e r t i e s , a s w e l l a s o t h e r 11 pharmacological characteristics. it has the ability to p a s s t h e b l o o d b r a i n b a r r i e r a n d h a s 12 neuromodulatory effects. it has a neuroprotective effect against heavy metals and chemical-induced 13,14 neurotoxicity. given curcumin's therapeutic properties, the current study looked into its neuroprotective potential against tartrazine-induced nissl rim alterations in the gray matter of adult male rats' motor cortex neurons. materials and methods it was a laboratory-based experiment and was carried out in the department of anatomy, islamic international medical college rawalpindi in collaboration with the national institute of health (nih), after seeking approval from the ethics review committee [riphah/irc/19/0373], islamic th international medical college, from 30 september th 2019 to 30 july 2020. the sample was drawn using a non-probability convenient sampling technique in a laboratory setting. the study was performed on 45 albino sprague dawley adult male rats as a mammalian model. two months old adult male rat weighing 300gm were included and rats weighing less than 300gm and female rats were excluded from the study. the ethical review committee of the islamic international medical college, rawalpindi, defined the criteria for animal care and handling. tartrazine and curcumin in powdered form was weighed first on electronic weighing scale according to a dose of 7.5 mg/kg/day and 200mg/kg /day respectively. then dissolved in tap water to make 20ml solution for each rat which was given daily to 30 5 rats of experimental group b & c via oral route . the rats were housed in cages at the national institute of health's animal house in chak shehzad, islamabad. forty-five rats weighing (250-300gm) were kept under standard temperature at 22 ± 0.5˚c in air-conditioned room and were shifted into clean stainless-steel cages under 12-hour light and dark cycle with 50% humidity. they were given food and water ad libitum for 7-days to acclimatize. rat pellets and water were used as food during the whole experiment. each group comprised of 15 male rats. group a (control group) was kept on standard diet orally throughout the experiment. experimental group b was given tartrazine at dose 0.031gm/day and those of group c same dose of tartrazine along with 0.9 gm/day curcumin by dissolving in tap water via oral route for four weeks. following 24 hours of l a s t d o s e a d m i n i s t r a t i o n , t h e r a t s w e r e anaesthetized with chloroform-soaked cotton balls till they lost consciousness (euthanasia). the brains were removed and washed in with cold saline. the brain tissues were fixed in 10% formaldehyde solution which were processed to obtain paraffin blocks, from which 5-μm-thick coronal sections were prepared and conserved for histopathological analysis. tissue was stained by using toluidine blue staining. the nissl's granules form a circular rim at the neuronal periphery. its thickness was measured at 11, 12, 4, and 6 o'clock positions in the neurons of motor cortex, by the line tool of image j under 40x power in toluidine blue stained sections to indicate the nissl's granules density in neurons. four images of each slide were taken by using eye piece camera yw-100 2.0 mp and then all images taken, were transferred to image j software. spss version 21 was used to enter and analyze the data, and the findings were expressed as mean standard deviation. the mean comparison of quantitative variables between control and experimental groups was done using one way analysis of variance (anova). the intergroup comparisons among groups was done using the post hoc tukey's test. significant was defined as a p-value less than 0.05. results the average standard deviation of nissl's rim thickness was found to be 1.77 ±0.284µm, 1.01±0.974 µm and 1.92±0.193 µm in groups a, b and c respectively (table i, figure 1a-1c). difference between the groups was analyzed by anova, which yielded highly significant result (p-value ˂ 0.001). on comparing the mean nissl's rim thickness measurements of group b with the group c and a, the difference in mean between the groups was determined to be statistically significant (p-values of 0.001). while between a and c the mean difference was found to be insignificant (p-value of 0.126) (table i). neuroprotective role of curcumin jiimc 2021 vol. 16, no.3 181 discussion the inadvertent use of food colors in daily edible food items and other non-food products has augmented the need of determining the adverse effects on vital organs of the body including brain. tartrazine has gained wide utilization in many foods such as canned juices, bakery items, jams and jellies, ice-cream and candies. the deleterious effects of tartrazine on the brain should be dealt with considerable attention because these can further lead to various behavioral and cognitive disorders 7 during both childhood and adulthood . in the present study, addition of the natural antioxidant, curcumin to diets containing tartrazine has improved cellular metabolism by increasing 1 5 capacities of cellular antioxidants . these ameliorating effects of curcumin on nervous tissue histology were in consonance with the previous 14,16 reports . coadministration of curcumin in group c markedly improved the nissl rim thickness highlighting its neuroprotective potential. following the neuronal cell injury there is dispersion of rough endoplasmic reticulum in order to repair the cell. central chromatolysis is the typical phenomenon involved, which is marked by a decrease in the number of nissl bodies and eosinophilic cytoplasm. this is a reactionar y alteration in injured neurons' 17 perikarya . although the histological parameter of nissl rim thickness on rat brain has not been studied with tartrazine but a study conducted by heba r. hashem in 2018 studied this parameter in rat cerebral cortex with complications of diabetes and it 18 showed significant reduction in nissl rim density . fig 1: 1a-1c: histopathological analysis of gray matter of motor cortex of rat brain in control group a and experimental groups b& c. fig 1a from control group showing normal nissl rim thickness represented as (a-b, a-outer margin to b-inner margin of rim) in the cortical neurons of motor cortex. while figure 1b showing significant decline in nissl rim thickness represented as a-b. fig 1 c showing the curcumin mediated amelioration in histological findings in the motor cortex. (toluidine blue stains. approximately 1600 x) table i: mean measurement of nissl rim thickness in micrometer among control (a) tartrazine treated group (b) versus the tartrazine + curcumin group (c). neuroprotective role of curcumin jiimc 2021 vol. 16, no.3 182 another study found that nutmeg's toxic effects on the primary visual occipital cortex in rats resulted in 19 changes in nissl rim density in rats . tartrazine causes neurotoxicity by triggering oxidative damage and peroxidation of lipids in cell membranes, affecting cellular activities by altering the physicochemical characteristics, fluidity, and integrity of cell membranes, making cells more 20 vulnerable to lipid peroxidation and cell death in . current study, a significant ameliorative effect of curcumin on nissl rim thickness was detected in cortical neurons. this showed that antioxidants like curcumin improves the viability of neuronal cells by exerting its strong endogenous role of ros 21 scavenger . because of its antioxidant properties, it has been demonstrated that curcumin has proven to be useful in lowering neuronal death in the substantia nigra thus improving the functional 22 outcomes in a variety of brain illnesses . thus, curcumin administration to tartrazine treated rats was found to significantly re-equilibrate antioxidant parameters back to normal values and 23 restored the alteration in neuronal architecture .the limitation of study was lack of availability of special axonal staining procedures and settings at low cost. the current work highlights the need of future exploration of neurotoxicity induced by azo food dyes. it is recommended that the advanced investigation tools should be chosen to access toxic brain injury like immunohistochemistry, genetic polymorphism, gene expression analysis, portable eeg and diffusion mri. conclusion curcumin administration markedly prevented the t a r t r a z i n e i n d u c e d o x i d a t i v e s t r e s s a n d neuroinflammation which was appreciated in the form of restoration of nissl rim thickness in the neurons of the gray matter of motor cortex. t h e refo re , i t i s co n c l u d e d t h at c u rc u m i n administration improves the tartrazine induced nissl rim changes in the gray matter of motor cortex of rat cerebrum. references 1. alsalman n, aljafari a, wani t, zargar s. high-dose aspirin reverses tartrazine-induced cell growth dysregulation independent of p53 signaling and antioxidant mechanisms in rat brain. biomed research international. 2019;2019:18. 2. leulescu m, rotaru a, pălărie i, moanţă a, cioateră n, popescu m et al. tartrazine: physical, thermal and biophysical properties of the most widely employed synthetic yellow food-colouring azo dye. journal of thermal analysis and calorimetry. 2018;134(1):209-231. 3. ameur f, mehedi n, kheroua o, saïdi d, salido g, gonzalez a. sulfanilic acid increases intracellular free-calcium concentration, induces reactive oxygen species production and impairs trypsin secretion in pancreatic ar42j cells. food and chemical toxicology. 2018;120:71-80. 4. hashem m, abd-elhakim y, abo-el-sooud k, eleiwa m. embryotoxic and teratogenic effects of tartrazine in rats. toxicological research. 2019;35(1):75-81. 5. bhatt d, vyas k, singh s, john p, soni i. tartrazine induced neurobiochemical alterations in rat brain sub-regions. food and chemical toxicology. 2018;113:322-327. 6. mohamed a, galal a, elewa y. comparative protective effects of royal jelly and cod liver oil against neurotoxic impact of tartrazine on male rat pups brain. acta histochemica. 2015;117(7):649-658. 7. bloom s, chiang, k, demehri s et al. the effect of dietary tartrazine on brain dopamine and the behavioral symptoms of attention deficit hyperactivity disorder. university of maryland; 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78(1):33-38 . 20. el golli n, bini-dhouib i, jrad a, boudali i, nasri b, belhadjhmida n et al. toxicity induced after subchronic administration of the synthetic food dye tartrazine in adult rats, role of oxidative stress. recent advances in biology and medicine. 2016; 02:20. 21. chen m, huang s, chang y, zheng x, zhou r, li d et al. peperine enhancement on neuroinflammatory effects of curcumin and its mediation via modulating toll like receptor-4 pathway. current research in neuroscience. 2017;8(1):1-9. 22. wang x, zhang z, zhang m, sun m, wang w, xie c. neuroprotective properties of curcumin in toxin-base animal models of parkinson's disease: a systematic experiment literatures review. bmc complementary and alternative medicine. 2017;17(1). 23. guo j, cao x, hu x, li s, wang j. the anti-apoptotic, antioxidant and anti-inflammatory effects of curcumin on a c r y l a m i d e i n d u c e d n e u ro tox i c i t y i n rat s . b m c pharmacology and toxicology. 2020;21(1). neuroprotective role of curcumin jiimc 2021 vol. 16, no.3 184 original�article abstract objective: to compare protective efficacy of cinnamon extract and green tea against bisphenol a induced histological changes in rat kidney. study design: randomized control trial. place and duration of study: the study was conducted at animal house of national institute of health sciences, th th islamabad from 16 september 2016 to 16 march 2017. materials and methods: sixty adult male sprague dawley rats were placed in 4 confines having 15 rats each. rats in control group a were given distilled water subcutaneously for 30 days. rats in experimental group b were given bisphenol a (bpa) s/c at dose of 30mg/kg/day for 30 days. rats in group c were given cinnamon (200mg/kg/day) orally along with s/c injection of bpa while group d rats received green tea orally along with s/c bpa injections. dissection was done after 30 days and right kidney of all rats were dissected out and examined grossly for weight and appearance and histologically for changes in glomerulus and bowman's capsule. data was entered and analyzed in spss version 22. mean and standard error was calculated for the quantitative variables. categorical variables were presented by frequency and percentage. one way analysis of variance (anova) was applied for the mean comparison of quantitative variables between control and experimental groups. post hoc tuckey's test was applied for the multiple comparisons among groups. chi square test was applied for the comparison of qualitative variables among groups. a p value less than 0.05 was considered as a significant value. results: gross and histological parameters were observed in experimental and control groups. deterioration of kidney structure was greatest in group b as compared to control group. although both group c and d protected kidney against these changes but group d offered more nephron protection than group c. conclusion: bpa adversely affects morphology and microstructure of kidneys by causing oxidative stress and green tea is more beneficial than cinnamon in ameliorating these nephrotoxic effects of bpa. key words: bisphenol a, cinnamomum zeylanicum, kidney, oxidative stress. polycarbonated plastics, is one of highest volume 3 environmental toxin produced worldwide. human 4 exposure to bpa occurs mainly through food as it is used inplastic food containers, soft drink bottles, toys, inner lining of metal cans and water supply pipes. significant bpa levels have been detected in 5 indoor and outdoor air, water , oil and canned food. it is used as color developer in electric invoices and paper towels. hence absorbed through dermal 6 contact. bpa causes oxidative stress induced tissue 7 damage in the kidneys as it is eliminated by kidneys, therefore, increased level of bpa are observed in 8 ckd. bpa affect embryology, physiology, histomorphology 9 of various organs of animals and humans. antioxidant therapies have nephron protective effect because they cause epithelial cell sparing and introduction kidneys, vital organs of human body, remove metabolic wastes of human body and conserve fluids 1 and electrolytes. the acute renal injury is induced by toxins ultimately progresses to chronic kidney disease which is now recognized as a global public 2 health problem. bisphenol a (bpa), a polymer of comparative effects of cinnamon extract and green tea against bisphenola induced damage in rat kidney huma beenish, rehana rana, shabana ali muhammad, asma ali khan correspondence: dr. huma beenish assistant professor, anatomy islamic international medical college riphah international university, islamabad e-mail: huma1186@gmail.com department of anatomy islamic international medical college riphah international university, islamabad funding source: nil; conflict of interest: nil received: sep 13, 2017; revised: jan 24, 2018 accepted: feb 06, 2018 comparative effects of cinnamon extract and green teajiimc 2018 vol. 13, no.1 12 of bpa. at the end of 30 days experimental duration, rats were anesthetized, kidneys were exposed through longitudinally cutting in the abdominal 11 region. right kidneys of all animals were dissected out and observed for gross appearance by comparing them with normal kidneys of control group. weight and gross appearance of each kidney was noted. transverse sections of kidney were taken and stained with hematoxylin and eosin. slides were examined under x4, x10 and x40 power of light microscope. the presence or absence of following qualitative parameters was confirmed by observing four random fields in each slide of kidney. 1. contracted glomerulus 2. swollen glomerulus 3. hemorrhage in glomerulus 4. ruptured bowman's capsule the glomeruli were labeled contracted when they appeared shrunken with increased urinary space as 17 compared to glomeruli of control group. the glomeruli with negligible urinary space were regarded as swollen. spss version 22 was used for data analysis. one way analysis of variance (anova) was applied for the mean comparison weight between control and experimental groups. post hoc turkey's test was applied for the multiple comparisons among groups. chi square test was applied for the comparison of qualitative variables among groups. a p value less than 0.05 was considered as a significant value. results mean weight of rat kidney was significantly decreased in group b (rats were given 30mg/kg/day bpa, subcutaneously) as compared to control group a. green tea administration in group d (rats given 200mg /kg /day green tea aqueous extract) significantly increased weight of kidney as compared to group c (rats given200mg/kg/day cinnamon aqueous extract). appearance of kidneys was swollen in 80% experimental animals in group b while in group d only 27% kidneys were swollen. the difference of appearance of kidneys was significant between all groups (p=0.00). (table i) (fig. 1). all experimental animals in group b possessed contracted glomeruli while group c and group d showed contracted glomeruli in 53.3 % and 13.3 % of experimental animals respectively. the difference of contracted appearance of glomeruli was significant 10 regeneration and cause apoptosis of my fibroblasts. cinnamon possess ant oxidative effects which protect kidney from damage caused by diabetes and 11 various toxins. active components of cinnamon i n c l u d e p o l y p h e n o l s , c i n n a m i c a c i d a n d cinnamaldehyde. on the other hand, green tea (camellia sinensis) also a nephron protective 12 antioxidant derived from plants. catechins present in green tea include epigallocatechin-3-gallate ( e g c g ) , e p i c a t e c h i n 3 g a l l a t e ( e c g ) , epigallocatechin (egc) and epicatechin (ec). beneficial effects of green tea include its ant oxidative, anti-inflammatory and ant carcinogenic 13 properties. it is also protective against renal injury. there were no histological studies seen for protection offered by green tea against bpa induced nephrotoxicity. this study has been designed to compare the modulatory effect of cinnamon n green tea consumption on daily basis to counteract the nephrotoxic changes caused by bpa. materials and methods this study was a randomized control trial. it was conducted in animal house of national institute of th health sciences, islamabad from 16 september th 2016 to 16 march 2017. research took time span of six months before results were achieved. ethical review committee gave approval of synopsis of the study prior to conduction experiment. research was carried out on sixty adult male rats of sprague dawley breed, weighing approximately 250 to 300 grams. female rats and rats with any conspicuous pathology were rejected. simple random sampling technique was used. under supervision of animal house nih, rats were kept in 4 confines with a number of 15 rats/confine. a standard laboratory condition indistinguishable to their class with adjusted dietary supplement was given under temperature of 27±3ºc. rats were randomly divided by lottery method into 4 groups. (15 animals in each group). rats in group a serving as controls were given 1ml refined water subcutaneously. group b rats were given 14 30mg/kg/day bpa, subcutaneously. group crats were given200mg /kg /day cinnamon aqueous 15 extract via gavage tube 2 hr before daily subcutaneous injection of bpa. group drats were 16 given 200mg/kg/day green tea aqueous extract. via gavage tube 2 hr before daily subcutaneous injection 13 comparative effects of cinnamon extract and green teajiimc 2018 vol. 13, no.1 tea against toxicity caused by bpa by measuring gross as well as microscopic parameters. it was found that nephrotoxicity caused by bpa is ameliorated by both cinnamon and green tea but green tea showed best results in protection of kidney against bpa induced damage. bpa leads to increase in kidney weight. results showed that both cinnamon and green tea reduced kidney weight but comparison of both showed that green tea caused significantly greater reduction in kidney weight than cinnamon.(p=.021). increase in kidney weight in group b is indicating underlying change in morphology of kidneys. the reduction in kidney weight observed in present study in group c is accordance with results of qusti who reported a similar decrease in kidney weight caused by treatment of diabetic rat kidney with cinnamon. author related this change with the ant oxidative 18 properties. noori brought to light that cinnamon is unable to decrease weight of kidney in absence of toxic insult. green tea polyphenols also act as antioxidants and 19 combat the oxidative stress induced injuries. decrease in weight of kidney in group d is potentiated by findings of hama douche. author demonstrated that increase in kidney weight caused by lead induced oxidative stress shows a relative 20 decrease after treatment with green tea. green tea polyphenols reduced the weight of diabetic rat kidney significantly along with reduction in serum 21 creatinine and mda levels. improvement in renal parameters in both groups c between all the groups (p=0.00). (table ii). in control group a none of experimental animals showed contracted glomeruli, while in group b contracted glomeruli were present in 100% of experimental animals. group c and group d showed contracted glomeruli in 53.3 % and 13.3 % of experimental animals respectively. swollen appearance of glomeruli was neither observed in control group a nor in experimental groups b, c and d. (table ii). hemorrhagic glomeruli were present in 86.67% experimental animals. in group b while in group c and d hemorrhage was present in 73.3 % and 26.7% of experimental animals respectively. the difference of hemorrhagic appearance of glomeruli was significant between all groups (p=0.00) (table ii). ruptured bowman's capsule was present in 86.7% of experimental animals in group b. in groups c 46.7% while in group d 20% experimental animals showed ruptured bowman's capsule. the difference in presence of ruptured capsule was significant between all groups. (table ii). table i: distribu�on of kidney weight (g) and appearance between experimental and control groups n=60 table ii: distribu�on of contracted glomerulus, swollen glomerulus, hemorrhage in glomerulus and ruptured bowman's capsule between experimental and control groups n=60 fig 1: distribu�on of mean weight between control and experimental groups discussion present study was designed to compare the nephron protective efficacy of cinnamon extract and green 14 comparative effects of cinnamon extract and green teajiimc 2018 vol. 13, no.1 induction of oxidative stress while epicatechin serve 20 as scavengers of free radicals. hence all above findings strengthen our results of positive effects of green tea on glomerular histology. in present study bpa caused rupture of bowman's capsule. although both cinnamon and green tea improved this parameter but green tea caused significant improvement in histology of bowman's capsule than cinnamon.(p=0.00) sakr noticed that same degenerative changes in renal corpuscle after c y p e r m e t h r i n t re a t m e n t a l o n g w i t h t h e i r 27 improvement with cinnamon administration. these results support our finding of improved capsular histology in group c but improvement was greater in green tea group d. in present study we found that bpa causes nephrotoxic effects in rat kidney. effects of bpa on human kidney should be explored with reference to its accumulation and excretion by human body. conclusion bisphenol a causes significant changes in histomorphology of rat kidney by induction of oxidative stress. present study shows that co administration of cinnamon and green tea along with b pa c a u s e s i m p r o v e m e n t i n g r o s s a n d microstructure of kidneys. comparison of both shows that green tea provides better nephron protection than cinnamon against bpa toxicity. references 1. ross mh, pawlina w. histology: lippincott williams & wilkins; 2006; p. 1103-33. 2. el nahas am, bello ak. chronic kidney disease: the global challenge. the lancet. 2005; 365: 331-40. 3. vandenberg ln, maffini mv, sonnenschein c, rubin bs, soto am. bisphenol a and the great divide: a review of controversies in the field of endocrine disruption. endocrine reviews. 2009; 30: 75-95. 4. usman a, ahmad m. from bpa to its analogues: is it a safe journey? chemosphere. 2016; 158: 131-42. 5. schecter a, malik n, haffner d, smith s, harris tr, paepke o, et al. bisphenol a (bpa) in us food. environmental science & technology. 2010; 44: 9425-30. 6. shelby m. ntp-cerhr monograph on the potential human reproductive and developmental effects of bisphenol a. ntp cerhr mon. 2008; 5: 7-9. 7. hassan zk, elobeid ma, virk p, omer sa, elamin m, daghestani mh, et al. bisphenol a induces hepatotoxicity through oxidative stress in rat model. oxidative medicine and cellular longevity. 2012; p. 1-6. 8. parra eg, herrero ja, elewa u, bosch rj, arduán ao, egido j. bisphenol a in chronic kidney disease. international journal and d along with maximum improvement in green tea group d is also supported by a study conducted by hasanein. author compared the affects of green tea cinnamon and black tea on renal function tests in obese diabetic rats. the kidney dysfunction associated with diabetic rats was found to be linked with oxidative damage caused by diabetes. both cinnamon and green tea exerted ant oxidative effects because of presence of polyphenols but rfts improved more in green tea 22 group. author did not focus the histological features of kidney in green tea and cinnamon treated groups. review of literature shows most studies on bpa and antioxidants have not focused on appearance of kidneys. study conducted by tan support our results 23 of swollen kidneys in group b. we were unable to find effects of cinnamon and green tea on gross appearance of kidneys in literature. hence all above literature supports our findings of maximum improvement in renal parameters with green tea as compared to cinnamon. structure of glomeruli was observed in four different fields of vision and all the glomeruli in group b were found to be contracted. group d showed significant improvement in this parameter than group c. improvement in morphological appearance of glomeruli in group c in present study is supported by work of morgan who showed glomerular congestion and hyper cellularity caused by bpa showed 15 improvement with cinnamon administration. this can be explained by presence of polyphenols in 24 cinnamon. qusti reported that diabetes causes damage to renal corpuscle shown by shrunken glomeruli which become close to normal appearing glomeruli histologically after treatment with 18 cinnamon. but present study proved that green tea causes more improvement in above mentioned histology of glomerulus than cinnamon. sardana noticed that degeneration in glomerular wall caused by gentamycin improved with catechins. he explained that catechins reduce nadph oxidase 25 activity. hence they reduce oxidative stress. various studies support improved glomerular 26 histology with green tea in present study. yokozawa showed that disturbed glomerular morphology in 21 diabetic kidney restored to normal with green tea. hama douche proposed similar positive impact of green tea against nephrotoxicity by lead. lead causes 15 comparative effects of cinnamon extract and green teajiimc 2018 vol. 13, no.1 based complementary and alternative medicine. 2016; 2016: 5614564. 19. carloni p, tiano l, padella l, bacchetti t, customu c, kay a, et al. antioxidant activity of white, green and black tea obtained from the same tea cultivar. food research international. 2013; 53: 900-8. 20. hamadouche n, hadi a. the protective effect of green tea extract on lead induced oxidative and damage on rat kidney. international journal of pharmacy and biological sciences. 2015; 6: 97-07. 21. yokozawa t, nakagawa t, oya t, okubo t, juneja lr. green tea polyphenols and dietary fibre protect against kidney damage in rats with diabetic nephropathy. journal of pharmacy and pharmacology. 2005; 57: 773-80. 22. hasanein ma, gawad h, el-megeid aaa. effect of water extract prepared from green tea, black tea and cinnamon on obese rats suffering from diabetes. world applied sciences journal. 2012; 20: 976-87. 23. tan bl, kassim nm, mohd ma. assessment of pubertal development in juvenile male rats after sub-acute exposure to bisphenol a and nonylphenol. toxicology letters. 2003; 143: 261-70. 24. azab ks, mostafa aha, ali em, aziz maa. cinnamon extract ameliorates ionizing radiation-induced cellular injury in rats. ecotoxicology and environmental safety. 2011; 74: 2324-9. 25. s a r d a n a a , k a l r a s , k h a n n a d, b a l a k u m a r p. nephroprotective effect of catechin on gentamicin-induced experimental nephrotoxicity. clinical and experimental nephrology. 2015; 19: 178-84. 26. veljkovic m, ilic s, stojiljkovic n, velickovic l, pavlovic d, radenkovic m, et al. beneficial effects of green tea extract in gentamicin-induced acute renal failure in rats/povoljni efekti ekstrakta zelenog caja na akutnu bubrežnu insuficijenciju uzrokovanu gentamicinom kod pacova. acta facultatis medicae naissensis. 2015; 32: 51-8. 27. sakr sa, albarakai ay. effect of cinnamon on cypermethrininduced nephrotoxicity in albino rats. int j adv res. 2014; 2: 578-86. of nephrology. 2013; 2013: 437857. 9. michalowicz j. bisphenol a–sources, toxicity and biotransformation. environmental toxicology and pharmacology. 2014; 37: 738-58. 10. wojcikowski k, wohlmuth h, johnson dw, rolfe m, gobe g. an in vitro investigation of herbs traditionally used for kidney and urinary system disorders: potential therapeutic and toxic effects. nephrology. 2009; 14: 70-9. 11. mhammad ha, jubrail ams, najeeb mk. impact of cinnamon extract on liver, kidneys and spleen of diabetic rats. inter j of chemical and biomolecular science. 2015; pp. 24854. 12. gad sb, zaghloul dm. beneficial effects of green tea extract on liver and kidney functions, ultrastructure, lipid profile and hematological parameters in aged male rats. global vet. 2013; 11: 191-205. 13. wang y, wang b, du f, su x, sun g, zhou g, et al. epigallocatechin-3-gallate attenuates unilateral ureteral obstruction-induced renal interstitial fibrosis in mice. journal of histochemistry & cytochemistry. 2015; 63: 2709. 14. badawi mm, soliman mg, kawi naa, abozaid nm. physiological and histopathological studies on bisphenol-a compound as xenoestrogen in male albino rats. the egyptian journal of hospital medicine. 2013; 50: 127-36. 15. morgan am, el-ballal ss, el-bialy be, el-borai nb. studies on the potential protective effect of cinnamon against bisphenol a-and octylphenol-induced oxidative stress in male albino rats. toxicology reports. 2014; 1: 92-101. 16. isbrucker r, edwards j, wolz e, davidovich a, bausch j. safety studies on epigallocatechin gallate (egcg) preparations. part 2: dermal, acute and short-term toxicity studies. food and chemical toxicology. 2006; 44: 636-50. 17. ahmed w, moselhy w, nabil t. bisphenol a toxicity in adult m a l e r a t s : h e m a t o l o g i c a l , b i o c h e m i c a l a n d histopathological approach. glob veternaria. 2015; 14: 228-38. 18. qusti s, el rabey ha, balashram sa. the hypoglycemic and antioxidant activity of cress seed and cinnamon on streptozotocin induced diabetes in male rats. evidence16 comparative effects of cinnamon extract and green teajiimc 2018 vol. 13, no.1 page 17 page 18 page 19 page 20 page 21 editorial since the idf's most recent figures were released in 2019, the prevalence of diabetes in pakistan has dramatically increased. 33 million adults in pakistan had diabetes in 2021, a 70% rise from 2019. after china (141 million) and india (74 million), pakistan presently has the third-highest number of persons with diabetes worldwide. diabetes caused 400,000 fatalities in the nation in 2021, more than any other disease in the middle east and north africa. in pakistan, an extra 11 million persons have impaired glucose tolerance (igt), putting them at a high risk of getting type 2 diabetes. pakistan has the highest national prevalence of diabetes in the world, with a frequency of one in four persons (26.7%) almost a 1 quarter. diabetes is a chronic illness with several underlying factors: insulin resistance, beta cell failure, incretin deficiency/resistance and inadequate renal tubular 2 handling of filtered glucose are few of them. number of pharmaco therapeutic agents like metformin, tzd, sulphonylurea, glinides, dpp-4 inhibitors, glp-1 receptor agonists, and sglt2 inhibitors along with various types of exogenous insulins are available to tackle these various 3 pathogenic mechanisms. even in the presence of so many advanced therapeutic options, achievement of glycemic/metabolic targets along with improving quality of life of our diabetic patients seems to be very difficult. there is something somewhere that is not working for our diabetic patients. control over the disease still seems remote and very challenging. this fact leads to the search of various nonpharmacological factors that can contribute to poor disease control. one of them can be allostatic load. allostatic load refers to the cumulative burden of chronic stress and life events. it involves the interaction of different physiological systems with environmental stress. when environmental challenges exceed the individual's ability to cope 4 then the allostatic overload ensues. stress has an important role in the glycemic control of a diabetic patients. diabetic patients not only have to face the stressors regarding their disease like frequent blood sugar checks, diet restrictions, strict exercise routine but have also to face anxiety regarding glycemic variations as well as must live with continuous fear of having acute or chronic complications of the 5,6 disease. this is in addition to concerns regarding their work, family or finances that are not directly related to their illness. in a number of studies this has been documented that stress or allostatic load leads to increased inflammatory/oxidative damage thus contributing to poor glycemic control and increased 7,8 incidence of complications in diabetic patients. so health care providers must address the allostatic load management like provision of the services of psychotherapists/support groups for the holistic care of our diabetic patients. there is a significant link between psychological stress and glycemic control. psychological stress affects the action of the pituitary gland and the sympathetic nervous system, which causes an increase in the levels of circulating catabolic hormones and a suppression of the anabolic hormones. people with type 1 diabetes experience elevated blood glucose levels because of this. stress results in behavioral modifications that can interfere with self-care. for instance, time constraints make it impossible to monitor blood glucose, which disrupts metabolic control. additionally, comfort-seeking, or coping behaviors, such as increased food consumption and decreased physical activity, may be brought on by stress. people with diabetes who engage in these behaviors run the risk of having their metabolic regulation disturbed. another factor that can play a limiting role in the control of disease of a diabetic patients is a dysbiosis of gut microbiota. insufficient glycemic control has been attributed to dysbiosis of gut microbiota that has significant impact on host metabolism specially glucose hemostasis. dysbiosis has been revealed to affect short chain fatty acid synthesis and result in correspondence: dr. asim zulfiqar department of medicine pakistan railway general hospital, rawalpindi e-mail: asimzulfiqar786@gmail.com received: may 10, 2023; accepted: june 01, 2023 91 department of medicine pakistan railway general hospital, rawalpindi https://doi.org/10.57234/jiimc.june23.1738 unmasking the mysteries of uncontrolled diabetes mellitus: “why the pharmacotherapeutic advances are not competently enough? asim zulfiqar a l t e ra t i o n o f i n s u l i n s i g n a l i n g p a t h w a y s , consequently developing inadequate glycemic 10 control. the potential risk factors for type 2 diabetes include obesity, an unhealthy lifestyle, and gut microbial dysbiosis. low intake of dietary fibers and consumption of meals high in fat and sugar have both been linked to a decrease in the diversity and abundance of the gut microbial community. the metabolic and functional pathways in the gut that are implicated in the onset of type 2 diabetes may be impacted by gut microbial dysbiosis. the production of short-chain fatty acids (scfas) and the composition of the gut microbiota are both significantly influenced by diet. the colony of commensal bacteria in the colon performs fermentation on the carbohydrates that are not 11 digested and absorbed in the small intestine. so for achieving metabolic/glycemic targets, minimizing acute/chronic complications, improving quality of life of our diabetic patients, health care providers will h a v e n o t o n l y t o p r e s c r i b e a p p r o p r i a t e pharmacotherapeutic agent but also need to address some other less considered but important non pharmacological contributing factors like allostatic load, dysbiosis etc. this fact necessitates a multidisciplinary approach that not only involve physicians, nurses but also psychotherapist, counsellors, dieticians, and patient support group. this holistic approach by recognizing the nonpharmacological missing links, is the need of the time for achieving control of our diabetic patients. references 1. sun h, saeedi p, karuranga s, pinkepank m, ogurtsova k, duncan bb, et al. idf diabetes atlas: global, regional, and country-level diabetes prevalence estimates for 2021 and projections for 2045. diabetes research and clinical practice. 2022;183:109119. 2. defronzo ra, ferrannini e, groop l, henry rr, herman wh, holst jj, et al. type 2 diabetes mellitus. nature reviews disease primers. 2015;1(1):1-22. 3. esposito k, chiodini p, bellastella g, maiorino m, giugliano d. proportion of patients at hba1c target< 7% with eight classes of antidiabetic drugs in type 2 diabetes: systematic review of 218 randomized controlled trials with 78 945 p a t i e n t s . d i a b e t e s , o b e s i t y a n d m e t a b o l i s m . 2012;14(3):228-33. 4. kolesnikova va, clarke pj, mukherjee b, sen s, mezuk b. psychosocial stress and hypothalamic-pituitary-adrenal a x i s s t re s s re a c t i v i t y : va r i at i o n s b y r a c e a n d socioeconomic status among adults at risk of diabetes. psychosomatic medicine. 2022;84(7):813-21. 5. juanamasta ig, aungsuroch y, gunawan j, suniyadewi nw, wati nmn. holistic care management of diabetes mellitus: an integrative review. international journal of preventive medicine. 2021;12. 6. mustafa m, jahan s, waseem m, ramzan t, latif d. comparing fasting homocysteine levels among healthy adults, diabetic and non-diabetic cardiac patients: jrcrs. 2018; 6 (2): 63-66. 7. sharma vk, singh tg. chronic stress and diabetes mellitus: interwoven pathologies. current diabetes reviews. 2020;16(6):546-56. 8. jahan s, parveen s, barnabas s, mehreen a. restless leg syndrome and sleep quality in diabetic patients with and without neuropathy. 9. riazi a, pickup j, bradley c. daily stress, and glycaemic control in type 1 diabetes: individual differences in magnitude, direction, and timing of stress-reactivity. diabetes research and clinical practice. 2004 dec 1;66(3):237-44. 10 bielka w, przezak a, pawlik a. the role of the gut microbiota in the pathogenesis of diabetes. international journal of molecular sciences. 2022;23(1):480. 11. ojo o, feng qq, ojo oo, wang xh. the role of dietary fibre in modulating gut microbiota dysbiosis in patients with type 2 diabetes: a systematic review and meta-analysis of randomised controlled trials. nutrients. 2020 oct 23;12(11):3239. jiimc 2023 vol. 18, no. 2 92 conflict of interest authors declared no conflicts of interest. grant support and financial disclosure authors have declared no specific grant for this research from any funding agency in public, commercial or nonprofit sector. data sharing statment the data that support the findings of this study are available from the corresponding author upon request. this is an open access article distributed under the terms of the creative commons attributionnoncommercial 2.0 generic license. https://doi.org/10.57234/jiimc.june23.1738 original�article abstract objective: to access the prevalence and associated causes of early childhood caries among the special children of local population. study design: descriptive cross-sectional study. place and duration of study: this study was conducted at different special schools of peshawar over a period of th th 3 months (10 october 202028 december 2020). materials and methods: sample size was calculated using g-power (3.1.9.2) using convenience sampling technique.153 children below 6 years of age with unerupted permanent molars were accessed for caries severity using decayed, missing, and filled teeth surfaces (dmfs) index using daylight/ artificial torch light. results: prevalence of ecc in our study model was found to be 77%. child's dietary habits and oral hygiene habits were found to be ominously allied with early childhood caries (p value = 0.000). while age, gender and parental education did not show any remarkable role in the widespread presence of ecc. conclusion: this study accentuates high prevalence of ecc (77%) among special children in peshawar. key words: dietary habits, early childhood caries (ecc), oral hygiene habits, prevalence, special children. 3,4 been accounted for to be as high as 70%. literature shows ecc has been found more frequent in low socioeconomic groups. in contrast to this, various studies in pakistan expressed the prevalence of ecc 5'6 7 from 27.9% to 51% and even 88.6% . few social and socioeconomic components have all the earmarks of being elements of ecc which incorporate restricted 7,8 access to caution, assets, and oral health learning . however, not much literature is available regarding prevalence of ecc in special children. the information on the prevalence and related elements of ecc is important to create embattled intercessions for the anticipation of consequent tooth decay and to diminish the number of children that requires emergency treatments. this study was meant to access the prevalence and associated causes of early childhood caries among the special children of local population of peshawar, kpk. materials and methods a descriptive cross-sectional study was conducted th over a period of 3 months from 10 september 2020 th to 28 december 2020 in different special schools of peshawar. sample size was calculated using g-power (3.1.9.2) with effect size 0.3, α error 0.01 and power 0.95 using convenience sampling technique. 153 children of age less than 6 years were included in the study whereas those with erupted first permanent introduction early childhood caries (ecc) has been on expansion in numerous nations and has become a huge and significant health issue particularly in publicly distraught populations. the american academy of 1 paediatric dentistry (aapd) has defined ecc as presence of one or more decayed (cavitated or non cavitated), missing (due to caries) or filled tooth surfaces in any primary tooth in child of 71 months of age or younger. different studies have been reported to determine prevalence of nursing caries worldwide. an audit nature of one literature proposes that in most established nations the prevalence of ecc is somewhere in the range of 1-12%. in less developed nations and among distraught factions in the developing nations the prevalence has factors affecting early childhood caries among special children in local population of peshawar, kpk 1 2 3 4 5 ifra sana khattak , madeeha bangash , laila mustafa , khadija sajid , aamir mehmood khan correspondence: dr. madeeha bangash hod paediatric dentistry rehman college of dentistry, peshawar e-mail: madeeha.bangash@rmi.edu.pk 1,2 5 department of paediatric dentistry/operative dentistry rehman college of dentistry, peshawar 3 department of paediatric dentistry shifa college of dentistry, islamabad 4 department of dentistry kohat institute of dental sciences, kohat received: november 10, 2021; revised: november 01, 2022 accepted: november 15, 2022 early childhood caries among special childrenjiimc 2023 vol. 18, no.1 4 https://doi.org/10.57234/jiimc.march23.1016 molars were omitted from the study. before the collection of data, ethical approval was obtained from ethical review board at rehman college of dentistry peshawar (ec ref no.: 2020-10-053) and written informed assent was also attained from the parents/guardians of kids residing there. the data was collected with the help of self-administered q u e s t i o n n a i r e s . t h e v a l i d a t i o n o f t h e s e questionnaire was done by piloting study. these questionnaires were sent to the parents of special children by email who also returned them via email. one questionnaire consisted of sociodemographic characteristics such as age, gender, parental education, oral hygiene habits and dietary habits. the second questionnaire consisted of decayed, missing filled surface (dmfs) score that was filled by the dentist. every child was examined by a single paediatric dentist, on a standard upstanding seat or in knee-toknee position with the help of wooden spatula in a satisfactory natural daylight or artificial light using torch. caries severity was accessed by decayed, missing filled surface (dmfs) index for deciduous teeth given by who. using an evaluator administered questionnaire parents and children were asked about their age, literateness level of their parents, oral hygiene measures comprising teeth cleaning aids. they were also inquired about dietary habits including frequency of sugar consumption, fibrous diet and diet high in carbohydrates. data analysis was performed using spss version 22. results the study populace included 153 special children in the range of 3-5 years. out of 153 children 124 (77%) were found to have ecc which included 50 (40.32%) female and 74 (59.67%) male. the females with ecc showed a mean dmfs of 42.38 ± 24.245 sd, whereas males showed a mean dmfs of 38.00 ± 24.247 sd. p value was statistically not significant. (table ii). when parental education was evaluated 11 (8.87%) of parents had higher level of education and knowledge with mean dmfs score of 33.58. 35(28.22%) had middle education level with mean dmfs of 33.70, while majority 78 (62.9%) had poor education level and knowledge with mean dmfs score of 43.84. thus, the occurrence of ecc was comparatively greater in children having parents with poor education level. p value was found slightly significant (p=0.000). (table ii). regarding dietary habits of special children majority of children consumed high carbohydrate and sugary snacks in between the suppers. about 73 (58.87%) children were habitual consumers of sugary snacks with mean dmfs score 44.09. about 42 (33.87%) children consumed frizzy drinks with mean dmfs score of 48.11 while very minor population 9 (7.25%) consumed fibrous diet with mean dmfs score 7.30. the occurrence of ecc was found less in children who consumed fibrous diet. p value was statistically highly significant (p= 0.000) (table ii). with respect to oral hygiene only 9 (7.25%) children used brush their teeth twice with mean dmfs score 11.431. 38 (30.64%) accustomed to brush their teeth only once a day with mean dmfs score of 25.44. while majority of the children 77 (62.09%) did not clean their teeth at all with mean dmfs score of 58.79. (table ii). table i: distribution of early childhood caries in special children (n= 153) ecc: early childhood caries dmfs: decayed, missing, filled surface. table ii: association of early childhood caries with age, gender, parental education, dietary habits, and oral hygiene habits jiimc 2023 vol. 18, no.1 5 early childhood caries among special children https://doi.org/10.57234/jiimc.march23.1016 discussion ecc is a pervasive and common disease of childhood. the american academy of paediatric dentistry (aapd) has defined ecc as presence of one or more decayed (cavitated or non cavitated), missing (due to caries) or filled tooth surfaces in any primary tooth in 1 child of 71 months of age or younger . the oral health of special children is disregarded part of child health and wellbeing, particularly in instances of ecc. these children comprise a populace that is at higher risk to caries considering their reliance and inability to communicate with their parents. the current study was thus planned to be directed among special children of peshawar. the principal purpose behind the enlistment of special children in the study was that there is no such research yet led in pakistan. different preventive techniques have been implemented to decrease the burden of ecc in 8 various nations . the world dental federation, who and international association of dental research have set out on setting up the global oral health 8 objectives for the year 2020 . shockingly most of included epidemiological studies demonstrates that ecc stays predominant among pre-school children 8 around the globe . deciding the pervasiveness pace of caries in special children is a troublesome cycle as the offspring of this age bunch are not easily reachable and are 9 truculent. in our study, caries prevalence apparently increased 10 with age, which is as per past studies. current study additionally indicated that caries frequency did not expand fundamentally with age. one possible reason for this could be that many special children with handicapped conditions and increased age are not even admitted to such schools because of their 11 medical conditions . in contrast other studies shows that as kids grow older, the number of erupted primary teeth increases which are then exposed to the oral environment and change in their dietary propensities and oral hygiene measures represent a 11,12,13 more noteworthy cariogenic challenge . this study also showed that male children (60.8%) were more affected than female (39.2%) children. this can likewise be related with increased physical activity that prompts the increase in demand for more food when contrasted with females. this 14 corroborates with the previous study. but in contrast some studies reported increase occurrence 15 of ecc in female children. this study like past studies did not show any strong correlation of parental education with prevalence of 16 ecc. however in contrast many other studies have shown strong associations between mother 17,18 education and occurrence of caries. in the current study 56.2% children consumed high carbohydrate snacks amid meals and it supports earlier studies which stated that consumption of sugary snacks in between the meals was a significant risk factor for ecc. the outcome likewise s u b s t a n t i a t e s t h e p r e v i o u s f i n d i n g s t u d y environment that utilization of sweet snacks multiple times each day was a remarkable risk factor 19,20 for ecc . frequent intake of sugary snacks, frizzy drinks upsurge the threat for caries. consequently, dietary proposals of restricting the snacking time amongst children and reassuring standard suppers is basic. we also found a significant correlation between oral hygiene and dental caries. special children neither comprehend nor have the physical expertise to keep up good oral hygiene. hence forth, parental help and direction is fundamental to lessen the menace of increasing caries. most children in this study either brushed never (51%) or once a day (32%). tooth brushing by the guardians or parental figures have the capability of eliminating the dental plaque more p< 0.05 = significant ** jiimc 2023 vol. 18, no.1 6 early childhood caries among special children https://doi.org/10.57234/jiimc.march23.1016 adequately ideally immersing the oral habitat with fluorides thus diminishing the risk of caries among 21 their children. the pervasiveness of ecc in our study was 77%. the likelihood of ecc was essentially higher in kids with poor oral hygiene and individuals who devoured high carbohydrate snacks in the middle of suppers multiple times a day. one of the objectives was to limit the effect of dental caries on individuals and society and figure out methodologies for early findings, counteraction, viable administration of dental caries. however, this prevalence rate had some limitations as there's a variety of syndromes associated with s p e c i a l c h i l d re n , e a c h b e i n g o f d i f fe re n t characteristics and medical condition and dental findings, while this study dealt with them in general. therefore, a detailed study is required in future considering the various medical conditions in specific. conclusion this study accentuates high prevalence of ecc among special children in peshawar and is correlated with poor oral hygiene and high carbohydrate snacks. our study alarms the call for a rapid need to carry out preventative and therapeutic health care programs for special children in our society. aggressive preventive measures should be implemented as these children are at very higher risk for dental caries. furthermore, clinicians should mark the predisposing factors resulting from the distinctive characteristics of these individual's underlying condition and treatment. references 1. american academy of pediatric dentistry. oral health policies. american academy of pediatric dentistry. pediatric dentistry. 2003;25(7 suppl):11-49. 2. mansoori s, mehta a, ansari mi. factors associated with oral health related quality of life of children with severeearly childhood caries. journal of oral biology and craniofacial research. 2019 jul 1;9(3):222-5. 3. folayan, morenike oluwatoyin, maha el tantawi, nourhan m. aly, ola b. al-batayneh, robert j. schroth, jorge l. castillo, jorma i. virtanen et al. "association between early childhood caries and poverty in lowand middle-income countries." bmc oral health 20, no. 1 (2020): 1-8. 4. pierce a, singh s, lee j, grant c, cruz de jesus v, schroth rj. the burden of early childhood caries in canadian children and associated risk factors. frontiers in public health. 2019 nov 12;7:328. 5. saleem, urooj, saeeda bibi, and brekhna jamil. "early childhood caries and its relationship with different risk factors in preschool children." journal of postgraduate medical institute 29, no. 1 (2015). 6. kirthiga m, murugan m, saikia a, kirubakaran r. risk factors for early childhood caries: a systematic review and metaanalysis of case control and cohort studies. pediatric dentistry. 2019 mar 15;41(2):95-112. 7. ahmad, s., khan, h. and misri khan, w.m., 2015. prevalence and patterns of early childhood caries among school children in peshawar. cell, 333, p.9101070. 8. hobdell m, clarkson j, petersen pe, johnson n. global goals for oral health 2020. international dental journal. 2003 oct 1;53(5):285-8. 9. damle, s.g., gandhi, m. and laheri, v., 2008. comparison of oral ketamine and oral midazolam as sedative agents in pediatric dentistry. journal of indian society of pedodontics and preventive dentistry, 26(3), p.97. 10. sudha, p., bhasin, s. and anegundi, r.t., 2005. prevalence of dental caries among 5-13-year-old children of mangalore city. journal of indian society of pedodontics and preventive dentistry, 23(2), p.74. 11. kumar, v., ankola, a., sankeshwari, r., jalihal, s., atre, s. and mallineni, s.k., 2021. determination of the oral health status and behaviors, treatment needs, and guardians' perception of oral health among preschool children attending integrated child developmental scheme anganwadi centers of belagavi, south india: a crosssectional study. journal of clinical and translational research, 7(4), p.436. 12. ibrahim s, nishimura m, matsumura s, rodis om, nishida a, yamanaka k, shimono t. a longitudinal study of early childhood caries risk, dental caries, and life style. pediatric dental journal. 2009 jan 1;19(2):174-80. 13. livny a, assali r, sgan-cohen hd. early childhood caries among a bedouin community residing in the eastern outskirts of jerusalem. bmc public health. 2007 dec;7(1):17. 14. kuriakose, s., prasannan, m., remya, k.c., kurian, j. and sreejith, k.r., 2015. prevalence of early childhood caries among preschool children in trivandrum and its association with various risk factors. contemporary clinical dentistry, 6(1), p.69. 15. olatosi oo, inem v, sofola oo, prakash p, sote eo. the prevalence of early childhood caries and its associated risk factors among preschool children referred to a tertiary care institution. nigerian journal of clinical practice. 2015 jun 1;18(4):493-501. 16. schroth, robert j., pattie moore, and douglas j. brothwell. "prevalence of early childhood caries in 4 manitoba communities." journal of the canadian dental association 71, no. 8 (2005). 17. jin bh, ma ds, moon hs, paik d, hahn sh, horowitz am. early childhood caries: prevalence and risk factors in seoul, korea. journal of public health dentistry. 2003 sep;63(3):183-8. 18. livny a, assali r, sgan-cohen hd. early childhood caries among a bedouin community residing in the eastern jiimc 2023 vol. 18, no.1 7 early childhood caries among special children https://doi.org/10.57234/jiimc.march23.1016 outskirts of jerusalem. bmc public health. 2007 dec;7(1):17. 19. us department of health and human services oral health coordinating committee. us department of health and human services oral health strategic framework, 2014–2017. public health reports. 2016 mar;131(2):24257. 20. marrs, jo-ann, sharon trumbley, and gaurav malik. "early childhood caries: determining the risk factors and assessing the prevention strategies for nursing intervention." pediatric nursing 37, no. 1 (2011). 21. dini el, holt rd, bedi r. caries and its association with infant feeding and oral health-related behaviours in 3–4-year-old brazilian children. community dentistry and oral epidemiology. 2000 aug;28(4):241-8. conflict of interest authors declared no conflicts of interest. grant support and financial disclosure authors have declared no specific grant for this research from any funding agency in public, commercial or nonprofit sector. data sharing statment the data that support the findings of this study are available from the corresponding author upon request. this is an open access article distributed under the terms of the creative commons attributionnoncommercial 2.0 generic license. jiimc 2023 vol. 18, no.1 8 early childhood caries among special children https://doi.org/10.57234/jiimc.march23.1016 1 editorial responding to coronavirus (covid-19) disease 1 2 tariq butt , erum butt in early december 2019, few pneumonia cases were identified caused by some unknown agent in the 1 wuhan, capital city of province hubei of china. the agent was later on identified as an enveloped rna 2 beta coronavirus which was subsequently named by who as covid-19 and the coronavirus disease 3,4 2019. till march 12, 2020, the worldwide 125048 cases and 4613 (3.69%) deaths in 117 countries have 5 6 been reported however, guan et al. reported 1099 patients with confirmed covid-19 with death rate of 1.4%. it is pertinent to note that during 1918-19 flu (h1n1) pandemic about 500 million people or onethird of the world's population became infected with flu virus with about 50 million deaths worldwide. in february 1957, h2n2 virus triggered a pandemic (“asian flu”) which result 1.1 million deaths worldwide. then in 1968 new flu (h3n2) pandemic 7 1 0 cause about 1 million deaths worldwide. although death rate of covid-19 disease appears to be less as compared to similar corona virus diseases 10,11 like sars (9.6%), mers (36%) and flu, the rapidity of the virus to spread within community make it alarming challenge and the covid-19 epidemic has created serious issues for the general and medical communities as regard to health & research. coronavirus has gripped the nations globally which resulted into the development of a lot of anxiety and panic. the people across the globe are infected through respiratory droplets. in response to the outbreak, various countries issued temporary travel restrictions, which may have slowed the spread of covid-19 somewhat. the efficiency of transmission of a respiratory virus depends on basic reproduction number which has been estimated as 2.2 for this virus by recent studies which result in extreme capability of virus transmission and thus there is dire need to be prepared against this virus to establish worldwide until at least reproduction number has 12,13 reduced to less than one. in pakistan till march 12, there were 20 confirmed cases of covid-19 infections and all of them came from iran. two of them has already been cured of the disease and sent 14 home. however, because of high transmission capability; we must be ready to prevent this virus to establish in pakistan. community spread in pakistan could require adopting certain policies such as avoidance of gatherings to minimize spread. these include isolating diseased individuals (even at home), closing 15 schools, and working from home when possible. centre for disease control and prevention (cdc), atlanta has advised to avoid visiting areas like china, korea, iran and italy where there are increased number of infected persons. these travel restrictions by various countries have definitely helped to reduce the spread of this virus. public awareness is essential in controlling of any outbreak, however, these awareness campaigns lead to the development of panic among public. panic has already been spread worldwide and world health organization (who) warned that increasing demand, buying due to fear and irrational use of personal protective equipment (ppe) has compromised supply globally and resulted in rising risk from covid-19 and other infective 16 agents. although we are still in the process of learning the actual pathogenesis, epidemiology and clinical presentation of this disease, li and 1 7 colleagues have shown a comprehensive description of the patients with the disease who reported sick infected with this virus in hubei province (wuhan city), china. they demonstrated that the old age and patients with some coexisting other diseases were predisposing factors for high mortality and morbidity. younger children were minimally affected. this type of information is essential to provide appropriate response to this outbreak. research has already been started to develop a 18 vaccine against this virus but this would require certain essential time period before launching for correspondence: professor of pathology & microbiology islamic international medical college riphah international university, islamabad e-mail: tariq.butt@riphah.edu.pk received: march 10, 2020; accepted: march 15, 2020 1 department of pathology islamic international medical college riphah international university, islamabad 2 shaigan pharmaceutical, rawalpindi outbreak as pandemic because in china, for example the spread of disease seems to be slowing and it could yet be contained worldwide if the correct measures are adopted. moreover, countries are already on high alert. however, when there is endless spread of the disease worldwide, who on march 11, 2020 declared the outbreak as pandemic. researchers are collaborating across the borders to communicate virus genome sequences and vaccine development is under way. there is need for continuous reconnaissance, rapid diagnosis and vigorous research to understand the actual characteristics of this organisms and human vulnerabilities to them and to develop operative measures to protect ourselves. references 1. huang c, wang y, li x, et al. clinical features of patients infected with 2019 novel coronavirus in wuhan, china. lancet 2020; 395: 497-506. 2. lu r, zhao x, li j, et al. genomic characterization and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. lancet 2020; 395: 565574. 3. world health organization. coronavirus disease (covid-19) outbreak, 2020 (https://www.who.int). 4. world health organization: pneumonia of unknown cause — china: disease outbreak news. who geneva: january 5, 2020 (https://www.who.int/csr/don/05-january-2020pneumonia-of-unkown-cause-china/en). 5. who situation report 52: coronavirus disease 2019 (covid19), 12th march 2020 6. guan w, ni z, hu y, liang w, ou cq, he jx et al. clinical characteristics of coronavirus disease 2019 in china. n engl j med 2020. (doi: 10.1056/nejmoa2002032). 7. l an gmu ir ad. e p id emio lo gy o f as ian influ en za, international conference on asian influenza. am rev respir dis 1961; 83: 2–14. 8. viboud c, simonsen l, fuentes r, flores j, miller ma, chowell g. global mortality impact of the 1957-1959 influenza pandemic. j infect dis. 2016; 213(5): 738-45. 9. glezen wp. emerging infections: pandemic influenza. epidemiol rev 1996; 18(1): 64-76. 10. kilbourne ed. influenza pandemics of the 20th century. emerg infect dis 2006; 12(1): 9-14. 11. de wit e, van doremalen n, falzarano d, munster vj. sars and mers: recent insights into emerging coronaviruses. nat rev microbiol 2016; 14: 523-534. public use. moreover, vaccine may not be useful to contain the current outbreak. enrolling of participants on february 21, 2020 has already been started for the trial of the experimental antiviral drug remdesivir. preventive measure and certain therapeutic agents including antiviral drugs lopinavir-ritonavir, rna polymerase inhibitor 19 remdesivir, interferon-1β and chloroquine are being used in getting this goal. one more option for trial could be use of hyperimmune globulin from 20 recovered individuals and monoclonal antibodies. 17 the incubation period as determined by li et al. are important in that it provide some opportunity for intervention to attack the virus by some measures to reduce the spread of the virus. genomic studies would be useful to determine host factors that predispose individuals to acquire infection of this virus. in pakistan this disease was already anticipated however, we should still expect a number of outcomes. first, domestic population and community take the epidemic seriously; therefore the situation demands public should be ensured confidence in dealing with the virus. second, there is a need to declare warfare on the disease. the government has to make it clear to the public whether our country is fully or partially prepared or just unprepared. the positive result of tests for covid-19 in 20 people has raised anxiety of public tremendously and they are worried about the capabilities of the government in dealing with the virus. third, infected people in the country there is always a possibility of spreading the disease from man to man, it is time for us to focus on curing those infected and minimizing the spread of the virus. so now we should keep emphasis on the treatment of them and thus decreasing the spread of covid-19. the government has to take measures nationally to win the war against this disease. health measures should include allocation of more funds and all resources to the disposal for government to fight against the coronavirus. covid-19 has crushed the economy worldwide, but it will be more damaging as it will shake global trust if we show poor response against this virus. there is always a chance of collaboration between various authorities and other countries, if we want to win the war. who initially tried to hold back the description of 2 jiimc 2020 vol. 15, no.1 transmission dynamics in wuhan, china, of novel coronavirus–infected pneumonia. n engl j med 2020. (doi: 10.1056/nejmoa2001316). 18. world health organization: draft landscape of covid-19 candidate vaccines — 18 february 2020. who geneva: (https://www.who.int/blueprint/priority-diseases/keyaction/list-of-candidate-vaccines-developed-againstncov.pdf). 19. world health organization r&d blueprint: informal consultation on prioritization of candidate therapeutic agents for use in novel coronavirus 2019 infection. geneva: w h o , j a n u a r y 2 4 , 2 0 2 0 ( h t t p s : / / a p p s .w h o . i n t / i r i s / b i t st re a m / h a n d l e / 1 0 6 6 5 / 3 3 0 6 8 0 / w h o h eo rdblueprint%28ncov% 29-2020.1-eng.pdf). 20. lane hc, marston hd, fauci as. conducting clinical trials in outbreak settings: points to consider. clin trials 2016; 13: 92-95. 12. holshue ml, debolt c, lindquist s, lofy kh, wiesman j, bruce h, et al. first case of 2019 novel coronavirus in the united states. n engl j med 2020; 382: 929-936. 13. zou l, ruan f, huang m, liang l, huang h, hong z, et al . sars-cov-2 viral load in upper respiratory specimens of i n fe c t e d p a t i e n t s . n e n g l j m e d 2 0 2 0 . ( d o i : 10.1056/nejmc2001737). 14. national institute of health, pakistan: covid-19 live dashboard (pakistan) & covid-19 daily situation report – pakistan; 12 march, 2020. 15. fong mw, gao h, wong jy, et al. non-pharmaceutical measures for pandemic influenza in non-healthcare settings — social distancing measures. emerging infect dis 2020; 26(5) (under printing). 16. who news: shortage of personal protective equipment rd endangering health workers worldwide, 3 march, 2020. 17. li q, guan x, wu p, wu p, wang x, zhou l et al. early jiimc 2020 vol. 15, no.1 3 original�article abstract objective: to determine the beneficial antipsychotic effects of aspirin plus atypical antipsychotic agents in the treatment of schizophrenia. study design: a double blind placebo controlled study. place and duration of study: the study was conducted in psychiatry ward of imam reza and shahid hashemi mental hospital in arak, from april to december 2011. materials and methods: this double blind placebo controlled study was conducted on 60 patients with schizophrenia. patients were assigned to case group who received an atypical antipsychotic agent (olanzapine, risperidone, clozapine) as the standard treatment of the schizophrenia plus aspirin 1000 mg /daily (aspirin or case group n=30), and 30 patients received standard treatment and placebo (control group, n=30). the panss questionnaire was used to evaluate patients at 0, 2,4,6 and 8 weeks after treatment. spss software was used for data analysis. student's t-test was applied and repeated measurement test to compare two groups results: the difference between two groups regarding positive and negative symptoms was not significant (repeated measure/p=0.20 and p =0.20 respectively). however, there was a significant difference between two groups regarding general and total symptoms (repeated measure/p=0.003 and p=0.032 respectively). the results did not show any remarkable related side effects to aspirin in two groups. conclusion: the trial revealed that aspirin 1000 mg /day in combination with antipsychotic drugs for 8 weeks is an effective agent for the reduction of general and total symptoms of schizophrenia. nonetheless, it did not modify the positive and negative symptoms. key words: aspirin, atypical antipsychotic, adjunctive therapy, schizophrenia. absence of characteristics of normal function and may appear with or without positive symptoms and 5,6 cognitive deficits lead to the executive dysfunction. several hypotheses were presented regarding the cause of schizophrenia, however, the exact reason of schizophrenia is not well known, although the most 7 scientists have been focused on dopamine system. 8,9 recently scientists have discussed the role of immune dysfunction and inflammation in patients with schizophrenia. a study in patients with schizophrenia demonstrated that higher blood levels of c-reactive protein (crp) or white blood cell count 10 (wbc) were related with worse symptoms. therefore, these scientists recommended that inflammation might play an important role in the development of cognitive deficits in patients with 11 schizophrenia , sommer et al. in a review of 26 double-blind studies showed acetylsalicylic acid (aspirin) is effective as an adjuvant agent in the 1 2 treatment of schizophrenia. some studies supposed that inflammation has a key role in schizophrenia, therefore, this study was steered based on the psycho-neuro-immunological hypothesis that a lipophilic anti-inflammatory introduction schizophrenia is a chronic disorder and 21 million of 1 people are involved globally. the symptoms of schizophrenia are usually categorized into positive, negative and cognitive symptoms. positive symptoms include hallucinations and delusional thoughts are diagnostic for schizophrenia. negative symptoms are lessened motivation, difficulty with social interaction and withdrawal. moreover, poor attention, limited working memory, and restricted executive functioning show the cognitive disorder in 1-4 these patients. it usually initiates in the third decade of life and it is rare in children and people 3 who are more than 45 years old. positive symptoms, reflect an excess or distortion of normal functions, negative symptoms, refer to a diminishment or the effect of aspirin on schizophrenia; a double blind placebo controlled study hamidreza jamilian, gevick hacoupian correspondence: mr. hamidreza jamilian assistant professor, psychiatry arak university of medical sciences, arak, iran e-mail: mjamilian@yahoo.com department of psychiatry arak university of medical sciences, arak, iran funding source: nil; conflict of interest: nil received: jun 13, 2017; revised: oct 18, 2017 accepted: oct 25, 2017 aspirin in schizophreniajiimc 2017 vol. 12, no.4 168 substance may lead to therapeutic benefits in schizophrenia. so this study was planned to determine the beneficial antipsychotic effects of aspirin plus atypical antipsychotic agents in the treatment of schizophrenia. materials and methods this double blind placebo controlled study was conducted on 60 patients in imam reza and shahid hashemi mental hospital in arak from april to december 2011. in this controlled trial 60 13 schizophrenic patients based on dsm-v criteria were randomized in two groups. the enrolled participants were counseled, and informed consent was obtained before randomization, as per the institution's protocol. moreover, the study protocol was approved by the ethics committee of arak university of medical sciences (irct registration n u m b e r : 2 0 1 1 0 8 1 9 7 3 7 3 n 1 ) . t h e h e l s i n k i declaration was respected and the patients were presented by a code and remained anonymous during the study. the criteria for enrollment were, schizophrenia based on dsm-iv criteria, age 15-55, at least, panss 60. on the other hand breastfeeding and pregnancy, peptic ulcer, aspirin or proton pump inhibitors contraindication and drug abuse were exclusion criteria. to randomization we used sequential numbers, in this case, the first number was given to the first patient and received an atypical antipsychotic agents (17 patients received olanzapine, 9 patients risperidone, and 4 patients clozapine) as standard treatment of the schizophrenia, also, aspirin 1000 mg /day (aspirin or case group, n=30) . sequentially the next number was given to next patient and received standard treatment, 14 patients received olanzapine, 11 patients risperidone, and 5 patients clozapine) and placebo (control group, n=30). each placebo tablet contained dextrin and was identical in appearance to the 500 mg aspirin tablet. pantoprazole 20 mg/daily was administered for all patients. aspirin and placebo were the same in shape, color, and taste. both participants and study staff (researcher, examiner, and analyzer) were masked to treatment allocation. the panss was used to evaluate patients at 0,2,4,6,8 weeks after treatment. the panss is a common and validated questionnaire in clinical studies and assessed the symptoms of schizophrenia based on positive and negative syndrome scale. the 30 items are arranged as 7 positive symptoms (p1-p7), 7negative symptoms (n1-n7) and 16 general psychopathology symptoms items(g1-g7).the patients in the psychiatric ward in imam reza and shahid hashemi mental hospitals were rated within the first week of admission and at weekly intervals for 8 weeks. baseline panss scores on the conceptual disorganization item and the total negative scale score predicted which patients would respond to antipsychotic treatment within 8 weeks. statistical analysis the data were analyzed using statistical package for social studies version 20.0 (spss inc, chicago, ill). categorical data are presented as numbers (%), and continuous data as mean ± sd. we used the student's t-test and repeated measurement test to compare two groups.α< 0.05 was considered significant. results sixty patients mean age 30.11±7.80 were enrolled in the trial. regarding sex and age distribution the difference between two groups was not significant (p=0.5)(table i). the mean±sd of positive and negative syndrome scale (panss) rating criteria in patients at admission, week 2,4,6 and 8 were assessed. the difference between two groups regarding positive symptoms was not significant at admission and week 2 (independent t-test /p=0.14 and 0.33 respectively) and was significant at week 4,6 and 8(independent t-test /p=0.001 ). table i: the demographic data of pa�ents regarding negative symptoms, the difference between two groups was not significant at admission, week 2,4,6,8 (independent t-test; p=0.14, p= 0.49, p=0.09,0.19 and p=0.29 respectively). there was no significant difference between two groups regarding general symptoms at admission and week 2 (independent t-test /p=0.08 and 0.1 respectively) and was significant at week 4,6 and 8(independent t-test /p=0.001 ). moreover, we did not detect significant difference between case aspirin in schizophreniajiimc 2017 vol. 12, no.4 169 characteris�c and control groups regarding total symptoms at admission week 2 and 4 (independent t-test /p=0.2, p=0.1, p=0.06 respectively) but we showed significant difference at weeks 6 and 8(independent t-test /p=0.002, p= 0.006 respectively)(table ii)(fig 1). generally, the difference between two groups regarding positive and negative symptoms was not significant (repeated measure/p=0.20 and 0.20 respectively). however, there was a significant difference between two groups regarding general and total symptoms (repeated measure/p=0.003 and 0.032 respectively) (table 2, fig1). we did not detect any remarkably related side effects to aspirin in two groups. discussion recent experiences have indicated the role of infection and inflammation in schizophrenia, these findings designated that prenatal bacterial or viral infections during pregnancy increased the risk of 1 4 , 1 5 s c h i z o p h r e n i a i n c h i l d r e n . m o r e o v e r, comprehensive studies revealed that the levels of interleukin-1 (il-1) and il-2, in the csf were higher among patients with schizophrenia than the general 16,17 population and complementary studies detected that high level of il-2 in the csf was a predictor of 18 relapse of schizophrenia among these patients. following these findings, some scientists practiced anti-inflammatory agents such as celecoxib and aspirin in schizophrenia as an adjunctive therapy and reported that with these anti-inflammatory agents 19-22 are disease modifier. in a controlled trial laan et al. examined the effect of aspirin in schizophrenia and revealed more improvement among patients treated with aspirin than the placebo group, regarding the panss positive and total scores, particularly in patients with cytokines elevation. furthermore, the authors did not reveal side effects 20 owing to the high dosage of aspirin. in the current controlled trial, we used aspirin 1000 mg /daily as adjunctive treatment with atypical antipsychotic agents on sixty patients mean age 30. 11±7.80 for 8 weeks. the difference between two groups regarding the improvement of positive and negative symptoms was not significant. however, there was a significant difference between two groups regarding the improvement of general and total symptoms. in accord with our findings, müller et al in 2002 revealed that celecoxib add-on treatment presented beneficial effect on treatment of schizophrenia, similar to our results positive and negative syndrome scale (panss) after five weeks treatment with celecoxib improved in two groups and difference between two groups was not significant while like our practice the celecoxib significantly improved the 21 total score. consistently 2 years later in another experience, muller et al. reported that celecoxib 2 2 significantly improved panss total scale. additionally, muller et al in 2010 evaluated the effect of celebrex on forty-nine patients with the first episode of schizophrenia and as oppose to our findings showed significant improvement in celebrex group regarding positive and negative fig 1: the changes of the nega�ve, posi�ve, general before and a�er 8 weeks treatment and total symptoms in two groups table ii: the mean±sd posi�ve and nega�ve syndrome scale (panss) ra�ng criteria in pa�ents aspirin in schizophreniajiimc 2017 vol. 12, no.4 170 symptoms scale (panss). also, they revealed significant improvement in the cgi (clinical global 23 impression) scale in celecoxib group. another trial in agreement to our work in iran by akhondzadeh et al. on 60 patients with schizophrenia showed risperidone plus celecoxib significantly improved general psychopathology symptoms, total panss 24 score and as oppose to us positive symptoms scales. the patients in our experience were well matched and the demographic characteristics, such as sex, age, and duration of the disorder, did not differ significantly between two groups and did not correlate with the therapeutic outcomes, so, we concluded that the therapeutic effect could be attributed to the aspirin. in line with our findings, müller et al in 2002 indicated that sex, duration, and severity of the disorder were not correlated with 21 therapeutic outcomes. previous studies have not explained any notable side effects in association with anti-inflammatory 19-21 agents, consistently we did not reveal any related side effects with the aspirin in this practice. some limitations such as relatively small sample size and short duration of the treatment adhered to this practice and it would be interesting to evaluate the aspirin efficacy in larger series of patients with schizophrenia over a longer period exclusively to examine effects of aspirin on negative symptoms. in theory, the effect of aspirin and other antiinflammatory agents without an antipsychotic medication would be more exciting; however, from ethics viewpoint is not acceptable. conclusion we detected that aspirin 1000 mg /day in 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23. muller n, krause d, dehning s, musil r, wolff sr, obermeier m, et al. celecoxib treatment in an early stage of schizophrenia: results of a randomized, double-blind, placebo-controlled trial of celecoxib augmentation of amisulpride treatment. schizophr res. 2010; 121: 118–24. 24. akhondzadeh s, tabatabaee m, amini h, ahmadi abhari sa, abbasi sh, behnam b. celecoxib as adjunctive therapy in schizophrenia: a double-blind, randomized and placebocontrolled trial. schizophr res. 2007; 90: 179–85. aspirin in schizophreniajiimc 2017 vol. 12, no.4 172 page 8 page 9 page 10 page 11 page 12 original�article abstract objective: to access the developmental status in children with severe acute malnutrition (sam). study design: hospital based observational cross sectional study. place and duration of study: department of pediatrics, the children's hospital and the institute of child health st multan from 1 january 2019 to 15 july 2019. material and methods: a total of 72 patients aged 6-36 months, diagnosed as severely acute malnourished according to world health organization criteria, were included in study. permission was taken from the irb ethical committee of the hospital. prior to study a performa was designed by trained staff and after the permission of parents complete data were collected from patients. all the children were assessed by using portage early education plan by a trained and expert clinical nurse to evaluate for the specific areas of development affected by malnutrition. portage early education plan has five development key areas applied up to 5 years. these are self-help, motor skills, cognition, social skills and language. complete data was analyzed by using spss version.21.0. mean comparison test was applied and chi square test was applied and p value less than 0.05 were considered as statistically significant (muac). results: out of 72 patients, 38(52.78%) were male and 34(47.22%) were female. male to female ratio was 1.11:1. mean comparison of mid upper arm circumference (muac) was correlated with developmental quotient (dq). mid upper arm circumference was found to be significant correlation with motor developmental quotient (dq) (p-value 0.005), cognition developmental quotient (dq) (p-value 0.048) and mean developmental quotient (dq) (p-value 0.03). it was found that significant association with low motor 2 2 developmental quotient (dq) (chi = 4.2, p-value= 0.032), low cognition developmental quotient (dq) (chi = 2 3.0, p-value= 0.042) and low mean developmental quotient (dq) (chi = 3.1, p-value= 0.038). conclusion: children with severe acute malnutrition have extreme developmental delay in all five domains i.e. self-help, motor skills, cognition, social skills and language. this highlights the importance of developmental therapy with management of malnutrition as recommended by who manifest of severe acute malnutrition after development therapy. to improve potential outcome of children with severe acute malnutrition, developmental assessment and therapy should be part of severe acute malnutrition program to timely identify and manage neuro disabilities in severe acute malnutrition. key words: mean score developmental quotient dq, mental developmental quotient dq, motor developmental quotient dq, neuro-developmental delay, portage early education program, severe acute malnutrition. introduction the first 1000 days of life (conception to 2 years of age) are particularly crucial for both nutrition and child development. deficiency of macronutrients as well as micronutrients during this phase has direct long term impact on child development and identifies as major risk factor for developmental delay and deficit in cognitive, motor, social skills and impact on school performance and psychomotor 1 development. according to national nutritional survey (nns) 2018, 17.7% children in pakistan are wasted, 40.2% children are stunted and 28.9 % under 2. 5 children are undernourished developmental status in children with severe acute malnutrition erum afzal, saadia khan, 1 2 3 4 5 6 ibad ali, kausar aftab, reema arshad, asad abbas correspondence: reema arshad research associate department of pediatrics and child health, aga khan university karachi e-mail: reemaarshad0@gmail.com 1,4 department of developmental pediatrics/ 2,3 department of preventive pediatrics the children's hospital and the institute of child health, multan 5 department of pediatrics and child health aga khan university karachi 6 institute of food sciences and nutrition bahauddin zakariya university, multan funding source: nil; conflict of interest: nil received: october 25, 2019; revised: october 09, 2020 accepted: october 13, 2020 developmental status in children with samjiimc 2020 vol. 15, no.4 245 a large number of data suggest that stunting at a young age leads to deficit in cognitive impairment 3, 4 and impaired neuromata development. according to lancet it is now estimated that 66% children in sub-saharan-african at risk for not reaching their 5 development potential. a large research gap exists in under developed countries where there is a high prevalence of sam but no data is available regarding the severity of development and behavioral disorders in children treated at nutrition rehabilitation centers. also there might be a s ign if ica nt o r n o s ign if ica nt d ifferen ce in developmental attainment between children with 6 kwashiorkor and marasmus. sam children may need comprehensively inter ventions to enhance 7 neurodevelopmental skills. appropriate physical assessment or cognitive tools along with nutritional assessment followed by exercise rehabilitation 8 reveals positive results in sam. the rationale for carrying out this study in pakistan is that our country is facing a huge burden of severe acute malnutrition in under 5 year's old children. there is not much local data available therefore this study was planned to assess the development status of children with severe acute malnutrition in order to bridge the gap and emphasis the need of developmental therapy for sam in addition to nutrition therapy. material and methods a hospital based observational cross sectional study was designed. this study was conducted in department of pediatrics, the children's hospital st and the institute of child health multan from 1 january 2019 to 15 july 2019. a total number of 72 patients aged 6-36 months who were diagnosed as severely acute malnourished according to who criteria were included in current study. simple random sampling technique was used to include maximum children. prior to study permission was taken from the ethical committee of the hospital. severe acute malnutrition is defined by a very low weight for height (below -3z scores of the median who growth standards), muac 11.5 cm or less, or by 2 the presence of nutritional edema. the children with primary malnutrition were enrolled for this study and all patients with malnutrition secondary to chronic disease were excluded. the parents who did not give the consent, and/or complete data and children with secondary malnutrition were excluded from current study. once the children with sam were admitted at nrc of ch & ich, multan. they were assessed for infections and illness i.e. diarrhea, liver dysfunction, electrolyte imbalance and pneumonia and have failed an appetite test (defined as an 9 inability to eat therapeutic food). during the stabilization phase, when all the children were stabilized, the complications were dealt with and therapeutic feeding was started and the children entered rehabilitation phase child's developmental was assessed. prior to study, a performa was designed by medical officer and after the permission of parents complete data were collected from patients. all relevant data were recorded on performa by the trained nursing staff of hospital. in ch&ich developmental pediatrics opd portage is applied by psychologist to patients with delayed development, mental age assessed and sessions are started to overcome deficits by psychiatrists. portage early education plan is internationally applied early childhood interventions service for pre-school children for special needs. a trained and expert clinical psychiatrist with more than 5 years of experience working with portage early education plan, administered and assessed the child in a quiet room with peaceful surroundings in the nutrition rehabilitation centre. during the assessment mother/care giver of the child was constantly present to comfort the child. portage early education plan has five development key areas applied up to 6 years. these are self-help, motor skills, cognition, social skills and language. each area had a specific checklist according to age. total numbers of checklist items up to 3 years are motor: 63, cognition: 40, selfhelp: 52, socialization: 43 and gross motor: 144.in addition, there is a section of infant stimulation activities, which has total 45 checklist item. child was assessed according to checklist items. when there were 10 consecutive negative items, the nurse at that point of checklist stops. positive items were obtained by subtracting failure items from total. developmental age was assessed by first subtracting failures from total to calculate positive items (total – failure = positive items). than the positive items were divided by total items and then multiplied by 12 to find out developmental age (development age=positive item/total item × 12). developmental age is used to access his/her developmental quotient jiimc 2020 vol. 15, no.4 246 developmental status in children with sam respectively by: dq=da/chronological age × 100). all the children were further assessed in all the clusters of both domains to evaluate for the specific areas of development affected by malnutrition. data collected was nonparametric. complete data was analyzed by using spss version.21.0. mean comparison test was applied and chi square test was applied and p value less than 0.05 were considered as statistically significant. operational definitions severe acute malnutrition severe acute malnutrition is defined by a very low weight for height (below -3z scores of the median who growth standards), by visible severe wasting, muac<11.5 1 , or by the presence of bilateral edema results out of 72 male to female ratio was 1.11:1. mostly patients 48(66.67%) belong to rural areas and 52(72.22%) patients belong to very low socioeconomic status and 44(61.11%) mothers were illiterate. mean age was 18.23 months and mean weight was 6.74kg. (table-i .) mean comparison of muac was correlated with developmental quotient (dq). muac was found to be significant correlation with motor qd (pvalue 0.005), cognition dq (p-value 0.048) and mean dq (p-value 0.03) (table iii). table i: socio-demographic characteris�cs in children with developmental delay table ii: weight for age distribu�on in children with sam table iii: mean comparison of muac and motor, mental and mean dq significant association was found between moderately stunted patients and low motor dq 2 2 (chi = 4.2, p-vlaue= 0.032), low cognition dq (chi = 2 3.0, p-vlaue= 0.042) and low mean dq (chi = 3.1,pvlaue= 0.038) (table: iv). table iv: height for age and motor, cogni�on and mean dq discussion portage early education program (peep) began in great britain and is now practiced worldwide for developmentally delayed children. the portage checklist is an ideal instrument for carrying out assessment and setting teaching objectives. it has five main sections each one having total number of items (motor: 140, cognition: 108, self-help: 108, 8 socialization: 83 and language: 218). the current hospital based observational cross sectional study included children with severe acute malnutrition. these children were assessed using portage early education program (peep) and all of them had low mental and motor dq. furthermore, our results show a significant difference in motor and mental dq of sam children with stunting and nonstunting. the socio-economic status was also found to be significantly related with under nutrition. our study is distinctive as it uses peep to assess developmental status of children with sam. first three years of life are generally counted as a very crucial for children's development. most recent studies focus on effects of undernutrition in young jiimc 2020 vol. 15, no.4 247 educa�on developmental status in children with sam children's development aged less than 36 months. our study also included under 5 years children with severe acute malnutrition and majority of children with 3sd sam also had low motor dq, low cognition dq and low mean dq. another study by dwivedi d et.al, also observed similar low motor and mental dq in indian children with sam. these studies show that severe acute malnutrition at early stages of child development is strongly linked with child performance on school level and it negatively effects fine motor skills, personal-social, language, gross motor skills and social-emotional competences of 10,11 sam children as compared to non-sam. there was a significant difference in motor and mental dq of sam children with stunting and non-stunting in our study. the comparison of stunted and nonstunted children with developmental quotient was analyzed between two groups which shows that patient with stunting has low development assessment scores as compared to non-stunted children. similarly conducted studies were also show 12 same results. however there were low emphasis on behavioral alterations and outcomes of children with sam and stunting e.g. higher negative impact, lesser physical activity, play and exploration and 13 interactions with other children. in the present study mostly male children 52.78% were affected by severe acute malnutrition similar results were also found in another research showing higher male to female ration of sam children, the reasons for this higher male to female ratio is still unknown as more importance is given to male child 14,15 in our culture and they are better taken care of children with sam show significant delay in development, but motor dq is affected more than mental dq, these findings were reinforced by different studies conducted in india on similar 1 1 , 1 6 t o p i c s . t h e c o m p a r i s o n o f m ua c a n d development quotient was done and it was reported that motor dq, mental dq and mean dq was significantly low in children having muac 11.5cm. higher muac and anthropometric z -scores, including height-for-age, were related to higher development. the findings show a direct relation of muac and motor dq, mental dq and mean dq but another study show that mental dq was insignificant and unrelated to muac, indicating muac as 17,18 irrelevant to mental dq. the socio-economic status is significantly related with under nutrition in our study as 72.22% children's had very low socioeconomic status and it slightly higher as compared to 19 study conducted by ullah et al. the overall low level of development in children with sam in this study is distressing. this study was conducted on a small sample size with limited resources. to produce more significant results more studies should also be conducted using portage early education program (peep) in different provinces of pakistan to assess which dimensions of child development is impaired during the acute stage of sam in children under 5 years of age. similar studies with different development assessment tools e.g bayley scales of infant development should be conducted to figure out the most suitable tool for our native culture. conclusion children with severe acute malnutrition have extreme developmental delay in all five domains i.e. self-help, motor skills, cognition, social skills and language. this highlights the importance of developmental therapy with management of malnutrition as recommended by who manifest of severe acute malnutrition after development therapy. to improve potential outcome of children with severe acute malnutrition, developmental assessment and therapy should be part of severe acute malnutrition program to timely identify and manage neuro disabilities in severe acute malnutrition. limitations of the study the limitations of this study includes small sample size and limited time duration. the developmental assessment was done in the rehabilitation stage only, there was no information about the developmental status of child before or after admission. children should be followed up after nutritional rehabilitation and developmental therapy to assess outcome. c u l t u r a l l y a d a p t e d a s s e s s m e n t t o o l s f o r development be designed and used for assessment as the international portals are not suitable for our local children. funding's and conflict of interest the research was funded by the authors and no external grant was taken or used for the purpose of this research. there is no conflict of interest in this study as well. jiimc 2020 vol. 15, no.4 248 developmental status in children with sam references 1. munthali t, jacobs c, sitali l, dambe r, michelo c. mortality and morbidity patterns in under-five children with severe acute malnutrition (sam) in zambia: a five-year ret ro s p e c t i ve re v i e w o f h o s p i ta l b a s e d re co rd s (2009–2013). arch public health. 2015; 73(1):23. 2. ministry of national health services, regulations and coordination. government of pakistan. national nutrition survey 2018. pakistan: unicef; 2018. 3. cusick se, georgieff mk. the role of nutrition in brain development: the golden opportunity of the “first 1000 days”. the journal of pediatrics. 2016; 175(1):16-21. 4. johnson sb, riis jl, noble kg. state of the art review: poverty and the developing brain. . 2016; j. pediatr 37(4):e20153075. 5. selvi gp, emary c. treatment of severe acute malnutrition through the integrated child development scheme in jharkand state, india. field exchange; 58. 2018; 6:34. 6. dereje n. determinants of severe acute malnutrition among under five children in shashogo woreda, southern ethiopia: a community based matched case control study. j nutr food sci. 2014; 4:5. 7. schoonees a, lombard mj, musekiwa a, nel e, volmink j. ready-to-use therapeutic food (rutf) for home-based nutritional rehabilitation of severe acute malnutrition in children from six months to five years of age. cochrane database syst. rev. 2019(5). 8. gutiérrez-hernández cc, harmony t, avecilla-ramírez gn, barrón-quiroz i, guillén-gasca v, trejo-bautista g, et all. infant scale of selective attention: a proposal to assess cognitive abilities. revista evaluar. 2017; 17(1). 9. trehan i, manary mj. management of severe acute malnutrition in low-income and middle-income countries. arch. dis. child. 2015; 100:283-7. 10. abessa tg, bruckers l, kolsteren p, granitzer m. developmental performance of hospitalized severely acutely malnourished under-six children in low-income setting. bmc pediatr.2017; 17:197. 11. dwivedi d, singh s, singh j, bajaj n, singh hp. neurodevelopmental status of children aged 6-30 months with severe acute malnutrition. indian pediatr. 2018; 55:131-3. 12. gonzález l, cortés-sancho r, murcia m, ballester f, rebagliato m, rodríguez-bernal cl. the role of parental social class, education and unemployment on child cognitive development. gac sanit. 2020; 34(1):51-60. 13. khandelwal n, mandliya j, nigam k, patil v, mathur a, pathak a. determinants of motor, language, cognitive, and global developmental delay in children with complicated severe acute malnutrition at the time of discharge: an observational study from central india. plos one. 2020; 15(6):10-7. 14. olsen mf, iuel-brockdorff as, yaméogo cw, cichon b, fabiansen c, filteau s, et all. early development in children with moderate acute malnutrition: a cross-sectional study in burkina faso. . 2020; 16:128-9.matern child nutr 15. van den heuvel m, voskuijl w, chidzalo k, kerac m, reijneveld sa, bandsma r, et all. developmental and behavioural problems in children with severe acute malnutrition in malawi: a cross–sectional study. j. glob. health. 2017; 7:204-16. 16. jain v, patel s, agarwal n, gaur a. assessment of neurodevelopmental abnormalities in children with severe acute malnutrition between the age of 6 months to 30 months. 2018; 09:18-20.int. j. biomed. res. 17. abera m, tesfaye m, hanlon c, admassu b, girma t, wells jc, et all. body composition during early infancy and mental health outcomes at 5 years of age: a prospective cohort study of ethiopian children. j. pediatr. 2018; 200:225-31. 18. daniel ai, bandsma rh, lytvyn l, voskuijl wp, potani i, van den heuvel m. psychosocial stimulation interventions for children with severe acute malnutrition: a systematic review. j. glob. health. 2017; 7:104-5. 19. ullah h, ullah b, karim s, tariq i, khan ak, mir s, et al. malnutrition amongst under-five years children in swat, pakistan: prevalence and risk factors. trop j pharm res. 2014; 13(8):1367-70. jiimc 2020 vol. 15, no.4 249 developmental status in children with sam original�article abstract objective: to determine the association of testosterone levels with insulin resistance in type 2 diabetes mellitus (t2dm). study design: a cross sectional observational study. place and duration of study: this study was conducted at department of chemical pathology army medical th th college rawalpindi from 11 nov 2014 to 11 nov 2015. materials and methods: the study included 110 male participants. two groups were made. group a, included 55 patients of t2dm selected randomly from endocrinology department of military hospital rawalpindi. group b included healthy controls. each group was further categorized on the basis of age and decade wise sub groups were made. fasting plasma glucose (fpg), serum testosterone levels, serum sex hormone binding globulin levels (shbg), glycosylated hemoglobin and fasting insulin levels were checked using fasting blood samples. the insulin resistance was calculated using homeostatic model for assessment of insulin resistance (homa‐ir). data obtained was analyzed by spss version 20. results: mean serum testosterone levels in group a (n=55) 9.36±5.06nmol/l was significantly lower (p� 0.0001) as compared to group b (n=55) 15.10±6.99nmol/l. fasting plasma glucose (11.50±3.35 vs. 4.23±0.63nmol/l), hba1c (6.86±0.35 vs. 5.05±0.45%), serum insulin (10.61±4.87 vs. 5.71±2.43µiu/ml) and insulin resistance calculated by homa‐ir (5.51±3.73 vs. 1.07±0.45) were significantly higher in group a as compared to group b. conclusion: the present study shows that a lower levels of serum testosterone are found in diabetic patients. moreover there is significant negative correlation of serum testosterone with insulin resistance. key words: type 2 diabetes mellitus, testosterone, insulin resistance, homeostatic model assessment‐insulin resistance. the serum. there are three phases of testosterone surge in a man's life i.e. during fetal life, shortly after birth and finally at puberty till 20 years of age, thereafter it starts decreasing with advancement of 4 age. testosterone exerts its physiological effects by activating androgen receptor either directly or through its metabolite 5α‐dihydrotestosterone (5α‐ dht). testosterone may also be aromatized to estradiol which in turn exerts its effects through 5 estrogen receptor α (er α). the bioavailable or free amount of testosterone depends on the level of shbg as it is specific carrier protein of testosterone. higher shbg levels will result in free testosterone levels to be low. conversely, shbg lower levels will in turn cause free testosterone levels to be high. free testosterone being the active form makes this relationship important. thus men with normal total testosterone but high shbg may have symptoms of low testosterone as free testosterone levels are low. men with low testosterone have low metabolic rate hence are prone to develop obesity, which in turn leads to introduction diabetes mellitus (dm) is a metabolic disorder with inappropriate glycemic levels either due to absolute insulin secretion deficiency or reduction in the 1 insulin effectiveness. several studies during the past few years have shown that male patients of t2dm have a significantly higher prevalence of low testosterone levels as compared to age matched 2,3 healthy males. the leydig cells of testes secrete male sex steroid hormone testosterone (95%). it circulates either as free form (2%) or bound to albumin and sex hormone binding globulin (shbg) in testosterone levels with insulin resistance in type 2 diabetes mellitus in men 1 2 3 4 mehnaz khattak , tariq mahmood ahmad , jawwad anis khan , asma hayat jiimc 2016 vol. 11, no.4 correspondence: dr. mehnaz khattak department of pathology foundation university medical college, islamabad e‐mail: mehnaz07@yahoo.com 1,3 department of pathology foundation university medical college, islamabad 2,4 department of pathology army medical college, rawalpindi funding source: nil; conflict of interest: nil received: july 15, 2016; revised: sep 12, 2016 accepted: nov 10, 2016 testosterone levels with insulin resistance in t2dm 153 6‐8 ir. visceral adiposity also causes aromatization of testosterone to estradiol in fat cells. high circulating levels of estradiol will in turn suppress the production of testosterone causing its deficiency. testosterone deficiency will then suppress lipolysis, reduce the metabolic rate leading to visceral fat 3,9,10 deposition and insulin resistance. hence a vicious cycle is initiated which plays the key role in pathogenesis of t2dm. low testosterone and diabetes often goes hand in hand. in fact men with t2dm are much likely to have low testosterone levels as men who don't have 11,12 t2dm. similarly numerous other studies have also highlighted ir and t2dm association with low serum 13‐15 testosterone levels. such study has not been carried out in our population. hence this study was planned to determine the association of testosterone levels with insulin resistance in type 2 diabetes mellitus (t2dm). materials and methods a cross sectional observational study was carried out at chemical pathology department, army medical th th college rawalpindi from 11 nov 2014 to 11 nov 2015. a total of 110 male individuals were included in the study by convenient sampling technique from the endocrinology department of military hospital rawalpindi. they were divided into two groups. group a consisted of 55 patients of t2dm and group b consisted of 55 healthy controls who had no major illness such as coronary heart disease, diabetes mellitus, thyroid disorders, and liver or kidney diseases. each group was further categorized on the basis of age decade. five ml venous sample was obtained from left median cubital vein after an overnight fast of 8‐12 hours from the participants under aseptic conditions. centrifugation of the blood was done at 4000 rpm for 5 minutes for separation of plasma. analysis of fasting plasma glucose (fpg) was done on fresh plasma. serum was frozen at ‐30˚c for estimation of serum testosterone, insulin and shbg levels. two milliliter of whole blood was collected in ethylenediaminetetraacetic acid (edta) containers for analysis of hba1c. chemistry auto‐analyzer selectra e was used to measure fpg. fully automated hormone analyzer, immulite 1000, based on the principle of chemi‐ luminescence immunoassay technique was used to measure serum testosterone, insulin and shbg levels. homa‐ir formula (fpg levels x fasting insulin levels/22.5) was used to calculate insulin resistance. ion exchange resin method was used to estimate hba1c levels. the data was entered on data base program spss version 20 and results of the test were subjected to appropriate statistical analysis. independent t‐test was used for comparing the quantitative data. pearson's correlation co‐efficient was used to analyze the association of serum testosterone with other variables. p‐value of < 0∙05 was considered statistically significant. results a total of 110 participants were included in the study. out of those 55 were diabetics and 55 were age and gender matched healthy subjects. comparison of biochemical profile of different analytes in diabetic patients (group a) and healthy controls (group b) are summarized in table i. the mean serum testosterone levels (mean ±sd) in diabetic patients is 9.36±5.06nmol/l as compared to healthy controls 15.10±6.99nmol/l with significant p‐value of <0.001. the mean serum insulin levels (mean±sd) in diabetic patients is 10.61±4.87µiu/ml as compared to healthy controls 5.71±2.43µiu/ml with significant p‐value of <0.001. the insulin resistance of diabetic patients is significantly higher i.e 5.51±3.73 as compared to healthy controls 1.07±0.45 ( p‐value <0.001). table i: comparison of the biochemical profile of the studied groups (n=110) note: *p‐value<0.05, **=p<0.01 jiimc 2016 vol. 11, no.4 testosterone levels with insulin resistance in t2dm 154 comparison of serum testosterone levels at different age groups in diabetic patients (group a) and healthy controls (group b) are summarized in table ii. significantly lower levels of serum testosterone was noted in all age groups of diabetic patients as compared to healthy controls. 11‐18 ho et al and various others with similar results. this study therefore establishes that serum testosterone levels are lower in type 2 diabetic males as compared to healthy controls. another important finding of this study is significant negative correlation of serum testosterone with insulin resistance. serum insulin levels are much higher in diabetic patients as compared to healthy controls. moreover there is significant insulin resistance in diabetic patients as calculated by homa‐ir. this finding is also in agreement with studies carried out by oh et al, grossman et al and 14‐19 goto et al. another important observation of the study was negative association of fasting plasma glucose (fpg) and hba1c with serum testosterone. this finding is in line with studies carried out by 20,21 dhindsa et al and elsagheir et al. the main limitation of our study is relative small sample size and financial constraints in carrying out costly endocrine tests. further well designed studies with larger sample are suggested to assess the management strategies of t2dm to address the testosterone deficiency. conclusion the present study shows lower levels of serum testosterone in diabetic (male) patients. moreover there is significant negative 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accuracy matters. the journal of clinical endocrinology and metabolism. 2004; 89: 520‐4. 8. grishkovskaya i, avvakumov gv, sklenar g, dales d, table ii: comparison of testosterone levels at different age groups note: *p‐value<0.05, **=p<0.01 correlation of serum testosterone levels with fpg, hba1c, serum insulin and insulin resistance in different age groups of diabetic patients is summarized in table iii. these results clearly shows s i g n i f i c a n t n e ga t i v e c o r re l a t i o n o f s e r u m testosterone with fpg, hba1c, serum insulin and insulin resistance. table iii: correla�on of testosterone levels with various parameters in diabe�cs discussion this study was under taken to assess the association of testosterone levels with insulin resistance in type 2 diabetes mellitus in men. the principal observation of this study is that mean testosterone levels in diabetic patients is significantly lower as compared to the healthy controls. this finding is in agreement with studies carried out by stellato et al, goto et al, jiimc 2016 vol. 11, no.4 testosterone levels with insulin resistance in t2dm 155 hammond gl, muller ya. crystal structure of human sex hormone‐binding globulin: steroid transport by a laminin g‐ like domain. the embo journal. 2000; 19: 504‐12. 9. saad f. the role of testosterone in type 2 diabetes and metabolic syndrome in men. arquivos brasileiros de endocrinologia e metabologia. 2009; 53: 901‐7. 10. grossmann m. low testosterone in men with type 2 diabetes: significance and treatment. the journal of clinical endocrinology and metabolism. 2011; 96: 2341‐53. 11. dhindsa s, prabhakar s, sethi m, bandyopadhyay a, chaudhuri a, dandona p. frequent occurrence of hypogonadotropic hypogonadism in type 2 diabetes. the journal of clinical endocrinology and metabolism. 2004; 89: 5462‐8. 12. haffner sm, shaten j, stern mp, smith gd, kuller l. low levels of sex hormone‐binding globulin and testosterone predict the development of non‐insulin‐dependent diabetes mellitus in men. mrfit research group. multiple risk factor intervention trial. american journal of epidemiology. 1996; 143: 889‐97. 13. stellato rk, feldman ha, hamdy o, horton es, mckinlay jb. testosterone, sex hormonebinding globulin, and the development of type 2 diabetes in middle‐aged men: prospective results from the massachusetts male aging study. diabetes care. 2000; 23: 490‐4. 14. oh jy, barrett connor e, wedick nm, wingard dl. endogenous sex hormones and the development of type 2 diabetes in older men and women: the rancho bernardo study. diabetes care. 2002; 25: 55‐60. 15. rhoden el, ribeiro ep, riedner ce, teloken c, souto ca. glycosylated haemoglobin levels and the severity of erectile function in diabetic men. bju international. 2005; 95: 615‐7. 16. goto a, morita a, goto m, sasaki s, miyachi m, aiba n, et al. associations of sex hormone‐binding globulin and testosterone with diabetes among men and women (the saku diabetes study): a case control study. cardiovascular diabetology. 2012; 11: 130. 17. ho ch, yu hj, wang cy, jaw fs, hsieh jt, liao wc, et al. prediabetes is associated with an increased risk of testosterone deficiency, independent of obesity and metabolic syndrome. plos one. 2013; 8: e74173. 18. laaksonen de, niskanen l, punnonen k, nyyssonen k, tuomainen tp, valkonen vp, et al. testosterone and sex hormone‐binding globulin predict the metabolic syndrome and diabetes in middle‐aged men. diabetes care. 2004; 27: 1036‐41. 19. grossmann m, thomas mc, panagiotopoulos s, sharpe k, macisaac rj, clarke s, et al. low testosterone levels are common and associated with insulin resistance in men with diabetes. the journal of clinical endocrinology and metabolism. 2008; 93: 1834‐40. 20. el saghier eo, shebl se, fawzy oa, eltayeb im, bekhet lm, gharib a. androgen deficiency and erectile dysfunction in patients with type 2 diabetes. clinical medicine insights endocrinology and diabetes. 2015; 8: 55‐62. 21. dhindsa s, ghanim h, batra m, kuhadiya nd, abuaysheh s, sandhu s, et al. insulin resistance and inflammation in hypogonadotropic hypogonadism and their reduction after testosterone replacement in men with type 2 diabetes. diabetes care. 2016; 39: 82‐91. jiimc 2016 vol. 11, no.4 testosterone levels with insulin resistance in t2dm 156 page 15 page 16 page 17 page 18 original�article abstract objective: to measure the serum levels of homocysteine and lipid profile in patients of subclinical hypothyroidism. study design: a case control observational study. place and duration of study: the study was conducted in biochemistry department of islamic international medical college, rawalpindi during a period of one year from march 2016 to february 2017. materials and methods: a total of 128 subjects were selected for the study from the medical outpatient department using convenient non probability sampling technique. selection criterion was age group of 20 to 55 years and exclusion criteria were history of diabetes, hypertension, cardiovascular or renal disease. selected patients were divided into two groups. in group i (selected as control) were sixty four healthy volunteers who presented for routine annual medical and physical examination. in group ii (patient's group) were 64 patients diagnosed as subclinical hypothyroidism based upon thyroid stimulating hormone (tsh) levels >4.12 mu/ml and normal free t3 (ft3) and t4 (ft4) levels on two consecutive measurements.lipid profile and homocysteine levels in the serum of the subjects of both groups were estimated. the collected data was entered in spss version 21 for analysis. descriptive data were given as mean ± standard deviation (sd). independent t test was used and p values less than 0.05 were considered statistically significant. results: group i (control) consisted of 82.81% females and 17.18% males. in group ii (sub clinical hypothyroid patients) were 87.5% females and 12.5% males. the mean ages of controls and subclinical hypothyroid patients were 33.65±5.98 and 35.20±7.55 years respectively. there was a significant increase in mean thcy in subclinical hypothyroid patients than in control group (mean ± sd, 12.67±2.35 μmol /l vs 3.76±1.59 μmol/l). serum total cholesterol in subclinical hypothyroid patients was significantly increased than the control group (mean ± sd, 195.25 ± 10.63 mg/dl vs 162.05 ± 17.39 mg/dl). there was a significant decrease in mean hdl-cholesterol in subclinical hypothyroid patients than in control group (mean ± sd, 48.11 ± 4.62 mg/dl vs 53.85 ± 6.55 mg/dl). there was a decrease in mean serum triglyceride in hypothyroid patients than in control group which was not statistically significant (mean ± sd, 111.25 ± 18.82 mg/dl vs 140.29 ± 17.69 mg/dl). conclusion: it was found in our study that the serum levels of homocysteine and lipid profile are increased in subclinical hypothyroidism. key words: atherosclerosis, homocysteine, lipid profile, subclinical hypothyroidism. cardiovascular disease which is caused by 3 dyslipidemia. dyslipidemia is increase of plasma cholesterol and triglycerides (tgs) and a low hdl cholesterol level which contributes to the progress of atherosclerosis. dyslipidemia is diagnosed by measuring plasma levels of total cholesterol, tgs, and individual lipoproteins and these are collectively termed as lipid profile. in addition to the increase in levels of cholesterol and ldl-cholesterol investigators have found serum homocysteine to be an independent risk factor for 4 atherosclerosis. hcy increases the possibility of cardiovascular disease by various mechanisms including endothelial dysfunction, oxidative stress, endoplasmic reticulum stress, smooth muscle cell proliferation and platelet aggregation. thyroid disease, namely hypothyroidism and introduction in developed, as well as developing countries cardiovascular disease namely the coronary heart disease remains the leading cause of mortality and 1 morbidity. in pakistan it is estimated that 410 out of 10,000 people die every year due to ischemic heart 2 disease. atherosclerosis is an important risk factor in levels of homocysteine and lipid profile in subclinical hypothyroidism 1 2 3 4 aqsa malik , amina rahim , yasir iqbal , abdul khaliq naveed correspondence: dr. aqsa malik assistant professor, biochemistry islamic international medical college riphah international university, islamabad e-mail: aqzamalik@gmail.com 1,2,4 3 department of biochemistry/ ophthalmology islamic international medical college riphah international university, islamabad funding source: nil; conflict of interest: nil received: mar 20, 2017; revised: june 25, 2017 accepted: october 25, 2017 atherosclerosis in subclinical hypothyroidismjiimc 2017 vol. 12, no.4 191 hyperthyroidism, constitutes one of the most common endocrine abnormalities. among the thyroid diseases, hypothyroidism is a disorder in which thyroid activity is reduced and does not produce enough thyroid hormones. it leads to hyper secretion of pituitary thyroid stimulating hormone 2 (tsh) and an increase in the serum level of tsh. its 5 prevalence worldwide is estimated to be 4-15 %. in 6 pakistan it is 4.1% mainly due to deficiency of iodine. t h y r o i d h o r m o n e s , t h y r o x i n e ( t 4 ) , a n d triiodothyronine (t3) play an important role in all major metabolic pathways by regulating protein, carbohydrate, and lipid metabolism; including synthesis, mobilization, and degradation. hypothyroidism is an endocrine disorder which presents with varied degree of thyroid dysfunction 7 and metabolic effects. it is a proven fact that patients with hypothyroidism are prone to develop cardiovascular disease. this is based upon autopsy f i n d i n g s r e v e a l i n g t h a t c o r o n a r y a r t e r y atherosclerosis is two times common in a 1 hypothyroid patient as compared to the control. this increased incidence of cardiovascular disease in hypothyroid patients has been attributed to increase in the levels of low-density lipoprotein and total 8 cholesterol. subclinical hypothyroidism is the earliest stage of thyroid dysfunction and is defined as increased serum thyroid stimulating hormone (tsh) concentrations with normal thyroid hormone levels and absence of clinical symptoms and signs of 9 hypothyroidism. it is yet to be proven that subclinical hypothyroid disease is prone to 10,11 atherosclerosis and we aimed to find it out in our study. in this study we measured serum lipid profile and plasma hcy concentrations of subclinical hypothyroid patients and compared them to control g ro u p t o f i n d a ny p re d i s p o s i t i o n t o wa rd atherosclerosis. materials and methods this was a case control observational study conducted at biochemistry department of islamic international medical college rawalpindi with the collaboration of department of medicine, pakistan railways hospital during a period of one year from march 2016 to february 2017. approval from the ethical review committee of the institute was attained before the commencement of the study. an informed verbal and written consent from the patients was taken to participate in the study. a total of 128 subjects were selected for the study from the medical outpatient department using convenient non probability sampling technique. selection criterion was age group of 20 to 55 years and exclusion criteria were history of diabetes, hypertension, cardiovascular or renal disease. selected patients were divided into two groups. in group i (selected as control) were sixty four healthy volunteers who presented for routine annual medical and physical examination. in group ii (patient's group) were 64 patients diagnosed as subclinical hypothyroidism based upon thyroid stimulating hormone (tsh) levels >4.12 mu/ml and normal free t3 (ft3) and t4 (ft4) levels on two consecutive measurements. after overnight fasting of 12 hours, 5 ml of blood was collected from the median cubital vein of each control and patient. sample of plain tube was left to clot for 30 minutes then centrifuged at 3500 × g for 5 minutes; the separated serum was divided into several aliquots and stored at −70°c until the estimation of total homocysteine and lipid profile. plasma homocysteine were measured using an elisa kit from cusabio according to the manufacturer's instructions in the biochemistry laboratory of islamic international medical college. serum levels of total cholesterol, hdl-cholesterol, ldl-cholesterol and triglycerides were determined using a cobas dimension rxl autoanalyzer (germany) in the pakistan railways hospital laboratory. the desirable levels for lipid profile parameters were total cholesterol (< 200 mg/dl), triglycerides (< 150mg/ dl), hdl-cholesterol (30-60 mg/dl) and ldl cholesterol (< 100 mg/dl). the collected data was entered into spss version 21 for analysis. gender was expressed as percentages. descriptive data were given as mean ± standard deviation (sd).independent t test was used and p values less than 0.05 were considered statistically significant. results group i (control) consisted of 82.81% females and 17.18% males. in group ii (subclinical hypothyroid patients) were 87.5% females and 12.5% males. (table i) the mean ages of controls and subclinical hypothyroid patients were 33.65±5.98 and 35.20±7.55 years respectively. there was a atherosclerosis in subclinical hypothyroidismjiimc 2017 vol. 12, no.4 192 significant increase in mean values of hcy levels in subclinical hypothyroid patients than in control group (mean ± sd, 12.67 ± 2.35 μmol /l vs 3.76 ± 1.59 μmol/ l; 95% confidence interval, respectively; p=0.002) (table ii). the mean thcy of subclinical hypothyroid patients was 8.91μmol/l higher than of control group. there was a significant increase in mean serum total cholesterol in subclinical hypothyroid patients than in control group (mean ± sd, 195.25 ± 10.63 mg/dl vs 162.05 ± 17.39 mg/dl; 95% confidence interval, respectively; p=0.000) (table ii). the mean serum total cholesterol of subclinical hypothyroid patients was 33.2 mg/dl higher than of control group. there was a significant decrease in mean values of hdl-cholesterol in subclinical hypothyroid patients than in control group (mean ± sd, 48.11 ± 4.62 mg/dl vs 53.85 ± 6.55 mg/dl; 95% confidence interval, respectively; p=0.000) (table ii). the mean values of hdl-cholesterol of hypothyroid patients were 5.74 mg/dl lower than of control group. there was a significant increase in mean serum ldlcholesterol in subclinical hypothyroid patients than in control group (mean ± sd, 126.79 ± 22.24 mg/dl vs 93.70 ± 14.58 mg/dl; 95% confidence interval, respectively; p=0.000) (table ii). the mean serum ldl-cholesterol of subclinical hypothyroid patients was 33.09 mg/dl higher than of control group. there was a decrease in mean serum triglyceride in hypothyroid patients than in control group which was not significant (mean ± sd, 111.25 ± 18.82 mg/dl vs 140.29 ± 17.69 mg/dl; 95% confidence interval, respectively; p=0.010) (table ii). to control. these findings are consistent with results 12 13 14 of duntas lh , bandi a et al and díez jj. it is postulated that in hypothyroidism there is reduced activity of hmg coa reductase which might lead to decrease in total cholesterol but our findings are on the contrary. the elevation of serum cholesterol might be because of rise in the levels of serum low density lipoproteins and intermediate density lipoprotein. furthermore the plasma concentration of cholesterol might also be increased due to decrease in the rate of cholesterol secretion in the bile and resulting reduced excretion in the feces. this happens due to decrease in number of low density lipoprotein(ldl) receptors on liver cells leading to decreased in activity of ldl receptors and decreased receptor-mediated catabolism of low density lipoproteins (ldl) and intermediate density lipoproteins. hdl-cholesterol (hdl) levels are elevated in hypothyroidism. it occurs due to the decreased activity of the cholesterol ester transfer protein (cetp) resulting in reduced transfer of cholesteryl esters from hdl to very ldl-cholesterol (ldl). but our findings were on the contrary. in our study we found that serum hdl levels were significantly decreased in subclinical hypothyroid patients compared to the control. these findings are in 15 consistent with the results of pandian bg and al16 hakeim hk who also reported decreased hdl levels in hypothyroid patients. table i: demographic characteris�c of control and subclinical hypothyroid pa�ents table ii:comparison of lipid profile and homocysteine levels between control and subclinical hypothyroid pa�ents discussion in our study we found serum total cholesterol (tc) and ldl-cholesterol (ldl) was significantly increased in subclinical hypothyroidism patients as compared atherosclerosis in subclinical hypothyroidismjiimc 2017 vol. 12, no.4 193 homocysteine( mol/l) in our study serum triglycerides (tg) levels were found increased in patients of subclinical hypothyroidism. this finding is consistent with the 17 18 reports of ali a and saleh aa who also reported high tg levels in hypothyroidism. the reason being, lipoprotein lipase activity is decreased in hypothyroidism which decreases the clearance of triglyceride rich lipoproteins. in our study we observed that hcy was significantly elevated in patients of subclinical hypothyroidism as compared to the control group. this finding is contrary to the 19 report of aldasouqisetal but is in accordance to 18 20 reports by saleh aa and al-habori ma. there are two postulated mechanisms of increase in homocysteine levels in hypothyroidism. either there is a rise in homocysteine formation due to direct effect of thyroid hormone on homocysteine metabolism in the liver or there is decreased in homocysteine clearance from the kidneys. decreased serum levels of thyroid hormone affect t h e h e p at i c a c t i v i t y o f f l avo p ro te i n m et hy lenetetrahyd rofolate reductase (mthfr) enzymes vital for remethylation of homocysteine to methionine. furthermore the conversion of r i b o f l av i n to t h e a c t i ve co e n zy m e f l av i n adeninedinucleotide becomes faulty leading to poor activity of mthfr and hence increased hcy levels. there were few limitations of this study, which include small sample size and it should have been a cohort study. despite this we believe that our study may prove helpful in further research related to homocysteine and lipid profile parameters in subclinical hypothyroidism. conclusion it was found in our study that the serum levels of homocysteine and lipid profile are increased in subclinical hypothyroidism. as these they are prone to atherosclerosis, therefore early screening and r e g u l a r m o n i t o r i n g o f t h e s e f a c t o r s a r e recommended in subclinical hypothyroid patients. references 1. iqbal sp, dodani s, qureshi r. risk factors and behaviours for coronary artery disease (cad) among ambulatory pakistanis. journalpakistan medical association. 2004; 54: 261-5. 2. nelson rh. hyperlipidemia as a risk factor for cardiovascular disease. primary care: clinics in office practice. 2013; 40: 195-211. 3. kahaly gj. cardiovascular and atherogenic aspects of subclinical hypothyroidism. thyroid. 2000; 10: 665-79. 4. bertoia ml, pai jk, cooke jp. plasma homocysteine, dietary b vitamins, betaine, and choline and risk of peripheral artery disease. atherosclerosis. 2014; 235: 94-101. 5. unnikrishnan ag, kalra s, sahay rk, bantwal g, john m, tewari n. prevalence of hypothyroidism in adults: an epidemiological study in eight cities of india. indian journal of endocrinology and metabolism. 2013; 17: 647-52. 6. jawa a, jawad a, riaz sh, assir mz, chaudhary aw, zakria m, et al. turmeric use is associated with reduced goitrogenesis: thyroid disorder prevalence in pakistan (thypak) study. indian journal of endocrinology and metabolism. 2015; 19: 347-50. 7. gore ac, chappell va, fenton se. edc-2: the endocrine society's second scientific statement on endocrinedisrupting chemicals. endocrine reviews. 2015; 36: 1-150. 8. mcleod ds, cooper ds, ladenson pw, whiteman dc, jordan sj. race/ethnicity and the prevalence of thyrotoxicosis in young americans. thyroid. 2015; 25: 6218. 9. ramasamy i. recent advances in physiological lipoprotein metabolism. clinical chemistry and laboratory medicine (cclm). 2014; 52: 1695-727. 10. soman b, rahaman ma, vijayaraghavan g. subclinical hypothyroidism and coronary artery disease: in relation to angiographic disease pattern in indian women. heart india. 2017; 5: 3-6. 11. suh s, kim dk. subclinical hypothyroidism and cardiovascular disease. endocrinology and metabolism. 2015; 30: 246-51. 12. duntas lh, brenta g. the effect of thyroid disorders on lipid levels and metabolism. medical clinics of north america. 2012; 96: 269-81. 13. bandi a, pyadala n, srivani n, borugadda r, maity sn, kumar rbn, et al. a comparative assessment of thyroid hormones and lipid profile among hypothyroid patients: a hospital based case control study. iaim. 2016; 3: 108-114. 14. díez jj, iglesias p. serum cholesterol and triglyceride levels in diabetic patients with subclinical hypothyroidism. endocrinología y nutrición (english edition). 2014; 61: 41925. 15. pandian bg, sireesha p, ng yp, parashuram n. monitoring the prevalence of metabolic syndrome among hypothyroid patients and assessing the effect of anti-hypothyroid treatment on it among the south indian population. journal of young pharmacists. 2016; 8: 104-7. 16. al-hakeim hk. serum levels of lipids, calcium and magnesium in women with hypothyroidism and cardiovascular diseases. journal of laboratory physicians. 2009; 1: 49-52. 17. ali a, sattar a, hameed a, maryam b. lipid profile in patients of primary hypothyroidism. annals of king edward medical university. 2013; 19: 29. 18. saleh aa. lipid profile and levels of homocysteine and total antioxidant capacity in plasma of rats with experimental thyroid disorders. the journal of basic & applied zoology. 2015; 72:173-8. 19. aldasouqi s, nkansa-dwamena d, bokhari s, alzahrani as, atherosclerosis in subclinical hypothyroidismjiimc 2017 vol. 12, no.4 194 khan m, al-reffi a. is subclinical hypothyroidism associated with hyperhomocysteinemia? endocrine practice. 2004; 10: 399-403. 20. al-habori ma, al-meeri am, al-nuzailyma, ali f. homocysteine level in relation to thyroid function tests in hypothyroid patients. asian j. med. pharm. 2014; 4: 101-6. atherosclerosis in subclinical hypothyroidismjiimc 2017 vol. 12, no.4 195 page 31 page 32 page 33 page 34 page 35 original article abstract objective: to investigate the effect of point mutation in fv leiden g1691a and fii g20210a gene on coagulation and recurrent spontaneous abortion (rsa) among sudanese women. study design: this was retrospective case control study. place and duration of study: the study was carried out from aug 2012 to dec 2014 at omdurman maternal hospital, sudan. materials and methods: the study included hundred pregnant females with a history of recurrent spontaneous abortion as (case group) and ninety five healthy reproductive sudanese women as (control group). the data was collected with the help of structured questionnaire and direct interview to collect information. identification of point mutation in factor v leiden g1691a and factor ii g20210a gene by polymerase chain reaction was performed; coagulometer was used for the measurement of pt and aptt. odds ratio and the 95% confidence interval (95%ci) were calculated for the presence of mutation between cases and controls and analyzed by spss program, version 17.0. results: the heterozygous alleles g/a in factor v gene was 8.0% in all cases related with three, four and five times of recurrent abortion and 6% was found in control group. heterozygous alleles of factor ii g/a prothrombin time (pt) and partial thromboplastin time (ptt) in women with recusant spontaneous abortion (rsa) were not affected significantly (p=0. 93 and p=0.69). conclusion: based upon the results it is concluded that the point mutation in factor v leiden g1691a and factor ii g20210a might play a role in recurrent spontaneous abortion loss among sudanese women. however these point mutations do not affect the coagulation profile. key words: factor v leiden g1691a, factor ii g20210a, rsa, sudanese pregnant women. week of gestation .the modern definition, however, is the spontaneous loss of 2 or more consecutive 1 pregnancies before 20 weeks of gestation. recurrent pregnancy loss is an experience which can be very painful for the couple. most of the miscarriages occur in the first trimester and affect 2 about 15% of all recognized pregnancies. rpl has many possible causes that can be categorized as genetic abnormalities, hormonal and metabolic d i s o rd e rs , u te r i n e a n a to m i c a b n o r m a l i t i e s , i n f e c t i o u s c a u s e s , i m m u n e d i s o r d e r s a n d 3 thrombophilic disorders. hereditary thrombophilias are a group of genetic disorders of blood coagulation resulting in a hypercoagulable state, which in turn can result in abnormal placentation. early in 4 pregnancy this may manifest as spontaneous loss. factor v leiden (f v l) and prothrombin gene (g20210a) mutations are the most common types of hereditary thrombophilias. most carriers of this mutation do not develop any clinical signs and remain undiagnosed because these conditions result point mutation in factor v leiden g1691a and factor ii g20210a and effect on coagulation profile and frequency of recurrent spontaneous abortions among sudanese women 1 2 3 asaad mohammed ahmed abd allah babker , fath elrahman mahdi hassan gameel , salaheldein gumaa elzaki , 4 5 6 amanda g elgoraish , lienda bashier eltayeb , hisham ali waggiallah jiimc 2016 vol. 11, no.3 correspondence: dr. hisham ali waggiallah department of clinical laboratory al-ghad international colleges for health sciences al riyadh, saudia arabia 1 department of clinical laboratory al-ghad international colleges for health sciences al-madinah al-munawarah, saudia arabia 2 department of hematology and immunohaematology college of medical laboratory science sudan university of science and technology khartoum, sudan 3,4 department of epidemiology tropical medicine research institute national centre for research, khartoum, sudan 5 department of medical parasitology faculty of medical laboratory sciences omdurman islamic university, khartoum, sudan 6 department of clinical laboratory al-ghad international colleges for health sciences al riyadh, saudia arabia funding source: nil ; conflict of interest: nil received: mar 17, 2016; revised: apr 21, 2016 accepted: aug 29, 2016 point mutation in factor v leiden g1691a and factor ii g20210a introduction recurrent pregnancy loss (rpl) is defined as three or th more consecutive pregnancy losses before the 24 108 in a small absolute risk of clinically significant 5 thrombosis. factor v leiden is a single point mutation involving a guanine to adenine transition at position 1691 in exon 10 of the factor v gene, which 6 leads to the synthesis of a variant factor v molecule. the prothrombin g20210a mutation involves guanine to adenine substitution at nucleotide 20210 7 of the prothrombin gene. fv leiden and factor ii g20210a mutations are associated with increased pro d u ctio n o f th ro mbin an d risk o f ven o u s 8 thrombosis. also factor v leiden mutation is found to be the most common inherited thrombotic risk factor associated with rpl its frequency in whites varies from 3% to 8% and 1 in 1000 are homozygous. it is rare in african americans, asians and native 9 americans. the incidence of genetic prothrombotic mutations in women with unexplained pregnancy loss was examined in various studies: some of these 10,11 studies supported the association. while others 1 2 , 1 3 r e p o r t e d n o a s s o c i a t i o n . t h e p r e s e n t retrospective case control study was conducted to evaluate the fv leiden g1691a and fii g20210a mutations and their affect on some coagulation profiles (pt and ptt) among women with a history of three or more consecutive pregnancy losses and healthy controls. this is the first study that investigated fv leiden g1691a and fii g20210a alleles and genotype distributions in the sudanese females with habitual rpl. materials and methods this was retrospective case control study. the genomic dna samples of one hundred and ninety five sudanese women who recruited and followed at omdurman maternal hospital were screened from aug 2012 to dec 2014. one hundred cases having a history of rpl were compared with ninety five healthy reproductive sudanese women as control group with a history of two or more successful live birth. cases and controls were tested for the fv leiden g1691a and fii g20210a. genomic dna was extracted from 3–5 ml of edta anti-coagulated 14 blood by salting. dna was extracted from the blood samples using master pure dna purification kit for blood gf-1 blood dna extraction kit, 50 preps (cat. no. gf-bd-050, vivantis technologies sdn. bhd., malaysia). fv leiden g1691a and fii. a 345-bp genomic dna fragment encompassing a part of the prothrombin gene that contains the mutation was amplified by pcr using specific primers forward (5'tct aga aac agt tgc ctg gc-3') and reverse primer (5'ata gca ctg gga gca ttg aag c-3). and 267-basepair (bp) segment of the factor v gene was amplified used specific forward primer (5'tca ggc agg aac aac acc at-3') and reverse primer 5'ggt tac ttc aag gac aaa ata cct gta aag c t 3. t h e rea ct io n p ro gra m wa s a s fo llows : denaturation at 94°c for 30 seconds, annealing at 51°c for 30 seconds, extension at 72°c for 30 seconds 15 for 35 cycles and 72 °c for 5 minute. a master mix was prepared by adding nuclease free water,10x b u f f e r, d n t p, t o w p r i m e r s , m g c l 2 ,ta q d n a polymerase and dna, the mixture was loaded into thermocycler according to the specific temperature profile. the working solution of 1x tbe is prepared from the stock solution (1 l) which contains the following: 89 mm tris base (108 gm), 89 mm boric acid (55 gm) 40 ml of 0.5m edta, adjust ph to 8.0.1.5% agarose was prepared from 1x tbe, and 5µl pcr products was loaded by mixing pcr products with 1µl loading dye, run on the gel for 30 mins and visualized on uv transllimantor. factor v digested with 10 µl of dna restriction enzyme mni1 at 37°cfor 18 h, subjected to 2% low melting point agarose and prothrombin product (10 μl) was digested with 20 u of hind iii, at 37°c for 16 h, and loaded into 2% low melting point agarose gel, eletropherosed at 90 volts for 60 mins . data were statistically described in terms of mean ± standard deviation (± sd), median and range, or frequencies (number of cases) and percentages where appropriate. odds ratio (or) and the 95% confidence interval (95%ci) were calculated for the presence of mutation between cases and controls and analyzed by spss prograrmme (version: 17.0). data were analyzed using the chi-square test to compareson the prevalence of mthfr mutation between patients and controls (the test considered significant when p.value <0.05). e t h i c a l c o n s e n t w a s o b t a i n e d f ro m e t h i c a l committee at hospital of omdurman maternity hospital (sudan). results the participants included 195 women subjects. out of them, 100 had a history of 3 or more events of recurrent fetal loss (abortion, miscarriage or still birth). their mean age± sd was 25 ± 4. ninety five jiimc 2016 vol. 11, no.3 point mutation in factor v leiden g1691a and factor ii g20210a 109 women were healthy the mean age of was 30 ± 4. the prothrombin time pt (p=0.93) and ptt (p=0.69) were normal among all women with r p l and controls. factor v leiden mutation distribution showed higher prevalence among study participant with r p l as compared to control group. the mutation was detected in 8 out of 100 (8.0%) and 6 out of 94 controls (6.4%). pvalue =0.66, odds ratio=1.28, 95% ci (0.42 to 3.84) the prevalence of heterozygous fvl mutation in recurrent miscarrige women was found to be 8 % but in control it found to be 6.4%. mutant allele (a) was seen only in 4 % of the cases. frequency of mutant allele (a) was 3.2 % and g allele occurred with a frequency of 96.8 % among controls. these results are statistically insignificant between the cases and controls group. prevalence of the prothrombin gene was 3% among cases with pvalue =0.091.but no mutant gene was detected among control group. according to the genotyping in cases showed (heterozygotes, 3.0%; homozygotes, 97.0%), alleles g (98.5%) and alleles a (1.5%) while in controls group show normal homozygous g/g (100%) and alleles g (alleles g). no significant association between cases carriage any of this mutation and risk with recurrent pregnancy miscarriage (table ii). the cases group was divided into subgroups based on time of recurrent abortion from second to eight times of repeated miscarriage. our data indicates that factor v gene mutation was most frequent in women with recurrent miscarriage. prothrombin mutation was found only among women with three time recurrent miscarriages with 100% and mthfr present in three, four and five times of recurrent miscarriage women with equal percentage 33.3% for each (table iii). digestion of factor v gene with mni1 enzyme on 2% agarose gel disolved in 1x tbe buffer, stanied with ethidium bromide , lane 1 molecular weight marker 50 bp, lane2 undigested pcr products lane 3 and 5 were hetrozygous mutant (ag), lane 4,6,7 and 8 ,9 and 10 were wild typ (aa), the 267 bp dna products digested with mni1. table i: frequency of factor v (leiden) muta�on among cases of recurrent pregnancy loss compared to controls table ii: frequency of prothrombin muta�on among cases of recurrent pregnancy loss compared to controls table iii: frequency of factor v (leiden) and prothrombin related to �mes of recurrent pregnancy loss 10 9 8 7 6 5 4 3 2 1 fig 1: pcr amplifica�on of fvl gene muta�on fig 2: pcr amplifica�on of prothrombin gene muta�on jiimc 2016 vol. 11, no.3 point mutation in factor v leiden g1691a and factor ii g20210a 110 digestion of prothrombin gene with hind iii on 2% agarose gel disolved in 1x tbe buffer, stanied with ethidium bromide , lane 1 molecular weight marker 100 bp, lane 2 (322 bp) , mutant(aa), control ,lane 3 and 5 were hetrozygous mutant (ga), lane 4,6 and 7 were wild type (gg), lane 8 undigested(345 bp). discussion one hundred sudanese women suffering from rpl as compared to ninety five healthy women. because inherited thrombophilia has been implicated as a 16 possible cause of rpl. gene defects frequently associated with rpl were prothrombin a20210g 17 and factor v leiden reported in many studies. due to their important roles in the coagulation pathway, this study was conducted to investigate the association between genetic polymorphisms of factor v and factor ii g20210a among women experiencing rpl. the frequency of polymorphic a allele was more prevalent in rpl patients (8%) than in controls (6.4%) and the g allele was less prevalent in rpl patients (98%) than in controls (100%).the prothrombin g20210a mutation our result revealed that the mutation not common among recurrent spontaneous aborted sudanese women they were found heterozygous g/a alleles with frequency 3% and did not found any mutated gene among control group. the frequency of polymorphic a allele was prevalent in rpl patients (1.5%) and the g allele was less prevalent in rpl patients (98.5%) than in controls (100%). our finding was consistence with 18 19 20 altintas et al, 2007 , freire et al , sottilotta et al 21 and dalmaz et al but it was inconsistent with mello 22 23 24 et al , behjati et al , and bagheri et al. prothrombin time (pt) and partial thromboplastin time (ptt) in women with rpl in this study were not affected significantly (p=0. 93 and p=0.69) respectively this is similar to the normal results reported by ghulam, et.al., (2014) among sixty three pakistanian women with history of three spontaneous abortions in their 25 first three months of pregnancy. also our finding in 26 pt and ptt were consistence with salamat et al and 27 shahida et al. the normal result of pt and ptt in women with v leiden g1691a, factor ii g20210a because the patient with these mutations makes fibrin at same rate as a person with normal factor v. it's just that later on, when the body tries to turn factor v off, the factor v leiden patient will keep on making fibrin. in future sample should be increased and study may extent to other provinces in sudan to cover up more races and tribes and make the study more accurate and precised. conclusion in our study we found that the polymorphism in v leiden g1691a and fii g20210a mutation do not increase risk for rpl in tested population and there are no any affect of these mutations in the prothrombin time (pt) and partial thromboplastin time (ptt). acknowledgement we are grateful to the patients and healthy individuals for participating in our study. references 1. meka a , nagaraja t, andal s, 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"factor v leiden g1691a and factor ii g20210a point mutations and pregnancy in north-west of iran." archives of gynecology and obstetrics. 2011; 28: 1311-5. 25. ghulam sn, rashid am, asghar kh , saeed ss , ikram uu. analysis of anti phospholipid antibodiesin women with recurrent spontaneous abortion. isra medical journal. 2014; 6: 23-7. 26. salamat n, saleem m, ahmed t. lupus coagulant and anticardiolipin antibodies in patients with recurrent fetal loss: a case control study. ann saudi med. 2000; 20: 450-3. 27. shahida m, amber i, lubna rd, ghulam r, shabbir hm, ikram u. levels of anti phospholipid antibodies in females with recurret abortions. ann. pak. inst. med. sci. 2011; 7: 156-9. jiimc 2016 vol. 11, no.3 point mutation in factor v leiden g1691a and factor ii g20210a 112 page 21 page 22 page 23 page 24 page 25 original�article abstract objective: to check the expression pattern of cyclin-d1 in stage i head and neck squamous cell carcinoma (h.n.s.c.c.) cases (evaluated based on history, clinical, medical, and radiological records) in our setting and evaluate the role of cyclin-d1 as a prognostic marker of h.n.s.c.c. (considering recurrence within five years and metastasis). study design: retrospective cohort study. place and duration of study: the study was carried out at armed forces institute of pathology (a.f.i.p.) rawalpindi working in conjunction with the department of radiation oncology, rawalpindi. the duration of th th study was from 7 march 2022-14 october 2022. materials and methods: the study comprised 92 patients from year 2015-16 of stage i diagnosed with squamous cell carcinoma of head and neck with complete five-year follow-up after fulfilling the inclusion and exclusion criteria. after collecting and matching the data on follow-up with record of the patients from department of radiation oncology, c.m.h., rawalpindi; paraffin-embedded blocks of these patients from year 2015/2016 were retrieved. fresh hematoxylin and eosin (h&e) slides were prepared, and diagnosis was reconfirmed, vimentin stain was applied to check the antigenicity of the tissue followed by application of cyclind1 immuno-histochemical marker (i.h.c.) marker with controls to check the expression pattern. results: in our study we included a total of 92 diagnosed cases of stage i h.n.s.c.c. with a complete 5-year follow-up. out of 92 cases male to female ratio was almost 3:1 with males comprising a total of 68 (73.9%) and females comprising 24 (26.1%). mean age of patients was 62.48+ 11.439 years. larynx was the most frequently involved site 34.8% (n=32), followed by tongue 23.9% (n=22) and buccal mucosa 13.0% (n=12). cyclin-d1 expression and tumor grade were revealed to have a statistically significant clinicopathological relationship (p value 0.001). a statistically significant association between the expression of cyclin-d1 and tumor recurrence (p value < 0.001) and duration of tumor recurrence (p value 0.003) was seen. the cyclin-d1 expression was also compared with metastasis which was also statistically significant (p value 0.003). conclusion: an increased risk of metastasis and recurrence is linked to increased levels of cyclin-d1 expression in the early years. hence it is valuable to include cyclin-d1 expression in the initial diagnostic work up of h.n.s.c.c. for an early prognostic assessment. further use of these results could be made for targeted treatment of head and neck malignancies. key words: cyclin-d1, five-year follow-up, head-and-neck squamous cell carcinoma, immuno-histochemical expression, prognosis. with distinct clinical and biological characteristics, causing an estimated 17,960 deaths worldwide each 1 year. h.n.s.c.c. has a substantial risk of both metastases and local recurrence, so aggressive treatments are typically performed to maximize the 2 likelihood of long-term control. these treatments may include surgery, radiotherapy, and/or chemotherapy. the high prevalence of this cancer requires special concern to devise authentic treatment protocols that are least invasive and show 3 better outcomes. despite advancements in cancer prevention and treatment, the five-year survival rate of a patient with head and neck squamous cell introduction among the top ten types of human cancer, head and neck malignancies are a diverse category of tumors prognostic value of cyclin-d1 expression in head-a nd-neck squamous cell carcinoma: a half-decade follow-up 1 2 3 4 5 6 azka haroon , muhammad nadeem zafar , nighat ara ,saadia muneer ,zunaira saeed , zainab asif sukhera correspondence: dr. azka haroon department of histopathology armed forces institute of pathology, rawalpindi e-mail: azkaharoon.haroon@gmail.com 1,2,4,5,6 department of histopathology armed forces institute of pathology, rawalpindi 3 department of oral pathology, army medical college, rawalpindi received: december 18, 2022; revised: march 13, 2023 accepted: march 14, 2023 prognostic value of cyclin-d1 in hnsccjiimc 2023 vol. 18, no.1 22 https://doi.org/10.57234/jiimc.march23.1600 carcinoma remains lower than that of other malignancies, such as colorectal, breast and 4 cervical. in conventional t.n.m. classification systems, the molecular heterogeneity of squamous cell carcinoma of the head and neck (h.n.s.c.c.) is 5 not taken into account. hence, it is imperative to understand how recent molecular markers that have been identified correlate with prognosis for h.n.s.c.c., as they may offer new methods for early diagnosis, evaluation of prognosis and treatment. cyclin-d1 a gene found on chromosome 11q13 plays 6 a major role in activation of cell-cycle progression. cyclin-d1 overexpression has been proposed by various international studies as a good marker for predicting poor prognosis in diagnosed cases of 6,7,8,9 h.n.s.c.c., but these studies show the lack of proper follow-up, the uncertainty of such results in oral squamous cell carcinoma (o.s.c.c.), and smaller 10 overall sample size. this study's objective was to assess the expression of cyclin-d1 on a larger sample of stage i h.n.s.c.c. cases with a documented complete five-year follow-up to determine its prognostic significance. so that if the association is proved then cyclin-d1 marker should be made part of the diagnostic protocol. patients with strong expression of cyclin-d1 on premier biopsy should be kept at close follow-up and treatment should be planned accordingly (targeted therapy can be given to patients such as cyclin-d inhibitors). if on the contrary this association is disapproved then we should stop investing time and money on this marker and evaluate better prognostic markers for the improvement in the treatment of patients with h.n.s.c.c. information in regard to this study was collected on data collection questionnaire in the form of variables, statistical analysis was performed using s.p.s.s. version 26.0, microsoft excel 2013 was used for diagrammatic representations, qualitative / categorical variables were presented as frequency and percentages, to compare various parameters chi-square test was performed and p-value of 0.05 was considered to be the essential level of significance. materials and methods a retrospective cohort study was carried out at armed forces institute of pathology (a.f.i.p.). this study had 92 patients in total. the approach of nonprobability convenient sampling was applied. the study was conducted after the approval of ethical review committee (letter number: mp-omp20th 1/read-irb/21/781, dated: 30 -december-2021). contact details of all cases diagnosed from armed forces institute of pathology (a.f.i.p.) of squamous cell carcinoma of head and neck region from january 1, 2015, to december 31, 2016 were taken from archives of histopathology department at armed forces institute of pathology (a.f.i.p.), rawalpindi, pakistan. the diagnosed patients of stage 1 h.n.s.c.c. were contacted for consent to participate in the research and five-year follow-up i.e., till december 31, 2021, and onwards. the data was matched with the record of these patients kept in the department of radiation oncology, c.m.h. rawalpindi. after collecting the data on follow-up of these patients, paraffin-embedded blocks of these patients from year 2015 to 2016 were retrieved. confounding factors were excluded by firmly following the exclusion criteria [patients lost to follow-up or could not be contacted, poorly fixed specimens, very scanty tissue specimens, extensive necrosis or the retrieved blocks failed to take vimentin stain to check the antigenicity of tissue, patients dying within the study period, patients who had irretrievably taken away paraffin sections, cases diagnosed with h.n.s.c.c. of conjunctiva or skin or cases diagnosed with any immuno-morphological subtype of squamous cell carcinoma or mixed forms (with more than one component) i.e. adenosquamous carcinoma ] and inclusion criterion [all stage i h.n.s.c.c. cases with a documented complete five-year follow-up (evaluated on the basis of history, clinical, medical and radiological records) in our setting at a.f.i.p. during the calendar year january 1, 2015december 31, 2016 (irrespective of age, gender or ethnicity)].h&e slides were prepared freshly for already diagnosed cases, but to eliminate bias the slides were viewed by three investigators separately. after confirmation of diagnosis on freshly prepared h&e slides, vimentin stain was applied to check the antigenicity of the tissue, followed by the application of cyclin-d1 immunohistochemical marker by leica microsystem (germany). lymph node tissue (mantle cell lymphoma) was used as positive control and appendix tissue was used as negative controls for cyclin-d1. when distinct brown nuclear staining was observed in ≥1% of the cells, the prognostic value of cyclin-d1 in hnsccjiimc 2023 vol. 18, no.1 23https://doi.org/10.57234/jiimc.march23.1600 tissue samples was considered positive for cyclin-d1. cytoplasmic staining was not considered. the quantification criteria by dhingra et al., was used to 9 quantify cyclin-d1 expression. the sections with an inter-observer difference of more than 10% were reexamined by means of a multi-headed light microscope to reach consensus. information was collected on data collection questionnaire in the form of variables, statistical analysis was performed using s.p.s.s. version 26.0, microsoft excel 2013 was used for diagrammatic representations, qualitative / categorical variables were presented as frequency and percentages, to compare various parameters chi-square test was performed and p-value of 0.05 was the essential level of significance. results a total of 92 diagnosed cases of stage i h.n.s.c.c. with a complete 5-year follow-up were included in the study. out of 92 cases male to female ratio was almost 3:1 with males comprising a total of 68 (73.9%) and females comprising 24 (26.1%). mean age of patients was 62.48+ 11.439 years. larynx was the most frequently involved site 34.8% (n=32), followed by tongue 23.9% (n=22) and buccal mucosa 13.0% (n=12). the chi-square test revealed a stat i st i ca l l y s i g n i f i ca nt c l i n i co p at h o l o g i ca l relationship between cyclin-d1 expression and tumor grade (p value 0.001) table i. the cyclin-d1 expression was also compared with recurrence within five years by using chi-square test which was statistically significant (p value < 0.001) table ii and a statistically significant association was also seen between cyclin-d1 expression and duration of tumor recurrence (p value 0.003) table iii. the cyclin-d1 expression was also compared with metastasis within five years by using chi-square test which was also statistically significant (p value = 0.003) table iv discussion cyclin-d1 is a gene located on chromosome 11q13 and plays a major role in activation of cell-cycle progression. cyclin-d is a cyclin-dependent kinase (c.d.k.) 4 and c.d.k. 6-binding cell cycle regulator. the stimulation of d.n.a. synthesis and the transition of cells between the g1/s phases are both 11 significantly influenced by this cyclin-cdk complex, 12 rendering it a genuine target during carcinogenesis. as a result, it has been determined that 30% of head 13 and neck s.c.c. have cyclin-d1 amplification. in our investigation, it was discovered that cyclin-d1 expression positively associated with tumor grade. when the histopathological grade increased, from well differentiated to poorly differentiated table i: case distribution based on overall cyclin-d1 expression score and tumor grade (n=92) p-value = 0.001 table ii: case distribution based on overall cyclin-d1 expression score with recurrence (n=92) p-value = 0.001 table iii: case distribution based on overall cyclin-d1 expression score with recurrence as per follow up duration (n=92) p-value = 0.003 table iv: case distribution based on overall cyclin-d1 expression score with metastasis (n=92) p-value = 0.003 prognostic value of cyclin-d1 in hnsccjiimc 2023 vol. 18, no.1 24 https://doi.org/10.57234/jiimc.march23.1600 h.n.s.c.c., the percentage of cyclin-d1 expression increased as well. in various studies, higher cyclin-d1 expression has been linked to poor histological 8 grade. according to chinnathambi et al., in year 2021cyclin-d1 immuno-expression was discovered in all patients, and it was substantially correlated with deteriorating tumor grade and positive lymph node disease. nevertheless, several authors discovered no clinical correlation. batool et al. in 2020 in her study described similar findings that the histological grade of h.n.s.c.c. was not substantially 14 correlated with cyclin-d reactivity. zand et al. in 2020 and nazar et al. in year 2020 also described that the results of their study demonstrated no link between expression of cyclin-d1 and grade of the 15, 16 disease. the main finding of our research was that the stage i diagnosed cases of h.n.s.c.c. showing an elevated expression of cyclin-d1 at the time of diagnosis were at a greater risk of developing recurrence in the earlier years of five-year period of follow-up as compared to those cases showing a weak or no expression of cyclin-d1 immuno-histochemical stain. another important finding of this study was that cyclin-d1 expression was found to positively correlate with tumor metastasis. an increase in cyclin-d1 expression at the time of diagnosis of stage i cases of h.n.s.c.c. was found to show an increased risk of developing tumor metastasis within the five year of diagnosis of tumor. various studies have been conducted on this molecular marker suggesting that strong positivity of cyclin-d1 expression in h.n.s.c.c. is related to metastasis and recurrence in operable cases of 9 h.n.s.c.c. sharada et al., in year 2018 and patel et al., in year 2017 described similar results in their studies that overexpression of cyclin-d1 has been seen to associate with an increased risk of metastasis 17,18 of lymph nodes and increased risk of recurrence. our research had this limitation that five year survival of the cases could not be included in the study to determine prognostic value of cyclin-d1 as it was a retrospective study and confounders could not be removed for those who died within five years; as exact cause of death could not be determined for those dying within study period (five years of diagnosis of h.n.s.c.c.).hence, prospective followup study is recommended including five year survival of cases as a variable to determine prognostic value of cyclin-d1 thus minimizing confounders by notifying exact cause of death of participants within the study period. conclusion this study showed a statistically strong association between recurrence, duration of developing recurrence and metastasis with increasing cyclin-d1 expression. therefore, an increased risk of metastasis and recurrence is linked to increased levels of cyclin-d1 expression in the early years. hence it is valuable to include cyclin-d1 expression in the initial diagnostic work up of h.n.s.c.c. for an early prognostic assessment. . further use of these results could be made for targeted treatment of head and neck 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10(4): 330-45. doi: 10.1159/000515304. 16. n a z a r m , n a z i , m a h m o o d m k , h a s h m i s n . immunohistochemical expression of cyclin d1 and ki-67 in primary and metastatic oral squamous cell carcinoma. a s i a n pa c j c a n c e r p re v. 2 0 2 0 ; 2 1 ( 1 ) : 3 7 4 1 . doi:10.31557/apjcp.2020.21.1.37. 17. sharada p, swaminathan u, nagamalini br, vinodkumar k, ashwini bk, lavanya v. a semi-quantitative analysis of immunohistochemical expression of p63, ki-67, cyclin-d1, and p16 in common oral potentially malignant disorders and oral squamous cell carcinoma. j ntr univ health sci. 2018; 7(2): 120-8. 18. denaro n, merlano mc, lo nigro c. further understanding of the immune microenvironment in head and neck squamous cell carcinoma: implications for prognosis. c a n c e r m a n a g r e s . 2 0 2 1 : 3 9 7 3 8 0 . d o i : 10.2147/cmar.s277907. conflict of interest authors declared no conflicts of interest. grant support and financial disclosure authors have declared no specific grant for this research from any funding agency in public, commercial or nonprofit sector. data sharing statment the data that support the findings of this study are available from the corresponding author upon request. this is an open access article distributed under the terms of the creative commons attributionnoncommercial 2.0 generic license. prognostic value of cyclin-d1 in hnsccjiimc 2023 vol. 18, no.1 26 https://doi.org/10.57234/jiimc.march23.1600 original�article abstract objectives: to determine the acceptance of long-acting reversible contraceptives (larc) and uptake of subdermal implants and follow-up response in women seeking contraceptive advice. study design: observational case series. place and duration of the study; gynecology opd and family planning center bolan medical complex hospital quetta, january 02, 2018, to december 30, 2019. materials and methods: women found eligible for long-acting reversible contraceptives, amongst those seeking contraceptive advice, were included in this study after informed consent. the women found eligible were given the choice of long-acting contraceptives. women, who opted for intrauterine contraceptive device were referred to the family planning center and those who accepted subdermal implants were sent to gynae minor operation theater after informed consent. microsoft excel was used for the analysis of data. mean and standard deviation was calculated for quantitative data. frequencies and percentages were calculated for qualitative data. results: a total number of 3670 women seeking contraception were advised long-acting reversible contraceptives. whereas 1423(38.77%) accepted long-acting reversible contraceptives amongst the women who opted for it, 64.23% accepted subdermal implants and 35.76% opted for intrauterine contraceptive devices. out of 1423 women who accepted long-acting reversible contraceptives, only 25 % turned out for follow-up. discontinuation of long-acting reversible contraceptives was observed in both subdermal groups st (8.09%) and intrauterine contraceptive device groups (4.51%) during 1 year of initiation. conclusion: acceptance of long-acting reversible contraceptives (larc) and uptake of subdermal implants is reasonable among the women seeking contraceptive advice. these contraceptive methods may be offered as first-line contraceptives for most women provided that the cost barrier is eliminated. key words: contraception, family planning, iucd, larc, subdermal implants. unintended pregnancies in pakistan is reported to be 2 between 16-46%. the contraceptive prevalence rate 1 is 34.2% in pakistan. in different parts of the country use of contraceptives shows uneven progress with high unmet needs for family planning. intrauterine contraceptive devices and subdermal implants are the most effective methods of long2 acting reversible contraception. the long duration of action of long-acting reversible contraceptives (larc), (3 to 10 years) makes them highly desirable methods of contraception, as they do not require maintenance, once in place. recent evidence shows 3,4,5 that larc methods are safe and convenient to use. these methods are highly effective with a low failure rate and the additional advantage of being cost3,7 effective in the long run. the world health organization (who) estimates that only one unintended pregnancy occurs among every 20008 implant user in the first year of use. currently, three larc methods are available in introduction rapid population growth remains a major concern in our country. in pakistan, the annual population growth rate is 1.41% and the fertility rate is 2.55 1 children born/women. high fertility rate and limited access to contraception are the main causes of rapid population growth. pakistan's population growth rate has declined from 3% in the late 1980s to the present estimated level of 1.41% per annum but it remains unacceptably high. the prevalence of larc acceptance, subdermal implant uptake, and follow-up response in women seeking contraceptive advice 1 2 3 4 5 rakhshanda neelofar , shama jogezai , fozia muhammad bakhsh , safia bibi , pari gul correspondence: dr. rakhshanda neelofar senior registrar department of gynecology bolan medical college, quetta e-mail: dr.rakhshinda.mushtaq@gmail.com 1,2,3,4 5 department of gynecology/radiology bolan medical college, quetta funding source: nil; conflict of interest: nil received: november 06, 2021; revised: march 10, 2022 accepted: march 14, 2022 larc acceptance and follow up responsejiimc 2022 vol. 17, no.1 32 pa k i sta n i . e . , c u i u c d, t h e l evo n o rge st re l intrauterine system, and the etonogestrel implant. fda has approved the cu-t380a for up to 10 years, the levonorgestrel intrauterine system for up to 5 years, and the etonogestrel implant for up to 3 years of continuous use. these methods do not contain estrogen and may be used in conditions where estrogen is contra-indicated like in women with uncontrolled hypertension, smokers aged >35 years, women with a personal history of a venous thrombotic event, or a family history of inherited 9 thrombophilia. unplanned pregnancy continues to be a major problem in balochistan due to limited access to family planning services. long-acting reversible contraceptive methods are less frequently used in balochistan. by increasing the uptake of long-acting reversible contraceptive methods, the high rate of unintended pregnancies can be reduced. keeping in view the low contraceptive prevalence rate and high unmet need, much is needed to be done by the state to avoid unintended pregnancies and associated complications. the capital investment in this regard needs to be increased to fill the gap between demand and supply. data regarding acceptance and uptake of the larc in baluchistan was not available in the literature. the objectives of this study were to determine the acceptance of long-acting reversible contraceptives, subdermal implant uptake, and subsequent follow-up response in women seeking contraceptive advice at bolan medical complex hospital (bmch) opd. this study aimed to provide baseline data to the service providers and policymakers to plan appropriate steps to address the problem of rapid population growth. so, research was planned to determine the percentage a c c e p t a n c e o f l o n g a c t i n g r e v e r s i b l e contraceptives (larc) and uptake of subdermal implants and follow-up response in women seeking contraceptive advice. materials and methods this observational study was carried out at gynecology opd of bolan medical complex hospital quetta. all women attending gynae opd and family planning center for contraceptive advice from january 02, 2018, to december 30, 2019, were included. women with risk factors for larc were excluded from the study. all possible ethical issues were addressed, and approval was obtained from the institutional ethical review board prior to the conduction of the study. informed consent was taken from respondents. data was collected on the prescribed form by the researchers themselves. women without any risk factors and genuine candidates for larc were given the choice of longacting contraceptives. they were explained about cost, advantages, and possible risks of larc. the patients who opted for iucd were referred to the family planning center and those who accepted subdermal implants were sent to gynae minor ot after informed consent., iucd was inserted in the family planning center by trained persons using the standard procedure under the supervision of the incharge chief medical officer. subdermal implants were inserted in minor gynae ot by consultant gynecologists, senior medical officers, and residents (under supervision) using standard methods. the women were called for follow-up after a month and then at 3 monthly intervals for 12 months to collect data regarding side effects of larc (menstrual irregularities) and to record their compliance with the chosen method. ms excel was used for the analysis of data. mean and standard deviation was calculated for quantitative data. frequencies and percentages were calculated for qualitative data. results a t o ta l n u m b e r o f 3 6 7 0 w o m e n s e e k i n g contraception, were advised long-acting reversible contraceptives. as shown in table-i, larc was a c c e p t e d b y 1 4 2 3 ( 3 8 . 7 7 % ) w o m e n a n d 2247(61.22%) refused it. amongst the women who opted for larc, 914(64.23%) accepted subdermal implants and 509(35.76%) opted for iucd. out of 1423 women who accepted larc, 356(25.01%) turned out for follow-up, while 1067(74.98%) lost from follow-up. [table-i] discontinuation of larc was observed in both subdermal groups [74 (8,09%)] and iucd groups [23(4.51%)] during the 1st year of their initiation. discussion pakistan has the second-highest fertility rate in south 13 asia. the contraceptive prevalence rate is low and the unmet need for family planning is very high in 11 pakistan (20%). a study conducted by asif, m.f et al revealed that the use of contraception was lowest in baluchistan with a contraceptive prevalence rate of 12 29 %. 33 larc acceptance and follow up responsejiimc 2022 vol. 17, no.1 table i: acceptance, uptake of different methods, follow up response, and discontinuation of larc implants. we have observed that the women who were initially interested in subdermal implants, knowing the cost of the implant never showed up. by eliminating the cost barrier, the uptake of larc may be increased. as reported by guiahi m that after the implementation of the affordable care act (aca) in america, the upfront cost of larc is reduced which 18 resulted in a substantial increase in uptake of larc. follow-up response was very poor, as only 25.01% turned out for follow up and 74.98 % were lost from follow-up. due to poor follow-up response, the continuation rate could not be assessed but it may be assumed satisfactory from the fact that the women, who turned up for follow-up were having menstrual irregularities. the larc discontinuation rate recorded during the study period was 8,09% in the subdermal implant group and 4.5% in the iucd group. the results of our study are comparable with the results of a study conducted by lendvay et al., who reported a 10% discontinuation rate among 19 subdermal implant users while the discontinuation rate among iucd users reported in our study is lower than the rates recorded by another study conducted 20 by azmat sk et al. (4.5% vs 16.3%). the limitation of our study is that the women's satisfaction and continuation rate could not be assessed due to poor follow-up response, which may be due to lack of adaptation of a convenient and efficient mechanism for follow-up. the health sector in pakistan is facing many challenges due to a lack of effective planning and inadequate performance. the results of our study will provide information to the policymakers in decision-making regarding the provision of contraceptive services in our province. keeping in view the poverty and poor access of women to health facilities, the provision of free commodities may further increase the uptake of highly effective larc and decrease the number of unplanned pregnancies. high maternal mortality in our country especially in baluchistan is mostly due to unintended pregnancies in women of high parity, in addition to lack of wellequipped health care facilities. efforts are needed to improve women's access to contraceptives. there seems to be a dire need to train the health care providers and to reduce the upfront cost of the larc. the capital investment in this regard needs to be increased and concrete actions must be taken to during the study period, 3670 eligible women were included in the study. after thorough counseling by gynecologists, medical officers, and post-graduate residents, 38.77% of them accepted the larc for birth spacing. the larc acceptance was found higher in our study (38.77 %) than previously reported by 13 the national institute of population study (26%). that reveals a slow rising upward trend in uptake of larc over 7 years. a study conducted by adedini et al also reported a slow but upward trend in uptake of larc as in malawi, the larc uptake increased from 0.46% in 2004 to 9.76% in 2016 and in zimbabwe, 14 from 1.04% in 2006 to 8.51% in 2015. larc was refused by 61.22 % of the study group due to fear of complications. the results of our study are comparable with the findings of a study conducted by sedgh g et. al., who reported fear of side effects as a cause of unmet need in 25% of the asian 15 population. regarding subdermal implant uptake, it was found to be 64.23%. to our surprise, most women preferred subdermal implants over iucd, as 35.76 % of the study population accepted iucd. a study conducted by khan et al also revealed that 16 most of the women were reluctant to choose iucd. subdermal implants are relatively new methods with fewer myths surrounding them. jacobstein et al., also reported that an increase in the use of implants 17 has largely improved the uptake of larc in africa. subdermal implants were mostly chosen by young women. the women in the study group were aged between 26-43 years and their parity ranged from para 3-11. the satisfactory uptake of the subdermal implants in this study can be attributed to the free provision of contraceptive commodities by ngos during the study period. the cost was found to be the major constraint in the uptake of the subdermal 34 larc acceptance and follow up responsejiimc 2022 vol. 17, no.1 control the population explosion. it will be beneficial to find out the trends and determinants of uptake of larc in baluchistan in the future. conclusion acceptance of long-acting reversible contraceptives (larc) and uptake of subdermal implants is r e a s o n a b l e a m o n g t h e w o m e n s e e k i n g contraceptive advice. these contraceptive methods may be offered as first-line contraceptives for most women provided that the cost barrier is eliminated. references 1. index mundi. [internet] pakistan demographic profile 2019. [updated 2019 december 7 cited 2020 september 20] available from www.indexmundi.com. 2. muhammad ah, camille rg, sidrah n. prevalence, and determinants of unintended pregnancies amongst women attending antenatal clinics in pakistan. bmc pregnancy and childbirth (2017) 17:156-66. 3. fekadu h, kumera a, yesuf ea. prevalence and determinant factors of long-acting contraceptive utilization among married women of reproductive age in adaba town, west arsi zone, oromia, ethiopia. j women's health care. 2017; 6(360):01-11. 4. waggoner mr, lanzi rg, klerman lv. pregnancy intentions, long-acting contraceptive use, and rapid subsequent pregnancies among adolescent and adult first-time mothers. journal of child and adolescent psychiatric nursing. 2012; 25(2):96–104. 5. tibaijuka l, odongo r, welikhe e. factors influencing use of long-acting versus short-acting contraceptive methods among reproductive-age women in a resource limited setting. bmc women's health. 2017; 17(1):25-31. 6. hasselback l, dicko m, viadro c. understanding and addressing contraceptive stockouts to increase family planning access and uptake in senegal. bmc health services research. 2017; 17(1):373-379. 7. shoupe d. larc methods: entering a new age of contraception and reproductive health. contraception and reproductive medicine. 2016; 1(1):4-13. 8. susan o, gathari n, mark k. long-acting reversible contraception uptake and associated factors among women of reproductive age in rural kenya.int. j. environ. res. public health 2019; (16) :1543-44. 9. david m. luesley d. obstetrics & gynecology an evidencerd based text for mrcog.3 ed.uk.crc press taylor &francis group;2016; 16(1):558-562. 10. trussell j, hassan f, henry n, pocoski j, law a, filonenko a. cost-effectiveness analysis of levonorgestrel-releasing intrauterine system (lng-ius) 13.5 mg in contraception. contraception. 2014;89(5):451–459. 11. moazzam a, syed ka, and hasan bh. assessment of modern contraceptive continuation, switching and discontinuation among clients in pakistan: study protocol of 24-months post family planning voucher intervention follows up. bmc health services research. 2018 18:359-367. 12. asif m. pervaiz z. socio-demographic determinants of unmet need for family planning among married women in pakistan. bmc public health; 2019, 1226(19):14-17 13. national institute of population studies, macro international inc. pakistan demographic and health survey 2012-2013. islamabad: government of pakistan; 2013. 14. adedini s, omisakin o, somefun o. trends, patterns, and determinants of long-acting reversible methods of contraception among women in sub-saharan africa. journal of plos global public health 2019; 14(6):19-35. 15. gilda s. lori s. ashford r. rubina h. unmet need for contraception in developing countries: examining women's reasons for not using a method, new york: guttmacher institute. 2016; 13(2) 01-92. 16. khan a, shaikh bt. an all-time low utilization of intrauterine contraceptive device as a birth spacing methoda qualitative descriptive study in district rawalpindi. pakistan 17reprod health. 2013;10 (1):10-16. 17. jacobstein, r. liftoff s: the blossoming of contraceptive implant uses in africa. glob. health sci. pract. 2018; (6): 1739. 18. guiahi m. religious refusals to larc in catholic settings. american journal of obstetrics and gynecology 2020; 4(222).23-30. 19. lendvay a, otieno-masaba r, azmat sk, wheeless a, hameed w, shaikh bt. effectiveness, safety, and acceptability of sino-implant (ii) during first year of use: results from kenya and pakistan. contraception. 2014; 89:197–203. 20. azmat sk, shaikh bt, hameed w, bilgrami m, mustafa g, ali m, et al. rates of iucd discontinuation and its associated factors among the clients of a social franchising network in pakistan. bmc women's health. 2012; 12:8-10. 35 larc acceptance and follow up responsejiimc 2022 vol. 17, no.1 conflict of interest authors declared no conflicts of interest. grant support and financial disclosure authors have declared no specific grant for this research from any funding agency in public, commercial or nonprofit sector. data sharing statment the data that support the findings of this study are available from the corresponding author upon request. this is an open access article distributed under the terms of the creative commons attributionnoncommercial 2.0 generic license. original�article abstract objective: to determine the frequency of different refractive disorders in patients visiting dhq hospital sargodha. study design: cross sectional study. place and duration of study: study was conducted at department of ophthalmology, dhq. hospital sargodha rd th from 3 february 2017 to 7 april 2017. materials and methods: a total of 5764 patients attending ophthalmology department of dhq hospital sargodha were screened for refractive disorders by measuring visual acuity and carrying out pin-hole test. after this auto refraction (using topcon refractometer) and subjective refraction examination (trial and error method) were carried out. retinoscopy was done in children, following which cycloplegic refraction was performed. the results of examination were recorded from hospital records and data analyzed using spss version 19. p value of <0.05 was taken as significant for chi square test. results: among refractive disorders, hypermetropia (28.29%) was most prevalent followed by astigmatism (28.32%), myopia (21.76%) and presbyopia (21.63%). females suffered more from refractive disorders (58.21%) as compared to men (41.79%). on the basis of age group, myopia was the most common disorder amongst children (2.44%), adolescent (4.67%) and early adulthood (9.81%) while presbyopia was most common in middle adulthood (17.23%) and late adulthood (2.38%). conclusion: hypermetropia, astigmatism, myopia and presbyopia are common refractive disorders in population of sargodha district of punjab, pakistan. refractive disorders are more common among females. with the exception of myopia, these tend to occur more in older age groups. key words: astigmatism, hypermetropia, myopia, presbyopia, refractive disorders. occurs when light is focused behind retina. again this can be because of decreased refractive power of eye or its reduced axial length. presbyopia is an insufficiency of accommodation while astigmatism results when parallel rays of light entering eye fail to 1 form a single focal point on retina. who launched its first report on vision in 2019 in an effort to address the challenges posed by uncorrected refractive errors. a whopping 2.6 billion people are estimated to be myopic and 1.8 billion suffering from presbyopia. it is also estimated that 1 billion people suffer from vision impairment that could have been prevented or is yet to be addressed. 123.7 million, of these 1 billion people suffer from 2 unaddressed refractive errors. the costs of the coverage gap for uncorrected refractive disorders and cataract globally are estimated to be 2 $14.3 billion us dollar. lack of basic healthcare infrastructure further compounds problems faced by low income countries like pakistan. while who report on vision and other global studies provide a introduction refractive errors result because of inability of eye to focus light onto the retinal plane. this leads to the blurring of vision. refractive errors are categorized into (i) myopia (ii) hypermetropia (iii) presbyopia (iv) astigmatism. myopia results when light entering eye is focused in front of retina either on account of increased refractive power of eye or because of increased axial length of eyeball. hypermetropia refractive errors in patients attending dhq hospital sargodha: a crosssectional study 1 2 3 4 ibtissam bin khalid , muhammad hunaid hassan , mazhar nasim , yahya umair azam correspondence: dr. ibtissam bin khalid house officer department of general surgery mayo hospital, lahore e-mail: ibtissambinkhalid@yahoo.com 1 department of general surgery mayo hospital, lahore 2 4 department of general surgery/medicine district headquarter hospital, gujranwala 3 department of orthopedics district headquarter hospital, sargodha refractive disorders in a local populationjiimc 2020 vol. 15, no.3 funding source: nil; conflict of interest: nil received: october 26, 2019; revised: august 29, 2020 accepted: august 29, 2020 163 in minus cylinder was used for astigmatism. the results of examination were recorded from hospital records and data analyzed using spss version 19. while performing chi-square test p-value of <0.05 was taken as significant. literature related to the study was sought using pubmed health, medline and manual google searches. results a total of 5,764 patients were included in the study. the mean age and standard deviation of study subjects was 37.43 and 18.40 respectively. the overall age-range of study participant was 3-105 yr. a majority of patients presented with combination of refractive disorders rather than a single disorder. table i shows distribution of different refractive disorders on the basis age and sex. table ii shows the distribution on the basis of gender (without taking age into consideration), while table iii indicates distribution in different age groups (without taking gender into consideration). rough estimate, these fail to highlight challenges faced at a local level and there is a need to supplement these with local level studies so as to get 3,4,5 a better picture of the task at hand . mapping of disease at district level will allow efficient distribution of limited health care resources. there is no record of a prior study on refractive disorders in sargodha district. addressing this scarcity of local level data and to highlight gender/age based variations in refractive disorders were the main aims of this study. sargodha district, punjab (pakistan) was selected for this purpose. sargodha district has an estimated population of 2.67 million as per 1998 .6 census dhq hospital sargodha provides health care services to a large chunk of this population which made it an ideal place for conducting a study with the objective of determining the frequency of different refractive disorders in patients visiting the hospital. materials and methods this was a cross-sectional study conducted at department of ophthalmology, dhq sargodha from rd th 3 feb 2017 to 7 april 2017. a total of 5,764 patients with refractive disorders visited the ophthalmology department during this period. the diagnosis of any of the refractive disorders was the inclusion criteria while emmetropic individuals and those with squint were not included in the study. permission was granted by the ethical review board of dhq hospital sargodha after reviewing the pilot study. on the basis of age, patients were classified as (i) children (012yr) (ii) adolescence (13-19yr) (iii) early adulthood (20-40yr) (iv) middle adulthood (41-65yr) (v) late adulthood (more than 65yr). patients were informed about the nature of study and its significance. in a brief interview in with the patient their name, age, sex and address were inquired. initially, visual acuity was determined and pin-hole test carried out by the medical officer in charge of refraction room. this was followed by auto refraction using topcon refractometer and subjective refraction examination (trial and error method) by consultant ophthalmologist. retinoscopy was carried out in children (0-12yr), following which they underwent cycloplegic refraction. myopia was defined as spherical equivalent values of less than -0.5 d, hypermetropia as greater than +0.5 d and emmetropia as spherical equivalent between -0.5 and +0.5 d. cut off value of greater or equal to 0.25 d table i: rela�ve propor�on of myopia, hypermetropia, as�gma�sm and presbyopia in different age groups table ii: gender differences in refrac�ve disorders females suffered more from all of the refractive disorders (58.21%) as compared to men (41.79%) and the difference was found to be significant. the difference between genders in hypermetropia was jiimc 2020 vol. 15, no.3 164 refractive disorders in a local population 10 population showed similar results. work by phillipa, yanchun, et alin uk indicated hypermetropia as the most common refractive disorder in 40+ year old 11 adults . similar findings were reported by a study 7, 12 conducted in mexicoand pakistan. myopia on the contrary was the most common refractive disorder amongst younger age groups; a finding supported by 11,13 multiple studies. while we found females to be suffering more from all refractive disorders, a detailed work on indian pediatric patients by ojha sushil, et al shows similar findings for myopia {girls (59.38%), boys (40.62%)}, hypermetropia {girls (84.21%), boys (15.79%)} and astigmatism {girls 9 (69.52%), boys (35.48%)}. on the contrary a study done in europe found astigmatism more common in men and hypermetropia in women. no statistically 10 significant difference was noted in case of myopia. similarly a uk based study found hypermetropia to be more common in females but didn't report any 11 similar differences with other refractive disorders . female children were found to be suffering more from combined refractive errors as compared to .14 male { or: 1.2 and or: 1.1 respectively} in india it is worth noting that prevalence of refractive disorders amongst males and females shows a great deal of variation depending upon the geographical area in question. for instance, myopia was more common in girls, hypermetropia in boys and no association of astigmatism was reported with gender in saudi 15 16 arabia , while in south africa myopia and astigmatism were more common in males whereas women suffered more from hypermetropia. this gender based variation in case of myopia might be due to hormonal factors as pointed out by a global 3 study into the trends of myopia and high myopia. the purpose of our study was not only to point out the trends in refractive disorders in different age groups but also to assess the burden of these disorders on the health care system of district sargodha. it can be argued that the data collected from dhq hospital sargodha is not an accurate representation of actual situation. the reliance on one source for data collection is a major limitation of this study and there is a need to carry out multiple studies at thq (tehsil headquarter) hospital level so as to carry out satisfactory mapping of refractive disorders. another limitation of the study was the failure to explain gender differences. future studies most significant (p<0.05) followed by presbyopia, astigmatism and then myopia. table iii shows distribution of different refractory errors in different age groups. myopia was most prevalent in 'early adulthood'. hypermetropia was relatively more prevalent in older age groups. a similar trend was seen with astigmatism. presbyopia was found to be virtually nonexistent in early age with majority of cases being in 'middle adulthood' and 'late adulthood' categories. table iii: age differences in refrac�ve disorders discussion the overall occurrence of refractive disorders was as following (i) hypermetropia (28.29%) (ii) myopia (21.76%) (iii) presbyopia (21.63%) (iv) astigmatism (28.32%). females suffered from all refractive disorders and this difference was statistically significant. myopia was most prevalent in early adulthood while the rest of refractive disorders occurred more in older age groups. earlier studies conducted in pakistan show mixed results in terms of magnitude of different refractive disorders. a study conducted in rural population of pakistan showed hypermetropia to be most common, followed by 7 myopia and astigmatism. the study shows prominent difference between myopia and hypermetropia in terms of magnitude. however this trend is not seen in case of our which can be explained by the fact that sargodha district is not yet fully developed and lies somewhere in a grey area between rural and urban classification. other studies, such as on 3-22 yr old patients in rural areas 8, 9 of paraguay and on pediatric patients in rural india indicate myopia as the most common refractive disorder which is consistent with our findings. a relationship between type of refractive disorder and the nature of area (rural or urban) might be there and requires further investigation. hypermaetropia was found to be most common refractive disorder in older age groups; this was reported by a number of studies. for instance, a study on european jiimc 2020 vol. 15, no.3 165 refractive disorders in a local population 27(1):8–12. 8. signes-soler i, hernández-verdejo jl, estrella lumeras ma, tomás verduras e & piñero dp. refractive error study in young subjects: results from a rural area in paraguay. international journal of ophthalmology. 2017; 10(3):467–472. 9. sushil ojha , babbar meenu , vaibhav jain, sharma reena, brijesh singh & sonali singh. pattern of refractive error in paediatric patients coming to rural tertiary care hospital of central india. indian journal of clinical and experimental ophthalmology.2016; 2(1):72-75. 10. williams k m, verhoeven v j, cumberland p, bertelsen g, wolfram c, buitendijk gh, et al. prevalence of refractive error in europe: the european eye epidemiology (e(3)) consortium. european journal of epidemiology.2015; 30(4):305–315. 11. cumberland p m, bao y, hysi pg, foster p j, hammond c j, rahi j s & uk biobank eyes & vision consortium. frequency and distribution of refractive error in adult life: methodology and findings of the uk biobank study. plos one. 2015; 10(10):1-14. 12. gomez-salazar f, campos-romero a, gomez-campaña h, cruz-zamudio c, chaidez-felix m, leon-sicairos n, et al. refractive errors among children, adolescents and adults attending eye clinics in mexico. int j ophthalmol. 2017; 10(5):796–802. 13. natung t, taye t, lyngdoh la, dkhar b, hajong r. refractive errors among patients attending the ophthalmology department of a medical college in north-east india. j family med prim care. 2017; 6(3):543-8. 14. sheeladevi s, seelam b, nukella p, modi a, ali r, keay l. prevalence of refractive errors in children in india-a systematic review. clin exp optom. 2018; 101(4):495–503. 15. alrahili nhr, jadidy es, alahmadi bsh, abdula'al mf, jadidy as, alhusaini aa, et al. prevalence of uncorrected refractive errors among children aged 3-10 years in western saudi arabia. saudi med j. 2017; 38(8):804–810. 16. mashige kp, jaggernath j, ramson p, martin c, chinanayi fs, naidoo ks. prevalence of refractive errors in the ink area, durban, south africa. optom vis sci. 2016; 93(3): 243–250. should address this and explore any association between sex hormones and refractive disorders. conclusion hypermetropia, astigmatism, myopia and presbyopia are common refractive disorders in population of sargodha district of punjab, pakistan. refractive disorders are more common among females. with the exception of myopia, these tend to occur more in older age groups. references th 1. shafi mj. clinical ophthalmology. 5 ed. karachi: paramount books; 2013. 243p. 2. world health organization. world report on vision [internet]. geneva: world health organization (who); 2019. 3. holden ba, fricke tr, wilson da, jong m, naidoo ks, sankaridurg p, et al. global prevalence of myopia and high myopia and temporal trends from 2000 through 2050. ophthalmology. 2016; 123(5):1036-42. 4. fricke tr, tahhan n, resnikoff s, papas e, burnett a, ho sm, et al. global prevalence of presbyopia and vision impairment from uncorrected presbyopia: systematic review, meta-analysis, and modelling. ophthalmology. 2018;125(10):1492-9. 5. rudnicka ar, kapetanakis vv, wathern ak, logan ns, gilmartin b, whincup ph, et al. global variations and time trends in the prevalence of childhood myopia, a systematic review and quantitative meta-analysis: implications for aetiology and early prevention. the british journal of ophthalmology. 2016; 100(7):882-90. 6. pakistan bureau of statistics. selected population and housing statistics of individual urban localities [internet]. islamabad: pakistan bureau of statistics; 2003. 7. abdullah as, jadoon mz, akram m, awan zh, azam m, safdar m, et al. prevalence of uncorrected refractive errors in adults aged 30 years and above in a rural population in pakistan. j ayub med coll abbottabad. 2015; jiimc 2020 vol. 15, no.3 166 refractive disorders in a local population 1 the question is, why should we aspire for excellence in hpe? are the current standards of medical education not par excellence? what is excellence in medical education? to understand this, we need to understand the historical narrative of health professions education. flexner presented a report in 1905 which brought a 1 major change in the delivery of medical education. before flexner, teaching and learning were d e c e n t r a l i z e d . l e a r n i n g w a s b a s e d o n apprenticeship. flexner report brought the centralized system of teaching in universities and hospitals. it promoted a system which was teacher centred, emphasized factual knowledge, autonomy of the disciplines and hospital based teaching. this a p p r o a c h w a s c h a l l e n g e d , w h e n m e d i c a l educationists presented new theories and strategies of learning. benjamin bloom presented the 2 3 taxonomy of cognition and attitude and dave gave the taxonomy of psychomotor skills. in early 1986 harden published the spices model of learning 4 strategy which was in total contrast to the teacher oriented strategy. in the 80's, burrows presented the idea of problem based learning.newer teaching methods, assessment tools and instruments have since been devised. newer curricula have emerged. problem based learning, competency based curriculum, osce, osler, oste, minicex , dops, cbl, cbd; the list is very exhaustive. there is a tremendous change occurring in medical education globally. geographic distribution of many diseases is changing. there have been dramatic shifts in the health care delivery and healthcare 5 professionals are more accountable now. the effects of this global change are evident in the national scenario as well. there is a need to produce health professionals that provide better care to patients.this has led to rapid increase in the educational institutions for health professionals, and hence for the curricular changes and adoption of newer teaching learning methodologies to equip the graduates with desirable outcomes. medical education is an on-going process which must adapt to the profession's changing dynamics with respect to technology, patient needs, and service-delivery. to produce medical graduates that provide excellent health care, we need defined standards of excellence in delivery of medical education to these professionals. this needs change in curriculum, in assessment methodology and r e q u i r e s i n t e n s i v e f a c u l t y d e v e l o p m e n t . implementing these changes is an uphill task. change management is a science. in case of health professionals, it requires changing the mind-set and training them in these new methods and techniques. in the good old days, a doctor would get a basic degree in his profession and could join academia on these grounds. he would then, with passage of time, learn the art of teaching and assessment. but in this era and age, this seems difficult without formal training in the art of teaching. this need was recognized long ago, when in formal education, a graduate had to have a licence to teach, that is to obtain a degree in teaching which could be a certificate, diploma or master in education. but in health professions, this need was recognized a little late. the first medical education department was set up in chicago illinois in 1950's. till 1997, only 7 mhpe registered programs were delivering masters in medical education. this number went up to 76 in 6 2012. according to the data available on faimer's 7 website, the number has reached up to 113. in addition to that, 24doctoral programs are now 8 offering phd in medical education. this is leading to the concept of professionalization of health professions education defined as the process of giving a professional character, identity, or status to hpe as a profession. it involves establishing a suitable and accreditable qualification, satisfying both editorial ------------------------------------------------aspiring for excellence in health professions education (hpe) rehan ahmed khan correspondence: dr. rehan ahmed khan associate professor, surgery iimc-t, pakistan railway hospital, rawalpindi e-mail: surgeonrehan@gmail.com 2 national and international needs of medical 9 education. it is very important to understand how the change was brought in flexner's time. teaching and training were based on apprenticeship system before flexner. the system was not centralized and there were no uniform standards, to give a doctor the license to treat a patient. this change took few decades to be fully implemented. it was difficult for the apprenticeship system to be completely abolished. now, when we are moving away from the traditional system to integrated system, with learning and assessment methods more suitable for student centred learning, the history is repeating itself. medical education is a continuing process. curriculum is a race track by definition, which needs to be revisited regularly. to achieve excellence we have to move forward and accept the change. pakistan has also seen the impact of this global change. before 2009, there were only few medical schools, who were delivering their curricula according to the global demands and changing international accrediting standards. however as a test run, pmdc awarded the responsibility of designing and implementing an integrated curriculum according to the changing needs of medical education. islamic international medical college stands out in this respect to be one of the few medical schools to develop mbbs curriculum which it has successfully implemented. the process needs to be understood nationally. it has been discussed in numerous meetings and conferences of medical education that after 2021 medical schools will be accredited based on delivering medical education according to the newer philosophies and demands of the professions which target excellence. till not very late, only cpsp (college of physicians and surgeons) was awarding a diploma in hpe. now there are 07 programs in pakistan which are delivering masters in hpe. the change is written very clearly on the wall. we have to move from traditional to integrated curriculum with the newer learning strategies and assessment tools across the national front. the clock is ticking fast. the world accrediting bodies are aiming at excellence in medical education.wfme, faimer and aspire are setting the standards globally. we need to realize this and adapt to the new system in time. in the beginning of the article we asked, what was excellence? excellence is defined as “the quality of being outstanding or extremely good.”excellence in medical education aims at producing best health professionals, so excellent health care is provided to the patients and eyes are no more set on standards 10 of minimal acceptable quality. in essence, we have to realize that we cannot provide our patients the best healthcare, if we don't aspire for excellence in medical education. references 1 . g i s h e n k , o v a d i a s , a r z i l l o s , a v a s h i a y, thaller sr. the current format and on going a d va n c e s o f m e d i ca l e d u cat i o n i n t h e u n i te d states. the j o u r n a l o f c r a n i o f a c i a l s u r g e r y 2014;25(1):35-8. 2. bloom bs. taxonomy of educational objectives. vol. 1: cognitive domain. new york: mckay. 1956. 3. dave r, editor taxonomy of educational objectives and achievement testing. international conference of e d u c a t i o n a l te s t i n g , b e r l i n , we s t g e r m a n y ; 1967. 4. h a r d e n r , s o w d e n s , d u n n w. e d u c a t i o n a l s t r a t e g i e s i n c u r r i c u l u m d e v e l o p m e n t : t h e spices model. medical education 1984;18(4):284-97. 5. o s m a n i s s . e f f e c t i v e l e a d e r s h i p t h e w a y t o e x c e l l e n c e i n h e a l t h p r o f e s s i o n s e d u c a t i o n . medical teacher 2013;35(11):956-8. 6. tekian a, harris i. preparing health professions education leaders worldwide: a description of m a s t e r s l e v e l p r o g r a m s . m e d i c a l t e a c h e r 2012;34(1):52-8. 7. tekian a. master's programs in health professions education. 2013. 8. tekian a. doctoral programs in health professions education. medical teacher 2014;36:73-81. 9. tekian a. professionalization in hpe. 2014. 10. greiner ac, knebel e. health professions education: a bridge to quality: national academies press; 2003. page 4 page 5 146 editorial gift authorship: an unethical practice in medical writing ishtiaq ahmed “i have often noticed that a bribe has that effect it changes a relation. the man who offers a bribe gives away a little of his own importance” (dgraham greene). the gift authorship is defined as “co-authorship awarded to a person who has not contributed 1 significantly to the study.” according to international committee of medical journal editors (icjme), authorship criteria guidelines, an “author” is generally considered to be someone who has made a substantive intellectual contributions to a published study, including the conceptualization, acquisition, analysis of data, drafting of the manuscript and 2 approval of the manuscript to be published. but these guidelines are not accepted or followed by all journals universally. instead of icjme author ship criteria, some of the journals has started using contributor lists, showing contribution or role of each person in place of or in addition to traditional 3 lists of authors. authorship is considered one of the most imperative aspect of the research which recognizes the research credit and is crucial for clinician because it is the primary criterion to judge their professional 4,5 progression and output. secondly, the entire departmental or institutional efficiency is also 3,4 judged on their publication record. due to this, the authorship list is a key information regarding their contribution in research performed and it is considered very important because incorrect information may award credit to undeserving person. moreover, if a clinician or scientists are giving false information's about contribution in research project or publication than how one should expect him to be any more honest about his findings or results? the authorship assignment is a candid decision which is usually troubled by many issues in all research disciplines. during manuscript writing, the principal authors should decide that who will qualify as an author and who will be recognized as 3 collaborators. there are several possible reasons for this unethical or malpractice in assigning gift authorship. the two main conditions which affect the solvency of authorship list are award of "gift or honorary" authorship and "ghost" authors i.e. 3,6 exclusion from manuscript. in first case usually these are the personals included unfairly who are the respected authorities of the institution or belong to department or unit and their inclusion can give more credibility or weightage to the research even if they have no participation in the work. they usually appear unfairly as an author in all publications generated by their department or institution and get unjustified recognition and material benefit from this unethical assignment. the second type i.e. ghost authors who really participated but they were considered prudent to be excluded because they have obvious conflict of interest which could affect the intent and credibility 7 of the manuscript. we should view the publication delinquencies as a range of felonies like pressurizing on gift authorship (e.g. as a departmental head) or neglecting a justified junior researcher from authorship is only a one step away from misappropriating results of a subordinate researches and thus committing a crime equivalent to plagiarism. moreover, inappropriate authorship practices like demand for gift author usually set a bad tradition which may likely to harm the associations between team fellows. the community of scholars suffers when a person is given credit for the work which is not his own, or he has no contribution or credit in shaping the ideas, outcomes, or the authorship is given to a person who was not involved integral ly in generation, description, implementation and description of the idea in research work. the reasons for this misconduct have been speculated as recognition need, promotion pressure, tenure issues, poor mentoring and correspondence: prof. ishtiaq ahmed professor of surgery al nafees medical college isra university, islamabad e-mail: surgish2000@yahoo.com received: august 04, 2020; accepted: august 10, 2020 department of surgery al nafees medical college isra university, islamabad 11 criteria. the problems regarding level of participation which merits authorship remains vague. the editors are usually unable to arbitrate over authorship disputes because it requires detailed and local knowledge of the institute where manuscript was produced. however, the institutions could play a better role in enforcing and setting up the authorship policies. disputes could be minimized, if authorship criteria were mutually agreed in writing, between all participants' at the beginning of research project. to me the authorship in medical writing is very important ethical concern which should be emphasized to the researchers and especially postgraduates. in my view this culture of “publish or perish” is mainly responsible for increasing trend in unethical research, medical writing or practice of plagiarism. this also leads to ethical issue in authorship, like order, gift or ghost authorship issues. in my observation and as reported in literature too, the gift authorship practice prevalent widely and on increase in recent years. the icmje (international committee of medical journal editors) has given clear and specific guidelines regarding authorship criteria which are followed by majority of medical 12 journals. according to this, contributors who failed to meet icjme criteria should be refrained from authorship but can be listed in acknowledgment section. among different possible reasons to award gift authorship, the commonest may be that the junior investigators often feel pressure in assigning authorship to their senior co-workers or to the seniors who might have significant role in shaping their future career. secondly, the junior academics are of impression that addition of senior colleagues as co-author will enhance the chances of publication. moreover, senior researchers sometime may assign gift authorship to give an impression of collaboration or good working relations or as a compensation for nepotisms. regardless of justification, this unethical practice of assigning gift authorship is deplorable for academic publications. the authorship should not be assigned or presumed as a veracious just on the basis of status or on association with researches or without a substantial contribution to the research project. in my view, this behavior from senior colleagues shows a sense of superiority and the believe that the rules merely don't apply to oneself, presumably because 8 financial conflict of interest. among different reasons why this gift authorship is regarded unethical are firstly, a not genuinely earned authorship may signify the gifted author's expertise falsely. secondly, gifted author is supposed as being more professional and skilled as compared to his peers. thirdly, this unethical contribution, gives biased professional advantage to this person over his associates. finally, a fabricated competency level is to be perceived about this individual and may be expected to achieve goals or tasks which may be 9 outside his competencies and expertise. why we should be worried about proper authorship nomination? it is argued that authorship abuse is a victimless crime having no impact on scientific growth or reliability of medical literature. authorship of a scientific paper matters a lot because the whole research and publication process relies on trust. the anecdotal evidence shows that the person who flouts authorship conventions can also pledge other types of publication or research related misconduct and this authorship abuse is not a victimless 4 corruption. in academic institutes, the promotion, job contract and remuneration are mainly influenced by the publications volume especially in the peer reviewed journals. the competences and expertise of the faculty is usually presumed on the basis high volume of publications. awarding honorary authorship to a published work is a misconduct which is dishonest and threatens the foundational assumptions on which a community of scholars 2 operates. in literature review, a self-administered, web-based published survey shows that among staggering total of 50%, the 39% of manuscripts has honorary, 9% has 10 ghost and 2% are having both types of authorship. bates and colleagues compared the authorship criteria and disclosure of contributions from author contribution forms of three medical journals and analyzed according to authorship criteria of icmje and observed that honorary authors varied in different journal, reaching up to 60% in the annals of 9 internal medicine to a low of 4% in jama. malički and colleagues studied that how authors describe their contribution to the paper submitted to the journal with reference to icjme authorship criteria and reported that only 15.6% has correctly or clearly declared their contribution according to icmje 147 jiimc 2020 vol. 15, no.3 medical journal. bmc med res methodol. 2012 12:189. doi: 10.1186/1471-2288-12-189. 6. jones jw, mccullough lb, richman bw. the ethics of bylines: would the real authors please stand up? j vasc surg 2005; 42:816-818. 7. reyes h b. ethical problems in scientific publications. rev. medium chile. 2018;146(3): http://dx.doi.org/10.4067/ s0034-98872018000300373 8. broome me. the 'truth, the whole truth and nothing but the truth. . .' nurs outlook 2008; 56:281-282. 9. zaki sa. gift author ship a cause of concern. lung india. 2011; 28(3):232-233. 10. mowatt g, shirran l, grimshaw jm, rennie d, flanagin a, yank v, et al. prevalence of honorary and ghost authorship in cochrane reviews. jama 2002; 287:2769-2771. 11. malički m, jerončić a, marušić m, malički ma. why do you think you should be the author on this manuscript? analysis of open-ended responses of authors in a general medical journal. bmc med res methodol 2012, 12:189. doi: http://www.biomedcentral.com/1471-2288/12/189. 12. uniform requirements for manuscripts submitted to biomedical journals: writing and editing for biomedical publication.2011. website [http://www.icmje.org ] accessed on 2020 apr, 3. 13. matías-guiu j, garcía-ramos r. author and authorship in medical journals. neurologia. 2009; 24(1):1-6. 14. bates t, anic a, marusic m, marusic a. authorship criteria and disclosure of contributions: comparison of 3 general medical journals with different author contribution forms. jama 2004; 292:86-8. references 1. jones jw, mccullough lb. is a gift authorship really a grift authorship? j vasc surg 2015; 61:1092-1093. http://dx.doi.org/10.1016/j.jvs.2015.02.006. 2. authorship guidelines. international committee of medical journal editors. 2019. website: [www.icmje.com]. accessed on march 5, 2020. 3. wager e. recognition, reward and responsibility: why the authorship of scientific papers matters. maturitas. 2009;(62):109–112 4. sharma bb, singh v. ethics in writing: learning to stay away from plagiarism and scientific misconduct. lung india. 2011; 28:148–150. 5. malički m, ana jerončić a, marušić m, marušić a. why do you think you should be the author on this manuscript? analysis of open-ended responses of authors in a general one is exclusive and merits special treatment. claiming off concepts and experiences as one's own, when they are not, and declining to recognize, in acknowledge or authorship or how others shape one's work and ideas is just simply deceitful and “alarming. in conclusion, gift authorship practice should be strongly discouraged and condemned in medical writing. the authorship credit and order should be based on the relative scholarly abilities and professional contributions of the collaborators. jiimc 2020 vol. 15, no.3 148 jiims final 33 original article abstract objective: to assess the quality of antenatal care provided to pregnant women in our set up at social security hospital rawalpindi. study design: cross sectional place and duration of study: department of obstetrics and gynaecology, social security hospital, islamabad from october to december 2011. materials and methods: women attending the antenatal opd were interviewed using a pre tested semi structured questionnaire. a total of 285 women were included in the study. they were interviewed at their first antenatal visit. results: mean age of study population was 30 years and parity ranged from 07.majority were house wives and had their monthly family income less than 10,000 rupees. majority of the patients 'were multigravidas. all (100%) patients were looked after by doctors in outpatient department (opd). about 34.78% patients were educated about complications of labour. only 16.84% and 28.42% patients got advice about antenatal exercises and episiotomy care respectively. more than half (56.8%) patients were counseled for delivery in hospital, 26.31% patients were given contraception advice. about 57% received specific dietary advice for pregnant ladies and 45.26% were told about importance of breast feeding. conclusion: our study concluded that adequate antenatal care does not mean merely establishment or improvement of health centers or antenatal clinics, adequate supply of medicines and reducing waiting time, but it also involves education of pregnant women about good antenatal care and different health related issues. key words: antenatal, labour, family planning, immunization, lactation. affecting antenatal care: maternal education, husband' education, marital status, household income, women's employment 5and history of obstetric complications. woman's parity is another factor which affects antenatal care; women with high parity tend to attend hospital less frequently, so parity has a significantly 6,7,8negative effect on antenatalattendance. the importance of quality antenatal care cannot be questioned. good care can reduce the maternal morbidity and mortality and result in a healthy perinatal outcome. in the present study we want to emphasize the importance of good care for women during pregnancy that will enable them to go safely through pregnancy and child birth, producing a healthy baby. a cross sectional study was conducted in octoberdecember 2011 in social security materials and methods introduction antenatal care is defined as the care of mother and fetus before birth. it is essential to reduce both the maternal and perinatal 1,2morbidity and mortality. systematic antenatal care was introduced first in the early 20th century, in europe and north america and is now almost universal in the 3d e v e l o p e d w o r l d . w o r l d h e a l t h organization (who) found that a new model with a reduced number of high quality antenatal visits did not result in worse maternal and perinatal outcomes than standard antenatal care that involved a 4greater number of visits. studies most commonly identified the following factors ------------------------------------------------quality of antenatal care provided at social security hospital, islamabad sughra shehzad, amina aftab, lalarukh, asma faisal correspondence: dr. sughra shahzad assistant prof. obs/gynae social security hospital islamabad medical & dental college islamabad. e-mail: sstts 80@gmail.com 33 34 hospital, islamabad. this hospital is providing health facilities to 318,000 registered patients (secured workers and their dependents). about 80 patients' daily visit the outpatient department in gynaecology department. in obstetric set up of social security hospital, antenatal care is provided by women medical officers' under the supervision of a gynecologist. record of antenatal visits is kept on specially designed antenatal cards to select high risk patients. antenatal record includes detailed history, findings of examination, details of investigations and ultrasonography. it also contains advice including hospital delivery especially in high risk patients, tetanus prophylaxis and warning signs of labour. the patients include wives of secured workers who are entitled in the hospital for free of cost treatment. so no patients are lost to follow up. inclusion criteria a total of 285 patients attending the antenatal opd were included in the study. they were interviewed at their first antenatal visit. data was collected through semi structured p r e t e s t e d q u e s t i o n n a i r e a n d b y interviewing the patients. the questionnaire was written in easy urdu, so that most of the patients could read and understand it. those not able to read urdu were interviewed by the women medical officers (wmo) of gynae department. t h e v a r i a b l e s i n c l u d e d w e r e s o c i o d e m o g r a p h i c f a c t o r s , h e a l t h information and satisfaction for resources. questionnaire sought information about bio data, factors affecting antenatal attendance and knowledge about antenatal services. data collected was entered on spss12 and was analyzed. the results were shown in percentage. the mean age of women was 30 years and parity ranged from zero to seven. most of the patients (84.2%) were less than 30 years old and 15.78% were more than 30 years. majority of them belonged to poor socioeconomic group as 89.47% had their monthly family income less than 10,000 rupees. only 5.26% patients had income between 10,00015,000 rupees and a similar proportion more than 15,000 rupees. majority (91.57%) patients were house wives and 8.42% were self-employed in mills and schools. in our study, 135 (47.36%) women were educated to secondary level, 57 (20%) had got primary education, 33 (11.57%) were graduates and 12 (4.21%) had master degree; however 48 (16.84%) patients were illiterate. in the study population, 22.1% patients were primigravidas, 74.3% were multigravida and 3.6% were grand multipara. all (100%) were attended by doctors (medical officers, specialists/ consultants) in opd. all women were aware of at least one or two methods of family planning. table i shows distribution of different factors which affect attendance of pregnant patients in antenatal care opd. table ii shows the education of women during antenatal visit. regarding different aspects of patient's education or instructions given to the patients by their attending doctors during their checkup, 99 patients ( 3 4 . 7 3 % ) w e r e c o u n s e l e d a b o u t complications or problems of labour, 201 ( 7 0 . 5 2 % ) w e r e c o u n s e l e d r e g a r d i n g immunization against tetanus, 129 (45.26%) were emphasized about benefits of breast feeding, its importance and standard results 34 35 methods of lactation. more than half (57.89%) patients were educated about specific dietary needs of pregnant ladies, and possible psychological problems in pregnancy and puerperium were discussed with 33 (11.57%) patients. only 48 (16.84%) ladies received information about antenatal exercises and 84 (28.42%) patients were counseled about the possibility and care of episiotomy. need for hospital delivery was emphasized during counselling of 56.84% patient. about 60% patients were satisfied with the overall care provided to them; however 40%showed their concerns over quality of care. most of them were unsatisfied about waiting time in outpatient department. most of them said that they had to wait for more than two hours. especially worth mentioning was their apprehension about delay in getting laboratory investigations. about 70% women were worried about g e t t i n g m e d i c i n e s a n d s h o r t a g e o f medicines. table-i: sociodemographic variables affecting antenatal attendance *women having more than five viable pregnancies. table-ii: education of women during antenatal visit discussion high quality antenatal care is a fundamental right of women to safeguard their health and attain a desirably healthy outcome of pregnancy. it not only includes detailed h i s t o r y , e x a m i n a t i o n , a p p r o p r i a t e investigations and ultrasonography but also contains advice including specific dietary needs for pregnant women, preparation of patient for labour and possible problems, hospital delivery especially in high risk 8patients. tetanus prophylaxis and warning signs of labour. counseling for breast feeding as well as contraceptive advice must also be included in the care of antenatal patients. in our study, mean age of the study population was 30 years, majority of them belonged to poor socioeconomic group, they 35 36 were unemployed and had got education up to secondary level. majority of them were multigravidas and only a minority were grand multiparas (patients having more than five viable pregnancies). this fact has also been observed in other surveys that women with high parity tend to seek advice 7, 8and care less frequently. in pakistan, only 30% patients utilize antenatal care services, while 70% do not. only one third of deliveries take place in hospitals. only 25% patients are counselled a b o u t w a r n i n g s i g n s o f p r e g n a n c y complications and less than half receive any 9post natal care. it has been emphasized in different studies that quality care has improved maternal and 10,11perinatal outcomes worldwide. about 8898% of all maternal deaths could be avoided by proper care and handling during 12,13pregnancy. awareness should be created 14for proper utilization of services. in this study, all pregnant women were attended by doctors. this is contrary to findings in another study conducted at a public sector hospital of hyderabad (sindh), most of the women reported that they received care 14from lady health visitors (lhv). although 100% patients were attended by doctors in our study, but their actual performance in taking care of women and their education regarding various health related issues was not up to the desired level. less than one third patients received advice about antenatal exercises, care of episiotomy and problems/ warning signs of labour. need for hospital delivery was discussed with half of the patients. the need for proper training of medical and paramedical staff for effective delivery of available services has 14,15also been emphasized in other studies. in addition to history taking, examination and advice of appropriate investigations, improvement of women's perception and counseling about standard antenatal care is 15also desirable. this involves giving i n f o r m a t i o n / e d u c a t i o n a b o u t complications of pregnancy, antenatal exercises, immunization, lactation and advice about family planning. information should also be given about care of e p i s i o t o m y . s p e c i f i c p s y c h o l o g i c a l problems in pregnancy and puerperium must also be addressed. good antenatal care also means hospital delivery especially in high risk patients. dietary advice for a pregnant and lactating mother must also be part and parcel of optimal care. medical and paramedical staff needs to be trained about the various educational needs of the patients and factors influencing patient satisfaction in order to improve quality of health 10,16care. most of our patients expressed their dissatisfaction about prolonged waiting time, inappropriate attitude of hospital staff and availability of medicines. among pregnant women, long waiting time, spending time during visit, inadequate supply of medicine and attitude of medical and paramedical staff were seen to be main 17areas of dissatisfaction in another study. need for up grading the existing facilities as well as adequate training of medical and para medical staff to improve delivery of the available facilities has also been emphasized 14, 18in different studies. our study concluded that adequate antenatal care does not mean merely establishment or improvement of health centers or antenatal clinics, adequate supply of medicines and reducing waiting time, but it also involves education of pregnant conclusion 36 37 women about good antenatal care and different health related issues. medical and para medical staff needs to be trained for improving counseling skills, so that patients receive the available services and education in a more effective manner. 1. world health organization. antenatal care: report of a technical working group. geneva: who, 1994. 2. world health organization. world health report 2005: make every mother and child count. geneva: who, 2005. 3. rooney c. antenatal care and maternal health, how effective is it? document who/ msm 92.4 geneva: who, 1992: 6-9 4. molzan j, bulut a. the quality of hospital based antenatal care in istanbul. studies in family planning 2006; 37: 4960. 5. simkhada b, teliligen er. factors affecting the utilization of antenatal care in developing countries: systematic review of the literature. j advnurs 2008; 61: 244-60. 6. thonneau p, toureb,cantrelle p. risk factors for maternal mortality; results of a case control study conducted in conakry (guinae). intl j obstet gynecol 1992; 39: 87-92. 7. world health organization. motherbaby package: implementing safe motherhood in countries. who, 1994: 24-5. 8. malone mi. the quality of care in an antenatal clinic in kenya. east african medical journal 1980; 57: 86-96. references 9. pakistan demographic and household survey 2006-7, islamabad: government of pakistan 2006-7. 10. chowdhury ri, islam ma, gulshan j, chakraborty n. delivery complications and health care seeking behaviorthe bangladesh demographic health survey 19992000. health and social care in community; 15: 25464. 11. sultan a, riaz r, rehman a, sabir sa. patient satisfaction in two tertiary care hospitals of rawalpindi. jrmc 2009; 13: 4143. 1 2 . t u r m e n t . s a f e m o t h e r h o o d . e a s t e r n mediteranean health journal 1998; 4: 15-17 13. ghada h. maternal mortality: a neglected and s o c i a l l y u n j u s t i f i a b l e t r a g e d y . e a s t e r n mediteranean health journal 1998; 4: 710. 14. nisar n, amjad r. patterns of antenatal care provided at a public sector hospital, hyderabad, sindh. j ayub med coll 2007; 19: 1113. 15. andaleeb ss, siddiqui n, khandakar s. patient satisfaction with healthservices in bangladesh. health policy and planning; 22: 26373 16. afzal m, khan a, rizvi f, hussain a. patient satisfaction level in outpatient department of a teaching hospital. jimdc; 2011; 1: 2629. 17. fawole ao, okunlola ma, adekunle ao. client's perceptions of the quality of antenatal care. journal of the national medical association 2008; 100: 10528. 18. ali m, ayaz m, rizwan h, hashim s, kuroiwa c. emergency obstetric care, availability, accessibility and utilization in eight districts in pakistan's north west frontier province. j ayub med coll abbottabad 2006; 18: 10-15. 37 38 instructions for authors the 'jiimc' agrees to accept manuscripts prepared in accordance with the “uniform requirements submitted to the biomedical journals” published in the british medical journal 1991; 302: 334-41. be of about 250 words. editorials are written by invitation. authors should keep one copy of their manuscript for reference, and send three copies (laser 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copyright of the jiimc and may not be reproduced without the permission of the conclusion reprints copyright editors or publishers. instructions to authors appear on the last page of each issue. prospective authors should consult them before riding their articles and other material for publication. the jiimc accepts only original material for publication with the understanding that except for abstracts, no part of the data has been published or will be submitted for publication elsewhere before appearing in this journal. the editorial board makes every effort to ensure that accuracy and authenticity of material printed in the journal. however, conclusions and statements expressed are views of the authors and do not necessarily reflect the opinions of the editorial board or the iimc. publishing of advertising material does not imply an endorsement by the iimc. 40 original article abstract objective: the objective of the study was to determine that how physical therapy teachers perceive 'professionalism' in pakistani context? study design: this was a qualitative case study. place and duration of study: the study was conducted in five different universities from five different cities of th th pakistan from 10 of january to 25 june 2013 at different time. materials and methods: semi structured interviews were conducted with 15 physical therapy teachers of 05 different universities from 05 different cities of pakistan. the physical therapy teachers with at least 5 years teaching experience in a university were included for data collection. the interviews were audio recorded; data verbatim transcribed and analyzed manually by open coding and in-vivo coding. thematic analysis was done in order to identify different elements of 'professionalism' in physical therapy teachers through finding the patterns in the data. member checking was done by three researchers in the study in order to validate the data. results: after thematic analysis based on emerging patterns from transcribed data, following important elements about 'professionalism' in the order of priority were identified; expert in subject with knowledge and skill, behavior and attitude towards the students, patients and staff, autonomy, serving and benefits to the community and accountability in health services, compassion, moral reasoning, reflective thinker, acquainted with professional ethics, trustworthiness, honest and team based approach. in response to the question about the professionalism in 'pakistani culture, the faculty responses in the order of priority were as follows; lack of resources, proper jobs, moral support, poor salary packages and financial support and religion boundaries, requirements of the community and cultural hurdle and poor context in the society, lack of governing body, council, responsibility and accountability. conclusion: it is concluded that for professionalism expertise in subject's domain & skills is the most important element. besides that behavior and attitude towards students and patients are the key components of professionalism. it is concluded that in pakistani culture, there is lack of professional behavior in physical therapy teachers/faculty. majority of the institutes don't concentrate on professionalism. key words: culture, context, faculty, professionalism. because pt teachers educate physical therapists. also pt has a close andprolongs interaction with patients during rehabilitation. it has been observed t h a t t h e r e i s i n c r e a s e d e v i d e n c e a b o u t 1 professionalism in medical litetrature. in north america and europe the international experts have been instrumental in defining professionalism. the professionalism is also d e s c r i b e d by t h e g e n e ra l m e d i ca l c o u n c i l ' s publication as the duties of a doctors, who providesgood health care, based on an updated continuous professional education, clinical teaching and bed side training, relationships with patients, 2 and colleagues. in pakistancurrently 60 academic institutions are offering 5 years entry level doctor of pt program (dpt). fifty seven institutions have been developed in past 15 years. there were only three academic introduction physical therapy is an emerging field of health sciences in pakistan. twenty two universities offer undergraduate and graduate programs in this discipline. to understand the 'professionalism' as core competency and phenomenon in real life practice of pt's teaching is very important. it is how do physical therapy teachers perceive 'professionalism' in pakistani context? 1 2 3 syed shakil ur rehman , shakeel ahmad , raheela yasmeen jiimc 2016 vol. 11, no.3 correspondence: dr. syed shakil-ur-rehman principal/associate professor riphah college of rehabilitation sciences (rcrs) riphah international university, islamabad e-mail: shakil.urrehman@riphah.edu.pk 1,2 riphah college of rehabilitation sciences riphah international university, islamabad 3 department of riphah academy of research and education riphah international university, islamabad funding source: nil ; conflict of interest: nil received: mar 27, 2016; revised: jun 06, 2016 accepted: aug 17, 2016 126 perception about professionalism among physical therapy teachers 3 institutions till 2000. therefore need and demand of knowledgeable, skilled and professional pt teaching staff has been increased in last 15 years. currently there are more than 1000 qualified physical therapy professionals in both academic and clinical 4 institutions. professionalism is one of the three key areas of interest and importance for a pt teacher, along with knowledge and skill. it is the behaviors and attitudes of physical therapist teachers which isimportant and role models for their students during teaching and training sessions. in medical and health sciences, professionalism is of global interest and the reason for this is the failure of traditional method of teaching due to non-professional behaviors and attitudes of teachers. the global awareness is continuously increasing about the teaching of professionalism to students of health and medical 5 sciences disciplines. china has made great changes in their education sy s t e m s i n c e 2 0 0 8 a n d m o s t l y u p g ra d e d thestandards in health professional education, along withnew addition of integrated courses and teaching 6 methods. the present study was designed to determine the core elements that describe 'professionalism' among the pt teachersin pakistani culture. the objective of the study was to determine h o w p h y s i c a l t h e r a p y t e a c h e r s p e r c e i v e 'professionalism' in pakistani context? materials and methods this was qualitative case study. the case study strategy is used to understand the social phenomenologyin order to retain the holistic and 7 meaningful characteristics of real life events. semi structured interviews were conducted with 15 physical therapy teachers of 05 different universities th from 05 different cities of pakistan, from 10 of th january to 25 june 2013 at different time. the universities included were, riphah international university islamabad and lahore, lahore university, gc university faisalabad, university of sargodha, and foundation university. consent was taken from faculty; no conflict of interest raised. the ethical approval was taken from riphah research ethical committee before the data collection. the physical therapy teachers with at least 05 years teaching experience in a university were included for data collection.the interviews were taken in english language. the interviews were audio recorded; data verbatim transcribed and analyzed manually by open coding and in-vivo coding. a code can be defined as, “a word or a short phrase that metaphorically assigns a salient, essence catching, and/or redolent attribute for a portion of language-based or visual data”. there are more than twenty different types of codes and with one single data set it is not necessary to use all of them. the data was analyzed two times and coding was done in two cycles. in first cycle single word to sentence in the paragraphs were interpreted as the code. open coding and in-vivo coding was done. in the second cycle constant comparison in data sets of different respondents, cross case results was done in order to form the categories and themes. thematic analysis was done in order to identify the different elements of 'professionalism' in physical therapy through finding the patterns in the data. this helps in answering the research question. member checking was done by three researchers in the study in order to validate the data.mainly data was analyzed at 'manifest level'. results after thematic analysis which was done manually, t h e f o l l o w i n g i m p o r t a n t e l e m e n t s o f 'professionalism' in the order of priority were identified; expert in subject and domain in knowledge and skill, behavior and attitude towards the students/patients/staff, autonomy, serving and benefits to the community and accountability health services, compassion, moral reasoning, reflective thinker, acquaint with professional ethics, trustworthiness, honest and team based approach. the perception of professionalism in 'pakistani context' the faculty responses in the order of priority were; lack of resources, proper jobs, moral support, poor salary packages, financial support, religion boundaries, requirements of the community, cultural hurdle, poor context in the society, lack of governing body, council, responsibility and accountability. other responses in orders are lack of knowledge professional ethics traininghonesty and teaching skills, also lack of literature access to literature, planning and team work. also there is curriculum fault and limited global perception. the importance of professionalism for a physical therapy teacher, most of the participants responded; 'it is one of the most important competency to be jiimc 2016 vol. 11, no.3 127 perception about professionalism among physical therapy teachers demonstratedby most ofphysical therapy teachers'. the level of professionalism for a physical therapy teachers in pakistani context, maximum responded that; 'it is one of the most important competency but very fewteachers practice act of professionalism'. substandard as compare to developed countries, the reasons for this is that, there is lack of ethical practice, lack of research and evidence based practice,lackofhigh quality education and talent equal or even more in initial phase of development of good theoretical background. there is no council, infrastructure, non-satisfactory level and lack of communication. the responses to improve professionalism in pt teachers were; proper training in research and teaching and excellence and teaching skills, conferences of national as well as international level, international level exposure, professional ethics and access to latest literature, establishment of council, approved service structure and salary package, continuous professional development , uniform curriculum regular updatation, specialized practice in pt, institution to institution collaboration, society awareness programme and vision development. in response to question that how much our pt i n s t i t u t i o n s c o n c e n t r a t e o n t e a c h i n g professionalism, the respondent said; “pt i n s t i t u t i o n s p a y v e r y l e s s a t t e n t i o n t o professionalism. very few said that pt institutions concentrate on professionalism”. globally, our physical therapy faculty members stand in order of priorities are below the level or the possible outcomes after achieving good level of professionalism, the following were identified; improve pt service and its quality and application of latest skills with evidence based practice, professional teacher and good researcher, benefits of students, community and patient, enhance quality of knowledge, professional ethical practice, recognition, responsibility, improve autonomous practice and international standards. discussion i n o u r s t u d y t h e i m p o r ta n t e l e m e n t s o f 'professionalism' in the order of priority were jiimc 2016 vol. 11, no.3 128 perception about professionalism among physical therapy teachers identified; expert in subject and domain in knowledge and skill, behavior and attitude towards the students/patients/staff, autonomy, serving and benefits to the community and accountability health services, compassion, moral reasoning, reflective thinker, acquaint with professional ethics, trustworthiness, honest and team based approach. in 2012 byszewski a et al in their study said “role modeling is single most important aspect of 8 professionalism”. a systematic review done by passi v et al in 2012, in which they studied that there are 5 main themes for supporting the development of professionalism in medical students. these include curriculum design, student selection, and teaching and learning 9 methods, role modeling and assessment methods. in our study there are five components of professionalism which are more important for our pt teachers in pakistan. these are accountability, ethical knowledge, lifelong learning, honesty, autonomy and reflection. in 2012 a study conducted by cruess sr and his colleagues on teaching professionalism and concluded that teaching professionalism requires cognitive base from each and every teaching community,which is a definition of profession, the attributes of the professional, and the relationship of medicine to the society which it serves. these should b e t a u g h t e x p l i c i t l y. t h e s u b s t a n c e o f professionalism must become part of each physician's identity and be reflected in observable behaviors. professionalism should be taught as “an ideal to be pursued” rather than as a set of rules and 10 regulations. according to our study after achieving good level professionalism in pt teachers in pakistani context; there will be improvement in teaching as well as pt services, which ultimately would have a very good impact on community. hur y in 2009 studied that medical professors need to encourage their students to increase their elevation. he studied on 31 core elements, significant perception gap were found in 28 elements. the 31 core elements were divided form 3 major domains – including professional knowledge, clinical skills, and professional attitude-all contained perception gaps, and professors' ratings generally were higher than 10 those of the students, a noteworthy observation. according to our study, strategies should be adopted to improve professionalism in pt teachers in pakistani context the responses were proper training in research and teaching and training and excellence in teaching skills, conferences of national as well as international level, international level exposure, professional ethics and access to latest literature, establishment of council, approved service structure and salary package continuous professional d e v e l o p m e n t , u n i fo r m c u r r i c u l u m re g u l a r updatation, specialized practice in pt, institution to institution collaboration, society awareness programme and vision development. cahalinlpin 2012 conducted a study onlinda crane lecture on professionalism as a core values in pt. the objective was to highlight the professionalism of linda crane with examples of the methods appropriate for physical therapist and to develop their own professionalism. she used a tool developed by the american pt association (apta), 11 named professionalism assessment tool. the study was conducted on small sample size of professionals due to lack of time with physical therapist. in future for generalized results large sample size with more universities are to be involved. conclusion it is concluded that for professionalism expertise in subject's domain & skills is the most important element. besides that behavior and attitude towards students and patients are the key components of professionalism. it is concluded that in pakistani culture, there is lack of professional behavior in physical therapy teachers. majority of the institutes don't concentrate on professionalism. references 1. cruess sr, cruess rl. teaching professionalism – why, what jiimc 2016 vol. 11, no.3 129 perception about professionalism among physical therapy teachers interna�onal standard. and how. facts, views & vision in obgyn. 2012; 4:259–65. 2. passi v, doug m, peile e, thistlethwaite j, johnson n.developing medical professionalism in future doctors: a systematic review.international journal of medical education.2010; 1: 19–29. 3. shakil-ur-rehman s, sahibzada nm. physical medicine and rehabilitation education–past, present and future. the journal of islamic international medical college quarterly. 2015; 92:112. 4. rathore fa, new pw, iftikhar a. a report on disability and rehabilitation medicine in pakistan: past, present, and future directions. archives of physical medicine and rehabilitation. 2011; 92:161-6. 5. al-eraky mm, donkers j, wajid g, van merrienboer jj. faculty development for learning and teaching of medical professionalism. medical teacher. 2015;37: 40-6. 6. zhang q, lee l, gruppen ld, ba d. medical education: changes and perspectives. medical teacher. 2013; 35:6217. 7. flyvbjerg b. five misunderstandings about case-study research. qualitative inquiry. 2006; 12: 219-45. 8. byszewski a, hendelman w, mcguinty c, moineau g. wanted: role models medical students' perceptions of professionalism. bmc medical education.2012; 12: 115. 9. passi v, doug m, peile jt, johnson n. developing medical professionalism in future doctors: a systematic review. international journal of medical education.2010; 1: 19. 10. hur y. are there gaps between medical students and professors in the perception of students' professionalism level? secondary publication.yonsei medical journal. 2009; 50: 751–6. 11. cahalin l p. the linda crane lecture professionalism & core values in pt: lessons learned from linda crane. cardiopulmonary pt journal. 2012; 23: 30–9. jiimc 2016 vol. 11, no.3 130 perception about professionalism among physical therapy teachers page 39 page 40 page 41 page 42 page 43 original�article abstract objective: to compare the effectiveness of case based learning and self directed learning through end-ofmodule assessment scores of two groups of students studying endocrine physiology in the second year mbbs program and through student's experience about it. study design: quasi experimental study. place and duration of study: foundation university, islamabad, department of physiology, conducted in 4 months duration, starting from april till august 2020. materials and methods: this study was conducted on second year mbbs students (group a) who were formally introduced to case-based learning sessions during endocrine module. the end-of-module physiology exam scores of this class were compared to endocrine module result scores of the previous class (group b), who had been taught through self-directed learning sessions during their endocrine module. dividing same class into two groups would deprive one group from new learning strategy therefore scores of previous classes taught through sdls were used. the number of sessions, learning objectives, facilitators, examiners, and assessment methods for both classes were ensured to be kept similar. results: quantitative analysis of scores between the two groups using spss 23 was statistically significant (pvalue = 0.001) through independent t test. out of 143 students in group a, 96.5% passed while in group b 95% were declared pass. the above average scorers were 52% in group a and 29% in group b. qualitative assessment of feedback questionnaire done by descriptive analysis, depicted positive impact of case-based learning sessions on students' self-perceived learning, communication skills and problem solving. conclusion: case-based learning sessions was found to be more effective learning strategy than self-directedlearning sessions. key words: case-based-learning, endocrine, module, self-directed-learning. learners, as sdl has been widely accepted as the most appropriate learning strategy to achieve this 1 goal. in 1975, malcolm knowles defined sdl as “a process in which individuals take the initiative, with or without the help of others, in diagnosing their learning needs, formulating goals, identifying human and material resources for learning, choosing and implementing appropriate learning strategies, and 2 evaluating learning outcomes. it is however important to note that in the systematic review conducted by murad et al., it was found that only 8% of published studies fulfilled the precise definition of 3 sdl as defined by knowles. likewise, the sdl time slots being offered in the curriculum of our medical students have also not been a true reflection of sdl as defined by knowles. students learn certain concepts on their own and any major queries would then be dealt with in classroom lectures. as such, our students often complained, about inadequate, and at times distracted learning during these sdl introduction teaching at foundation university has been hybrid since 2009, employing both the conventional learning strategies as well as modern-day innovative methods like problem-based learning sessions (pbls), tutorials and self-directed learning sessions (sdls). specifically, sdls were included in the curriculum, keeping in mind the rapid advances in medical education and the importance of developing our future physicians into self-directed life-long is case based learning better than self directed learning? a quantitative analysis of endocrine physiology exam scores and students' feedback sadia ahsin, hira ashraf, madiha imran, gule naghma saeed correspondence: dr. hira ashraf assistant professor department of physiology foundation university medical college, foundation university islamabad e-mail: hira.ashraf@fui.edu.pk department of physiology foundation university medical college, foundation university islamabad funding source: nil; conflict of interest: nil received: september 07, 2020; revised: may 01, 2021 accepted: may 04, 2021 is cbl better than sdljiimc 2021 vol. 16, no.3 195 sessions, without guidance from facilitators. in the opinion of the study authors, while acknowledging the much-documented benefits of sdl learning strategy, its true effectiveness can be evaluated only w h e n c o m p a r e d t o o t h e r c o m p a r a b l e methodologies, where students are guided towards focused learning while keeping the spirit of selflearning, e.g, through case based learning (cbl). case based learning is also an educational strategy where contextualized questions based upon real patient clinical scenarios are posed to students who are pre-informed about the content to be discussed. the case discussion is under supervision of a facilitator who is also well prepared. the implementation and assessment of cbl in various disciplines, including basic sciences, is also 4,5 documented in literature. though the idea and implementation of sdls in curriculum was whole heartedly embraced by the faculty, but due to student's dissatisfaction, it was considered prudent to change the learning methodology, but before introduction of new learning method i.e., cbl, into the curriculum of basic sciences at fuic, some tangible rationale was needed in the form of better or comparable assessment results for at least one module. towards this end, a study was planned where assessment results of one group of students taught through sdl and lectures was compared with the results of the second group of students who were taught through cbls and same lectures. with this rationale current study aimed to compare the endof-endocrine module assessment scores of two groups of students studying endocrine physiology either through sdl or cbl in addition to their lectures. it was also aimed to record the perception of these methods from those students who had experienced both methods through structured questionnaire. therefore, the objective of this study was to compare the effectiveness of cbl and sdl through end-of-module assessment scores of two groups of students studying endocrine physiology in the second year mbbs program and through student's experience about it. materials and methods this quasi-experimental study was conducted at department of physiology of foundation university, in the students of second year mbbs, for the duration of 4 months, starting from april till august 2020. ethical approval for the study was obtained from ethical review committee of university. the entire 2nd year mbbs class of session 2018 comprising of 143 students was included in group a through convenience sampling. the previous modules of the same class had been taught through lectures as well as sdl sessions. since cbl was considered new method for students therefore they were formally introduced to case based learning methodology. the endocrine module runs over a duration of 8 weeks. the cbl sessions were prepared according to recommended guidelines where pre reading material and case scenario was provided to the students and subject experts, a week prior to 6 main discussion. physiology of pituitary, pancreas, thyroid, parathyroid, adrenal and gonadal hormones was covered, with one hormonal dysfunction scenario for one cbl session each week with a total of 8 cbls. students identified learning objectives, key concepts in the physiological functioning of hormones and consequences of their hypo or hyper functioning. the case summary was organized by facilitators. the end of module physiology scores of this class were compared to same exam result of class of 2017 (group b), who had been taught through lectures and one physiology sdl per week in total 8 weeks of their endocrine module. since the learning objectives devised for both sdls and cbls encompassed physiology of various hormones, therefore only physiology scores were extracted from the total module scores. dividing same class into two groups would have deprived one group from new learning strategy therefore scores of previous classes taught through sdls were used. however, the number of sessions, learning objectives, facilitators, examiners, and assessment methods for both classes were ensured to be kept similar, to avoid confounding factors. the subject pass percentage as per pakistan medical and dental council is 50% therefore, it was decided to compare percentage of pass and fail students, number of average scorers (50-70% scores) and number of above average scorers (above 70%) in both groups. the feedback about cbl from students was collected from group a because only they had exposure to both sdl and cbl in their academic year. it was collected through selfadministered, structured questionnaires after their end of module exam. questionnaire comprised of 8 is cbl better than sdljiimc 2021 vol. 16, no.3 196 questions with responses on likert scale. quantitative analysis of scores between the two groups was done using spss 23 where statistically significant difference with p value = < 0.05 was calculated through independent t test. assessment of student's perceptions was done through feedback questionnaires by descriptive analysis using percentages and frequencies. results there were 143 students who attended cbls along with lectures (group a, n=143) and same number of students attended sdl sessions along with lectures (group b, n=143). out of 143 students (group a) the pass percentage was 96.5% (138) while 3.4 % (5) failed to clear the modular exam. in group b, 95% (136) were declared pass while 4.8% (7) students couldn't score the pass percentage (50%). the mean score in percentage of cbl+ lecture group and sdl+ lecture group along with standard deviation is shown in table i. the difference of scores between the two groups was significant at p-value of 0.003 applying t-test. discussion the current study was planned to evaluate the outcome of incorporation of cbl sessions, instead of sdl time slots, in the endocrine module timetable of second year mbbs class of 2018. there are multiple ways to evaluate a learning intervention in literature including knowledge assessment and surveys, therefore, both have been employed in the current 7 study. the module exam physiology results of group a, who were taught through cbl sessions in addition to lectures showed better overall scores compared to group b, who were taught through same lectures and dedicated 08 sdl time slots in timetable of endocrine module. mean percentage score obtained by group a students was significantly higher 68.35±8.15 compared to 65.55±8.83 of group b with a p value of 0.003. similar results were derived by datta a et al., who found that post-test mean scores of cbl groups were significantly higher than that of didactic lecture groups when both were compared 8 after teaching two clinical pathology topics. the strength of our study is that a series of cbls was conducted throughout the endocrine module, to evaluate their outcome in formal exam results. another strong point of our study is that basic physiological aspects of each hormone were taught in lecture before the cbl session, as literature search suggests that true effectiveness of cbl can be achieved when students have already acquired table i: comparison of mean score in percentage of cbl (group a) and sdl (group b) (n= 143) *p-value significant (less than and equal to 0.05%) the number of students scoring above average scores (71-85 %) was 75 (52%) in group a while 42 (29%) students scored above average marks in group b. the number of students scoring average percentage (51-70%) was 67 (45%) in group a while 94 (65%) in group b. table ii. students' feedback questionnaire scores analysis (figure in parenthesis indicates score for that choice) (n = 143) is cbl better than sdljiimc 2021 vol. 16, no.3 197 7 foundation knowledge of the topic. in our study, although the pass percentage of group a was higher than group b, their difference did not reach statistical significance. although the number of 'average scorers (50-70%)' was more in group b i.e 95 (65%) compared to 67(45%) in group a, yet it was interesting to find that this difference was compensated by considerably more 'above average scorers (above 70%)' in group a, 75(52%) compared to group b, 42(29%). this suggests that students of group a had better in-depth understanding of the subject compared to group b. these findings are comparable to the results of sahiba k et al., where authors found that incorporation of cbl method in biochemistry was superior in imparting knowledge to students. their claim was supported by significant difference between pre and post cbl mcq test scores 9 of students. questionnaire based inclination of students towards cbl sessions compared to sdls also suggests its effectiveness as a student-preferred learning tool. students considered it effective for knowledge retention and exam preparation which was reflected in their exam scores too. the clinical correlation with the acquired physiological concepts could be the reason of better perceived knowledge retention. as bunmi s et al., concluded in their cohort study that perceived clinical relevance was a contributing factor to the retention of basic science knowledge in their students and they suggested that curriculum planners should make clinical relevance a 10 more explicit component of medical teaching. the impact of cbl has been evaluated in various studies which concluded that students not only enjoyed the sessions but felt that cbl enhanced their 11-18 understanding. these conclusions are similar to the results of our study. our students considered cbls enjoyable, the reason could be the interactive and focused discussion with facilitators and the clinical application of their already acquired basic science theoretical knowledge. an interesting finding in our study was the low number of students who were in favor of sdls. this clearly shows the lack of readiness of our students towards self-directed learning, even at university level. current study does not indicate why students were not in favor of sdl, however cultural factors have been shown to impede sdl assimilation in medical students across different cultural groups. for asian students, the pressure of high achievement and traditional reliance on teachers has been documented as the main restraining factor in failure 14 to adapt sdl strategies. current study results motivate us to plan more cbls for other modules that are being run during basic sciences years of medical students. however, the importance of making our future physicians' lifelong learners through self-directed learning cannot be overlooked. therefore, it is recommended and planned, not to totally replace sdls with cbls, but to incorporate a few dedicated sdl time slots in every module in addition to cbls. true comparison of cbl and sdl by dividing the same class into two groups would have been gold standard but this was limitation of our study as authors did not want to deprive half of the class from new learning strategy. conclusion cbl was found to be more effective learning strategy than sdl, as reflected in student's physiology scores of endocrine module exam. student's perception about cbl was concluded as it being a helpful and enjoyable tool for learning. references 1. pai km, rao kr, punja d, kamath ajtamj. the effectiveness of self-directed learning (sdl) for teaching physiology to f i r s t y e a r m e d i c a l s t u d e n t s . a u s t ra l a s m e d j . 2014;7(11):448. 2. knowles ms. self-directed learning: a guide for learners and teachers. eric. 1975. 3. murad mh, coto-yglesias f, varkey p, prokop lj, murad aljme. the effectiveness of self-directed learning in health professions education: a systematic review. med educ. 2010;44(11):1057-68. 4. srinivasan m, wilkes m, stevenson f, nguyen t, slavin sjam. comparing problem-based learning with case-based learning: effects of a major curricular shift at two institutions. acad med. 2007;82(1):74-82. 5. ricchi a, martelli e, molinazzi mt, vaccari s, messina mp, banchelli f, neri i. survey of students of the degree course in obstetrics, on learning using case-based learning (cbl) method in the area of professional teachings. clin ter. 2018 sep-oct;169(5): e213-e216. doi: 10.7417/ct.2018.2081. pmid: 30393807. 6. jamkar a, burdick w, morahan p, yemul v, singh gjijos. proposed model of case based learning for training undergraduate medical student in surgery. indian j surg. 2007;69(5):176-83. 7. mclean sfjjome, development c. case-based learning and its application in medical and health-care fields: a review of w o r l d w i d e l i te ra t u re . j m e d ed u c c u r r i c d e v. is cbl better than sdljiimc 2021 vol. 16, no.3 198 2016;3:jmecd. s20377. 8. datta a, ray jjiaoim. case based learning in undergraduate pathology–a study to assess its efficacy and acceptability as teaching-learning tool. int arch med. 2016;3(6):93-100. 9. chhabra n ka, kukreja s, gill m. introduction of case-based learning as a teaching/learning tool to enhance students' knowledge in biochemistry. curr trends diagn treat. 2017;1:96-9. 10. malau-aduli bs, lee ay, cooling n, catchpole m, jose m, turner rjbme. retention of knowledge and perceived relevance of basic sciences in an integrated case-based learning (cbl) curriculum. bmc med educ. 2013;13(1):139. 11. kamat sk, marathe pa, patel tc, shetty yc, rege nnjijop. introduction of case based teaching to impart rational pharmacotherapy skills in undergraduate medical students. indian j pharmacol. 2012;44(5):634. 12. hansen wf, ferguson kj, sipe cs, sorosky jjajoo, gynecology. attitudes of faculty and students toward casebased learning in the third-year obstetrics and gynecology clerkship. am j obstet gynecol 2005;192(2):644-7. 13. massonetto jc, marcellini c, assis psr, de toledo sfjbme. student responses to the introduction of case-based learning and practical activities into a theoretical obstetrics and gynaecology teaching programme. bmc med educ. 2004;4(1):26. 14. bowsher g, parry-billings l, georgeson a, baraitser p. ethical learning on international medical electives: a casebased analysis of medical student learning experiences. b m c m e d e d u c . 2 0 1 8 a p r 1 1 ; 1 8 ( 1 ) : 7 8 . d o i : 10.1186/s12909-018-1181-7. pmid: 29642906; pmcid: pmc5896122. 15. frambach jm, driessen ew, chan lc, van der vleuten cpjme. rethinking the globalisation of problem-based learning: how culture challenges self-directed learning. med educ. 2012;46(8):738-47. 16. chandrasekar h, gesundheit n, nevins ab, pompei p, bruce j, merrell sb. promoting student case creation to enhance instruction of clinical reasoning skills: a pilot feasibility study. advances in medical education and practice. 2018;9:249. 17. jauregui j, bright s, strote j, shandro j. a novel approach to medical student peer-assisted learning through case-based simulations. western journal of emergency medicine. 2018;19(1):193. 18. thistlethwaite je, davies d, ekeocha s, kidd jm, macdougall c, matthews p, et al. the effectiveness of case-based learning in health professional education. a beme systematic review: beme guide no. 23. medical teacher. 2012;34(6):e421-e44. is cbl better than sdljiimc 2021 vol. 16, no.3 199 original�article abstract objective: to evaluate the serum phosphate level of children with severe acute malnutrition and effect of therapeutic feeds (f75 and f100) on serum phosphate levels. study design: prospective observational study. place and duration of study : the study was conducted at stabilization center of children's hospital and st th institute of child health multan from 1 march 2018 to 30 march 2019. materials and methods: the total 270 children with severe acute malnutrition, who were under 5 years of age and admitted to the stabilization center for complicated sam during study duration were included in the study. initial management of the patients were started by following who protocols for severe acute malnutrition management and the baseline labs along with serum phosphate levels were sent for evaluation. patients were admitted at stabilization centre for the management plan as per guidelines. once the patients were stabilized in one week approximately the transition towards rehabilitation phase of severe acute management started. serum phosphate levels were assessed at admission, at stabilization (day 7 of admission) and at the time of discharge. data was analyzed using spss version 21. results: the mean age of our patients was 22 ± 2 months. the male to female ratio were 1:2. hypophosphatemia was documented in 180 (66%) patients with mean 0.96 ± 0.40 mmol/ltr < (1.45 – 1.78mmol/ltr) serum phosphate levels at the time of admission. during transition phase the phosphate levels were 1.1± 0.45 mmol/l and after rehabilitation phase 1.45 ± 0.45 mmol/l on average of 15 days of management. after using f75 and f100 therapeutic feeds in stabilization, transition, and rehabilitation phase 178 (98.9%) children were treated and had normal serum phosphate level at the time of discharge. conclusion: hypophosphatemia is commonly present in sam children. introduction of therapeutic feeds f75 and f-100 during stabilization phase and rehabilitation phase significantly improves phosphate levels in sam children with low phosphate levels. key words: hypophosphatemia, nutrition rehabilitation, phosphorous, severe acute malnutrition, serum phosphate levels, therapeutic feeds. children. according to national nutrition survey of pakistan (nns) 2018, percentage of underweight children was 28.9% (almost one in three children), stunting was seen in 40.2% (almost 4 in 10 children) 1,2 and wasting in 17.7%. therapeutic feeds as per who guidelines for management of sam are f75; which provides 75 kcal/100ml and f-100 which provides; 100 kcal/100 ml. f-75 is starter feed and f3 100 is the growth catch-up formula. malnourished children during initial stabilization phase are particularly at risk of developing re-feeding sy n d ro m e a n d e l e c t ro l y t e i m b a l a n c e s a s hypokalemia, hypomagnesemia, hypophosphate 4 that increases the risk of mortality. during refeeding the body converts from catabolism to anabolism and a shift occurs from fat to carbohydrate metabolism which elicits insulin release and increased cellular introduction early childhood less than five years of age is an important period for child survival, growth, and development. adequate nutritional intake currently is necessary for normal growth and development of serum phosphate level in patients with severe acute malnutrition at nutrition stabilization centre, children hospital, and institute of child health multan 1 2 3 4 5 6 saadia khan , reema arshad , saliha gillani , sundas irshad , tehseen ikram , nazia batool correspondence: reema arshad research associate department of pediatrics and child health, aga khan university karachi e-mail: reemaarshad0@gmail.com 1,4,5,6 department of preventive pediatrics the children's hospital and the institute of child health, multan 2 department of pediatrics and child health, aga khan university karachi 3 department of pharmacology nishter medical university, multan received: january 31, 2023; revised: june 14, 2023 accepted: 15, june 2023 jiimc 2023 vol. 18, no. 2 serum phosphate level in children with sam 105https://doi.org/10.57234/jiimc.june23.1647 uptake of electrolytes, including phosphate (i.e., natural occurring form of mineral phosphorous). if the diet contains insufficient amounts of phosphorous this may exacerbate phosphorous depletion. serum electrolytes are not routinely monitored; therefore, adequate phosphorous content in the diet is essential to prevent depletion. to prevent refeeding syndrome, the who's guidelines on in patient management of sam includes a stabilization phase with a low energy formula i.e., f-75 as well as gradual transition from stabilization phase (f-75) to rehabilitation phase (f100). f75& f100 therapeutic feed by who provided about 35mg/kg/dl of phosphorus on 130ml/kg/day feed from f75 to 156mg/kg/day of phosphorus during rehabilitation phase from 200ml/kg/day 0f 5 f100. in previous studies frequency of phosphate levels in children with sam varies from 72.9% 93% 6 , 7 w i t h l i m i t e d l o c a l d a t a . s t u d i e s o n hypophosphatemia in sam children are usually focused on stabilization phase and at first day of admission. hence it was planned to document phosphorous levels in sam children and to evaluate improvement in phosphate levels after using therapeutic feeds i.e., f75 and f-100. hence this study was aimed to evaluate the base line serum phosphate levels in children with sam and monitoring levels during transition and after rehabilitation phase for improvement after using who therapeutic feeding formulas. materials and methods a prospective observational study was conducted at stabilization center of children's hospital and st institute of child health multan pakistan from 1 th march 2018 to 30 march 2019. simple random sampling technique was used and 270 the children whose parents/guardians gave consent and were less than five years and admitted to the stabilization center with a diagnosis of uncomplicated sam i.e., weight/height or length <3sd or mid upper arm circumference ( muac) < 8 11.5cm were included in the study . after taking ethical board irb letter (chm-19-13, 03.01.2019) & informed written consent 290 patients fulfilling the inclusion criteria were enrolled during the study duration with sam admitted to stabilization centre. after explaining the risks and benefits of this research, written informed consent was taken from the children's parents/guardians. the children whose guardian refused consent or had chronic illness or secondary malnutrition were excluded from the study. a questionnaire was designed by the lead researcher and filled by the nursing staff of stabilization center. all children were managed according to who 8 guidelines. during initial stabilization phase f75 i.e 75 kcal/100 ml, 0.9 gm protein /100 ml was used to stabilize the patients orally or through nasogastric tubes 130 ml/kg/ day depending on the condition of patient. a child feeding 130 ml/kg/day f75 during stabilization phase gets 31mg/kg/day phosphorous. stabilization phase lasts for upto 7 days usually. d u r i n g re h a b i l i t a t i o n p h a s e a c h i l d g e t s 210ml/kg/day feed of f-100 which contains 152mg phosphorous/kg/day. after initial registration and admission baseline labs were sent to the clinical laboratory of ch & ich. patients were daily monitored for vital signs, weight, height, and edema. serum phosphate levels were measured at the time of admission, during the transition phase from stabilization to rehabilitation th approx. at 7 day of admission according to who protocols of sam management and during rehabilitation prior to discharge. data was analyzed using spss version 21, mean and averages of frequency was calculated and significant value <5 was considered significant. operational definition: serum phosphate level (1.45 – 1.78mmol/dl) were n o r m a l a n d < 1 . 4 5 m m o l / d l w e r e 9 hypophosphatemia . results the total 270 children with severe acute malnutrition up to 5 years of age were included in the study. the mean age of the children included in the research was 22 ± 2 months. the male to female ratio was 1:2 (table i). hypophosphatemia was documented in 180 (66%) patients with mean serum phosphate levels at the time of admission was 0.96 ± 0.40 < (1.45-1.78mmol/ltr) (table ii). after using f75 and f100 therapeutic feeds during transition phase of the management of sam patients the mean serum phosphate levels were improved to 1.1 ± 0.45 and after rehabilitation phase on an average of 15 days of management serum phosphate levels raised to 1.45 ± 0.45 mmol/lit. out of 270 children suffering from jiimc 2023 vol. 18, no. 2 106 serum phosphate level in children with sam https://doi.org/10.57234/jiimc.june23.1647 sam, who were treated with f75 and f100 therapeutic feeds in transition and rehabilitation phase 178 (98.9%) children improved with a normal serum phosphate levels. only two patients still had hypophosphatemia and were further investigated and diagnosed to be suffering from fanconi syndrome (table ii). study by menezs et.al., also reported significant a s s o c i a t i o n b e t w e e n m a l n u t r i t i o n a n d 10 hypophosphatemia. at the time of discharge phosphate levels in our study was 0.7% while in 5 another study it was found to be 17% or more. higher prevalence in the study by kimutai et al could be explained by difference in study population as they enrolled only children with edematous malnutrition. prevalence of edema was 20% in our study which was higher than the study done by 14 kimutai et al which reported 12.3%. early detection and monitoring of serum phosphate levels are mandatory in sam children to prevent re15-17 feeding syndrome. out of total about 66% children had hypophosphatemia in the present study. it also shows that malnourished children (sam) must be treated as per who guidelines and phosphorous supplementation in stabilization and rehabilitation phase is mandatory using therapeutic feed for better treatment outcome and to reduce re1 8 , 1 9 feeding syndrome. the therapeutic feeds prepared by who recipes for sam children proves to be effective for correcting the phosphate levels of sam children. similar results were documented by 10,16,20 menezes et al. the study was conducted in a public sector territory care hospital, the findings represent a wide range of population and can therefore be generalized for all sam children with medical complications during stabilization, transition, and rehabilitation phases. there are a few limitations of the study. postdischarge phosphate levels were not assessed in these children. a multicenter study with large sample size needs to be conducted in future to evaluate the association of hypophosphatemia among sam children with other factors. conclusion hypophosphatemia is commonly present in sam children. introduction of therapeutic feeds f75 and f-100 during stabilization phase and rehabilitation phase significantly improved phosphate levels in sam children with poor phosphate levels. references 1. bhutta z, soofi s, zaidi s, habib a. pakistan national nutrition survey, 2018. 2. bhutta z, berkley j, bandsma r, kerac m, trehan , et. al, a severe childhood malnutrition. nat rev dis primers. 2019;3(1):17067-69. doii: 10.1038/nrdp.2017.67 table i: baseline characteristics, anthropometry, and complications of sam children (n=270) table ii: serum phosphate levels of sam children (n=270) discussion this study shows that hypophosphatemia is very common in children with sam as supported by 6,10-12 similar result in other study. use of therapeutic feeds (f75 and f100) as per who guidelines significantly improves serum phosphate levels; mean 0.96 ± 0.4 to 1.45 ± 0.45 mmol/ltr after an average of 15 day stay. in our study frequency of hypophosphatemia among sam children was 66% during stabilization phase, 35.5 % during transition phase and only 0.7 % during rehabilitation phase. this prevalence is significantly 6,10 lower than reported by the previous studies. data suggest that prevalence of hypophosphate in critically ill children at icu was 71.6% which prolonged the hospital stay but was not directly 13 linked to increased mortality. however, in the present study we did not include the critically ill children in need of emergency care or on ventilators. jiimc 2023 vol. 18, no. 2 107 serum phosphate level in children with sam 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6:206 https://doi.org/10.12688/wellcomeopenres.16771.1. 17. namusoke h, hother al, rytter mj, kaestel p, babirekereiriso e, fabiansen c, girma t, et al. changes in plasma phosphate during in-patient treatment of children with severe acute malnutrition: an observational study in uganda. am j clin nutr. 2016;103(2):551-558. 18. manary m, hart c, whyte m. severe hypophosphatemia in children with kwashiorkor is associated with increased mortality. j paediatr. 2018;133(3): 789–791. doi: 10.1016/s0022-3476(98)70153-2. 19. ahmed ny, doaa s, effat h, eman b, ibrahim a, et. al. phosphate disturbance in critically ill children: incidence, associated risk factors and clinical outcomes. ann surg.2017; 210 (2):118-123. https://doi.org/10.1016/ j.amsu.2017.07.079. 20. arunpandiyan s, rajesh s, preeti s, anju j, anju s, et. al. serum phosphate profile of children with severe acute malnutrition treated with locally prepared therapeutic feeds: a prospective observational study int j clin. 2021; . 10(2): 35-42.doi: https://doi.org/10.14740/ijcp458. conflict of interest authors declared no conflicts of interest. grant support and financial disclosure authors have declared no specific grant for this research from any funding agency in public, commercial or nonprofit sector. data sharing statment the data that support the findings of this study are available from the corresponding author upon request. this is an open access article distributed under the terms of the creative commons attributionnoncommercial 2.0 generic license. jiimc 2023 vol. 18, no. 2 108 serum phosphate level in children with sam https://doi.org/10.57234/jiimc.june23.1647 original�article abstract objective: to determine the frequency of chikungunya virus (chikv) infection in the tertiary care hospital of st st karachi during the time from 1 january 2017 till 31 december 2018. study design: this was a retrospective cross-sectional study. place and duration of study: the study was conducted in the department of microbiology, dow diagnostic st st reference and research laboratory, karachi, pakistan from 1 january 2017 till 31 december 2018. materials and methods: serum of suspected patients of chikungunya virus infection was separated from venous blood samples and checked for immunoglobulin m (igm) antibodies against chikungunya virus infections by applying a micro titer plate assay elisa). data was collected after enzyme-linked immunosorbent ( the approval of ethical committee of dow university of health sciences by pacslink software and analysis was accomplished by using statistical package for social science spss version 17.0 for frequencies of age group, gender, and igm positive chikungunya virus infection. results: out of 4329 venous blood samples collected from suspected patients of chikungunya virus infection. 1181(27%) showed the presence of igm of chikungunya virus (chkv) infection. majority of the patients were in the third decade of their lives with median age of 38.74 years. the proportion of males was slightly more 605 (51%) than females 575 (48%) (table i). age group 16-44 years showed high prevalence 627 (53%) as compared to other age groups (2017-2018) (figure: 1). incidence of chikv was higher in october and november 2017(37.8%), than 2018 (figure: 2). conclusion: this study concluded that the frequency of chikungunya virus infection was higher during the st st period from 1 october till 31 november 2017. key words: chikungunya virus, infection control, serology markers, tertiary care hospital, viral diseases. observed 4-7 days after the bite of a mosquito. arthralgia is the main symptom involving the ankle joint, knee joint, lower back, wrist, and phalanges. fever comes with rigors and chills and has a distinctive biphasic trend. other symptoms including nausea, fatigue, headaches, muscle pains and 3 rashes. the disease is self-limiting, but it may take a 4 prolonged course before it abates. high-risk population includes newborns infected around the time of birth, older adults (>65 years), patients with medical condition such as increased blood pressure, 5 diabetes, or heart disease. aedes albopictus and aedes aegypti are responsible for the spread of the virus. these mosquitoes are mostly found in tropical and subtropical locations and frequently bite during daylight. the proximity of mosquito breeding to human habitation is a significant risk factor for c h i k u n g u n y a . c o m p l i c a t i o n s i n c l u d e t h e involvement of urinary, cardiovascular, cerebral, and digestive systems. if the virus is transferred via the vertical route of transmission, it may lead to neurointroduction the name chikungunya derives from makonde, which means to become contorted. chikungunya virus (chikv) is an enveloped, single-stranded, positive sense flavivirus that is sustained in nature 1 between humans and aedes mosquito. these vectors are found all over the globe and are responsible for many outbreaks. female mosquitoes are responsible for the transfer of virus because blood meal is special ingredient for the development of egg. the virus used to divide in the salivary gland 2 of mosquitoes. the chikv symptoms can be frequency of chikungunya virus infection in the tertiary care hospital of karachi fouzia zeeshan khan, fatima fasih, mohammad sohaib tauheed, saba hassan, sambreen zameer correspondence: dr. fouzia zeeshan khan assistant professor department of pathology dow university of health sciences, karachi e-mail: fouzia.zeeshan@duhs.edu.pk department of pathology dow university of health sciences, karachi funding source: nil; conflict of interest: nil received: june 16, 2020; revised may 02, 2021 accepted: may 04, 2021 chikungunya virus infection in karachijiimc 2021 vol. 16, no.3 146 disability due to severe encephalopathy. currently, chikv fever has affected more than 50 countries. the global distribution of a. aegypti is expanding due to global travel and trade, including the virus. it has become a public health problem in asia, africa, europe, and america. in late 2004, there was a massive outbreak in eastern africa that extended to india and east asia in a span of 2 years, which 6 affected approximately 2 million people. a study conducted by muhammad et al proposed detection 7 of chikv during dengue outbreak in 2011 in lahore . in september 2016, national institute of health (nih) had issued a warning concerning the risk factors involved in chikungunya disease after its outbreak in india. so, after the nih warning due to lack of appropriate measures pakistan had its first chikungunya outbreak in the populated area of karachi, including malir, shah faisal, saudabad and neighborhoods, where over 3000 people have been infected in nov 2016. in addition, pakistan had a burden of other viral infections including crimeancongo hemorrhagic fever, dengue in 2016. world health organization and health authorities had a 8 serious concern about these viral emergencies. chikv infection suspicion is based on clinical and epidemiological criterion, but disease confirmation required laboratory testing. laboratory diagnosis involves detection of viral rna and serological testing. serological tests are the most used for the diagnosis of chikv. a combination of molecular and igm antibody detection assays is suggested for diagnosis of chikv infection. chikungunya igm antibodies are appeared and detectable after 3-5 days of chikungunya viral infection and elevated for 3 -6 months. in addition, chikv igg antibodies appear after two weeks of infection and remain elevated for 9 years. after chikv emerged in karachi during 2016, and an outbreak eventually was declared when 10 evidence of local transmission was confirmed. babar et al reported higher rate of chikv infection in 11 the duration of december 2016 till may, 2017. the current outbreak of 2016-17 in pakistan was termed as a mysterious disease related to warm climate and 12 substandard sanitary state of the town. due to the higher number of cases observed in the duration of 2016-2017, we planned this study with the objective to assess the incidence of chkv infection in our setup st st during the period of 1 january 2017 till 31 december 2018. materials and methods it was a retrospective cross-sectional study, conducted with convenience sampling technique in the department of microbiology, dow diagnostic reference and research laboratory, karachi, st st pakistan, during the time from 1 january 2017 till 31 december 2018. the patients were suspected cases of chikungunya virus infection. they were advised for the detection of igm antibody of chikungunya virus by their physician. the permission for conducting this study was taken from the institutional review board of dow university of health sciences. the retrospective, non-parametric data was retrieved from pacslink (laboratory data software) then it was shifted to spss software for final evaluation. venous blood samples were collected from suspected patients of chikungunya virus infection. 5 ml venous blood received in yellow cap gel tubes, after centrifugation for 10 minutes, serum was separated for further testing. 10 microliter serum was checked for immunoglobulin m (igm) antibodies against chkv infections by applying a micro titer plate elisa assay. the test was done according to the kit manufacturer's protocol (euroimmun, elisa reader statfax) and inferred either positive or negative based on absorbance with respect to cutoff values. data analysis was accomplished by using statistical package for social science (spss version 17.0) for frequencies of age group, gender, and igm positive chikungunya virus infection. we included only those blood samples of patients who were registered for detection of igm of chikungunya virus infection irrespective of age and gender. exclusion criteria included clinical samples of patients registered for detection of igm of chikungunya virus with inadequate serum volume, improper labeling, and absence of demographic information. results a total of 4329 blood samples of suspected patients were registered for the testing of the occurrence of igm of chikv infection during the period from st st 1 january 2017 till 31 december 2018. out of total (4329) blood sample 1181 (27%) were showed the presence of igm antibodies of chikv. majority of them were in the third decade of their lives with median age of 38.74 years. males were slightly more chikungunya virus infection in karachijiimc 2021 vol. 16, no.3 147 605(51%) than female 575(48%) (table:1). age group 16-44 showed high prevalence of igm 627(53%) as compared with other age groups (figure: 1). incidence of chkv was higher in october and november 2017(37.8%), than 2018 (figure: 2). in economic burden on patients. our study discovered a high incidence of chkv during the period of october and november in 2017; however, the emergence of chikv was not highly reported during 2018. naik et al also reported highest incidence in monsoon period starting from july till 13 october. similarly one more study from india 1 4 endorsed our finding. intense breeding of mosquitoes occurs from july till october, before and after monsoon rains. the stagnant water is converted into small ditches, which results in the growth of insects, thereby imposing a substantial burden on the control of mosquito-borne infections. the outbreak is linked with warm climate and inadequate sanitary conditions. the poor hygienic system of karachi including open drains and feculent morasses are brilliant breeding habitats for mosquitoes. vector control is the most significant strategy in controlling the transmission of chkv 15 infection. furthermore, a study found that besides abiotic factors (temperature & humidity), habitat also plays a major role in the growth of mosquitoes a. aegypti resides in water collected close to residential 16 areas. current study reported high prevalence in age group 16-44 years with male predominance, 17-19 endorsed by other studies. however, lubna et al contradicted the results of our study and showed 20 higher prevalence in females. our study estimated igm antibodies in the serum of 27% suspected cases of chkv. another study revealed 38.06% cases were 21 positive by igm antibodies. a conclusive lab diagnosis can be made by evaluating acute-phase serum or plasma by pcr, igm and neutralizing 22 antibodies. development of igm antibodies occurs at the end of the first week of infection. therefore, samples should be obtained from a convalescent period of illness otherwise igm antibodies will be replaced by igg antibodies. chikungunya is usually m i s d i a g n o s e d a s d e n g u e t h a t r e s u l t s i n 23 complications and further spread of disease. since three decades, statistical analysis of diagnosed and undiagnosed viral infections showed no indication of the prevalence of chikv in 24 pakistan. however, poor diagnostic tools could be one of the reasons or unlike other viral infections, which present with the same symptomatic manifestations. the eco-tourism and global travelling have brought about outstanding changes fig 1: frequency of chikungunya virus infection in different age groups from 2017-2018 (n=4329) table i: gender wise distribution of chikungunya virus infection from 2017-2018 n=4329 fig 2: month wise frequency of chikungunya virus infection in year 2017-2018 discussion since its identification in 1953, there have been multiple epidemics of chikv infections throughout 2 africa and asia. the emerging chkv infection in pakistan has become a serious threat with a significant effect on public health because of its epidemics and devastating symptoms which results chikungunya virus infection in karachijiimc 2021 vol. 16, no.3 148 in the epidemiology of ckhv in pakistan. a study found phylogenetic close strains of chkv in india and 25 pakistan. local health authorities should take serious action against the occurrence of a regional epidemic of arbo viral diseases during the monsoon 1 5 season. nih had alerted and advised the government to be vigilant across border travelling. there is increasing spread of infectious diseases to other parts of the country due to lack of preventive measures and screening for viral diseases at airports, 26 railway stations and at the pakistan–india border. we have no prophylaxis measures like vaccines, to fight against chikv. only supportive treatments are provided to symptomatic patients. the constant reporting of clinical cases of chikv in pakistan is alarming. moreover, continuous incidence in the last two years is justified that if proper precautions will not be taken, then devastating complications of 27 chikv may occur in pakistan. we acknowledge number limitations of our study such as lack of history from suspected cases of chikungunya virus infection and unavailability of confirmatory test (rtpcr) to all igm positive. despite all these limitations, detection of igm antibodies is cost effective initial tool for finding of acute phase chikungunya virus infection. our data also helped us in detecting seasonal variations in emergence of chikungunya virus infection. conclusion an emerging epidemic of chkv infection in pakistan is distressing issue. this study found that the frequency of chikungunya virus infection was higher during the period of october and november 2017 with male predominance and age group 16-44years. the important measures for the control of chkv infection including surveillance programs, proper disposal of waste, vector control, and public awareness programs through available resources, efficient diagnostic tools and development of good health care system should be established on an urgent basis. references 1. barr kl. human west nile virus disease outbreak in pakistan 2015-2016. frontiers in public health. 2018; 6:384. 2. darwish ma, hoogstraal h, roberts tj, ahmed ip, omar f. a sero-epidemiological survey for certain arboviruses (togaviridae) in pakistan. transactions of the royal society of 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hu w, et al. co-distribution and co-infection of chikungunya and dengue viruses. bmc infectious diseases. 2016;16(1):84. 24. organization wh. chikungunya reported in pakistan. 27 february 2017. 25. liu s-q, li x, zhang y-n, gao a-l, deng c-l, li j-h, et al. detection, isolation, and characterization of chikungunya viruses associated with the pakistan outbreak of 2016–2017. virologica sinica. 2017;32(6):511-9. 26. the express tribune. chikungunya outbreak traced back to india. 2016. 27. elbers a, koenraadt c, meiswinkel r. mosquitoes and culicoides biting midges: vector range and the influence of climate change. rev sci tech. 2015;34(1):123-37. chikungunya virus infection in karachijiimc 2021 vol. 16, no.3 150 original�article abstract objective: to determine the prevalence of blindness and partial sight among the indoor diabetic patients of a teaching hospital. study design: observational/cross-sectional study. place and duration of study: the departments of medicine, surgery, obstetrics and gynecology and st th ophthalmology at pakistan railway hospital rawalpindi from 1 november 2018 to 30 november2019. materials and methods: history and clinical information of 200 indoor diabetic patients (400 eyes) admitted in the departments of ophthalmology, medicine, surgery and obstetrics & gynecology were noted on organized and institutionalized questionnaire. detailed ocular examination was performed by a qualified ophthalmologist. only visual acuity (va) criteria was used to define visual impairment. the data was evaluated using spss version 21. results: two hundred indoor diabetic patients (400 eyes) were included in the study. among them 91 (45.5%) were males and 109 (54.5%) were females. the number of patients having age below 30 years were 7 (3.5%), between 30 to 60 years of age were 84 in number (42%) and 109 patients (54.5%) were over 60 years of age. no visual impairment was found in 38 patients (19%). there was partial sight in 97 patients (48.5) and blindness was recorded in 65 patients (32.5%) of the total. cataract as the cause of visual impairment was found in 63 patients (38.8%). diabetic retinopathy was the cause in 55 patients (33.9%). diabetic macular edema was found in 35 patients (21.6%) and age-related macular degeneration in 7 patients (4.3%). glaucoma was found in 2 patients (1.2%). visual impairment in our patients was significantly associated with age, duration of diabetes, bmi, hypertension, heart disease, peripheral neuropathy, pregnancy (p<0.05). conclusion: it is concluded that the prevalence of visual impairment among diabetic patients is quite high. there is an increased risk of visual impairment with the increase in the age, duration of diabetes and other associated risk factors such as hypertension, heart disease, increased bmi and peripheral neuropathy. key words: blindness, diabetes mellitus, diabetic retinopathy, prevalence, visual impairment. 3 its adult population has diabetes. in pakistan, we have an expected 7.5 million individuals known to have diabetes, and number is to be expanded to 16.1 4 million by year 2045. the increase in the frequency of dm proposes that more individuals with this condition will turn out to be visually impaired if steps are not taken to anticipate the occurrence of dm and its visual complications. dm is driving reason for the visual impairment among various regions of the world. diabetic retinopathy causes 12000 to 24000 new 5 cases of blindness every year in united states. changes in the way of life have expanded the danger of diabetes as well as visual impairment in many 6 developing countries. in oman, the prevalence of visual impairment in diabetics is 28.4%. with increase in the incidence of dm, the odds of visual misfortune are on the rise. it is entrenched that in the introduction diabetes mellitus (dm) is a multifactorial disease responsible for many complications including visual 1 impairment. according to who, by 2025, there will be 300 million diabetics of which 75% will be in th developing countries with pakistan as the 4 country 2 in the list. pakistan exhibits a rise in diabetes. more than 10% of prevalence of visual impairment among indoor diabetic patients at teaching hospital of rawalpindi 1 2 3 4 muhammad shafeh shehzad , muhammad usayd khan , saqib jan shah , aneeq ullah baig mirza correspondence: muhammad shafeh shehzad student final year mbbs islamic international medical college riphah international university, islamabad e-mail: shafeh89@gmail.com 1,2,3 4 student final year mbbs/department of ophthalmology islamic international medical college riphah international university, islamabad prevalence of visual impairment in dmjiimc 2020 vol. 15, no.3 funding source: nil; conflict of interest: nil received: november 15, 2019; revised: september 06, 2020 accepted: september 07, 2020 183 duration of diabetes, existence of one or more comorbidities including hypertension, heart disease, renal disease and neuropathy were noted. biological assessment included bmi, smoking and pregnancy. detailed ophthalmic examination was done by a qualified ophthalmologist which included snellen's visual acuity and pinhole vision to rule out refractive errors. slit-lamp examination for anterior segment and funduscopic with maximum mydriasis was done for the posterior segment. where there was more than one cause of visual impairment, the irreversible cause was mentioned. only visual acuity (va) criteria was utilized to depict visual impairment in our study using the us definitions which defines partial sight as 20/200 (6/60) < va < 20/40 (6/12) and blindness is defined as 9 va of < 20/200 (6/60) in the better eye. when describing both blindness and partial sight, the term visual impairment (vi) was used. the main diagnostic group of the causes of visual impairment were cataract, age-related macular degeneration (armd), glaucoma and diabetic retinopathy (dr). diabetic retinopathy was further classified into nonproliferative diabetic retinopathy (npdr) and 10 proliferative diabetic retinopathy (pdr). the data collected was of non-parametric type and was evaluated using spss version 21. chi-square statistics was utilized to evaluate the relations. the confidence level (ci) of 95% was set. a p-value of less than 0.05 was deemed statistically significant. results two hundred indoor diabetic patients (400 eyes) were included in the study. demographic findings are shown in table i. upcoming 15 years, roughly 2% of diabetics may turn lawfully blind, and around 10% may create serious 7 visual impairment. thus, for the avoidance of visual impairment at around the world, tending to visual complications of diabetes is required. it is assessed that the pervasiveness of hypertension in type 2 8 diabetes is 50%. in pakistan, a research conducted 10 years ago showed the prevalence of non-proliferative diabetic retinopathy (npdr) in 25.14% and proliferative 8 diabetic retinopathy (pdr) in 11.11% of cases. variations in the incidence of diabetes suggests that the current status of visual impairment in the diabetics is expected to be different from that reported previously. the objective of our study is to determine the prevalence and reasons of blindness and partial sight among the indoor diabetic patients of a teaching hospital and to assess the effect of duration, type, gender, hypertension, body mass index (bmi), heart disease, smoking, pregnancy, neuropathy and nephropathy on incidence and progression of visual impairment. our information will be valuable for future correlations and give benchmark data to screen the advancement towards the reduction in visual impairment because of diabetic eye difficulties. materials and methods in this observational/cross-sectional study, all the ambulant patients who were diabetic and admitted in the departments of medicine, surgery, obstetrics & gynecology and ophthalmology at pakistan st railway hospital rawalpindi from 1 november 2018 th to 30 november 2019 were examined in detail. the number of indoor diabetic patients thoroughly examined to check for the visual impairment was 200 (400 eyes). the sampling technique used was nonprobability consecutive sampling. the study was approved by the ethics review committee of islamic international medical college. type 1 and type 2 diabetic patients above the age of 20 years were included in the study. the patients who were non-ambulatory due to their deteriorated clinical condition were excluded from the study. informed verbal consent was taken before examination. history and clinical information were noted on structured questionnaire. age, gender, type and table i: age and gender. n=200 type 1 dm was found in 6 patients (3%) and type 2 in 194 patients (97%). patients having span of diabetes mellitus for under 5 years were 70 (35%), those with the length of illness between 5 to 10 years were 47 (23.5%) and those over 10 years was found in 83 patients (41.5%). prevalence of visual impairment in dmjiimc 2020 vol. 15, no.3 184 prevalence of the stages of diabetic retinopathy was also assessed among the patients. npdr was found in 126 eyes (31.5%) and pdr was found in 56 eyes (14%). it was similarly noticed that with the increase in the duration of diabetes mellitus, the significant cause for visual impairment was seen as dr with a prevalence of 50.6% in individuals with duration of diabetes greater than 10 years as shown in figure 2. prevalence of the visual impairment is shown in table ii. table ii: prevalence of visual impairment. (n=200) patients of dm with associated systemic diseases were 131 hypertensives (65.5%), 77 patients (38.5%) had some sort of adult onset heart disease, peripheral neuropathy was found in 123 patients (61.5%), and renal disease was found in 73 patients (36.5%). during the biological assessment according to bmi 12 patients (6%) were underweight, 116 (58%) were normal in range and 72 patients (36%) were found to be overweight. 43 patients (21.5%) were active smokers. our study comprised of 7 female pregnant patients (3.5%). the main causes of visual impairment among the diabetic patients found in our study are mentioned in table iii and figure 1. table iii: causes of visual impairment (n=162) our study showed that cataract was the major cause of visual impairment overall with prevalence of 38.8% and diabetic macular edema was main reason of blindness with an occurrence of 47.6% among blind people as shown in figure 1. fig 1: causes of visual impairment. fig 2: changes in the causes of visual impairment with the increase in dura�on of dm visual impairment in our patients was significantly connected with age (p=0.001), duration of diabetes (p=0.00001), bmi (p=0.01), hypertension (p=0.02), heart disease (p=0.041), peripheral neuropathy (p=0.044), pregnancy (p=0.01). visual impairment was also significantly related with causes of visual impairment including cataract (p<0.001), dr (p<0.001), stage of dr (p<0.001), dme (p<0.001), armd (p<0.001), glaucoma (p<0.001). however, our study didn't show a significant association with gender (p=0.11), type of dm (p=0.45), smoking (p=0.34) and renal disease (p=0.53). discussion for the reduction of visual problems, we need information of the occurrence and reasons for visual impairment among the individuals with dm. our study gives such information to the health care experts to plan effective management for the patients. our study reports high prevalence of partial sight (48.5%) and blindness (32.5%) among the diabetic prevalence of visual impairment in dmjiimc 2020 vol. 15, no.3 185 population. the prevalence of stages of dr can be compared with previous study held in a developing country where ratio of npdr was 31.1% and pdr was 22% among 13 the diabetic patients. in another previous research of a developing country npdr was detected in 54.8%, this higher value in their research was because the patients which were included mainly presented in the eye departments when they got their condition of the eyes worst. in a previous research of a developed country npdr was found in 17 11.66% and pdr in 0.36%. the lower number of patients with both pdr and npdr compared to our research are because of better health facilities including early screening programs throughout the country. by comparing our results with a researchconducted 10 years ago in the same hospital as ours showed 18 increase in the prevalence of npdr and pdr. npdr increased from 25.14% to 31.5% and pdr increased from 11.11% to 14%. this increase in patients may be because of the low socioeconomic status of the area of study due to which they cannot afford the 5 treatment. in our study, the incidence of visual impairment was not statistically associated with gender, but it was associated with age hence it increased with the increase in the age. the other risk factors that had significant associations included increased bmi, hypertension, heart disease and peripheral neuropathy. smoking was not statistically associated with visual impairment. this was compared with a previous study among tunisian diabetic patients which also had a significant relation of the above19 mentioned risk factors. however, in contrast to the mentioned study, our study did not show a significant correlation of renal disease with the visual impairment, this may be because our collection of data on renal disease was based on the history alone. it is noted in our study that visual impairment was associated with the duration of diabetes. with the increase in the span of diabetes it was seen that visual impairment also increased. visual impairment was also significantly associated with complications such as cataract, dr, dme, armd and glaucoma. the associations of duration of diabetes, advanced stage dr, dme and cataract with visual impairment were 20 also seen in the previous studies. patients. cataract was the significant reason for visual impairment in our investigation with a frequency of 38.8%. our study also recorded a high prevalence of 31.5% with npdr and 14% with pdr. diabetic macular edema (dme) was found to be the major reason of blindness with incidence of 47.69% of the blind population in our study. this can be compared with a study of another developing country where it was found that partial impairment was found in 39.3% of the patients and 15.7% were blind. the higher rate of blindness in our study can be due to the fact that our study was performed on indoor patients who are admitted with increased comorbidities. it was likewise noticed that there were more patients of higher age group included in the study. it was noted that with increasing age more patients were found to be visually impaired which is also mentioned in another 5 previous study. by comparing our study with a study conducted in a developed country like england showed significant difference in visual impairment and blindness. their study showed data of visual impairment in 2.84% and 7 blindness in 1.13%. this difference is because of better health care facilities provided in developed countries. a past report of jordanian diabetic's demonstrated cataract as the major source of visual impairment in 11,12 diabetics with incidence of 37.8%. cataract is similarly seen as the main source of visual 5, 13, 14, 15 impairment in other developing countries. our study also showed that in individuals with the increase in duration of dm of over 10 years, dr was seen as the main source of visual impairment. this can be compared with a previous study which additionally indicates that with increasing duration of dm, dr is seen as the main source of visual 16 impairment. some previous studies also show that 12, 13, dme as the main source of blindness in diabetics. 15 age related macular degeneration (armd) was seen as the main source of visual impairment in the 7 developed nations like england. an investigation of the developed nation indicated that dr was seen as driving reason for visual impairment among the 7 working age population of individuals with dm. however, in our study, cataract was the major cause of visual impairment among the working age prevalence of visual impairment in dmjiimc 2020 vol. 15, no.3 186 government health facilities in the mopani district, south africa. african vision and eye health. 2014 4; 73(1):8-15. 6. resnikoff s, pararajasegaram r. blindness prevention programmes: past, present, and future. bulletin of the world health organization. 2001; 79:222-6. 7. prasad s, kamath gg, jones k, clearkin lg, phillips rp. prevalence of blindness and visual impairment in a population of people with diabetes. eye. 2001; 15(5):640. 8. basit a, hydrie mz, hakeem r, ahmedani my, masood q. frequency of chronic complications of type 2 diabetes. j coll physicians surg pak. 2004; 14(2):79-83. 9. pascolini d, mariotti sp. global estimates of visual impairment: 2010. british journal of ophthalmology. 2012 1; 96(5):614-8. 10. solomon sd, chew e, duh ej, sobrin l, sun jk, vanderbeek bl, wykoff cc, gardner tw. diabetic retinopathy: a position statement by the american diabetes association. diabetes care. 2017 1; 40(3):412-8. 11. massin p, kaloustian e. the elderly diabetic's eyes. diabetes & metabolism. 2007 1; 33: s4-9. 12. al-till mi, al-bdour md, ajlouni km. prevalence of blindness and visual impairment among jordanian diabetics. european journal of ophthalmology. 2005; 15(1):62-8. 13. al akily sa, bamashmus ma, gunaid aa. causes of visual impairment and blindness among yemenis with diabetes: a hospital-based study. emhj-eastern mediterranean health journal. 2011; 17(11):831-837. 14. khandekar r, mohammed aj. visual disabilities among diabetics in oman. saudi medical journal. 2005; 26(5):83641. 15. hajar s, al hazmi a, wasli m, mousa a, rabiu m. prevalence and causes of blindness and diabetic retinopathy in southern saudi arabia. saudi medical journal. 2015; 36(4):449. 16. song p, yu j, chan ky, theodoratou e, rudan i. prevalence, risk factors and burden of diabetic retinopathy in china: a systematic review and meta-analysis. journal of global health. 2018; 8(1). 17. rodriguez-poncelas a, miravet-jiménez s, casellas a, barrot-de la puente jf, franch-nadal j, lópez-simarro f, mata-cases m, mundet-tudurí x. prevalence of diabetic retinopathy in individuals with type 2 diabetes who had recorded diabetic retinopathy from retinal photographs in catalonia (spain). british journal of ophthalmology. 2015 1; 99(12):1628-33. 18. mirza aub, babar f, zulfiqar a, arif a. frequency of clinically visible diabetic retinopathy among indoor diabetic patients in a teaching hospital of rawalpindi. pak j pathol. 2009; 20(4):122-7. 19. kahloun r, jelliti b, zaouali s, attia s, yahia sb, resnikoff s, khairallah m. prevalence and causes of visual impairment in diabetic patients in tunisia, north africa. eye. 2014; 28(8):986. 20. jeppesen p, bek t. the occurrence and causes of registered blindness in diabetes patients in århus county, denmark. acta ophthalmologica scandinavica. 2004; 82(5):526-30. this study has some limitations so the outcomes ought to be perused with caution. the hospital based indoor contextual analysis for the most part chooses the patients which are bed bound already in crumbled condition when contrasted with outdoor patients. study was directed in a single teaching hospital so the results may not be summed up for the entire population. other limitations included cross sectional nature and the data collection of associated risk factors were based on previous health records. regardless of these confinements this investigation gives important information which can characterize the magnitude of the issue in population. our study provides a baseline data for future comparison studies in this region and other developing countries. in addition, our data will also be useful for the health care providers to minimize the comorbidities such as visual impairment associated with diabetes. aggressive screening programs should be inculcated in primary health care. proper eye care services should be provided at affordable rates. conclusion it is concluded that the prevalence of visual impairment among diabetic patients is quite high. there is an increased risk of visual impairment with the increase in the age, duration of diabetes and other associated risk factors such as hypertension, heart disease, increased bmi and peripheral neuropathy. references 1. lotfy m, adeghate j, kalasz h, singh j, adeghate e. chronic complications of diabetes mellitus: a mini review. current diabetes reviews. 2017 1; 13(1):3-10. 2. shera as, jawad f, maqsood a. prevalence of diabetes in pakistan. diabetes research and clinical practice. 2007 1; 76(2):219-22. 3. jawaid sa. proceedings of an advance course in management of diabetes mellitus. pakistan journal of medical sciences. 2002; 18(1):55-60. 4. basit a, fawwad a, qureshi h, shera as. prevalence of diabetes, pre-diabetes and associated risk factors: second national diabetes survey of pakistan (ndsp), 2016–2017. bmj open. 2018 aug 1; 8(8): e020961. 5. mabaso rg, oduntan oa. prevalence and causes of visual impairment and blindness among adults with diabetes mellitus aged 40 years and older receiving treatment at prevalence of visual impairment in dmjiimc 2020 vol. 15, no.3 187 untitled-2 untitled-1 case�report abstract association of acute myeloid leukaemia with bone marrow plasmacytosis is a rare phenomenon with diverse underlying pathogenetic mechanisms. we report a case of a 75 years old diabetic male diagnosed as suffering with plasmacytosis. there were no lytic bone lesions or bence‐jones proteinuria. serum protein electrophoresis did not show a monoclonal band. a presumptive diagnosis of aml with reactive plasmacytosis was made. possible conditions which can be considered in differential diagnosis are discussed. key words: acute myeloid leukaemia, multiple myeloma, reactive plasmacytosis. showed 75%blast cells and an increase in the plasma cells to 15% (fig 1). bm trephine showed prominent plasma cells present interstitially as well as in small clumps (fig 2). diagnosis of aml with plasmacytosis was considered and further investigations were done to rule out concomitant mm. skeletal survey did not show any lytic lesions. urine examination for bence‐jones proteins was negative. s e r u m p r o t e i n e l e c t r o p h o r e s i s r e v e a l e d hypoalbuminaemia and a polyclonal increase in gamma globulins. no paraprotein band was detected. serum free light chain assay was not done due to non availability. analytical immunocytometry revealed 'aml with differentiation' (fab type: aml‐ m2). cytogenetics showed a normal karyotype. a presumptive diagnosis of aml‐m2 with reactive plasmacytosis was made and patient was shifted to the oncology ward but he died the next day before chemotherapy could be initiated. (total duration of stay at the hospital was 12 days). discussion reactive bm plasmacytosis is characterized by an increase in the percentage of plasma cells above the normal, i.e. more than 3% but generally it does not 5 exceed 20%. it is seen in chronic infections, autoimmune diseases, connective tissue disorders, diabetes mellitus and malignancies. rare causes include angioimmunoblastic lymphadenopathy and multicentric castleman's disease. in aml , reactive bm plasmacytosis may be due to the presence of e i t h e r s o m e c o n c o m i t a n t , o r p r e c e d i n g inflammatory or infectious disorder and the plasma cells are considered to proliferate due to persistent 3 antigenic stimulation. paracrine stimulation by interleukin (il)‐6 secreted by leukaemias cells has 2,6,7 also been proposed as a cause. our patient was a known diabetic and patients with diabetes mellitus introduction association of acute myeloid leukaemia (aml) with bone marrow (bm) plasmacytosis is a rare phenomenon with only a few cases reported in the 1 l i t e r a t u r e . t h e u n d e r l y i n g p a t h o g e n e t i c mechanisms causing bm plasmacytosis in patients of aml appear to be diverse as shown in the table. in the literature it has been mainly reported to occur in patients of aml as reactive proliferation discovered at the time of diagnosis; after induction‐ chemotherapy and rarely with simultaneous 2‐4 occurrence of multiple myeloma (mm). we report a case of aml with reactive plasmacytosis in an elderly diabetic and discuss the differential diagnosis. case report a 75‐year‐old male patient presented with complaints of low grade fever and lassitude of two month duration in the medical opd of military hospital rawalpindi. he was a known case of type 2 diabetes mellitus for the past 25 years. on examination, he was pale and emaciated. blood counts revealed pancytopenia with hemoglobin of 9 6.7 g/dl, white blood cell count of 1.8x10 /l and 9 platelet count of 87x10 /l. peripheral film showed rouleaux formation and esr was 130 mm at the end of first hour. serum urea and creatinine levels were raised (15.8 mmol/l and 225 μmol/l respectively). serum calcium levels were normal. his bm aspirate acute myeloid leukaemia with plasmacytosis 1 2 3 yasmin akhtar , saqib qayyum ahmad , shahid jamal jiimc 2016 vol. 11, no.4 correspondence: dr. yasmin akhtar department of haematology army medical college, rawalpindi e‐mail: aftersunset79@yahoo.com 1 2,3 department of haematology / pathology army medical college, rawalpindi funding source: nil; conflict of interest: nil received: aug 30, 2016; revised: oct 10, 2016 accepted: nov 20, 2016 aml with plasmacytosis 189 are prone to acute and chronic infections, which might have been responsible for reactive plasmacytosis. aml with reactive plasmacytosis has to be differentiated from a very rare, simultaneously 4,7 occurring aml with concomitant mm. this is important because the latter requires different therapeutic approach. clues from history, clinical examination, and presumptive. cytological features may help to differentiate reactive plasmacytosis from mm but no discriminatory cut‐off value of plasma cells percentage in the bm has been defined. normally, plasma cells are scattered interstitially and may be seen associated with macrophages and around the 5 capillaries. in reactive plasmacytosis, the plasma cells have mature nuclear and cytoplasmic characteristics, although binucleate forms may also be seen. a few small clumps may also be seen in case of reactive plasmacytosis but the number of plasma 5 cells in the clumps is generally less than ten. the presence of plasma cell dysplasia and plasmablasts is strongly suggestive of multiple myeloma. cytological features in our patient favoured reactive plasmacytosis. patients with mu ltip le myelo ma ( mm) o r monoclonal gammopathy of undetermined significance have an increased inherent risk of developing acute myeloid leukemia (aml) which is 4 independent of prior chemotherapy. a common aetiologic agent could be responsible for some cases o f co n co m i ta nt a m l a n d m m . a m l i s a morphologically, genetically, phenotypically and b i o l o g i c a l l y h e t e r o g e n e o u s d i s o r d e r a n d 2 plasmacytosis is seen in 6‐7 % of cases of aml. does aml with reactive plasmacytosis also qualify as a separate entity in the classification of aml? microscopic examination of the stained smear of bm from a patient of aml with reactive plasmascytosis has distinctively identifiable features comprising of blasts cells and conspicuously increased plasma cells. however no unique clinical, phenotypic, cytogenetic, molecular and biologic properties have been identified to merit its classification as a homogenous separate entity. conclusion aml with plasmacytosis is a heterogenous phenomenon. reactive plasmacytosis in aml must be differentiated from aml with mm as the latter requires different therapeutic approach. references 1. rangan a, arora b, rangan p, dadu t. florid plasmacytosis in a case of acute myeloid leukemia: a diagnostic dilemma. indian j med paediatr oncol. 2010; 31: 36‐8. 2. rosenthal ns, farhi dc. reactive plasmacytosis and lymphocytosis in acute myeloid leukaemia. hematology pathology. 1994; 8: 43‐51. table: causes of aml with plasmacytosis aml= acute myeloid leukaemia, il= interleukin, mm=mul�ple myeloma fig 1: bone marrow aspirate and trephine showing blast cells and plasma cells indicated by white arrows and black arrows respec�vely (magnifica�on: 40x). presence of a monoclonal band on serum protein electrophoresis, serum free light chain assay, and whole body magnetic resonance imaging (mri) for bone lesions, help in the diagnosis of a concomitant mm. our patient did not have any bony lytic lesions, bence jones proteinuria, or a monoclonal para‐ protein band. serum free light chain assay was required to rule out myeloma with more certainty but not done due to non availability. hence our diagnosis of aml with reactive plasmacytosis was jiimc 2016 vol. 11, no.4 aml with plasmacytosis 190 3. al shughair n, al dawsari g, gyger m, mohamed g, roberts g. clinical significance of plasmacytosis in the day+14 bone marrow of patients with acute myeloid leukaemia undergoing induction chemotherapy. j clinpathol. 2007; 60: 520–3. 4. mailankody s, pfeiffer rm, kristinsson sy, korde n, bjorkholm m, goldin lr, et al. risk of acute myeloid leukemia and myelodysplastic syndromes following multiple myeloma and its precursor disease (mgus). blood . 2011; 118: 4086‐92. 5. wei a, juneja s. bone marrow immunohistology of plasma cell neoplasms. j clinpathol. 2003; 56: 406‐11. 6. hyun bh, kwa d, gabaldon h, ashton jk. reactive plasmacytic lesions of the bone marrow.am j clinpathol. 1976; 65: 921‐8. 7. wulf gg, jahns streubel g, hemmerlein b, bonnekessen k, wörmann b, hiddemann w. plasmacytosis in acute myeloid leukemia: two cases of plasmacytosis and increased il‐6 production in aml blast cells. ann hematol. 1998; 76: 273‐ 7. jiimc 2016 vol. 11, no.4 aml with plasmacytosis 191 page 51 page 52 page 53 jiims.cdr abstract objective: to evaluate the overall faculty performance by comparison of self-assessment with peer and student assessment. study design: a comparative cross sectional survey. place and duration of study: study was conducted from january to june 2012 in riphah college of rehabilitation sciences, riphah international university islamabad. materials and methods: this research study was conducted among students of doctor of physical therapy (dpt), post-professional doctor of physical therapy (ppdpt), and master of science in speech language pathology (ms-slp), and faculty members at riphah college of rehabilitation science (rcrs), riphah international university islamabad. the total sample size was 730, including 700 students and 30 faculty members. a questionnaire was developed according to likert scale, and after a pilot study on 20 student and 10 faculty member to determine the reliability. the questionnaire was circulated among all the 30 faculty members and 700 students, including 500 undergraduate and 200 post graduate students of all the 3 programs. the data was analyzed and wilcoxon (kruskal-wallis) was applied at 95% level of significance for all the 3 groups. the group “a” included assessment of the performance of the faculty members done by the students, group “b” done by other faculty members, and group “c” included self assessment done by faculty members. the averages were calculated to determine the overall performance of the faculty members as assessed by themselves, other faculty members, and the by students as well, afterwards the averages of 3 groups were compared. results: the overall performance of the faculty members was graded as 71% (p=0.015) as evaluated by the students, 77% (p=0.009) as evaluated by other faculty members, and 73% (p=0.011) as evaluated by the faculty members through self assessment. conclusion: it is concluded that there was no significant difference in the performance of the faculty members, as assessed themselves, by the students and the other faculty members. key words: faculty performance, self assessment, students' feedback. 94 original article faculty members outcomes. though it is not very much popular in the literature concern with medical and rehabilitation fields, but it is the most useful practice in business sector. the performance evaluation technique focuses on multiple perspectives and levels performance leading to results that are considered to be highly convincing and a powerful phenomenon to bring change in behavior. this feedback also known as m u l t i s o u r c e f e e d b a c k , m u l t i r a t e r assessment, peer evaluation and full-circle appraisal. peer evaluation provides developmental feedback which is always used to assess competency and behavior r a t h e r t h a n p e r s o n a l i t y a n d 2 professionalism. introduction faculty evaluation is always vital for the f a c u l t y d e v e l o p m e n t i n a c a d e m i c institutions for further improvement and enhancement. this evaluation process helps the organization to arrange the faculty d e v e l o p m e n t p ro g r a m s f o r f u r t h e r improvement in the performance of the 1 faculty members. accreditation council for graduate medical education (acgme) develops variety of assessment ''tools'' for performance of ------------------------------------------------comparison of self-assessment with peer and student assessment in evaluating the overall performance of the faculty correspondence: dr. syed shakil-ur-rehman principal/assistant professor riphah college of rehabilitation sciences riphah international university islamabad imran amjad, syed shakil-ur-rehman, asghar khan , khalid farooq danish, ilyas babar awan, sikandar ghayas khan 95 one frequently used method for identifying e d u c a t i o n a l n e e d s i s t h e m a i l e d questionnaire. generally, educational program planners gather initial information about a particular audience and design an a p p ro p r i a t e q u e s t i o n n a i re t o e l i c i t information from that audience regarding its perceived importance of identified 3 topics. a l t h o u g h t h e l i t e r a t u re re l a t e d t o conducting educational needs, assessment is quite plenteous, specific literature related to the tools and methods which are useful in the process is somewhat less abundant. randol g. waters, used the modified borich model to describe the educational needs of extension in field, faculty and indentifying the faculty development needs. researchers would recommend the use of this need a s s e s s m e n t m o d e l i n d e t e r m i n i n g educational needs of similar groups of 4 clients. this study analyzes the outcomes of peer reviews of faculty members and the outcomes of students' feedback. before this the general practice was getting feedback from the students or by the faculty member's separately. this particular research includes self assessment by the faculty members themselves, compared with the students' 5 feedback. this comparative cross sectional research survey was conducted among students of doctor of physical therapy (dpt), postprofessional doctor of physical therapy (ppdpt), and master of science in speech language pathology (ms-slp), and faculty m e m b e r s a t r i p h a h c o l l e g e o f rehabilitation science (rcrs), riphah international university islamabad. the faculty performance was evaluated for semester spring 2012 and for the period of 6 months, from january-june 2012. the total sample size was 730, including 700 students and 30 faculty members. materials and methods a questionnaire was developed according to likert scale, and after a pilot study on 20 student and 10 faculty member to determine the reliability. the questionnaire was circulated among all the 30 faculty members a n d 7 0 0 s t u d e n t s , i n c l u d i n g 5 0 0 undergraduate and 200 post graduate students of all the 3 programs. the details about the study sample are summarized in table i. the questionnaire has 10 questions, which covered all of the following 10 important domains for performance of the faculty members: 1. knowledge of the subject 2. up-to-date knowledge 3. communication skills 4. students' participation in class 5. distribution of material among students 6. punctuality 7. regularity 8. the use of virtual learning system vls 9. the use of campus management system cms 10. following islamic ethical values the data was analyzed and wilcoxon (kruskal-wallis) was applied at 95% level of significance for all the 3 groups. the group “ a ” i n c l u d e d a s s e s s m e n t o f t h e performance of the faculty members done by the students, group “b” done by other faculty members, and group “c” included self assessment done by faculty members. the averages were calculated to determine the overall performance of the faculty members as assessed by themselves, other faculty members, and the by students as well, afterwards the averages of 3 groups were compared. a total of 730 students and faculty members participated in this research study; majority (77%) was female. mean age of the u n d e r g r a d u a t e s t u d e n t s w a s 2 3 , postgraduates 27 and faculty members 30 years. the majority of participants were results 96 from under grade (68%), followed by post grade (27%), and faculty members (4%). the background of the students and faculty members were from physical therapy and speech therapy. the overall performance of the faculty table i: summary of study sample (n=730) table ii: comparison of overall faculty performance (n=730) no. of members was graded as 71% (p=0.015) as evaluated by the students, 77% (p=0.009) as evaluated by other faculty members, and 73% (p=0.011) as evaluated by the faculty members through self assessment. table-ii nigel k. ll. pope conducted a research study on “the impact of stress in self and peer assessment” and published in a research journal the assessment and evaluation in higher education in 2005. they concluded that the peer assessment and evaluation method is very effective for the evaluation discussion the performance of the students and faculty 6 members. keith topping carries out a comparative cross-sectional survey on “assessment b e t w e e n s t u d e n t s c o l l e g e s a n d universities” and published in research journal the review of educational research in 1998. this study strongly supports the peer evaluation method for finding students and faculty outcomes at the colleges and 7 universities level. davis and john conducted a comparative c ro s s s e c t i o n a l re s e a rc h s u r v e y o n “comparison of faculty, peer, self, and nurses assessment in obstetrics and gynecology residents” and published in a research journal the obstetrics and gynecology in 2002. they had evaluated the performance of residents placed in 97 obstetrics and gynecology wards, through self assessment, peer assessment and by the nurses. they concluded that there was no significant difference among the all 3 8 groups. f. dochy and colleagues carries out a review research study on “the use of self, peer, and co-assessment in higher education” and published in an international research journal named the studies in higher education in 1999. they considered the peer review method effective and develop r e c o m m e n d a t i o n s f o r e d u c a t i o n a l institutions. they also stated in the conclusion after the completion the research review that peer review method made the s t u d e n t s m o r e r e s p o n s i b l e w h i l e responding the evaluation and assessment 9 at the higher education level. matthew ohland and colleagues conducted a r e v i e w r e s e a r c h s t u d y o n “ a comprehensive assessment of team members effectiveness: development of behaviorally anchored scale for self and peer evaluation“, and published in a r e s e a r c h j o u r n a l t h e a c a d e m y o f management, learning, and education in 2012. they find three studies which supports the effectiveness of peer review method for the evaluation and assessment of 10 the effectiveness team members. it is concluded that there was no significant difference in the performance of the faculty members, as assessed by the students, themselves, and the other faculty members. 1. darling-hammond l, amrein-beardsleya. conclusion references haertel e & rothstein j. evaluating teacher evaluation. phi delta kappan 2012; 93:8-15. 2. schmoker m. the madness of teacher evaluation frameworks. phi delta kappan 2012; 93:70-1. 3. hill h c, kapitula l & umland k. a validity argument approach to evaluating teacher valueadded scores. american educational research journal 2012; 48:794-831. 4. madden t j, dillon w r & leak r l. students' evaluation of teaching: concerns of item diagnosticity. journal of marketing education 2010; 32:264-74. 5. johnson d w, johnson r t & smith k a. cooperative learning returns to college what evidence is there that it works? change: the magazine of higher learning 1998; 30: 2635. 6. davis j d. comparison of faculty, peer, self, and nurse assessment of obstetrics and g y n e c o l o g y r e s i d e n t s . o b s t e t r i c s & gynecology2012; 99: 647-51. 7. topping k. peer assessment between students in colleges and universities. review of educational research 1998; 68: 249-76. 8. pope n k l. the impact of stress in self-and peer assessment. assessment & evaluation in higher education 2005; 30: 51-63. 9. dochy f j r c, segers m & sluijsmans d. the use of self-, peer and co-assessment in higher education: a review. studies in higher education 1999; 24: 331-50. 10. ohland m w, loughry m l, woehr d j, bullard l g, felder r m, finelli c j. the comprehensive assessment of team member effectiveness: development of a behaviorally anchored rating scale for self-and peer evaluation. academy of management learning & education 2012; 11: 609-30. untitled-2 jiims final 14 original article abstract objective: to seek relationship between cord problems (like long cords, short cords, nuchal cord and cord knots) and its effects on fetus as well as mode of delivery. study design: descriptive (case series) place and duration of study: obs/gynae wards railway hospital, rawalpindi from september 2006 to august 2007. materials and methods: it was a descriptive case series study. hundred patients with umbilical cord problems, detected at delivery were included.effects of these cord problems on mode of delivery and fetal outcome were observed. results: twenty two percent patients had long cord, 14% had short cords.41% had single nuchal cord, 22% had double loop of cord around the neck, and 4% patients had triple loops of nuchal cord. it was observed that 4% patients were having true kanots in umbilical cord and and only 26% patients had false knots in umbilical cord. in the patients with cord problems, rate of svd was more than 70% and lscs < 20%. these problems did not show significant effects on birth weight and apgar scores when present alone.but multiple cord problems in a single pregnancy were associated with fetal complications. conclusion: long and short umbilical cords, umbilical cord knots and nuchal cords had no significant effects on mode of delivery and apgar score in 5 minutes. but multiple umbilical cord problems in same case may pose problems to the fetus and early diagnosis can prevent fetal harm. key words: long cords, short cords, true knots, false knots, nuchal cord, apgar score. if oligohydramnios, amniotic bands, or limitations of fetal motion occur for any reason, the umbilical cord will not d e v e l o p t o a n a v e r a g e l e n g t h . amniocentesis performed to produce oligohydramnios in pregnant rats at 14-16 days result in significant reduction of umbilical cord length.1 twisting of the cord about the fetus may be the reason for excessive cord length. one loop of cord is present around the neck in 21% of fetuses, 2 loops in 2.5%, and 3 loops in 0.2%. when 3 loops are present, the cord is usually longer than 70 cm. true knots occur in the cord in 1% of fetuses, leading to a perinatal loss of 6.1% in such cases. false knots are developmental 2,3variations with no clinical importance. nuchal cord (nc) is defined as the umbilical cord being wrapped 360 degrees around the fetal neck. it is one of the most introduction at birth, the normal mature cord is about 5060 cm in length and 12 mm in diameter. a long cord is defined as more than 70 cm and a short cord as less than 30 cm. there may be as many as 40 spiral twists in the cord, as well as false knots and true knots. when umbilical blood flow is interrupted at birth, the intra-abdominal sections of the umbilical arteries and vein gradually 1become fibrous. it appears from indirect evidence in the human fetus that the length of the umbilical cord at term is determined by the amount of amniotic fluid present during the first and second trimesters and by the mobility of the fetus. ------------------------------------------------maternal and fetal outcome of pregnancies with umbilical cord problems shumaila sharif, saadia sultana, fareesa waqar, azra saeed, shamsunnisa sadia correspondence: dr. shumaila sharif senior registrar gynae/obs department islamic international medical college pakistan railway hospital, rawalpindi 14 15 common complications of the umbilical cord and any pregnancy might be 4,5,6complicated with a nuchal cord. if a nuchal cord occurs in a pregnant woman with decreased fetal movements, it should be considered to be at high risk, particularly 7,8for foetuses with multiple nuchal cords. an entangled cord around the fetal neck does not seem to increase the risk of 9induction failure. our study is planned to see the maternal and fetal outcome in patients with short and long umbilical cord, umbilical cord knots, and nuchal umbilical cord. the purpose of present study was to determine the frequency of the umbilical cord problems and determine the effect of umbilical cord problem on the mother and the neonate. descriptive (case series) study was carried out in the department of obs/gynea, pakistan railway hospital, rawalpindi, from sep 2006 to aug 2007. hundred delivering women were included in the study by non-probability convenient sampling. inclusion criteria: full term delivered ladies and babies with �short umbilical cord �long umbilical cord �nuchal cord �umbilical cord knots. exclusion criteria: �preterm deliveries �deliveries with associated medical problems. �congenitally anomalous babies. data was collected using a proforma. hundred patients who delivered in railway hospital with cord problems were included materials & methods in this study. the information obtained from patients was taken on a proforma after the informed consent of patients and their relatives. patients were evaluated through comprehensive history, general physical, systemic examination and investigations. in the hospital, mode of delivery of the patient, maternal and fetal outcome and well being were recorded. the variables were short umbilical cord, long umbilical cord, knots in the umbilical cord, nuchal umbilical cord, identified at delivery, and maternal outcome i.e. spontaneous vertex delivery, caesarean section, and fetal outcome i.e. intrauterine growth restriction, intrauterine fetal death, poor apgar sore, and early neonatal death. fetal growth restriction was assessed by abdominal ultrasonography performed during antenatal time with biparietal diameter and femur length. after birth by measuring weight, length and head circumference of baby and comparing it with the standard centile chart. apgar score at one minute and five minutes to assess the activity of the baby after birth. long umbilical cord, knots in the umbilical cord, nuchal umbilical cord, identified at d e l i v e r y , a n d m a t e r n a l o u t c o m e i . e . spontaneous vertex delivery, caesarean section, and fetal outcome i.e. intrauterine growth restriction, intrauterine fetal death, poor apgar sore, and early neonatal death and fetal growth restriction was assessed by abdominal ultrasonography with biparietal diameter and femur length, after birth by measuring weight, length and head circumference of baby and comparing it with the standard centile chart. apgar score at one minute and five minutes to assess the activity of the baby after birth. 15 16 results cases collected with long cord of > 70 cm length, were 22.6%. rate of spontaneous delivery was 66.6%, operative vaginal delivery was 11.1% and lower segment caesarean section 22.2%. apgar score in 5 min was 10/10 in 96.2% babies and nicu a d m i s s i o n s w e r e r e q u i r e d 1 4 . 8 % babies.breakup of various cord problems are shown in table i, maternal and fetal outcome are shown in table ii and table iii respectively. patients were identified having short cords < 30 cm were 11.7% out of these patients 85.7% had spontaneous vaginal delivery ,7.1% had operative vaginal delivery and7.1% had lscs.apgar score in 5 min was 10/10 in 100% babies. in this study 40.3% patients were having single nuchal cord, either double loop of cord around the neck, or tripple loops of nuchal cord.fifty percent of them had spontaneous vaginal delivery,25% patients had operative vaginal delivery and 25% had lscs. ninety three point seven percent babies were born with good apgar score.only 2% needed admission in nicu. regarding true knots in umbilical cord 4% patients had these knots and 50% of them had svd, 25% had operative vaginal delivery and 25% had lscs due to fetal distress. babies born with apgar 10/10 in 5 min were 75% and 0/10 apgar was in only one baby.fifty percent babies needed nicu admission in this group. twenty one point eight percent. patients had false knots in umbilical cord 73% had vaginal delivery, 11.5% had operative delivery due to prolonged 2nd stage of labor and only 15.3% patients underwent lscs due to different indications. 100% babies born with apgar score of 10/10 after 5 min. and only 3 babies out of 26 needed nicu admissions mainly for observation table-i: umbilical cord problems in the study population (n=100) table-ii: umbilical cord problems and maternal outcome table-iii: umbilical cord problems and foetal outcome discussion every fetus should have the opportunity to begin life with all its god-given talents and abilities. realistically, this may not be possible, but some physically normal newborns could benefit from a reduction in the risks of a cord mishap. it is estimated that learning disabilities are due to some type of cord complications. the issue of cerebral palsy is important, but currently no solution and few insights exist as to its origin. preventing the stillbirth of a normal infant would be an important step in identifying cord-related harm. what is the size of the problem, and what best describes each part of the problem of umbilical cord mishap? causes of differences in cord length are 16 17 unknown; however the length of the cord is thought to reflect movement of the fetus in utero. short cords are associated with fetal movement disorders and intrauterine constraints, as well as placental abruption and cord rupture. excessively long cords are associated with fetal entanglement, the 10knots and thrombi. even knots in the cord do not automatically cause distress, since blood flow is not impeded unless the knot is tight.risk factors for having a true knot in the umbilical cord i n c l u d e a d v a n c e d m a t e r n a l a g e , multiparity, previous miscarriages, obesity, prolonged gravidity, male fetus, long cord, m a t e r n a l a n e m i a , m a t e r n a l c h r o n i c 11,12hypertension and hydramnios. 13a study was conducted by carey jc. in oklahama city usa to determine if the presence of a single or multiple nuchal cord encirclement has a negative effect on fetal growth. the mean birth weight was no different in the presence of a single or multiple nuchal cord encirclement than with no encirclement and conclusion was that birth weight in unaffected by a single or multiple nuchal cord encirclement. one s t u d y c o n c l u d e d t h a t g r o s s c o r d abnormalities like true knots, long cords, nuchal cords predispose the fetus to stasis induced vascular ectasia and thrombosis, thus leading to vascular obstruction and adverse neonatal outcome including iugr 14and still birth. i n a n o t h e r s t u d y , b y s h r e s t h a , a t kathmandu medical college, carried out to find the incidence of nuchal cord at delivery, intrapartum complication and perinatal 15outcomes in the cases with nuchal cord. incidence of single nuchal cord was highest intrapartum complications like fetal heart rate irregularities and meconium staining of liquor was increased in nuchal cord group but it was not statistically significant. instrumental delivery was high in nuchal cord group but not significantly. however caesarean section rate was high in this group with out nuchal cord. apgar score <7 at 1 minute was significantly low in nuchal cord group. but apgar score at 5 minutes and admission to neonatal unit was not more common. they concluded that nuchal cord is not associated with adverse perinatal outcome. in one study conducted in china, nuchal cord was one of the nine factors which showed significant association with 16autism. our study also shows that nuchal cord is not associated with adverse prenatal outcome. a study by baergen, and colleagues showed that infants with excessively long umbilical cords are found to be at a significantly i n c r e a s e d r i s k o f b r a i n i m a g i n g a b n o r m a l i t i e s a n d / o r a b n o r m a l 17neurological follow-up. another study by itakura it was concluded that abnormally long cords are associated with repeated coiling of cord around fetal neck and consequently can result in fetal growth 18restriction, distress and even demise. fortunately the outcome was good in our study inspite of multiple abnormalities of umbilical cord that could have resulted in fetal compromise or demise. study by sornes concluded that knots in umbilical cord are associated with increased incidence of fetal distress; meconium stained liquor and tenfold increased risk of 19intrauterine fetal death. but in this study above complications was not significant and did not adversely affect the fetal and maternal outcome. 17 18 conclusion references our study showed statistically significant no adverse effect on maternal and fetal outcome.there was only one still birth in our study having single loop of cord around neck, true knots, and long cord.these findings are not statistically significant. this is due to small sample size of our study. and this warrants further evaluation in future prospective studies with larger number of patients 1. laughlin d, knuppel ra. maternal placental fetal unit; fetal & early neonatal physiology. in: decherney ah, nathan l.current obstetric and gynecologic diagnosis and treatment. ninth edition. usa: the mcgraw-hill companies; 2003. 173-4. 2. costantini s, mistrangelo e. combined simple and complex cord knots associated with an encirclement. minerva ginecol 2005; 57:213-5 3. hershkovitz r, silbestein t, sheiner e, shohamvardi i, holcberg g, katz m, etal. risk factors associated with true knots of the umbilical cord. eur j obstet gynecol reproad biol 2001; 98:36-9. 4. dursun p, salman mc, ozyuncu o, aksu t nuchal cord type b associated with an excessively long umbilical cord as a cause of still birth. clin exp obstet gnecol 2004; 31:158-9 5. kumari s, sexena a, monga d, malik a, kabra m, kurry rm ,, significance of cord problems at birth. indian pediatr 1992;29:301-5. 6. mastrobattista jm, hollier lm, yeomans er, ramin sm, day mc, sosa a, et al. effects of nuchal cord on birthweight and immediate neonatal outcomes. am j perinatol. 2005; 22:85-6 7. schaffer l, burkhadt t, zimmermann r, kurmanavicius j, nuchal cord in term and postterm deliveries. obstet gnacol 2005;106:23-8. 8. clapp jf, stepanchak w, hashimoto k, ehrenberg ii, lopez b. the natural history of antenatal nuchal cords. am j obstet gynecol 2003;189:488-93 9. ghi t,emidio ld,massaudi r, casadio p,pilu g,pelusi g. nuchal cord entanglement and outcome of labour induction. prenat med 2007;1:57-60. 10. heifetz sa. the umbilical cord: obstetrically important leisions. clin obstet gynecol. 1996;39:571-87. 11. ramon y cajal cl,martinez ro. four dimentional ultrasonography of a true knot of t h e u m b i l i c a l c o r d . a m j o b s t e t gynecol.2006;195:896-8. 12. deutsch ab, miller e, spellacywn, mabry r. ultrasound to identify cord knotting in monoamniotic monochorionic twins.twin res hum genet.2007;10:216-8. 13. c a r e y j c , r a y b u r n w f . n u c h a l c o r d encirclements and birth weight. j reprod med, 2003;48:460-2. 14. tant birojn p, saleemuddin a, sirois k,crum cp, boyd tk, t woroger s. gross abnormalities of the umbilical cord : related placental histology and clinical significance. placenta 2009;30:1083-8. 15. shrestha ns, singh n. nuchal cord and perinatal outcome. kathmandu univ j (kumj) 2007; 5:3603. 16. zhang x , chao c ,tian j,miao rj,xi w,picciotto ih,cai l. prenatal and perinatal risk factors for autism in china.j autism dev disord 2010;40:1311-21. 17. baergun rn, malicki d, behling c, benirschke k. morbidity, mortality and placental pathology in excessively long umbilical cord: retrospective study. pediator dev pathol 2001;4:144-53 18. itakura a, kuranchi o, muzutani s, tomoda y. intrauterine growth retardation and fetal disease associated with the excessively long (160 cm) umbilical cord. archives of gynaecology and obsestrics 1994;2:55-59 19. sornes t. umbilical cord knots. acta obstet gynaecol scand 2000;79:157-9 18 original�article abstract objective: to assess the willingness of medical students to volunteer for assisting frontline doctors during the covid-19 pandemic. study design: cross-sectional study. th th place and duration of study: this study was conducted from 12 june 2020 to 20 july 2020 on medical students of rawalpindi medical university. materials and methods: an online survey was conducted among 282 undergraduate medical students selected via convenience sampling. spss version 25 was used for analysis. results: more than half of the participants (52.1%) were unwilling to volunteer during the covid-19 pandemic. most of those who wanted to volunteer preferred to do so by providing indirect healthcare via telemedicine. the most popular reason for preferring to volunteer was an ethical inclination to help the frontline workforce. the main barriers towards volunteering the possibility of being vectors for viral transmission, included consuming personal protective equipment that healthcare personnel needed, and contracting covid-19. no significant association was found between gender (p=0.567), age group (p=0.793), year of study (p=0.911), or boarder/non-boarder status (p=0.243), and willingness to volunteer. conclusion: the majority of medical students were unwilling to volunteer for assisting frontline doctors during the covid-19 pandemic. key words: covid-19, medical education, medical students, pandemics, volunteerism. students should be utilized during such times of crisis, with some medical schools offering final year students the opportunity to graduate early and start 5 working on the frontlines. in pakistan, student taskforce against covid-19 started by final year medical students at agha khan 6 university hospital recruited over 500 members. in april 2021, the punjab government called upon third to final year medical students to volunteer in 7 hospitals and quarantine facilities. however, these recruitment drives were conducted without surveys on medical student views towards volunteerism during the pandemic. medical students are prospective clinicians in training who can be called for assistance if healthcare systems are overwhelmed in dealing with this pandemic. students may also have apprehensions regarding joining the workforce against a deadly pandemic at a premature stage of their medical career. therefore, the objective of this study was to assess the willingness of medical students to volunteer for assisting frontline doctors during the covid-19 pandemic. introduction in late december 2019, wuhan, a metropolitan city in china, experienced an outbreak of atypical pneumonia which was later be identified as a novel 1 viral disease covid-19. on march 11, 2020, world health organization officially declared covid-19 to 2 be a global pandemic. governments imposed lockdowns to curb the spread of covid-19 which 3 brought educational activities to a halt. many medical colleges suspended on-campus classes as well as clinical rotations. the american association of medical colleges (aamc) supported the suspension of direct patient-medical student 4 interaction during this period. on the other hand, some were of the view that the services of medical willingness of medical students to volunteer for assisting frontline doctors during the covid-19 pandemic: a cross-sectional study 1 2 3 4 maheen nazir , alishba ashraf , sidra hamid, zuhair ali rizvi correspondence: maheen nazir th 4 year mbbs student e-mail: maheennazir32@gmail.com 1,2 3 mbbs students/department of physiology rawalpindi medical university, rawalpindi 4 department of anesthesiology shifa international hospital, islamabad funding source: nil; conflict of interest: nil received: january 18,2021 revised: october 13, 2021 accepted: october 15, 2021 medical students and pandemic volunteerismjiimc 2022 vol. 17, no.1 46 materials and methods this cross-sectional study was conducted on the undergraduate medical students of rawalpindi th th medical university from 12 june 2020 to 20 july 2020. ethical approval was granted by institutional research forum (erc number: 81rmu/2020/iref). participants were recruited via non-probability convenience sampling before online classes commenced for our study population. the sample size was calculated to be 282 for an estimated population of 1050 students. students enrolled in clinical years (3rd, 4th, 5th year) were included in the study. pre-clinical year students (1st and 2nd year) were excluded. data was collected using a pilot-tested, online, selfstructured questionnaire designed using google forms which had questions and statements collected 8-11 from various online articles. the content and construct of the questionnaire were validated by a senior faculty member. it was disseminated in all official class whatsapp and facebook groups. the response rate was 100%. confidentiality of the participants was maintained and informed consent was taken. the first part of the survey asked about demographic details namely age, gender, year of study, boarder/non-boarder status and whether students wanted to volunteer or not. the second section explored why the students were willing or unwilling to volunteer. the third section assessed the responses of students to nine general statements regarding volunteerism during the covid-19 pandemic via the options of “agree”, “disagree” and “undecided”. statistical software program spss version 25.0 was used for data analysis. frequencies and percentages were calculated for categorical variables. the associations between variables were assessed using the chi-square test and binomial logistic regression analysis. adjusted odds ratios and 95% confidence intervals were calculated. a p-value of less than 0.05 was considered significant. results the cross-tabulation between demographic characteristics of the sample and willingness to volunteer is displayed in table i. the mean age was 21.9±1.26 years. out of the 282 participants, the majority were females (205, 72.7%) and nonboarders (177,62.8%). more students (147, 52.1%) were unwilling to volunteer to assist frontline doctors during the covid-19 pandemic compared to those who were willing to volunteer (135, 47.9%). no significant association was found between gender, age group, year of study or boarder/non-boarder status, and the willingness to volunteer. ta b l e i : a s s o c i a t i o n b e t w e e n d e m o g r a p h i c characteristics and willingness to volunteer (n=282) table ii shows the ways by which students preferred to volunteer to assist doctors. the majority of students wanted to contribute by providing indirect health care via telemedicine at the university campus. assisting with direct care of covid-19 patients was the least popular choice. table ii: means by which students preferred to volunteer 47 medical students and pandemic volunteerismjiimc 2022 vol. 17, no.1 figure 1 and figure 2 show the reasons given by students for opting or not to volunteer during this pandemic, respectively. the most common reason for preferring to volunteer was an ethical inclination to assist their seniors in the health care field. the most common reason for not preferring to volunteer was the concern that students may transmit the infection to others, especially their parents and other family members. say yes to volunteering (odds ratio=0.333, p=0.001, <0.05) compared to those who disagreed. students who agreed with the statement “volunteering for assistance in healthcare, whether online or in person, is a wise decision” were significantly more likely to say yes to volunteering compared to those who disagreed (odds ratio=3.295, p=0.000, <0.05). most s t u d e n t s ( 9 4 . 7 % ) a g r e e d t h a t p a n d e m i c management training should be incorporated into the syllabus irrespective of whether they wanted to volunteer or not (p=0.304,>0.05). fig. 1: reasons students gave for their willingness to volunteer fig. 2: reasons students gave for their unwillingness to volunteer most students were not in favour of giving final year medical students the option of graduating early to join the medical workforce (183, 60.9%, p=0.000). among the 99 students who agreed, fewer students were from fourth year (25, 26.8%) and final year (27, 31.3 %) compared to third year (47,45.6%). table iii shows the predicted probability, adjusted odds ratios and 95% confidence intervals from the binomial logistic regression analysis of the association between the response “agree” to the 9 general statements and “yes” response to the question assessing willingness to volunteer. those who agreed with the statement “students who volunteer should only be allowed to provide indirect care via telemedicine" were significantly less likely to table iii: binary logistic regression analysis for the association between response “agree” and response “yes” to volunteering 48 medical students and pandemic volunteerismjiimc 2022 vol. 17, no.1 discussion our study showed that more students were unwilling to volunteer during the pandemic (52.1%) and fewer were willing to volunteer (47.9%). similar to our results, an indonesian study reported that around 12 48.8% of the students were willing to volunteer. in contrast to our results, many studies such as surveys from uganda (80%), china (86%) and germany (70%) reported that more students were willing to 13,14,15 volunteer. the varying government pandemic response and the severity of the pandemic at the time of data collection could be responsible for the global differences in the willingness to volunteer. among the students interested in volunteering, the majority wanted to assist with telemedicine services and only 21.5% of participants were interested in providing direct care to covid-19 patients. this is similar to results from china and nigeria where medical activities such as administrative work and telemedicine were more popular among students 14,16 than direct care of patients. the most common reason given by students for willingness to volunteer was an ethical inclination to help the frontline workforce during this pandemic. similar surveys from indonesia, china, and brazil reported this sense of duty to be a major driving force behind the 12,14,17 willingness to volunteer. students did not wish to volunteer for three main reasons: the fear of being viral transmission vectors to their families, depleting personal protective equipment (ppe) that more experienced staff needed, and contracting covid-19 themselves. this is in accordance with results from indonesia and poland where the fear of transmission of covid-19 to relatives and contraction of the disease were 12,19 major barriers towards considering volunteerism. their fears are justified as even graduate doctors 20 faced severe ppe shortages during the pandemic. nearly 95% of the students agreed that pandemic management training should be incorporated into the syllabus which is the same percentage reported 16 in a similar nigerian study. since medical students are future clinicians, early incorporation of pandemic management in their curriculum is imperative to create a workforce that is well prepared for the c u r r e n t a n d p o t e n t i a l f u t u r e p a n d e m i c 21 emergencies. the limitations of our study were the possible selection bias that occurred while sampling and that it only included participants from a single publicsector medical university. studies that include both public and private sector medical institutes throughout the country should be conducted to obtain a more representative sample of medical students. further studies should investigate the effect of important variables such as family income, relia n c e o n info r m at io n s o u rc es , p rev io u s volunteering activities, and knowledge about the infection and infection control measures on willingness to volunteer. conclusion the majority of medical students were unwilling to volunteer to assist the frontline doctors during the covid-19 pandemic. references 1. munster vj, koopmans m, van doremalen n, van riel d, de wit e: a novel coronavirus 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[internet];2020[cited 2020 august 15]; available from https://www.dawn.com/news/1545384 8. kalet al, jotterand f, muntz m, thapa b, campbell b: hearing the call of duty: what we must do to allow medical students to respond to the covid-19 pandemic. wmj. 2020; 119(1):6-7. 49 medical students and pandemic volunteerismjiimc 2022 vol. 17, no.1 9. o'connor-terry c, gowda t, zuchelkowski b, minney s, kwon j: medical students have a powerful role in addressing community needs in the covid-19 pandemic: an experience from the us. international journal of medical students. 2020; 8(1):70-2. 10. gallagher th, schleyer am: “we signed up for this!”—student and trainee responses to the covid-19 pandemic. nengl j med. 2020; 382:96. 11. medical students can give vital help in the covid-19 crisis. [internet];2020[cited 2020 august 15]; available from: https://blogs.scientificamerican.com/observations/medic al-students-can-give-vital-help-in-the-covid-19-crisis/ 12. lazarus g, findyartini a, putera am, gamalliel n, nugraha d, adli i, et al. willingness to volunteer and readiness to practice of undergraduate medical students during the covid-19 pandemic: a cross-sectional survey in indonesia. bmc medical education. 2021;21(1):1-2. 13. olum r, kajjimu j, kanyike am, chekwech g, wekha g, nassozi dr, et al. perspective of medical students on the covid-19 pandemic: survey of nine medical schools in uganda. jmir public health and surveillance. 2020; 6(2):19847-10. 14. yu nz, li zj, chong ym, xu y, fan jp, yang y, et al. chinese medical students' interest in covid-19 pandemic. world j virol. 2020; 9(3): 38-46 15. drexler r, hambrecht jm, oldhafer kj. involvement of medical students during the coronavirus disease 2019 pandemic: a cross-sectional survey study. cureus. 2020;12: e10147. 16. adejimi aa, odugbemi ba, odukoya oo, okunade ks, taiwo ao, osibogun a. volunteering during the covid-19 pandemic: attitudes and perceptions of clinical medical and dental students in lagos, nigeria. nigerian postgraduate medical journal;28(1):1-13 17. tempski p, arantes-costa fm, kobayasi r, siqueira ma, torsani mb, amaro bq, et al. medical students' perceptions and motivations during the covid-19 pandemic. plos one. 2021;16(3):e0248627. 18. byrne mh, ashcroft j, alexander l, wan jc, arora a, brown me, et al.covidready2 study protocol: cross-sectional survey of medical student volunteering and education during the covid-19 pandemic in the united kingdom. bmc medical education. 2021;21(1):1-7. 19. bazan d, nowicki m, rzymski p. medical students as the volunteer workforce during the covid-19 pandemic: polish experience. international journal of disaster risk reduction. 2021;55(1):102-109. 20. ahmed j, malik f, bin arif t, majid z, chaudhary ma, ahmad j, malik m, khan tm, khalid m. availability of personal protective equipment (ppe) among us and pakistani doctors in covid-19 pandemic.cureus.2020;12: e8550. 21. o'byrne l, gavin b, mcnicholas f. medical students and covid-19: the need for pandemic preparedness. j med ethics. 2020; 46(9):623-626. 50 medical students and pandemic volunteerismjiimc 2022 vol. 17, no.1 conflict of interest authors declared no conflicts of interest. grant support and financial disclosure authors have declared no specific grant for this research from any funding agency in public, commercial or nonprofit sector. data sharing statment the data that support the findings of this study are available from the corresponding author upon request. this is an open access article distributed under the terms of the creative commons attributionnoncommercial 2.0 generic license. jiims final.cdr 20 original article abstract objectives: to determine the frequency of use of topical steroids by acne patients and to observe various cutaneous side effects in these patients. study design: descriptive study materials and methods: this study was conducted in dermatology out patient department, pakistan railway hospital, rawalpindi from february 15 to april 15, 2012. total 110 patients were enrolled in the study. all the patients were having clinical diagnosis of acne vulgaris. patients of both genders with age range of 1335 years were included in the study. frequency of patients using topical steroids to treat acne was calculated and cutaneous side effects of topical steroids were noted. results: out of 110 patients of acne, 76 were females (69%) & 34 were males (31%). age range of patients was from 13 to 35 years. topical steroids were used by 68 patients (62%) with acne vulgaris. mean duration of application of topical steroids ranged from 2weeks to 5months. most commonly used steroid was betamethasone valerate(62%), followed by clobetasol propionate(29%) and flucinolone acetonide(8%). out of 68 patients using topical steroids cutaneous side effects were seen in 50 patients in the form of aggravation of existing lesions in 18 patients(36%), perioral dermatitis 12 patients(24%), telangiectasias 8 patients(16%), increased facial hair growth 7 patients(14%), tinea incognito in 3 patients(6%) and acne rosacea in 2 patients(4%). conclusion: this study shows that a large number of patients are using topical steroids to treat acne lesions. use of topical steroids is a misconcept in treating the lesions of acne vulgaris and their use is associated with various cutaneous side effects including aggravation of acne lesions, skin atrophy, telangiectasias, perioral dermatitis, hirsutism, acne roacea and tinea in cognito. key words: topical corticosteroid, retinoids, lasers topical corticosteroids constitute one of the largest groups of drugs being used in dermatology. topical corticosteroids were first synthesized in 1930”s in the form of cortisone. hydrocortisone was first described in 1951 for topical use and, subsequently, the super-potent steroids 6,7were introduced in 1974. clinical effectiveness of glucocorticoids is related to its four basic properties; a n t i p r o l i f e r a t i v e e f f e c t s , immunosuppressive, vasoconstrictive, and 8,9anti-inflammatory effects. topical corticosteroids used in various dermatological diseases can lead to an increased risk of side effects that have b e c o m e m o r e p r e v a l e n t s i n c e t h e 9,10introduction of higher potency steroids. local side effects such as epidermal t h i n n i n g , d e r m a l s t r i a e , a t r o p h y, introduction acne is a chronic inflammatory disease of pilosebaceous unit. most commonly it affects the face (99% of cases), less frequently it also affects the back and chest. it is c h a r a c t e r i z e d b y i n c r e a s e d s e b u m production, formation of open and closed 1,2comedones, papules and pustules. the condition usually starts in adolescence and frequently resolves by mid-twenties. various treatment modalities are available to treat acne ranging from antibiotics, 2,3retinoids and lasers. as in more than 90% of cases it involves face it has an important impact on appearance of an individual and 4, 5psychosocial effects. --------------------------------------------------asma khalid, rushqia mukhtar injudicious use of topical steroids, a misconcept in treatment of patients with acne vulgaris correspondence: dr. asam khalid sr & hod dermatology iimc-t, pakistan railway hospital rawalpindi 20 21 telangiectasia, tinea incognito, purpura, can occur and long term use can lead to steroid 10,11,12rosacea. these local adverse effects of topical steroids are known, but are poorly characterized with respect to their true incidence. abuse of topical steroid as cosmetic cream is quite common now a days including their use to treat acne. some patients might have good response initially, but on continuation of application of topical steroids acne worsens and other cutaneous side effects begin to appear that is the time when 13,14patients come to seek medical advice. in this study we find out frequency of patients using topical steroids to treat acne before visiting dermatologist. we also observed various cutaneous side effects that were appearing due to the use of topical steroids. the study was conducted in dermatology out patient department, pakistan railway hospital, rawalpindi. duration of study was two months from 15th february 2012 to 15th april 2012. a total of 110 patients with acne vulgaris were enrolled in the study. sampling was done by non-probability convenient sampling. all the patients were having clinical diagnosis of acne vulgaris based on the presence of papules, pustules, comedones and post acne scars. an informed verbal consent was ensured from every study subject. all the patients were having involvement of face and in some patients there was also involvement of upper trunk. patients of both genders with age range of 13-35 years were included in the study. patients with drug induced (systemic) acne were excluded as were the patients who used topical steroids for some other reason and later on materials and methods developed acne form eruption on face. patients qualification/ occupation was also noted and they were asked about person prescribing steroid whether friend, colleague, or pharmacist. duration and potency of steroid used was also noted. duration of use of topical steroids was from 2 weeks to 5 months. percentage of patients using topical steroids to treat acne was calculated. cutaneous side effects of topical steroid were also noted. spss 13 was used to analyze the data. out of 110 patients, 76 were females (69%) & 34 were males (31%). patients were between 13 to 35 years of age. out of 110 patients topical steroids were used by 68 patients (62%). mean duration of application of topical steroid ranged from 2 weeks to 5 months. most commonly used steroid was betamethasone valerate(62%), followed by clobetasol propionate(29%) and flucinolone acetonide(8%). reason for early withdrawal or short duration of use was aggravation of acne lesions and other cutaneous side effects. most common side effect observed was aggravation of existing lesions with appearance of new lesions. (figure1) other side effects included perioral dermatitis (figure2), increased hair growth on face ( f i g u r e 3 ) t e l a n g i e c t a s i a s a n d a c n e rosacea(figure4) involving facial skin (table i). in most of the patients, use of topical corticosteroid was suggested by their f r i e n d s a n d c h e m i s t s f o l l o w e d b y beauticians, relatives and in some cases on general practitioner's advice (table ii). acne is a polymorphic, inflammatory skin disease. it is one of the most frequent skin results discussion 21 22 15,16diseases. even in western countries the prevalence of acne in adolescents is between 50% and 95%. acne is a disease primarily of adolescence. it is triggered by initiation of androgen production by the adrenal glands and gonads, and it usually subsides after the 17, 18end of growth. corticosteroids have been in use for over 50 years. topical corticosteroids were first synthesized in 1930's in the form of cortisone. later on fluorinated and other p o t e n t t o p i c a l s t e r o i d s w e r e figure 1: aggravation of existing acne lesions figure 2: perioral dermatitis figure 3: increased hair growth on face figure 4: acne rosacea table i:frequency of side effects of topical steroids in study population(n= 62) table ii: frequency of prescriber of topical steroids in study population (n=62) 22 23 19,20,21introduced. topical steroids belongs to a class of compounds with a broad effect on immune regulatory functions. they have both anti-inflammatory and immune m o d u l a t i n g e ff e c t s . va r i e d c l i n i c a l presentations are seen with prolonged and 22,23continuous use of topical steroids. topical corticosteroids are one of the most w i d e l y u s e d t h e r a p e u t i c a g e n t s i n 10,11,12dermatology. they provide rapid s y m p t o m a t i c r e l i e f i n a l m o s t a l l inflammatory dermatosis, especially in the short term. even incorrect use, for instance in infectious dermatosis, produces an initial 24,25improvement in the symptoms. in our study patients were misusing topical steroids to treat acne to get their acne lesions resolve soon. a study was done in india regarding use of topical steroids to treat various dermatoses. a total of 2926 patients with facial dermatoses were screened, of which 433 (14.8%) were using topical steroids and out of them 104 (24%) of patients were using 13them for acne. a study done in iraq reported that 7.9% of the dermatology clinic 21attendees are misusing topical steroids. in a study on facial topical steroid misuse from china, the proportion of patients applying 20topical steroids to the face was 28.5%. almost 15% of the dermatology outpatients with facial dermatosis are already using topical steroids when they contact a specialist. alarmingly, in more than 93% of these cases, the topical steroids is either not needed at all, used for much longer than needed, of the wrong potency or is instituted without a diagnosis of the underlying 6,7,19condition. we have seen in our study that the suggestions to use them were given by friends, relatives, pharmacy, beauty parlors and even doctors. basic purpose of starting the steroid cream in all of them was to treat acne lesions and also to look fairer and beautiful .it was found in this study that betamethasone valerate was the most commonly used topical corticosteroid, may be due to this being the most cost-effective and easily available amongst all. in our study use of topical steroids was most common in teenage group and mostly in females. patients were also asked about their qualification. misuse of topical steroids was also seen in patients who have done their graduation or were above graduates. i n p a k i s t a n d i ff e re n t c o r t i c o s t e ro i d molecules, ranging in potency from mild to super-potent, are available for topical use on the skin. these molecules are marketed under a variety of brand names by multiple pharmaceutical companies. most of these formulations are available at every medical store with or without a prescription. because of inadequate policing of medicine shops by the authorities these topical steroids are sold without any prescription. so the patients have free access to them. cutaneous side effects of topical steroids have been studied in various studies in western world mainly in context of their use 11, 12in atopic dermatitis. in our region, due to free availability of topical steroids as over the counter drugs, side effects are also seen in context of treating acne .besides that their use as wonder drug to become fairer is increasing. as indicated by the data in this study, the problem of topical corticosteroid misuse is significant,and unless urgent steps are taken on all possible fronts we will continue to face these side effects of topical steroids. 23 24 aw a r e n e s s p r o g r a m m e s r e g a r d i n g indications and contraindications of topical steroids need to be conducted to general community and general practitioners to avoid misuse of topical steroids. this study shows that use of topical steroids to treat acne lesion in our population is quite common. this misconcept in patients with acne vulgaris is associated with cutaneous misconcept in patients with acne side effects including aggravation of population is quite common. this acne lesion, skin atrophy telangiectasias, perioral dermatitis, lesions in our, hirsutism, acne rosacea and various other side effects. awareness programs should be conducted to make people aware of these side effects. this study highlight the need for provision of better information and education to patients and possibly general practitioners regarding the safety, potency a n d a p p r o p r i a t e u s e o f t o p i c a l corticosteroids. 1. smithard a, glazebrook c, williams hc. acne prevalence, knowledge about acne and psychological morbidity in mid-adolescence: a community-based study. br j dermatol 2001; 145:274-9. 2. nast a, dréno b, bettoli v, degitz k, erdmann r, finlay ay et al. european evidence-based (s3) guidelines for the treatment of acne. j eur acad dermatol venereol 2012;26:1-29. 3. amado jm, matos me, abreu am. the prevalence of acne in the north of portugal. j eur acad dermatol venereol 2006; 20:1287-95. 4. purdy s, langston j, tait l. presentation and management of acne in primary care: a retrospective cohort study. br j gen pract 2003; 53:525-9. 5. webster gf. acne vulgaris: state of the science. arch dermatol 1999; 135:1101-2. 6. lee ssm, rapp y. the modern topical steroid. conclusion references int j dermatol 1975; 14:412-21. 7. r o b e r t s o n d b , m a i b a c h h i . to p i c a l corticosteroids. int j dermatol 1982; 21: 59-67. 8. motghare v, thawani v, parate sm.topical use of corticosteroids in dermatology.indian j dermatol 1995; 40:159-62. 9. rathi sk, kumrah l.topical corticosteroidinduced rosacea-like dermatitis: a clinical study of 110 cases. indian j dermatol venereol leprol 2011; 77: 42-6. 10. abidi a, ahmad f, singh sk, kumar a. study of reservoir effect of clobetasol propionate cream in an experimental animal model using histamine-induced wheal suppression test. indian j dermatol 2010; 55: 329-33. 11. charman cr, morris ad, williams hc. topical corticosteroid phobia in patients with atopic eczema. br j dermatol 2000; 142:931-6. 12. callen j, chamlin s, eichenfield lf, ellis c, girardi m, goldfarb m et. al. a systematic review of the safety of topical therapies for atopic dermatitis. . br j dermatol 2007;156:203-21 13. saraswat a, lahiri k, chatterjee m, barua s, coondoo a, mittal a, et al. topical corticosteroid abuse on the face: a prospective, multicenter study of dermatology outpatients indian j dermatol venereol leprol 2011; 77: 1606. 14. rathi s. abuse of topical steroid as cosmetic cream: a social background of steroid dermatitis. indian j dermatol 2006; 52:154-5. 15. batool s, mustafa g, hanif m, mahmood n, sadia f, hassan m. perception of acne patients regarding its pathogenesis and treatment j sheikh zayed med coll 2010; 1:60-4. 16. tahir cm.pathogenesis of acne vulgaris: simplified.j pak assoc derma 2010; 20:93-7. 17. cunliffe wj. management of adult acne and acne variants. j cutan med surg 1998; 2:7-13. 18. simonart t, dramaix m. treatment of acne with topical antibiotics: lessons from clinical studies. br j dermatol 2005; 153:395-403. 19. mahe a, ly f, aymard g, dangou jm. skin diseases associated with the cosmetic use of bleaching products in women from dakar, senegal. br j dermatol 2003; 148:493-500. 20. lu h, xiao t, lu b, dong d, yu d, wei h, et al. facial corticosteroid addictive dermatitis in guiyang city, china. clin exp dermatol 2009; 35:618-21. 24 25 21. al-dhalimi ma, aljawahiri n. misuse of topical corticosteroids: a clinical study from an iraqi hospital. east mediterr health j 2006; 12:847-52. 22. solomon ba, glass at, rabbin pe. tinea incognito and "overthecounter" potent topical steroids. cutis 1996; 58:295-6. 23. hengge ur, ruzicka t, schwartz ra, cork mj. adverse effects of topical glucocorticosteroids. j am acad dermatol 2006;54:1-15 24. ljubojeviae s, basta-juzbasiae a, lipozeneiae j. s t e ro i d d e r m a t i t i s re s e m b l i n g ro s a c e a : aetiopathogenesis and treatment. j eur acad dermatol venereol 2002;16:121-6 25. amado jm, matos me, abreu am. the prevalence of acne in the north of portugal. j eur acad dermatol venereol 2006; 20:1287-95. 25 untitled-1 original�article abstract objective: purpose of the study was to determine the challenges, complications and outcome of laparoscopic hysterectomy (lavh & tlh). study design: case series study. st place and duration of study: the study was conducted in civil hospital bahawalpur from 1 october 2016 to th 30 september 2017. materials and methods: patient presenting with dub (dysfunctional uterine bleeding) and small fibroid were included. parameters studied were duration of surgery, complications, conversion to open, patient satisfaction and hospital stay. data was collected on performa and shifted to spss version 20. results: out of 11 patients included, 3 patient underwent lap-assisted vaginal hysterectomy and in 8 patient tlh was performed. one patient was converted to open due to uncontrolled bleeding. one patient developed vesico-vaginal fistula. minor postoperative wound infection (2 patients) and wound infection (1 patient) was managed conservatively. conclusion: the challenges/complications of tlh are its technique, training, use of gadgetry, unfamiliar anatomy, bleeding and gas leakage. proper training, use of uterine manipulator, best assisting technique and use of energy devices make outcome acceptable, easy and achievable. key words: � hysterectomy, lap-assisted vaginal hysterectomy (lavh), total laparoscopic hysterectomy (tlh), uterine manipulator. factors are disease process and extent, experience of the surgeon, availability of multidisciplinary approach, gadgets, size of the fibroid and size of uterus. the history of vaginal hysterectomy dates back to 120 a.d. the first hysterectomy was claimed by charles clay in 1943 in manchester. procedures done 3 were without anesthesia and mortality up to 70%. in 1930s richardson started total abdominal 3 hysterectomy with acceptable results. first laparoscopic hysterectomy was done in 1988 by 3 harry rich in pennsylvania. minimal access laparoscopic surgery has become a normal nowadays in most fields of surgery. namely lap-assisted vaginal hysterectomy (lavh) and total laparoscopic hysterectomy (tlh) are mostly performed in different centers. what is difference between lavh and tlh? in lavh the fallopian tubes, ovarian vessels, round and broad ligament are ligated and cut laparoscopically. calpotomy and ligation of uterine vessel is secured trans-vaginally. in tlh all these steps are performed laparoscopically. lavh is a popular approach as it can be performed with limited experience. total laparoscopic introduction abdominal hysterectomy is a procedure which is done, when health of the female patient becomes compromised, due to dysfunctional uterine bleeding 1 or symptomatic fibroids. if medical management fails and health is at risk, hysterectomy may be treatment of choice if family of the patient is complete. it needs initial management of pain, anemia and vaginal bleeding. treatment options are open tah, partial laparoscopic hysterectomy, lap assisted vaginal hysterectomy, total laparoscopic 2 hysterectomy, and vaginal hysterectomy. the decision, regarding which operative technique is to be used depends on many factors. the important a journey from lap-assisted vaginal hysterectomy (lavh) to total laparoscopic hysterectomy (tlh) 1 2 3 4 5 muhammad ishaque khan , akbar hussain mujahid , musrat akhter , alina saeed , faiza ishaque correspondence: dr. muhammad ishaque khan associate professor, surgery quaid e azam medical college, bahawalpur e-mail: ishaquedr69@yahoo.com 1,5 department of surgery quaid e azam medical college, bahawalpur 2,4 3 department of surgery/ gynecology and obstetrics civil hospital, bahawalpur funding source: nil; conflict of interest: nil received: apr 19, 2017; revised: feb 18, 2017 accepted: feb 20, 2017 a journey from lavh to tlhjiimc 2018 vol. 13, no.1 3 4 also the details of post-operative complication management analyzed. these variables are good guide for success of surgery. consent was signed by the patient after sufficient details of procedures and their ethical rights were discussed. anonymity was observed in all cases. a workshop was arranged with hands on training. all surgical procedures were performed by the same surgeons in both surgical and gynecological departments. position of the patient was dorsal lithotomy with pneumoboots. three ports used were umbilical 10 mm for camera, 10mm port on right flank at the same level and 5 mm port in left flank. the cuffed nob of uterine manipulator was inserted in cervical canal and cuff inflated. the colpotomizer was moved forward until it fits on the cervix. the formal inspection of abdomen and pelvis was done. dissection was started by cutting fallopian tubes, ovarian vessels, broad and round ligament with ultrasonic dissector after coagulation with bipolar. two leafs of peritoneum were dissected until uterine vessels was visible. vessels were ligated by extra corporeal knots and cut by ultrasonic dissector. bladder was pushed with peritoneum. now colpotomizer can be felt and calpotomy was done with hook. uterus was removed from vagina. and cuff closed laparoscopically or vaginally. the uterine manipulator used was made locally (fig 1). hysterectomy (tlh) has become possible in some centers by use of uterine manipulator, colpotomizer and energy source (thunder beat, ligasure & bipolar 4 cautery). the journey from lavh to tlh is demanding. it needs training, patience, careful selection of the patients, energy devices and a multidisciplinary approach. selection of patient i.e. small fibroids, nonhyperemic uterus facilitated to prevent preoperative c o m p l i c a t i o n a n d p o s t o p e r a t i v e m i n o r complications for example blood loss, pain and fever due to infection. this study will be helpful for the surgeons/ gynecologists committed to advance laparoscopic procedures. purpose of the study was to determine the challenges, complications and outcome of laparoscopic hysterectomy (lavh & tlh). materials and methods this was a case series prospective study. the study was conducted as a joint venture of surgery and gynecological departments of civil hospital, st bahawalpur. duration was from 1 october 2016 to th 30 september 2017. a total 11 patients were selected. a non-randomized convenient sampling was done. selection criteria was patients having dysfunctional uterine bleeding or symptomatic fibroids measuring up to 7 cm. patients with comorbidities, previous abdominal surgeries, large fibroids and large sized uterus were excluded. data was collected on a predesigned performa by one of author. the variables included were age, duration of symptom, operative procedures (laparoscopic vaginal assisted hysterectomy or total laparoscopic hysterectomy), operative details (duration of surgery, energy sources and extra devices used, per-operative complication and conversion), post-operative details (complications and hospital stay) and patient satisfaction. this data was shifted to spss version 20 for statistical analysis. preoperative data analyzed to conclude what is common age, presenting symptom and reason to do the surgery in our institute? the selection of operative procedure lavh & tlh was dependent on improvement in expertise, size of the fibroid, anatomical difficulties and availability of energy sources. mean hospital stay was noted in each patient. post-operative complications were noted at each follow up. patient satisfaction level was noted. fig 1: uterine manipulator with colpotomizer uterine manipulator with colpotomizer made at civil hospital bahawalpur. how it is used can be seen by visiting (https://youtu.be/8auksq-wlhs). results during study period 11 patients fulfilled criteria and were included in the study. age range was 35-60 a journey from lavh to tlhjiimc 2018 vol. 13, no.1 easy and doable. it is worth mentioning that tlh is different in many aspects from other modalities. practical problems, logistics (energy sources, 6 gadgetry), pelvic anatomy, learning curve , operative 7 time and expertise are different from other type of surgery. surgery in our cases was done for dub and small fibroids. there are studies in which tlh done for 8 benign and malignant disease. some surgeons did lavh in big fibroids and difficult anatomy but in 9 routine they did tlh. for case selection history, clinical examination, usg, and special cases ct scan 10 was used as diagnostic tool. uterine manipulator & energy sources (thunder beat (olympus), bipolar and harmonic (ethicon)) has key role in total laparoscopic hysterectomy. to get familiarity with energy devices we used thunder beat and bipolar for other procedures initially. we started with laparoscopic assisted vaginal hysterectomy (lavh) due to larger fibroid unfamiliarity with anatomy and time factor but with passage of time we shifted to total laparoscopic hysterectomy (tlh). authors did not find any research in which energy devices are not used. surgeons usually use bipolar energy source but in difficult anatomy harmonic/ thunder beat. they also used bipolar before 11 harmonic. we in our setup started with thunder beat and extra corporeal knotting for uterine vessels. but in later cases we used both bipolar and harmonic according to anatomy and size of the fibroid. in most cases associated extra corporeal knots were applied. for gas leakage we used strategy used by rk mishra by placing gauze pack and inflated gloves initially. later we used inflated cuff. different type of vaginal manipulator are used by different surgeons. initially we used fan liver retractor to manipulate uterus per vaginum. a uterine manipulator was devised locally fig 1 (based on rumi-2 manipulator) and used. the benefits are visualization of pelvis anatomy, minimal years & mean age was 48 years. all patients presented with per vaginal bleeding refractory to medical treatment. lower abdominal pain was in three patients. four patients were severely anemic having hemoglobin level less than 7 gm. /dl. seven patients presented with dub, while 4 patients presented with fibroids 2-5 cm. in 3 patients lavh was done and in 8 patients tlh was done. lavh was done in patient having bigger fibroid (more than 5 cm) and difficult to deal by tlh. in patients having smaller fibroid (less than 5 cm) tlh was done. however in 2 out of 8 patients undergone tlh bleeding was controlled by vaginal approach. one patient was converted to open surgery due to uncontrolled bleeding. duration of surgery was 4 hours and 30 minutes; which improved to 3 hours. average time for surgery was 3 hours and 30 minutes. we used of different energy sources. in 7 patients thunder beat and in 4 patients ultrasonic dissector & bipolar cautery was used. a uterine manipulator with colpotomizer was used in all patients undergone tlh. post-operative course was uneventful in 7 patients. early complications in 1 patient was portside infection & in two patients were mild p/v bleeding which were managed conservatively. one patient developed vesico-vaginal fistula repair was done after three months (table i). intravenous antibiotic p ro p hy l ax i s w i t h c ef t r i axo n e 1 g ra m wa s administered at the time of induction of anesthesia & post operatively for 72 hours. hospital stay was 3-7 days postoperatively. foley's catheter was left for 1 week. first follow up was after 1 week, later after 15 days and then monthly for 3 months. eight patients were well satisfied while 2 patients were equivocal and one patient was unsatisfied with this modality of treatment. discussion the current study highlights different challenges and complication of laparoscopic hysterectomy and their practical solutions. total laparoscopic hysterectomy is defined by laparoscopic ligation of uterine/ovarian vessels with removal of uterus, vaginally or 5 abdominally with closure of vaginal cuff. during this study period some important facts were understood. multidisciplinary approach by involvement of surgeon, gynecologist and urologist had made tlh table i: post-opera�ve course of tlh at civil hospital 5 a journey from lavh to tlhjiimc 2018 vol. 13, no.1 adhesions in early phase. 5. a multiple discipline involvement makes the procedure safe and easy. conclusion tlh is a technically demanding procedure. there are challenges regarding the training, use of gadgetry, unfamiliar anatomy, bleeding and gas leakage. proper training, use of uterine manipulator, best assisting technique and use of energy devices make it easy and achievable. references 1. carlson kj, nichols dh, schiff i. indications for hysterectomy. new england journal of medicine. 1993; 328: 856-60. 2. müller a, thiel fc, renner sp, winkler m, häberle l, beckmann mw. hysterectomy—a comparison of approaches. deutsches ärzteblatt international. 2010; 107: 353-9. 3. sutton c. 1 hysterectomy: a historical perspective. baillière's clinical obstetrics and gynaecology. 1997; 11: 122. 4. farthing a. total laparoscopic hysterectomy. gynecologic and obstetric surgery: challenges and management options. 2016; 245: 480-5. 5. walsh ca, walsh sr, tang ty, slack m. total abdominal hysterectomy versus total laparoscopic hysterectomy for benign disease: a meta-analysis. european journal of obstetrics & gynecology and reproductive biology. 2009; 144: 3-7. 6. wattiez a, soriano d, cohen sb, nervo p, canis m, botchorishvili r, et al. the learning curve of total laparoscopic hysterectomy: comparative analysis of 1647 cases. the journal of the american association of gynecologic laparoscopists. 2002; 9: 339-45. 7. richardson re, bournas n, magos al. is laparoscopic hysterectomy a waste of time? the lancet. 1995; 345: 3641. 8. dall'asta a, patrelli ts, franchi l, rolla m, sianesi n, modena ab, et al. total laparoscopic hysterectomy. ann. ital. chir. 2013; 84: 645-8. 9. king cr, giles d. total laparoscopic hysterectomy and laparoscopic-assisted vaginal hysterectomy. obstetrics and gynecology clinics. 2016; 43: 463-78. 10. bristow re. total laparoscopic hysterectomy. te linde's atlas of gynecologic surgery. 2013; 14: 35-7. 11. einarsson ji, suzuki y. total laparoscopic hysterectomy: 10 steps toward a successful procedure. reviews in obstetrics and gynecology. 2009; 2: 57-64. 12. gimbel h, zobbe v, andersen bm, filtenborg t, gluud c, tabor a. randomised controlled trial of total compared with subtotal hysterectomy with one-year follow up results. bjog: an international journal of obstetrics & gynaecology. 2003; 110: 1088-98. blood loss, dynamic access to pelvic structures, uterine vessels and vagina due to access on many angles. vault closure can be done laparoscopically or per vaginally. in a case series study by gimbel and zobbe cuff closure was done laparoscopically but in a few cases where tissue edema was moderate, per vaginal 12 cuff closure was done. we in our first 9 cases did per vaginal cuff closure but in succeeding cases cuff closed laparoscopically. per-operative detail can be a good guide of improvement in expertise. the duration of surgery can never supersede the safety but it can be clue to the improvement in procedures and gadgets. different studies revealed that time of 13 procedure was 1 hours and 30 minutes to 3 hours. time for surgery in our study was noted to be from 3 hours to 4 hours and 30 minutes. in most of the advance laparoscopic centers patient is discharged next day if patient is vitally stable. patient remains catheterized for 4-7 days and is first follow up catheter is removed. next follow up is done in fortnightly then monthly for three months. we also used the same policy. satisfaction level is almost the same when compared with studies of other authors. in most studies 30 mg ketorolac intravenous at the end of the procedure given and four doses after that. for postoperative pain management we use diclofenac suppositories at induction, injection tramadol i/v and inj. lignocaine 1% at port site at the end of the procedure. pain management was excellent in most of cases. authors find some limitation in current study. firstly it is not study of single method or technique. secondly the practical aspects are highlighted without much stress on statistical aspects. thirdly number of patients is less due to time constraint and heavy workload. authors want to share few practice points and suggestion: 1. a training workshop with hands on practice must be mandatory before tlh is started. 2. vaginal manipulator and energy sources has key role. 3. patient safety is priority. so never hesitate to convert in case of any problem. 4. don't do surgery for big fibroid or patients with 6 a journey from lavh to tlhjiimc 2018 vol. 13, no.1 prospective randomized study. human reproduction. 1999; 14: 2996-9. 13. perino a, cucinella g, venezia r, castelli a, cittadini e. total laparoscopic hysterectomy versus total abdominal hysterectomy: an assessment of the learning curve in a 7 a journey from lavh to tlhjiimc 2018 vol. 13, no.1 page 8 page 9 page 10 page 11 page 12 untitled-2 untitled-1 original�article abstract objective: to check the frequency of stress urinary incontinence and to assess the awareness about pelvic floor muscle training for stress urinary incontinence among pregnant women. study design: cross sectional observational study. place and duration of study: the study was conducted from april 02, 2017 to july 30, 2017, at the department of obstetrics and gynecology islamic international medical college, pakistan railway teaching hospital, rawalpindi. materials and methods: a total of 322 pregnant women between gestational ages of 12 to 38 weeks were selected by convenience sampling technique. a structured closed questionnaire was used for data collection. all data were analyzed in spss version 21 and percentages and mean were calculated. results: the frequency of stress urinary incontinence among our study population was 32.9%. awareness about pelvic floor muscle training was seen in only 9% of women in general and 27% of women suffering from stress urinary incontinence. conclusion: frequency of stress urinary incontinence in our pregnant population is high. awareness about pelvic floor muscle training and its benefits is very scant and very few pregnant women suffering from stress urinary incontinence are doing pelvic floor muscle training. this highlights the need of improving antenatal care. key words: pelvic floor muscle training (pfmt), pregnancy, stress urinary incontinence (sui). women suffer in silence and do not report symptoms unless questioned, which prevents the exact incidence of stress urinary incontinence difficult to assess. pregnancy, childbirth and aging all are the risk 7,8 factors. weak pelvic floor other than stress urinary incontinence, can also lead to fecal incontinence, prolapse of pelvic structures and sexual difficulties. pelvic floor muscle training (pfmt) is repetitively selective voluntary contraction and relaxation of specific pelvic muscles. pelvic floor muscle training (pfmt) raises bladder, prevents decent in bladder neck during increased abdominal pressure. it is the first line conservative treatment for prevention of stress urinary incontinence in women during 9,10 pregnancy and afterwards and is considered safe. there is evidence from literature, cochrane review, that pelvic floor muscle training can prevent stress urinary incontinence up to six months following delivery. studies have not revealed any detrimental effect of pelvic floor muscle training on the process 11,12 of labor and delivery. the objectives of this study is to check the frequency of stress urinary incontinence in pregnant women because most women do not report the problem considering it related to pregnancy and childbirth and are unaware of the benefits pelvic floor muscle training can introduction stress urinary incontinence (sui) is involuntary leakage of urine with physical activity. it occurs when intravesical pressure exceeds urethral closure pressure in the absence of detrusor muscle contraction. it may also occur due to bladder neck hypermobility or poor urethral closure pressure. it interferes with women's quality of life and is the commonest cause of incontinence among women of 1, 2, 3 all ages and during pregnancy. the reported prevalence of stress urinary incontinence during 4, 5, 6 pregnancy in literature varies from 17.9% to 71%. this variation can be due to different selection criteria and definitions used in studies. quality of life of more than 50% pregnant women is effected which 2 worsens with advancement of pregnancy. many pelvic floor muscle training to prevent stress urinary incontinence in pregnancy rubab riaz, fareesa waqar, saadia sultana correspondence: dr. rubab riaz department of gynecology and obstetrics islamic international medical college riphah international university, islamabad e-mail: rubabriaz2004@gmail.com department of gynecology and obstetrics islamic international medical college riphah international university, islamabad funding source: nil; conflict of interest: nil received: mar 02, 2017; revised: june 03, 2017 accepted: oct 05, 2017 pelvic floor muscle training in pregnancyjiimc 2017 vol. 12, no.4 177 provide. increased frequency and low awareness about stress urinary incontinence and pelvic floor muscle training is expected ,respectively, in our population due to repeated pregnancies, poor nutrition and failure to seek help by considering it non amendable and shameful. materials and methods a cross sectional study was conducted over 4 months periods from april 02 to july 30, 2017 at the department of obstetrics and gynecology in islamic international medical college, pakistan railway teaching hospital rawalpindi. sample size calculation yielded 322 women done by who creative research system survey software, assuming that the percentage of incontinent women in the study population would be 50% with 5% estimated error and a confidence level of 95%. women were selected by convenience sampling technique. permission from institution's ethical committee was taken before conducting the study. a modified questionnaire for stress urinary incontinence diagnosis (quid) was used for data collection, frequency of stress urinary incontinence and 9 awareness about pelvic floor muscle training. the questionnaire for urinary incontinence diagnosis had 3 sections, section 1 included demographic variables, and section 2 had questions for stress urinary incontinence diagnosis. section 3 was about women's awareness and knowledge of pelvic floor muscle training with pictorial details in urdu. informed consent was taken and questionnaire was completed by interviewing women visiting clinic for routine antenatal care (study population). all women between gestational ages 12 to 38 weeks were included in the study. exclusion criteria included women diagnosed with urinary tract infection, preterm labor and preterm premature ruptured membranes. all women who reported mild to severe symptoms of stress urinary incontinence were considered as incontinent. the data from questionnaire was entered in spss version 21 and results were calculated in percentages and mean with standard deviation for demographic variables. results age range of our study population was between 18 years to 43 years, mean age was 29.16 ± 4.946 years. mean bmi was 26.97 ± 2.002. eighty two percent of women were parity 1 and above. study results showed that 32.9% of pregnant women suffered from stress urinary incontinence ranging from mild to severe form. fifty percentage of women suffering from stress urinary incontinence were above the age of 30 years and bmi above 30 was seen in 70% of women suffering from stress urinary incontinence .chronic constipation and cough was seen in only 1% of effected women (table 1). nine percent of women in general had awareness about pelvic floor muscle training, while awareness about pelvic floor muscle training in effected women was 27% out of which only 3% were performing of it. table i: frequency of risk factors among women with stress urinary incon�nence discussion the study shows that 3 out of 10 pregnant women in our population is suffering from stress urinary incontinence. the women do not complaint about the problem during routine ante natal visit until inquired and they also lack knowledge and benefits about pelvic floor muscle training. advanced age, obesity and multiparty is seen as a risk factor for stress urinary incontinence in our study. literature backs aging, parity and obesity as known risk factors for stress urinary incontinence. one study reports 20% increase in urethral 13 hypermobility following first vaginal delivery. according to norwegian epincot study, association with cesarean section is also noticeable and 14 comparable to risk in nulliparous. poor knowledge and motivation about pelvic floor muscle training seen in the study can be due to multiple reasons. one reason can be the busy antenatal clinic, where less time is given to hear all complaints from the women and less time given to provide extra teachings. another reason can be the pelvic floor muscles which are not visible, so women do not know the right way to perform the exercise. also anemia, protein and other nutritional deficiencies are common in our population and can make it difficult pelvic floor muscle training in pregnancyjiimc 2017 vol. 12, no.4 178 15 for women to hold muscles. pelvic floor muscle training is considered free of cost, safe and effective method to prevent and treat stress urinary incontinence in pregnancy and post-partum. a cochrane review summarized the results of 5 randomized trials and shows that women undergoing intensive pelvic floor muscle training in early pregnancy were 56% less likely to report urinary incontinence in late pregnancy and around 30% less likely to report urinary incontinence in 6 16 months postpartum. a meta-analysis reports improvement in stress urinary incontinence ranging from 48% to 93% with effective pelvic floor muscle training (6-8 second contraction, 3 sets of 8-12 contraction, and 2-4 days per week). the response is 17 seen in one to three weeks. evidence shows that at least 8 to12 weeks of pelvic floor muscle training is 18,19 required to see the good results. health education in the form of antenatal class is beneficial and some centers recommend teaching pelvic floor muscle training as early as 10 weeks in the booking antenatal 20 class. limitation of our study is that the level of severity for stress urinary incontinence is not defined. this study is useful as it identifies the frequency and importance of inquiring about symptoms of stress urinary incontinence and we plan to review our policy of routine antenatal care. conclusion the study concludes that frequency of stress urinary incontinence is not far less than the prevalence seen elsewhere in the world, around 3 out of 10 pregnant women. awareness about pelvic floor muscle training in pregnant women is very scant. pregnancy provides women an opportunity to visit a health care provider multiple times, discuss issues effecting quality of life and get teachings like pelvic floor muscle training. but our antenatal teaching is falling behind in this particular area and require revision. references 1. sang bb. risks factors for development of stress urinary incontinence during pregnancy in primigravidae: a review of literature. eur j obstet gynecol reprod biol. 2014; 178: 2734. 2. sansawang b, sangsawang n. stress urinary incontinence in pregnant women: a review of prevalence, pathophysiology and treatment. int urogynecol j. 2013; 24: 901-12. 3. lamin e, parilo lm. pelvic floor muscle training: underutilization in usa. cur urology rep. 2016; 17: 10. 4. ozerdogan n, begi nk. urinary incontinence: its prevalence, risk factors and effects on quality of life of women living in a region of turkey. gyneco obstet invest. 2004; 58: 245-50. 5. tingthong w, buppasiri p. prevalence of urinary incontinence in pregnant women at 37 tertiary care hospitalsin khonkaen province. thai j obstet gynecol. 2014; 22: 37-43. 6. hansen bd, suare j. urinary incontinence during pregnancy and 1 year after delivery in primigravidae women compared with controlled group of multiparaous women. neuro urol urodyn. 2012; 31: 475-80. 7. paival l , ferla l. pelvic floor muscle training in group vs individual or home treatment of women with urinary incontinence: systemic review and meta-analysis. int urogynecol. 2017; 2: 351-9. 8. macintosh l, anderson e. conservative treatment of stress urinary incontinence in women. a 10 year (2004-2013) scoping. review of literature. urol nurs. 2015; 35: 179-86. 9. catherine s, bradley md. the questionnaire for urinary incontinence diagnosis (quid): validity and responsiveness to change in women undergoing non-surgical therapies for treatment of stress predominant urinary incontinence. neuro urol urodyn. 2010; 25: 727-34. 10. sahakia j. stress incontinence and pelvic floor exercises in pregnancy. br j nurs. 2012; 21: 10-2. 11. bo k. effects of antenatal pfmt on labor and birth. obstet gynecol. 2009; 113: 1279-84. 12. boyle r, hay s. pelvic floor muscle training for prevention and treatment of urinary and stress incontinence in pregnant women and women who have recently given birth. cochrane. 2012. 13. dickie kj, shek kl. the relationship between urethral mobility and parity. bjog. 2010; 117: 1220-4. 14. rontveil g. urinary incontinence after vaginal delivery or cesarean section. n engl j med. 2003; 348: 900-7. 15. oliveira cd, seleme m. urinary incontinence in pregnancy and its relation with sociodemographic variables and quality of life. rev assoc med bras. 2013; 59: 460-6. 16. bo k. to do or not to do? pelvic floor muscle training during pregnancy and after child birth. journal of the association of chartered physiotherapist in women's health. 2011; 108: 13-7. 17. petricia bn. pelvic floor muscle training and adjunctive therapies for the treatment of sui in women: a systemic review. b m c women's health. 2006; 6: 11. 18. bo k, murkved s. effects of pelvic floor muscle training during pregnancy and softer child birth on prevention and treatment of urinary incontinence: a systemic review. b j sports. 2012; l48: 4. 19. charles p. pelvic floor muscle training for incontinence during pregnancy. bjog. 2012; 119: 1270-80. 20. national collaborating center for women and child health (uk). antenatal care: routine care for the healthy pregnant women. london: rcog press. 2008. pelvic floor muscle training in pregnancyjiimc 2017 vol. 12, no.4 179 page 17 page 18 page 19 original�article abstract objective: to determine the effect of portage early education program (peep) on the neurodevelopment of cerebral palsy children. study design: the quasi-experimentalpre and post design place and duration of study: developmental pediatrics department, the children hospital, and the institute of child health multan from 1st january 2020 to 24 december 2020. materials and methods: we enrolled 58 children of 2 to 10 years of age, both gender, diagnosed as spastic cerebral palsy for this study. all the children were assessed preand post-program using peep and gmfm (gross motor function measure) twice 6 months apart. they were advised regular weekly peep based therapeutic sessions at hospital by multidisciplinary team, and continuation of these therapies at home. data was analyzed by using ssps version 16. the mean difference in the scores of the developmental levels, initial and after 6months was compared by using paired t test. results: out of 58 study subjects, male were prominent; 42(72.41%). most of the participants had quadriplegia type of spastic cerebral palsy 26(44.83%), with gross motor function level 5, [24(42.86%)]. the mean comparison of developmental quotient of children calculated at initial stage and after six months in areas of gross motor, cognition, self-help, socialization, and gross motor function measure was found statistically significant(p-value<0.001) conclusion: children with cerebral palsy are associated with delayed development in certain developmental domains other than involvement of motor and posture. peep is an effective tool for improvement in development of cp children key words: cerebral palsy, portage early education program, spastic quadriplegia. diagnosis is mostly clinical. important etiology i n c l u d e s b ra i n i n j u r y o r a b n o r m a l b ra i n development, pre and post maturity, cerebral leukomalacia, periventricular–intraventricular hemorrhage, hypo perfusion injuries and cerebral 2,3 infections or inflammations , although, the brain damage is not progressing, but its manifestations keep on changing with development of child, resulting in limited participations in the different life 4 areas and activities. similarly cp is a motor disorder but it has associated problems of sensation, perception, cognition, communication and behavior, 1 musculoskeletal problems and epilepsy which manifest as complications like intellectual or learning disability (40%); epilepsy (30%); movement disorders (20%); visual impairment (16%); malnutrition, gastro esophageal reflux, obesity, hydrocephalus (14%) and developmental problems. these problems must be managed by involving 2, 5 multidisciplinary team. early intervention results in the better outcome of the patient symptoms. introduction cp is a broad term which is defined internationally as follows: “cerebral palsy describes a group of permanent disorders of the development of movement and posture, causing activity limitation that are attributed to non-progressive disturbances that 1 occurred in the developing fetal or infant brain.” cp has prevalence of 1.5–5.6 cases per 1000 live births. cp is classified by geographical classification, physiological classification, and gross motor 2 function classification system (gmfc system). effect of portage early education program on the neurodevelopment of children with cerebral palsy erum afzal, mohammad khalid iqbal, nadia iqbal, kausar aftab correspondence: dr. erum afzal assistant professor department of developmentalbehavioral pediatric children hospital and the institute of child health, multan e-mail: erumafzal@yahoo.com department of developmentalbehavioral pediatric children hospital and the institute of child health, multan received: may 24, 2021; revised: february 24, 2022 accepted: march 03, 2022 peep for children with cerebral palsyjiimc 2022 vol. 17, no.2 103 treatment modalities includes physiotherapy, occupational therapy, psychotherapy, speech and developmental therapy and inclusive education for these children. the portage early education program (peep) began in great britain and is now practiced worldwide for developmentally delayed children. it is based on the idea that genetic and environmental factors have a great role in the development of the 6 brain, in both functional and structural aspects. the brain plasticity is more during early life. during this period, the environmental factors also strengthened 6 adaptive and compensatory skills therefore intervention started in infantile period reveals better 7 results. it emphasize the importance of hospital b a s e d a n d h o m e t h e ra p y b y p a re nt s fo r improvement of the children with delayed developmental. there is a critical role of timely intervention for the better outcome of children with special needs. peep includes therapeutic tasks for almost all developmental domains. it not only involves individualized intervention but emphasize great importance to the parental role as a therapist. because better results are achieved with parental 8 participation and execution. although studies about intervention in global developmental delay and autism are present in literature but studies on the outcomes of children 7 with cp are surprisingly few in the present study, we applied the peep to children with cp and observed effect of peep on the neurodevelopment of cerebral palsy children. materials and methods this quasi-experimentalpre and post design was carried out in outpatient department (opd) of developmental and behavioral pediatrics of ch&ich multan. we enrolled 58 children presented with delayed development, abnormal muscle tone, and 1, 2 hyperreflexia, clinically diagnosed as cp , ages between 2 to 10 years, both gender from january 2020 to december 2020 by convenient sampling. the children having degenerative brain disorders, myopathies, neuropathies, inborn error of metabolism, chromosomal abnormalities, severe hearing deficit, and did not gave consent, were excluded. these disorders were diagnosed on clinical features, examination findings and available investigations. sample size was calculated through 9 stata 15, using paired t-test for correlated means. p ro c e d u re o f t h e st u d y wa s to l d to t h e parents/guardian after taking written consent. for all cp children detailed history was taken from parents/guardian. their socioeconomical status was noted. complete neurological examination was done in all children. type of cp was determined. peep and gmfm (gross motor function measure) was used to assess developmental levels in all domains and functional severity of motor function respectively. a trained and expert clinical psychologist with more than 10 years of experience working with peep, administered and assessed every child for his/her interests, deficit and learning capacities, in a quiet room with peaceful surroundings. portage has five development key areas along with infant stimulation, applied up to 6 years of mental age. these are gross m o t o r ( g m ) , c o g n i t i o n ( c ) , s e l f h e l p ( s h ) , socialization(s) language (l). each area had a specific checklist according to age. total number of items are motor: 140, cognition: 108, self-help: 105, socialization: 83 and language: 218 and infant stimulation: 45. all patients were assessed according to checklist items. when there were 10 consecutive negative items, at that point of checklist stops. positive items were obtained by subtracting failure items from total. developmental age was assessed by first subtracting failures from total to calculate positive items (total – failure = positive items). then the positive items were divided by total items and then multiplied by 12 to find out developmental age (development age=positive item/total item × 12). developmental age is used to access his/her d e v e l o p m e n t a l q u o t i e n t i n a l l a r e a s b y : dq=da/chronological age × 100). she assessed the mental age in all 5 domains and individualized training programs (ieps) were developed according to each child's development levels and needs. sessions were started to overcome deficits by psychologist, speech therapist, occupational and physiotherapist. the sessions / training program was performed on every visit on weakly basis in the department for at least half hour, during which parents were also trained. parents were advised to spend at least 2 hours per day for continuation of these therapies/activities at home. after 6 months the resulting effects were re-evaluated by assessing peep and gmfm. approval was taken from the institutional ethical peep for children with cerebral palsyjiimc 2022 vol. 17, no.2 104 committee. no conflict of interest was involved in this study. no financial support was provided by the institution or pharmaceutical company. all the data was entered on preformed performa. statistical analysis was done by using ssps version 16. the mean difference in the scores of the developmental levels/quotients, initial and after 6monthsof therapy was compared by using paired t test. p < .05 was considered statistically significant     and 95% confidence interval was used. results out of 58 patients 42(72.41%) were male with male to female ratio of 3:1. most of the children 28(48.29%) were age group >4-7years (table i). mostly children were diagnosed having spastic quadriplegic type 26(44.83%) with level 5 gmfm 24(42.86) (table ii). dq of cp children in areas of gm, c, sh, s, l and gmfm was found statistically significant with therapy (table iii). spastic quadriplegic type 2, with level 5 gmfm. all the recruited cp children have delayed development in all developmental domains (gm, sh, c, s, l), these were assessed and trained using peep, which is an effective tool for the treatment of cp for neurodevelopmental rehabilitation. portage guide is a perfect checklist for assessment and training in structured settings. due to its, interesting, scientific, logical, and easy applicable nature, it has been used w o r l d w i d e fo r e a r l y i n t e r v e n t i o n fo r t h e 7 development and training of cp children . our children showed good improvement after 6 months of therapy weakly at hospital by multidisciplinary team and home by parents/family member on daily basis. these findings were similar to others as, sorensen, kristian described the better outcome of cerebral palsy with regular intervention in longitudinal study 10 conducted in norway. a study carried in china where they rehabilitated the children with global developmental delay including cerebral palsy using peep for 6 months period, they found marked improvement in development of the children with r e g u l a r d e v e l o p m e n t a l , o c c u p a t i o n a l a n d physiotherapy and they found peep an effective 9 tool. a study was planned in lebanon for rehabilitation of children with special needs, which also favored the importance of regular therapy and described portage as an effective tool for home 11 therapy. this favors of our results. sharon barak also d e s c r i b e d t h e i m p ro v e m e n t i n f u n c t i o n a l 12 independence of cp children with regular therapy. similar results were obtained by iona novak in systematic review of intervention of cp children and 13 adults. early intervention services and follow up table i: basic characteristics of participant (n=58) table ii: type of cp & gmfm (n=58) table iii: comparison of developmental profile between children initial and after six months of peep therapy discussions in this study dq of cp children in areas of gm, c, sh, s, l and gmfm was found statistically significant with therapy (table iii). the current hospital-based research showed that most children were male, age group >4-7years, of peep for children with cerebral palsyjiimc 2022 vol. 17, no.2 105 program results in the better outcome of cp children, 14 indicated by ekaterina in moldeve. a study done in national institute of rehabilitation medicine (nirm) islamabad described that early and regular physiotherapy results in improvement in gm 15 functions in cp .verschuren in netherland also found physiotherapy as effective in gross motor 16 outcome of the cp children , while heilkam et al described no significant improvement in infant outcome with only physiotherapy intervention, but 17 family quality of life improved. we found predominantly male child with age range 4-7years and poor socioeconomic status, these 11 findings are like another one. limitations of this study includes that national data showing peep intervention in cp is very less. the current study is of limited time duration. although our result showed positive effects with only 6 months of peep implementation, further research is needed to prove the long-lasting effects with continuation of intervention for longer duration. results must be compared to control group. conclusion peep is an excellent effective interventional system for neurodevelopment of cp children with delayed development, which covers therapy in all developmental areas for a long time for better outcome. references 1. rosenbaum p, paneth n, leviton a, goldstein m, bax m, damiano d et al. a report: the definition and classification of cerebral palsy april 2006. dev. med child neural suppl. 2007; 109:8-14. 2. khan aa, ahmad k, ayaz sb, ayyub al, akhlaq u. cerebral palsy in pakistani children: a hospital based survey. cukurova medical journal. 2014; 39(4):705-711. 3. agarwal a, verma. cerebral palsy in children: an overview. j clin orthop trauma. 2012 dec; 3(2): 77–81. 4. surveillance of cerebral palsy in europe: a collaboration of cerebral palsy surveys and registers. surveillance of cerebral palsy in europe (scpe). dev med child neurol. 2 0 0 0 d e c ; 4 2 ( 1 2 ) : 8 1 6 2 4 . d o i : 10.1017/s0012162200001511. pmid: 11132255. 5. sawyer j.r. cerebral palsy. in: canale s.t., beaty j.h., editors. campell's operative orthopedics. 11th ed. mosby elsevier; philadelphia: 2008. pp. 1333–1399. 6. georgieff mk, brunette ke, tran pv. early life nutrition and neural plasticity. dev psychopathol 2015; 27:411–23. 7. lobo ma, paul da, mackley a, maher j, galloway jc. instability of delay classification and determination of early intervention eligibility in the first two years of life. res dev disabil. 2014 jan;35(1):117-26. 8. russell f. portage in the uk: recent developments. child care health dev 2007; 33:677–83. 9. xiumei liu, md, xue-ming wang, ms, jing-jing ge, ms, and xiu-qing dong, bs. effects of the portage early education program on chinese children with global developmental delay. medicine (baltimore). 2018 oct;97(41): e12202.: pmc6203492.pmid: 30313024 10. sorensen, kristian, vestrheim, ida e, lerdal bjorn, skranes, jon. functional skills among preschool children with cerebral palsy assessment before and after early intervention. developmental neurorehabilitation. 2020 nov; 23 (8): 519-525, 11. sarouphim k, mcgi, kassem s.use of the portage curriculum to impact child and parent outcome in an early intervention p r o g r a m i n l e b a n o n . 2 0 2 0 s e p t e m b e r ; d o i : 10.1080/09575146.2020.1818186 12. barak s, hutzler y, and dubnov-raz g. physical exercise for people with cerebral palsy: effects, recommendations and barriers. harefuah. 2014 may; 153(5):266-72, 305. 13. novak i, morgan c, fahey m,edmondson mf,galea c,hines a, et al. state of the evidence traffic lights 2019: systematic review of interventions for preventing and treating children with cerebral palsy. current neurology and n e u ro s c i e n c e re p o r t s . 2 0 2 0 fe b ; 2 0 ( 2 ) : 3 . d o i : 10.1007/s11910-020-1022-z. 14. gincota e, bufteac, andersen, larisa,jahnsen rb.early intervention and follow-up programs among children with cerebral palsy in moldova: potential impact on impairments?.bmc pediatrics. 2020; 20(29). 15. mahmood q, habibullah s, babur mn. potential effects of traditional massage on spasticity and gross motor function in children with spastic cerebral palsy: a randomized controlled trial. pak j med sci. 2019 sep-oct; 35(5):12101215. doi: 10.12669/pjms.35.5.478. pmid: 31488980; pmcid: pmc6717488. 16. verschuren o, darrah j, novak i, ketelaar m,wiart l. health enhancing physical activity in children with cerebral palsy: more of the same is not enough. phys ther. 2013; 94:1-9. 17. hielkema t, boxum ag, hamer eg, la bastide-van gemert s, dirks t, reinders-messelink ha, et al. learn2move 0-2 years, a randomized early intervention trial for infants at very high risk of cerebral palsy: family outcome and infant's functional outcome. disabil rehabil. 2020 dec; 42(26):3762-3770. doi: 10.1080/09638288.2019.1610509. peep for children with cerebral palsyjiimc 2022 vol. 17, no.2 106 conflict of interest authors declared no conflicts of interest. grant support and financial disclosure authors have declared no specific grant for this research from any funding agency in public, commercial or nonprofit sector. data sharing statment the data that support the findings of this study are available from the corresponding author upon request. this is an open access article distributed under the terms of the creative commons attributionnoncommercial 2.0 generic license. peep for children with cerebral palsyjiimc 2022 vol. 17, no.2 107 original�article abstract objective: to evaluate and compare the chondroprotective effects of hyaluronic acid and triamcinolone at radiographic level in rat model of osteoarthritis. study design: laboratory based randomized control trial. place and duration of study: this study was conducted in pharmacology department, army medical college, rawalpindi, from may to july 2019. materials and methods: osteoarthritis was induced by medial meniscus and anterior cruciate ligament resection in right knee joints of twenty-four rats. they were divided in three groups with eight rats in each. group i, ii and iii were treated with intra articular saline, hyaluronic acid, and triamcinolone once weekly for four weeks respectively. after one week, radiographs of corresponding knee joint of anesthetized rats were taken. results: collective comparison of radiographs of control, hyaluronic acid and triamcinolone groups exhibited a p value of 0.001 while intergroup comparison of group i and ii, group i and iii and group ii and iii depicted p value of 0.05, 0.01 and 0.01 respectively. conclusion: intra articular administration of hyaluronic acid and triamcinolone exhibited chondroprotective effects at radiological level in a rat model of osteoarthritis. on comparison of treatment groups, it was concluded that hyaluronic acid has better chondroprotective effects as compared to triamcinolone. key words: chondroprotective effects, hyaluronic acid, osteoarthritis, rat model, triamcinolone. world. approximately 10% males and 18% females aged over 60 years are suffering from oa all around the globe. basis of oa is degradation and chronic inflammation of the connective tissue of the joint, including the cartilage. due to long term damage to chondroblasts, chondrocytes and extra cellular matrix caused by oxidative stress, as well as inflammatory factors and mitochondrial dysfunction that cause dna damage are the leading factors of initiation and progression of oa. currently few options are available for treatment and prevention of oa and many drugs are in the phase of 2,3,4 investigation. treatment of oa in modern era drug is still limited to viscosupplement substances, nonsteroidal anti-inflammatory drugs (nsaids) and 5 corticosteroids. hyaluronic acid (ha), a macro molecule of repeating unit of d glucuronic acid and d acetyl glucosamine, is major constituent of synovial fluid which helps to facilitate lubrication and shock absorption in joints. it is used in oa for viscosupplementation. it is a naturally occurring substance present in synovial fluid. it restores the viscoelasticity of the synovial introduction osteoarthritis (oa) is the most common joint disease of old age, heterogeneous in character, affecting 1 commonly joints of the hand, knee, hip and spine. it is one of the leading causes of long term pain and disabilities. overall old age population is increasing with improvement in health service in modern era. so with increase in old age people, incidence and prevalence of oa is progressively increasing. it affects around 240 million people all around the radiographic evaluation and comparison of chondroprotective effects of hyaluronic acid and triamcinolone in a rat model of osteoarthritis 1 2 3 4 5 noaman ishaq , muhammad bilal shahid , samia yasin , nausheen ata , muhammad waqar aslam khan , 6 malik sikandar mehmood correspondence: dr. noaman ishaq e-mail: noamanishaq@yahoo.com 1 department of pharmacology bakhtawar amin medical and dental college, multan 2 department of surgery mayo hospital lahore 3 bhu chak 60 gb jaranwala, primary and secondary health department, punjab 4,6 department of pharmacology army medical college, rawalpindi 5 department of pharmacology cmh kharian medical college, kharian funding source: nil; conflict of interest: nil received: march 02, 2021; revised: august 16, 2021 accepted: august 20, 2021 chondroprotection by hyaluronic acid and triamcinolonejiimc 2021 vol. 16, no.3 165 fluid, may have anti-inflammatory and antinociceptive properties. it also stimulates denovo ha 6,7 synthesis. triamcinolone, an intermediate acting synthetic corticosteroid, is quite effective and is one of the most common drugs used to relieve symptoms in oa. it shows anti-inflammatory activity via inhibition of gene expression of prostaglandins and other inflammatory substances. so, it not only relieves pain but shows functional improvement and chondroprotective effects. it also influences macrophage activation and eventually decreases 8,9 osteophytosis and cartilage degeneration. definite cure of oa is not currently available. ha, triamcinolone, and many other drugs are investigational and are used to reduce symptoms and delay the progression of disease. aim of this s t u d y i s t o e v a l u a t e a n d c o m p a r e t h e chondroprotective effects of ha and triamcinolone at radiographic level in a rat model of oa. material and methods it was a laboratory based randomized control trial that was carried out in department of pharmacology and therapeutics, army medical college (amc), rawalpindi in collaboration with national institute of health (nih), islamabad. ethical approval certificate was endeavored from ethical review committee of “centre for research in experimental and applied medicine (cream)”, amc. tenure of rat's intervention was two months from may 2019 to july 2019. they were kept and nurtured in animal house of nih during the complete study period. preliminary twenty-four (24) adult male or non-pregnant female rats of sprague dawley breed, approximately 10 weeks old and weighing about 500 grams were selected through nonprobability convenient sampling. they were randomly assigned in three (03) groups with eight (08) rats in each group. group i, ii and iii were labelled as control, ha and triamcinolone groups respectively. rats were kept in standard environment with temperature ranged 25±5˚c, adequate humidity, and 12 hours day night cycle. free excess to clean drinking water and standard rodent diet ad libitum was ensured during the whole study period. surgical procedure was performed to induce oa in right knee joint of all rats. before surgery rats were anesthetized with intraperitoneal injection of 5% xylazine and 1% 10 ketamine. skin of the joint was shaved in a sterilized environment. then a para patellar incision was made on medial side for complete exposure of the joint. anterior cruciate ligament and medial meniscus were identified and transected. aseptic closure of wound with surgical stapler was done after the completion of the surgery. animals were allowed to 11 move freely in the cage for two weeks thereafter. then intra articular drugs were administered in the corresponding joint of the rats. rats of control, ha and triamcinolone groups were injected with 0.2 ml of normal saline, 0.2 ml ha, and 70 µl (1.4 mg/ml) triamcinolone respectively once weekly for 04 12,13,14 weeks. thereafter animals were anesthetized with intraperitoneal injection of xylazine 10% and ketamine 1%, transported to radiology department of a private institute of rawalpindi where their knee joints were radiographed. 500ma digital x ray machine china operated at 220 v with a 0.3 sec exposure time was used for radiography. kellgren and lawrence system was considered to grade the severity of the oa. according to kellgren and lawrence grading system grade 0 characterizes no radiographic features of oa, grade 1 represents doubtful joint space narrowing (jsn) and possible osteophyte lipping, grade 2 portrays definite osteophytes and possible jsn on anteroposterior weight-bearing radiograph, grade 3 depicts multiple osteophytes, definite jsn, sclerosis, possible bony deformity while grade 4 describes large osteophytes, marked jsn, severe sclerosis and definite bony 15,16 deformity. after radiographic grading with kellgren and lawrence system, animals were euthanized with toxic dosage of chloroform. obtained data was analyzed using ibm spss version 23. groups were analyzed through kruskul wallis test followed by post hoc tukey hsd test. the differences between two interpretations were considered statistically significant if the p value was equal to or less than 0.05 (p≤0.05) results two radiographs (25%) of group i (control group) depicted severe changes of oa and graded as grade 04, while four (50%) radiographs depicted moderate, and two (25%) radiographs depicted minimal changes of oa and they were graded as grade 03 and grade 02 respectively. figure 01 is an x-ray of a rat of control group that has characteristic features of sclerosis and possible joint deformity. grade of this chondroprotection by hyaluronic acid and triamcinolonejiimc 2021 vol. 16, no.3 166 x-ray is 03. most of the radiographs of group i feature osteophytes, jsn and bone deformity. radiographic changes of group ii (ha group) that received ia injection of ha described no radiographic changes of oa in two radiographs (25%), doubtful changes in four (50%) and minimal changes in two (25%) radiographs and they were graded as grade 0, grade 01, and grade 02 respectively. figure 02 is an xray of a rat of ha group that depicts the feature of minimal changes of oa. grade of this x-ray is 02. no or doubtful changes of oa were the feature of radiographs of this group. radiographic changes of group iii (triamcinolone group) that received ia injection of triamcinolone depicted as moderate radiographic changes of oa in four (50%), minimal changes in three (37.5%) and doubtful changes in one (12.5%) radiograph and were graded as grade 03, grade 02 and grade 01 respectively. figure 04 is an x-ray of rat of triamcinolone group that depicts moderate changes of oa. grade of this x-ray is 03. most of the radiographs showed features of osteophytes and jsn in this group. when kruskul wallis test was applied between all the three groups, p value was 0.001 that was statistically significant thus claiming the chondroprotective effects of hyaluronic acid and triamcinolone at radiographic levels. intergroup comparison of groups via post hoc tukey hsd test depicted p values as showed in table 01. comparison of ha group and triamcinolone group exhibited p value of 0.01 that confirmed ha has superior chondroprotective effects as compared to triamcinolone. fig 1: radiograph of a rat of group i (control group) fig 2: radiograph of a rat of group ii (hyaluronic acid group) fig 3: radiograph of a rat of group iii (triamcinolone group) chondroprotection by hyaluronic acid and triamcinolonejiimc 2021 vol. 16, no.3 167 discussion viscosupplement substances, nonsteroidal antiinflammatory drugs (nsaids) and corticosteroids are group of drugs that are investigational but frequently 17 used in the management of ha, a osteoarthritis. viscosupplements, is a natural component of synovial fluid that helps to facilitate lubrication and shock absorption in joints. it is one of the many investigational molecules in the treatment of oa. viscosupplementation with intra articular ha has positive outcome in pain alleviation and joint 18 function improvement in oa. triamcinolone, a synthetic corticosteroid is being used in the management of oa for decades. triamcinolone binds to intracellular glucocorticoid receptors and down regulates the expression of genes in prostaglandins synthesis and leukotrienes release. moreover, it also enhances lipocortin expression that modulates anti-inflammatory effects. these factors ultimately lessen the inflammation of 19,20 synovium and other articular structures in oa. this animal study is planned to evaluate and compare the chondroprotective effects of ha and triamcinolone. human admissible dosage of these drugs that was proficiently effective in rat model was selected by substantial search and literature review. oa was induced by medial meniscus and anterior cruciate ligament resection in the rats. after that they were randomly divided in control group, ha group and triamcinolone group with eight rats in each group. control group was intra articularly t re a t e d w i t h s a l i n e w a t e r w h i l e h a a n d triamcinolone groups were treated with intra articularly ha and triamcinolone respectively. later, when intervention protocol was completed, chondroprotective effects of these drugs were analyzed by radiographs. when radiographic grades of treatment group were statistically compared with control group, we found a significant p value of 0.001 that confirmed the chondroprotective effects of ha and triamcinolone. our research work is supported by 2016 research work of zhiwei zhang who found that ha reduces radiographic osteophytosis grading (p<0.05) as compared to saline treated rats' model of 21 osteoarthritis. likewise ai tong worked to evaluate the chondroprotective effects of cocktail of mesenchymal cells and ha in chemical induced rat model of oa. he assessed rats through magnetic resonance imaging and found significant (p <0.05) 22 chondroprotective effects of this mixture. their results also favor our outcome regarding ha. similarly, research work of yunus emre proved that ha exhibit chondroprotective effects at histological 23 level (p =0.04) in rat model of oa. in 2017 yashashri c. shetty did research work on chemical induced models of rats. his results confirmed that triamcinolone reduces the histopathological severity of disease (p<0.01) as 24 compared to disease control group. likewise research of jeffrey s. kroin declares that triamcinolone lessens allodynia as compared to mice of control group (p value <0.01). their work at tissue level expressed that triamcinolone has potent antiinflammatory effects (p value <0.01) via inhibiting 25 expression of il1β and tnfα. furthermore in vitro research of e. frank also confirmed that triamcinolone has some chondroprotective effects on damaged and swollen cartilage (p value <0.05) via i n h i b i t i n g s u l f a t e a s s i m i l a t i o n a n d glycosaminoglycan loss. results of these studies s t r e n g t h e n i n g o u r o u t c o m e r e g a r d i n g 2 6 chondroprotective effects of triamcinolone. consequently chondroprotective effects of ha and triamcinolone that is confirmed by current research and supported by previous research favor the use of these investigational drugs in patients of oa and table i: intergroup comparison of radiographs when post hoc tukey test hsd is applied graph 1: kellegren and lawrence grading of oa knee joints of rats of all groups chondroprotection by hyaluronic acid and triamcinolonejiimc 2021 vol. 16, no.3 168 provides a template for future studies. when radiographs of ha group was statistically compared with triamcinolone group, it was found that ha is more efficacious than triamcinolone. these results are according to the research work of yashashri c. shetty who found that ha has better chondroprotective effects than triamcinolone in 27 chemically induced murine model of oa (p <0.001). likewise, human study by soad a elsawy portrayed better chondroprotection offered by ha as 28 compared to triamcinolone (p=0.01). similarly, meta-analysis by egemen ayhan and colleagues also verified that ha has superior chondroprotective 29 efficacy as compared to triamcinolone. acknowledgement we are highly obliged to dr. hussain ali, head of research animal facility, national institute of health (nih), islamabad for his supervision regarding osteoarthritis induction and intra articular drug administration in rats. we also owe special thanks to pharmacology department, army medical college, rawalpindi, for providing us opportunity to carry out this research work. conclusion intra-articular administration of 0.2 ml (10mg/ml) hyaluronic acid and 70 µl (1.4 mg/ml) triamcinolone once weekly for 04 successive weeks reduced severity of osteoarthritis in rat model at radiographic level. upon comparison of hyaluronic acid and triamcinolone, it was concluded that former has better chondroprotective effects as compared to triamcinolone in rat model of osteoarthritis. references 1. reginster jy, arden nk, haugen ik, rannou f, cavalier e, bruyère o, et al. guidelines for the conduct of pharmacological clinical trials in hand osteoarthritis: consensus of a working group of the european society on clinical and economic aspects of osteoporosis, osteoarthritis and musculoskeletal diseases (esceo). sem arth rheum. 2018; 48(1):1-8. 2. bertalan z, ljuhar r, norman b, ljuhar d, fahrleitnerpammer a, dimai hp, et al. combining fractal-and entropybased bone texture analysis for the prediction of osteoarthritis: data from 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intra-articular corticosteroids. egy rheumatol rehab. 2017; 44(4):143-6. 29. ayhan e, kesmezacar h, akgun i. intraarticular injections (corticosteroid, hyaluronic acid, platelet rich plasma) for the knee osteoarthritis. world j orthop. 2014; 5(3):351-61. chondroprotection by hyaluronic acid and triamcinolonejiimc 2021 vol. 16, no.3 170 original�article abstract objectives: to determine the knowledge and attitude of healthcare workers about covid-19 pandemic to predict the confidence level to face the pandemic. study design: cross sectional study. st th place and duration of study: the study was conducted from 1 march 2020 to 30 march 2020 in medical teaching institute, qazi hussain ahmed medical complex nowshera, and an affiliated teaching hospital of nowshera medical college. material and methods: a total of 158 participants were selected via convenient sampling, irrespective of age and gender. a pre-validated questionnaire was administered to assess the knowledge and attitude of the respondents about covid-19 pandemic. relevant information's were collected and data was entered in spss version 25 for descriptive and regression analysis to assess the knowledge and attitude of healthcare providers towards covid-19. results: eighty one (51.3%) were males and 77(48.7%) females. the age was from 20 to 50 years. the distribution on basis of education was; 57(36.1%) medical students, 33(20.9%) general practitioners, 29 (18.6%) bachelor degree holders and 35(22.2%) with post graduate qualification in medicine. we observed a significant difference in male gender (vs female gender) regarding; knowledge of outbreak (p=0.002,or: 7.2), biology of 2019-ncov(p=0.07,or: 3.37), worries about the shortage of food in lock down situation(p=0.005,or: 4.1) and confidence level (p=0.07,or: 4.2). a significant difference was observed in population groups based on education levels regarding; treatment approach (p=0.001), denial of biological war (p=0.001) and government role in pandemic in provision of health care (p=0.001). a significant difference in opinion was noted in different age group regarding; food shortage in lockdown (p=0.005, or: 4.1) and level of confidence (p=0.07, or: 4.2). conclusion: healthcare workers have sufficient knowledge about covid-19 pandemic, its prevention, precautionary measures during the rapid rise period of outbreak. the approach towards treatment options and denial of misconception like biological war, is more positive in educated group having medical qualification. key words: covid-19, knowledge and attitude, pandemic, regression analysis. world experienced outbreak of sever acute respiratory distress syndrome (sars) and h1n1 (homophiles influenza) in 2009, middle east respiratory syndrome (mers) in saudi arabia in 1 2012 and corona virus disease (covid) in 2019. the outbreak in 2019 was totally different with presentation of pneumonia of unknown cause, later on the chinese centre for disease control and prevention and local cdc attributed it to a novel virus belonging to corona family and was termed as 20192 ncov. corona virus disease termed as covid-19 is an emerging highly contagious respiratory disease that is caused by novel corona virus. it was first reported from wuhan china in december 2019. its main clinical symptoms are fever, dry cough, fatigue, 3 myalgia and dyspnea. case fatality rate of 2.3% has introduction according to the world health organization, the viral diseases continue to emerge and are representing serious health issues in time and future. in 2002-03 knowledge and attitude of healthcare workers to predict the confidence level to combat covid-19 2 3 4 hamzullah khan, faridullah shah, shehzadi neelum, muhammad zakir 1 correspondence: dr. hamzullah khan associate professor department of hematology nowshera medical college, nowshera e-mail: hamzakmc@gmail.com 1 3 department of hematology / gynecology and obstetrics nowshera medical college, nowshera 2 department of pediatric medicine postgraduate medical institute, lady reading hospital, peshawar 4 department of medical gases engineering qazi hussain ahmed medical complex, nowshera funding source: nil; conflict of interest: nil received: april 21, 2020; revised: november 20, 2020 accepted: november 22, 2020 confidence level of healthcare workers to combat covid-19jiimc 2020 vol. 15, no.4 212 been reported from china that is lower than sars 4 (9.5%) , mers (34.4%) and h7n9 (39%). in pakistan the literature so for covering the prevalence and incidence is deficient, however the so far reported data from government sources declares 4000 confirmed cases with 54 deaths. punjab is the province with the highest number of corona cases 5 reaching 2000. people adherence to preventive and precautionary measures is essential, which largely depends on the knowledge, attitude and practice of people toward covid-19 in accordance with kap theory. italy, the second most affected country, with 888 cases of sars-cov infection with history of travel to the epidemic area were initially reported in lombardia and veneto regions. they attributed these infections with poor compliance of the people towards precautionary measures during the early 6 stages of current epidemic in the country. the levels of understanding and the importance of isolation and social distancing are the key to contain this virus. that demands for the execution of a survey in our population to determine the preparedness of our population for the pandemic that has almost hit our country. present study was therefore designed as to assess the knowledge and attitude of the regarding the pandemic to predict the confidence level to face the pandemic. material and methods a quantitative cross-sectional research design was utilized in march, 2020. this study was conducted in medical teaching institute, qazi hussain ahmed medical complex nowshera, an affiliated teaching hospital of nowshera medical college. a sample size 7 of 158 was calculated through raosoft an online sample size calculator, with confidence interval of 95%. ethical approval was obtained from the institutional ethical review board of nowshera medical college via notification no77/nmc/irb th dated 6 feb 2020, before the execution of the survey. prior informed consent was obtained from all the respondents and they were assured of confidentiality. the convenient sampling techniques was used for the present study. all the respondents irrespective of age and gender with minimum qualification of bachelor degree. respondents with qualification less than bachelor degree were th excluded from the study with an exception for 4 year medical students of nowshera medical college that were included in the study. a pre-validated questionnaire comprising 13 items, were administered. a total of 158 of the respondents were assessed for their knowledge and attitude regarding covid-19. the questionnaire had three parts. there were pre-requisite demographic information of the respondents regarding their name, age, email, qualification and nature of employment. part 1. information about the knowledge of the respondents about covid-19 biology, transmission, precautions, treatment options and preventive measures. part 2. information about the responders' contacts with covid-19 infected patients, testing method and place, treatment, isolation and quarantine and other related issues. part 3. information about the lockdown, necessities for lockdown, worries about the situation and handling is food shortage and health issues and confidence level in this situation. the questionnaire was distributed though email and in hard copies and the responders were given option to submit it via email or by hand. data was entered in spss version 25 for descriptive analysis and correlation analysis. there were two types of categorical variables in the study, one ordinal variable like age and education level of the respondents. second were nominal variables like gender and opinion of the respondents (yes/no) for assessing their knowledge and attitude. frequency and percentage were calculated for categorical variables. binary logistic regression analysis was used to predict the relationship of knowledge and attitude of the respondents with different outcomes of the pandemic wave and further to predict the level of satisfaction based on their knowledge and attitude to combat covid-19. results a total of 158 respondents were included in the study. the categorization based on age, gender and qualification is shown in table i. a significant difference was noted among gender groups using binary logistic regression analysis for different variables to predict the confidence level based on their knowledge and attitude as mentioned in table ii. jiimc 2020 vol. 15, no.4 213 confidence level of healthcare workers to combat covid-19 the male gender reported to be more confident with their religious believes, precautions and level of awareness and cleanliness would help them to pass thorough this crucial time successfully as compared to their counterparts(p=0.07,or: 4.2) (table ii). it was found that difference in age groups were significantly associated with difference in knowledge about 2019ncov biology (p=0.002, or: 7.3) and in treatment approaches (p=0.017). likewise the level of confidence in present wartime was more in elderly age group as compared to the youngsters (p=0.008). (table iii). moreover a significant difference in treatment approach was noted in different groups based on education (p=0.001). based on strategic and geopolitical conflicts, sometimes it is correlated that covid-19 is not a disease rather a biological war that was denied by the group with postgraduate qualification in medicine (p=0.001, or: 23). the odds ratio of 23 documents a strong denial of covid19 being a biological war. discussion knowledge is a key to success, the more you know about a disease the more easily it can be managed to reduce morbidity and mortality. kap strategy is an important tool to assess the preparedness level and to predict the confidence level of the community to combat covid-19. in present study an acceptable amount of knowledge about the outbreak was noted in different gender groups (p=0.002, or: 7.2. the male population dominated in knowledge about the biology of 2019ncov (p=0.07, or: 3.37). female table i. demographic informa�on of the respondents table ii. regression analysis of gender group with different variables in assessing kap of the respondents towards covid-19 jiimc 2020 vol. 15, no.4 214 home? confidence level of healthcare workers to combat covid-19 population and respondents of younger age group were more worried about the food and health issues in lock down situation during the pandemic. in the same way the level of education significantly differed in term of treatment approaches and precautionary measure (p=0.001), denial of biological warfare (p=0.001) and in the opinion that government should provide food and health facility in lock down to the incumbents. china has successfully achieved desired results by their impared knowledge, attitude and 8 practices towards covid-19. zhong bl et alalso reported a significant difference in knowledge score regarding covid-19 of male vs female gender (or: 0.81, p<0.001) that matches our 9 findings. the china is expected to have won the battle due to their level of basic knowledge about the disease. they used kap strategy in the sars and covid-19 epidemic where about 90% of the residents believed that they know the disease, how to prevent and what precautionary measures need 10, 11. to be taken in our society male is earning live hood for family. high exposure risk of male population indirectly increases the chances of 12 infection with covid-19. similarly the younger the age the more is stigma/fear of food shortage and healthcare issues during the lockdown (p=0.005, or: 4.1). it has been observed that younger age people especially the students, are at a higher risk to sars-cov-2 infection because of their frequent exposure to crowded places for study 13 and other activities of their choice. so, the students have a strong fear of consequences of lockdown as compared to the elderly population. the confidence level of male population to fight the pandemic was more than female gender in present 9 study. zhong bl et al have also observed that the majority (90.8%) of the participants in their study were optimistic to get succeeded in winning the war against corona virus, that strongly correlates our findings. studies from china have reported that education level of clients increases the confidence 35 times more to win the battle against covid-19, (or: 3.13-5.04, p<0.001) that matches our findings 9,14 . studies from china have reported that there is no evidence of bio-warfare associated with covid-19 pandemic. it has been clarified in the research papers published, that the outbreak in the city of wuhan was a natural epidemic and not part of any warfare, that supports our findings regarding the 3,15 denial of biological war. the findings of our kap are similar in outcome and 9. statistics of the zhong bl et al saudi arabia also succeeded to the maximum to combat the pandemic and to safeguard their citizens and the pilgrim by ensuring public adherence to preventive measures that was influenced by their knowledge and attitude toward covid-19 which is closely in concordance 16 with our findings. in china the residents' attitudes and practices towards covid-19 proved fruitful in table iii. regression analysis of age categories with different variables in assessing kap of the respondents towards covid-19 jiimc 2020 vol. 15, no.4 215 confidence level of healthcare workers to combat covid-19 winning the battle against covid-19. but like our findings the attitude towards confidence of winning significantly differed across categories of gender, age 9 and education (p<0.05) that matches our findings. the limitation of this study was limited number of the respondents that make us cautious in generalizing these findings to the populations of the district as it was selected in one setting/hospital/ institution. future studies should focus on the subject matter with large population with representation of all sectors to have a better outcome to predict/suggest the findings for decision making by the higher authorities to prevent disastrous pandemic. it is further suggested that healthcare workers should understand the basics of 2 0 1 9 n c o v, i t s c l i n i c a l p r e s e n t a t i o n a n d precautionary measures to contain virus and to avoid its spread in general community. conclusion healthcare workers have sufficient knowledge about covid-19 pandemic, its prevention, precautionary measures during the early outbreak across the country. female gender is more worried about the shortage of food in case of lockdown. references 1. world health organization. 2019-ncov outbreak is an emergency of international concern. 2020. available at http://www.euro.who.int/en/health-topics/emergencies/ pages/news/news/2020/01/2019-ncov-outbreak-is-anemergency-of-international-concern (accessed feb 16, 2020). 2. hui dsc, zumla a. severe acute respiratory syndrome: historical, epidemiologic, and clinical features. infect dis clin north am. 2019; 33(4):869-89. 3. 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;395:507-13. 4. munster vj, koopmans m, van doremalen n, van riel d, de wit e. a novel coronavirus emerging in china key questions for impact assessment. n engl j med. 2020;382:692-4. 5. " c o r o n a v i r u s i n pa k i s t a n c o n f i r m e d c a s e s " . www.covid.gov.pk/. retrieved 6 april 2020. 6. porcheddu r, serra c, kelvin d, kelvin n, rubino s. similarity in case fatality rates (cfr) of covid-19/sars-cov-2 in italy and china. j infect dev ctries. 2020; 14(2):125-8. 7. raosoft® sample size calculator [internet]. seattle, wa, usa: raosoft inc.; 2004. [accessed 2019 jan 13]. available at: http://www. raosoft.com/samplesize.html. 8. zhonghua liu xing bing xue za zhi. the novel coronavirus pneumonia emergency response epidemiology team. the epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (covid-19) in china. chin j epidemiol. 2020;41:145-51. 9. zhong bl, luo w, li hm, zhang qq, liu xg, li wt et al. knowledge, attitudes, and practices towards covid-19 among chinese residents during the rapid rise period of the covid-19 outbreak: a quick online cross-sectional survey. int j biol sci 2020; 16(10):1745-52. 10. zhou x, xiu c, chu q. prevention and treatment knowledge and attitudes towards sars of urban residents in qingdao. prev med trib. 2004;10:407-8. 11. chen, s. cao, j. xin, and x. luo, “ten years after sars: where was the virus from?” journal of thoracic disease, 2013; 5(2): s163. 12. duell n, steinberg l, icenogle g, chein j, chaudhary n, di giunta l. et al. age patterns in risk taking across the world. j youth adolesc. 2018;47:1052-72. 13. pawlowski b, atwal r, dunbar r. sex differences in everyday risk-taking behavior in humans evolutionary psychology. 2008; 6: 29-42. 14. munster vj, koopmans m, van doremalen n, van riel d, de wit e. a novel coronavirus emerging in china key questions for impact assessment. n engl j med. 2020;382:692-4. 15. romanoff l. china's new coronavirus: an examination of the facts. global research, centre for research th globalization. 2020.retreived, 26 jan 2020, available at http://l-hora.org/?p12777&lang=en 16. al-hanawi mk, angawi k, alshareef n, qattan amn, helmy hz, abudawood y, et al. knowledge, attitude and practice toward covid-19 among the public in the kingdom of saudi arabia: a cross-sectional study. front public health. 2020; 27(8):217. jiimc 2020 vol. 15, no.4 216 confidence level of healthcare workers to combat covid-19 original�article abstract objective: to determine in-vitro antimicrobial susceptibility pattern of multidrug resistant (mdr) strains of gram-negative eskape pathogens using vitek 2 compact system. study design: descriptive cross sectional study. place and duration of study: the study was conducted at pakistan railway hospital (prh) rawalpindi in st st collaboration with armed forces institute of pathology (afip) rawalpindi from 1 september 2018 to 1 september 2019. material and methods: a total of 320 clinical specimens were collected. the samples included urine, blood, pus, wound, effusions, c.s.f and sputum. after processing the isolates by standard microbiological methods, the antibiotic susceptibility pattern was carried out using vitek 2 compact system. results: a total of 190 clinical isolates of gram-negative eskape pathogens isolated from 320 clinical specimens. among them 150 mdr gram negative eskape pathogens were detected. out of 190 gram-negative eskape pathogens, (30.5%) were members of the family enterobacteriaceae and (69.4%) were from non enterobacteriaceae. the commonest isolated organism was acinetobacter baumannii, 36% followed by pseudomonas aeruginosa, 33.7%, klebsiella pneumoniae, 26.3% and enterobacter spp. 4.2%. from all isolates 88% of klebsiella pneumoniae, 86.9% of acinetobacter baumannii and 73.4% of pseudomonas aeruginosa were found mdr. conclusion: rapid identification and susceptibility testing of gram-negative eskape pathogens by vitek-2 compact system helps in reducing total consumption of antibiotics. mdr was observed in majority of gramnegative eskape pathogens except for enterobacter spp. these pathogens revealed comparatively better susceptibility against minocycline, tigecycline, and colistin. key words: colistin, enterobacteriaceae, eskape pathogens, multidrug-resistance, vitek 2 compact system. a n d fo u r g ra m-n e gat i ve b a c i l l i ( k l e bs i e l l a p n e u m o n i a e , a c i n e t o b a c t e r b a u m a n n i i , 1 pseudomonas aeruginosa, and enterobacter spp). these superbugs are widely distributed and are 2 frequently resistant to antibiotics. they have the capability of 'escaping' the biocidal action of antibiotic and communally representing new paradigms 1 in transmission, pathogenesis, and resistance. today they are considered to be major threats and are responsible for two-thirds of all healthcareassociated infections (hcais) in both developed and 3 developing world. they lead to increase morbidity & mortality, due to severe and life-threatening infections, especially if the host is debilitated or immunosuppressed (e. g. aids, cancer and transplant patients, patients with autoimmune 4 diseases, old age, neonates). the world health organization selected anti-microbial resistance (amr) as the theme for world health day 2011. their slogan was “combat drug resistance – no action introduction in the last decade along with the problem of healthcare associated infections (hcais), the prevalence of multidrug-resistant (mdr) organisms in hospitals has been greatly increased. the most frequently isolated six mdr bacterial species around the world have been grouped under the acronym eskape in 2008 by infectious diseases society of america. it includes two gram-positive cocci (enterococcus faecium and staphylococcus aureus) antibacterial susceptibility pattern of gram-negative eskape pathogens isolated from hospitalized patients 3 4 5 6 shazia taj , shahina yasmin , rabia mubariz , tariq butt , abdul bari , uzma musarat 1 2 correspondence: dr. shazia taj demonstrator/lecturer department of pathology islamic international medical college riphah international university, islamabad e-mail: aneesramiz@gmail.com department of pathology islamic international medical college riphah international university, islamabad funding source: nil; conflict of interest: nil received: september 17, 2020; revised: november 02, 2020 accepted: november 03, 2020 susceptibility pattern of gram negative eskape pathogensjiimc 2020 vol. 15, no.4 231 4 today, no cure tomorrow.” eskape pathogens with built in abilities have a variety of mechanisms to find new ways to be resistant to multiple classes of current antibiotics. gram-negative eskape pathogens are particularly concerning because their multidrug-resistant phenotypes frequently present clinicians with few 5 therapeutic choices. the important mechanisms of antibiotic resistance are: chromosomally-encoded enzymes such as extended-spectrum betalactamase (esbls), cephalosporinases (ampc) and carbapenemase. in addition decreased permeability through porin channels loss due to mutations and 6 activation of multi-drug efflux pumps. acquisition of plasmids and mobile genetic elements carrying multiple resistance genes also contributes to the development of multidrug-resistant phenotypes. a recent study found 2,609,911 new patients with hcais annually in the european economic area and the european union. acinetobacter species and the klebsiella pneumoniae were extremely resistant to multiple anti-microbials. the lack of new anti-biotics 7 has mounted huge burden in european union. in southeast asian countries a systematic review and meta-analysis regarding hcais found an overall prevalence rate of 9.1%. the most common microorganisms being a. baumannii, p. aeruginosa, and 8 the klebsiella species. in order to keep regular monitoring of mdr at species level the changing trends in the susceptibility patterns of gram-negative eskape pathogens should be known. it is essential for detection or at least controlling the outbreaks, identifying the population most at risk, designing and evaluating intervention strategies. this study was therefore, planned to know the susceptibility pattern of all the gram negative eskape pathogens isolated at our set up. material and methods it was a descriptive cross-sectional study, conducted at prh rawalpindi in collaboration with afip rawalpindi, after getting formal approval from institutional ethical review committee. all the samples coming to microbiology labs for culture and sensitivity report were processed. gram negative eskape pathogens (klebsiella pneumoniae, acinetobacter baumannii, pseudomonas aeruginosa & enterobacter species) recovered from these clinical specimens were included in our study. duplicate samples were excluded from the study. a demographic proforma specially designed for this purpose was filled to avoid duplication of samples. three hundred and twenty samples from different sources like urine, blood, pus, wound, throat infection, nose infection, effusions, c.s.f and sputum were collected from hospitalized patients. the samples were inoculated on suitable culture media depending upon the type of specimen. cled agar was used for inoculation of urine specimens. blood agar and macconkey agar were taken for all other specimens. the culture plates were incubated aerobically at 37°c for 24 hours & re-incubated for next 24 hours if growth was not sufficient. after incubation, bacterial isolates were identified by performing gram staining and standard biochemical tests which included catalase test, oxidase test, and analytical profile index (api). sub-culture of mixed colonies for gnr was done on macconkey agar to obtain a pure culture. escherichia coli atcc 25922 was used for quality control. a total of 320 samples were collected from different clinical samples. culture positive samples (n=190) were included in the study. these isolates were stored in glycerol broth, as mics was runs in batches by using vitek-2 compact system (biomérieux). preserved specimens were thawed at room temperature then subculture on macconkey agar and incubated for 2448 hours at 37°c. antimicrobial susceptibility tests were performed with ast-n222 cards which contained the dehydrated form of the following antimicrobial agents. amikacin, ticarcillin, ticarcillinclavalanic acid, piperacillin, tazobactam-piperacillin , ceftazidime, ciprofloxacin, imipenem, levofloxacin, minocycline, tobramycin, trimethoprim-sulfamethoxazole, gentamicin, meropenem, & colistin. the susceptibility breakpoints were those recommended by clsi. data analysis was done by using spss 21. for qualitative variables (gender of patient, type of samples and organisms isolated), percentages and frequencies were calculated. descriptive numerical (continuous) variables of age (years) was calculated in terms of mean ± sd (standard deviation). results three hundred and twenty different samples obtained from hospitalized patient were processed. jiimc 2020 vol. 15, no.4 232 susceptibility pattern of gram negative eskape pathogens one hundred and ninety (59.3%) gram-negative eskape isolates were included in the study. the pathogens belonging to family enterobacteriaceae (klebsiella pneumoniae & enterobacter species) were 58(30.5%) and non enterobacteriaceae ( ac in eto b a c ter b a u m a n n ii & ps eu d o m o n a s aeruginosa) were 132(69.4%). acinetobacter baumannii 68(36%) was the commonest isolate, followed by pseudomonas aeruginosa 64(33.7%), klebsiella pneumoniae 50(26.3%) and enterobacter spp. 8(4.2%). they were mostly recovered from medical intensive care unit patients' specimens, followed by surgical intensive care unit, and pulmonology ward. isolates were mostly yielded from pus, followed by blood, and urine specimens. the distribution of gramnegative eskape pathogens recovered from different specimens is presented in table i. out of the total isolates, 54.7% were recovered from male patients and 45.3% from female patients. mean age of the patients was 47.19 years ± 19.91 sd. majority 44 (23%) of the subjects had ages between 40-49 years. among all 190 isolates, 150 were found to be mdr ( 8 8 % o f k l e bs i e l l a p n e u m o n i a e , 8 6 . 9 % o f a c i n e t o b a c t e r b a u m a n n i i a n d 7 3 . 4 % o f pseudomonas aeruginosa). there were only 8 isolates of enterobacter spp. which were found sensitive to most of antibiotics, we excluded them from final analysis. antibiotic sensitivity testing by vitek-2 compact system showed that the resistance frequency of acinetobacter baumannii against ticarcillin, ticarcillin-clavulanate and tazobactam-piperacillin was 96.6%. highest resistance was observed in case of ciprofloxacin (100%). colistin was again the most successful antibiotic. the resistance frequency of klebsiella pneumoniae against ticarcillin and piperacillin was 100% with a maximum mic of ≥128 μg/ml and cefipime and ceftazidime with an mic of ≥ 64 μg/ml. the resistance frequency of pseudomonas aeruginosa against ticarcillin and tazobactam-piperacillin was 95.7% with a maximum range of ≥ 128 μg/ml. colistin was effective against (62%) of the total isolates of pseudomonas aeruginosa tested. none of the isolates was 100% susceptible to all of the tested anti-microbials. furthermore, 25.4% (15/59) of a. baumannii and 27.2% (12/44) of k. pneumoniae isolates were found to be extensively drug resistant because they showed resistance to all antimicrobial agents evaluated. the antibacterial susceptibility pattern of mdr strains of non-enterobacteriaceae is displayed in table ii and antibacterial susceptibility pattern of mdr strains of k. pneumoniae is shown in table iii. table i: distribu�on of gram-nega�ve eskape pathogens recovered from different specimens table ii: an�bacterial suscep�bility pa�ern of mdr strains of non-enterobacteriaceae by vitek2 compact system r: resistance i: intermediate s: sensi�ve table iii: an�bacterial suscep�bility pa�ern of mdr strains of k. pneumoniae by vitek2 compact system r: resistance i: intermediate s: sensi�ve jiimc 2020 vol. 15, no.4 233 susceptibility pattern of gram negative eskape pathogens discussion it is worrisome to note the high rates of resistance of non enterobacteriaceae members of gram negative eskape pathogens i.e. acinetobacter baumannii and pseudomonas aeruginosa to the commonly used flouroquinolone (ciprofloxacin) in our study i.e. 77.9 % and 81.3% respectively, while klebsiella p n e u m o n i a e s h o w e d 5 8 % r e s i s t a n c e a n d enterobacter spp. 100% sensitivity to ciprofloxacin. in present study mdr acinetobacter baumannii, was the most common pathogen recovered from clinical specimens (36 %). similar findings have been reported in another study conducted in an intensive care unit of monterrey, mexico, in which acinetobacter baumannii, was also found to be the 2 most common isolate. multidrug resistant acinetobacter baumannii and klebsiella pneumoniae are now emerged as one of the very important healthcare-associated infections to control and treat. patients admitted in intensive care unit (icu) and those with central intravenous catheters and respiratory devices are the main 9 targets of these organism. mdr acinetobacter baumannii demonstrated high r a t e o f r e s i s t a n c e t o c i p r o f l o x a c i n 3 8 % piperacillin,78% & ceftazidime 45% in the previous 10 studies by bruno et al., and simgamsetty et al., which were contradictory to the results found in our study, that is resistance to ciprofloxacin was 96.4%, to ceftazidime 96.6% and to piperacillin 96.6%. viaggi et al., reported 96% klebsiella pneumoniae isolates resistant to meropenem (mic>16 mg/l) while (92%) were resistant to tigecycline (mic >1 mg/l), colistin (mic >2 mg/l), and gentamicin (mic 11 >2 mg/l). our result showed only 31.7% resistance of klebsiella pneumoniae to colistin (mic >16), 84.1% to gentamicin and 86.4% to meropenem having mic of >16. colistin is considered as one of the therapeutic option against isolates of acinetobacter baumannii 1 2 and klebsiella pneumoniae. pseudomonas aeruginosa mdr isolates in our study showed > 90% resistance to ticarcillin, meropenem, cefipime, ceftazidime and piperacillin, while 74.5% sensitivity to cotrimoxazole, but contradictory findings were 13 observed by shashwati et al., and ibrahim of thi14 qar university. they reported that majority of pseudomonas aeruginosa isolates were susceptible t o c e f e p i m e , c e f o p e r a z o n e s u l b a c t u m , meropenem, levofloxacin, & amikacin. a study conducted by ghazal et al., demonstrated 93.7% of pseudomonas aeruginosa resistant against ceftazidime, 72% against ciprofloxacin and 52% 15 against amikacin. it is comparable with our study which revealed almost similar susceptibility pattern. the study being laboratory based is the limitation of this research. no clinical outcome of antibiotic therapy was determined. a multicenter study should be carried out involving all main hospitals of the city to establish mdr pattern in gram-negative eskape pathogens. however, this study will help doctors in our locale while deciding antimicrobial options for treating infectious diseases. conclusion it is concluded that rapid identification and susceptibility testing of gram-negative eskape pathogens by vitek-2 compact system helps in earlier switches in antibiotic therapy, and reducing total consumption of antibiotics. moreover mdr , was observed in majority of gram-negative eskape pathogens except for enterobacter spp. in our setup. most of gram-negative eskape isolates were found to be susceptible against colistin, tigecycline and minocycline. these antibiotics could be the good therapeutic options for infections due to eskape pathogens. however, it is recommended that colistin has to be used cautiously due to more significant adverse effects like neurotoxicity and nephrotoxicity and should be kept for use for more resistant gram negative eskape pathogens. future prospects the anticipated regional variations of mdr, requires consistent checking of disease control processes and ordinary surveillance of antimicrobials susceptibility profile in our hospitals. it should be the joint effort of microbiologists and clinical practitioners in introducing current and suitable antimicrobials according to amr trend and locally designed antibiogram. references 1. boucher hw, talbot gh, bradley js, edwards je, gilbert d, rice lb, et al. bad bugs, no drugs: no eskape; an update from the infectious diseases society of america. clin infect dis. 2009; 48(1):1–12. 2. llaca-díaz jm, mendoza-olazarán s, camacho-ortiz a, flores s, garza-gonzález e. one-year surveillance of eskape jiimc 2020 vol. 15, no.4 234 susceptibility pattern of gram negative eskape pathogens pathogens in an intensive care unit of monterrey, mexico. chemotherapy 2013; 58(6): 475–81. 3. khaled dw, abdullah ba. antibiotic resistant infection of the bacterial group eskape. scientific j med res 2018; 2(8):166-71. 4. chaudhry d, tomar p. antimicrobial resistance: the next big pandemic. int j community med public health 2017; 4(8): 2632-6. 5. pogue jm, kaye ks, cohen da, marchaim d. appropriate antimicrobial therapy in the era of multidrug-esistant human pathogen 2015; 21(4): 302–12. 6. we i n ste i n r a , l o ga n l k . c a r b a p e n e m re s i sta nt enterobacteriaceae: an emerging problem in children. clin infect dis 2012; 55(6): 852–9. 7. haque m, sartelli m, mckimm j, abu bakar m. health careassociated infections-an overview. infection and drug resistance 2018; 11(1): 2321–33. 8. ling ml, apisarnthanarak a, madriaga g. the burden of healthcare-associated infections in southeast asia: a systematic literature review and meta-analysis. clin infect dis. 2015; 60(11):1690–9. 9. xia y, lu c, zhao j, han g, chen y, wang f, et al. a bronchofiberoscopy-associated outbreak of multidrugresistant acinetobacter baumannii in an intensive care unit in beijing, china. bmc infect dis 2012; 12: 335-45. 10. simgamsetty s, yarlagadda p, yenigalla b, myneni r. ease with vitek 2 systems, biomerieux in identification of nonlactose fermenting bacteria including their antibiotic drug susceptibility: our experience. int j res med sci 2016; 4(3): 813–7. 11. sbrana f, malacarne p, viaggi b, costanzo s, leonetti p, leonildi a, et al. carbapenem-sparing antibiotic regimens for infections caused by klebsiella pneumoniae carbapenemase-producing k. pneumoniae in intensive care unit. clin infect dis 2013; 56(5):697–700. 12. biswas s, brunel jm, dubus jc, reynaud-gaubert m, rolain jm. colistin: an update on the antibiotic of the 21st century. expert rev anti infect ther 2012; 10(8): 917–34. 13. shashwati n, kiran t, dhanvijay a. study of extended spectrum β-lactamase producing enterobacteriaceae and antibiotic coresistance in a tertiary care teaching hospital. j nat sci biol med 2014; 5(1): 30–5. 14. ibrahim hk. screening and sensitivity of non-lactose fermenting bacteria to antibiotics by vitek-2 compact system. university of thi-qar j science (utsci) 2019; 7(1): 79-83. 15. ghazal l, qureshi ah, iqbal n. antibiotic susceptibility pattern of gram negative bacilli isolated from different clinical specimens in a tertiary care hospital. jimdc 2018; 7(2): 112–17. jiimc 2020 vol. 15, no.4 235 susceptibility pattern of gram negative eskape pathogens original�article abstract objective: the objective of this study was to determine the effect of thoracic spine mobilization on heart rate, respiratory rate, blood pressure and blood oxygen saturation. study design: it was a quasi experiment study. place and duration of study: the study was conducted in the department of physical therapy and rehabilitation center, pakistan railway hospital rawalpindi. the duration of study was 04 months from july 01 to october 30, 2015. materials and methods: ninety six healthy adult individuals were selected for the study by convenient sampling technique. the inclusive criteria of healthy individuals aged 20‐60 years with normal vitals; blood pressure: 90/60 mmhg diastolic, 140/100 mmhg systolic, breathing: 12‐25 breaths per minute, pulse: 60 ‐ 120 beats per minute and temperature: 98.6 degrees fahrenheit. subjects with spinal injury or deformity were not included in the study. pre and post values of heart rate, respiratory rate, blood pressure and blood oxygen saturation after thoracic spine mobilization were obtained. the data were statistically analyzed by spss version 21. results: mean age of the study population was 27.9+4.7, male to female ratio was 1:1. majority of the study participants (45%) had normal bmi. thoracic spine mobilization caused significant change in oxygen saturation. the heart rate (hr), respiratory rate (rr), both systolic and diastolic blood pressure (bp) had no significant association with the age, gender or the bmi of study participants. however blood oxygen saturation showed a statistically significant association with above mentioned variables. conclusion: it is concluded that mobilization on thoracic spine (t1‐t4) causes a sudden elevation in heart rate, respiratory rate, blood pressure and no major change in blood oxygen saturation. key words: blood pressure, heart rate, manual therapy, respiratory rate, thoracic spine mobilization. rate, blood pressure, rate of respiration, body temperature, sweating, gastrointestinal motility and secretion, as well as other visceral activities that maintain homeostasis. the sympathetic system prepares the body for energy expenditure, emergency or stressful situations, i.e., fight or flight. sympathetic preganglionic neurons are shorter than 1 sympathetic postganglionic neurons. most organs receive innervations from sns and peripheral nervous system (pns), which usually have opposing actions. however some organs do not have a 2 response to parasympathetic stimulation. control of lung primary ventilation involve specific groups of 3 receptors. resistive load on breathing in a healthy subject can stimulate aortic baroreceptors and 4 susequently causes an impact on the ans. in a study carried on patients with chronic neck pain, respiratory functions of the subjects in terms of forced vital capacity (fvc), forced expiratory volume at one second (fev1), and peak expiratory flow (pef) were measured via cardio touch equipment after thoracic mobilization and self‐stretching exercises. introduction the mobilization of the spine specially thoracic spine not only activates the mechanoreceptor inside the capsule of face joint which regulate the intrinsic muscle control of the spine but also have some influence to activate the sympathetic nervous system(sns). as we know the sympathetic part of the autonomic nervous system (ans) regulate heart effects of thoracic spine mobilization on vitals and blood oxygen level in healthy individuals 1 2 3 tamjeed ghaffar , abdul ghafoor sajjad , akhtar rasul jiimc 2016 vol. 11, no.4 correspondence: dr. abdul ghafoor sajjad hod & assistant professor department of physical therapy and rehabilitation riphah college of rehabilitation sciences riphah international university, islamabad e‐mail: abdul.gahfoor@riphah.edu.pk 1 department of physical therapy and rehabilitation islam college of physical therapy, sialkot 2 department of physical therapy and rehabilitation riphah college of rehabilitation sciences riphah international university, islamabad 3 department of physical therapy and rehabilitation school of physical therapy sargodha medical college, sargodha funding source: nil; conflict of interest: nil received: apr 15, 2016; revised: june 07, 2016 accepted: aug 09, 2016 effects of thoracic spine mobilization on vitals 163 the results of the study indicated that thoracic mobilization is effective treatment strategy for 5 improving pulmonary functions. reduction in lung function may be due to thoracic spine motion and costochondral joint restriction might affect the functions of respiratory system. when hypomobility of the joint is identified, joint mobilization techniques are applied that may influence in improving lung function. physical therapeutic approaches for the thorax include thoracic mobilization, stretching of the respiratory muscles, and strengthening of the respiratory muscles. such respiratory rehabilitation reduces respiratory problems in patients with respiratory dysfunction. autonomic output to the heart may be influenced by high velocity and low amplitude 6 manipulations of the thoracic spine. physical therapy can promote effective health outcomes by minimizing the deleterious effects of pathological conditions, including the coronary artery disease, arterial hypertension (htn), diabetes mellitus, atherosclerosis, osteoporosis, alzheimer and 7 parkinson's disease. physiotherapists frequently apply spinal manipulative therapeutic techniques to relieve pain syndromes of musculoskeletal origin and to enhance the joint movement quality. in a study, grade iii mobilization technique in posterior‐anterior direction was centrally applied to the cervical spine; as a result both respiratory and cardiovascular values were affected. during the application of the technique there was a significant increase in respiratory rate, heart rate, systolic and diastolic blood pressure when it was compared with control 8 group. manual therapy intervention to the thoracic spine was able to modify heart rate variable in women with fibromyalgia. considering this we can justify that there is a correlation between autonomic dysfunction and symptom severity or quality of life of the patients. some studies have shown that spinal manipulation is able to modulate autonomic nervous 9 activity. yates et al examined the effect of chiropractic manipulation of t1–t5 spine segments in patients with arterial hypertension. he observed a reduction in systolic and diastolic blood pressure and anxiety level. brain budgell et al in 2006 used high‐ velocity and low‐amplitude manipulation of the thoracic spine which showed a different result in output of heart as compared to sham procedure 6 group. elderly people can improve and maintain their cardiopulmonary circulation and also increase their oxygen intake through continuous physical training. in a society where aging is becoming a longer process due to increased average life expectancy, research on interventions to improve respiratory function in the elderly should be actively 9 conducted. the anatomical relation of thoracic spine with the sympathetic nervous system is well defined and most of the studies showed the relationship of manual therapy effects on sns. in pakistan no such study has been conducted to find the relationship of thoracic spine mobilization and sns in healthy individuals or the patients having cardiac or other associated problem. from clinical perceptive it is advised that physical therapist should take special consideration of patients while applying thoracic mobilization. the result of this study will create awareness regarding the fruitful effects of thoracic mobilization on cardiovascular and pulmonary system. the purpose of this study is to determine the effect of thoracic mobilization on heart rate, respiratory rate, bp and blood oxygen saturation. materials and methods it was quasi experimental study done in the department of physical therapy and rehabilitation center, pakistan railway hospital rawalpindi. the duration of study was 04 months from july 01 to october 30, 2015. ninety six healthy individuals having age between 20 to 60 years with normal vitals, systolic bp 140/100 mm of hg, diastolic bp 90/60 mm of hg, breathing: 12 ‐ 25 breaths per minute, hr 60 ‐ 120 beats per minute and temperature 98.6 degrees fahrenheit were selected for this study. those who had abnormal vitals, any previous spinal injury or surgery, spinal deformities were excluded from the study. in order to determine the effect of thoracic mobilization on heart rate and respiratory rate, self‐ designed questionnaire was used and data was collected by the therapist himself. informed consent was taken from every subject prior to participation in study. only participants who were vitally stable were given kaltenborn grade 3 thoracic mobilizations. heart rate, respiratory rate and other readings were taken before thoracic mobilization. 5 set with 15 repetitions were given on thoracic spine (t1 to t4 jiimc 2016 vol. 11, no.4 effects of thoracic spine mobilization on vitals 164 level) with the gap of 10 to 15 seconds. after thoracic spine mobilization again heart rate, respiratory rate and other readings were measured again. the telemetry operon om12 apparatus was used for measuring pre and post readings. the telemetry operon om12 complete built‐in module design ensures stable and reliable performance, unique all‐ lead ecg on‐one‐screen display, which can facilitate the diagnosis and analysis of cardiac disease. the oxygen saturation was measured through digital pulse oxy meter. questionnaire consisted of two components, the first component comprised of 10 questions to assess the physical fitness of the subjects. the second component was used to measure the pre and post variables readings. the data was analyzed using spss 21 software. paired t test was applied to compare the pre and post mean difference and p‐values. as shown in the table ii the hr, rr, both systolic and diastolic bp have no significant association with age, gender or the bmi of study participants. however blood oxygen saturation shows a statistically significant association with above mentioned variables. fig 1: collec�ng ini�als and final readings through telemeter fig 2: thoracic spine mobiliza�on results the mean age of participant was 27.9+4.7, male to female ratio was 1:1 and majority of the subjects had normal bmi. (fig 3) as shown in table i, after thoracic spine mobilization the pre and post mean values of heart rate, respiratory rate, systolic and diastolic bp, and blood oxygen saturation shows a statistically significant difference. fig 3: bmi of the par�cipants table i: pre and post mean value of heart rate, respiratory rate, systolic blood pressure table ii: associa�on of heart rate, respiratory rate, systolic and diastolic blood pressure and blood oxygen satura�on with age, gender and bmi jiimc 2016 vol. 11, no.4 effects of thoracic spine mobilization on vitals 165 discussion the results of present study showed that thoracic spine mobilization resulted in sudden elevation of hr, rr, systoikc and diastolic bp and blood oxygen level in healthy individuals. the blood oxygen saturation showed significant relation with age, gender and bmi. it provides objective evidence that application of mobilization technique elicits change in sns. the previous studies show that spinal mobilization and manipulation causes marked effect on hr and rr. reis ms et al saw the effect of thoracic posteroanterior thoracic mobilization on heart rate variability; they also concluded that one session of maitland mobilization on thoracic spine decreases the hr from 81± 10 to 77 ± 9 and improves pain on nprs from 6 ± 1 to 4 ± 1. similarly, in this study, difference (8.1%) in heart rate was observed before and after posteroanterior mobilization i.e. an increase in heart rate was noticed after thoracic 10 mobilization. ward j et al (2013) observed the effect of upper thoracic spine manipulation on cardiovascular response; their study shows that cardiovascular physiologic response is not affected in the short term by anterior upper thoracic spine chiropractor mobilization/manipulative therapy in young normotensive individuals. contrary to this, the study d ep icted s h o rt term effect af ter th o racic 11 mobilization on cardiovascular system. yung e et al (2014) observed the blood pressure and heart rate response to anterior to posterior directed glide to spine in young pain free individuals. this study showed that the ap glide caused the statistically significant response that results in a minor drop in hr as compared to placebo group. in both groups, there was a small but statistically significant reduction in 12 systolic bp after thoracic mobilization. mc guiness j et al (1997) observed the influence of a cervical mobilization technique on respiratory and cardiovascular function results shows significant increase in respiratory rate, heart rate, systolic and 13 diastolic blood pressure. conclusion it is concluded that mobilization on thoracic spine t1‐t4 will cause a sudden elevation in hr, rr, bp and blood oxygen saturation. there is a significant relation of blood oxygen saturation with age, gender and bmi. references 1. gordan r, gwathmey jk, xie lh. autonomic and endocrine control of cardiovascular function. world j cardiol. 2015; 7: 204‐14. 2. kishi t. heart failure as an autonomic nervous system dysfunction. j cardiol. 2012; 59: 117‐22. 3. widdicombe jg, sterling gm. the autonomic nervous system and breathing. archives of internal medicine. 1970; 126: 311‐29. 4. van gestel aj, steier j. autonomic dysfunction in patients with chronic obstructive pulmonary disease (copd). jotd. 2010; 2: 215. 5. hwangbo pn, hwangbo g, park j, lee s. the effect of thoracic joint mobilization and self‐stretching exercise on pulmonary functions of patients with chronic neck pain. jpts. 2014; 26: 1783. 6. budgell b, polus b. the effects of thoracic manipulation on heart rate variability: a controlled crossover trial. journal of manipulative and physiological therapeutics 2006; 29: 603‐ 10. 7. zanesco a, antunes e. effects of exercise training on the cardiovascular system: pharmacological approaches. pharmacology & therapeutics. 2007; 114: 307‐17. 8. mcguiness j, vicenzino b, wright a. influence of a cervical mobilization technique on respiratory and cardiovascular function. manual therapy. 1997; 2: 216‐20. 9. kim cb, yang jm, choi jd. the effects of chest expansion resistance exercise on chest expansion and maximal respiratory pressure in elderly with inspiratory muscle weakness. journal of physical therapy science. 2015; 27: 1121. 10. reis ms, durigan jlq, arena r, rossi bro, mendes rg, borghi silva a. effects of posteroanterior thoracic mobilization on heart rate variability and pain in women with fibromyalgia. rehabilitation research and practice. 2014;2014. 11. ward j, coats j, tyer k, weigand s, williams g. immediate effects of anterior upper thoracic spine manipulation on cardiovascular response. journal of manipulative and physiological therapeutics. 2013; 36: 101‐10. 12. yung e, wong m, williams h, mache k. blood pressure and heart rate response to posteriorly directed pressure applied to the cervical spine in young, pain‐free individuals: a randomized, repeated‐measures, double blind, placebo‐ controlled study. journal of orthopaedic & sports physical therapy. 2014; 44: 622‐6. 13. mcguiness j, vicenzino b, wright a. influence of a cervical mobilization technique on respiratory and cardiovascular function. manual therapy. 1997; 2: 216‐20. jiimc 2016 vol. 11, no.4 effects of thoracic spine mobilization on vitals 166 page 25 page 26 page 27 page 28 original�article abstract objective: to study the ameliorative effect of ginger against histological changes induced by cadmium in testes of albino rats. study design: randomized control trial. place and duration of study: the research was conducted at animal house, national institute of health (nih), st islamabad. the research was carried out for one year of duration from 1 november 2017 to 28 november 2018. material and methods: forty-five male adult albino rats were included via simple random sampling technique. using balloting method, each subject was randomly allocated into one of the three groups. distilled water was orally given to rats of control group i. the rats of group ii were provided with cadmium chloride while group iii received cadmium as well as ginger in selected doses orally for 28 days. dissection was done after 28 days and testes were observed for histological changes. results: the use of ginger ameliorates the gross and microscopic changes induced by cadmium in testes of albino rats of group iii as compared to group ii rats, which received only cadmium. among microscopic qualitative parameters, infiltration, congestion and necrosis were markedly reduced by use of ginger in group iii rats. conclusion: the use of ginger improves the histological changes induced by cadmium in testes of albino rats. key words: cadmium chloride, ginger, rats, testis. 2 stress. however, the tissue damage caused by cadmium may be ameliorated by the use of certain herbal agents acting as antioxidants like ascorbic a c i d , z i n c , ga r l i c , t u r m e r i c , c i n n a m o n a n d 3 g i n g e r. g i n g e r h a s b e n e f i c i a l e f f e c t s o n cardiovascular system, reproductive system and 4 gastrointestinal system. the concentration of volatile oils present in ginger is 1% to 3%. the main constituents are sesquiterpenes, beta-bisabolene and zingiberene. zingiberol and zingiberenol are other; all play an active role as anti-oxidants, antimicrobials and anti-inflammatory when introduced in mammals. hence, ginger has been used in multiple clinical trials to check its efficacy as a protective 5 agent against harmful substances. cadmium is one of the important components used in rechargeable nickelcadmium batteries, aircraft industry and television picture tubes. hence, there's a certain degree of probable exposure to the 6 personnel working in one of these industries. besides acute and chronic kidney damage, cadmium causes carcinoma of lung, kidney and prostate. cadmium has acute and chronic effects on various organs of body including lungs, kidney, prostate and the ameliorative effect of ginger on cadmium induced histological changes in testes of albino rats 1 2 3 4 5 6 naseer ud din sheikh ,rehana rana , shabana ali , hira waqas cheema , huma beenish , arsalan manzoor mughal correspondence: dr. naseer ud din sheikh senior lecturer department of anatomy rawalpindi medical university, rawalpindi e-mail: naseerrmc@gmail.com 1,6 department of anatomy rawalpindi medical university, rawalpindi 2,3,4,5 department of anatomy islamic international medical college riphah international university, islamabad funding source: nil; conflict of interest: nil received: september05, 2019; revised: october 12, 2020 accepted: october 13, 2020 genitoprotective effect of gingerjiimc 2020 vol. 15, no.4 introduction testis is an important sexual organ which enables spermatogenesis and secretion of male sex hormones. this function is highly necessary for c o n t i n u i t y o f l i fe . a m o n g m a m m a l s , w h e n considering a rat, the structure of rat testis is comparable to humans and has been a source of 1 comparative study. its testis measures 1x2x1.5cm. environmental toxins affect the function of testis; cadmium is one of them. it acts as catalyst in the production of reactive oxygen species; decreasing protein bound sulfhydryl groups and glutathione, thus increasing lipid peroxidation and oxidative 250 7 bones. ginger has been proved to be an effective antioxidant for cadmium induced damage on organs 8 9 such as liver and kidenys. however, there is minimal evidence in literature, specifically the local research base, which proves the advantages of ginger against cadmium in the reproductive system. hence, the aim of this study was to assess the protective role of ginger against cadmium induced toxicity in testicular cells on a gross and microscopic level. material and methods the study was carried under supervision of animal house at national institute of health (nih), islamabad. the study was conducted from 1st november 2017 to 28th november 2018. a total of 45 male rats were procured by employing simple 10 random sampling technique with balloting method and were kept in a controlled standard living environment at the animal house of nih. the study design was randomized controlled trial. prior to the initiation of the study, the research was approved by et h i ca l re v i e w c o m m i tte e ( e rc ) o f i s l a m i c international medical college (iimc). eight weeks old healthy male albino rats of sprague dawley strain weighing 140-220 gm were selected for the study, while those with any congenital or pathological abnormalities were excluded. the rats were randomly allocated into 3 groups of 15 rats each and were kept in cages, in a controlled standard living environment in a well-ventilated room with cycles of 12 hour day and night, and temperature maintained between 20 to 26 °c. group i (control) rats received distilled water as drinking water for 28 days. group ii rats received orally a solution of cadmium (03mg/kg/day) as cadmium chloride for 28 days. group iii rats consumed orally a solution of cadmium (03mg/kg/day) as cadmium chloride along with ginger 500mg/kg/day for 28 days. all rats were euthanized and dissected after 28 days. testes were explored and taken out of scrotum. the tissues were fixed, embedded in paraffin blocks and stained with eosin and haematoxyline. the slides were examined in detail under 10x and 40x power of light microscope. gross features including color, appearance, texture and weight were noted. microscopic examination was performed to observe parameters including the presence of congestion of blood vessels in stroma, infiltration of inflammatory cells in stroma and change in epithelial height in seminiferous tubules in micrometers. data was entered and analyzed using statistical package for social sciences (spss) version 22. mean and standard error were calculated for the quantitative variables. categorical variables were represented by frequency and percentage. chi square test was applied for comparison of qualitative variables. data was tested for normality with kolmogorov-smirnov and shapiro-wilk tests. one way analysis of variance (anova) was applied for the mean comparison of quantitative variables between control group i and experimental groups ii and iii.post hoc tukey's test was applied for multiple comparisons of these three groups. the results were analyzed and considered significant with p value less than 0.05. results the color of testes ranged from pink, yellow and light pink in group i, ii and iii respectively. group i showed normal appearance while group ii and group iii s h owe d s h r u n ke n a n d swo l l e n a p p e a ra n c e s respectively. the texture of the testes was soft in case of group i while group ii and group iii were having hard textures. (table i) regarding weight of the testes, in group ii (mean=1.96, sem=0.074) it was reduced compared to group i (mean=2.43, sem=0.105) and again increased in group iii (mean=2.30, sem=0.087) which received ginger (p<0.001). table ii shows the group wise multiple comparisons. all blood vessels were normal and congestion (figure table i: color, appearance and texture of the three groups 1a) was absent in all rats of group i while testes of rats of group ii were congested. in group iii, 47% of rats showed congestion of blood vessels while 53% showed normal blood vessels. there was significant jiimc 2020 vol. 15, no.4 251 genitoprotective effect of ginger d i f fe r e n c e ( p < 0 . 0 0 1 ) b e t w e e n p r e s e n c e o f congestion of blood vessels in all groups (table iii). inflammatory cells were absent in all testes of rats of group i while present among all rats of group ii. in group iii, 53% of testes showed infiltration of inflammatory cells while 47% rat's testes showed no infiltration. results were significant in all groups. (p< 0.001) (figure 1).all the testes of group i showed mean epithelial height (58.500µm) of seminiferous tubules. in group ii the mean epithelial height of seminiferous tubules was 44.833 µm. in group iii the mean epithelial height of seminiferous tubule was 54.000µm. significant difference was found in mean epithelial height in all groups.(p<0.0001) (table iv) w h i l e m u l t i p l e g ro u p s c o m p a r i s o n s h o w e d significant difference among all groups. discussion 1 1 exposure to cadmium is inevitable and the subsequent deleterious effects on the testes are h i g h l y l i ke l y. b e i n g a n i m p o r ta nt o rga n fo r spermatogenesis, the testes also play an important role in production of male sexual hormones and 12 male growth and development. however, heavy metals such as arsenic, cadmium and nickel bring molecular changes in the structure of testicular cells which lead to decline in the functional ability of the 13 organ. however, as proven with the current study these effects can be reduced, if not prevented, by maintaining levels of herbs such as ginger. hence, testicular viability, potency and function can be preserved. other materials used in various studies have been proven to be potent in delaying testicular toxicity such as quercetin, grape seed extracts, zinc 14,16 and magnesium. ginger, on the other hand, has been proved to have protective role by antagonizing 17 reactive oxygen species. congestion of vessels was seen as an effect of cadmium in our study, it was 100% in group ii, but with the use of ginger it reduced down to 46.7%. in the study conducted by de souza, cadmium was given to three different groups at different doses of 0.1 and 1.2mg per kg for 8 weeks, they showed 1 8 co n ge st i o n i n b l o o d ve s s e l s . m a n ca d a l s o conducted a study in which cadmium chloride was given in doses of 1mg and 10mg for 45 and 90 days respectively and testis showed congestion in blood 19 vessels. in a study by el-sharkawya, when ginger extract was given, then congestion in blood vessels 20 was remarkably decreased in testes of rats. 21 22 the works of schlaepfer and mouro showed that seminiferous epithelium damage by cadmium r e s u l t s f r o m h y p o x i a d u e t o a l t e r a t i o n i n intratesticular blood flow. this effect leads to accumulation of inflammatory cells within the 23 testis. these findings were further validated with the current study in which group ii had the highest degree of inflammatory cells, but since group iii had reduced inflammatory cells, it proves the protective role of ginger in reducing the cadmium induced inflammatory response. the study can be further extended by investigating the dose dependent effects of cadmium. moreover, the effects of route of administration and duration of use can be studied as well. as immunological effects table ii: mul�ple comparison of weight (g) of tes�s among control and experimental groups of albino rats table iii: group wise distribu�on of conges�on of blood vessels and focal necrosis among control and experimental groups of albino rats table iv: group wise distribu�on of height of seminiferous epithelium among control and experimental groups of albino rat's p ≤0.001 jiimc 2020 vol. 15, no.4 252 genitoprotective effect of ginger of cadmium have been suggested at cellular level, so c y t o i m m u n o l o g i c a l a n a l y s i s m a y b e 23 included. furthermore, the changes at the level of genetic expression may be considered. this would give a deeper view on the mechanisms behind the protective effects of ginger and may be extended t o w a r d s o t h e r c h r o n i c a u t o i m m u n e a n d inflammatory diseases. conclusion cadmium exposure causes gross and histological changes in the testes of albino rats. the use of ginger significantly reduces the development of the changes; effectively providing complete protection to at least half of the exposed population. further larger scale and long-term trials are recommended to have an insight on exact mechanisms. references 1. hegazy aa, ahmad mm, aziz ja, abdalmotaleb na. postnatal changes in the structure of rat testis. cell res. 2019; 3(2):1-9. 2. marettová e, maretta m, legáth j. toxic effects of cadmium on testis of birds and mammals: a review. animal reproduction science. 2015; 155:1-10. 3. khafaga af, abd el-hack me, taha ae, elnesr ss, alagawany m. the potential modulatory role of herbal additives against cd toxicity in human, animal, and poultry: a review. environmental science and pollution research. 2019; 26(5):4588-604. 4. banihani sa. ginger and testosterone. biomolecules. 2018; 8(4):119. 5. jeena k, liju vb, kuttan r. antioxidant, anti-inflammatory and antinociceptive activities of essential oil from ginger. indian j physiolpharmacol. 2013; 57(1):51-62. 6. turner a. cadmium pigments in consumer products and their health risks. science of the total environment. 2019; 657:1409-18. 7. đukić-ćosić d, baralić k, javorac d, djordjevic ab, bulat z. an overview of molecular mechanisms in cadmium toxicity. current opinion in toxicology. 2020; 19:56-62. 8. baiomy aa, mansour aa. genetic and histopathological responses to cadmium toxicity in rabbit's kidney and liver: protection by ginger (zingiberofficinale). biological trace element research. 2016; 170(2):320-9. 9. gabr sa, alghadir ah, ghoniem ga. biological activities of ginger against cadmium-induced renal toxicity. saudi journal of biological sciences. 2019; 26(2):382-9. 10. l a m m e r s w j , b a b b i e e . s a m p l i n g te c h n i q u e s . fundamentals of behavioral research textbook. 2005:1-23. 11. watanabe y, nogawa k, nishijo m, sakurai m, ishizaki m, morikawa y, et al. relationship between cancer mortality and environmental cadmium exposure in the general japanese population in cadmium non-polluted areas. international journal of hygiene and environmental health. 2020 jan 1; 223(1):65-70. 12. chen q, deng t, han d. testicular immune regulation and spermatogenesis. semin cell dev biol. 2016; 59:157-65. 13. rinaldi m, micali a, marini h, adamo eb, puzzolo d, pisani a, et al. cadmium, organ toxicity and therapeutic approaches: a review on brain, kidney and testis damage. current medicinal chemistry. 2017; 24(35):3879-93. 14. nna vu, ujah ga, mohamed m, etim kb, igba bo, augustine er, et al. cadmium chloride–induced testicular toxicity in male wistar rats; prophylactic effect of quercetin, and assessment of testicular recovery following cadmium chloride withdrawal. biomedicine & pharmacotherapy. 2017; 94:109-23. 15. alkhedaide a, alshehri zs, sabry a, abdel-ghaffar t, soliman mm, attia h. protective effect of grape seed extract a ga i n st ca d m i u m i n d u c e d te st i c u l a r d ysf u n c t i o n . molecular medicine reports. 2016; 13(4):3101-9. 16. li r, luo x, li l, peng q, yang y, zhao l, et al. the protective effects of melatonin against oxidative stress and inflammation induced by acute cadmium exposure in mice testis. biological trace element research. 2016; 170(1):15264. 17. morvaridzadeh m, fazelian s, agah s, khazdouz m, rahimlou m, agh f, et al. effect of ginger (zingiberofficinale) on inflammatory markers: a systematic review and metaanalysis of randomized controlled trials. cytokine. 2020; 135:155-224. 18. de souza predes f, diamante ma, dolder h. testis response to low doses of cadmium in wistar rats. international journal of experimental pathology. 2010; 91(2):125-31. 19. manca d, ricard ac, trottier b, chevalier g. studies on lipid peroxidation in rat tissues following administration of low and moderate doses of cadmium chloride. toxicology. 1991; 67(3):303-23. 20. el-sharkawya ee, el-nisr bn. lactational cadmium exposure induced alterations in the hematological indices and oxidative status in brain, liver and testes of rat pups. scientific journal of veterinary advances. 2012; 1(3):70-81. 21. schlaepferww.sequential study of endothelial changes in acute cadmium intoxication.laboratory investigation; a journal of technical methods and pathology. 1971; 25(6):556-64. 22. mouro vg, siman va, da silva j, dias fc, damasceno em, do carmo cupertino m, et al. cadmium-induced testicular toxicity in mice: subacute and subchronic route-dependent effects. biological trace element research. 2020; 193(2):466-82. 23. deng b, pakhomov ov, bozhok ga. long-term effects of acute cadmium exposure on testis immune privilege. regulmechbiosyst. 2020; 11(2):180-5. jiimc 2020 vol. 15, no.4 253 genitoprotective effect of ginger 185 original�article abstract objective: to explore the perceptions of local communities of rawalpindi and islamabad about the characteristics of a good physician and their expectations regarding attributes of a good physician. study design: exploratory sequential a mixed method research. place and duration of study: different localities of rawalpindi and islamabad from september 2017 to february 2018. materials and methods: data for this research was collected using three focus group discussions followed by a cross-sectional survey. for quantitative data, a pre-tested structured questionnaire was administered to 804 respondents between the age group of 25-65 years, selected through non-probability convenience sampling technique. all the data was gathered after taking informed consent and confidentiality was ensured. a qualitative content analysis was carried out using inductive approach and the quantitative data was analyzed using spss version 22. results: out of the 804 study participants, 57% were females and 43% were males with a mean age of 35.1 +11.8 years. amongst highlighted qualities, 77.1%, ranked honest and trustworthy as a first priority, 73.4%, marked second priority to being a good communicator, third and fourth priorities were kind and respectful (82.5%) and good care provider (69.4%). there was no difference in prioritizing the characteristics among both genders and this finding was statistically significant (p=0.004), however education had a very significant role in prioritizing these characteristics (p=0.000) i.e., for uneducated participants priority was respect while for educated community honesty appeared as a priority. conclusion: the current study concluded that honesty, trust, politeness, respect and care are the main characteristics of a good doctor desired by the community. these non-cognitive attributes can be used as the basis for curriculum development in medical education. the evaluation of such instructional programs should be the focus of future research. key words: caseattributes, characteristics, community, good physician, perceptions. the characteristics of a good doctor has been shifted over to the patients with highlighting the shared decision-making concept between doctor and the 2 patient. therefore now it is the patient who c h a ra c te r i ze s t h e b a s i s o f p a t i e n t d o c t o r 3 relationship, rather than doctors themselves. most of the patients are well aware of the qualities that 4 they desire their doctors to possess. the patients and their relatives associate goodness with integrity, safety, honesty, kindness, care and competency. all of these characteristics are important since they are aware of that the decisions of their doctors can affect the outcome of their illness, even the declaration of life and death, or between having the benefit of 5 speedy recovery and suffering serious disability. a good doctor is the combination of all the traits, being integrated, composed, understanding and caring. nevertheless also must be knowledgeable, skilled, and prepared enough to deliver best for introduction patient centered care has become the mainstay of patient-doctor relationship that caters for all the aspects of patient care including physical, 1 psychological, emotional, and social issues. hence, t h e q u a l i t y o f p at i e nt d o c to r re l at i o n s h i p determines the accomplishment of treatment and 1 outcome as a whole. the responsibility to appreciate perceptions of community about the characteristics of a good physician: a mixed method research 1 2 3 4 5 6 farah rashid , usman zafar , khadija muhammad , iffat atif , maham mumtaz , aleena saeed correspondence: dr. usman zafar assistant professor department of medicine islamabad medical and dental college, islamabad e-mail: usman.zafar@imdcollege.edu.pk 1 2 department of community medicine/medicine islamabad medical and dental college, islamabad 3,5,6 4 department of ophthalmology/ community medicine yusra medical and dental college, islamabad funding source: nil; conflict of interest: nil received: july 15, 2021; revised: september 03, 2021 accepted: september 06, 2021 characteristics of a good doctorjiimc 2021 vol. 16, no.3 6 saving lives of his patients. good physicians must put an effort to improve the quality of patients' lives by continuous and enduring hard work with a complete range of resources that will contribute to 7 their patients' healing. there has been a lot of effort done to redefine the relationship between the patients and their 8 physicians. the medical professionalism has been defined to be based on a set of values, attributes and relationships that can serve as a yardstick by which patients can measure their expectations and make the decisions regarding their treatment by shared 9 understanding. the investigations of patient-doctor relationship were focused on different aspects of patient interaction including communication and 6-9 honesty between doctors there is evidence that suggests the importance of the participation of patients in the decision making throughout their 10 treatment process. for doctors to effectively take on these challenges and demands of their professional lives, they must have a certain degree of 11 character strength. this research has been carried out to explore the perceptions of community about the characteristics of a good physician. it highlights a very crucial issue of how these strengths could be endorsed in practice. the research is also in accordance with the pmdc seven-star competencies for a good doctor. the main objective of this research is to explore the perception of the local community about the qualities they want to observe in their doctors. materials and methods the research approach used in current study was exploratory sequential, a mixed method research. the survey was conducted in twin cities of rawalpindi and islamabad from september 2017 to february 2018. sample size was calculated by who sample size calculator, keeping confidence interval at 95%, and knowledge of characteristics of a good physician to be 50%, sample size turned out 385. however, total of 804 participants belonging to different socioeconomic strata and educational status were selected through non-probability convenience sampling technique from different localities of rawalpindi and islamabad. ethical approval was taken from ethical review committee of yusra medical and dental college. informed consent was taken from the respondents explaining them the purpose of this study and confidentiality of data was ensured. the qualitative data was collected through focus group discussions (fgds) followed by a structured questionnaire for quantitative data. initially three fgds were conducted. these fgds were held in local community centers. participants were invited without any monetary incentive. informed consent was taken by the research team with surety of data confidentiality. there were 10-12 participants in each fgd, for male and female participants separate fgds were held. majority of the participants were married, minimally educated and were in the age group of 25-45 years. one separate fgd was held for youngsters between the age group of 18-24, all students and unmarried. all fgds were audio-taped with the permission of each group. field notes were also taken during the sessions. transcripts were developed in english. information gathered through notes was cross-checked before and during the data processing by the research team members for quality assurance and validation. a qualitative content analysis was carried out using inductive approach in which identified themes emerge from a group of categories with common meanings, followed by coding. themes and sub-themes were identified through consensus of the research team. f o r c r o s s s e c t i o n a l s u r v e y, a s t r u c t u r e d questionnaire was developed and pilot testing was done. the main themes that emerged in fgds were used to design the questionnaire. the rationale for this approach lies in first exploring a topic before deciding what variables (qualities of a good physician) need to be measured and the community was asked to rank those (themes) qualities according to their priorities. cronbach's alpha was 0.87. the response rate was 95%. data on demographics, source of income, housing, literacy status was collected from each participant. along with these, questions related to community's preferred choices for the characteristics of a good physician were asked. spss version 22 was used to analyze the data. frequency distributions were calculated. for inferential statistics, chi square test was performed, with a p-value of less than 0.05 being significant. results for qualitative data main themes identified through various focus group discussions about the jiimc 2021 vol. 16, no.3 186 characteristics of a good doctor characteristics of a good physician were honest, trustworthy, good communicator, respectful and good care provider. table i shows details of themes and sub-themes (n=590) respect and being kind stood third, furthermore 81.2% (n=653) of participants expressed good care-provider as fourth quality necessary for a good physician. the details of these findings are depicted in figure i.table i: themes and sub-themes emerged from fgds about characteristics of a good physician in a cross-sectional survey, out of 804 participants, 57% (462) were females and 43% (342) were males with a mean age of 35.1 +11.8 years, 67% (541) of the individuals belonged to lower and middle socioeconomic status and 33% (263) were from high social class. the first and foremost characteristic of a good physician reported by 80% (n=644) participants was honesty and trust, 77% (n=620) ranked good communication skills as second quality. with 73.4% fig 1: characterictics of a good physiscian priority wise on application of chi-square, no difference in prioritizing the characteristics among both genders were found and this finding was statistically significant (p=0.004), however education had very significant role in prioritizing these characteristics (p=0.001) i.e., for uneducated participants first priority was respect while for educated community honesty appeared as first priority(table ii). table ii: comparison of characteristics of a good physician (first priority) various demographic variables * significant p-value discussion patient's personal experiences and experiences of family and friends structure the perspectives about jiimc 2021 vol. 16, no.3 characteristics of a good doctor 187 2 what to look for in a physician, opinion regarding the good doctor is considerably different from other 3, 4 professionals. a good doctor can be defined as good only when he or she has certain combinations of 5 attributes. even though it is difficult to find numerous qualities in a single person, yet the 6 medical profession demands for such combinations. the current research is novel in a sense that it focused on patients' perspective of qualities in a good physician and it holds a very significant place because limited work has been done in pakistan. the doctors do not know exactly what their patients expect from them, they only try and do what they 7 think is the best. according to the findings of this study, with 80% vote honesty and trust turned out to be the most wanted quality the public wants in a 8,9 doctor and endorsed by various other studies. patients must be able to trust doctors with their lives and health,' according to the gmc's good medical practice – the main ethical advice document for doctors operating in the uk. it goes on to say that doctors “should be honest and open and act with integrity' and 'never abuse your patients' trust in you 10 or the public's trust in the profession” everyone deserves to be treated with respect and politeness. 73.4% of the local community wants their doctor to be respectful and kind. when a patient is in pain, and the first thing a doctor can do to ease his pain is to talk to him politely. subsequently he feels at ease to share his problem in detail without any 1 1 , 1 2 hesitation. patients should have a good understanding of their disease so that if they know the severity of the condition they would look after themselves with better care and visit the doctor 12 again as scheduled to improve their health. our findings replicate the findings of research conducted in university of birmingham. the research concluded that the top-quality patients wanted in a doctor were honesty and on third number highest voted quality 13 was politeness. another quality as highlighted by 77% of the respondents was good communication skills. patients are looking for doctors that are good communicators and have up-to-date clinical 14 knowledge and skills. they also expect practitioners to be concerned and sympathetic, to include them in the decision-making process, including an explanation of their symptoms, treatment, or investigation, to devote appropriate time and energy, and offer them guidance on health 15 promotion and self-care. out of total 81% of the participants voted good care th provider as a 4 priority with involvement of the patient in their treatment. the conventional model of decision-making claimed that only the doctor was adequately educated and experienced to decide what should be done, and that patient engagement should be limited to granting or refusing treatment consent. however, this paternalistic approach 16 appears to be outmoded presently many patients . now want to be informed about their disease and treatment alternatives, as well as to be actively 17,18 involved in the decision-making process. there is mounting evidence that people who actively participate in treatment decisions and healthcare 18 management have better health outcomes. what's particularly intriguing about this study is that many of the characteristics, attributes, or virtues discovered were non-cognitive rather than cognitive skills, which are often overlooked in medical 18,19 education programs. if a number of non-cognitive activities are actually vital for a successful doctor, as this study implies, they should be given more 19 attention in medical education. however, there are fundamental issues regarding whether these virtues can be taught, and even if they can be, whether they can survive in today's culture, where self-interest, 19,20 not altruism, is the guiding principle. it's been debated whether virtue can be taught. however, aristotle stated that “we learn by doing, and that the greatest way to do so is to emulate a 20 virtuous person”. to meet the community's ambitions, we need virtuous physicians as teachers in medicine. these values and attitudes must be inculcated into the personalities of future 21 physicians. conclusion the current study concluded that honesty, politeness, respect and good care, are the main character strengths and attributes that the patients want to see in their physician. it is important to address that how these attributes could be inculcated in medical curriculum and endorsed in practice. the evaluation of such instructional programs should be the focus of future research. jiimc 2021 vol. 16, no.3 188 characteristics of a good doctor references 1. bennett d, solomon y, bergin c, horgan m, dornan t. possibility and agency in figured worlds: becoming a 'good doctor'. med edu. 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abstract objective: to study the frequency of adhd symptoms in medical students and its association with their physical activity, screen time and sleep pattern. study design: cross sectional descriptive study. place and duration of study: this study was carried out among first year and second-year medical students of rawalpindi medica l university, rawalpindi from june 2017 to august 2017. materials and methods: data was collected using a self-administered questionnaire derived from literature. sleep deprivation was assessed using epworth sleepiness scale. adhd symptoms were assessed using adult adhd self report scale (asrs-v1.1) symptom checklist. significance value was set at p<0.05. the questionnaires were distributed among three hundred medical students and sample size of 271 was met after discarding responses with missing information and not meeting inclusion criteria. data was analyzed using spss version 23. chi square test was used to determine the association of adhd symptomology with sleep pattern, physical activity, and screen time. results: 12.17% (n=33) respondents fell in adhd spectrum as they scored more than 4 in asrs v1.1. significant relation was not established between adhd symptoms and sleep deprivation (p=0.58). the relation between physical activity and adhd symptom turned out to be significant (p=0.045). total screen time and adhd did not show a significant relation(p=0.266). similarly, tv hours were not significantly associated with adhd symptoms (p=0.932). however, laptop usage hours per day (p=0.04) and phone usage hours per day (p=0.007) were significantly related to adhd symptoms. conclusion: lack of physical activity and prolonged screen time have significant correlation with self-reported adhd symptoms in medical students. however, sleep deprivation is not significantly associated with adhd symptomology. hence, cutting down the screen time particularly laptop and mobile usage hours and increasing the time of physical activity might help in preventing and alleviating adhd symptoms. key words: attention deficit hyperactivity disorder, exercise, preclinical years, screen time, sleep. and academic incompetence. adhd has the potential to make an individual more susceptible to 3 substance abuse disorders as well. the mean prevalence of pediatric mental problems in pakistan is estimated to be 15.8% with adhd being the most 4 common diagnosis. growing evidence suggests that individuals with probable adhd show more 5,6 involvement in sedentary lifestyle. similarly, screen time has also been reported to have significant 7 a s s o c i a t i o n w i t h a d h d s y m t o m s . s l e e p disturbances act as an independent risk factor for 8,9 adhd or they may appear as a symptom. a study disclosed that students with adhd had lower scores in adaptation to college, self-esteem and social skills compared with the control. the gradual decline in the grades of adhd identified students owes to their inability to focus during lectures in the classrooms, lack of interest in task completion and task introduction adhd is amongst common chronic neuro developmental disorder, which is characterized primarily by impulsivity, hyperactivity, and 1 inattention. two third of the children diagnosed with adhd experience persistence of the symptoms 2 in adulthood as well. the prevalence of adhd in 14 adults varies from 1.2% to 7.3% . adults show a broad spectrum of behavioral and psychiatric issues comprising of anxiety, depression, memory deficits frequency of attention deficit hyperactivity disorder symptoms in medical students and associated factors-a cross sectional study 1 2 3 faqeeha batool , fatima khaliq , sidra hamid, correspondence: fatima khaliq house officer rawalpindi medical university, rawalpindi e-mail: fatimakhawaja28@gmail.com 1,2 3 house officer/department of physiology rawalpindi medical university, rawalpindi received: july 24,2020 revised: september 20, 2021 accepted: october 06, 2021 adhd symptoms in medical students jiimc 2022 vol. 17, no.2 108 11,12 comprehension. adhd in adults has not been extensively studied in pakistan. limited number of research are available especially in adult students. the negative impact of adhd symptoms on academic performance and learning abilities has been well documented which rationalizes the need for further research in this domain. the occupational and social implications of adhd impair quality of life to a great extent and if left undiagnosed can adversely impact an individual's life. given the lack of evidence, this study was designed to find the frequency of adhd symptomology in medical students and to determine its association with physical activity, sleep pattern and screen time. in case positive associations are found, the standard protocol and guidelines should be modified in a way that any individual diagnosed with adhd should be screened for abnormal patterns or duration of screentime, physical activity and sleep. the objective of this study was to determine the frequency of adhd in medical students and its association with physical activity, sleep pattern and screen time. materials and methods it was a cross-sectional study, carried out among firstand second-year medical students at rawalpindi medical university, rawalpindi and extended from june 2017 to august 2017. data was collected from firstand second-year students only because of division of preclinical and clinical year students into distant campuses. therefore, collection of data got limited to preclinical years only because of constraint of distance. the sample size was calculated using who calculator which came out to be 271. however, proformas were initially distributed among 300 students via nonrandomized convenient sampling technique. confidentiality and anonymity of the respondent was maintained, and participant provided a response upon his consent. after filtering out responses with missing information, 271 out of 300 proformas were considered appropriate for analysis based on inclusion and exclusion criteria. the student with preexisting diagnosed psychiatric illness or sleep disorder and with exam score of less than 70% was excluded from study. questionnaire with missing information was also excluded. the proforma was reviewed by institutional research forum for ethical issues and was approved for administration after gaining ethical approval from institutional ethical th research forum (ref.rmu/pr-15 /2018, date: 10 february ,2018). the adult adhd self-report scale15 version 1.1 (asrs-v1.1) screener was used to screen adults with adhd. asrs-v1.1 screener is a symptom checklist of the 18-question world health organization asrs, which evaluates all 18 diagnostic and statistical manual of mental disorders, text revision, 4th edition, criterion a symptoms of adhd. data was collected by distributing proformas in medical students manually. with 45 responses collected initially, cronbach's alpha was calculated for determining internal consistency. it came out to be 0.74. only then was asrs administered in targeted audience. the proforma consisted of four sections. first section comprised of demographic profile asking the subject's name, age, mbbs year, academic scores, and status (day scholar or boarder). second section included questions about subject's physical activity and screen time in a week. physical activity status was evaluated as sedentary or active by considering number of times a student exercised a week for at least 30 minutes. laptop, television, and phone usage hours per day were determined separately and later summed up to determine their total daily screen time. the third section was a standardized epworth sleepiness scale comprising of eight questions aimed at evaluating subject's tendency to doze off while being engaged in eight different situations. score ranging from 0 to 3 was to be assigned to each situation based on criteria; 0 if the subject never dozed off, 1 if there was slight chance of dozing, 2 if there was moderate chance of dozing and 3 if there was high chance of dozing. later all the item scores were summed up to acquire a grand score. three score ranges categorized sleep habits as normal, borderline or abnormal based on the criteria: 0-10 normal, 10-12 borderline and 12-24 abnormal. the fourth section of the form was adult adhd self report scale (asrs-v1.1) symptom checklist consisting of eighteen questions consistent with the dsm-v criteria. however, this questionnaire is a general assessment and not a confirmatory tool. its results only declared the patient as being either symptomatic or not. out of the eighteen questions, first six questions were stronger predictors of adhd. jiimc 2022 vol. 17, no.2 109 adhd symptoms in medical students the questions generally were about attention span, ability to remember important things, ability to procrastinate on important tasks and patience. the scoring scheme was based on five-point likert scale consisting of five response levels namely never, rarely, sometimes, often, very often. if four or more question statements received often/very often response, the subject was considered to have symptoms highly consistent with adhd. data was then entered into spss. nonparametric data was analyzed using spss version 20 for a confidence interval of 5 and confidence level of 95%. association of screen time, physical activity and sleep pattern with adhd symptoms was determined using chi square test. the significance value was set at p<0.05. results relation of adhd status with demographic characteristics the frequency of self-reported adhd symptoms was 12.17% (n=33). these adhd vulnerable students met the criteria of dsm v. remaining 87.8% (n=238) did not meet the screening criteria of adhd and thus were not considered adhd vulnerable. out of the total sample size of 271, 30.6% (n=83) participants st were 1 year mbbs students while 69.4% (n=188) nd were 2 year mbbs students. out of 83 first year mbbs students, almost 10% (n=)8 were adhd symptomatic. whereas 13.5% (n=25) of 188 second year mbbs students showed adhd symptoms. adhd status did not vary significantly between first and second-year students (p=0546). 44.6% (n=121) participants were non-boarders while 55.4%(n=150) were boarders. 12.5% (15 out of 121) of the day scholars were diagnosed with adhd symptoms. on the other hand, 12% (18 out of 150) of the boarders exhibited the symptoms. however, the relation was not significant (p=1.00). 65.5% (n=25) of adhd vulnerable were female but relationship was not significant (p=0.117). relation of adhd symptomology with sleep mean epworth scale score came out to be 9.69 (sd=3.36). 53.9% (n=146) had normal sleep pattern, 26.6% (n=72) had borderline pattern and 19.6% (n=53) had abnormal sleep pattern. mean epworth scale score did not vary significantly between males and females (p=0.668), between day scholars and boarders (p=0.802) and between firstand secondyear students (p=0.0,321). a significant relation was not found between self-reported adhd status and sleep pattern (p=0.58). however, total adhd score had positive correlation with total epworth scale score (r=0.158, p=0.009) showing greater tendency of respondents with disturbed sleep pattern to d e v e l o p a d h d s y m p t o m s . a m o n g a d h d symptomatic students, about 42% (n=14) had normal sleep pattern while 56% (n=132) of those without adhd symptoms had normal sleep pattern. 42.42% (n=14) of adhd vulnerable students had normal sleep pattern,9 (27.27%) was at the borderline while 10 (30.30%) turned out to have abnormal sleep. table i: relation of total adhd score with demographic characteristics table ii: relationship of adhd symptomology with sleep relation of adhd symptomology with screen time mean total screen time was 6.75 hours per day (sd=2.24). mean screen time of males was significantly higher than females (p=0.006). mean screen time of day scholars and boarders was found to be same (6.7 hours, sd 2.2, p=0.574). similarly, mean screen time did not vary significantly between firstand second-year students (p=0.992). mean screen time of adhd symptomatic students (7.4 jiimc 2022 vol. 17, no.2 adhd symptoms in medical students 110 hours, sd 2.76) was slightly higher than those with no adhd symptomology (6.7 hours, sd 2.15). however, relationship was not significant (p=0.078). out of 33 adhd symptomatic students, a vast majority i.e., 85% (n=28) had screen time of more than 2 hours a day. total adhd score showed significant positive correlation with total screen time (r=0.176, p=0.004). this leads us to an inference that those with higher screen time are more vulnerable to develop adhd symptoms. adhd vulnerable students exercised once per week for half an hour and 21.2 (n=7) exercised twice or more than twice weekly on regular basis. a significant correlation was not found between total physical activity hours and total adhd score (r= -0.31, p=0.606). discussion the objective of this study was to study the presence of adhd symptoms in medical students and contribute to this domain of research in medicine left partially and incompletely addressed as compared to 13 the western world. the frequency of self-reported adhd came out to be 12.17% which was high in 10 comparison to 7.6% in korean college students . physical activity and laptop and mobile usage hours were found to have significant association with adhd symptomology in our study. significant relationship did not exist between abnormal sleep time and adhd. however, growing evidence suggests that sleep disorders are more common in individuals with adhd. it was depicted in a research that those with clinically relevant adhd symptoms had high prevalence of insomnia and reported longer as well 16 as shorter sleep duration more often . a research claimed that adhd identified children had an average total sleep time of 8 hours 19 minutes whereas the individuals in control group had average 17 sleep time of 8 hours 52 minutes. adhd suspects find it hard to go to sleep. one research stated that treating sleep problems may eventually lead to diminution of inattention and hyperactivity in 18 children. our study revealed a significant relationship between physical activity and adhd symptoms. in a recent study, it was shown that those with adhd were significantly less likely to meet recommended levels of physical activity as compared to those 20 without adhd. interventional studies have also demonstrated that physical activity helps in 19 improving adhd symptoms. however, it has also been observed that a significant relationship between physical activity and adhd symptoms does 5 not exist . to facilitate the respondents, separate questions were designed to inquire about laptop, mobile and television usage time. later, each time span was added up to evaluate overall screen time. significant relations were only obtained between adhd and laptop and mobile usage hours table iii: relation of adhd symptomology with screen time relation of adhd status with physical activity out of total 271 students, 42.8% (n=116) did not exercise at all, 23.6% (n=64) exercised once, 21% (n=57) two to three times weekly, 5.5% (n=15) four times and 7% (n=18) more than five times weekly. a significant relation was found between physical exercise and adhd symptoms (p=0.045). among adhd symptomatic respondents, 51.5% (n=17) reported to have never exercised regularly. whereas, among adhd asymptomatic individuals, 41% (n=99) had never exercised regularly. 27.3% (n=9) of the table iv: relation of adhd symptomology with physical activity jiimc 2022 vol. 17, no.2 111 time time time time time adhd symptoms in medical students screen screen screen screen independently. a significant relationship between high screen time and adhd symptoms has been 5 found in previous studies also. a recent study also revealed that children with adhd are less likely to 21 limit screen time to less than 2 hours per day. the findings of our study support the need for ongoing efforts to address lifestyle factors among the medical students. they also stimulate further investigation about the needs of youth with adhd from both public health and clinical perspectives. limitations our research study has few limitations. the research results cannot be generalized due to small sample size and usage of nonrandom convenient sampling technique owing to constraint of time. we also had no information about occurrence of adhd symptoms in childhood of the participants. conclusion adhd is found to have high prevalence in our study signifying the need to address it at a profound level in our society via thorough investigations. prolonged screen exposure and lack of physical activity have significant association with adhd symptomology. this highlights the importance of cutting down the screen time of the suspects and increasing their time of physical activity. further epidemiological studies are warranted to 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. https://doi.org/10.5665/sleep/32.3.343. 17. gau s, chiang h. sleep problems and disorders among adolescents with persistent and subthreshold attentiondeficit/hyperactivity disorders. sleep. 2009;32(5):671-679. https://doi.org/10.1093/sleep/32.5.671. 18. hoza b, martin cp, pirog a, shoulberg ek. using physical jiimc 2022 vol. 17, no.2 112 adhd symptoms in medical students activity to manage adhd symptoms: the state of the evidence. current psychiatry reports. 2016 dec 1;18(12):113. https://doi.org/10.1007/s11920-016-07493. 19. cook bg, li d, heinrich km. obesity, physical activity, and sedentary behavior of youth with learning disabilities and adhd. journal of learning disabilities. 2015 nov;48(6):56376. https://doi.org/10.1177/0022219413518582. 20. tandon ps, sasser t, gonzalez es, whitlock kb, christakis da, stein ma. physical activity, screen time, and sleep in children with adhd. j phys act health. 2019 jun 1;16(6):416-22. https://doi.org/10.1123/jpah.2018-0215. conflict of interest authors declared no conflicts of interest. grant support and financial disclosure authors have declared no specific grant for this research from any funding agency in public, commercial or nonprofit sector. data sharing statment the data that support the findings of this study are available from the corresponding author upon request. this is an open access article distributed under the terms of the creative commons attributionnoncommercial 2.0 generic license. jiimc 2022 vol. 17, no.2 113 adhd symptoms in medical students original�article key words: dengue fever, dengue hemorrhagic fever, diagnosis of dengue. conclusion: this study depicts that children more than five year of age more commonly suffer from dengue fever with full recovery within 96 hours of admission. as vaccine is not available in pakistan, these patients need timely diagnosis and critical monitoring during disease course to prevent mortality. abstract objective: to review clinico-pathological data of dengue infection in paediatric patients admitted during epidemic of 2015. study design: this was a cross-sectional study. materials and methods: febrile patients, aged 1-12 year of both genders (fulfilling the criteria of dengue infection according to the reporting form designed by dengue advisory expert group for dengue infection) were included. their clinical features, blood counts and dengue markers were recorded and followed up during hospital stay. findings were subjected to spss 20 for statistical analysis. place and duration of study: the study was conducted at department of pediatrics during the epidemic from st st 1 july to 31 december, 2015. results: a total of 133 febrile patients, half of them were male, were included after confirmation of diagnosis on dengue markers. more than two third 79.7% patients were above five years of age with mean age 8.5+ 3.2 year and mean duration of fever was 5.88+2.14 days. headache was the most prominent symptom in 54.9% febrile patients followed by vomiting 52.6%. hepatomegaly was seen in 36.8% patients. dengue fever was the most common presentation followed by dengue haemorrhagic fever and dengue shock syndrome. patients with dengue haemorrhagic fever and dengue shock syndrome had restlessness, abdominal pain and cold clammy skin on presentation. leukopenia was more frequent than thrombocytopenia. and in some cases, cause of dengue shock syndrome (dss) is considered to have immune-pathologic 1 basis. dengue infects around fifty million people annually 2,3,4 around the globe. incidence of dengue fever has increased by thirty folds over the last fifty years and there is an estimation that 390 million people in 128 5,6 countries are at risk of this dreadful viral disease. pakistan had its first outbreak of dengue in 1994 and since then few epidemics were reported till 2011 when a major epidemic of dengue fever occurred in punjab especially in lahore and adjoining areas. in this outbreak more than 21580 confirmed cases and 7 317 deaths were recorded. diagnosis of dengue fever is usually based on its clinical presentation, hematological abnormalities and positive viral serology. clinical manifestations of dengue fever are variable and are influenced by the 8 age of the patient. it remained throughout the year in this region and different clinical manifestations have been observed during different epidemic introduction dengue fever (df) is caused by mosquito borne viruses and clinically results in biphasic fever, m y a l g i a , a r t h r a l g i a , r a s h , l e u k o p e n i a , thrombocytopenia and lymphadenopathy, whereas dengue hemorrhagic fever (dhf) is severe often fatal febrile disease which results in increased capillary permeability, abnormalities of hemostasis dengue infection in pediatric patients admitted in a tertiary care hospital in rawalpindi 1 2 3 4 5 6 najaf masood , muddassar sharif , juneda sarfraz , khushdil khan , muhammad khalid masood , riffat omer correspondence: dr. najaf masood associate professor department of pediatrics sims services hospital, lahore e-mail: najaf03@yahoo.com 1,5,6 department of pediatrics sims services hospital, lahore 2,4 department of pediatrics benazir bhutto hospital, rawalpindi 3 department of public health szabmu, islamabad funding source: nil; conflict of interest: nil received: november 14, 2019; revised: march 05, 2020 accepted: march 16, 2020 dengue infection in pediatric patientsjiimc 2020 vol. 15, no.1 4 periods as described in study conducted in north 9 india. rawalpindi also experienced high disease burden since 2011, therefore this study was conducted on pediatric patients to review clinicopathological data of dengue infection admitted in a tertiary care hospital in rawalpindi during the epidemic of 2015. materials and methods this was cross-sectional study, conducted at pediatric department of a tertiary care health facility after approval from research and ethical committee rmc and allied hospital rawalpindi. febrile patients aged 1-12 year of both gender were included according to the reporting form designed 10 by dengue advisory expert group. the children suffering from fever 2-9 days with two or more symptoms (headache, myalgia, arthralgia, retro-orbital pain, abdominal pain, rash, bleeding manifestations, irritability and reduced urine output with positive dengue markers were included in the study. patients who had previous history of leukopenia, thrombocytopenia or prolonged history of fever and patients with negative dengue markers were excluded. patients with fever and two or more symptoms according to reporting form were admitted in pediatric ward. blood complete picture was sent to the haematology department of hospital. on the basis of leukopenia (total leucocyte count <4000/cmm) or thrombocytopenia (platelet <100,000/cmm) patients were classified as probable dengue fever. later on the presence of dengue markers ns1, igm and igg positivity for dengue infection was confirmed by enzyme linked immunesorbent assay from hospital laboratory. all patients were admitted in pediatric dengue ward and monitored for vital signs, urine output, and ultrasound chest/abdomen to rule out any evidence of plasma leak. they were followed up till time of discharge for improvement of symptoms and platelet count. results this study included total 133 febrile patients, half of them were male, after confirmation of diagnosis on dengue markers. more than two third 79.7% patients were above five year of age with mean age 8.5+3.2 year. demographic data of patients according to disease spectrum is described in table i. duration of fever was 2-9 days with mean duration 5.88+2.14 days. headache was the most prominent symptom in 54.9% febrile patients followed by vomiting 52.6%, myalgia 45.1%, abdominal pain 41.4% , retro-orbital pain and sore throat 21.8% each, arthralgia 19.5%, rash 14.3%, cough 13.5% and diarrhoea 10.5% . majority of the patient 88.7% did not bleed during course of illness. only 11.3% patients had bleeding in form of epistaxis, hematemesis, malena, hematuria or petechie, hence it was not found statistically significant in our study. mean pulse rate was 93.4+17.3 beats/min. most of the patients were maintaining their blood pressure with mean systolic and diastolic pressure of 92.3+14.2 and 58.9+12.7 respectively. hepatomegaly was seen in 49 patients while splenomegaly was present in 11 patients. patients with dhf and dss had restlessness 3.75% and abdominal pain 7.5% while 3.8% patients had cold clammy skin on presentation. clinical manifestations are described according to disease spectrum in table ii. blood complete picture revealed mean haemoglobin 12.07+1.73 gm %, mean total 3 leukocyte count 4809+3091/mm and platelet count 3 103936+65687.97/ mm. leukopenia (total 3 leukocyte count less than 4000/mm ) was observed in 48.87% patients while thrombocytopenia less 3 than 50,000 /mm was seen in only16.54 %. nonstructural protein 1(ns1) was positive in 63.9% and igm for dengue was detected in 41.27% patients. df was the most common presentation in 72.2%, dhf was diagnosed in 19.5% while dss was in 7.5% patients. dss was observed more frequent in older age group, among ten patients of dss, 7 were of more than ten year of age. ultrasound was normal in patients with dengue fever. findings of fluid leak were observed in dhf and dss patients. among 36 patients 10 (7.5%) developed pleural effusion and gall bladder wall oedema. pelvic ascites was as frequently observed as abdominal ascites. laboratory findings are further described in table iii. patients with dengue fever improved with antipyretics and oral fluids. about 30.1% patients received intravenous normal saline and dextran 40 was administered in 4.5% patients. blood transfusion was done in 8.3% patients. platelet count improved within 4 days in 88.7% patients. more than two third 85.7% patients discharged from hospital within 96 jiimc 2020 vol. 15, no.1 5 dengue infection in pediatric patients hours with no mortality observed during epidemic period in the tertiary care hospital of the study. features of disease regarding management and course of illness, according to severity of illness are further described in table iv. table i: demographic features of the sample table ii: clinical manifesta�ons in dengue pa�ents table iii: laboratory data in dengue pa�ents table iv: management variables in dengue pa�ents jiimc 2020 vol. 15, no.1 6 dengue infection in pediatric patients discussion dengue is an epidemiologically important mosquito borne viral disease. significant population of various age groups has suffered from the disease in last two decades in pakistan. in this study 133 patients were included during six months of epidemic in rawalpindi. we found two thirds of study population between 5-12 years of age. same age group is found more affected from dengue infection in different 11,12 13 studies conducted in pakistan and india. we had no gender difference in this study which is contrary to a study conducted at southern india where 14 77.31% patients are male. fever was present in 100% patients followed by headache, vomiting, myalgia, abdominal pain, retro-orbital pain, sore throat, arthralgia, rash, cough and diarrhoea. frequency of symptoms are consistent with other 11,14. studies. rash is one of the prominent clinical feature of dengue also noted in 64.5% patients in one 15 study conducted in india but we observed rash only in 4.3% patients. bleeding in dengue infection is a common event. its causes are multifactorial. in this study majority of the patient (88.7%) did not bleed during course of illness which is contrary with the 16,17 study conducted in indonesia and philippines. hepatomegaly was present in 36.8% in our study that is not as frequent as in study done by joshi r in mumbai in which hepatomegaly is present in more 13 than half (66%) patients. age less than five year, spontaneous bleed, hepatomegaly, free fluid in 3 serosal cavities, leukopenia less than 4000/ mm and 3 thrombocytopenia <50,000/mm are significant risk 18,19 factors in pediatric patients suffering from dhf. none of these findings were found significant in this study. we found two third of patients with dengue fever with mean duration of fever 5.88+2.14 days. therefore, non-structural protein 1(ns1) was the most frequent marker of dengue fever as compared to igm for dengue fever. this observation is on par 14,19 with finding of different studies. pleural effusion and gall bladder wall edema were the most frequent ultrasound findings in this study which is consistent 20 with study conducted in india. normal saline and dextran found useful in dengue haemorrhagic fever 21,22 and dengue shock syndrome patients. same was observed in this study. blood transfusion was done in 8.3% patients in current study which is not 8. almas a, parkash o, akhter j. clinical factors associated with mortality in dengue infection at a tertiary care center. s o u t h e a s t a s i a n j tr o p m e d p u b l i c h e a l t h . 2010;41(2):333–40. 12. siddiqui fj, haider sr, bhutta za. endemic dengue fever: a seldom recognized hazard for pakistani children. j infect 11. ahmed s, arif f, yahya y, et al. dengue fever outbreak in karachi 2006 a study of profile and outcome of children under 15 years of age. jpma. 58: 4-8. 10. masud f, butt tk, ali m. guidelines for treatment of dengue fever/dengue hemorrhagic appendix 4 b – reporting form for (confirmed. case).2012: 84-5 9. chandrakanta, kumar r, garima, agarwal j, jain a, nagar r. changing clinical manifestations of dengue infection in north india. dengue bulletin – volume 32, 2008;118-125. 7. who. dengue fever pakistan. http://www.emro.who.int /pak/programmes/dengue -fever.html. 6. brady oj, gething pw, bhatt s, messina jp, brownstein js, hoen ag, et al. refining the global spatial limits of dengue virus transmission by evidence based consensus. plosnegl trop dis. 2012;6; e1760. 5. 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 4. khan e a. dengue fever: a major public health problem of our time. rmj. 2016; 41(2): 139-141 3. ahmed s, mohammad ww, hamid f, akhter a, afzal rk, mahmood a.j. the 2011 dengue hemorrhagic fever outbreak in lahore an account of clinical parameters and pattern of hemorrhagic complications. coll physicians surg pak. 2013 jul;23(7):463-7. comparable with one of the indian study in which 23 only 1.8% children receive blood transfusion. early detection and timely management of the disease can prevent mortality. in our study more than half of patients 85.71% discharged from hospital within 96 hours with no mortality observed during epidemic period. these findings are concordance with another 24 indian study. conclusion this study depicts that children more than five year of age more commonly suffer from dengue fever with recovery within 96 hours of admission. as vaccine is not available in pakistan, these patients need timely diagnosis and critical monitoring during disease course to prevent mortality. references 1. kliegman rm, stanton bf, st geme jw, schor bf. th philadelphia, nelson text book of pediatrics, 20 edition. 2015; 269:1629. 2. khurram m, qayyum w, faheem m, umar m, bushra ht, khan m u, khan n. characteristics of dengue shock syndrome during 2014 dengue epidemic in rawalpindi, pakistan. rmj. 2016; 41(2): 142-147. jiimc 2020 vol. 15, no.1 7 dengue infection in pediatric patients 15. selvan t, nagaraj m, saravanan p, somashekar. a study of clinical profile of dengue fever in children. int j contemppediatr. 2017 mar;4(2):534-537. 13. joshi r, baidv. profile of dengue patients admitted to a tertiary care hospital in mumbai. the turkish journal of pediatrics. 2011; 53: 626-631. 14. mishra s, ramanathan r, agarwalla sk. clinical profile of dengue fever in children: a study from southern odisha, india. scientifica (cairo). 2016;6391594. devctries. 2009; 3(4):306-312. 16. basuki ps, budiyanto, puspitasarid, et al, application of revised dengue classification criteria as a severity marker of dengue viral infection in indonesia. southeast asian j trop med public health. 2010 sep;41(5):1088-94. 17. hayes cg, manaloto cr, gonzales a, ranoa cp. dengue infections in the philippines: clinical and virological findings in 517 hospitalized patients. am j trop med hyg 1988; 39:110-116 18. pothapregada s, kamalakannan b, thulasingham m. risk factors for shock in children with dengue fever. indian j crit care med. 2015 nov; 19(11): 661–664 19. gupta v, yadav tp, pandey rm, risk factors of dengue shock syndrome in children. j trop pediatr. 2011 dec;57(6):451-6. 20. sharma nl, balasubramanyam v, kandati j et al. clinical and laboratory profile of dengue fever in children during an outbreak one year study at tertiary care hospital, chennai, tamilnadu, india. int j contemppediatr. 2017 jan;4(1):110115 21. santhosh vr, prashanth g. patil, mg. srinath, ak, jain a, archana m. sonography in the diagnosis and assessment of dengue fever. jclin imaging sci. 2014; 4:14. 22. wills ba, nguyen md, ha tl, dong th, tran tn, le tt, tran vd, nguyen th, nguyen vc, stepniewska k, white nj, farrar jj. comparison of three fluid solutions for resuscitation in dengue shock syndrome. nengl j med. 2005 sep 1;353(9):877-89. 23. tambekar h, sharma s, rational use of blood components in children with dengue by using who and nvbdc guidelines. int j contemp pediatr. 2019 mar;6(2):786-790. 24. vinod h. ratageri, t.a. shepur, p.k. wari, s.c. chavan, i.b. mujahid1 and p.n. yergolkar. clinical profile and outcome of dengue fever cases. indian j pediatr. 2005; 72 (8): 705710. jiimc 2020 vol. 15, no.1 8 dengue infection in pediatric patients jiimc 2016 vol. 11, no.3 137 ajinomoto group is one of the leading global producers of the flavor enhancer monosodium glutamate (msg). since early 20th century, ajinomoto has gathered a substantial amount of data related to msg safety and use. based on that database, we are commenting here-below on the recent article by abbasi et al., entitled “effect of vitamin c on monosodium glutamate (ajinomoto) induced changes in the ovary of rats” (jiimc 11(2), 2016, 66-70). the article described a rat study with msg and vitamin c. the authors extensively speculated that msg ingestion may cause harmful effects on human female fertility and ovarian functions. we argue that the study by abbasi et al. was burdened by m e t h o d o l o g i c a l p r o b l e m s a n d a l a c k o f reproducibility. in addition, we conclude that the authors neglected glutamate metabolism in mammalian bodies in interpreting the results. 1) the doses of msg or the mode of msg treatment were not described, thus one cannot conclude if there was any relevance to human n u trit io n . if msg was mixed into th e experimental diet, the authors needed to explain how that was achieved since conventional rat diets are granulated. if msg was applied in drinking water, the authors needed to describe how taste was masked. 2) no data on diet intake, water intake or body weight were provided, but the authors mentioned that the control group was characterized by a lower terminal mean body weight when compared to body weight of msg–treated rats. therefore, the observed ovarian differences could have been attributed to the changes in body weight and not to the treatments per se. in other words, in the absence of body weight information, it is impossible to toxicologically interpret the observed changes. 3) it is not clear where the tested msg was obtained from, who was the producer and whether it contained impurities or other substances which may have affected the observed results. 4) the authors indicated that "ajinomoto" was a common name of all msg used in pakistan. indeed, "ajinomoto" is a trademark registered by ajinomoto co., inc. in more than 170 countries, including countries in central and south asia. however, while the “ajinomoto” is one of the most popular seasoning brands worldwide, it is not the only msg brand on the market. mentioning “ajinomoto” brand name in a title of a scientific article without describing the source of the tested msg, or its purity, was disparaging and academically unjustified. 5) as the authors mentioned, a molecule of msg contains glutamate and sodium. however, sodium intake from msg was not controlled for even though the authors attributed all observed changes to glutamate alone. one cannot preclude that at least some effects were attributable to sodium. in that respect, we note that there was no information on how control rats were treated or what control diet was composed of. adult rats ingest standard diet at approximately 12% of their body weight, thus we suppose the studied female rats ingested daily approximately 30 – 40 g of a chaw diet. if that diet was based on milk casein, as is usually the case, it contained 10% glutamate, so the rats were eating 3 – 4 g of glutamate from the diet alone without msg added (i.e., 1). no attention was given to that “diet-contained” glutamate source. 6) authors extensively speculated on msg use in humans. adult humans ingest about > 10 g glutamate per day from a normal diet. this volume includes 0.5 – 1.0 g per day of glutamate added to food as a flavor enhancer, whether in a form of msg or included in other condiments rich in glutamate (bouillon cubes, soy sauces, mushrooms etc.). in simple words, msg is only a small portion of ingested glutamate. considering that all food free glutamates are metabolized identically, it is disproportionate to speculate solely on msg – especially if the speculation is based on a rodent study only. 7) importantly, histopathological evaluation of the tissues was not described. specifically, was the evaluation done visually only; and were the persons conducting the observations blinded? letter to the editor food-added monosodium glutamate does not induce changes in the ovaries 8) finally, the authors selectively used references and omitted scientific papers on the lack of dietary msg effect on reproductive functions (24). instead, the authors used pharmacological studies with msg or non-scientific articles published online (see ref. 17 in the original article). at this point, it is appropriate to mention that less than 5% of orally ingested glutamate from food (including msg) is absorbed from the gut into the systemic circulation. the rest is used as an oxidative substrate by the intestinal mucosa (5-8). other food components, which are inevitably ingested along with food-added glutamate, further suppress circulating glutamate levels (9-10) and therefore increasing blood glutamate levels by food-added msg is extremely difficult. in the absence of a high circulating glutamate, any changes in ovarian physiology are impossible to attribute to foodderived glutamates, such as msg. key words: monosodium glutamate, metabolism, ovaries. references 1. seeber rm, smith jt, wadell bj. plasma leptin-binding activity and hypothalamic leptin receptor expression during pregnancy and lactation in the rat. biol reproduction 2002; 66: 1762-67. 2. semprini me, d'amicis a, mariani a. effect of monosodium glutamate on fetus and newborn mouse. nutr. metab. 1974; 1: 276-84. 3. yonetani s, matsuzawa y. effect of monosodium glutamate on serum luteinizing hormone and testosterone in adult male rats. toxicol. lett. 1978; 1: 207-11. 4. yonetani s, ishii h, kirimura j. effect of dietary administration of monosodium l-glutamate on growth and r e p r o d u c t i v e f u n c t i o n s i n m i c e . o y o ya k u r i (pharmacometrics) 1979; 17: 143-52. 5. neame kd, wiseman g. the transamination of glu and asp during absorption by the small intestine of the dog in vivo. j. physiol. 1957; 135: 442-50. 6. reeds pj. enteral glutamate is almost completely metabolized in first pass by the gastrointestinal tract of infant pigs. am. j. physiol. 1996; 270: 413-18. 7. reeds pj. intestinal glutamate metabolism. j. nutr. 2000; 130: 978s-82s. 8. reeds pj. dispensible and indispensible amino acids in humans. j. nutr. 2000; 130: 1835s-40s. 9. stegink ld, filer lj, baker gl, bell ef. plasma glutamate concentrations in 1-year-old infants and adults ingesting monosodium l-glutamate in consommé. pediatr. res. 1986; 20: 53-8. 10. stegink ld, pitkin rm, reynolds wa, filer lj jr, boaz dp, 138 brummel mc. placental transfer of glutamate and its metabolites in the primate. am. j. obstet. gynecol. 1975; 122: 70-8. correspondence: miro smriga department of external scientific affairs group and intellectual property rights ajinomoto co. inc. 1-15-1 kyobashi, chuo-ku, 104-8315 tokyo, japan e-mail: miro_smriga@ajinomoto.com miro smriga, kosuke tomori, tatsuo igarashi department of external scientific affairs group and intellectual property rights ajinomoto co. inc. received: july 13, 2016; accepted: aug 19, 2016 jiimc 2016 vol. 11, no.3 the dose of msg was 0.08 mg per kg body 1-3 weight. and it was mixed in their pallet diet. daily diet intake of one rat is 10-12grams. weight of one rat is approximately 300grams. so the weight of fifteen rats in experimental group a was 15 * 300 = 4500gm/4.5kg. the estimated dose of msg for fifteen rats was 0.08 * 4500 = 0.036grams. approximate dose of msg per rate per day will be 0.024grams. the dose of msg for four weeks was 0.024 * 30 = 0.72grams. high quality msg free from impurities was obtained from asia scientific traders, rawalpindi manufactured by zinef company china. i followed the tradition in academic literature 4-6 where msg is commonly known as ajinomoto. the major component of msg is glutamate that 7 is 78% and literature showed that glutamate is harmful component of msg not the sodium.5 indeed glutamate is a major component of protein rich food like tomatoes, fermented beans, soya sauce and fish sauce. h i sto p at h o l o g i ca l eva l u at i o n wa s d o n e microscopically under the supervision of histopathologist. references 1. eweka ao, eweka a, om’iniabohs fa. histological studies of the effects of monosodium glutamate of the fallopian tubes of adult female wistar rats. north american journal of medical sciences. 2010; 2: 146. 2. zia ms, qamar k, hanif r, khalil m. effect of monosodium glutamate on the serum estrogen and progesterone levels comments by author effect of vitamin c on msg induced changes in the ovaries of rat letter to the editor 7. afeefy aa, mahmoud ms, arafa ma. effect of honey on monosodium glutamate induced nephrotoxicity (histological and electron microscopic studies). journal of american science. 2012;8:146–156. 44. jiimc 2016 vol. 11, no.3 in female rat and prevention of this effect with diltiazem. journal of ayub medical college, abbottabad: jamc. 2014; 26: 18. 3. zia m, qamar k, butt s. effect of monosodium glutamate on the epithelial height of fallopian tube of rat and its prevention with diltiazem. 2013. 4. eweka a, adjene j. histological studies of the effects of monosodium glutamate on the medial geniculate body of adult wister rat. electron j biomed. 2007; 22: 9-13. 5. osman heh. study of the role of antioxidant (vitamin c) on modulation toxicity of chronic use of monosodium glutamate in liver of albino rats: faculty of medicine, taif university; 2012. 6. eweka a, om’iniabohs f. histological studies of the effects of monosodium glutamate on the ovaries of adult wistar rats. annals of medical and health sciences research. 2013; 1:37-44. correspondence: dr. sumaira abbasi department of anatomy islamic international medical college riphah international university, islamabad e-mail: sumaira.abbasi@gmail.com sumaira abbasi, rehana rana, kaukab anjum department of anatomy islamic international medical college riphah international university, islamabad funding source: nil ; conflict of interest: nil received: july 13, 2016; accepted: aug 19, 2016 139 letter to the editor page 50 page 51 page 52 original�article abstract objective: to assess patient satisfaction with telemedicine services. to find out the difficulties encountered by patients with telemedicine. to assess whether telemedicine services can be continued in future. study design: cross sectional survey. place and duration of study: the study was conducted at shifa international hospital, islamabad from july 1, 2020, to september 30, 2020. materials and methods: it was a cross-sectional survey in which two hundred patients were interviewed at the end of tele-consultation according to a proforma after taking informed consent and using non-probability consecutive sampling technique. data was analyzed using spss version 22. results: among 200 patients, 61.5% were males and 38.5% were females and the mean age was 43.45 + 11.964 years. 73.5% patients used telemedicine for the first time and 52.0% patients used this service for consultation regarding fever and covid-19 suspected symptoms. among these patients, only 6.5% could not clearly hear the voice of doctor during consultation, 6.5% could not clearly see the picture of doctor on screen. 56.5% patients agreed and 42.0% strongly agreed that telemedicine saves their time, expenditure and prevents the discomfort of travelling to hospital. most patients (60.5%) were satisfied with the telemedicine services offered. majority of patients (81.0%) reported that they will recommend telemedicine to others and will use it even after the covid-19 pandemic. conclusion: study concluded that overall satisfaction level of patients with telemedicine was high. audio visual connection problems were found in a small percentage of patients. participants were willing to use this service even after the covid-19 pandemic and they would recommend others to use telemedicine. key words: covid-19, patient satisfaction, pandemic, telemedicine. 3 worldwide. the covid-19 pandemic made telehealth services a significant tool for providing the 4 health care. the use of telehealth services was 5 limited worldwide until march 2020. telehealth, w h i c h i n c l u d e s a sy n c h ro n o u s e v i s i t s a n d synchronous audio-only or video visits, has been used by over 9 million medicare beneficiaries 6 between 17 march and 13 june, 2020. in pakistan, current surge in telemedicine took place due to fear of contracting the covid-19 and to maintain the social distancing. during last several months, social distancing has caused this technology to become even more significant as a support system 7 and in increasing utilization of the telemedicine. moreover, telemedicine centers were made and practiced in the government and private sector in pakistan at a vast level for the first time with good experience in offering support to the health care personnel and medical advice to the patients 8, 9 utilizing technology. during current pandemic telemedicine may be helpful for protection of health care workers, triage of suspected covid-19 patients before arrival in hospital and for patients with introduction in response to difficult time of covid-19, health care systems need paradigm shift, otherwise technology was still advanced few years back, but nobody went 1 for telemedicine especially in country like pakistan. telemedicine has been described by world health organization (who) as “the delivery of healthcare services by all healthcare professionals utilizing technology for exchange of valid information regarding diagnosis, treatment, and prevention of 2 disease and injuries.” the trend of telemedicine is exponentially increasing patient satisfaction and difficulties encountered with telemedicine during covid-19 pandemic 1 2 3 4 muhammad ashraf , faryal shoaib , hashaam ghafoor , alishba ashraf khan correspondence: dr. muhammad ashraf consultant medical specialist shifa international hospital, islamabad e-mail: drmashraf2@gmail.com 1,2 department of medicine, shifa international hospital, islamabad 3 department of anaesthesia hamad medical corporation doha, qatar 4 mbbs student rawalpindi medical university, rawalpindi rreceived: september 26, 2021; revised: april 17, 2022 accepted: august 25, 2022 patient satisfaction with telemedicinejiimc 2022 vol. 17, no.3 208 chronic medical illnesses who cannot come to hospital. the patient satisfaction is a growing concern in all 1 0 aspects of healthcare. as with traditional modalities of health care delivery, telemedicine also relies on reports of patient satisfaction because the patients are the only source of information about how they are treated and the therapy met their expectations, if the patients are not satisfied, the 11 service is rendered obsolete. as the telemedicine services are being provided to patients in private hospitals in these days, it is important to improve the services according to patient's satisfaction. the objectives of the study are to know the patient satisfaction, to find the difficulties encountered by patients with a view to improve these services and to assess whether telemedicine services can be continued in future. materials and methods it was a descriptive cross-sectional study in which 200 patients were included and non-probability consecutive sampling technique was used. the study was conducted at shifa international hospital, islamabad. the duration of study was three months (from july 1, 2020, to september 30, 2020). all patients who fulfilled the inclusion criteria and availing telemedicine services in internal medicine clinics were enrolled. the patients were interviewed at the end of tele-consultation to answer the questions according to the proforma after taking informed consent. the study was approved by institutional review board and ethics committee. data was analyzed using spss version 22. basic descriptive statistical analysis was done including frequencies, means, standard deviation and proportions. chi's square test was also applied on categorical variables. p-value of less than 0.05 was considered significant. results among 200 patients, 66 (33.0%) were up to 40 years old and 134 (67.0%) were more than 40 years. the mean age of the patients was 43.45 + 11.964 years. among these patients, 123 (61.5%) were male and 77 (38.5%) were females. out of 200 patients, more than half 104 (52.0%) used tele-consultation for fever or suspected covid-19 symptoms while 96 (48.0%) patients used it for other medical problems. out of 200 patients, 147 (73.5%) used telemedicine for the first time, 45 (22.5%) used 1-3 times and only 8 (4.0%) patients used it >3 times (figure i). table i shows the details of the questions asked fig. 1: frequency distribution of patients according to number of telemedicine visits mainly to schedule an appointment, audio visual quality and overall satisfaction and response of patients according to proforma. overall, 193 (96.5%) out of 200 patients were satisfied with telemedicine services. table i: frequency distribution of patients according to satisfaction and difficulties encountered with telemedicine patient satisfaction with telemedicinejiimc 2022 vol. 17, no.3 209 among 200 patients, 162 (81.0%) reported that they will recommend telemedicine to others and will use it even after the covid-19 pandemic is over. table ii shows significant association (p=0.000) between age and overall patients' satisfaction with telemedicine while insignificant association (p=0.082) between age and use of telemedicine by patients even after the covid-19 pandemic is over. by patients even after the covid-19 pandemic is over. table ii: association between age and satisfaction table iii indicates significant association (p=0.035) between gender and overall patients' satisfaction with telemedicine and significant association (p=0.005) between gender and use of telemedicine table iii: association between gender and satisfaction discussion during covid-19 pandemic, a rapid increase in the telemedicine trend is being observed not only among developed countries but also among developing countries including pakistan. most of the patients in our study (67.0%) were more than 40 years old and 33.0% patients were upto 40 years of age while the mean age of the patients was 43.45+11.964 years. the findings of a recent study carried out by richards ae and coworkers (2021) indicated that mean age of 17 the patients was 63.1 + 14.6 years. another study conducted by orrange s and associates (2021) also confirmed that most of the respondents were elderly as the mean age of the patients was 55.8+16.0 13 years. in our study male patients were in majority (61.5%) while remaining proportion (38.5%) was of females. the findings of our study are comparable with a study performed by ahsan mf and collaborators (2020) who also asserted that majority (75.6%) of the 12 patients were male and only 24.4% were female. however, a study undertaken by ramaswamy a and teammates (2020) exhibited different results that most of the patients (61.3%) were females and 38.7% 18 were male patients. as the trend of telemedicine is increasing during patient satisfaction with telemedicinejiimc 2022 vol. 17, no.3 210 covid-19 pandemic, study disclosed that more than half (52.0%) of the patients used this service for fever or suspected covid-19 while 48.0% patients used this service for other medical problems. this indicates that although telemedicine was used mainly by suspected covid -19 patients, a significant percentage of patients with other chronic illnesses have also utilized telemedicine services. this may also be due to limited access to outpatient clinics and face to face consultations during peak of this pandemic. the results of this study are different to the results of study done by magadmi mm and fellows (2020) who highlighted that only 18.1% patients used telemedicine for covid-19 and majority (81.9%) used this service for other medical 2 problems. the findings of our study further indicated that majority (73.5%) of patients used telemedicine service for the first time and 26.5% patients used this service more than one time. almost similar results were reported in a study by adams l and comrades (2021) who showed that 71.9% patients had their first experience with t e l e m e d i c i n e w h i l e 2 8 . 1 % p a t i e n t s u s e d 19 telemedicine for more than one time. so our study indicates that telemedicine services were new to these patients and those using this service for the second or third time were more likely to follow up again. our study revealed that a significant majority of patients was satisfied with appointments and paying consultation fee online. among these patients, 75.0% reported that they can clearly hear the voice of doctor during consultation and 75.0% also said they can clearly see the picture of doctor on screen while audio visual communication was not satisfactory for just 25% of patients. so, the main difficulties encountered were technical in the form of poor audio-visual signals perhaps due to internet connection problems. the difficulties with audio visual connections during telemedicine consultations may be more than that reported in our study especially in rural areas of the country where mobile phone signals and internet quality is not well e sta b l i s h e d . o u r st u d y, h oweve r, d i d n o t differentiate between patients from rural and urban areas. similar results were reported in a study performed by orrange s and associates (2021) who elucidated that 88.2% patients were satisfied with 13 sound and 65.5% with video quality. the findings of another study carried out by hentati f and companions showed better results than our study and that only 17.8% patients faced technical 20 difficulties. the study done in india by acharya rv and rai jj indicated that problems encountered were 15 47 % in technical issues. study further highlighted that majority of patients confirmed that they can use the system easily and have no fear to face camera. among the patients, 76.0 % reported that waiting time of teleconsultation is less as compared to face-to-face consultations. the results of this study are comparatively different from a study undertaken by magadmi mm and fellows (2020) who stated that 70.0% patients were unsatisfied with waiting time of 2 tele-consultations. in our study majority (98.5%) of telemedicine users believed that telemedicine saves their time, expenditure, and discomfort of travelling to the hospital. this indicates that telemedicine can be useful especially for remote and rural areas of country which have poor health facilities and difficult road access to the cities. in our study 91.5% patients affirmed that telemedicine staff was cooperative. similarly, haxhihamza k and colleagues also reported in their study that majority of the patients (89.3%) 4 were satisfied with telemedicine staff. when the overall satisfaction level among patients regarding telemedicine was evaluated, study showed very encouraging results that significant majority (96.5%) was satisfied with telemedicine during covid-19 pandemic. the findings of our study are much better than the study conducted by alharbi kg and colleagues (2021) who reported that overall patients' satisfaction level with telemedicine was 21 68.1%. the results of our study are also consistent with the study done by khalid t et al which showed that 99.4% patients were overall satisfied with 22 telemedicine. the results of our study showed significant association (p<0.05) between age and overall satisfaction level of patients with telemedicine. patients more than 40 years of age were more satisfied. the study carried by magadmi mm and fellows also showed significant association between age and overall satisfaction level of patients with 2 telemedicine. however, our study showed insignificant association (p>0.05) between age and patient satisfaction with telemedicinejiimc 2022 vol. 17, no.3 211 use of telemedicine after covid-19 pandemic . patients' satisfaction plays a vital role and boosts the utilization of health care services. majority (83.5%) of the patients said that they will recommend telemedicine to others due to its usefulness. these findings are like a study done by parker k and chia m who stated that more than 90.0% patients confirmed 23 to recommend others to use telemedicine. the study further highlighted that 81.0% patients wished to use telemedicine even after the covid-19 pandemic. almost similar results were reported in a study done by sathiyaraj a and colleagues who stated that 80.0% patients wanted to use 6 telemedicine in future. similar results were observed in studies by lopez c et al and aashima et al, in which patients showed strong preference for continued usage of telemedicine even after the 14,16 pandemic. this indicates that telemedicine services can be utilized in future by the patients even after the pandemic and telemedicine can be incorporated in regular health services. conclusion study concluded that overall patients were satisfied with telemedicine during covid-19 pandemic. audio visual connection problems were the main difficulties encountered by a small percentage of patients. majority of patients were willing to use telemedicine after the pandemic and were desirous to recommend others to use telemedicine. the study has limitations that it did not include the opinion of provider and consultants. the benefits of telemedicine during covid-19 period are enormous; hence, further studies are needed on large scale to assess the patient satisfaction and difficulties encountered with telemedicine to get further benefits from this service and incorporate telemedicine in regular health care. references 1. abdel nasser a, mohammed alzahrani r, aziz fellah c, jreash dm, almuwallad nta, bakulka dsa, et al. measuring the patients' satisfaction about telemedicine used in saudi arabia during covid-19 pandemic. cureus 2021; 13(2): e13382. 2. magadmi mm, kamel fo, magadmi rm. patients' perceptions and satisfaction regarding teleconsultations during the covid-19 pandemic in jeddah, saudi arabia. res square 2020; 1: 1-19. 3. khan za, zahoor aw, afzal i, butt u, siddiqui am, khan z, et al. evaluation of patient perception and satisfaction toward the use of telemedicine during pandemic of novel coronavirus in pakistan. telemed j e-health 2021 jan 15. doi: 10.1089/tmj.2020.0343. online ahead of print. 4. haxhihamza k, arsova s, bajraktarov s, kalpak g, stefanovski b, novotni a, et al. patient satisfaction with use of telemedicine in university clinic of psychiatry: skopje, north macedonia during covid-19 pandemic. telemed ehealth 2021; 27(4): 464-7. 5. hawrysz l, gierszewska g, bitkowska a. the research on patient satisfaction with remote healthcare prior to and during the covid-19 pandemic. int j environ res public health 2021; 18: 5338. 6. sathiyaraj a, lopez h, surapaneni r. patient satisfaction with telemedicine for prechemotherapy evaluation during the covid-19 pandemic. future oncol 2021; 17(13): 15931600. 7. khan uz. telemedicine in the covid-19 era: a chance to make a better tomorrow. pak j med sci 2020; 36(6): 1405-7. 8. humayun a, shahabuddin s, afzal s, malik aa, atique s, iqbal u. healthcare strategies and initiatives about covid19 in pakistan: telemedicine a way to look forward. comp methods prog biomed update 2021; 1: 100008. 9. nagra mh, ehsan s, ahmad u, ali m, hussain ha, bakar a. implementation of a telemedicine service during covid-19 pandemic in pakistan. j clin practice 2021; 75(8): e14310. 10. cleary pd. a hospitalization from hell: a patient's perspective on quality. ann intern med 2003; 138: 33-9. 11. labarberas pa, mazursky d. a longitudinal assessment of consumer satisfaction/dissatisfaction: the dynamic aspect of the cognitive process. j marketing res 1983; 20: 393-404. 12. ahsan mf, irshad a, malik k, rashid i, shahzad a, waqar sh, et al. patient satisfaction at telemedicine center in covid19 pandemic – shaheed zulfiqar ali bhutto medical university, (szabmu) islamabad. pak armed forces med j 2020; 19(2): s578-83. 13. orrange s, patel a, mack wj, cassetta j. patient satisfaction and trust in telemedicine during the covid-19 pandemic: retrospective observational study. jmir hum factors 2021; 8(2): e28589. 14. lópez c,valenzuela ji, calderón je, velasco af, fajardo r. a telephone survey of patient satisfaction with realtime telemedicine in a rural community in colombia. j telemed telecare 2011; 17(2): 83-7. 15. acharya rv, rai jj. evaluation of patient and doctor perception toward the use of telemedicine in apollo tele health services, india. j fami med prim care 2016; 5: 798803. 16. aashima, nanda m, sharma r. a review of patient satisfaction and experience with telemedicine: a virtual solution during and beyond covid-19 pandemic. telemed e-health 2021 mar 12. doi: 10.1089/tmj.2020.0570. online ahead of print. 17. richards ae, curley k, christel l, zhang n, kouloumberis p, kalani ma, et al. patient satisfaction with telehealth in neurosurgery outpatient clinic during covid-19 pandemic. interdisciplinary neurosurg 2021; 23: 101017. 18. ramaswamy a, drangsholt s, ng e, culligan pj, schlegel pn, hu jc. patient satisfaction with telemedicine during the covid-19 pandemic: retrospective cohort study. j med patient satisfaction with telemedicinejiimc 2022 vol. 17, no.3 212 internet res 2020; 22(9): e20786. 19. adams l, lester s, hoon e, van der haak h, proudman c, hall c, et al. patient satisfaction, and acceptability with telehealth at specialist medical outpatient clinics during the covid-19 pandemic i australia. intern med j 2021; 51(7): 1028-37. 20. hentati f, cabrera ci, d'anza b, rodriguez k. patient satisfaction with telemedicine in rhinology during the covid-19 pandemic. am j otolaryngol 2021; 42(3): 102921. 21. alharbi kg, aldosari mn, alhassan am, alshallal ka, altamimi am, altulaihi ba. patient satisfaction with virtual clinic during coronavirus disease (covid-19) pandemic in primary healthcare, riyadh, saudi arabia. j fam community med 2021; 28: 48-54. 22. khalid t, tariq r, alia s, athar r. teledermatology using whatsapp messenger during covid 19 pandemic; our experience of a cost-effective solution to reach out patients in limited resource. j health infor dev countr 2021; 15(1): 18. 23. parker k., chia m. patient, and clinician satisfaction with video consultations in dentistry part one: patient satisfaction. br dent j 2021; 1-6. conflict of interest authors declared no conflicts of interest. grant support and financial disclosure authors have declared no specific grant for this research from any funding agency in public, commercial or nonprofit sector. data sharing statment the data that support the findings of this study are available from the corresponding author upon request. this is an open access article distributed under the terms of the creative commons attributionnoncommercial 2.0 generic license. patient satisfaction with telemedicinejiimc 2022 vol. 17, no.3 213 original�article abstract objective: to determine effectiveness of single dose of oral dexamethasone with multiple doses of oral prednisolone in relapse of symptoms in children with acute exacerbations of asthma. study design: this was a randomized controlled trial. st st place and duration of study: the study was conducted from 1 january to 31 december 2016 at the emergency department of children's hospital, pakistan institute of medical sciences (pims), islamabad. materials and methods: total 302 patients were included in the study with 151 children in each group receiving either dexamethasone or prednisolone. sampling technique was consecutive and non-probable. children of age 2 to12 years with previous history of asthma diagnosed by a physician presenting with acute exacerbations in emergency were included after consent. after assessment of pediatric respiratory assessment measure (pram) score by the study physician, the patient was either given a single dose of dexamethasone 0.3mg/kg with maximum dose of 12mg or 1mg/kg of oral prednisolone with maximum dose of 40mg followed by two doses for next 2 days after discharge. patients were reassessed for pram score at day 4. the patients were then called at day 14 for the assessment of relapse of symptoms of asthma like cough, wheeze and breathing difficulty. data was documented by the study physician on a proforma. spss version 20 was used for entry and analysis of data. data was presented as mean with standard deviations. percentage was calculated from descriptive variables. chi-square test was used for nonparametric data. p value was significant if less than 0.05. results: there was no significant difference in relapse of symptoms of asthma on day 14 between dexamethasone and prednisolone.10 patients i.e. 6.6% in prednisolone and 12 i.e. 7.9% in dexamethasone group had relapse of symptoms of asthma on day 14 with a 'p' value of 0.65 which was not significant. conclusion: single dose dexamethasone is as effective as multiple doses of prednisolone as measured by relapse of symptoms in children with acute exacerbation of asthma. key words: asthma, dexamethasone, prednisolone, relapse. a chronic inflammatory disorder characterized by 5 airway hyper responsiveness. bronchoconstriction leads to airway edema in response to certain triggers leading to cough, shortness of breath, chest tightness and wheeze along with variable limitation 6 of expiratory airflow. patients with asthma experience exacerbations with worsening of their symptoms. in 2019 british thoracic society (bts) guidelines recommend inhaled β agonist as first line 2 treatment for asthma along with early use of 7 steroids. systemic corticosteroids for shorter duration are mainstay for asthma exacerbations 8 which are moderate to severe. corticosteroids decrease relapses of illness, admission to hospitals and the requirement for bronchodilators. the steroid recommended is prednisone/prednisolone orally for five days, as oral is as effective as 9 intramuscular and intravenous route. however; prolonged duration of treatment with prednisolone introduction 1 asthma is one of the common pediatrics illnesses. it is a frequent cause of presentation in the emergency department and hospitalization. in children it is estimated that asthma causes an estimated loss of 2 14.4 million school days. asthma is a worldwide problem with an estimated 300 million affected 3 individuals. global initiative of asthma (gina) 4 reports a prevalence of 4-5% in pakistan. asthma is dexamethasone versus prednisolone in relapse of symptoms in children with acute exacerbations of asthma 1 2 3 hijab shaheen , shagufta sohail , noshina riaz correspondence: dr. noshina riaz assistant professor department of pediatrics yusra medical and dental college, islamabad e-mail: noshi_17@hotmail.com 1 department of pediatrics pakistan institute of medical sciences, islamabad 2,3 department of pediatrics yusra medical and dental college, islamabad funding source: nil; conflict of interest: nil received: january 18, 2019; revised: march 10, 2020 accepted: march 16, 2020 dexamethasone vs prednisolone in acute exacerbations of asthmajiimc 2020 vol. 15, no.1 33 for 3-5 days and its bitter taste leading to vomiting 10 may decrease compliance with it. dexamethasone is tried as an alternative to prednisolone. it has a long half-life (36 to 72 hours) as compared to prednisolone (12 to 36 hours) so it requires fewer 10 doses as compared to prednisolone. furthermore it tastes better and costs less. it can be given orally or via intramuscular route ensuring compliance. a number of studies have published which compared single or two days per oral or intramuscular dexamethasone with 3 or 5 days of prednisone or prednisolone. there is increasing documentation t h a t s h o r t d u r a t i o n o f t r e a t m e n t w i t h dexamethasone is as effective as prednisolone in asthma exacerbations which are mild or moderate in severity. asthma is a common illness in our community. although there are multiple trials available in the literature to support equivalence of dexamethasone versus prednisolone, there is no study conducted in this regard locally. secondly the available guidelines are still supporting use of prednisolone in asthma exacerbations. so we decided to carry out this comparative study in our local population in the emergency department to compare the relapse rate of symptoms in children with acute exacerbations of asthma receiving either oral dexamethasone or prednisolone. materials and methods it was a randomized control trial conducted at the emergency department, children's hospital, pakistan institute of medical sciences (pims), st st islamabad from 1 january 2016 till 31 december 2016.total sample size was 302 cases and 151 patients were included in each group receiving either dexamethasone or prednisolone. consecutive, nonprobable sampling technique was used. permission from the hospital ethical committee was taken before the commencement of study. inclusion criteria was children of age 2 to 12 years, both male and female with previous history of asthma as diagnosed by a physician , who present with acute exacerbation of asthma in emergency department. asthma exacerbation was interpreted as acute attack of asthma with symptoms of cough, wheeze, dyspnea and oxygen saturation of less than 95% and w i t h p e d i a t r i c r e s p i r a t o r y a s s e s s m e n t 11 measure(pram) score of more than or equal to 6. this score takes into account 5 items to evaluate severity of asthma. suprasternal retractions, scalane muscle contraction, air entry in chest, wheeze and oxygen saturation with individual score of 0-4 for each sign. total score from 1-3 shows mild exacerbation, 4-7 shows moderate exacerbation and 8-12 reveals severe exacerbation of asthma. patients with silent chest, cyanosis, drowsy, unable to verbalize, having marked tachycardia and respiratory distress, having known exposure to tuberculosis, fever more than 39.5c°,use of corticosteroids in previous 4 weeks and those having significant comorbid were excluded from the study . eligible participants were identified during clinical consultation in emergency department and pram score was assessed by the study physician. informed w r i t t e n c o n s e n t w a s o b t a i n e d f r o m parents/guardians. randomization was done by lottery method. the study physician was responsible for randomization, dispensing , accountability and collection of medicinal products and maintenance and documentation of patient's record and data. study packs of the medicines were made; each labeled clearly with name of the m e d i c a t i o n “ p r e d n i s o l o n e ” o r “dexamethasone.”the randomized patient was either given a stat dose 0.3mg/kg dexamethasone orally (maximum 12mg) or prednisolone orally in 1mg/kg dose (maximum 40mg) followed by two doses after discharge. if the patient was randomized to the group of dexamethasone that was the only dose. if the patient was randomized to have prednisolone, two doses were provided to the patient prior to discharge from emergency department for next two subsequent day intake to complete 3 days of treatment. subjects and parents/guardians were trained to administer prednisolone on second and third day of treatment. patients were asked to bring the empty (dose) packs on the fourth day and were reassessed for pram score .patients were then called after two weeks and enquired about symptoms of relapse of asthma. a relapse was interpreted as a visit to physician for symptoms of wheeze, breathing difficulty and cough 10 within two weeks of inclusion in the study. patients who vomited after oral steroids, whose condition deteriorated and required hospitalization, those did not appeared for day 4 pram score reassessment or jiimc 2020 vol. 15, no.1 34 dexamethasone vs prednisolone in acute exacerbations of asthma were lost to follow up at two weeks were excluded from the study. spss version 20 was used for entry and analysis of non-parametric data. data was presented as mean with standard deviations. percentage was calculated from descriptive variables. chisquare test was used. p value was significant if less than 0.05. results total 302 patients were finally enrolled in the study and 151 children were included in each group. regarding age of patients, 71 i.e. 47% in prednisolone and 93 i.e. 61.5% in dexamethasone group were between 2-7 years of age while 80 i.e. 52.9% in prednisolone and 58 i.e. 38.4% in dexamethasone group were between 8-12 years of age. mean age was 7.48± 2.53 years in prednisolone and 7.07± 2.16 in dexamethasone group. 96 i.e. 63.5% in prednisolone and 80 i.e. 52.9% in dexamethasone group were male while 55 i.e. 36.4% i n p r e d n i s o l o n e a n d 7 1 i . e . 4 7 . 0 2 % i n dexamethasone group were female. pram score for each patient either in the dexamethasone or prednisolone group at time of induction in study was calculated and distribution of all patients according to the score is shown in table i. majority of the patients either in dexamethasone or prednisolone group had a score of 9 or 10 at induction. no patient having pram score of 12 was included in either group because of associated co-morbidities. patients i.e. 7.9% in dexamethasone group had relapse of symptoms of asthma like cough, wheeze or breathing difficulty documented on day 14 follow up, whereas 141 i.e. 93.3% in prednisolone and 139 i.e. 92% in dexamethasone group had no relapse of symptoms. this difference was not statistically significant with 'p' value of 0.65. discussion this study suggests that in children with acute exacerbation of asthma, there was no significant difference in relapse of symptoms either treated with prednisolone or dexamethasone on a 14th day follow up. dexamethasone is as effective as prednisolone and can be used as an alternative to prednisolone in management of exacerbations of asthma. it requires lesser/fewer doses than prednisolone; effects are equivalent but not inferior to prednisolone. the results of our study are comparable to a trial done by cronin et al. comparing dexamethasone to 10 prednisolone for acute exacerbations of asthma. they concluded that a single oral dose of dexamethasone (0.3mg/kg) was non inferior to a 3 days treatment of prednisolone (1mg/kg/day) as measured by mean pram score on day 4.no significant difference was also observed in both groups receiving either dexamethasone or prednisolone in hospital admissions or number of return unscheduled visits after treatment to hospital. keeney et al.in their analysis regarding risk of relapse of symptoms between dexamethasone and prednisolone at day 5 and 10-14 days found no 12 significant difference. however they included studies comparing both oral and intramuscular dexamethasone with oral prednisolone in their analysis. a double blind, randomized controlled trial was conducted in india to compare the efficacy of oral dexamethasone to prednisolone in treatment of moderate exacerbation of bronchial asthma in 2 children. they also concluded that single dose of dexamethasone was as effective as three doses of prednisolone as no significant difference was observed in mean time in hours to attain a pram score of less than 2 and number of bronchodilator nebulization in both groups randomized to receive either dexamethasone or prednisolone. paniagua et al in a randomized, non-inferiority trial table i: distribu�on of pa�ents according to pram score the mean pram score at baseline was calculated as 8.90 ± 1.40 in prednisolone and 8.86 ± 1.49 in dexamethasone group. it was 0.92± 0.33 for prednisolone and 0.96 ± 0.25 for dexamethasone th group on 4 day of treatment. the mean change in pram score from baseline to reassessment at day 4 w a s 7 . 9 8 fo r p r e d n i s o l o n e a n d 7 . 9 0 fo r dexamethasone group. only 10 patients i.e. 6.6% in prednisolone and 12 jiimc 2020 vol. 15, no.1 35 dexamethasone vs prednisolone in acute exacerbations of asthma compared efficacy of two doses dexamethasone (0.6 mg/kg/dose) to five days of oral prednisolone (1.5 mg/kg/day, followed by 1mg/kg/day on days 213 5) in children with asthma exacerbations. both groups showed no difference related to persistence of symptoms and unscheduled emergency department visits at day 7. they also suggested dexamethasone as an effective alternate to prednisolone. a cochrane review by norman sell et al which reviewed 18 randomized studies comparing dexamethasone to prednisolone suggested a comparable (not superior) efficacy and safety of 14 dexamethasone to prednisolone. however, it suggested larger studies with oral steroids to make conclusions as different studies had used different doses and duration of steroids and different methodologies to measure results. our study suggests dexamethasone as a potential alternate for prednisolone. longer half-life as compared to prednisolone leading to less frequent dosing, better taste, lesser cost and similar efficacy as documented by insignificant difference in relapses of both groups makes it a better alternative therapy. limitation of our study was small sample size in each group and only children of two to twelve years were included in our study so findings are required to be confirmed with a larger trial. secondly this study was conducted in the emergency department of the hospital and further studies are required to apply this management to ambulatory outpatient clinics as well. conclusion single dose dexamethasone is as effective as multiple doses of prednisolone as measured by relapse of symptoms in children with acute exacerbation of asthma. references 1. wei j,luy,f han f, zhang j, liu l, chen q.oral dexamethasone versus oral prednisone for children with acute asthma exacerbations: a systemic review and metaanalysis. front pediatr.2019; 7:503. 2. prasannavenkatesh k, gunasekaran d, pandi k, srinivasaraghavan r, anandhi c, soundararajan p. singledose oral dexamethasone compared with three day course of oral prednisolone in children with moderate exacerbation of asthmaa pilot double blinded randomized controlled trial. j clindiag res. 2018; 12(2):sc01-03. 3. dharmagesc,perretjl,custovica.epidemiology of asthma in children and adults.frontpediatr. 2019; 7:246. 4. basharat s, jabeen u, zeeshan f, banoi, bari a, rathore aw. adherence to asthma treatment and their association with asthma control in children.j pak med assoc.2018 may;68(5):725-28. 5. kumari v, jagzape tb. bronchialasthma: prevalence and risk factors among children in urban population from raipur, chhattisgarh.indian j allergy asthma immunol 2019;33:4550. 6. pavordi d, beasley r, agusti a, anderson gp, bel e, brussel g, etal. after asthma: redefining airways diseases. lancet. 2017;391:350-400. 7. bts/sign. british guideline on management of asthma.(2019).available online at:https://www.britthoracic.org.uk/quality-improvement/guideline/asthma. 8. al-shamrani a, al-harbi as, bagais k, alenazi a, alqwaiee m. s, management of asthma exacerbation in emergency departments. int j pediatr adolesc med.2019 jun;6(2):6167. 9. mathew jl. oral dexamethasone versus oral prednisolone in acute asthma:a new randomized controlled trial and updated meta-analysis:evidence based medicine viewpoint. indian pediatr.2018 feb15;55(2):155-59. 10. cronin jj, mccoy s, kennedey u, an fhailí sn wakai a, hayden j, crispino g, barrett mj, walsh s, o'sullivan r. a randomized trial of single-dose oral dexamethasone versus multi-dose prednisolone for acute exacerbations of asthma in children who attend the emergency department. ann emerg med.2016 may; 67(5):593-601. 11. thaweerujirot c, daengsuwan t. comparison between pediatric respiratory assessment measure (pram) score and wood's asthma score to assess acute asthma exa c e r b at i o n . a s i a n pa c j a l l e rg y i m m u n o l . 2 0 1 9 sep;37(3):123-129. 12. keenayge, gray mp, morrison ak, levas mn, kessler ea, hill gd, etal. dexamethasone for acute asthma exacerbations in children: a meta-analysis.pediatrics.2014 mar;133(3):493499. 13. paniagua n, lopez r, munoz n, tames m, mojica e, aranaarri e, etal. randomizedtrial of dexamethasone versus prednisolone for children with acute asthma exacerbations. j pediatr.2017 dec;191:190-196. 14. normansell r, kew km, mansour g. differenent oral corticosteroid regimens for acute asthma. cochrane database syst rev.2016;5:cd011801. jiimc 2020 vol. 15, no.1 36 dexamethasone vs prednisolone in acute exacerbations of asthma original�article abstract objective: to investigate the prevalence of bullying-victimization in adolescents and to subsequently explore impact of socio-demographic variables. study design: this cross-sectional research design. place and duration of study: the study was conducted in department of psychology, university of gujrat and data was collected from february to may 2019. materials and methods: stratified sampling technique was applied to select 608 students, with age range between 16 to 19 years, from the private-public colleges of sarai alamgir with the permission of principals and teachers. urdu version of adolescent peer relationship inventory (apri) along with demographic form was administered on the students with their informed consent. results: in 608 college students, 246(59.3%) were males and 169(40.8%) females. the prevalence for bullying in low, moderate and high categories was 57.2%, 21.1% and 21.7% respectively. whereas 47.7%, 28%, and 24.3% of victimization in adolescents was prevalent in low, moderate and high categories. hierarchical regression analysis found that gender, family system, and institution type are significant risk factors for predicting bullying-victimization syndrome and contributed to 19% of variance explained. significant differences existed between gender, in which male students suffered more by bullying-victimization syndrome 2 as compared to female students (χ =103.50, p<0.001). however, adolescents living in joint family system were 2 significantly victimized more than the one living in nuclear family systems (χ =5.55, p<0.05). there were 2 significant differences in bullying behaviours of the students studying in public and private colleges (χ =4.20, p<0.05). students studying in public colleges expressed more bullying behaviour than students studying in private colleges. conclusion: the phenomenon of bullying and victimization is prevalent in the adolescents studying at college level. demographic variables of gender, family system, and institute type served as risk factors for bullying and victimization syndrome. key words: adolescent, adolescent health, bullying, peer influence, victims. present study is necessitated. empirical research has posited the point that emotional distress, depression, and even suicidal ideation are linked w i t h b u l l y i n g v i c t i m i z a t i o n s y n d r o m e i n 2-3 adolescents. in addition, frequent fights and harassment has been found to shrink academic 4 achievements of the adolescents , effect their future careers indirectly and making concerned issue worth studying. internationally, the phenomenon of bullyingvictimization syndrome is widespread. the peak prevalence rate of bullying and victimization in 11 to 15 years old children across 40 baltic and european countries was found to be 45.2% in boys, and 35.8% 5 in girls. in 1,529 chinese adolescents with fifteen years mean age, 6% showed high traditional bullyingvictims prevalence and 2% showed high cyber bullyvictims prevalence rate in males with high introduction a recent survey with 17.2% depression and 21.4% anxiety in adolescents between eleven to eighteen 1 years in pakistan , set an alarm for investigation of possible factors playing role in contributing to emotional distress in pakistani youth. in early adolescence, peer group influences played a significant role in the mental health, inclusion of the phenomenon of bullying and victimization in the socio demographic risk factors of bullying and victimization in adolescents: prevalence based study sameera shafiq, sidra batool correspondence: sameera shafiq (ph. d. scholar) lecturer department of psychology university of gujrat, gujrat e-mail: sameerashafiq@yahoo.com department of psychology university of gujrat, gujrat received: july 6, 2021; revised: march 03, 2023 accepted: 03, march 2023 socio-demographic risk-factors of bullyingjiimc 2023 vol. 18, no.1 50 https://doi.org/10.57234/jiimc.march23.642 6 interparental problems , thus acme the importance of gender, and family support. a systematic list of identified risk factors for bullying and victimization in the review of literature, relevant to the present study 7 8 were found to be age , urban/rural setting , family 9-10 9-11 7-8 system , socio-economic status , and gender. thus, literature review has highlighted the importance of various socio-demographic variables as playing role in bullying and victimization of the adolescents. in pakistan, research based on study of prevalence and demographic correlates of bullying were based on the sample of either school children or university early adult students. negligence is observed in identifying crucial factors of peer violence in early adolescents studying in colleges. these college students comprised part of youth and are approximately 29% of the general population. therefore, sample of college students cannot be i g n o re d fo r i nve st i gat i o n o f b u l l y i n g a n d victimization that might affect their prognosis for mental health in adulthood. thus, implications of the findings of the present study would point out towards conducting effective intervention plans in college students, screened for risk factors, identified in the present study. the objectives of the present study included investigation of the prevalence of occurrence of bullying and victimization in college adolescents. moreover, socio-demographic risk factors have also been explored to understand the phenomenon in detail in pakistani youth. materials and methods the present cross-section research was conducted at the department of psychology, university of gujrat, gujrat. the data was collected from february to may 2019. stratified random sampling technique was used and two strata were identified as private and public college domains. a list of institutions (both public and private) in sarai alamgir was taken from district office, gujrat. randomly two public and two private colleges were selected from the provide list. 14 taro yamane formula was used to calculate the sample and 608 students were contacted randomly in their classes. moreover, the students exhibiting any mental or physical disorder were excluded. ethical approval was taken from advanced studies a n d r e s e a r c h b o a r d w i t h r e f e r e n c e n o : uog/asrb/psychology/15177. inclusion criteria focused on the students who were more than 16 and less than 19 years of age. the students with age below 15 and above 20 were excluded from the 12 study. demographic sheet along with urdu version 13 of adolescent peer relations instrument (apri) with 36 items and two subscales of bullying and victimization, each having three components verbal, social, and physical aspects was used in the present study. it is likert type scale with six categories of responses having scored one to six. the cronbach alpha reliability coefficient of apri on the present sample was 0.88, showing strong index of acceptance. prior to taking informed consent from the students, formal permission was taken from the principals and concerned teachers. the students were approached in the classrooms. written informed consent with introduction to the research study was taken. confidentiality was maintained and they were informed of their right to withdraw at time from the study. any queries and concerns were addressed appropriately, and satisfactory answers were given. the parametric data obtained was analysed in spss21. frequencies and percentages were calculated for low, moderate, and high levels of bullying and victimization. inferential statistics was used to calculate the significant results with p value less than 0.05 level. a hierarchical regression analysis, conducted in two steps to analyse the effects of socio-demographic variables along with selfregulation on bullying and victimization of adolescents. before conducting hierarchical regression analysis, the categorical variables such as gender, class, profession, residential area, family system and intuition type were dummy coded where st boys, 1 year, arts group, rural area, joint family, and public served as a reference point and the remaining served as a dependent category. chi-square was calculated to investigate the association of predicting variables such as gender, family system, and institution type with three levels (low, moderate, and high) of bullying and victimization syndrome in adolescents. results the high prevalence rate of bullying is 21.7% and victimization is 24.3% in 608 college students, selected by stratified sampling technique in privatepublic colleges of sarai alamgir (table-i). in step-i of hierarchical regression analysis, socio-demographic socio-demographic risk-factors of bullyingjiimc 2023 vol. 18, no.1 51https://doi.org/10.57234/jiimc.march23.642 variables such as age, class, line of professional studies (such as arts, science), residential area, and family monthly income with ambivalent research findings were entered. in step-ii, empirically significant socio-demographic variables such as gender, family system, and institution type were entered. consequently, two models emerged. the first model showed that age, class, profession, residential area, and monthly income did not significantly predict peer relationship of adolescents. the second model showed that gender (β= -.427, p<.001), family system (β= -.090, p<.001), and institution type (β= -.127, p<.001) significantly predicted the relationships of adolescents with their friends, explaining 19% variance in the scores of bullying and victimization (f=17.90; p<.001). the negative signs in gender, family system, and institution type showed that girls, nuclear family, and private colleges have less impact on bullying and victimization as compared to boys, joint family, and public colleges (tableii). chi-square analysis 2 showed significant gender differences in bullying (χ = 2 103.50, p<0.001) and victimization (χ 82.49, = p<0.001) as boys suffered more than girls. similarly, significant victimization occurred in adolescents 2 living in joint families (χ 5.50, p<0.001) as compared = 2 to nuclear counterpart. public colleges (χ 4.20, = p<0.001) exhibited significant bullying than private colleges in adolescents (table-iii). table i: levels, frequencies, and percentages of bullying and victimization in adolescents (n=608) f=frequencies, %=percentages table ii: hierarchical regression analysis for sociodemographic variables in peer relationship in adolescents (n=608) table iii: association of predicting socio-demographic risk-factors for bullying and victimization in adolescents (n=608) ***p<0.001 ***p<0.001, *p<0.05 discussion the findings of the present research showed that the average percentage of bullying is 22.25% and victimization is 17.45% which implied that the high bullying prevalence rate (21.7%) in college students of sarai alamgir and this result is relatively like findings from other districts. a cross-sectional study conducted (2020) in five districts of punjab namely lodhran, rahim yar khan, bahawalpur, faisalabad, multan; and two districts of sindh namely thatta, and nawabshah showed that 26.6% children were bullied at school and 17.9% were bullied away from school. 18.6% children were victimized at school and 1 5 16.3% away from school . however, 24.3% victimization prevalence is high in college students of sarai alamgir as compared to other provinces of pakistan. still this frequency of occurrence of bullying-victimization problem in our study is relatively low as compared to prevalence rate of faisalabad (2021) which was reported to be 49% bullying and 36% victims in adolescents with mean 16 age fifteen years. yet a controlled randomized trial (2017) of school children in hyderabad showed relatively high bullying-victimization percentage in boys and girls, reported as 72.6% and 46.4% 17 respectively. similarly, in district gujrat, 42.6% school children reported victimization and 50.5% 18 reported being bullied. the findings implied that socio-demographic risk-factors of bullyingjiimc 2023 vol. 18, no.1 52 https://doi.org/10.57234/jiimc.march23.642 high prevalence of violence against children and adolescents in pakistani schools and colleges, contributed to poor emotional-behavioural physical 19,20 and mental health in youth. thus, alarming condition of increasing incidences of bullying and victimization implied for the introduction of counselling services at college level to handle and m a n a g e t h e a f f e c t e d c a s e s w i t h p r o p e r psychotherapeutic inter vention. though in comparison to the other cities of pakistan, district gujrat has showed relatively low prevalence of bullying and victimization yet has set an alarm to take notice of the situation by screening youth for possible mental issues on one hand, and introduce coping strategy based interventions on other hand. socio-demographic variables such as age, class, line of professional studies (such as arts or science), residential area, and monthly in-come were found to be insignificant predictors of bullying-victimization syndrome in early adolescents. the results are consistent with the findings of the previous studies. no significant differences were found with respect to age, and urban or rural area in cyber bullying across 21 sindh, pakistan in adolescent . age has been found to be non-significant predictor of bully-victim cases i n t h e st u d e nt s st u d y i n g u n d e r pa k i sta n i 21 universities. in present study, socio-demographic variables such gender (girls versus boys), family system (joint versus nuclear family) and institutional type (private college versus public college) are found to be significant predictors of bullying-victimization syndrome in early adolescents. findings of past research revealed that 950 university adolescents in pakistan show significant gender differences with reference to traditional bullying-victimization phenomenon in which boys are high in bullying and low in 9,22 victimization as compared to girls. the patriarchal pattern of pakistani society would serve as plausible explanation for such a discrepancy of aggression expression in the form of fights and harassments in adolescents. female students also exhibited victimization, yet the prevalence is low than male students. in addition to gender, family context and values are found to be associated with the bullying 23-24 phenomenon in adolescents . the research findings of the present study show that adolescents experienced significant victimization while living in joint family system as compared to nuclear family system. perhaps family's over intrusion or negligence has caused sufferings for the adolescents as they would have become more dependent on the circle of the friends for their secondary need satisfaction and might have become prone to their victimization. moreover, earlier research indicated that students studying in public schools are more victim of bullying 25-26 as compared to private counterparts in pakistan . these findings are consistent with the results of the present study with implications to launch strategic changes in the environmental elements of the government schools that foster reduction of fights and victimization issues in the adolescents. conclusion there is 21.7% bullying and 23.4% victimization prevalence among adolescents studying in various colleges of sarai alamgir. being male, living in joint family system and studying in public colleges serve as risk factors for high experiencing of peer related violence in the form of bullying and victimization. male students face significantly more incidences of bullying and victimization as compared to female students. victimization is significantly high in joint family systems as compared to nuclear family systems of the adolescents. the students of public colleges show significant high incidences of bullying as compared to private colleges. therefore, policy makers should initiate steps for recruitment of psychologists and school psychologists in public colleges of punjab and enforce laws for better handling issues of grievances. limitations and suggestions the present quantitative research has not explored the perceptions of the students regarding the concepts of bullying and victimization. in future, qualitative study could be designed to gauge the issue in-depth and enrich narration could be published for devising intervention strategies to sooth traumatic experiences of youth as a result of bullying and victimization. the current study has only focused on sarai alamgir. further, study might use multistage cluster sampling technique to collect data from various cities of punjab and get a better picture of the study variables in detail. some important factors effecting the bullying and victimization are missing. personality variables long with parental socio-demographic risk-factors of bullyingjiimc 2023 vol. 18, no.1 53https://doi.org/10.57234/jiimc.march23.642 interaction could be studied to understand the bullying-victimization syndrome in detail in future. disclaimer this article along with its abstract has not been published in any conference. the data for the article was taken from mphil thesis of sidra batool, conducted under supervision of ms. sameera shafiq, lecturer, department of psychology, university of gujrat, gujrat. references 1. khalid a, qadir f, chan sw, schwannauer m. 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in public, commercial or nonprofit sector. data sharing statment the data that support the findings of this study are available from the corresponding author upon request. this is an open access article distributed under the terms of the creative commons attributionnoncommercial 2.0 generic license. socio-demographic risk-factors of bullyingjiimc 2023 vol. 18, no.1 55https://doi.org/10.57234/jiimc.march23.642 original�article abstract objective: to determine the frequency of dental midline deviation in different age groups of school children of lahore, pakistan. study design: observational cross-sectional study. th th place and duration of study: the study was performed in 7 different schools of lahore, from 11 march to 30 may 2019. materials and methods: a total sample of 300 children (190 girls, 110 boys) was taken whose ages were between 8 to 16 years. midline deviations were observed with scale in millimeters, by taking the philtrum as a reference landmark. the statistical analysis was implemented with spss version 20. qualitative data like gender, midline deviation and type of dentition was presented in the form of frequency and percentage. data was stratified for gender and dentition. post-stratification chi -square test was applied with p-value ≤ 0.05 considered as significant. results: frequency of midline deviation was found to be 69.7% of which mandibular midline deviation was more frequent (45.7%) followed by maxillary midline deviation (12.7%), with the severity of 2mm being most common (42.3%). deviation of both midlines was observed in 11.3% of students. the difference of frequency of midline shift in gender (p=0.924) and dentition (p=0.109) was insignificant. conclusion: the study concluded that the most frequently observed dental deviation was mandibular midline deviation towards right side relative to facial midline. no significant differences were displayed regarding gender and dentition. key words: cupid's bow, dental asymmetry, incisive papilla, philtrum, smile esthetics. midline deviations and can even appreciate 1 mm 5 deviation of dental midline. the magnitude to which the maxillary and mandibular dental midlines deviate from the facial midline is often recorded, with an aim that these midlines should be coincident after orthodontic treatment. it is an essential aspect of functional occlusion and serves as a clinical 6,7,8 template to achieve maximum intercuspation. an individual's facial midline (constructed from glabella, base of the nose, nasal apex, upper lip cupid's bow and central point of the chin) is used as a 4,9,10 reference line to evaluate dental midline. the incisive papilla between the maxillary central incisors is normally found below the center of the 10 philtrum. one of the studies reported that the patients tend to relate their maxillary midline to the 8,11 upper lip. the philtrum is generally considered to be a valid facial landmark for assessment of 6,11 midline. however, this may be misleading due to the presence of a variable degree of asymmetry in facial structures, therefore, the incisive papilla could be an alternate intraoral landmark as it follows the introduction frontal symmetry and balanced smile are the 1,2 appraisal standards of facial appearance. any discrepancy in facial and dental harmony of 3 corresponding parts can cause asymmetry. midline deviations are most obvious of all the dental and occlusal asymmetries, as dental midline is a focal point in smile esthetics. the effect of harmonized facial and dental midlines on clinical outcome of 4 orthodontic treatment is undebatable. orthodontists are considerably less tolerant of frequency of dental midline deviation in school children of lahore, pakistan: a crosssectional study 1 2 3 4 faiza rana , faiza malik , esha rana , rabia tabassum correspondence: dr. faiza rana demonstrator department of orthodontics sharif medical and dental college, lahore e-mail: dr.faizarana03@gmail.com 1,2 3 department of orthodontics/ operative dentistry sharif medical and dental college, lahore 4 department of orthodontics university medical and dental college, faisalabad received: may 29, 2021; revised: june 02, 2022 accepted: june 04, 2022 dental midline deviation in school childrenjiimc 2022 vol. 17, no.2 81 9 direction of the deviation. e m p h a s i s o n d e nto a l ve o l a r e st h et i c s h a s heightened among orthodontists and patients. although an ideal occlusion is still an important goal of treatment, the ideal esthetic outcome is crucial for 7,8 patient's and orthodontist's gratification. the treatment for existing discrepancies in midline may involve tooth movement, dental extractions, orthopedic treatment, or even orthognathic 7 surgery. in pakistan there has not been much previous research done to determine the frequency of maxillary and mandibular dental midline asymmetry. so, this cross-sectional survey was conducted to determine the frequency of dental midline deviation in different age groups of school children of lahore, pakistan. this provided some valuable local data base to create awareness among school children regarding their orthodontic treatment need. materials and methods this was an observational cross-sectional survey, th performed in 7 different schools of lahore, from 11 th march to 30 may 2019. the study was done on a sample of 300 school children belonging to grade 310, selected via non-probability consecutive sampling technique to determine the frequency of dental midline deviation. sharif medical research center approved the study, followed by ethical approval with the letter number smdc/smrc/19421. prior permission was taken from the school principals. the inclusion criteria were children of both genders, aged 8 years and above, irrespective of the type of dentition and malocclusion. children with unerupted or impacted incisors, missing or extracted teeth, history of orthodontic treatment, restoration of anterior teeth, craniofacial anomalies like cleft lip and/or palate, were excluded. data was collected by clinical intraoral observation and examination of children after taking written informed consent from their parents. all data was collected by the primary researcher. to avoid visual fatigue, number of students examined per day was kept to a maximum of 30, which corresponded to the number of students in one class. maxillary and mandibular dental midline deviations were measured with a clear plastic scale to the nearest millimeter by taking the philtrum (cupid's bow) as a reference landmark (figure 1). data was non-parametric and statistical analysis was performed with ibm spss version 25. qualitative data like gender, midline deviation and type of dentition were presented in the form of frequency and percentage. the magnitude and side of midline deviation was also noted. data was stratified for gender and dentition. post-stratification chi -square test was applied with p-value ≤ 0.05 considered as significant. results overall, the sample consisted of 300 students (190 females, 110 males) out of which, 157 (52.3%) were in the mixed dentition group and 143 (47.7%) were in the permanent dentition group. the mean age of the sample was 11.5 ± 2.5 years, ranging from 8-16 years. frequency of midline deviation was found to be 69.7% (table i) of which mandibular midline deviation was more frequent (45.7%) followed by maxillary midline deviation (12.7%). deviation of both midlines was observed in 11.3% of students. table ii represents the severity of dental midline deviation. in most of the patients, dental midlines were shifted from the facial midline by 2mm (42.3%), that was more likely towards right side of the face. table iii shows the difference of midline deviation among gender (p = 0.924) and dentition (p = 0.109), which was statistically insignificant. fig. 1: measuring maxillary dental midline deviation from philtrum of upper lip table i: frequency of midline deviation dental midline deviation in school childrenjiimc 2022 vol. 17, no.2 82 discussion this cross-sectional study was conducted to provide valuable local database of maxillary and mandibular dental midline deviation and to give awareness of orthodontic treatment among school children. we used philtrum as a reference for the evaluation of dental midline deviation as this is a valid facial landmark and patients generally relate their midline 11 to the upper lip. dental midline is a vital element in smile design. midline should be perpendicular to incisal plane and 12,13 incisive papilla. the parallelism between the maxillary dental midline and facial midline is more fundamental than the coordination between these midlines. a minor midline deviation is acceptable if connector between the maxillary central incisors is 4 vertical. d e n t o fa c i a l a t t ra c t i v e n e s s i s r e d u c e d b y discrepancies between dental and facial midlines. the maximum amount of deviation acceptable to orthodontists before it has negative impact on smile esthetics, has been documented to be 1mm to 5,7,8,14,15 2mm. ker et al and springer et al observed that almost 3 mm of deviation is acceptable by 16,17 layperson. beyer and lindauer reported that 2mm midline shift was detectable by almost 18 everyone. according to kokich and shapiro, a 4mm maxillary midline deviation was not noticed by laypersons, whereas a 2mm deviation in incisor a n g u l a t i o n w a s r e g a r d e d a s r e m a r k a b l y 4,5 unattractive. therefore, dental and facial esthetics 7,16 are of fundamental concern in orthodontics. in the present study, lack of midline coincidence was found to be 69.7%. sheats et al conducted a study at virginia commonwealth university and found 46% lack of midline coincidence in orthodontic 7,19 population. they also concluded that the most frequently seen trait of asymmetry was mandibular midline deviation from the facial midline and maxillomandibular midline deviation. thilander et al 20 registered midline deviation in 13.2% subjects. they found that it increased with age and was more frequent in lower arch. borzabadi et al observed noncoinciding dental midlines in 23.7% of urban iranian 21 sample. this study also concluded that mandibular midline deviation was the most seen asymmetry (45.7%). jain et al. noticed midline deviation in 77% of 22 orthodontic patients. of overall dental midline deviation, 21% patients had maxillary midline deviation and 43% had mandibular midline deviation 22 which is almost twice of maxillary midline deviation. bhateja and fida observed that most frequent asymmetry seen was non-coinciding dental midlines 23 in 78.2% of patients. mandibular midline deviation was observed in 67.5% of patients whereas, maxillary 23 midline deviation was found in 14.3% of patients. however, the side of deviation was not recorded. the severity of midline deviation in majority of patients was found to be 2 mm in this study, which is similar to the findings of bhateja et al who reported 23 the severity of about ¼ of lower incisor width. moreover, this study found that midline deviation was mostly towards right side of the face which is in contrast to khan et al and eskelsen et al who revealed that dental midline is mostly shifted towards left side 24,25 of the face. the current study, having a cross-sectional design, had some limitations. the method of evaluating midline deviation was relatively inadequate at times, mostly in the evaluation of centric occlusion and centric relation (co-cr) shifts. the co-cr shift was not investigated in this study, therefore, a possibility of mandibular midline deviation due to underlying table ii: severity of midline deviation table iii: stratification of midline deviation with respect to gender and dentition p-value > 0.05 shows insignificant statistical difference. dental midline deviation in school childrenjiimc 2022 vol. 17, no.2 83 functional shifts was there. exact assessment of cocr is essential to evaluate the probable origin of such deviations. conclusion this study concluded that mandibular midline deviation was the most frequently observed midline deviation followed by maxillary midline deviation. the common severity of deviation was 2mm most likely towards right side of the face. no statistically significant differences were displayed regarding gender and dentition. references 1. sriphadungporn, c., chamnannidiadha, n. perception of smile esthetics by laypeople of different ages. prog orthod. 2017; 18:18. 2. williams r, rinchuse d, zullo t. perceptions of midline deviations among different facial types. am j orthod dentofacial orthop 2014; 145:249-55. 3. bhardwaj a, miglani a and gupta m. decoding the facial asymmetry. j dent specialities 2020;8(1):13–17. 4. sabri r. the eight components of balanced smile. j clin orthod march 2005; 3:155-167. 5. melo m, ata-ali j, ata-ali f, bulsei m, grella p, cobo t, et al. evaluation of the maxillary midline, curve of the upper lip, smile line and tooth shape: a prospective study of 140 caucasian patients. bmc oral health 2020; 20: 42. 6. narmada s, kumar kp, raja s. management of mid-line discrepancies: a review. j ind acad dent spec res 2015; 2:45-8. 7. priya s, sumathi a. prevalence of maxillary midline shift in female patients. drug invent. /today. 2019:11(1):77-80. 8. rossini g, parrini s, castroflorio t, fortini a, deregibus a, debernardi cl. children's perceptions of smile esthetics and their influence on social judgment. angle orthod 2016; 86 (6): 1050–1055. 9. al-murtadha r, el-housseiny s, el-beialy ar. maxillary midline and other deviations. austin j dent. 2016; 3(1): 1030. 10. ferreira jb, silva le, caetano mto, motta afj, curysaramago aa, mucha jn. perception of midline deviations in smile esthetics by laypersons. dental press j orthod. 2016;21(6):51-7. 11. khan mf, sharaz s, shariff m, alam mk, binhomran fm, almathami sa. discord between the facial and maxillary midline and intermaxillary midline among the population o f a s i r, s a u d i a r a b i a . p e s q u i s a b r a s i l e i r a e m odontopediatria e clínica integrada 2019; 19: e4700. 12. parrini s, rossini g. laypeople's perceptions of frontal smile esthetics:a systematic review. am j orthod dentofacial orthop 2016; 150:740-50. 13. mavani s, ramesh tr, patel n and patel v. evaluation of coincidence of facial midline to dental midline and maxillary midline to mandibular midline in undergraduate students. int. j. adv. res. 2017; 5(2):2364-2369. 14. sadrhaghighi ah, zarghami a, sadrhaghighi s, mohammadi a, eskandarinezhad m. esthetic preferences of laypersons of different cultures and races regarding smile attractiveness. indian j dent res 2017; 28:156-61. 15. öz aa, akdeniz bs, canlı e, çelik s. differences among the perceptions of dental professionals and laypersons. turk j orthod 2017; 30: 50-5. 16. ker aj, chan r, fields hw, beck m, rosenstiel s. esthetics, and smile characteristics from the layperson's perspective: a computer-based study. j am dent assoc 2008; 139:131827. 17. springer nc, chang c, fields hw, beck fm, firestone ar, rosenstiel s, et al. smile esthetics from the layperson's perspective. am j orthod dentofacial orthop 2011; 139:91101. 18. almanea r, modimigh a, almogren f, alhazzani e. perception of smile attractiveness among orthodontists, restorative dentists, and laypersons in saudi arabia. j conserv dent 2019; 22:69-75. 19. sheats rd, mcgorray sp, musmar q, wheeler tt, king gj. prevalence of orthodontic asymmetries. semin orthod 1998; 40:138-45. 20. thilander b, pena l. prevalence of malocclusion and orthodontic treatment need in children and adolescents in bogota, colombia. an epidemiological study related to different stages of dental development. eur j orthod 2001; 23:153-167. 21. borzabadi-farahani a, eslamipour f. malocclusion, and occlusal traits in an arban iranian population. an epidemiological study of 11to 14-year-old children. eur j orthod 2009; 31:477–84. 22. jain s, jain v. prevalence of midline shift in orthodontic patients. int j current innov res. dec 2015;1(10):287-290. 23. bhateja n, fida m, shaikh a. frequency of dentofacial asymmetries: a cross-sectional study on orthodontic patients. j ayub med coll abbottabad 2014;26(2):129-133. 24. khan m, kazmi s. coincidence of dental midline with facial midline in a sample of pakistani population. j coll physicians surg pak. mar 2019;29(3):210-213. 25. eskelsen e, fernandes cb, pelogia f. concurrence between the maxillary midline and bisector to the interpupillary line. j esthet restor dent 2009; 21:37-41. dental midline deviation in school childrenjiimc 2022 vol. 17, no.2 84 conflict of interest authors declared no conflicts of interest. grant support and financial disclosure authors have declared no specific grant for this research from any funding agency in public, commercial or nonprofit sector. data sharing statment the data that support the findings of this study are available from the corresponding author upon request. this is an open access article distributed under the terms of the creative commons attributionnoncommercial 2.0 generic license. dental midline deviation in school childrenjiimc 2022 vol. 17, no.2 85 untitled-2 original�article abstract objective: to investigate the accuracy of hba1c in diabetic patients with chronic liver disease (cld). study design: cross-sectional/ observational study. place and duration of study: fauji foundation hospital, rawalpindi (ffh), from july 2019-july 2020. materials and methods: this study was carried out on 100 subjects divided in two groups i.e. group a and group b. group a included diabetics with cld (chronic hepatitis c) and group b included diabetics without cld. each group consisted of 50 known type 2 diabetes mellitus (t2dm) participants, who were randomly selected from liver and medical opd of ffh, rawalpindi. blood samples of the participants were analyzed for hcv, hba1c and liver enzymes. chemical analysis was carried out at the department of pathology ffh, rawalpindi. for statistical analysis version 21 of spss was used. results: our study showed that hba1c levels were low in group a (6.6±1.10% vs. 9.58±2.09% p < 0.05) when compared to group b. group a showed significantly higher levels of alanine aminotransferase (alt) than group b (74.65±21.84 u/l vs. 38.44±23.79 u/l p<0.05). serum albumin was also lower in group a in comparison to group b (29.52±2.21g/l vs. 36.24±3.99 g/l p<0.05). hba1c levels showed significantly negative association with alt in group a (r-0.418 p<0.05) while in group b the negative correlation was not significant statistically (r0.197 p=0.171). a significant negative association of hba1c with albumin was also seen in group a (r-0.391 p<0.05) regression analyses showed a significant relationship between hba1c and alt in group a. conclusion: our study concludes that hba1c levels are significantly decreased in diabetic patients with cld (chronic hepatitis c) than diabetics without cld. therefore, hba1c is not a reliable predictor for long-term glycemic monitoring in diabetic patients having cld. key words: chronic liver disease, chronic hepatitis c, cirrhosis, diabetes mellitus, hba1c. diabetes. hepatic glucose metabolism is significantly 4,6 affected by cld. there are many causes for cld, of which hepatitis c 7 virus (hcv) is most common. hcv is one of the most alarming health problems globally, with an incidence 8 of 200 million (3.3%) of the world's population. “till the year 2017 around 4 million individuals were infected with hcv in the united states and 2.7 million 9 of them were careers.” nearly 30,000 new cases of 10 hcv have been diagnosed annually. the hcv infected people in pakistan is approximated to be 11 more than 10 million. the organ primarily affected by hcv is the liver which then progresses to cirrhosis, 12 chronic liver failure and hepatocellular carcinoma. ghani ur rehman et al. in 2017 revealed that almost one-third of the hcv patients were diabetic. our data records showed that 26.42% of the hcv 13 infected patients were found to have t2dm. the high prevalence of hepatitis c in t2dm has been shown by multiple epidemiological studies, and have also postulated the progression of hepatitis c into development of dm. hcv infection & age as introduction from a decade or so liver disease been recognized as 1,2 a major complication of type 2 diabetes. chronic liver disease (cld) generally takes the clinical form of chronic hepatitis, its long term complications include 3 cirrhosis and hepatocellular carcinoma (hcc). chronic liver disease is accompanied by significantly impaired glucose homeostasis. in cld, around 80% of patients show glucose intolerance, while in 30–60% of patients there is presence of frank hba1c levels in diabetic patients with chronic liver disease 1 2 3 4 5 6 mehnaz khattak , sami saeed , jawwad anis khan , sadaf durrani , hasan ikram , umme farwa correspondence: dr. mehnaz khattak assistant professor fauji foundation hospital, rawalpindi e-mail: mehnaz07@yahoo.com 1,2 department of pathology fauji foundation hospital, rawalpindi 3,6 department of pathology foundation university medical college, islamabad 4 department of biochemistry khyber medical college, peshawar 5 department of pathology army medical college, rawalpindi funding source: nil; conflict of interest: nil received: september 25, 2020; revised: february 04, 2021 accepted: february 12, 2021 hba1c and chronic liver diseasejiimc 2021 vol. 16, no.1 14 documented by mason et al. were independent 14,19 predictors for dm. the american diabetes association (ada) and world health organization (who), both, regard hba1c as the most reliable chemical tool for diagnosis as well 20 as prognosis of glycemic control in t2dm. the use of hba1c for the diagnosis of t2dm is supported by 21 plenty of literature. the turnover of erythrocytes is increased in cld patients, while there is a decrease in 22 serum albumin level. therefore, glycated albumin (ga) and hba1c should not be utilized as tools in cld diabetic patients for monitoring of chronic plasma 23 glucose control. 24,29 literature search showed that many studies have been carried out to see the reliability of hba1c in diabetics with cld in respect to cirrhosis but hardly any studies have been done to see accuracy of hba1c in diabetic population having chronic hepatitis c infection and non-such study has been found to be carried out in pakistan so far. our study aimed to determine hba1c accuracy in t2dm patients with chronic hepatitis c which is first stage of cld to t i m e l y avo i d c o m p l i c at i o n s l i ke c i r r h o s i s , hepatocellular carcinoma along with the subsequent death rate. the objective of the present study was to provide information on how reliable is hba1c in patients having diabetes with chronic hepatitis c and what alternative parameters can be utilized to check the previous 3-4 months control of diabetes in such patients. materials and methods this was a cross sectional/observational study. it was carried out at the pathology department ffh, rawalpindi from july 2019 to july 2020 after approval from the institutional ethical committee. the inclusion criteria of the study were hundred known diabetic patients with and without cld fulfilling criteria of chronic hepatitis c (lasting > 6 months). the exclusion criteria included those who were free of illness like acute liver disease, renal disease/failure, hepatitis b or any other virus, pregnant females and those who did not want to be included in the study. the study subjects were split in two groups (group a & group b). group a included diabetics with cld (chronic hepatitis c) and group b included diabetics without cld. each group consisted of 50 known diabetic participants. patients were randomly selected from liver and medical opd of ffh, rawalpindi. proper consent was taken after explaining the aims and objectives of the study to all participants. blood sample was collected from all participants under aseptic conditions. centrifugation of blood for 5 minutes at 4000rpm was carried out to separate the serum for the evaluation of liver function tests including alt, alp, albumin, and bilirubin. these parameters were measured using chemistry autoanalyzer dimensions rxl. hba1c was analyzed using fully automated analyzer beckman coulter. statistical analysis was carried out using version 21 of spss. quantitative data was expressed as mean± standard deviation (sd). comparisons between the two groups were made using independent t-test. to show relationship of the variables with hba1c pearson's correlation co-efficient was used. regression analysis was used to show the relationship between the dependent variables and the independent variables. results were considered as significant with p< 0.05 and highly significant with p<0.001. results data was stated as mean± sd. comparison of the two groups was done using independent t-test with considering p < 0.05 as statistically significant. the present study included 100 participants divided into group a and b. group a, diabetics with chronic hepatitis c, included 50 participants with mean age of 61.32±10.70 years while group b, diabetics without chronic hepatitis c, also consisted of 50 participants with mean age of 57.44±11.08 years. low levels of hba1c were seen in group a than group b (6.6±1.10% vs. 9.58±2.09% p<0.05). group a reported significantly higher level of serum alt as compared to group b (74.65±21.84u/l vs. 38.44±23.79u/l p<0.05). group a also showed lower serum albumin as co m p a re d to g ro u p b ( 2 9 . 5 2 ± 2 . 2 1 g / l v s . 36.24±3.99g/l p<0.05). the comparison between the groups is summarized in table i.the association of hba1c with different parameters is shown in table ii. hba1c levels were negatively associated with alt in group a (r-0.418 p<0.05) while in group b the negative correlation was not significant statistically (r-0.197 p=0.171). similarly, albumin showed a significant negative correlation with hba1c in group hba1c and chronic liver diseasejiimc 2021 vol. 16, no.1 15 a (r-.391 p<0.05), while negative correlation of alp and bilirubin were not significant in both the groups. the correlation of alt with hba1c in group a is 2 shown in figure 1 with (r =0.175 p<0.05)) calculated by linear regression analysis while group b results are 2 plotted in figure 2 (r =0.039 p=0.171) the alt results are plotted on x-axis and hba1c on y-axis long term management and treatment. the average pakistani can ill afford to bear the costs of such expensive treatments. hence there was dire need to correlate hba1c with cld and see if the results of hba1c in cld depicted the actual levels or not. multiple studies have been carried out to see the reliability of hba1c in diabetics with cld in respect to cirrhosis but hardly any studies have been done to see accuracy of hba1c in diabetic population having chronic hepatitis c infection. our study is aimed from this aspect as diabetes and chronic hepatitis c, account for major cause of chronic disease in pakistan. in our study it was observed that hba1c level was significantly lesser in the diabetic patients with cld in comparison to diabetic patients without cld. alt level was significantly more in the diabetics having cld while serum albumin was seen to be significantly lower in this group, which may be sign of progression of the disease to cirrhosis. koga et al. in their study observed that in cld patients the measured hba1c levels were lower than 23 estimated hba1c levels. lahousen et al. in their work measured hba1c for the evaluation of long-term plasma glucose control in chronic hepatitis patients, with compensated cirrhosis and in ribavirin treated chronic hepatitis patients. the levels of hba1c in all cases were seen to be below the diabetic range 30 . the results of all these studies are in concordance with this study. nadelson et al. performed their study in 2016, in which they observed that hba1c was not a reliable biomarker of glycemic index in cirrhotic patients with 25 hba1c levels ranging between 5-6%. table i: comparison of demographic, clinical and biochemical characteris�cs of the study groups note: *significance at p <0.05, **significance at p <0.01, ***significance at p< 0.001 table ii: correla�on of hba1c (%) with different parameters in the study groups r is coefficient of correla�on, * significance at p<0.05, ** significance at p<0.01, *** significance at p<0.001 2 fig 1: correla�on of alt with hba1c in group a (r =.175 p=.003) calculated by linear regression analysis 2 fig 2: correla�on of alt with hba1c group b (r =.039 p=.171) calculated by linear regression analysis hba1c and chronic liver diseasejiimc 2021 vol. 16, no.1 16 discussion chronic liver disease and diabetes are two major chronic illnesses afflicting a major segment of pakistan's population. the cost in terms of number of work hours lost due to illness is enormous. moreover, both diseases require mf bashir et al. in their study showed that alt was significantly higher in diabetics with hepatitis c (hcv) but they showed hba1c higher in hcv plus diabetics. this could be because their patients did not fulfill the 31 chronic hepatitis c criteria. our study also showed a significant negative correlation of hba1c with alt and albumin in the diabetics with cld as compared to diabetics without cld. similar results were shown by christman et al. who observed that low hba1c was associated with elevated liver enzymes (alt) and low albumin 32 levels. the limitation of our study includes a small sample size. it is suggested that hba1c should be used with caution & fasting plasma glucose levels should be relied upon more along with liver function tests and red blood cell indices when prolonged glycemic control in type 2 diabetic patients with cld is monitored. studies to investigate newer options for monitoring glycemic levels are required 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wo r l d j o u r n a l o f gastroenterology. 2004;10(15):2284-6. 31. bashir m, haider m, rashid n, riaz s. association of biochemical markers, hepatitis c virus and diabetes mellitus in pakistani males. tropical journal of pharmaceutical research. 2013;12(5). 32. christman al, lazo m, clark jm, selvin e. low glycated hemoglobin and liver disease in the u.s. population. diabetes care. 2011;34(12):2548. hba1c and chronic liver diseasejiimc 2021 vol. 16, no.1 18 original�article abstract objective: to assess the practices of diabetic patients visiting public hospitals of rawalpindi with regards to diabetic foot complications and its prevention. study design: descriptive cross-sectional survey. place and duration of study: the study was conducted in public hospitals of rawalpindi within a duration of one and a half year. (november 2018-march 2020) materials and methods: a descriptive cross-sectional survey was conducted on diabetic patients in the diabetic clinic situated in public hospitals of rawalpindi. by using convenient sampling technique 200 patients were interviewed. sample size was calculated using who calculator, with error of 5%, confidence level of 95%. walk in (unscheduled) diabetes mellitus patients were approached and asked for willingness to participate in study after being given a brief introduction about the study. foot care practices were compared with the examination findings. results: the mean age of respondents was 50 ±12.44 years. only 21.5% of patients were practicing good foot care 43%had satisfactory practices and 35.5% had poor practices. education of the patients had significant statistical association with good foot care practices (p-value <0.0001). gender also showed significant association with good foot care practices (p-value <0.013) while age and socioeconomic status had no significant statistical association with good foot care practices. conclusion: foot care practices adopted by the patients are highly inadequate and proper guidelines need to be provided to patients in addition to the insurance of proper foot care practices if diabetic foot associated complication is to be prevented. key words: diabetic foot, diabetes mellitus, foot self care, practices, shoes. 4 diabetic foot have been consistently rising. within the diabetic population, foot problems are known to be an important factor leading to general ill 5 health and mortality. the major underlying reason for why diabetic patients require hospital admissions is complications associated with diabetic foot 6 syndrome. it was found that at least two or more risk factors that could potentially lead to diabetic foot were present in 10% of patients at the time of initial 7 presentation with diabetes mellitus. amputations performed due to diabetes associated complications makes up 60% of the total number. of lower limb 8 amputations carried out in the united states. diabetic foot has serious financial implications for 9 the patients and adversely affects their lifestyle. there have been studies that state prevalence of 10 diabetes in pakistan is 13.9%. however, with proper guidance and adequate measures the amputation rate of diabetic foot associated complications can be 11 decreased by 49-85%. proper daily foot inspection 12 was only performed by 17% of diabetic patients. introduction diabetes mellitus is characterized by a collection of metabolic disorders which commonly includes hyperglycemia, the underlying cause of which is either impaired production or action of insulin or 1 both. the number of people afflicted with diabetes 2 has been increasing over the past thirty-five years. world health organization defines diabetic foot as neuropathy and vasculopathy associated infection 3 and destruction of the deep tissues of lower limbs. diabetes is associated with numerous complications, however, in the last ten years, problems regarding foot care practices among diabetic patients visiting public hospitals in rawalpindi 1 2 3 rameen tariq , sarah rahman , sidra hamid correspondence: rameen tariq rd 3 year mbbs student rawalpindi medical university, rawalpindi e-mail: rameentariq715@gmail.com 1,2 rd 3 year mbbs student/assistant professor 3 department of physiology rawalpindi medical university, rawalpindi funding source: nil; conflict of interest: nil received: april 20, 2020; revised: march 01, 2021 accepted: april 19, 2021 foot care practices in diabeticsjiimc 2021 vol. 16, no.3 151 considering all the variables that contribute in the development of diabetic foot it is apparent that the severity of this condition is dependent upon patient cooperation regarding foot care practices dictated by medical practitioners. hence further research to assess the implementation of these practices may assist in gaining control over this complication. the rationale of this study was to assess the practices of diabetic patients visiting puetic foot complications and its prevenblic hospitals of rawalpindi with regards to diabtion. materials and methods a descriptive cross sectional survey was conducted on diabetic patients in the diabetic clinic situated in public hospitals of rawalpindi. the study was conducted within a duration of one and a half year. (november 2018-march 2020). based on who calculator, the estimated sample size was found to be 200, with error of 5%, confidence level of 95%. 13 previous study used for calculation. convenient systematic sampling technique was used. formal permission was obtained from ethical review board of the college to conduct the study. the inclusion criteria consisted of patients with diabetes mellitus who had consented to the study, both males and females above 18 years of age. the exclusion criteria consisted of patients who had undergone amputation, patients with gangrenous foot, foot ulcers, foot infections, and patients not willing to participate in the study. walk in (unscheduled) diabetes mellitus patients visiting public a hospital of rawalpindi were approached and asked for willingness to participate in study after being given a brief introduction about the study. the participants were interviewed by the researchers. the questionnaire was in the form of a pre-tested structured interview sheet with questions adopted 10, 12, 13 from various studies conducted in pakistan. the questionnaire was translated into the urdu language by a bilingual translator. the first part of the questionnaire consisted of questions regarding age, gender, education and duration of diabetes. the second part of the questionnaire included, questions to determine practice regarding foot care. the dependent variable was foot care practices in diabetics and the independent variables included education, gender, and duration of diabetes. data was analyzed using spss version 25. mean with standard deviation was calculated for quantitative data like age and practice scores with relation to education. frequencies and percentages were estimated for qualitative variables like gender, age groups, education level, occupation and various foot care practices and examination findings. the chi+square test was used to associate the following non-parametric variables; results of foot care practices with educational background and gender. seventeen questions were asked regarding foot care practices. each correct answer was given one mark. poor practices: score is less than 50% (<9) satisfactory practices: score is 50%-70% (>9<12) good practices: score is greater than 70% (>12) results a total of 200 respondents were selected. the mean age of respondents was 50 ±12.44 years. out of 200 respondents190 (95%) of the total respondents were married. 130(65%) of the total 200 respondents had no previous knowledge about diabetes before contracting the disease. demographic data in (table i) table i: demographic profile of patients interviewed from a total of 200 respondents 43 (21.5%) scored > 7 0 % ( g o o d ) , 8 6 ( 4 3 % ) s c o r e d b e t w e e n 5070%(satisfactory) and 71 (35.5%) scored <50% (poor). different types of footwear were preferred by the patients. most of the patients,90 (45%) preferred foot care practices in diabeticsjiimc 2021 vol. 16, no.3 age (years) 152 sandals whereas 44 (22%) of the patients preferred open toes, 38(19%) preferred boots and 24 (12%) preferred house slippers. athletic shoes and orthofeet shoes were preferred by 2 patients (1%) each. majority of patients, 169 (84.5%) stated they wear shoes most of the day. with respect to exercise 110 (55%) of the patients were involved in some sort of physical activity like walking, jogging, bicycling etc. while 90(45 %) patients did not practice any routine exercise. when asked about blood sugar control, 59(29.5%) reported that they check their blood sugar levels daily and 130(65%) of patients checked their last blood sugar levels a month ago while 11(5.5%) of patients did not remember when they last checked their blood sugar levels. the gender has shown an effect on foot care practices (p=0.013), similarly the contribution of education was also significant with respect to foot care practices (p<0.0001). age however has shown no association with foot care practices (p=0.35). the role of education is further strengthened by the fact that the mean score of the illiterate population was 9±1.87 and mean score for the postgraduates was 12.2 ±1.82. (table iii) (table iv). table ii: questions asked to determine practice regarding foot care table iii: relationship of practices regarding foot care with gender table iv: relationship of practices regarding foot care with education discussion the findings of this study indicated that a significant percentage of the diabetic population had poor foot care practices. furthermore, gender and education had shown to be significant with respect to the quality of foot care practices. only 21.5% of respondents in this study had good practices. this value is lower than that of a study conducted in ethiopia (39%) and this dissimilarity may be attributed to differences in level of education of patients and amount of direct guidance provided by the healthcare professionals in the respective 14 countries. however a recent study conducted in india stated that only four out of every ten 15 individuals had good practice of foot care. a study in iran also reported that only 8.8% of respondents had 16 good scores of foot care practices. the individual frequencies showed that only 42.5% foot care practices in diabeticsjiimc 2021 vol. 16, no.3 153 of patients had been taught how to properly care for their feet but even so 96% of washed their feet daily. this difference can be due to the performance of ablution as an islamic perquisite for daily prayers and a study from shifa hospital islamabad confirmed the role of ablution with respect to the quality of foot 12 care. according to our study education impacted the quality of foot care practices as majority of the patients with post graduate level education also had good practices. this is consistent with another study 13 conducted in jinnah hospital lahore. a possible reason for this can be that there is a greater chance of the patient's comprehension of any foot care guidance material if the patient has a greater 17 education level. secondly, since most of the respondents in this study were categorized as illiterate, hence adopting educational interventions regarding better foot care practices in a visual or 18 auditory manner may prove more effective. this study showed the percentage of males (29.2%) with good foot care practices were nearly double that of the females (14.4%). another study in saudi arabia also reported poor kap scores in diabetic 19 females. a contributing factor could be that females have less awareness and education about proper 17 foot care practices. however another study reported that females had 2.07 times better foot 14 self-care than males. these differences across multiple studies can be due to varying levels of literacy of the respondents or sociocultural 16,18 differences. age was not shown to be a significant factor as is supported by the following study conducted in a 20 tertiary care hospital in pakistan. this study also showed that most of the respondents wore sandals (45%) and only 8.5% wore special protective shoes. a study in india also confirmed that majority of patients wore chappals (open 21 footwear). this may be due to hot weather conditions throughout most of the year, so naturally 18 many people may choose open footwear. another potential explanation for this may be that majority of the patients attending public hospitals were unemployed and thus less capable of affording appropriate therapeutic footwear. effective and affordable footwear is recommended especially for high-risk patients with foot deformities and 22 neuropathy. limitations of our study are that the current study sample did not represent the entire population of pakistan with several different ethnicities. in addition, relevant measures of blood glucose, urine glucose, cholesterol and blood pressure were not taken which could have further elaborated new findings. it is recommended that further studies with a wider sampling frame and larger sampling size be conducted to accurately assess the factors responsible for inadequate foot care practices. furthermore, the effectiveness of current educational interventions regarding foot care practices needs to be re-evaluated and tailored to the literacy levels of the population. conclusion this study indicates that foot care practices currently adopted are inadequate. it is necessary to provide patients information about the disease (diabetes mellitus) itself and its complications one of which is diabetic foot. this goal could only be achieved with the combined efforts of our healthcare centers and patients. references 1. mellitus d. diagnosis and classification of diabetes mellitus. diabetes care. 2005 ;28(s37): s5-10. 2. lavery la, wunderlich rp, tredwell jl. disease management for the diabetic foot: effectiveness of a diabetic foot prevention program to reduce amputations and hospitalizations. diabetes research and clinical practice. 2005;70(1):31-7. 3. moulaei k, malek m, sheikhtaheri a. monitoring of external predisposing factors for diabetic foot: a literature review and physicians' perspectives. medical journal of the islamic republic of iran. 2019; 33:159. 4. aalaa m, malazy ot, sanjari m, peimani m, mohajeri tehrani mr. nurses' role in diabetic foot prevention and care; a review. journal of diabetes & metabolic disorders. 2012;11(1):1-6. 5. guell c, unwin n. barriers to diabetic foot care in a developing country with a high incidence of diabetes related amputations: an exploratory qualitative interview study. bmc health services research. 2015;15(1):1-7. 6. dikeukwu ra, omole ob. awareness and practices of foot self-care in patients with diabetes at dr yusuf dadoo district hospital, johannesburg. journal of endocrinology, metabolism and diabetes of south africa. 2013;18(2):1128. 7. chiwanga fs, njelekela ma. diabetic foot: prevalence, knowledge, and foot self-care practices among diabetic foot care practices in diabeticsjiimc 2021 vol. 16, no.3 154 patients in dar es salaam, tanzania–a cross-sectional study. journal of foot and ankle research. 2015;8(1):1-7. 8. bell ra, arcury ta, snively bm, smith sl, stafford jm, dohanish r, et al. diabetes foot self-care practices in a rural, triethnic population. the diabetes educator. 2005;31(1):7583. 9. al-hariri mt, al-enazi as, alshammari dm, bahamdan as, al-khtani sm, al-abdulwahab aa. descriptive study on the knowledge, attitudes, and practices regarding the diabetic foot. journal of taibah university medical sciences. 2017;12(6):492-6. 10. syed f, arif ma, afzal m, niazi r, ramzan a, hashmi ue. foot-care behaviour amongst diabetic patients attending a federal care hospital in pakistan. diabetic foot. 2019;13:5. 11. bakker k, apelqvist j, schaper nc, international working group on the diabetic foot editorial board. practical guidelines on the management and prevention of the diabetic foot 2011. diabetes/metabolism research and reviews. 2012;28:225-31. 12. saeed n, zafar j, atta a. frequency of patients with diabetes taking proper foot care according to international guidelines and its impact on their foot health. jpma. the j o u r n a l o f t h e p a k i s t a n m e d i c a l a s s o c i a t i o n . 2010;60(9):732. 13. hasnain s, sheikh nh. knowledge and practices regarding foot care in diabetic patients visiting diabetic clinic in jinnah hospital, lahore. jpma. the journal of the pakistan medical association. 2009;59(10):687. 14. tuha a, faris ag, andualem a, mohammed sa. knowledge and practice on diabetic foot self-care and associated factors among diabetic patients at dessie referral hospital, northeast ethiopia: mixed method. diabetes, metabolic syndrome and obesity: targets and therapy. 2021;14:1203. 15. pavithra h, akshaya km, nirgude as, balakrishna ag. factors associated with awareness and practice about foot care among patients admitted with diabetes mellitus: a cross sectional research from a medical college hospital of southern india. nepal journal of epidemiology. 2020;10(3):897. 16. pourkazemi a, ghanbari a, khojamli m, balo h, hemmati h, jafaryparvar z, et al. diabetic foot care: knowledge and practice. bmc endocrine disorders. 2020;20(1):1-8. 17. desalu oo, salawu fk, jimoh ak, adekoya ao, busari oa, olokoba ab. diabetic foot care: self reported knowledge and practice among patients attending three tertiary hospital in nigeria. ghana medical journal. 2011;45(2). 18. sari y, upoyo as, isworo a, taufik a, sumeru a, anandari d, et al. foot self-care behavior and its predictors in diabetic patients in indonesia. bmc research notes. 2020;13(1):1-6. 19. saadia z, rushdi s, alsheha m, saeed h, rajab m. a study of knowledge attitude and practices of saudi women towards diabetes mellitus. a (kap) study in al-qassim region. the internet journal of health. 2010;11(2). 20. khatak mb, marwat zi, usman m, sljjad a. evaluation of foot care knowledge and practices among diabetic patients attending tertiary care hospital. kjms. 2014;7(2):184-9. 21. taksande ba, thote m, jajoo un. knowledge, attitude, and practice of foot care in patients with diabetes at central rural india. journal of family medicine and primary care. 2017;6(2):284. 22. a m e r i c a n d i a b e t e s a s s o c i a t i o n . m i c r o v a s c u l a r complications and foot care: standards of medical care in diabetes—2019. diabetes care. 2019;42(supplement 1): s124-38. foot care practices in diabeticsjiimc 2021 vol. 16, no.3 155 original article abstract objective: to determine the effect of zinc on salt induced bone damage in rats. study design: laboratory based randomized control trial. place and duration of study: the anatomy department of islamic international medical college, rawalpindi, hosted the conduction of research with the cooperation of national institute of health, islamabad. the study th th commenced on 17 september 2015 and completed on 17 march 2016. materials and methods: forty five female sprague dawley rats, 10-12 weeks old were used in the study. the animals were randomly divided into 3 groups. the rats in experimental group a fed on high salt diet (8%nacl) whereas animals in experimental group b were given high salt diet supplemented with zinc (50mg/kg/day) for eight weeks however, the diet of control group was not tempered with. blood samples were drawn at the start of intervention through tail vein and at the end of the experiment by intracardiac puncture for hormonal assay. all rats were dissected, left humeri and femora were removed, decalcified and five micrometer (µm) sections were obtained after tissue processing. tissues were stained with haematoxylin and eosin (h&e) for histological parameters. the quantitative data was analyzed by using statistical package for social sciences (spss) version 21 and was expressed as mean + s.d. one way analysis of variance (anova) followed by post hoc tukey test was applied for inter group comparison of parameters. t-test was applied for intragroup comparison of values. result having p-value <0.05 was considered statistically significant. results: marked histological changes were identified in the experimental groups. these changes were of greater severity in high salt diet group as compared to the zinc supplemented group in which reverse beneficial effects were observed. fall in serum calcium and alkaline phosphatase levels were deemed substantial in group a with respect to group b. conclusion: zinc has a protective role against high salt exposed diet induced damage on the histomorphology of bone tissue. key words: cortical bone, hypercalciuria, osteoblast, salt, zinc. researches, precise associations of the trace elements with bone health are not clear as yet. inverse of negative balance between bone formation and resorption has been evaluated with the help of 3 trace elements. st low bone mass is a silent epidemic of the 21 century and figures are set to increase worldwide. considering the elements which affect bone metabolism is of utmost importance for the prevention of osteoporosis. although nutrition is an important determinant of bone health, but the 4 effects of the micronutrients is little understood. bone is a systematized tissue which acclimates and changes according to certain factors and its organization varies due to diverse functional 5 requirements. the net result of unaltered healthy bone mass is sustained by a balanced bone 6 formation and resorption activity. imbalance results in a progressive metabolic ailment called 7 8 osteoporosis, becoming a public health problem, introduction the world is under continuous threat of increase 1 d i e t re l a t e d n o n c o m m u n i c a b l e a i l m e n t s . unbalanced and excessive salt intake is often closely associated with development of hypertension and 2 other cardiovascular diseases. however, awareness regarding relationship of zinc to sodium induced osteoporosis is still in a gray area. despite of previous effect of zinc on salt induced impaired remodeling in long bones of rats 1 2 3 kaukab anjum , rehana rana , sumaira abbasi jiimc 2016 vol. 11, no.3 correspondence: dr. kaukab anjum assistant professor, anatomy wah medical college, wahcantt e-mail: kanjumq@gmail.com 1 department of anatomy wah medical college, wahcantt 2 department of anatomy islamic international college riphah international university, islamabad 3 department of anatomy federal medical & dental college, islamabad funding source: nil ; conflict of interest: nil received: mar 24, 2016; revised: apr 07, 2016 accepted: aug 01, 2016 effect of zinc on bones of salt loaded rats 113 9 u ps ett i n g 2 0 0 m i l l i o n p e o p l e wo r l d w i d e . characterized by lessened structural integrity and proneness to fractures, it is more prevailing than 10 myocardial infarct, breast cancer and stroke it is imperative to explore and develop nutritional strategies for osteoporosis prevention as the life threatening outcomes and increase in annual cost associated with disease morbidity requires a quick 11 fix. 12 salt being most ubiquitous of food flavorings and a 13 known risk factor for osteoporosis, imposes hazards on human wellbeing. high urinary excretion of calcium with increase salt intake leads to impaired 14 bone health. human population has exceeded the daily limit of 15 2000 mg of na /day as recommended by who. different communities have different intakes (western 2300-4300 mg na/day , asian 5300mg16 6000mg of na/ day) sodium in this range is adversely affecting people including osteoporosis, hypertension , increase urinary tract stones and 17 stroke. it took 75 years to realize that zinc is a crucial trace 18 element although it has been used therapeutically in ayurveda but its nutritional significance in public 19 health was recognized recently. as it is a vital 20 element and human body contains only 2-3 grams. 21 even a small deficiency is a disaster. zinc can be a hidden link for the prevention of osteoporosis due to 22 its regulatory role in bone metabolism. it has the ability to stimulate the differentiation and proliferation of osteoblasts and inhibiting osteoclast 22 like cells formation from bone marrow zinc ,by stimulating apoptotic cell death of mature osteoclasts can inhibit bone resorption and have 23 direct positive effect on bone metabolism. other than bones which act as a zinc sink zinc is stored in 24 muscles and skin. so free available quantity is negligible and only food source can be utilized when 25 required to prevent conditions like bone loss, 26 27 gastric ulcers night blindness. therefore, this experimental study will highlight the potential benefits of zn supplementation in reducing bone loss more accurately and eventually will give desired awareness to masses regarding positive link between zinc and bone health. materials and methods the study was a laboratory based randomized control trial carried out in the anatomy department of islamic international medical college rawalpindi. it was initiated after the approval of the ethical review committee. the research was carried out with the collaboration of national institute of health (nih) islamabad and army medical college. it took six months to complete this study. inclusion criteria were forty five, 12 weeks old, adult female sprague dawley rats weighing 250-300g. pregnancy, male rats and any evident pathology were also considered as exclusion factors. forty five rats grouped by using random number table method, selected by non-probability convenient sampling, were randomly divided in to three groups (15 animals in each group) and were allowed to adjust in well aired new environment in a temperature range of 20-26°c. the rats in group a 28 (n=15) were given diet having 8% nacl for eight weeks. rats in group b (n=15) were given high salt diet supplemented with zinc at a dose of 50mg/kg 29 body weight. the rats of group c (n=15) served as controls, they were given standard laboratory diet. water was provided ad libitum. the dose of nacl and zinc was set based on previous studies. dissection was done after eight weeks. blood was drawn through intracardiac puncture for assessing serum calcium and alkaline phosphatase (alp) level at the end of intervention. the left humeri and femora of rats were removed and immediately fixed in 10% neutral buffered formaldehyde for 2 days. decalcification was performed using aqueous solution of 5-10% nitric acid for 24-48 hours. transverse sections from the mid diaphysis were obtained, processed and embedded in paraffin wax 30 to form blocks. five μm thick sections were obtained by mounting blocks on rotary microtome. haematoxylin and eosin was used for histological study of specimen. cortical bone thickness of diaphysis of humeri and femora was measured with the help of ocular micrometer. the thickness of cortical bone was measured by counting the number of divisions of eye piece of linear ocular micrometer, placed perpendicularly from underneath the periosteum to endosteum. cortical bone width of opposite side was measured in a same manner per section under 4x objective and results were averaged. parametric data was analyzed by using statistical jiimc 2016 vol. 11, no.3 effect of zinc on bones of salt loaded rats 114 package for social sciences (spss) version 21. quantitative data was expressed as mean + s.d. one way analysis of variance (anova) followed by post hoc tukey test was applied for inter group comparison of parameters.t-test was applied for intra group comparison of values. result having pvalue <0.05 was considered statistically significant. results mean thickness of the humeral cortical bone was 5 3 . 7 6 6 ± 9 . 0 6 6 μ m i n c o n t r o l g r o u p c , 53.666±7.596μm in experimental group b and lowest of all, 41.8000±15.254 μm in experimental group a. the results were significant (p˂0.05) amongst different groups (table i) (fig 2, 3). the difference between group c and a was 11.966 μm, being highly significant (p=0.014).the result between group c and b was insignificant (p=1.000) with difference of 0.100μm. the mean cortical thickness of group b was greater than group a with difference of -11.866μm (p˂0.05) (table ii) (fig 1). mean thickness of the femoral cortical bone was 4 4 . 6 0 0 ± 8 . 4 3 7 μ m i n c o n t r o l g r o u p c , 39.366±10.677μm in experimental group b and lowest of all, 30.433±9.350μm in experimental group a. the results of difference in cortical bone thickness were significant between groups (p˂0.05). the difference between group c and a was 14.166 μm, the result was highly significant (p=0.001).the insignificant difference of 5.233μm (p=0.300) was recorded between group c and b. the mean of thickness was greater in group b than group a difference being -8.933μm (p=0.036). mean random initial and final serum calcium was 8.680±0.90333 mg/dl and 8.5333±0.9559mg/dl in control group c, 7.826±0.6123 mg /dl and 7.153±1.364mg/dl in experimental group a and 8.666±0.952 mg/dl and 8.816±0.9635mg/dl in experimental group b initial calcium levels revealed p-value of 0.010 whereas the final levels were different in all groups (p=0.004).the mean difference between initial and final value in control group c was 1.3800, 0.3466 in experimental group a and -1.0333 in experimental group b. decrease in calcium level was highly significant between experimental group c and a (p=0.004), insignificant (p=0.672) between group c and b and there is significant result between group a and group b (p=0.038) (table iv). initial and final mean serum alkaline phosphatase level was 487.800±51.669 u/l and 478.066±53.620 u/l in control group c, 466.200±45.874u/l and 349.9333±56.0484 u/l in experimental group a and 486.066±47.373 u/l and 416.666±62.009 u/l in experimental group b (table iii) (fig 5). initial serum alkaline phosphatase showed inconsequential value in all the groups (p=0.405) whereas the final levels were significant (p=0.000) the mean of difference between initial and final value in control group c was 9.7333 u/l,116.2666 u/l in experimental group a and 69.4000 u/l in experimental group b. comparison among groups demonstrated the highest decrease in alkaline phosphatase level between group c and a being 109.2000 u/l with significant value (p=0.000).the mean of decrease between group c and group b was 42.4666 u/l (p=0.021) which was less group a and b -66.7333 u/l (p=0.038 table ii: mean cor�cal bone thickness in humerus and femur (µm) of all groups table i: mul�ple comparison of cor�cal bone thickness among all groups of humerus and femur by post hoc tukey test discussion bone acclimates and changes under the influence of certain elements and its organization varies due to 5 diverse functional requirements. the healthy bone mass is sustained by a balanced between bone jiimc 2016 vol. 11, no.3 effect of zinc on bones of salt loaded rats *p<0.05 115 6 formation and resorption activity. life style, genetic and dietary factors have impact on its prevalence. although dietary factors have limited influence but are nonetheless crucial because they modulate the achievement of maximum peak bone mass and subsequent better bone health. by developing nutritional strategies for osteoporosis prevention, the annual cost and debilitation associated with its morbidity can be lessened. the present study focused on determining the beneficial effects of zinc on high salt diet induced bone damage in long bones of rats by observing m i c ro s c o p i c q u a n t i tat i ve a n d b i o c h e m i c a l parameters. the results suggested that zinc supplementation can prevent the high salt induced deleterious effects on bones. 31 alp is a marker enzyme of osteoblast activity 32 reevaluated by ahmed who documented the decrease in calcium, alp levels and subsequent impaired bone integrity after salt loaded diet. decrease in the osteoblast activity due to salt overload can be the reason of low alp levels. furthermore, decline in the alp activity has been demonstrated in animal models of experimental 33 induced osteoporosis. as ˃ 99% of na and 95% of the calcium are reabsorbed in the kidneys, it is speculated that impaired renal function may be responsible for na induced calciuria and temporarily 14 depress calcium levels. substandard kidney function also causes hypophosphatemia and fall in 1, 25 (oh) 2 d3. all these events lead to less intestinal absorption of calcium as well as decrease availability 16 to bones. reduction in the biomarkers of bone formation (alp) and significant increase in the biomarkers of bone resorption has been observed due to high pth secretion secondary to low calcium levels and consequently increase in bone 16 remodeling. in line with other publications, 34 creedon also observed the decrease in calcium levels due to sodium induced increase urinary excretion of calcium. as a compensatory mechanism, the pth secretion increases which causes calcium mobilization from bones at the expense of bone 15 loss. 22 as zn is a cofactor of alp which is an enzyme expressed by osteoblasts close to the blood vessels and is a valuable index for bone tissue development. administration of zinc results in increase of enzyme fig 1 : cross-sec�on of humerus diaphysis of a13 showing decreased cor�cal bone thickness (cbt). h&e, x4. fig 2: cross-sec�on of humerus diaphysis of b7 showing increased cor�cal bone thickness (cbt). h&e, x4. table iii: ini�al-final serum calcium (mg/dl) and alkaline phosphatase (u/l) level of all groups *p ˂ 0.05 table iv: mul�ple comparison of final calcium (mg/dl) and alkaline phosphatase (u/l) level *p ˂ 0.05 jiimc 2016 vol. 11, no.3 effect of zinc on bones of salt loaded rats 116 35 activity indicating enhance osteoblastic activity. increase in levels of calcium and alp with significant difference (p˂0.05) in the present study is also 36 validated by otsuka who observed increase in levels after measured zinc discharge on bone mineral density from injectable zn-containing b-tricalcium phosphate. it could be attributed to intensified differentiation of osteoblastic cells to raise alp 37 activity. zinc plays an important role in preventing osteoporosis by stimulating bone formation, 31 reported by ma by demonstrating increase in calcium and alp in the femoral-diaphyseal and metaphyseal tissues. decrease in calcium content by bone resorbing factors can be prevented by zinc 19 supplementation. our outcome is in agreement with above results, further firming up my research. cross section of long bones reveals four different bone types: periosteum, cortical bone, endosteum and cancellous bone. femur diaphysis is mainly 38 composed of compact bone and cancellous bone forms a very thin layer on the inner aspect of 5 diaphysis of long bones. the cortical bone thickness is an important parameter to evaluate bone quality 39 and strength so in the present study the bone damage is assessed by measuring the cortical bone thickness in cross sections of mid diaphysis. it is revealed that humerus and femur of control group has maximum thickness of 50.7um and 44.6um respectively followed by experimental group b who took salt and zinc supplementation whereas the lowest dimensions are found in experimental group a fed on high salt diet. 32 my results are in harmony with the work of ahmed who observed decline in the thickness of cortical bone of rats. he anticipated that high salt intake can be related with increased plasma levels of creatinine, urea, phosphate and potassium due to deranged kidney function which finally led to bone changes. furthermore increased serum phosphate inhibits 1αhydroxylase and produced fall in 1, 25(oh) 2 d3. as a result intestinal absorption of calcium is decreased with subsequent increase in pth secretion leading to increase osteoclastic activity. degenerative changes in osteoblasts, osteocytes and hyperactivity of osteoclasts results in inaccurate bone remodeling with decrease in cortical bone 40 thickness. changes in bone remodeling which is mediated by bone cells, increased osteoclastic activity and multiple resorption cavities can be the 41 reason of decrease in the thickness of cortical bone. my result is in conformity with the results of all above periodicals sharing a common point that salt intake results in osteoporosis with decrease in cortical bone thickness. increase in cortical bone thickness after zinc supplementation in experimental group b is documented in the present study. as many published studies has confirmed that zinc has positive role in improving bone health , it is further strengthened by 22 brzoska who reported the shielding effect of zinc diet on bone homeostasis. he postulated that increase in the bone alkaline phosphatase activity may be due to zinc adequacy. increase in the osteocalcin level produced by osteoblasts after zinc supplemented diet might have resulted in increase in 42 cortical bone thickness. zinc is required for growth of osteoblasts and zinc showed decreased was bone 43 resorption. conclusion this research indicates that zinc supplementation can be considered an appropriate dietary strategy to reduce risk of osteoporosis. cortical bone thickness, alkaline phosphatase activity and calcium levels w e r e c o n s i d e r a b l y i n c r e a s e d a f t e r z i n c administration showing that zinc has protective role against high salt induced impaired remodeling in long bones of rats. recommendations effects of high salt diet can be studied for longer period of time to assess significant gross changes in long bones of rats. effects of highs salt and zinc can be observed on the osteocytes apoptosis to evaluate their role in development and prevention of osteoporosis. comparison of high salt diet induced effects can be studied between male and female rats to assess the difference in the degree of damage. references 1. boutayeb a, boutayeb s. the burden of non communicable diseases in developing countries. international journal for equity in health. 2005; 4: 1. 2. strazzullo p, d elia l, kandala nb, cappuccio fp. salt intake, stroke, and cardiovascular disease: meta-analysis of prospective 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page 31 page 32 case�report abstract swine flu is an acute respiratory disease also referred as novel a/h1n1, caused by influenza type a virus. although currently in post pandemic phase, swine flu is considered as a major emerging disease and in this situation notification of every case is essential to interrupt transmission of disease. therefore, we are reporting this case of 35 year male presented with one week history of sore throat, fever and constitutional symptoms, investigated for swine flu, and successfully treated with an excellent outcome. key words: respiratory disease, h1n1inflenza, swine flu. have been isolated from many hosts including human beings, birds (chicken and ducks), pigs, horses etc. in humans, any preexisting chronic c o n d i t i o n , c i ga re tte s m o k i n g a n d a l c o h o l consumption correlate with enhanced influenza 4 v i r u s ‐ a s s o c i ate d m o r b i d i t y a n d m o r ta l i t y. the signs and symptoms of swine flu in humans are similar to seasonal influenza and characterized by fever, cough, sore throat, headache, malaise, muscle 5 pain, nasal congestion, chills and fatigue. the high risk patients include children, elderly, pregnant women, people with chronic conditions and 5 immunosuppressed. the ministry of health confirmed first swine flu case in pakistan on august 10, 2009, the only source of 6 virus being migrant people from abroad. there has been an increase in the number of swine flu cases and consequential deaths in various parts of punjab 6 and federal capital. during 2014, swine flu outbreak was observed in multan, khanewal, taunsa, and dera ghazi khan districts of southern punjab from where more than 10 cases of swine flu and five mortalities 6 were reported. we are lacking medical, technical and diagnostic facilities and reporting of even a few cases in this situation is really alarming and needs 6 attention. we present a case of swine flu successfully treated in our hospital. case report a 35 year male patient, accountant by profession, admitted with the complaints of sore throat and high grade fever with chills, rigors and cough, initially dry and later on productive for the last one week. he gave history of few episodes of sweating and palpitations. there was no other urinary or bowel introduction swine flu is an acute respiratory disease caused by a 1 relatively new strain of influenza virus a/h1n1. in june 2009, pandemic of a/h1n1 flu spread in more than two continents, almost 375,000 laboratory confirmed cases and thousands of deaths reported 2 to who in nearly 214 countries. the first global estimates by cdc‐led collaboration showed an estimated range of deaths between 151,700 and 575,400 people who perished worldwide from 2009 h1n1 virus infection during the first year the virus circulated. these global estimates were more than 15 times higher than the number of laboratory 3 confirmed cases and deaths reported to the who. consequently, localized epidemics are thought to be expected and considerable efforts are required to deal with this global threat. 3 pandemic (h1n1) 2009 is an influenza a virus 4 belongs to family orthomyxoviridae. the major virus component determining epidemiologic dynamics is ha antigen, which serves as the hemagglutinin attachment protein to enable binding and infecting 4 cells. influenza viruses are highly resilient in the environment, low temperature and low humidity favor aerosol transmission, explaining seasonal 4 variation in temperate climates. influenza viruses early diagnosis and prompt treatment – an approach to hamper swine flu outbreak 1 2 3 4 faiza batool , iffat atif , farah rashid , hussam shabbir jiimc 2016 vol. 11, no.4 correspondence: dr. iffat atif assistant professor, community medicine yusra medical and dental college, islamabad e‐mail: iffat.atif@hotmail.com 1,4 2,3 department of medicine/ community medicine yusra medical and dental college, islamabad funding source: nil; conflict of interest: nil received: aug 19, 2016; revised: sep 08, 2016 accepted: nov 14, 2016 swine flu ‐ an emergent global threat 185 complaint. he was a non‐smoker, non‐addict and gave family history of diabetes and ischemic heart disease. on general physical examination he had 0 raised pulse rate and a temperature of 102 f. the examination of respiratory system revealed bilateral coarse crepitations all over the chest. cardiac and other systemic examinations were within normal limit. complete blood count revealed total leukocyte 9 count – 4 x 10 /l, hemoglobin – 14.3 g/dl and platelet 9 count – 193 x 10 /l. esr, liver function tests, serum electrolytes, renal function tests, random blood glucose and trop‐t were normal. urine analysis was also within normal limits. mp smear, blood culture, dengue serology ns‐1, typhidot were all negative. o 2 saturation was 80 to 85% at room air without oxygen. arterial blood gases showed hypoxia. the patient was put on anti malarial drugs and broad spectrum antibiotics. he responded well and became afebrile initially, later on developed dyspnoea and generalized body weakness. chest x‐ray was done showing bilateral lung infiltration in mid lung zone, suggestive of small airway inflammatory disease. ecg was also done which showed serial non specific t‐wave inversion in chest leads. no abnormality was detected on echocardiography with normal ejection fraction. a probable diagnosis of pneumonia (typical, atypical and viral) was made. the nasopharyngeal swab was sent for h n serology to national institute of health 1 1 to rule out viral pneumonia (swine flu) and the report was awaited. in the meanwhile he was put on broad spectrum antibiotics and antiviral treatment (tamiflu 150 mg bd). daily complete blood count 9 reports showed platelet count dropped to 80 x 10 /l 9 and tlc dropped to 2 x 10 /l. serum ck and ldh were markedly raised suggestive of viral pneumonias. d‐ dimers was negative (<200) and pulmonary embolism was ruled out. c‐reactive proteins were mildly raised. computed tomography of chest showed bilateral infiltrates in both lung fields and spirometry revealed severe restrictive lung disease. the patient was given intravenous steroids to treat acute interstitial pneumonia. after 5 days the report arrived which was positive for h n , intravenous 1 1 steroids discontinued thereafter and antibiotics along with antiviral treatment was continued for 7 days. the patient was isolated and strict barrier nursing was observed. the patient started to recover with gradual improvement of symptoms. all the investigations were repeated and were within normal limits, ecg changes reverted back to normal, chest x‐ray showed decreased haziness and o 2 saturation increased. the patient was retained in the hospital for 10 days, his condition improved markedly. the case was notified to who and ministry of health. the edo health's surveillance team visited the hospital and the patient to collect the epidemiological data and confirmation of the findings. the antiviral treatment (tamiflu tablets) was provided by them and the entire team appreciated early diagnosis and prompt treatment of the case. discussion the clinical continuum of the novel swine influenza infection is both self limited illness and in severe outcomes it can lead to respiratory failure and death similar to that seen among persons infected with earlier strains of swine origin influenza viruses and 5 seasonal influenza viruses. the modes of transmission of influenza viruses in humans including swine influenza are mainly through the dissemination of large droplets and droplet nuclei expelled during coughing and sneezing of an infected 6 person. there is also potential for transmission through direct contact with the patient and through contaminated fomites. in humans, it is most contagious during the first 5 days of the illness and 5,6 can remain contagious for up to 10 days. recommendations to prevent spread of the virus among humans include using standard infection control against influenza including frequent hand washing and use of mask, especially after being out in public. anyone with flu‐like symptoms such as a sudden fever, cough, or muscle aches should be isolated, contact a doctor to be tested and must not 6 socialize. it has been recommended that patients with confirmed or suspected swine influenza infection should be placed in strict isolation and health care workers providing direct care for patients 7 should observe strict barrier nursing precautions. after patient report to the health care setup, prompt sample collection and quick diagnosis help to reduce 8 case fatality rate. during pandemics, health authorities may be uncertain about the spread and severity of the jiimc 2016 vol. 11, no.4 186 swine flu ‐ an emergent global threat disease and the effectiveness and safety of available interventions. this was the case during the swine flu 8 (h1n1) pandemic of 2009–2010. during an infectious disease outbreak, it is crucial to be trained about the concerns, knowledge, attitudes, and b e h a v i o r o f t h e c o m m u n i t y t o i m p r o v e communication efforts by public health officials and 8,9 clinicians. a great concern did not transform into h i g h e r c o n f o r m i t y w i t h p r e c a u t i o n a r y recommendations, possibly due to the low level of 9 knowledge about the disease among general public. therefore, it is imperative to create awareness about mode of spread, preventive measures, availability of vaccines and effective medical treatment to prevent 10,11 the disease transmission. during the global h1n1 influenza a pandemic 2009–2010, swine flu vaccines were expeditiously licensed and a mass vaccination program for high risk 1 2 groups was introduced in uk. the rapid development of h1n1 vaccines to prevent further morbidity and mortality became public health priority and the first vaccines were licensed in 12,13 october 2009. a mass vaccination program for high risk groups was launched in uk from october 2009 onwards and no significant safety issues were 13 identified. the groups recommended to receive h1n1 influenza vaccine include; pregnant women, household contacts and caregivers for children younger than 6 months, healthcare and emergency medical services personnel, all people from 6 months through 24 years of age and persons aged 25 through 64 years who have health conditions associated with higher risk of medical complications 13 from influenza. although swine flu is currently in its post pandemic phase, there is always a risk of re‐emergence of disease in susceptible population and localized outbreaks of varying scale with significant level of 14 h1n1 transmission are expected. understanding the perceptions of people and their potential resources to infectious disease threats would assist health officials to develop measures to respond this 14 situation. the effectively treated case of swine flu described here implies the fact that the physicians must consider swine influenza infection in the differential diagnosis of patients with acute febrile respiratory illness for delivering good quality management and treatment. the collaborative efforts of physicians, public health agencies and community education can facilitate to tackle this disease which has now become an emergent global menace. acknowledgement: we are grateful to national institute of health, who, ministry of health and public health surveillance team for their cooperation and support. references 1. world health organization, posted by new york times. journal watch editors. 2009. june 11. 2. influenza a. (h1n1) – update 12. geneva: world health o r g a n i z a t i o n ; 2 0 0 9 . a v a i l a b l e f r o m : http://www.who.int/csr/don/2009_05_03a/en/index.htm l [last accessed on 2009 may 26]. 3. centers for disease control and prevention [last updated o c t o b e r 1 5 , 2 0 0 9 ] . a v a i l a b l e f r o m : http://www.cdc.gov/h1n1flu/vaccination/public/vaccinati on_qa_pub.htm. 4. gl, byahatti sm. an insight into the swine‐influenza a (h1n1) virus infection in humans. lung india. 2011; 28: 34–8. 5. balkhy hh, abolfotouh ma, hathlool rh, al jumah ma. awareness, attitudes, and practices related to the swine influenza pandemic among the saudi public. bmc infectious diseases 2010. 6. ministry of health, provincial government of punjab, pa k i sta n . ava i l a b l e f ro m : htt p : / / w w w. m ht f. o rg / organization/ministry‐of‐health‐provincial‐government‐ of‐punjab‐pakistan/[last updated:2016 aug 10]. 7. carlsen b, glenton c. the swine flu vaccine, public attitudes, and researcher interpretations: a systematic review of qualitative research. bmc health services research. 2016; 16: 1. 8. patavegar bn, kamble m, langare patil s, shah s, sharma g, chandra t, et al. awareness and practices regarding swine flu among interns and nursing staff: a cross‐sectional study at tertiary care hospital, pune. international journal of health sciences and research (ijhsr). 2015; 5: 1‐5. 9. kawanpure h, ugargol ar, padmanabha bv. a study to assess knowledge, attitude and practice regarding swine flu. ijhsr. 2014; 4: 6‐11. 10. vincent a, awada l, brown i, chen h, claes f, dauphin g, et al. review of influenza a virus in swine worldwide: a call for increased surveillance and research. zoonoses and public health. 2014; 61: 4‐17. 11. nelson mi, gramer mr, vincent al, holmes ec. global transmission of influenza viruses from humans to swine. journal of general virology. 2012; 93: 2195‐203. 12. mackenzie is, macdonald tm, shakir s, dryburgh m, mantay bj, mcdonnell p, et al. influenza h1n1 (swine flu) vaccination: a safety surveillance feasibility study using self‐reporting of serious adverse events and pregnancy outcomes. british journal of clinical pharmacology. 2012; 73: 801‐11. jiimc 2016 vol. 11, no.4 187 swine flu ‐ an emergent global threat 13. han yk, michie s, potts hw, rubin gj. predictors of influenza vaccine uptake during the 2009/10 influenza a h1n1v ('swine flu') pandemic: results from five national surveys in the united kingdom. preventive medicine. 2016; 84: 57‐61. 14. patel pb, patel mj, prasad r, patel k, jadawala h, bansal rk. health care seeking interval and fatality rate in swine flu (h1n1) epidemic in surat city. national journal of community medicine. 2015; 6: 25‐9. jiimc 2016 vol. 11, no.4 188 swine flu ‐ an emergent global threat page 47 page 48 page 49 page 50 original�article abstract objective: to assess the outcome of laparoscopic cholecystectomy (lc) in the treatment of acute cholecystitis. study design: quasi experimental study. place and duration of study: the study was conducted at surgical unit i, department of general surgery, st st pakistan institute of medical sciences, islamabad from 1 jan 2013 to 31 dec 2018. materials and methods: all those patients who reported within 72 hours of onset of symptoms of acute calculus cholecystitis were included. patients of acute pancreatitis, choledocholithiasis, with comorbids and previous abdominal surgery were excluded. three port lc was performed in patients of acute cholecystitis after diagnosis by consultant skilled surgeon. data were collected in a proforma that included demographics of the patient, operative findings, operating time, intraor post-operative complications and duration of hospital stay. data was collected and spss version 20 was used for analysis. results: total 143 patients of acute calculous cholecystitis were studied with 38 males and 105 females. the mean age of patients was 46.23 years ranged from 22 to 76 years. the mean operative time was 68.1 ± 25.31 minutes with conversion rate of 2.1%. the overall rate of complication was 24.5 per cent and no serious bile duct injury was noted in any patient. bleeding (5.6%) and biliary injury (2.1%) were intraoperative complications. port site infection (6.3%), chest infection (3.5%) and biliary leak (2.8%) were major postoperative complications. the mean total hospital stay was 4.16 (3–8 days). conclusion: laparoscopic cholecystectomy can be performed safely in patients with acute calculous cholecystitis within 72 hours of the onset of symptoms. key words: acute cholecystitis, biliary injury, cholelithiasis, laparoscopic cholecystectomy, post site infection. cholecystectomy was performed in selected cases, but with advances in instrumentation, improved visualization due to new cameras, increased knowledge of the hepato-biliary anatomy and improved surgical skills, surgeons began performing laparoscopic cholecystectomy even in acute cholecystitis, which was initially considered a 3 relative contraindication. lc for the surgical treatment of patients with acute 4, 5 cholecystitis remains debatable, in particular the timing of lc with respect to inflammation, oedema and calot's triangle adhesions. more complications like excessive bleeding, increased chance of common bile duct injury and conversion are known to be associated with lc for the treatment of acute 6 cholecystitis. nevertheless, some surgeons recommended early lc as preferred treatment for acute cholecystitis, with increased experience and 7 improvement of the instruments. several randomized controlled trials comparison of early lc (performed within 7 days of symptoms onset) with delayed lc (usually performed 4 to 6 weeks after symptoms onset) reported benefits with early lc of introduction gall stone disease has a worldwide prevalence of 10 – 15% and around 20 percent of patients with cholelithiasis present with acute calculus 1 cholecystitis. laparoscopic cholecystectomy (lc) has been accepted as the gold standard in treating chronic symptomatic cholecystitis calculus since 2 1992. however lc was not previously considered as a preferred treatment in patients with acute cholecystitis. conservative management was done followed by elective cholecystectomy after 6 – 8 weeks of interval time. surgeons had concerns regarding increased complication rate and high chances of conversion. initially laparoscopic outcome of laparoscopic cholecystectomy in patients of acute cholecystitis 1 2 3 4 5 s h waqar , muhammad tariq abdullah , sajid ali shah , zafar iqbal malik , fatima shahzad correspondence: dr. s h waqar department of general surgery pakistan institute of medical sciences, islamabad e-mail: waqardr@yahoo.com 1,2,3,4 department of general surgery pakistan institute of medical sciences, islamabad 5 al nafees medical college, islamabad funding source: nil; conflict of interest: nil received: may 18, 2020; revised: july 15, 2020 accepted: july 22, 2020 outcome of laparoscopic cholecystectomyjiimc 2020 vol. 15, no.3 149 positive murphy's sign, leukocytosis, oedematous distended and/or thickened gall bladder, presence of stones and pericholecystic fluid on ultrasound examination were the criteria considered for acute cholecystitis. patients with choledocholithiasis, previous abdominal surgery, acute pancreatitis and comorbid like hypertension, heart disease, diabetes were excluded from the study. patients underwent lc on first available list within 72 hours by consultant surgeon skilled in laparoscopy and was performed using three ports. the study parameters in terms of difficulty in dissection during surgery, operating time, intraoperative and postop complications, postoperative hospital stay, and need to convert to open cholecystectomy were studied. data were collected and entered in a pre-designed proforma that included demographics of the patient, operative findings, operative time, intra or postoperative complications and hospital duration. the social sciences statistical package (spss version 20) was used for the entry and analysis of the collected data. descriptive statistics for both qualitative and quantitative data was determined. the mean and standard deviation was determined for quantitative factors, such as age and gender. we estimated the frequency and percentages of qualitative data such as gender, difficulties in dissection and the need for open surgery conversion. results among 143 patients with acute calculous cholecystitis, 38 were males and 105 were females with a ratio of males and females of 1:3.1. the mean age of patients was 46.23 years, ranged from 22 to 76 years. majority of patients belonged to fourth and fifth decade. patients' demographics and preoperative clinical data is presented in table i. ultrasound findings are shown in table ii. the mean operative time was 68.1 ± 25.31 minutes. laparoscopy was successful in 140 cases, and three cases were converted into open cholecystectomy. the reasons for conversion were unclear and distorted anatomy of calot's triangle due to thick dense adhesions, edema and exudates, bile leakage from cystic duct with suspicion of injury to common bile duct, and unexplained bleeding. three patients had biliary injury, two to common hepatic duct and one to accessary duct in gall bladder fossa, during surgery and were managed preoperatively. shorter hospital stay, decreased cost and same level of clinical safety with no major morbidity or mortality 8 discrepancy. however sample size of the trials was not big except gutt et al who recently reported a randomized controlled multicenter trial of 618 9 patients. with this emerging supportive data, still only a minority of surgeons are performing early lc in patients with acute cholecystitis. once the surgeons had experience in laparoscopic surgery, early lc for acute cholecystitis in the western countries became popular in the 1990's. tokyo guidelines 2018 (tg13) of japanese society of hepato-biliary-pancreatic surgery stated that the ideal management for acute cholecystitis due to cholelithiasis is early lc, mainly before 72�h of the 10 symptom onset. few studies showed that urgent lc should be the first choice therapy for ac in patients 11,12 who are fit for operative intervention. the purpose of this study is to evaluate the surgical outcomes of lc for acute calculous cholecystitis within 72 h of symptom onset, as this subject is less addressed in our local setup. keeping in consideration the results of recent research favouring early lc in acute cholecystitis, this trial is planned with the purpose of evaluating the outcome of lc in patients with acute cholecystitis. the objective of the study is to assess the outcome of lc in the treatment of acute cholecystitis in terms of difficulty of procedure, operative time, duration of hospital stay and incidence of complications. materials and methods this interventional quasi experimental study was conducted in surgical unit i, department of general st st surgery, pims, islamabad from 1 jan 2013 to 31 dec 2018. sample size of 143 patients with acute cholecystitis due to cholelithiasis was calculated by using who formula taking power of study = 80 and selected by convenient sampling. study was conducted after taking approval from hospital ethical committee. patients were included for inclusion after having written informed consent. patients who presented within 72 hours of symptoms of acute cholecystitis in emergency department were included in the study. diagnosis of acute calculus cholelithiasis was made by either senior postgraduate, senior registrar or assistant professor using clinical, laboratory and radiological findings. right hypochondrium tenderness with jiimc 2020 vol. 15, no.3 150 outcome of laparoscopic cholecystectomy discussion the application and timing of lc in patients of acute cholecystitis is still controversial, despite of guidelines published that advocate early lc during 13 same hospital admission. recently, few studies indicate that lc is feasible and considered safe for acute cholecystitis with various complications and 14,16 conversion rates. but are these complications and conversions appropriate to surgeons and especially patients who are at the end of suffering? therefore, further studies are required to obtain definitive results. with this background and intent, we studied the outcome of lc in acute cholecystitis as well as evaluating feasibility and safety in our local setting. mean age of patients in this study was 43.26 ± 11.28 (22 – 76 years), which is in consistent with the 8,17 regional studies but less than the european studies 18,19 (58 years). in the present study, the mean operating time was 68.1min (35 – 116) that is comparable to 2,20 other studies. we started lc in patients of acute cholecystitis after many years of experience of lc in cholelithiasis; so less operative time is possibly due to increase in skills and gaining more confidence. jarrar m s et al stated that the length of the operation for delayed lc group was significantly longer than for the early lc group (97 minutes versus 82.17 minutes, 21 p=0.003). lc was successfully completed in 140 patients and only three cases were converted to open cholecystectomy. this conversion rate of 2.1% is in 22 consistent with rehman et al (2.4%) and 1 abdelkader m et al (2%) but less than reported by 2 farooq a et al (5%). reasons for conversion to open were difficult anatomy and bleeding. the inflammation associated with acute cholecystitis results in an oedematous plane around the gall bladder, which promotes the dissection. this feature was observed in almost all cases therefore, operative and postoperative data was shown in table iii. there was no death in this study. the overall complication rate was 24.5 per cent and no major bile duct injury occurred in any patient. postoperative pain was experienced with variable degree of intensity. visual analog scale (vas) was used to measure pain intensities. 81 (56.6%) patients had mild pain, 54 (37.8%) had moderate pain, and eight (5.6%) had severe pain as calculated by vas. the average duration of hospital stay was 4.16 (3–8 days). table i: pa�ent’s demographics and preopera�ve clinical data (n=143) table ii: pre-opera�ve ultrasound findings table iii: opera�ve and post-opera�ve data (n=143) jiimc 2020 vol. 15, no.3 151 outcome of laparoscopic cholecystectomy sign references 1. abdelkader am, ali he. laparoscopic cholecystectomy for management of acute calculus cholecystitis within and after 3 days of symptom beginning: a retrospective study. egypt j surg 2018; 37:46-52. 21. 2. farooq a, zia l, khalid m. outcome of same admission laparoscopic cholecystectomy for acute cholecystitis in a district hospital. annals of king edward medical university 2019; 25(1): 81-5. 3. chhajed r, dumbre r, fernandes a, phalgune d. early versus delayed laparoscopic cholecystectomy for acute cholecystitis: a comparative study. international surgery journal 2018; 5(10): 3381-85. 4. rajcok m, bak v, danihel l, kukucka m, schnorrer m. early versus delayed laparoscopic cholecystectomy in treatment of acute cholecystitis. bratisl lek listy. 2016; 117(6):328-31. 5. thangavelu a, rosenbaum s, thangavelu d. timing of cholecystectomy in acute cholecystitis. j emerg med. 2018; 54(6):892-7. 6. song gm, bian w, zeng xt, zhou jg, luo yq, tian x. laparoscopic cholecystectomy for acute cholecystitis: early or delayed?: evidence from a systematic review of discordant meta-analyses. medicine (baltimore). 2016; 95(23):e3835. 7. wakabayashi g, iwashita y, hibi t, takada t, strasberg sm, asbun hj et al. tokyo guidelines 2018: surgical management of acute cholecystitis: safe steps in laparoscopic cholecystectomy for acute cholecystitis (with videos). j hepatobiliary pancreat sci. 2018; 25(1):73-86. 8. tayeb m, rauf f, bakhtiar n. safety and feasibility of laparoscopic cholecystectomy in acute cholecystitis. j coll physicians surg pak. 2018; 28(10):798-800. 9. gutt cn, encke j, k¨oninger j, harnoss jc, and weigand k, kipfmülleret k al. acute cholecystitis: early versus delayed cholecystectomy, a multicenter randomized trial (acdc study, nct00447304). annals of surgery 2013; 258(3): 385–93. 10. okamoto k, suzuki k, takada t, strasberg sm, asbun hj, endo i et al. tokyo guidelines 2018: flowchart for the management of acute cholecystitis [published correction appears in j hepatobiliary pancreat sci. 2019; 26(11):534]. 11. roulin d, saadi a, di mare l, demartines n, halkic n. early versus delayed cholecystectomy for acute cholecystitis, are the 72 hours still the rule? a randomized trial. ann surg 2016; 264(5): 717-22. 12. arslan onuk za, gündüz ur, koç ü, kızılateş e, gömceli i̇, akbaş sh, bülbüller n et al. same-admission laparoscopic cholecystectomy in acute cholecystitis: the importance of 72 hours and oxidative stress markers. ulus travma acil cerrahi derg. 2019; 25(5):440-6. 13. patel pp, daly sc, velasco jm. training vs practice: a tale of opposition in acute cholecystitis. world j hepatol 2015; 7(23): 2470-3. 14. lyu y, cheng y, wang b, zhao s, chen l. early versus delayed laparoscopic cholecystectomy for acute cholecystitis: an up-to-date meta-analysis of randomized controlled trials. surg endosc 2018; 32(12):472841. 15. kohga a, suzuki k, okumura t, yamashita k, isogaki j, dissection in majority of these cases was easy, associated with lesser needs to convert to open cholecystectomy. the ease of dissection also resulted lesser mean operative time and low morbidity. the patients had lesser severity of postoperative pain and nausea/vomiting episodes. laparoscopic cholecystectomy is more likely to be successful within the 72 hours following the onset of symptoms and operation in the next available elective list. this approach is associated with lesser 23 incidence of major complications. we agree that several main technical aspects need to be taken into account when conducting laparoscopic surgery for acute cholecystitis. we used some modifications to handle these technical difficulties, like decompression of the gall bladder, use of retrieval bag, subhepatic drain and widening of epigastric wound. the overall complication rate was 24.5% that is comparable to rate reported by other 16,18 researchers. intraoperative two patients with bleeding and one with bile duct injury were converted to open cholecystectomy. limitations of the study are less sample size and single centered study. future studies are recommended as randomized control trials for outcome of early versus late lc in patients of acute calculus cholecystitis to strengthen the evidence of beneficial effect of lc in acute cholecystitis. in summary, recent literature favors laparoscopic cholecystectomy in acute cholecystitis, although the timing of operation is debatable. evidence suggests that lc within 72 hours of onset of symptoms is both 24 safe and cost effective. patients with acute cholecystitis who are discharged without undergoing surgery may have a high risk of presenting with gall stone complications. so early lc in patients of acute cholecystitis is a favorable option in experienced hands. conclusion laparoscopic cholecystectomy can be performed safely in patients with acute calculus cholecystitis in expert hands and should be done within 72 hours of the onset of symptoms. it is more effective in terms of patient safety, less operative time, and less duration of hospital stay without increase in morbidity or mortality. jiimc 2020 vol. 15, no.3 152 outcome of laparoscopic cholecystectomy 21. jarrar ms, chouchène i, fadhl h, ghrissi r, elghali a, ferhi f, et al. early versus delayed laparoscopic cholecystectomy for lithiasic acute cholecystitis during emergency admissions. results of a monocentric experience and review of the literature. tunis med 2016; 94: 519-24. 22. rehman s, afzal m, butt qm. outcomes of laparoscopic cholecystectomy in acute cholecystitis. pakistan armed forces medical journal 2017; 67(1): 58-61. 23. griniatsos j. factors predisposing to conversion from laparoscopic to open cholecystectomy. ann laparosc endosc surg 2018; 3: 12. 24. sage's guideline for the clinical application of laparoscopic biliary tract surgery. january 9, 2019. (accessed june 14, 2020) available at https://www.sages.org/publications/ guidelines/guidelines-for-the-clinical-application-oflaparoscopic-biliarytract-surgery/. sanaka mr. nationwide trends of hospital admissions for acute cholecystitis in the united states. gastroenterol rep (oxf) 2017; 5(1): 36-42. kawabe a, kimura t. outcomes of early versus delayed laparoscopic cholecystectomy for acute cholecystitis performed at a single institution. asian j endosc surg 2019; 12(1): 74-80. 16. khalid s, iqbal z, bhatti aa. early versus delayed laparoscopic cholecystectomy for acute cholecystitis. j ayub med coll abbottabad 2017; 29(4): 570-3. 17. yokota y, tomimaru y, noguchi k, noda t, hatano h, nagase h, et al. surgical outcomes of laparoscopic cholecystectomy for acute cholecystitis in elderly patients. asian j endosc surg. 2019; 12(2):157-161. 18. jensen kk, roth no, krarup pm, bardram l. surgical management of acute cholecystitis in a nationwide danish cohort. langenbecks arch surg. 2019; 404(5):589-597. 19. terho pm, leppäniemi ak, mentula pj. laparoscopic cholecystectomy for acute calculous cholecystitis: a retrospective study assessing risk factors for conversion and complications. world j emerg surg. 2016; 11:54. 20. wadhwa v, jobanputra y, garg sk, patwardhan s, mehta d, jiimc 2020 vol. 15, no.3 153 outcome of laparoscopic cholecystectomy review�article� abstract objective: child health in pakistan is the greatest significant national issue that needs to take serious attention. rd pakistan ranks is 23 in global under-five mortality. in terms of development, the country is ranked at 125 out of 169 countries. this study aims to highlight the matter of under-five mortality and related government practices. materials and methods: this is a review, to assess child mortality trends in pakistan. we analyzed results from surveys, reports, journals that were related to child survival and death. we have selected data from 1989 to 2013 and recent researches from different data bases and gray literature like demographic, health and socioeconomic surveys. we analyzed socio-economic and health indicators to assess the current situation. results: it was found that under-five mortality in pakistan is 117 per thousand live births in 1990-91. mortality rate decreased to 94 per thousand live births in 2007 demographic health survey. in 2012-13, this rate declined to 89 per thousand live births. at the provincial level, we found the highest child mortality in punjab where under-five child mortality rate was 133 and 105 in 1991 and 2013 respectively. conclusion: we want to lessen child mortality through given human services offices and their uses, instruction, mindfulness projects and neediness eradication. although pakistan could not achieve the millennium development goals for child mortality, sustainable development goals provide another opportunity to urgently work towards reducing child mortality at the national level. key words: indicator, maternal health, mortality, socio-economic. these records for right around 46% of weight of 5 diseases. as indicated by unicef, in pakistan three 6 million youngsters are conceived each year. almost 400,000 babies deaths occur in the initial twelve 7 months of their life. “health for all” its signatory particular after almaata declaration in 1978, although, pakistan has demonstrated its dedication to the united nations' in the most recent plan of millennium development st goals (mdgs) into the 21 century. pakistan's child mortality goal under mdgs was to reduce child 8 mortality by three quarters between 1990 and 2015. we can assess national wellbeing matters through this marker in like manner. still, that basic to genuine rd consideration. globally, pakistan's rank is 23 in 9 u n d e r f i v e m o r t a l i t y w h i l e , i n t e r m s o f development, it is ranked at 125 out of 169 10 countries. in this study, we review various factors that influence child mortality in pakistan including socio-economic factors, demographic child health indicators, lack of knowledge and practices of the parents, and barriers in the health care delivery system, which hinder progress towards mdg 4 and alma atta declaration goals. introduction the child mortality rate is one of the health indicators that signifies the national status of health. pakistan has poor health indicators as infant mortality rate is 74 per 1,000 live births and under-five mortality rate 1 is 89 per 1000 live births. pakistan's child mortality rate is second highest after india in the south asian 2 region. according to who health statistics of 2014, pakistan 3 spends only 2.6% of its gdp on health. out of this, public sector spending accounted for 1.16% while a 4 larger share (1.17%) is spent by private sector. the ebb and flow wellbeing circumstance in pakistan is best portrayed as one where illnesses related with a work in progress (irresistible sicknesses and nourishing lacks) have yet not been controlled and socio-economic and demographics estimate of child mortality rates from 1989 to 2013: a review of literature 1 2 saima raheem baig , shuja ur rehman correspondence: saima raheem baig assistant professor, social sciences sindh madressatul islam university, karachi e-mail: srbaig100@gmail.com 1 department of social sciences sindh madressatul islam university, karachi 2 department of social work university of karachi, karachi funding source: nil; conflict of interest: nil received: jun 12, 2017; revised: sep 15, 2017 accepted: nov 10, 2017 trend of child mortalityjiimc 2017 vol. 12, no.4 213 objective to review the trend of child mortality in pakistan from 1989 to 2013 and find out the situation during this time series and to highlight socio-economic and demographic indicators as well. demographic indicators pakistan is the sixth most populated country in the world with a population of approximately 180 million. about 37% of pakistan's population is below 14 years of age, 59% is between 15 and 64 years of age while 4% is above 65 years of age. two-third of 1 1 pakistanis live in rural areas. average life expectancy has increased from 34 years in 1947 to 65 years in 2015. between 1950 and 2011 pakistan's urban population expanded over seven fold and total population increased by over four fold. currently, 12 annual population growth rate stands at 1.45%. socio-economic indicators pakistan has poor child health indicators despite a higher per capita income than the average for lowincome countries. according to pakistan's economic survey 2012, pakistan's economic growth is slow having average annual growth rate of 3.7% in 2012. gross national income (gni) per capita in pakistan is us$ 1,120, still, approximately one quarter (23%) of the population lives below the international poverty 13 line of us$ 1.25 purchasing power parity (ppp). source of drinking water. this proportion drops to 19% for rural population who rely mainly on unprotected surface sources with inadequate chlorination putting them at risk of water-borne diseases. thirteen percent resident use non-flush toilet and 13% of population has no access to toilet 15 facility. however, this sanitation situation is promotes infectious disease. mdg4 achievements many countries have achieved mdg goal 4 to reduce child mortality and improving child survival through major reduction in some of the leading causes of under-five deaths such as diarrhea, pneumonia, and measles even before 2015. pakistan has not been able to meet the deadline of 2015 even in the presence of several child survival programs implemented with the collaboration of unicef such as oral rehydration, integrated management of neonatal and childhood illness imci, breastfeeding promotion, immunization, and growth monitoring. other programs also contribute to improvement in child survival such as who control of diarrheal disease, extended program on immunization (epi) and acute respiratory infections-ari, government of pakistan national program for family planning and primary health care (npfp) also known as lady health worker (lhw) program, maternal newborn and child health care program (mnch), and national nutrition program (nnp). almost programs focus on primary findings and management of the maternal and childhood illness. presently, impulse to all projects development main drivers of mortality under five years and grown-up mortality related with social causes in like manner drinking water sources, sanitation and hygienic condition, human services practices and practices in regards to basic leadership, medicinal services getting and regenerative wellbeing. it is source foundations of youngster passing and furthermore known to the social causes. ecological background pakistan has a 1,046 kilometer (650 miles) long coastline along the arabian sea and gulf of oman in the south. it is bordered by iran and afghanistan in the west, india in the east and china in the north. pakistan's economy is predominantly agrarian about 16 and 75% population lives in rural areas. pakistan is administratively divided into four table i: demography and social health status source: 1. pslm 2014-15 above displayed pointers completely make to uncertainty to decrease child mortality, in these table investigate the education status is still low notwithstanding monstrous increment in the general adult mindfulness, 57% in 2015. female literacy level is low at 45% particularly as compared to male literacy rate of 68%., which is an expression 14 of low social development. only about 27% of population has access to tap water as the main trend of child mortalityjiimc 2017 vol. 12, no.4 214 provinces: sindh, punjab, baluchistan and khyber pakhtunkhwa (kpk). sources we considered both gray literature and electronic d a t a b a s e s s e a r c h e d b y p u b m e d [http://www.ncbi.nlm.nih.gov/pmc/], medline [https://www.ncbi.nlm.nih.gov/pubmed/] and undata [http://data.un.org/] and gray literature i.e. surveys, statistical, developmental and gazette reports was manually searched from various governmental institutions and international nongovernmental organizations. inclusion we included all those publications that were published in english from 1989 to 2015 and that were about child and maternal health indicators. we also included maternal health studies that identified socio-economic and demographic causes and consequences of under-five mortality. we contemplated 16 investigate articles and others were 24 surveys, reports and polices that all were fulfill the walled in area to models. exclusion abstracts, editorials, clinical trials and reports were not part of our review. we also excluded conference papers and proceedings. presentation in this study we analyzed trends of child mortality and related indicators extracted from child health studies. we examined all data in four categories by age, year, ecological background, and socioeconomic and demographic indicators. the reference management software endnote version x6 was used to manage all literature for this review. results our findings show the trend of child mortality in pakistan from 1989 to 2013. we examined all data in various countries in the region. data assembled from different sources is presented in table i. fig 1: map of pakistan with child mortality rate the above map shows the current status of child mortality in various regions of pakistan. punjab is the most populous province and produces most of the country's agricultural output. punjab also has the highest under-five mortality rate of all provinces. baluchistan has a dry desert climate and it is rich in natural resources including contains natural gas and minerals. baluchistan has the second highest child mortality rate in the country. sindh is pakistan's second largest province known for its agricultural output. it is bound in the west by the indus river and baluchistan, in the north by punjab, in the east by the indian states of gujarat and rajasthan, and in the 17 south by the arabian sea. child mortality rate in sindh is lower than punjab and baluchistan. however, developmental indicators such as access to tap water, toilet facility and literacy rate are lower in 18 sindh than other provinces. kyber pakhtun khwa (kpk) produces timber as well as citrus and dried fruits. kpk has a lower child mortality than other 19 provinces. there is a need to explore the social causes of child mortality at the national level and follow specific strategies to reduce child mortality. materials and methods design this is a review paper to explore socio-economic and demographic indicators of child mortality and designed for awareness and improvement concerning child mortality trends in pakistan. it is based on observational research strategy and chose meta-analysis with the fixation well-being pointer accomplishments for think about it. table i: progress toward millennium development goal 4 trend of child mortalityjiimc 2017 vol. 12, no.4 215 1. population reference bureau 2012 2. child mortality report 2012, available at: w w w. childinfo.org /files/child_mortality_ report_2012.pdf 3. source: unicef child survival report pakistan has committed to the united nations “health for all' declaration. as part of this declaration, pakistan aims to achieve reduction of its under-five mortality ratio from 140 per 1000 live births to 43 per 1000 live births between 1990 and 2015. however, above data shows pakistan's progress towards mdg4 has not been on track. while under-five mortality declined from 117 per 1000 live births to 89 per 1000 live births between 1990 and 2014, pakistan's under-five mortality is still higher than most others countries in the region. disturbing state of the youngster mortality in the punjab territory at 105/1000 live births. tragically, watched poorest outcomes in the baluchistan there was pattern proceed onward most astounding (111/1000 live births) death rate according to last pdhs 2012-13 as contrast with first pdhs information that was discovered (101/1000 live births) mortality proportion in 2006-07. while, region of sindh had most noteworthy rate (106/1000 live births) in pdhs 1990-91 and pdhs 2007 discovered (101/1000 live births) and further declined (93/1000 live births) in pdhs 2013. kpk likewise on a similar tract we discovered most astounding rate (98/1000 live births) in pdhs 199091 while pdhs 2007 discovered (75/1000 live births) and declined in (70/1000 live births) death rate in the pdhs 2013. discussion association with maternal health the child morbidity and mortality rate is associated with high fertility which is considered to be a risk factor of newborn mortality. maternal health status is significant in child health and mortality. antenatal care (anc) allows skilled health personnel to instruct fig 1: trends of child mortality in pakistan source: pakistan demographic health survey 2013-14 in the above figure we see the data of child mortality from 1990 to 2013. for comparison, mortality has been distributed into four categories by age group. neonatal mortality was highest (55/1000 live births) in 2013. although it was low (51 /1000 live births) in 1990-91 pdhs. post-neonatal mortality was highest (39/1000 live births) in the period of first pdhs (1990-91) and declined (19/1000 live births) in current pdhs (2013-14). we found infant mortality was highest (91/1000 live births) in first pdhs (199091) and declined (74/1000 live births) in pdhs 2013. similarly, child mortality was highest (17/1000 live births) in 1990-91 and declined (17/1000 live births) in pdhs 2013. overall under-five mortality rate was highest (117/1000 live births) in 1990 and decreased (89/1000 live births) in pdhs 2013. we examined provincial distribution of child mortality according to pdhs information. we discovered territory of punjab had most noteworthy rate (133/1000 live births) of general mortality amid first pdhs 1990-91, despite the fact that it declined (97/1000 live births) in the pdhs 2007. its shows table ii: provincial distribu�on of the child mortality trend of child mortalityjiimc 2017 vol. 12, no.4 216 mothers about how to take care of themselves and their baby during and after pregnancy. the world health organization (who) recommended at least 20 three and preferably four anc visits to identify any pregnancy and delivery complications. overall, in pakistan, only 28.4% women receive four or more anc visits. 70.1% women only receive less than four anc visit. however, in rural areas of pakistan only 19.8% women acquired who recommended number of visits and 78.9% obtain less than three 21 visits. low birth spacing has been found to increase the risk of infant and child mortality in many 22 studies. association with morbidity and immunization globally, morbidity is substantially reduced among children that received vaccines. in developing countries where vaccine-preventable diseases are the main causes of mortality among infants and children, it increasingly significant to demonstrate the effect and value of immunization programs, which must compete with other cost-effective 23 interventions for extremely limited resources. a report from guinea-bissau showed lower than expected mortality associated with bcg and measles vaccines, and increased mortality after diphtheriatetanus-pertussis (dtp) and oral poliovirus vaccine (opv) vaccinations. according to who guidelines, parents should give the children a bcg vaccine, three doses of dpt, polio vaccine, and measles vaccines 24 from birth to 23 months. in pakistan the proportion of fully immunized children increased from 78% in 2008-09 to 81% in 2010-11.14-15 moreover, breast feeding has been found to be protective against child mortality and preventive for diarrhea and ari 25 deaths. according to demographic surveys broke-down make mindfulness about significance of child vaccination over the land zones of provincial and urban ranges of the pakistan then it is watched that is similarly more remarkable to the zones of country 26,27 territories. association with nutrition deaths among children under five years of age were found to be associated with self-reported poor maternal health. it may also be associated with low birth weight, under-nutrition or illness exposure among children of mothers in poor health. as expected, child's age remained the most powerful 28 determinant of child's death. this could be due to greater susceptibility of infants to communicable 29 childhood illnesses. in pakistan, poor nutrition effects at least 10 million children and avoid almost 30 123,000 deaths each year. although, estimated proportions of deaths are associated with under nutrition and it is linked to an underlying cause of 31,32 death. association with education pakistan's situation of health and literacy rate of mothers is not satisfactory. although literacy level has been increasing in population aged 10 years and above, unfortunately overall literacy rate in pakistan is low when compared to other south asian association for regional cooperation (saarc) countries. overall, pakistan has a literacy rate of 58 33 percent. mother's education has very strong association with child mortality and maternal health. women who at least have basic education are more likely than illiterate mothers to adjust the size of their families according to their capabilities, and are more likely to provide better care for their children and 34 send them to school. association with family planning in preventing child deaths family planning is also a significant variable. socio-economic factors such as the family's place of residence, spouse education, and employment have also been correlated with family planning. a long time period between births allows a mother more time to recover from gestation and delivery. this also provides opportunity to provide breastfeeding, proper food and nutrition to 35 existing children. a korean study found that some maternal education is associated with shorter birth 3 6 spacing. the effects of birth interval are fundamentally associated and dependent on the use of family planning methods of the mothers. children born after a short interval of one year have a higher mortality rate, suggesting child should be born after 37,38 more than one year. health system in pakistan, the provincial health department is responsible for making provincial health policy in accordance with national health policy and to translate it into strategic plans, whereas the primary implementation responsibility lies with districts within each province. provincial governments are also responsible for providing funds to districts for trend of child mortalityjiimc 2017 vol. 12, no.4 217 health execution and for supervising district government performance. the district health department is an effective part of the public health sector in pakistan. it is responsible for management of budget, establishment of routine curative besides preventive, annual district health planning and promotion of healthcare services. planning functions spread out to designing healthcare services in accordance with community needs and formulation of policies pertaining to institution of user charges in health facilities in 39 districts. the public sector in pakistan consists of physically established health care network, comprising of more than 13,663 health facilities ranging from primary to tertiary care centers. there are approximately one thousands two hundred seventy beds per 83,028 population. while there are 5,377 dispensaries included with 1,179 beds. there are about 602 rural health centers (rhcs) with 10,377beds. additionally, there are 5,428 basic health unit/ sub health centers with 6,581. there are also 697 maternal and child 40 health centers with 345 beds. still, this expanded infrastructure is ineffectively equipped and poorly maintained resulting in low utilization, limited coverage and inadequate access to essential basic services. to fill this space, private sector serves about 70% of population health needs, with a fee-for-service system. private sector facilities range from nursing homes, dispensaries, small clinics, drug sellers, traditional healers, to big tertiary care hospitals offering varying quality of services. specialist discovered genuine and open perceptions of different markers amid the information audit and assess the raw numbers identified with general and maternal wellbeing, for example, pregnancy, labor and delivery period, and also child wellbeing sicknesses, treatment, health facility centers execution and socio statistic profile of the family. these survey exhibited the genuine state of the country that occupant in lower groups. to rehash comes about now request is expanding for a national passing registry framework and set up database on the reasons for child mortality. conclusion health and education indicators have improved in pakistan over the last decade. key improvements recorded in rates of newborns, infant, less five years and maternal mortality but still, off track on the mdgs 2015 targets. pakistan had lagging or making slow progress in 23 of the 32 mdg targets stated on, these targets are associated to education and health. badly, needed efforts for implementation on the sdgs targets for achievement of reduce child mortality by 2030. while, we had been want to decrease child mortality through given medicinal services, instruction, awareness projects and deprivation eradication. in spite of the fact that pakistan couldn't accomplish the mdgs objectives for child mortality, yet now feasible improvement objectives gave another chance to direly work towards diminishing child mortality in the nation. references 1. nips. pakistan demographic health survey 2013-2014. in: studies p, editor. islamabad: international inc. calverton 2014. p. 120. 2. progress report 2013-15 [internet]. 2015. available from: 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[ c i t e d 3 0 o c t o b e r 2 0 1 6 ] . a v a i l a b l e f r o m : http://www.who.int/countries/pak/en/. 4. zaidi s. pakistan health \economic network: landscaping health financing work in pakistan report islamabad: 2010; p. 12. 5. masud h. health policy: what does it mean in pakistan? policy actors' perspectives [mph]: umea university. 2011: p: 4. 6. universal children's day – children in pakistan have the right to be counted [internet]. unicef. 2011. 7. one child dies every minute in pakistan [internet]. 2011 [cited 28-1-2016]. available from: https://tribune.com.pk/ story/131565/one-child-dies-every-minute-in-pakistanreport/. 8. commission p. medium term development frame work 2005-2010. islamabad: government of pakistan. 2005; p: 85-91. 9. under five mortality [internet]. unicef. 2012 [cited 28-012 0 1 6 ] . ava i l a b l e f ro m : htt p s : / / w w w. u n i c ef. o rg / sowc2012/pdfs/under-five-mortality-rankings.pdf. 10. human development report [internet]. undp. 2010. available from: http://passthrough.fw-notify.net/ download/677722/ http://hdr.undp.org /sites/default /files/reports/270/hdr_2010_en_complete_reprint.pdf. 11. the world fact book: population growth [internet]. cia. 2 0 0 2 [ c i t e d 2 7 j u l y 2 0 1 6 ] . a v a i l a b l e f r o m : https://www.cia.gov/library/publications/the-worldfactbook/fields/2002.htmll. 12. the world fact book: south asia [internet]. cia. 2002 [cited 2 7 s e p t e m b e r 2 0 1 6 ] . a v a i l a b l e f r o m : https://www.cia.gov/library/publications/the-worldfactbook/geos/pk.html. trend of child mortalityjiimc 2017 vol. 12, no.4 218 13. highlight pakistan economic survey 2011-12. islamabad: government of pakistan. 2012. 14. pakistan social and living standard measurement survey 2014-15 [internet]. government of pakistan 2015 [cited 25o c t o b e r 2 0 1 6 ] . p. 3 3 8 . a v a i l a b l e f r o m : htt p : / / w w w. p b s . go v. p k /s i te s / d efa u l t / f i l e s / p s l m / p u b l i c a t i o n s / p s l m _ 2 0 1 4 1 5 _ n a t i o n a l p ro v i n c i a l district_report.pdf. 15. pakistan social and living standard measurement survey 2014-15 [internet]. government of pakistan 2015 [cited 25o c t o b e r 2 0 1 6 ] . p. 1 6 1 3 0 . a v a i l a b l e f r o m : http://www.pbs.gov.pk/sites/default/files/pslm/publicatio n s / p s l m _ 2 0 1 4 1 5 _ n a t i o n a l p r o v i n c i a l district_report.pdf. 16. pakistan statistics [internet]. undp. 2012 [cited 25october-2016]. available from: http://undp.org.pk/aboutpakistan.htm. 17. baig, saima r. a study of social causes involved in child mortality with special reference to peri-urban areas of karachi. [phd]. karachi: university of karachi. 2014. 18. division s. city report karachi population and housing census 1998. islamabad: statistical division. 2004. 19. nips. pakistan demographic health survey 2006-2007. in: studies p, editor. islamabad: international inc. calverton. 2008. 20. usaid. family advancement for life and health: baseline household survey karachi. 2010; p. 43. 21. nips. pakistan demographic health survey 2006-2007. in: studies p, editor. islamabad: international inc. calverton. 2008: p. 104. 22. d'souza rm, bryant jh. determinants of childhood mortality in slums of karachi, pakistan. journal of health & population in developing countries. 1999; 2: 33-44. 23. henderson rh. vaccinations in the health strategies of developing countries. scandinavian journal of infectious diseases. 1990; 76: 7-14. 24. kristensen i, aaby p, jensen h. routine vaccinations and child survival: follow up study in guinea-bissau, west africa. bmj (clinical research ed). 2000; 321: 1435-8. 25. victora cg, smith pg, vaughan jp, nobre lc, lombardi c, teixeira am, et al. evidence for protection by breast-feeding against infant deaths from infectious diseases in brazil. lancet (london, england). 1987; 2: 319-22. 26. van de poel e, o'donnell o, van doorslaer e. what explains the rural-urban gap in infant mortality: household or community characteristics? demography. 2009; 46: 827–50. 27. arif gm, ibrahim s. diarrhoea morbidity differentials among children in pakistan. the pakistan review. 1998, 37: 205-30. 28. university ak and pakistan institute of development. national nutritional survey 2001-2002. islamabad planning commission. 2002. 29. phalkey rk, aranda jc, marx s, hofle b, sauerborn r. systematic review of current efforts to quantify the impacts of climate change on under nutrition. proceedings of the national academy of sciences of the united states of america. 2015; 112: 4522-9. 30. black re, morris ss, bryce j. where and why are 10 million children dying every year? the lancet. 2003; 361: 2226-34. 31. rice al, sacco l, hyder a, black re. malnutrition as an underlying cause of childhood deaths associated with infectious diseases in developing countries. bulletin of the world health organization. 2000; 78: 1207-21. 32. world hunger and poverty facts and statistics 2013. [cited 0 5 o c t o b e r 2 0 1 6 ] . a v a i l a b l e f r o m http://www.worldhunger.org. 33. statistics bo. pakistan social and living standards measurement survey 2011, islamabad: government of pakistan. 2011; p. 114. 34. ann vm. education is key to reducing child mortality the link between maternal health and education. un chronicle. 2007; 44: 58. 35. contraception and reproduction: health consequences for women and children in the developing world. washington dc: national academy of sciences. 1989. 36. ramarao s, townsend j, askew i. correlates of inter-birth intervals: implications of optimal birth spacing strategies in mozambique: frontiers in reproductive health, population council. 2006; 32: 175–84. 37. conly, shanti r. family planning and child survival. the role of reproductive factors in infant and child mortality: an analysis. washington, d.c., population crisis committee [pcc]. 1991. 38. dean sv, lassi zs, imam am, bhutta za. preconception care: promoting reproductive planning. reproductive health. 2014; 11: s2. 39. masud h. health policy: what does it mean in pakistan? policy actors' perspectives [policies] : umea university. 2011. 40. baig sr. a study of social causes involved in child mortality with special reference to peri-urban areas of karachi. [phd]. karachi: university of karachi. 2014. trend of child mortalityjiimc 2017 vol. 12, no.4 219 page 53 page 54 page 55 page 56 page 57 page 58 page 59 untitled-2 original�article abstract objective: the purpose of this study was to determine the immediate effects of dry needling on pain and function among individuals with myofascial trigger points due to patellofemoral pain syndrome. study design: it was a single centered quasi experimental study. place and duration of study: it was performed at university of lahore teaching hospital from august 2018 to january 2019. materials and methods: thirty participants aged between 20 to 40 years were recruited. participants obtained a single treatment session of dry needling. function and pain was assessed at baseline and at 72 hours of trigger point dry needling. mean and standard deviation were reported, pre and post intervention scores were compared using wilcoxon signed rank. p value of less than 0.05 was considered significant. results: significant improvement was measured in pain (92.7±15.9) at 72 hours of intervention as compared to baseline value (89.0±12.2) on knee society score. the function score (73.6±11.1) was also improved. 90% individuals showed positive ranks on the lower extremity functional scale at 72 hours after the dry needling intervention. conclusion: dry needling cause's immediate and clinically significant reduction in pain and improvement in function of knee joint in the subjects with patellofemoral pain syndrome at 72 hours post treatment session. the immediate effects were studied but it is suggested that dry needling should be studied for its long term effects in patients with pfps. dry needling needs further investigation to be accepted as an isolated intervention for patients with patellofemoral pain. key words: acupuncture therapy, anterior knee pain syndrome, myofascial pain syndrome, patellofemoral pain syndrome, trigger areas. 3 squats, running and prolonged sitting. this challenging condition is recurrently seen with 4 chronic symptoms in 70-90% of individuals. in the past decades, several treatment strategies have been utilized for the treatment of 5 patellofemoral pain syndrome. an increasingly attention gaining method of treatment for the patellofemoral pain syndrome is dry needling, also 6 referred as westernized acupuncture. dry needling is considered as an emerging intervention strategy. it is the insertion of a solid needle into the skin and myofascial trigger area for the reduction of neuromuscular pain and restoration of range of motion. this technique is cheap, less invasive and can be performed with minimal risk but 7 the actual mechanism behind is yet to be elucidated. according to literature, the proposed mechanism of action is that dry needling generates localized and centralized nervous system responses, augmented 8,9 blood flow, improved oxygenation and reduced 10,11 peripheral and central pain sensitization. it has introduction patellofemoral pain syndrome is one of the most frequent injuries of the knee joint as well as the most common orthopedic illness. the incidence rate of this condition was found to be 1.5 to 7.3% in united 1 states. this syndrome is common among athletic 2 and nonathletic teenagers. the syndrome is caused due to daily life activities exerting compression on the joint for example descending stairs, performing immediate effects of dry needling on pain and function among individuals with patellofemoral pain syndrome 1 2 3 iqra khan , ashfaq ahmad , samreen sadiq correspondence: iqra khan assistant professor department of physiotherapy bakhtawar amin medical and dental college, multan e-mail: khan_iqra88@yahoo.com 1 department of physiotherapy bakhtawar amin medical and dental college, multan 2 department of physiotherapy university of lahore, lahore 3 department of physiotherapy lahore medical and dental college, lahore role of dry needling in patellofemoral syndromejiimc 2020 vol. 15, no.3 funding source: nil; conflict of interest: nil received: november 20, 2019; revised: august 18, 2020 accepted: august 19, 2020 167 with reference number as irb-uol-fahs/508/2019. those patients with patellofemoral pain syndrome diagnosed by orthopedic physician based on the inclusion criteria were taken in the study. inclusion criteria also comprised of patients who presented with complain of anterior knee pain almost for six months and had knee pain ranging from three to six on numeric pain rating scale. patients who experienced knee pain during at least two activities such as ascending and descending stairs, squatting, prolonged sitting periods with knee joint flexion, jumping activities and running were also included. those patients were excluded from the study who had history of arthritis, any surgical procedure around knee, meniscal injury, muscle or ligamentous rupture. exclusion criteria also constituted individuals who previously received acupuncture therapy or dry needling technique for knee extensor muscle in last six months. participants obtained a single treatment session of dry needling. they were instructed to fill the outcome measure questionnaire before the treatment and upon the second visit which was after 72 hours of intervention. the patient was instructed to lie supine and palpation of quadriceps muscle was performed on the effected side. three of the quadriceps muscles were targeted having two more painful areas each. the needling therapy was performed using classic plus sterile acupuncture needle 0.25*40mm. needles being inserted for approximately six to ten secondsand the motion sparrow pecking was used. quick in and out motion with coning was performed so that the twitching response can be achieved. the motions continue for a while until twitching can no more be elicited. subjects were asked to report any side effect noticed during anytime of the intervention. the intervention was executed by experienced and certified physical therapist. knee society score was used to assess function and pain at baseline and at 72 hours of trigger point dry needling. it is composed of two domains pain and function. each domain is graded as 0 to 100 scores; the greater value represents better function and less pain. grading for the knee society score is 80-100 being excellent, 70-79 being good, and 60-69 being fair and below 60 is considered as poor. the lower extremity functional scale was used to evaluate the functional level. it is scored on 5-point scale and total been reported that there is also a role of pain gate 12 theory in alleviating pain. previous clinical studies have revealed that dry needling initiates a localized action resulting in increased range of motion and decreased pain at the 13 tender point. elizabeth et al conducted a systematic review comparing the effects of dry needling to standard care in different painful body areas, and it was concluded that there is less evidence available in 14 the favor of dry needling. there is increasing demand of use of dry needling by physical therapists and certified professionals for the 15 trigger points in various body parts. despite the positive effectiveness of dry needling in pain relief, improved range of motion and quality of life, the utilization of dry needling is yet to be established and demonstrated. it is essential to continually evaluate and review the existing evidence to counter or favor the use of dry needling in myofascial trigger point 16 release. recent investigations have depicted that dry needling can provide a positive effect on pain in 17 various musculoskeletal conditions. to our knowledge there has not been a single study targeting patellofemoral syndrome with dry needling, its management is largely based on the expert opinions. a literature gap exists when considering the effect of dry needling as management strategy among patients with patellofemoral trigger points for pain reduction and improvement in overall function. therefore, the purpose of current study was to evaluate the immediate effects of dry needling as an intervention on the pain and function in the patients having myofascial trigger points due to pfps. materials and methods a single centered quasi experimental study was performed at university of lahore teaching hospital from august 2018 to january 2019. thirty participants aged between 20 to 40 years were recruited for the study. the sample size calculation was done using who sample size calculator keeping level of significance as 95%, standard deviation as 4.58 study power kept as 90%. the sampling technique used was non probability convenient sampling. informed consent was obtained from each participant of the study. the study was approved by institutional review board at university of lahore jiimc 2020 vol. 15, no.3 168 role of dry needling in patellofemoral syndrome discussion patellofemoral pain syndrome is a multifaceted and complex clinical issue. numerous biomechanical and neuromuscular etiological factors cause the joint reaction forces contributing to pain and poor 18,19 function. a number of intervention strategies have been advised due to variations in etiological factors. dry needling is an innovative therapeutic intervention that is supported by recent 14,20,21 researches. effects of dry needling have been studied widely in subjects complaining low back 22,23,24,25 26,27,28 pain cervical pain and shoulder girdle 20,29,30 pain. limited researches have evaluated the dry needling impact on less prevalent musculoskeletal 31 conditions including plantar fasciitis and score is 80. minimally detectable change recorded for this is 9 points. data was analyzed using spss version 21. the normality of collected data was checked and it came out to be non-parametric on shapiro-wilk test. mean and standard deviation were reported, pre and post intervention scores were compared using wilcoxon signed rank test. p value of less than 0.05 was considered significant. results between august 2018 to january 2019 total of the thirty consecutive subjects met eligibility criteria for the study. there were 22 (73%) female and 08 (27%) male study participant. the mean age calculated was 29.7 years with standard deviation being 9.5. mean intensity of knee pain was calculated at baseline numeric pain rating scale during squatting (4.1±2.3), upgoing (1.7±1.9) and down going (2.3±1.8) the stairs. (table i) pain and function level was measured by knee society score test and within-group mean change scores were evaluated showing p value less than 0.05 in both function (p=0.003) and pain (p=0.001) subscales. (table ii) the scoring was done at baseline and at 72 hours of intervention depicting the improvement through mean and standard deviation values. the baseline scores were less than the 72 hours recorded scores for kss function score, showing that the function was improved after the needling intervention. wilcoxon signed rank test was used to evaluate the function level through the lower extremity functional scale before and after intervention. (table iii) none of the subjects reported any adverse event to discontinue the treatment, and there have been no experience of minor side effects like blackouts, nausea, lethargy or weakness after the dry needling session. table i: par�cipants self-reported baseline demographics and variables f: female, m: male, nprs: numeric pain ra�ng scale, y: years table ii: knee society score within-group mean change scores kss: knee society score, s.d: standard devia�on table iii: wilcoxon signed ranks test – ranks a based on nega�ve ranks jiimc 2020 vol. 15, no.3 169 role of dry needling in patellofemoral syndrome patients recruited, and the study setting for the patient selection was a single hospital. secondly, the study did not include follow up period as the results were calculated at 72 hour interval only. it could not be predicted whether the long term evaluation will have same results. the study did not include the control group for comparison. future studies should target the other muscles involved in the patellofemoral syndrome that are gluteal, lateral rotators and trunk musculature. additionally, multicenter studies should be done to increase generalizability of the results and dry needling to be used in conjunction with other specific treatment strategies like manual therapy and taping. conclusion dry needling cause's clinically significant reduction in pain and improvement in function of knee joint in the subjects with patellofemoral pain syndrome at 72 hours post treatment session. the immediate effects were studied but it is suggested that dry needling should be studied for its long term effects in patients with pfps. dry needling needs further investigation to be accepted as an isolated intervention for patients with patellofemoral pain. references 1. glaviano nr, kew m, hart jm, saliba s. demographic and epidemiological trends in patellofemoral pain. international journal of sports physical therapy. 2015;10(3):281. 2. babadi n, roostayi mm, rahimi a, baghban aa, sarmadi a, roostaei h. the effect of different hip rotation angles on electromyography activity of the quadriceps muscle during closed kinetic chain tasks in healthy females. journal of physical therapy science. 2018; 30(8):1112-6. 3. şahin m, ayhan ff, borman p, atasoy h. the effect of hip and knee exercises on pain, function, and strength in patientswith patellofemoral pain syndrome: a randomized controlled trial. turkish journal of medical sciences. 2016; 46(2):265-77. 4. smith be, selfe j, thacker d, hendrick p, bateman m, moffatt f, et al. incidence and prevalence of patellofemoral pain: a systematic review and meta-analysis. plos one. 2018; 13(1):e0190892. 5. venere k, ridgeway k. trigger point dry needling: the data do not support broad applicability or robust effect. journal of manual & manipulative therapy. 2016; 24(1):2-4. 6. koppenhaver sl, walker mj, su j, mcgowen jm, umlauf l, harris kd, et al. changes in lumbar multifidus muscle function and nociceptive 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journal of athletic training. 2015;50(4):366-77. 35. mills k, blanch p, dev p, martin m, vicenzino b. a randomised control trial of short term efficacy of in-shoe foot orthoses compared with a wait and see policy for anterior knee pain and the role of foot mobility. br j sports med. 2012;46(4):247-52. 36. leibbrandt dc, louw q. the effect of mcconnell taping on knee biomechanics: what is the evidence? : stellenbosch: stellenbosch university; 2015. 33. sutlive tg, golden a, king k, morris wb, morrison je, moore jh, et al. short-term effects of trigger point dry needling on pain and disability in subjects with patellofemoral pain syndrome. international journal of sports physical therapy. 2018; 13(3):462. 34. ferber r, bolgla l, earl-boehm je, emery c, hamstra-wright k. strengthening of the hip and core versus knee muscles for the treatment of patellofemoral pain: a multicenter 2016;30:401. 32. blasco-bonora pm, martín-pintado-zugasti a. effects of myofascial trigger point dry needling in patients with sleep bruxism and temporomandibular disorders: a prospective case series. acupuncture in medicine. 2017;35(1):69-74. jiimc 2020 vol. 15, no.3 172 role of dry needling in patellofemoral syndrome original�article abstract objective: this study was conducted to determine the effects of virtual reality training on dynamic balance in chronic stroke patients. study design: quasi experimental design. st st place and duration of study: the study was conducted from 01 july 2015 to 31 december 2015 in the department of physical therapy, pakistan railway hospital rawalpindi. materials and methods: eight patients of chronic stroke with balance impairment were included through purposive non-probability sampling. the intervention was provided for 6 weeks including virtual reality training for 10-15 minutes per day, 4 days/ week to all patients. dynamic balance was measured using berg bbalance test and mobility was assessed through timed up and go test. tinetti performance oriented mobility assessment was used to assess both the mobility and dynamic balance. the pre and post mean was compared through spss 21 version. results: mean score of berg balance scale was 35±08 and after 6 weeks of intervention score was 53.33±2.65. mean score and standard deviation of tinetti performance oriented mobility assessment scores which were initially 12.37±8.21 and after 6 weeks of intervention score was 25±02.09. mean score and standard deviation of timed up and go scores which was initially; 29.08±15.03 and after 6 weeks of intervention score was 8.96±3.4. overall improvement was seen in dynamic balance of stroke patient, along with increased confidence in performing activities of daily living. conclusion: this study demonstrates improvement in dynamic balance after virtual reality training, indicating that virtual reality can play an important role in rehabilitation of balance impairment in chronic stroke. key words: dynamic balance, stroke, virtual reality training, xbox. 4 population. the stroke disability is directly linked with the loss of balance, gait disturbance, functional 5 loss and increase risk of fall. the negative consequences of impairments include the restricted community participation, lack of activities of daily 6,7 living and marked restrictive role in the society. the appropriate stroke rehabilitation is progressive, dynamic and goal oriented process which aimed to enable a stroke person to reach optimal functional 8 level. there are multiple approaches designed to enhance the level of independence in stroke patients 9 include bobath treatment progressive resisted 10 training, proprioceptive neuromuscular facilitation 11 12 pnf, constraint induced movement therapy cimt 13 and task oriented training. these all approaches mainly focus on repetition of activities but there is lack of interesting and encouraging activities for maximum repetitions. but patients find such approaches boring and no incentive in performing 14 such activities. in recent times a concept of virtual reality training introduction the cerebrovascular accident or stroke is neurological condition of sudden onset which leads to focal neurological deficits due to lack of 1 appropriate blood supply to brain the global annual prevalence of stroke is 15 million and one third of nd them die secondary to stroke. the stroke is the 2 th most common cause of death worldwide and 4 in 2 low income countries. the annual incidence of 3 stroke in pakistan is 250 per 10,0000. the economic loss and social burden is greater in young stroke effect of virtual reality training on dynamic balance of chronic stroke patients 1 2 3 anam zafar , arshad nawaz malik , tahir masood correspondence: dr. arshad nawaz malik associate professor & hod department of physical therapy shifa tameer-e-millat university, islamabad e-mail: physiomalik1@gmail.com 1,2 department of physical therapy shifa tameer-e-millat university, islamabad 3 department of physical therapy isra institute of rehabilitation sciences, islamabad funding source: nil; conflict of interest: nil received: sep 12, 2017; revised: feb 15, 2018 accepted: feb 16, 2018 virtual reality trainingjiimc 2018 vol. 13, no.1 21 rehabilitation sciences. the informed consent was taken and the treatment procedure was briefly explained to the patients. the standardized test for balance and mobility including berg balance test (bbt), timed up and go (tug) and performance oriented mobility test (poma) were used at baseline, after 02, 04 and 06 weeks. the bbt used for analysis of dynamic balance while tug is reliable tool for assessment of mobility. the poma is a valid tool for the assessment of both gait and balance. task oriented training included the reaching activities, standing balance, marked gait training, sit to stand practice and in addition to that 1015minutes virtual reality training through exergaming was provided. virtual reality training was given using kinect. virtual training was given for 6 at nd st weeks with 4 days per week, 1 and 2 day of 1 week were orientation session where patient got tutorial about the game, later on with each week difficulty wa s i n c re a s e d to m a i n ta i n a c h a l l e n g i n g environment for patient. the trained therapist assessed the patients and performed the functional tasks. the data was analyzed through spss 21 version and the mean and standard deviation was compared. (table i) the data was compared with pre and post training at baseline and after 02, 04 and 06 week. the mean difference was analyzed for difference at multiple time periods. through exer-gaming has been introduced for 15 physical rehabilitation of stroke patients. the virtual reality (vr) is a computer generated environment which delivers the sensory gesture and make the person with imaginary objects and incidents are real. in such vr environment patients perform task like walking, moving objects, picking 16 and throwing which feel like real activity. there is positive impact of virtual reality training through exer-gaming with neural plasticity in post stroke 1 7 patients. the vr training has significant improvement in functional outcome and level of motivation in stroke patient but the just mention in the beginning and then specific equipment is too expensive to use for patients. so there are few commercial video games are available like xbox are 5 being used for the purpose of stroke rehabilitation. the xbox with kinect is effective to enhance the activity level, functional recovery motivation, interest, engagement, repetition and chronic activity 18 of daily life in stroke patients the exer-gaming through x box is effective for physical performance and also have greater positive effect on emotional 19 functions and to promote selective attention. the main issue regarding the motivation of patient towards training is considered in the current study. the vr training with x box has significant addition in stroke rehabilitation in terms of functional outcome with enhance level of motivation. it can be cost effective regarding financial, time, manpower and in future can be integral part of home based stroke 2 0 rehabilitation. this study will provide the framework for using vr training and would be an addition to existing literature. the purpose of this study was to determine the effect of additional virtual reality training on dynamic balance in chronic stroke patient. materials and methods this was quasi interventional pilot study conducted st st from 01 july to 31 december 2015 in department of physical therapy, pakistan railway hospital rawalpindi. eight chronic stroke patients, above 40 year of age, who were able to stand without support for at least 30 seconds were included through purposive sampling technique. the exclusion criteria were cognitive impairment, severe balance loss and vision impairment. the ethical approval was taken from ethical committee of riphah college of table i: virtual reality training protocol results eight patients followed intervention for 6 weeks out of which, 7 were males and 1 female. the mean age of the patients was 52.23±6.45 year. table ii: descrip�ve analyses of timed up and go test 22 virtual reality trainingjiimc 2018 vol. 13, no.1 discussion the current study reveals that virtual reality training has better outcome regarding balance in stroke patients. the balance training mainly focuses on stability functions like equal weight bearing; attainment of the motor strategies is usually loss during stroke and is needed to perform the fast and safe postural changes. this training can directly improve stability and balance and indirectly improve the safety and gait speed of the chronic stroke population. in this study improvement in dynamic balance was assessed using berg balance scale and improvement was reported after two weeks of intervention, but significant improvement was observed after 4 weeks of intervention. the study reported low fall risk after 4 weeks and also found 16 berg balance is good tool for assessment of balance. a study conducted by wagner henrique souza silva et al. also suggested that stroke patients have significant improvement in dynamic balance after virtual reality training. they also recommended that virtual reality have positive effect in addition to conventional therapy to improve functional independence and dynamic balance in chronic 21 stroke patients. the mobility was assessed through timed up and go test and it was reported that after 06 weeks of training, there was significant improvement in mobility level of stroke patients. ki hun cho elaborated the result of time up and go and found t h a t v i r t u a l r e a l i t y g r o u p h a s s i g n i f i c a n t improvement in mobility level as compare to the 5 traditional training in chronic stroke. similar studies in literature are suggesting that the additional virtual re a l i t y t ra i n i n g h a s b e tt e r re s u l t i n s t ro ke improvement. the virtual reality treatment is a u g m e n t e d r e h a b i l i t a t i o n a l o n g w i t h t h e 22 conventional treatment. the virtual reality training has linked in the formation of neural reorganization 23 and re learning of stroke patients. the clinical improvements reported here confirm the positive relationship between balance function and other aspects of functional mobility and gait previously published. previous studies also suggest the importance of balance ability besides muscle s t r e n g t h a s a n i m p o r t a n t d e t e r m i n a n t o f performance in gait functions in individuals with stroke. a systemic review conducted by marcela the table ii shows mean score and standard deviation of tug scores (measure level of mobility in seconds) which was initially; 29.0875(±15.036) after 2 weeks improved to be: 21.987(±9.931), then after 4 weeks of intervention tug score was; 13.362(±4.2), and after 6 weeks of intervention score was 8.966(±3.4). fig 1: graphic representa�on of poma test the fig 1 shows an improvement in score of performance oriented mobility assessment scale used to measure dynamic balance and gait. mean score of poma initially is 12, which after 2 weeks of intervention improve to 16, further after 4 weeks of intervention mean score is 23, and reach 25 after 6 weeks of intervention. fig 2: graphic representa�on of berg balance test the fig 2 shows an improvement in score of berg balance scale used to measure dynamic balance. mean score berg balance scale initially is 35, which after 2 weeks of intervention improve to 43.8, further after 4 weeks of intervention mean score is 51.1, and reach 53.3 after 6 weeks of intervention. 23 virtual reality trainingjiimc 2018 vol. 13, no.1 with a video-game system improves dynamic balance in chronic stroke patients. the tohoku journal of experimental medicine. 2012; 228: 69-74. 6. lord se, mcpherson k, mcnaughton hk, rochester l, weatherall m. community ambulation after stroke: how important and obtainable is it and what measures appear p r e d i c t i v e ? a r c h i v e s o f p h y s i c a l m e d i c i n e a n d rehabilitation. 2004; 85: 234-9. 7. yang yr, tsai mp, chuang ty, sung wh, wang ry. virtual reality-based training improves community ambulation in individuals with stroke: a randomized controlled trial. gait & posture. 2008; 28: 201-6. 8. hashmi m, khan m, wasay m. growing burden of stroke in pakistan: a review of progress and limitations. international journal of stroke. 2013; 8: 575-81. 9. graham jv, eustace c, brock k, swain e, carruthers si. the bobath concept in contemporary clinical practice. topics in stroke rehabilitation. 2009; 16: 57-68. 10. flansbjer ub, miller m, downham d, lexell j. progressive resistance training after stroke: effects on muscle strength, muscle tone, gait performance and perceived participation. journal of rehabilitation medicine. 2008; 40: 42-8. 11. a ko s i l e c o , a d e g o ke b a , j o h n s o n o . ef fe c t s o f proprioceptive neuromuscular facilitation technique on the functional ambulation of stroke survivors. journal of nigeria society of physiotherapy. 2012; 18: 22-7. 12. rehman b, rawat p, agarwal v, verma sk. a study on the effectiveness of bobath approach versus constraint induced movement therapy (cimt) to improve the arm motor function and the hand dexterity function in post stroke patients. int j physiother res. 2015; 3: 912-8. 13. rensink m, schuurmans m, lindeman e, hafsteinsdottir t. task-oriented training in rehabilitation after stroke: systematic review. journal of advanced nursing. 2009; 65: 737-54. 14. g i l g ó m ez j a , l l o ré n s r , a l c a ñ i z m , c o l o m e r c . effectiveness of a wii balance board-based system (ebavir) for balance rehabilitation: a pilot randomized clinical trial in p a t i e n t s w i t h a c q u i r e d b r a i n i n j u r y. j o u r n a l o f neuroengineering and rehabilitation. 2011; 8: 30. 15. burdea g, coiffet p. virtual reality technology. presence: teleoperators and virtual environments. 2003; 12: 663-4. 16. weiss pl, rand d, katz n, kizony r. video capture virtual reality as a flexible and effective rehabilitation tool. journal of neuroengineering and rehabilitation. 2004; 1: 12. 17. amft cs, eng k, lehmann i, schmid l, kobashi n, thaler i, et al. using mixed methods to evaluate efficacy and user expectations of a virtual reality–based training system for upper-limb recovery in patients after stroke: a study protocol for a randomised controlled trial. trials. 2014; 15: 350. 18. sin h, lee g. additional virtual reality training using xbox kinect in stroke survivors with hemiplegia. american journal of physical medicine & rehabilitation. 2013; 92: 871-80. 19. chen st, chiang i, liu ezf, chang m. effects of improvement o n s e l e c t i v e at t e n t i o n : d e v e l o p i n g a p p r o p r i a t e somatosensory video game interventions for institutionaldwelling elderly with disabilities. turkish online journal of cavalcanti moreira et all focusing use of vr or the improvement of gait in post-stroke patients demonstrated that the use of vr promotes changes in gait parameters. this also concluded that suggest that vr is a promising method to improve the gait of 2 4 patients with stroke. commonly increase in functional strength and balance reduce risk of fall in older adults, virtual reality treatment is therefore beneficial in improving balance and reducing fall risk. abel angel rendon et all conducted a study to evaluate effect of virtual reality on dynamic balance of older adults by randomized control trial show significant improvement in vrg in the 8-foot up & g o te st a n d t h e a c t i v i t i e s s p e c i f i c b a l a n c e confidence scale. proving that virtual reality gaming is a useful clinical tool for improving dynamic balance 25 and balance confidence in older adults. malik reported in case report that virtual reality through exer-gaming has significant effect in enhancing the 26 dynamic balance in chronic stroke. the study design and the sample size was one of major limitation in study. further research needed to determine and compare the effects of virtual reality training on elderly and stroke patients. conclusion it is concluded that virtual reality training improves dynamic balance, mobility and functional status of chronic patients. it provides a safe environment to the patient to perform real life task without the risk of fall which is an important factor in increasing patient's confidence in mobility. references 1. durukan a, tatlisumak t. acute ischemic stroke: overview of major experimental rodent models, pathophysiology, and therapy of focal cerebral ischemia. pharmacology biochemistry and behavior. 2007; 870: 179-97. 2. organization wh. the top 10 causes of death. geneva switzerland: who; 2014 [cited 2015 20th july 2015]; available from: http://www.who.int/mediacentre/ factsheets/fs310/en/. 3. neurology pso. stroke in pakistan. karachi: pns society; 2 0 1 5 [ c i t e d 2 0 1 5 1 5 t h j u l y ] ; a v a i l a b l e f r o m : http://www.pakstroke.com/pages/membership.asp. 4. truelsen t, heuschmann p, bonita r, arjundas g, dalal p, damasceno a, et al. standard method for developing stroke registers in low-income and middle-income countries: experiences from a feasibility study of a stepwise approach to stroke surveillance ( s t e p s stroke). the lancet neurology. 2007; 6: 134-9. 5. cho kh, lee kj, song ch. virtual-reality balance training 24 virtual reality trainingjiimc 2018 vol. 13, no.1 villavicencio is, leder r, et al. neural reorganization accompanying upper limb motor rehabilitation from stroke with virtual reality-based gesture therapy. topics in stroke rehabilitation. 2013; 20: 197-209. 24. moreira mc, de amorim lima am, ferraz km, benedetti rodrigues ma. use of virtual reality in gait recovery among post stroke patients–a systematic literature review. disability and rehabilitation: assistive technology. 2013; 8: 357-62. 25. rendon aa, lohman eb, thorpe d, johnson eg, medina e, bradley b. the effect of virtual reality gaming on dynamic balance in older adults. age and ageing. 2012; 41: 549-52. 26. malik an, zafar a. high level activity training through virtual reality in chronic stroke survivor: a case report. 2017; 4: 36-9. educational technology-tojet. 2012; 11: 409-17. 20. m a l i k a n . e xe rg a m i n g : a n o v e l to o l i n s t r o ke rehabilitation. journal of riphah college of rehabilitaion sciences. 2015; 3: 48-9. 21. silva whs, lopes glb, yano km, tavares nsa, rego iao, cavalcanti fadc. effect of a rehabilitation program using virtual reality for balance and functionality of chronic stroke patients. motriz: revista de educação física. 2015; 21: 23743. 22. betker al, desai a, nett c, kapadia n, szturm t. gamebased exercises for dynamic shortsitting balance rehabilitation of people with chronic spinal cord and traumatic brain injuries. physical therapy. 2007; 87: 138998. 23. espina fo, fernández del castillo i, palafox l, pasaye e, 25 virtual reality trainingjiimc 2018 vol. 13, no.1 page 26 page 27 page 28 page 29 page 30 untitled-1 abstract background: emergency peripartum hysterectomy (eph) is a major surgical procedure. there appears to be a rise in the rate of emergency peripartum hysterectomy (eph) in the developed world. peripartum hysterectomy is high risk but a life saving operation. it is usually associated with significant maternal and fetal morbidity and mortality. obstetricians should identify patients at risk and anticipate the complications, as early intervention and proper management results in optimal outcome. objective: to determine the incidence, indications, risk factors, complications and management of eph over the last eleven years. study design: a descriptive study. place and duration of study: all cases of eph performed in the period between january 2001 and december 2011 were included in the study. study was conducted at railway teaching hospital, rawalpindi (in northern pakistan). materials and methods: data of all the cases of eph cases operated during the study period was collected from the hospital obstetric record. data of basic demographics, mode of delivery, maternal and fetal outcome along with associated complications was collected and entered into the statistical package for social sciences version 14.0 (spss inc., chicago, il, usa) for further analysis. indications, pre-op planning, type of operation, emergency decision, blood loss, transfusion, complications, were compared and cross-tabulated. statistical analysis included: chi-square and fisher exact tests, where appropriate, and two-sample t test. results: total deliveries were 13560 in 11 years. twenty six eph cases were performed among deliveries, giving an incidence of 1.8 per 1000 deliveries i.e. one in 566 deliveries. the indications were uterine atony (34.61%), ruptured uterus (23.07%) and cervical/vaginal tears (11.53%), placenta praevia (11.53%), invasive placental adhesion [accreta, increta, percreta (11.53%)]. a significant association between previous uterine surgery and abnormal placentation was shown (p=0.02), especially those with previous caesarean (p=0.003). one maternal and six perinatal mortalities were recorded. four perinatal deaths were of non booked patients, handled by traditional birth attendants/private clinics. out of two perinatal deaths of booked patients, one was pre-term and other was delivered by forceps. maternal morbidity was prevalent, including twenty three intensive care admissions, three disseminated intravascular coagulopathies, three bladder injuries, three re-explorations, multiple blood, ffps & platelet transfusions, two pulmonary embolism & one cardiorespiratory failure. maternal death was of non booked patient with previous scar, home delivery, uterine rupture and brought to hospital with un-recordable bp and very weak pulse. conclusions: incidence of peri-partum hysterectomy is increasing. it is a major operation, and almost always an emergency with significant blood loss. an early decision should be made to save life of the patient and prevent complications. the most important risk factor for peripartum hysterectomy in our patients is hemorrhage, most notably caused by uterine atony, uterine rupture, placenta previa and abnormally adherent placenta. keywords: peripartum hysterectomy, uterine atony, maternal morbidity, perinatal mortality 103 original article unfpa and the world bank: 2010. trends in m a t e r n a l m o r t a l i t y : 1 9 9 0 t o 2 0 0 8 ) . approximately one-half of these deaths are preventable. peripartum hysterectomy is removal of pregnant uterus after 20 weeks gestation at or near time of delivery (performed within 24 hours of a delivery) but within the first 6 weeks postpartum. it is a technically difficult but life saving procedure especially introduction women are the pillars of social & economic development. their health & well being is vital for future generations. an estimated 3 , 5 8 0 0 0 m a t e r n a l d e a t h s o c c u r r e d worldwide in 2008. (who, unicef, ------------------------------------------------emergency peripartum hysterectomy in pakistan railway teaching hospital rawalpindi: eleven years review saadia sultana, muhammad nadim akbar khan, shamsunnisa sadia, noor mah khan, fareesa waqar, azra saeed, umber jalil correspondence: dr. saadia sultana associate prof. obs/ gynae pakistan railway hospital, iimc-t, rawalpindi e-mail: mushpk99@yahoo.com 104 when performed as an emergency. its complications are 4 times than those of an elective procedure. intraoperative and postoperative complications are much more than that of gynecological hysterectomy. its mortality is 5 times greater than an elective procedure. life-threatening haemorrhage resulting from uterine rupture and atony has become rare events in the developed world. but it is still a major problem in obstetric care in 1d e v e l o p i n g c o u n t r i e s . p e r i p a r t u m hysterectomy may be performed in emergency as a last resort to save the life of a woman with persistent bleeding or as planned procedure, often in conjunction with cesarean delivery. it is performed in 0.05 to 0.1 percent of deliveries. it is one of the life saving surgical procedures performed at the department of obstetrics and gynaecology of the railway teaching hospital. moreover, it is considered one of the most serious complications in obstetrics 2with adverse outcomes for women. t h e m a i n c o m p l i c a t i o n s re l a t e d t o emergency peripartum hysterectomy i n c l u d e d i s s e m i n a t e d i n t r a v a s c u l a r 3coagulation (dic), transfusions , need for re-laparotomy because of persistent bleeding, febrile morbidity, major surgical 4complications or maternal death. many studies have estimated an incidence rate of 0.8 and 1.5 per 1,000 deliveries in 5 united states. incidence is higher in developing countries due to decrease compliance of patients and lack of availability and utilization of antenatal care services especially in the rural areas. there also is a rise of eph in the developing 6 world. some risk factors for peripartum hysterectomy have been identified, including prior cesarean delivery, mode of delivery or multiple births. a prior cesarean delivery is associated with an increased rate of abnormal placentation, including placenta previa, accreta & increta in 7 subsequent pregnancies. the purpose of this study was to determine the incidence of peripartum hysterectomy, the indications, risk factors, the perinatal a n d m a t e r n a l o u t c o m e s a n d t h e c o m p l i c a t i o n s a s s o c i a t e d w i t h t h e procedure at the railway teaching hospital, rawalpindi, pakistan. this would help highlight the importance of lack of availability and utilization of antenatal services. identify avoidable factors and the need to organize health care services. it can be a contribution towards improvement of maternal and fetal outcome objective of the study was to determine the i n c i d e n c e , i n d i c a t i o n s , m a t e r n a l characteristics, risk factors, maternal and perinatal outcomes and complications of emergency peripartum hysterectomy (eph) at railway teaching hospital, rawalpindi. these hysterectomies were performed by consultants with negligible differences in their operating techniques. this was a descriptive study, carried out at gyne /obs department of pakistran railway teaching hospital, islamic i n t e r n a t i o n a l m e d i c a l c o l l e g e , rawalpindi.from january 01, 2001 to december 31, 2011. pakistran railway teaching hospital is located at the junction of rawalpindi & islamabad (capital of pakistan), which are twin cities. a large number of afghan refugees of different castes and tribes; who migrated to pakistan got settled in these localities. our hospital is one of the undergraduate and post graduate teaching hospitals. data of all the eph cases operated were obtained from the hospital obstetric record. each case record was analyzed in details with special emphasis on maternal characteristics demographic data (age, parity, booked or emergency case etc.), indications for hysterectomy (hysterectomy for any indication during pregnancy, labor materials and methods 105 and puerperium has been included), type of o p e r a t i o n p e r f o r m e d , p r o b l e m s encountered during operation, maternal & peri-natal outcome, morbidity, mortality & causes of maternal morbidity and mortality were studied. during this period there were 13,560 deliveries, out of which 11,960 were vaginal deliveries and 682 caesarean sections were performed. during the study period, 26 women were noted to have undergone an emergency peripartum hysterectomy, giving an incidence is 1.8 per 1000 deliveries i.e. 1 in 566 deliveries. data regarding their basic demographics, mode of delivery, maternal and fetal outcome, along with associated complications was then collected and entered into a database developed in microsoft access 2000. this was then imported into the statistical package for social sciences version 17.0 (spss inc., chicago, il, usa) for statistical analysis. as noted above, 26 women were identified who underwent an emergency peripartum hysterectomy from a total of 13,560 deliveries (table i). out of which 11,960 were vaginal deliveries and 682 had caesarean sections. therefore, the incidence of peripartum hysterectomy is 1.8 per 1000 deliveries i.e. 1 in 566 deliveries. out of 26 w o m e n w h o u n d e r w e n t e m e rg e n c y peripartum hysterectomy, eighteen cases were non booked (73.1%) & only eight were booked (26.8%). it means that majority of these patients had received no antenatal care prior to their presentation to the hospital. this is really alarming situation. majority of these patients belonged to very low socioeconomic group. as shown in table ii, only five patients were primi-paras. most of the patients were h a v i n g 2 4 c h i l d re n ( 6 5 % ) . g r a n d multiparas were 21.9%. as shown in table iii, the main indication for peripartum hysterectomy was severe results haemorrhage caused by uterine atony 09 (34.61%). other indications included ruptured uterus 60 (23.07%); morbidly adherent placenta 03 (11.53%); placenta praevia 03 (11.53%); cervical/vaginal tears 03 (11.53%) and two patients reported with dic (7.69%). in our series of patients, the commonest table i: no. of deliveries, caesarean hysterectomy & booking (n=13560) table ii: age distribution of the patients & their percentages( n=26) table iii: outline of indications of eph (n=26) 106 indication for an eph was uterine rupture in 6 (23.07%) cases. two of these cases were due to previous one scar in labour. one each is due to accidental haemorrhage, prolonged labour, instrumental delivery and oxytocin abuse. some cases appeared to be related to presentation of multipara and grand mutipara to traditional birth attendants (tbas). cases of obstructed labor are due to m a l p re s e n t a t i o n a n d c e p h a l o p e l v i c disproportion neglected by tbas (or “dai”). both the patients of lower segment caesarean section were tried for vaginal birth after caesaren (vbac) at home by tbas. in majority of patients of our study, eph was p e r f o r m e d b e c a u s e o f p o s t p a r t u m hemorrhage (pph) mainly due to uterine atony. other indications were abruption plcentae with covualaire uterus, and placenta percreta. these findings are very much similar to a study from the province of sindh, pakistan, where eph were mainly 8 performed due to uterine rupture. there was one (3.84%) maternal death. this table iv: maternal morbidity and mortality in patients with eph (n=46) patient died due to cardio-respiratory failure. twelve (44%) patients stayed for 12 days or less, 11 (40%) for 13-22 days and 2 stayed for 24-35 days. the hospital stay of these patients ranged from 7 to 35 days, with a mean of 14 days. this represents huge financial burden on the patients and health care system of the country with serious economic and social consequences. parity of patients ranged from 0–13. one patient was primigravida, required hysterectomy due to abnormally adherent placenta, three were requiring eph due to rupture of a previous caesarean scar; while the rest were multiparas. sixty nine percent of patients were grand multipara (≡ 5 previous deliveries). to t a l a b d o m i n a l h y s t e re c t o m y w a s performed on 17 patients out of 26; nine u n d e r w e n t s u b t o t a l h y s t e re c t o m i e s . subtotal hysterectomy is also an acceptable 9 option in technically difficult situations. almost all surgeries were performed in emergency (24/26); only 2 were performed as elective procedure. majority of the complications noted were infections (wound infection, fever and urinary tract infection) followed by complications related to the surgery itself. all patients who underwent eph received blood transfusion table v: fetal and neonatal outcomes (n=26) during or in the immediate postoperative period. there were 8 (30.77%) perinatal deaths noted in this series of patients. six were 107 stillborn, 4 of which were due to a ruptured uterus and 2 were because of abruptio placentae. there were two neonatal deaths due to neonatal sepsis and aspiration pneumonia. in our study 26 women underwent eph from a total of 13,560 deliveries. out of these, 11960 were vaginal deliveries and 682 caesarean sections. therefore, the incidence of eph in our hospital is 1.8 per 1000 deliveries i.e. 1 in 566 deliveries. whereas, in a study conducted in turkey, 34 cases of eph 10 were performed over a 10-year period. similarly, in a study from new york, 48 cases o f p e r i p a r t u m h y s t e r e c t o m y w e r e performed over 8-year period; with an 11 incidence of 1.4 per 1000 births. compared to a study performed in australia where only 33 eph were documented among 33,998 births over a 10-year period, the incidence documented was 0.85 per 1000 births; our rate of eph is approximately 212 fold higher. our study is representing an alarmingly high number of eph at a tertiary care hospital of a developed city of pakistan there is an increasing trend in eph 1980s to 2013. we have found three studies which reported an increased trend of eph. an increased incidence of eph from 1998 to 2003 was also found by whiteman et al; as reported earlier. a danish study reported a statistically significant risk of eph in 1995-2004. while calgary health region of canada found no statistically significant difference in incidence rates from 1999-2006. but, the number of eph was not very sufficient to 13 interpret the results. hence, all these rates are not accurate estimates and comparisons could only become significant when the populations would be similar in demographic factors such as age etc, time periods being evaluated are similar and management discussion protocols would be evidence based. our results are revealing that the most important cause for eph is hemorrhage most importantly due to uterine atony, uterine rupture & retained placenta, 15 findings consistent with previous reports. the causes of eph noted in our patients are very much different from the developed countries where abnormal placentation resulting in hemorrhage was the most common cause. a study publised by netherlands, found that the main cause for eph was placenta accreta (50%). uterine 16 atony was found in 27% of cases. a turkish study noted that uterine rupture was the cause in almost 21% of the cases & uterine 17 atony was responsible in 42% of the cases. a study conducted in saudi arabia and another of korea, also revealed that uterine 18 atony is the most common cause. despite practicing evidence based medical advances, regular drills and improvement of protocols; hemorrhage continues to be an i m p o r t a n t c o n t r i b u t o r t o m a t e r n a l morbidity and mortality. in our study, we tried to explore factors that could be recognized antenatally and could be rectified with in time preventative measure. abnormal placentation has also been consistently documented in other studies to be associated with previous uterine 19 surgeries. these life-threatening abnormal placental complications require aggressive blood t r a n s f u s i o n , s u b s e q u e n t b l e e d i n g complications, hysterectomy, and longer 20 maternal hospital stays. with advanced radiological facilities, prehand diagnosis of abnormal placentation can guide clinicians to plan for delivery with uterotonics, transfusion services, uterine balloon compression devices, interventional 21 radiologists and standby of surgeons. involvement of interventional radiologist and invasive treatment must be decided within 30 minutes if other measures have 108 failed. assisted vaginal delivery has also been 22 related to risk of eph. a study indicated the association of damage to cervical/ vaginal tissues, resulting in 23 hemorrhage and leading to hysterectomy. another important hypothesis is about uterine scarring, especially with cesarean deliveries, also increases the risk of eph, e v e n w i t h o u t a b n o r m a l l y a d h e re n t placenta/ placenta previa.multiple cesarean sections, as well as vbac were also found to 24 be associated with eph. in our study multiple gestation could not be proved to be significantly associated with eph, as has been described in some studies. some reported that multiple gestations had significantly increased risk of eph e.g. francois et al. according to these studies, tocolysis require for preterm labour and overdistended uterus by more than one fetus is a major facto towards uterine atony and hemorrhage. however, they failed to adjust the confounding factors such 25 gestational age & mode of delivery etc. unfortunately our study has some limitations also. the most significant is that our inferences depend on the hospital records, their accuracy about the diagnoses and management and records or notes on birth certificates and discharge forms. we tried our best to countercheck and recheck t h e r e c o r d s a b o u t d i a g n o s i s a n d management, birth certificates, to reduce biased classification of different risk factors and confounders, as also suggested by some 26,27 other studies. for example the diagnosis of “retained placenta” limited the options and make it difficult to distinguish between different abnormally adherent placenta e.g. placenta accreta, increta or percreta. without doing a review of patients' notes, we were unable to determine the indication for eph, the amount and the type of hemorrhage (antepartum, intrapartum, postpartum). lastly, the number of cases for some of the factors that were studied was relatively small. some of the very important inferences are: ! incidence of eph is significantly high and the most important indication of eph is hemorrhage mainly due to uterine atony, uterine rupture, placenta previa & abnormally adherent placenta. ! important risk factors to be considered are multiparity, previously scarred u t e r u s , n o n b o o k e d p a t i e n t s & deliveries carried out by tba. ! significant maternal and perinatal morbidity and mortality is the main outcome of eph e.g. icu admissions, a r r a n g e m e n t f o r b l o o d & i t s c o m p o n e n t s , m a n a g e m e n t o f coagulopathies/thromboembolism & injuries of adjacent visceras results in huge psychological & financial burden on the patient, family & society. 1. p l a u c h e w c . c a e s a re a n h y s t e re c t o m y : indications, technique, and complications. clin obstet gynecol 1986; 29:318. 2. saeed f, khalid r, khan a, masheer s, rizvi jh. peripartum hysterectomy: a ten-year experience at a tertiary care hospital in a developing country. tropical doctor 2010; 40:18–21. 3. briery cm, rose ch, hudson wt, planned v s e m e rg e n t c e s a re a n h y s t e re c t o m y. a m j obstet gynecol 2007; 197:151–4. 4. kwee a, bots ml, visser gh, bruinse hw. emergency peripartum hysterectomy: a prospective study in the netherlands. eur j obstet gynecol reprod biol 2006;124:187–92. 5. whiteman mk, kuklina e, hillis sd. incidence and determinants of peripartum hysterectomy. obstet gynecol 2006;108:1486–92. 6. awan n, bennett mj, walters wa. emergency peripartum hysterectomy: a 10-year review at the royal hospital for women, sydney. australian and new zealand journal of conclusions references 109 obstetrics and gynaecology 2011;51:210–5. 8. knight m, kurinczuk jj, spark p, brocklehurst p. c e s a r e a n d e l i v e r y a n d p e r i p a r t u m hysterectomy. obstet gynecol 2008;111:97–105. 9. nisar n, sohoo na. emergency peripartum hysterectomy: frequency, indications and maternal outcome. journal of ayub medical college abbottabad 2009;21:48–51. 10. saeed f, khalid r, khan a, masheer s, rizvi jh. peripartum hysterectomy: a ten-year experience at a tertiary care hospital in a developing country. tropical doctor 2010; 40:18–21. 11. demirci o, tuðrul as, yýlmaz e, tosun o, demirci e, eren ys. emergency peripartum hysterectomy in a tertiary obstetric center: nine years evaluation. journal of obstetrics and gynaecology research 2011; 37:1054–60. 12. kastner es, figueroa r, garry d, maulik d. e m e r g e n c y p e r i p a r t u m h y s t e r e c t o m y : experience at a community teaching hospital. obstetrics and gynecology 2002;99:971–5. 13. awan n, bennett mj, walters wa. emergency peripartum hysterectomy: a 10-year review at the royal hospital for women, sydney. australian and new zealand journal of obstetrics and gynaecology 2011; 51:210–5. 14. sakse a, weber t, nickelsen c, secher nj. peripartum hysterectomy in denmark 19952004. acta obstet gynecol scand. 2007; 86:1472–5. 15. glaze s, ekwalanga p, roberts g, et al. peripartum hysterectomy: 1999 to 2006. obstet gynecol 2008; 111:732–8. 16. habek d, becarevic r. emergency peripartum hysterectomy in a tertiary obstetric center: 8year evaluation. fetal diagn ther 2007; 22:139–42. 17. kwee a, bots ml, visser gh, bruinse hw. emergency peripartum hysterectomy: a prospective study in the netherlands. european journal of obstetrics gynecology and reproductive biology 2006; 124:187–92. 18. zorlu cg, turan c, iºik az, daniºman n, m u n g a n t , g ö k m e n o . e m e r g e n c y hysterectomy in modern obstetric practice. changing clinical perspective in time. a c t a o b s t e t r i c i a e t g y n e c o l o g i c a scandinavica 1998;77:186–90. 19. yamani zamzami ty. indication of emergency peripartum hysterectomy: review of 17 cases. archives of gynecology and obstetrics 2003;268:131–5. 20. usta im, hobeika em, musa aa, gabriel ge, nassar ah. placenta previa-accreta: risk factors and complications. am j obstet gynecol 2005;193:1045–9. 21. nisar n, sohoo na. emergency peripartum hysterectomy: frequency, indications and maternal outcome. journal of ayub medical college abbottabad 2009; 21:48–51. 22. dabelea v, schultze pm, mcduffie rsj. intrauterine balloon tamponade in the management of postpartum hemorrhage. am j perinatol 2007; 24:359–64. 23. roethlisberger m, womastek i, posch m, husslein p, pateisky n, lehner r. early postpartum hysterectomy: incidence and risk factors. acta obstetricia et gynecologica scandinavica 2010;89:1040–4. 24. johnson jh, figueroa r, garry d, elimian a, maulik d. immediate maternal and neonatal effects of forceps and vacuum-assisted deliveries. obstet gynecol 2004;103:513–8. 25. kacmar j, bhimani l, boyd m, shah-hosseini r, peipert j. route of delivery as a risk factor for emergent peripartum hysterectomy: a casecontrol study. obstet gynecol 2003; 102:141–5. 26. francois k, ortiz j, harris c, foley mr, elliott jp. is peripartum hysterectomy more common in multiple gestations? obstet gynecol 2005; 105: 1369–72. 27. lydon-rochelle mt, holt vl, cardenas v. the reporting of pre-existing maternal medical conditions and complications of pregnancy on birth certificates and in hospital discharge data. am j obstet gynecol 2005; 193:125–34. page 40 page 41 page 42 page 43 page 44 page 45 page 46 original�article abstract objective: to assess the perception of medical students about teaching professionalism in medical colleges. study design: descriptive cross sectional study. place and duration of study: the study was conducted in the department of obstetrics and gynecology, th th railway general hospital, rawalpindi, from 10 june, 2016 to 10 december, 2016. materials and methods: a semi structured, amended and validated questionnaire was used to collect the data. the questionnaire was distributed among 55 final year male and female medical students. 27 (49.1%) participants were male and 28 (50.9%) were female students. the questionnaire comprised of 9 items to determine various aspects of students' perception about teaching medical professionalism in medical school. results: fifty five students participated. only 20% of the students' responses were positive about their preknowledge regarding the medical professionalism course. 30.9% students agreed for keeping professionalism course in medical schools. however, half of students' responses remained neutral. majority of students (49.1%) disagreed with the effectiveness of lecturing to teach the professionalism. majority of students (58.2%) approved the use of mcqs for the evaluation of professionalism course. the majority of males (82.1%) and females (70.2%) agreed with the effectiveness of course evaluation by mcqs. conclusion: a large majority of students were clear about the objectives of medical professionalism course and had opinion that the medical professionalism course should be taught with the use of technology rather than in the form of lectures and this course should be evaluated in the form of mcqs. key words: medical professionalism, questionnaire, student feedback. a continuing commitment to excellence and 2,3 scholarship, leniency and sacrifice. medical professionalism characterizes the roles and distinctiveness of medical students and physicians. the significance of medical professionalism has been highlighted as multiple reports of misconduct and ethics violation have been published in the science literature pertaining to the medical community. worldwide medical professionalism has received increased attention by medical educationist. today, every society with various cultural backgrounds expects that the medical students must be real p r o f e s s i o n a l s r a t h e r t h a n m e r e l y a c t i n g professionally. medical professionalism is one of the top priorities for the medical students, physicians and medical educators. during training, medical students undergo both p e r s o n a l a n d p r o f e s s i o n a l d e v e l o p m e n t . perceptions, in particular to required traits, are associated with the profession change, and impacted by encounters at their respective institutions. a recent study found that medical introduction medical professionalism, according to the royal college of physicians (rcp) can be defined as: 'a set of values, behaviors, and relationships that underpins the trust the public has in doctors', which includes 'integrity, compassion, altruism, continuous improvement, excellence and working in partnership 1 with members of the wider healthcare team. various attributes of professionalism in medicine have been identified, including high ethical and moral standards, core humanistic values, rolemodeling, scrutiny of behavior, professional identity, learning professionalism in medical college: perspectives of medical students fareesa waqar, wajiha shadab, saadia sultana, shumaila sharif correspondence: dr. fareesa waqar professor & hod, gynecology and obstetrics islamic international medical college pakistan railway hospital, rawalpindi e-mail: fareesa.waqar@riphah.edu.pk department of gynecology and obstetrics islamic international medical college pakistan railway hospital, rawalpindi funding source: nil; conflict of interest: nil received: aug 03, 2017; revised: jan 29, 2018 accepted: feb 06, 2018 professionalism in curriculum the students' perspectivejiimc 2018 vol. 13, no.1 41 representatives on areas of importance that could be improved upon. the data was entered into the microsoft excel software and analyzed by using spss version 21.0 statistical software. in descriptive analysis, means with standard deviation of the continuous variables were computed. frequencies and percentages of the categorical variables such as gender and age were calculated. mean values and standard deviation were analyzed for each individual question. results fifty five students participated in the study. the response rate was 100%. 27 participants were male students (49.1%) and 28 participants were female students (50.9%). out of 55 students, 30.9% agreed and 20% of the students disagreed for keeping current professionalism course in medical education while about half of the students remained neutral regarding the topic. the results indicate that only 20% of the students' responses were positive when asked about their pre knowledge regarding the professionalism course, of which 50.4% were males and 60% were females. as far as the lectures are concerned in order to perceive the professionalism course 29.1% of the total students “agreed” and 49.1% of students “disagreed”. out of the total agreed, 51% were males, whereas19.1% males disagreed. of total agreed 44.1% were females while 20.5% females disagree. about the perspicuity of professionalism objectives total 45.5% of students agreed while 54.5% disagreed, out of total agreed, 20% were males and 80% were females. almost 80% students agreed about the usage of technology during the lectures among which, 58% were males and 42% were females. however 20 (36.4%) students agreed when asked about the interaction and support provided by the tutors and almost same number 23 (41.8%) of students were neutral of this question in which 44.4% were males and 29% were female. 83.6% students “disagreed” when queried about the inclusion of grades into final evaluation” and 10.9% replied as neutral. in addition, 78.2% students remained neutral or 10.9% students disagreed about “the professionalism course assists in learning of the other subjects”. regarding the participant's' reply on multiple students thought that society requires them to be professional in all their dealings and negates the social aspect of their lives as an individual. participants felt that they were always being viewed with high expectations of professionalism at all times 2 from their choice in clothing to their activities. in this modern digital age of social media and networking, medical personnel need to be ever more careful and be able to demonstrate professionalism in their 4,5 online lives. it has now become the current emphasis of medical educationists that professionalism must be taught explicitly during undergraduate medical studies. with recent emphasis of medical institutions in inculcating professionalism and certain behavioral attributes into medical students, it is of interest to see the change in the level of professionalism as students' progress in their medical training and more importantly how they perceive the professional environment around them. the current study aimed to assess the perception of medical students about teaching the course on professionalism in medical colleges. materials and methods this descriptive cross sectional study was conducted in the department of obstetrics and gynecology, th railway general hospital, rawalpindi from 10 june, th 2016 to 10 december, 2016. by using random sampling technique, fifty five final year medical students were invited to respond to the questionnaire. after explaining the purpose of the study, informed consent of the participant students was obtained and their confidentiality was ensured. a semi structured amended questionnaire was used to collect the data. initially it was a 12 item questionnaire which was then converted to a 9 item questionnaire after validation and then used for this cross sectional survey. the likert scale was employed throughout the questionnaire. in likert scale 1 and 2 were considered as disagreed, third was considered neutral, 4 and 5 were considered as agreed. amendments, finalization and validation of the questionnaire were done by involving senior faculty from medical education department, senior clinical faculty and students' representatives. the validity of questionnaire was ensured by getting the views of a b o v e m e n t i o n e d f a c u l t y a n d s t u d e n t s 42 professionalism in curriculum the students' perspectivejiimc 2018 vol. 13, no.1 course in medical school. similar findings were presented in a study which demonstrated that the professionalism courses should be taught in colleges in order to cultivate more polished professional skills in medical students, which in turn permits 8 concentrating on appropriate proficient conduct. another study reported that medical schools in us 9 are teaching professionalism as a separate course. when inquired about lectures as a method for teaching the professionalism course 29.1% of the students agreed and an overwhelming majority approximating to 49.1% of students disagreed. a lancet review in 2001 stressed upon the necessity of teaching professionalism in the form of lectures to medical students and suggested that rigorous 10 research would be required in this area. regarding perceptions on the assessment system, most of the students reported that the professionalism course should be evaluated by mcqs. previous studies have shown that there are no strategies on the most operative ways of supporting medical students to 11 develop high standards of medical professionalism. 12 according to hendelman et al. most of medical institution had a professionalism curriculum in place for the pre clerkship phase but lack of formal program in the clerkship years. the present study identified a lack of knowledge or interest by the medical students in the current professional course. the most obvious reasons for the lack of interest in professionalism course was the assessment which students have not considered helpful and felt uncomfortable for having it on a weekly basis. students agreed with use of technology during the lectures and showed a significant positive value. however, these attributes develop over time and are inculcated at all levels of medical training. the findings of this study demonstrate that 45.5% students agree that the objectives of the professionalism course were easy to understand throughout the course. an overwhelming majority of students (83.6%) disagree when asked about including their professionalism grade in their final a s s e s s m e nt a s t h i s affe c te d t h e i r o ve ra l l performance in the course and shows that they are 13 not ready to take it up full time. feudtner et al. found that 62% of medical students believed that during the course of their clerkship, their ethical options question, overall 58.2% students replied by selecting the option that the course should be evaluated by mcqs while 30.9% students reported that the professionalism course should not be evaluated by mcqs, also it was concluded that the majority of males (82.1%) and females (70.2%) were in favor of course evaluation being based on the mcqs. however, 90% students did not agree for the course evaluation to be in the form of essays f u r t h e r m o r e 7 2 . 8 % d i d n o t w a n t g r o u p presentations to be a method of course evaluation. table i: percep�on of medical students about professionalism course discussion medical professionalism is generally depicted as attributes of expert brilliance, honesty and 6,7 benevolence. this study planned to investigate the students' perception towards the professionalism course in medical schools. it was found that, only a few student responses were positive about their preknowledge regarding the medical professionalism course (20%) and approximately 30.9% medical students agreed for keeping the professionalism 43 professionalism in curriculum the students' perspectivejiimc 2018 vol. 13, no.1 principles have been eroded. medical schools place the foundation for fostering the medical professionalism to practice the issues 14 among practicing clinicians. it is thus imperative that professionalism is incorporated into the 1 5 , 1 6 1 7 undergraduate curriculum. cruess et al. emphasized that a profession requires specialist knowledge and skills acquired through training and education and the professional is expected to use these attributes to serve the humanity. conclusion the medical professionalism course needs to be included in medical education in order to make the students understand the goals and importance of the medical professionalism course in academic and clinical practice. a large majority of students were c l e a r a b o u t t h e o b j e c t i v e s o f m e d i c a l professionalism course and had opinion that the medical professionalism course should be taught with the use of technology rather than in the form of lectures and this course should be evaluated in the form of mcqs. references 1. simoni ad. teaching medical professionalism: a lesson in perspective from plato's protagorasbr j gen pract. 2017; 67: 123. 2. finn g, garner j, sawdon m. 'you're judged all the time!' students' views on professionalism: a multicentre study. med educ 2010; 44: 814-25. 3. trimble m. the profession of medicine and its rivals. the ulster medical journal. 2016; 85:76-9. 4. ross s, lai k, walton jm, kirwan p, white js. “i have the right to a private life”: medical students' views about professionalism in a digital world. medical teacher. 2013; 35: 826–31. 5. jawaid m, khan mh, bhutto sn. social network utilization (facebook) &amp; e-professionalism among medical students. pakistan journal of medical sciences. 2015; 31: 209–13. 6. abim foundation, acp-asim foundation, european federation of internal medicine. medical professionalism in the new millennium: a physician charter. ann intern med 2002; 136: 243-6. 7. kassirer jp. managing care should we adopt a new ethic? n engl j med. 1998; 339: 397-8. 8. steneck nh. fostering professionalism and integrity in research. university of st. thomas law j. 2008; 5: 522-43. 9. swick hm, szenas p, danoff d, whitcomb me. teaching professionalism in undergraduate medical education. jama. 1999; 282: 830-2. 10. stephenson a, higgs r, sugarman j. teaching professional development in medical schools. lancet. 2001; 35: 867-70. 11. vimmi p. developing medical professionalism in future doctors: a systematic review international journal of medical education 2010; 1: 19-29. 12. hendelman w, byszewski a. a national survey: medical professionalism in canadian undergraduate programs 2007. 13. feudtner c, christakis da, christakis na. do clinical clerks suffer ethical erosion? students' perceptions of their ethical environment and personal development. acad med 1994; 69: 670-9. 14. papadakis ma, loeser h, healy k. early detection and evaluation of professionalism deficiencies in medical students: one school's approach. acad med. 2001; 76: 1100-6. 15. irvine d. the doctor's tale. oxford: radcliffe medical press, 2003. 16. hilton sr, slotnik hb. proto-professionalism: how professionalization occurs across the continuum of medical education. med educ. 2005; 39: 58-65. 17. cruess rl, cruess sr. steinert y. teaching medical professionalism. cambridge: cambridge university press, london 2009. 44 professionalism in curriculum the students' perspectivejiimc 2018 vol. 13, no.1 page 46 page 47 page 48 page 49 untitled-1 original�article abstract objective: to compare peer assisted learning (pal) and teacher assisted learning (tal) in small group format comprising undergraduate dental students. study design: comparative cross-sectional study. place and duration of study: this study was conducted in islamic international dental college, islamabad, from january 2019 to june 2019. nd material and methods: four batches of 2 year bds comprising of 75 students were randomly divided into two groups. dental material topic was selected for an interactive two-hour session, where one group was taught by teacher and other through peer. session was followed immediately by a short test comprising of multiplechoice questions of single correct answer to assess students' performance. moreover, a likert scale-based questionnaire was used to identify the perception of students about these sessions. comparison of mcqs test scores among the two groups was done using independent sample t test while mannwhitney test was applied for the likert based questionnaire. for data analysis spss version 23 was used. results: test results (marks) of tal had a mean value of 13.72±1.55 and pal as 12.34±2.3 with a significant p value of 0.01. analysis of likert scale-based data revealed that in pal session competency level, grasping of concepts, student teacher interaction and motivation were significant factors, whereas level of interest and difficulty, time management, student participation and clinical correlation of the concerned topic were. conclusion: teacher assisted learning was found to be better as compared to peer assisted learning in our set up in terms of test scores and students' perception. nonetheless, pal can be utilized as an important supplement in online synchronous teaching especially during current pandemic situation. key words: peer assisted learning (pal), small group discussion (sgd), students' feedback, students scores, teacher assisted learning (tal). academic sustenance interference widespread in higher education as stated by dr. deanne martin in 3 1973. this concept of peer instruction was then incorporated by eric mazur at harvard university in the 1990s in an attempt to improve his student's 4 conceptual understanding with promising results . educators from a variety of countries have later used this method in diverse context to engage hundreds of 5,6 thousands of students in active learning. over the past decade pal has been a topic of interest for the researchers in the field of medical education which undergoes continuous reforms in teaching learning methodologies according to learning outcome of the students. with the incorporation of pal in various developed countries as an adjuvant learning strategy, an increase in the participation of students in the learning process was observed along with 7 enhanced critical thinking capability . majority of these researches used pal at undergraduate level for 7,8 skill based learning involving psychomotor skills. commonly adopted teaching methodologies are introduction peer assisted learning (pal) has gained significant momentum over recent years as a novel pedagogical learning methodology that is based on exchange of knowledge among individuals who are at similar 1,2 social grouping and are not professional teachers. peer assisted study sessions is derived from the model of supplemental instruction, can be termed as peer-assisted learning that encounters a type of comparative evaluation of peer assisted learning and teacher assisted learning using small group discussion 1 2 3 4 5 6 uzma mussarat , fatima ehsan , abeerah zainub , muhammad hamza bin saeed , uzma hassan, saira jahan correspondence: dr. uzma masarat hod pathology islamic international dental college, islamabad e-mail: uzma.massarrat@riphah.edu.pk 1 2 3 department of pathology/physiology /biochemistry / 4 5 community dentistry / dental materials islamic international dental college,islamabad 6 department of physiotherapy riphah institute of rehabilitation sciences, riphah international university, islamabad funding source: nil; conflict of interest: nil received: february 08, 2021; revised: october 21, 2021 accepted: october 29, 2021n peer assisted learning vs teacher assisted learningjiimc 2022 vol. 17, no.1 56 interactive lectures, small group discussions (sgds), problem based learning (pbl) and practical 9 demonstration in basic medical/dental sciences. in most of the developing medical universities a hybrid educational system is on its way with increasing attempts to shift from the traditional rote learning to 10 more active student centered conceptual system. the literature review has shown that discussion with each other enhances cognitive development, motivation and confidence among students and build a deeper understanding of what they are 11,12 learning. this methodology is based on the theories of social constructivism and cognitive congruence where theorists suggest that learning is 5 not a solitary struggle. the general consensus woven is that compared to traditional lecture-based pedagogy, peer instruction has led to increased academic self-efficacy as in large-sample studies of pal reporting lower failure rates even in tough 13 courses. in comparison to the traditional lecture method, pal is rich with opportunities for feedback from student-to-student, teacher-to-student, and st u d e nt to te a c h e r e n r i c h i n g co l l a b o rat i ve 14 learning. recent local studies in this regard comparing effectiveness of peer assisted and facilitator assisted learning have mainly focused on 15,16 clinical/practical subjects, so to further explore the acceptance and perceived usefulness of pal in basic dental sciences, we compared it with teacher assisted learning in a small group setting. materials and methods this comparative cross-sectional study was conducted at islamic international dental college, islamabad from january 2019 to june 2019. written approval for research study was obtained from islamic international medical college of riphah international university under reference number: riphah/iimc/erc/19/307. informed consent of learners was obtained for participation in the study. non-probability convenience sampling technique was used for this grouping. second year students attending regular classes of dental materials were included in the study while qualified doctors acting st th as tutors and dental students of 1 yr, 3rd yr and 4 yr were not included in the study. each class has four batches (i.e., a, b, c and d comprising of 15-19 students in each) with a total of 75 students. two of the batches (c &d) were selected for pal and the other two batches (a & b) assigned for tal. a two-hour session of sgd, which was part of their regular timetable was selected for this purpose. students were informed beforehand about the trial and four of the students (two for each batch) were selected on voluntary basis as peer tutors. one week prior to the activity the topic was taught to these four selected peer tutors. students in pal group (c & d) were taught in two different rooms by these peer tutors under the supervision of teacher and for the students of tal (a & b) sgd was arranged for the same topic in traditional way, in two separate rooms where subject specialists conducted the discussion. subject selected for this trial was dental materials of basic dental sciences. assistant professor of the dm chose the topic as well as designed the assessment, comprising of 15 mcqs of one correct option c a t e g o r y i n c l u d i n g c 1 ( r e c a l l ) a n d c 2 (comprehension) level questions. in both the groups test was conducted after the discussion along with a 10 likert scale based feedback questionnaire . three subject specialists vetted these mcqs to validate their construct. students perceptions about peer assisted learning were congregated by using a questionnaire with a likert scale that was selfconstructed based on relevant literature and was validated by three medical educationist . test marks (i.e., quantitative data) were analyzed using independent sample t-test. likert scale based feedback responses were statistically analyzed using mann-whitney u test through spss 23. results the class of 2nd year bds comprised of 75 students and among them 69 (92%) participated in the study. a total of 37 out of 69 (53%) students were part of the teacher assisted learning (tal) group, while 32 (47%) students were part of pal group. data analysis shown in table i depicted that test results (obtained marks) of students in teacher assisted learning group had mean±s.d as 13.72±1.55 while test scores of students in pal group had mean±s.d as 12.34±2.34 with the p<0.05 which was significant. question category-based data analysis shown in table ii depicted that in c1 level questions, tal group had 20 correct responses out of 37 total responses (56%) as compared to pal group who had 14 correct responses out of 32 (44%) and it was statistically 57 jiimc 2022 vol. 17, no.1 peer assisted learning vs teacher assisted learning significant (p<0.05). statistical analysis for c2 category showed that 37 participants of tal attained 21 correct responses (59%) in comparison with pal, where out of 32 only 13 responses were correct (41%) and it was not significant as p>0.05. discussion pal is embraced by medical educationalists for many years in the developed world with growing global 17 acceptance all around . despite many advantages, we still need to ascertain how to maximize its suitability in our context and cultural background. present study results show a significant difference in favor of tal as compared to pal when comparing overall student assessment scores. these findings may be due to the fact that teaching by experienced faculty or teachers to instruct their students enhance the comprehension and success among students. our findings are in accordance with a study conducted at dental institute of karachi with final year undergraduate students on the subject of orthodontics. in this study author narrates that comparing overall mean change in test scores of students, significantly better results were revealed 19 by expert assisted learning as compared to pal. similarly, another local study is conducted in st foundation university islamabad on 1 year medical students comparing pal in small groups with all students as an adjunct to traditional large group lectures. scores of pal sessions were not better than 15 eal sessions in this study. however student's views regarding these pal sessions were not included in these studies. better scores obtained by students of tal group in our study may be elucidated due to the fact of acquaintance in our students with traditional f a c u l t y l e a d t u t o r i a l s , w h e r e e x t e r n a l encouragement act as a guiding factor in provoking critical thinking among students as compared to selfmotivation which is integral part of peer tutoring. results of present study are in line with a study conducted by hodgson and bearman, who narrates that students' performance after teaching from subject specialist was better as compared to peertable i: comparison of test marks between tal & pal table ii: comparison of correct responses based on question category likert-scale based feedback questionnaire showed that there was a significant difference between tal and pal in terms of teacher competency (p =0.002) , student teacher interaction (p=0.023), addressing queries (p =0.001) and motivation (p =0.034) while this was not significant (p>0.05) as far as lesson enjoy ability (p =0.054), clinical correlation (p =0.065), time adequacy (p =0.406) and participation (p =0.814) was concerned. the frequency distributions of both the groups' responses as well as questions have been shown in the fig.1 and fig. 2. fig. 1: frequency distribution of feedback from teacher assisted learning group fig. 2: frequency distribution of feedback from peer assisted learning group 58 jiimc 2022 vol. 17, no.1 peer assisted learning vs teacher assisted learning 22 learning. in contrast, during this study mcqs categorization based on c1&c2 level of cognition, c2 category result (depicting lower order thinking) but a step ahead than simple recall (c1) exposed no significant difference in the pal and tal test scores. these findings are in favor of a study conducted on dental students in the university of sharjah which evaluated the role of pal in team-based learning. a meta-analysis issued by rees et al revealed that there was no difference in students taught by peers 16 with those taught by faculty. results obtained from students survey and focus groups suggested that it was a valuable strategy for enhancing students' 18 learning. this encourages to initiate attempts for incorporating pal as a supplemental teaching strategy. regarding student's feedback they were more comfortable with the facilitator rather than their peer tutor. so far in most of the international studies pal has a greater or equal impact on student learning. this could partly be explained by the fact that students experience a college culture which is still quite formal, and teacher centered. further pal here is still in its developmental stages and rather 13 new for students. keeping in mind the racial difference it was observed in an american study that asian students preferred listener role as compared to white americans and were less comfortable in class discussions (eddy et al, 2015) she highlighted that in jumping towards active learning where classrooms are transformed from facilitator centered to student centered we need to focus on students dynamics to understand their experiences and the various barriers to participate equally in classroom 20 discussion. findings of present research based on likert scale analysis including competency of teachers, addressing queries, student teacher interaction and motivation level during class are supported by a study conducted at islamic international medical college by afsheen zafar which accentuates the role of an expert or subject specialist in academic set up. she adopted an innovative approach of pal in large class format highlighting that teacher's feedback and background collaborative learning still remained the most valued 21 aspect of this format. we cannot deny the social interactive theory which emphasizes the role of social interaction among students of same age group in educational set up. hence our study result favors the finding of menezes et al who also found in his study that interest is expressed in both styles of knowledge acquisition (pal versus traditional) where 57% students recorded no difference in learning in both styles of 8 learning and 80 % notified no difference in teaching. nonetheless, there is more research needed to fully measure the potential benefits of pal in our local set up especially in today's era of blended learning. we need to find ways of utilizing this pal in synchronous teaching which may help to alleviate faculty load in addition to enriching students learning. study limitations this study could be improved if the sample size, total no. of pal sessions and more assessment results would be added to generate a valued and effective response. future work more extensive research and training on the process of pal for acceptability and better results. conclusion teacher assisted learning is proved to be more inspiring approach for student learning as compared to peer assisted learning in our set up based on test scores and students' perception. nevertheless, pal can be applied as an imperative support and valuable ' learning tool in upraising student s performance especially as a supplement in online synchronous mode of teaching in medical and dental institutes acknowledgments: researchers would like to thank and appreciate the second year bds students at islamic international dental college for participation and cooperation. this study was presented at icme 2019 at pak-china friendship center islamabad. references 1. burgess a, mcgregor d, mellis c. medical students as peer tutors: a systematic review. bmc medical education. 2014;14(1):1-8. 2. gayef a, editor team based learning in medical education. shs web of conferences; 2019: edp sciences. 3. dawson p, van der meer j, skalicky j, cowley k. on the effectiveness of supplemental instruction: a systematic review of supplemental instruction and peer-assisted study sessions literature between 2001 and 2010. review of educational research. 2014;84(4):609-39. 4. carey mc, chick a, kent b, latour jm. an exploration of peer-assisted learning in undergraduate nursing students in paediatric clinical settings: an ethnographic study. nurse 59 jiimc 2022 vol. 17, no.1 peer assisted learning vs teacher assisted learning education today. 2018;65:212-7. 5. de menezes s, premnath d. near-peer education: a novel teaching program. international journal of medical education. 2016;7:160. 6. friel o, kell d, higgins m. the evidence base for peer assisted learning in undergraduate medical education: a scoping study. mededpublish. 2018;7;1-15 7. kauffman ca, cendan j. the effect of participation in a small-group discussion session on medical student learning of intestinal pathophysiology. medical science educator. 2018;28(2):309-13. 8. menezes a, burgess a, clarke aj, mellis c. peer-assisted learning in medical school: tutees' perspective. advances in medical education and practice. 2016;7:31. 9. rahman ar, faruque m, alam kk, tasnim s, azeez mu. how practice of peer assisted learning facilitates better learning among the dental students of bangladesh. bangladesh journal of medical education. 2018;9(2):16-8. 10. tricio j, montt j, orsini c, gracia b, pampin f, quinteros c, et a l . s t u d e n t e x p e r i e n c e s o f t w o s m a l l g r o u p learning-teaching formats: seminar and fishbowl. european journal of dental education. 2019;23(2):151-8. 11. hodgson y, benson r, brack c. using action research to improve student engagement in a peer-assisted learning programme. educational action research. 2013;21(3):35975. 12. hodgson y, brack c, benson r. introducing case-based peerassisted learning in a professional course. journal of university teaching & learning practice. 2014;11(2):4. 13. burgess a, mcgregor d. peer teacher training for health professional students: a systematic review of formal programs. bmc medical education. 2018;18(1):1-12. 14. nourkami-tutdibi n, tutdibi e, schmidt s, zemlin m, abdulkhaliq h, hofer m. long-term knowledge retention after peer-assisted abdominal ultrasound teaching: is pal a successful model for achieving knowledge retention? ultraschall in der medizin-european journal of ultrasound. 2020;41(01):36-43. 15. ahsin s, saad k, afzal a. comparison of academic performance in peer assisted and expert-assisted learning through test scores. pakistan journal of physiology. 2018;14(4):47-50. 16. rees el, quinn pj, davies b, fotheringham v. how does peer teaching compare to faculty teaching? a systematic review and meta-analysis. medical teacher. 2016;38(8):829-37. 17. balta n, michinov n, balyimez s, ayaz mf. a meta-analysis of the effect of peer instruction on learning gain: identification of informational and cultural moderators. international journal of educational research. 2017;86:66-77. 18. williams b, reddy p. does peer-assisted learning improve academic performance? a scoping review. nurse education today. 2016;42:23-9. 19. ehsan aa. peer-assisted learning (pal) as an instructional tool in undergraduate dental education. medical education. journal of college physicians surg pak, 30 (2020), pp. 1184-1187 20. eddy sl, brownell se, thummaphan p, lan m-c, wenderoth mp. caution, student experience may vary: social identities impact a student's experience in peer discussions. cbe—life sciences education. 2015;14(4):1-45. 21. zafar a, rehman a. peer assisted learning in a large class format. mededpublish. 2017;6.1-1022. 22. hodgson y, bearman m, schneider-kolsky m. lessons learned in implementing peer-assisted learning. int j innovat sci math educ 2012;20(3):19–30. 60 jiimc 2022 vol. 17, no.1 conflict of interest authors declared no conflicts of interest. grant support and financial disclosure authors have declared no specific grant for this research from any funding agency in public, commercial or nonprofit sector. data sharing statment the data that support the findings of this study are available from the corresponding author upon request. this is an open access article distributed under the terms of the creative commons attributionnoncommercial 2.0 generic license. peer assisted learning vs teacher assisted learning original�article abstract objective: the study was conducted to assess the feasibility, safety, effectiveness, and postoperative complications of mini cholecystectomy in our setup. study design: it was a descriptive observational study design. nd th place and duration of study: this study was conducted from 02 september 2013 to 30 september 2017 in the department of surgery, pak red crescent teaching hospital, affiliated with pak red crescent medical & dental college, lahore. materials and methods: a total of 143 symptomatic patients with cholelithiasis, irrespective of age and sex were included in this by convenient sampling. the data of all patients were collected for age, sex, size of incision, operation time, complication, postoperative hospital stay and analyzed with spss version 21. results: out of 143 patients 132 (92.30%) were female and 11 (7.69%) were male. mean age of the patients was 38±10.38 years. average incision size was 4±0.65 cm. the mean operating time was 39.12±8.66 minutes. the mean hospital stay was 2 days. minor post-operative complications like hemorrhage, minor biliary leak and superficial surgical site infection was seen in 7 patients. conclusion: the present study shows that mini-cholecystectomy is effective, safe procedure with short operating time, fewer complication, less postoperative stay and it is feasible not only in chronic cholecystitis, but also in an acutely inflamed gallbladder even in empyema. key words: cholelithiasis, cholecystectomy, gall bladder, mini cholecystectomy. 4 parts of the third world countries. in early 1990s, it was shown that the conventional large subcostal incision in cholecystectomy could be replaced by a m u c h s m a l l e r i n c i s i o n , g i v i n g a s h o r t e r convalescence. this new modification was named as mini-cholecystectomy. it was first described by 7 dubois and berthelot, and their favorable results were reported at the same time laparoscopic cholecystectomy was introduced into the uk in 8-10 1990. most of the previous studies on minicholecystectomy done on chronic cholecystitis and excluded acute cholecystitis patients. we decided to analyze the safety and feasibility results of this procedure both in chronic and acute cases. the objective of this study was to assess the feasibility, s a f e t y, e f f e c t i v e n e s s , a n d p o s t o p e r a t i v e complications of mini cholecystectomy in our setup. materials and methods this descriptive observational study was conducted nd th from 02 september 2013 to 30 september 2017 conducted in the department of surgery, pak red crescent teaching hospital, affiliated with pak red crescent medical & dental college, lahore. the study was approved by the ethical review committee introduction cholecystectomy is one of the most common operations performed by departments of general or 1,2 gastro-intestinal surgery worldwide. conventional cholecystectomy has enjoyed supremacy as treatment of choice for gallstones almost more than 3 a century. the introduction of laparoscopy in 1990s 4 opened up a new chapter in the surgical history. the procedure progressed at such a speed that it has become the gold standard for management of 4 cholelithiasis. this procedure requires costly 5 equipment and need of additional training of the surgeon, moreover learning curve of this technique is very slow. due to these factors this procedure has 6 still not replaced the open cholecystectomy in most the rationality of mini-cholecystectomy: a study of 143 cases at pak red crescent teaching hospital 1 2 3 abid hussain , aqeel ahmad , kishwar naheed correspondence: dr. aqeel ahmad assistant professor, surgery pak red crescent medical and dental college, lahore e-mail: aqeelsurg@yahoo.com 1,2 3 department of surgery/ gynecology and obstetrics pak red crescent medical and dental college, lahore funding source: nil; conflict of interest: nil received: aug 23, 2017; revised: dec 08, 2017 accepted: dec 11, 2017 the rationality of mini-cholecystectomyjiimc 2018 vol. 13, no.1 8 i n c i s i o n , o p e r a t i o n t i m e , c o m p l i c a t i o n , postoperative hospital stay. data were analysed using spss version 21. descriptive statistics were applied. frequency and percentage were calculated for categorical variables like gender whereas mean and standard deviation were calculated for numerical variables like age and incision size. results out of 143 patients, 132 (92.30%) were females and 11 (7.69%) were males. mean age of the patients was 38 ± 10.38 years. youngest patient was 16 years old and eldest was 70 years old. the minimum incision size was 3 cm and the maximum size was 5 cm. average incision size was 4 ± 0.65 cm. the procedure was performed safely in all the cases and none of the p a t i e n t w a s c o n v e r t e d t o c o n v e n t i o n a l cholecystectomy. the mean operating time was 39.12 ± 8.66 minutes. the mean hospital stay was 2 days. during dissection dense adhesions was found in 13 patients (9.09%) and obscure anatomy was encountered in 9 patients (6.29%), which were handled safely with meticulous dissection. perioperative findings are given in table i. of our institution. a total of 143 symptomatic patients with cholelithiasis, irrespective of age and sex were included in this by convenient sampling. written informed consent was taken. complete blood count, liver function test, viral screening and clotting profile were performed. a routine preoperative abdominal ultrasound scan was performed a day before surgery. patients with cbd stones were excluded from the study. all operations were performed under general anesthesia. an equal or less than 5 cm transverse skin crease incision was made, starting from the midline approximately two finger breadths below xiphisternum, extending laterally towards the right subcostal margin. after division of the subcutaneous tissue, anterior rectus sheath, medial part of the rectus muscle and post rectus sheath were divided in turn. the peritoneum was picked up with two clips and divided between them. gall bladder was located and grasped. in case of distended gall blabber, it was aspirated because the empty gall blabber is easier to grasp for dissection. abdominal pack was inserted over the omentum and transvers colon and with the help of small deaver retractor it was retracted towards the pelvis. a second deaver retractor was placed over the abdominal pack, medial to the gall bladder and is used to retract segment 4 of the liver upwards, thus exposing the common bile duct and porta hepatis. any adhesions between hartmann's pouch, omentum and duodenum was divided carefully under direct vision. the calot's triangle was then dissected and cystic duct and artery was skeletonized and divided between the ligatures. gall bladder was removed from its bed. the gall bladder bed was checked for hemostasis and for any accessory bile duct. a subhepatic drain was left for 24 hrs. the wound was closed in layers. post-operative patients were encouraged to be ambulant and pass urine. all the patients were reassessed in the morning for any post-operative complication. drain was removed 24 hrs after the operation. oral fluid was allowed if there was no nausea and on adequate bowel sounds. on second post-operative day soft diet was allowed and patient th was discharged. they were called back on the 8 post-operative day for skin suture removal and reviewed fortnightly thereafter for one month. the data of all patients were collected for age, sex, size of table i: periopera�ve findings table ii: postopera�ve complica�on post-operative complications were seen in 7 patients (4.90%) the details are given in table ii. post-operative minor ooze (hemorrhage) from gall bladder bed was stopped spontaneously. postoperative minor biliary leak was managed conservatively. wound infection was treated with removal of sutures and wound irrigation along with 9 the rationality of mini-cholecystectomyjiimc 2018 vol. 13, no.1 group. shorter hospital stay also decreases the overall cost of the mini-cholecystectomy when 25,26 compared with traditional open cholecystectomy. motivated (encouraging) early mobilization can reduce hospital stay significantly. in our study the average hospital stay was two days which is 3,17,27 18,19 consistent with local and international data. the wound infection rate in our study was well below 28 with published regional data. many studies found, it is a cost-effective 23,5 procedure. it is found more cost-effective than 29 laparoscopic cholecystectomy and even from 3 0 , 3 1 c o n v e n t i o n a l o p e n c h o l e c y s t e c t o m y. nevertheless, minicholecystectomy is not appropriate for obese patients, they are more s u i t a b l e c a n d i d a t e s f o r l a p a r o s c o p i c 1 cholecystectomy. more effort should be put in to improve the minicholecystectomy technique rather than by-passing it e s p e c i a l l y i n c e n t e rs w h e r e l a p a ro s c o p i c cholecystectomy is not available. with this technique we can still offer to the patients of rural population better cosmetically accepted scar, less morbidity and cost-effective procedure. conclusion the present study shows clearly that minicholecystectomy is effective, safe procedure with short operating time, fewer complication, less postoperative stay and it is feasible not only in chronic cholecystitis, but also in an acutely inflamed gallbladder even in empyema. it may be recommended as a procedure of choice especially in rural centers, where laparoscopic facilities are not yet available. references 1. shulutko am, kazaryan am, agadzhanov vg. minilaparotomy cholecystectomy: technique, outcomes: a prospective study. int j surg. 2007; 5: 423-8. 2. thomas s, singh j, bishnoi pk, kumar a. feasibility of daycare open cholecystectomy: evaluation in an inpatient model. anz j surg. 2001; 71: 93-7. 3. s a e e d n , n a s i r t, b u r k i b, c h a n n a g a . m i n i cholecystectomy: a feasible option. j ayub med coll abbottabad. 2010; 22: 68-70. 4. chalkoo m, ahangar s, durrani am, chalkoo s, shah mj, bashir mi. mini-lap cholecystectomy: modifications and innovations in technique. int j surg. 2009; 8: 112-7. 5. mehrvarz s, mohebi ha, kalantar motamedi mh. laproscopic cholecystectomy versus small incision antibiotics. delayed primary closer was done in all these cases. discussion more than 2000 cases of mini laparotomy cholecystectomy have been reported worldwide without any deaths or major common bile duct 8-10 injuries since the first report in 1982. many 3,11 authors reported that, it is a safe procedure and it c a n b e a n a l t e r n a t i v e t o l a p a r o s c o p i c 1,12 cholecystectomy. mini-cholecystectomy produces 1 ''minimal trauma'' to the patients. it has a similar l eve l o f i nva s i ve n e s s to t h e l a p a ro s co p i c 13,14 approach. amount of trauma inflicted by surgeon is directly proportional to the length of incision and 15 division of muscles. many studies show small transverse incision for gall bladder surgery have 16 proved to be less painful than vertical incision. this reduction of abdominal wall trauma by use of short 17 incision should be accompanied by rapid recovery. we used transverse incision in our study, and in most of the cases the size was less than ≤ 5 cm which is 17,18,19 comparable with other studies. most of the previous studies on mini-cholecystectomy excluded acute cholecystitis patients. however, we were able to perform the procedure in cases of acute inflammation, mucoceles and empyema. we performed decompression of gallbladder as a routine in all cases to facilitate the visualization and dissection of the triangle of calot's. the present study shows clearly that mini-cholecystectomy is effective, safe and feasible not only in chronic cholecystitis, but also in an acutely inflamed gallbladder even in empyema. watanapa p. also found mini-cholecystectomy is an effective surgical procedure for an inflamed gall bladder regardless of 20 the degree and type of inflammation. operative time was longer at the initial phase of the study but, as we went through the learning curve, the operative time decreased sharply. the average operating time 21 in our study was comparable with local and 17,22,23 international data. assalia and colleagues compared mini-lap c h o l e c y s t e c t o m y w i t h c o n v e n t i o n a l o p e n cholecystectomy and showed no differences with regard to operative time, operative difficulty or 24 complication rate. however, significantly lower analgesic requirements as well as shorter hospital stay were found in the mini-lap cholecystectomy 10 the rationality of mini-cholecystectomyjiimc 2018 vol. 13, no.1 surgical procedures: variation among districts. br j surg. 1987; 74: 884-9. 20. watanapa p. mini-cholecystectomy: a personal series in acute 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p a ro s c o p i c cholecystectomy in patients: a prospective cohort study. isra med j. 2017; 9: 80-3. 13. barkun js, barkun an, sampalis js, fried g, taylor b, wexler mj, et al. randomised controlled trial of laparoscopic versus mini cholecystectomy. the mcgill gallstone treatment group. lancet. 1992; 340: 1116-9. 14. ros a, carlsson p, rahmqvist m, ba¨ckman k, nilsson e. nonrandomised patients in a cholecystectomy trial: characteristics, procedures, and outcomes. bmc surg. 2006; 6: 17. 15. singla s, singla m, singla s, thami g, malik p, aggarwal n. comparitive study between minicholecystectomy versus l a p c h o l e c y s t e c t o m y. i n t e r n a t i o n a l j o u r n a l o f contemporary medical research. 2016; 3: 2209-11. 16. armstrong pi, burgess rw. choice of incision and pain following gall bladder surgery. bi'i sutg. 1990; 77: 746-8. 17. khan n, haleem a, ahmed i, jan a. cholecystectomy through minilaparotomy incision, gomal j med sci. 2009;7: 92-5. 18. moss g, yroy, eddy ac, lund gk, beall ac. raising the o u t c o m e s t a n d a r d s f o r c o n v e n t i o n a l o p e n cholecystectomy. army j surg. 1996; 172: 383-5. 19. morgan m, poul e, devlin hb. length of stay for common 11 the rationality of mini-cholecystectomyjiimc 2018 vol. 13, no.1 page 13 page 14 page 15 page 16 original�article abstract objective: to determine the effect of mobilization (headache snag and reverse headache snag) to treat cervicogenic headache. study design: randomized control trial. st th place and duration of study: the study was conducted from 1 january to 30 july 2015 in riphah rehabilitation center, riphah international university lahore. materials and methods: a sample of 42 patients with cervicogenic headache, 30-60year age were included through non probability purposive sampling techniques and randomly divided into two groups (headache snag and reverse headache snag). the demographic data was recorded and informed consent was taken from all participants. eight weeks of treatment session was provided to both group and assessment of th improvement in cervicogenic headache was done at baseline, after 04, 06 and at the end of 8 week. results: the sample had 57 % male and 43% female distribution. patients with acute cervicogenic headache were 48% and chronic cervicogenic headache were 52%. the p value (p<0.05) showed that there was a significant difference in the improvement of headache at 06 weeks and 08 weeks in patients treated with headache snag. there was no difference in outcome of headache scale in both treatment approaches (headache snag and reverse headache snag) after 04 weeks. conclusion: the mobilization is very effective in the management of cervicogenic headache. the headache snag is more effective as compared to the reverse headache snag in the reduction of pain and headache scale. key words: cervicogenic headache, mobilization, pain, quality of life. 3 headache is short term. the prevalence of ceh from the general population aged 30-44 year through selfreported questionnaire and it was 0.17% and the prevalence is more in females as compare to males in the general population.50% headache is co related 4 with the use of medication and migraine was 42 %. it is characterized by dull pain and stiffness in the back of the head and neck and often radiate to the forehead. pain is often on one side of head and may 5 proceed to shoulder and arm on same side. cervicogenic headache has various symptoms including the refereed pain to the posterior side of head from the cervical region. the referred pain can be from the muscle and joints around the cervical 6 region. risk factors may include two types of events like repetitive activities or whiplash injuries which can cause cervicogenic headache. sedentary life style, stress, dehydration, bending forward and shoulder forward activities and slouched posture can 7 also be a major risk factor for cervicogenic. the findings of ceh include the decreased range of motion, painful upper cervical joints, muscular tightness especially the upper back cervical muscles 8 in the later phase of ceh. the following techniques are used in the treatment of the ch: medical therapy, introduction the cervicogenic headache can be defined as the chronic semi-crainal headache and the etiology is the upper cervical vertebrae. the prevalence of chronic 1 unilateral headache is 15-20%. globally it is estimated that prevalence of headache is 47% in adults which is symptomatic at least once in a last year. 1.7 to 4% adult population have headache on 15 2 or more days in a single month. the cervicogenic headache (ceh) is defined as “the pain that arises from cervical region to posterior head” it affects the quality of life of persons. the whiplash injury is one of major contributing factor for headache; this type of role of mobilization to improve cervicogenic headache 1 2 3 hafiz naeem ur rasul , atif dustagir , arshad nawaz malik correspondence: dr. hafiz naeem ur rasul department of physical therapy and rehabilitation sciences national cricket academy, lahore e-mail: hafiznimi@gmail.com 1 department of physical therapy and rehabilitation sciences national cricket academy, lahore 2 department of physical therapy and rehabilitation sciences riphah international university, lahore 3 department of physical therapy and rehabilitation sciences shifa tameer-e-millat university, islamabad funding source: nil; conflict of interest: nil received: nov 18, 2017; revised: jun 08, 2018 accepted: jun 10, 2018 cervicogenic headachejiimc 2018 vol. 13, no.2 81 acupuncture, local botulinum toxin injection, neural 9 10 therapy , cervical epidural corticosteroid injection 11,12 greater occipital nerve (gon) block, physical therapy, massage, traction, kinezitherapy and surgical treatment. it shows that the good results are obtained by a combination of physical therapy, 11-13 manual therapy and kinezitherapy. patients group who are given snags showed significantly greater improvement in neck disability index (ndi), 14 when compared to the control group. upper cervical spine mobilization showed better results than massage therapy with regard to headache pain 15 scale parameters and neck range of motion. the evidence suggested that the manual therapy, soft tissue mobilization and exercises for neck region have greater improvement as compared to other a l t e r n a t i v e s t r a t e g i e s . t h e n o n i n v a s i v e 16 management is also integral part of radiculopathy. the data base showed the evidence based literature of cervical manipulation and mobilization and they reported that the mobilization of the cervical joints with appropriate strengthening exercises was more effective outcome in ceh in terms of pain intensity as 17 compared to other treatment strategies. the exercises have significant effects on the pain intensity, range of motion and activity of daily life in ceh but there are limited improvements in other 18 secondary outcomes. the mobilization and mobilization with combination to other approaches have strong effect on the neck pain. the reviews reported that there is some evidence of improvement in the pain, functional disability, quality of life, global perceived effect on 19 the ceh. the main purpose of this study was to comapre the effects of headache snag and reverse headache snag for treating cervicogenic headache. materials and methods this was a randomized control trial and conducted st th from 1 january to 30 july in riphah rehabilitation center, riphah international university lahore. the non-probability sampling was used to collect the data and randomly divided into two groups. groupa: patients in this group were treated with headache snag. group-b: patients in this group were treated with reverse headache snag. sample selection was done on the following inclusion and exclusion criteria. the inclusion criteria include age 30–60 years, both gender; cervicogenic headache (clinically diagnosed) and patient with radiculopathy, trauma and systemic illness were excluded from the study. total 50 patients, who met the selection criteria, were enrolled for the study. the sample was calculated through software while considering the literature reference. informed consent was taken from each patient stating about the safety of the study and their right to withdraw from the study at any time. demographic details (name, age, sex,) were noted along with the necessary medical history. then patients were divided into two groups by using card allocation method. in group-a patients were treated with headache snag and in group-b patients with reverse headache snag. each patient received two treatment sessions per week with maximum eight treatment sessions over the period of four 15 weeks. three patients were dropped from sample, one because of conveyance issue while remaining two moved out of city. the treatment procedure was done by the researcher himself and all the information regarding the demographic data were gathered by using a pre-designed performa. improvement regarding the outcomes of the treatment was measured using visual analogue scale and headache pain scale. the measurement was taken before the study and then after 04, 06 and th at the end of 8 week of treatment. spss version 21 was used for data analysis and t independent samples test was used to compare the two groups. results total 50 patients were recruited including 27 male and 23 females. 48% of the sample was categorized as acute while 52% was chronic cervicogenic 33% patients had sedentary life style while 67% have active life style. 60% patients were computer user while 40% were not routine users. 86% used the hard pillow while 14% were users of soft pillow. the table shows that the mean age of sample was 40.17±9.42, mean computer use was 4.19 ±1.7 hours and mean sleeping hours were 6.21±0.951. there was no significant difference at baseline and 04 weeks (p>0.05) and it showed that both groups were homogeneous at the time of recruitment. there was a significant difference at 06weeks and 08 weeks (p<0.05) and it showed significant difference in the improvement of symptoms in two groups. headache snag is more effective after 06 and 08 weeks of treatment than reverse headache snag. (table i and ii). jiimc 2018 vol. 13, no.2 cervicogenic headache 82 discussion the results show that headache snag technique is more effective as compared to reverse headache snag to treat cervicogenic headache. although initially there was no significant difference in outcome but continuous application of headache snag was effective and showed good results long term. the improvement was recorded in headache scale and visual analogue scale after 04, 06 and 08weeeks of application of both manual techniques. snag is considered a comprehensive mobilization in reducing the pain intensity and improving the functional status of patients. a study conducted by muhammad khan to determine the effect of upper cervical sustained natural apophyseal glide (snag) with posterior anterior mobilization showed that there was significant difference in disability index and pain scale. the results are similar with this study finding that the snag mobilization has more effective than other treatment approaches in 20 reducing pain in cervicogenic headache. a systematic review was conducted by stephanie racick in 2013 to determine the evidence based and effective treatment approach in the treatment of cervicogenic headache. they included the study r e l a t e d w i t h m o b i l i z a t i o n , m a n i p u l a t i o n , strengthening and other treatment options and concluded that mobilization with other approaches is effective in reducing pain in patients of cervicogenic headache. (54) janusz kocjan conducted a study in 2015 to determine the effectiveness of snag in ceh. they compared the cervical rotation in conjunction with snag mobilization. the result showed better improvement 21 when compared to other mobilization techniques. the reverse snag is used to mobilize the cervical segments for mobility and improving the joint movement. a study conducted in 2014 by susan a. reid on the comparison of maitland and mulligan snag for the treatment of cervicogenic dizziness. they compared the both techniques 1 and 2 weeks and concluded that the both technique are effective in reducing the pain and frequency of dizziness in 22 patients with cervicogenic dizziness. the literature showed that the different approaches are effective for the pain relief, dizziness intensity reduction and improvement of range of motion. the study finally concluded that there is limited evidence in the literature about the snag although there is relief in pain scale and other symptoms related with 23 cervicogenic headache. the study conducted by armed in 2014 on the effectives of snag glide and manipulation on the cervical disorder. they took measurement on neck disability index, ranges and visual analogue scale for the recording of improvement in the patients with cervical impairment. they used manipulation while in current study mobilization was used to assess the effects on pain. finally they concluded that the mobilization snag with manipulation has good effects and showed the significant statistical difference as compares to the other treatment options like simple exercise alone in improving the pain and disability index in patients with cervical 24 disorder. the limited sample size and lack of quantitative equipment for detecting change are major limitation in study. further studies with physiological biomarker, radiological findings and with larger sample size are recommended. conclusion mobilization is very effective in the management of cervicogenic headache. the headache snag is more effective as compared to the reverse headache snag in the reduction of pain on headache scale. the mobilization should be included in the appropriate management of cervicogenic headache. table i: comparison of groups for headache scale table ii: comparison of groups for visual analogue scale jiimc 2018 vol. 13, no.2 cervicogenic headache 83 references 1. grgic v. [cervicogenic headache: etiopathogenesis, characteristics, diagnosis, differential diagnosis and therapy]. lijecnicki vjesnik. 2007; 129: 230-6. 2. van suijlekom h, van zundert j, narouze s, van kleef m, mekhail n. cervicogenic headache. pain practice: the official journal of world institute of pain. 2010; 10: 124-30. 3. vincent mb. cervicogenic headache: a review comparison with migraine, tension-type headache, and whiplash. current pain and headache reports. 2010; 14: 238-43. 4. shaheen z, kurji z, mithani y. are health care resources allocated equitably in pakistan? international journal of nursing education. 2014; 6: 82-7. 5. france s, bown j, nowosilskyj m, mott m, rand s, walters j. evidence for the use of dry needling and physiotherapy in the management of cervicogenic or tension-type headache: a systematic review. cephalalgia. 2014; 34: 9941003. 6. bogduk n, govind j. cervicogenic headache: an assessment of the evidence on clinical diagnosis, invasive tests, and treatment. the lancet neurology. 2009; 8: 959-68. 7. ellis mj, leddy jj, willer b. physiological, vestibulo-ocular and cervicogenic post-concussion disorders: an evidencebased classification system with directions for treatment. brain injury. 2014; 29: 238-48. 8. zito g, jull g, story i. clinical tests of musculoskeletal dysfunction in the diagnosis of cervicogenic headache. manual therapy. 2006; 11: 118-29. 9. karadas o, ozturk b, ulas uh, kutukcu y, odabasi z. the efficacy of botulinum toxin in patients with cervicogenic headache: a placebo-controlled clinical trial. balkan medical journal. 2012; 29: 184-7. 10. wang e, wang d. treatment of cervicogenic headache with cervical epidural steroid injection. current pain and headache reports. 2014; 18: 442. 11. lauretti gr, correa sw, mattos al. efficacy of the greater occipital nerve block for cervicogenic headache: comparing classical and subcompartmental techniques. pain practice : the official journal of world institute of pain. 2015 ; 15: 654-61. 12. knackstedt h, bansevicius d, aaseth k, grande rb, lundqvist c, russell mb. cervicogenic headache in the general population: the akershus study of chronic headache. cephalalgia : an international journal of headache. 2010; 30: 1468-76. 13. wu jx, fan rj, song wx, chen p. [effect of cervical paravertebral block combined with acupuncture intervention on cervicogenic headache]. zhen ci yan jiu = acupuncture research / [zhongguo yi xue ke xue yuan yi xue qing bao yan jiu suo bian ji]. 2013; 38: 411-4. 14. shin ej, lee bh. the effect of sustained natural apophyseal glides on headache, duration and cervical function in women with cervicogenic headache. journal of exercise rehabilitation. 2014; 10: 131-5. 15. youssef ef, shanb as. mobilization versus massage therapy in the treatment of cervicogenic headache: a clinical study. journal of back and musculoskeletal rehabilitation. 2013; 26: 17-24. 16. hurwitz el, carragee ej, van der velde g, carroll lj, nordin m, guzman j, et al. treatment of neck pain: noninvasive interventions: results of the bone and joint decade 2000–2010 task force on neck pain and its associated disorders. journal of manipulative and physiological therapeutics. 2009; 32: s141-s75. 17. racicki s, gerwin s, diclaudio s, reinmann s, donaldson m. conservative physical therapy management for the treatment of cervicogenic headache: a systematic review. journal of manual & manipulative therapy. 2013; 21: 11324. 18. harden rn, cottrill j, gagnon cm, smitherman ta, weinland sr, tann b, et al. botulinum toxin a in the treatment of chronic tension-type headache with cervical myofascial trigger points: a randomized, double-blind, placebo-controlled pilot study. headache: the journal of head and face pain. 2009; 49: 732-43. 19. gross a, miller j, d'sylva j, burnie sj, goldsmith ch, graham n, et al. manipulation or mobilisation for neck pain: a cochrane review. manual therapy. 2010; 15: 315-33. 20. khan m, ali ss, soomro rr. efficacy of c1-c2 sustained natural apophyseal glide (snag) versus posterior anterior vertebral mobilization (pavms) in the management of cervicogenic headache. journal of basic and applied sciences. 2014; 10: 226-30. 21. kocjan j. effect of a c1-c2 mulligan sustained natural apophyseal glide (snag) in the treatment of cervicogenic headache. journal of education, health and sport formerly journal of health sciences. 2015; 5: 79-86. 22. reid sa, rivett da, katekar mg, callister r. comparison of mulligan sustained natural apophyseal glides and maitland mobilizations for treatment of cervicogenic dizziness: a randomized controlled trial. physical therapy. 2014; 94: 466-76. 23. reid sa, rivett da, katekar mg, callister r. efficacy of manual therapy treatments for people with cervicogenic dizziness and pain: protocol of a randomised controlled trial. bmc musculoskeletal disorders. 2012; 13: 201. 24. el-sodany am, alayat msm, zafer ami. sustained natural apophyseal glides mobilization versus manipulation in the treatment of cervical spine disorders: a randomized controlled trial. international journal. 2014; 2: 274-80. jiimc 2018 vol. 13, no.2 cervicogenic headache 84 page 37 page 38 page 39 page 40 171 original�article abstract objective: to know the public opinion about the role of infodemic in spreading fear & panic among the public of pakistan and to assess the effect of fear created by infodemic on their health. study design: this was a cross sectional survey. th th place and duration of study: the study was conducted from 14 july 2020 to 25 august 2020 in rawalpindi, pakistan. materials and methods: an online cross-sectional survey was conducted using a pre-validated questionnaire th th from 14 july 2020 till 25 august 2020. people of age >12 years were invited to participate in an online survey through google forms. a written consent was obtained from all the participants before filling the questionnaire. data was analyzed using statistical package for social sciences spss version 24. results: total 541 participants took part in this survey. 320 (59%) of which females and 221 (41%) were males. majority 224(41%) reported that category of misinformation and fake news about covid-19 had the most impact in creating fear and panic among people. 80% (432) reported that infodemic played a role in creating fear and panic among people, 310(57.4%) participants reported that infodemic created fear on them, 304(56.2%) reported their health was affected, 182(33.6%) had effects on psychological health, 17(3%) had effect on physical health while 105(19.4%) had effects on both psychological and physical health. conclusion: infodemic caused by media played a major role in creating fear and panic among people. fear created by infodemic during the covid-19 outbreak is associated with negative psychological outcome in our population. key words: covid-19, fear, pandemic, public health. “information” and “epidemic” which means the overwhelming amount of information regarding a problem which makes it difficult to find the accurate 4 information and its solution. this was a real challenge during the times of global health crisis. due to media, the phenomenon of spread of information, misinformation and rumours has been 5 dramatically increased which posed a serious problem for public health both psychologically and 6 physically. “we're in the midst of the social media misinformation age and these rumours and 7 conspiracy theories have real consequences.” electronic media is the most used source of information in pakistan. but the role of media concerning covid-19 is kind of disappointing. on one hand, media played its role in creating awareness regarding the disease, but on the other hand provision of unfiltered information affected health of public both psychologically and physically. media covered the news about covid-19 however, often the media coverage was without opinion of medical experts, doctors and even without 8 scientifically proven evidence. media disseminated more information about rising death toll, rate of introduction corona virus (covid-19) is an infectious disease caused by a newly found corona virus in china in 1 december 2019. covid-19 outbreak was declared 2 as a “pandemic” by w.h.o on 11 march 2020. this caused a wave of fear, anxiety and panic among people throughout the world. in addition to the fear of disease, it's contagious and deadly nature; there was an information overload which created even more fear and panic among people. “we're not just fighting an epidemic; we're fighting 3 an infodemic” these were the words of who director general while th addressing a conference on 15 february 2020. infodemic is the term coined from the words effect of covid-19 related infodemic on health of general public of pakistan 1 2 azeema noor , tahira sadiq correspondence: dr.azeema noor house officer department of medicine iimc, rawalpindi e-mail: azeema.noor123@gmail.com 1 2 department of medicine/community medicine iimc, rawalpindi funding source: nil; conflict of interest: nil received: august 24, 2020; revised: june 01, 2021 accepted: july 06, 2021 fighting the infodemicjiimc 2021 vol. 16, no.3 9 infectivity, some fake news about herbal cures of disease, covid-19 being a “conspiracy” and not actually a natural disease and other such news. in other words, there was an avalanche of such information which created fear and panic among people. fear is an emotional response of human beings which can have positive as well as negative effects. in context of health crisis, fear effected people psychologically causing negative symptoms like anxiety, depression, poor brain function as well as 10 physically by weakening the immune system. when fear is out of proportion, it becomes the source of various psychiatric disorders having long term 11 effects. humanitarian crisis is a public health issue and the goal of public health is physical, psychological and 12 social wellbeing of entire population which was greatly threatened in the above mentioned circumstances. there was no study to assess the effects of infodemic during the time of health crisis on the health of public of pakistan. the purpose of this study was: · to know public opinion about the role of infodemic in spreading fear and panic among the public of pakistan during covid-19. · to assess the effect of fear created by infodemic on their health. materials and methods this was a cross-sectional survey conducted from th th 14 july 2020 till 25 august 2020 in rawalpindi/ islamabad. sample size was calculated using “raosoft”, with total population of pakistan 220.8 million, confidence interval of 95% and the margin of error of 5%, the recommended sample size was 385. and the additional sample of 156 was collected. total 541 participants took part in study. sampling technique used was non-probability convenience sampling. instrument used for data collection was 13 pre-validated questionnaire used with permission from author. the inventory was modified with respect to local context. only adolescent and adult citizens were included in the study. children and people with clinical mental illness were excluded. responses were collected after written informed consent at the start of questionnaire from respondents and their anonymity was assured. data was collected from participants from different cities of pakistan. questionnaire was self-administered online via google forms due to covid-19 restrictions. forms with incomplete information were rejected. questionnaire consisted of 4 sections; first section addressed the demographic variables of gender, age and qualification. second section addressed the category of information that had the most impact in creating fear and panic among people. third section addressed the opinion about the role of infodemic in spreading fear and panic among public of pakistan and the impact of fear caused by infodemic on their health. final section addressed the opinion regarding need of information filtering by media. the data was analysed using spss version 20. tables and figures were drawn using microsoft excel. chi square test was employed to establish the association between qualitative variables. confidence interval of 95% was used. p values of less than 0.05 were considered statistically significant. tables and figures were drawn in terms of frequencies and proportions. results the research revealed some interesting figures about the effects of infodemic on public health. data is presented in the form of tables, figures, and bar charts. the participants comprised of 41% males and 59% females. majority of participants aged 18-60 years (92%). approximately 70% had received the university degree (table i) section 2: figure 1 shows the response of participants about the category of information that table i: demographic information of respondents fighting the infodemicjiimc 2021 vol. 16, no.3 172 mostly caused fear. it shows that majority responded that the category of “misinformation and fake news” had the most impact in creating fear and panic among people. age group based response about category of information that mostly caused fear is shown in fig 1: category of information that mostly caused fear figure 2 which shows that in all the age groups the category of “misinformation & fake news about covid-19” was the response of majority of participants. section 3 comprised of the opinion about spread of fear and panic among people by infodemic to which fig 2: age group-based response about category of information that mostly caused fear majority 432(80%) had a positive response shown in figure 3. majority of participants 310(57.4%) reported that publishing more news related to covid-19 i.e., covid19 related infodemic created fear on them. figure 4 shows 304(56.2%) participants reported that their health was affected either in terms of physical, psychological or both i.e., physical and psychological health by the fear created by infodemic while 237(43.8%) reported they were not afraid. gender based response is shown in figure 5. in females, 61% reported that their health was fig 3: opinion about fear and panic among people by infodemic fig 4: health aspect affected by fear affected. while 50% males reported the effects on their health. section 4 comprised of opinion regarding need of information filtering by media. majority of fig 5: health aspect effected by fear (gender-based response) participants 496(91.7%) reported that there is need of information filtering by media. opinion of participants that covid-19 related infodemic has caused fear and panic among people has significant association with age group p=0.017, category of information that had most impact in creating fear and panic p=0.04, health aspect fighting the infodemicjiimc 2021 vol. 16, no.3 173 effected by fear p<0.001 and the need of information filtering p=0.02. the category of information that had most impact in creating fear & panic has significant association with the opinion of participants that covid-19 related infodemic created fear on them p=<0.001, health aspect effected by fear p=<0.001 and the need of filtering of information p=0.03 the opinion of participants that covid-19 related infodemic created fear on them has significant association with the health aspect effected by fear i.e p<0.001.however there was no significant association of any variable with gender and qualification of participants. discussion this study was conducted to explore the effects of infodemic on the health of public of pakistan. we found that majority had the opinion that there is more spread of fear and panic among people due the infodemic which had negative health outcomes. our f i n d i n g t h a t m a j o r i t y ( 4 1 % ) r e p o r t e d “misinformation and fake news” played the main role in creating fear and panic among people is consistent with the study conducted in italy that 14 there were almost 46000 new posts on twitter daily during march 2020 which was related to misinformation about covid19. a survey conducted in uk indicated that 46% of adults in uk were exposed to misinformation about covid19 and 40% of uk adults are 'finding it hard to know what is true 15 or false about the virus' . another study conducted in us reported that due to misinformation/fake news 64% of the adults had confusion about basic 16 information related to current events . it was stated by who director general that the most contagious thing about covid-19 might be the misinformation and stated that “social media panic travelled faster 17 than the covid-19 spread” there is negative health outcome associated with infodemic with health of 35% respondents affected psychologically. psychological health of people is affected more as there is more spread of fear by the infodemic (p<0.001). similar results are reported by a study conducted in china during march 2020 concluded that there is high prevalence of mental health problems associated with social media 18 exposure during covid-19. the study conducted in 13 iraq also reported that the majority of participants had effects on psychological health due to fear which might have played a role in decreasing the immunity of people. a chinese survey found that 53.8% of respondents rated the psychological impact of the outbreak as moderate or severe; 16.5% reported moderate to severe depressive symptoms; 28.8% reported moderate to severe anxiety symptoms, and 19 8.1% reported moderate to severe stress levels . another survey conducted in china in which 52370 people participated concluded that 35% people had 20 psychological distress. a study conducted in china with 17865 participants concluded that negative emotions increased after the declaration of covid-19 21 pandemic. a study conducted in usa reported that covid-19 pandemic has profound psychological and social effects which will persist for a long time in 22 future. the problem is the filter failure due to which there is a need to have filters for information provided by media as expressed by 91% of participants but there is very little evidence to support this result. this study has various limitations. this was a cross sectional study which cannot fully establish the cause and effect relationship of unfiltered media e x p o s u r e a n d p s y c h o l o g i c a l h e a l t h . t h e methodological choices were constrained due to lockdown and quarantine situation. we were not able to compare the mental health of participants before, during and after covid-19. the research sample consisted of pakistani public of mainly rawalpindi and islamabad so it's difficult to establish 23 the generalization of results. further studies should investigate the long-term health effect and psychological outcome of covid19 outbreak on health of public of pakistan once the pandemic is over. conclusion this study concludes that infodemic caused by media played a significant role in creating fear and panic among people. fear created by infodemic is associated with negative health outcome during the covid-19 outbreak in pakistan. references 1. who/europe | coronavirus disease (covid-19) outbreak. [ i n t e r n e t ] a v a i l a b l e f r o m : https://www.euro.who.int/en/health-topics/healthemergencies/coronavirus-covid-19. 2. coronavirus disease (covid-19) outbreak. [internet] 2020 fighting the infodemicjiimc 2021 vol. 16, no.3 174 jul 30 available from: https://www.euro.who.int/ en/health-topics/health-emergencies/coronavirus-covid19. 3. ghebreyesus ta. munich security conference. in: world health organization. [internet] 2020. available from: htt ps : / / w w w.w h o . i nt / d g /s p e e c h e s / d eta i l / m u n i c h security-conference. 4. vaezi a, javanmard s. infodemic and risk communication in the era of cov-19. adv biomed res. 2020 jun 1; 9(1):10. available from: https://www.advbiores.net/article doi: 10.4103/abr.abr_47_20. 5. zarocostas j. how to fight an infodemic. lancet (london, england). nlm (medline); 2020 feb 29; 395(10225):676. available from: www.thelancet.com https://doi.org/ 10.1016/s0140-6736(20)30461-x. 6. naeem, s.b., bhatti, r. and khan, a. an exploration of how fake news is taking over social media and putting public health at risk. health information and libraries journal. 2020; 37(3): 233-239 https://doi.org/10.1111/hir.12320. 7. cohen j. scientists 'strongly condemn' rumors and conspiracy theories about origin of coronavirus outbreak. american association for the advancement of science. 2020 feb 19; https://doi.org/10.1126/science.abb3730. 8. bilal, latif f, bashir mf, komal b, tan d. role of electronic media in mitigating the psychological impacts of novel c o r o n a v i r u s ( c o v i d 1 9 ) . p s y c h i a t r y r e s e a r c h nlm(medline). 2020; 289: 113041 https://doi.org/10. 1016/j.psychres.2020.113041.(https://www.sciencedirect. com/science/article/pii/s0165178120309380). 9. petchot k. 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[internet] cdc foundation 2020. available from: https://www.cdcfoundation.org/what-public-health. 13. ahmad a, murad h.the impact of social media on panic during the covid-19 pandemic in iraqi kurdistan: online questionnaire study. j med internet res 2020;22(5): e19556 url: https://www.jmir.org/2020/5/e19556/ doi: 10.2196/19556. 14. meadows c. more than 46,000 twitter posts a day point to coronavirus misinformation, investigation finds – society of editors. [internet]. [cited 2020 oct 4]. available from: https://www.societyofeditors.org/soe_news/more-than4 6 0 0 0 t w i t t e r p o s t s a d a y p o i n t t o c o r o n a v i r u s misinformation-investigation-finds/. 15. ofcom. half of uk adults exposed to false claims about coronavirus. ofcom. 2020 [internet]. [cited 2020 oct 4]. available from: https://www.ofcom.org.uk/aboutofcom/latest/features-and-news/half-of-uk-adultsexposed-to-false-claims-about-coronavirus. 16. murphy, j. (2007), international perspectives and initiatives. health information & libraries journal, 24: 6268. https://doi.org/10.1111/j.1471-1842.2007.00704.x. 17. depoux a, martin s, karafillakis e, preet r, wilder-smith a, larson h. the pandemic of social media panic travels faster than the covid-19 outbreaks. journal of travel medicine. 2020 ;27(3) https://doi.org/10.1093/jtm/taaa031. 18. gao j, zheng p, jia y, chen h, mao y, chen s, et al. (2020) mental health problems and social media exposure during covid-19 outbreak. plos one 15(4): e0231924. https://doi.org/10.1371/journal.pone.0231924 . 19. ho cs, chee cy, ho rc. mental health strategies to combat the psychological impact of covid-19 beyond paranoia and panic. annals of the academy of medicine, singapore. 2020;49(1):1–3. 20. qiu j, shen b, zhao m, et ala nationwide survey of psychological distress among chinese people in the covid19 epidemic: implications and policy recommendations general psychiatry 2020;33: e100213. doi: 10.1136/gpsych2020-100213. 21. li s, wang y, xue j, zhao n, zhu t. the impact of covid-19 epidemic declaration on psychological consequences: a study on active weibo users. international journal of environmental research and public health [internet] 2020;17(6):2032. available from: http://dx.doi.org/ 10.3390/ijerph17062032. 22. sher l. the impact of the covid-19 pandemic on suicide rates qjm: an international journal of medicine. 2020; 1 1 3 ( 1 0 ) : 7 0 7 7 1 2 h t t p s : / / d o i . o r g / 1 0 . 1 0 9 3 / qjmed/hcaa202. 23. chao m, xue d, liu t, yang h, hall bj. media use and acute psychological outcomes during covid-19 outbreak in c h i n a . j a n x i e t y d i s o r d . 2 0 2 0 a u g 1 ; 7 4 . https://doi.org/10.1016/j.janxdis.2020.102248. fighting the infodemicjiimc 2021 vol. 16, no.3 175 original�article abstract objective: to determine the frequency of women having pregnancy with severe anemia, its maternal complications and feto-maternal outcome. study design: descriptive case series study. place and duration of study: this study was conducted at obstetrics and gynecology department, cmh / skbz th th al-nayhan hospital muzaffarabad from 15 april 2014 to 20 oct 2014. materials and methods: a total of 186 pregnant women admitted for delivery with gestational age ≥ 34 weeks were included in the study. demographic information regarding age, gestational age and parity was taken on predesigned performa. intra-partum and post-partum observations were made for maternal complications like pregnancy-induced hypertension and postpartum hemorrhage. perinatal complications like low birth weight and apgar score < 7 at 5 minutes were noted. results: mean age of women in the study sample was 26.76±3.36 years. mean gestational age of women was 38.46±0.63 weeks. thirty-five (19%) women were diagnosed with anemia among which 12(6.5%) women had severe anemia, 4(2.2%) had mild, and 19(10.2%) had moderate anemia. the frequency of pih (37.14%), pph (17.14%), low birth weight (62.68%) and apgar score < 7 (60%) was noted higher in anemic patients. conclusion: severe anemia during pregnancy significantly increases the chance of adverse perinatal and maternal outcomes in terms of pih, pph, low birth weight and apgar score. key words: apgar score, fetomaternal outcome, induced hypertension, low birth weight, pregnancy, postpartum heamorrahge, severe anemia. 2 almost double in developing countries. the average prevalence rate is 56% in developing countries with a great variation with respect to different regions of 3 the world ranging from 35% to 100%. some women have iron deficiency anemia at start of pregnancy, which begins to exacerbate due to physiological changes of mother due to pregnancy. this complication begins in first trimester and increases with passage of pregnancy. according to who definition the women having hemoglobin level of 11 gm/dl or less is considered as anemic during 4 pregnancy. there are many risk factors which contribute to pregnancy anemia including iron deficiency which is co n s i d e re d m a i n ca u s e o f a n e m i a . o t h e r contributing factors are deficiency of b12 or thalassemia trait, which are also a very common cause of anemia. the prevalence of anemia is very s high especially in third trimester and have a very significant adverse impact on maternal health during 5 pregnancy and fetal outcome. very severe adverse consequences are related with anemia in pregnancy for mother and fetus. these adverse effects are not bounded during pregnancy, neonatal and infant period only, but this increases introduction pregnancy is a vital part of a woman's life but it is period of greater risks of different complications for mother and fetus. one of the most prevalent complication is anemia, which is being faced throughout the world. this challenge is more commonly faced in developing countries due to poor 1 nutritional status. according to the estimates of (who), anemia has a prevalence of 23% in developed countries with feto-maternal outcome in pregnancy with anemia 1 2 3 4 zubina adnan , ayesha nayyar , shaista nayyar , adnan mehraj correspondence: dr. zubina adnan department of gynae cmh /skbz al-nayhan hospital muzaffarabad e-mail: zadnan76@hotmail.com 1 department of gynae & obse cmh/skbz /al-nayhan hospital muzaffarabad 2 department of hematology islamic international medical college riphah international university, islamabad 3 department of radiology sahiwal medeical collegw sahiwal 4 department of surgery cmh, muzaffarabad funding source: nil; conflict of interest: nil received: oct 06, 2017; revised: may 28, 2018 accepted: june 01, 2018 pregnancy with anemiajiimc 2018 vol. 13, no.2 57 all the women were recruited for the study by nonprobability consecutive sampling method. the study was started after taking formal written permission from hospital ethical committee. informed written consent was taken from all patients who fulfilled the inclusion and exclusion criteria. all women admitted for delivery with gestational age ≥ 34 weeks were included in the study. pregnant women with known history of thalessemia and sickle cell anemia, women with ante-partum hemorrhage and no available previous report of hb were excluded from the study. demographic information regarding age, gestational age and parity were taken on predesigned performa. blood sample was taken from each patients and sent to the laboratory for hemoglobin level. the who's anaemia classification and categorization was adopted for functional definition of haemoglobin conditions; anaemic (serum hb 5-11g/dl), and nonanaemic (serum hb>11g/dl) the anemic group was further divided into mild (9-10.9 g/dl), moderate (78.9 g/dl) and severe anemia (< 7 g/dl). intra-partum and post-partum observations were made for maternal complications like hypertension and postpartum hemorrhage. perinatal complications like low birth weight and apgar score < 7 at 5 minutes were noted. all data was analyzed using spss version 21. mean and standard deviation was calculated for numerical variables. frequency and percentages were calculated for categorical variables. effect modifiers like age, parity and gestational age was controlled by stratification. post stratification chi square test was a p p l i e d t o c o m p a r e p r e g n a n c y i n d u c e d hypertension, pph, mode of delivery, apgar score (< 7) at 5 minutes, low birth weight in anemic pregnant and non-anemic pregnant women. p-value <0.05 was considered significant. results in this sample of 186 women the mean age was 26.76±3.36 years with minimum and maximum age of 22 and 37 years respectively. parity status showed that most of the 62(33.3%) women had 2 children, followed by 61(32.8%) women with parity 3, and 21(11.3%) women had parity 1, there were 17(9.1%) women whose parity was 0, and 16(8.6%) & 9(4.8%) women had parity 4 & 5 respectively. mean gestational age of women was 38.46±0.63 weeks, ranging from 37 to 40 weeks. in our study sample, the chances of non-communicable diseases during adulthood as well. studies have also shown relationship of low birth weight in next generation with anemia during pregnancy. anemia is preventable complication of pregnancy and it can easily be diagnosed and treated with easily available techniques and tools which are affordable and can be implemented in even primary health care 6, 7 settings. the frequency of maternal complications is very high a m o n g s eve r a n e m i c p re g n a nt wo m e n i n comparison with normal pregnant women. in a study it was noted that in anemic pregnant patients the maternal complications like pregnancy induced hypertension (36% vs. 10%), infections (16% vs. 5%) and post-partum heamorahhge (14% vs. 5%) was significantly higher in contrast to normal pregnant 5 women. similarly the fetal outcome like low birth weight (57.62% vs. 42.37%), and apgar score < 7 (57.57% vs. 42.42%) was also significantly distressed in anemic patients. some studies have shown significantly very high difference in low birth weight (64% vs 10%) in anemic and non-anemic pregnant 8 women. antenatal iron-folic acid supplementation reduces low birth weight and preterm in both 9 developed and developing country settings. studies conducted in pakistan show a high percentage of anemia during pregnancy so this study had been planned to find out the adverse effects of a n e m i a d u r i n g p r e g n a n c y o n m a t e r n a l complications (like pregnancy induced hypertension and post-partum hemorrhage) and fetal outcome in terms of low birth weight in our local target population in comparison with normal controls. the aim of this stud is to determine the frequency of women having pregnancy with severe anemia, its maternal complications and feto-maternal outcome. materials and methods in this descriptive case series study, a total of 186 pregnant women were included from obstetrics and gynecology dept. cmh / skbz al-nayhan hospital muzaffarabad. this study was conducted in a period th th of seven months from 15 april to 20 oct 2014. the sample size was calculated by using who sample size calculator taking confidence level of 95 %, 2 anticipated population proportion p = 14% , and absolute precision required = 5%. pregnancy with anemiajiimc 2018 vol. 13, no.2 58 discussion anemia is a pregnancy complication which can be prevented easily and fetal and maternal morbidity and mortality related to anemia can be minimized. 35(19%) women diagnosed with anemia. as per who criteria there were 151(81.2%) women who had normal hb level, among anemic women 4(2.2%) had mild, 19(10.2%) had moderate and only 12(6.5%) women had severe anemia. (fig 1). there were 29(16%) women with pregnancy induced hypertension. post-partum heamorahhge was seen in 17(9%) women. there were 62(33%) fetus who had low birth weight. apgar score <7 was observed in 84(45%) babies. (fig 2). in our study sample 35 women were anemic and among these 13 (37.14%) women had pregnancy induced hypertension. while among 151 nonanemic women only 16 (10.59%) had pregnancy induced hypertension. a statistically significant (pvalue=0.000) association was present between anemia and pregnancy induced hypertension. among anemic women 6 (17.14%) suffered from post-partum hemorrhage, while among non-anemic only 11 (7.29%) suffered from post-partum hemorrhage. which shows statistically insignificant (p-value=0.068) association between anemia and post-partum hemorrhage. (table i). the results showed that among anemic women the fetal outcome was significantly poor as compared with non-anemic women. among women with anemia 22 (62.86%) had low birth weight babies as compared to non-anemic mothers in which 40 (26.49%) had low birth weight babies showing a statistically significant (p-value=0.000) association between mother's anemic status and low birth weight babies. similarly, among babies of anemic mothers, apgar score <7 at 5 minutes was observed in 21 (60%) babies as compared to 63 (41.72%) babies of non-anemic mothers who had apgar score <7 at 5 minute. there was no statistically significant (p-value=0.05) association between anemia and apgar score <7 at 5 minutes. (table ii). fig 1: bar chart showing frequency distribu�on of different categories of anemia fig 2: bar chart showing distribu�on of maternal complica�ons & fetal outcome table i: maternal complica�ons in the cases of pregnancy with anemia (n= 35) * difference is significant at 5% level of significance ** difference is not significant at 5% level of significance table ii: perinatal complica�ons like low birth weight and apgar score < 7 at 5 minutes in pregnancy with anemia * difference is significant at 5% level of significance ** difference is not significant at 5% level of significance pregnancy with anemiajiimc 2018 vol. 13, no.2 59 th score <7 at 5 minute and 41.72% non-anemic women's babied had apgar score <7 at 5minute. ram hari ghimire in his study explored the association between anemia and maternal and perinatal complications. in his results he reported that pregnancy induced hypertension and postpartum hemorrhage was significantly high is women who were anemic (pih =36%, pph= 14%) as compared to (pih=10%, pph=5%) in non-anemic women. results regarding fetal complication among anemic and non-anemic mothers showed that apgar score <7 was 18% and 5% among anemic and non-anemic mothers and low birth weight of fetus was observed as 22% and 9% in anemic and non5 anemic mothers. lone et al, in a multivariate analysis of their study population showed that the risk of low birth weight babies in the anemic population was 1.9 times 22 higher. a local study from rawalpindi reported the number of low birth weight infants (64%) was highly significant in the anemic mothers than the non23 anemic (10%). the anemia during pregnancy increases the chances of obstetric haemorrhage, infection rate and obstetric shock and trauma due to labour complication etc. this increases the chance of maternal mortality by five times as compared with non-anemic women. similarly, in severe anemic patients having hemoglobin less or equal to 6 gm/100ml the chance of high cardiac output failure r i s e s s i g n i f i ca nt l y s p e c i f i ca l l y i n ca s e s o f h y p e r t e n s i o n a n d p r e e c l a m p s i a . t h e s e complications are less likely to occur in patients having mild or moderate anemia. but in these patients having mild or moderate anemia the child can come up with some speech learning or 24 behavioral problems. anemia in pregnancy has been found as a significant contributing risk factor for adverse perinatal and maternal outcomes. special attention should be given to minimize the anemia especially during pregnancy. conclusion in this study anemia was observed in 19% pregnant women, in which 2.2% women had mild, 10.2% moderate and 6.5% women had severe anemia. t h e re w e re s i g n i f i c a n t l y h i g h e r m a t e r n a l complications among anemic women as compared the prevalence of anemia is very high with great variations in different regions around the globe. it varies from 15% in western countries to 75% in developing countries of africa and asia. in developing countries its prevalence ranges from 33% 5, 10, 11 to 75% in different regions. the incidence of iron deficiency anemia in pakistan has been report quite high by different studies. a high incidence of 50% was found despite routine iron therapy in a study conducted in karachi. similar high incidence of iron deficiency anemia among pregnant women has been reported from other developing 12-14 countries of africa and india. women having anemia during pregnancy often feel body aches and fatigue. there are many causes of anemia in pakistan. the main contributing causes are poor economic conditions, repeated pregnancies with short interval, gender bias, worm infestation and lack of health seeking behavior. the major causative factor for anemia in pakistan is iron 15 deficiency during and at the start of pregnancy. the anemia a common pregnancy complication increases the risk of low birth weight and intra 16 uterine growth retardation. in this study 35(19%) women had anemia. as per who criteria 151(81.2%) women had normal hb level, 4(2.2%) had mild, 19(10.2%) moderate and only 12(6.5%) women had severe anemia. two local studies one from sindh and the other from multan reported (52%) of patients presented with moderate anemia, 12% with severe anemia requiring blood transfusions, and 36% of pregnant women were mildly anemic. 3 while study from multan showed severe anemia in 8%, mild anemia in 44% 12 and moderate anemia in 48% of patients. this prevalence of anemia in this study 19% was comparable to studies conducted in trinidad and tobago (15.3%), thailand (20.1%), zurich (18.5%), 17-21 hawassa (15.3%), and gondar town (22%). in this study pregnancy induced hypertension was present in 37.14% women who were anemic and present in 10.60% in women who were not anemic. post-partum heamorahhge was seen in 17.14% women who were anemic and in 7.28% women who were not anemic. among 62.86% anemic mothers the babies were low weight while 26.49% among non-anemic women babies had low birth weight. there were 60% women whose fetus had apgar pregnancy with anemiajiimc 2018 vol. 13, no.2 60 13. rai n, nandeshwar s, rai p. a study on magnitude of anaemia and its sociodemographic correlates among pregnant women in sagar city of bundelkhand region, madhya pradesh, india. int j community med public health. 2016; 3: 128-32. 14. awan mm, akbar ma, khan mi. a study of anemia in pregnant women of railway colony, multan. pak j med res. 2004; 43: 11-4. 15. khan da, fatima s, imran r, khan fa. iron, folate and cobalamin deficiency in anaemic pregnant females in tertiary care center at rawalpindi. j ayub med coll abbottabad. 2010; 22: 17-21. 16. badshah s, mason l, mckelvie k, payne r, lisboa pj. risk factors for low birthweight in the public-hospitals at peshawar, nwfp-pakistan. bmc public health. 2008; 8: 197. 17. uche-nwachi e, odekunle a, jacinto s, burnett m, clapperton m, david y, et al. anemia in pregnancy: associations with parity, abortions and child spacing in primary healthcare clinic attendees in trinidad and tobago. african health sciences. 2010; 10: 66. 18. sritippayawan s, wong p, chattrapiban t. iron deficiency anemia during pregnancy in the lower north of thailand prevalence and associated factors. malaysian j pub health med. 2012; 12: 1-5. 19. abriha a, yesuf me, wassie mm. prevalence and associated factors of anemia among pregnant women of mekelle town: a cross sectional study. bmc res notes. 2014; 7: 888. 20. alem m, enawgaw b, gelaw a, kenaw t, seid m, olkeba y. prevalence of anemia and associated risk factors among pregnant women attending antenatal care in azezo health center gondar town, northwest ethiopia. journal of interdisciplinary histopathology. 2013; 1: 137-44. 21. stevens ga, finucane mm, de-regil lm, paciorek cj, flaxman sr, branca f, et al. global, regional, and national trends in haemoglobin concentration and prevalence of total and severe anemia in children and pregnant and nonpregnant women for 1995–2011: a systematic analysis of population-representative data. the lancet global health. 2013; 1: e16-e25. 22. lone f, qureshi r, emmanuel f. maternal anemia and its impact on perinatal outcome in a tertiary care hospital in pakistan. east mediter health j. 2004; 10: 801-7. 23. ahmad mo, kalsoom u, sughra u, hadi u, imran m. effect of maternal anemia on birth weight. j ayub med coll abbottabad. 2011; 23: 77-9. 24. goonewardene m, shehata m, hamad a. anemia in pregnancy. best pract res clin obstet gynaecol. 2012; 26: 324. with non-anemic women. the fetal complications that is low birth weight and apgar <7 at 5 minute has also been found significantly associated with maternal anemia. references 1. khatana a, yadav k. study of fetomaternal outcome in patients of moderate and severe anaemia in > 28 week pregnancy, j med sci clin res. 2017; 5: 25071-6. 2. melku m, addis z, alem m, enawgaw b. prevalence and predictors of maternal anemia during pregnancy in gondar, northwest ethiopia: an institutional based cross-sectional study. anemia. 2014; 7: 771. 3. ghimire rh, ghimire s. maternal and fetal outcome following severe anemia in pregnancy: results from nobel medical college teaching hospital, biratnagar, nepal. j nobel med coll. 2013; 2: 22-6. 4. nair m, choudhury mk, choudhury ss, kakoty sd, sarma uc, webster p, et al. association between maternal anaemia and pregnancy outcomes: a cohort study in assam, india. bmj global health. 2016; 1: e000026. 5. rizwan f, qamarunisa h, memon a. prevalence of anemia in pregnant women and its effects on maternal and fetal morbidity and mortality. pak j med sci. 2010; 26: 92-5. 6. dayal s, dayal a. prevalence & consequences of anemia in pregnancy. int j med res review. 2014; 2: 2969. 7. kalaivani k. use of intravenous iron sucrose for treatment of anemia in pregnancy. the indian j med res. 2013; 138: 16-7 8. ahmad mo, kalsoom u, sughra u, hadi u, imran m. effect of maternal anemia on birth weight. j ayub med coll abbottabad. 2011; 23: 77-9. 9. christian p, shahid f, rizvi a, klemm rd, bhutta za. treatment response to standard of care for severe anemia in pregnant women and effect of multivitamins and enhanced anthelminthic. am j clin nutr. 2009; 89: 853-61. 10. rehu m, punnonen k, ostland v, heinonen s, westerman m, pulkki k, et al. maternal serum hepcidin is low at term and independent of cord blood iron status. eur j haematol. 2010; 85: 345-52. 11. olatunbosun oa, abasiattai am, bassey ea, james rs, ibanga g, morgan a. prevalence of anaemia among pregnant women at booking in the university of uyo teaching hospital, uyo, nigeria. bio med res int. 2014; 8: 849080. 12. singh s, singh s, singh pk. a study to compare the efficacy and safety of intravenous iron sucrose and intramuscular iron sorbitol therapy for anemia during pregnancy. j obstet gynecol india. 2013; 63: 18–21. pregnancy with anemiajiimc 2018 vol. 13, no.2 61 page 13 page 14 page 15 page 16 page 17 original article abstract objective: to identify the influence of problem based learning strategy on the learning styles of final year medical students who have been taught through the student centered teaching curriculum over a period of 5 years. study design: a descriptive study. place and duration of study: the study was conducted at islamic international medical college in april 2013. materials and methods: learning styles of students of final year medical students of riphah international university taught in an integrated student centered curriculum over 5 years of medical school were identified by using the learning style orientation inventory. results: a total of 90 students were recruited in the study, out of which 40 % were males and 60% were females. 51.1% were observational learners, 15.55% were experiential learners, 11.1% were structured learners. the least number of students were discovery (4.44%) and group learners (3.33%). conclusion: our study shows inclination towards group learning in only 8.8% students (both preference and mixed methods) all of which were females. maximum students still preferred to be observational learners who are passive dependent superficial learners and not open to new experiences and analytical thinking. these findings suggest that further research to look for factors that can inculcate deeper learning habits in the students is needed. key words: learning styles, student centered learning, problem based learning, final year medical students. 8,9 students to find solutions. learning is student centered occurring in small groups of 8-10, led by a facilitator. the focus of learning is a problem selected to enhance the curricula and becomes a means to stimulate a learning process. the group meets twice weekly. they attempt to find explanation to phenomena, events or cases, correlating them in the given problem and building up on their previous knowledge. students generate questions and find answers on their own. the solution may be single or multiple and students are given the opportunity to use all possible sources of information. this teaching approach helps students to develop motivation fo r s e l f d i r e c t e d l e a r n i n g , c o l l a b o ra t i o n , communication, problem solving and critical 10,11,12 thinking skills which are important for the training of medical students appropriate to meet the 13 demands of modern medical practice. riphah international university has recently adopted a student centered curriculum in the medical school. they have introduced problem based learning, small group discussions and case based learning as an adjunct to the traditional didactic system of lecturing. this study aims to identify the influence of student centered curriculum with use of problem based learning strategy on individual learning preferences of final year medical students at the end of a 5 year teaching program. there are a number of introduction the challenges faced by doctors in this modern era of medical practice have become diverse. researchers in medical education are becoming increasingly aware of the use of variety of teaching methods that may ultimately improve the retention of ever increasing knowledge along with development of problem solving skills and adaptability to new 1,2,3 situations. teaching methodologies are designed to increase retention of knowledge, enhance integration and application of concepts to the clinical contexts. to achieve expertise in clinical skills, a medical student is required to develop problem solving skills, intrinsic drive to analyze and apply knowledge and develop self directed learning 4 habits. such high order cognition requires students to use a diverse array of learning styles and strategies chosen to suit a certain learning situation. problem based learning has been implemented differently in different medical curricula as adjunct or alternative 5,6,7 to traditional didactic teaching. problem based learning was first introduced at mcmaster university in 1960, using problems or case as stimulants for ------------------------------------------------learning styles of final year mbbs students taught through problem based learning strategy over a period of five years asma shabbir, samiya naeemullah, afsheen zafar, mahwish rabia correspondence: dr. asma shabbir associate professor, pediatrics iimc, pakistan railway hospital, rawalpindi e-mail: asma.shabbir@riphah.edu.pk jiimc 2014 vol. 9, no. 3 learning styles of students taught through pbl 99 varieties of theories and models for measuring learning styles of students. cassidy has mentioned that it is difficult to choose any specific instrument 9 for evaluation of student's learning styles. we have selected the learning style orientation inventory (lsoi) designed by annette j. towler and robert l. 14 dipboye. this instrument defines five different learning styles namely discovery, group learning, experiential learning, structured and observational learning styles. the survey was conducted by using the “learning style orientation measure”. it allows identification of learning preferences in relation to their teaching environment. it consists of a 54 item questionnaire. 14 items are assigned to discovery style, 7 items to group learning, 13 items to experiential learning, 11 items to structured learning and 9 items to observational learning.  discovery learners enjoy a broad range of learning situations like interactional lectures and active reflective activities promoting abstract thought and deal with complex issues.  group learners enjoy group activities with o t h ers en h a n cin g gro u p d yn a mics a n d collaborative learning, stimulating group activities with one on one discussion. each individual takes his own responsibility to learn for the group to work effectively. it is one of the methods of collaborative in depth learning with teaching and learning going on simultaneously among the students.  experiential learners enjoy taking initiative and like to experience practically. they enjoy learning in role plays and simulations and do not feel comfortable with passive learning.  structured learners rely on their own information processing strategies for effective learning to occur. they prefer to impose their own structure of learning in situations.  observational learners are passive learners dependent upon external cues to help them learn. they require concrete direct experiences which are provided and planned by the authorities in the form of didactic lectures, field trips, video films etc. they do not enjoy activities requiring active learning strategies for analytical and logical critical thinking. they are not open to new experiences and do not do well in learning situations that are autonomic and student centered. they are more likely to be dependent superficial learners. materials and methods the undergraduate program of riphah international university is a 5 years bachelor in medicine and surgery. it is implementing an integrated modular system incorporating student centered learning strategies like problem based learning and small group discussions along with traditional didactic teaching. this batch had studied through the modular system in which each module incorporated at least 2 to 3 pbl sessions making a total of 8 to 10 pbl each year over a four year modular teaching program. final year comprised of clerkships in various clinical specialties. this study is a cross sectional survey inducting final year medical students through non-probability convenience sampling who have been taught through the student centered medical curriculum. the information was collected by inducting the final year mbbs students after consent who filled the lsoi proforma. the data was collected, scored, analyzed and interpreted by the researchers. the survey was conducted by using the “learning style orientation measure”. it allows identification of learning preferences in relation to their teaching environment. it consists of a 54 item questionnaire. 14 items are assigned to discovery style, 7 items to group learning, 13 items to experiential learning, 11 items to structured learning and 9 items to observational learning. results out of 90 students, 36 (40%) were males and 54 (60%) were females. maximum number of students were found to be observational learners making a total of 46 (51.1%). these were followed by 14 (15.55%) experiential learners and 10 (11.1%) were structured learners. group and discovery learners were least in number with 3 (3.33%) and 4 (4.44%) each in these groups (table i). among the male students 17 (47.22%) were observational learners and 9 (25%) were experiential learners (table ii). females showed the same pattern with 29 (53.7%) being observational learners and 17 (30.9%) experiential learners. in contrast to male students who had no preference for group learning, only 3(5.5%) preferred group learning. 2 (3.7%) were jiimc 2014 vol. 9, no. 3 100 learning styles of students taught through pbl discovery learners and 5(9.25%) were structured and experiential learners each among females. (table iii) mixed modality learning was identified in 3 (8.3%) males and 10(18.5%) females. dolmans and schmidt, problem based learning enhances the retention, integration and application of knowledge of basic sciences to the clinical sciences along with development of essential skills for problem solving, developing independent study habits and self directed learning, enhancing intrinsic 4,10 interest in the subject. pbl graduates develop a more patient centered approach with better interpersonal skills required for a good doctorpatient relations developing a more humanistic and 15 holistic attitude to medical practice. the results of our study show a predominance of observational learners (51.1%) among the students. the more striking aspect is such a low percentage of group learners i.e., 5.55% as single preference and 9.25% with mixed preference. all group learners were females. problem based learning has time and again been associated with improved in depth learning with development of conceptual understanding, problem solving , critical thinking and self directed 1 6 , 1 7 , 1 8 learning. however, our results show a predominance of observational surface learners after studying in a student centered environment. groves has documented similar results in her study where she has reported a change from deep learning towards a more surface approach over her study 13 period with significant decreases in learning scores. novak et al has also noted an increase in avoidant behavior and decrease in active participation among groups in pharmacy students after going through a 19 pbl curriculum. “stress” has been implicated as an important factor that can result in failure of pbl 20 teaching methods. discomfort between students and facilitators may also be one factor as not only students but facilitators also have to adjust their 19 teaching styles to the new teaching modalities. furthermore, factors like new teaching environment, excessive work load and a robust subject matter in medicine can also be important determinants for 14,21 success of student centered small group learning. medical curricula are content heavy with a lot of pressure to acquire large amount of knowledge. this may trigger the shift towards more superficial learning styles against a more conceptual and time 13 consuming approach. one more aspect that needs to be explored in this context is the type of a s s e s s m e n t u s e d t o a s s e s s c o n c e p t u a l table i: learning styles of all final year students (n= 90) table ii: learning style distribution of male students (n= 36) table iii: learning style distribution of female students (n= 54) discussion problem based learning has turned out to be a widely used educational approach in the last decade. it has been incorporated with the belief that it adds to key attributes to the training of doctors who need to be equipped to meet the demands of modern medical practice. according to barrows and tamblyn and jiimc 2014 vol. 9, no. 3 101 learning styles of students taught through pbl understanding and critical thinking. it is believed that assessment drives learning. if the assessment is not jiimc 2014 vol. 9, no. 3 102 learning styles of students taught through pbl original�article abstract objective: to determine the effectiveness of circuit class versus individual task specific training to improve upper limb functions in post stroke pateints. study design: double blinded randomized controlled trial. st st place and duration of study: this study was carried out from january 1 2016 to december 31 2016 at physiotherapy department fauji foundation hospital peshawar. materials and methods: a total of 60 subjects with post-acute phase of stroke and upper limb impairments were enrolled in this study. the subjects were randomly allocated into two groups, experimental (n=30) treated with circuit based task specific training and control (n=30) treated with individual task specific training. the pateints in both groups were assessed using motor assessment scale at the beginning of treatment and 6 weeks after training program. results: the mean age of pateints was 58 and 59 years in control and experimental group respectively. there were more left hemiplegics as compared to right hemiplegics in both groups. the patients in circuit training group showed better results as compared to the patients in individual task specific training group with respect to upper limb functions, advanced hand activities and hand functions six weeks after treatment. conclusion: post-acute stroke survivors show better results in upper limb functions, advanced hand activities and hand functions with by task specific trainings in circuit groups as compared to individual task specific trainings. key words: circuit class training, motor assessment scale, rehabilitation stroke, task specific training. not regain proper functional use of paretic arm which leads to difficulty in achieving activities of daily life (adls) and proper engagement in 3 community. at 6 months post stroke, about 25-53% of pateints remain dependent at least at one adl task, which often involve use of bilateral or unilateral arm activities . it has been reported that 55% to 75% of patients suffering from stroke have difficulty in 2-3 grasping, holding and manipulating objects . there are different approaches being proposed to improve upper extremity function after stroke such 4 a s f u n c t i o n a l t ra i n i n g , n e u r o fa c i l i t a t i o n 4-7 8-9 techniques and strengthening and reported with mixed results. majority of these studies have small 9 sample sizes with limited generalizable effects. while increase in strength following strength training, especially in chronic stroke reported no 8 indication for functional use of paretic arm. there is now mounting evidence that both motor and functional change in the paretic extremities is a s s o c i a t e d w i t h f o r c e d u s e o f a f f e c t e d 10,11 extremity. indeed cortical re-organization had been demonstrated following task specific training, 12 intensive movement therapy, constraint induced introductions according to w.h.o about 85% of deaths due to 1 stroke occur in middle and low income countries. there is no well designed population based survey on stroke prevalence in pakistan but estimated average incidence rates is 250/100,000, which is 2 higher than incidence rates in western nations. about 70-80% of individuals who sustain stroke have upper extremity impairments and many of them do effectiveness of the circuit class training versus individual task specific training for improving upper limb functions in post-acute stroke patients 1 2 3 rabia basri , gouhar rahman , maryam naseem correspondence: dr. gouhar rahman consultant physiotherapist department of physical rehabilitation agency headquarter hospital, landikotal khyber agency e-mail: goharsaif33@gmail.com 1 department of physical therapy rafsan center of neurological rehabilitation peshawar 2 department of physical rehabilitation agency headquarter hospital, landikotal khyber agency 3 department of zoology peshawar university, peshawar funding source: nil; conflict of interest: nil received: july 18, 2017; revised: oct 28, 2017 accepted: nov 16, 2017 circuit class training versus individual task specific trainingjiimc 2017 vol. 12, no.4 180 10 movement therapy cimt, rhythmic auditory cueing 13 14,15 (batrac) and robotic aided exercise training. task specific training(tst) which is now evident for 16,17 stroke rehabilitation established that positive cortical reorganization occur in human cortex which is driven by activity and repetitive practice of new task, furthermore it had been concluded that recovery of motor function in patients with stroke is best facilitated by intensive and task specific 18 treatment. based on the motor relearning theory, tst emphasizes on repetition of functional task not 16 the isolated movement patterns. observational studies showed that patients receiving treatment after stroke spend large parts of the day inactive and appear to have the presence of therapist to practice all new skills. providing task specific treatment to a group of patients in post stroke in circuit class had been proposed as a new method of increasing amount of time patients spend 19 actively participated in task specific practice circuit class therapy can be defined as the therapy provided to more than 2 pateints involving tailored interventions, with the focus on functional tasks received within the group settings, provided to pateints with similar or different degree of functional abilities and that involves a staff to pateints ratio no 20 more than 1:3. practically this can involve the subjects physically moving among the stations or circuits according to the functional need within the group setting, optimally the stations are targeted at repetitions of e.g. range of motion exercises, electrotherapy sessions, strengthening exercises, 7,8 balance and gait training etc. participants are c o n t i n u o u s l y m o n i t o r e d a n d p r o g r e s s e d 21 accordingly. there are number of benefits associated with circuit training. it is beneficial for the patients and health system as it is cost effective and for therapist as well as time and energy saving treatment model. studies therefore investigated the effects of circuit trainings with the aim to establish it as alternative approach for stoke rehabilitation. interestingly most of studies favored circuit training program over individual training program in improving different functional parameters post stroke. however, most of the circuit based tasks from the published studies were focused on the leg strength, walking speed, distance and balance etc. only few studied circuit class training 18 effects on upper limb functional parameter also results of these studies cannot be generalized to all 6 stroke population due to very small sample size and d u e t o b a s e l i n e d i f f e r e n c e s i n s u b j e c t s characteristics in as those studies as they enrolled pateints with wide range of neurological impairment other than stroke and other baseline differences in groups for evaluating effects of circuit training 19,22 program. the approaches should be utilized to implement circuit trainings as alternative treatment model in stroke setup of peshawar as a evidence based practice. a randomized controlled trail was therefore conducted to examine the effects of circuit based training programs versus individual training on recovery of upper limb functions in post stroke patients. materials and methods a double blinded randomized controlled trail was done in physiotherapy department at fauji foundation hospital peshawar. sixty subjects with post-acute phase stroke and upper limb impairments were enrolled. recruitment method included selfreferred pateints, pateints referred by clinicians or physiotherapist from other hospitals. previous medical charts of the patients were reviewed for duration of hospital stay, diagnosis, side of the brain injury, onset of stroke and patients were evaluated for the eligibility criteria i.e., stroke with unilateral motor deficits, patients between 3-8 months of stroke, age 45-65years, able to participate in group and >1 grade on manual muscle testing (mmt) for upper limb including hand, <2 on ashworth scale of spasticity at the affected upper extremity. the exclusion criteria included, poor cognition, patients previously received physiotherapy, medically non stable patients, patients with pain in upper limb ;>3 on visual analogue scale, history of significant psychiatric illness, patients having moderate to severe visual impairments. the ethical approval was taken from fauji foundation hospital peshawar. the informed consent was based on helsinki ethical 22 considerations. in this program evaluation, each therapy model, delivered for 1.5hour/day, 5week for 6 weeks. both group received standard physiotherapy treatment, one group at individual level and another group in a circuit's class. jiimc 2017 vol. 12, no.4 181 circuit class training versus individual task specific training individual task specific training: patients participated in a total 1.5hour/day for 6 weeks with the 1:1 patient to therapist ratio. activities performed number of repetitions, time on task and progressions of those activities were determined individually by treating therapist. circuit class training: patients participated in the 1.5hour/day of physiotherapy session with >1:1 patients to therapist ratio. the whole study consisted up-to 5:1 patients to therapist ratio. the circuits were divided up-to 3specific stations (figure 1), 15-20 minutes on each circuit as tailored to patients activity level. in station 3 electrical stimulation for wrist extensor provided to those patients reported wrist extension less than 20 degrees ( frequency, 100hz: 150micro-second with on time 10 seconds and off time 10 seconds ramp 1s and treatment time 10-15 minutes). each exercise session had a brief warm up and cools down period for 5 minutes in which subjects performed upper extremity stretches and active and assisted range of motion exercises. these exercises were specific to pateints as directed by physiotherapist. any adverse symptom e.g. pain, fatigue etc. were reported to therapist. progression: each functional activity was progressed such that the level of difficulty, complexity and repetition numbers matched to each individual's ability. it was ensured that pateints were performing tasks with sufficient challenge. the overall rehabilitation goals were made independently to conduct of study. outcome measure: the outcome measures were three subscales of the motor assessment scale mas (1 upper arm functions, 2) hand movements and 3) advanced hand activities). mas developed by carr et al. to evaluate functional ability skills after stroke. it uses a 9 point ordinal scale. this instrument has revealed high test re test consistency(r=0.98), interrater reliability(r=0.95) with high construct validity (0.88). this instrument can be used to document 24 motor recovery at any stage of stroke. non-parametrical test was used for the statistical analysis because it was convenience sampling, using spss version 19. man-whitney u test was used to examine between group differences for baseline and final treatment scores. results the means and standard deviations were calculated for descriptive parameters of study given in the table i. there were no statistically significant differences between groups for age, stroke onset, gender, length of hospital stay and hemi-paretic side as p< 0.05. in both groups the number of left hemiplegics was more as compare to right hemiplegics. in both groups the attendance rate was 100% for 6 week training program and all subjects were able to perform the exercise plane as prescribed by experienced physiotherapist. 19,23 fig 1: table i: subjects characteris�cs at baseline lhp= le� hemiparesis rhp= right hemiparesis lohs=length of hospital stay sd= standard devia�on jiimc 2017 vol. 12, no.4 182 circuit class training versus individual task specific training table ii indicates that there was no statistical significant difference at baseline between groups for upper limb functions (ulf), hand movements (hm) and for advanced hand activities (aha) as p value was >0.05. the association of post treatment scores showed that there was major variations in the experimental group for study parameters as p value was <0.05. the group a indicates control group that received individual task specific training and group 2 indicates experimental group (circuit class training) in tables below. the mean rank for upper arm function of individual task specific training itst and circuit class training cct group were 25 and 35, respectively (p=0.01), hand movement for itst and ct were 20 and 40 (p=0.00). the statistical analysis shows that circuit group was 10% more effective to individual group on upper limb functions, 20 more effective on hand movements and 12% more effective on advanced hand activities. circuit class training is potentially cost effective to health care system by decreasing therapist to pateints ratios. thirdly, circuit class training consists of peer support and social interactions that may 18 enhance compliance to exercise programs. the present study indicates that circuit class training for 4 week durations promoted a significant improvement in upper limb functions of stroke pateints. the more significant effects for functional improvement in circuit group can be due to many reasons including the maximum repetition of activity, social interactions of pateints and less inactive time duration in such circuits. if the circuit trainings are able to prevent the inactive time durations and associated secondary complications, it would presumably lead to health cost saving in long run. the health care system is therefore promoting the community based rehabilitation programs. the results of present study are consistent with studies 26 done by blennernshesset et al and pang et al. and they also concluded for better effectiveness of circuit class training on upper limb functions post stroke. 6 the pilot study conducted by dean et al concluded the significant effects of circuit training on upper limb functional group. these studies examined and compared the improvement of upper limb with lower limb functional improvement that is the control group practiced the mobility task while the experimental group practiced the upper limb tasks. it is well known fact that recovery after stroke is immediate in lower limb as compare to upper limb which recovers slow comparatively due to nature of 27 blood supply of brain the baseline similarities of the groups cannot be excluded in phenomena called generalizability. study limitations and future recommendations: small sample size was one of the limitations of this trial. the trial was conducted on post-acute stroke patients and the result of this study cannot be implemented on chronic stroke subjects. future studies therefore needed to have larger sample size with extensive assessment tools to consider diversity in functional abilities of upper limb. also there is need to divide stroke subjects with subgroups with different impairment level so the results would be generalizable to stroke population. conclusion this study suggests that circuit based task specific table ii= baseline and post-treatment analysis between groups discussion a number of systematic reviews have suggested that task based intense treatment should be the top 25 priority for stroke patients functional recovery. the recent studies emerged with an approach that task based training can be organized into circuit with series of work stations. circuit class training stratifies at-least 3 key features of efficient and effective training. first by utilizing different work stations, circuit class training allows patients to extensively practice training in a meaningful and progressive way. second circuit class training is efficient use of therapist time in which pateints actively engaged in practice when compared to individual training. the ulf=upper limb func�ons hm=hand movements ahc= advanced hand ac�vi�es cct= circuit class training itst= individual task specific training b= before treatment a=a�er treatment jiimc 2017 vol. 12, no.4 183 circuit class training versus individual task specific training training is more effective as compared to individual task specific training for improving functional parameters of upper limb among post-acute stroke patients. references 1. pang my, eng jj, dawson as, mckay ha, harris je. a community-based fitness and mobility exercise program for older adults with chronic stroke: a randomized, controlled trial. journal of the american geriatrics society. 2005; 53: 1667-74. 2. cunningham p, turton aj, van 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controlled trial. australian journal of physiotherapy. 2004; 50: 219-24. 27. barnes mp, dobkin bh, bogousslavsky j. recovery after stroke: cambridge university press. 2005. 184 circuit class training versus individual task specific training page 20 page 21 page 22 page 23 page 24 original�article abstract objective: this study aimed to determine the association of premature ventricular contractions burden of less than 20% with nt-pro bnp levels in patients with preserved left ventricular function. study design: case control analytical study. place and duration of study: it was conducted in physiology department of islamic international medical th college (iimc) in collaboration with armed forces institute of cardiology (afic) during the period of 18 april th 2016 to 20 march 2018. materials and methods: the study comprised a total of fifty participants which included 40 diagnosed patients of premature ventricular contractions (pvcs) and 10 healthy subjects (with no pvcs). pvcs burden was calculated by holter monitoring report and echocardiography was done to determine left ventricular ejection fraction. patients with burden>20% and ejection fraction<50% were excluded. in all these patients nt-probnp levels were measured and statistical analysis was done using spss version 25. student's t-test and pearson correlation tests were applied to see its association with pvcs burden. results: ventricular ectopic burden<20% has nt-probnp higher than controls but the increase is insignificant with p value of 0.056. pearson correlation test showed no correlation of premature ventricular contractions <20% with nt-pro bnp levels with r value of 0.1. conclusion: it can be concluded that the patients with pvcs burden less than 20% has no correlation with ntpro bnp so they should not be considered as high risk patients. key words: cardiomyopathy, nt-probnp, pvcs, pvcs burden, ventricular ectopy. activates the blocked area after ventricular recovery, 4 resulting in an ectopic beat. in the triggered activity, the preceding action potential produce after depolarizations which results in ectopic beat. automaticity points to presence of an ectopic focus of pacemaker cells in the ventricle with sub threshold potential for firing. basic rhythm of heart raises these 3,1 cells to potential resulting in an extra beat. frequent ventricular ectopic beats have a high risk of 5 developing dilated type cardiomyopathy. rapid pacing due to pvcs results in lv dyssynchrony resulting in lv dilatation and ultimately reduced 6 ejection fraction. during this process changes in neurohormonal pathway occurs which bring about 7 release of bioactive peptides. probnp splits into bnp (32 amino acid) and n-terminal probnp (76 amino acid). probnp is mainly synthesized and secreted by cardiac myocytes in response to myocardial wall 8 stretch. nt-probnp levels are found to be raised in patients of left ventricular dysfunction and 9 ventricular dilatation. in comparison of diagnostic significance of bnp with nt-probnp, for left ventricular dysfunction, both are equivalent, but in 10,9 some groups nt-probnp is found to be superior. introduction ventricular ectopy or premature ventricular contraction is defined as an extra heartbeat, originating from the ventricles and comes before the 1 normal heart beat. premature ventricular contractions (pvcs) is common with an estimated 2 prevalence of 1% to 4% in the general population. the mechanisms for ventricular ectopy production 3 include re-entry, triggered activity and automaticity. occurrence of re-entry takes place due to presence of one way block and an area of slow conduction. during ventricular activation slow conduction area association of n-terminal pro brain natriuretic peptide with ventricular ectopy 1 2 3 shazadi ambreen , humaira fayyaz , azmat hayyat correspondence: dr. shazadi ambreen demonstrator department of physiology islamic international medical college riphah international university, islamabad e-mail: shazadiambreen@hotmail.com 1,2 department of physiology islamic international medical college riphah international university, islamabad 3 department of electrophysiology armed forces institute of cardiology, rawalpindi funding source: nil; conflict of interest: nil received: august 10, 2018; revised: february 26, 2020 accepted: february 29, 2020 association of nt pro bnp with ventricular ectopy jiimc 2020 vol. 15, no.1 19 pvcs were long considered benign until they were found to be associated with risk of developing pvcs 11 induced cardiomyopathy. high pvcs burden is associated with development of cardiomyopathy but sometimes high burden patients do not develop cardiomyopathy and patients with the burden of 4% can develop cardiomyopathy. currently no risk profile defines a group of patients at high risk of pvcs 12 induced cardiomyopathy. role of nt-probnp as a biochemical marker to predict cardiomyopathy needs to be studied. this study aimed to determine the association of moderate ventricular ectopic burden (less than 20%) with n-terminal probnp levels in patients with preserved left ventricular function, thus assessing it's importance as a determinant to stratify high risk patients. materials and methods a case control study was conducted in physiology department of islamic international medical college rawalpindi, in collaboration with electrophysiology department of armed forces institute of cardiology th th (afic) from 18 april 2016 to 20 march 2018 after approval from ethical review committee (erc). a total of 50 patients were taken among which 40 were diagnosed patients of premature ventricular contractions with pvcs burden≤20%. patients were diagnosed on 24 hours holter monitoring report and their pvcs burden was calculated by dividing total number of pvcs by total analyzed beats in 24 hours. echocardiography was done in all the patients to assess their heart status. inclusion criteria were specified as, age between 18-60 years, lv ejection fraction less than 50% and patients with pvcs burden less than 20. patients with pvcs burden >20% and ejection fraction <50% were excluded from the study. patients out of age range of 18-60 years were excluded from the study. ten age matched healthy subjects with no pvcs were taken as controls. in all these patients, venipuncture technique was used to collect the blood sample. nt-probnp levels were measured in all blood samples using elisa kit and statistical analysis was done by using spss version 25. data was normally distributed so parametric tests were applied. pearson correlation test was applied to determine the correlation of nt-probnp with moderate pvcs burden (burden<20%) and student's t-test was applied to compare mean nt-probnp levels of pvcs patients with control subjects (having no pvcs). results baseline characteristics are shown in table i which shows 47±6 years as the mean age of the pvcs patients. among the total of 40 patients 18 were females and 22 were males. table i: baseline characteris�cs of par�cipants fig 1: comparison of mean nt-pro bnp in pvc’s pa�ents and controls figure 1 mean nt-probnp levels in pvcs patients are 0.86±0.47ng and in control group 0.74±0.49ng which shows that nt-probnp levels are high in pvcs as compared to controls but the increase is insignificant with p value of 0.56.p value ≤0.05 was considered to be significant. table ii shows correlation of pvcs burden <20% with nt-probnp. pearson correlation test was applied and r value of 0.1 shows no correlation of ventricular ectopic burden < 20% with n-terminal pro bnp levels. jiimc 2020 vol. 15, no.1 20 association of nt pro bnp with ventricular ectopy discussion the current study was aimed to evaluate the association of nt-probnp with pvcs burden less than 20% in patients with preserved lv function left (left ventricular ejection fraction <50%). levels of nt-pro bnp were not significantly raised in pvcs patients as compared to control groups. hence the results suggest no correlation of nt-probnp with pvcs burden less than 20%. a study by skranes et al, illustrates the association of n-terminal pro bnp with pvcs which contradicts the present study findings. the contradiction may be due to the reason that current study is done on patients with pvcs burden less than 20% while that study was done on frequent pvcs (pvcs>24%) patients. that study also differed from the current study as it was 13 done in community based population. in another study conducted on animals (dogs), nt-probnp and interleukin 6 (il-6) were measured in all pvcs burden (25%, 33% and 50%). in all these pvcs burden of 25%, 33% and 50%, pvcs induced cardiomyopathy (lvef<50%) was present among 11.1%, 44% and 100% of animals but no increase in nt-probnp or il 6 14 was observed in any of these burdens. this finding is in line with present study. another study aimed to identify the risk factors shows that the individuals with low socioeconomic s t a t u s , i n c r e a s e d w a i s t h i p r a t i o , b o d y height>median and sokolow-lyon index have higher frequency of pvcs. at the same time the study demonstrates that the patients with higher ntp ro b n p l e ve l s h ave f re q u e nt p vc s ( p vc s 15 burden>24%). but the present study showed no association of nt-pro bnp with pvcs which could be due to the fact that present study determined the nt-probnp levels in patients of mild to moderate pvc burden (pvcs<20%) rather than frequent pvcs 15 burden. sajadieh et al conducted a study on middle aged and elderly patients which demonstrates that in the absence of any known cardiac disease, the ntprobnp levels are higher in patients with frequent 16 pvcs as compared to those with no pvcs. in present study myocardial wall stress was not measured as this facility was not available in the center. conclusion it is concluded from the present study that ntprobnp levels are not raised in pvcs patients with burden of less than 20% as well as no correlation of nt-probnp is found with pvcs in burden of less than 20%. thus declining its importance as a determinant to stratify the patients at high risk references 1. antzelevitch c, burashnikov a. overview of basic m e c h a n i s m s o f c a r d i a c a r r h y t h m i a . c a r d i a c electrophysiology clinics. 2011. 2. cha ym, lee gk, klarich kw, grogan m. premature ventricular contraction-induced cardiomyopathy: a treatable condition. circ arrhythmia electrophysiol. 2012; 5(1):229–36. 3. gaztañaga l, marchlinski fe, betensky bp. mechanisms of cardiac arrhythmias. rev española cardiol (english ed [internet]. 2012; 65(2):174–85. 4. tse g. mechanisms of cardiac arrhythmias. j arrhythmia [internet]. 2016; 32(2):75–81. 5. yalin k, gölcük e. frequent premature ventricular contractions and cardiomyopathy, chicken and egg situation. j atr fibrillation. 2017; 10(2):1–5. 6. marchlinski fe, tschabrunn cm. premature ventricular complex–induced cardiomyopathy: providing insights on the pathogenesis*. j am coll cardiol. 2018; 72(23):2883–5. 7. gopinathannair r, etheridge sp, marchlinski fe, spinale fg, lakkireddy d, olshansky b. arrhy thmia-induced cardiomyopathies mechanisms, recognition, and management. j am coll cardiol. 2015; 66(15):1714–28. 8. weber m, hamm c. role of b-type natriuretic peptide (bnp) and nt-probnp in clinical routine. heart. 2006; 92(6):843–9. 9. bay m, kirk v, parner j, hassager c, nielsen h, krogsgaard k, et al. nt-probnp: a new diagnostic screening tool to differentiate between patients with normal and reduced left ventricular systolic function. heart [internet]. 2003; 89(2):150–4. 10. hall c. essential biochemistry and physiology of (nt-pro) bnp. eur j heart fail. 2004; 6(3):257–60. 11. o'quinn mp, mazzella aj, kumar p. approach to management of premature ventricular contractions. curr treat options cardiovasc med. 2019; 21(10). 12. al-khatib sm, stevenson wg, ackerman mj, bryant wj, callans dj, curtis ab, et al. 2017 aha/acc/hrs guideline for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: a report of the american college of cardiology/american heart association task force on clinical practice guidelines and the heart rhythm society. hear rhythm. 2018; 15(10):e73–189. table ii: correla�on of ventricular ectopic burden <20% with nt-probnp levels r is pearson correla�on coefficient p value<0.05 was considered to be significant. jiimc 2020 vol. 15, no.1 21 ectopy association of nt pro bnp with ventricular ectopy 13. skranes jb, einvik g, namtvedt sk, randby a, hrubos-strøm h, brynildsen j, et al. biomarkers of cardiovascular injury and stress are associated with increased frequency of ventricular ectopy: a population-based study. bmc cardiovasc disord [internet]. 2016;16(1):233. 14. schey kl, luther jm, rose kl. hhs public access. 2016; 13(3):1–21. 15. von rotz m, aeschbacher s, bossard m, schoen t, blum s, schneider s, et al. risk factors for premature ventricular contractions in young and healthy adults. heart. 2017; 103(9):702–7. 16. sajadieh a, nielsen ow, rasmussen v, ole hein h, hansen jf. increased ventricular ectopic activity in relation to creactive protein, and nt-pro-brain natriuretic peptide in subjects with no apparent heart disease. pace pacing clin electrophysiol. 2006; 29(11):1188–94. jiimc 2020 vol. 15, no.1 22 association of nt pro bnp with ventricular ectopy original�article abstract objective: to determine the efficacy of chlorhexidine 4 % versus dry cord in neonatal cord care to prevent infections and reducing healing time in a hospital setting. study design: randomized controlled trial. place and duration of study: at department of paediatrics cantonment general hospital, rawalpindi from 1 december 2016 to 30 november 2017. materials and methods: total 200 newborns were divided into two groups by randomization using lottery method; group a comprising of 100 newborns were applied with chlorhexidine 4% on umbilical cord, once a day for a week and group b 100 newborns were advised conventional dry cord care. they were called for follow up visit after 1 week and later contacted telephonically till the separation of umbilical cord. newborns with delayed healing or any signs of infection were called again for follow up examination. the day of separation of umbilical cord and signs of infection were recorded for each neonate. results: the mean duration of separation and healing of umbilical cord in group a (chlorhexidine 4%) and group b (dry cord care) was 8.35±3.73 and 6.98±2.59 days respectively. the difference in healing and duration of separation of umbilical cord in two groups was statistically significant (p= 0.003). signs of infection observed in group a and group b were 5% and 4% respectively. hence statistically insignificant (p=0.73). conclusion: the umbilical cord care with 4% chlorhexidine or conventional dry method has similar results in terms of frequency of infection in a hospital setting. however healing time in terms of mean duration of separation of umbilical cord is prolonged with the application of 4% chlorhexidine to the cord stump. key words: chlorhexidine 4 %, dry cord care, newborn, umbilical cord care. substances to umbilical cord like ash, oil, lead based compounds (surma) and rarely cow dung are being 3 practiced in rural areas of pakistan. even in urban areas like karachi, 74 % mothers were applying various substances to the cord stump like mustard oil, coconut oil, butter and turmeric in a study 7 conducted by gul s et al. approaches that reduce chances of neonatal infections include hand washing, skin cleansing with antiseptics such as chlorhexidine, use of clean birth kits and early 3 breastfeeding. according to a new recommendation for umbilical cord care issued by who in january 2014, for newborns who are born at home in high mortality settings, chlorhexidine 4% should be applied to the cord stump daily for 1 week. for newborns who are born in hospital or at home in low neonatal mortality setting, clean dry cord care is 8 r e c o m m e n d e d . d r y c o r d c a r e w a s t h e recommendation of who in 1998 but in 2016 researchers working on chlorhexidine found that mothers were fond of applying one or the other 9 substance on the cord stump. these traditional practices led to the development of who introduction among deaths noted in children younger than 5 1 years, neonatal deaths account for more than 40%. in high mortality settings, about half of neonatal deaths are caused by infections involving sepsis, 2 pneumonia, meningitis and tetanus neonatorum. in 3 pakistan 30% of neonatal deaths are due to sepsis. such a high rate of mortality needs to be addressed by certain cost effective interventions like use of topical antiseptics that limit the growth of bacteria 4 around the umbilical stump. one of the important causes of neonatal mortality is 5 omphalitis. any delay in separation of umbilical cord increases the chances of infection as it is ideal for 6 bacterial colonization. application of harmful comparison of umbilical cord care: chlorhexidine 4% versus dry cord care noshina riaz, rida tahir, sidra tul muntaha, shahid aziz, rubina zulfqar correspondence: dr. noshina riaz department of paediatrics yusra medical and dental college, islamabad e-mail:noshi_17@hotmail.com department of paediatrics yusra medical and dental college, islamabad funding source: nil; conflict of interest: nil received: july 07, 2018; revised: january 25, 2019 accepted: february 26, 2019 chlorhexidine versus dry cord carejiimc 2019 vol. 14, no.1 8 on umbilical cord , once a day for one week and group b 100 newborns were advised conventional dry cord care. they were called for follow up visit after 1 week and later contacted telephonically till the separation of umbilical cord. newborns with delayed healing or any signs of infection were called again for follow up examination. the duration of separation of umbilical cord and signs of infection were recorded for each neonate. enrolled subjects completed this study. signs of infection were further categorized into mild (redness, swelling or pus restricted to the cord stump), moderate (redness, swelling or pus extending to the skin at the base of the cord stump less than 2 cm) and severe (inflammation extending more than 2 cm from the cord stump, with or without 3 pus). data were analyzed using spss version 23. frequency and percentage were calculated for categorical variables like gender whereas mean and standard deviation were calculated for numerical variables. categorical comparisons were made using the chi square test. numerical comparisons like mean duration of separation of umbilical cord was made using independent samples t-test. a p value < 0.05 was considered statistically significant. results the study population included 106 (53%) male and 94 (47%) female babies. group a included 27 (41.54%) male and 38(58.4%) female babies. group b included 34 (52.3%) male and 31(47.7%) female newborns. gestational age, weight and mode of delivery in both groups are shown in table i. more late preterm were enrolled in group a than group b i.e. 66.7% versus 33.3%.low birth weight neonates were 66.7% in group b while 33.3% in group a. more neonates delivered by svd i.e. 80.4% in group b while 61.8% by caesarean section in group a. these differences had no statistically significant effect on frequency of infection and umbilical cord extraction time. the mean duration of separation and healing of umbilical cord in group a and group b was 8.35±3.73 and 6.98±2.59 days respectively. the difference in healing and duration of separation of umbilical cord in two groups was statistically significant (p= 0.003) as shown in table ii. infection observed in group a and group b was 5% and 4% respectively. hence statistically insignificant (p=0.73) as shown in table recommendation of using chlorhexidine gel instead 8 of applying harmful substances to the cord stump. regarding safety profile of chlorhexidine , it is generally safe and is extensively used in medical settings since 1950. only few side effects like contact sensitivity, dermatitis, urticaria and photosensitivity have been reported. percutaneous absorption of chlorhexidine when used as a body wash or for cord care has no reported side effects .however this absorption is more likely to occur when used on 10 premature and underweight neonates. a high quality evidence suggests that chlorhexidine cord care in the community setting reduces 50% chances 11 of omphalitis. a metanalysis revealing the efficacy of chlorhexidine 4% in reducing the risk of omphalitis, concludes a reduction of 27 to 56% compared to dry cord care. however the protection 12 is most fruitful in the 1st week of life. who recommends dry cord care as a suitable method, t h o u g h s e v e r a l s t u d i e s s u p p o r t t h i s 6 recommendation. still this method is controversial. two african trials conducted at tanzania and zambia failed to show superiority of chlorhexidine over dry 8 cord care. there is much controversy over the umbilical cord separation time as some studies favor chlorhexidine while others show dry cord care to be more effective in reducing umbilical cord extraction 13,14,15,16 time. other than one community based study , none of such study is found in a hospital setting in pakistan. this study was planned to determine the effectiveness of chlorhexidine 4 % in comparison to dry cord care in hospital setting. also to compare the extraction time of umbilical cord in both groups and risk of possible omphalitis. materials and methods this randomized controlled trial was conducted at department of paediatrics cantonment general hospital, rawalpindi from 1 december 2016 to 30 november 2017 with non-probability consecutive sampling technique. all babies delivered in cantonment general hospital were included in study. any sick newborn that required admission to hospital was not included in the study. informed written consent was taken from parents. gestational age, gender, weight and mode of delivery were noted. all newborn were randomized based on lottery method into two groups. group a comprising of 100 newborns were applied with chlorhexidine 4% 9 chlorhexidine versus dry cord carejiimc 2019 vol. 14, no.1 chlorhexidine group and 5.9 ±1.5 days in dry cord care group that is statistically insignificant but contrary to our results as it was prolonged in 3 chlorhexidine group. a community based study was conducted in bangladesh to assess the effect of cord cleansing with chlorhexidine 4% on neonatal mortality. it was found to be lower in neonates who received single application of 4% chlorhexidine in comparison with dry cord care. there was no effect of application of chlorhexidine for a week to reduce neonatal mortality. however there was a significant difference of serious cord infection in this group 1 versus dry cord care . this finding is again contrary to our results. moreover mortality risk was not assessed in our study. a cochrane review published in july 2004 included 21 hospital studies. the conclusion of the review stated that topical application of various agents to the cord was not superior to dry cord care in terms of systemic 17 infections as found in our study. a study conducted in india compared the effectiveness of chlorhexidine with dry cord care and results showed the superiority of chlorhexidine over dry cord care. the mean time to cord separation was 8.92±2.77 days (shorter) in former group and 10.31±3.23 days in latter. this is in contrast to our findings as it was vice versa. however no difference was noted in terms of umbilical sepsis 18 as in our study. a meta-analysis published by bhutta et al showed the effect of umbilical cord cleansing with chlorhexidine versus dry cord care on omphalitis and neonatal mortality in community settings in developing countries. three trials were included that were done in nepal, pakistan and bangladesh. in pakistan trial there was no difference in the time of separation of cord. however, nepal and bangladesh trial showed longer separation time in c h l o r h ex i d i n e g ro u p ( 1 . 0 8 a n d 2 . 4 1 d ays respectively) compared to dry cord care group, 19 consistent with our results. khairuzzaman et al in bangladesh found that chlorhexidine reduces the risk of mild omphalitis with single application of chlorhexidine and moderate omphalitis both in single and multiple chlorhexidine cleansing group as compared to dry cord care group. none of the neonates developed severe infection in their study. this is in contrast to our study as both groups had similar frequency of mild infection and only 1% developed moderate infection in chlorhexidine iii. mild infections were seen in 4% babies in both groups . moderate infection was found in only 1 baby in group a. none of the neonate developed severe infection in both groups. table i: gesta�onal age, weight and mode of delivery in group a and b (n=200) table ii: days of separa�on of umbilical cord in group a and group b (n=200) table iii: frequency of infec�on in group a and group b (n=200) discussion the present study shows that there was no significant difference between chlorhexidine 4 % and dry cord care group regarding signs of infection in a hospital setting. however duration of separation of umbilical cord was prolonged by application of chlorhexidine to the cord stump. this did not have an effect on the frequency of infection in both groups. in a community based study conducted in a rural district of pakistan, topical application of chlorhexidine 4% reduced the incidence of omphalitis by 42% in comparison with the dry cord care. this finding is contrary to our results as no difference was observed between the two groups. the mean cord separation time was 6.2±1.3 days in 10 chlorhexidine versus dry cord carejiimc 2019 vol. 14, no.1 6. golshan m, hossein n. impact of ethanol, dry care and human milk on the time for umbilical cord separation. j pak med assoc 2013; 63:1117-19. 7. gul s, khalil r, yousafzai mt, shoukat f. newborn care knowledge and practices among mothers attending pediatric outpatient clinic of a hospital in karachi, pakistan. int j health sci (qassim) 2014;8(2):167–75. 8. who recommendations on postnatal care of the mother a n d n e w b o r n . g e n e v a : w o r l d h e a l t h o r g a n i z a t i o n ; 2 0 1 3 o c t . a v a i l a b l e : www.healthynewbornnetwork.org/bitstream/10665/976 03/1/9789241506649_eng.pdf 9. chlorhexidine working group (cwg) 2016. 7.1% chlorhexidine digluconate for umbilical cord care: introduction and scale up. accessed 26 september 2016.available: www.coregroup.org/.../core webinar 10. mullany lc, darmstadt gl, tielsch jm. safety and impact of chlorhexidine antisepsis interventions for improving neonatal health in developing countries. pediatr infect dis j. 2006; 25:665–75. 11. sinha a, sazawal s, pradhan a, ramji s, opiyo n. chlorhexidine skin or cord care for prevention of mortality and infections in neonates. cochrane database of systematic reviews 2015; (3):cd007835. 12. imdad a, mullany lc, baqui ah, arifeen se, tielsch jm, khatry sk, et al . the effect of umbilical cord cleansing with chlorhexidine on omphalitis and neonatal mortality in community settings in developing countries: a metaanalysis.bmc public health. 2013. 13. kapellen tm, gebauer cm, brosteanu o, labitzke b, vogtmann c, kiess w, et al. higher rate of cord-related adverse events in neonates with dry umbilical cord care compared to chlorhexidine powder. results of a randomized controlled study to compare efficacy and safety of chlorhexidine powder versus dry care in umbilical cord care of the newborn. neonatology 2009; 96:13-8. 14. mullany lc, darmstadt gl, khatry sk, leclerq sc, katz j, tielsch jm, et al. impact of umbilical cord cleansing with 4.0% chlorhexidine on time to cord separation among newborns in southern nepal: a cluster-randomized, community-based trial. pediatrics 2006; 118:1864-71. 15. abbaszadeh f, hajizadeh z, jahangiri m. comparing the impact of topical application of human milk and chlorhexidine on cord separation time in newborns. pak j med sci 2016; 32:239-43. 16. mullany lc, shah r, arifeen se, mannan i, winch pj, hill a, et al. chlorhexidine cleansing of the umbilical cord and separation time: a cluster-randomized trial. pediatrics 2013; 131:708-15. 17. karumbi j,mulaku m, aluvaala j, english m ,opiyo n. topical umbilical cord care for prevention of infection and neonatal mortality. pediatr infect dis j. 2013; 32(1): 78–83. 18. gathwala g, sharma d, bhakhri bk. effect of topical application of chlorhexidine for umbilical cord care in comparison with conventional dry cord care on the risk of neonatal sepsis: a randomized controlled trial.j trop pediatr. 2013; 59(3):209-13. 19. giridhar l, sambasiva rr, lakshmi g, swamy kb. umbilical cord care practices among the newborns of gadaba and group. however severe category of infection was not 20 found in both groups similar to the above study. a study conducted in gadaba and konda dora tribes for umbilical cord care practices showed that 96% of gadaba and 95.3% of konda dora newborns were applied with oils or ash of vegetative origin and also 19 different powders. our study also revealed the fact that despite of proper counselling regarding cord care, mothers used to apply different substances like oil, spirit, pyodine, onion and powder to the cord stump. current study supports the who recommendation of preference of dry cord care in low neonatal mortality settings. dry cord care is simple, cheap and cost effective. limitation of our study is that actual practice of hand washing cannot be monitored in both groups. further studies are required to prove the efficacy of chlorhexidine 4 % in hospital settings. conclusion the umbilical cord care with 4% chlorhexidine or conventional dry method has similar results in terms of frequency of infection in a hospital setting. however healing time in terms of mean duration of separation of umbilical cord is prolonged with the application of 4% chlorhexidine to the cord stump. references 1. arifeen se, mullany lc, shah r, mannan i, rahman sm, talukder mrr et al. the effect of cord cleansing with chlorhexidine on neonatal mortality in rural bangladesh: a community-based, cluster-randomised trial. lancet 2012; 379(9820):1022-8. 2. mitra dk, mullany lc, harrison m, mannan i, shah r, begum n, et al; projahnmo study group in bangladesh. incidence and risk factors of neonatal infections in a rural bangladeshi population: a community-based prospective study. j health popul nutr. 2018; 37(1):6. 3. soofi s, cousens s, imdad a,bhutta n, ali n, bhutta za . topical application of chlorhexidine to neonatal umbilical cords for prevention of omphalitis and neonatal mortality in a rural district of pakistan: a community-based, clusterrandomised trial. lancet. 2012; 379(9820):1029–36. 4. liu l, johnson hl, cousens s, perin j, scott s, lawn je, et al. global, regional, and national causes of child mortality: an updated systematic analysis for 2010 with time trends since 2000. lancet 2012; 379(12):2151–61. 5. okpaleke mh. using 7.1% chlorhexidine gel for umbilical cord care: implication for whorecommendation for a standard cord care practice. asian journal of research in medical and pharmaceutical sciences 2017; 1(2):1-6. 11 chlorhexidine versus dry cord carejiimc 2019 vol. 14, no.1 cord for prevention of umbilical infection: a hospital based study in bangladesh. bangladesh j child health 2018; 42 (1): 4-8. konda dora tribes. indian journal of maternal and child health.2011; 13(4). 20. khairuzzaman md, rouf ma, sarker mma, hossain i, matin a, mowla g et al. chlorhexidine cleansing of the umbilical 12 chlorhexidine versus dry cord carejiimc 2019 vol. 14, no.1 original�article abstract objective: to compare the effectiveness of oral intermittent isotretinoin treatment vs daily isotretinoin therapy in patients with moderate to severe acne vulgaris. study design: randomized controlled trial. st th place and duration of study: the study was conducted for 06 months (1 march to 30 august 2021) at department of dermatology, pakistan railway hospital, rawalpindi. materials and methods: a total of 100 patients with moderate to severe acne selected through random sampling were divided into two groups a & b, each having 50 patients. in group a, a daily dose of 0.5-0.75mg/kg of oral isotretinoin was given only for 01 week, every 4th week for 04 months. group b patients were given the same dose of oral isotretinoin once daily regularly for 04 months. the clinical improvement was measured as difference in gags score calculated before and after the treatment using global acne grading system (gags). the results were compared & analysed by using paired t-test. results: the age, weight, and gags scores of the patients in both groups were comparable at the baseline. the gags score at baseline was 29.94 + 4.42 in group a, while in group b, the score was 29.84 + 4.69. after 04 months of treatment, the difference in gags from baseline in group a was 17.44 + 4.07 in group a compared to 19.09 + 5.02 in group b. the p value of 0.006 was significant to prove the association of results. conclusion: the oral intermittent isotretinoin therapy is more effective than daily continuous isotretinoin therapy in patients with moderate to severe acne vulgaris. key words: acne vulgaris, global acne grading system, isotretinoin. hyperkeratinisation and later invasion of the follicle by the propionibacterium acnes are the key 3 underlying factors. acne vulgaris has serious impact on affected individuals with negative effects on selfesteem, social isolation and cosmetic disfigurement 4 by causing permanent facial scarring. there are multiple treatment options available which can be used alone or in various combinations. these include topical agents like salicylic acid, benzoyl peroxide, antibiotics, and retinoids. among the systemic therapy, there are tetracycline, 5 macrolides, clindamycin, and isotretinoin. the sensitivity of various antibiotics has decreased over the last two decades, and oral isotretinoin has 6 emerged as a treatment of choice. it is fda approved and its efficacy is well established in a conventional dose of 0·5–1·0 mg/kg per day for a period of 4 to 8 months, reaching to a cumulative 7 dose of 120 mg/kg. however, at this dose it is frequently associated with many side effects like dryness of skin, cracked lips chapped lips, 8 hyperlipidaemia, and elevated liver enzymes. introduction one of the most frequently occurring skin disorders, mainly affecting adolescents is acne vulgaris, with 1 the prevalence of 87% worldwide. it varies among 2 countries and different ethnic groups. the pathophysiology of this disease is multifactorial, an intense inflammatory process involving the pilosebaceous units with altered androgen activity at puberty, enhanced sebum production, follicular effectiveness of oral intermittent vs oral continuous isotretinoin therapy in patients with moderate to severe acne vulgaris; a randomized controlled trial 1 2 3 lubna rani faysal , riffat iqbal , bilqees fatima correspondence: dr.lubna rani faysal hod dermatology islamic international medical college, riphah international university islamabad e-mail: lubna.rani@riphah.edu.pk 1 department of dermatology islamic international medical college, riphah international university islamabad 2 department of dermatology aimc jinnah hospital, lahore 3 department of dermatology fmdc fauji foundation hospital, rawalpindi funding source: nil; conflict of interest: nil received: october 21, 2021; revised: march 01, 2022 accepted: march 07, 2022 oral intermittent isotretinoin therapy in acne vulgaris jiimc 2022 vol. 17, no.1 14 the efficacy of low dose isotretinoin is well established through a number of clinical trials with better clinical outcome, good safety profile, and cost9 ,10 effectiveness in moderately severe acne vulgaris. an intermittent regimen with low dose oral isotretinoin has gained popularity over last decade but there is lack of literature on comparative studies with different regimens of intermittent oral 11 isotretinoin in south asia. the objective of this study was to assess the effectiveness of intermittent isotretinoin therapy in comparison to continuous daily isotretinoin therapy in our population. materials and methods this randomized controlled trial was carried at department of dermatology, pakistan railway hospital, affiliated with islamic international medical college. the duration of study was 06 months. a sample of 100 patients (50 in each group a & b) was calculated with 95% confidence interval and 80% power using the open-source calculator, open epi version 3, after approval from the ethical review committee (ref no. riphah/iimc/irc/21/51). a strict inclusion criterion was applied, all the patients selected in the study had gags > 19 (below 19 = mild acne) and the age limit of >12 years was followed. the married females, patients who had any topical or oral anti-acne medication 04 weeks prior to study were not enrolled in the study. the patients using medication for any other systemic illness were also excluded. after informed verbal consent, the patients in group a were given oral intermittent th isotretinoin, once daily for 01 week, every 4 week for 04 months. patients in group b were given continuous isotretinoin once daily for 04 months regularly. the clinical improvement was measured as difference in gags score calculated before (at baseline) and after the treatment (at the end of 04 months) using global acne grading system (gags). a standard proforma was used to record the personal profile, weight (to calculate dose of the drug), dose of isotretinoin, gags scores, liver enzymes & fasting triglyceride level. the treatment side effects like dry chapped lips, dry skin, elevated triglycerides, and liver enzyme were also recorded at baseline, 01, 02 and 04 months of treatment. the data was entered and analysed in spss version 21. mean reduction in gags score was compared in both groups by using paired t-test as the data was parametric. results out of 100 total patients, with 50 patients in each group, only one patient in group a was dropped due to raised triglycerides and transaminases. the mean age of participants in group a was 19.8 + 3.09 years and in group b was 19.86 +3.23 years with mean weight of 59.14 + 12.35 kg in group a and 57.54 + 9.12 kg in group b. the gender distribution in both groups is shown in figure 1. the mean gags score at the baseline was 29.94 + 4.42 in group a and 29.84 + 4.69 in group b. the gags score at 01, 02, and 04 months after the treatment with p-values comparison is given in table 1. the overall decrease in the gags scores were 17.44 + 4.07 in group a and 19.09 + 5.02 in group b with the p value of 0.006, table 1. most frequent side effects were dry skin and dry lips, reported by more patients in group b compared to group a, table ii. fig:1 gender distribution in both groups table i: global acne grading system score (gags score) 15 oral intermittent isotretinoin therapy in acne vulgaris jiimc 2022 vol. 17, no.1 table ii: side effects of treatment continued for a period of 6 months. the gags score was calculated in all the groups before and 6 months after the completion of treatment. the results suggested the better efficacy of low dose isotretinoin in both continuous & intermittent regimens over the 15 high dose therapy. the sample size was less as compared to our study, but the outcome was comparable to our results regarding better efficacy of intermittent low dose therapy over conventional treatment regimen. in a study conducted by faghihi g et al., low-dose isotretinoin was compared with standard dose in 60 patients with moderately severe acne. there were two treatment groups, one received the regular dose of isotretinoin (0.5 mg/kg/day) and the other received low-dose isotretinoin (0.25 mg/kg/day), for a period of 06 months. the results were noted at 6 months and at 12 months after the completion of treatment. the improvement in acne score was more in low dose group and the most frequent side effects like xerosis cutis & loss of hair were 17% in the lowdose group vs 33.2% in the conventional dose group. the results are similar to our study in terms of outcome & lower incidence of side effects in the low 16 dose isotretinoin group. the difference was of continuous vs intermittent dosing schedules, but the common thing was effectiveness of low dose either given as a continuous dose or as intermittent dosing schedule. the opposite findings were noted in a 17 study conducted in india. it was a comparative trial on a sample of 100 patients, with 50 in each group a & b. group a was given isotretinoin at a low dose of 20 mg once daily for 4 months while group b was given the same dose but in intermittent regimen, once daily for 1 week out of every 4 weeks. the outcome was improvement in the global acne grading system (gags) score at 6 months in both groups. the study suggested that low-dose continuous treatment is most suitable for patients with moderate to severe acne vulgaris. the difference in the findings may be due to the reason that we calculated the dose according to the weight of patients in both groups which seems more appropriate & logical, while sethi et al. used a fixed dose of 20 mg /day irrespective of the weights of the patients in both groups. mandekou-lefaki et al., in 2003, conducted a comparative study on patients with different severity discussion in this study, intermittent isotretinoin regimen was found more effective with few & less severe side effects. at 04-month, acne severity was decreased, as measured by gags score, from 29.94 + 4.42 to 17.44 + 4.07 in intermittent isotretinoin regimen group compared to daily isotretinoin regimen group where gags score decreased from 29.84 + 4.69 to 19.09 + 5.02. this difference was significant with pvalue of 0.006. the concept of oral intermittent isotretinoin 12 treatment is not new. the comparative trials are lacking, except for few comparative studies there are mostly single group trials. goulden et al. used the intermittent regimen in patients with moderately 13 severe acne in 1997. the efficacy of oral intermittent isotretinoin therapy was later confirmed by kaymak et al. in 2006. the study included all three categories of mild, moderate & severe acne patients. the results were promising in all the patients but a comparative group was 14 missing. in another randomized controlled trial, conducted by lee et al., in 2011, the conventional therapy of isotretinoin was compared with low doses continuous & intermittent therapy. a total of 60 patients were divided into 3 groups; in group a, the isotretinoin daily dose was 0.5–0.7 mg/kg/day, in group b the daily dose was 0.25–0.4 mg/kg/day, and the group c took the intermittent regimen at the dose of 0.5–0.7 mg/kg/day for 7 days followed by a 3weeks break in every month. the treatment 16 oral intermittent isotretinoin therapy in acne vulgaris jiimc 2022 vol. 17, no.1 of acne, using conventional therapy @ 0.5–1.0 mg/kg/day in one group & a low dose regimen @ 0.15–0.40 mg/kg/day in the other group, up to cumulative dosage of 120 mg/kg. there were total of 64 patients divided into 2 groups. the low doses were effective in terms of clinical improvement, safety profile & better effect on scars. the conventional therapy was having added advantage 18 of less recurrences. although it was given in continuous regimen but here again the low dose was equally effective as compared to the conventional dose. in another multicentre study by akman et al, 66 patients with moderate to severe acne were enrolled into 03 treatment groups, two groups with intermittent unconventional dose in different regimen and one group with conventional dose for 19 06 months. the group 1 received isotretinoin for the first 10 days of each month, group 2 received each day in the first month, afterwards the first 10 days of each month for 5 months and for group 3 it was daily dose for 6 months. the dosage was 0.5 mg/kg/day in all groups. the follow-up was done for 12 months. there were statistically no significant differences in the outcome among all the treatment groups in patients with moderate acne, except for the significant difference in patients with severe acne, between group 1 and group 3. the conclusion was same as our study, intermittent isotretinoin treatment is an effective alternative in the management of moderate acne with a lower incidence of side effects. in another study with patients of moderately severe acne vulgaris, a fixed daily dose of 20 mg of isotretinoin was given to half of the patients while the remaining half were treated with the alternate dose regimen for 24 weeks. both the regimens were well tolerated by the patients but the alternate day regimen was more effective in treatment of 20 moderate acne. there are many studies in favor of low dose intermittent isotretinoin as an effective treatment for moderate acne vulgaris, and the results of our study are also consistent with efficacy of intermittent, low dose regimen with few & less severe side effects. conclusion the oral intermittent isotretinoin therapy is more effective as compared to continuous daily isotretinoin therapy in patients with moderate to severe acne vulgaris. references 1. bhate k, williams hc. epidemiology of acne vulgaris. british journal of dermatology. 2013 mar;168(3):474-85. 2. bagatin e, timpano dl, guadanhim lr, nogueira vm, terzian lr, steiner d, florez m. acne vulgaris: prevalence and clinical forms in adolescents from são paulo, brazil. anais brasileiros de dermatologia. 2014 may; 89:428-35. 3. tanghetti ea. the role of inflammation in the pathology of acne. journal of clinical and aesthetic dermatology. matrix medical communications; 2013;(06):27-35. 4. vilar gn, dos santos la, filho jfs. quality of life, self-esteem and psychosocial factors in adolescents with acne vulgaris. an bras dermatol. 2015;90(5):622–9. 5. tan au, schlosser bj, paller as. a review of diagnosis and treatment of acne in adult female patients . international j o u r n a l o f wo m e n ' s d e r m ato l o g y. e l s ev i e r i n c ; 2018;(04):56–71. 6. l a y t o n a . t h e u s e o f i s o t r e t i n o i n i n a c n e . dermatoendocrinol . 2009;1(3):162. 7. bagatin e, costa cs, rocha ma, picosse fr, kamamoto cs, pirmez r, ianhez m, miot ha. consensus on the use of oral is o t ret in o in in d ermato lo gyb ra z ilia n so ciet y o f dermatology. anais brasileiros de dermatologia. 2021 mar 24; 95:19-38. 8. bettoli v, guerra-tapia a, herane mi, piquero-martín j. challenges and solutions in oral isotretinoin in acne: reflections on 35 years of experience. clinical, cosmetic and investigational dermatology. 2019; 12:943. 9. amichai b, shemer a, grunwald mh. low-dose isotretinoin in the treatment of acne vulgaris. j am acad dermatol. 2006;54(4):644–6. 10. sardana k, garg vk, sehgal vn, mahajan s, bhushan p. efficacy of fixed low-dose isotretinoin (20 mg, alternate days) with topical clindamycin gel in moderately severe acne v u l ga r i s . j e u r a c a d d e r m a t o l ve n e re o l . 2 0 0 9 may;23(5):556–60. 11. dhaked dr, meena rs, maheshwari a, agarwal us, purohit s. a randomized comparative trial of two low-dose oral isotretinoin regimens in moderate to severe acne vulgaris. indian dermatology online journal. 2016 sep;7(5):378. 12. torzecka jd, dziankowska-bartkowiak b, gerlicz-kowalczuk z, wozniacka a. the use of isotretinoin in low doses and unconventional treatment regimens in different types of acne: a literature review. advances in dermatology and allergology. 2017 feb;34(1):1. 13. goulden v, clark sm, mcgeown c, cunliffe wj. treatment of acne with intermittent isotretinoin. british journal of dermatology. 1997 jul;137(1):106-8. 14. kaymak y, illter n. the effectiveness of intermittent isotretinoin treatment in mild or moderate acne. j eur acad dermatology venereol. 2006;20(10):1256–60. 15. lee jw, yoo kh, park ky, han ty, li k, seo sj, et al. effectiveness of conventional, low-dose and intermittent oral isotretinoin in the treatment of acne: a randomized, 17 oral intermittent isotretinoin therapy in acne vulgaris jiimc 2022 vol. 17, no.1 c o n t r o l l e d c o m p a ra t i v e s t u d y. b r j d e r m a t o l . 2011;164(6):1369–75. 16. faghihi g, mokhtari f, fard nm, motamedi n, hosseini sm. comparing the efficacy of low dose and conventional dose of oral isotretinoin in treatment of moderate and severe acne vulgaris. journal of research in pharmacy practice. 2017 oct;6(4):233. 17. shetti sa, nagesh hn, hanumantharaya n. a randomized, open-label, comparative study of efficacy of low-dose continuous versus low-dose intermittent oral isotretinoin therapy in moderate-to-severe acne vulgaris. national journal of physiology, pharmacy and pharmacology. 2017;7(9):941-6. 18. mandekou-lefaki i, delli f, teknetzis a, euthimiadou r, karakatsanis g. low-dose schema of isotretinoin in acne vulgaris. international journal of clinical pharmacology research. 2003 jan 1;23(2-3):41-6. 19. akman a, durusoy c, senturk m, koc ck, soyturk d, alpsoy e. treatment of acne with intermittent and conventional isotretinoin: a randomized, controlled multicenter study. a r c h i v e s o f d e r m a t o l o g i c a l r e s e a r c h . 2 0 0 7 dec;299(10):467. 20. dhaked dr, meena rs, maheshwari a, agarwal us, purohit s. a randomized comparative trial of two low-dose oral isotretinoin regimens in moderate to severe acne vulgaris. indian dermatology online journal. 2016 sep;7(5):378. 18 oral intermittent isotretinoin therapy in acne vulgaris jiimc 2022 vol. 17, no.1 conflict of interest authors declared no conflicts of interest. grant support and financial disclosure authors have declared no specific grant for this research from any funding agency in public, commercial or nonprofit sector. data sharing statment the data that support the findings of this study are available from the corresponding author upon request. this is an open access article distributed under the terms of the creative commons attributionnoncommercial 2.0 generic license. original�article abstract objective: to find the frequency of hyperandrogenism and hirsutism in females with polycystic ovary syndrome. study design: descriptive case series. th place and duration of study: department of gynaecology and obstetrics nishtar hospital multan from 21 th october 2016 to 9 april 2017. materials and methods: eighty polycystic ovary syndrome patients with in reproductive age group (15 – 49 18 years) were included in the study through non probability consecutive sampling technique. hirsutism was examined by fg scoring system and the assessment of hyperandrogenism was by measurement of serum testosterone levels. spss 23.2 was used for data analysis. frequency and percentage was calculated for categorical variables like hirsutism, hyperandrogenism mean and standard deviation was calculated for quantitative variables like age, bmi, height , weight, serum levels of fsh, lh, and testosterone. t test was applied to check the statistical significance. effect modifiers and confounders like age, height, weight and bmi were controlled by stratification of data. post stratification chi square test was used to check effect modification. p value < 0.05 was taken as significant. results: among total 80 patients, the mean age of the patients was 28.93±8.24 years. only one (0.5%) patient in our study group had normal weight, 21 (27.4%) women were overweight and remaining 58 (72.1%) patients were obese. the mean fsh, lh and testosterone levels were 6.62±5.3 iu/l, 14.01±7.65 iu/l and 65.13±23.75 ng/dl respectively. total of 34 (43.7%) patients had hyperandrogenism. a total of 59.5% (n=48) patients had hirsutism (fg score >8). among 34 patients with hyperandrogenism, 57.8% (n=20) had hirsutism and out of 46 patients without hyperandrogenism 60.7% (n=28) had hirsutism; this difference was not statistically significant; p=0.685. conclusion: the observations of our study concluded that a significant numbers of patients with pcos had hyperandrogenism and there was no difference in the number of patients with hirsutism between hyper androgenic and non-hyper androgenic pcos patients. key words: ferriman gallweyscoring, hirsutism, hyperandrogenism, polycystic ovary syndrome. which was given immediately after joint consensus between eshre and asrm (european society for human reproduction and embryology and american society for human reproduction) in rotterdam in 1 2003. two out of following three criteria must be fulfilled for pcos definition; anovulation or oligo, hyperandrogenism (clinical or biochemical elevation of testosterone), and polycystic ovaries assessment especially by using ultrasound (ovarian volume 2 >10ml). clinical sign and symptoms of pcos include irregular menstrual cycle, obesity, hirsutism and sub fertility 3 or infertility. out of these clinical manifestations, hirsutism appearance is observed obviously with hyperandrogenism and metabolic abnormalities of pcos. the dominating percentage of hirsutism in females with polycystic ovary syndrome is 73.9%.but introduction polycystic ovary syndrome (pcos) is considered to be the one of the commonest endocrine impairment with unknown etiology in women of different reproductive ages. the condition was also explained 1 by stein and leventhal in 1935. the new criteria for defining pcos is referred as rotterdam criteria, frequency of hyperandrogenism in females with polycystic ovary syndrome 1 2 3 sumera mehnaz, rahat akhtar, nadia taj correspondence: dr. sumera mehnaz pac hospital kamra e-mail:umair_ali363@yahoo.com 1 department of obstetrics & gynaecology pac hospital kamra 2,3 department of obstetrics & gynaecology nishtar medical university, multan funding source: nil; conflict of interest: nil received: dec 1, 2017; revised: sep 15, 2018; accepted: sept 19, 2018 hyperandrogensim in pcosjiimc 2018 vol. 13, no.3 112 syndrome who had met the inclusion criteria of our study were selected, who were also going for proper examination to the department of obstetrics & gynecology, nishtar hospital multan. informed consent was taken from all the patients one by one. the complete history and thorough clinical examination was conducted for assessment of different features of pcos and to easily exclude other causes of hirsutism. biochemical work was done to record fsh, lh and serum testosterone level on the second day of regular menstrual cycle as well as on any day when the irregular menstrual cycle take place. normal values of levels of all these hormones were also present on performa report on which biochemical work was recorded. assessment of abdominopelvic ultrasound for polycystic ovary was done by ovarian volume >10ml and was used to rule out any tumor of ovary and adrenal gland. the patients who were fulfilling specific inclusion criteria of hirsutism and pcos were examined by fg scoring system. if total core was >8 then it was considered as diagnosis of hirsutism. data was analyzed by spss version 23.2. frequency and percentage was calculated for categorical variables like hirsutism and hyperandrogenism, mean and standard deviation was calculated for quantitative variables like age, bmi, height, weight, serum levels of fsh, lh, and testosterone, t test was applied to check the statistical significance. effect modifiers and confounders like age, height, weight and bmi were controlled by stratification of data and post stratification chi square test was use to check effect modification. p value < 0.05 was taken as significant. results a total number of 80 female patients were included in this study. only one (0.5%) patient in our study group had normal weight, 21 (27.4%) women were overweight and remaining 58 (72.1%) patients were obese. the mean age, bmi, height and weight of patients were 28.93±8.24 years, 32.44±4.25 bmi, 157.3 ±6.6 cm and 79.98±8.43 kg (table i). the mean serum fsh, lh and testosterone level of patients w e r e 6 . 6 2 ± 5 . 3 1 i u / l , 1 4 . 0 1 ± 7 . 6 5 i u / l and65.13±23.75 ng/dl respectively (table ii). the main outcome variables of this study were hyperandrogenism and hirsutism. among all p a t i e n t s o f p c o s 4 4 % w e r e f o u n d w i t h a n o t h e r s t u d y s h o w s f r e q u e n c y o f 4 hyperandrogenism in pcos is 38%. abnormal growth of terminal hair especially androgen dependent pattern, is seen in females that 5 are suffering from hirsutism. the involving sites are 1 chest, face, lower abdomen, crural areas and areola. in some of the severe cases lower back, shoulder, upper arm and upper abdomen are also involved in abnormal hair growth. it is very common disorder that has a bad affect on 5-15% females of reproductive life. in 1961 ferriman-gallwey (fg) scoring system was given to diagnose this hirsutism 6 ratio in female population. in conditions like, congenital adrenal hyperplasia, androgen secreting tumors and cushing syndrome, there is always a direct relationship and association present between 7 serum level of testosterone and hirsutism. however no sure and definite association has yet been found between serum testosterone level and hirsutism in 8 pcos. in such type of cases alpha reductase activity, h e r i t a b i l i t y, s o c i o e c o n o m i c , d i e t a r y a n d environmental features are considered to be 9 responsible for hirsutism. the frequency ratio of pcos patients with hyperandrogenism and hirsutism have not been studied locally. the aim of this study is to calculate frequency of hyperandrogenism and association of hirsutism with hyperandrogenism in females especially with pcos. our study will provide local reference for future research and management g u i d e l i n e s f o r p a t i e n t s o f p c o s a n d hyperandrogenism with hirsutism. materials and methods with the ethical approval from the ethical committee of the institution this descriptive case series was conducted. the study was conducted th th over six months from 21 october 2016 to 9 april 2017. sample size was calculated with who sample size calculator using following data level of significance = 5%, confidence level = 95%, sample size n = 80 patients. patients were included using non probability consecutive sampling technique. other causes of hirsutism, congenital adrenal hyperplasia, cushing's syndrome, hyperprolactinemia, androgen secreting tumors were excluded from study. a specially designed performa that had a complete demography of the patient to record all finding points of this study. eighty cases of polycystic ovary jiimc 2018 vol. 13, no.3 113 hyperandrogensim in pcos discussion total and free circulating dehydroepiandrosterone sulfate (dheas) and testosterone levels are mostly above from normal in 50–75% women who are suffering from pcos, the free testosterone (ft) circulating in blood is considered as the one of the very important predictive marker of pcos in 60% 10 pcos patients who were with increased level.in this study, we have proposed to know the, free testosterone (ft), dheas, and prevalence of elevated testosterone in free and combined form as well, in the large cohort of patients suffering from pcos. by using of this information, we will be able to examine and calculate the utility of nonspecific standards in the evaluation of hyperandrogenemia especially present in pcos and sensitivity of elevated serum hormone. from this evidence we can conclude that the hyperandrogenism is remained as very important part of pcos and rotterdam criteria hyperandrogenism and 56% had normal levels (fig. 1). total of 59.5% (n=48) patients had hirsutism. among 34 patients with hyperandrogenism, 57.8% (n=20) had hirsutism and out of 46 patients without hyperandrogenism 60.7% (n= 28) had hirsutism; this difference was not statistically significant; p=0.685(table iii). hence there was no difference in the number of patients with hirsutism between hyper androgenic and non-hyper androgenic pcos patients. when the patients were categorized into different age, bmi, height and weight categories, it was noted that majority of patients i.e. 56.25% (n=45) were falling in the age group 36-49 years and 43.75% (n=35) were aged from 15-35 years. 42.6 %( n=34) patients have bmi ranging from 36-40, 36.28% (n=29) patient have bmi from 25-35 and 21.26% (n=17) having bmi from 41-49. similarly, 48.76 % (n=39) patients have height range from 140-150c, 31.27% (n= 25) patients have height range from 163173cm and 2.05% (n=16) patients have height range from 151-162 cm. 68.78% (n=55) have weight ranging from 60-90 kg and 31.27% (n=25) have weight ranging from 91-120 kg (table i). table i: demographics parameters of pa�ents table ii: distribu�on of serum level of different hormones in study pa�ents fig 1: hyperandrogenism in study group table iii: comparison of hirsu�sm and hyperandrogenism jiimc 2018 vol. 13, no.3 114 hyperandrogensim in pcos syndrome (pcos) and 85 healthy were in control group belonging from the south-eastern region of turkey. this shows that hirsutism incidence was lower in hyper androgenic pcos patients comparative to nonhyperandrogenic pcos patients. opposite to it another study designed in europe indicates the direct correlation between hirsutism and hyperandrogenism in the females suffering from pcos. however the present day study does not show a n y s i g n i f i c a n t r e l a t i o n s h i p b e t w e e n hyperandrogenism and hirsutism in females suffering from pcos. in our study the mean age of group was 28.93±8.24 years but in the study by demir et al the mean age was younger i.e. 25.0 ±4.4 years. it indicates that in our study the late presentation of females suffering w i t h p c o s m ay b e d u e to d i ffe re n c e i n socioeconomic and environmental factors of both areas...72.1% women were obese with bmi > 30and 27.4 % women were overweight in our study, however in the study by demir et al 19.5 % women were obese and 16.1% women were overweight. similar to our study however opposite to demir et al, in 2004 in united states another study was launched, in which 60% women suffering from pcos were obese, at that time in common adult population about double the rate was observed. according to the study by demir et al the mean testosterone level was 69.5±23ng/dl but in our study the mean testosterone level was 65.13±23.75 ng/dl. a meta-analysis has been done on 3464 patients suffering from pcos and 37% of patients have been found with elevation of serum tt level, comparing it with a previous study by turkey in which 62% of patients had elevated serum tt level. in recent study 43.7% patients show hyperandrogenism. it is different from turkey study but similar to a metaanalysis. it might be possible that the socioeconomic factors as well as the ethnic heterogeneity of people suffering from hirsutism have different levels of serum total testosterone. the very important key to find pcos is hyperandrogenism and it also help to determine the severity of pcos as well as. among women suffering from pcos the incidence of hirsutism is different in different woman and it shows to depend upon two factors that is the degree of distribution of hairs on body and each woman's 17 sensitivity to the pattern of body hair. the 11 includes this in major symptoms of pcos. in one of the very common endocrine disorder, nearly 7% women in their reproductive age are affected by the excess amount of androgen. by the exclusion of specific endocrine disorder of excess androgen .i.e. non-classic adrenal hyperplasia (ncah). androgen-secreting neoplasm and hyper androgenic insulinresistant acanthuses nigerians syndrome, pcos is mostly diagnosed in majority of f e m a l e s w h o w e r e s u f f e r i n g f r o m 3 hyperandrogenism. by the exclusion, we have got a result that pcos is one of those problems about which it is very difficult to enlist some standards. both the biochemical as well as clinical manifestation of hyperandrogenism 12 had been observed in women suffering from pcos. one of the important clinical evidences of hyperandrogenism is male-pattern hair loss, hirsutism and acne but in this study we have just explained only one manifestation that is hirsutism of hyperandrogenism. the elevated and accurate signs of clinical hyperandrogenism and hirsutism 3 might be subjected to individual observer biases . the diagnosis of pcos could be more difficult within 13 the ethnic variability. however, contrary to the past trends and methods to make some suitable standards for diagnosing the pcos, in present time the hyperandrogenemia and elevated hormone levels are considered to be the standards to diagnosis the pcos the hormonal 14 evaluation of pcos. most of the past studies had normative standards based mostly on small sample 15 size of control patients. the previous studies show hirsutism scores and level of androgen, but these studies are unable to demonstrate the relation between severity of hyperandrogenism and clinical hirsutism. coskun et al. reported that elevated hirsutism and level of androgen in the patients and control subjects from the mediterranean region of turkey, suggesting these people of this region mostly have much hair on body with high density. but their study is unable to find out the relationship between hirsutism score and androgen level. demir et al conducted a study to find the severity of hirsutism in the patients suffering from pcos and its relationship with total testosterone (tt) serum levels in 87 patients suffering from polycystic ovary jiimc 2018 vol. 13, no.3 115 hyperandrogensim in pcos hyper androgenic and non-hyper androgenic pcos patients. references 1. goodman nf, cobin rh, futterweit w, glueck js, legro rs, c a r m i n a e . a m e r i c a n a s s o c i a t i o n o f c l i n i c a l endocrinologists, american college of endocrinology, and androgen excess and pcos society disease state clinical review: guide to the best practices in the evaluation and treatment of polycystic ovary syndrome-part 1. endo pract. 2015;21(11):1291300. 2. pasquali r, zanotti l, fanelli f, mezzullo m, fazzini a, morselli labate am et al. defining hyperandrogenism in women with polycystic ovary syndrome: a challenging perspective. j clin endo & metabol. 20161;101(5):2013-22. 3. goodman nf, cobin rh, futterweit w, glueck js, legro rs, c a r m i n a e . a m e r i c a n a s s o c i a t i o n o f c l i n i c a l endocrinologists, american college of endocrinology, and androgen excess and pcos society disease state clinical review: guide to the best practices in the evaluation and treatment of polycystic ovary syndrome-part 2. endo pract. 2015;21(12):1415-26. 4. legro rs, arslanian sa, ehrmann da, hoeger km, murad mh, pasquali r et al. diagnosis and treatment of polycystic ovary syndrome: an endocrine society clinical practice guideline.j clin endo & metabol. 20131;98(12):4565-92. 5. menon m, ramachandran v. antithyroid peroxidase antibodies in women with polycystic ovary syndrome. j obstet and gynecol india. 20171;67(1):61-5. 6. palomba s, de wilde ma, falbo a, koster mp, la sala gb, fauser bc. pregnancy complications in women with polycystic ovar y syndrome. hum repro update. 201527;21(5):575-92. 7. foroozanfard f, talebi m, samimi m, mehrabi s, badehnoosh b, jamilian m et al. effect of two different doses of vitamin d supplementation on metabolic profiles of insulin-resistant patients with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial. horm and metabol rese 2017;49(08):612-7. 8. caldwell as, middleton lj, jimenez m, desai r, mcmahon ac, allan cm et al. characterization of reproductive, metabolic, and endocrine features of polycystic ovary syndrome in female hyperandrogenic mouse models. endocrinol. 20141;155(8):3146-59. 9. sadrzadeh s, painter rc, lambalk cb. developmental origins of polycystic ovary syndrome (pcos), a case control study comparing birth weight in women with pcos and control group. gynecol endocrinol.20162;32(10):856-9. 10. livadas s, pappas c, karachalios a, marinakis e, tolia n, d r a ko u m e t a l . p r e v a l e n c e a n d i m p a c t o f hyperandrogenemia in 1,218 women with polycystic ovary syndrome. endo.2014;47(2):631-8. 11. conway g, dewailly d, diamanti-kandarakis e. the polycystic ovary syndrome. a position statement from the european society of endocrinology. repro endocrinol. 2015;25:32-52.. 12. pinola p, puukka k, piltonen tt, puurunen j, vanky e, sundström-poromaa i et al. normo-and hyperandrogenic evaluation of hirsutism scores and androgen level has been done by many previous studies; however a r e l a t i o n s h i p b e t w e e n t h e s e v e r i t y o f hyperandrogenism and clinical hirsutism has not been explained clearly. deugarte et al. concluded that most of the time the diagnosis of hirsutism depends on the perception as well as mentality of patient instead of total mfg score of patients. different studies provide different incidence of hirsutism in patients suffering from pcos.some population groups have been evaluated in which rates ranging from nearly 17% and 100%. an incidence of hirsutism of 87% has been observed by the turkish study using the fg scoring system, forcing the authors to report that large amount of body hair is the hallmark of women living in the mediterranean region. the present study indicates that fg scores of ≥ 8 were present in the 60% of 190 pcos patients. this is lesser than coskun et al., who studied a same ethnic population with comparing social and geographical characters and might be correlated to the ethnic. hirsutism was present almost in 15% of control group in the study from demir et al, which is very contrasting and different to past reported rates of 4.6 – 10% in the general population. the increased rate of hirsutism in the common population of the demir study is according to past studies explaining much higher body density of body hair in the 18 mediterranean region and asia as well. all the local studies based on local population are deficient of suitable knowledge and data. therefore due to lack of proper statistical data regarding this in all local studies, we are unable to find the exact magnitude of pcos present in our country. there are some barriers in our study like a single hospital is not enough for the representation of whole population and limited subjects are available. we need large multicentre case control trials to estimate hyperandrogenism and its relationship with hirsutism in females suffering from pcos. to understand this important thing of association between severity of hirsutism and serum level of testosterone must be studied. conclusion the observations of our study conclude that a significant numbers of patients with pcos had hyperandrogenism and there was no difference in the number of patients with hirsutism between jiimc 2018 vol. 13, no.3 116 hyperandrogensim in pcos strategies for the treatment of polycystic ovary syndrome (pcos) women: the role of myoinositol (mi) and d-chiroinositol (dci) between diet and therapy. polycystic ovary syndrome (pcos): clinical aspects, potential complications and dietary management. hauppauge, ny: nova science publishers. 2016. 17. clark nm, podolski aj, brooks ed, chizen dr, pierson ra, lehotay dc et al. prevalence of polycystic ovary syndrome phenotypes using updated criteria for polycystic ovarian morphology: an assessment of over 100 consecutive women self-reporting features of polycystic ovary syndrome. repro sci.2014;21(8):1034-43. 18. kelley ce, brown aj, diehl am, setji tl. review of nonalcoholic fatty liver disease in women with polycystic ovary syndrome. world j gastroenterol. 2014; 20(39): 14172. women with polycystic ovary syndrome exhibit an adverse metabolic profile through life. fertil and steril. 2017; 107(3): 788-95. 13. moran c, arriaga m, arechavaleta-velasco f, moran s. adrenal androgen excess and body mass index in polycystic ovary syndrome. j clin endocrinol & metabol. 2015; 100(3): 942-50. 14. ezeh u, yildiz bo, azziz r. referral bias in defining the phenotype and prevalence of obesity in polycystic ovary syndrome.j clin endocrinol & metabol.2013;98(6):108896. 15. joham ae, teede hj, ranasinha s, zoungas s, boyle j. prevalence of infertility and use of fertility treatment in women with polycystic ovary syndrome: data from a large community-based cohort study. j women's health. 2015;24(4):299-307. 16. porcaro g, bizzarri m, monastra g, filati p, unfer v. jiimc 2018 vol. 13, no.3 117 hyperandrogensim in pcos original�article abstract objective: the purpose of this in vitro study was to investigate variations in the root canal morphology of mesiobuccal root of maxillary first permanent molars in local population of rawalpindi and islamabad. study design: descriptive cross sectional study. st place and duration of study: the study was conducted from 1 january to 30th june 2017 at islamic international dental hospital (iidh), riphah international university, pakistan. materials and methods: mesiobuccal root of eighty two maxillary first permanent molar teeth collected from islamabad and rawalpindi were analyzed using the clearing technique. convenience sampling technique was used. data was analyzed by using spss version 24. descriptive statistics were used. frequency and percentages were calculated for types of canal configuration. results: the frequency of a single canal orifices in the mesiobuccal root of maxillary first molar was 48.7% (type i, iii, v and others), that with two canal orifices was 50% (type ii, iv, vi and others), whereas with three canal orifices was 1.23% . conclusion: according to the results of this study, a second canal is common occurrence in local population of rawalpindi and islamabad. the distribution of canal configurations of our population differs from other populations suggesting ethnic/racial divergence. key words: canal configuration, maxillary first molar, second mesiobuccal canal. 1,8 treatment and insufficient apical seal. all these factors can decrease the prognosis of the 9 endodontic treatment. morphologically, maxillary permanent first molar is 10,14 one of the tooth with most variations. current literature highlights that the most common variation in permanent maxillary first molars is the presence of 1,3 second canal in the mesio-buccal root [mb2]. the frequency of second mesio-buccal canal in caucasian population was found to lie between 2815,16 62%. the frequency of the second canal is 17,20 reported to be higher in the asiatic population. weine et al reported presence of two root canals in mesio-buccal root of maxillary first molar teeth in 13 54% cases of the japanese sub-population. factors contributing to the variation of morphology are 20 21,23 24,26 ethnic/racial background, age and gender of the population. there is a paucity of research in this area in pakistani population, which is limited to one study that was carried out in turner dental school, manchester. the study found that the prevalence of mb2, in 33 extracted teeth collected from punjab dental 18 hospital lahore, were 53%. considering this the objective of the study was to determine the root introduction the principal aim of carrying out endodontic treatment is to shape and clean all the pulpal spaces, 1,2,3 thoroughly. root canal morphology of the teeth is 4,5 often very complex and extremely variable. false presupposition regarding root canal morphology of tooth leads to inaccurate diagnosis, inappropriate debridement, ledge formation and instrument 6 , 7 separation during endodontic treatment. subsequently, it results in an inadequate root canal root canal configuration of the mesio-buccal root of maxillary first permanent molars in local population 1 2 3 4 mansoor khan , rana muhammad ahmad khan , muhammad qasim javed , alia ahmed correspondence: dr. muhammad qasim javed assistant professor department of conservative dental sciences and endodontics qassim university, saudi arabia e-mail: qasim_javed83@yahoo.com 1 department of operative dentistry foundation university college of dentistry, rawalpindi 2 department of operative dentistry pakistan institute of medical sciences, islamabad 3 department of conservative dental sciences and endodontics qassim university, saudi arabia 4 department of operative dentistry islamic international medical and dental college, riphah international university, islamabad funding source: nil; conflict of interest: nil received: march 29, 2018; revised: september 14, 2018 accepted: october 15, 2018 mesio-buccal root canal configuration of maxillary first molarjiimc 2018 vol. 13, no.4 210 canal configuration of the mesio-buccal root of permanent maxillary first molars by utilizing clearing 10 technique on extracted teeth collected from dental hospitals in rawalpindi and islamabad. this knowledge will contribute to the sparse statistics in pakistan and will be valuable in the clinical training of pakistani dental students. materials and methods current descriptive cross-sectional study was carried out at islamic international dental hospital, riphah st th international university from 1 january to 30 june 2017. convenience sampling technique was used. 150 extracted permanent maxillary first molars from residents of rawalpindi and islamabad, pakistan were collected. the study was approved by the ethical review board of iidh. teeth with fully formed roots, closed apex, intact floor of pulp chamber and intact external morphology apical to the cementenamel junction were included in the study. on the other hand, teeth exhibiting root resorption, root fracture, calcified canals, root caries apical to cemento-enamel junction, or root canal treated were excluded. extracted permanent maxillary first molar teeth were collected from four dental hospitals based in rawalpindi and islamabad by the investigators over a period of the six months and examined with naked eye. out of 150 teeth, adherent soft tissue along with the fragments of 27 bone and calculus were removed from the 82 teeth that were included in the study, by manual scaling before storage in 10% formalin prior to transport to the study site. on completion of specimen collection, the laboratory process was initiated where each tooth was prepared by creating an endodontic access cavity with diamond fissure burs (mani, tochigi, japan) by holding tooth in hand. after locating orifice using an endodontic explorer, teeth were put in 5.25% sodium hypochlorite (pd, switzerland) for two days to dissolve the remnants and debris of pulp. thorough rinsing of all the teeth was performed with running water for four hours with the aim of cleaning the debris from the root canals. subsequently, demineralization of teeth was done by using 5% nitric acid for 3 days (merck, darmstadt, germany) at 0 room temperature (25-30 c). the solution of nitric acid solution was changed daily. at the end of the demineralization stage, the specimens were again rinsed for 4 hours in running water. before the next step of dehydration of the tooth, the root canals were injected with india ink (bdh, uk), for canal elaboration. the dehydration procedure was comprised of sequential rinses of ethyl alcohol (merck, darmstadt, germany), beginning with eighty percent solution for the duration of night, succeeded by ninety percent solution for sixty minutes and then hundred percent solutions for sixty minutes. methyl salicylate (merck, darmstadt, germany) was utilized for making the teeth transparent. the teeth were dehydrated for two hours in methyl salicylate. examination was carried out using a magnifying glass at 5 x magnifications by holding teeth in forceps. a standardized data collection proforma was used for recording the details of canal configuration. three of the authors first identify canal configurations individually. for 20% of the canal configurations difference of observation was noted, upon initial examination by individual operators. then these disputed teeth were configured by mutual consensus of the three operators. all the collected data was analyzed using statistical package for social sciences (spss version 24). descriptive statistics were used. frequency and percentages were calculated for types of canal configuration. results on the basis of inclusion criteria, 82 first maxillary permanent molar teeth were included in the study. isthmuses (complete or partial) were observed in 37 (45.1%) of mesio-buccal roots in the present study. 78 (95.1%) of teeth fell into vertucci classification (table-i and figure-2), whereas, 4 teeth (4.9%) either fell into other classification or remain unclassified (figure-1). among them one tooth had 3 canals in mesio-buccal root all joining at apical third (gulabivala type i (3-1)) (figure1c). the remaining three teeth (3.69%) had one mesio-buccal canal with a pinhole at apical third (figure-1a and 1b). fig 1: configura�on of canals other than vertucci's classifica�on jiimc 2018 vol. 13, no.4 mesio-buccal root canal configuration of maxillary first molar 211 discussion procedural errors that occur during the course of endodontic treatment of permanent molars teeth highlight the importance of better understanding of morphology of root canal systems. failure of endodontic treatment of first maxillary permanent molar is most likely because of missed second mesio8 , 2 8 1 3 buccal canal. weine and colleagues has emphasized the importance of a mb2 in the mesiobuccal root of maxillary first molars. therefore, the purpose of current study was to investigate the variations in the root canal morphology of mesiobuccal root of maxillary first molar teeth. the findings of the current research differ from those noted in other populations. the difference is particularly noted in relation to the presence of type iii, v and vi root canal configurations as noted in table ii. the results of the present study are in line 29 with the results of research by shahriaretal on 29 iranian population. shahriaretal reported two canals in the mesioobuccal roots in 58.4% and one canal in 37.96% of cases. this correlation between the results of two studies may be attributed to the geographic region and ethnicity as suggested by sert 24 and bayirli sert and bayirli argued that gender and ethnic origin must be given due consideration while carrying out the preoperative evaluation for root 24 canal therapy. in caucasians, type i canal configuration was 15 reported to be as high as 72% which is much higher 29 18 than the frequency in iranian and pakistani population. the two populations in which type iii canal configuration were present other than this 30 31 study were australian and turkish. in most of the studies type v and type vi canal configuration were 18 21 30 not present except wastietal, pienda, pt robyn 29 and shahriaretal. table i: configura�on of the mesiobuccal root of permanent maxillary first molars according to vertucci 2 classifica�on fig 2: canal morphology of transparent teeth according 2 to vertucci's classifica�on table ii: root canal configura�on of the mesial root of maxillary first permanent molar teeth based on vertucci's classifica�on. (*studies carried out in usa) the highest incidence of type i canal configuration 15 was 72% in american population. it ranged between 5.9-72%, whereas in current study it was 39% which is very close to study carried out on 29 iranian population by shahriaretal and previous 18 study on pakistani population by wastietal, 37.9% and 33.3%, respectively. highest incidence of type ii canal configuration was also in american population 11 37% as reported by seidbergetal. in the present study, it was 21.95% which was again consistent with 29 the results of iranian study and previous study done 18 on pakistani population that was 24.08% and 23.3%, respectively. type iii canal configuration was 19,30,31,32 found in few populations. its highest incidence 30 was in australian population at 27.3% whereas in pakistani population it was 1.23%. highest incidence 33 of type iv was 59.9%, in the current study it was found in 21.95% that is close to results of 29 18 shahriaretal and wastietal which are 24.08% and 23.3% respectively. type vi canal configuration in the jiimc 2018 vol. 13, no.4 mesio-buccal root canal configuration of maxillary first molar 212 mesiobuccal root of permanent maxillary first molars, beside this study (7.3%), was only present in 29 18 two studies shahriar et al 4.38% and wastietal 6.8% which are again very consistent with our results as close proximity of the ethnic/ racial origin and same geographical location. in the current study, type i (3-1) gulabivala canal configuration and was found to be in 1.23% of teeth that was previously 19 reported only in thai population in 1.9% of the samples, moreover, loops/pinholes were found in 3.67% of teeth at the apical end whereas the their incidence was reported as high as 66.7% in the italian 34 population . isthmuses (complete or partial) were frequently observed 37 of teeth (45.1% of the mb roots) in our study, which are reported to be as high 35,37 as 100% in some previous studies. the frequency of mb2 found in the current study is 50% which is in agreement with the previous study conducted by 1 8 wastietal at 53%. in american population 11,15 frequency of mb2 is in the range of 28-33% while 33,34,38 in european population it is 78-80% low incidence of mb2 in american studies may be due to their racial variation from our population. thus, it is important to be aware of such variations to achieve a 39 successful endodontic treatment. in spite of the morphological knowledge of mb root of maxillary first molars, in clinics, location of mb2 canal is almost 40,41 always challenging. sometimes mb2 can be difficult to locate and treat, because it may share an 25,34 orifice with mb1 canal. so proper protocol must be followed while carrying out the endodontic treatment. moreover, clinician should have adequate knowledge of canal morphology, schedule adequate clinical time and look for the mb2 by removing mesial dentinal protuberance overlying 25,42 canal orifice under optimum magnification. additionally, the variation and inconsistency of incidence of mb2 among different studies can be result of insufficient sample size in most of the studies, methods used for the study (in vivo/in vitro), method of canal localization (roentgenographic examination, root sectioning, root clearing or computed tomography), age of the patient when tooth got extracted, ethnicity, geographic location and operators variability. the limitations of the current research include convenient sampling technique and the lack of demographic information particularly regarding the age, gender and the ethnicity of the individuals from which specimens were collected. additionally, the sample was collected form rawalpindi and islamabad; hence, cautious approach should be taken while generalizing the results of the study. thus, future multicenter studies are recommended across pakistan. this will provide the better understanding of the correlation between the race/ethnicity and morphological variations in the maxillary first permanent molar teeth. conclusion in the light of the findings of the current study, the frequency of mb2 in the mesio buccal root of first maxillary permanent molar teeth in the local residents of rawalpindi and islamabad is high. moreover, the frequency of pattern of root canal system, in the maxillary first permanent molars in local population of rawalpindi and islamabad, differs from other populations but is very close to northwest iranian population. the multi-ethnic nature of today's urban populations means that dentists treat an increasing number of patients of different and mixed racial/ethnic origin. references 1. cohen s, hargreaves km, pathways of pulp. new delhi; elsevier, 2011. 2. walton r, torabinejad m. principles and practice of endodontics, 5th ed. philadelphia: w.b. saunders co., 2014. 3. european society of endodontology. quality guidelines for endodontic treatment: consensus report of the european society of endodontology. int endod j 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configuration of canal systems in the mesial buccal root of maxilary 1st and 2nd molar. j endod. 1990;16(7):311-7. 42. blaine mc, william hc, cecilia csd. root and canal morphology of the human permanent maxillary first molar: a literature review. j endod. 2006;32(9):813-21. jiimc 2018 vol. 13, no.4 mesio-buccal root canal configuration of maxillary first molar 214 original�article materials and methods: a total of 200 patients diagnosed clinically as 'allergic rhinitis', were selected by convenient sampling. clinical diagnosis was made on the basis of history and complete ent examination and findings recorded. detailed history for intermittent or persistent symptoms of nasal congestion, watery rhinorrhea, nasal itching with sneezing and ocular symptoms as paroxysmal redness, itching and watering of eyes was taken. detailed physical examination including complete ent examination carried out and a record of presence of post nasal drip, hypertrophic pale or bluish boggy mucosa covered with thin secretion was made. blood samples were taken for serum ige levels and total eosinophil count. the data was analyzed for frequencies by spss 24. since the data was not parametric, non-parametric tests were applied. results: gender distribution showed a male predominance with males 58.5% (117) and females 41.5% (83). rd th most of the patients were among the age group 3 to 5 decades. serum ige was raised in 152 (76%) patients, while total eosinophil counts were raised in 104 (52%) patients. serum ige levels were found significant as p ≤ 0.50, while total eosinophil count was not found significant as p ≥ 0.50. conclusion: serum ige levels and total eosinophil counts are good reflector of allergic rhinitis. although serum ige levels appear to be very significant in diagnosing allergic rhinitis, total eosinophil count has yet to be established as a significant diagnostic tool. being expensive tests, only serum ige levels should be advised in patients with suspicion of allergic rhinitis, and total eosinophil count should not be advised routinely. key words: allergic rhinitis, serum ige levels, total eosinophil count. abstract objective: to determine the significance of serum ige level and total eosinophil count in establishing diagnosis of allergic rhinitis. study design: a descriptive study. place and duration of study: ent department islamabad medical complex, from december 2016 to december 2018. most common cause of chronic rhinitis and affects 3 10-20 % of the population. previously it was considered as a localized disease but now it has been acknowledged as a part of a systemic disorder. the close functional and immunological relationship between the upper and lower respiratory tracts, on provocation, not only causes inflammation in the upper respiratory tract but also involves the lower respiratory tract. therefore, mostly it accompanies 4 allergic asthma and eczema. in an atopic individual, whenever the nasal mucosa comes in contact with certain allergens, the inflammatory cells including the mast cells, b cells, t cells, eosinophils and macrophages infiltrate the nasal mucosa. the t cells release the cytokines that result in production of the 5 ige by the plasma cells. the ige binds with the mast cells resulting in release of the inflammatory mediators like histamine and leukotrines, that are responsible for the inflammatory reaction causing vascular dilatation, increased vascular permeability, introduction rhinitis is defined as inflammation of the nasal mucosa resulting in nasal congestion, rhinorrhea, itching of the nasal mucosa, and sneezing. it may occur as a result of infection, allergy, vasomotor imbalance (nares), and may be drug induced or idiopathic. the term 'allergy' was first introduced by clemens 1 von pirquet in 1906. allergic rhinitis is defined as ige 2 mediated inflammation of the nasal mucosa. it is the serum ige levels and total eosinophil count in allergic rhinitis 1 2 3 mirza khizar hameed , atif sharif , mahum khizar correspondence: dr. mirza khizar hameed department of ent foundation university medical college, islamabad e-mail: mirzakhizar@yahoo.com 1,3 department of ent foundation university medical college, islamabad 2 department of ent islamabad medical complex, islamabad funding source: nil; conflict of interest: nil received: april 21, 2020; revised: august 05, 2020 accepted: august 06, 2020 diagnosis of allergic rhinitisjiimc 2020 vol. 15, no.3 154 so far we have not seen any study that could show how accurate is the diagnosis of allergic rhinitis made on the basis of history and physical 14 examination. moreover, there are not many studies on the diagnosis of allergic rhinitis. as most of these patients are managed on the basis of clinical diagnosis, and are subjected to a life-long anti allergic treatment, a need was felt that this long term treatment should be advised evidence based, after confirming the diagnosis on the basis of laboratory tests. this was the rationale behind the present study with an objective to determine the significance of serum ige level and total eosinophil count in establishing diagnosis of allergic rhinitis. materials and methods a descriptive study was carried out in islamabad medical complex ent department from december 2016 to december 2018. approval of hospital ethical committee for this study was taken beforehand. a total of 200 patients diagnosed clinically as 'allergic rhinitis', were selected by convenient sampling after taking informed consent from them for this study. clinical diagnosis was made on the basis of history and complete ent examination and findings recorded on a preformed performa. detailed history for intermittent or persistent symptoms of nasal congestion, watery rhinorrhea, nasal itching with sneezing and ocular symptoms as paroxysmal redness, itching and watering of eyes was taken. detailed physical examination including complete ent examination carried out and a record of presence of post nasal drip, hypertrophic pale or bluish boggy mucosa covered with thin secretion was made. inclusion criteria comprised of at least three of the following symptoms: nasal congestion, watery rhinorrhea, itching of nose with sneezing, post nasal drip, whether intermittently or persistently, for at least two years. presence of turbinate hypertrophy with pale or bluish boggy mucosa covered by thin secretions was recorded. exclusion criteria included any active infection or trauma of respiratory tract, local use of steroid nasal spray or drops, intake of systemic steroids, antihistamine, montelukast or mast cell stabilizers in past one month, age below 12 years or above seventy years, and pregnancy. patients were called one month after cessation of any local or systemic medicine intake for their watery rhinorrhea, mucus secretion and smooth 6 muscle contraction. in the next stage, these mediators induce a further cellular inflammatory response, the late phase response, responsible for 7 recurrent nasal congestion. allergic rhinitis may be divided into two types; intermittent or persistent, as previously described as 8 seasonal and perennial. on the basis of severity it may be divided into mild, moderate and severe forms for management purposes. traditionally the diagnosis is clinical, on the basis of history and physical examination. history of nasal congestion, itching, and sneezing, watery rhinorrhea, along with itchiness, redness and watering of eyes is fairly 9 common. in most of the cases there is an association with asthma. there may be a positive family history. certain environmental factors as dust, pollens, humidity, fumes, exposure to furred animals, tobacco, fumes or intake of drugs as beta blockers, nsaids, aspirin, ace inhibitors, certain hormones 10 may be the triggering factors. physical examination may reveal a transverse nasal crease on the dorsum (allergic salute), dark circles around the eyes (allergic shiners), turbinate hypertrophy with pale or bluish boggy mucosa covered by thin watery secretion, nasal polyps, post nasal drip, prominent lymphoid follicles on posterior pharyngeal wall (cobble stoning), adeno-tonsillar hypertrophy, ome, wheeze, skin eczema etc. besides the history and physical examination, certain allergic tests are also carried out to reach the diagnosis, as the clinical features may appear similar in other types of non-infective rhinitis. these tests include skin prick tests for specific allergens. allergen specific ige tests (rasts/ elisa) are considered equally effective in reaching the diagnosis as they 11 indicate atopy, but are considered a bit expensive. since there is an established association of eosinophilia with allergic respiratory disease, nasal smears for eosinophilia and systemic eosinophilia are also considered an important investigative tool 12 for the diagnosis of allergic rhinitis. although allergic rhinitis badly affects the quality of life of the patients, most of them do not appreciate this and do not seek treatment. even the primary physicians fail to diagnose these patients hence some sort of screening tests need to be carried out in 13 such patients with such a longstanding history. jiimc 2020 vol. 15, no.3 155 diagnosis of allergic rhinitis one-sample binomial test (non parametric) shows significance level to be 0.50. serum ige levels were found significant as p ≤ 0.50, while total eosinophil count was not found significant as p ≥ 0.50. discussion allergic rhinitis is one of the commonest chronic 15 disorders that affect the quality of life badly. though it is quite common with an incidence of 10 20% of population suffering from it, the diagnosis presents a significant challenge due to similarity of its clinical picture with other forms of non-infective 16 rhinitis. our study shows gender distribution with a male predominance. similarly a study by jagadeeshwar et al (2001) also shows a male predominance in 17 patients with allergic rhinitis. jung et al (2011) also show a male predominance among patients with 18 allergic rhinitis. but in another study carried out by khan (2013) shows a female predominance in 19 patients with allergic rhinitis. but our study results can be explained as convenience sampling was done. in our study, the incidence seems to be more in rd th 20 patients of 3 to 5 decades. wheatley & togias rd th (2015) show it to peak its prevalence in the 3 and 4 21 decades. muddaiah & venkatarangaih (2020) also rd th show an increased incidence in age group 3 to 4 decades. droste et al (1996) also shows an increased th incidence in the 5 decade with a male 22 predominance. although the patients were selected on the basis of convenience sampling, the disease appears to have similar age incidence even in other studies. being an allergic disorder, allergic rhinitis has a wellestablished association with eosinophils. in our study, raised eosinophil count has been observed in only 52% of the patients, and thus it fails to appear as a significant indicator of allergic rhinitis. similar to our observations, patel & nagpal (2014) also observe that although there is a strong correlation with nasal smear eosinophilia but allergic rhinitis has absolutely no correlation with systemic 23 eosinophilia. but another study by mostafa et al (2020) reveals that the absolute eosinophil count was positive in 70.4% patients with allergic rhinitis, 24 so it is considered a good indicator of the disease. baldacci et al (2001) also consider serum eosinophil count as an important though less used investigation 25 for monitoring the clinical course of ar. another in our study the gender distribution shows a male predominance with males 58.5% (117) and females 41.5% (83) as shown in figure: 1 symptoms. blood samples were taken for serum ige levels and total eosinophil count. serum ige levels were measured by chemi-luminescent micro particle immunoassay (cmia) cobas methodology, while total eosinophil counts were measured by cell dyn ruby methodology: mapss. the data were analyzed for frequencies by spss 24. since the data was not parametric, non-parametric tests were applied. results fig 1: gender distribu�on (n= 200) rd most of the patients were among the age group 3 to th 5 decade as shown in the figure: 2. fig: 2: age distribu�on (n= 200) serum ige was raised in 152 (76%) patients, while total eosinophil counts were raised in 104 (52%) patients as given in figure 3. fig 3: serum ige level & total eosinophil count (n= 200 jiimc 2020 vol. 15, no.3 156 diagnosis of allergic rhinitis 3. dykewicz ms, hamilos dl. rhinitis and sinusitis. j allergy clin immunol. 2010; 125:s103–15. 4. al-rabia mw. diagnostic accuracy of sige, total ige and eosinophils percentage among patients with asthma, allergic rhinitis, and atopic dermatitis in saudi arabia. ijhsr, oct 2016; 6 (10): 3339. 5. church ds, church mk, scadding gk. allergic rhinitis: impact, diagnosis, treatment and management. aug 2016; immunology. 6. navines-ferrer a, serrano-candelas e, molina-molina gj, martin m. ige-related chronic diseases and anti-ige-based treatments. j immunol res, nov 2016: 1-12. id 8163803, http://dx.doi.org/10.1155/2016/8163803. 7. small p, kim h. allergic rhinitis. allergy asthma clin immunol. nov 2011; 7(suppl 1): 1-3. doi: 10.1186/17101492-7-s1-s3. 34 asymptomatic people. with all this evidence, we can infer that there is no single laboratory test that can replace clinical diagnosis of allergic rhinitis or considered superior to it and the diagnosis has to be made while considering both the clinical and 18 laboratory based evidence. in the light of above evidence we can recommend that in the presence of positive clinical evidence, the patients should undergo serum ige assays as it is positive in 76% of the patients. and only those patients in whom serum ige levels are raised, should be recommended long term anti allergic treatment. since the scope of our study is limited, carried on only 200 patients, it is further recommended that more studies need to be carried out at larger scales to find out a suitable and cost effective evidence based strategy and guidelines be made at national level for diagnosis of allergic rhinitis in patients needing long term anti-allergic treatment. conclusion serum ige levels and total eosinophil counts are a good reflector of the disease (allergic rhinitis). although serum ige levels appear to be very significant in diagnosing allergic rhinitis, total eosinophil count has yet to be established as a significant diagnostic tool. being expensive tests, only serum ige levels should be advised in patients with clinical diagnosis of allergic rhinitis before advising long term anti allergic treatment. references 1. galli sj, tsai m, piliponsky am. the development of allergic inflammation. nature. 2008; 454(7203): 445–454. 2. choudhari sy, sangavi ab. a clinical study of inhalant allergens in patients with allergic rhinitis. int j otorhinolaryngol head neck surg. 2017 apr;3(2):380-384 study by prabakaran et al (2018) shows that in case of only nasal symptoms, the total eosinophil counts do not go beyond normal range, but when nasal symptoms are associated with respiratory symptoms 26 then serum eosinophil levels are found elevated. in another study, sharma et al (2019) in a study claim serum eosinophil counts and serum ige levels as reliable investigation tools for the diagnosis of 27 allergic rhinitis. interestingly, in a study by poznanovic & kingdom (2007) a correlation between raised eosinophil count and mucosal sinus disease on ct scan has been established while no correlation 28 was found with raised ige levels. this finding points towards significance of raised eosinophil counts during an active sinus disease. in yet another study, koh et al (2013) also showed a positive relationship between allergic disease and serum ige levels as well 29 as total eosinophil count. on these various findings we can infer that a high eosinophil count may be present during an active disease, otherwise it may not be very significant in diagnosing allergic rhinitis. our study shows serum ige levels to be raised in 76% of the patients, which is very similar to the study by vijayan et al (2019), in which they show a rise of 30 serum ige in 80% of the patients. in a study by chaudhary et al (2017) s ige levels were found to be 2 raised in 100% of patients. another study by chowdary et al (2003) also reveals raised s ige in acute phase of allergic rhinitis, but serum eosinophils are not raised at all, although they recommend that s ige and serum eosinophil counts should be carried out in all the patients with 11 suspicion of allergic rhinitis. satwani et al (2009) also claim s ige to be a good predictor of allergy 31 especially in children. jung et al (2011) also claim total serum ige as a strong predictor of allergic 18 rhinitis. cakanlar et al (2015) also shows total ige as 32 an important indicator of allergic rhinitis. hameed et al (2020) consider it obligatory to carry out serum ige in any patient with a clinical diagnosis of an 33 allergic disorder. in view of these studies, we can easily claim serum ige to be a significant indicator of allergic rhinitis. traditionally, the diagnosis of allergic rhinitis is made on the basis of history and clinical examination, and on the basis of response to 24 empirical treatment. even the presence of specific ige just points towards sensitization even among jiimc 2020 vol. 15, no.3 157 diagnosis of allergic rhinitis skin test reactivity, specific ige, total ige, and eosinophils with nasal symptoms in acommunity based population study. j allergy clin immunol, 1996; 97: 922-32. 23. patel ak, nagpal tp. comparison of blood absolute eosinophil count and nasal smear eosinophils with symptoms and severity of clinical score in patients of allergic rhinitis. indian j allergy asthma immunol 2014; 28 (2): 7477. 24. mostafa hs, qotb m, hussein ma. allergic rhinitis diagnosis: skin-prick test versus laboratory diagnostic methods. egypt j otolaryngol 2019; 35:262–268. 25. baldacci s, omenaas e, oryszczyn mp. allergy markers in respiratory epidemiology. eur respir j 2001; 17: 773-790. 26. parabakaran j, dhanapal e, prasanna v, jayagar s. correlation between blood eosinophil count and nasal smear eosinophils with severity of clinical score in allergic rhinitis patientsa cross sectional study. jmscr 2018; 6 (7): 1134-37. 27. sharma m, khaitan t, raman set al. determination of serum ige and eosinophils as a diagnostic indicator in allergic rhinitis. indian j otolaryngol head neck surg. 2019 nov; 71(suppl 3):1957-1961. doi: 10.1007/s12070-018-1383-7. 28. poznanovic sa, kingdom tt. total ige levels and peripheral eosinophiliacorrelation with mucosal disease based on computed tomographic imaging of the paranasal sinus. arch otolaryngol head neck surg. 2007; 133(7): 701-704. 29. koh hs, lee ks, han dh et al. relationship between serum total ige, specific ige, and peripheral blood eosinophil count according to specific allergic diseases. allergy asthma respir dis. 2013 jun; 1(2):123-128. 30. vijayan n, karthikeyan p, venkataramanujam nc et al. the association of absolute eosinophil count, serum immunoglobulin e and spirometry with co-morbid bronchial asthma in patients with allergic rhinitis. romanian j rhinol, 2019, 35 (9): 151154. doi: 10.2478/rjr2019-0018 31. satwani h, rehman a, asraf s, hassan a. is serum total ige levels a good predictor of allergies in children? jpma, 2009; 59 (10): 698702. 32. cakanlar fn, ceylan e, kanbay a. relationship between serum total ige, specific ige and serum total eosinophil counts in asthma bronchiale patients. world allergy organ j, 2015; 8: 25. 33. hameed rm, ahmed mm, abood haan, hussein am. to evaluate total serum immunoglobulin e level and factors that effect on this level in iraqi asthmatic children. biomed biotechnol res j 2019; 3: 240244. 34. crobach mj, hermans j, kaptein aa, ridderikhoff j, petri h, mulder jd. the diagnosis of allergic rhinitis: how to combine the medical history with the results of radioallergosorbent tests and skin prick tests. scand j prim health care, 1998; 16 (1): 30-36. doi: 10.1080/028134398750003377. 12. okano m, nishizaki k, nakada m, kawarai y, goto s, satoskar ar, satoskar aa, takehisa t, masuda y. prevalence and prediction of allergic rhinitis using questionnaire and nasal smear examination in school children. acta otolaryngologica supplement 1999; 540: 58-63. 13. guerra s, sherrill d, martinez f, barbee ra. rhinitis as an independent risk factor for adult-onset asthma. j allergy clin immunol. 2002; 109(3):419–25. 14. conner sj. evaluation and treatment of the patient with allergic rhinitis. j fam pract october 2002; 51 (10): 883-890 15. chawes blk, kreiner-moller e, bisgaard h. objective assessments of allergic and nonallergic rhinitis in young children. allergy 2009: 64: 1547–1553. 16. karli r, balbaloglu e, uzun l et al. correlation of symptoms with total ige and specific ige levels in patients presenting with allergic rhinitis. ther adv respir dis. 2013; 7(2): 75–79. doi: 10.1177/ 1753465812468500. 17. jagadeeshwar k, venumadhav v, sangram v et al. a study on serum ige levels, peripheral eosinophils and individual symptoms in patients with non-infective rhinitis and asthma and related conditions. int j pharm pharm sci, 2012; 4 (1): 88-92. 18. jung yg, kim kh, kim hy et al. predictive capabilities of serum eosinophil cationic protein, percentage of eosinophils and total immunoglobulin e in allergic rhinitis without bronchial asthma. 2011; 39: 2209 – 2216. 19. khan m, khan ma, shabbir f, rajput ta. 2013. association of allergic rhinitis with gender and asthma. j ayub med coll abbottabad, 25 (1-2):120-122. 20. wheatley lm, togias a. allergic rhinitis. n engl j med. 2015 j a n u a r y 2 9 ; 3 7 2 ( 5 ) : 4 5 6 – 4 6 3 . d o i : 10.1056/nejmcp1412282. 21. muddaiah d, venkatarangaih s. a study on total serum ige levels and absolute eosinophil count in allergic rhinitis patients. j. evolution med dent sci. 2020; 9 (02): 76-80, doi: 10.14260/jemds/2020/17j. 22. droste hj, kerkhof m, de monche jgr et al. association of 8. corsico ag, amici md, ronzoni v et al. allergen-specific immunoglobulin e and allergic rhinitis severity. allergy rhinol (providence). 2017 mar; 8(1): e1–e4. doi: 10.2500/ar.2017.8.0187. 9. bousquet j, khaltaev n, cruz aa, denburg j, fokkens ahlstedt s, murray cs. in vitro diagnosis of allergy: how to interpret ige antibody results in clinical practice. prim care respir j. 2006; 15(4):228-36. 10. nagare p, chavan s, jain p, burgute s. study of clinicopathological profile in patients of allergic rhinitis. indian journal of basic and applied medical research, march 2019; 8 (2): 374 – 380. 11. chowdary vs, vinaykumar ec, rao jj et al. a study on serum ige and eosinophils in respiratory allergy patients. indian j allergy asthma immunol 2003; 17(1): 21-24. jiimc 2020 vol. 15, no.3 158 diagnosis of allergic rhinitis case�report abstract in this case report, we share our experience of complication with use of intra-abdominal polypropylene sutures. the patient presented with intestinal obstruction resulting from the herniation of small intestine through the polypropylene suture loop due to a knot placed on the uterine fundus around seven years prior during an uncomplicated low segment cesarean section with bilateral tubal ligation. an exploratory laparotomy was performed and suture material was cut to release the obstructed gut. meticulous care needs to be taken when using suture material intra abdominally by either burying the suture material or keeping the suture short. key words: intestinal obstruction, intraperitoneal sutures, prolene. significant tenderness or rebound on palpation. bowel sounds were absent. x-ray of abdomen showed dilated small bowel loop with air fluid levels. patient had no previous history of tuberculosis and no reported exposure to tuberculosis. ultrasound of abdomen showed free fluid in pelvis and dilated small bowel. patients findings were consistent with peritonitis due to intestinal obstruction, a suspicion of abdominal tuberculosis and adhesions couldn't be ruled out. a ct-scan abdomen was done to delineate the cause of obstruction, which showed significantly dilated ileum with few calcified mesenteric lymph nodes. patient was managed conservatively at first with nasogastric tube, fluids and nil per oral. patient symptoms settled in a day and the x-ray of abdomen became normal. patient was discharged after observing for any deterioration in starting oral fluids. however, patient returned to the hospital after a day with similar symptoms of pain, distention and similar x-ray abdomen. an exploratory laparotomy was performed with lower midline abdominal incision. dilated bowel loop was traced back to the transition point, a visible polypropylene suture was identified containing a herniated ileum passing through the suture loop. the suture was anchored on the fundus of the uterus running through the body in a continuous fashion and a single suture loop of the suture was free on the fundus. the free loop seemed to have eroded through the uterine wall. two more polypropylene sutures were visible a distance away, used for bilateral tubal ligation. no comment on the type of previous surgery performed can be made because no history of any surgical procedure apart from cesarean section and bilateral tubal ligation seven introduction polypropylene is a synthetic, monofilament, non1 absorbable suture. the suture is best suited for use on the skin, hernias, vascular anastomosis and closing rectus sheaths or linea alba. its use intraperitoneally is very limited due to its propensity to erode through and into the surrounding tissue. federal drug authority in america has issued several warnings regarding the use of prolene and prolene meshes due to an increase in the number of mesh driven tissue erosions reported by patients over the 2 years, specifically in pelvic surgeries. however, small bowel obstructions have previously been reported with intracorporeal suturing with barbed and v-lock 3 sutures. to our knowledge, no previous case of intestinal obstruction has been reported with polypropylene sutures used for previous intraabdominal surgery. this case highlights the potential problems that can arise from the use of this suture intra-abdominally. case report a 30 year old female presented with sudden severe colicky abdominal pain. patient had associated greenish non bloody vomiting with obstipation. the abdomen was mildly distended and there was polypropylene suture loop as a cause of small bowel obstruction 1 2 umar bashir , afsheen zafar correspondence: dr. umar bashir resident general surgery department of general surgery islamic international medical college, riphah international university, islamabad e-mail: umer.bashir@gmail.com 1,2 department of general surgery islamic international medical college, riphah international university, islamabad funding source: nil; conflict of interest: nil received: may 10, 2019; revised: june 08, 2019 accepted: june 10, 2019 small bowel obstructionjiimc 2019 vol. 14, no.2 95 3 post operatively. however, as this case highlights, any non-absorbable suture has the ability to cause intestinal obstruction for an indefinite period of time if left intraperitoneally. inadvertant loops can form after erosion in the tissue in which they are originally used. although prolene is not commonly used intraperitoneally, its use in fixing meshes, especially in pelvic surgeries, is well known. moreover, it is at times used to mark or hitch viscera to the abdominal wall. it should be kept in mind that its use in these situations is not completely risk free. due to this reason, surgeons should be extra careful when using these sutures intraperitoneally. meticulous use of sutures, keeping a short length of the suture intraperitoneally and burying them wherever possible are all suggested to decrease the risk of such complications. references 1. selvi f, cakarer s, can t, topcu si̇, palancioglu a, keskin b, et al. effects of different suture materials on tissue healing. journal of istanbul university faculty of dentistry. 2016;50(1):35. 2. haylen bt, sand pk, swift se, maher c, moran pa, freeman rm. transvaginal placement of surgical mesh for pelvic organ prolapse: more fda concerns—positive reactions are possible. international urogynecology journal. 2012; 23(1):11-3. 3. salminen hj, tan ws, jayne dg. three cases of small bowel obstruction after laparoscopic ventral rectopexy using the v l o c ® s u t u r e . te c h n i q u e s i n c o l o p r o c t o l o g y. 2014;18(6):601-2. 4. khan mi, ali ms, khan i, iqbal m, parveen s, shah sh. tuberculosis of intestine. journal of surgery pakistan (international). 2016 ;21:2. 5. liu jun, sun chang yi. diagnostic value of plain and contrast radiography and multislice ct in diagnosing intestinal obstruction in different location. indian journal surgery. 2015; 4: 1248-51. years prior could be obtained. the free loop of suture had ileum in it and was compressing the lumen of the bowel causing obstructive symptoms. the suture was cut and removed, bowel checked for viability and abdomen closed in a layered fashion. patient had a complete recovery after the surgery. discussion i n t e s t i n a l o b s t r u c t i o n i s v e r y c o m m o n l y encountered in surgical practice. although the cause of obstruction can be identified in majority of the cases based on history, examination and imaging studies, there are still dubious cases in which no definite cause is identifiable on initial studies. when no mechanical cause of obstruction is found on imaging, there is a high tendency of such patient being labelled as having chronic disease such as tuberculosis due to high prevalence of the disease in 4 our setup and difficulty in diagnosing it. one needs to keep a high index of suspicion for rare causes of intestinal obstruction. although we have advances in imaging like multi slice scans, msct patient symptoms should never be overlooked. multi slice ct scans have a diagnostic accuracy of about 91% to determine intestinal obstruction. these msct scans are less reliable for small bowel as compare to large bowel obstruction with a diagnostic accuracy of 98% for large and 78% for small bowel. to conclude, ct scans can't delineate all causes of intestinal obstruction and persistent or recurrent pain is an indication for 5 prompt surgical intervention. i n t ra p e r i t o n e a l s u t u re s c a u s i n g i n t e s t i n a l obstruction is very rare. recently v-lock and barb suturing in laparoscopic surgery has been reported as a cause of intestinal obstruction either due to intestinal herniation through the loop or adhesions small bowel obstructionjiimc 2019 vol. 14, no.2 96 original�article abstract objective: to determine the association between doppler parameters of average peak portal vein velocity and flow direction and child pugh classes of patients suffering from the chronic liver disease. study design: it was a descriptive study. place and duration of study: the study was conducted from december 2013 to january 2015 at the radiology department of holy family hospital, rawalpindi, pakistan. materials and methods: selected chronic liver disease (cld) patients were examined with gray scale and doppler usg for assessment of portal vein (pv). average peak portal venous velocity (pvv) and direction of flow in the main portal vein were recorded. doppler findings were correlated with clinical features and laboratory findings in three classes (a,b & c) of patients using child pugh criteria to establish any probable association between them (appendix: i). results: out of total 115 cld patients studied, 47.8% were in child pugh class c. the main portal vein average pvv (cm/sec) in 24.34% patients with child pugh class a was 18.75 + 1.88, in 27.82% patients with child pugh class b was 14.25 + 0.98 and in 47.82% patients with child pugh class c was 8.15 + 1.84. this showed significant fall in portal vein average pvv with advancing child pugh class of cirrhosis. only 10.4% patients showed continuous hepatofugal flow and 4.3% showed bidirectional flow. it was recorded only in child pugh class c patients. conclusion: doppler findings of average peak velocity in the main portal vein fall progressively with worsening of the child pugh class. in addition, the direction of flow is also reversed in cases of the child pugh class c cirrhosis. key words: child, cirrhosis, cld, doppler, direction, flow, hypertension, hepatic, liver, portal, pugh, transplant, ultrasound, vein, velocity. introduction pakistan has been positioned in intermediate prevalence zone for viral hepatitis b and c that is responsible for >75% of cirrhosis and hepatocellular 1 carcinoma (hcc) in who emro region. the burden of the disease and its end-stage complications are a huge challenge for the healthcare providers because a majority of patients remain asymptomatic and unaware, leading to a silent epidemic and therefore resulting in significant morbidity and mortality in our 2,3 country. the chronic liver disease leads to many complications such as portal hypertension ( as cites , hyp ers p len is m, varices ) , systemic dysfunction (hypoalbuminemia, coagulopathy), hepatopulmonary and hepatorenal syndromes, encephalopathy, hepatocellular carcinoma, and the notorious cirrhosis which is the common endpoint of a w i d e va r i et y o f c l d p ro c e s s e s ca u s i n g 4 , 5 hepatocellular necrosis. the world health organization (who) has defined cirrhosis as “a association of portal vein doppler parameters with chronic liver disease child pugh classes: a single center experience at rawalpindi, pakistan 1 2 3 4 5 6 abdul ahad farooq , ahsen farooq , muhammad rashid , junaid haris farooq , salma umbreen , rabia waseem correspondence: dr. abdul ahad farooq senior registrar rawalpindi institute of cardiology, rawalpindi associate consultant radiologist quaid-e-azam international hospital, islamabad e-mail: docahad@gmail.com 1 department of radiology rawalpindi institute of cardiology, rawalpindi quaid-e-azam international hospital, islamabad 2 department of radiology islamic international medical college, rawalpindi riphah international university, islamabad 3 department of medicine / nephrology krl hospital, islamabad 4 department of internal medicine charleston area medical center charleston, west virginia, usa 5 department of radiology wah medical college, wah 6 department of radiology hitec institute of medical sciences, taxila funding source: nil; conflict of interest: nil received: october 24, 2018; revised: february 13, 2019 accepted: march 06, 2019 association of portal vein doppler & child pugh classes of patients with cldjiimc 2019 vol. 14, no.1 33 onwards was included in the study. child pugh classification (a, b and c) was done as per standard 7 criteria by the medical and radiological department. (appendix 1). patients having portal vein thrombosis (pvt) were excluded from the study. informed consent was obtained from all the patients fulfilling the inclusion criteria. patients were subjected to conventional grayscale and doppler ultrasound using toshiba nemio ultrasound machine equipped with multi-frequency linear and curvilinear transducer probes. the examination was performed or supervised at least by a registrar level radiologist. all the patients were examined preferably in the supine position. during the examination, every patient was required to hold breath in deep inspiration, to avoid motion artifacts. the scanning of the portal vein was carried out longitudinally throughout its entire length from an anterior abdominal subcostal and/or right intercostal approach. it was analyzed for the presence or absence of intra-luminal thrombus, blood flow velocity in cm/s and direction of blood flow within the portal vein. all the findings were reconfirmed by another consultant radiologist. data were collected by the principal investigator on the study proforma. data were entered and analyzed by statistical package for the social sciences (spss) version 22. descriptive statistics were calculated. the quantitative variable of the study included; average peak venous velocity in the main portal vein compared with different child pugh classes a, b & c and expressed as mean ± sd. the qualitative variable of the study included; the direction of portal vein blood flow compared with different child pugh classes a, b & c and expressed as frequency. results a total of 125 cld patients presented from december 2013 till january 2015. ten patients were excluded from the study because of either incompletely available medical record or loss to follow up and portal vein thrombosis in 2 cases. therefore, a total number of 115 cld patients without pvt were included in this study. the age ranged from 21-77 years with a mean age of 40.6+11.54 years. most of them (43, 37.4%) ranged between 31-40 year age group. males were 70 (60.87%) and females 45 (39.13%) with m:f of 1.6:1 approximately. majority of patients (47.8%) were in diffuse process characterized by fibrosis and conversion of normal liver architecture into 6 structurally abnormal nodules.” the child pugh classification system is the most commonly used tool for clinically predicting the prognosis in cirrhosis. child and turcotte first presented their criteria in 7 1964 that was later revised by pugh in 1973. chronic liver disease, especially in asymptomatic patients has been diagnosed mainly by the liver 8 biopsy which helps in its staging and grading. however, the risks and limitations associated with this invasive method have led to the development of safer methods of investigation. grayscale usg is now an integral part of the routine liver examination and doppler studies have been considered as the gold standard tool for evaluating the velocity and direction of blood flow in the portal 4,9 venous system. it is a non-invasive, rapid and costeffective investigation and well accepted by the 4,10 patients. in pakistan, now there are centers offering liver transplant as prospective management of cld, therefore, use of child pugh classification and doppler studies have become a vital assessment tool. only a few studies have been conducted evaluating the role of doppler ultrasound in the assessment of chronic liver disease patients in 2 pakistan. the aim of this study was to explore the value of doppler ultrasonography in the assessment of pv hemodynamics in cld patients and to determine the association between doppler parameters of ppv and flow direction and child pugh classes of the pakistani patients suffering from the chronic liver disease. materials and methods this descriptive cross-sectional study was conducted in the department of radiology in collaboration with the department of medicine at holy family hospital rawalpindi. approval was taken from the hospital ethical committee. nonprobability convenience consecutive sampling technique was used. using who sample size calculator, the sample size of 115 was calculated by taking a confidence level of 95 % and population mean of 18.33. all the patients of either gender and of age more than 20-year, having clinical, biochemical and radiological evidence of chronic liver disease, presenting to the departments of medicine and radiology from december 2013 34 jiimc 2019 vol. 14, no.1 association of portal vein doppler & child pugh classes of patients with cld aetiologies. since long, liver biopsy has been considered as the gold standard for diagnosing, staging and grading the liver damage in cld, 8 especially in asymptomatic patients. this invasive method has several risks and limitations, including morbidity and mortality, sampling error, diagnostic inaccuracy, interobserver and intraobserver 11 variability, and difficulties in follow-up. therefore, it led to the development of safer methods for evaluation of cld and its complications. the noninvasive grayscale and doppler usg studies have now been considered as an essential part of the investigation battery for assessing the cld 9,10. patients. with increasing accessibility of liver transplant facility for the management of end stage cld world over, the use of child pugh classification as a valuable indicator of the prognosis in cld patients 9 have become vital as well. combined together imaging, pathological and clinical assessment methods help explore new therapeutic avenues. the role of ultrasound imaging in the evaluation of 4,12,13,14,15 cld / cirrhosis is well known. doppler usg is an important diagnostic modality for the analysis of 9,10,16,17 the hepatic vasculature and blood flow. the standard dynamics of blood flow in the hepatic artery, hepatic veins, and the portal vein, have been 4,9,10,15,17 well defined in the literature. changes in hepatic blood flow dynamics might be alternate markers for significant parenchymal changes in 9.10,11 chronic liver diseases and their complications. the child pugh classification is mostly used to stage chronic liver disease based on clinical and laboratory parameters that is ascites, encephalopathy, bilirubin and albumin levels, and prothrombin time. there are three stages of the child pugh classification system, 7 a, b and c depicting increasing severity of cld. (appendix-i) on doppler us, the characteristic portal vein hemodynamic features of liver cirrhosis include reducing blood-flow velocity, absent pulsatility, and change in flow direction from hepatopetal to 9,10,11,15,16,17 hepatofugal in more advanced cases. the normal portal vein velocity ranges from 16 to 40 15,16 cm/sec with variations caused by respiration. portal venous flow velocities progressively fall with rising portal venous pressure because back pressure limits forward velocity that is characteristic for portal hypertension and also due to collaterals formation, child pugh class c (table-i). doppler findings of the average peak venous velocity (pvv) and the direction of blood flow in the main portal vein were evaluated in all the subjects and were compared with child pugh classes a, b, and c. the main portal vein average pvv (cm/sec) in 28 (24.34%) patients with child pugh a was 18.75 + 1.88, in 32 (27.82%) patients with child pugh b was 14.25 + 0.98 and in 55 (47.82%) patients with child pugh c was 8.15 + 1.84 (table-ii). only 17 (14.7%) patients demonstrated non hepatopetal flow (hepatofugal / bidirectional), 12 (10.4%) showed continuous hepatofugal flow and 5 (4.3%) showed bidirectional flow (table-iii). it was recorded only in child pugh class c patients. table i: distribu�on of child pugh classes a, b, and c among the pa�ents table ii: comparison of average peak venous velocity in the main portal vein in child pugh classes a, b, and c table iii: pa�erns of flow in the main portal vein among child pugh's classes a, b, and c. discussion accurate evaluation of liver parenchymal damage and altered vascular hemodynamics is crucial for therapeutic decisions, surveillance, and assessment of the prognosis in chronic liver diseases of various 35 jiimc 2019 vol. 14, no.1 association of portal vein doppler & child pugh classes of patients with cld % of patients which all corresponds to the child pugh 9 class c. afif, et al in 2017, studied the maximum velocities in portal vein, hepatic vein and hepatic artery and hepatic artery resistive index in liver cirrhosis patients of the singapore population. they found that flattening of the hepatic vein waveforms was related to the degree of liver cirrhosis. the cirrhotic patients showed higher maximum hepatic vein velocity. however, they had lower maximum portal vein velocity and there was a further decrease in average maximum portal vein velocity as the severity of liver cirrhosis worsened. in our study of 115 pakistani cld patients, the main portal vein average pvv was 18.75 + 1.88, 14.25 + 0.98 and 8.15 + 1.84 cm/sec in the child pugh classes a, b and c respectively (table-ii). this showed a significant fall in portal vein average pvv with the increasing severity grade of cirrhosis based on the child pugh class. the results are consistent with results of chawla et al, shi et al and by vyaset al 19,20,21 studies. normal individuals display a hepatopetal portal 15,16,17 venous blood flow. in deteriorating cld, portal venous flow progressively slows down with rising portal venous resistance and pressure, first nearing the level of stagnation demonstrated by the 16,17 phenomenon of a to-and-fro (bidirectional) flow. later with advancing cirrhosis, obstruction of the hepatic venules and sinusoids due to fibrosis and architectural distortion, and further by arterioportal and porto-systemic shunting, eventually leading to hepatofugal (reversed) portal venous flow and fall in 4,16,17 velocity. in our study, only 4.3% patients showed bidirectional flow and 10.4% showed continuous hepatofugal flow (table-iii). it was recorded only in the child pugh class c. none of the patient in the child pugh class a and b demonstrated hepatofugal flow. gaiani et al have 22 reported the similar patterns. it implies that with more reversal of the portal venous flow, there is increased deterioration of liver function and hence poorer the child pugh score. despite the single center's small study and some limitations of the final diagnoses and follow up, the results of our study are by and large supported by the various international studies. this study imparts a deeper insight into the non-invasive and costeffective mode for the assessment of progression 4,16 which is caused by cirrhosis in most of the cases. with this background, not many studies have been conducted evaluating the role of doppler ultrasound in the assessment of chronic liver 2 disease patients in pakistan. likewise, few regional studies have examined the association of doppler parameters of direction and velocity of flow in the 9,18 main portal vein with the child pugh class. o u r s t u d y h a s d e t e r m i n e d t h a t d o p p l e r ultrasonography is a valuable modality for the assessment of portal vein hemodynamics in the pakistani patients suffering from the chronic liver disease. it has established an association between doppler findings of average peak velocity and flow direction in the main portal vein and child pugh classes of cirrhosis. doppler findings of average peak velocity in the main portal vein fell progressively with worsening of the child pugh class. in addition, the direction of flow was also reversed in cases of the child pugh class c cirrhosis. a study by mittal, et al published in 2011, have examined the association of doppler findings of flow velocity and direction in the main portal vein with the child pugh class in the iranian population. this study shows average peak portal venous velocity of 18.33 + 2.22,14.59 + 3.57 and 10.96 + 2.33 cm/s in the child pugh class a, b and c respectively and nonhepatopetal flow (hepatofugal or bidirectional) in 12 appendix i: child pugh classifica�on for liver cirrhosis 36 jiimc 2019 vol. 14, no.1 association of portal vein doppler & child pugh classes of patients with cld iranian journal of radiology. 2011; 8(4): 211. 10. el-shabrawi mhf, el-raziky m, sheiba m, el-karaksy hm, elraziky m, hassanin f, et al. value of duplex doppler ultrasonography in non-invasive assessment of children with chronic liver disease. world j gastroenterol. 2010, 16(48): 6139–44. 11. zytoon aa, allah an, faisal a. the prediction of liver disease status using doppler observations of the hepatic and portal venous system compared with liver biopsy in patients with chronic hepatitis c. research and reports in focused ultrasound. 2014; (2): 1-11. 12. gerstenmaier jf, gibson rn. ultrasound in chronic liver disease. insights imaging. 2014; 5(4): 441-55. 13. afzal s, masroor i, beg m. evaluation of chronic liver disease: does ultrasound scoring criteria help?. int j chron dis. 2013; 31(7), 1-6. 14. memon sk. ultrasonographic findings of liver in chronic liver disease and its complications and their association with the duration of the disease. j coll physicians surg pak. 2017; 27(3): 127-30. 15. rumack cm, levine d. diagnostic ultrasound e-book. elsevier health sciences; 2017. 16. mcnaughton da, abu-yousef mm. doppler us of the liver made simple. radiographics. 2011; 31(1):161-88. 17. iranpour p, lall c, houshyar r, helmy m, yang a, choi ji, et al. altered doppler flow patterns in cirrhosis patients: an overview. ultrasonography. 2016; 35(1): 3–12. 18. afif am, chang jp, wang yy, lau sd, deng f, goh sy et al. a sonographic doppler study of the hepatic vein, portal vein and hepatic artery in liver cirrhosis: correlation of hepatic hemodynamics with clinical child pugh score in singapore. ultrasound. 2017; 25(4): 213-21. 19. chawla y, santa n, dhiman rk, dilawari jb. portal hemodynamics by duplex doppler sonography in different grades of cirrhosis. dig dis sci. 1998; 43(2): 354-7. 20. shi bm, wang xy, mu ql, wu th, xu j. value of portal hemodynamics and hypersplenism in cirrhosis staging. world j gastroenterol. 2005; 11(5): 708-11. 21. vyas k, gala b, sawant p, das hs, kulhalli pm, mahajan ss. assessment of portal hemodynamics by ultrasound color doppler and laser doppler velocimetry in liver cirrhosis. indian j gastroenterol. 2002; 21(5): 176-8. 22. gaiani s, bolondi l, li bassi s, zironi g, siringo s, barbara l. prevalence of spontaneous hepatofugal portal flow in liver cirrhosis. clinical and endoscopic correlation in 228 patients. gastroenterology. 1991; 100(1): 160-7. and subsequent management of the patients suffering from the deadly disease of chronic liver disease in pakistan. conclusion doppler ultrasonography is a valuable modality for assessing the complex hemodynamics of hepatic vasculature (portal vein in our study), in patients with chronic liver disease and its progression as well. doppler findings of average peak velocity in the main portal vein fall progressively with worsening of the child pugh class. in addition, the direction of flow is also reversed in cases of the child pugh class c cirrhosis. the findings of our study are in line with other published studies. refrences 1. butt as. epidemiology of viral hepatitis and liver diseases in pakistan. euroasian journal of hepato-gastroenterology. 2015; 5(1): 43. 2. umar m, bilal m. hepatitis c, a mega menace: a pakistani perspective. journal of pioneering medical sciences. 2012; 2(2): 68. 3. khalid a, farooq jh, jahangir s. hepatitis c virus risk and protective factors in pakistan. lap lambert academic publishing (october, 2017). 4. gupta ak, garg a, khandelwal n. diagnostic radiology: gastrointestinal and hepatobiliary imaging. jp medical ltd; 2017; 215-30. 5. schuppan d, afdhal nh. liver cirrhosis. the lancet. 2008; 371(9615): 838-51. 6. anthony pp, ishak kg, nayak nc, poulsmn he, scheuer pj, sobin lh. the morphology of cirrhosis: definition, nomenclature, and classification. bulletin of the world health organization. 1977; 55(4): 521-40. 7. pugh rn, murray-lyon im, dawson jl, pietroni mc, williams r. "transection of the oesophagus for bleeding oesophageal varices". . br. j. surg. 1973; 60: 646–49 8. samuel do, oluleke i, omotara sm. safety of liver biopsy as a day procedure in abuth zaria, nigeria. j coll physicians surg pak. 2012; 22(10): 675-76. 9. mittal p, gupta r, mittal g, kalia v. association between portal vein color doppler findings and the severity of disease in cirrhotic patients with portal hypertension. 37 jiimc 2019 vol. 14, no.1 association of portal vein doppler & child pugh classes of patients with cld original�article abstract objective: to determine the frequency of jaundice at a cut off level of <2.8 gm/dl of the cord blood albumin in full term babies. study design: descriptive case series study. place and duration of study: this research was done in pediatric department, holy family hospital, th th rawalpindi from 27 july 2013 to 27 january 2014. materials and methods: seventy term neonates, delivered by any mode of delivery and normal birth weights were included. cord blood albumin level was sent. neonates were divided into two groups. group i was having cord blood albumin levels equal to or less than 2.8gm/dl and group ii had level above 2.8gm/dl. they were followed in opd at 72 hrs of life for development of jaundice. jaundice was assessed clinically by kramer dermal zones method and confirmed by serum total bilirubin level estimation. all information was recorded in predesigned proforma. data was analyzed by using spss version 23. chi square was used to calculate frequency of jaundice in two groups of neonates. results: mean cord blood albumin level was 3.23±0.86 gm/dl. frequency of jaundice was significantly high in group i-71.9% versus 15.8% in group ii (p=0.0005). stratification analysis was performed with respect to gender for frequency of jaundice. it was again significantly high in group i compared to group ii, irrespective of sex. (p=.001 and.002 respectively). conclusion: it is concluded that full term babies having cord blood albumin level <2.8 gm/dl are at risk to develop neonatal jaundice. key words: albumin, cord blood, jaundice neonatal. 4 hyperbilirubinemia. it is one of the commonest cause of admission in neonatal units worldwide. bilirubin is produced in reticuloendothelial system as the end product of heme catabolism. biliverdin is formed from heme and is reduced to water insoluble bilirubin. it is then transported bound to albumin to 5 the liver. a study done in karachi reported that neonatal jaundice was the third common cause, accounting 6 for 13.5% of all neonatal admissions. extreme neonatal hyperbilirubinemia has long been known to cause the clinical syndrome of kernicterus, or chronic bilirubin encephalopathy (cbe). kernicterus is commonly characterized by choreoathetoid cerebral palsy (cp), impaired upward gaze, and sensorineural hearing loss, whereas cognition is relatively spared. the chronic condition of kernicterus may be, but is not always, preceeded in the acute stage by acute bilirubin encephalopathy (abe). this acute neonatal condition is also due to hyperbilirubinemia, and is characterized by lethargy and abnormal behavior, evolving to frank neonatal encephalopathy, 7 opisthotonus, and seizures. introduction jaundice is the visible manifestation in skin and sclera of elevated serum bilirubin. neonatal jaundice may not appear until serum bilirubin exceeds 5 to 7 mg/dl. significant neonatal jaundice means any level of bilirubin requiring intervention like 1 phototherapy and exchange transfusion. jaundice is observed during the first week of life in approximately 60% of term and 80% of preterm 2 neonates. a study in west indies showed the incidence of clinically significant jaundice in this age, 3 as 4.6%. n e a r l y 8 % t o 1 1 % o f n e o n a t e s d e v e l o p cord blood albumin as a predictor of significant hyperbilirubinemia in term neonates 1 2 3 rubina zulfqar , tariq mehmood , komal rehman correspondence: tariq mehmood associate professor holy family hospital rawalpindi medical university, rawalpindi e-mail: rzulfqar57@gmail.com 1 department of paediatrics islamabad medical and dental college, islamabad 2,3 holy family hospital rawalpindi medical university, rawalpindi funding source: nil; conflict of interest: nil received: march 04, 2019; revised: november 26, 2019 accepted: december 27, 2019 cord blood albumin as predictor of hyperbilirubinemiajiimc 2020 vol. 15, no.1 37 it is already established from literature, that low levels of serum albumin at the time of birth are a predictor of significant hyperbilirubinemia. the early prediction of jaundice can help in timely intervention and reduction in morbidity and mortality associated with hyperbilirubinemia. in our country less work has been done on this subject. the aim of our study was to determine the frequency of jaundice at a cut off level of <2.8 g/dl of cord blood albumin in full term babies. materials and methods this descriptive case series study was done in pediatric department, holy family hospital (hfh) th rawalpindi from 27 july 2013 to 27th january 2014. seventy neonates delivered in holy family hospital, were included by using consecutive sampling technique. after approval from hospital ethical committee and informed consent from each parent, 2 ml of cord blood was taken for serum albumin and sent to the laboratory. term neonates with gestational age between 37 to 42 weeks, born by any mode of delivery, of both genders and normal birth weights were included. prematurity, rh, or abo incompatibility, already admitted patients and those having crp >6 were excluded from the study. on the basis of cord blood albumin levels, neonates were divided into two groups, one having cord blood albumin less than or equal to 2.8gm/dl(group i) and the other having cord blood albumin more than 2.8gm/dl (group ii). they were followed in opd at 72 hrs of life for development of jaundice. jaundice was assessed clinically by kramer dermal zones method and confirmed by serum total bilirubin level estimation. neonates were assessed for the need of phototherapy/exchange transfusion. data was analyzed by using spss version 23. for qualitative variables like gender and jaundice, frequency and percentages were calculated. chi square was used to calculate frequency of jaundice in two groups of neonates. p value less than 0.5 was significant. q u a n t i t a t i v e va r i a b l e , a l b u m i n l e v e l w a s represented as mean and standard deviation. stratification was done with respect to gender and observed effect on outcome. results out of 70 neonates, 44(62.86%) were male and 26(37.14%) were female. spontaneous vaginal delivery (svd) was the mode of delivery of 49 (70%) and 21(30%) were born by lower segment caesarean section (lscs). the neonates were divided into two groups on the basis of cord blood albumin level. they were followed in opd at 72 hrs of life for development of jaundice. clinically jaundice was observed in 29 (41.43%) neonates at 72 hours of life. mean serum albumin level was 3.23±0.86 gm/dl (25.8 gm/dl) as shown in (table i). there were 32(45.71%) neonates in group i and 38(54.29%) in group ii. comparison of frequency of jaundice among neonates in two groups of cord blood albumin is shown in (table ii). it was significantly high in group i [71.9% (23/32) versus 15.8% (6/38)] as compared to group ii (p=0.0005). stratification analysis was performed with respect to gender for frequency of jaundice. it was again significantly high in group i in both male and female neonates. [p=.001 and.002 respectively (table iii)]. table i: mean serum albumin level in full term neonates table ii: comparison of frequency of jaundice in group i &ii on basis of cord blood serum albumin. (n = 70) spss version 23 (chi-square test = 22.51) jiimc 2020 vol. 15, no.1 38 cord blood albumin as predictor of hyperbilirubinemia discussion in the present study, we assessed the ability of cord blood albumin as a predictor of significant hyperbilirubinemia in neonates. out of 70 babies 32 were in group i and 38 in group ii. frequency of jaundice was significantly high in group i (71.9%) as compared to group ii (15.8%). sex and mode of delivery had no significant correlation with hyperbilirubinemia. jaundice is a common clinical condition and constitutes one of the major causes of morbidity 8 d u r i n g t h e n e o n a t a l p e r i o d . n e o n a t a l hyperbilirubinemia (nh) needs appropriate and timely treatment, no matter whether it arises from 9 physiological or pathological causes. physical examination is not a reliable measure of the blood level of serum bilirubin. the concept of prediction of jaundice offers an attractive option to pick neonates at risk of significant neonatal hyperbilirubinemia. in these situations, it would be desirable, to implement early treatment and thereby minimize the risk of 10 bilirubin dependent brain damage. maisels and kring showed that male sex has more risk of readmission for neonatal hyperbilirubinemia. it could be explained on the basis that in developing countries male children are given more care in comparison to the females, because of the gender 11 discrimination prevalent in the society. our study resembles the study done by taksande et al, which also states that there is no relation between neonatal hyperbilirubinemia and the sex of the 12 baby. in this study 70% neonates were delivered by svd and 30% were born by lscs. taksande et al and aiyappa's studies state that there is no significant association between the mode of delivery and neonatal hyperbilirubinemia, as is seen in our study. 10,12 in our study, frequency of jaundice in neonates was 41.43% at 72 hours of life. in trivedi et al's study, it was 33.88%, who followed full term neonates till 13 seventh day of life. in our study, frequency of jaundice was significantly high in group i71.9% versus group ii-15.8%. (p<0.0005). aiyappa also divided neonates into two groups, based on cord blood serum albumin, but those with serum albumin level >than 2.8gm/dl were labelled as group i, different from our group i. in his study 126 babies were under group 1 and 39 under group 2. jaundice was observed in 34% of neonates from group i and in 71.7% from group ii. the total bilirubin 12 levels were significant in group ii, (p<0.001) . this was consistent with our study. in trividi et al's and reshad m et al studies, cord blood albumin ≤ 2.8gm/dl, like in our study was also a r i s k i n d i c a t o r i n p r e d i c t i n g n e o n a t a l 13,14 hyperbilirubinemia. in studies of choudhary re, meena kj and mishra ak, neonates were divided into 3 groups based on serum levels of <2.8g/dl, 2.8-3.3gm/dl and >3.3gm/dl. in these studies it was found that most of the neonates with albumin less than 2.8 gm/dl developed jaundice within 72 hrs after birth, which was again 15,16,17 similar to our study. in these studies it was concluded that it is probably safe to discharge neonates with levels more than 3.3gm/dl. neeraj rajpurohit et al, in their study found that cord blood serum albumin ≤ 2.6 gm/dl was associated 18 with increased risk of neonatal hyperbilirubinemia . they also took cord serum bilirubin and found it more sensitive than cord serum albumin in predicting significant neonatal hyperbilirubinaemia. cord blood serum bilirubin was not taken in our study. bhat ja and khairy ma in their studies found cord blood albumin as a better and early, indicator of hyperbilirubinemia compared to cord blood bilirubin and bilirubin/albumin ratio. neonates with cord blood albumin < 2.4g/dl and ≤3 g/dl were at risk in 19,20 their studies respectively. neonatal hyper bilirubinemia remains the most common cause for 21 readmission. by predicting the newborns, who are likely to develop significant neonatal jaundice early, we can effectively design and implement the follow-up plan. table iii: comparison of frequency of jaundice in male and female neonates in group i and ii spss version 23 [chi-square test = 12.088 (m), 9.905(f)] jiimc 2020 vol. 15, no.1 39 cord blood albumin as predictor of hyperbilirubinemia neonatal hyper bilirubinemia is a cause of concern for the parents as well as the pediatricians. early discharge of healthy term newborns after delivery has become a common practice because of medical and social reasons and economic constraints. as far as the limitations of our study are concerned, we could have followed the neonates longer, and measured both cord blood bilirubin and albumin levels. so, future studies are suggested comparing cord blood albumin with cord blood bilirubin. conclusion it is concluded from our study that full term babies having cord blood albumin level <2.8 gm/dl are at risk of developing significant hyperbilirubinemia. cord blood albumin can be used as a predictor for hyperbilirubinemia, and for early review of jaundice especially in developing countries, where regular follow up is difficult. references 1. nahar z, shahidullah md, mannan a, dey sk, mitra u, selimuzzaman sm. the value of umbilical cord blood bilirubin measurement in predicting the development of significant hyperbilirubinemia in healthy newborn. bangladesh j child health. 2009; 33(2): 50-4. 2. ambalavanan n, waldemar a, carlo md. jaundice and hyperbilirubinemia in newborn. in: behrman re, kleigman rm, jenson hb, stanton bf, editors. nelson text book of pediatrics. philadelphia: saunders; 2011: 60011. 3. trotman h, henny –harry c. epidemiology of neonatal jaundice at the university hospital of the west indies. west indian med j. 2012; 61(1):37-42. 4. s a n a u l l a h , k h a i sta r a h m a n , m e h d i h e d ayat i . hyperbilirubinemia in neonates: types, causes, clinical examinations, preventive measures and treatments: a narrative review article. iran j public health. 2016 may; 45(5): 558–568. 5. robert m. kliegman, joseph w.st geme iii, nathan j blum, samir s. shah, robert c tasker, karen m. wilson. nelson text book of pediatrics. ed 21, vol 2; 953-54. 6. tikmani ss, warraich hj, abbasi f, rizvi-a, darmstad gl, zaidi a. incidence of neonatal hyperbilirubinemia. trop med int health. 2010; 15(5):502-5. 7. wusthoff jc and loe mi. impact of bilirubin-induced neurologic dysfunction on neurodevelopmental outcomes. semin fetal neonatal med. 2015; 20(1): 52–57. 8. rubartelli f, dani c. neonatal jaundice. in: kurjak a, chervenak fa, editors. textbook of perinatal medicine. new york: informa healthcare; 2006; 1, 58–68. 9. olusanya bo, ogunlesi ta, slusher tm. why kernicterus is still a major cause of death and disability in low-income and m i d d l e i n c o m e c o u n t r i e s ? a r c h d i s c h i l d . 2014;99(12):1117-21. 10. taksande a, vilhekar k, jain m, zade p, atkari s,verkey s. p r e d i c t i o n o f t h e d e v e l o p m e n t o f n e o n a t a l hyperbilirubinemia by increased umbilical cord blood bilirubin. ind medica. 2005; 9(1):5-9. 11. maisels mj, kring e. length of stay, jaundice and hospital readmission.pediatrics. 1998; 101:995-8. 12. aiyappa gkc, shriyan a, raj b. cord blood albumin as a predictor of neonatal hyperbilirubinemia in healthy neonates int j contemp pediatr. 2017; 4(2):503-6. 13. trivedi dj, markande dm, vidya bu, bhat m, hedge pr... cord serum bilirubin and albumin in neonatal hyperbilirubinemia. int. j. int sci. inn. tech. sec. a, 2013; 2(2):39-42. 14. reshad m, ravichander b, raghurman ts. a study of cord blood albumin as a predictor of significant neonatal hyperbilirubinemia in term and preterm neonates int j res med sci. 2016;4(3):887-890. 15. chaudhry re , naveed ka, rahim ak, chaudhry rz. decreased cord blood albumin: a predictor of neonatal jaundice. jiimc 2016; 2(4): 149-52. 16. meena k j, singh s, verma r c, sharma r. utility of cord blood albumin as a predictor of significant neonatal jaundice in healthy term newborns. pediatric 2015; 12(4). 66. 17. mishra ak, sanyasi naidu c. association of cord serum albumin with neonatal hyperbilirubinemia among term appropriate-for-gestational-age neonates. int j pediatr adolesc med. 2018;5(4):142-144. 18. rajpurohit n, kumar s, sharma d, choudhary m, purohit s. to assess predictive value of cord blood bilirubin and albumin for significant neonatal hyperbilirubinemia: a prospective study from india. j pediatr neonatal care. 2015;2(1): 60-65 19. bhat j, sheikh s, ara r. cord blood bilirubin, albumin, and bilirubin albumin ratio for predicting subsequent neonatal hyperbilirubinemia. 2019; 59(5). 20. k h a i r y m . a et a l . ea r l y p re d i c to rs o f n e o n ata l hyperbilirubinemia in full term newborn. paediatrics and neonatology, 2019; 60; 285-90. 21. farhat r, rajab m. length of postnatal hospital stays in healthy newborns and re-hospitalization following early discharge. n am j med sci. 2011; 3(3):146-8. jiimc 2020 vol. 15, no.1 40 cord blood albumin as predictor of hyperbilirubinemia untitled-1 untitled-1 untitled-2 untitled-1 untitled-2 404 not found untitled-2 case�report abstract a 5 years old male child presented with fever, repeated chest infection, short stature and developmental delay. on examination; he had massively enlarged spleen measuring 10 cm below left costal margin. he was advised bone marrow examination by pediatric consultant to find out the cause for splenomegaly. bone marrow examination revealed hypercellular marrow with numerous mononuclear storage cells having fibrillary cytoplasm, morphologically resembling gaucher cells. the bone marrow trephine biopsy also revealed heavy infiltration in the form of sheets of storage cells both interstitial and paratrabecular in distribution. these cells showed strong pas positivity confirming the diagnosis of gaucher disease. key words: enzyme replacement therapy, gaucher disease, glucoceribrosidase, splenomegaly. history of strabismus for which he was operated upon about one and half year ago. there was no family history of similar illness in other siblings. on examination he was afebrile. his occipito-frontal circumference was 40.5cm. he had short neck with 13kg body weight and 96 cm height. spleen was 10 cm enlarged. he was advised bone marrow examination to find out the cause of splenomegaly his blood complete picture showed hypochromia and microcytosis. the x-ray wrist joint showed radiological bone age of 32±06 months. the x-ray skull, chest and pelvis showed no abnormality. bone marrow examination revealed hypercellullar marrow with numerous storage cells mostly mononuclear with occasional binucleated forms; having fibrillary cytoplasm, morphologically resembling gaucher cells. bone marrow trephine biopsy showed moderately hypercellular marrow. there was marked infiltration in the form of sheets of storage cells having granular pink cytoplasm and strong pas positivity; confirming the diagnosis of gaucher disease. in some of the areas the infiltration was in the form of group of cells with interstitial as well as paratrabecular pattern. introduction g a u c h e r d i s e a s e i s t h e m o s t c o m m o n sphingolipidosis. it was first described by philippe gaucher in 1882 in a patient with massive splenomegaly. gaucher disease is the most prevalent form of lysosomal storage disorders with autosomal ressesive mode of inheritance. it is caused by deficiency of enzyme glucocerbrosidase leading to accumulation of its substrate; glucocerebroside in recticuloendothelial cells of the body, also called 1 glucosylceramide. there are three phenotypic presentations of gaucher disease; type1 nonneuropathic is the most common form. it should be considered in all cases of unexplained splenomegaly and hepatomegaly. pancytopenia may occur due to 2 bone marrow suppression. gaucher disease type2and type-3 are characterized by neurological 1 involvement. case report mr muhammad ali ahmad 5 years old boy presented in paeds opd of railway hospital rawalpindi with complaints of fever and repeated chest infection. he had short stature and developmental delay. he was st 1 child of consanguineous marriage. he was born at full term by spontaneous vaginal delivery. he had gaucher disease: a case with unexplained splenomegaly 1 2 3 4 5 6 ahsan ahmad alvi , ayesha nayyar , rabiah asghar , muhammad nadeem akbar khan , ayesha elahi , ammar naqvi correspondence: brig (r) prof dr. ahsan ahmad alvi hod path lab islamic international medical college pakistan railway hospital, rawalpindi e-mail: ahsan.ahmad@riphah.edu.pk 1,2,3,5,6 4 department of haematology/ chemical pathology islamic international medical college pakistan railway hospital, rawalpindi received: nov 15, 2017; revised: feb 05, 2018 accepted: feb 07, 2018 jiimc 2018 vol. 13, no.1 45 fig 1: bone marrow aspira�on smear showing gaucher cells gaucher disease with massive splenomegaly 1 neuropathic gaucher disease type-2 and type-3. in the past the diagnosis of gaucher disease was made by the presence of gaucher cells in the bone marrow aspiration and trepine biopsy. the classical features of these storage cells include a diameter of 20–100μm with eccentrically placed nucleus and striated cytoplasm having “wrinkled tissue paper 5 appearance. the gaucher cells show strong periodic acid-schiff positivity. enzyme assay for βglucoserebrosidase deficiency is the present day gold standard method for the diagnosis of gaucher 5 disease. other investigations include, blood complete picture, liver function tests , serum ferritin levels, ultrasound abdomen, chest x-ray, x-ray lower limbs and magnetic resonance imaging (mri) of 5 bone and abdomen. imiglucerase as enzyme replacement therapy (ert) is available for gaucher's 6 disease, but is expensive. conclusion gaucher disease should be one of the differential diagnoses in all age group patients with unexplained 7 splenomegaly. bone marrow transplantation is the only curative option in these patients with gene therapy as the future therapeutic modality. references 1. stirnemann j, belmatoug n, camou f, serratrice c, froissart r, caillaud c, et al. a review of gaucher disease pathophysiology, clinical presentation and treatments. international journal of molecular sciences. 2017; 18 : 441. 2. shafiq m, danish a, iqbal h. an unusual case of adult type gaucher’s disease. journal of rawalpindi medical college (jrmc). 2013; 17 : 306-7. 3. thomas as, mehta a, hughes da. gaucher disease: haematological presentations and complications. bjh. 2014; 165: 427-40. 4. grabowski ga. gaucher disease and other storage disorders. american society of hematology. 2012; 2012: 13–8. 5. nagral a. gaucher disease. journal of clinical and experimental hepatology. 2014; 4 : 37-50. 6. shah u, nadeem n, husen y, fadoo z. imiglucerase treatment in gaucher disease. j ayub med coll abbottabad. 2007; 19: 56-9. 7. binesh f, yousefi a, ordooei m, ma b. case report gaucher’s disease , an unusual cause of massive splenomegaly , a case report. 2013; 3: 173–5. discussion gaucher disease is the most prevalent form of lysosomal storage disorders with autosomal recessive inheritance. its prevalance is around 1/40,000 to 1/60,000 births in general population. the highest incidence is in ashkenazi jews, 1 in 850 1 individuals. it is characterized by accumulation of glucocerebroside in the macrophages due to deficiency of enzyme β-glucoserebrosidase. 90% of the gaucher disease patients present with moderate 3 to massive splenomegaly. the molecular genetics of gaucher disease involves gba1 gene, located on chromosome 1 (1q21). more than 400 mutations have been found in the gba1 gene. the common mutations in ashkenazi jews 1 comprised of n370s, l444p and 84gg. the n370s allele is also prevalent in other population of europe, 4 north america, and israel. l444p mutation in homozygous state is strongly associated with fig 2: bone marrow trephine biopsy showing sheets of gaucher cells fig 3: bone marrow trephine biopsy showing gaucher cells with diffuse pas posi�vity 46 jiimc 2018 vol. 13, no.1 gaucher disease with massive splenomegaly page 50 page 51 editorial rheuminations 1 2 prashant kaushik , aarya a. kaushik i'll be honest…it has been 35+ years since i started medical school [mbbs]. and in the realm of medicine at large, and immunology/rheumatology in specific, we are still struggling to find a 'cure' for chronic systemic inflammatory immune-mediated diseases also known as 'autoimmune rheumatic diseases (ard)'. rheumatology is still in its cradle having gotten the recognition as a subspecialty of medicine only in 1972. i have seen the field evolve in terms of understanding the orchestrated 'play' of the immune cells along with cytokines etc. over the past 3 decades, all of which has led to the concept and birth of 'biologic' disease modifying anti-rheumatic drugs [b-dmards]. the first b-dmard to get approved by the food and drugs administration [fda] was etanercept, a tnf-alpha receptor fusion protein in 1998. infliximab, a chimeric monoclonal antibody against tnf soon followed in 1999. ever since then, there has been a flurry of b-dmards including 3 more in the same family of tnfantagonists, 2 in the interleukin [il]-6 antagonist class, 1 blocker of the second co-stimulatory t-cell signaling: ctla-4ig, 3 il-1 antagonists, b-cell depleting chimeric monoclonal antibody directed against cd-20 etc. also, 3 oral janus-kinase inhibitors have joined the 'gang' and are called targeted synthetic dmards. i still remember the pre-b-dmard era when rip roaring rheumatoid arthritis was still around, and with my ustaad saheb (mentor), all what we had to offer pharmaceutically were the conventional synthetic [cs] dmards including methotrexate, hydroxychloroquine, sulfasalazine, leflunomide and [the younger generation can hold their breath] cyclosporine, d-penicillamine, chlorambucil…gold i n j e c t i o n s a n d e v e n c y c l o p h o s p h a m i d e ! st corticosteroids have been around since 1950! the 1 and “so far” […well, i/you might be next one!] the only nobel prize winning revelation in the realm of rheumatology. the availability of the b-dmards has changed the entire paradigm of pharmaceutical treatment in rheumatology. they are all quite effective yet extremely expensive making them literally unaffordable in the parts of the world, where healthinsurance coverage is suboptimal/non-existent, more so, given the indefinite duration of therapy. although the b-dmards tend to target a specific pathway in the immune system, they are still fraught with some rather challenging adverse drug effects (ade) including infections: bacterial, mycobacterial [especially reactivation of tuberculosis, more so, in the parts of the world where this disease is endemic] fungal and from other pathogens; malignancies, increased incidence of cardiovascular and cerebrovascular events, thromboembolic events etc. all in all, b-dmards are a double-edged sword! they all come with 'a price to pay'! now, let's reflect upon the burden of ard in the community. rheumatoid arthritis, a potentially crippling and life-threatening disease affects at least 1% of the population, with more than 13 million patients in america itself! axial and peripheral spondyloarthritis is now being recognized more and more. various other autoimmune diseases including systemic lupus erythematosus, sjogren's syndrome, scleroderma, autoimmune myopathy including dermatomyositis and polymyositis, vasculitides, and some more novel entities like igg-4 related disease, checkpoint-inhibitor chemotherapy associated rheumatic diseases: the list continues to grow! what can be done to prevent, slow, stop and reverse ard? in fact, the answer is the other side of the question itself! human body has a tremendous capacity of healing itself! only, if we are willing to make healthy choices. truth is self-effulgent! it does correspondence: dr. prashant kaushik, mbbs chief of rheumatology, nhs, tahlequah, ok associate professor of medicine, osu chs cn associate program director, im residency, nhs e-mail: prashantkaushik2508@gmail.com received: november 29,2022; accepted: december 14, 2022 236 1 prashant kaushik mbbs, mnams, facp, facr, rh msus 2 aarya a. kaushik a.b. candidate '24, harvard university english and music secondary in global health and health policy staff writer, the harvard crimson poetry editor, the harvard advocate research associate, joslin diabetes center doi: https://doi.org/10.57234/1621 not require a lab-proof! however, as 'scientists', we are always inclined to see/measure the outcomes. well, it is out there now! systemic inflammatory diseases can be prevented and reversed!!! here are the revelations about some of these ailments including coronary heart disease, diabetes mellitus and even prostate cancer from just a few extremely humbling articles published quite recently. the lifestyle heart trial showed that it is possible to significantly reduce coronary stenoses and risk of cardiac events using aggressive lifestyle changes, and without lipid-lowering medications. a strong doseresponse relationship between self-reported adherence and angiographic changes was found, with excellent adherence during the study. overall, self-reported adherence was highly correlated with 1 percentage of stenosis. it has also been shown that an intense lifestyle treatment can reduce the 2 expenses on cardiac health/procedures drastically. interestingly, adherence to a whole food plant-based nutritional program was found to be more important than the type of diet consumed. more adherent subjects showed greater improvements in weight and cardiac parameters. thus, the intensity of the intervention may be more important than the 3 specific diet for weight loss. by limiting the daily caloric consumption to 600 c a l o r i e s , d e c r e a s e d p a n c r e a t i c a n d l i v e r triacylglycerol stores, improved maximal insulin 4 sensitivity. it's very humbling! , a 12-the dietfits month randomized clinical trial demonstrated that epigenetics must be part of the measures assessed in lifestyle diet intervention studies. diet determines 5 the expression of many genes! the direct study was the first large rigorous trial to show such success in remission of diabetes in a clinical practice setting. diabetes-remission was strongly associated with weight loss in a dose 6,7 response relationship. a fasting-mimicking diet (fmd) demonstrated that the power of dietary interventions may include reprogramming of tissues to restore lost metabolic function, such as beta cells in the pancreas. once confirmed in humans, this could elevate lifestyle medicine intervention as a 'primary' modality for type 2 diabetes mellitus treatment. also, should this treatment lead to beta-cell neogenesis in humans, it 8 could make type 1 diabetes mellitus reversible. from diabetes 'care' to diabetes 'cure': in a seminal article published about 5 years ago, creative ways to implement lifestyle interventions were reiterated. those services would include coaching, information, 9 and communications technology. intensive nutrition and lifestyle changes can even 10 modulate gene expression in the prostate cancer. so, in a nutshell, all chronic lifestyle mediated diseases have systemic inflammation, alteration in the gut microbiome, oxidative stress, allostatic load, and many other features in common! well, then the answer becomes simple! it is possible to prevent, slow, stop the progression and even reverse all these diseases with 'the exact same' 4-pronged approach: eat well, move more, think right, and love all! the s a g e g e n e r a t i o n a l w i s d o m o f d a d i / n a n i (grandmothers) has no ade! it's work, yes, but 'its works'! references 1. ornish d, scherwitz lw, billings jh, et al. intensive lifestyle changes for reversal of coronary heart disease. jama. 1998 dec 16;280(23):2001-7. doi: 10.1001/jama.280.23.2001. erratum in: jama 1999 apr 21;281(15):1380. pmid: 9863851. 2. hambrecht r, walther c, möbius-winkler s, gielen s et al. percutaneous coronary angioplasty compared with exercise training in patients with stable coronary artery disease: a randomized trial. circulation. 2004 mar 23;109(11):1371-8. doi: 10.1161/01.cir.0000121360.31954.1f. epub 2004 mar 8. pmid: 15007010. 3. dansinger ml, gleason ja, griffith jl, selker hp, schaefer ej. comparison of the atkins, ornish, weight watchers, and zone diets for weight loss and heart disease risk reduction: a randomized trial. jama. 2005 jan 5;293(1):43-53. doi: 10.1001/jama.293.1.43. pmid: 15632335. 4. lim el, hollingsworth kg, aribisala bs, chen mj, mathers jc, taylor r. reversal of type 2 diabetes: normalisation of beta cell function in association with decreased pancreas and liver triacylglycerol. diabetologia. 2011 oct;54(10):250614. doi: 10.1007/s00125-011-2204-7. epub 2011 jun 9. pmid: 21656330; pmcid: pmc3168743. 5. gardner cd, trepanowski jf, del gobbo lc, et al. effect of low-fat vs low-carbohydrate diet on 12-month weight loss in overweight adults and the association with genotype pattern or insulin secretion: the dietfits randomized clinical trial. jama. 2018 feb 20;319(7):667679. doi: 10.1001/jama.2018.0245. erratum in: jama. 2018 apr 3;319(13):1386. erratum in: jama. 2018 apr 24;319(16):1728. pmid: 29466592; pmcid: pmc5839290. 6. lean me, leslie ws, barnes ac, et al. primary care-led weight management for remission of type 2 diabetes (direct): an open-label, cluster-randomised trial. lancet. jiimc 2022 vol. 17, no.4 237 doi: https://doi.org/10.57234/1621 2018 feb 10;391(10120):541-551. doi: 10.1016/s01406736(17)33102-1. epub 2017 dec 5. pmid: 29221645. 7. adamson aj, sniehotta ff, mathers jc, et al. primary careled weight management for remission of type 2 diabetes (direct): an open-label, cluster-randomised trial. lancet. 2018 feb 10;391(10120):541-551. doi: 10.1016/s01406736(17)33102-1. epub 2017 dec 5. pmid: 29221645. 8. cheng cw, villani v, buono r, et al. fasting-mimicking diet promotes ngn3-driven β-cell regeneration to reverse diabetes. cell. 2017 feb 23;168(5):775-788.e12. doi: 10.1016/j.cell.2017.01.040. pmid: 28235195; pmcid: pmc5357144. 9. van ommen b, wopereis s, van empelen p, et al. from diabetes care to diabetes cure-the integration of systems biology, ehealth, and behavioral change. front endocrinol ( l a u s a n n e ) . 2 0 1 8 j a n 2 2 ; 8 : 3 8 1 . d o i : 10.3389/fendo.2017.00381. pmid: 29403436; pmcid: pmc5786854. 10. ornish d, magbanua mj, weidner g, et al. changes in prostate gene expression in men undergoing an intensive nutrition and lifestyle intervention. proc natl acad sci u s a. 2 0 0 8 j u n 1 7 ; 1 0 5 ( 2 4 ) : 8 3 6 9 7 4 . d o i : 10.1073/pnas.0803080105. epub 2008 jun 16. pmid: 18559852; pmcid: pmc2430265. jiimc 2022 vol. 17, no.4 238 doi: https://doi.org/10.57234/1621 jiimc december 2015 final new.cdr original article abstract objective: to determine the histomorphogical effects of radiations from conventional and advanced mobile phones on the developing kidney of chick embryo. study design: randomized control trial. place and duration of study: the study was conducted at army medical college, (nust), rawalpindi, pakistan from january 30, 2012 to january 30, 2013. materials and methods: fifty fertilized, zero day, off white colored eggs of fayoumi breed were selected according to inclusion criteria. two groups ii and iv were exposed to conventional mobile phone radiations, and two groups iii and v were exposed to advanced mobile phone radiations for 15 and 30 minutes per 24 hours respectively. group i was the control. the data was analyzed by spss 17 and, anova test was applied to determine statistical significance. results: the mean proximal and distal tubular diameters were decreased in the experimental groups. the mean proximal tubular diameter decreased significantly when comparing group i with groups ii, iii, iv and v and no statistical significance was found when comparing the experimental groups. the mean proximal luminal diameter decreased in experimental groups with statistically significant result between groups i and iii and between i and v showing that the effects were more in advanced cell phone groups when compared with the control. regarding distal tubular diameter the results were statistically significant between i and iii, ii and iii and ii and iv. mean distal luminal diameter decreased in the experimental groups with statistically significant result when comparing ii and iv and, iv and v. the distal tubules responded to either the increase in the time of exposure from 15 to 30 minutes or when the chick embryo was exposed to advanced cell phone radiations as the results were more significant between the experimental groups, where p<0.05 was considered significant. conclusion: from this experimental study we can conclude that prolonged exposure to mobile phone radiations can lead to decrease in tubular as well as luminal diameter in the proximal and distal tubules of the developing kidneys of chick embryo. key words: mobile phones, chick embryo, metanephros. cancer development. one such interphone study was carried out by cradis e et al, (2010) to observe the association of gliomas, schwanomma, parotid 1 tumors and meningioma. the results were unconvincing because of the faulty study design and methodology. an increased risk of glioma after ten years or more use of cell phones was reported in a 2 study carried out in germany moreover, another study showed that there was no risk of acoustic 3 neuroma in the first ten years of cellular phone use. in some studies, the harmful effects of these radiations were seen. the reproductive capacity of drosophila melanogaster was observed to be 4 decreased after mobile phone radiation exposure. a study was conducted on 77 university students and 5 deranged values of tsh and t4 were found. in few studies the radiations were useful like in bone 6 healing and in some, there were found no increased risk of salivary gland tumors because of the mobile introduction the electromagnetic radiations from the mobile phone are classified as 2b, by international agency for cancer research (iarc), which means it is a possible carcinogenic. there have been a number of epidemiological studies conducted, looking for a relationship between cell phone use and brain effects of cell phone radiations on the metanephros tubules in a chick embryo model 1 2 3 4 5 sabah rehman , shadab ahmed butt , naureen waseem , hina kundi , abdul rasool qamar effects of cellular radiations in a chick embryojiimc 2015 vol. 10, no.4 correspondence: dr. saba rehman department of anatomy army medical college, nust, islamabad e-mail: sabahrehman@live.com 1,2,5 department of anatomy army medical college, nust, islamabad 3 department of anatomy al nafees medical college, isra university islamabad 4 department of anatomy margalla institute of health sciences islamabad received: february 11, 2015; accepted: november 15, 2015 275 7 phone induced radiations. the effects of increased usage of these modern and advanced cell phones have been questioned by 8 agarwal et al. who studied the effects of cell phone radiation on male fertility. prenatal exposure of 900mhz to rat kidney resulted in increase in kidney volume and decrease in number of glomeruli 9 (ulubay, 2015). the current study was conducted to observe and compare the effects of the radiations from the two types of cell phones. one using conventional mobile phone, will be exposed to the gsm radiations, whereas the advanced mobile phone user will be exposed to both type of radiations as it is used for multipurposes (voice and message communication, internet usage). as cell phones are kept close to body, the kidneys are essentially exposed to the radiations. the developing tissue is exposed as well, and the pregnant women are prone to get exposure and can later have an effect on the developing fetal tissues. the study was conducted to observe how cellular radiations can effect the renal histomorphology of a developing renal tissue. the additional features in a cell phone expose the tissues to radiations of wi-fi and bluetooth. keeping in view, the study was conducted to observe the effects of the simple and conventional talk and text cell phones and, advanced and modern cell phones on the developing renal tissue. materials and methods the study was carried out in army medical college rawalpindi in collaboration with poultry research th institute rawalpindi for one year 30 january 2012 to th 30 january 2013. the experiment was carried out with permission of ethical committee on animal experiments, of the army medical college, rawalpindi. it was a randomized lab based control trial. fifty fertilized eggs were divided into five groups, by simple random sampling. a still-air incubator which was wooden and manual, with measurements of 24 inch (length) x 24 inch (width) x 12.5 inch (height) and having capacity of 100 eggs was used for the project. zero day eggs were bought for experimental purpose. fertile eggs of normal shape i.e., oval, off-white colored and medium sized of fayoumi breed were selected and 10 incubated at 37 ºc and humidity range of 5060%. unfertilized, refrigerated, abnormal shaped eggs (foot-ball shaped, pear shaped), eggs with color other than off-white and, tiny sized eggs were excluded. group i (control), group ii (experimental, 15 minute gsm radiation exposure), group iii (experimental, 15 minute gsm and wi-fi radiation exposure), group iv (experimental, 30 minute gsm radiation exposure), group v (experimental, 30 minute gsm and wi-fi radiation exposure). the temperature was monitored by mercury thermometer. the humidity was maintained by filling the plastic pans with water and monitored by hygrometer. the eggs were marked with 'x' on one side and 'o' on the other side with lead pencil so that egg turning is not missed. they were turned thrice a day manually, after every eight hours. the time of exposure to gsm radiations was 15 minutes (23 missed calls) and 30 minutes (45 missed calls), daily, in the ii and iv groups in groups iii and v, the gsm exposure was for 15 minutes (23 missed calls) daily. in group iii, wi-fi radiations were induced by downloading files for 15 minutes. in group v, the time of exposure to gsm radiations was 30 minutes (45 missed calls) and to wi-fi radiations was also 30 minutes daily. after 15 days incubation, the chick embryos were dissected by crack opening the shell at the broader end. the inner and outer shell membranes were removed and, the living embryos were decapitated and fixed in 10 % formalin for 48 hours and after fixation. they were dissected and the kidneys were exposed in the posterior abdominal wall of the chick embryo. then they were processed and embedded. tissues were cut into 5 microns thick sections. the sections were stained with hematoxylin and eosin (h&e) for routine histological study of kidney (fig 1) and pas stain to see the basement membranes and brush border of cells. micrometry was carried out for measurement of the diameters and epithelial height. maximum tubular diameter was taken from the basement membrane of the cells on one side to the basement membrane of the cells on the opposite side in rounded tubules. three tubules in were selected randomly in three different fields (one tubule in one field) at x40 in one slide per specimen. the external diameter of tubule was measured by oculometer. three readings per slide were taken and their average as final reading for that specimen. jiimc 2015 vol. 10, no.4 effects of cellular radiations in a chick embryo 276 maximum luminal diameter was taken from the apical surface of one cell to the apical surface of the opposite cell in the rounded tubules and same procedure repeated. the data was entered in data base using start package for social services (spss version 17). the results were expressed as mean and standard error of mean. the significance difference was determined using one way analysis of variance (anova) for multiple comparisons. results were considered significant at p<0.05. results the (h&e) stained slides were observed for changes in the histomorphology of developing metanephros of chick embryo. mean tubular (external) and mean luminal (internal) diameters of proximal tubules in the control group, in metanephros were 40.53±.08µm and 12.51±1.00µm respectively. the proximal tubular diameters were decreased in all the experimental groups. the mean proximal tubular diameter in the metanephric tissue of the experimental groups is mentioned in table ia. the results of proximal tubular diameters were statistically significant when comparing control group i with the experimental groups and comparable between groups ii and iii, ii and iv, and iii and v. the mean proximal luminal diameter in metanephric tissue of experimental groups are mentioned in table ib. the results were statistically significant between groups i and iii and between i and v (table i). mean tubular (external) and mean luminal (internal) diameters in the distal tubules of the control group in the metanephric tissue were 25.84±1.04µm and 9.06±0.38µm respectively. the mean distal tubular diameter of the metanephric tissue in experimental groups are mentioned in table iia. the values of mean in experimental groups were lower than the control group. the results of distal tubular diameter of metanephros were decreased in the experimental groups and statistically significant between groups i and iii, groups i and v, groups ii and iii and between groups ii and iv. the mean distal luminal diameter in the distal tubules of metanephric tissue in experimental table ia: proximal tubular diameter in control and experimental groups ii, iii, iv and v (metanephros) table ib: proximal luminal diameter in control and experimental groups ii, iii, iv and v (metanephros) jiimc 2015 vol. 10, no.4 effects of cellular radiations in a chick embryo 277 groups is mentioned in table iib. the results were statistically significant between group ii and iv and, group iv and v. discussion the current study focused on the tubular and luminal diameter of the proximal and distal tubules of the developing metanephros. the tubular diameters were observed to be decreased in the experimental groups. the diameters decreased in all the experimental groups showing that there is effect of electromagnetic radiations on the diameters of developing tubules. in case of proximal tubular diameter the results showed that the diameter decreased statically in experimental groups than the control and proximal luminal diameter decreased also in the experimental groups with statistically significant result between i and iii and i and v showing advanced cell phone radiations was affecting the internal diameters. the mean distal tubular and luminal diameters decreased in the experimental groups but a trend of added decrease in mean diameter of tubules both externally and internally was noted in the group iii. table iia: distal tubular diameter in control and experimental groups ii, iii, iv and v (metanephros) table iib: distal luminal diameter in control and experimental groups ii, iii, iv and v (metanephros) fig 1: photomicrograph showing mesonephros (me) and metanephros (mt) in control group, lumen of tubules of mesonephros is more prominent (h&e, approx. x 200) fig 2: metanephros in control group at 400x, h&e, p=proximal, d=distal tubules fig 3: photomicrograph of metanephros in experimental group (iv), (h&e, approx. x 400) p; proximal tubule, d; distal tubule jiimc 2015 vol. 10, no.4 effects of cellular radiations in a chick embryo 278 that led to an aspect of study already seen in effects of gsm radiations on chick embryo growth in which emfs exposure to them delayed the process of growth in the exposed embryos, there was a partial and then a trend of growth enhancement on progressively increasing the exposure levels was 11 noticed. the tubules appeared to recover from growth disruption after increase in the time of exposure as seen in the propensity of increase in the mean diameters in group iv and v in both proximal and distal tubular diameters. hence, the advanced cell phone radiations after 15min/day exposure for 15 post-incubation days affected the development of the tubules of metanephros by decreasing their diameters hence, retarding the growth more as compared to conventional mobile phone radiations. whereas, after 30min/day exposure for 15 postincubation days, the tubular diameters showed improvement, depicting growth enhancement, that was more prominent after exposure to conventional mobile phone radiations than after advanced mobile phone radiations exposure. 12 al-glaib (2008) observed increase in the tubular diameters in mice kidney because of gsm mobile phone radiations but accini et al in 1988 in his study on effects of electromagnetic radiations on rabbits 1 3 o bs e r ve d n e c ro s i s o f t h e re n a l t u b u l e s . degeneration of renal tubules was noted in a study after exposure to electromagnetic radiations in mice 14 for, 12 days. moreover, study can be conducted further on other developing tissues in chick embryo or other animal model and effects can be correlated. conclusion from this experimental study we can conclude that prolonged exposure to mobile phone radiations can lead to decrease in tubular as well as luminal diameter in the proximal and distal tubules of the developing kidneys of chick embryo. references 1. cardis e, deltour i, vrijheid m, combalot e, moissonnier m, tardy h et al. brain tumor risk in relation to mobile telephone use: results of the interphone international case-control study. int. j. epidemiol. 2010; 39: 675-94. 2. schuz j, bohler e, berg g, schlehofer b, hettinger i, schlaefer k et al. cellular phones, cordless phones, and the risks of glioma and meningioma (interphone study group, germany). am. j. epidemiology. 2006; 163: 512-20. 3. schoemaker mj, swerdlow aj, ahlbom a, auvinen a, blaasaas kg, cardis e et al. mobile phone use and risk of acoustic neuroma: results of the interphone case control study in five north european countries. british journal of cancer. 2005; 93: 842-8. 4. panagopoulos dj. effect of microwave exposure on t h e o v a r i a n d e v e l o p m e n t o f d r o s o p h i l a melanogaster. cell biochem. biophys. 2012; 63: 12132. 5. mortavazi s, habib a, karami ag, doost rs, pour abedi a, babaie a. alteration in tsh and thyroid hormones following mobile phone use. oman med. j. 2009; 24: 274-8. 6. satter ss, islam ms, rabbani rs, talukder ms. pulsed electromagnetic fields for the treatment of bone fractures. bangladesh med. rescounc. bull. 1999; 25: 6-10. 7. hardell l, hallquist a, hansson m, carlberg m, gertzen h, schildt e et al. no association between the use of cellular or cordless telephones and salivary gland tumours. occup. environ. med. 2004; 61: 6759. 8. agarwal a, singh a, hamada a, kesari k. cell phones and male infertility: a review of recent innovations in technology and consequences. international. braz. j. urol. 2011; 37: 432-54. 9. ulubaya m, yahyazadehb a, denizb og, kıvrakb eg, altunkaynakb bz, erdemb g et al. effects of prenatal 900 mhz electromagnetic field exposures on the histology of rat kidney. international journal of radiation biology; 2015; 91: 35-41. 10. hamburger v, hamilton hl. a series of normal stages in the development of the chick embryo. journal of morphology; 1951; 88: 49-92. 11. zareen n, khan my, minhas la. dose related shifts in the developmental progress of chick embryos exposed to mobile phone induced electromagnetic fields. j ayub med coll abbottabad. 2009; 21: 1130-4. 12. al glaib b, al dardfi m, al tuhami a, elgenaidi a, dkhil m a technical report on the effect of electromagnetic radiation from a mobile phone on mice organs. libyan j med. 2008; 3: 8-9. 13. accinni l, de martino c, mariutti g. effects of radiofrequency radiation on rabbit kidney: a morphological and immunological study. exp. mol. pathol. 1988; 49: 22-37. 14. khayyat li. the histopathological effects of an electromagnetic field on the kidney and testis of mice. eurasia j. biosci. 2011; 5: 103-9. jiimc 2015 vol. 10, no.4 effects of cellular radiations in a chick embryo 279 original�article abstract objective: to determine the treatment outcomes of tuberculosis patients registered under directly observed treatment short course (dots) program at holy family hospital, rawalpindi. study design: descriptive case series. place and duration of study: tb dots clinic, holy family hospital, rawalpindi from september 2015 to march 2016. materials and methods: a total of 75 tuberculosis patients were enrolled by consecutive sampling. data was collected by means of structured proforma in which demographic details of patients were entered along with information regarding site of tb and treatment outcomes and success of outcomes. “cured” was labeled for those patients who finished six months treatment with negative sputum microscopy result for acid fast bacillus (afb) at the end of treatment. “treatment completed” was labeled for those patients who finished six months treatment, but no sputum microscopy result for afb at the end of treatment. data was analyzed using spss version 17. results: majority (61.3%) of patients coming to tb center were females showing increased frequency of women having tuberculosis in the setting. most of the patients belonged to urban area i.e. 65.3%. in our study, a healthy finding was observed that the commonest treatment outcome was treatment completed (65.3%) followed by 21.3% of cured ones and treatment failure was very low (2.7%). conclusion: majority of the tuberculosis patients registered under directly observed treatment short course program at holy family hospital, rawalpindi had successful treatment outcomes. it is recommended that patients with unsuccessful treatment outcomes should be followed up for health education as well as treatment accordingly. key words: dots, tuberculosis, outcomes. incidence of tb by 2015”. the most important & effective measure to control tb is early detection of tb and completing treatment of those who get diagnosed of disease and get cured. most of tb mortality and morbidity (95%) is reported in low and 3 middle-income countries. pakistan ranks fifth amongst “22 high burden countries (hbcs)”, contributing around 63% of disease burden in e a s t e r n m e d i t e r r a n e a n r e g i o n ( e m r o ) . government of pakistan initiated “dots strategy (directly observed treatment short course)” recommended by who for effective control of this menace in 1995 and declared tb a national health 4 emergency in 2001. lot of researches have been carried out globally on the tb treatment outcomes, as evident by a study conducted in ethiopia which has evaluated pattern of tuberculosis and its “treatment outcomes” over past few years. 64.6% were declared as treatment completed, 18% as 3 cured, 5.1% defaulted, 5.4% transferred out. a study introduction world health organization (who) announced tuberculosis (tb) as a worldwide “public health 1 emergency” in 1993. tuberculosis (tb) is one of the 2 most debilitating diseases of the world. global health report of who, 2010 shows 9.4 million patients of tuberculosis in overall world. mdgs target set for tb control is to “halt and reverse the treatment outcomes of tuberculosis patients under directly observed treatment short course program at a tertiary care hospital of rawalpindi 1 2 3 farhan hassan , sidra tul muntaha , fazal mahmood correspondence: dr. farhan hassan senior demonstrator department of community medicine rawalpindi medical university, rawalpindi e-mail: farhan.25hd@hotmail.com 1 department of community medicine rawalpindi medical university, rawalpindi 2 department of pediatrics yusra medical & dental college, islamabad 3 department of community medicine hbs medical & dental college, islamabad funding source: nil; conflict of interest: nil received: january 24, 2019; revised: may 12, 2019 accepted: may 14, 2019 treatment outcomes of tuberculosisjiimc 2019 vol. 14, no.2 56 outcomes were labeled as “successful” if it came out to be either “cured” or “treatment completed”; and as “unsuccessful” if came out to be as “treatment failure”, “defaulted”, “died” or “transferred out”. “cured” was labeled for those patients who finished six months treatment with negative sputum microscopy result for acid fast bacillus (afb) at the end of treatment. “treatment completed” was labeled for those patients who finished six months treatment, but no sputum microscopy result for afb at the end of treatment. “treatment failure” was labeled for those patients who remained sputum positive for afb at five months despite correct intake of medication. “defaulted” was labeled for those patients who interrupted their treatment for two consecutive months or more after registration. “died” was labeled for those patients who died during the course of treatment. “transferred out” was labeled for those patients whose treatment outcomes are unknown due to transfer to another health facility. the data was entered and analyzed in statistical package for social sciences (spss) version 17. frequency and percentages were calculated for variables like gender, age categories, treatment outcomes and success of outcomes. results total of 75 patients participated in the present study, out of them 29 were males and 46 were females. out of 75 patients, 34 patients were aged between 18-25 years as shown in table no. i. 26 were from rural areas and 49 from urban areas. 27 patients were pulmonary sputum positive and 12 were pulmonary sputum negative and 36 were extra pulmonary cases. frequency of treatment outcome and success of outcome is shown in table ii and iii respectively. cross tabulations of success of outcome with age category and gender is shown in table iv and v respectively. of india showed that with dots, the cure rate was 2 94.6%. a similar study has been carried out in karachi on tb treatment outcomes which showed successful outcome in 47.2% patients and 47.2% were lost to follow up and defaulted, 5.6% were 5 treatment failure. a study done in kohat showed 32.6% cure rate, 41.3% treatment completed and 6 25% default rate. the key to control of tb includes case finding as early as possible and its prompt treatment. monitoring of treatment outcomes is important to evaluate dots programme which in turn prevents development of 7 resistant tb. the present study was aimed to evaluate the dots program in a tertiary care setup in terms of assessment of treatment outcomes of tb patients registered under dots programme at holy family hospital, rawalpindi. this will add to the current knowledge about dots program efficiency in study setting in terms of treating tb patients to achieve successful treatment outcomes. this study will be helpful for public health authorities to take action accordingly as per who standards. materials and methods it was a descriptive case series conducted at tb dots clinic, holy family hospital, which is a tertiary care teaching hospital attached with rawalpindi medical university, rawalpindi, pakistan. duration of study was six months (from september 2015 to march 2016). non probability consecutive sampling was used and sample size was 75. all newly diagnosed cases of pulmonary as well as extrapulmonary tuberculosis of both male as well as female gender aged 18-65 years were included in study. cases transferred-in from other health facilities were excluded from the study. data was entered in proforma. age, sex, place of residence and site of tuberculosis were entered in proforma. all the patients underwent six months treatment for tuberculosis using anti-tuberculosis therapy (att). during initial two months (intensive phase), four drugs namely isoniazid, rifampicin, ethambutol and pyrazinamide were given. only two drugs isoniazid and rifampicin were given in next four months treatment (continuation phase). patients were followed till the end of the treatment course and relevant information was entered in proforma. finally “treatment outcomes” were entered by the conclusion of treatment course. treatment table i: age distribu�on jiimc 2019 vol. 14, no.2 treatment outcomes of tuberculosis 57 incidence of women having tuberculosis in the settings. risk of tuberculosis in females may be clarified by the difference in exposure to mycobacterium tuberculosis which in turn may be related to gender specific differentiation of labor, traditional seclusion practices and socialization arrangements. higher frequency of advanced disease might be observed due to poorer quality of health of females compared to males with respect to n o u r i s h m e n t . a c c o r d i n g t o wo r l d h e a l t h organization (who), at few places, for example iran, afghanistan and areas of pakistan bordering afghanistan, higher number of females in comparison to males are diagnosed as tb patients, however worldwide, considerably higher number of males in comparison to females develop the disease 8 and expire due to tb per annum. similar results were seen in the province of yazd, in iran, where average yearly rate of tb was higher in females being 31.0 per 9 100,000. demographics of tuberculosis in district mansehra also showed that most of the patients registered at the district tuberculosis control office (dto) were females (57%) as compared to males 10 (43%). in our research work, most of the study population belonged to urban area i.e. 65.3%. this portrayal is alike to most countries with low-incidence and 11 selected high-incidence countries. certain social conditions may have an effect on urban localities, for instance, homelessness or those conditions that make other residents prone to tuberculosis, like high population density and deteriorating public health infrastructures. health facilities in city localities may be in somewhat easy range. in rural localities, patients have to move from far flung areas every so often. another positive result was found in a study conducted in usa where frequency in big metropolises stayed greater than double, compared to what was stated for other areas of usa. insistently, more frequency of tb in big cities was linked to presence of risk factors in people, for advancement 12 to tuberculosis. another finding portrayed by our investigation was site of tuberculosis where the most common site was extra pulmonary tuberculosis (48%). this is line with another research conducted in usa on extra pulmonary tuberculosis (eptb) depicting that though there is a decline reported in the occurrence discussion in our study, majority (61.3%) of patients coming to tb centers were females showing increased table ii: frequency of treatment outcomes table iii: frequency of success of outcome table iv: cross tabula�on of success of outcome with age table v: cross tabula�on of success of outcome with gender jiimc 2019 vol. 14, no.2 treatment outcomes of tuberculosis 58 treatment in tb cases having pulmonary disease, getting treatment at dots clinics differs from one place to another and reveals the level of threat posed to close contacts of the patients as well as development of multidrug-resistant tb. it is clear in our findings that the overall success rate of outcome was 86.7% in the study participants which is quite satisfactory, though room for improvement is still there. the reason for reasonable success rate might be “directly observed treatment short course (dots) strategy” that makes tb cases to ingest anti-tb medicines under the surveillance of liaison persons. improved compliance to the treatment leads to better tb cure rate. such outcomes were observed in a research conducted at southern ethiopia, where 85.2% “treatment success rate” was documented. the main reason behind this improved success rate may be the improved compliance of tb patients to the treatment in the study setting under “dots” which highlights the 18 significance of the strategy. as this study has been conducted in a limited context of only one hospital setting so the results of this study are not generalizable. conclusion majority of the tuberculosis patients registered under directly observed treatment short course program at holy family hospital, rawalpindi had successful treatment outcomes. it is recommended that patients with unsuccessful treatment outcomes should be followed up for health education as well as treatment accordingly. references 1. assessing tuberculosis under-reporting through inventory studies. geneva: world health organization; 2012. 2. panigatti p, ratageri vh, shivanand i, madhu pk, shepur ta.profile and outcome of childhood tuberculosis treated with dots--an observational study. indian j pediatr. 2014; 81(1):9-14. 3. getahun b, ameni g, medhin g, biadgilign s. treatment outcomes of tuberculosis patients under directly observed treatment in addis ababa, ethiopia. braz j infect dis. 2013;17(5):521-528. 4. chughtai aa, maclntyre cr,wang ya, gao z, khan w. treatment outcomes of various types of tuberculosisin pakistan, 2006 and 2007. emhj. 2013; 19(6):535-541. 5. waheed z, irfan m, haque as, khan mo, zuberi a, ain n et al. treatment outcome of multi-drug resistant tuberculosis treated as out-patient in a tertiary care centre. pak j chest med. 2011;17(3):4-10. of pulmonary tuberculosis in the u.s.a. but it has not been supplemented by a drop in prevalence rate of 1 3 extra pulmonary tuberculosis. so eptb is contributing to the burden of infection and does not obtain explicit responsiveness in global control strategies resulting in certain diagnostic challenges. in australia, eptb counts for more than forty percent of cases and it turns to greater than 50%, if coex i st i n g p u l m o n a r y t b i s a l s o ta ke n i nto consideration. these figures have been purportedly cumulating in western countries & australia. moreover extra pulmonary tuberculosis manifests different presentations that renders it perplexing as for as diagnosis is concerned, quite often connected to delay in diagnosis, leading to higher possibility of severe disease and death, predominantly “tb 14 meningitis”. from a public health standpoint, there is thus a necessity to address this set of patients, as they do add to the total problem of disease and they do have a substantial influence on available resources of national health systems. in our study, a healthy finding was observed that the commonest treatment outcome was treatment completed (65.3%) followed by 21.3% of cured ones and treatment failure was very low (2.7%). it shows that national government is trying to fulfill its obligation for treating tb patients and to control the spread of the disease. other contributory factors are political commitment by government, better-quality laboratory facilities, an uninterrupted provision of m e d i c i n e s , a n d a m o n i t o r i n g sy s t e m fo r documentation & evaluation. finally, the direct observation of treatment has resulted in effective treatment completion and cure rates. similar results were found in a research conducted in northwest ethiopia where the outcomes were categorized as cured 19.9%, treatment completed 50.3%, lost to follow up 05%, treatment failure in 1.7% and died 15 0.6%. likely outcomes were seen in researches conducted at bangalore with cure rate of 65.7%, and tamil nadu with cure rate of 75%. for purpose of understanding, who recommends to achieve “85% 16 cure rate”. in contrast to our results, a study conducted at south africa reported 30% of failed treatment, died and lost to follow up in their 17 patients. the core reason for the high failed treatment may be the non-compliance of the cases in the study settings. therefore, frequency of failed jiimc 2019 vol. 14, no.2 treatment outcomes of tuberculosis 59 1979;109(2):205-17. 14. pollett s, banner p, o'sullivan m, ralph a. epidemiology, diagnosis and management of extra-pulmonary tuberculosis in a low-prevalence country: a four year retrospective study in an australian tertiary infectious diseases unit. plos one. 2016;11(3):e0149372. 15. moges b, amare b, yismaw g, workineh m, alemu s, mekonnen d et al. prevalence of tuberculosis and treatment outcome among university students in northwest ethiopia: a retrospective study. bmc public health. 2015;15(1). 16. yasin m, ahmad z, suleman a. prevalence of treatment failure among pulmonary tuberculosis patients in a tertiary care teaching hospital. j bacteriol mycol open access. 2016; 3(4): 273-276. 17. peltzer klouw j. prevalence and associated factors of tuberculosis treatment outcome among hazardous or harmful alcohol users in public primary health care in south africa. african health sciences. 2014;14(1):157-166. 18. gebrezgabiher g, romha g, ejeta e, asebe g, zemene e, ameni g. treatment outcome of tuberculosis patients under directly observed treatment short course and factors affecting outcome in southern ethiopia: a fiveyear retrospective study. plos one. 2016;11(2):e0150560. 6. tahir nb, uddin qt, sajid m, khattak am. treatment outcomes of tuberculosis patients registered at dots centre kohat. khyber med univ j. 2014;6(3): 131-134. 7. park k. epidemiology of communicable diseases. nd preventive and social medicine. 22 ed. bhanot. india. 2013:166-83. 8. [internet]. who.int. 2017 [cited 25 january 2017]. available f r o m : h t t p : / / w w w . w h o . i n t / t b / c h a l l e n g e s / hiv/tb_women_factsheet.pdf?ua=1 9. salarri mh, kalantari ab. characteristics of tuberculosis patients in yazd province, islamic republic of iran, 1997-99. east mediterr health j. 2004; 10(1-2):175-9. 10. kamal m, ali s, hussain sj, abbasi ma. demographics of tuberculosis in district mansehra. j ayub med coll abbottabad. 2015;27(4):890-3. 11. abubakar i, crofts j, gelb d, story a, andrews n, watson j. investigating urban–rural disparities in tuberculosis treatment outcome in england and wales. epidemiol infect. 2008;136(01):122-27. 12. oren e, winston c, pratt r, robison v, narita m. epidemiology of urban tuberculosis in the united states, 2000–2007. am j public health. 2011;101(7):1256-1263. 13. farer ls, lowell am, meador mp. extrapulmonary tuberculosis in the united states. am j epidemiol. jiimc 2019 vol. 14, no.2 treatment outcomes of tuberculosis 60 original�article abstract objective: to determine knowledge, attitudes and practices of physical therapist towards evidence based practice and to identify the barriers faced by them regarding their practice study design: a cross sectional study. place and duration of study: physical therapists of rawalpindi and islamabad working in different clinical st th setups from 1 december 2020 to 20 may 2021 materials and methods: a cross sectional survey was conducted and 205 physical therapists were randomly recruited from rawalpindi and islamabad working in different hospitals to respond to a self-administered questionnaire. first part of the questionnaire was about demographics and the second part highlighted the knowledge, attitude and clinical practice among physical therapists. results: the study results showed that majority of physical therapists had a clinical experience of less than 10 years and only 19% had more than 10 years' experience. 47.3% physical therapists had a clear understanding of evidence based practice. they had a positive attitude towards its implementation; they are interested in enhancing their skills. 45% of them consider that evidence based clinical practice helps in decision making regarding patient care. conclusion: physical therapists have sufficient knowledge and a suitable attitude towards the use of evidence based practice but only a few of them incorporate it in their practice. insufficient time for implementation of evidence-based practice is the most prevalent barrier. key words: attitude, decision making, evidence based practice, patient, physical therapist. internet browsers like google scholar, pubmed. physiopedia, medline, books, journals and other 2 resources. evidence-based practice is an essential component of clinical care. it is an effective tool to facilitate the process of rehabilitation, which remains in the domain of care provided by a rehabilitation doctor or a team on one-to-one 3 interaction. the driving force for evidence-based practice comes from payer and healthcare facility pressures for cost effectiveness, greater access of information, and greater consumer perception about treatment options. ebp demands alteration in education of students, more research oriented clinical practice and collaborative environment 4 between health care providers and researchers. knowledge includes clear understanding of ebp that how it is recognized and formulated. they must be aware of different medical search engines and 5 accessible to guidelines related to practice. nilsagard et al stated that health care providers are keen to enhance their skills, have self-directed learning so they can incorporate ebp in their daily 6 practice. attitude shows how much physical introduction evidence based practice is defined as “ the conscientious, explicit and judicious use of current best research available to make decisions about 1 individual patient care.” it has been extensively used by all health care professionals in different clinical setups. many medical organizations and agencies had flourished this concept and provided guidelines for the consumers which are easily accessible all over the world through different knowledge, attitudes and practices of clinical physical therapists regarding evidence based practice 1 2 3 4 5 6 zoya mehmood , asmar fatima , bintal wajeeh satti , huma riaz , suhail karim , tehmina nazir correspondence: dr. zoya mehmood lecturer department of rehabilitation sciences shifa tameer-e-millat university, islamabad e-mail: zoya_dpt.ahs@stmu.edu.pk 1 department of rehabilitation sciences shifa tameer-e-millat university, islamabad 2,6 department of rehabilitation sciences allied college of health sciences, multan 3 physiotherapist, central health clinic, (derby uk) 4,5 department of rehabilitation riphah college of rehabilitation sciences, islamabad funding source: nil; conflict of interest: nil received: may 30, 2021; revised: march 03, 2022 accepted: march 09, 2022 evidence based practice among physical therapistsjiimc 2022 vol. 17, no.1 51 therapist are interested in learning and gaining skills and experiences regarding ebp and identifies clinical experience and scientific studies. a study conducted on japanese physical therapists determined that majority of them had knowledge about ebp and important factor was positive attitude, knowledge and behaviour of evidence-based practice and clinical guidelines was engagement in research 7 activities. practice involves the use of clinical guidelines in daily practice, how the pts face patient 5 participation limitation in their clinical settings. the idea of ebp signifies the alteration of health services from traditional treatment and facilities depending upon the perceptions and expertise to another zone of care totally relying on data-based, clinically 6 related research work. the inability to carry out any of these functions may constitute a barrier to the application of evidence in practice. limited time for extracting and gathering research data and for its application to individual patient has been reported by many authors as chief concern that clinicians are unable to amalgamate relevant research in their mode of treatment. limited access to data also has 6 been proven to be another major concern. according to the kap study held in australia most of the pts read research literature at least monthly. a few of respondents reported critically appraising 7 research reports. it also states that fresh graduates value their ebp skills but they are powerless to 8 implement these skills the purpose of this study was to observe the knowledge attitude and practices of physical therapist in rawalpindi and islamabad as majority of the studies were conducted in other cities of pakistan and its barriers were not identified. materials and methods a quantitative research based on cross sectional survey was conducted from december 2020 to may 2021. sample size was n=200 participants. this sample size was calculated by using rao software for cross sectional survey with the confidence interval 95% and 5% margin of error. non probability convenient sampling technique was used and 205 physical therapists were recruited from rawalpindi and islamabad working in different hospitals and clinical settings to respond to self-administered 6 questionnaire. informed consent was taken from all the physiotherapists prior to the participation in the study. participants were recruited in the study based on inclusion criteria of; personals belonging to physiotherapy profession who had clinical experience of more than 6 months were allowed to participate in the study. a self-structured questionnaire was validated by conducting a pilot study and then modification were made upon recommendations of expertise in the field. the questionnaire comprised of 38 questions with 60 variables. this questionnaire was distributed into four sections. first section was about demographics having 8 questions. next part was about knowledge of ebp among physiotherapists having 10 questions with majority responses like 1= strongly disagree, 2= disagree, 3=neutral, 4=agree, 5=strongly agree. the third section was about attitude towards integrating ebp in physiotherapy practice. participants were asked to rate their response to a set of 10 statements from 1= strongly disagree, 2= disagree, 3= neutral, 4= strongly, agree 5= agree. final section was about the understanding and practice of ebp with 9 questions focussing on pts practicing and final question was on barriers of ebp with responses 1= most barrier ,2= less barrier ,3= least barrier. the data was analysed on spss-21(statistical package for social sciences) results a cross-sectional survey was conducted in the physical therapy departments of islamabad and rawalpindi hospitals. this survey recorded a response rate of (n=205) physical therapists. the results showed that 85(41.4%) were male and 120(58.5%) were female physiotherapist.80% physiotherapist had a clinical experience of less than 10 years and 19.2% had experience more than 10 years. 50.7% physiotherapists had bspt degree as an entry level degree, 45.3% had dpt degree. 77.8% pts have had participated in continuing educational courses.47% of physical therapists had clear understanding of ebp (mean ±s. d=4.13±1.04).44% pts had online access to different databases for gaining information about diseases and making treatment protocols (mean±sd= 4.17±0.99). the other important factors are shown in figure 1. 46% physical therapist found ebp necessary in daily practice (mean±sd=4.32±0.803).43.8% physical therapists are very keen in learning skills because it has increased quality of care (mean±sd=4.33±0.82). 52 evidence based practice among physical therapistsjiimc 2022 vol. 17, no.1 for some pts previous work experience is more important than research findings in making treatment protocol (35.5%) and some prefer research on experience (16.7%) as shown in graph no 2.54% physical therapists implemented ebp in daily practice (mean±sd= 3.76±0.85) but pts workload is increasing and is causing hurdle in keeping up to date with evidence (mean±sd= 3.76±0.89) as shown in figure 3. outlook towards integration of ebp. the positive attitude of pts towards ebp in their practices is found to be associated with sufficient knowledge. this is a st 1 comprehensive study assessing ebp among pts in twin cities working in various government and private hospital and clinics.female constituted the majority of study respondents, correlating with the participants of study conducted in south africa by taukobong et al on knowledge, attitude and practice about health promotion amongst pts in south africa. mostly physical therapists had a clear understanding 7 of ebp as reported by ross iles and megan davidson. pts were gaining information from online databases about diseases and their treatment protocols. another study conducted by diane u jette et al stated that majority (70%) physical therapists were of the view that they had sufficient information and knowledge about the databases like medline and 9 cinahl. this study results favored current study results as majority of physiotherapists are aware of evidence based practice in pakistan. most of the contributors had a positive attitude as they agree and strongly agree that application and use of ebp in day 10 to day practice is obligatory. this current study findings are in coherent with other studies conducted elsewhere, in which physiotherapists considered the role of ebp as important in promoting the health of their patients as reported by shirley et 11 al regarding strong implementation of ebp. they believed that ebp helps in cdm patient care so they show interest in increasing use of ebp and improving fig. 1: percentage of knowledge of evidence based practice among physiotherapists fig. 2: shows percentage of attitude of physiotherapists towards evidence based practice fig. 3: shows percentage of practice of evidence based practice among physiotherapists insufficient time is the common obstacle faced by the physical therapists (63. 1%). other barriers are shown in table i. discussion majority of physical therapists are knowledgeable about evidence based practice and have a positive table i: barriers regarding evidence based practice 53 evidence based practice among physical therapistsjiimc 2022 vol. 17, no.1 the skills necessary to incorporate ebp into their 12 practice. physical therapists had identified a significant role to play in patient care and prevention yet had realized a wide gap exists between their ideal and actual levels of involvement as said by johansson 13 et al. in 2010. the results of this study signify that further studies are needed to assess the content of ebp in the curriculum of the different medical institutions. focus should also be put on knowledge and use of ebp integration at undergraduate, graduate and continuing professional development levels. lack of time has been one of the major barriers perceived by the physical therapists in twin cities of pakistan. in a study carried by susanne heiwe et al, it has also been found as a most common 3 barrier that has increased over time. there is a need of organization which regulate practice guidelines for pts, so that they can implement ebp in their daily clinical practice. institutes, rehabilitation centers and hospitals should have access to online databases. conclusion physical therapists of twin cities have a clear understanding of evidence based practice and they are interested in enhancing their skills for patient's betterment and its implementation. insufficient time is the most common barrier in applying ebp during clinical practice. references 1. lobiondo-wood g, haber j. nursing research e-book: methods and critical appraisal for evidence-based practice. elsevier health sciences; 2021 jun 29. 2. yates c. evidence-based practice: the components, history, 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17, no.1 conflict of interest authors declared no conflicts of interest. grant support and financial disclosure authors have declared no specific grant for this research from any funding agency in public, commercial or nonprofit sector. data sharing statment the data that support the findings of this study are available from the corresponding author upon request. this is an open access article distributed under the terms of the creative commons attributionnoncommercial 2.0 generic license. untitled-2 jiimc march 2016.cdr original article abstract objective: to determine the usefulness of anti-cyclic citrullinated peptide and anti-mutated citrullinated vimentin antibody in the diagnosis of seronegative rheumatoid arthritis. study design: descriptive cross-sectional. place and duration of study: this study was conducted over a period of one year from january, 2010 to december, 2010. subjects were recruited from fatima memorial hospital, rheumatology outpatient department, lahore. the research work was conducted at the department of physiology and cell biology of university of health sciences, lahore. materials and methods: a total of 58 known patients of rheumatoid arthritis fulfilling the american college of rheumatology (acr) criteria were included in the study. after selection of subjects, written informed consent was obtained. the venous blood sample was taken and secured in vacutainers. serum was extracted by centrifugation and stored at -20°c till analysis. sera of all study subjects were tested by elisa for presence of rheumatoid factor, anti-mcv and anti-ccp antibodies. the data obtained was analyzed by using spss version 17. the diagnostic significance of anti-ccp and anti-mcv antibody for the diagnosis of sero-negative rheumatoid arthritis patients was determined. results: serum accp antibody was positive in 9 out of 28 rf-ive patients. so the sensitivity of serum accp in rfive group (n=28) was 32.1%. serum amcv antibody was present in 11 out of 28 rf-ive patients. the sensitivity of serum amcv in rf-ive group was 39.2%. conclusion: anti-ccp and anti-mcv had a higher sensitivity for the diagnosis of seronegative ra. keywords: rheumatoid arthritis (ra), rheumatoid factor (rf), anti-mutated citrullinatedvimentin antibody (anti-mcv), anti-cyclic citrullinated peptide antibody (anti-ccp). progressive disease that produces significant morbidity and premature mortality in many 1 patients. many studies have shown that the disease progresses rapidly within first two years of onset and 2 can lead to irreversible erosive joint destruction. the diagnosis of ra depends primarily on history and clinical findings. the gold standard for the classification of ra is the american college of 3 rheumatology criteria (arnett, et al., 1988). this criterion was not designed for diagnosing ra, but rather to harmonize research in population and family studies for epidemiologic purposes. but they are ubiquitously used as a diagnostic aid. patient must satisfy four out of seven criteria to be classified as ra. acr criteria includes: 1)morning stiffness of more than one hour for at least six weeks 2)arthritis and soft tissue swelling of more than 3 of 14 joints/ joint groups,present for at least six weeks. 3) arthritis of hand joints and wrist, present for at least 6 weeks. 4) symmetric arthritis, present for atleast 6 weeks. 5) subcutaneous nodules 6) rheumatoid factor at a introduction rheumatoid arthritis (ra) is a common systemic autoimmune disease of multifactorial etiology characterized by chronic inflammation of synovial joints that often leads to joint destruction. rheumatoid arthritis typically produces symmetrical swelling of peripheral joints of hand and feet, but may affect the large joints as well. rheumatoid arthritis has a worldwide prevalence of 0.5-3%, being 2-3 times more in women than in men, most frequent during fourth and fifth decade of life. once established, rheumatoid arthritis is a lifelong diagnostic usefulness of anti-cyclic citrullinated peptide and anti-mutated citrullinated vimentin antibodies in the diagnosis of seronegative rheumatoid arthritis patients 1 2 3 4 bushra gohar shah , asma saeed , mohammad faisal khan , hamid javaid quershi jiimc 2016 vol. 11, no.1 correspondence: dr. bushra gohar shah assistant professor, physiology avicenna medical college, lahore e-mail: drbushragoharshah@gmail.com 1 2 3 department of physiology /pharmacology / biochemistry avicenna medical college, lahore 4 department of physiology akhtar saeed medical & dental college, lahore funding source: hec ; conflict of interest: nil received: november 10, 2015; accepted: march 06, 2016 accp and amcv antibodies in seronegative ra 3 level above the 95th percentile. 7) radiological changes suggestive of joint erosion/ and or periarticular osteopenia. by the time clinical diagnosis of ra is made, irreversible joint erosions usually have occurred. ongoing research has shown that early therapeutic intervention results in earlier disease control and 2 consequently less joint damage. there is no single test or finding that can diagnose rheumatoid arthritis. rheumatoid factor is the only serological test included in the acr criteria. however, this auto-antibody lacks specificity. it may be found in patients with other autoimmune diseases and infectious disorders. it may also be present in sera of apparently healthy elderly individuals. upto 25% of patients with rheumatoid arthritis have negative rheumatoid factor test 4 (seronegative). therefore, disease-specific auto antibodies are needed for early diagnosis. currently available data suggest that the diagnosis of ra can be made by testing antibodies to citrulline containing peptides such as anti-perinuclear factor(apf), anti-keratin antibody (aka), antifillagrin antibody and anti-cyclic citrullinated peptides (anti-ccp) antibody. these all belong to the family of anti-citrullinated protein/ peptide antibody 5 (acpa). all these antibodies recognize the antigenic 6 epitope containing citrulline, which is generated by post-translational modification of naturally occurring amino acid arginine by the activity of 7 enzyme peptidyl arginine deiminase (pad). citrullinated peptides have been synthesized as 6 antigens for diagnostic immunoassays. several assays for detecting anti-citrullinated peptide antibodies (acpa´s) have been developed employing filaggrin derived peptides (ccp-assay), viral citrullinated peptides (vcp-assay), mutated 8 citrullinatedvimentin (mcv-assay). the anti-mcv assay (elisa) for the detection of antibodies against citrullinatedvimentin uses an antigen with a genetically modified sequence, which is most 8 abundant in patients with rheumatoid arthritis. positivity of these markers in the rheumatoid factor negative ra patients would suggest their additional benefit in the early diagnosis of this subgroup of patients, which are often diagnosed and treated late. it is expected that the results of the present study will help the clinicians in early diagnosis and timely management of this debilitating disease. the aim of this study was to investigate the diagnostic value of antibodies against mutated citrullinatedvimentin (anti-mcv) and antibodies to cyclic citrullinated peptides (anti-ccp) in the diagnosis of seronegative rheumatoid arthritis patients. materials and methods this descriptive cross sectional study was conducted over a period of one year from january, 2010 to december, 2010. fifty-eight subjects were recruited from fatima memorial hospital, rheumatology outpatient department, lahore, by convenient sampling technique. the research work was conducted at the department of physiology and cell biology of university of health sciences, lahore. a total of 58 patients attending the rheumatology outpatient department of fatima memorial hospital, lahore were recruited in the study. all the patients fulfilled the american college of rheumatology criteria for ra and were diagnosed by the rheumatologist. the study was approved by the ethical and review committee of university of health sciences, lahore. informed written consent was taken from each study participant. a purposefully designed proforma was used to record data of the subjects including age, gender, disease duration, clinical characteristics and medication used. the venous blood samples were taken and secured in vacutainers. serum was extracted by centrifugation and stored at -20°c till titer of anticcp and anti-mcv antibodies. rheumatoid factor titers were determined by elisa (highton, et al., 1986) using commercially available immulisa anti-rf antibody igm elisa kit (immco diagnostics, usa), with an automated eia analyzer [coda, bio-rad laboratories, hercules, ca, usa].results were interpreted as follows:rf-igm value of less than 7 iu/ml was considered as negative. rf-igm value of 7-9 iu/ml was considered as borderline. rf-igm value of more than 9 iu/ml was considered as positive. serum anti-mcv antibody levels were determined by 9 elisa using elisa kit (cusabio biotech co., ltd, china), with an automated eia analyzer [coda, biorad laboratories, hercules, ca, usa]. serum anti10 ccp antibody levels were determined by elisa using commercially available elisa kit (immco jiimc 2016 vol. 11, no.1 4 accp and amcv antibodies in seronegative ra diagnostics, usa), with an automated eia analyzer [coda, bio-rad laboratories, hercules, ca, usa]. 25u/ml was taken as cut-off value for anti-ccp antibodies. the data was entered into spss version 17. diagnostic sensitivity of anti-ccp and anti-mcv antibodies for the diagnosis of rheumatoid arthritis in sero-negative patients were calculated by table of 2 x 2. statistical analysis was done to determine the usefulness of the diagnostic sensitivities of anti-ccp and anti-mcv antibodies. p value of < 0.05 was considered to to be statistically significant. results the study population (n=58), comprised of 58 rheumatoid arthritis patients, out of which 38 were females and 20 were males. mean ±sem age of the ra patients was 44±1.2 years. median (iqr) disease duration was 5(4-8) years. median (iqr) anti-ccp antibodies titer (iu/ml) was 10.8(0.00-340.5). median (iqr) anti-mcv antibodies titer (iu/ml) was 19.7(14.2-30.06). (table i) sub-grouping of ra group was done on the basis of presence or absence of rf, accpab, or amcv ab in the sera. subgroups were named rf+ive group (gp), rf-ivegp, accp+ivegp, accp-ivegp, amcv+ivegp, amcv-ivegp. rf testing by elisa technique, was done in a total of 58 ra patients. out of the ra patients (n=58), 30 (52%) were rf+ive and 28 (48%) were rf-negative. in the ra group (n=58), 34 (58%) were accp+ ive and 24(41.4%) were accp –ive. the sensitivity of serum accp antibodies for ra was calculated to be 58.6%. serum accp antibody was positive in 9 out of 28 rfive patients. so the sensitivity of serum accp in rfive group (n=28) was 32.1%. in the ra group (n=58), 20(34.5%) patients were amcv+ and 38(65.5%) were amcv –ive, at cutoff value of 25u/l (table i). the sensitivity of serum amcv antibodies for ra was calculated to be 34.5% at the manufacturer's cutoff value of 25u/l. serum amcv antibody was present in 11 out of 28 rf-ive patients. the sensitivity of serum amcv in rf-ive group was 39.2%. discussion a close relationship exists between autoimmunity and antibodies; despite this, some patients are p e rs i ste n t l y n e ga t i ve fo r d i s e a s e s p e c i f i c autoantibodies. these conditions have been defined as seronegative autoimmune diseases. although the prevalence of seronegative autoimmune diseases is low, they may represent a practical problem because they are often difficult and challenging cases for the 11 clinicians/rheumatologist. about 80% of the patients affected by ra are positive for rf, the rest 20-25% being seronegative. a more disease specific marker for ra may help in diagnosing early disease and seronegative ra patients resulting in reduced joint damage. it is therefore important to differentiate between ra and other forms of arthritis early after the onset of symptoms. therefore, a specific and sensitive serological marker, which is present very early in the disease, is needed so that the rheumatologist are able to target the use of potentially toxic and expensive drugs to those patients, where the benefits clearly outweighs the risk. keeping in view the need of a more sensitive marker, especially in the seronegative cases, the present study aimed to evaluate the sensitivity of anti-ccp and anti-mcv antibodies in local pakistani seronegative ra subjects. in seronegative cases of arthritis, the differential diagnosis is not easily established in the early disease course. especially seronegative patients need the determination of an additional marker for ra besides rheumatoid factor to confirm diagnosis. the high specificity of anti-ccp antibodies has been reported in rf-neative ra patients. in the present study, 9 out of 28 seronegative patients were positive for anticcp antibodies. so, the sensitivity of anti-ccp antibodies in the seronegative sub-group was 32.1%. tablei: serum rf, accp and amcv status in the ra group (n=58) jiimc 2016 vol. 11, no.1 5 accp and amcv antibodies in seronegative ra in a study, conducted by alexiou, et al., sensitivity in seronegative group was reported to be 34.9%, which 12 is almost comparable to our results. similarly, 13 mobini, et al., found sensitivity in seronegative 14 group to be 33.3%, whereas vanichapuntu, et al., found sensitivity value of 20% in the seronegative 15 sub-group whereas serdaroglu, et al., reported sensitivity of 14.3% in seronegative group. thus, anti-ccp antibody serves as a better diagnostic marker in the diagnosis of ra, especially in the seronegative group. the sensitivity of anti-mcv in the sero-negative ra group was 39.2%, as 11 out of the 28 rf-ive patients were anti-mcv positive. this finding is supported by recent results of other authors, that the higher sensitivity of anti-mcv especially in the seronegative patients makes it a more valuable marker in 16 17 the diagnosis of ra. wagner, et al., reported sensitivity of anti-mcv in the sero-negative group of 43% and sensitivity of anti-ccp to be 30.8%. in seronegative ra patients, the sensitivity of anti-mcv 18 was superior over anti-ccp. soos, et al., reported sensitivity of anti-mcv in the sero-negative group to 19 be 29.4%. narvaez, et al. documented sensitivity of 23% in their series of sero-negative ra patients. limitations of the study small sample size was the limitation of this study. further studies with greater number of ra patients are recommended. conclusion both anti-ccp and anti-mcv antibodies can be used for the early diagnosis of sero-negative patients of rheumatoid arthritis. moreover anti-mcv antibody has a significantly higher sensitivity as compared to anti-ccp antibodies for the diagnosis of seronegative ra recommendations clinicians must be aware of the implications of delayed diagnosis in ra. keeping in view the costeffectiveness, this study emphasizes the utility of rf initially for the diagnosis of ra, reserving acpa's for seronegative ra patients where strong clinical suspicion exists. acknowledgement this research was funded by the higher education commission of pakistan. references 1. lee dm, weinblatt me. rheumatoid arthritis. lancet 2001; 358: 903-11. 2. combe b. progression in early rheumatoid arthritis. best pract res clinrheumatol 2009; 23: 59-69. 3. saraux a, berthelot jm, chales g, le henaff c, thorel jb, hoang s, et al. ability of the american college of rheumatology 1987 criteria to predict rheumatoid arthritis in patients with early arthritis and classification of these patients two years later. arthritis rheum 2001; 44: 2485-91. 4. marianna, mn. rheumatoid factors: what do they tell us? j rheumatol. 2002; 29: 2034-40. 5. zendman aj, van venrooij mj, pruijn gj. use and significance of anti-ccp autoantibodies in rheumatoid arthritis. rheumatology. 2006; 45: 20-5. 6. schellekens ga, de jong ba, van den hoogen fh, van de putte lb, van venrooij wj. citrulline is an essential constituent of antigenic determinants recognized by rheumatoid arthritisspecific autoantibodies. j. clin invest 1998; 101: 273-81. 7. vossenaar er, zendman aj, van venrooij wj, pruijn gj. pad, a growing family of citrullinating enzymes: genes, features and involvement in disease. bioessays 2003; 25: 1106-18. 8. bang h, egerer k, gauliard a, berg w, fredenhagen g, feist e, et al. mutation and citrullination modifies vimentin to a novel autoantigen for rheumatoid arthritis. arthritis & rheumatism. 2007; 56: 2503-11. 9. coenen d, verschueren p, westhovens r, bossuyt k. technical and diagnostic performance of 6 assays for the measurement of citrullinated protein/peptide antibodies in the diagnosis of rheumatoid arthritis. clin chem. 2007; 53: 498-504. 10. bizzaro n, mazzanti g, tonutti e, villalta d, tozzoli, r. diagnostic accuracy of the anti-citrulline antibody assay for rheumatoid arthritis. clin chem. 2001; 47: 1089-93. 11. alessandri c, conti f, conigliaro p, mancini r, massaro l,valesini g. seronegative autoimmune diseases. ann ny acad sci. 2009; 1173: 52-9. 12. alexiou i, germenis a, ziogas a, theodoridou k, sakkas li. diagnostic value of anti-cyclic citrullinatedpeptide antibodies in greek patients with rheumatoid arthritis.bmc musculoskeletal disorders. 2007; 8: 37. 13. mobini m, kashi z, mahdavi, mr. the role of rheumatoid factor and anti-cyclic citrullinated peptide antibody in diagnosis of rheumatoid arthritis. ircmj. 2010; 12: 100-3. 14. vanichapuntu m, phuekfon p, suwannalai p, verasertniyom o, nantiruj k, janwityanujit s. are anti-citrulline autoantibodies better serum markers for rheumatoid arthritis than rheumatoid factor in thai population? rheumatol int. 2010; 30: 755-9. 15. serdaroglu m, cakirbay h, deger o, cengiz s, kul s. the association of anti-ccp antibodies with disease activity in rheumatoid arthritis.rheumatol int. 2008; 28: 965-70. 16. ladislav s, walter g, peter s. laboratory biomarkers or imaging in the diagnostics of rheumatoid arthritis?bmc medicine. 2014; 12: 49. 17. wagner e, skoumal m, bayer pm, klaushofer k. antibody against mutated citrullinatedvimentin: a new sensitive jiimc 2016 vol. 11, no.1 6 accp and amcv antibodies in seronegative ra marker in the diagnosis of rheumatoid arthritis. rheumatolint 2009; 29: 1315-21. 18. soos l, szekanecz z, szabo z, fekete a, zeher m, horvath if, e t a l . c l i n i c a l e v a l u a t i o n o f a n t i m u t a t e d citrullinatedvimentin by elisa in rheumatoid arthritis. j rheumatol. 2007; 34: 1658-63. 19. narvaez j, sirvent e, narvaez ja, bas j, gomez-vaquero c, reina d, et al. usefulness of magnetic resonance imaging of the hand versus anticycliccitrullinated peptide antibody testing to confirm the diagnosis of clinically suspected early rheumatoid arthritis in the absence of rheumatoid factor and radiographic erosions.semin arthritis rheum.2007; 38: 101-9. jiimc 2016 vol. 11, no.1 7 accp and amcv antibodies in seronegative ra original�article abstract place and duration of study: the study was conducted on people living in cities of islamabad and rawalpindi, pakistan during march-june 2018. study design: . observational cross-section study results: p p majority (94.7%) of the participants, irrespective of their gender ( -value=0.19) and marital status ( value=0.08), were in favour of educating children about sexual abuse prevention. around 42% participants tried themselves to educate children on this topic and males' participation in it was observed to be less than females ( -value=0.005). optimal age to educate children was considered between 5-9 years. a positive p response was shown by participants, when the extent and ways of child sexual abuse prevention education were discussed. conclusion: majority of the adults are in favour of educating children to protect themselves from sexual abuse so they are able to recognize and react effectively to potentially dangerous situations. materials and methods: data was collected from 228 people by non-probability convenient sampling. people of both genders with any marital status, above 18 years of age and with minimum high school education or above were considered eligible for this study. a self-designed structured questionnaire was used to collect data which was analysed using spss version 23. p value ≤ 0.05 was considered significant. key words: child abuse, educational activities, preventive measures, public health, sexual abuse. objective: this research was planned to assess attitude of adults towards educating children about sexual abuse prevention. 4 are relatives and only 10 % are strangers. the highest vulnerable age group among both genders is reported to be the children between the ages of 11 to 5 15 years and then 6 to 10 years. like other countries of the world, csa is a serious problem in pakistan as well and has recently gained lot of attention. according to a data collected by a non-governmental organization, sahil, about 11 cases of csa are reported from across the pakistan 7 every day. almost 17,862 cases of csa have been 8 reported in the country from 2013 to 2017 and still many remains undisclosed due to the feeling of guilt and shame, fear of perpetrator's threats, lack of trusted confidante, or to maintain the reputation of family. worldwide hild abuse prevention programs are c created to provide knowledge to children to recognize abuse, teach skills that decrease the risk for abuse, normalize the disclosure process and csa has an adverse effect on child's physical, social, spiritual and mental health. health consequences includes depression, anxiety, post-traumatic stress disorder, unwanted pregnancy, hiv acquisition, 1,6 sexual disorientation, and drug addiction. the estimated global prevalence of csa is 19.7% for 3 females and 7.9% for males. about 60% of the child sexual abusers are non-relative acquaintances, 30% introduction worldwide, child sexual abuse (csa) is a massive challenge for public health, human rights and social 1 justice. the world health organization (who) defines it as: "the involvement of child in a sexual activity that he or she does not fully comprehend, is unable to give informed consent to, or for which the child is not developmentally prepared “or else that 2 violate the laws or social taboos of society”. attitude of adults towards educating children to protect themselves from sexual abuse in pakistan 1 2 3 haddaya umar , wardah umar , sidra hamid correspondence: haddaya umar nd 2 year mbbs student e-mail: haddayaumar@gmail.com 1 student rawalpindi medical university, rawalpindi 2 student al-nafees medical college isra university, islamabad 3 department of physiology rawalpindi medical university, rawalpindi funding source: nil; conflict of interest: nil received: december 17, 2018; revised: october 29, 2019 accepted: october 30, 2019 jiimc 2019 vol. 14, no.4 212 attitude towards child sexual abuse education in order to know the age at which children should be given csa education different age groups were made. among them the most favored group by participants was children between the ages of 5 to 7 years (by 27% participants), followed by children between 7 to 9 years (24.9%), 9 to 11 years (16.90%), 3 to 5 years (15.60%) and above 11 years (15.50%). few questions were planned to assess adults' participation in trying to aware their children (or other children having close relation with them) about csa by their own. self-participation of 222 out of 228 participants could be assessed. only 93 (42%) tried it and among them 77 were satisfied by their way of counseling with majority being females. it was observed that males' participation in giving children csa awareness was less (p-value= 0.005) as compared to females as only 28 male participants tried to educate children on their own. adults' views regarding extent of educating children are shown in table i. about a csa case around them. about 94.7% of the participants agreed that the child must be given education about csa prevention and among them 75.2% approved csa awareness through public programs like television shows, school based programs, activities at public places, etc. both males and females, irrespective of their gender, approve educating children about csa prevention as p-value of 0.08 was obtained after applying chi-square test. similarly there is an insignificant association between marital status and approval of csa prevention education (p-value of 0.19) stating that both married and unmarried participants favored it equally. unmarried females favored educating children the most as 98.7% agreed to it. whereas, 94.4% of married females, 93.1% of unmarried males, and 89.7% of married males were in its favour. different ways were suggested to prevent csa and among them the most favored one reflected the importance parents' attitude towards their children which enable them to share things openly with them. the details of other ways are further mentioned in table ii according to 89% (n=203) participants, csa affects both the mental and physical health of the child and only 11% (n=25) participants believed that it affects his/her mental health only. provide a pathway for children who may be 9 experiencing abuse to report the abuse. though several attempts have been taken to develop and implement such programs in pakistan as well but adults' view regarding its need has attracted very little attention from research point of view. therefore, this study was planned to assess adults' attitudes towards development of such educational programs in order to protect children from sexual abuse. materials and methods data was entered and analyzed using statistical package for social sciences (spss) version 23. chisquare tests were applied to calculate p values for determining relation between adults approving educating children about csa prevention on basis of their gender and marital status. p value ≤ 0.05 was considered significant. descriptive statistics were used to analyze rest of the data. results data was collected by means of a self-designed questionnaire which was distributed online and in hand. it included demographic profile (i.e. gender, age, marital status, and education) and a set of questions through which adults' opinions towards csa prevention education and their participation could be observed. different ways and extent of protecting and educating children about csa were suggested and the participants were asked to select the most suitable one/s. out of the 228 participants, 42.5% (n=97) were males and 57.5% (n=131) were females. only 40.8% (n=93) of the participants were married (39 males and 54 females) and 59.2% (n=135) were unmarried (58 males and 77 females). a cross-sectional study was conducted in the twin cities of pakistan, islamabad and rawalpindi, during march to june 2018. data from 228 participants was collected using nonprobability convenient sampling after getting approval from ethical committee of rawalpindi medical university. adults of both genders of any marital status above 18 years of age, who were residents of islamabad or rawalpindi, were asked to participate in this study voluntarily. whereas, people with no or less than high school education and those who were reluctant or not comfortable with filling form were excluded. more than 50% of the participants i.e. 115 knew jiimc 2019 vol. 14, no.4 attitude towards child sexual abuse education 213 potentially abusive situations. about 83% believed that it can lead to considerable decrease in number of cases reported and according to 76.8% csa prevention education can lead to earlier disclosure of csa cases by victims. whereas, adults' concern about csa education leading to negative impacts are mentioned in table iii. this table also explains the concerns of individuals disapproving csa education. table i: extent of educa�ng children about csa table ii: ways of csa preven�on the counseling about csa prevention education can leave multiple impacts on the child's mind. according to 87.7% participants it enables the child to deal with table iii: concerns regarding impacts of csa preven�on educa�on discussion the results of the present study shows that majority of participants approve teaching children about csa prevention especially during the time period when they are attending elementary school i.e. 5 to 11 years old. their participation in giving csa prevention education to children on their own, interest in suggesting ways and extent of educating children shows their concern towards contributing to safety of children. a research conducted on mother’s knowledge and perception about csa in jordan showed that 74% of mothers who were part of study, stated that 10 educating children about csa can prevent it. similarly another study conducted in china also showed that 89.8% of parents supported csa 11 prevention education for their kids. a randomized controlled trail on elementary students in us these negative impacts could become serious concern, only if the education is done in inappropriate ways. thus, this sensitive issue of educating the child about sexual abuse must be dealt carefully as it attracts individual, religious, institutional, and societal concern. jiimc 2019 vol. 14, no.4 attitude towards child sexual abuse education 214 prevention. the knowledge about csa, attitudes, self-efficacy to take action, and awareness are all key capabilities related to creating conditions of safety for our children. our study includes educated people as they are more open towards new change and more willing to children about new things as compared to people with little or no education. thus there is need of further study in which opinions of people with little or no education are considered and compared with those of people who have received higher education. also the opinions of people belonging to low socioeconomic status should also be assessed as csa is more prevalent in such areas. 2. world health organization. guidelines for medico-legal care for victims of sexual violence. world health organization 2003; 2003. 144 p. available from: apps.who.int/iris/bitstream/handle/10665/42788/92415 4628x.pdf;sequence=1. majority of adults are in favor of educating children about csa especially during the time period when children are attending elementary school. adult’s interest in suggesting ways and extent of educating children shows their concern towards contributing to safety of children by preparing them to deal with potentially harmful situations. 4. julia whealin, ph.d. child sexual abuse. national center for post-traumatic stress disorder, us department of veterans affairs. 2007-05-22 available from https://web.archive.org /web/20090730101002/http://www.ptsd.va.gov/public/p ages/child-sexual-abuse.asp. 5. wasif s. 10% increase in child abuse cases in pakistan. the express tribune [internet]. the express tribune. 2017 [cited 22 march 2017]. available from: https://tribune.com.pk /story/1363150/rise-10-increase-child-abuse-casespakistan. 7. geo news. 11 cases of child sex abuse reported in pakistan every day: report [internet]. 2018. available from: https://w w w. geo.tv/latest/176272-up-to-11-child 6. srivastava k, chaudhury s, bhat ps, patkar p. child sexual abuse: the suffering untold. ind psychiatry j. 2017; 26(1):13. 3. pereda n, guilera g, forns m, gomez-benito j. the prevalence of child sexual abuse in community and student samples: a meta-analysis. clin psychol rev. 2009; 29(4):32838. conclusion references 1. mathews b, collin-vezina d. child sexual abuse: raising awareness and empathy is essential to promote new public health responses. j public health policy. 2016 aug; 37(3):304-314. concluded that children in younger grades gains better knowledge about csa and ability to recognize, refuse and report unsafe touches while being 12 enrolled in a csa prevention program. this study also justifies our result in which most participants are in favour of educating children between 5 to 9 years of age. in our study, importance of parental role in preventing csa is also observed (refer to table ii). rudolph j et al., also suggested in their study that parents can protect their children from csa directly through the strong external barriers provided by their availability, supervision, monitoring, and involvement; and indirectly by promoting children's self-efficacy, competence, well-being, and selfesteem, which will help them become less likely targets for abuse and more able to respond 13 appropriately and disclose abuse if it occurs. a study conducted in australia showed that the presence of a guardian can decrease the risk of csa by 86% which also reflects the importance of parent's/guardian's 14 role. about 75.2% of our participants were in favor of educating children about csa prevention in public including in schools and only 25.5% believed that only parents should give such education to their children (table ii). a study conducted in china also showed that 87.3% of parents were willing to let their children acquire csa prevention knowledge in 11 schools. school based prevention programs are reported to play a crucial role in preventing csa as it potentially reaches all children. studies showed that such programs had proved to show an improvement in knowledge, disclosure, and protective behavior at 12,15 risk situations. in our study about 35% participants considered media as an effective tool in preventing csa. from past few years, media is playing an active role in csa awareness. many articles, advertisements, serials, talk-shows, movies, are based on this topic but it hasn't shown any effect on decreasing csa rate. a study conducted in usa by rheingold aa et al., focusing on independent effect of media in preventing csa, concluded that media campaigns might have increased knowledge of csa at the time of intervention but it alone had no significant effect 16 on preventing csa. to date, there are abundant studies that show the importance of educating children about csa jiimc 2019 vol. 14, no.4 attitude towards child sexual abuse education 215 15. kerryann walsh, karen zwi, susan woolfenden, shlonsky a. school-based education programmes for the prevention of child sexual abuse. cochrane database syst rev. 2015. 13. rudolph j, zimmer-gembeck mj, shanley dc, hawkins r. child sexual abuse prevention opportunities: parenting, programs, and the reduction of risk. child maltreat. 2018; 23(1):96-106. 16. rheingold aa, campbell c, self-brown s, de arellano m, resnick h, kilpatrick d. prevention of child sexual abuse: evaluation of a community media campaign. child maltreat. 2007; 12(4):352-63. 14. leclerc b, smallbone s, wortley r. prevention nearby: the influence of the presence of a potential guardian on the severity of child sexual abuse. sex abuse. 2015; 27(2):189204. protection unit: grade and gender as moderators of csa prevention concepts in elementary students. child abuse & neglect. 2019; 96:104101. 11. chen j, chen d. awareness of child sexual abuse prevention education among parents of grade 3 elementary school pupils in fuxin city, china. health education research. 2005; 20(5):540-547. 12. nickerson a, tulledge j, manges m, kesselring s, parks t, living ston j et al. randomized controlled trial of the child sexual-abuse-cases-reported-in-pakistan-every-dayreport. 10. alzoubi f, ali r, flah i, alnatour a. mothers' knowledge & perception about child sexual abuse in jordan. child abuse & neglect. 2018; 75:149-158. 8. cruel numbers – sahil [internet]. sahil.org. available from: http://sahil.org/cruelnumbers/. 9. blakey j, glaude m, jennings s. school and program related factors influencing disclosure among children participating in a school-based childhood physical and sexual abuse prevention program. child abuse & neglect. 2019; 96:104092. jiimc 2019 vol. 14, no.4 attitude towards child sexual abuse education 216 untitled-1 original article abstract objective: this study aimed to assess the correlation between oral health and general health in children having intellectual disabilities. study design: cross‐sectional, questionnaire based study. place and duration of study: this study was conducted at step to learn school, islamabad and rawalpindi, frommay to june 2014. materials and methods: a sample of 88 children were selected from two branches of 'step to learn', a special school for children with intellectual disabilities. body mass index (bmi) was used to assess general health, while oral health was measure by the decayed, missing, filled teeth (dmft) index. dental surgeons and dental students conducted the examination. pearson's correlation coefficient was used to compare the correlation between bmi and dmft. the data was analyzed using the software spss (v 17.0). results: out of 88 children, data of 85(96.59%) was recorded. no significant correlation was found between oral health and general health (r = ‐0.06). conclusion: the general health of children with intellectual disabilities does not impact their oral health. subsequent oral and general health educational initiatives should be conducted separately. key words: intellectual disabilities, general health, oral health. studies have highlighted the importance of oral h y g i e n e i n c h i l d r e n h a v i n g i n t e l l e c t u a l 3‐5 disabilities; however, very few studies have been conducted on this issue in pakistan. studies have also shown that oral health is the most ignored angle 7 for these people. general health conditions are apparently more important than oral health as the connection between oral and general health is not 8 , 9 p r o p e r l y a p p r e h e n d e d . t h i s i s f u r t h e r substantiated by the fact that oral health problems have been reported to be in the top ten secondary conditions among the childrenwith intellectual disabilities. such children are more vulnerable and 4 socially excluded in the society. in pakistan, there is a paucity of oral health care services for children with intellectual disabilities. the major barriers are described by using penchansky and thomas: model of access, five themes of which are availability, accessibility, accommodation, 5,9,10 affordability and acceptability. availability measures the degree to which the dentist has the resources such as personnel and technology to meet the needs of these children, e.g. in pakistan, the ratio of dentists to population is small and no department is available to specifically cater for the needs of these children. accessibility determines the geographical location of the dental clinic and how conveniently the client can reach there. another aspect is introduction intellectual disability is a generalized disorder appearing before adulthood characterized by significantly impaired cognitive functioning and deficits in two or more adaptive behaviors. it is classified as an intelligence quotient score of under 70 and further categorized as mild, moderate, severe 1‐3 and profound. disability is a general term that includes impairments, activity confinements and participation restriction. impairment is a problem in body function or structure; an activity confinement is a difficulty faced by a person in performing a task or an action while participation restriction is a problem experienced by a person in life situations. previous studies have reported that the children with intellectual disabilities have similar incidence of caries and more frequent extractions as compared to the general population, still they have a higher level 4‐6 of unmet dental needs. numerous international oral health and general health in children having intellectual disabilities: a cross sectional study maryam rehman, ridha humayun kabir, anum zehra, komal syeda, noor fatima health problems in children with intellectual disabilitiesjiimc 2015 vol. 10, no.4 correspondence: maryum rehman department of community dentistry islamic international dental college riphah international university, islamabad email: maryamrehman_1946@hotmail.com department of community dentistry islamic international dental college riphah international university, islamabad received: february 11, 2015; accepted: november 15, 2015 242 whether the client can physically access the premises e.g. children with impaired physical health have difficulty in climbing the stairs but elevators are not frequently available accommodation reflects the willingness of the dentist to prioritize the needs of these children e.g. there is no particular department with extended opening hours to accommodate these children or which schedules an appointment as per convenience. on top of that, the dentists usually hesitate in accepting the case. affordability refers to the socioeconomic status of the children's families and the fee of the dentist e.g. the oral health care services are very costly thus making it unaffordable for children with intellectual disabilities from lower 5 strata of society. finally, acceptability depicts the comfort level of these children and the dentists regarding the treatment. the dentists are unequipped for such cases and their hesitation increases the anxiety level of these children. the children with intellectual disabilities should be given equitable care as is the moral and professional obligation of the dentists. they share the same entitlement to good oral health as the rest of the 1 society. although a few studies have been carried out to assess the correlation between the general and oral health of intellectual disabilities, the evidence available is limited. also, this correlation has not been investigated among individuals with a south asian ethnicity. the aim of this cross sectional study was to assess any correlation between oral health and general health in children having intellectual disabilities. materials and methods this cross‐sectional study set out to assess the association between general and oral health. for the purpose of data collection, a school for children with intellectual disabilities, 'step to learn' (stl) was selected. stl has two branches: one in islamabad and the other in rawalpindi. a dental team comprising of dental surgeons and dental students from islamic international dental college (iidc) visited the two branches of stl for data collection. the two branches of stl had a students' strength of about a 100 students. the dental team visited the two branches on two separate days. before the dental visit, the school administration obtained informed consent from the students' parents. caries, experience, measured using the 'decayed, missing and filled teeth (dmft) index was used as an indicator for oral health. the dmft is a validated index for the assessment of dental caries that has been used for measuring caries experience for about 11 a century to measure general health, bmi was used. the examination was carried out by the students. each station was assigned a particular task. one of the stations was allocated to calculate the bmi using a commercial weighing scale and measuring tape. three stations were designated to check the dmft using tongue depressors and torches. for behavioral management, positive reinforcements and tell‐ show‐do techniques were used e.g. after the children successfully let the dental surgeons examine their oral cavity and record weight and height they were given stickers. students frequently demonstrated the use of weighing scale by getting up on it and the children were shown how dmft is done by observing the process on another child. statistical package for social sciences (spss v 17.0) was used to insert, consolidate and analyze the data. mean and standard deviation were used to describe bmi and dmft. pearson's correlational analysis was used to analyze any association between bmi and dmft. results our sample size compromised of 88 children out of which 29 (33%) were females and 59 (67%) were males. table i illustrates the frequency distributions of the various conditions of the children. multiple disorders i n c l u d e d c h i l d re n h av i n g m o re t h a n o n e aforementioned condition along with growth r e t a r d a t i o n , c e r e b r a l p a l s y a n d p h y s i c a l table i: distribu�on of the condi�ons of children bmi and dmft of 85 pa�ents were checked. the bmi frequencies have been illustrated in table ii. three of the pa�ents were non‐compliant. jiimc 2015 vol. 10, no.4 243 health problems in children with intellectual disabilities condi�ons frequency (%) au�sm down’s syndrome hearing and speech impairment intellectual disability mul�ple total missing total 43(49.4) 4(4.6) 21(24.1) 3(3.4) 16(18.4) 87(100) 1 88 impairments. condition of one of the children could not be specified. dmft score was generally high as every child had a different limitation and this made the result variable. two of the children had severe physical disabilities due to which bmi could not be calculated and one child was uncooperative. majority of the children were found to be underweight. interestingly, a greater part of the sample had a dmft score of zero. the dmft score of the obese child was zero. the overweight children had less dmft score than the underweight children while the dmft score of the children having normal bmi was found to be the highest. since there was only one obese child, the result was not conclusive. table iii illustrates the frequencies of dmft scores. three of the patients were non‐compliant. table ii: frequencies of ranges of bmi table ii: frequency of dmft scores the mean dmft score was 2.15 +3.15, while mean dmft score for children having normal bmi was calculated to be 2.92±3.70, the score of 1.89±3.03 was calculated for the underweight category, 1.50±1.29 for overweight and zero for the obese. (fig i) the prevalence of dental caries in the sample was fig 1: mean dmft scores for different bmi categories found to be 48.2%. a very weak negative correlation was found between dmft and bmi (r = ‐0.06). discussion the present study found a very weak correlation between general and oral health of children with intellectual disabilities. reasons for this could be that the sample size was too small and the dmft score was low. another factor could be that females are more prone to caries but this is not a universal 12 phenomenon. the prevalence of dental caries in this sample was found to be 48.2% as compared to 53.5% found in children with intellectual disorders in guangzhou, 13 china and 79.6% in young athletes with intellectual 14 disorders in indonesia. the low dental caries prevalence in our study could be explained by our low sample size. furthermore, our sample was selected from a private school where both the parents and care givers of the children reported paying special attention to the hygiene of children. male to female ratio was not accounted for throughout the study so this is not an accurate representation of this community. the sample size was too small to find any significant correlation or pattern between dmft and bmi. alternatively, oral health was well maintained. results were inconclusive because some of the children had severe physical impairments which made them unable to get their heights and weight measured a c c u r a t e l y. t h e r e f o r e , t h e d e n t i s t s u s e d approximation for such cases. additionally the dmft score results proved to be an underestimation rather than overestimation. the children were provided jiimc 2015 vol. 10, no.4 244 health problems in children with intellectual disabilities bmi range frequency (%) normal underweight overweight obese total missing total 25(29.4) 55(64.7) 4(4.7) 1(1.2) 85(100) 3 88 with tooth brushes and tooth pastes to encourage oral hygiene and good behavior. they were also demonstrated the correct tooth brushing technique. the parents were advised not to give too many sweets to the children as a reward for good behavior. they were also advised against regular snacking. the guardians and parents of these children were invited and their queries were facilitated. moreover, they were given the contact details of the islamic international dental hospital (iidh) where they could be further accommodated. the limitations of the study were that the participation of the students was low due to absence of registered students and apprehensions by a few as reported by the school administration. furthermore, children with intellectual disabilities who do not attend school were not considered in this study. therefore, socioeconomic status could have been a possible confounder for the study. conclusion since no correlation could be determined between oral and general health of children with intellectual disabilities, both should be dealt separately. oral health and general health education for children with intellectual disabilities and their caregivers should be provided. it would be beneficial if educational programs covering basic items of oral health care are introduced to train the children as 4,9,15 well as the parents and caretakers. references 1. daly b, batchelor p, treasure et, rg w. essential dental public health. second ed: oxford university press;2013. 2. britain g. valuing people: a new strategy for learning disability for the 21st century: department of health; 2001. 3. gibbs m, priest h. exploring the physical health needs of people with learning disabilities: facilitation student engagement in learning, using kolb’s experiential learning cycle. nurse education in practice.2010; 10:115‐8. 4. faulks d. reducing inequalities in oral health for persons with special needs. france2007. 5. fisher k. health disparities and mental retardation. journal of nursing scholarship. 2004; 3648‐53. 6. newton j. restrictive behaviour management procedures with people with intellectual disabilities who require dental treatment. journal of applied research in intellectual disabilities. 2009; 22: 118‐25. 7. nowak aj. dentistry for the handicapped patient: cv mosby; 1976. 8. ml b. the oral systemic disease connection. an update for the practicing dentist. j am dent assoc.2006; 137: 5‐6. 9. owens pl, kerker bd, zigler e, horwitz sm. vision and oral health needs of individuals with intellectual disability. mental retardation and developmental disabilities research reviews. 2006; 12: 28‐40. 10. arnold c, brookes v, griffiths j, maddock s, theophilou s. guidelines for oral health care for people with a physical disability. report of bsdh working group. 2000. 11. klein h, palmer ce, knutson jw. studies on dental caries. public health rep. 1938; 53: 751‐65. 12. jindal a, mcmeans m, narayanan s, rose ek, jain s, marazita ml, et al. women are more susceptible to caries but individuals born with clefts are not. international journal of dentistry. 2011; 2011: 1‐11. 13. liu z, yu d, luo w, yang j, lu j, gao s, et al. impact of oral health behaviors on dental caries in children with intellectual disabilities in guangzhou, china. international journal of environmental research and public health. 2014; 11: 11015‐27. 14. trihandini i, wiradidjaja adiwoso a, erri astoeti t, marks l. oral health condition and treatment needs among young athletes with intellectual disabilities in indonesia. international journal of paediatric dentistry. 2013; 23: 408‐14. 15. aapd. definition of special health care needs. pediatr dent. 2008; 30: 15. jiimc 2015 vol. 10, no.4 245 health problems in children with intellectual disabilities original�article abstract objective: to determine the preventive effect of turmeric on mosquito coil smoke induced emphysema in rat lungs. study design: randomized control trial. place and duration of study: the study was completed in six months duration in the department of anatomy, islamic international medical college, rawalpindi, in collaboration with national institute of health (nih), islamabad. materials & methods: twenty one adult male albino rats were divided into 3 equal groups. control group x was kept in fresh air. experimental group m was exposed to mosquito coil smoke for eight weeks. group t received oral turmeric 300mg/kg body weight and had a coil smoke exposure as well. all rats were dissected after 8 weeks and lung tissue was examined microscopically. the statistical significance of the results was calculated by applying pearson chi square test and the obtained results were compared statistically. results: marked emphysema was observed in the histological sections of rat lungs from experimental group m showing alveolar septal destruction and bullae formation in the lung tissues of all animals (100%) in group m. emphysema was present in 1 out of 7 rats in group t thus group t showed a significant protection with only 15% of animals with emphysematous lungs. conclusions: mosquito coil causes emphysema in the lung tissue and turmeric proves to be protective against this damage. key words: turmeric, pulmonary emphysema, smoke. mosquitoes. repellency is a characteristic of the 3 personal protection chemicals. mosquito coil repellents are widely used in domestic households to 1,4 combat mosquito menace. they are known to be an efficient mosquito repellent, are inexpensive and easy 3 to use but produce smoke . coils being cheap are widely used in asia. in 1996, who reported that the annual worldwide consumption of mosquito coils is 4 estimated to be 29 billion pieces and pollutant concentration from their emission is greater than the 5 who standards. they are burnt in closed rooms and are kept near the sleeping place to keep the mosquitoes at bay. coils although effective against mosquitoes, cause indoor air pollution and users are exposed to them usually for the whole night (approximately 8 hours) and for several months 1 every year , badly affecting various human organs 6 like liver, testis and kidneys specifically lungs and become a cause of debilitating respiratory disorders. lung damage, even cancer has been shown to occur by exposure to the coil smoke. studies have revealed that long term exposure to the coil smoke can induce 7 asthma and persistent wheeze in children and is introduction “he who has health has hope and he who has hope has everything.” but a tiny creature, named “mosquito” has always been spreading life threatening diseases like malaria and dengue fever 1 specially in tropical and subtropical countries, a major public health concern and a great hindrance to the socioeconomic development for the developing 2 nations. in the endeavor to protect himself, man has invented various means for protecting against effect of turmeric on mosquito coil induced emphysema in rat lungs 1 2 3 4 saira jawed, rehana rana, shazia muazzum, sabiha muhummad haq correspondence: dr. saira jawed assistant professor department of anatomy hbs medical & dental college, islamabad e-mail: sairajawed371@gmail.com 1,4 department of anatomy hbs medical & dental college, islamabad 2 department of anatomy islamic international medical college riphah international university, islamabad 3 department of anatomy rawal institute of health sciences, islamabad funding source: nil; conflict of interest: nil received: march 21, 2017; revised: august 06, 2018 accepted: september 02, 2018 effect of turmeric on emphysema in rat lungsjiimc 2018 vol. 13, no.3 141 international university. a total of 21 albino rats (sprague dawley), all healthy adult males weighing 250-300g were used for this study. rats were purchased from the animal house of national institute of health (nih) islamabad. they were kept in a well ventilated room and were allowed to acclimatize for a week. the animals were kept in smoke exposure chambers at a temperature of 27±3ºc with a 12hr light/dark cycle with access to drinking water and standard laboratory diet ad libitum. they were exposed to mosquito coil smoke for 7 hours per day for 8 weeks. animals were randomly divided into three groups and were kept in the same environmental conditions and received identical care. group t was taken as control group. experimental group m was exposed to mosquito coil smoke for eight weeks. group t received oral turmeric 300mg/kg body weight (through gastric gavage needle) and had a coil smoke exposure as well. all rats were sacrificed at the end of 8 weeks and left lungs were dissected out and preserved in the containers containing 10% formalin. tissue processing and embedding was done in paraffin. slides were prepared and stained with hematoxylin and eosin. microscopic study was done first at low power, x10, and then at high power, x40 objective. slides were studied for presence or absence of emphysema. bullae formation and destruction of alveolar septa was taken as a criteria to label emphysema. the data obtained as presence or absence of emphysema in each rat was coded and entered in spss for analysis applying a pearson chisquare test. p-value of <0.05 was taken as significant. results the alveoli of the control group x showed normal honey comb like structure with well-formed alveolar wall. in experimental group t, which received turmeric along with inhalation of coil smoke, emphysema developed in only one rat; 6 out of 7 rats remained protected against the damaging effect of coil smoke in group t (fig 1a). lung tissue of all the animals in group m, which received only coil smoke showed emphysema with alveolar septal destruction and bullae formation (figure 1b). statistical analysis was performed by using spss version 21. emphysema was taken as a dependent dichotomous nominal variable whereas coil smoke and curcumin were independent variables. pearson chi square test 8 teratogenic most severe poisoning has been reported in infants. a chemical barrier is created by the airborne insecticide particles present inside and around the houses that prevents mosquitoes from entering. coils that contain pyrethrins deter almost 3 45% to 80% mosquitoes and reduce their biting rat. burning the mosquito coil causes evaporation of insecticide and a large amount of sub micrometer particles and gaseous pollutants are released which 2 reach the lower respiratory tract. release of particulate matter by burning 75-137 cigarettes equals that of burning one mosquito coil. emission of formaldehyde from burning one coil is estimated to 9 be as high as burning 51 cigarettes. nature has always been kind and rightly labelled as a great physician and turmeric is a nature's gift for 10 health. curcumin(3-4%) is the main bioactive component of turmeric. turmeric holds a place of honor in traditional medicine of subcontinent for decades. it has been used as a food additive for centuries in asia. besides being the kitchen queen, it has been a center of attraction as a digestive aid, treatment for fever, inflammation, wounds, and infections as well as a remedy of various ailments including blood disorders. thus it is a traditional 11 herbal medicine. in the present days, curcumin is proved to be a potent anti-inflammatory and anti12 microbial agent. certain studies have proved that curcumin has p r e v e n t i v e e f f e c t s a g a i n s t t h e t r a c h e a l responsiveness and lung pathology in asthmatic 13 14 rats ventilator-induced and acute lung injury in 15 rats. an extensive literature search reveals that the local and international literature lacks in research with the same setup which could prove the effects of turmeric for prevention against histological alterations (damage) in lungs with allethrin based pyrethroids. hence the study was conducted with the objective of determining the preventive effect of turmeric on mosquito coil smoke induced emphysema in rat lungs. material and method the randomized controlled experimental study was carried out in 6 months duration in the department of anatomy, islamic international medical college, rawalpindi, in collaboration with national institute of health (nih), islamabad, after an ethical approval from the institutional review committee of riphah effect of turmeric on emphysema in rat lungsjiimc 2018 vol. 13, no.3 142 discussion emphysema is an abnormal, persistent expansion of the respiratory portion of the lung, distal to the terminal bronchioles resulting from tissue 16,17 destruction. in the lungs of all (100%) rats in group m, alveolar wall destruction and foci of collapsed alveoli with subsequent dilatation of contiguous alveolar spaces and formation of large irregular spaces (emphysematous change) was seen. pathogenesis of emphysema involves imbalance between elastase and anti-elastases and an imbalance between oxidants (free radicals) and antioxidants. elastase and oxidants are derived from 1 8 neutrophils and macrophage which were widespread in the rats of group m. the finding can be attributed to the injury of lung tissue by oxidants released by smoke exposure. cigarette smoke is 18 chemotactic to neutrophils and macrophages elastolytic and proteolytic enzymes, released by macrophages, have destructive effects on lung 19,20 airways. same phenomenon may be implied in mosquito coil smoke exposure because the burning of coil releases similar chemicals in even higher 9 concentration as compared to cigarette smoke. emphysematous change has also been observed by 21 franks in a smoke related study. after an exposure period of 16 weeks, smoke induced emphysema has also been observed in the lungs of rats by ji-hyun lee 22 in a study done in south korea. pulmonary emphysema has also been induced by cigarette smoke in an experimental study on rats conducted in canada to evaluate the role of neutrophils and macrophage released elastolytic enzymes in the 23 progression of emphysema. a recent study shows deranged lung function parameters in school 24 children due to pyrethroid exposure. emphysema has also been observed in mice after an exposure to 25 coil smoke for 120 days while in our study the histological alterations have been observed in rats in a 40 days exposure period. a recent study has proved that curcumin has p r e v e n t i v e e f f e c t s a g a i n s t t h e t r a c h e a l responsiveness and lung pathology in asthmatic 13 rats. it has also shown its efficacy during ventilatorinduced lung injury in rats by inhibiting the oxidative 14 stress and inflammatory response. a study proves that if the chemical stability of curcumin is improved than it shows incredible property of preventing the was applied. the data was entered by coding the presence and absence of emphysema. the statistical significance for the observed results was compared between the two experimental groups. results showed alveolar septal destruction and emphysema with bullae formation in the lung tissues of all animals (100%) in group m (fig 2). emphysema was absent in 6 out of 7 rats in group t; thus group t showed a significant protection with only 15% of animals with emphysematous lungs. the difference was statistically significant with a p value of 0.000 that is <0.05. difference of results can clearly be observed in graph (fig 2). fig 1: (a) lung of rat in group t showing preserved alveolar structure having honey comb appearance (arrow). (b) lung of rat in group m showing destroyed alveoli (arrow) and increased alveolar space or emphysema (double arrow). fig 2: graph showing frequency of emphysematous change in group x, m and t effect of turmeric on emphysema in rat lungsjiimc 2018 vol. 13, no.3 143 mosquito repellent coil and cigarette smoke. int j pharm biol sci. 2011;1(4):462–7. 2. deepa vk, premarajan kc, kar ss. pattern, costs and sociodemographic determinants of personal protection measures against mosquitoes in rural and urban communities of trivandrum district of kerala. age (omaha). 2012;410(419):829. 3. ogoma sb, moore sj, maia mf. a systematic review of mosquito coils and passive emanators: defining recommendations for spatial repellency testing methodologies. parasites and vectors. 2012;5(1):287. 4. shu-chen c, ruey-hong w, li-jie s, ming-chih c, huei l. exposure to mosquito coil smoke may be a risk factor for lung cancer in taiwan. j epidemiol. 2008;18(1):19–25. 5. wang l, zheng x, stevanovic s, xiang z, liu j, shi h, et al. characterizing pollutant emissions from mosquito repellents incenses and implications in risk assessment of human health. chemosphere [internet]. 2018;191:962–70. a v a i l a b l e f r o m : http://www.sciencedirect.com/science/article/pii/s00456 53517315138 6. taiwo vo, nwagbara nd, suleiman r, angbashim je, zarma mj. clinical signs and organ pathology in rats exposed to graded doses of pyrethroids-containing mosquito coil smoke and aerosolized insecticidal sprays. african j biomed res. 2008;11(1):97–104. 7. tarasub n, tarasub c, ayutthaya wdn. protective role of curcumin on cadmium-induced nephrotoxicity in rats. j environ chem ecotoxicol. 2011;3(2):17–24. 8. upadhyay j, rana m, juyal v, rana a, bisht ss. effect of pesticide exposure on the female rats and their pups throughout their gestation period. res j pharm technol. 2017;10(8):2535–7. 9. liu w, zhang j, hashim jh, jalaludin j, hashim z, goldstein bd. mosquito coil emissions and health implications. environ health perspect. 2003;111(12):1454. 10. niazi ju, poonia p, gupta v, kaur n. pharmacotherapeutics of curcuma longa-a potent patent. ijppr. 2010;1:24–30. 11. lal j. turmeric, curcumin and our life: a review. bull env pharmacol life sci. 2012;1(7):11–7. 12. sakurai r, li y, torday js, rehan vk. curcumin augments lung maturation, preventing neonatal lung injury by inhibiting tgf-β signaling. am j physiol lung cell mol physiol [internet]. 2011;301(5):l721--l730. available from: http://ajplung.physiology.org/content/301/5/l721 13. shakeri f, roshan nm, kaveh m, eftekhar n, boskabady mh. curcumin affects tracheal responsiveness and lung pathology in asthmatic rats. pharmacol reports [internet]. 2018; available from: http://www.sciencedirect.com /science/article/pii/s1734114018300021 14. wang x, an x, wang x, bao c, li j, yang d, et al. curcumin ameliorated ventilator-induced lung injury in rats. biomed pharmacother [internet]. 2018;98:754–61. available from: http://www.sciencedirect.com/science/article/pii/s07533 32217351466 15. zhang y, liang d, dong l, ge x, xu f, chen w, et al. antiinflammatory effects of novel curcumin analogs in experimental acute lung injury. respir res [internet]. 2015 mar;16(1):43. available from: https://doi.org/10.1186 15 acute lung injury in rats. however, literature lacks in proving the protective effects of turmeric against the lung injury induced by allethrin based coil smoke. group t had remarkable preservation of lung tissue i n w h i c h o n l y 1 5 % o f a n i m a l s s h o w e d emphysematous change. turmeric has shown to prevent the emphysematous changes induced by 23 cigarette smoke. turmeric contains curcuminoids which are antioxidant and therefore can protect against the development of emphysema. as a potent immunomodulatory agent it can attenuate the activation of t cells, b cells, macrophages, 26 neutrophils and natural killer cells. and thus the tissue destructing enzymes released by these cells. it a l s o a ffe c t s t h e re l e a s e o f i n f l a m m a to r y 27 cytokines. ,therefore, can possibly protect the lung tissue from the histological alterations induced by coil smoke in the rat lungs. inhaling toxic chemicals daily is inevitable these days especially in the underdeveloped countries, where combustion of biomass and synthetic materials like mosquito coils are used as the main mode of prevention from the mosquitoes because of the fear of contracting lethal diseases like dengue fever and malaria. turmeric supplementation in the diet could possibly protect lungs against environmental pollutants especially pyrethroids. because of the limited duration, effect of prolonged exposure of pyrethroids on lungs and the preventive effects of turmeric on other body organs could not be studied. further human based studies of prolonged duration are recommended. conclusion the present study clearly demonstrates that mosquito coil smoke adversely affects the lungs and induces histological damage causing emphysema and turmeric prevents it. therefore alternative ways like nets and herbal products should be used to protect oneself from mosquitoes. exposure to the toxic repelling agents should be avoided by human population. turmeric has protective properties and saves the lung tissue from toxic effects of pyrethroids and can be used as a dietary supplement for preventing against environmental pollutants. references 1. phal da. a comparative study of elemental analysis in effect of turmeric on emphysema in rat lungsjiimc 2018 vol. 13, no.3 144 induced emphysema. am j physiol lung cell mol physiol [internet]. 1998;275(6):l1134--l1144. available from: http://ajplung.physiology.org/content/275/6/l1134 24. rathore p, sheikh s, ruqaya, lathiya n. effect of insecticides (pyrethroids) on lung function parameters in school children. pakistan j physiol [internet]. 2017 mar 31;13(1 seo r i g i n a l a r t i c l e ) . a v a i l a b l e f r o m : http://www.pjp.pps.org.pk/index.php/pjp/article/view/26 1 25. abdulla al-mamun m, ataur rahman m, habibur rahman m, hoque kmf, ferdousi z, matin mn, et al. biochemical and histological alterations induced by the smoke of allethrin based mosquito coil on mice model. bmc clin pathol [internet]. 2017 aug;17(1):19. available from: https://doi.org/10.1186/s12907-017-0057-9 26. moghaddam sj, barta p, mirabolfathinejad sg, ammaraouchiche z, garza nt, vo tt, et al. curcumin inhibits copdlike airway inflammation and lung cancer progression in mice. carcinogenesis. 2009;30(11):1949–56. 27. sciberras jn, galloway sdr, fenech a, grech g, farrugia c, duca d, et al. the effect of turmeric (curcumin) supplementation on cytokine and inflammatory marker responses following 2 hours of endurance cycling. j int soc sports nutr. 2015;12(1):5. /s12931-015-0199-1 16. riede u-n, werner m. color atlas of pathology: pathologic principles, associated diseases, sequelae. thieme; 2004. 17. klatt ec. robbins and cotran atlas of pathology [internet]. elsevier saunders; 2015. (robbins pathology series). a v a i l a b l e f r o m : h t t p s : / / b o o k s . g o o g l e . c o m . p k /books?id=k_ptbgaaqbaj 18. goljan ef. rapid review pathology [internet]. elsevier; 2 0 1 8 . ( r a p i d r e v i e w s e r i e s ) . a v a i l a b l e f r o m : https://books.google.com.pk/books?id=qlqataeacaaj 19. ta ra s e v i c i e n e s te wa r t l , vo e l ke l n f. m o l e c u l a r pathogenesis of emphysema. vol. 118, the journal of clinical investigation. 2008. p. 394–402. 20. strate bwa van der, postma ds, brandsma c, melgert bn, luinge ma, geerlings m, et al. cigarette smoke – induced emphysema a role for the b cell ? (16). 21. franks tj, galvin jr. smoking-related “interstitial” lung disease. arch pathol lab med. 2014;139(8):974–7. 22. lee j-h, lee d-s, kim e-k, choe k-h, oh y-m, shim t-s, et al. s i mva stat i n i n h i b i t s c i ga rette s m o k i n g i n d u c e d emphysema and pulmonary hypertension in rat lungs. am j respir crit care med. 2005;172(8):987–93. 23. ofulue af, ko m, abboud rt. time course of neutrophil and macrophage elastinolytic activities in cigarette smokeeffect of turmeric on emphysema in rat lungsjiimc 2018 vol. 13, no.3 145 original�article abstract objective: to compare ketoprofen and diclofenac sodium as a preemptive analgesic in impacted third molar surgery in terms of mean pain score and mean time of first analgesic postoperatively. study design: double blinded, parallel arm randomized controlled trial (rct). th th place and duration of study: the study was conducted from 15 april, 2016 to 5 november, 2016 at oral and maxillofacial surgery department of islamic international dental hospital, riphah international university. materials and methods: eighty patients requiring surgical extraction of impacted mandibular third molar were selected by using randomized sampling technique. these patients were randomly assigned two groups using lottery method, resulting in sample size of 40 in each group. preoperatively diclofenac sodium was administered intramuscularly in group a and ketoprofen in group b using double blinded technique. pain score was measured 3 hours after surgery using visual analogue scale (vas) and the time of first analgesic consumption post-operatively was recorded in hours. statistical package for social sciences (spss version 16) was used for data analysis and independent sample t test was applied to compare mean pain score and time of first rescue analgesics between two groups with 0.05 as a level of significance. results: results showed that mean pain score was less in ketoprofen group (3.42+1.08) than diclofenac sodium group (4.02+1.20) with significant p-value of 0.02. time interval for first analgesic post-operatively was also measured in hours. results were highly significant revealing prolonged analgesic effect in ketoprofen group with p-value of 0.007. conclusion: preemptive ketoprofen provides better and prolonged pain control as compared to diclofenac sodium in impacted third molar surgery. key words: diclofenac sodium, ketoprofen, preemptive analgesia, pain score. 2,3,4 to the severe post-operative discomfort and pain. numerous studies have reported that postoperative pain reaches to its peak at 6-8 hours after surgery 2,3,4,5 and require strong analgesics. trauma to periosteum and bone during surgery results in the initiation of nociceptive stimulus by generation of prostaglandins and leukotrienes leading to 6,7 peripheral sensitization and acute pain. certain active mediators results in transmission of nerve impulses to brain leading to central sensitization and hyper excitability of neurons in central nervous 6,7 system. non-steroidal anti-inflammatory drugs (nsaids) are widely used to relieve pain of mild to moderate intensity and have analgesic, anti-inflammatory and 2,4 anti-pyretic effects. nsaids are non-selective 2 , 4 , 7 cyclooxygenase (cox) enzyme inhibitors. ketoprofen and diclofenac sodium both belong to nsaids and are commonly prescribed for pain 2 control after third molar surgery. biological half-life introduction successful pain management is one of the main factors that have allowed surgery to progress to the 1 current status. it relies solely on the surgeon to attempt every possible approach to eliminate 1 postoperative pain and discomfort in patients. surgical removal of impacted mandibular third molar is a common procedure carried out in routine dental practice which requires reflection of extensive mucoperiosteal flap and bone guttering which leads does diclofenac sodium provide better preemptive analgesia than ketoprofen in impacted third molar surgery? a randomized controlled trial correspondence: dr. asma pervaiz department of oral and maxillofacial surgery islamic international dental hospital riphah international university, islamabad e-mail: asmaparvez_14@hotmail.com department of oral and maxillofacial surgery islamic international dental hospital riphah international university, islamabad funding source: nil; conflict of interest: nil received: dec 27, 2017; revised: jul 09, 2018 accepted: jul 16, 2018 diclofenac sodium a preemptive analgesic jiimc 2018 vol. 13, no.3 122 providing an evidence-based standard for treating pain and discomfort. materials and methods this was a quantitative research employing double blinded randomized control trial methodology to compare ketoprofen and diclofenac sodium as preemptive analgesics in impacted mandibular third th molar surgery. this study was conducted from 15 th april, 2016 to 5 november, 2016 at oral and maxillofacial surgery department of islamic international dental hospital, riphah international university. we used simple randomized sampling technique and total sample size was 80 patients with impacted mandibular third molar. all patients were between age group 18-35 years. these patients were randomly assigned to group a and b using lottery method. double blinded technique was used while administering the drugs where neither operator nor patient knew about the medicine being received preoperatively and all procedures were carried out by the same operator to control bias. ethical approval of the study was obtained from the e t h i c a l c o m m i t t e e o f i i d h ( r e f . n o . iidc/irc/2015/03/003). this was a minimal to no risk study as special care was taken to exclude all the patients who have contraindications for nsaids. a written informed consent was taken from all the patients before intervention. all the participants of the study were fully explained about the procedure, aim of research and all possible side effects. no participant was forced or pressurized to participate. the participants were ensured that the data will not be used for any other study without their consent. the criteria of inclusion were any patient reporting in the study setting with mesioangular class ii class b mandibular impaction during the study period. the criteria of exclusion were any patient with pericoronitis, pain on the day of surgery, medical conditions in which nsaids are contraindicated and other oral surgical indications. intramuscular (im) injection of ketoprofen 100mg was given to one group and diclofenac sodium 75 mg to other group 30 minutes prior to the surgical procedure. then inferior alveolar nerve was blocked with 2% lignocaine and 1:80,000 epinephrine before the procedure was performed. paracetamol 500 mg was prescribed as postoperative analgesic. patients were advised to record the pain scores 3 hours of ketoprofen is 2-2.5 hours and is readily distributed into the central nervous system and crosses the blood brain barrier within 15 minutes, due to its high 2,7 level of liposolubility. diclofenac has a biological 7 half-life of 1.2-2 hour. preemptive analgesia is administration of analgesics preoperatively before the initiation of nociceptive 8,9,10,11 stimulus and provides better pain relief. it blocks the nociceptive stimulus thus preventing or reducing 9,11 the peripheral and central sensitization. idea of 7 preemptive analgesia gained attention in 1980's. preemptive analgesia emphasizes on both the 10,11 prevention and treatment of postoperative pain. several studies have compared and documented the effectiveness of two different drugs as a preemptive analgesic in the literature. velásquez et al compared ketoprofen and diclofenac sodium as a preemptive analgesic in third molar surgery, stating that ketoprofen is better than diclofenac sodium in terms of prolonging the time interval needed for the first 2 analgesic postoperatively. they also reported that ketoprofen is better than diclofenac sodium in terms 2 of postoperative pain control . mario et al demonstrated that preoperative oral ketorolac plus s u b m u c o s a l t r a m a d o l r e s u l t s i n r e d u c e d consumption of analgesics after third molar surgery 5 than oral ketorolac alone with p-value of 0.04. there is little or no published research comparing diclofenac sodium and ketoprofen as a preemptive analgesic in third molar surgery in pakistan. the evidence to suggest which of the two nsaids work better for preemptive analgesia is inconclusive. further research in this area is warranted. this study aimsto fill this research gap bycomparing the analgesic effect of ketoprofen and diclofenac sodium in providing preemptive analgesia in third molar surgery in a tertiary care dental setup in islamabad, pakistan. this study will not only provide an evidence-based practice to minimize the pain intensity after surgical removal of third molar and to reduce the need of taking a large number of analgesics after surgery, but will also serve as a published literature in comparing ketoprofen and diclofenac sodium, so as to serve as a baseline for further research in pakistan. this study is also expected to improve the patient's perception towards dental treatment which is mostly considered as a painful experience by patients by diclofenac sodium a preemptive analgesic jiimc 2018 vol. 13, no.3 123 mean age in group a was 28.98+4.00 sd and that for group b was 29.00+4.42 sd with an insignificant statistical difference (p=0.97) among both groups both groups as shown in table ii. postoperatively with the help of visual analogue scale, ranging from 0-10(0 denotes absence of pain and 10 denotes severe pain) and the time of taking first analgesic after surgery. we used mean pain score as a tool to measure pain that has long been used to measure pain all over the world. thus, the tool we used to measure pain is valid optimizing the validity of our research. this study can be reproduced in any part of the world and in any community using the same methods ensuring that this is a reliable research design. the study setting is a teaching institute of islamabad, which is the capital of country. the population of islamabad belongs to different parts of the country and is of different socioeconomic status. so we can somewhat generalize our results to whole country. the data was analyzed using statistical package for social sciences (spss version 16). the independent variables are gender and age. the dependent variables are mean pain score and the time of first rescue analgesic in hours. frequencies were measured for qualitative variable such as gender. mean and standard deviation were calculated for quantitative variables such as age, pain score and time of first analgesic (hours) postoperatively. independent sample t test was applied to compare mean pain score and time of first rescue analgesics between two groups and p-value of <0.05 was considered as significant. results this double blinded randomized controlled trial aimed at comparing ketoprofen and diclofenac sodium administered through im route 30 minutes preoperatively in patients for surgical removal of impacted third molars. patients in group a were administered with im diclofenac sodium 75mg, and in group b with im ketoprofen 100mg. group a contained 19(47.5%) male patients and 21(52.5%) female patients while group b contained 25(62.5%) male patients and 15(37.5%) female patients. gender distribution in both groups is shown in table i. table i: gender distribu�on in group a and b table ii: mean age for group a and b the results for independent sample t test revealed a significant difference between the mean pain scores at 3 hours among two groups that is; mean pain score at 3 hours was 4.02+1.20 in diclofenac sodium group(a) and 3.42+1.08 in ketoprofen group(b) with p-value 0.02 at 95% confidence interval as shown in table iii. table iii: mean pain score at 3 hours post-opera�vely result clearly showed that ketoprofen provided better pain control than diclofenac sodium as a preemptive analgesic. results of independent sample t test for the comparison of time interval in two groups at which first analgesic was taken post operatively revealed that mean time interval for first rescue analgesic post-operatively was 2.90+1.24 hours in diclofenac group (a), and was 3.61+1.02 hours in ketoprofen group (b), with p-value of 0.007 at 95% confidence interval, so there was significant difference between both groups as shown in table iv. st table iv: mean �me interval for 1 rescue analgesic (hours) diclofenac sodium a preemptive analgesic jiimc 2018 vol. 13, no.3 124 pain scores at 3 hours among two groups that is; mean pain score at 3 hours was 4.02+1.20 in diclofenac sodium group and 3.42+1.08 in ketoprofen group. this demonstrates that patients administered with ketoprofen pre-operatively reported significantly less pain at 3 hours posto p e rat i ve l y a s c o m p a re d to t h e p at i e n t s administered with diclofenac. we also report the comparison of time interval in two groups at which first analgesic was taken post operatively. the results of our study revealed that mean time interval for first rescue analgesic post-operatively was significantly less in diclofenac group (2.90+1.24 hours) as compared to the ketoprofen group (3.61+1.02 hours) demonstrating that pre-operatively administered ketoprofen provided longer post-operative pain control than diclofenac sodium. the results of our study are consistent with a similar double blinded randomized control trial carried out by velásquez et al. they also compared analgesic effect of ketoprofen and diclofenac and report a significantly prolonged pain control with ketoprofen 2 (p value 0 .006) supporting our results. velásquez et al, however suggest that the mean pain score at 3 hours post operatively was insignificant between 2 two groups. the results of tai et al also support result of our study who compared ketoprofen 200 mg and diclofenac 100 mg in multiple doses for 4 days after third molar surgery demonstrating that ketoprofen provides significantly better pain control with the p-value of 13 0.086. tai et al, however do not evaluate surgical difficulty level of impaction. our study includes only mesioangular class ii and class b impactions and excludes all the cases with surgical time above 60 mins. the results of our study are also consistent with the results of shah et al, which state that ketoprofen induced a longer duration of analgesic 14 effect. on the other hand, niemi et al compared analgesic effect of intravenous (iv) diclofenac 1 mg/kg and ketoprofen 1.35 mg/kg 30 minutes before and 4 hours after surgery, and also prescribed 0.03mg/kg iv oxycodone as the rescue medication in first 24 hours. the results demonstrate a lower requirement of oxycodone in the diclofenac group in comparison 15 with the ketoprofen with p-value of <0.01. the difference of the results of this study from our results it showed that ketoprofen provided pain control for longer duration than diclofenac sodium. discussion the practice of treating pain after surgical trauma is now being replaced by preventive approaches that aim to block transmission of the painful nerve 2 impulses before and during surgery . pre-operative administration of nsaids provides better and prolonged pain relief by blocking the release of prostaglandins and leukotrienes, thus blocking peripheral and central sensitization leading to reduced number of analgesics taken post2,6 operatively and better patient compliance . this study compares the preemptive effect of im ketoprofen with im diclofenac sodium and reports that ketoprofen provides better and prolonged pain control in comparison to diclofenac. the results for independent sample t test in our study clearly revealed a significant difference between the mean table v: summary of discussed literature diclofenac sodium a preemptive analgesic jiimc 2018 vol. 13, no.3 125 results of this study may not be used to ascertain effectiveness of both drugs for other types of rd mandibular 3 molar impaction. this study includes sample from just one dental hospital in islamabad, thus it can affect the generalizability of the results. there is a need of further and extensive research to compare effects of different types of analgesics in pakistan, so as to provide an evidence-based approach towards pain free experience for patients in this era of surgical advancement. conclusions based on this study we conclude that preemptive analgesia is a better option in minor oral surgical procedures. preemptive analgesics works best in the cases of inflammation, reduces the post-operative morbidity and pain by blocking the release of prostaglandins and peripheral and central sensitization of pain. nsaids are more commonly used as preemptive analgesics and according to this study ketoprofen 100mg provides better analgesic effects than diclofenac sodium 75mg in terms of reducing pain intensity and pain control for longer duration. references 1. rejab af. comparison of the intramuscular and sub-mucous postoperative analgesic effect of tramadol hcl after minor oral surgery. international journal of enhanced research in science technology & engineering, 2014: 3: 122-9. 2. velásquez gc, santa lc, espinoza ma. ketoprofen is more effective than diclofenac after oral surgery when used as preemptive analgesic: a pilot study. j oral facial pain headache. 2014; 28: 153-8. 3. prashar d, pahwa d, kalia v, jindal g, kaur r. a comparative evaluation of the effect of diclofenac sodium with and without per-orally administered methylprednisolone on the sequelae of impacted mandibular third molar removal: a cohort randomized double-blind clinical trial. indian j dent. 2016; 7: 11–6. 4. orozco-solís m, garcía-ávalos y, pichardo-ramírez c, tobías-azúa f, zapata-morales jr, aragon-martínez oh, et al. a single dose of diclofenac or meloxicam for control of pain, facial swelling, and trismus in oral surgery. med oral patol oral cir bucal. 2016; 21: 127–34. 5. isiordia-espinoza ma, pozos-gullen aj, martinez-rider r. preemptive analgesic effectiveness of oral ketorolac plus local tramadol after impacted mandibular third molar surgery. med oral patol oral cir buccal. 2011; 16: 776-80. 6. kaczmarzyk t, wichlinski j, stypulkowska j. preemptive effect of ketoprofen on postoperative pain following third molar surgery. a prospective, randomized, double blind clinical trial. int j oral maxillofac surg. 2010; 39: 647-52. 7. sarzi-puttini p, atzeni f, lanata l. pain and ketoprofen: what can be explained on the basis of not considering the level of difficulty of the surgery. in another study kaczmarzyk t et al, compared analgesic effect of orally administered ketoprofen 100mg, 60 min preoperatively and 60 min postoperatively and reported that the mean pain score in pre-operative group was 45.7+10.53 and in postoperative group was 33.10+7.91 with p value of 6 0.031. the study also compared mean time interval in minutes for first rescue analgesic in both groups and reported that the mean time interval for first rescue analgesic is less in pre-operative group (336.75+10.43 minutes) as compared to that in postoperative group (409.93+12.69 minutes) with p6 value of 0.0013. their results showed better and prolonged pain control with post-operative 6 ketoprofen. our study however does not evaluate the analgesic effect of post-operative administration of nsaids. there is an extensive literature that compares diclofenac and ketoprofen with other medicines in terms of pain control. manani et al, showed that ketoprofen is more effective in pain control compared with naproxen and have higher analgesic 16 properties. in another study lopez et al compared antiinflammatory properties of diclofenac sodium with methylprednisolone in a third molar surgery and suggests that despite of less inflammation observed in methylprednisolone group, there is no significant 17 difference in the reduction of trismus. nazar et al compared intramuscular (im) diclofenac sodium with tenoxicam for the pain relief. it stated that im diclofenac sodium produced significant pain relief 18 compared to tenoxicam. all studies discussed here are summarized in table v. the extensive literature supports the results of our s t u d y a n d s u g g e s t s t h a t p r e o p e r a t i v e administration of ketoprofen not only reduces the severity of post-operative pain but also prolongs the onset time of post-operative pain in comparison to pre-operatively administered diclofenac. there are few limitations in the present study. age and gender were not matched at the baseline. this may have biased the results since pain threshold may vary across gender and age variations. another shortcoming is the selection of only mesioangular impaction with class b and type ii. therefore, the diclofenac sodium a preemptive analgesic jiimc 2018 vol. 13, no.3 126 diclofenac sodium a preemptive analgesic jiimc 2018 vol. 13, no.3 2018; 445-62. 13. tai ym, baker r. comparison of controlled-release ketoprofen and diclofenac in the control of post-surgical dental pain. j r soc med. 1992; 85:16–8. 14. shah s, soomro m, kella u, talpur a, dino dal w. comparative study of non-steroidal anti-inflammatory drugs in postoperative pain. j surg pak. 2003; 8: 2-5. 15. niemi l, tuominen m, pitkänen m, rosenberg ph. comparison of parenteral diclofenac and ketoprofen for postoperative pain relief after maxillofacial surgery. acta anaesthesiol scand. 1995; 39: 96–9. 16. manani g, corliano l, zanette g, pizzali m, borreggine d, calzigna l. ketoprofen and naproxen in acute postoperative orthopedic pain. acta anaesth italica. 1993; 44: 73-80. 17. lópez carriches c, martínez gonzález jm, donado rodríguez m. the use of methylprednisolone versus diclofenac in the treatment of inflammation and trismus after surgical removal of lower third molars. med oral patol oral cir bucal. 2006; 11: 440-5. 18. nazar mn, puthiriraj v. analgesics following mandibular t h i r d m o l a r s u r g e r y. i n t e r n a t i o n a l j o u r n a l o f pharmaceutical and clinical research. 2014; 6: 13-19. is its role in clinical practice? reumatismo. 2010; 62: 17288. 8. alipio j, carlos l, santana td. comparative study of tramadol combined with dexamethasone and diclofenac sodium in third-molar surgery. j craniomaxillofac surg. 2012; 40: 694-700. 9. shah r, mahajan a, shah n. preemptive analgesia in third molar impaction surgery. natl j maxillofac surg. 2012; 3: 144-7. 10. kumar m, godhi s, lall ab. preoperative intravenous tramadol versus diclofenac for preventing postoperative pain after third molar surgery: a comparative study. j maxillofac oral surg. 2011; 10: 306-9. 11. mony d, kulkarni d, shetty l. comparative evaluation of preemptive analgesic effect of injected intramuscular diclofenac and ketorolac after third molar surgery-a randomized controlled trial. journal of clinical and diagnostic research: jcdr. 2016; 10: 102. 12. helander em, eskander jp, juneau cl, novitch mb, prabhakar a, dekerlegand am, et al. preemptive analgesia, regional anesthesia, and prevention of chronic postoperative pain. essentials of regional anesthesia. 127 untitled-1 untitled-1 untitled-2 original�article abstract objective: to evaluate the performance of chromagar and api 20c aux for the documentation of different candida species. study design: descriptive cross-sectional study. place and duration of study: the study was conducted in the department of microbiology at afip (armed forces institute of pathology), cmh rawalpindi and army medical college rawalpindi in collaboration with departments of pathology (microbiology) at pakistan railways teaching hospital (prh), islamic international th th medical college rawalpindi from 01 april 2017 to 30 september 2017. materials and methods: collectively 100 isolates of candida yielded from hvs clinical samples. phenotypic tests including growth on chromagar candida and api 20c aux were used for reporting different candida species. clinical candida isolates along with reference institutional control strains of candida species were used in the study. data was analyzed using simple descriptive statistics (frequencies, percentages) for each categorical variable. results: among 100 candida isolates 92 (92%) isolates of candida were identified correctly to level of species by chromagar candida, in comparison to 100% identification of candida species using api 20c aux. results of present study revealed that chromagar candida can be used to report three species of candida considering the morphology and colour of colonies of these particular species, and to distinguish them as c. albicans, c. tropicalis, and c. glabrata. conclusion: both phenotypic tests chromagar plates and api 20 c aux are effective in the documentation of candida species. however api 20 c aux is found to be more accurate than chromagar because less commonly isolated candida species cannot be documented using chromagar. moreover being less costly; use of chromagar candida is helpful in rapid identification and constructing suitable therapeutic plan for patient's management in laboratories with limited resources. key words: candida species, hvs, identification methods. 1980s, a steady rise in incidence as well as prevalence of these infections has been found contributing significantly to morbidity and mortality. mycotic infections are frequently found in patients 1,2,3 with depressed immunity like cancer patients receiving chemotherapy, transplant patients and aids patients who are more prone to develop 4 infections caused by candida. infections due to candida albicans remains the most frequent etiology of human diseases due to genus candida, but the incidence of infections due to non albicans candida is 5,6 also increasing. there is a variety of methods for identifying candida species from clinical samples, among them chromagar candida differential medium is commonly used to isolate presumptive c. albicans, c. dubliniensis, c. tropicalis and c. krusei. its sensitivity and specificity is considered satisfactory introduction fungal infections have worldwide spread. since comparative evaluation of chromagar and api 20c aux in isolation and identification of candida species 1 2 3 uzma mussarat malik , abdul bari khan , muhammad luqman satti correspondence: dr. uzma mussarat malik department of pathology islamic international dental college riphah international university, islamabad e-mail: uzma_arslan5@yahoo.com 1 department of pathology islamic international dental college riphah international university, islamabad 2 department of pathology islamic international medical college riphah international university, islamabad 3 department of microbiology armed forces institute of pathology, afip rawalpindi funding source: nil; conflict of interest: nil received: feb 29, 2018 revised: may 10, 2018 accepted: may 15, 2018 efficacy of chromagar and api 20 c auxjiimc 2018 vol. 13, no.2 85 7,8 for these species. the biochemical characterization is done using the api® 20c aux (biomerieux, france), which relies on variations in the assimilation of 9 carbohydrates. however, it presents limitations related to cost and to distinguish between some 7 species. presently the emergence of non albicans candida species is a major problem to be addressed 10,11 in several institutions. in 70% to 90% vulvovaginal candidiasis cases, c. albicans is found to be main causative agent to be followed by c. glabrata causing 5,6,12 10% 20% of vaginal candidiasis. most species of candida are involved in causing vulvovaginitis but c. krusei, c. parapsilosis ,and c. tropicalis are 13 infrequent causative agents. conventional methods used for candida species identification like assimilation and fermentation reactions are described as clumsy and beyond the range of expertise in local laboratories. evaluation of identification methods in resource-limited settings for candida species such as microscopy, colonial morphology and biochemical studies require unique research studies for effective management and 14 prompt diagnosis of fungal infections. candida vaginitis is usually diagnosed without proper diagnostic procedures but there is possibility that women may be uninfected or may be suffering from another illness. culture on sabouraud's dextrose agar (sda) for diagnosis of fungal infections is considered as gold standard, while isolation and identification using different phenotypic assays can 15,16 take up to 2 – 4 days. rapid identification of mycotic infections is possible with use of different brands of chromogenic media. these chromogenic agars, reduces the time required for the identification of yeast by distinguishing common candida species on the basis of specific color that generated because of reaction of substrate with enzymes secreted by microorganisms after 0 17,18 incubation for 48 hours at 37 c. use of api 20c aux kit for identification of candida species including c.albicans and non albicans candida is easier and has greatly reduced the laboratory time involved in the speciation of candida 19, 20 isolates. owing to limited knowledge and practice of these phenotypic methods, this study was aimed to compare and evaluate the efficacy of chromagar and api 20c aux in identification of candida species. materials and methods a descriptive cross-sectional study was conducted st th from 01 april 2017 to 30 september 2017 after approval from research and ethical review committee. non-probability convenient sampling was done and non-parametric data were collected. the data of candida species were analyzed by using frequencies distribution test on spss (version 20) software. a total of 100 candida isolates were collected from microbiology labs of armed forces institute of pathology (afip), army medical college (amc) and islamic international medical college (iimc) in collaboration with combined military hospital (cmh), military hospital (mh) and railway hospital rawalpindi respectively. study included hvs s p e c i m e n s o f p re g n a nt , n o n p re g n a nt a n d postmenopausal women that revealed growth of , candida species on sabouraud s culture plate. direct gram-stained smear examination was done for all collected candida isolates after culture on sabouraud's dextrose agar (sda) (oxoid, uk) incubating at 37 °c for 24 – 48 hours. institutional control strains were used to compare the results of present study. conventional methods, such as germ tube test, macroscopic appearance and structural description of colonies i.e. colour, size and texture on sabouraud's dextrose agar (sda), and chromagar candida were used to confirm the growth of control strains. chromagar candida medium in each liter contained peptone (10 g), glucose (20 g), agar (15 g), and chloramphenicol (0.5 g) and chromogenic mixture. (2 g), while ph of the medium was maintained at 6.1 according to instructions of manufacturer. candida colonies of study samples from sda agar were inoculated onto chromagar. specimens were streaked for isolation onto the surface of the medium. the plates were kept for incubation at 30°c for 48-72 hrs in an inverted position. forty two hours incubation time is obligatory for complete color development of candida colonies. the diverse species of candida species revealed dissimilar colours of colonies i.e. c. albicans colony appeared light to medium green, c. tropicalis colonies gave dark blue to metallic-blue colour and c.glabrata colonies looked light mauve to mauve. moreover, these colonies were flat with a whitish border. other candida species like c. krusei can give rise to light to efficacy of chromagar and api 20 c auxjiimc 2018 vol. 13, no.2 86 dark mauve colour. rest of non albicans candida species produced light creamy to light pink colour that were later on identified with api kit. api 20 c aux (biomerieux, france) was used to p e r fo r m c a r b o hyd rate fe r m e ntat i o n te st s . dehydrated substrates were added in 20 different cupules which allowed the performance of 19 assimilation tests. semi solid minimal medium was used to inoculate the cupules and the growth of yeast was seen when utilized the added substrate as the soul carbon source. the reactions were read by linking them to growth controls and documentation was done by referring to the analytical profile index. colonies and were termed as c. tropicalis, while 68 (68%) samples showed green coloured colonies of candida albicans. among rest of 8 samples, 4 samples showed light pink colonies and 4 samples revealed blue to mauve coloured colonies which after api testing identified as c.famata 4(4%), c. guilliermondii 2(2%), saccharomyces cerevisiae 1(1%) and c. lusitaniae 1(1%). moreover, candida albicans was found to be dominant over the non albicans species. the comparative identification results are shown in table i. fig 1: api 20c aux results of api were finally compared with the culture results and speciation of candida was also done. results results of germ tube test revealed 68 out of 100 isolates were positive for germ tube and remaining 32 were negative as shown in fig 2. fig 2:f requency of germ tube posi�ve isolates among 100 samples grown on chromagar plates, 16 (16%) showed pinkish purple growth and were labeled as c. glabrata, 8 (8%) revealed blue coloured table i: iden�fica�on of samples using chromagar and api 20c aux the api 20 c aux tests recognized the candida species on the basis of fermentation and utilization of different sugars. the confirmatory test by api yielded seven species of candida in total i.e. c. albicans, c. glabrata, c. tropicalis, c. guilliermondii, c. famata, saccharomyces cerevisiae and c. lusitaniae. api test results were matched with chromagar results, germ tube test results and microscopy of these selected samples. overall chromagar identified strains correctly with more than 90% discrimination while comparing with api 20 c aux results. the results of api are tabulated in table 1. the api 20 c aux system correctly identified about 100% of the isolates compared to 92% by chromagar culture technique. the chromagar culture plates correctly identified all organisms except 8 isolates. these 8 isolates revealed pink to efficacy of chromagar and api 20 c auxjiimc 2018 vol. 13, no.2 87 purple coloured colonies that were identified differently using api 20c aux. the reason for this deviation is because chromagar has been known to identify frequently found species of candida i.e. c. albicans, c. glabrata, c. tropicalis. discussion in developing countries especially where resources are limited, deficiency of training skills and nonavailability of proper reagents that are contributory factors in making final diagnosis of mycotic infections, identification of fungal infections to species level become quite difficult. moreover to m i n i m i z e t h e m o n e t a r y b u r d e n o n t h e underprivileged patients, laboratories only perform germ tube test and limit their report only to 21 identification of c. albicans. in present study, all 100 candida isolates gave distinct colours on chromagar thus helped in the recognition of candida species causing vulvovaginitis in study population. this data conforms to finding of 22 a study conducted by horvath et al. there is nonconformance of our data with a study conducted by grace l et al who reported 78% identification of 23 candida species using chromagar. this finding might be due to direct subculture of specimen on chromagar plates. lynn l et al reported that chromagar readily identify c. albicans, c.glabrata, 22 c.krusei, and c. tropicalis. diagnosis of vaginal candidiasis is usually based on clinical symptoms and direct microscopic examination as stated by nyirjesy 24,25 et al and faraji et al ; although microscopic examination of clinical samples is quick, easy method and may recognize the probable causative agent, but cdc recommend that vaginal culture is mandatory 26 to confirm the diagnosis. in this study, different laboratory methods were used for prompt diagnosis of candida species, among these gram staining and germ tube test were found easy and trustworthy techniques for the documentation of candida spp. chromagar is found to be a novel medium enabling isolation and identification of different candida species. this media correctly identified 92% of candida strains which is in accordance with the prior 27 study done by ozcan et al.in 2010. based on different colors and morphology of colonies “chromagar candida”, provided a fast and convincing recognition of frequently found yeasts species, which would ordinarily be missed during conventional plating on solid medium. according to nejad et al the major advantage of “chromagar candida” was its ability to detect the presence of 28 mixed species, and results of this study prove that use of chromagar was helpful in correct identification of c.albicans, c.glabrata and c.tropicalis depending on the colour and morphology of colonies. chromogenic culture media 29 are very helpful in identification of c. albicans but its main limitation is less power of discrimination 30 among non albicans candida species. in present study, 92 % of candida isolates were correctly identified after growth on chromagar , in contrast to the study conducted by dalia et al they stated that this medium correctly identified c. albicans with excellent sensitivity and specificity, but revealed 31 lower sensitivity for non albicans candida. the data suggested that species which were identified by chromagar were almost the same as were confirmed by api 20c aux. it means that in the presence of chromagar, germ tube test to confirm c.albicans can be excluded. on completion of study it is acknowledged that chromagar medium is appropriate and affordable diagnostics medium in a resource-limit setting because approximate cost per culture for complete identification of candida using sda, corn meal agar, and api 20c aux in pakistan is around rs. 1,200 while chromagar candida is around rs. 250 per specimen culture. additionally, 4 5 samples can be inoculated on one chromagar plate without compromising its effectiveness that makes it more cost efficient. present study supports the statement that the most suitable and popular procedure for candida species identification is the use of commercially available kits for carbohydrate assimilation and / or enzyme 31 detection. in the present work, all candida isolates were correctly identified to the species level by api 20c aux. results of present study about effectiveness of api 20c are in accordance with other 32,33,34,35 studies. api tests are evaluated as best methods for the final documentation of all candida species but owing to the fact that in our present hospital settings where limited resources are available this technique is difficult to practice on routine basis. comparison of chromagar and api 20c aux (biomerieux, france) reveals that use of chromagar is less costly while api identification efficacy of chromagar and api 20 c auxjiimc 2018 vol. 13, no.2 88 method is costly and laborious but api 20 c has an advantage that it can identify more species of non albicans candida as compared to chromagar, which can identify only three to four commonly involved candida species. conclusion this study reveals chromagar candida and api 20c aux having good potential to rapidly identify candida species. in resource limit settings, chromagar can be used as useful adjunctive medium in the clinical laboratory but for identification of yeasts at species level, the use of api 20c aux with a wider database is preferable. api 20c is better for the diagnosis of candidiasis especially due to less frequently found candida species and should be adopted as routine diagnostic procedure in the clinical microbiological laboratories. this study has involved evaluation of two phenotypic methods in identification of candida species in small number of cases with vaginal candidiasis because of cost and availability issues. future studies including large sample size and comparison of these two methods with other diagnostic methods used for identification of candida species are needed. moreover comparison and evaluation of these two methods in identifying candida species in cases other t h a n v u l v o v a g i n a l c a n d i d i a s i s a r e a l s o recommended. references 1. arendrup mc, fuursted k, gahrn-hansen b, jensen im, knudsen jd, lundgren b, et al. seminational surveillance of fungemia in denmark: notably high rates of fungemia and numbers of isolates with reduced azole susceptibility. journal of clinical microbiology. 2005; 43: 4434-40. 2. espinel-ingroff a, canton e, peman j, rinaldi m, fothergill a. comparison of 24-hour and 48-hour voriconazole mics as determined by the clinical and laboratory standards 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for the presumptive identification and differentiation of yeasts. clinical microbiology & infection. 2010;16: 666. 35. guzel ab, ilkit m, akar t, burgut r, demir sc. evaluation of risk factors in patients with vulvovaginal candidiasis and the value of chromid candida agar versus chromagar candida for recovery and presumptive identification of vaginal yeast species. medical mycology. 2011; 49: 16-25. efficacy of chromagar and api 20 c auxjiimc 2018 vol. 13, no.2 90 page 41 page 42 page 43 page 44 page 45 page 46 original�article abstract the case is about a male 7-year-old child who was referred to our ponseti clinic in lady reading hospital for bilateral neglected clubfeet management. the patient was assessed through pirani assessment form for club foot severity. this patient was treated through ponseti technique and as a result the patient went through serial casting in the lrh-mti club foot clinic. tenotomy was also performed for achieving maximum desired correction. at first visit before cast the pirani score for both feet was 6/6 and after first cast the pirani score was reduced to 5/6 bilaterally while after 2nd cast pirani score dropped to 4/6 for the right foot and for the left the score was 5/6. assessment after 3rd cast revealed that pirani score reduced to 3/6 for left side and 2.5 for right side while on 4rth cast the pirani score was 1.5/6 for both side. after removal of the fifth cast the pirani scoring was, 1/6 for right side and 1.5/6 for the left side. patient was progressed to tenotomy and the pirani score interestingly dropped to 0/6 bilaterally. patient x was then progressed to the preventive phase. key words: clubfeet, ctev, dennis brown splint neglected,ponseti, serial casting. 6 undergone some surgical intervention. clubfoot treatment was described in india as early as 1000 b.c. the first written description of clubfoot was given to us by hippocrates (circa 400 b.c.). he described methods for manipulative correction remarkably similar to current non-operative methods. hippocrates treated clubfoot as soon as possible after birth. his technique involved repeated manipulations of the involved foot with his hands, followed by the application of strong bandages to 7 maintain correction. the next description of repeated stretching comes from arcaeus, who in 1658 wrote a chapter on the treatment of clubfoot where he describes his stretching technique as well as two mechanical devices for maintaining the 8 t h correction. in the mid-18 century, scarpa introduced his treatment which included forceful manipulation, not gentle stretching, and application of a complicated mechanical device, later known as scarpa's shoe. his treatment method was never successful in other hands and for that reason was not 7 widely accepted. in the year 1806, timothy sheldrake published an essay entitled distortions of the legs and feet of children. sheldrake used bandages like hippocrates, and claimed that most of 1 his patients could be cured in two to three months. in 1823, delpech performed subcutaneous tenotomy of the achilles tendon in two patients with 9 acquired talipes equinovarus. kite then became the leading advocate of the conservative treatment of clubfoot for many years in the early and mid 1900's. introduction clubfoot was first depicted in ancient egyptian tomb 1 paintings. congenital talipes equino varus (ctev) or clubfoot is a common structural congenital deformity in which affected children have abnormal bone structure in their ankle having four components equinus, hind foot varus, fore foot adduction and cavus or medial subluxation of 2,3 navicular bones. neglected clubfoot comprises feet 4 that had not been treated in the past. clubfoot incidence varies from about 1 in 1000 live births with approximately 50% of cases bilateral. in clubfoot male to female ratio is 2.5:1 and 24.4 % have family 3 history of idiopathic talipes equino varus. when untreated it can affect patient's mobility, productivity 5 and cosmetic look. neglected clubfoot deformities in older children is considered a difficult surgical problem as the foot in these patients is stiff with some amount of pain and almost always had already effectiveness of ponseti technique in children with bilateral neglected clubfoot: a case report on a 7 years old child correspondence: ubaid ullah department of physical therapy icrc club foot clinic lady reading hospital peshawar, pakistan e-mail:ubaidullah_khan12@yahoo.com department of physical therapy icrc club foot clinic lady reading hospital peshawar, pakistan funding source: nil; conflict of interest: nil received: jan 12, 2018 ; revised: sept 14, 2018 accepted: sept 15, 2018 ponseti techniquejiimc 2018 vol. 13, no.3 1 2 ubaid ullah, sayed zulfiqar ali shah 162 knee joints in 10 degrees genu valgum and calcaneocuboid joint were very prominent. pirani scoring chart and a clubfoot detail assessment form was used as standard parameters to find the severity of the clubfoot deformity. the pirani score was 6/6 for both feet with slight rigidity in left foot. while assessing the cavus, it was found that the arch of the foot was higher than normal. while examining for adductus, it was observed that in both feet the forefoot was abducted towards the midline. in detailed assessment it was noted that the heel of the patient was in varus and angled towards the midline. the foot was in equinus position. he continued the meticulous clubfoot cast application and molding that he had learned from hoke. kite corrected each component of the deformity separately instead of simultaneously. it was through his attempt to understand the pathophysiology of clubfoot, as well as his ability to learn from the mistakes of his predecessor, that ponseti developed his current method of treatment for clubfoot. his understanding of the anatomy of the tarsus of the normal foot and of the clubfoot was greatly enhanced by the work of farabeuf's precis de 10 manual operatoire, first published in 1872. since 1996, however, the non-surgical ponseti method of 10,11 correction has become increasingly popular. i n i t i a l l y re s e r v e d fo r e a r l y c o r re c t i o n o f uncomplicated idiopathic patients, today the ponseti method is being adapted for complex non-idiopathic patients and for patients presenting up to and 12 beyond 2 years of age. widely implemented in highincome countries, the ponseti method has been described as highly suitable for healthcare settings with scarce resources and is being increasingly used 13 in low and middle income countries as well. the ponseti technique is flexible because it gives the opportunity to recast patients who lose their 14 corrections. successful correction of club foot is reported in 90-98% of cases treated by ponseti method. ponseti technique consist of intervention phase and maintenance phase, intervention phase consists of serial manipulations and casting to correct the clubfoot deformity and percutaneous tenotomy of the achilles tendon to correct the ankle equinus. maintenance phase consist of wearing of foot abduction braces for 2-3 years to maintain the 15 gained correction. case report patient characteristics patient x was a 7-year-old child and was referred to our ponseti clinic for club foot management. the reason behind the neglect was economic status and family support. later, on presentation to our ponseti clinic his family was assured that his whole treatment will be sponsored by icrc. detailed examination was performed to identify the type of club foot and an associated effect on the body. it was observed that the patient was walking on lateral border of the feet, and forefeet were internally rotated. it was noticed that the hip joints were in slight internal rotation, intervention patient was treated through ponseti technique serial casting with minor surgery (tenotomy). patient had six visits, went through 5 serial casts with a minor surgery after final cast in the following order on the head of talus for both feet. feet were held in press position for 8 seconds to stretch of abductor hallucis longus, tibialis posterior muscles and ligament. manipulation force was maintained, and pop cast was applied for a week. at the second visit pirani score was reduced to 5/6 bilaterally. patient developed minor skin irritation on medial side of the thigh in left side while the right side was normal. manipulation was performed again with more stretch bilaterally on the abductor hallucis longus, tibialis posterior muscles to keep feet in little supinated position and maximum abduction. again, cast was applied but this time the medial side of the cast on thigh of left side kept a bit low from the groin to give room to the affected area of the skin. ponseti techniquejiimc 2018 vol. 13, no.3 163 le� foot varus: present cavus: present abductus(-30 to 70): -30 equines(-50 to 30): -50 pirani scores(hind foot): · posterior crease : (0.5) · empty heal : (1) · rigid equines : (1) pirani scores(midfoot): · talar head coverage : (1) · medial crease: (0.5) · curved lateral border: (1) total score= 5 right foot varus: present cavus: present abductus(-30 to 70): -30 equines(-50 to 30): -50 pirani scores(midfoot): · talar head coverage: (1) · medial crease: (1) · curved lateral border: (1) total score= 6 right foot varus: present cavus: present abductus®(-30 to 70): -30 equines®(-50 to 30): -50 pirani scores(hind foot): · posterior crease : (1) · empty heel : (1) · rigid equines : (1) pirani scores(midfoot): · talar head coverage : (1) · medial crease: (1) · curved lateral border: (1) upon fourth visit we observed that there was a bilateral mild damage to the pop cast, but the feet position was same not much disturbed, only the toes were in mild adducted position. old cast was removed, and patient was reassessed and amazingly the pirani score was reduced to 3/6 for left side and 2.5 for right side with only adduction in big metatarsal in both sides feet. manipulation was performed, and pop cast applied, dyanacast applied over the pop cast for the maintenance of the position. on arrival for of the patient x for the fifth visit position was assessed in dyanacast was found normal. then the old cast was removed, and patient was reassessed. this time pirani score was 1.5/6 for both side. we observed only equinus bilaterally and pirani scores(hind foot): · posterior crease : (0.5) · empty heal : (1) · rigid equines : (1) pirani scores(midfoot): · talar head coverage : (1) · medial crease: (0.5) · curved lateral border: (1) total score= 5 ponseti techniquejiimc 2018 vol. 13, no.3 164 st 1 serial cast: pirani score for both feet was 6/6. treatment was started with 15 repe��ons of manipula�on le� foot varus: present cavus: present abductus (-30 to 70): -30 equines®(-50 to 30): -50 pirani scores (hind foot): · posterior crease: (1) · empty heel: (1) · rigid equines: (1) nd 2 serial cast: on third visit pirani score dropped to 4/6 for the right foot and for the left the score was 5/6. a relapse was observed in the left side due to the damage to pop cast. so the position given in the second cast got recurrent and no improvement was seen in left foot. the right-side foot improved with cavus and adduction corrected. manipulation was applied, and more stretch was applied to the abductor hallucis longus, tibialis posterior longus, flexor digitorum longus lateralis and counter pressure was applied to the head of talus for over correction of left foot, for the right side gentle force applied and same procedure done as left side. cast was applied to maintain correction gained through manipulation. total score= 6 then blade was turned 90 degrees, perpendicular to the tendon. a cut was applied to the tendon from medial to lateral direction. a “pop” sound was felt after the release of the tendon. an additional 10 to 15 degrees of dorsiflexion was gained after tenotomy. pop cast was applied, and more abduction was given on the left side for achieving the best possible result. foot abduction brace after 3 weeks the pop cast was removed and pirani scoring was performed and interestingly the score was 0/6 bilaterally. patient x was proceeded to another phase of treatment the preventive phase in which abduction brace “dennis brown splint” was applied. dennis brown splint was fixed in 70-degree abduction and 20-degree dorsiflexion. only mild abduction limitation in left side. on the bases of the above observation on the fifth visit we decided that left side foot will need over correction in post tenotomy pop cast. right side was only having equinus and empty heel so normal cast applied with maximum equinus release. previous pop cast observed which was normal so after removal of the cast the pirani scoring was done which was, 1/6 for right side and 1.5/6 for the left side. finally, it was decided to perform tenotomy for the patient x to gain the maximum desired correction. after proper positioning, knife (bp blade-15/11 size) was placed parallel to tensed tendoachillis approximately 1 cm above the insertion at calcaneus. pirani scores(midfoot): · talar head coverage : (0.5) · medial crease: (0.5) · curved lateral border: (0.5) total score= 4 le� foot varus: present cavus: corrected abductus: (-30 to 70): 0 equines: (-50 to 30): -20 pirani scores(hind foot): · posterior crease : (0) · empty heal : (1) · rigid equines : (1) pirani scores(midfoot): · talar head coverage : (0.5) · medial crease: (0) · curved lateral border: (0.5) total score= 3 right foot varus: corrected cavus: corrected abductus: (-30 to 70): 0 equines: (-50 to 30): -20 pirani scores(hind foot): · posterior crease : (0) · empty heal : (0.5) · rigid equines : (1) pirani scores(midfoot): · talar head coverage : (0.5) · medial crease: (0) · curved lateral border: (0.5) total score= 2.5 ponseti techniquejiimc 2018 vol. 13, no.3 165 rd 3 serial cast: le� foot varus: present cavus: mild abductus®(-30 to 70): -10 equines®(-50 to 30): -30 pirani scores(hind foot): · posterior crease : (0.5) · empty heal : (1) · rigid equines : (1) pirani scores(midfoot): · talar head coverage : (1) · medial crease: (0.5) · curved lateral border: (1) total score= 5 right foot varus: present cavus: mild abductus®(-30 to 70): 0 equines®(-50 to 30): -30 pirani scores(hind foot): · posterior crease : (0.5) · empty heal : (1) · rigid equines : (1) th 4 serial cast: intervention phase consists of serial manipulations and casting to correct the clubfoot deformity and percutaneous tenotomy of the achilles tendon to correct the ankle equinus. maintenance phase consist of wearing of foot abduction braces for 2-3 6 years to maintain the gained correction. ponseti techniques is proved successful around the 19 world in both developed and developing countries. a study on ponseti clubfoot techniques reported that this technique has reduced the need for extensive soft tissue release and major clubfoot surgery, and has changed clubfoot operation 20 patterns in nigeria. our study reported pirani score as (arrival 6/6, after st 1 cast 5/6 bilaterally, after second cast left 5/6 and right 4/6, after cast third left 3/6 and right 2.5/6, after fourth cast 1.5 bilaterally and after fifth cast left le� foot varus: corrected cavus: corrected abductus: (-30 to 70): +30 equines: (-50 to 30): -10 pirani scores(hind foot): · posterior crease : (0) · empty heal : (0.5) · rigid equines : (1) pirani scores(midfoot): · talar head coverage : (0) · medial crease: (0) · curved lateral border: (0) total score= 1.5 right foot varus: corrected cavus: corrected abductus: (-30 to 70): +30 equines: (-50 to 30): 0 pirani scores(hind foot): · posterior crease : (0) · empty heal : (0.5) · rigid equines : (0.5 ) pirani scores(midfoot): · talar head coverage : (0) · medial crease: (0) · curved lateral border: (0) total score= 1 discussion club foot or congenital talipes equinovarus (ctev) is o n e o f t h e m o s t c o m m o n c o n g e n i t a l 16 musculoskeletal deformities. ctev patients have an inward rotation of the foot, with four components: cavus, forefoot adductus, hind foot varus treatments available can be conservative (such as splinting or 17 stretching) or surgical. it is important that to have a uniform system for diagnosis, classification and follow-up to gauge the success of treatment. pirani's classification is simpler and more recent. pirani scoring system has proved to be useful in ponseti management of clubfeet. pirani score is widely used in the prediction of tenotomy and number of casts 18 required. ponseti technique consist of two phases, an intervention phase and a maintenance phase. the ponseti techniquejiimc 2018 vol. 13, no.3 166 th 5 serial cast: le� foot varus: corrected cavus: corrected abductus (-30 to 70): +20 equines (-50 to 30): -10 pirani scores(hind foot): · posterior crease : (0) · empty heal : (0.5) · rigid equines : (1) pirani scores(midfoot): · talar head coverage : (0) · medial crease: (0) · curved lateral border: (0) total score= 1.5 right foot varus: corrected cavus: corrected abductus (-30 to 70): +20 equines (-50 to 30): -10 pirani scores(hind foot): · posterior crease : (0) · empty heal : (0.5) · rigid equines : (1) pirani scores(midfoot): · talar head coverage : (0) · medial crease: (0) · curved lateral border: (0) total score= 1.5 tenotomy: results of ponseti techniques in the neglected club feet children. sufficient deformity correction was gained in age ranging 1.5 years to 4 years children in a 22 study conducted in malawi. a study conducted in istanbul, turkey favors the results of our study, reported the efficacy of ponseti technique using 23 pirani score in children aging more than 20 months. it is concluded that ponseti method is safe and effective in managing children with neglected clubfeet. the ponseti method markedly reduces the need for the operative treatment and the complications associated with operative treatment. in the developing world, where most neglected clubfeet occur, strategies should be formulated to reach every child with clubfeet for early intervention. hospitals should make it mandatory to perform feet assessment after child birth and to guide the parents about clinics performing clubfeet management through ponseti technique. recommendation we recommend the use of ponseti technique in older children with neglected clubfeet. ponseti technique is safe and effective and it should be the treatment of choice for patients with both early presentation and neglected clubfeet. references 1. sheldrake t. distortions of the legs and feet in children. london google scholar 1806 2. honein ma, paulozzi lj, moore ca. family history, maternal smoking, and clubfoot: an indication of a gene-environment i n t e ra c t i o n . a m e r i c a n j o u r n a l o f e p i d e m i o l o g y 2000;152(7):658-65. 3. khan nu, askar z, hakeem a, et al. idiopathic congenital clubfoot: our experience with the ponseti method of treatment. pak j surg 2010;26(1):70-74. 4. kulkarni rm, rathore a, negandhi r, et al. treatment of neglected and relapsed clubfoot with midfoot osteotomy: a retrospective study. international journal of paediatric orthopaedics 2015;1(1):38-43. 5. uiiah s, inam m, arif m. club foot management by accelerated ponseti technique. rawal medical journal 2014;39(4) 6. beaty jh. congenital anomalies of lower extremity. campbell's operative orthopedics 1992:2061-158. 7. dobbs mb, morcuende ja, gurnett ca, et al. treatment of idiopathic clubfoot: an historical review. the iowa orthopaedic journal 2000;20:59. 8. amin r. non operative treatment modalities of clubfoot. orion 2004;18 9. little wj. a treatise on the nature of club-foot and analogous distortions: longman, brown, green, and score was 1.5/6 and right 1/6. after tenotomy pirani scoring was performed and interestingly the score was 0/6 bilaterally. a retrospective study which reviewed 17 children (24 feet) with congenital idiopathic club foot who presented after walking age, clinically, 16 feet (66.6%) were considered to have a good result, with a plantigrade foot and no pain, without the need for further surgery. dynamic supination was present in 12 four feet, but caused minimal disturbance of gait. another prospective study by birhanu ayana and peter j klungsoyr on 22 children aged 2–10 years that the midfoot was corrected to pirani 0 in all feet after the casts and in patients up to the age of 4 years, hyper abduction up to 60–70 degrees was achieved in the final cast. in the older children, abduction was 21 only possible up to 30–40 degrees. a study on treatment idiopathic club foot through ponseti reported that the mean pirani score at presentation was: hind-foot contracture score 2.5 (2 to 3), midfoot contracture scores 2.5 (2 to 3), and a total score of 5.0 (4 to 6). the mean pirani score after treatment for the feet which responded to treatment was: hind-foot score 0.5 (0 to 1), mid-foot score 0 and a total of 0.5 (0 to 1). tenotomy was required in 85 (85%) of feet. a study from brazil by laurenco et al. (2007) has also reported successful results in 17 12 children having average age of 3.9 years. in under developed countries, studies have shown good ponseti techniquejiimc 2018 vol. 13, no.3 167 post tenotomy picture 17. a reliable & valid method of assessing the amount of deformity in the congenital clubfoot deformity. orthopaedic proceedings; 2008. the british editorial society of bone & joint surgery. 18. van bosse hj. ponseti treatment for clubfeet: an international perspective. current opinion in pediatrics 2011;23(1):41-45. 19. adegbehingbe o, oginni l, ogundele o, et al. ponseti clubfoot management: changing surgical trends in nigeria. the iowa orthopaedic journal 2010;30:7. 20. ayana b, klungsøyr pj. good results after ponseti treatment for neglected congenital clubfoot in ethiopia: a prospective study of 22 children (32 feet) from 2 to 10 years of age. acta orthopaedica 2014;85(6):641-45. 21. tindall aj, steinlechner cw, lavy cb, et al. results of manipulation of idiopathic clubfoot deformity in malawi by orthopaedic clinical officers using the ponseti method: a realistic alternative for the developing world? journal of pediatric orthopaedics 2005;25(5):627-29. 22. yagmurlu mf, ermis mn, akdeniz he, et al. ponseti management of clubfoot after walking age. pediatrics international 2011;53(1):85-89. longmans 1839. 10. kite j. non-operative treatment of congenital clubfeet. southern medical journal 1930;23(4):337-44. cooper dm, dietz fr. treatment of idiopathic clubfoot. a thirty-year follow-up note. jbjs 1995;77(10):1477-89. 11. lourenço a, morcuende j. correction of neglected idiopathic club foot by the ponseti method. bone & joint journal 2007;89(3):378-81. 12. spiegel da, shrestha op, sitoula p, et al. ponseti method for untreated idiopathic clubfeet in nepalese patients from 1 to 6 years of age. clinical orthopaedics and related research 2009;467(5):1164-70. 13. ponseti iv. relapsing clubfoot: causes, prevention, and treatment. the iowa orthopaedic journal 2002;22:55. 14. beaty jh. congenital anomalies of lower extremity. campbell's operative orthopaedics 2008:1125-27. 15. parker se, mai ct, strickland mj, et al. multistate study of the epidemiology of clubfoot. birth defects research part a: clinical and molecular teratology 2009;85(11):897-904. 16. gray k, pacey v, gibbons p, et al. interventions for congenital talipes equinovarus (clubfoot). cochrane database of systematic reviews 2012(4) ponseti techniquejiimc 2018 vol. 13, no.3 168 untitled-1 original�article abstract objective: to evaluate the effects of aqueous and methanolic extracts of cichorium intybus seeds on gentamicin induced nephrotoxicity in rats. study design: experimental study place and duration of study: study was conducted from 15 january to 31 march 2017 at national institute of health sciences (nih) in collaboration with riphah institute of pharmaceutical sciences (rips). materials and methods: forty healthy sprague dawly rats weighing 300-350gms were randomly divided in four groups with 10 rats each. group a was the control group that received no medications. group b was given gentamicin 80mg/ kg body weight / day for 10 days intraperitoneally (ip). group c was given gentamicin 80mg/ kg body weight / day ip and aqueous extract of cichorium intybus seeds 500mg/kg body weight/ day through gavage tube for 10 days. group d was given gentamicin 80mg/ kg body weight / day ip and methanolic extract of cichorium intybus seeds 500mg/kg body weight / day through gavage tube for 10 days. serum urea and creatinine were measured at day zero, 6, and 11. the values were compared within and between the groups. results: elevated levels of serum urea and creatinine were found in group b indicating renal damage. whereas administration of aqueous and methanolic extracts of cichorium intybus seeds reduced the elevated levels of serum urea and creatinine in group c & d. however more reduction was produced in group c. conclusion: concomitant administration of aqueous and methanolic extracts of cichorium intybus seeds exerted nephroprotective effect on gentamicin induced nephrotoxicity in rats. aqueous extract produced greater protection as compared to methanolic extract. key words: cichorium intybus seeds, gentamicin, nephroprotective effect, nephrotoxicity. therapeutically used drugs may result in acute or 2 chronic renal failure. across the globe approximately 19-25% cases of nephrotoxicity in critically ill 1 p at i e nt s re s u l t s f ro m n e p h ro tox i c d r u g s . nephrotoxicity is indicated by the raised levels of 3 serum urea and creatinine. drug groups which cause nephrotoxicity include immunosuppressant, anticancer drugs, radio contrast media and .4 antibiotics aminoglycosides (ags) is among one the widely prescribed antibiotic group throughout the world 4 being cost effective. aminoglycosides are bactericidal antibiotics which irreversibly inhibit protein synthesis by binding to specific 30s-subunit ribosomal protein through interference of initiation of complex of peptide, breaking of polysome into 5 monosomes and misreading of mrna. the major adverse effects caused by aminoglycosides are ototoxicity and nephrotoxicity, which limits their use. aminoglycosides are excreted unchanged through 7 glomerular filtration without metabolism. during the process of concentration and reabsorption introduction kidneys play a vital role in the body performing important functions for example excretion of metabolic waste, drugs, homeostasis maintenance 1 and extracellular environment regulation. direct or indirect exposure of drugs and different chemicals to k i d n e y s r e s u l t s i n n e p h r o t o x i c i t y. m a n y effects of aqueous and methanolic extracts of cichorium intybus seeds on gentamicin induced nephrotoxicity in rats 1 2 3 4 5 6 muhammad tahir , noman sadiq , sameer ahmed , amanat ali , noor nasir rajpoot , uzma riaz correspondence: dr. muhammad tahir assistant professor department of pharmacology women medical and dental college, abbottabad e-mail: m.tahir9044@gmail.com 1 department of pharmacology women medical and dental college, abbottabad 2 departmant of physiology cmh kharian medical college, kharian 3,4 departmant of pharmacology hbs medical and dental college, islamabad 5 department of medicine sir ganga ram hospital lahore 6 departmant of pharmacology watim dental college, islamabad funding source: nil; conflict of interest: nil received: july 04, 2018; revised: october 23, 2018; accepted: november 11, 2018 effects of cichorium intybus seeds on nephrotoxicityjiimc 2018 vol. 13, no.4 184 proximal tubular cells are mainly exposed to damage by the drugs. free radicals generated due to oxidative stress causes mitochondrial damage in tubules resulting in cytotoxicity. inflammation in glomerulus and tubules is induced by nephrotoxic drugs which ultimately result in fibroses of renal 8 tissue. from ancient days medicinal plants have been widely used as a source of medication providing a cheap source of treatment for a majority of world's population. herbal plants have got nephroprotective 9 effect. several plants along with their extracts have got protective effect against nephrotoxic drugs due to their anti-oxidant, anti-inflammatory and diuretic 10 properties. cichorium intybus , generally called chicory ( kasni ) is vertical woody perennial plant distributed in europe, mediterranean region, 11 northern asia and pakistan. all parts of cichorium intybus is known to have antimicrobial, gastroprotective, hepatoprotective, anti-diabetic, antimalarial, anti-inflammatory and anti-oxidant effects due to the presence of phytocompounds like 12,13 polyphenols , alkaloids, flavonoids and tannins. previous studies have shown anti-oxidant effects of either aqeous or methanolic extracts of cichorium intybus roots, leaves and stem against gentamicin induced nephrotoxicity or hepatotoxicity in animal 10 model. evaluation of both aqueous and methanolic extracts of cichorium intybus seeds against gentamicin induced nephrotoxicity in literature is lacking. present study was designed to evaluate the effect of both aqueous and methanolic extracts of cichoriumintybus seeds against gentamicin induced nephrotoxicity in rat's model. materials and methods this experimental randomized control trial was th st conducted from 15 january 2017 to 31 march 2017 in the department of pharmacology and therapeutics, islamic international medical college, rawalpindi in collaboration with the riphah institute of pharmaceutical sciences and animal house at national institute of health (nih), islamabad. forty healthy adult male sprague dawly rats were included through simple random sampling and the study was conducted after approval from ethical review committee of islamic international medical college, riphah international university (riu), islamabad. rats weighing between 300-350 grams with normal serum urea and creatinine levels were included in the study. rats were first allowed to get acclimatized for one week in the nih animal house in 50-70% o humidity at a room temperature of 24+2 c with a 12 14 hour light and dark cycle. rats were randomly divided into four groups of ten rats each (n=10). group a was normal control, given diet and water ad libitum for ten days. group b was administered gentamicin at 80 mg/kg intraperitoneally once daily for ten days. group c was administered gentamicin 80mg/kg intraperitoneally along with aqueous extract of cichorium intybus seeds orally mixed in 2ml distal water through gavage tube at a dose of 10 500mg/kg once daily for ten days. group d was administered gentamicin 80mg/kg body weight once daily intraperitoneally along with methanolic extract 500mg/kg orally mixed in 2ml distilled water 15 through gavage tube once daily for ten days. dried seeds of cichorium intybus were purchased and authenticated from herbarium department of national agriculture and research centre (narc) islamabad. aqueous extract of cichoriumintybus seeds was prepared at rips, islamabad by using fine homogenized powder of chicory seeds which were mixed with distilled water, the whole solution was boiled for 2 hours and after cooling was filtered through filter paper what man no 3. the aqueous extract was formed by using vacuum rotary 16 evaporator and was frozen dried. to obtain the methanolic extract, 1 kg of cichorium intybus seeds powder was soaked in 8 l of methanol (95%) for 24 h. the extract was filtered using what man paper no 3 and the filtrate was evaporated (78 °c) to dryness using a rotary evaporator; 25.64 g of dried methanolic extract were obtained giving an extraction yield of 2.56% (w/w based on the dried 17 starting weight). sampling at day 0 and day 6 were th done via lateral tail vein. sampling at day 11 was done through cardiac puncture. biochemical analysis of serum urea and serum creatinine was estimated through commercially available kits by merk and auto analyzer micro lab 300 on photometric system. statistical analysis of collected parametric data was done by using spss version 21 and mean ± standard error of mean was calculated. one way anova and post hoc tuckey tests were applied to compare the mean difference between control and rest of the groups and mean difference in between the groups. effects of cichorium intybus seeds on nephrotoxicityjiimc 2018 vol. 13, no.4 185 p value of <0.05 was considered statistically significant. results mean initial serum urea for group a (normal control group) was 23.70 ± 1.521 mg/dl. mean initial serum urea for group b (disease control group) was 24.00 ± 1.732 mg/dl. mean initial serum urea for group c (aqueous extract experimental group 1) was 25.56 ± 1.744 mg/dl. mean initial serum urea for group d (methanolic extract experimental group 2) was 22.10 ± 1.912 mg/dl. there was no significant difference in the serum urea levels among these groups on day 0 (p value .589). serum urea on day 6 for group a (normal control group) was 24.70 ± 1.633 mg/dl, for group b (disease control group) was 83.30 ± 2.119 mg/dl, for group c (aqueous extract experimental group 1) was 67.10 ± 1.703 m g / d l & fo r g ro u p d ( m e t h a n o l i c ex t ra c t experimental group 2) was 84.00 ± 1.592 mg/dl. there was significant difference in the serum urea levels among these groups on day 6 (p value .000). this suggests that nephrotoxicity was induced by gentamicin. mean serum urea on day 11 for group a (normal control group) was 24.70 ± 5.165 mg/dl , for group b (disease control group) was 97.90 ±4.332 mg/dl, for group c (aqueous extract experimental group 1 ) was 51.30 5.755 mg/dl& for group d (methanolic extract experimental group 2) was 73.60mg/dl ±4.695. there was significant difference in the values of group c & d (p value .000). this suggests that nephrotoxicity in group c (aqueous extract treated group) was improved more than group d (methanolic extract treated group). mean initial serum creatinine for group a (normal control group) was 0.750 ± 0.0654 mg/dl. mean initial serum creatinine for group b (disease control group) was 0.740 ± 0.0562 mg/dl. mean initial serum creatinine for group c (aqueous extract experimental group 1) was 0.770 ± 0.0559 mg/dl. mean initial serum creatinine for group d (methanolic extract experimental group 2) was 0.770 ± 0.0667 mg/dl. there was no significant difference in the serum creatinine levels among these groups on day 0. (p value .980). mean serum creatinine on day 6 for group a (normal control group) was 0.750 ± 0.0619 mg/dl, for group b (disease control group) was 2.490 ± 0.0849 mg/dl, for group c (aqueous extract experimental group 1) was 1.450 ± 0.0601 mg/dl& for group d (methanolic extract experimental group 2) was 1.730 ± 0.0517 mg/dl. there was significant difference in the serum creatinine levels among these groups on day 6 (p value .000). this suggests that nephrotoxicity was induced by gentamicin. mean serum creatinine on day 11 for group a (normal control group) was 0.750, ± 0.0619 mg/dl, for group b (disease control group) was 2.490, ± 0.0849 mg/dl, for group c (aqueous extract experimental group 1 ) was 1.450 0.0601 mg/dl& for group d (methanolic extract experimental group 2) was 1.730 ± 0.0517 mg/dl. there was significant difference in the values of group c & d (p value .024). this suggests that nephrotoxicity in group c (aqueous extract treated group) was improved more than group d (methanolic extract treated group). table i: comparison of serum urea and crea�nine levels among groups by anova at day 0 table ii: comparison of serum urea and crea�nine levels among groups by anova at day 06 table iii: comparison of serum urea and crea�nine levels among groups by anova at day 11 effects of cichorium intybus seeds on nephrotoxicityjiimc 2018 vol. 13, no.4 186 discussion gentamicin is widely used to induce nephrotoxicity in animal models for research purposes and has been stated by numerous researchers for analyzing nephroprotective effects of natural plants. key phenomenon elaborating the gm induced nephrotoxicity is damage by reactive oxygen 1 8 species. review of literature showed that production of ros lead to lipid peroxidation causing necrosis and denaturation of proteins. various studies have concluded that the nephroprotective effects of natural plants are due to the presence of 19,20 antioxidants. the current study was designed to investigate the protective effects of aqueous and methanolic extracts of cichorium intybus seeds in gentamicin induced nephrotoxicity in rats via biochemical parameters. it was found that gentamicin induced nephrotoxic changes were improved by both aqueous and methanolic extracts of cichorium intybus seeds but aqueous extract showed better nephroprotective effects against gentamicin induced nephrotoxicity. in present study, gm induced nephrotoxicity is indicated by raised level of serum creatinine and urea as concluded previously 21 by nitha and janardhanan. the process glomerular filtration causes the accumulation of gentamycin in the proximal tubules of kidney. gm produced ros causes oxidative stress and tubular injury and is indicated by raised serum creatinine and urea. our study in accordance with findings of study by tanweer khaliq who induced nephrotoxicity in albino rabbits with gentamicin intraperitoneally in a dose of 80 mg/kg and observed raised levels of 10 biochemical markers. similarly our study is in correlation with another study performed by v. chinnapa reddy showing the nephrotoxic effects of gentamicin in rats which were indicated by raised 16 levels of serum urea and creatinine. current study is consistent with the study of tanweer khaliq who compared the nephroprotective effect of aqueous extract of cichorium intybus seeds against gentamicin induced nephrotoxicity in which he used aqueous extract of cichorium intybus seeds in doses of 250 mg/kg administered via gavage tube. his study also evidenced the nephroprotection due to presumed antioxidant properties of cichorium 10 intybus seeds. review of literature shows that studies have been done on exploring nephroprotective effect of cichorium intybus in combination with other herbal 10 extracts and medical compounds like silymarin. no individual study was done on aqueous and methanolic extract of cichorium intybus seed indicating dosage use regarding submaximal, ceiling effect and toxicity. current study shows the nephroprotective effect of both aqueous and methanolic extract of cichorium intybus seeds. further studies are needed to elaborate the mechanism of higher response of methanolic extract as compare to aqueous extract of cichorium intybus seeds for reducing elevated renal markers. in addition administration through different routes and higher dosage can be tried to see the effect. table iv: mul�ple comparison of serum urea and crea�nine levels among all groups by post hock tuckey test effects of cichorium intybus seeds on nephrotoxicityjiimc 2018 vol. 13, no.4 187 conclusion aqueous and methanolic extracts of cichorium intybus seeds exhibited protective effects against gentamicin induced nephrotoxicity in rats. aqueous extract cichorium intybus seeds have exerted greater nephroprotective effect in comparison to methanolic extract. references 1. hussein o, germoush m, mahmoud a. ruta graveolens p r o t e c t s a g a i n s t i s o n i a z i d / r i f a m p i c i n i n d u c e d nephrotoxicity through modulation of oxidative stress and inflammation. glob j biotechnol biomater sci: 2016;50 (1):17-22. 2. singh rk, gautam rk, karchuli m. nephrotoxicity: an overview. journal of biomedical and pharmaceutical research: 2014;3(4):41-7. 3. kandasamy k, chuah jkc, su r, huang p, eng kg, xiong s, et al. prediction of drug-induced nephrotoxicity and injury mechanisms with human induced pluripotent stem cellderived cells and machine learning methods. scientific reports: 2015;5(2): 45-55. 4. shi k, caldwell sj, fong dh, berghuis am. prospects for circumventing aminoglycoside kinase mediated antibiotic resistance. frontiers in cellular and infection microbiology. 2013;3:22-28. 5. katzung bg, masters sb, trevor aj. basic & clinical pharmacolo gy. 12th ed: mcgraw-hill medical new york; 2016. 6. filazi a, sireli ut, pehlivanlar-onen s, cadirci o, aksoy a. comparative pharmacokinetics of gentamicin in laying hens. kafkas üniversitesi veteriner fakültesi dergisi: 2013;19(3):495-98. 7. ramirez ms, tolmasky me. aminoglycoside modifying enzymes. drug resistance updates: 2010;13(6):151-71. 8. kim s-y, moon a-r. drug-induced nephrotoxicity and its b i o m a r k e r s . b i o m o l e c u l e s a n d t h e r a p e u t i c s : 2012;20(3):268-72. 9. maharana l, dadhich op. review on role of herbal drug in the prevention and management of kidney disease. ayushdhara:2016;1(1): 15-20. 10. khaliq t, mumtaz f, rahman z, javed i, iftikhar a. nephroprotective potential of rosa damascena mill flowers, cichorium intybus linn roots and their mixtures on gentamicininduced toxicity in albino rabbits. pak vet j: 2015;35:43-47. 11. hozayen wg, el-desouky ma, soliman ha, ahmed rr, khaliefa ak. antiosteoporotic effect of petroselinum crispum, ocimum basilicum and cichorium intybus l. in glucocorticoid-induced osteoporosis in rats. bmc complementary and alternative medicine: 2016;16(1):165169. 12. saxena r, sulakhiya kb, rathore m. cichorium intibus linn.: a review of pharmacological profile. international journal of current pharmaceutical research: 2014;6(4):11-15. 13. shad m, nawaz h, rehman t, ikram n. determination of some biochemicals, phytochemicals and antioxidant properties of different parts of cichorium intybus l.: a comparative study: j anim plant sci. 2013;23(4):1060-66. 14. al-yahya m, mothana r, al-said m, al-dosari m, alsohaibani m, parvez m, et al. protective effect of citrus medica'otroj'extract on gentamicin-induced nephrotoxicity and oxidative damage in rat kidney. digest journal of nanomaterials &biostructures (djnb): 2015;10(1):15-19. 15. reddy vc, amulya v, lakshmi c, reddy k, praveen d, pratima d, et al. effect of simvastatin in gentamicin induced nephrotoxicity in albino rats. asian j pharm clin res: 2012;5:36-40. 16. ali a, jehangir a, ayub f. hepatoprotective effect of aqueous extract of cichorium intybus roots on isoniazid induced hepatotoxicity. jiimc. 2016; 11(3): 99-102. 17. watcho p, watio hm, wankeu-nya m, ngadjui e, defo pd, nkeng-efouet pa, et al. androgenic effects of aqueous and methanolic extracts of ficus asperifolia in male wistar rats. b m c co m p l e m e nta r y a n d a l te r n at i ve m e d i c i n e : 2017;17(1):42-46. 18. weber ej, himmelfarb j, kelly ej. concise review: current and emerging biomarkers of nephrotoxicity. current opinion in toxicology: 2017; 4: 16-21. 19. chen q, cui y, ding g, jia z, zhang y, zhang a, et al. pea3 protects against gentamicin nephrotoxicity: role of mitochondrial dysfunction. american journal of translational research: 2017; 9(5):2153-58. 20. duscha s, boukari h, shcherbakov d, salian s, silva s, kendall a, et al. identification and evaluation of improved 4ʹ-o-(alkyl) 4, 5-disubstituted 2-deoxystreptamines as nextg e n e r a t i o n a m i n o g l y c o s i d e a n t i b i o t i c s . m b i o : 2014;5(5):e01827-14. 21. nitha b, janardhanan kk. aqueous-ethanolic extract of morel mushroom mycelium morchella esculenta, protects cisplatin and gentamicin induced nephrotoxicity in mice. food and chemical toxicology: 2008; 46(9): 3193-99. effects of cichorium intybus seeds on nephrotoxicityjiimc 2018 vol. 13, no.4 188 untitled-2 original�article abstract objective: the objective of this study was to determine the correlation of bacterial density with severity of the degree of neutrophilic infiltrate, atrophy and intestinal metaplasia after analyzing the density of h. pylori semi quantitatively in chronic gastritis patients. study design: the study was a cross sectional correlational study. nd place and duration of study: the study was conducted in army medical college rawalpindi from 2 december st 2011 to 1 december 2012. materials and methods: a total of one hundred gastric antral biopsies of h. pylori associated chronic gastritis including all ages and both genders were included in the study. most of the specimens that were received from the department of gastroenterology military hospital rawalpindi were fixed in 10% formaline. the tissue was processed in histopathology department. giemsa stain was used for demonstration of h. pylori. the density of h. pylori, activity, atrophy and intestinal metaplasia were graded using a detailed histopathological classification. spss 17 was used to analyze the findings. relationship between density of h. pylori and other variables was calculated through spearman's rank correlation test. the findings were considered to be statistically significant if p value was found to be less than 0.05 (p<0.05). results: an overall significant weak positive correlation was observed between grades of h. pylori density and degree of neutrophilic activity (r 0.416). there was significant but weak relationship between grades of h. s= pylori density and grades of atrophy (r 0.306). intestinal metaplasia also revealed very weak association with s= grades of h. pylori density (r 0.287). s= conclusion: in conclusion this study shows the semi quantitative determination of histological parameters and corroborates that, the greater the load of h. pylori infection, the more is the degree of neutrophilic activity, atrophy and intestinal metaplasia. key words: atrophy, chronic gastritis, helicobacter pylori, intestinal metaplasia. classified according to the underlying etiology i.e. helicobacter pylori (h. pylori), autoimmunity, bile reflux, allergic response, nsaids and the 2 histopathologic pattern. infection with h. pylori denotes a key factor in the etiology of several gastrointestinal ailments, ranging from chronic active gastritis to peptic ulceration, gastric malt 3 lymphoma and gastric adenocarcinoma. worldwide as a minimum 50% of people are infected, however an exact estimate is difficult, because precise data is 4 unavailable from unindustrialized countries. the h. pylori gastritis prevalence is high in developing asian 5 countries. like all developing countries, pakistan also has high h. pylori prevalence. according to a research carried out in islamabad pakistan, 88 percent dyspeptic gastritis patients had h. pylori 6 infection. almost half of this world's population is colonized with h. pylori, and majority of infected individuals introduction gastritis a clinical condition with upper abdominal discomfort is characterized by inflammation of the gastric mucosa and is the commonest condition 1 observed in biopsies of stomach. gastritis is histopathological evaluation of h. pylori density and its correlation with activity, atrophy and intestinal metaplasia 1 2 3 4 henna khalid , alia zubair , nazma kiran , aiza sadia correspondence: dr. henna khalid assistant professor, histopathology department of pathology watim dental college, rawalpindi e-mail: hennakhalid@rocketmail.com 1 department of histopathology watim dental college, rawalpindi 2 department of histopathology hbs medical college, islamabad 3 department of histopathology rashid latif medical college, lahore 4 department of histopathology army medical college, rawalpindi funding source: nil; conflict of interest: nil received: oct 02, 2017; revised: feb 20, 2018 accepted: feb 22, 2018 correlation of h. pylori density with adoptive responsesjiimc 2018 vol. 13, no.1 26 military hospital, rawalpindi. the specimens were stored in 10% formal saline and were collected in pathology lab. each sample was given a laboratory number. the related clinical information was taken from laboratory. data included age, sex, symptoms, history, concomitant medication (intake of antibiotics, proton pump inhibitors, and nonsteroidal anti-inflammatory) and results of endoscopic investigations. the collected data was entered in already designed patient's proforma. the tissue was processed in histopathology laboratory and slides were stained with hematoxylin and eosin. giemsa stain was used for demonstration of h. pylori. gastric biopsies of 100 patients diagnosed as h. pylori gastritis were included in the study. the updated sydney system uses a scale of 0-3 for scoring the histopathological features of chronic gastritis. we used a detailed histopathological classification in order to improve assessment and 13 avoid minor degrees of alteration. the following histopathological parameters were examined on each slide: density of h. pylori, inflammatory activity, atrophy and intestinal metaplasia. each category (mild, moderate, and severe) was further subdivided into two, resulting in a score on a scale of 0-6 (none, 14 0; mild, 1-2; moderate, 3-4; severe, 5-6). this classification also provides numerical data for statistical analysis and has been used in previously in 15 other studies. before grading biopsy specimens, two pathologists reached a consensus on the scoring of gastritis through interactive sessions using a multiheaded microscope. subsequently all biopsy specimens were graded. according to this classification, the histopathological parameters were graded as follows. 14 the h. pylori density was graded as follows: 1) 0: none 2) 1: h. pylori seen only in one place 3) 2: just a few h. pylori seen 4) 3: dispersed h. pylori seen in separate foci 5) 4: numerous h. pylori in separate foci 6) 5: almost complete coverage of gastric surface by layer of h. pylori 7) 6: uninterrupted coverage of gastric surface by a dense layer of h. pylori the degree of inflammatory activity was categorized 7 develop chronic inflammation. in long duration disease, intestinal metaplasia and gastric atrophy are 8 observed. conferring to the western data, intestinal metaplasia and atrophy are premalignant disorders 9 seen in patients with h. pylori chronic gastritis. simple gastritis may progress and can lead to atrophy, intestinal metaplasia, dysplasia and gastric carcinoma. the fundamental step is in these events is 10 atrophy. hence, the role of h. pylori in progression of gastric carcinoma seems to be the initiation of atrophy, indicating that research should focus on this event. moreover, the bacterial density has been 11 correlated with gastric inflammation. a study was carried out at army medical college rawalpindi showing that the density of h. pylori in biopsy proven gastritis is positively correlated with chronic 12 inflammatory infiltrate. the sydney system was devised by a group of experts in sydney, australia in 1990. the new updated sydney system devised in housten, texas in 1994 uses none, mild, moderate, severe grades for the 13 histopathological features of chronic gastritis. a detailed histopathological classification can be used to improve assessment and avoid minor degrees of alteration. this study was designed to analyze the density of h. pylori in patients of chronic gastritis and to address whether there was a correlation between bacterial density and severity of degree of neutrophilic infiltrate, atrophy and intestinal metaplasia. the objectives of the current study were to determine the correlation of bacterial density with severity of the degree of neutrophilic infiltrate, atrophy and intestinal metaplasia after analyzing the density of h. pylori semi quantitatively in chronic gastritis patients. materials and methods the present cross-sectional correlational study was carried out in the pathology department of army medical college in collaboration with military nd hospital rawalpindi, pakistan from 2 december st 2011 to 1 december 2012. one hundred gastric antral biopsies of chronic gastritis patients of all ages and both sexes were included in the study. gastric biopsies of patients who were receiving or had received h. pylori eradication treatment were not included in the study. most of the specimens were received from the department of gastroenterology 27 jiimc 2018 vol. 13, no.1 correlation of h. pylori density with adoptive responses patients were included in the study, out of which 68 were male and 32 cases were females. the median age of the patients was 54.15 years (range; 18-85 years). figure 1 demonstrates the different grades of h. pylori density observed in 100 biopsies of h. pylori associated chronic gastritis. according to neutrophils density in gastric mucosa 14 per biopsy: 1) 0: no crypt involved 2) 1: one crypt is involved 3) 2: two crypts are involved 4) 3: up to 25% crypts are involved 5) 4: 25-50% crypts are involved 6) 5: > 50% crypts are involved 7) 6: all crypts are involved 14 atrophy in gastric biopsies was graded as: 1) 0: no change 2) 1: areas where a few gastric crypts are lost or changed into intestinal type metaplastic epithelium 3) 2: small areas in which gastric crypts are lost or changed into intestinal type metaplastic epithelium 4) 3: up to 25% gastric crypts lost or changed into intestinal type metaplastic epithelium 5) 4: 25-50% of gastric glands lost or changed into intestinal type metaplastic epithelium 6) 5: > 50% of gastric crypts lost or changed into intestinal type metaplastic epithelium 7) 6: only a few small areas in which gastric crypts are enduring the extent of intestinal metaplasia was categorized according to the amount of gastric tissue replaced by 14 metaplastic epithelium: 1) 0: none 2) 1: only one crypt is replaced by metaplastic epithelium 3) 2: 1-4 crypts are replaced by metaplastic epithelium 4) 3: two dispersed foci 5) 4: many foci in one gastric biopsy 6) 5: >50% gastric epithelium is replaced by metaplastic epithelium 7) 6: only a small focal area of epithelium is not replaced by metaplastic epithelium spss 17 was used to analyze the findings. frequency and percentages represent quantitative variables. relationship between density of h. pylori and other variables was calculated through spearman's rank correlation test. the findings were considered to be statistically significant if p value was found to be less than 0.05 (p<0.05). results one hundred h. pylori associated chronic gastritis fig 1: grades of h. pylori density in pa�ents of chronic gastri�s (n=100) fig 2: photomicrograph of gastric biopsy showing nearly complete surface covered by a layer of h. pylori (grade 5 of h. pylori coloniza�on) (giemsa stain x 400) maximum number of 44 patients revealed no inflammatory activity (grade 0). table i illustrates number of cases in each grade of h. pylori density, showing different grades of neutrophilic activity. table i: different grades of neutrophilic inflammatory ac�vity and their associa�on with grades of h. pylori density 28 jiimc 2018 vol. 13, no.1 correlation of h. pylori density with adoptive responses in the present study, highest percentage of cases (n=59) was found in moderate grade h. pylori density followed by mild and marked grades. these findings are similar to results of a study done at mayo 1 6 hospital. some authors suggested highest 17 percentages in mild grade while some in marked 18 grade of h. pylori density. number of factors contribute to these discrepancies including difference in h. pylori strains, sample size and study design. 'activity' is a variable component of h. pylori linked chronic gastritis. activity consists of numbers of neutrophils within the lamina propria, intraepithelial location and intraluminal location to form pit abscesses in current study, the inflammatory . activity was found to be 56% with maximum number of patients in moderate grade. in contrast 83% neutrophilic activity was reported in a study done in 19 2008 in japan. the present study shows a weak positive association between h. pylori density and activity of chronic gastritis (r =0.416) and the results s are similar to few other studies which also suggest that the neutrophilic activity shows a direct 19,20,21 association with the density of h. pylori. the possible cause is that h. pylori are an effective source of mediators that induce activation and chemotaxis of neutrophils. the variability of different strains of h. pylori which induces upregulation of cd11b/cd18, chemotaxis of neutrophils along with oxidative burst response in 22 neutrophils. the extent of neutrophil activation and recruitment is determined by various factors like bacterial colonization, virulence, persistence, and the resultant innate and acquired host immune 23 responses. it is well established fact that h. pylori are involved in 24 development of atrophy and intestinal metaplasia. in our study, there was an increase in grades of the atrophy with the increasing grades of h. pylori density in the gastric mucosa (r 0.306). the results s= are similar to other studies which also show a statistically significant and positive correlation between the intensity of h pylori and the degree of 25, 26, 27 atrophy. among the many risk factors, h. pylori infection is considered as the most important risk factor of 28 intestinal metaplasia. the present study showed a statistically significant but very weak relation spearman's rank correlation revealed a significant weak positive (r 0.416) relation between grades of s= h. pylori density and grades of neutrophilic inflammatory activity. among 100 patients, maximum number of 49 cases revealed no loss of gastric glands (grade 0 of atrophy). the detail of different grades of atrophy and their association with grades of h. pylori density are evident in table ii. table ii: grades of atrophy and their associa�on with grades of h. pylori density the statistical analysis done with spearman's rank correlation suggested a weak positive relation (rs= 0.306) between grades of h. pylori density and grades of atrophy. fifty one biopsies included in the study showed different grades of intestinal metaplasia and 49 biopsies revealed no intestinal metaplasia (grade 0). detail of different grades is shown in table iii. table iii: grades of intes�nal metaplasia and their associa�on with different grades of h. pylori density spearman's rank correlation suggested a very weak positive correlation among grades of h. pylori density and grades of intestinal metaplasia (r 0.287).s= discussion h. pylori organisms are the most important bacteria causing inflammation and chronic infection of the stomach. a number of studies show ambivalent results in relationship of h. pylori density and degree of activity, atrophy and intestinal metaplasia. in this study we determined the density of h. pylori semi quantitatively and found a weak positive correlation between bacterial density and these pathological findings of chronic gastritis. 29 jiimc 2018 vol. 13, no.1 correlation of h. pylori density with adoptive responses 2014; 26: 182-5. 7. peek rm jr, blaser mj. helicobacter pylori and gastrointestinal tract adenocarcinomas. nat rev cancer. 2002; 2: 28-37. 8. guarner j, goepfert rh, mohar a, sanchez l, halperin d, ley c, et al. gastric atrophy and extent of intestinal metaplasia in a cohort of helicobacter pylori-infected patients. hum pathol. 2001; 32: 31-5. 9. micu g, staniceanu f, zurac s, popp c, bastian a, gramada e et al. regression of precancerous epithelial alteration in patients with helicobacter pylori chronic gastritis. rom j intern med. 2010; 48: 89-99. 10. kodama m, murakami k, okimoto t, abe t, nakagawa y, mizukami k, et al. helicobacter pylori eradication improves gastric atrophy and intestinal metaplasia in long term observation. digestion. 2012; 85: 126-30. 11. gallo n, zambon cf, navaglia f, bsso d, guariso g, grazia pm, et al. helicobacter pylori infection in children and of intestinal adults: a single pathogen but a different pathology. helicobacter. 2003; 8: 21-8. 12. khalid h, zubair a, malik tm, ayyub m, muhammad i. a histopathological analysis of chronic inflammatory infiltrate in patients of h pylori associated chronic gastritis. pak armed forces med j. 2015; 65: 36-41. 13. grieken nct, weiss mm, meijer ga, bloemena e, lindeman j, offerhasu gja, et al. rapid quantitative assessment of gastritis corpus atrophy in tissue sections. j. clin. pathol. 2001; 54: 63–9. 14. aydin o, egilmez r, karabacak t, kanik a. interobserver variation in histopathological assessment of helicobacter pylori gastritis. world j gastroenterol. 2003; 9: 2232-5. 15. chen xy, hulst rwm, bruno mj, ende a, xiao sd, tytgat gnj, et al. inter observer variation in the histopathological scoring of helicobacter pylori related gastritis. j clin pathol. 1999; 52: 612-5. 16. qamar s, bukhari m, asrar a, sarwar s, niazi s. evaluation of antral gastric biopsies. a study of 50 patients at mayo hospital. annals kemu. 2010; 16: 45-50. 17. pruthi s, nirupama m, chakraborti s. evaluation of gastric biopsies in chronic gastritis: grading of inflammation by visual analog scale. med j dpu. 2014; 7: 463-7. 18. naeem s, haque a, riaz a. spectrum of morphological changes induced by helicobacter pylori in chronic gastritis. i j p. 2007; 5: 13-7. 19. tanko mn, manasseh an, echejoh go, mandong bm, malu ao, okeke en, et al. relation between helicobacter pylori, inflammatory (neutrophil) activity, chronic gastritis, gastric atrophy and intestinal metaplasia. niger j clin prac. 2008; 11: 270-4. 20. maharjan s, ranabhat s, tiwari m, bhandari a, osti bp, neopane p. helicobacter pylori associated chronic gastritis and application of visual analogue scale for the grading of the histological parameters in nepal. biomed j sci & tech res. 2017; 1: 1-7. 21. fareed r, abbas z, shah ma. effect of helicobacter pylori density on inflammatory activity in stomach. j pak med assoc. 2000; 50: 148-51. 22. hansen tk, hansen ps, norgaard a, nielsen h, lee a, andersen lp. helicobacter felis does not stimulate human between the density of h. pylori and intestinal metaplasia (r =0.287). two other studies also s determined a significant correlation between density of h. pylori and degree of intestinal 29,30 metaplasia. in contrast to the results of present study, another study documented statistically significant drop in the rate of h. pylori colonization 31 density with the increase in intestinal metaplasia. the possible explanations are, because intestinal metaplasia is often focal process, h. pylori may stay alive on the gastric epithelium in the surroundings of intestinal metaplasia. moreover, there is a fact that the experience of the endoscopist affects the 32 detection rate of intestinal metaplasia. the limitations of present study are that it is performed in a single institution based with limited number of cases, although the patients come from variety of ethnic groups and socioeconomic backgrounds. large scale multicenter studies may be of help to improve the statistical power of this study. conclusion a f te r s e m i q u a n t i tat i ve d e te r m i n at i o n o f histopathological parameters of h. pylori associated chronic gastritis, it is concluded, that, the greater the density of h. pylori, the larger the degrees of neutrophilic activity, intestinal metaplasia and a t ro p hy. c o m p re h e n s i v e h i s t o p a t h o l o g i c a l classification can be used in gastric biopsies to improve assessment and avoid minor degrees of alteration. references 1. rugge m, russo vm, guid m. review article: what have we learnt from gastric biopsy? aliment pharmacol ther. 2003; 17: 740-68. 2. srivastava a, lauwers gy. pathology of non-infective gastritis. histopathology. 2007; 50: 15–29. 3. kusters jg, van vliet ah, kuipers ej. pathogenesis of helicobacter pylori infection. clin microbiol rev. 2006; 19: 449-90. 4. salih, ba. helicobacter pylori infection in developing countries: the burden for how long? saudi. j. gastroenterol. 2009; 15: 201–7. 5. tanih nf, dube c, green e, mkwetshana n, clarke am, ndip rn. an african perspective on helicobacter pylori: prevalence of human infection, drug resistance, and alternative approaches to treatment. ann trop med parasitol. 2009; 103: 189-204. 6. mehmood k, awan aa, muhammad n, hasan f, nadir a. helicobacter pylori prevalence and histopathological findings in dyspeptic patients. j ayub med coll abbottabad. 30 jiimc 2018 vol. 13, no.1 correlation of h. pylori density with adoptive responses severity of gastritis. gastroenterology research and practice. 2017; 6: 1-5. 28. kim n, park ry, cho si, lim sh, lee kh, lee w, et al. helicobacter pylori infection and development of gastric cancer in korea: long-term follow-up. j clin gastroenterol. 2008; 42: 448–54. 29. ozdil k, sahin a, kahraman r, yuzbasioglu b, demirdag h, calhan t, et al. current prevalence of intestinal metaplasia and helicobacter pylori infection in dyspeptic adult patients from turkey. hepatogastroenterol. 2010; 57: 1563-6. 30. s h a f i i m , n i k z a d s e , k a s i r i h , n a g h i p o u r m . histopathological evaluation of chronic gastritis with and without helicobacter pylori colonization: a study from iran. malaysian j pathol. 2008; 30: 27 – 30. 31. grgov s, stefanovic m, katic v. the relationship between the density of helicobacter pylori colonisation and the degree of gastritis severity. arch. gastroentero hepatol. 2002; 21: 3 – 4. 32. padda s, ramirez fc. accuracy in the diagnosis of shortsegment barrett's esophagus: the role of endoscopic experience. gastrointest. endosc. 2001; 54: 605–8. neutrophil oxidative burst in contrast to `gastrospirillum hominis' and helicobacter pylori. fems immunol med microbiol. 2001; 30: 187-95. 23. m u h a m m a d j s , s u g i y a m a t, z a i d i f s . g a s t r i c pathophysiological ins and outs of helicobacter pylori: a review. j pak med assoc. 2013; 63: 1528-33. 24. zhang c, yamada n, wu yl, wen m, matsuhisa t, matsukura n. helicobacter pylori infection, glandular atrophy and intestinal metaplasia in superficial gastritis, gastric erosion, erosive gastritis, gastric ulcer and early gastric cancer. world j gastroenterol. 2005; 11: 791–6. 25. kato s, nakajima s, nishino y, ozawa k, minoura t, konno m, et al. association between gastric atrophy and helicobacter pylori infection in japanese children: a retrospective multicenter study. digestive diseases and sciences. 2006; 51: 99–104. 26. topal d, goral v, yilmaz f, kara ih. the relation of helicobacter pylori with intestinal metaplasia, gastric atrophy and bcl-2. turk j gastroenterol. 2004; 15: 149-55. 27. basir h, ghobakhlou m, akbari p, dehghan a, rabiei ma. correlation between the intensity of halic colonization and 31 jiimc 2018 vol. 13, no.1 correlation of h. pylori density with adoptive responses page 31 page 32 page 33 page 34 page 35 page 36 original�article abstract objective: the objective of this study was to determine the attitude of physical therapy and speech language pathology students toward persons with disability. study design: descriptive analytical st st place and duration of study: from 1 july to 31 december 2014 at riphah college of rehabilitation sciences, riphah international university islamabad. materials and methods: a sample of 246 (81 post graduate, 145 under graduate and 20 speech language pathologists) was recruited through purposive sampling. both gender and willing students were included in study. the standard tool for attitude toward disabled person (atdp), a & b performa was circulated to all participations. brief demographic information was included and finally statistical analysis was drawn through spss-20. results: the mean age of under graduate, post graduate physiotherapy students and speech language pathologists was 22.3±3.12, 25.7±2.81 and 27.6±27 years respectively. the statistical analysis showed that there was a significant difference in personal and professional attitude towards disability of under graduate and post graduate physiotherapy students (p 0.001). the comparison showed that there was no significant < difference in personal and professional attitude towards disability of post graduate physiotherapy students and speech language pathologists (p=0.481, p=0.275) respectively. conclusion: the study concluded that the attitude of speech language pathologists is more positive than physiotherapy students and graduates. the attitude of under graduate physiotherapy students is more positive as compared to the post graduates. there is dire need to modify and upgrade the curriculum about the significance of disability in under grad. key words: disabled persons, physiotherapy students, personal attitude, professional attitude. interaction of person's characteristics with the environment's characteristics. in earlier decades it was considered that the disability is a consequence of biological process and the individual is responsible 3 for disability. later they related it with some social and psychological aspects and the biopsychosocial model was introduced. now the disability is to be considered as the human right issue by different organizations. disability is now understood to be a human rights issue. the people are not disable by their bodies but by the society and disability is a contextual variable with dynamic over time and 4 circumstance. the icf model the most modern and well defined have discussed not only the single aspect of disability rather explore the multiple perspective of disability like employment, disability 5 eligibility and social aspects. the disablement process explained that disability is not an individual trait but a lack of linkage between personal disability 6 and the environment. so the main responsibility lies on the society and the environment of the persons introduction the disability is a condition which limits personal, physical and mental ability or situation of being 1 disabled. it can be considered as the incapacity, 2 defect and disorder. the disability is basically an rehabilitation professional attitude towards persons with disability 1 2 3 4 5 arshad nawaz malik , imran amjad , muhammad naveed babur , furqan ahmed siddiqi , hafiz naeem ul rasul correspondence: dr. arshad nawaz malik associate professor physical therapy and rehabilitation sciences shifa tameer-e-millat university, islamabad e-mail: physiomalik1@gmail.com 1 department of physical therapy and rehabilitation sciences shifa tameer-e-millat university, islamabad 2 department of physical therapy and rehabilitation sciences riphah international university 3 department of physical therapy and rehabilitation sciences isra university, islamabad 4 department of physical therapy and rehabilitation sciences foundation university, rawalpindi 5 department of physical therapy and rehabilitation sciences pakistan cricket board, lahore funding source: nil; conflict of interest: nil received: dec 08, 2017; revised: jul 12, 2018 accepted: jul 16, 2018 disability perceptionjiimc 2018 vol. 13, no.3 118 different perspective of disabilities. this study will contribute in enhancing the positive attitude and also creating the awareness among health professionals. the study was aimed to evaluate the attitudes of different rehabilitation professionals towards disabilities and to determine the difference of professional and personal attitude among them. materials and methods a descriptive cross sectional study design was used and a sample of (n=246) rehabilitation professionals was recruited through purposive sampling from riphah international university, islamabad. the st st study was conducted from1 july to 31 december 2014. the sample included 145 under graduate doctors of physical therapy dpt final year students, 81 post graduate students and 20 speech and language pathologists. both gender and willing students were included while students with disability were excluded from the sample. the demographic details were recorded and written informed consent was taken from all participants. the standard tool “attitude towards disabled person” (atdp) designed and developed by yurker (1960) was used to evaluate the perception of attitude. this tool has been widely used for the measurement of attitude of people towards 15 disability. there are two types of questionnaire a & b, the part of atdp, includes the personal and professional performa. the score of scale ranges from 0 120 and the interpretation shows that the high score reflects positive attitude towards disability. the process of distribution of both the questionnaire was to divide the class subjects into two groups. one group was asked to fill the personal performa keeping in mind the personal attitude towards disability. other group was asked to fill the professional with perception of professional attitude towards disability and then vice versa. after completing the process the participants were asked to fill the other performa. this process assured the random distribution and avoidance of influence of perception of students. the data was analyzed through spss-20. the descriptive analysis including the frequency, percentage and mean were calculated while “independent t test” was used to compare the means between groups. results t h e m e a n a ge o f u n d e r g ra d , p o st g ra d 7 with disability. the attitudes are a complex collection of beliefs, 7 feelings and values. the attitude of society towards 8 the disable was always negative and discriminative. people thought that disability was because of their sins and the disable person is solely responsible for 8 his/her disability. this attitude created a distance and discriminative behavior among society which leads to increase the gap between disable and able 8 persons. the health care provider should be different regarding the attitude towards disability as compare to the non health care people. the health care providers have direct and long term relationship with people with disabilities. the literature showed the positive attitude of health professionals as 8 compare to the other professionals. the role of physical therapist in disability is also very challenging and the aim is to restore, maintain, and promote not only optimal physical function but optimal wellness 9 and fitness. the role of physical therapist is to improve quality of life of person with disabilities and play an effective role in multidisciplinary team. in literature different studies conducted on the assessment of attitudes of health professionals towards disability. there is difference of perception of attitude in different cultural system and multi10 model societies. parents and teachers have a vital 11 role to play in shaping and modeling attitudes. there are comparative studies in literature which shows the difference in attitude of different health p ro fe s s i o n a l s i n c l u d i n g t h e p hys i o t h e ra py, occupational therapy, nurses, medical staff and 12 other related persons. it was supposed that the attitude of rehabilitation professionals must have positive findings as they have close relationship 8 during the rehabilitation of person with disability. the professional graduates have more positive attitude than students because they have more 13 interaction with disability. there are some confounding in the survey of rehab nurses, occupational therapy and physiotherapy and the study concluded that the occupational therapy has m o re p o s i t i ve f i n d i n g s t h a n o t h e r re h a b professional. the confounding includes the age, clinical setting, cultural system and the experience which have greater effect on attitude towards 14 disability. in pakistan, there is limited literature to explore the disability perceptionjiimc 2018 vol. 13, no.3 119 disability of under grad and post grad physiotherapy students and the under grad students have more positive attitude than post grad students. the results also depict that there is no difference in post grad and speech language pathologists but speech language pathologists have more positive attitude towards disability. the literature shows that the occupational therapists have high and more positive score as compared to the physiotherapists the score of occupational therapy students are also above the average while physiotherapists have low 13 score in attitude towards disability. there is a difference in the attitude of final year and first year medical students towards disability, although it was not compared in this study. the personal attitude was greater than professional attitude in the final 14 year students. the personal attitude reflects the cultural and other related factors' contribution and it is frequently more positive than professional attitude. it is difficult to modify and change the personal attitude while the professional attitude can be enhancing with the direct contact with person with disability. the focus should be to improve the professional attitude through training and other clinical oriented 15,16 workshop related disability. a study on students of occupational and physiotherapy showed that the score of physiotherapy is less than occupational 17 therapy. the medical education has significant impact on the development of attitude towards disability which leads to positive attitudes among health professionals. in one study the final year and house officers have similar attitudes towards 18 disability. the gender has also an influence on the attitude and especially the personal attitude can be changed towards gender. but the professional attitude has not be inclined because of gender issue in attitude 19 towards disability. the curriculum of the health professional has significant outcome and plays a key role in the development of attitude and enhancing t h e p o s i t i v i t y i n a tt i t u d e i n h e a l t h c a re 20,21 professionals. conclusion the study concludes that the attitudes of speech language pathologist is more positive than physiotherapy students and graduates. the attitude of under grad physiotherapy students is more physiotherapy students and speech language pathologists were 22.3±3.12, 25.7±2.81 and 27.6±27 years respectively. the total sample has distribution of 58.94% undergrad, 32.93% post grad and 8.13% speech and language pathologists.(fig 1) the statistical analysis showed that there was a significant difference in personal and professional attitude towards disability of under grad and post grad physiotherapy students (p 0.001, p 0.000) < < respectively. (table i) the und-grad students have positive attitude towards disability as compared to post grad. the comparison showed that there was no significant difference in personal and professional a t t i t u d e t o w a r d s d i s a b i l i t y o f p o s t g ra d physiotherapy students and speech language pathologists respectively (p=0.481, p=0.275). (table ii) fig 1: shows the sample of different categories table i: personal and professional a�tude of undergrad and post grad pt students table ii: personal and professional a�tude of post grad pt students and speech language pathologist discussion the summary of results state that there is difference in attitude (both personal and professional) towards disability perceptionjiimc 2018 vol. 13, no.3 120 positive as compared to the post graduates. there is a need to enhance the level of education, modify the existing curriculum and arrange workshops to improve the attitude of students towards disability. future research should be conducted to explore the perception of students and clinicians about the significance of disability and person with disability. references 1. inc. m-w. merriam-webster's collegiate dictionary: merriam-webster; 2004. 2. dictionary oe. oxford english dictionary online. mount royal college lib, calgary.2004;14. 3. stucki g. international classification of functioning, disability, and health (icf): a promising framework and classification for rehabilitation medicine. american journal of physical medicine & rehabilitation. 2005; 84: 733-40. 4. douglas g, corcoran c, pavey s. the role of the who icf as a framework to interpret barriers and to inclusion: visually impaired people's views and experiences of personal computers. british journal of visual impairment. 2007; 25: 32-50. 5. cerniauskaite m, quintas r, boldt c, raggi a, cieza a, bickenbach je, et al. systematic literature review on icf from 2001 to 2009: its use, implementation and operationalisation. disability and rehabilitation. 2011; 33: 281-309. 6. verbrugge lm, jette am. the disablement process. social science & medicine. 1994; 38: 1-14. 7. shakespeare t. the social model of disability. the disability studies reader. 2006; 2: 197-204. 8. tervo rc, palmer g. health professional student attitudes towards people with disability. clinical rehabilitation. 2004; 18: 908-15. 9. jette du, bacon k, batty c, carlson m, ferland a, hemingway rd, et al. evidence-based practice: beliefs, attitudes, knowledge, and behaviors of physical therapists. physical therapy. 2003; 83: 786-805. disability perceptionjiimc 2018 vol. 13, no.3 10. westbrook mt, legge v, pennay m. attitudes towards disabilities in a multicultural society. social science & medicine. 1993; 36: 615-23. 11. aiden hs. creating the 'multicultural coexistence'society: central and local government policies towards foreign residents in japan. social science japan journal. 2011; 14: 213-31. 12. stachura k, garven f. a national survey of occupational therapy students' and physiotherapy students' attitudes to disabled people. clinical rehabilitation. 2007; 21: 442-9. 13. au kw, man dw. attitudes toward people with disabilities: a comparison between health care professionals and students. international journal of rehabilitation research. 2006; 29: 155-60. 14. white mj, olson rs. attitudes toward people with disabilities: a comparison of rehabilitation nurses, occupational therapists, and physical therapists. rehabilitation nursing. 2012; 23: 126-31. 15. plachy lm. attitudes toward disability in occupational therapy students. 1995. 16. lyons m. enabling or disabling? students' attitudes toward persons with disabilities. the american journal of occupational therapy. 1991; 45: 311-6. 17. daruwalla p, darcy s. personal and societal attitudes to disability. annals of tourism research. 2005; 32: 549-70. 18. duckworth s. the effect of medical education on the attitudes of medical students towards disabled people. medical education. 2009; 22: 501-5. 19. hutzler y, zach s, gafni o. physical education students' attitudes and self-efficacy towards the participation of children with special needs in regular classes. european journal of special needs education. 2005; 20: 309-27. 20. thompson tlc, emrich k, moore g. the effect of curriculum on the attitudes of nursing students toward disability. rehabilitation nursing. 2012; 28: 27-35. 21. estes jp, deyer ca, hansen ra, russell jc. influence of occupational therapy curricula on students' attitudes toward persons with disabilities. the american journal of occupational therapy. 1991; 45: 156-9. 121 50 editorial thalassaemia in pakistan suhaib ahmed correspondence: maj. gen. (r) dr. suhaib ahmed professor of haematology islamic international medical college riphah international university, islamabad e-mail: suhaib.ahmed@riphah.edu.pk received: may 12, 2018; accepted: may 25, 2018 thalassaemia is the commonest single gene disorder 1,2 of globin chain synthesis all over the world . it is found as thalassaemia minor when the defect is inherited from one of the parents and as thalassaemia major when the defect is inherited from both of the parents. studies of thalassaemia in pakistan have shown that 5% of the population have 3 thalassaemia minor. based on this figure it is estimated that each year in pakistan approximately 5000 children with thalassaemia major are born and the total number of children with thalassaemia 4 major may be over 50,000. thalassaemia major is a serious disorder in which the affected child is unable to synthesize its own haemoglobin. the child remains well for the initial three to four months but after this the signs and symptoms of anaemia start appearing. the child looks pale, becomes irritable, and fails to thrive. diarrhoea and frequent respiratory tract infections are other frequent symptoms. examination may show hepato-splenomegaly. the lab investigations show moderate to marked hypochromic microcytic anaemia, numerous nucleated red cells and 5 markedly raised hb-f. an early diagnosis and blood transfusions may halt further deterioration. the child has to be put on lifelong blood transfusions. as a result of regular blood transfusions a large amount of extra iron starts accumulation in the body. this iron can be very harmful for many important organs like heart and endocrine glands. the extra iron must be removed from the body by using iron chelating medicines. stem cell transplantation is a curative treatment of thalassaemia major. when done early in life over 80% disease free survival can be 6 achieved. the facilities for stem cell transplant are available at several places in pakistan but the procedure is expensive and due to the limited capacity it can be offered to only a small number of 7 patients. there are more than 50,000 patients of thalassaemia major in pakistan. unfortunately the treatment facilities for such large number of patients are not adequate. most of the patients are treated at the centres run by nongovernmental organizations (ngo) who have limited resources. consequently the outcome is also not good. a report published in this issue of the journal gives a detailed description of the outcome in a large number of patients at a 8 local treatment centre. most of the children were chronically under-transfused and were also markedly iron overloaded. majority had growth retardation below the fifth centile for the pakistani population. the median age at death was just ten years. although this is a single centre study but the situation at the other centres in pakistan, with few exceptions, is not expected to be different. thalassaemia minor (carrier) is an asymptomatic disorder and most people do not even know about their abnormality. most people with thalassaemia minor are detected during blood testing for some other reason or when they get married to another carrier and give birth to a child with thalassaemia major. thalassaemia carriers usually have haemoglobin within the normal range, mcv < 75 fl and mch < 25 pg. the diagnosis can be confirmed by haemoglobin electrophoresis that typically shows hb-a above 4.0%. a small number (<3%) 2 thalassaemia carriers are silent i.e. their red cell indices and hb-a levels are within the normal range. 2 such carriers can be missed on routine screening 5 methods and pcr is required to detect them. thalassaemia is an autosomal recessive disorder. a child with thalassaemia major is born only when both of the parents have thalassaemia minor. in a carrier couple there is a 25% probability in each pregnancy that the child may inherit abnormality from both of the parents. marriage of a carrier to a non-carrier will not result in thalassaemia major. the births of children with thalassaemia major can be avoided by premarital carrier screening and avoiding department of haematology islamic international medical college riphah international university, islamabad 51 jiimc 2018 vol. 13, no.2 marriage between two carriers. the carrier couples who are already married can be offered prenatal diagnosis and selective termination of pregnancy if the fetus is found to be affected. based on these two approaches excellent results have been achieved in many high risk populations in the mediterranean 9 countries and lately in iran. the birthrate of children with thalassaemia major in most of these countries has been brought down to almost zero. the success of thalassaemia prevention programs in the mediterranean region and iran has largely been attributed to a political will by the government, public awareness through mass communication media, allocation of funds, and the provision of 9,10 quality diagnostic services. pakistan has one of the largest numbers of thalassaemia major children in the world and providing treatment facilities to these children is far beyond the available health 2 resources. the burden of disease is likely to increase with the passage of time if no measures are taken to implement a thalassaemia prevention program. the facilities for carrier screening of thalassaemia are available since early eighties. prenatal diagnosis for thalassaemia is also available in pakistan since 11 1994. a study on the extended families of children with thalassaemia major in pakistan has clearly shown it to be the most cost effective method for 12 large scale application. however, in spite of the two basic facilities for thalassaemia prevention there has not been any appreciable reduction in the birth incidence of thalassaemia major in pakistan. there are several impediments, including the lack of awareness and the high cost, to the use of these 13 measures in pakistan. the government of punjab has initiated a thalassaemia prevention program (ptpp) that aims at providing free of cost carrier screening in the extended families of children with thalassaemia and the general public. ptpp also offers free of cost prenatal diagnosis (https://ptpp. punjab.gov.pk/). the program is in its early stages and it would take several years to see its long term benefits. there is need to initiate such programs in the other provinces of the country and to establish a central coordination cell in the federal ministry of 5,14 health. references 1. angastiniotis m, modell b. global epidemiology of hemoglobin disorders. ann n y acad sci. 1998; 850: 251-69. 2. modell b, darlison m. global epidemiology of haemoglobin disorders and derived service indicators. bulletin world health org. 2008; 86: 480-7. 3. khattak mf, saleem m. prevalence of heterozygous thalassaemia in the northern areas of pakistan. j pak med assoc. 1992; 42: 32-4. 4. ahmed s. an approach for the prevention of thalassaemia in pakistan. phd thesis, university of london 1998. ava i l a b l e a t h tt p : / / d i s c o v e r y. u c l . a c . u k / 1 3 1 7 9 1 6 /1/299931.pdf. 5. ahmed s. genetic haemoglobin disorders in pakistan. grc publication, rawalpindi 2018. 6. lucarelli g, isgro a, sodani p, gaziev j. hematopoietic stem cell transplantation in thalassemia and sickle cell anemia. cold spring harb perspect med. 2012; 2: 1-11. 7. shamsi ts, hashmi k, adil s, ahmad p, irfan m, raza s, et al. the stem cell transplant program in pakistan—the first decade. bone marrow transplantation. 2008; 42: s114. 8. ahmed s, wazir zj, qayyum ia. clinical and haematological picture of multi-transfused thalassaemia major patients at a center in pakistan. j islam int med col. 2018. (in press). 9. cao a. results of programmes for antenatal detection of thalassaemia in reducing the incidence of the disorder. blood rev. 1987; 1: 169-76. 10. zeinalian m, nobari rf, moafi a, salehi m, hashemzadehchaleshtori m. two decades of pre-marital screening for beta-thalassemia in central iran. j community genet. 2013; 4: 517–22. 11. ahmed s, saleem m, petrou m, sultana n, raashid y, waqar a. prenatal diagnosis of -thalassaemia in pakistan: experience in a muslim country. prenatal diagnosis. 2000; 20: 378-83. 12. ahmed s, saleem m, modell b, petrou m. screening extended families for genetic haemoglobin disorders in pakistan. n engl j med. 2002; 347: 1162-8. 13. naseem s, ahmed s, vahidy f. impediments to prenatal diagnosis for beta thalassaemia: experiences from pakistan. prenat diagn. 2008; 28: 1116-8. 14. ahmed s. genetic haemoglobin disorders in pakistan. nat j health sci. 2017; 2: 95-9. page 6 page 7 untitled-2 untitled-2 original�article abstract objective: to determine the association of pro-inflammatory markers with suicidality in patients suffering from major depressive episode. study design: descriptive cross sectional study. place and duration of study: the study was conducted at department of pathology in collaboration with the department of psychiatry, pakistan railway hospital, islamic international medical college, rawalpindi from th th 18 april, 2017 to 17 march, 2018. materials and methods: seventy five subjects recruited through convenient non-probability sampling technique were divided into three groups i.e. group 1 (patients of major depressive episode with suicidality), group 2 (patients of major depressive episode without suicidality) and group 3 included healthy controls. patients of major depressive episode and suicidality were diagnosed through hamilton rating scale for depression and beck scale for suicidal intention successively. pro-inflammatory markers i.e. interleukin-1ß, interleukin-6 and c-reactive protein were measured in the serum of all participants. data was analyzed through statistical package for social sciences version 21. simple descriptive statistics (frequencies, percentages) were computed for each categorical variable. mean and standard deviation were calculated for the numerical data. independent t test and one way anova was applied to determine the statistical significance. p value of < 0.05 was considered significant. results: out of 75 enrolled patients, pro-inflammatory markers i.e. interleukin-1ß, interleukin-6 and c-reactive protein were raised in patients of major depressive episode with suicidality. conclusion: pro-inflammatory markers i.e. crp, il-1ß and il-6 are markedly raised in patients of major depressive episode with suicidality. so, from the results it is concluded that pro-inflammatory markers have an association with suicidality in patients of major depressive episode and treating inflammation in them can improve their symptoms and reduce suicidal rate. key words: crp, il-1ß, il-6, inflammation, major depressive episode, pro-inflammatory markers and suicidality die of suicide per year in the united states and the global death rate was nearly 800000 in the year 2014 1 calculated by world health organization (who). it was predicted by who in 2011 that one million people would die by the year 2030 due to suicide, 1 that will contribute to 1.4% of all the deaths globally. the real number of deaths may be higher because suicidal deaths are normally not reported due to societal issues and criminalization of suicide in many 1 societies. suicidal attempts are also insufficiently reported. almost twenty or more than that suicide attempts occur for every completed suicide, so suicide attempts are more frequent than completed 1 suicide. there is emerging evidence that this behavioral phenotype is independently associated with a pro-inflammatory state in the body, and that it 2 is not linked to the severity of depression per se. introduction suicide is the second major cause behind the death of youngsters among the 15–29 age group in the 1 world. according to one estimation, 40,000 people the association of pro-inflammatory markers with suicidality in patients suffering from major depressive episode 1 2 3 4 5 aqsa liaqat , muhammad nadim akbar khan , athar muneer , ama tul naval , fakhra noureen correspondence: dr. aqsa liaqat senior lecturer department of pathology hbs medical and dental college islamabad e-mail:aqsach@gmail.com 1 department of pathology hbs medical and dental college islamabad 2,3,5 department of pathology/psychiatry islamic international medical college riphah international university, islamabad 4 department of pathology watim medical and dental college, islamabad funding source: nil; conflict of interest: nil received: may 24, 2018; revised: january 09, 2019 accepted: february 19, 2019 pro-inflammation markers and suicidalityjiimc 2019 vol. 14, no.1 13 of pro-inflammatory markers with suicidality in patients of major depressive episode (mde) patients. the objective of our study is to find the association of pro-inflammatory markers (il-1β, il-6 & crp) with suicidality in patients suffering from major depressive episode (mde). materials and methods this observational cross sectional study was conducted at chemical pathology department in collaboration with psychiatry department of pakistan railway hospital, islamic international th medical college, rawalpindi from 18 april, 2017 to th 17 april, 2018 after getting permission from ethical review committee of riphah international university. sample size was decided based on the data from similar previous studies. participants from both genders were enrolled through non-probability convenient sampling after taking informed consent. seventy-five participants were inducted in the study between the ages of 18 to 65 years and divided into three groups each having twenty-five participants. group 1 had twenty-five patients of major depressive episode (mde) with suicidality, group 2 had twenty-five patients of mde without suicidality and group 3 had twenty-five healthy adults. participants having any acute or chronic infection or inflammation, obesity, allergies, pregnancy and lactating mothers were excluded. participants of mde and suicidality were diagnosed based on hamilton rating scale for depression (hrsd) and beck scale for suicidal intent respectively by a qualified psychiatrist in opd of psychiatry department. after filling demographic data, patients were directed towards pathology lab and 5 ml of venous blood was withdrawn in plain vacutainers considering all necessary measures to avoid pre-analytical errors. samples were transported in crushed ice to cream lab of army medical college, rawalpindi for refrigerated centrifuge at 4° c. serum was extracted and stored at -80 ̊ c. crp levels of all samples were analyzed through visual agglutination semi quantitative method. il-1ß and il-6 were analyzed by elisa method. data was analyzed through statistical package for social sciences (spss) version 21. simple descriptive statistics (frequencies, percentages) were computed for each categorical variable. mean and standard deviation were calculated for numerical data. independent t test and one way many studies have shown that suicide is associated with an increase in inflammatory markers in the 2 body. “cytokine-induced sickness behavior” (i.e., lethargy, fatigue, depression, failure to concentrate, anorexia, sleep problems, reduced sense of personal hygiene and social withdrawal) has been shown to be linked and mediated by pro-inflammatory cytokines 3 i.e. il-1 and il-6. another important mechanism underlying suicidality is the activation of kynurenine pathway for the catabolism of tryptophan. abnormalities in this pathway lead to certain b i o l o g i c a l m e c h a n i s m w h i c h a s s o c i a t e s 4 inflammation with suicidality and depression. tryptophan catabolism through kynurenine pathway produces certain neuroactive substances especially 5 quinolinic acid (quin) and kynurenic acid (kyna). the inflammatory cytokines especially il-1ß, il-6 and ifn-γ are potent activators of indole amine 2, 3 d i o x y g e n a s e ( i d o 1 ) a n d t r y p t o p h a n 2 . 3 dioxygenase (tdo2). these two enzymes regulate 6,7 the initial steps in kynurenine pathway. tryptophan is the precursor of serotonin neurotransmitter, so catabolism of tryptophan through this pathway down regulates the amount of serotonin in the 8 body. this mechanism can directly lead to lower levels of monoamines in the csf and serum of 1 suicidal victims. a meta-analysis by black & miller published in 2015 has shown that levels of il-1 β, il-6 & tnf-α are elevated in the body fluids of those psychiatric patients who attempted suicide or have 2 strong suicidal ideation. identification of specific inflammatory markers and important co-existing biological factors can inform us regarding the risk of suicidal behavior. further, treatments targeting the constituents of the inflammatory pathway are nowadays undergoing trials for a variety of psychiatric conditions, and this approach can lead to the development of novel therapeutic tools for the 9 prevention of suicide. our proposition is that patients who contemplate or attempt suicide have an inflammatory state in their bodies which can be detected by measuring pro-inflammatory markers like interleukin-1 β, interleukin 6 and c-reactive 10,2 protein (crp) in the serum. in the extant literature review, no single study has documented the association of il-1 β, il-6 & c-reactive protein 2 together with the existence of suicidality. further, no local studies are available to relate the association 14 jiimc 2019 vol. 14, no.1 pro-inflammation markers and suicidality discussion the results of present study show that in healthy adults, levels of cytokines are undetectable. in 2013, kleiner et al. also published a study in which it was concluded that in normal healthy people levels of cytokines were undetectable due to the absence of 9 any inflammatory stimulus. due to the absence of inflammation in healthy adults, crp levels are also undetectable or within normal range in them. in patients of major depressive episode without suicidality, the levels of pro-inflammatory markers like interleukin-1ß, interleukin-6 were high as compared to healthy adults. this shows that some degree of inflammation is also present in patients of major depressive episode irrespective of absence of anova were applied to determine the statistical significance. p value of < 0.05 was considered significant. results total 75 patients were divided into three equal group i.e. group 1 consisted of patients of mde with suicidality, group 2 consisted of mde patients without suicidality and group 3 consisted of healthy adults with no history of somatic or psychiatric illness. descriptive statistics of age (years) was calculated in terms of mean and standard deviation. mean age (years) of participants was overall 33.32+8.93 whereas mean age (years) of mde patients with suicidality was 28.44±6.70 and of mde patients without suicidality was 37.8±8.10. the mean age (years) of healthy adults was 33.72+8.93. distribution of gender was calculated in terms of frequency and percentage of male and female patients. there were 39 (52.0%) male participants, of these 11 (44.0%) were present in group 1 (mde with suicidality), 13 (52.0%) male patients were included in group 2 (mde without suicidality) and 15 (60.0%) male participants were present in group 3 (healthy adults). there were 36 (48.0%) female participants included in the study, of these 14 (56.0%) were present in group 1 (mde with suicidality), 12 (48.0%) female patients were included in group 2 (mde without suicidality) and 10 (40.0%) were present in group 3 (healthy adults). the association of proinflammatory markers (il-1 β, il-6 and crp) with suicidality in patients suffering from major depressive episode (mde) was assessed using table i: comparison of pro-inflammatory markers between groups 1 and group 2 p<0.05 was taken as level of significant g r o u p 1 : m d e w i t h s u i c i d a l i t y group 2: mde without suicidality table ii: comparison of pro-inflammatory markers between groups 1 and group 3 independent t test. the results came out to be statistically significant for all the three markers i.e. pvalue < 0.05 as shown in table i and table ii. pro-inflammatory markers (crp, il-1ß and il-6) were compared among three groups using one way anova. the results showed statistically significant difference for all pro-inflammatory markers (p value<0.001) as shown in table iii. p<0.05 was taken as level of significance group 1: mde with suicidality group 3: healthy adults table iii: comparison of pro-inflammatory markers among three groups (n=75) p<0.05 was taken as level of significant 15 jiimc 2019 vol. 14, no.1 pro-inflammation markers and suicidality low or high risk for suicidality, crp levels were raised 16 in acute cases. in another recent study, gibbs et al. did research work on indoor psychiatric patients with and without suicidal behavior. they found out that mde patients with high degree of suicidality had greater inflammation and increased levels of crp when compared to mde patients without suicidality 17 and healthy adults. in 2015, black and miller in their m e t a a n a l y s i s o f m a ny s t u d i e s b a s e d o n inflammation and suicidality also concluded that inflammation was strongly associated with 2 suicidality in mde patients. conclusion it is concluded that pro-inflammatory markers are significantly high in mde patients with suicidality. this also throws light on the association of proinflammatory markers with suicidality and importance of treating patients with antiinflammatory drugs in medicine resistant depression with suicidality. limitations this study was conducted in a single outdoor patient department. due to financial constraints and limited time duration availability, a small group of patients was included. there are some other proinflammatory markers and anti-inflammatory markers mentioned in literature like tnf-ɑ, il-2 etc. they can be considered for further studies. a longitudinal study can be conducted in future to observe the effect of anti-inflammatory drugs in these patients. references 1. brundin l, bryleva ey, thirtamara rajamani k. role of inflammation in suicide: from mechanisms to treatment. neuropsychopharmacology : official publication of the american college of neuropsychopharmacology. 2017;42(1):271-83. 2. black c, miller bj. meta-analysis of cytokines and chemokines in suicidality: distinguishing suicidal versus nonsuicidal patients. biological psychiatry. 2015;78(1):2837. 3. courtet p, giner l, seneque m, guillaume s, olie e, ducasse d. neuroinflammation in suicide: toward a comprehensive model. the world journal of biological psychiatry. 2016;17(8):564-86. 4. lotrich fe, ferrell re, rabinovitz m, pollock bg. labile anger during interferon-alpha treatment is associated with a polymorphism in tumor necrosis factor-alpha. clinical neuropharmacology. 2010;33(4):191-7. 5. schwarcz r, bruno jp, muchowski pj, wu hq. kynurenines in suicidality in them. however, the levels are not as much elevated as in patients of major depressive episode with suicidality. in 2013, a study conducted by valkanova v et al. also concluded that levels of 10 crp and il-6 were high in depressed patients. in 2007, a study conducted by kim yk et al. also showed that levels of cytokines were high in depressed 14 patients. hughes mm et al. also found out during their study that inflammation and inflammatory markers play a vital role in the pathogenesis of d e p r e s s i o n a n d t h e r a p i e s t a r g e t i n g t h i s 11 inflammation might prove beneficial. in 2005, schiepers oj et al. published their review article regarding cytokines and depression. they concluded after reviewing many studies related to the subject that cytokines play a pivotal role in the central regulation of certain behavioral changes linked to 12 depression. in this study it is observed that suicidality in mde patients is not directly linked to the severity of depression. another important finding is that certain behavioral traits like aggression, loss of hope and hostile behavior are specially highlighted in patients of mde with suicidality as compared to mde patients without suicidality. in 2006, brezo j et al. reviewed some studies and concluded similar finding that certain behavioral traits were linked to suicidality 13 directly. in 2015, deshong hl et al. presented a “five factors model” which was based on similar personality traits. they concluded that these behavioral traits could predict future risk of 14 suicidality in mde patients. so, these findings during this study are in accordance to the previous 13, 14 studies. importantly among these behavioral aspects “hopelessness” which is a very important factor in diagnosing psychiatric patients especially with suicidality was previously identified to be associated with raised interleukin-6 levels and this 15 finding is also observed and concluded in this study. crp was markedly raised in patients of suicidality when compared to non-suicidal depressed patients and healthy individuals. this shows that level of inflammation is higher in patients of suicidality as compared to the non-suicidal depressed patients. courtet at al. also worked on crp in both patients with suicidality and non-suicidality and found that high crp levels were associated with suicidality in mde patients. they also found that irrespective of 16 jiimc 2019 vol. 14, no.1 pro-inflammation markers and suicidality 11. hughes mm, connor tj, harkin a. stress-related immune markers in depression: implications for treatment. the international journal of neuropsychopharmacology. 2016. 12. schiepers oj, wichers mc, maes m. cytokines and major depression. progress in neuro-psychopharmacology & biological psychiatry. 2005;29(2):201-17. 13. brezo j, paris j, turecki g. personality traits as correlates of suicidal ideation, suicide attempts, and suicide completions: a systematic review. acta psychiatrica scandinavica. 2006; 113(3):180-206. 14. deshong hl, tucker rp, o'keefe vm, mullins-sweatt sn, wingate lr. five factor model traits as a predictor of suicide ideation and interpersonal suicide risk in a college sample. psychiatry research. 2015;226(1):217-23. 15. mitchell am, possel p, sjogren e, kristenson m. hopelessness the "active ingredient"? associations of hopelessness and depressive symptoms with interleukin-6. international journal of psychiatry in medicine. 2013;46(1):109-17. 16. courtet p, jaussent i, genty c, dupuy am, guillaume s, ducasse d, et al. increased crp levels may be a trait marker of suicidal attempt. european neuropsychopharmacology: t h e j o u r n a l o f t h e e u r o p e a n c o l l e g e o f neuropsychopharmacology. 2015; 25(10):1824-31. 17. gibbs hm, davis l, han x, clothier j, eads la, caceda r. association between c-reactive protein and suicidal behavior in an adult inpatient population. journal of psychiatric research. 2016; 79:28-33. the mammalian brain: when physiology meets pathology. nature reviews neuroscience. 2012;13(7):465-77. 6. schwieler l, larsson mk, skogh e, kegel me, orhan f, abdelmoaty s, et al. increased levels of il-6 in the cerebrospinal fluid of patients with chronic schizophrenia-significance for activation of the kynurenine pathway. journal of psychiatry & neuroscience : jpn. 2015;40(2):12633. 7. urata y, koga k, hirota y, akiyama i, izumi g, takamura m, et al. il-1beta increases expression of tryptophan 2,3dioxygenase and stimulates tryptophan catabolism in endometrioma stromal cells. american journal of reproductive immunology (new york, ny : 1989). 2014;72(5):496-503. 8. maes m, leonard be, myint am, kubera m, verkerk r. the new '5-ht' hypothesis of depression: cell-mediated immune activation induces indoleamine 2,3-dioxygenase, which leads to lower plasma tryptophan and an increased synthesis of detrimental tryptophan catabolites (trycats), both of which contribute to the onset of depression. progress in neuro-psychopharmacology & biological psychiatry. 2011;35(3):702-21. 9. kleiner g, marcuzzi a, zanin v, monasta l, zauli g. cytokine levels in the serum of healthy subjects. mediators of inflammation. 2013;2013:434010. 10. valkanova v, ebmeier kp, allan cl. crp, il-6 and depression: a systematic review and meta-analysis of longitudinal studies. journal of affective disorders. 2013;150(3):736-44. 17 jiimc 2019 vol. 14, no.1 pro-inflammation markers and suicidality original�article in addition to the above mentioned lab tests, total antioxidant capacity (tac) was measured for both the groups. statistical package for social sciences (spss) version 23.0 was used for entering and analyzing all data. descriptive statistics were described for nominal data; mean and standard deviation were described for quantitative variables which included serum tac, fbg, serum hdl-c, serum triglycerides, waist circumference and bp measurement. results: the mean age of metabolic disease group was 48.14 + 10.48 years, and that of control group was 23.04 + 5.82 years tac recorded levels were found to be considerably higher in the control group (18.13 ± 12.90 . mmol/l) as compared to the metabolic syndrome group (4.56 ±.7.43). serum hdl-c (37.09 + 6.37 mg/dl) vs (43.09 + 46.15 mg/dl) levels were lower in ms individuals. whereas, triglycerides (240.03 ± 93.19) vs (107.41 ± 56.50), fpg (139.43 ±57.56) vs (69.66 ± 30.46), bp (133.86 mm hg + 13.59) vs (120.00 + 0.00) were found to be higher in ms patients as compared to control group. conclusion: tac gets depleted in ms individuals more as compared to healthy individuals. estimation of tac at an early stage can be useful for early detection of metabolic syndrome and further to prevent its complications such as dm, cvd and other metabolic disorders. key words: cardiovascular disease, diabetes mellitus, high density lipoprotein cholesterol, metabolic syndrome, total antioxidant capacity. abstract objective: to determine the association between total antioxidant capacity (tac) with metabolic syndrome study design: a cross sectional study design. place and duration of study: the study was conducted at department of chemical pathology, islamic nd nd international medical college pakistan railways hospital, rawalpindi. one year (2 sep 2018 to 2 september 2019). materials and methods: a total of 88 subjects, 44 with metabolic syndrome and 44 controls were recruited through non probability convenient sampling. group i comprised of 44 metabolic syndrome individuals from both genders. patients having fpg ≥ 100mg/dl were investigated for tg and hdl-c and their waist circumference and bp was measured. according to aha/nhlbi guidelines, the individuals were labeled with ms on fulfilling three or more than three criteria i.e fasting plasma glucose > 100mg/dl, serum triglycerides > 150mg/dl, hdl-c ≤ 40mg/dl in men and ≤ 50 in women, blood pressure > 130/85 and waist circumference > 40” 8 in men or > 35” in women. group 2 comprised of 44 healthy individuals. resistance, dyslipidemias and abdominal obesity collectively contribute to the condition termed as 1 metabolic syndrome (ms). the incidence of ms is on 2 the rise globally. the individuals who are labeled to have metabolic syndrome are more prone to adverse 3 cardiovascular incidents and death due to cvd. classical cardiovascular risk factors include low hdlc , h y p e r t r i g l y c e r i d e m i a , h y p e r t e n s i o n a n d 4 dysfunctions in glucose metabolism. in addition, metabolic syndrome also causes a significant impact 5 on health care cost and resource utilization. a stringent clinical criteria, described by the american heart association and the national heart, lung and the association of total antioxidant capacity with metabolic syndrome 1 2 3 4 5 rubina shafi , muhammad nadim akbar khan , ammar ul hassan , muhaaimin nawaz , fakhra noureen , 6 shazia qayyum correspondence: dr. rubina shafi lecturer department of pathology islamic international medical college riphah international university, islamabad e-mail: rubina.shafi@riphah.edu.pk 1,2,3,5,6 department of pathology islamic international medical college riphah international university, islamabad 4 islamabad medical & dental college, islamabad funding source: nil; conflict of interest: nil received: november 20, 2019; revised: march 16, 2020 accepted: march 19, 2020 association of tac with msjiimc 2020 vol. 15, no.1 14 introduction a group of disorders including hypertension, insulin blood institute (aha/nhlbi, 2009)used to define ms is described below. if any three of the following are met, the patient would be classified as having metabolic syndrome; 1. serum triglyceride rising above 150 mg/dl (or t h e p a t i e n t i s o n d r u g t h e r a p y f o r hypertriglyceridemia). 2. circumferential waist of patients rises above around 102 cm in affected males and around 88 cm in affected females. 3. high density lipoprotein cholesterol (hdl-c) levels ≤ 40 mg/dl for males (or the patient is on drug therapy for improving hdl-c level); or ≤ 50 mg/dl for females (or the patient is on drug therapy for improving hdl-c level). 4. glucose levels rise above 100 mg/dl in the fasting state (or the patient is on drug therapy for hyperglycemia). 5. blood pressure readings are higher than 130/85 mm hg (or the patient is on drug therapy for 6 hypertension). moreover, the contribution of oxidative stress phenomenon in the pathology of the metabolic disorders is considerably significant in relation to 7 ms. oxidative stress, can be understood as a disturbance in balance between free radicals genesis and the physiological capacity to counter the destructive process brought about by antioxidants. oxidative stress has an integral contribution towards the progression of ms, diabetes mellitus (dm) and 8 cardiovascular diseases (cvd). to manage the oxidative stress, many antioxidant defense systems operate through enzymatic or non-enzymatic systems. non-enzymatic antioxidant comprises of glutathione, beta-carotene, vitamin a, c and e, whereas enzymatic pathways include intracellular antioxidant enzymes catalase (cat), glutathione reductase (gr), glutathione (gpx), and superoxide 9 dismutase (sod). total antioxidant capacity (tac) is used as an instrument for diagnostic purposes and 10 for treating cvd and dm. moreover, the levels of tac are used as biological marker to monitor 11 oxidative stress in humans. rationale behind the study, measurement of tac can play a significant role in assessing oxidative stress and taking timely action to prevent ms complications such as dm, cvd and 11 other metabolic disorders. this study was aimed to determine the association between total antioxidant capacities (tac) with metabolic syndrome materials and methods a cross-sectional study was conducted at the department of chemical pathology at the pakistan railways hospital rawalpindi over the period of one nd nd year (2 sep 2018 to 2 sep2019). study started after the approval from the ethical review committee, riphah international university, islamabad. an overall of 88 subjects, 44 cases and 44 controls were included in this study. adults from both genders having ms were included. patients with acute infections, chronic diseases like ra, sle, pregnant and lactating women were excluded. patients already on antioxidant and lipid lowering drugs were also excluded. two groups of subjects were recruited for the study. group 1 this group comprised of 44 metabolic syndrome individuals from both genders. patients having fpg ≥ 100mg/dl were investigated for tg and hdl-c and their waist circumference and bp was measured. according to aha/nhlbi guidelines, the individuals were labeled with ms on fulfilling three or more than three criteria i.e. fasting plasma glucose> 100mg/dl, serum triglycerides> 150mg/dl, hdl-c ≤ 40mg/dl in males and ≤ 50 in females, blood pressure > 130/85 and waist circumference > 102cm in males or > 88cm in females. group 2 a total of 44 healthy individuals of both genders was recruited from faculty and lab staff of prh as controls. patient was seated comfortably and 5ml of venous blood was taken in plain sample vacutainer. the collected blood sample was centrifuged at 1000xg for 15 min to extract serum and then this serum was stored at -70c. all of the data was then entered and analyzed using, statistical package for social sciences (spss) version 2 3 . 0 . d e s c r i p t i ve stat i st i c s ( f re q u e n c i e s a n d percentages) weredescribed for nominal data, such as age and gender. mean and standard deviation values were described for quantitative variables including the serum total anti-oxidant capacity, fasting blood glucose, serum hdl-c, serum triglycerides, waist circumference and blood pressure measurements. kolmogrov-smirnov test was then applied to test the normality of the association of tac with msjiimc 2020 vol. 15, no.1 15 distribution of the data. since all variables were found to be irregularly distributed, the nonparametric mann whitney u test was applied to compare the various variables between the two groups, one with the metabolic diseases and the other control group of normal individuals. p value <0.05 was found to be statistically significant. results a total of 88 subjects were encompassed according to the inclusion criteria of the study. descriptive statistics of age (in years) were calculated as mean and standard deviation. mean age of all the recruited subjects was 38.59 + 15.19 years. the recorded mean age of metabolic syndrome group was 48.14 + 10.48 years, and the mean age of control group was 23.04 + 5.82 years. majority of subjects 36.3% were between 41-50 years, 31.3% participants were between 51-60 years. about 8.5% participants were between 33-40 years and 11.1%participants were between 61-70 years.only2.27% participants were between 21-30 years in (table i). table i: descrip�ve sta�s�cs of age (n = 88) a significant difference was found between values of different risk factors of ms (obesity, hypertension; and high fasting plasma glucose, triglycerides and hdl-c levels). the results showed that the values for ms patients were found to be considerably raised than those recorded for the control group. the affiliation between the total antioxidant capacity with hdl-c showed a positive correlation whereas tac showed negative correlation with abdominal obesity, blood pressure, triglycerides and fasting blood glucose. (table ii). tac values were found significantly high in the control group (18.13 ± 12.90 mmol/l) as compared to the ms group 4.56 ± 7.43mmol/l in (table iii) a valid instrument to quantify ms is by measuring tac levels (table iii). the comparison was done between the ms and control groups. tac levels were found to be severely depleted in the ms patients, in comparison to the control group. table ii: kolmogrov smirnov significance values for different variables for normality tests table iii: mean, sd and p values for different elements of ms (n = 88) *p<0.05 was taken as level of significant discussion the present study has been carried out to determine the association between tac with ms. both males and female between those 18-65 years of age were recruited. these results depict that incidence of ms increases with age. ervin rb has also documented the increased incidence of ms in middle and old aged 12 people. however, weiss et al found that ms is also common among children and young adults. zhiyan li et al has documented similar findings about the i n c r e a s e d p r e v a l e n c e o f m s a m o n g m a l e 13 population. in our study it has been found that serum hdl-c levels were suggestively lower in ms group (37.09 + 6.37 mg/dl) as compared to control group comprising of healthy adults(43.09 + 46.15 mg/dl). in present study we have found that hdl-c has a positive correlation with total (tac). this positive correlation indicates the antioxidant activity. hdl-c exerts its anti atherogenic and antiinflammatory properties, including anti oxidative 14 activity by scavenging reactive oxygen species ros. in our study, the mean serum tg(>150 mg/dl) in ms patients and control subjects was 240.03 ± 93.19 and 107.41 ± 56.50 respectively. the raised levels of triglycerides in ms individuals indicate reverse correlation between triglycerides and tac. bitla et al, abbasian et al and zheng et al have also reported an 15 inverse relation between triglycerides and tac. in association of tac with msjiimc 2020 vol. 15, no.1 16 present study it has been found that the levels of fpg(≥ 100mg/dl) were much higher in ms individuals (139.43 + 57.56 mg/dl) as compared to healthy adults (69.66 + 30.46 mg/dl). exposure to prolonged periods of hyperglycemia causes non-enzymatic 16 glycation of extracellular proteins. the study, by maxwell et al and ceriello et al have reported similar findings raised plasma glucose levels in ms 17 subjects. in present study, the mean and sd of systolic bp(mmhg) was 133.86 + 13.59, and 120.00 + 0.00 in ms patients and control groups respectively. the difference of systolic and diastolic bp was evidently raised in ms group as compared to control group due to increased ros production, redox17 signaling and decreased tac in ms. sanchezrodriguez et al, in his study reported a negative correlation amongst bp and tac similar to our 18 study. in this study the mean waist circumference (cm) was 37.84 + 3.67, and 31.91 + 3.12 in ms and co nt ro l g ro u p re s p e c t i ve l y. i n c re a s e d wa i st circumference in ms subjectis due to dysregulations of adipokines and development of ms which further reduces tac. the waist circumference showed an inverse correlation with tac. research work conducted and documented by chrysohoou et al and h a r t w i c h e t a l r e a c h e d t o s i m i l a r 19 conclusions. according to the results of this study tac has a positive correlation with hdl-c; however it has an inverse correlation with tg, fpg, bp and waist circumference. tac levels were found significantly increased in the control group (18.13 ±12.90 m m o l / l ) i n c o m p a r i s o n t o t h e m s g r o u p (4.56±7.43mmol/l).a number of studies have been done to study the relationship between the components of ms & mda i.e an oxidant bio20 marker. to conclude, this study, it can be stated that the oxidative stress in ms is worsened as a result of increased activity of the biochemical pathways which in turn influences increase in the rate of transport of ros and thus enhancing the changes in 21 antioxidant protection. this study has certain limitations. the sample size was small and study was conducted at single center, hence, restricting us to generalize the findings of our study. conclusion tac gets depleted in metabolic syndrome individuals more as compared to healthy individuals. estimation of tac at an early stage can be useful for early detection of metabolic syndrome and further to prevent its complications such as dm, cvd and other metabolic disorders. references 1. abbasian m, delvarianzadeh m, ebrahimi h, khosravi f, nourozi p. relationship between serum levels of oxidative stress and metabolic syndrome components. diabetes & metabolic syndrome: clinical research & reviews. 2018. 2. tehrani fr, tohidi m, dovom mr, azizi f. a population based study on the association of thyroid status with components o f t h e m e t a b o l i c s y n d r o m e . j d i a b e t e s m e t a b . 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ñ©©©ò²·½»ò±®¹ò«µñþ untitled-1 case report abstract parvo b 19 virus can cause different diseases in human. it can cause myocarditis which if not treated in time can prove fatal. here we are presenting a case of 43 years old immune‐competent male who was found to be infected with parvo b 19 virus, which was diagnosed by positive serology and pcr technique. he was successfully treated and ison regular follow up. every clinician should consider the possibility of pvb 19 in any patient presenting with acute myocarditis. key words: myocarditis, parvo b 19 virus. complete picture showed lymphocytosis. blood culture and sensitivity, crp, sputum afb, urine r/e and c/s, usg abdomen, trop t, ck mb, ast, ldh, rft, lft, serology for ebv, cmv, adenovirus and enterovirus and angiography were all normal. 2 d echo showed ef 20 %with dilated la, lv and severelv systolic dysfunction, global hyperkinesia with no effusion. parvo b 19 virus igm was positive and was further confirmed by pcr. cardiac mri showed increased signal intensity at septal wall on t2 weighted image. myocardial perfusion spect with t1‐201 after physiological stress and at rest revealed fixed perfusion defect (partial thickness mi/scarred myocardium of inferior wall) and multiple areas of moderate to severe fixed defects scattered all over left ventricular myocardium plus severe global hyperkinesia with 20 % ef and poor lv function. he was admitted in intensive care unit and was treated with iv diuretics and inotropic support. he remained admitted in hospital and became stable in one week.his ef improved to 55% after one week of treatment. he was discharged after ten days of hospitalization and pvb 19 igm was repeated at the time of discharge, which was negative with negative pcr. at the time of discharge he was advised aceinhibitors, digoxin, beta blockers, and low dose aspirin. he was properly counseled regarding his illness and follow up. discussion acute myocarditis is aninflammatory condition of 1 myocardium due to various pathogens. patient can present with different clinical features which may be fulminant or non‐fulminant. different infections, drugs, toxins and systemic diseases have been found 2 to cause myocarditis. parvo b19 virus, humanherpes introduction parvo b 19 is the only member of family parvoviridae,discovered in 1974 and is pathogenic in 1‐3 humans. it can cause fatal myocarditis leading to 4‐6 heart failure if not treated in time. we are presenting a case of parvo b 19 myocarditis who presented with acute myocarditis and was successfully treated with antiviral therapy andinotropic support. case report a 43 years old serving soldier presented with one week history of flu like illness, dry cough, low grade intermittent fever with myalgia. he took treatment from some local general practitioner buthis symptoms did not resolve. after about 3 days, he also developed signs of acute heart failure which were progressive and found to be nhya class iv accompanied by orthopnea and frothy sputum. his past, personal, social, drug and family history were insignificant. physical examination revealed pulse of 90/minute which was irregularly irregular, low volume. bp was 90/75 mmhg with no postural hypotension, temperature 990 f and respiratory rate of 20/minute. chest auscultation revealedbilateral few basal creptitations. ecg showed af, lad,lbbb, t wave inversion in i, ii,iii,avl,avfand v3 to v6.blood parvo b 19 myocarditis in immunocompetent patient 1 2 3 4 5 asif nadeem , abidullah khan , muhammad farooq , mumtaz malik , zulifiqar congo parvo b 19 myocarditisjiimc 2015 vol. 10, no.4 correspondence: maj. dr. abidullah khan 63 medical battalion, multan cantt e‐mail: drabid2424@yahoo.com 1,5 department of medicine cmh, multan 2,4 department of medicine 63 medical battalion multan cantt 3 department of medicine islamic international medical college riphah international university, islamabad received: february 11, 2015; accepted: november 15, 2015 280 virus 6 and enterovirus are some of the most common viral causes of acute myocarditis. pvb19 can cause fatal myocarditis because it affects 3 myocardial endothelial cells. clinical features can vary from simple flu like illness to heart failure, 4 arrhythmias or pseudo myocardial infarction. myocarditis is found in 42% of cases with unexplained deaths in individuals under 35 years of age. exact incidence and prevalence of fulminant myocarditis is not known but it is seen in 10 % of 1,5‐8 biopsy proven myocarditis. an accurate and rapid diagnostic approach is very crucial in the management of viral myocarditis. serology, cardiac mri, angiography and cardiac biopsy are some of the crucial diagnostic 6 investigations. additional viral pcr (quantitative) and for viral genome and immunohistochemistry for cardiac inflammation and necrosis also help in 6‐8 diagnosis. this will help in accurate diagnosis and targeted treatment. when diagnosis is confirmed, treatment of underlying cause is the main life saving step. in addition to specific treatment of the underlying cause, intense hemodynamic support likeinotropic support, intra‐aortic balloon pumps and ventricular assistance devices can also be used to save life of the patient depending upon the clinical condition of the patient. heart transplantation is the last option in developed countries where facilities 7,8 are available. seven percent of the patients presenting with 2,5‐7 fulminant myocarditis will have fatal outcome. mortality rates are different due to various patient 5,7‐8 risk factors. after acute phase of treatment, patient should be managed with standard heart failure medications with beta blockers, angiotensin‐ converting enzyme inhibitors, angiotensin receptor blockers (arbs), calcium channel blockers (ccb), and digoxin. regular follow up is very necessary as 5‐7 recurrence has been reported. references 1. cooper lt jr. myocarditis. n engl j med 2009; 360: 1526‐38. 2. kindermann i, kindermann m, kandolfr. predictors of outcome in patients with suspected myocarditis. circulation 2008; 118: 639‐48. 3. mccarthy re, boehmer jp, hruban rh. long‐ term outcome of fulminant myocarditis as compared with acute (nonfulminant) myocarditis. n engl j med 2000; 342: 690 ‐ 5. 4. maron bj. sudden death in young athletes. n engl j med 2003; 349: 1064 ‐ 75. 5. dennert r, crijns hj, heymans s. acute viral myocarditis. eur heart j 2008; 29: 2073 ‐ 82. 6. escher f, kuhl u, sabi t. immunohistological detection of parvovirus b19 capsid proteins in endomyocardial biopsies from dilated cardiomyopathy patients. med scimonit 2008; 14: 333‐8. 7. gupta s, markham dw, drazner mh, mammen pp. fulminant myocarditis. nat clinpractcardiovasc med 2008; 5: 693 ‐ 706. 8. mossong j, hens n, friedrichs v, davidkin i, broman m, litwinska a, et al. parvovirus b19 infection in five european countries: seroepidemiology, force of infection and maternal risk of infection. epidemiol infect 2008; 136: 1059 ‐ 68. parvo b 19 myocarditisjiimc 2015 vol. 10, no.4 281 original�article abstract objective: to determine the common pattern of leisons identified in hyterectomy specimens and to correlate the histopathological findings with clinical indications. study design: a descriptive study. place and duration of study: study was conducted in the department of obstetrics and gynaecology of red st st crescent medical college hospital from 1 july 2015 to 1 july 2017. st st materials and methods: in the period between 1 july 2015 to 1 july 2017 data including age, parity, presenting complaints and indication for hysterectomy was obtained from patients. the type of hysterectomy was also reported. specimens were preserved in 10% formalin. histopathology results of all hysterectomy specimens were collected. results: during two year study a total of 100 hysterectomies were performed. the patient age ranged between 35-60 years with an average of 45 years old and peak parity was 4-8. the most common presenting complaint was menstrual irregularities followed by lower abdominal pain. hysterectomy with bilateral salpingo oophrectomy was performed in 75% of cases. hysterectomy alone was performed in 15% and in 10% of cases vaginal hysterectomy was performed. in 35% cases the indication of hysterectomy was fibroid uterus followed by dysfunctional uterine bleeding in 15% of cases. the commonest histopathological diagnosis made was chronic cervicitis i.e in 42% cases, which was an incidental finding followed by fibroid uterus in 40% of cases. conclusion: this study confirms that benign diseases are more common than their malignant counterparts and the most common pathology identified is chronic cervicitis.the clinical and histopathological correlation is 100% in case of leiomyoma, cervical and endometrial polyps. seventy four cases were correlated clinically with histopathological diagnosis. key words: leiomyoma, menorrhagia, total abdominal hysterectomy, vaginal hysterectomy. symptom relief and patient satisfaction. it provides definitive cure to many diseases involving uterus as well as adnexa, eg, fibroids, dub, adenomyosis, endometriosis, pelvic inflammatory disease, pelvic organ prolapse and malignancy. histopathological examination of surgical specimens carries ethical, legal, diagnostic and therapeutic significance. a variety of conditions in gynecological practice require removal of a uterus that may show no gross or microscopic pathology when examined by the pathologist. removal of a normal uterus may be indicated and permitted in the treatment of ovarian, fallopian tube and vaginal cancer, pelvic inflammatory disease, endometriosis, dub, pelvic organ prolapse, pelvic pain and pelvic tuberculosis. t h e d i a g n o st i c va l u e o f h i sto p at h o l o g i ca l examination is well explained in patients with genital cancer where adjuvant treatment is dependent upon grade and extent of invasion of disease. similarly diagnosis of adenomyosis is only established by introduction abdominal hysterectomy means complete removal of uterus through abdominal route. hysterectomy is t h e m o s t c o m m o n l y p e r f o r m e d m a j o r gynaecological surgery throughout the world. it is performed in 560 / 100,000 women per year in the 1 2 us and 414 / 100,000 women per year in finland. hysterectomy rate varies from place to place depending upon patient and clinician related 3 factors. hysterectomy is a successful operation in terms of clinico-pathological study of hysterectomy at pak red crescent medical and dental college 1 2 3 kishwar naheed abid hussain , riasat ali correspondence: dr. kishwar naheed associate professor, gynecology and obstetrics pak red crescent medical and dental college, lahore e-mail: drkishwarnaheed@gmail.com 1 2 3 department of gynecology and obstetric /surgery /anatomy pak red crescent medical and dental college, lahore funding source: nil; conflict of interest: nil received: oct 27, 2017; revised: feb 07, 2018 accepted: feb 12, 2018 clinico-pathological study of hysterectomyjiimc 2018 vol. 13, no.2 62 histopathological examination, while dub is a diagnosis of exclusion. conversely, many patients may be suspected of having a malignancy on preo p e r a t i v e a s s e s s m e n t e . g . t h o s e w i t h postmenopausal bleeding and histopathological examination may aid to rule out this suspicion. the purpose of this study was to correlate various indications of abdominal hysterectomy with the histopathological findings of the specimens, thus determining the percentage of the pre-operative clinical diagnoses that were confirmed on histopathological examination. we also wanted to determine the frequency of unexpected disease, thus high lighting the need for subjecting each specimen for histopathological examination. failing this may result in sub-optimal care or treatment and over treatment of certain diseases, in particular the malignant conditions. materials and methods this descriptive study was conducted in the department of gynae/obs department at red crescent teaching hospital. it was retrospective analysis of 100 patients who had hysterectomy as an elective procedure had specimen including the appendages examined histopathologically over 2 st st year between 1 july 2015 and 1 july 2017. study protocol was approved by institutional ethical committee. the study included all women undergoing planned abdominal hysterectomy. data was recorded on proformas, including demographic characteristics and clinical features. only one dominant diagnosis was considered and documented as an indication for the procedure. hysterectomy specimens were saved in 10% formalin and sent for histopathological examination. abdominal hysterectomy for uterine malignancies and for emergency conditions e.g o b s t e t r i c a l h a e m o r r h a g e w e r e e x c l u d e d . histopathology reports were analysed and compared with the clinical indications of surgery. data were analysed using spss version 22. frequency and percentage were calculated for categorical variables. results the age group of patients ranged from 35 to 65 years with mean age of 50 years (table i). 50 % of patients belonged to the age group between 45 -55 yrs. 35% between 41 44 yrs . 8 % were <40 years . 7% were >55 yrs. 63 .8% had parity of >5 . 4 % were nulliparous.” in this study 100 cases of hysterectomy were studied at red crescent medical college dina nath. the various indications for hysterectomies are depicted in table i. all were for benign indications. the most co m m o n i n d i cat i o n fo r hyste re c to my wa s leiomyoma (35%). this was followed by adenomyosis (15%) and dysfunctional uterine bleeding (15%). the m o s t c o m m o n c l i n i c a l p r e s e n t a t i o n w a s menorrhagia. some of the cases presented with dysmenorrhea, low backache and dyspareunia. the most common type of hysterectomies were total abdominal hysterectomy with bilateral saplingooophrectomy followed by total abdominal hysterectomy. histopathology reports of all hysterectomies were reviewed (table ii). seventy four cases were correlated clinically with histopathological diagnosis. twenty three had a different diagnosis than the clinical one (table iii). table i: clinical indica�on for hysterectomy and age distribu�on of study popula�on (n= 100 ) table ii: pa�ern and frequency of uterine histopathology iden�fied in 100 hysterectomy cases jiimc 2018 vol. 13, no.2 clinico-pathological study of hysterectomy 63 discussion hysterectomy offers a definitive cure for women with heavy bleeding associated with fibroids who 4 have completed child bearing. although expensive 5 in the short term and not without risk ,it may provide a cost effective option for women who are less likely to benefit from more conservative approaches. the abdominal route has been most commonly used for large uteri although the vaginal route can be used by 6 experienced operators, usually after gnrh pre treatment. a large cohort study of 37,298 hysterectomies performed in uk for benign indications reported an operative complication rate of 3.5 %, a post operative complication rate of 9% and an overall 7 mortality rate of 0.38 per 1000. mortality was 0.25 per 1000 in women undergoing hysterectomy for m e n st r u a l p ro b l e m . t h e ro l e o f s u b to ta l hysterectomy remains unclear. women undergoing subtotal hysterectomy should be warned about a 7% 8 risk of occurrence of ongoing menstrual bleeding. hysterectomy may have long term implications for 9 bladder function; a systemic review estimated a long term increase in the odds of developing urinary incontinence following hysterectomy. a recent scottish study found an increased risk of pelvic floor o r u rin a r y in co nt in en ce s u rger y fo llowin g hysterectomy for heavy menstrual bleeding 10 compared with endometrial ablation. few studies have been done in our community regarding histopathological analysis of hysterectomy s p e c i m e n s a n d re l a t i o n s h i p b e t w e e n t h e preoperative clinical diagnosis and histopathological 11 diagnosis the commonest type of surgical resection was total abdominal hysterectomy with bilateral salpino-oophrectomy (tah with bso) (58%)followed 12 by tah (total abdominal hysterectomy)(38.3%). the aim of our study is to analyse the common pathologies identified in hysterectomy specimens and to correlate the findings with the clinical indications. the commonest estimated age range of hysterectomy in our study is 41-50 years which is similar to that reported by gousia rahim rather and 13,14 prveen s tayyab s. the commonest presenting complaints in our study were menorrhagia followed by polymenorrhagia. the rashmi verma study also revealed that menstrual disturbance was the most 15 important indication for hysterectomy. this was also seen by shergill sk and riffat jaleel, who found that abnormal menstrual flow was the commonest 16,17 complaint in 66% of cases. in this study main indication for hysterectomy was leiomyoma 35 (35% ) cases. similar is found in studies by sumatra et al and leung pl followed by endometrial hyperplasia 18,19 (16%), dub(10%)cases. only few studies have compared pre-operative c l i n i c a l d i a g n o s i s w i t h h i s t o p a t h o l o g y o f hysterectomy specimens. we have found that 74% of our pre operative diagnosis were confirmed on histopathology like fibroid uterus, uterine polyps and utero vaginal prolapse and cervical polyp have 100% diagnosis confirmed on histopathology and same 20 was reported by g gupta etal. chronic cervicitis is an extremely common condition in adult female, at least at the microscopic level, chronic cervicitis was commonest finding in our study 42% which was an incidental finding. same results were obtained by 13 ghousia rahm rather etal. leiomyoma was the second most common histopathological diagnosis. f i b ro i d wa s m o st co m m o n i n d i cat i o n fo r 21 hysterectomy. 35 cases has preoperative indication of leiomyoma in our study and was confirmed in 40 cases (100%). adenomyosis was an indication for hysterectomy in 10 cases. adenomyosis is rarely diagnosed pre operatively and is still largely under diagnosed as it has no specific symptoms of its 22,23 own in our study only 7 cases were diagnosed. the clinicopthological correlation between preoperative and histopathological examination was more than table iii: histopathological reports inconsistent with preop diagnosis jiimc 2018 vol. 13, no.2 clinico-pathological study of hysterectomy 64 90% especially in benign conditions in dr vandana 24 study. hysterectomy is one of the most frequently performed major surgical procedures in women 25 worldwide. there is high incidence of benign conditions in our study .strong clinicopathological correlation has been found in the cases. seventy four c a s e s w e r e c o r r e l a t e d c l i n i c a l l y w i t h histopathological diagnosis. the result of the study is in concordance with the previously published data as regards to the commonest pathologies identified in hysterectomies and the commonest surgical route for hysterectomy. references 1. farquhar cm, steiner ca. hysterectomy rates in the united states. 1990 – 1997. obstet gynecol. 2002; 99: 229-34. 2. vuorma s, teperi j, hurskainen r, keshimaki i, kujansuu e. hysterectomy trends in finland in 1987 – 1995 – a register based analysis. acta obstst gynecol scand. 1998; 77: 770-6. 3. rather gr, gupta y, bharadwaj s. patterns of lesions in hysterectomy specimens; a prospective study. j.k.science. 2013; 15: 63-8. 4. rcog, rcr .clinical recommendations on the use of uterine artery embolization (uae) in the management of uterine fibroids.3rd edna. london: rcog and rcr. 2013. 5. marret h, fritel x, ouldamer l. cngof (french college of gynaecology and obstetrics). therapeutic management of uterine fibroids tumours: updated french guidelines. eur j obstet gynaecology reprod biol. 2012; 165: 156-64. 6. national collaborating centre for women's and children health. heavy menstrual bleeding. london: rcog press. 2007. 7. maresh mhj, metcalfe ma, mcpherson k. the value national hysterectomy study. 2002; 109: 302–12. 8. national collaborating centre for women's and children's health. heavy menstrual bleeding. london rcog press. 2007. 9. brown js, sawaya g, thom dh, grady d. hysterectomy and urinary incontinence: a systemic review .lancet. 2000; 356: 535-9. 10. cooper k, lee aj, raja ea, timmaraju v, bhattacharya s. outcomes following hysterectomy or endometrial ablation for heavy menstrual bleeding: retrospective analysis of hospital episodes statistics in scotland. bjog. 2011; 118: 1171-9. 11. samaila modupeol oa, adesiyun ag. clinic pathological assessment of hysterectomies in zaria. eur j gen med. 2009; 6: 150-3. 12. ebinesh a, sharada ms, krishna mc. clinic pathological correlation of abdominal hysterectomy specimens. international journal of science and research. 2015; 4: 1084-9. 13. rather rg, gupta y, bardhwaj s. pattern of lesion in hysterectomy specimens. a prospective study .jk science. 2013 ; 15: 63-8. 14. perveen s, tayyab s. a clinic pathological review of elective abdominal hysterectomy: pjs. 2008; 13: 26-9. 15. verma r. histopathological study of hysterectomy specimens in tertiary centre of rual bihar. international journal of recent scientific research. 2016; 7: 9021-3. 16. jaleel r, ayesha khan, soomro n. clinic pathological study of abdominal hysterectomies. pak jmed sci. 2009; 25: 6304. 17. shergill sk, shergill hk, gupta m. clinic pathological study of hysterectomies. j indian med assoc. 2002; 100: 238-9. 18. leung pl. an audit on hysterectomy for benign diseases in public hospitals in hong kong med j. 2007; 13: 187-93. 19. siwatch s, kundu r, mohan h, hurra a. histopathological audit of hysterectomy specimen in tertiary care hospital. sirilanka journal of obstetrics and gynaecology. 2012; 34: 155-8. 20. gupta g, thane dk, kotas v. hysterectomy: a clinicopathological correlation of 500 cases. the internal j gynaecol obs. 2009; 14: 1. 21. nazneen r, monir f, yeasmin s, akhter s, bakshi l, sutana k. evaluation of total abdominal hysterectomy over the decade in holy family red crescent medical college hospital-a retrospective observational study. bangldesh med j. 2015; 44: 87-91. 22. sarfaraz t, tariq h. histopathological findings in menorrhagia: a study of 100 hysterectomy specimens. pak j pathol. 2005; 16:83-5. 23. bukhara u, sadia s. analysis of the underlying pathological leisions in hysterectomy specimens. pak j patho. 2007; 18: 110-2. 24. g a n ga d h a ra n v, p ra s a n t h i c . h y s t e re c t o my – a clinicopathological correlation in a rual setting. indian journal of basic and applied medical research. 2016; 5: 815. 25. sinhsane h, nishty gm. a study on clinicopathological analysis of hysterectomies. international journal of reproduction, contraception, obstetrics and gynaecology. 2017; 6: 466-9. jiimc 2018 vol. 13, no.2 clinico-pathological study of hysterectomy 65 page 18 page 19 page 20 page 21 jiimc june 2016.cdr original article abstract objective: to determine the frequency of internet addiction among medical students and its effects on their academic performance. study design: cross sectional comparative study. th place and duration of study: the study was conducted at army medical college, rawalpindi from 5 january to th 15 may 2015. materials and methods: data collection tool was a closed ended, self-administered questionnaire, 'young's internet addiction test'. duly filled questionnaires were returned by 322 mbbs students. the 'young's internet addiction questionnaire' consists of 20 items with responses on a 5 point likert scale. the total score which ranged from 20 to 100 was categorised into mild (normal), moderate (problem) and severe internet addiction. scores ≤ 49 were classified as normal, 50-79 as moderate, and 80-100 as severe internet addiction. academic nd performance of the students was measured as the percent marks obtained in 2 professional mbbs examination. students with marks 50 and above were declared as 'pass' and below 50 as 'fail'. data was analysed using spss version 22. simple linear regression was applied to determine the effect of internet addiction on academic performance. results: there were 175 male and 147 female students in the study with mean age of 19.27±1.01 years. two hundred and sixty-eight (83.2%) students were in normal category, 52 (16.1%) in moderate and 2 (0.6%) in severe category. there was significant difference in the proportion of students who passed or failed the exam in the two categories (normal vs moderate + serious) being low pass and high fail in 'moderate+serious' categories (p=0.02). the mean internet addiction score was negatively correlated with academic performance (p=0.01). conclusion: excessive internet usage by medical students may lead to internet addiction which may adversely affect their academic performance. key words: computer, internet addiction, young's internet addiction test. tremendous amount of information available on internet which is just a click away. it is horrible for a today's student to think of the academic/research activities without internet. internet has connected the people from fields of science and education all 2 over the world. accomplishment of academic goals has become extremely easy in today's technology 3 enabled epoch. amount of information available on internet is greater than present in world's largest libraries and with just a single click one can have 4 access to the huge databases. however, internet is a double edged sword; its appropriate use can undoubtedly facilitate the academic process like a magic wand whereas inappropriate use can wreak 5 havoc. inventors of the internet would have never thought that internet usage could also have a downside, named as bad as 'addiction'. internet addiction is defined as “inability to stop internet overuse, tendency to perceive offline time as meaningless, excessive irritation and ag gression during introduction information technology revolution of present era is primarily based upon internet. it has permeated into our lives to such an extent that life without internet seems meaningless. every walk of life, education, research, business, military etc and even day to day 1 chores are heavily dependent on internet. there is effect of internet addiction on academic performance of medical students 1 2 3 4 muhammad alamgir khan , ahsan ahmad alvi , faizania shabbir , tasif ahmed rajput jiimc 2016 vol. 11, no.2 correspondence: prof dr. muhammad alamgir khan department of physiology army medical college, rawalpindi e-mail: docalamgir@gmail.com 1 department of physiology army medical college, rawalpindi 2 department of pathology islamic international medical college riphah international university, islamabad 3 department of physiology rawalpindi medical college, rawalpindi 4 department of pharmacology shifa college of pharmaceutical sciences shifa tameeremillat university, islamabd funding source: nil ; conflict of interest: nil received: feb 01, 2016; revised: mar 20, 2016 accepted: may 25, 2016 48 internet addiction and medical students 49 data collection tool was a closed ended, selfadministered questionnaire, 'young's internet addiction test' which was developed by young in 1998. the questionnaire is fully validated with high 17 reliability index. the questionnaire was distributed to 350 students of different classes of mbbs however, duly filled questionnaire were returned by 322 students at a response rate of 92%. the 'young's internet addiction questionnaire' consists of 20 items with responses on a 5 point likert scale. the total score which ranged from 20 to 100 was categorised into mild (normal), moderate (problem) and severe internet addiction. scores ≤ 49 were classified as normal, 50-79 as moderate, and 80-100 as severe internet addiction. academic performance of the students was measured as the percent marks obtained in 2nd professional mbbs examination. students with marks 50 and above were declared as 'pass' and below 50 as 'fail'. data was analysed using spss version 22. mean and standard deviation was calculated for numerical variables like age of participants, marks obtained in professional exam, total likert scale scores whereas frequency and percentage for categorical variables like gender and categories of each item of the questionnaire. simple linear regression was applied to determine the effect of internet addiction on academic performance. reliability was determined through internal consistency by applying cronbach's alpha test. the alpha value was set at 0.05. results there were 175 male and 147 female students in the study with mean age of 19.27±1.01 years. table i illustrates frequency and percentage of students falling in each category of internet addiction i.e. normal, moderate and serious. table ii shows cross tabulation of internet addiction categories (moderate + severe) with exam outcome status (pass/fail). the two variables are associated as indicated by the p-value (0.02). table iii shows overall mean score of the instrument along with mean academic performance in terms of percent marks in professional examination. the table also shows significant and inverse correlation between the two variables (r=-0.13, p=0.01). table iv shows parameters of simple linear regression for prediction of academic performance from internet addiction scores. academic performance can significantly be 6 deprivation”. it is also described as internet d e p e n d e n c e , p at h o l o g i ca l i nte r n et u s e o r 7 compulsive internet use. internet addiction can be compared to other types of addictions regarding 8 risks and consequences. it is especially prevalent in college/university students and can accompany or 9 herald other psychiatric disorders. the user feels himself unable to refrain from the use of internet and 'carried away' with it resulting in wastage of time and energy. this leads to substantial deterioration in p e r f o r m a n c e , h e a l t h a n d i n t e r p e r s o n a l relationships. the students are trapped in a vicious cycle which may lead to extremely adverse 10 outcomes. they find refuge in internet and tend to 11 elope from reality. internet addiction has evolved as a major public health issue in the recent years and has gained attention of the researchers all over the 12 world. internet in the form of smart phones and tablets has 13 become an integral part of every student's life. although a small fraction of students use internet for educational activities in a controlled way, however, a large percentage just keep wasting time by visiting 14 'non-educational' sites. research has shown that proportion of time a student spends on internet for educational purpose versus non-educational activity 15 could significantly determine his success. college students, being young and psychologically immature are naturally vulnerable to internet addiction, hence it is the responsibility of society, institutions, teachers and parents to adopt measure which can 16 keep the youth away from this nuisance. there is debate about advantages and disadvantages of internet usage among young students as the research data regarding internet addiction in students and its effects on their academic performance is scant. hence, the current study was planned to determine the frequency of internet addiction among medical students and its effects on their academic performance. materials and methods this cross sectional study was conducted at army medical college, rawalpindi from january to may 2015. the study was commenced after getting formal approval from ethical review committee of army medical college. non-probability convenience sampling was used to include medical students in the study after getting the written informed consent. jiimc 2016 vol. 11, no.2 internet addiction and medical students 50 same finding is supported when the data was analysed by converting total internet score into the three categories i.e. normal, problem and serious according to 'young's internet addiction' test guidelines. the results revealed that over 80% students were in normal category whereas about 17% had some degree of internet addiction. academic performance of the students was significantly and negatively correlated with total internet addiction score. this means, the more the students were nearer to internet addiction on the scale, the less was their academic performance as reflected by their marks in the professional examination. when the data were analysed by considering the frequency of students within each category who passed and failed the examination, almost similar picture was seen. ninety-four percent students in 'normal' category passed the exam and 6% failed whereas about 85% in 'problem plus serious' category passed the exam and 15% failed. the difference in proportion of students who passed or failed the exam in each category was found significant. after analysing the data from multiple perspectives, tests of statistical significance revealed that low academic performance was not by chance but due to the variable under study that is internet addiction. all these factors acting jointly push the students away from books leading to poor academic performance. stavropoulos v and colleagues conducted a study to recognizing internet addiction, prevalence and re l a t i o n s h i p t o a c a d e m i c a c h i e v e m e n t i n adolescents enrolled in urban and rural greek high 18 schools. they also used 'young's internet addiction' questionnaire and found a frequency of 3.1% for seriously addicted students. they found that internet addiction had negative correlation with academic performance as was the finding in our study. however, the frequency of severe internet addiction, they found was higher as compared to our study (0.6%). this may be due to the fact that study conducted by stavropoulos had a larger sample size as compared to ours (2090 vs 322). the other reason may be that a large percentage of our students especially boys reside in hostels where internet is not provided. akhtar carried out a study to determine internet addiction in university students and its 19 effects on academic performance. the scale predicted from internet addiction score as is evident from the p-value (0.016). value of cronbach alpha was 0.90 reflecting high reliability. table i: frequency of different categories of internet addic�on among the students (n=322) table ii: frequency and percentage of students with different categories of internet addic�on (n=322) table iii: correla�on between internet addic�on score and academic performance (n=322) table iv: simple linear regression analysis of internet addic�on as predictor of academic performance (n=322) discussion the average internet addiction score of our study (scale average) is about 38 which almost corresponds to 'occasional' category of the likert scale. the total internet addiction score ranges from 20 to 100 whereby 20 relates with almost no usage of internet and 100 relates with total internet addiction. the scale average of our study reflects that the use of internet by medical students is occasional and it is overall much away from internet addiction. the jiimc 2016 vol. 11, no.2 internet addiction and medical students 51 6. widyanto l, griffiths m. internet addiction: a critical review. internat j ment health addict. 2006; 4: 31-51. 7. young ks. internet addiction: a new clinical phenomenon and its consequences. am behav sci. 2004; 48: 402-15. 8. griffiths md, kuss dj, billieux j, pontes hm. the evolution of internet addiction: a global perspective. addict behav. 2016; 53: 193-5. 9. wu jy, ko hc, lane hy. personality disorders in female and male college students with internet addiction. j nerv ment dis. 2016. 10. wallace p. internet addiction disorder and youth: there are growing concerns about compulsive online activity and that this could impede students' performance and social lives. embo rep. 2014; 15: 12-6. 11. ghamari f, mohammadbeigi a, mohammadsalehi n, hashiani aa. internet addiction and modeling its risk factors in medical students, iran. indian j psychol med. 2011; 33: 158-62. 12. coniglio ma, muni v, giammanco g, pignato s. excessive internet use and internet addiction: emerging public health issues. ig sanita pubbl. 2007; 63: 127-36. 13. choi sw, kim dj, choi js, ahn h, choi ej, song wy, et al. comparison of risk and protective factors associated with smartphone addiction and internet addiction. j behav addict. 2015; 4: 308-14. 14. fernandez villa t, alguacil ojeda j, almaraz gomez a, cancela carral jm, delgadorodriguez m, garcia-martin m, et al. problematic internet use in university students: associated factors and differences of gender. adicciones. 2015; 27: 265-75. 15. li y, zhang x, lu f, zhang q, wang y. internet addiction among elementary and middle school students in china: a nationally representative sample study. cyberpsychol behav soc netw. 2014; 17: 111-6. 16. van rooij aj, prause n. a critical review of "internet addiction" criteria with suggestions for the future. j behav addict. 2014; 3: 203-13. 17. young ks. internet addiction: the emergence of a new clinical disorder. cyberpsychology & behavior. 1998; 1: 23744. 18. stavropoulos v, alexandraki k, motti-stefanidi f. recognizing internet addiction: prevalence and relationship to academic achievement in adolescents enrolled in urban and rural greek high schools. j adolesc. 2013; 36: 565-76. 19. akhter n. relationship between internet addiction and academic performance among university undergraduates. educ res rev. 2013; 8: 1793-6. average of her study was 39.23 and she reported that internet addiction scores were negatively and significantly correlated with grade point average of the students (r=-0.130, p=0.039). the results reported by akhtar were comparable to our study. excessive usage of internet in students leads to internet addiction due to which they cannot spend enough quality time on studies. they lose capacity to concentrate and focus on studies due to late night internet sessions. even they sacrifice extracurricular activities for internet due to which they remain aloof and their mental and physical health deteriorate. academic performance of a student depends not only upon his mental/physical health but also the degree of his time/self-management. to extrapolate the findings on to the general population, multicenter studies need to be conducted with a large sample size that is representative of the general population to draw reliable parametric inferences. conclusion excessive internet usage by medical students may lead to internet addiction which may adversely affect their academic performance. parents/teachers need to take preemptive measures to avoid this and to remain vigilant especially for students whose academic performance is persistently low as internet addiction may be one of the reasons. references 1. bhat m. internet revolution. br dent j. 2007; 202: 645. 2. jia r. computer playfulness, internet dependency and their relationships with online activity types and student academic performance. j behav addict. 2012; 1: 74-7. 3. chen sy, tzeng jy. college female and male heavy internet users' profiles of practices and their academic grades and psychosocial adjustment. cyberpsychol behav soc netw. 2010; 13: 257-62. 4. tao d, demiris g, graves rs, sievert m. transition from in library use of resources to outside library use: the impact of the internet on information seeking behavior of medical students and faculty. amia annu symp proc. 2003:1027. 5. gray nj. health information on the internet--a doubleedged sword? j adolesc health. 2008; 42: 432-3. jiimc 2016 vol. 11, no.2 internet addiction and medical students original�article abstract objective: to report the caries frequency of proximal surfaces of permanent first molars. study design: descriptive study. place and duration of the study: department of operative dentistry, dow dental college, dow university of st st health sciences karachi. one month from 1 october 2015 to 31 october 2015. materials and methods: the study was conducted on retrospective data of 374 patients presenting to the department of operative dentistry, dow university of health sciences. diagnosis of dental caries was made on selected periapical radiographs using criteria provided by senel. caries data and other independent variables e.g. age; gender, arch and side were analyzed with spss for windows version 17. chi square test was used to measure association between proximal caries and qualitative variables such as gender, age group and tooth group. results: there were more mesial proximal lesions (56.4%) than distal lesions (43.6) in all age groups except for 41-50 years and above 50 years (p=0.109). when maxillary and mandibular teeth were compared with proximal surfaces, mesial surface of maxillary first molar was found to be more carious statistically (p=0.000326) conclusion: mesial surface of maxillary permanent first molar was associated with increased risk for dental caries. key words: caries diagnosis, dental caries, permanent first molar, mesial proximal surface 3 visual clinical examination might be enough. proximal surfaces on the other hand, are more likely 4-6 to be under-diagnosed even with radiographs. previous caries experience especially in early childhood might also be used to assign a higher risk 7 of developing proximal caries. the proximal surfaces of first molar therefore, must be thoroughly examined and accurately diagnosed. it has been reported that proximal decay is the most common 8,9 reason for endodontic therapy in this tooth. site specific studies have been published internationally reporting a different caries incidence for proximal and smooth surfaces of permanent first molar. lith reported an increased incidence of dental caries in 10 mesial surface of first molar. distal surface of first molar was found more at risk in a study that reported caries risk in proximal surface according to eruption 11 order. a swedish longitudinal study on adolescents 12 also found more caries incidence on distal surface. in contrast, proximal surface of first molar was not 1 considered at more risk in another study. although there is abundant caries data on local population, site specific studies have not been conducted so 13,16 far. few studies reported caries incidence, however data on specific sites was pooled and tooth introduction permanent first molar due to its early eruption and posterior location is most caries prone and most 1,2 treated tooth in dentistry. a different caries risk has been associated with its different surfaces. a study from usa reported a higher caries incidence for buccal and occlusal surface as compared to 1 proximal. hopcraft reported a possible association of age with site of tooth, occlusal caries been more common in young while proximal caries was 2 observed more in older subjects. similarly, early diagnosis of caries in these teeth is of paramount importance. for occlusal and smooth surfaces, only caries susceptibility of proximal surfaces in permanent first molars: a cross sectional survey 1 2 3 arshad hassan , javeria ali khan , syed abrar ali correspondence: dr. javaria ali khan operative dentistrydepartment of dow dental college, dow university of health sciences, karachi e-mail: javkhan_78@hotmail.com 1,2 department of operative dentistry dow dental college, dow university of health sciences,karachi operative dentistry 3 department of hamdard university dental hospital, karachi funding source: nil; conflict of interest: nil received: november 08, 2018; revised: february 11, 2019 accepted: march 10, 2019 caries in proximal surfaces of first molarsjiimc 2019 vol. 14, no.1 38 molars based on our inclusion and exclusion criteria. the basic descriptive details of our sample are summarized in table no. i. the mesial surface was found to be carious (n=211, 56.4%) more than the distal surface (n=163, 43.6%). the association of proximal carious surface to the age groups (p=0.109) and gender (p=0.423) was found to be insignificant (table no. ii). the percentage of mesial and distal surfaces was found to be equal for <20 age group, where-as for age group 20-40 mesial surface had an increased occurrence. however, age group 40-50 had both surfaces equally affected and in >50 age group an increased percentage of distal carious lesions was found (graph no. i). the association of proximal decay on mesial surface of maxillary permanent first molar was found to be significant (p=0.00032) (table no. iii). 17,18 level site specific data was not provided. it was therefore, the objective of this study to report the site specific caries data for proximal surface of permanent first molar. the aim of the study was to evaluate the caries frequency of mesial and distal surfaces of permanent first molar. materials and methods this descriptive study was undertaken at the department of operative dentistry, dow dental college. the study was based on retrospective patient data stored in the records of the department. duration of study was one month, during the month of october 2015. ethical approval for the study was obtained from the institutional review board (irb585/duhs/approval/2015/110). the sample size for this study was calculated at 95% confidence level and 80% power, a sample size of 362 was calculated(62% 19 occurrence of class 2 lesions). sample size calculation was made by using open epi version 2 (open source calculator ss-proper). we included 374 permanent first molars in our study by consecutive sampling method based on following criteria. we included permanent first molars in either arch, teeth with primary proximal decay and radiographs of acceptable quality. cases with more than one carious first molar were also included. the exclusion criteria included teeth with secondary carious lesions and a tooth with both the proximal surfaces involved. selected radiographs were viewed under standard conditions. an illuminator was used to view and score selected radiographs. a calibrated examiner made all the readings. the radiographic diagnosis of dental caries was made according to the criteria modified from senel, where 0 was scored for no caries and 1 for caries confined to enamel or 20 involving dentin. a specially designed proforma was used to collect the data. data analysis was performed with spss version 17 for windows. mean and standard deviation of qualitative variable like age and percentages of qualitative variables e.g. gender and proximal surface were calculated. chi square test was used to determine association between the two proximal surfaces and categorical variables like gender, age group and tooth group was determined with chi square test at 95% of significance. results the current study included 374 permanent first table i: basic demographic data mean sd table ii: associa�on of proximal caries frequency with age 39 jiimc 2019 vol. 14, no.1 caries in proximal surfaces of first molars 10 with lith. this longitudinal study followed patients from 6 years of age till age 20, and found this condition remained at an elevated level throughout the period of study. they also found a high frequency of carious and restored distal surface of second premolar, a finding which may partly explain a high caries rate on mesial surface of first molar. this was one of a limitation of our study that we did not consider the caries status of adjacent teeth. bachelor on the other hand reported buccal pits and occlusal fissures in first molars to be most caries susceptible, 1 while proximal surfaces were found to be less prone. better access to health care facilities, a regular checkup and fluoride intake may be responsible factors for a different disease pattern in this american study. a longitudinal swedish with a cohort study design found distal surface of first molar to be more caries affected as compared to mesial 12 surface. since the methodology of this study differed considerably from our study due to its cross sectional study, this fact could help explain the differences in results. a difference in the proximal surface morphology and enamel maturation has been proposed previously as a possible reason for 21 the conflicting result of our and other studies. the mesial surface of maxillary first molar presents a flatter surface with a more buccally placed contact area with a concavity cervical to this contact area. distal surface on the other hand, has a more convex profile and a wider contact area and a minimal sub contact concavity. this anatomical difference may be responsible for increased plaque retention and caries experience. in contrast, the mandibular first molar lack a concavity and it's both mesial and distal 22 contact areas are broad and much flatter. these observations support our results of significantly greater involvement of the maxillary first molar when compared to the mandibular first molar. edward and burchell have proposed another interesting association, that the proximal surfaces of a tooth that erupts earlier and thus exposed for 11,23 longer periods of time are more susceptible. this explanation however don't support the results that were derived in our study. the distal surface of the first molars have a longer exposure time to the oral environment as second molar is one of the last teeth to erupt. whereas the mesial surface forms a contact with deciduous second molar immediately after discussion we included data of 374 permanent first molars in our cross-sectional study. we found carious lesions more frequently on mesial proximal. also mesial surface of maxillary first molar was found to be more carious statistically. however a reverse trend was observed for age group of >50 where distal surface was found to be affected more. moreover, the association of proximal decay with age and gender was non-significant. dmft score of pakistan is high. in 12 year olds it has increased from 1.2 in 1998 to 14 1.6. therefore, it is important to be aware of local demography before one can draw any conclusions or make comparisons with other studies. our study was the first of this kind that was done locally. although local caries burden is known, site specific study on 13,14 permanent first molar was lacking. our results differ from studies reported from other parts of the world. regional variation in rate and pattern of dental caries may be responsible for these differences. our main finding that mesial surface of first molar may be more caries susceptible agrees table iii: associa�on of proximal caries frequency with individual tooth graph no.1 rela�onship between age groups and proximal caries 40 jiimc 2019 vol. 14, no.1 caries in proximal surfaces of first molars of cavitations in proximal caries lesions at various magnification levels in vitro. j dent. 2006; 34(10):817-22. 5. hopcraft ms, morgan mv. comparison of radiographic and clinical diagnosis of approximal and occlusal dental caries in a young adult population. community dent oral epidemiol. 2005; 33(3):212-8. 6. tantradi p, sreenivasan v, kadaganche h. role of bitewing in enhancing the assessment of dmfs index in a group of indian adolescents. indian j dent res. 2010; 21(2):266-9. 7. alm a, wendt lk, koch g, birkhed d. prevalence of approximal caries in posterior teeth in 15-year-old swedish teenagers in relation to their caries experience at 3 years of age. caries res. 2007; 41(5):392-8. 8. tareen sk, qureshi a, rehman s. frequency and distribution of teeth requiring endodontic treatment in patients attending a free dental camp in peshawar. j khyber coll dent. 2012; 3(1):7-11. 9. vohra f, ahmed i, zaki m, shaikh a. an evaluation of etiologic factors for root canal therapy. j pak dent assoc. 2005; 14(3):154-7. 10. lith a, lindstrand c, grondahl hg. caries development in a young population managed by a restrictive attitude to radiography and operative intervention: ii. a study at the surface level. dentomaxillofac radiol. 2002; 31(4):232-9. 11. edward s. dental caries on adjacent approximal tooth surfaces in relation to order of eruption. acta odontol scand. 1997; 55(1):27-30. 12. stenlund h, mejare i, kallestal c. caries incidence rates in swedish adolescents and young adults with particular reference to adjacent approximal tooth surfaces: a methodological study. community dent oral epidemiol. 2003; 31(5):361-7. 13. haleem a, khan a. dental caries and oral hygiene status of 12 years old school children in pakistan. pak j med res. 2001; 40(4):138-42. 14. khan a, ijaz s, syed a, qureshi a, padhiar i, sufia s. oral health in pakistan: a situation analysis. dev dent. 2004; 5(2):35-44. 15. mohiuddin s, nisar n, dawani n. dental caries status among 6 and 12 years old school children of karachi city. j pak dent assoc. 2015; 24(01):39-45. 16. qazi h, azam s, khurram s, zia a. prevalence of dental caries in the permanent dentition of patients seeking orthodontic treatment in bara kahu. pak oral dent j. 2011; 31(2):371-3. 17. shah s, tul muntaha s, munir m. incidence of caries in 6 – 12 years children visiting punjab dental hospital, lahore & sardar begum dental college and hospital, peshawar. pak oral dent j. 2008; 1(28):117-22. 18. azam s, khurram s, hassan m, iqbal f, iqbal s. distribution of dental caries and its relationship to risk factors. pak oral dent j. 2011; 31(2):453-6. 19. rehman k, khan s, shah s. frequency of class ii type carious lesions in first permanent molars and their association with pulp. pak oral dent j. 2009; 29(1):119-22. 20. şenel b, kamburoğlu k, üçok ö, yüksel s, özen t, avsever h. diagnostic accuracy of different imaging modalities in detection of proximal caries. dentomaxillofac radiol. 2014; 39:501-11. eruption and is therefore less exposed. in a study by 24 norblad and larmas no such association was found. in fact the early contact formation could be used to explain the greater risk of mesial surface. also in case of a carious deciduous second molar, it can inoculate its permanent neighbor with infection. 25 studies have shown this relationship. this fact combined with a high prevalence of dental caries in local pediatric population supports the results of our 14 study. conclusions we found mesial surface of maxillary first molars with greater caries frequency. limitations we report following limitations of our study ! we did not take the caries status of adjacent tooth into account. this can alter the caries susceptibility and help explain the results better. ! we did not consider the overall oral hygiene status of the patients and this can potentially act as a confounder. ! our study was a snap shot; a better design may be a longitudinal one which is also a limitation of our study. ! single calibrated examiner made all the readings and inter-examiner reliability could not be calculated. ! our results conflict with published data. acknowledgement we would like to acknowledge the house officers of dow dental college for their help in data collection. disclaimer st the findings of this research were presented in the 1 i n t e r n a t i o n a l c o n fe re n c e o f i n t e r n a t i o n a l association for dental research, pakistan section in lahore. references 1. batchelor pa, sheiham a. grouping of tooth surfaces by susceptibility to caries: a study in 5-16 year-old children. bmc oral health. 2004; 4(1):2. 2. hopcraft ms, morgan mv. pattern of dental caries experience on tooth surfaces in an adult population. community dentistry and oral epidemiology. 2006; 34(3):174-83. 3. ricketts dn, ekstrand kr, kidd ea, larsen t. relating visual and radiographic ranked scoring systems for occlusal caries detection to histological and microbiological evidence. oper dent. 2002; 27(3):231-7. 4. kielbassa am, paris s, lussi a, meyer-lueckel h. evaluation 41 jiimc 2019 vol. 14, no.1 caries in proximal surfaces of first molars 24. nordblad a, larmas ma. caries and fillings in the permanent dentition of cohorts of schoolchildren in espoo, finland. community dent oral epidemiol. 1986; 14(5):2713. 25. vanderas ap, kavvadia k, papagiannoulis l. development of caries in permanent first molars adjacent to primary second molars with interproximal caries: four-year prospective radiographic study. pediatr dent. 2004; 26(4):362-8. 21. dirks ob, editor the distribution of caries resistance in relation to tooth surfaces. ciba foundation symposiumcaries-resistant teeth; 1965: wiley online library. 22. fuller jl, denehy ge, hall sa. concise dental anatomy and morphology: university of iowa college of dentistry; 1999. 23. burchell c. caries increments at interproximal sites following the establishment of a contact point. caries res. 1984; 18:188-. 42 jiimc 2019 vol. 14, no.1 caries in proximal surfaces of first molars jiimc june 2016.cdr original article abstract background: mers is one of the newly emerging infectious diseases. since it is confined mostly to the arabian peninsula, all those returning from this region are likely to bring this infection. hence, with the huge number of hajj/umrah pilgrims returning each year from saudi arabia, health care workers should be well aware of the various aspects of this disease. objective: to measure the level of awareness of doctors about middle eastern respiratory syndrome (mers) infection. study design: a cross-sectional, descriptive study. place and duration of study: the study was conducted in the medical and pediatric units of holy family th th hospital, rawalpindi from 24 august to 5 september, 2014. materials and methods: study population consisted of qualified and registered medical practitioners. demographic details about the respondents of the study were collected. awareness about mers infection was assessed by a questionnaire. responses were classified as correct/ incorrect, enumerated and converted into percentages. results: eighty five percent of the respondents knew about the causative organism. most of the doctors were aware of the signs and symptoms (75%), mode of spread (51%) and the treatments available (51%). however, most of them lacked knowledge about preventive methods (72%) and diagnostic techniques (59%). conclusion: awareness about mers among doctors working in medical and pediatric units of holy family hospital is quite high but knowledge regarding preventive measures is suboptimal. key words: doctors, mers (middle eastern respiratory syndrome), mode of transmission, pakistan, reservoir. 4 rate of 40%. the symptoms include complaints like fever, chills, cough, dyspnoea and muscle aches and pains. gastrointestinal symptoms are also reported like diarrhoea and vomiting as well as abdominal pain. patients older than 40 years of age had higher 4,5 mortality rates than younger patients. those suffering from co-morbidities like diabetes, renal failure and heart failure are more likely to die from 6,7 this infection. diagnosis requires detection of mers-cov nucleic acid by polymerase chain reaction (rt-pcr) in upper and lower respiratory tract secretions, such as in sputum, tracheal aspirate 8 and in bronchoalveolar lavage. although most of these cases are clustered in countries of the arabian peninsula with saudi arabia as the hub, yet travellers to this region can carry this infection far and wide as shown by the appearance of secondary cases in uk, jordan, egypt, austria, etc. the source of this infection is the dromedary camel, known to harbor the virus causing mers but the mode of transmission, whether direct or indirect, is 9 still unclear. human-to-human transmission has been brought to introduction middle east respiratory syndrome caused by coronavirus (mers-cov) has been recognized as an emerging viral infection that is also potentially lethal. according to world health organization, by june 2015, as many as 1289 cases of mers-cov had been 1 identified and confirmed on laboratory reports. since the first reported case in september 2012 in 2 saudi arabia 455 deaths have occurred worldwide and almost 300 cases have been identified within 3 saudi arabia. it is the sixth corona virus with the potential to cause severe acute respiratory syndrome and multiorgan failure in humans. this viral infection is potentially lethal with a mortality knowledge about mers (middle eastern respiratory syndrome) among doctors in holy family hospital, rawalpindi abida sultana, sayema awais, fazal mehmood correspondence: dr. sayema awais department of community medicine rawalpindi medical college, rawalpindi e-mail: drsayema@yahoo.com department of community medicine rawalpindi medical college, rawalpindi funding source: nil ; conflict of interest: nil received: mar 04, 2016; revised: april 12, 2016; accepted: may 25, 2016 doctors' knowledge about mersjiimc 2016 vol. 11, no.2 71 notice with the appearance of hospital-acquired and community acquired cases. in a study that followed up 280 contacts of 26 index patients, the transmission rate was found to be 5% (i.e. 12 cases of 10 mers-cov were identified). health care workers (hcw) are shown to be at greatest risk of acquiring the infection. according to a study in jeddah, hcw constituted 20.9% of the patients diagnosed with mers. those who were symptomatic were also found to have had contact with a health care facility or a confirmed case of mers or with someone who had fever with respiratory complaints within the last 11 14 days. to date, there is no vaccine available against mers 12 nor is there any specific treatment being offered. investigators have found that nosocomial and zoonotic transmission is the most important mode of 13 spread of this infection. the preventive measures that are recommended for those coming in contact with animals particularly camels in the arabian peninsula include rigorous hygienic measures such as hand-washing and avoiding contact with diseased animals. consuming raw meat or milk from camels should be strictly avoided and animal products must be subjected to pasteurization and cooking or other processing that renders it safe for consumption. moreover all those who suffer from immunecompromising conditions, diabetes, chronic lung diseases and renal failure are considered at high risk 14 for developing mers-cov infections. health care workers are recommended to wear personal protective equipment including mask, gown, gloves and goggles besides practicing hand washing before and after handling mers-cov infected/ suspected 15 patients or his/ her surroundings. the most recent outbreak of mers-cov has occurred in south korea. this is also the largest outbreak outside kingdom of saudi arabia. the most important feature of this outbreak is that the transmission of infection was not limited to south korea alone but mers was exported to a third country, china; thus highlighting the existence of human-to human transmission of this virus. it is a third generation transmission of infectionfrom index case to contacts, and from the secondary case to another person who had no contact with the index 16 case. this outbreak in korea highlights the fact that even a single imported case of mers-cov can be a 17,18 huge risk that can trigger the spread of infection. since transmission of mers is mainly nosocomial, knowledge about control of infection and preventive measures in order to intercept the transmission of the virus particularly in hospitals, is extremely crucial 18,19 in containing an epidemic. with millions of hajj and umrah pilgrims returning from saudi arabia in addition to a regular turnover of expatriates visiting throughout the year, pakistan is at particularly high risk of developing such epidemics. with the arrival of even a single case, an epidemic can be triggered and mers can spread like wildfire all over pakistan. in addition, the low literacy level of the pakistani population and a general lack of awareness about health issues especially newly emerging diseases make pakistan more vulnerable to the threat of mers. in pakistan's context, knowledge and training of doctors and health personnel in the control of newly emerging infections like mers is also suboptimal since refresher courses and continued medical education is not mandatory. to the best of our knowledge, no studies regarding assessment of knowledge about mers virus/ mers syndrome have been undertaken except one study c o n d u c t e d i n s a u d i a ra b i a . ke e p i n g t h i s rationale/scenario in mind, this study aimed to assess level of knowledge among doctors regarding middle eastern respiratory syndrome (mers-cov) in a tertiary care hospital of rawalpindi. materials and methods this was a cross-sectional, descriptive study in which the study population consisted of doctors including house officers, postgraduate trainees, medical officers (mos), woman medical officers (wmos), assistant principal medical officers/ woman medical officers (apmo/apwmo), registrars, assistant and associate professors. all these doctors were registered with pakistan medical and dental council and were working in medical and paediatric units of holy family hospital, rawalpindi. holy family hospital is a multidisciplinary 850-bedded hospital located in the densely populated city of rawalpindi close to its junction with the capital, islamabad. it provides both out-patient and in-patient facilities. th data was collected from 24 august to 5th september, 2014. informed written consent was taken from the respondents and anonymity was maintained. doctors' knowledge about mersjiimc 2016 vol. 11, no.2 72 using the prevalence of insufficient knowledge about mers i.e. 4%20, margin of error 4.99%, significance level 95%, the sample size calculated using sample size calculator was 60. convenience sampling technique was used. the questionnaire was developed to assess the knowledge of the doctors about middle east respiratory syndrome (mers). the questions asked were about the causative organism, mode of spread of infection, clinical signs and symptoms, diagnostic tests available, awareness about treatment options, and prevention of mers. multiple choice questions were designed and included in the questionnaire. the questionnaire was approved by the research supervisor and was distributed and collected by medical students. data collected was non-parametric and was entered in spss version 20.0. those giving the correct answers were enumerated and percentages were calculated. results a total of 60 questionnaires were distributed. among these 41 were postgraduate trainees, 14 were medical officers/ woman medical officers, 3 were senior registrars/ consultants and 2 were apmo/ apwmo. regarding the age distribution, majority (56%) were 21-30 years of age. only 5% were 51-60 years of age. most of them (63%) had been working for a period of one to five years as a doctor (table i). discussion in our study, despite the fact that only a small percentage of our sample consisted of senior consultants, the majority of the doctors were aware of the newly emerging infectious disease of mers. the most important knowledge gap was regarding the preventive measures required for the containment of this infection. less than one-third of the respondents were aware of the appropriate methods of prevention. to the best of our knowledge, there has been only one similar study on the subject of awareness about mers-cov conducted in the kingdom of saudi arabia among health care workers (hcws) including nurses, pharmacists and technical staff besides 20 doctors. in contrast, our study population consisted of only doctors. since mers is a major public health problem in the arabian peninsula, it is no wonder that the knowledge of hcws in ksa is better in almost all aspects of the disease than in our study. like the study in ksa with 96% respondents correctly table i. demographic data of study par�cipants table ii: percentage and number of doctors who were knowledgeable about different aspects of mers (n=60) 95% (n=57) of the doctors were aware of the abbreviation while 5% (n=3) did not know what mers stands for. of the 57 doctors who knew about the abbreviation, 48(85%) knew that the causative organism was corona virus. most of the respondents were aware of the clinical picture but the most apparent knowledge gap was observed regarding the methods of prevention. only 11 (18.3%) knew about the appropriate methods of prevention to be adopted while handling a case of mers infection. the percentage and number of doctors who gave the correct answers are given in table ii. doctors' knowledge about mersjiimc 2016 vol. 11, no.2 73 identifying the signs and symptoms of mers, in our study the most correct answers (75%) were about the clinical signs and symptoms of mers. whereas 94% of the hcws in saudi study were aware of the important preventive measures, only 18% answered correctly in our study. the next important knowledge gap is regarding the diagnostic method most suitable for detection of mers infection. only 41% pakistani doctors are aware of it, whereas 76.5% hcws replied correctly about the diagnostic method in the saudi study. in contrast, the participants (doctors) in our study are more knowledgeable about management in mers infection (51%) whereas among hcws in ksa, only 40% knew appropriate management. this is to be expected since the educational background is much broader for doctors than for nurses, pharmacists and technical staff who were also included in the participants of the study in ksa. conclusion our study shows that although the awareness among doctors regarding signs and symptoms and treatment of mers virus/syndrome is high, the level of knowledge about preventive methods is suboptimal. recommendations our study has highlighted the fact that the major emphasis in our clinical setup is laid on treatment and not on prevention. there is an urgent need to educate the medical community about new and reemerging infections that can spread rapidly. for this purpose, continued medical education programmes must be instituted. references 1. world health organization. global alert and response: disease outbreak news. middle east respiratory syndrome coronavirus (mers-cov) – republic of korea. [updated on 1 2 j u n e 2 0 1 5 ] . [ a c c e s s e d o n 1 3 j u n e 2 0 1 5 ] . h tt p : / / w w w.w h o . i n t /c s r / d o n / 1 2 j u n e 2 0 1 5 m e rs korea/en/ 2. zaki am, boheeman s, bestebroer tm, osterhaus ad, fouchier ra. isolation of a novel coronavirus from a man with pneumonia in saudi arabia. n engl j med. 2012; 367: 1814–20. 3. world health organization: middle east respiratory syndrome coronavirus (mers-cov). summary and l i t e r a t u r e u p d a t e a s o f 9 m a y 2 0 1 4 . [http://www.who.int/csr/disease/coronavirus_infections/ mers_cov_update_09_may_2014.pdf] [accessed on 13 june 2015]. 4. alsahafi aj, cheng ac. the epidemiology of middle east respiratory syndrome coronavirus in the kingdom of saudi arabia, 2012-2015. int j infect dis. 2016; 45: 1-4. 5. zumla a, hui ds, perlman s. middle east respiratory syndrome. lancet 2015; 386: 995-1007. 6. assiri a, al-tawfiq ja, al-rabeeah aa, al-rabiah fa, alhajjar s, al-barrak a, et al. east respiratory syndrome coronavirus disease from saudi arabia: a descriptive study. lancet infect dis. 2013; 13: 752-61. 7. arabi ym, arifi aa, balkhy hh, najm h, aldawood as, ghabashi a, et al. clinical course and outcomes of critically ill patients with middle east respiratory syndrome coronavirus infection. ann intern med 2014; 160: 389-97. 8. world health organization. laboratory testing for novel coronavirus. interim recommendations, 21 december 2012. available at: http://www.who.int/csr/disease/coronavirus_infections/l aboratorytestingnovelcoronavirus_21dec12.pdf. 9. memish za, cotten m, meyer b. human infection with mers coronavirus after exposure to infected camels, saudi arabia, 2013. emerg infect dis. 2014; 20: 1012-5. 10. drosten c, meyer b, müller ma, corman vm, al-masri m, hossain r, et al. transmission of mers-coronavirus in household contacts. n engl j med. 2014; 371: 828-35. 11. oboho ik, tomczyk sm, al-asmari am, banjar aa, al-mugti h, aloraini ms, et al. 2014 mers-cov outbreak in jeddah--a link to health care facilities. n engl j med. 2015; 372: 84654. 12. du l, tai w, zhou y, jiang s. vaccines for the prevention against the threat of mers-cov. expert rev vaccines. 2016 mar 17. 13. shehata mm, gomaa mr, ali ma, kayali g. middle east respiratory syndrome coronavirus: a comprehensive review. front med. 2016 jan 20. 14. world health organization. middle east respiratory syndrome coronavirus (mers-cov) fact sheet n°401. [updated june 2015]. http://www.who.int/mediacentre/factsheets/merscov/en/ [ accessed on july 25,2015]. 15. world health organization. infection prevention and control during health care for probable or confirmed cases of novel coronavirus (ncov) infection. interim guidance 6 may 2013. http://www.who.int/csr/disease/coronavirus_infections/i pcncovguidance_06may13.pdf. [accessed on july 27,2015]. 16. korea centers for disease control and prevention. middle east respiratory syndrome coronavirus outbreak in the republic of korea, 2015. osong public health res perspect. 2015; 6: 269-78. 17. who. mers-cov outbreak largest outside kingdom of saudi arabia: briefing notes on mers-cov (updated on 2 june 2015). available from: http://www.who.int/mediacentre/news/mers/briefingnotes/2-june-2015-republic-of-korea/en/ (accessed on 19 march, 2016). 18. liu s, chan tc, chu yt, wu jt, geng x, zhao n, et al. comparative epidemiology of human infections with middle east respiratory syndrome and severe acute respiratory syndrome coronaviruses among healthcare doctors' knowledge about mersjiimc 2016 vol. 11, no.2 74 personnel. plos one 2016; 11: e0149988. 19. assiri a, mcgeer a, perl tm, price cs, al rabeeah aa, derek md, cummings at, et al. hospital outbreak of middle east respiratory syndrome coronavirus. n engl j med 2013, 369: 407–16. 20. khan mu, shah s, ahmad a, fatokun o. knowledge and attitude of healthcare workers about middle east respiratory syndrome in multispecialty hospitals of qassim, saudi arabia. bmc public health 2014: 14: 1281. doctors' knowledge about mersjiimc 2016 vol. 11, no.2 75 original�article abstract objective: to determine the frequency of patient compliance with universal face mask policy during covid-19 pandemic using simple observable criteria. study design: cross sectional study place and duration of study: pakistan railway hospital, rawalpindi during the third wave of covid-19 pandemic over a period of one month from 15 march 2021 to 15 april 2021. materials and methods: a total of 266 patients were recruited from the general population of patients visiting our hospital after undergoing screening for covid-19 at the filter clinic. face mask compliance was defined as the wearing of a disposable surgical mask while employing correct techniques as per the world health organization and national institute of health guidelines for hospital settings. results: majority of the patients (79.9%) wore a surgical face mask as recommended for hospital settings. however, only 41% employed the correct mask wearing technique. patients under strict supervision in outdoor clinics were more likely to wear mask as compared to their indoor counterparts (76.79% vs 51.76%). correlation was significant at a level of 0.492. one third (34.2%) of the patients did not cover their face, nose, and chin completely. an overwhelming majority (129/183 or 70.49%) admitted reusing the mask multiple times. conclusion: the study findings indicate that while majority of the general population of patients visiting our hospital wore a face mask, compliance with correct mask wearing technique as per recommended guidelines was poor. our results support strict implementation of universal masking policies for hospitals in pakistan as part of a multifaceted strategy to minimize transmission of infection in health care settings. key words: covid-19, face mask, health care worker, hospital-acquired covid-19 infection, patient compliance. hospital-acquired covid-19 infection, hospitals are at risk of becoming a potential hub of disease spread to community. as many as 55% of hospital-acquired covid-19 infections are a result of direct patient to patient 3 transmission. while physical distancing is the most important way to prevent the spread of covid-19 from person to person, there is very limited space at the hospital to do this safely. in outpatient clinics and waiting areas it may be particularly difficult to maintain social distancing. in december 2020, world health organization (who) issued interim guidelines recommending universal face masking within both 4 outdoor and indoor health care settings. a universal masking policy requires all medical and non-medical staff, patients, and visitors to always wear a face mask while in hospital. universal face masking limits covid-19 transmission from patient to health care 5 provider and vice versa. there is a strong correlation between universal masking in hospitals and lower 6,7 rate of infectivity amongst hcw. the model has introduction one in every five health care workers (hcw) dealing with covid-19 patients is at risk of contracting nosocomial covid infection during patient 1 encounter. break through covid 19 infection has been reported in 25% of fully vaccinated hcw during 2 the covid-19 delta variant surge. with more and more hcw and vulnerable patients contracting non-compliance with universal masking policy by patients during covid-19 pandemic: a major threat to health care worker in pakistan 1 2 3 4 5 6 shamaila burney , mishaal fazal , mati ur rehman , saerah iffat zafar , samia kauser , kiran fatima correspondence: dr. shamaila burney islamic international medical college, riphah international university, islamabad e-mail: shamaila.burney@riphah.edu.pk 1,3,5,6 department of medicine islamic international medical college, riphah international university, islamabad 2 mbbs student fazaia medical college, air university islamabad 4 department of radiology armed forces institute of radiology and imaging, rawalpindi received: november 15, 2021; revised: april 20, 2022 accepted: may 31, 2022 facemask non-compliance by patientsjiimc 2022 vol. 17, no.3 152 been implemented with proven reduction in hospital 8 acquired covid-19 infection. over 40% of covid-19 infected patients/visitors may 9 be asymptomatic carriers. furthermore, a negative screening test at the time of admission, does not completely rule out the possibility of covid-19 10 infection. such individuals may become an undetected source of hospital acquired covid-19 infection for hcw and other patients. safety of our health care workers thus relies heavily on face mask compliance by patients and visitors. present study was conducted to determine the patient compliance with universal face masking in our hospital. the findings of this research could be used to improve strategic management of covid-19 pandemic in a resource limited hospital setting. materials and methods the study was conducted at pakistan railway hospital rawalpindi during the third wave of covid19 pandemic, over a period of one month from 15 march 2021 to 15 april 2021. it was a cross-sectional study. with 51% prevalence of face mask in general community, the sample size was calculated as 165 using who sample size calculator with a confidence level of 95%, and a 11 relative precision of 15. the study was initiated after the approval of institutional ethical review committee. a total of 266 patients aged 18 years and above were included by random convenient sampling after taking informed consent. the study subjects were selected from various points after undergoing initial screening at the covid filter clinic. these included patients presenting to general outpatient department (opd) clinics and indoor patient departments (ipd)/green zone, where mask wearing was a mandatory requirement as per our hospital policy. covid suspect patients admitted in yellow zones and those in critical areas such as emergency room (er) and intensive care unit (icu) were excluded from the study. medical/allied health sciences students and hospital employees were also excluded from the study to control the confounding effect resulting from their knowledge differences with the general population. two trained investigators assessed the face mask compliance in patients during their physician encounter in opd or ipd. a pilot study validated, structured observational checklist, based on who and nih guidelines on face mask use, storage, and disposal in the context of health care settings was 4,12 used as the survey tool. data was collected by visually observing face mask compliance as per given operational definition as well as asking certain direct questions. rational use of face mask was defined as w e a r i n g o f a o n e t i m e u s e d i s p o s a b l e medical/surgical mask as recommended for hospital 4 settings. correct manner of mask use was assessed as a score out of 5 and included following simple observable criteria for study purposes: (1) face mask must cover nose, mouth and chin completely; (2) it must not be worn under the chin or on the hair; (3) it should have two elastic ties that do not overlap and a metallic clip at the top (4) the face mask must not be touched or manipulated once worn; (5) it should not be lowered while talking. each correct practice was awarded 1 mark and 0 was marked for noncompliance. for face masks to be effective in preventing infection, their storage and disposal are equally important. surgical mask is a one-time use product that must be discarded after single use. it should be stored in a separate paper or plastic bag when not in use e.g., during eating/drinking. it is to be removed from behind and thrown away in a closed bin. data was analyzed using ibm spss version 23.0 with a table i: patients' demographic characteristics and settings facemask non-compliance by patientsjiimc 2022 vol. 17, no.3 153 margin of error of 5%. categorical data was calculated as frequencies and percentages. cross tabulations and correlation matrix was checked for interaction between the variables. pearson's chisquare test was used to look for any statistically significant difference in variables and face mask compliance. p-value of less than 0.05 was considered significant at 95% confidence interval. results a total of 266 patients were included in our results. table i shows the patient characteristics and settings. majority of the patients in our study (229/266 or 86.09%) wore a face mask while 37/266 (13.90%) patients did not. out of the 229 patients who wore a mask, 183/229 or 79.9% wore the recommended surgical mask while 43/229 (18.77%) wore a fabric mask and 3/229 (1.31%) used a n 95 mask. an overwhelming majority (129/183 or 70.49%) admitted reusing same mask multiple times. a sealed paper/plastic bag was used to store the mask by only 9/183 (4.92) patients. very few patients (28/183 or 15.30%) discarded their used mask in a closed bin. figure 2 depicts these face mask practices. fig. 1 reasons for non-compliance mask wearing technique was assessed for the 183 patients who wore a surgical mask. a score of 5/5 was achieved by only 65/183 (41%) patients. table ii: depicts the criteria observed and patient behavior fig. 2: face mask practices fewer ipd patients (44/85 or 51.76%) wore surgical mask as compared to 139/181 (76.79%) opd patients. correlation was significant at a level of 0.492. ipd patients were also less likely to cover their face completely as compared to their opd counterparts (21/43 or 48.8% vs 41/138 or 29.7%). there was no significant correlation between gender and face mask compliance in terms of wearing the right type of mask and overall compliance score. however, males were more likely to touch the mask than females with p value of 0.129. although not directly included in the study population, 148/266 (55.6%) of the patients were accompanied by attendants. almost one-third of them (45/148 or 30.4 %) did not wear a face mask. discussion face mask non-compliance by patients poses a significant threat to hcw and other patients. while majority of the patients (87%) in this study wore a face mask, actual compliance as per operational definition was very low. one in every five patients wore a non-surgical fabric mask or other barrier masks such as hijab/bandana/handkerchief which 13 are not recommended for hospital settings. data suggests that face mask compliance in health care settings may be suboptimal despite a universal 14 masking policy. a hospital-based study conducted in pakistan early in pandemic, reported that although 90.4 % of the study population was compliant with wearing a face mask only 62.1% of them used a facemask non-compliance by patientsjiimc 2022 vol. 17, no.3 154 15 surgical mask. the relatively good compliance with wearing of surgical face mask in our study is more likely the result of a strict internal mask policy at our hospital rather than increased community awareness. a comparison of results from various inhospital settings further confirms this. patients under strict supervision in opd clinics were more likely to wear mask (139/181 or 76.79%). on the contrary, patients admitted in wards were less compliant (44/85 or 51.76%). it may be argued, that wearing of mask may be difficult for some patients due to underlying illness. however, only stable patients with no breathing difficulty were included in our study. furthermore, the results of our study prove that only 14% patients considered underlying illness to be a barrier to face mask wearing. correct mask usage is as important as wearing a 13 mask and is critical in limiting disease spread. in the present study, correct mask wearing technique was employed by only 41% of the patients. results of our study are comparable to a hospital-based study reported by kumar et al, in which 64.7% of the study population had a suboptimal score with respect to 16 correct mask usage. according to the results of a malaysian study, 11.2% patients/visitors did not 17 cover their face completely with face mask. in comparison, one third of our subjects (34.2%) did not cover their face, nose, and chin completely. manipulation of face mask can increase the risk of 18 self-contamination. a significant number (40.8%) of patients in our study were found to touch their face masks while 31.14% lowered their masks during conversation. this contrasts with other regions such as china, south korea, and europe where face touching behaviors were negligible and observed in 19 1.1%, 2.2% and 6.1% respectively. face masks when not properly maintained, stored, and discarded can themselves become a potential source of disease 20 spread. an alarmingly high proportion of patients in our study (71%) did not discard their one-time surgical masks after use and admitted reusing same mask for several days. an even higher number (84.6%) of patients did not throw the used mask into a closed bin after use. this is in keeping with the results of an italian study in which 50.3% people reused masks for extended periods and 70.5% threw 21 used masks in general waste. earlier a local community-based survey reported by fazal et al also concluded that 73.2% of the study population did not exercise safe mask disposal and 60% of the public 22 discarded the used masks in general waste. pakistan railways hospital is an iso 9001-2015 certified, 350-bedded semi-government teaching hospital affiliated with islamic international medical college, riphah international university. it has on an average 650 outpatient visits per day. soon after the covid-19 pandemic hitting pakistan, the hospital was quick to implement necessary policies in line with national guidelines. hospital infection control measures with reduction in the number of entry/exit points, strict hand hygiene/face mask policy & thermal detection were undertaken. the covid-19 filter clinic screens all patients for covid-19 symptoms and ensures only patients wearing surgical masks are allowed to proceed further. despite these checks and balances, the results of our study reflect the general apathy of our public towards the pandemic. our study has some limitations. it was conducted in a single semi-government hospital hence results cannot be extrapolated to rest of pakistan. the study was conducted over a short duration and the sample size is therefore small. our hospital policy requires all hospital staff to wear face mask hence they were excluded. compliance of an attendant accompanying the patient at the time of his physician encounter was however observed and reported separately. the major strength of our study is its direct observational design which is an accurate reflection of participant's actual practice. the study does not evaluate the association between facemask non-compliance and rate of hospital acquired infection amongst hcw. more studies are required to determine this important aspect as well as temporal relationship between covid19 infection in hcw and larger community. conclusion the study provides preliminary data highlighting sub optimal face mask compliance by the general population of patients despite a facility-wide universal face mask policy at our hospital. strategies to increase awareness and promote rational use of face masks in patients visiting hospitals during covid 19 pandemic will be helpful in minimizing hospital acquired covid-19 infection amongst health care workers and patients alike. telehealth and home care facemask non-compliance by patientsjiimc 2022 vol. 17, no.3 155 rather than hospital focused system are viable options to be considered in this public health crisis. references 1. the lancet. covid-19: protecting health-care workers. lancet. 2020;395(10228):922. 2. milan sharma. breakthrough covid-19 infections 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hw. wearing face masks regardless of symptoms is crucial for preventing the spread of covid-19 i n h o s p i t a l s . i n f e c t c o n t r o l h o s p e p i d e m i o l . 2021;42(1):115–6. 9. gudbjartsson df, helgason a, jonsson h, magnusson ot, melsted p, norddahl gl, et al. spread of sars-cov-2 in the icelandic population. n engl j med. 2020;382(24):2302–15. 10. watson j, whiting pf, brush je. interpreting a covid-19 test result. bmj [internet]. 2020;369(may):1–7. available from: http://dx.doi.org/doi:10.1136/bmj.m1808 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 [internet]. 2020;15(5):1–15. available from: http://dx.doi.org / 10.1371/journal.pone.0233668 12. ministry of national health services regulations and coordination. govt. of pakistan. guidelines for mandatory use of face mask. 2020;(december):1–5. 13. j. picard a , g. cornec a , r. baron a ps. wearing of face masks by healthcare workers during covid-19 lockdown: what did the public observe through the french media? j hosp infect. 2020;617–20. 14. datta r, glenn k, pellegrino a, tuan j, linde b, kayani j, et al. increasing facemask compliance among healthcare personnel during the covid-19 pandemic. infect control hosp epidemiol. 2021;2019:1–7. 15. sarfraz s, raza r, aziz k, umar m, noreen k, shehryar m. compliance on the use of different types of face mask by healthcare workers, and general public in tertiary care hospital of rmu during covid-19 pandemic. j rawalpindi med coll. 2020;24(supp-1):71–6. 16. kumar j, katto ms, siddiqui aa, sahito b, jamil m, rasheed n, et al. knowledge, attitude, and practices of healthcare workers regarding the use of face mask to limit the spread of the new coronavirus disease (covid-19). cureus. 2020;(april). 17. gunasekaran gh, gunasekaran ss, gunasekaran ss, hanim bt abdul halim f. prevalence and acceptance of face mask practice among individuals visiting hospital during covid19 pandemic: observational study. hilos tensados. 2019;1:1–476. 18. matusiak ł, szepietowska m, krajewski p, białynicki-birula r, szepietowski jc. inconveniences due to the use of face masks during the covid-19 pandemic: a survey study of 876 young people. dermatol ther. 2020;33(4). 19. chen yj, qin g, chen j, xu jl, feng dy, wu xy, et al. comparison of face-touching behaviors before and during the coronavirus disease 2019 pandemic. jama netw open. 2020;3(7):1–10. 20. kwon jh, burnham cad, reske ka, liang sy, hink t, wallace ma, et al. assessment of healthcare worker protocol deviations and self-contamination during personal protective equipment donning and doffing. infect control hosp epidemiol. 2017;38(9):1077–83. 21. scalvenzi m, villani a, ruggiero a. community knowledge about the use, reuse, disinfection and disposal of masks and filtering facepiece respirators: results of a study conducted in a dermatology clinic at the university of naples in italy. j community health [internet]. 2 0 2 1 ; 4 6 ( 4 ) : 7 8 6 – 9 3 . a v a i l a b l e f r o m : https://doi.org/10.1007/s10900-020-00952-3 22. fazal m, khawar t, raza z, maryam l, bilal a, burney s. compliance and etiquettes of using face masks in public during covid-19 pandemic: a community-based survey from islamabad, pakistan. pakistan j public heal. 2021;11(2):79–86. facemask non-compliance by patientsjiimc 2022 vol. 17, no.3 156 conflict of interest authors declared no conflicts of interest. grant support and financial disclosure authors have declared no specific grant for this research from any funding agency in public, commercial or nonprofit sector. data sharing statment the data that support the findings of this study are available from the corresponding author upon request. this is an open access article distributed under the terms of the creative commons attributionnoncommercial 2.0 generic license. facemask non-compliance by patientsjiimc 2022 vol. 17, no.3 157 jiimc march 2016.cdr original article abstract objective: to observe the effect of different extracts of syzygium aromaticum (50% ethanolic and 50% aqueous) on the weight of streptozotocin (stz) induced diabetic rats in comparison with insulin. study design: randomized control trial. place and duration of study: the study was conducted at national institute of health islamabad from july 2011 to december 2011. materials and methods: forty adult rats of sprague dawaley specie with weight ranging between 200-250 g were selected and were equally divided into 5 groups (i-v) with eight rats in each group. groupi was control. diabetes was induced to group iiv by a single intraperitoneal injection of stz and rats with fasting blood glucose above 200mg/dl were selected. after receiving the injection of stz, the animals were weighed on day zero i.e 48 hours (post stz ). group-ii was diabetic control , group iii received 50% aqueous extract while group iv received 50% ethanolic extract of syzygium aromaticum at a dose of 750 mg/kg body weight respectively for sixty days. group v received 70/30 humulin insulin, 0.6 units/kg body weight subcutaneously, bid for sixty days. after two months of study on day 60 the animals were weighed again, changes in the weight which occurred with both extracts were compared with the changes in the weight which occurred with the standard drug insulin. results: group-iv receiving 750 mg/kg body of 50% ethanolic extract showed marked improvement in the weight as compared to group iii receiving 50% of the same dose of aqueous extract. group v receiving insulin showed improvement in the weight which is almost closer to the increase in weight which occurred in group iii diabetic rats. conclusion: 750 mg/kg body weight of 50% ethanolic extract of syzygium aromaticum caused more improvement in the weight of diabetic rats than the increase in the weight with the 50% aqueous extract of the same dose and the drug insulin. key words: diabetes mellitus, weight improvement , syzygium aromaticum extract. 2 hyperglycemia (type2dm). it is a complex disorders that disturbs the metabolism of protein, fat and carbohydrates leading to weight loss. several oral hypoglycemic agents lowers blood glucose and improve weight but have many side effects. traditional antidiabetic plants might provide new oral hypoglycemic compounds, with less side effects and can counter the high cost and poor availability of 3 antidiabetic drugs for rural populations. medicinal plant like syzygium aromaticum has antidiabetic potential, its effect on stz induced diabetic rats have been studied and its extract lowered the blood 4 glucose level. streptozotocin (stz) a nitrosourea compound is used to induce insulin-dependent 5 diabetes mellitus in experimental animals. it causes irreversible damage to the pancreatic beta cells resulting in degranulation and loss of capacity to 5 secrete insulin. the cytotoxic action of stz is mediated by reactive oxygen species, which causes a r a p i d d e s t r u c t i o n o f b c e l l s l e a d i n g t o introduction diabetes mellitus (dm) is a very common disease throughout the world. in pakistan the incidence of 1 diabetes mellitus is 22.04%. in this disease there is destruction of the insulin producing beta cells of pancreas (type1dm) and resistance to insulin action i n l i ve r a n d p e r i p h e ra l t i s s u e l e a d i n g to comparison of extracts of syzygium aromaticum on the weight of stz induced diabetic rats 1 2 3 4 5 zunnera rashid chaudhry , asif naseer , sana rasheed chaudhry , erum rasheed chaudhry , faiza rasheed chaudhry correspondence: dr. zunnera rashid chaudhry assistant professor, pharmacology rawal institute of health sciences, islamabad e-mail: zunnerasif@gmail.com 1 department of pharmacology rawal institute of health sciences, islamabad 2 department of medicine cmh, loralai 3 department of physiology postgraduate medical institution, lahore 4 department of biochemistry islamic international medical college, rawalpindi 5 department of ophthalmology mughal eye hospital,lahore funding source: nil ; conflict of interest: nil received: october 09, 2015; accepted: march 06, 2016 effect of extracts of syzygium aromaticum on weightjiimc 2016 vol. 11, no.1 24 6 hyperglycemia. a single intraperitoneal injection of stz with the dosage range between 40-60 mg/kg 6 body weight is very effective. this high blood glucose causes the formation of advanced glycosylation end-products which injures the 7 pancreatic beta cell through oxidative stress. increased serum glucose causes increase catabolism in skeletal muscles leading to increase breakdown of muscle protein and loss of adipose tissues causing a 8 decrease in body weight. a herbal plant syzygium aromaticum (clove), with the scientific name (l)merrill and perry syn eugenia caryophyllata, also known as “laung ” belongs to the species 9 aromaticum, family myrtacea and genus syzygium. it is widely cultivated in indonesia, sri lanka. syzygium aromaticum is commonly used as local anesthetic in dentistry and as flavoring agent in food. it treats gastrointestinal symptoms and act as ant10 inflammatory, insecticidal, and antioxidant agent. syzygium aromaticum extract acts like insulin in hepatocytes by reducing phosphoenolpyruvate carboxykinase and glucose 6-phosphatase gene 11 expression. the active ingredient in clove is 12 eugenol. it improves gut motility by increasing the secretion of gastro-intestinal enzyme and relieves 13 indigestion. many studies have shown that ethanolic and aqueous extract of syzygium aromaticum improves and increases the weight of diabetic rats. the aim of the present study isto compare the improvement in the weight of the diabetic rats which occurs with both extracts of syzygium aromaticum in comparison with the changes in the weight which occurs with the standard drug insulin. materials and methods present study was carried out in national institute of health sciences islamabad in the department of plant and science from july to december 2011. it was a randomized comparative trial in which forty adult healthy male sprague dawley rats were selected, rats belonging to both genders with weight more than 250 gm and less than 200 gm were not included in the study. for acclimatization the rats were kept at animal house of nih for one week at room temperature of 260c and humidity of 70% with 12 hours dark and light cycle was maintained. rodent pellet containing proteins, fats, minerals, vitamins, fibre and water were available throughout the 14 study. dried syzygium aromaticum buds about 250gms were verified from the national university of science and technology islamabad, department of plant sciences (nust/ncvi/mqh/zrc/001). about 125g of syzygium aromaticum buds were soaked into 50% aqueous solution and the same amount was soaked in 50% ethanolic solution. each was stirred with magnetic stirrer for twenty four hours in the flask at room temperature. after 24 hours the filtrates were separated and kept in a separate flask. this process was repeated thrice , the filtrates were then concentrated under reduced o pressure of 40 c in a rotary evaporator. the prepared extracts was stored at a temp of -20°c to be used for 15 further experiment. after one week of acclimatization, all the experimental groups with fasting blood glucose level between 70-135 mg/dl were induced diabetes with a single intraperitoneal injection of freshly dissolved streptozotocin (60 mg/ kg body weight) in 0.1ml 16 citrate buffer (ph 4.5). forty eight hours after receiving the injection of stz blood samples were taken from the tail vein of experimental animals. quantitative estimation of blood glucose was done by using glucometer and glucose oxidase based test 17 strips. (abbott axsym system, usa). rats with fasting blood glucose above 200mg/dl were selected. the animals were divided into five groups with eight rats in each group. all the rats received rodent pallets and water ad libitum for sixty days in addition 10 ml/kg of 0.9% saline solution was given to first group . second group was (diabetic control. third and fourth group received 750mg/kg body wt of 50% aquoeus and 50% ethanolic extract respectively by gavage. insulin (humulin 70/30) with the dose of 0.6 units/kg body wt , subcutaneously 18 twice daily was adminstered to fifth group. the weight of the diabetic rats was estimated on day zero i.e forty eight hours after receiving streptozotocin and after 2 months of the study at 19 day60. data was analyzed using spss version 20. weight of diabetic rats were expressed in mean ± sd and the results were compared by using one way anova followed by post-hoc tukey test p-value of < 0.05 was considered significant. result in the beginning of the study on day zero there was significant difference in the body weight between all effect of extracts of syzygium aromaticum on weightjiimc 2016 vol. 11, no.1 25 the groups (p<0.001). group i had higher body weight as compared to other groups (p < 0.001). there was insignificant difference in the body weight between all the four diabetic groups (p > 0.05). at the end of the study on day 60 body weight was significantly higher in group-i as compared to all the four diabetic groups (p < 0.001). the weight of group ii diabetic rats was significantly lower than other groups (p < 0.001). group-iii and group v showed significantly lower body weight than group-i and group-iv but higher than group ii . however there was insignificant difference between group-iii and group-v(p=0.941) the rats belonging to group-iv showed significantly higher body weight than other diabetic groups (p < 0.001) but significantly lower than group i. from the above result significant increase in the weight of group iv rats, receiving 750 mg/kg body weight of 50% ethanol extract of syzygium aromaticum was seen. simultaneous administration of insulin (humulin) also resulted in significant (p<0.001) improvement in the weight of group v as compared to the group ii (diabetic control) but this increase in weight is closer to the increase in weight which occurred in group iii diabetic rats . table i shows the mean and standard deviation of weight taken on day zero and day 60. used 50% aqueous and 50% ethanol extract with the dose of 750mg/kg body weight respectively. there is significant reduction in the weight of group ii diabetic rats as compared to control group i. on comparing the improvement in the weight of the group iii, group iv and group v with the diabetic group ii it is observed that syzygium aromaticum ethanol extract causes 8% improvement and the syzygium aromaticum aqueous extract causes 5.6 % increase in the weight which is close to the increase in the weight which occurred with insulin receiving group 5.5% . tajuddin et al., (2003) used 50% 20 ethanol extract of clove in rats. in our study similar concentration of ethanolic extract showed more impovement in the weight as compared to aquoeous extract and insulin. namasivayam et al., (2008) conducted a study on the genus syzygium and concluded that the aqueous extract of the syzygium also possess the potential of improving the weight of 21 diabetic rats. singh et al., (2007) studied the effect of ethanolic extract of syzygium on diabetic rats and concluded that ethanolic extract lowered the blood 22 glucose and improved the weight of diabetic rats. in diabetes mellitus free radicles and reactive oxygen specie are produced which damages nucleic acid, carbohydrates , proteins and lipids, this may lead to 23 weight loss. musabayane et. al.,(2010) on doing the analytical chemistry of constituents of syzygium aromaticum mainly eugenol and olaenic acid suggested that both act as antioxidant and are the major scavenger of free radicals, thus preventing 24 the weight loss. many studies have reported that aqueous and ethanolic extracts of plants causes glucose lowering effect by activation of pancreatic beta cells , improving its granulation, increasing 25 insulin production and have insulin mimetic effect. khan et al.,(2006) in one of his study on the syzygium aromaticum suggested that this herbal plant has the potential to stimulate the functioning cells of islet of langerhans and causes regeneration of pancreatic 26 beta cells thus increasing insulin release. laizuman et al., (2010) suggested that improvement in the weight of diabetic rats by syzygium can be by either due to release of insulin from pancreatic beta cell or from the bound form and insulin also inhibit gluconeogenesis from proteins thus preventing loss 27 of proteins and maintan body weight. insulin causes increase food intake and retains energy leading to table i: body weight of all study groups on day zero and day 60 all values have been expressed as mean±sd ** = highly significant * = significant from group-i ¶ = significant from group-ii ¥ = significant from group-iii € = significant from group-iv π = significant from group-v discussion in the present study the results have proved that syzygium aromaticum ethanolic extract improves the weight of diabetic rats. in this study the effect of differents extracts of syzygium aromaticum on the weight of streptozotocin induced diabetic rats is seen and the results are compared with the standard drug insulin at a dose of 0.6 units/kg body weight. we effect of extracts of syzygium aromaticum on weightjiimc 2016 vol. 11, no.1 26 the improvement in the weight of diabetic rats. willing et al.,(1990) suggested that insulin stimulates daily food intake and body weight gain in diabetic 28 rats. so we can say that improvement in the weight of diabetic rats by syzygium aromaticum can be due to the stimulation of functioning pancreatic beta cells, to increase the release of insulin or this may be due to regeneration of beta cells. admin, (2013) suggested that syzygium aromaticum activates digestive enzymes , aid in digestion , smoothens the lining of digestive tract and has myorelaxant action. he further reported that high amount of carbohydrates, protein , dietary fibers, multivitamins and minerals are present in clove which maintain 29 the weight of body. lester et al., (2004) suggested that eugenol the main constituent of syzygium causes stimulation of gastric secretion and improves 30 digestion. in our study the ethanolic extract caused more improvement in the weight than the aqueous extract we can say that this effect is probably because the constituents of the syzygium aromaticum are more soluble in the ethanol solution than the aqueous solution . san et al., (1995) suggested that syzygium aromaticum compounds 31 have more solubility in the ethanolic solution . we can say in our study that the possible mechanism by which ethanol extract improves the weight of diabetic rats is that the free radical scavenging property of ethanolic extract is more than aqueous or it may be due the presence of antioxidant active principles in the ethanol extract in excess amount than aqueous extract. this improvement in weight can also be due to the induction of insulin secreting pancreatic β cells of islets of langerhan or it may be due to enhanced transport of blood glucose to the peripheral tissue and proper glucose utilization by 32 diabetic rats. the antispasmodic and myorelaxant property of the compounds of syzygium aromaticum can also lead to the improvement in the body 33 weight. conclusion our results from this study indicate that 50% ethanolic extract of syzygium aromaticum at a dose of 750 mg/kg body weight has more potential to improve the weight of diabetic rats than the 50% aqueous extract of the same dose and the drug insulin because of its insulin mimetic action , free radical scavenging property and the increased solubility and 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t s o f l a n g e r h a n s b y n i g e l l a s a t i v a i n streptozotocin-induced diabetic rats. tohoku j exp med. 2003; 201: 213-19. 33. wang r, yang b. extraction of essential oils from five cinnamon leaves and identification of their volatile compound compositions. innovative food science and emerging technologies. 2009; 10: 289-92. effect of extracts of syzygium aromaticum on weightjiimc 2016 vol. 11, no.1 28 original�article abstract objective: to explore the factors that enhance and hamper learning of medical nursing students using clinical skill lab. study design: basic qualitative study. place and duration of study: this study was carried out from 03 april to 29 september 2017, in clinical skill lab of fazaia medical college, islamabad affiliated hospital. materials and methods: one to one semi structured interviews was conducted and qualitative data was collected. literature search was done extensively before formulating the interview questionnaire. this was followed by expert validation. audio recording was done of all the interviews, the same were transcribed, coded and analyzed both manually and by importing it into pro 11 version of nvivo; this was followed by thematic analysis. results: twenty participants, 6 males and 14 females participated in the study, with minimum of 6 to 9 months training in csl. all the participants confirmed that the training in the csl increased their motivation and confidence, a large majority agreed that their teachers/facilitators demonstrated the skills in a professional manner, the facilitators were vigilant during the teaching sessions and observed the trainees while they practiced, most of the trainees acknowledged that they had completed their training utilizing all the equipment. the participants appreciated the learning in csl, the knowledge, skills, experiences and confidence, they acquired. however they mentioned the shortage of space, time given and equipment provided for their training. conclusion: all the csl trainees strongly endorsed this method of hands on training, they narrated that inspirations, motivation, training and guidance provided by the instructors enhanced their learning in csl, while shortage of time for practice, space in csl and manikins hampered their learning. key words: clinical skill lab, confidence, manikins, motivation. presentations to help the health care students to learn and understand ranging domains of 1,2 knowledge, skills and attitudes. however various medical careers are adopting new teaching and learning methodologies, these new teaching modalities have also been adopted and the change has been initiated for better learning and 3 contributing towards patient care. the health care policy makers have overwhelmingly advocated the incorporation of quality initiatives in learning and teaching that would ensure all aspects of patient 4 safety. they stress the need to acquire adequate level of skill expertise and understanding of its application before trainees manage the real patients. the policy managers have also emphasized and promoted the use of simulation based training to address the issues 5 of patient safety. the students of this era are trained from their school days using innovative teaching methodologies and technologies. introduction in health sciences didactic teaching and training had been traditional. this is intended to acquire as much knowledge as possible. many medical institutes in south asia are still following the traditional teaching. regional medical institutions commonly adopt d e m o n s t ra t i o n s , va r i o u s t y p e s o f l e c t u re learning in clinical skill lab: the users' perspective 1 2 3 rizwan hashim , raheela yasmeen , salman ali correspondence: dr. rizwan hashim professor chemical pathology department of pathology fazaia medical college air university, islamabad email: riznajmi20011@hotmail.com 1 3 department of pathology/ pediatrics fazaia medical college air university, islamabad 2 department of health and medical sciences islamic international medical college riphah international university, islamabad funding source: nil; conflict of interest: nil received: november 07, 2018; revised: november 22, 2018 accepted: november 24, 2018 learning in clinical skill lab jiimc 2018 vol. 13, no.4 215 therefore, once they enter the health care careers h e re to o a d o p t i o n o f u p g ra d e d te a c h i n g methodologies and utilization of latest technologies is the way forward to bridge the gap of learning the new procedures and complex skills that need to be learnt by the health care providers for better patient 6 outcome. the development of csl is one of the many initiatives that have been taken by the health care trainers to address the issues on innovative 7,8 technologies for learning and patient safety. the development of csl is one of the many initiatives that have been taken by the trainers. hence, to a d d r e s s t h e p a t i e n t c o n c e r n s , e f f e c t i v e methodologies for teaching that provide appropriate equipment and environment for learning are genuine and compelling reasons for the training institutes to establish clinical skill labs (csl). however, despite provision of some csl, there is dearth of literature in the local context that had explored the factors that hamper or enhance the 9 learning of students using csl. materials and methods this basic qualitative study was conducted in a csl of hospital affiliated with fazaia medical college, islamabad from 03 april to 29 september, 2017. this center provides the training to nursing (male and female) students. the nursing course total duration is 4 years. the nursing students were trained for 6 to 9 months in csl. they learn various techniques and procedures during their training in csl. at the end of the course the trainees are evaluated before they are allowed to transfer their skills to real patients. twenty medical nursing students; 6 male and 14 female, consented to participate in the study. the csl trainees were informed regarding their voluntary participation. all trainees gave their informed written consent, the undertaking and assurance was given to participants regarding securities of information, anonymity and confidentiality. the trainees were also informed that there will be no reward or payment given to them for their participation. the permission from institutional review board (irb) of fazaia medical college was taken. only those nursing students were included in the study who completed minimum of 6 months training in the csl. all participants of the study had one to one semi structured interview with the researcher. extensive literature search was done before formulating the questionnaire, the main areas of interest that were pertinent to this research were identified and the questions were framed accordingly. the areas were explored in further details to find the answer to the study research question. to enhance the research quality and give sequence to the questions, before the real interviews were carried out, the validation of questionnaire was done, using the questions that had to be used. pilot interviews were conducted with 3 nursing students. the research question and the tools were aligned, followed by deductive coding and thematic analysis. triangulation was done by taking field notes, member checking and interviewee comparisons. the analysis of qualitative data was done by using nvivo pro 11 software. results the total number of participants who volunteered for the study was 20, (6 males and 14 females). all the participants had undergone a training of minimum 6 to 9 months in the csl. the training comprised of using plastic models, low and high fidelity equipment/manikins/devices. along their training in csl, the participants also worked in the wards as per schedule of their duties. all the participants confirmed that the training in the csl increased their motivation for learning clinical subjects and procedures, p4: “each individual performs on manikins and our interest increases”. “we get the inspiration from our instructor.” p5: “this experience motivated me in doing my work in a better way,” they also expressed that this training also improved their confidence, p2: “i gained confidence to perform my skills …...” p3: “i felt confident while attending the patients.” p4: “csl builds confidence in us.” they commonly reflected positively regarding the experience and expertise they gained through the training in the csl. they also indicated that csl training was important to them, when they performed various clinical skills on real patients in the wards or the outpatient department. p6: “csl training is much important to treat patients.” p14: “we are taught many clinical skills in csl.” p16: “csl provided a great opportunity to learn many skills and procedures.” the bulk of the participants approved that their teachers/facilitators demonstrated the skills during their teaching sessions and that the trainees learning in clinical skill lab jiimc 2018 vol. 13, no.4 216 developed the desired level of expertise. p3: “our instructor took keen interest to make us learn.” p5: “we practiced on manikins many times.” popularly the opinions of the nursing student matched that the facilitators were vigilant during their teaching sessions, they observed the trainees while they practiced. p3: “the instructor asked us to conduct presentation and practice on manikins.” p6: “my instructor in csl taught me the basics of nursing and helped us to work and practice on manikins…” p9: “i practically performed many procedures in the csl.” masses of the trainees indicated that they had completed the training utilizing all the equipment table i: the responses to the open ended ques�on codes, sub themes, and themes of text analysis by nvivo pro 11 learning in clinical skill lab jiimc 2018 vol. 13, no.4 217 patients were used to practice various skill and p r o c e d u r e s , c o n c e p t o f d e v e l o p i n g c o r e competencies during training of health care professionals, technology enabled teaching devices and manikins, increasing number of students being inducted in each session, now the health professional training institution are gradually moving towards adding the clinical skill lab on their premises. however medical literature is deficient in documenting the factors that enhance or hamper the learning of students using csl. this study explores these factors. due to ever changing demands of society and deeper understanding of various disease mechanisms, e d u c a t o rs h av e b e e n e n c o u n t e r i n g m a ny educational challenges and are involved in the dynamic process to reform the curriculum and 10 teaching methodologies. nevertheless the efforts are underway, even in developing countries to bridge the gaps in teaching and learning by providing opportunities for training 11 and practice in safe environment. this is to keep 12 both trainees and the patients away from harm , this is where csl setup provides the concepts of safe environment for practice and learning. this study reflects the responses of those who use the csl for their training. the responses received from the participants in this study revealed that they were happy and excited to attend the sessions of the clinical skill lab. they learnt many procedures like suturing and resuscitation. this was achieved, as a wide range of manikins and equipment were available. the same observations were noted in a study where clinical skill labs provided learning opportunities with provision of various equipment 13,14 that ranged from low to high fidelity. the nursing students also expressed their feelings that they practiced in a safe environment in the csl and they understood that their practice will not harm anyone and it's safe to make mistakes. the same is also reported in literature that csl are venues where training practice of skills and its applications are 11 carried out in environment that is safe. the csl are established to ensure that students are provided with the required and adequate exposure 15 to the clinical cases in a standardized manner. all the participants in this study confirmed that their training in the clinical skill lab enhanced their that was arranged for their learning. p13: “i learnt many procedures that were necessary for a medical nursing student.” p14: “our teacher taught us many clinical skills on manikins.” a few of them acknowledged that they were fearful that something might go wrong in the csl that could damage the equipment. predominantly the trainees replied that they were not fearful and were convinced that they were working in an environment where no harm would occur to any person or equipment while they gained the required experience and practice. p6: “the training helped to work and practice with manikins without hesitation,” it was commonly expressed by the trainees that they feared they could have hurt the real patients had they not learnt and practiced the procedures in the csl. moreover, many of the students expressed their confidence that they could transfer the skills to the real patients that they had learnt in the csl, p12: “it is impossible to do efficient work in wards without csl training,” mostly, the trainees appreciated the training for v a r i o u s p r o c e d u r e s l i ke c a r d i o p u l m o n a r y resuscitation, how to administer various treatments, manage patients, the basic nursing skills, passing of cannula in the vein, passing catheter in urethra, passing the nasogastric tube, endotracheal tube, to take blood pressure and temperature. p6:“we learnt many procedures like passing of ng tube, cpr….,” p12: “i learned passing of endotracheal tube and how to give enema,” p16: “csl provided great opportunities to learn skills and procedures,” all the trainees also expressed their feelings of gaining confidence with the training of csl and that their work in the wards became more efficient. they felt motivated and excited while getting the training courses and practicing procedures in clinical skill lab. however, majority also expressed their concern regarding the shortage of: space and time for training and the numbers of manikins. p18 “we could not practice on manikins due to shortage of time,” p19 “….. there was shortage of time, less space and less manikins. the summary of codes, sub themes and themes of text analysis are presented in table i. discussion until recently, clinical skills were taught using real patients. due to many concerns like trainees and patients safety, distress to the patients where real learning in clinical skill lab jiimc 2018 vol. 13, no.4 218 motivation for learning the procedures, similar findings were supported by other local studies where clinical skill lab was used for integrating basic sciences subjects and the participants felt motivated 15 using csl. the students using the csl in this study also expressed that they felt more confident by using the csl equipment ,the literature has quoted similar benefits of csl where students using csl gained 16 confidence while using simulation. most of the students expressed their confidence that they shall be able to transfer their learnt skills to real patients. this is an important attribute of learning in csl. various students have reported similar findings where simulation training helped in transferring of 17 skills for clinical application. this study noted that the training in the csl was important to the students as they understood that they would perform the same procedure on real patients, other studies also narrated that simulated settings were more effective for training and long term preservation of the 13,18 skills. the majority of participants in this study agreed that their facilitators demonstrated the skills during their teaching session; this was aimed to make them understand the various steps that were required to carry out different procedures. it was also observed by the participants that the trainers/facilitators were vigilant during their teaching sessions, they observed the training and that the trainees learnt in an organized manner. the literature has also i d e n t i f i e d s i m i l a r f i n d i n g s t h at s k i l l s a re strengthened through time and consolidated 19 through demonstration of skills. the students also shared their views that in csl the facilitators demonstrated them various procedure and skills. the trainers supervised and observed the trainees while they practiced. similar finding have been reported in studies in malaysia where supervisors reflected regarding the trainees development of various competencies during their 2,15 supervisory sessions. majority of the students expressed their confidence that they could transfer the learnt skills to the real patients. research supports this claim of the students that use of simulators was received optimistically both by the educators and students, as 20 it enhanced the transferability of the skills. it is well understood that there will be no replacement for physician and teachers in medical education but technological advancements will provide the facilitators many platforms for designing more creative and interesting training sessions that have better learning outcomes and also improve 21 quality care for patients. educational technologies are taking hold and can 22 provide the experiences never imagined before. as medical educators, we need to encourage our students to practice and enhance their level of expertise in skills in venues that are both safe for students and patient. the study also emphasized that most nursing students perceived that they needed institutional support for csl equipment maintenance and enhancement both in numbers and fidelity, they r e q u i r e d d e d i c a t e d s t a f f f o r t e a c h i n g , demonstrations and managing the csl facilities. they also expressed that the duration of sessions needed to be enhanced to provide more opportunities for practice and learning. our findings are in contrast with literature in a study carried out in saudi arabia where most students had the opinion that adequate staff, institutional support and learning sessions of desired durations were 23,24 provided. overall the trainees expressed their feeling of satisfaction, excitement and happiness regarding their training in csl. conclusion all the trainees in the csl strongly endorsed this method of hands on training. the trainees identified the factors that enhanced their learning, these were: training, guidance, inspiration and motivation for learning provided by the trainers, the variety of manikins models and equipment provided for learning, the personal and equipment safety and safe environment arranged for practice. the factors that hampered their learning were: shortage of space in csl, the allocated time for training and the relatively less number of manikins available for practice. recommendations from the study it is suggested that while designing the course content for training in csl for nursing students their representatives need to be involved to augment the factors that enhance their learning and eradicate the factors that hamper their learning. future study learning in clinical skill lab jiimc 2018 vol. 13, no.4 219 for determining the core factors that enhance or hamper the learning of the nursing students using csl, future studies can be designed to capture the perspective of the users to take preventive and corrective actions for optimizing the learning of csl users. limitation future studies require the increase in sample size of the participants who receive their training in csl and belong to various institutes. conflict of interest no funding was received from anywhere for this project. there is no conflict of interest of any author. references: 1. costa ml, van rensburg l, rushton n. does teaching style matter? a randomised trial of group discussion 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et al. the importance of simulation in nursing education. world j educ technol 2017;9(1):2–7. 14. hope a, garside j, prescott s. rethinking theory and practice: pre-registration student nurses experiences of simulation teaching and learning in the acquisition of clinical skills in preparation for practice. nurse educ today 2011;31(7):711–5. 15. hashim r, qamar k, khan ma, rehman s. role of skill laboratory training in medical education students&rsquo; perspective. j coll physicians surg pak 2016;26(3):195–8. 16. wright a, moss p, dennis dm, harrold m, levy s, furness al. the influence of a full-time , immersive simulation-based clinical placement on physiotherapy student confidence during the transition to clinical practice. adv simul 2018;3(3):1–10. 17. seidman pa, maloney lm, olvet dm, chandran l. preclinical simulation training of medical students results in better procedural skills performance in end of the year three objective structured clinical evaluation assessments. med sci 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traditional curriculum in pakistan. j pak med assoc. 2013; 63(11): 1409–14. learning in clinical skill lab jiimc 2018 vol. 13, no.4 220 original�article abstract objective to find out the frequency of non-adherence in patients with anxiety and depression, receiving : treatment in teaching hospitals. study design: a cross-sectional descriptive study place and duration of study: the study was conducted at pakistan railway hospital, rawalpindi and riphah st st international hospital, islamabad from1 june 2018 to 31 december 2018. materials and methods: after approval from ethics review committee (erc) and informed consent of the participants, those meeting inclusion criteria; 310 patients (n=310) were included in this study. out of these 151(n=151) patients were suffering from depression, while 159(n=159) were having anxiety. patients with mixed anxiety and depression were excluded. demographic details (age, gender, education, marital status) were recorded. international classifications of diseases (icd-10) diagnostic guidelines and clinical assessment was used to confirm diagnosis of anxiety and depression. the morisky medication adherence scale (mmas-8) was used to measure levels of non-adherence. data was analyzed using spss-20 and results compiled accordingly. results: out of 151(n=151) depressed patients 81.4% have low to medium adherence to pharmacological treatment, while out of 159(n=159), patients with anxiety 78% have medium to low adherence to prescribed treatment. medication non-adherence was statistically significant in both anxious and depressed patients. conclusion: patients suffering from anxiety and depression show significant nonadherence to pharmacological treatment. key words: anxiety, depression, medication adherence, medication non-adherence. per who, the different components contributing to poor adherence can be classified into five categories: financial issues, treatment related elements, patients-related variables, condition-related 2 elements, and services related elements. non-adherence may be intentional or unintentional 3 behavior. if a patient does not take the medicine because of forgetfulness or lack of access, it is called unintentional. in contrast, if the patient does not follow the prescription because of his or her personal beliefs or perception of medicine, then it is known as 3 intentional non-adherence. with respect to depression, studies have clearly shown that patients who are non-adherent are more likely to have increased severity of the illness, experience more relapses, have greater number of hospital emergency visits/hospitalizations and decreased 4 remission rates. those factors which have consistently been demonstrated to have a negative impact on medication adherence rates in patients suffering from psychiatric disorders include patient related fa c to rs ( yo u n g , u n m a r r ied , m a le) , psychological factors (i.e. poor insight, denial of illness), medication-related factors (i.e. side effects), introduction the who (world health organization) defines adherence as “the extent to which a person's behavior (including medication-taking) corresponds with agreed recommendations from a healthcare 1 provider”. it includes the initiation of the treatment, implementation of the prescribed regime, and 1 continuation of the pharmacotherapy. nonadherence to prescribed medicines is common in patients with chronic diseases, which leads to 2 adverse consequences. the who, in its 2003 report stated that nonadherence may have a far more 2 profound effect on the recovery of the patients. as medication non-adherence in anxiety and depression masood khokhar, shafaq masood, ather muneer, uzzama waheed, farwa aftab, irum bibi correspondence: muhammad masood khokhar professor department of psychiatry islamic international medical college riphah international university, islamabad e-mail: masoodkhokhar2@yahoo.com department of psychiatry islamic international medical college riphah international university, islamabad funding source: nil; conflict of interest: nil received: june 09, 2019; revised: february 06, 2020 accepted: february 26, 2020 medication non-adherence in anxiety and depressionjiimc 2020 vol. 15, no.1 41 and social/environmental factors (i.e. quality of 5,6 therapeutic alliance, family support). non adherence leads to poor clinical outcome, increased morbidity, mortality and wasteful increase in health care expenditure. mental health issues are common around the world. in this respect anxiety disorders account for 16% of the worldwide prevalence of mental disorders, whereas, the prevalence of mood disorders is around 12%. another dimension of this issue is the fact that more severe psychiatric disorders have higher 8 association with non-adherence. a systematic literature review revealed that adherence depended on the type and severity of psychiatric disorders (major depressive disorder: 28– 52%, bipolar disorder 20–50 %, schizophrenia: 20– 72% and 8 anxiety disorder 57%). the importance of adherence was emphasized in another paper which 9 had been widely cited in the literature. thus measuring and monitoring adherence is important 10 for both researchers and clinicians. also, exact assessments of adherence will help to enhance proper medicine use in patients with mental disorders. despite the fact that non-adherence to prescribed treatment leads to excessive morbidity and mortality, this issue has not been given due attention by researcher in pakistan; therefore there is a need to study this domain of clinical services in patients with common mental disorders. the objective of this study was to find the frequency of non-adherence in patients with anxiety and depression receiving psychiatric treatment in hospital setting. materials and methods this cross sectional descriptive study was conducted in pakistan railways hospital, rawalpindi and riphah international hospital, islamabad which are teaching hospitals of islamic international medial college, st rawalpindi. the duration of study was from 1 june st 2018 to 31 december 2018. approval was obtained from the ethics review committee (erc) of islamic international medical college; riphah international university and informed consent was obtained from the participants. data collection was done by the teaching faculty with help of final year medical students and students of psychology, who were undergoing internship training and were working under direct supervision of the teaching faculty. by using convenient sampling technique, three hundred and ten (n=310) patients from both genders between ages 18-60 years, meeting the inclusion criteria were invited to participate in the study. out of these 151(n=151) patients were suffering from depression, while 159(n=159) were having anxiety. patients with mixed anxiety and depressive disorders, other psychiatric disorders or having comorbidities were excluded. demographic details (age, gender, education, marital status) were recorded and international classifications of diseases (icd-10) diagnostic guidelines and clinical assessment, was used to confirm diagnosis of anxiety and depression. after 3-6 months of out-patient follow up, the morisky medication adherence scale (mmas-8) was used to measure levels of nonadherence. data was analyzed using spss-20 and results compiled accordingly. the morisky medication adherence scale (mmas-8) consists of eight items with two types of responses to detect barriers to adherence. items 1-7 are dichotomous (yes/no response), and item 8 is a 4point likert scale (from “never” to “always”) to measure factors such as forgetfulness. mmas-8 has been validated with good sensitivity and specificity 11,12 in patients with chronic diseases. hence, it is an acceptable self-report measure for adherence to medication. patients who required assistance were provided guidance to understand the questionnaire. results table: i demographic & clinical variables of depressive pa�ents (n=151) medication non-adherence in anxiety and depressionjiimc 2020 vol. 15, no.1 42 as shown in table i, out of 151 (n=151) depressed patients 68.2% were females and 31.8% were males. similarly 90.8% of the participants were between age 26-60 years and 60.3% have educational level below intermediate. 39.7% have low adherence (mmas score<6), while 41.7% had medium adherence (mmas score <8). as far as severity of depression is concerned 45% had mild depression while 55 % moderate to severe depression. medication adherence decreases. the relationship is highly significant. table: ii demographic & clinical variables of anxiety pa�ents (n=159) as shown in table ii out of 159 (n=159) patients with anxiety disorder, 71.1%) were females and 28.8% were males. similarly 82.4% were between age 2660 years and 65.4% had education below intermediate. 30.8% of the patients had low adherence (mmas score<6), while 47.2% had medium adherence (mmas score <8). out of the total sample 117(73.8%) had mild anxiety while26.4% had moderate to severe anxiety. table: iii pearson correla�on mmas-8 & depression (n= 151) **p<0.01 as shown in tables iii there is a negative relationship between medication adherence and depression. it means as the severity of depression increases the table: iv pearson correla�on mmas-8 & anxiety (n= 159) *p< 0.05 as shown in tables iv there is a statistically significant negative relationship between medication adherence and anxiety. as the anxiety increases the medication adherence decreases. discussion the current study shows that 81.4% of depressed patients have low adherence to pharmacological treatment, while 78% of patients with anxiety also have low adherence to prescribed treatment. moreover medication adherence has a negative correlation with anxiety and depression severity, which means when the level of anxiety and depression increases the adherence to medication decreases. the exact cause of this association cannot be pin pointed because of the cross-sectional study design; however, the lack of interest and motivation and poor concentration in depressed patients may be a contributory factor. similarly fear of medication and possible side effects or dependence may be a reason for non-adherence in patients with anxiety. a study carried out in pakistani population showed that out of 100 psychiatric patients receiving outdoor treatment 18(18%) were non-compliant. this study defined non-compliance as attending the opd after a lapse of 15 days or more from the recommended date of follow up visit. the main reasons for noncompliance to follow-up treatment were denial of 13 disease and non-affordability of treatment. the sample size in this study was small and no particular diagnosis was mentioned, which meant that patients with all mental disorders were included in that study. in our study only patients with anxiety and depression were included and frequency of low adherence to medication was quite significant as already mentioned. previous studies on this subject had also shown that non-adherence was common in 14-18 patients with depression. in a study on nonadherence in 367 males patients with major depressive disorder receiving outpatients care, 63.1% of the participants stopped taking medication non-adherence in anxiety and depressionjiimc 2020 vol. 15, no.1 43 frequency/percentage pearson correla�on 14 medications without consulting their physicians. however, this study was based upon a retrospective chart-review, while our study involved direct interaction with patients and we measured nonadherence with a valid and reliable scale. in a systematic review of thirty-two observational studies, it is found that white ethnicity and older age is associated with better adherence to treatment, while severity of depression does not play an 15 important role in predicting compliance. however, this review was limited to studies in the english and spanish populations. in another cross sectional study involving 103 psychiatric patients, 72(69.9%) 16 patients were non-adherent. in this study the sample size was small and different measurement tools other than mmas-8 were used for adherence. patients with a variety of psychiatric diagnosis were included. in yet another qualitative study, 30 patients with depression were interviewed in depth and it was found that the factors specific to patients and side effects of antidepressants were the main 17 contributory factors towards non-adherence. in contrast, our study has a descriptive design and depression severity is inversely related to nonadherence. in a recent study depression with recurrent episodes, decrease or loss of interest and atypical symptoms were found to be risk factors for non-adherence, whereas selective noradrenaline reuptake inhibitor (snri) treated first episode was a 18 protective factor against non-adherence. the authors in this study did not mention any association with severity of depression. our study is focused on anxiety and depression severity and their relationship with non-adherence, as there was no local evidence available on this subject. however, both studies indicate that clinical characteristics of the patient may play an important role in medication non-adherence. in another recent study stressed that the management of major psychiatric disorders 19 is highly affected by medication non-adherence. the authors recommended an integrated approach to reduce the burden of medication non-adherence and stressed that doctors should pay much more attention on educating patients with risk of nonadherence. the above mentioned discussion clearly shows that non-adherence is a major issue in psychiatric patients, particularly those suffering from depression. in pakistan, there is a knowledge gap regarding various demographic and clinical variables involved in treatment non-adherence in psychiatric patients. studies in pakistan have found that the prevalence of anxiety and depression ranges from 22 20 -60%. in order to deliver effective treatment, we need to fully understand the issue of non-adherence by generating local evidence on this subject. in clinical practice it is a common observation that an empathetic relationship and medication related education of patients can improve adherence to treatment. however, we need to carry out more studies in order to understand and manage nonadherence related factors in patients with anxiety and depression. conclusion patients with anxiety and depression show significant nonadherence to treatment. this nonadherence is highly significant in patients with depression, and its severity shows an inverse relationship with adherence. further studies are needed to clarify the role of psycho-education, therapeutic alliance and the role of socio-cultural factors in non-adherence to treatment in patients with anxiety and depression. by generating local evidence and better understanding on medication non-adherence, the clinician will be better able to identify this issue and prevent its adverse consequences on patients and health care delivery. references 1. sabaté e. adherence to long-term therapies: evidence for action. geneva, switzerland: world health organization; 2003. 2. brown m. t., bussell j. k. medication adherence: who cares? mayo clinic proceedings. 2011; 86(4):304–14. 3. unni ej, farris kb. unintentional non-adherence and belief in medicines in older adults. patient educ couns. 2011; 83(2):265-68. 4. ho sc, chong hy, chaiyakunapruk n, tangiisuran b, jacob sa. clinical and economic impact of non-adherence to antidepressants in major depressive disorder: a systematic review. j affect disord. 2016. 15(193):1-10. 5. hurley f. cramer j. spilker b. patient compliance in medical practice and clinical trials. raven press; 1991. statistical approach to subgroup analyses: patient compliance data and clinical outcomes; pp. 243–250. 6. osterberg l, blaschke t. adherence to medication. new engl j med. 2005;353(5):487–97 7. burkhart pv, sabaté e. adherence to long-term therapies: evidence for action. j nurs scholarsh. 2003;35(3):207 8. dimatteo m. r, giordani p. j, lepper h. s, croghan t. w. medication non-adherence in anxiety and depressionjiimc 2020 vol. 15, no.1 44 patient adherence and medical treatment outcomes: a meta-analysis. medical care. 2002; 40(9):794–811. 9. lindenfeld j, jessup m. 'drugs don't work in patients who don't take them' (c. everett koop, md, us surgeon general, 1985). eur j heart fail. 2017 nov; 19(11):1412-13. 10. farmer k c. methods for measuring and monitoring medication regimen adherence in clinical trials and clinical practice. clinical therapeutics. 1999;21(6):1074–90 11. tan x., patel i, chang j review of the four item morisky medication adherence scale (mmas-4) and eight item morisky medication adherence scale (mmas-8) innovations in pharmacy. 2014; 5(3):165. 12. morisky d. e, green l. w, levine d. m. concurrent and predictive validity of a self-reported measure of medication adherence. medical care. 1986; 24(1):67–74. 13. rao mh, soomro ibm. non-compliance awareness and attitude of psychiatric patients regarding outpatient followup at civil hospital, karachi. j dow uni health sci. 2008; 2(1):36-40. 14. sawada n, uchida h, suzuki t, watanabe k, kikuchi t, handa t, et al. persistence and compliance to antidepressant treatment in patients with depression: a chart review. bmc psychiatry. 2009;9:38. 15. rivero-santana a, perestelo-perez l, pérez-ramos j, serrano-aguilar p, de las cuevas c. sociodemographic and clinical predictors of compliance with antidepressants for depressive disorders: systematic review of observational studies. patient prefer adherence. 2013; 7:151–69 16. alekhya p, sriharsha m, priya darsini t, reddy s, venkata ramudu r. treatment and disease related factors affecting non-adherence among patients on long term therapy of antidepressants. j depress anxiety. 2015; 4(2)18. 17. ho sc, jacob sa, tangiisuran b. barriers and facilitators of adherence to antidepressants among outpatients with major depressive disorder: a qualitative study. plos one 2017; 12(6):4-11. 18. zhou q, wu zg, wang y, et al. clinical characteristics associated with therapeutic nonadherence of the patients with major depressive disorder: a report on the national survey on symptomatology of depression in china. cns neurosci ther. 2019; 25(2):215-22. 19. semahegn a, torpey k, manu a, assefa n, tesfaye g, ankomah a. psychotropic medication non-adherence and associated factors among adult patients with major psychiatric disorders: a protocol for a systematic review. . syst rev. 2018; 7(1):3-10. 20. ahmed, b, enam, s, iqbal, z, murtaza, g, bashir, s. depression and anxiety: a snapshot of the situation in pakistan. international journal of neuroscience and behavioral science. 2016; 4(2): 32-36. medication non-adherence in anxiety and depressionjiimc 2020 vol. 15, no.1 45 jiimc june 2016.cdr original article abstract objectives: ! to study the frequency of diabetes in patients with active pulmonary tuberculosis. ! to determine the impact of diabetes on radiological findings in tuberculosis. ! to study the association of atypical radiological manifestations with glycemic control in diabetes associated tuberculosis. study design: a descriptive study. place and duration of study: the study was conducted in medical department of pakistan air force hospital mianwali from august 2013 to july 2014. materials and methods: seventy five new cases (18 years and above) of active pulmonary tuberculosis were selected by non-consecutive convenient sampling. all patients received standard anti-tuberculous treatment (att) for six months. fasting blood glucose and chest x-ray were performed in all patients. glycosylated hemoglobin (hba1c levels) were checked to assess the glycemic control in diabetic patients. radiographic features of the two groups; diabetic vs. non diabetic and within diabetic population; poor vs. optimal glycemic control, were then compared. results: thirty three (33/75 or 44%) patients were found to be diabetic. radiological changes were more frequently atypical in diabetic group as compared to non diabetic population (21/33 or 63.6% vs. 8/42 or 19%). nine of the 12 diabetic patients with poor glycemic control i.e. hba1c levels >7% had cavitations, lower zone involvement and bilateral changes as compared to 11/21 patients with optimal glucose control i.e. hba1c <7% and the difference was significant (9/12 or75% vs.11 /21 or 52.3%, p value <0.001). conclusion: a high index of suspicion for diagnosis of diabetes is required for tb patients with atypical radiological manifestations. poor glycemic control is related with atypical findings on chest x-ray in pulmonary tuberculosis. key words: atypical chest x-ray, diabetes, glycemic control, pulmonary tuberculosis. (tb-hiv) co-epidemic of sub-saharan africa in 80's and 90's, as one disease seems to fuel the other in 2 the same manner. a recent study on association between tuberculosis and diabetes in the developing region of africa has shown that countries with rising diabetes prevalence have depicted a simultaneous 3 increase in the prevalence of tuberculosis. there is now sufficient evidence to suggest that tb patients with diabetes are more likely to experience an aggressive course of disease with more chances of treatment failure, multi-drug resistant tb (mdr-tb), 4 relapse and death. literature review reveals that diabetes frequently alters the radiological 5 manifestations of pulmonary tuberculosis. atypical findings are common with lower zone involvement, cavitations, multiple and/or bilateral lesions which are often misdiagnosed as pneumonia, lung abscess etc with delay in treatment. recently it has also been suggested that poor glycemic control may be linked 6 to atypical radiological findings in such patients. introduction the re-emerging global pandemics of type 2 diabetes mellitus (dm) and tuberculosis (tb) is a serious threat to the attainment of millennium development goals (mdg's) for tuberculosis especially in the low and middle income countries of 1 the world. the looming co-epidemic of tuberculosisdiabetes (tb-dm) in south asia is being compared to the tuberculosishuman immunodeficiency virus effect of glycemic control on radiological manifestations of pulmonary tuberculosis –a hospital based study 1 2 3 shamaila burney , omer awwab khan , saerah iffat zafar correspondence: dr. shamaila burney assistant professor, medicine islamic international medical college riphah international university, islamabad e-mail: drshamailaburney@hotmail.com 1,2 department of medicine islamic international medical college riphah international university, islamabad 3 department of radiology pakistan air force hospital, islamabad funding source: nil ; conflict of interest: nil received: feb 16, 2016; revised: apr 07, 2016; accepted: may 09, 2016 jiimc 2016 vol. 11, no.2 diabetes and pulmonary tuberculosis 52 despite such conclusive evidence, unfortunately no separate guidelines/protocols for treatment of tuberculosis patients with diabetes currently exist. world health organization (who) and the international union against tuberculosis and lung disease in 2011 issued a global recommendation of bidirectional screening for early detection and 7 management of both diseases. countries like china and india have already incorporated these recommendations into their tb-dm screening programs. however, in pakistan, a country with one of the highest figures for both tuberculosis and diabetes, serious gaps between recommendations (including national tb guidelines) and current practices still exist. present study was conducted to highlight the association of tb and dm and to investigate the impact of glycemic control on radiological manifestations of patients with coexistent tb and dm in our hospital setting. published data on this association is still scarce. to our knowledge, no such study has been conducted in pakistan so far. materials and methods this descriptive study was conducted in the medical department of pakistan air force hospital mianwali from august 2013 to july 2014. the study was initiated after the approval of study proposal by the hospital ethics committee after incorporating its suggestions to protect the patient's confidentiality. seventy five new cases (18 years and above) of active pulmonary tuberculosis were selected by non consecutive convenient sampling after informed consent. exclusion criteria included relapse cases, patients with extra pulmonary tb, type 1 diabetes, i m p a i r e d fa s t i n g g l u c o s e , p r e g n a n c y a n d e n d o c r i n o l o g i c a l d i s o r d e rs . pa t i e n t s w i t h immunocompromised states/comorbids such as hiv, chronic renal failure, cirrhosis or malignancies that could cause possible stress hyperglycemia and hence act as confounders were not included. similarly patients taking drugs known to cause hyperglycemia such as steroids, beta agonists and thiazide diuretics were also excluded from the study. active pulmonary tb was diagnosed when a patient with clinical features of tb met at least one of the following three criteria; a positive sputum smear, a positive sputum 8 culture, or a positive chest radiograph. patients were divided into two groups; diabetes-associated tb patients (dmtb group) and non diabetic tb only patients (tb-only group). all patients received 4 drugs standard att in the initiation phase and 2 drugs in the continuation phase and treatment was monitored by parameters defined by the national tb 8 guidelines. screening for diabetes mellitus was done by twice measured fasting blood glucose levels. diagnostic criteria for diabetes followed the who 9 guidelines; > 126 mg/dl fasting plasma glucose. att transiently elevates glucose levels, therefore samples for blood glucose were taken before beginning att and repeated at 12 weeks. hba1c levels were performed in all diabetic patients (previously known or newly diagnosed on screening) to determine the level of glycemic control. dmtb patients were then further subdivided into two groups. patients with hba1c levels > 7% were considered as having poorly controlled diabetes while patients with hba1c < 7% had optimal 10 glycemic control. chest x-ray findings that were c o n s i d e r e d a t y p i c a l i n c l u d e d l o w e r zo n e involvement, bilateral involvement, large cavities 5,11 (>2cm) and/ or multiple cavitations. radiographic features of the two groups with poor and optimal glycemic control were then compared. data was analyzed using ibm spss 20. categorical data was calculated as frequencies and percentages. mean and standard deviation was calculated for age. the chi-square test was used to test the statistical significance of categorical variables such as hba1c levels and atypical chest x-ray and p-value of less than 0.05 was considered significant at 95% confidence interval. results there were 35 male and 40 female patients. only 6% were below 40 years of age while 26% patients were 70 years or older. out of 75 new cases of pulmonary tuberculosis, 33 (44%) were found to be diabetic and constituted the tbdm group while 42/75 (56%) were non diabetic and constituted tb-only group. in the tbdm group, 20/33 (60.6%) were known diabetics and 13/33 (39.3%) were newly diagnosed detected on screening. poorly controlled diabetes (hba1c >7%) was observed in 12/33 (36.3%) diabetic patients and required insulin for sugar control. in 21/33 (63.6%) patients, hba1c was < 7% and g l yc e m i c c o n t ro l wa s a c h i e v e d w i t h o ra l hypoglycemic agents. in none of the 33 diabetic 53 jiimc 2016 vol. 11, no.2 diabetes and pulmonary tuberculosis patients blood sugar was controlled with diet alone. radiological changes were more frequently atypical in dmtb group as compared to tb-only group (21/33 or 63.6% vs. 8/42 or 19%). (table i). radiological manifestations and poor glycemic control as dmtb patients with hba1c levels >7% were more likely to have lower zone involvement, cavitations and/or bilateral changes as compared to non diabetic tb patients (76.9% vs. 55%, p value <0.001). literature review reveals that screening for dm in tb patients yields high prevalence of dm ranging from 1.9% to 35% depending on the geographical 12 location. in the present study, 44% of tb patients had co existing dm, a rate more than thrice the prevalence of diabetes in pakistan (12.1% in males 13 and 9.8% in females). the frequency of newly diagnosed diabetes was 39.3% in our study which is 14,15,16 also higher than most previous studies and highlights the significance of screening for diabetes in all patients with tuberculosis. pulmonary tb has a propensity to affect upper lobes of the lungs. it is still a matter of debate whether or not the presence of diabetes alters the radiological 5,17 manifestations of ptb. previously authors have reported that chest x ray findings are frequently atypical in tb patients having diabetes; with lower zone involvement, cavitations, bilateral changes and 18,5 multi lobe involvement. the study by parezguzmann was most striking in this aspect who determined that diabetes was the most significant 5 factor in development of lower lung lesions. in one of the more recent studies conducted, patel et al also reported a high frequency of atypical chest x-rays in 19 patients with coexistent tb and dm. however other 17 authors do not report any significant difference. literature search revealed that data regarding association of radiological manifestations with glycemic control is scarce. earlier, park et al suggested that poor glycemic control was linked to a 18 higher incidence of cavitatory lesions. in a recently conducted indian study, avathu et al studied 70 diabetic patients with ptb and concluded that atypical changes were more frequently seen in diabetic patients with hba1c levels >7% and poor glycemic control as compared to those with optimal 10 control. a most recent large scale study conducted in taiwan also reported significant correlation between poor glycemic control and atypical 6 radiological features. the findings of the present study are thus in agreement with these few studies. tuberculosis was a deadly threat to diabetic patients table i: frequency of atypical chest x-ray in diabe�c and non-diabe�c tb pa�ents (n=75) table ii: atypical chest x-ray in tb pa�ents with poor glycemic control the presence of atypical changes was associated with poor glycemic control and insulin use. nine of the 12 diabetic patients with poor glycemic control (hba1c levels >7%) had cavitations, lower zone involvement and/or bilateral changes as compared to 11/21 patients with optimal glucose control (hba1c <7%), (table ii). the difference was statistically significant (9/12 or75% vs.11 /21 or 52.3%, p value<0.001). discussion in our study, 63.6% of patients in tbdm group were seen to have atypical radiological manifestations as compared to 19% patients in the tb-only group. glycemic control is an important aspect of tb management and may have an effect on radiological manifestations. an attempt was thus made to correlate the two in the present study. interestingly, a significant association existed between atypical 54 jiimc 2016 vol. 11, no.2 diabetes and pulmonary tuberculosis in the pre-insulin era. poor diabetes control possibly exacerbated by co-existent tuberculosis affects innate cytokine responses. suboptimal glycemic control not only predisposes to tuberculosis, it often leads to poor att response. this could result in higher chances of complications with treatment failure, relapse and case fatality. anti tuberculous drugs and oral hypoglycemic agents have complex interactions with one another and diabetes patients 2 may have lower concentrations of anti-tb drugs. while drugs such as rifampicin are known to cause transient hyperglycemia, some of the newer oral hypoglycemic agents such as gliptins can lower the e f f i c a c y o f at t. re s u l t a n t t b a s s o c i a t e d hyperglycemia often worsens the glycemic control of 20 diabetes necessitating timely switching to insulin. in the present study, 36.3% of the patients with tb had uncontrolled hyperglycemia (hba1c >7%), and required insulin for sugar control. although we did not have a comparison group of diabetes-only patients, it is noteworthy that in none of the tbdm patients blood sugar could be controlled with diet alone. a significant number of newly diagnosed diabetics also had poorly controlled diabetes. previously, a similar study from lahore (pakistan) had determined the frequency of diabetes in tb patients as 25.9% and that of the newly diagnosed cases as 14 5.69%. balakrishnan et al have reported the frequency dm in tb as 44% in india, a country with s i m i l a r d e m o g r a p h i c a n d s o c i o e c o n o m i c 15 background. the incidence of newly diagnosed diabetes cases in their study was 21%. paf hospital mianwali is one of the peripheral hospitals in mianwali district catering for the needs of all the patients affiliated with pakistan armed forces from district mianwali, chakwal, khushab, di khan, layyah and bhakkar. moreover it has a high turnover of civilian patients. the limitations of our study include a relatively small sample size due to limitation of resources and a high number of patients being lost to follow up by virtue of peripheral location of our hospital. in addition we also applied stringent exclusion criteria such as exclusion of patients with impaired fasting glucose and including only patients who were followed up until complete duration of treatment. despite these limitations, our study not only augments previous local studies in terms of a high occurrence of dm in patients with pulmonary tb, it also highlights other clinical aspects such as maintaining strict glycemic control with frequent monitoring and possible switching to insulin, when treating tb patients with coexisting dm. further large scale studies from other regions of pakistan are needed to explore these aspects in detail. similarly standards and protocols have to be developed at hospitals and national level for diagnosis and treatment strategies for management of diabetes mellitus in newly diagnosed cases of tuberculosis. conclusion we conclude that optimal glycemic control is an integral component of tb treatment. a high index of suspicion for diabetes is required for tb patients with atypical radiological manifestations. active screening for diabetes in all patients with tuberculosis can be a more cost-effective way of controlling and preventing both diabetes and tuberculosis. references 1. stevenson cr, farouhi ng, roglic g, williams bg, lauer ja, dye c, et al. diabetes and tuberculosis: the impact of diabetes epidemic on tuberculosis incidence. bmc public health 2007; 7: 234. 2. ruslami r, aarnoutse re, alisjahbana b, van der ven aj, van crevel r. implications of the global increase of diabetes for tuberculosis control and patient care. trop med int health. 2010; 15: 1289-99. 3. goldhaber-fiebert jd, jeon cy, cohen t, murray mb. diabetes mellitus and tuberculosis in countries with high tuberculosis burdens: individual risks and social determinants. intl j epidemiol 2011; 40: 417-28. 4. baker ma, harries ad, jeon cy, hart je, kapur a, lonnroth k, et al. the impact of diabetes on tuberculosis treatment outcomes: a systematic review. bmc med. 2011; 9: 81. 5. pérez-guzman c, torres-cruz a, villarreal-velarde h, salazar-lezama ma, vargas mh. atypical radiological images of pulmonary tuberculosis in 192 diabetic patients: a comparative study. int j tuberc lung dis 2001; 5: 455-61. 6. chiang c-y, lee j-j, chien s-t, enarson da, chang y-c, chen y t, e t a l . g l yc e m i c c o nt ro l a n d r a d i o g ra p h i c manifestations of tuberculosis in diabetic patients. plos one 2014; 9: e93397. 7. world health organization/international union against tuberculosis and lung disease. provisional collaborative framework for care and control of tuberculosis and d i a b e t e s . w h o / h t m / t b / 2 0 1 1 . 1 5 . g e n e v a , switzerland:who,2011.http://whqlibdoc.who.int/publicat ions/2011/9789241502252_eng.pdfaccessed august 2013. 8. national guidelines for the control of tuberculosis in pakistan.http://ntp.gov.pk/uploads/national_guidelin 55 jiimc 2016 vol. 11, no.2 diabetes and pulmonary tuberculosis e_on_tb_case_management_rev_jan_2015.pdf 9. world health organization. definition and diagnosis of diabetes mellitus and intermediate hyperglycemia: report of a who/idf consultation. geneva, switzerland: who, 2006.http://www.idf.org/webdata/docs/who_idf_defini tion_diagnosis_of_diabetes.pdf accessed august 2013. 10. avuthus s, mahishale v, patil b, eti a. glycemic control and radiographic manifestations of pulmonary tuberculosis in patients with type 2 diabetes mellitus. sub-saharan afr j med. 2015; 2: 5-9. 11. sen t, joshi sr, udwadia zf. tuberculosis and diabetes mellitus: merging epidemics. j assoc physicians india. 2009; 57: 399-404. 12. jeon cy, harries ad, baker ma, hart je, kapur a, lonnroth k, et al. bi-directional screening for tuberculosis and diabetes: a systematic review. tropical medicine and international health. 2010; 15: 1300-14. 13. shera as, basit a, fawwad a, hakeem r, ahmedani my, hydrie mz, et al. pakistan national diabetes survey: prevalence of glucose intolerance and associated factors in the punjab province of pakistan. prim care diabetes. 2010; 4: 79-83. 14. usmani ra, nasir mi, wazir s, pervaiz z, zahra t, akhtar m etal. diabetes mellitus among tuberculosis patients in a tertiary care hospital of lahore. j ayub med coll abbottabad. 2014; 26: 61-3. 15. balakrishnan s, vijayan s, nair s, subramoniapillai j, mrithyunjayan s, wilsonn, et al . high diabetes prevalence among tuberculosis cases in kerala, india. plos one. 2012; 7: e46502. 16. ogbera ao, kapur a, razzaq ha, harries ad, ramaiya k, adeleye o, et al. clinical profile of diabetes mellitus in tuberculosis.bmj open diabetes res care. 2015;3: e000112. 17. bacakoglu f, basoglu ok, cok g, sayiner a, ates m. pulmonary tuberculosis in patients with diabetes mellitus. respiration. 2001; 68: 595-600. 18. park sw, shin jw, kim jy, park iw, choi bw, choi jc, et al. the effect of diabetic control status on the clinical features of pulmonary tuberculosis. eur j clin microbiol infect dis. 2012; 31: 1305-10. 19. patel ak, rami kc, ghanchi fd. radiological presentation of patients of pulmonary tuberculosis with diabetes mellitus. lung india. 2011; 28: 70. 20. niazi ak, kalra s. diabetes and tuberculosis: a review of the role of optimal glycemic control. j diabetesmetab disord. 2012; 11: 28. 56 jiimc 2016 vol. 11, no.2 diabetes and pulmonary tuberculosis case�report endocrown is a conservative restorative option for extensively damaged posterior teeth. the primary objective is to attain a bonded biomimetic reconstruction, i.e., to reconstruct a tooth without any excessive preparation for post or core. the clinical procedure is less complex for both dentist and patient as compared to conventional crowns with post and core. this article highlights case report of a mutilated molar treated by composite endocrown after an adequate endodontic treatment with a follow up of 6 months' time span. abstract key words: biomimetic reconstruction, composite, endocrown, endodontic treatment, resin cement. and cementation will be discussed to ease its use. case report a 21 year old male patient visited operative department of islamic international dental hospital, pakistan with a chief complaint of pain in right mandibular molar since last one week. on examination, root canal was initiated 6 months back but was not completed due to unfortunate circumstances. clinically there was an extensive loss of coronal structure, with a decreased interocclusal space between the maxillary and mandibular molar. occlusogingival height of the remaining crown structure was 4mm.the radiographic findings revealed unobstructed canals and remnants of temporary restorative material in chamber along with periodical changes. (fig. 1) endocrown, a monoblock single piece construction, is an effective alternative for endodontically treated molars with severely broken down coronal 3 structure. it helps in maintaining the structural integrity by excluding the steps of post and corecementation, crown lengthening and also reduces the effect of hybrid layer degradation by decreasing 4 the number of adhesive interfaces. the purpose of this article is to present clinical case of a molar restored with composite endocrown after endodontic treatment. the steps of its fabrication the propensity of a root canal treated tooth to fracture due to changes in biomechanics as a result of tissue loss is an argumentative topic for dentists. several factors such as pathologic processes, steps of endodontic procedure and extensive restorations causes the loss of coronal and radicular structure, thus making the tooth more fragile and prone to 1 fracture. in order to prevent these deleterious effects dentists adopt a more conservative approach such as bonded overlay and endocrown instead of full coverage crowns with the aid of recent advances 2 in adhesive techniques. introduction “endocrown” a novel approach for restoration of endodontically treated teeth: a case report 1 2 3 4 5 romana yaqoob , anum moiz , sohaib siddique , huma zahir , usman ibrahim correspondence: dr. romana yaqoob department of dentistry islamic international dental hospital riphah international university, islamabad e-mail: romanayaqoob.ry@gmail.com 1,2,3,4 department of dentistry islamic international dental hospital riphah international university, islamabad 5 department of dentistry ibrahim dental and implants center, rawalpindi funding source: nil; conflict of interest: nil received: february 28, 2019; revised: july 15, 2019 accepted: august 14, 2019 jiimc 2019 vol. 14, no.4 “endocrown” a novel approach fig 1: pre-opera�ve radiographic image a conservative approach of restoring the tooth with an endocrown was decided as the treatment option after explaining and taking patients consent. root canal treatment was done by hi flex rotary system using 2% naocl as an irrigant. triple antibiotic paste was placed as an intracanal medicament for 5 days. obturation was done using hi flex gutta percha points. 217 appropriate shade with a shade guide was chosen. an impression was taken with a polyvinyl siloxane material and sent to the laboratory along with the shade information. an endocrown may be produced from composite or mineral ceramic and, because of the slightly lower cost and ease of repair of any potential damage, the patient chose the composite endocrown. on next visit cementation was done. the tooth was etched with 37% phosphoric acid for 15 seconds, with the application starting from the margins in enamel. afterward preparation was washed and air dried. (fig.5 and fig.6). to embed the endocrown, a self-etch bonding system (espe single bond universal adhesive) was used, which was spread on the surface of preparation and then light-cured. (fig.7). a dual cured composite resin cement (rely x ultimate clickeradhesive resin cement) was spread on the surface of the preparation. the endocrown was seated, and any excess cement was removed and the restoration was polymerized and finished after evaluating any occlusal interference fig 8. ! palatal and lingual cusps can be simply reduced by 2 to 3 mm with a butt-joint. the tooth was prepared to achieve a butt-joint margin.the appropriate reduction of the buccal and lingual walls was done. the lateral retentions of the pulp chamber walls and the orifices were sealed with two-step adhesive and flowable resin composite. the cervical margins were leveled with a tapered diamond-coated bur. the pulp chamber was prepared with the same diamond-coated tip with an internal taper of 8 to 10 degrees. the preparation margins had a width of 1.5 mm and core exceeding the height of 3mm. (fig.3 and fig.4) interocclusal space was carefully evaluated and occlusal reduction done to achieve a clearance of 2mm. guidelines for full occlusal coverage according to 1 rocca et al: ! the ultra-conservative buccal cusp coverage (1.5 mm) on the contrary, for buccal cusps there are 3 options: ! the conventional buccal cusp coverage (2–3mm) ! the full buccal cusp coverage fig 2: post obtura�on radiograph fig 3: pre op clinical image fig 4: clinical image of prepared tooth fig 5: composite endocrown jiimc 2019 vol. 14, no.4 218 “endocrown” a novel approach options are decreased stress concentration as a result of lesser number of adhesive restorative interfaces, conservative preparatory design maintaining biologic width and increased surface area for bonding provided through pulp chamber which is equal or even superior to post in radicular 4 dentin. endocrowns overall success rate is quite promising although there are some limitations such as depth of pulp chamber should not be less than 3 mm and the width of cervical margin be more than 2mm, adhesion is difficult to achieve or presence of only 11 negligible tooth structure. for ensuring longevity of the endocrowns case selection is a critical step. further studies are required to assess its durability in the long term. 1 1. rocca gt , rizcalla n, krejci i. fiber-reinforced resin coating for endocrown preparations: a technical report. oper dent. 2013 may-jun;38(3):242-8 it is proven by a systematic review that survival rate and in vitro fracture strength of endocrown is equal or better than the conventional treatments, hence it is indicated for all molars especially those with loss of coronal structure, calcified or constricted canals, and is also reliable in patients with bruxism and 10 unfavorable occlusal relationship. 2. bitter k, kielbassa am. post-endodontic restorations with adhesively luted fiber-reinforced composite post systems: a review american journal of dentistry 2007; 20(6) 3533-60. 3. dogui h, abdelmalek f, amor a, douki n. endocrown: an studies have shown that albeit endocrowns are desirable option for restoration of all the teeth in the arches, but they should be restricted to the restoration of posterior teeth especially molars, because their performance in molars against the action of masticatory forces is much better as compared to premolars. other reasons include limited bond strength of adhesive systems because of smaller pulp chamber area and adhesive surface 5 of premolars. a long lever arm may be created because of premolar crowns configuration resulting in greater endocrown height as compared to width, increasing the risk of adhesive interface fracture and 6 displacement. however when their use is limited to restoration of molar teeth, they have shown satisfactory performance in achievement of esthetic 7,8,9 and functional recovery and bond strength. refrencesdiscussion in modern era of dentistry, endocrowns are conservative, easier and effective alternative option 1 for restoring an endodontically treated tooth. it achieves retention macro mechanically through pulp chamber and micromechanically by adhesive 2,3 cement. the benefits of endocrown over other fig 6: intaglio surface of endocrown fig 7: lu�ng cement fig 8: cemented endocrown jiimc 2019 vol. 14, no.4 219 “endocrown” a novel approach utilizing the monobloc technique. pract periodontics aesthet dent 1995;7:83–94. 8. göhring tn, peters ao. restoration of endodontically treated teeth without posts. am j dent 2003;16:313–18. 9. biacchi gr, basting rt. comparison of fracture strength of endocrowns and glass fiber post-retained conventional crowns. oper dent 2012;37:130–3. 10. rocca g.t & serge. b – alternativetreatment for restoration of non-vital teeth. revue d' odonto stomatology 2008; 37: 259 -272 11. bernhart j, brauning a, altenburger mj, wrbas kt. cerec 3d endocrowns-two-year clinical examination of cad/cam crowns for restoring endodontically treated molars. int jcompt dent 2010; 13:141-154 alternative approach for restoring endodontically treated molars with large coronal destruction.case rep dent. aug 30; 2018:1581952. 4. biacchi gr, mello b, basting rt. the endocrown: an alternative approach for restoring extensively damaged molars. j esthetrestor dent. 2013 dec;25(6):383-90 5. bindl a, richter b, mörmann wh. survival of ceramiccomputer-aided/manufacturing crowns bonded to preparations with reduced macro retention geometry. int j prosthodont 2005;18:219–24. 6. valentina v, aleksandar t, dejan l, et al. restoring endodontically treated teeth with all-ceramic endocrowns—case report. serbian dent j 2008;55:54–64. 7. pissis p. fabrication of a metal-free ceramic restoration jiimc 2019 vol. 14, no.4 220 “endocrown” a novel approach original�article abstract objective: to determine the nephroprotective effect of aqueous extract of carica papaya seeds in aminoglycoside induced acute nephrotoxicity in rats. study design: quasi experimental study. place and duration of study: the study was conducted from april 2016 to march 2017 at “department of pharmacology and therapeutics” and “multidisciplinary laboratory of islamic international medical college, riphah international university”, islamabad in collaboration with national institute of health (nih), islamabad. materials and methods: thirty sprague dawley rats were divided into 3 groups i.e., a, b and c with 10 rats in each group. group b and c were given aminoglycoside; gentamycin in 80 mg/kg) via intraperitoneal route once th daily for 5 consecutive days to induce acute nephrotoxicity. at day 6 , nephrotoxicity was confirmed by measuring serum urea and creatinine. aqueous extract of carica papaya seeds (1000 mg/kg) was started once daily through oral route in group c for 5 consecutive days. all animals were given standard diet pellets manufactured at nih. results: mean serum urea and creatinine for group a (control group) at day 0 was 24.70 mg/dl 5.16 and 0.750 mg/dl 0.1958 respectively. mean serum urea and creatinine for group b (disease control group) was 78.60 mg/dl 3.921 and 1.920 0.1229 at day 6th. this suggested induction of nephrotoxicity by gentamycin. mean th serum urea and creatinine for group c (aqueous extract treated group) at 11 day was 50.60 mg/dl 5.910 and 1.380 mg/dl 0.1932 after 5 days treatment with aqueous extract of carica papaya seeds. conclusion: aqueous extract of carica papaya seeds has significant nephroprotective effects on aminoglycoside induced acute nephrotoxicity in rats. key words: aminoglycoside, carica papaya, gentamycin, nephrotoxicity. 2 chronic renal failure. adverse reactions to drugs occur in approximately 6 % of admitted patients in hospitals and amongst these approximately 7 % 3 patients suffer drug-related toxicities. nephrotoxic drugs may be responsible for 19% – 25% of acute 4 kidney injury in critically ill patients receiving them. due to the intrinsic functions of kidneys for drug metabolism, concentration and excretion, they are vulnerable to toxicity due to drugs and their metabolites. many patients suffer from druginduced nephrotoxicity that can cause either acute injury to kidneys or chronic damage. many widely used marketed drugs including anti-cancer drugs, antibiotics, immunosuppressants and radio contrast 5 agents are nephrotoxic. nephrotoxicity is characterized by raised serum urea and creatinine 6 levels. aminoglycosides used for the treatment of gram-negative bacteria have been a vital component of antibiotic armamentarium. this is peculiar to their 7 cost effectiveness and efficacy. aminoglycosides are not metabolized in the body and eliminated 8 unchanged in the urine by glomerular filtration. due introduction a total of 25% of cardiac output is received by kidneys. they serve as main organs for maintenance of homeostasis of circulatory fluid. kidneys also serve as primary organs for elimination and detoxification of xenobiotic elimination and 1 detoxification. direct or indirect exposure of drugs and different chemicals to kidneys result in nephrotoxicity. many drugs may result in acute or nephroprotective effect of aqueous extract of carica papaya seeds 1 2 3 sameer ahmed , akbar waheed , attiya munir correspondence: dr. sameer ahmed senior lecturer department of pharmacology and therapeutics, hbs medical and dental college, islamabad e-mail:drchsameer@gmail.com 1 department of pharmacology hbs medical and dental college, islamabad 2 department of pharmacology islamic international medical college riphah international university, islamabad 3 department of pharmacology rawalpindi medical university, rawalpindi funding source: nil; conflict of interest: nil received: july 05, 2018; revised: february 18, 2019 accepted: march 02, 2019. nephroprotection by carica papaya seedsjiimc 2019 vol. 14, no.2 61 the animal house of nih, islamabad according to the recommendations agreed by the universities federation for animal welfare, alongside fresh water supply of 250 ml in inverted water bottles anchored on the enclosures in a particular inclined position. group a was taken as control group throughout the experiment. group b and c (10 rats each) were given aminoglycoside drug gentamycin (80 mg/kg) via intraperitoneal route for 5 consecutive days for 11 induction of acute nephrotoxicity. blood samples were collected via tail vein and serum urea and serum creatinine were measured at day 6 to see that 1 3 n e p h ro tox i c i t y h a s d eve l o p e d . a f te r t h e confirmation of nephrotoxicity on day 6, group c was started with administration of aqueous extract of carica papaya seeds (1000 mg/kg) dissolved in 14 distilled water for 5 consecutive days. after terminal sampling through cardiac puncture serum urea and creatinine were measured again at day 11 to see the effect of aqueous extract of carica papaya seeds on renal function. carica papaya plants were grown locally. seeds were collected from ripened fruits of papaya. seeds were air dried. the dried seeds of carica papaya were identified and authenticated by herbarium section of national agricultural research centre (narc) islamabad. coarse powder was made. in 1.0 l of distilled water, approximately 200 g powder was soaked. the mixture was kept for 48 hours with intermittent shaking. after 48 hours, the extract was filtered using whattman filter paper no.1. the filtrate was dried via rotary evaporator through evaporation. the extraction yielded 5.61 w/w dry matter. the extract was then stored in a refrigerator 15 at 4°c till usage. the data was analyzed using microsoft excel 2010 and spss 20. multiple comparisons were done through tuckey test and group mean differences were observed. a p-value of <0.05 was considered as statistically significant. results at day 6 mean value of serum urea for group a (control group) was 24.70 mg/dl 1.633. mean serum urea for group b (disease control group) and group c were 81.00 mg/dl ± 1.247 and 82.70 mg/dl ± 2.587. there was significant difference (p value less than 0.05). this suggested induction of acute nephrotoxicity by aminoglycoside drug gentamycin. to their potent ability to cause nephrotoxicity and ototoxicity, dosage limitations of aminoglycosides 9 pertain. gentamycin, an important aminoglycoside antibiotic, is used widely due to its potent antibiotic a c t i v i t y a g a i n s t v a r i o u s g r a m n e g a t i v e 10 microorganisms. however, its use is greatly limited by nephrotoxicity, accounting for 10 – 15 % of all 10 cases of acute renal failure. aminoglycosideinduced nephrotoxicity is confirmed by rise in serum creatinine, serum urea, and marked decrease in 1 1 g l o m e r u l a r f i l t rat i o n rate . d r u g i n d u c e d nephrotoxicity at renal tubular level more commonly affects proximal tubular cells due to high exposure to drug and its metabolites during processes of drug concentration and reabsorption through the glomerulus. mitochondria are damaged in tubular cells, tubular transport system is disturbed and there is increased oxidative stress due to generation of free radicals leading to cytotoxicity. nephrotoxic drugs fiberize the kidney due to inflammation in glomerulus and proximal tubular cells and damage to 12 surrounding renal cellular matrix. current research was aimed to see the effect of carica papaya seeds on acute drug-induced nephrotoxicity and to support it biochemically. present study aims to find out the effect of extract of carica papaya seeds in aminoglycoside induced acute nephrotoxicity. materials and methods a quasi experimental study including 30 sprague dawley rats was performed in the “department of p h a r m a c o l o g y a n d t h e r a p e u t i c s ” a n d “ m u l t i d i s c i p l i n a r y l a b o r a t o r y o f i s l a m i c international medical college, riphah international university”, islamabad in collaboration with national institute of health (nih), islamabad for duration of one year. a total of 30 sprague dawley rats were acquired and divided into 3 groups; a, b and c with 10 rats each through random selection via balloting method. authorization of the study was made by the ethics review committee of islamic international medical college (riphah international university) and was implemented within the frame of rules specified by the national institute of health for animal experiments. rats weighing more than 300 grams and with normal baseline serum urea and creatinine levels were included in the experiment. all rats were served with standard food pellets manufactured at nephroprotection by carica papaya seedsjiimc 2019 vol. 14, no.2 62 discussion kidneys function as main organ to detoxify and e l i m i n a t e xe n o b i o t i c s . xe n o b i o t i c s w h i c h accumulate in renal tubular cells can damage the 1 kidneys acutely. acute kidney injury (aki) being a common clinical complication possesses high mortality and morbidity. according to the statistics, the incidence rate of chronic kidney disease followed by an episode of aki is 7.8 per 100 patients per year. the rate of end stage renal disease (esrd) is 4.9 per 100 patients per year. gentamycin, an important aminoglycoside antibiotic, has potent antibiotic spectrum but its clinical use has been greatly reduced due to nephrotoxicity that accounts for 10 to 15 % of all cases of acute renal failure in drug 10 induced kidney damage. gentamycin due to its cost effectiveness and high potency and more liability to cause toxicity in kidneys is widely used for inducing 13 nephrotoxicity in experimental models. baseline serum urea and serum creatinine were measured at day 0 i.e., beginning of the experiment. gentamycin was administered intraperitoneally to group b and group c for five consecutive days. at day 6 mean serum urea and serum creatinine were again measured. mean serum urea and creatinine of group b (disease control group) and group c were significantly raised when compared with the control group a suggesting that gentamycin produced acute nephrotoxic changes in the kidney and altered the renal function. after measuring the serum markers; group c was started with administration of aqueous extract of carica papaya seeds dissolved in distilled water via oral route. the aqueous extract was administered for five consecutive days. at day 11, again serum markers were measured and the values of serum urea and serum creatinine were found to have been reduced than day 6 in group c which received aqueous extract of carica papaya seeds. there was significant difference statistically between the disease control group i.e., group b and the aqueous extract treated group i.e., group c (p value less than 0.05). the difference in serum markers showed nephroprotection by carica papaya seed extract. gentamycin resulted in increased levels of serum markers i.e serum urea and creatinine in group b and group c after five days intraperitoneal administration of drug in dose of 80 mg/kg when mean serum urea for group c (aqueous extract treated group) at day 11 was 50.60 mg/dl±1.869 after 5 days treatment by aqueous extract of carica papaya seeds. there was significant difference (p value <0.05) which supported the nephroprotection by the herb. table i: mean values of serum urea of all groups at day 0, 6 and 11 mean value of serum creatinine for group a (control group) was 0.750 mg/dl 0.0619. mean value of serum creatinine for group b (disease control group) and group c were 1.980 ± .0467 and 2.030 ± .0667 respectively. there was significant difference (p value .000). this suggested induction of nephrotoxicity by aminoglycoside drug gentamycin. mean serum creatinine for group c (aqueous extract treated group) was 1.380 ± .0611 after 5 days treatment by aqueous extract of carica papaya seeds. table ii: mean values of serum crea�nine of all groups at day 0, 6 and 11 nephroprotection by carica papaya seedsjiimc 2019 vol. 14, no.2 means±sd means±sd means±sd means±sd means±sd means±sd 63 15. okewumi ta, oyeyemi aw. gastro-protective activity of aqueous carica papaya seed extract on ethanol induced gastric ulcer in male rats. african journal of biotechnoogy. 2012; 11(34):8612-5 16. umana ue, timbuak ja, musa sa, asala s, hambolu j, anuka aj. acute and chronic hepatotoxicity and nephrotoxicity: study of orally administered chloroform extract of carica papaya seeds in adult wistar rats. international journal of scientific and research publications. 2013; 3(4):1-8. research. 2014;3(4):41-47. 4. hussein o, germoush m, mahmoud a. ruta graveolens p r o t e c t s a g a i n s t i s o n i a z i d / r i f a m p i c i n i n d u c e d nephrotoxicity through modulation of oxidative stress and i nf l a m m at i o n . g l o b j b i o te c h n o l b i o m ate r s c i . 2016;1(1):17-22. 5. kandasamy k, chuah jkc, su r, huang p, eng kg, xiong s et al. prediction of drug-induced nephrotoxicity and injury mechanisms with human induced pluripotent stem cellderived cells and machine learning methods. scientific reports. 2015; 5(1):12337.doi: 10.1038/srep12337. 6. tahira a, saleem u, mahmood s, hashmi fk, hussain k, bukhari ni et al. evaluation of protective and curative role of α-lipoic acid and selenium in gentamicin-induced nephrotoxicity in rabbits. pak j pharm sci. 2012; 25(1):10310. 7. shi k, caldwell sj, fong dh, berghuis am. prospects for circumventing aminoglycoside kinase mediated antibiotic resistance. frontiers in cellular and infection microbiology. 2013; 3:22.doi : 10.3389/fcimb.2013.00022 8. filazi a, sireli ut, pehlivanlar-onens,cadircio, aksoy a. comparative pharmacokinetics of gentamicin in laying hens. journal of the faculty of veterinary medicine, kafkas university. 2013; 19(3):495-8. 9. ramirez ms, tolmasky me. aminoglycoside modifying enzymes. drug resistance updates. 2010;13(6):151-71. 10. chen q, cui y, ding g, jia z, zhang y, zhang a et al. pea3 protects against gentamicin nephrotoxicity: role of mitochondrial dysfunction. am j transl res. 2017; 9(5):2153-62. 11. sepehri g, derakhshanfar a, saburi l. does propylthiouracil increase the gentamycin-induced nephrotoxicity in rat?.iranian journal of basic medical sciences. 2013; 16(11):1190-5. 12. kim sy, moon a. drug-induced nephrotoxicity and its biomarkers.biomolecules and therapeutics. 2012; 20(3):268-72. 13. ajami m, eghtesadi s, pazoki-toroudi h, habibey r, ebrahimi sa. effect of crocus sativus on gentamicin induced nephrotoxicity. biological research. 2010; 43(1):83-90 14. uduak u, timbuak j, musa s, hamman w, hambolu j, anuka j. acute hepatotoxicity and nephrotoxicity study of orally administered aqueous and ethanolic extracts of carica papaya seeds in adult wistar rats. asian journal of medical sciences. 2013; 5(3):65-70. compared to group a i.e., control group. these findings were found to be in accordance with findings of a study by (ajami m et al; 2010), in which nephrotoxicity was induced in male wister rats via gentamycin in same dose and there was resultant increase in levels of serum markers i.e., serum urea 1 3 a n d c r e a t i n i n e . a f t e r t h e i n d u c t i o n o f nephrotoxocity, the protective effect of aqueous extract of carica papaya seeds was observed when 1000 mg/kg dose of aqueous extract of carica papaya seeds was administered to group c. this was consistent with the study performed by umana et al., 2013) in which same dose of chloroform extract of carica papaya seeds was utilized in rats for toxicity 1 6 studies. in current study aqueous extract preparation of carica papaya seeds was utilized which revealed improvement in levels of serum urea and serum creatinine in group c after previous induction of nephrotoxicity by gentamycin. the results indicated that aqueous extract of carica p a p a y a s e e d s p o s s e s s t h e p o t e n t i a l o f nephroprotection in gentamycin induced acute nephrotoxicity. however, the cost of experiment limited the study of phytochemical constituents of the extract preparation. the duration of experiment can however be prolonged in further studies to assess complete reversal of nephrotoxicity and to study other extract preparations of carica papaya too. conclusion aqueous extract of carica papaya seeds have significant protective effect as shown by the improvement of kidney function after gentamycin induced acute renal injury. references 1. weber ej, himmel farb j, kelly ej. concise review: current a n d e m e r g i n g b i o m a r k e r s o f n e p h r o t o x i c i t y. current.opinion in toxicology.2017; 4:16-21. 2. tahir m, sadiq n, ahmed s, ali a, rajput nn, riaz u. effects of aqueous and methanolic extracts of cichorium intybus seeds on gentamycin induced nephrotoxicity in rats. journal of islamic international medical college. 2018;13(4):184-9. 3. singh r, gautaum rk, karchuli m. nephrotoxicity: an overview. journal of biomedical and pharmaceutical nephroprotection by carica papaya seedsjiimc 2019 vol. 14, no.2 64 jiimc march 2016.cdr original article abstract objective: to assess and compare the level of hypovitaminosis d in diabetic and non-diabetic patients of coronary artery disease (cad). study design: cross-sectional observational. place and duration of study: the study was conducted from may 2014 to november 2014 at pakistan railways hospital, islamic international medical college, rawalpindi. materials and methods: a total of 149 patients of coronary artery disease were selected in this studyby convenient sampling technique including 77 male and 72 female patients. out of 149 patients, 75 were diabetic and 74 non-diabetic. these participants were assessed for their individual serum vitamin d levels(ng/ml). family history of coronary artery disease and treatment modalities was also obtained from all the patients. the data was analyzed through spss 21. descriptive statistics and t test were used to analyze the data. results: the serum levels of vit d among diabetic and nondiabetic patients suffering from cad were 16.4(±9.7) ng/ml and 17.4(±7.9)ng/ml respectively. these values suggest a deficiency of vit d in both diabetic and non-diabetic patients suffering from cad. however the difference in vit d levels of the two subgroups of cad was statistically not significant (p = 0.4).however vitamin d levels were found to be significantly lower in patients with positive family history of cad (p=0.04). conclusion: there is no significant difference in the level of hypovitaminosis d in diabetic and non-diabetic cad patients. key words: vitamin d, vitamin d receptor, type 1 diabetes mellitus, type 2 diabetes mellitus, hypovitaminosis d, islet β cells, insulin secretion, insulin sensitivity. 3,4 risk for development of diabetes mellitus. diabetes mellitus is a very common condition which affects over 300 million people worldwide and 5 accounts for significant morbidity and mortality. ziegler et al found that vitamin d administration in type 1 diabetes can protect the function of pancreatic islet β cells. deficiency of vitamin d has been investigated to affect the synthesis and secretion of insulin both in human and animal 6 models. vitamin d supplementation not only restores the synthesis but also secretion of insulin a n d t h e r e f o r e d e c r e a s e s b l o o d g l u c o s e 7 concentration. palomer et al also reported that vitamin d deficiency can predispose to glucose intolerance and vitamin d supplementation improves insulin secretion in type 2 diabetes 8 mellitus. both genetic and environmental factors are known to be etiological in causing type 1 diabetes mellitus (t1dm), a chronic disorder that results from autoimmune response against the beta cells of the pancreatic islets of langerhans at early stages of life. it is hypothesized that vitamin d has a role in the therapy of t1dm due to its immune-modulating effects. chronic insulinitis is found in islet cells introduction vitamin d is a secosteroid prohormone which is synthesized in the skin from 7-dehydrocholesterol by ultraviolet b-irradiation. almost 80 percent of vitamin d is provided through cutaneous synthesis while 20 percent is obtained from various dietary 1 resources. vitamin d has been known for its key role in bone metabolism and calcium homeostasis. however its extra-skeletal effects have attracted much attention because of recent discovery of vit d receptor (vdr) expression in almost all tissues of the body including immune, endocrinal, vascular and 2 myocardial cells. vit d deficiency is considered as a risk factor for diabetes type-2 diabetes and higher plasma levels of vitamin d are shown to decrease the vitamin d status in diabetic and non-diabetic patients of coronary artery disease aamnah sajid, abdul khaliq naveed, amena rahim, bilal sajid vit d status in cad patientsjiimc 2016 vol. 11, no.1 correspondence: dr. aamnah sajid biochemistry department islamic international medical college riphah international university, islamabad e-mail: aamnahsajid18@gmail.com biochemistry department islamic international medical college riphah international university, islamabad funding source: nil ; conflict of interest: nil received: march 26, 2015; accepted: january 14, 2016 11 involving cd8+, cd4+ t cells, b lymphocytes and macrophages. it has been reported that vitamin d inhibits the production of ifn-γ and il-2 cytokines which are responsible for the destruction of 9 pancreatic islet cells. vitamin d also reduces the activity of apcs and regulates the production of 10 cd4+ lymphocytes. cytokines cause apoptosis. 1,25(oh)2d3 protects beta cells by reducing exposure of mhc-1 molecules. as a result a20 protein which inhibits apoptosis is activated and a decrease in expression of a transmembrane cell 9 surface receptor occurs. the major factors involved in the etiology of type 2 diabetes mellitus are insulin resistance, disorders of pancreatic beta cells and inflammation. vitamin d facilitates pancreatic beta cell function through direct actions in which vitamin d is activated in pancreatic beta cells by intracellular 1-αhydoxylaseenzyme. vitamin d not only increases insulin secretion but also enhances beta cell survival through the effects of cytokines. vitamin d also has indirect actions in which it regulates calbindin, a calcium-binding protein present in beta cells. calcium then influences insulin secretion because this process is calcium dependent. in this way calcium indirectly affects insulin secretion via calcium binding protein calbindin. one more mechanism involved can be that low vitamin d levels cause secondary hyperparathy roidism. parathyroid hormone then inhibits insulin secretion and also causes resistance in target cells because of its effects 9 on regulation of calcium levels. an inverse relationship of insulin resistance was found at vit d levels between 16 and 36ng/ml in 10 arecent study. other cross-sectional, case control, prospective observational and longitudinal studies showed that higher vit d concentrations were associated with a lower risk for diabetes mellitus type 2 and lower levels were negatively correlated with diabetes and glycosylated haemoglobin levels. however these studies did not reveal consistent results, neither vitamin d supplementation was found to improve glucose control in type 2 diabetes 11 in all the subjects. the levels of blood glucose and vitamin d have been shown to be different in third national health and nutritional examination survey and a negative correlation was found in healthy white postmenopausal women and in mexican american men and women but not in hispanic black population. this finding suggests that the effect of vitamin d may 12 differ by ethnicity. the present study was undertaken to assess and compare the level of hypovitaminosis d in diabetic and non-diabetic patients of cad because of paucity of research work on this therapeutically important subject. materials and methods this study was conducted at department of biochemistry iimc rawalpindi. it was a crosssectional observational study. the study was conducted from may 2014 to november 2014. blood samples were drawn from 149 patients of coronary artery disease comprising of 77 males and 72 females from opd, emergency department and icu of railways general hospital rawalpindi, a 480 bedded teaching hospital affiliated with iimc. these patients were divided into two groups: group i consisted of diabetic patients of coronary artery disease while group ii comprised of patients without diabetes. patients of coronary artery disease between ages of 40 years to 55 years were included in the present study. patients with renal, liver, parathyroid and thyroid disorders were excluded from the study. patients taking vitamin d and calcium supplements and those on medication that affect vitamin d metabolism such as anticovulsants were also not recruited in this study. venous blood was drawn from the patients which was centrifuged at 300 rpm for separation of serum and then stored at -20 degree centigrade in laboratory freezer till further analysis. serum levels of 25(oh)d was measured by enzyme linked immunosorbent assay. statistical analysis was carried out for finding out significant p values (p<0.05) and t test was used to evaluate the data. spss version 21 was used for data processing. a total of 149 patients with coronary artery disease were selected to participate in the study that fulfilled the inclusion criteria and gave informed consent. all the participants were assessed for their individual serum vitamin d levels (ng/ml). the diabetic patients were questioned about the mode of treatment, either oral hypoglycaemic agents or insulin therapy to control their diabetes. vit d status in cad patientsjiimc 2016 vol. 11, no.1 12 discussion this study was undertaken to assess the role of vitamin d in diabetes mellitus and to measure its levels in diabetic and non-diabetic patients of cad. our results did not reveal statistically significant difference in vitamin d levels between diabetic and non-diabetic sample population (p= 0.4). this finding which is in contrast to many other observational studies may possibly be due to multiple confounding factors like obesity, sun exposure and/or methodological and measurement limitations. however cumulative percentage of vitamin d deficiency and insufficiency in the study population has been found to be about 93% which matches with one of the studies carried out by bellen et al. in which 13 hypovitaminosis d was reported in 95% of cases. a study performed by daga et al. in north india showed that 91% of diabetic patients had hypovitaminosis d and the mean concentration was 7.88(±1.2)ng/ml. in non-diabetic patients the mean concentration was 16.46(± 7.83) ng/ml. this finding 14 is in line with our results for non-diabetic patients. hypovitaminosis d is reported worldwide mainly due to dietary insufficiency and use of sun protection clothing and sun screen. studies on this subject in saudi arabia, turkey, australia, arab emirates and india have shown that 30-50% of children and adults had vitamin d levels of less than 20ng/ml. a japanaese study has shown a prevalence of vitamin results out of a total of 149 patients selected to participate in the study, 77 were male and 72 were female patients. of these, 75 male and female patients were diabetic whereas 74 were non-diabetic male and female participants. the mean age of the male participants was 49.1+4.1(in years) and of the female participants was 47.4+4.5(in years). the mean serum vitamin d level in diabetics was 16.4 ng/ml and in non-diabetics was 17.4 ng/ml(fig 1). however the difference was not statistically significant (p value= 0.4)(table i). the serum vitamin d level in the female diabetic participants was 16.8 ng/ml and in the male diabetic participants it was 16.0 ng/ml. the serum vitamin d level in nondiabetic female patients was 19.0 ng/ml and in male non-diabetic participants it was 15.9 ng/ml. vitamin d deficiency was considered when the serum vitamin d was < 20ng/ml, insufficiency if the serum vitamin d was between 21-29ng/ml and normal if serum vitamin d was > 30 ng/ml. vitamin d deficiency was seen in 100(67.1%), insufficiency was seen in 39(26.2%) and normal vitamin d was present in 10(6.7%) of the participants. the percentage of deficiency and insufficiency was 93% in the sample population. family history of coronary artery disease was present in 63(84.0%) of the diabetic patients and in 53(71.6%) of the non-diabetic patients. vitamin d levels in patients with and without family history of cad were 7.7(±9.2)ng/ml and 14.2(±7.1)ng/ml respectively. the difference was significant (p= 0.04)(table ii). fig 1: percentage of hypovitaminosis in the study popula�on table i: comparison of vitamin d levels between diabe�c and nondiabe�c pa�ents table ii: comparison of vitamin d levels between pa�ents with family history of coronary artery disease and pa�ents with no family history of coronary artery disease vit d status in cad patientsjiimc 2016 vol. 11, no.1 13 d deficiency in 75% of the study population which is consistent with the findings of our study. the results of a study carried out in the united kingdom also revealed the prevalence of vitamin d levels (below 20ng/ml) in more than 80% of the research 15 participants. our study also revealed comparable results. an interesting and therapeutically useful finding in this study is that patients taking oral hypoglycemic drugs had significantly lower vitamin d levels as compared to those on insulin therapy (p = 0.05). another finding of the present research is a significant difference in vit d levels while comparing results of patients with and without family history of coronary artery disease ( p = 0.04). the conclusive statement of a study carried out by bellan et al. on this subject is “at variance with previous reports, we were unable to disclose negative effects of low 25(oh)d concentration on plasma glucose levels both in fasting conditions and after the oral glucose challenge after correction for multiple variables known to affect glucose 16 metabolism”. another study postulates that vitamin d is needed to improve production and action of insulin in both diabetic and non-diabetic patients but the relationship between vitamin d, insulin resistance and β cell function is inconsistent. additionally interventional studies with vitamin d in any form have also shown conflicting results. therefore, interpretation of the results is difficult in view of lack 17 of placebo-controlled studies. conclusion the results of the present study revealed that serum levels of vit d in diabetic patients of coronary artery disease were not significantly lower than nondiabetic patients of coronary artery disease in our study. it is inferred from the current findings that diabetes mellitus is a multifactorial disease resulting f ro m co m p l ex i nte ra c t i o n o f ge n e t i c a n d environmental factors. vitamin d could only be one of the environmental variables and not an independent potential predictor of diabetes mellitus but rather could be a mediator of metabolic disturbances responsible for the longterm health outcomes. further large well-designed, randomized controlled studies are suggested to assess and clarify the correlation between vitamin d and glucose homeostasis in diabetes mellitus. references 1. keinreich k, tomaschits a, verheyen n, pieber t, gaksch m, glubler mr, et al. vitamin d and cardiovascular disease. nutrients. 2013; 5: 3005-21. 2. goleniewska b, kacprzak m, zielinska m. vitamin d level and extent of coronary stenotic lesions in patients with first acute myocardial infarction. cardiol j.[online] 2013. available from: doi: 10.5603/cj.a 2013.0048. [accessed 16th february 2014]. 3. pittas a, l au j, hu f, dawson hughes b. the role of vitamin d and calcium in type 2 diabetes. a systematic review and meta-analysis. j clinendocrinolmetab. 2007; 92: 2017-29. 4. pittas a, nelson j, mitri j, hillmann w, garganta c, nathan d, et al. plasma 25-hydroxyvitamin d and progression to diabetes in patients at risk for diabetes: an ancillary analysis in the diabetes prevention program. diabetes care. 2012; 35: 56573. 5. a h m a d i e h h , a za r st, l a k k i s n , a ra b i a . hypovitaminosis d in patients with type 2 diabetes mellitus: a relation to disease control and complications. isrn endocrinology. [online] 2013. available from: doi: 10.1155 /2013/641098. [accessed 24th march 2015]. 6. gua j, xiao z, xue x, liu x, lu y, yin x, et al. 25hydroxyvitamin d is closely related with the function of the pancrejatic islet β cells. pak j med sci.2013; 29: 809-13. 7. norman aw, frankel jb, heldt am, grodsky gm. vitamin d deficiency inhibits pancreatic secretions of insulin. science.1980; 209: 823-5. 8. palomer x, gonzalez clemente jm, blanco vaca f. role of vitamin d in the pathogenesis of type 2 diabetes mellitus. diabetes obesmetab. 2008; 10; 185-97. 9. harinayaran cv. vitamin d and diabetes mellitus. hormones. 2014; 13: 163-81. 10. heaney r, french c, nguyen s, ferreira m, baggerly i, brunel l, et al. a novel approach localizes the association of vitamin d status with insulin resistance to one region of the 25-hydroxyvitamin d continuum. adv nutr. 2013; 4: 303-10. 11. kostoglou athanassiou i, athanassiou p, gkountouvas a, kaldrymides p. vitamin d and glycemic control in diabetes mellitus type 2. ther adv endocrinol metab. 2013; 4: 122-8. 12. scragg r, sowers m, bell c. serum 25 hydroxyvitamin d diabetes andethnicity in the third national health and nutrition examination survey.diabetes care. 2004; 27: 2813-8. vit d status in cad patientsjiimc 2016 vol. 11, no.1 14 13. jehle s, lardi a, felix b, hulter hn, stellar c, krapf r. effect of large doses of parenteral vitamin d on g l y c a e m i c c o n t r o l a n d c a l c i u m / p h o s p h a t e metabolism in patients with stable type 2 diabetes m e l l i t u s : a ra n d o m i s e d , p l a c e b o co nt ro l l e d , prospective pilot study. swiss med wkly. [online] 2014.available from: doi: 10.4414/smw.2014.13942. [accessed 24th march 2015]. 14. riachy r, vandewalle b, belaich s. beneficial effect of 1,25dihydroxyvitamin d3 on cytokine-treated human pancreatic islets. j endocrinol. 2001; 169: 161-8. 15. bellan m, guzzaloni g, rinaldi m, merlotti e, ferrari c, tagliaferri a. altered glucose metabolism rather than naïve type 2 diabetes mellitus (t2dm) is related to vitamin d status in severe obesity. cardiovasc diabetol. 2014; 13: 57. 16. bayani ma, banasaz b, saeedi f. status of vitamin d in diabetic patients and compared it with healthy individuals. caspian j intern med. 2014; 5: 40-2. 17. griz lhm, bandeira f, gabbay mal, dib sa, freese de carvalho e. vitamin dand diabetes mellitus-an update-2013.arq bras endocrinol metab.2014;58:18. vit d status in cad patientsjiimc 2016 vol. 11, no.1 15 untitled-1 original�article abstract objective: to determine the frequency of various causes of upper gastrointestinal bleeding on the basis of endoscopic findings. study design: a descriptive observational study. st place and duration of study: study was done from 1 , january, 2015 to 31st december, 2017 at pakistan railway general hospital rawalpindi. material and methods: the study was carried out in the department of medicine at railway hospital. the record of patients admitted with upper gi bleed through indoor/outdoor was retrieved from the endoscopy unit. 100 patients fulfilling inclusion criteria were selected in the study. the relevant data and endoscopic findings were documented on performa. the data was analyzed retrospectively. results: out of 100 patients selected, 58(58%) were males and 42(42%) females. the mean age of 52.20 years ± sd 15.88.the most common cause was esophageal varices (47.90%), followed by gastritis/esophagitis 23%, peptic ulcer 14.58%. the malignant condition contributed 1.58 %. while in 9(9%) of patients, no cause of bleeding was identified. conclusion: variceal hemorrhage is the most frequent cause of upper gastrointestinal bleeding in our population. key words: endoscopy, peptic ulcer, ugib, upper gastrointestinal bleed, variceal bleed. 4, 5, 6 hemodynamic stability saves life. ugib has been classified as variceal or non-variceal as they have different underlying mechanism, treatment algorithm and prognosis. in cirrhotics, variceal bleed is responsible for 70% of ugiband is 6 major cause of death. variceal bleed has higher mortality as compared to non-variceal bleed. 7,8 mortality during first episode is 15-20%. nonvariceal causes include peptic ulcer, esophagitis, 8, 9 gastritis, mallory weiss tear, and malignancies. the epidemiology of peptic ulcer is changing. peptic 10 ulcer is still common cause of ugib but incidence is decreasing. peptic ulcer bleeding is less severe, 11 occurs in older age group. upper gastrointestinal endoscopy is the initially 4 recommended procedure because of its safety. the sensitivity and specificity of upper gi endoscopy for the diagnosis of ugib is 92-98% and 30-100% 12 respectively. timely endoscopy has vital role in 6 modern management of ugib. endoscopic management has shown to reduce morbidity, duration of hospital-stay, risk of re-bleeding, and 5, 6, 13 overall health care cost. no large scale studies are available in pakistan about introduction upper gastrointestinal bleeding (ugib) is defined as bleeding derived from a source proximal to ligament 1 of treitz. it is a common life-threatening medical 2 emergency associated with mortality of 5-15% . its 2, 3 incidence is 50-150 per 100,000 people per year. it is two times more common in males in all age groups, however mortality is same in both sexes. the patients can present with insignificant bleed to catastrophic hemorrhage. in approximately 80-85% cases, bleedings stop spontaneously while in 15-20% bleeding is continuous or recurrent. initial evaluation of patients presenting with gi bleeding is very essential. intensive resuscitation to achieve endoscopic findings in patients with upper gastrointestinal bleeding at pakistan railway general hospital, rawalpindi. a retrospective review of 100 cases correspondence: dr. samia kausar department of medicine islamic international medical college riphah international university, islamabad e-mail: samia.kausar@riphah.edu.pk department of medicine islamic international medical college riphah international university, islamabad funding source: nil; conflict of interest: nil received: april 30, 2018; revised: aug 25, 2018 accepted: sept 12, 2018 endoscopic findings in patients with upper gi bleedingjiimc 2018 vol. 13, no.3 samia kausar, shamaila burney, zunera jahanzeb, muhammad farooq, asim zulfiqar, omar awab 146 percentages. results out of 100 patients there were 58 (58%) males and 42(42%) females. the male to female ratio was 1.4:1. the mean age of patients was 52.20 ±15.58 sd years. the age range was between 18 to 80 years. the source of bleeding was endoscopically identified in 91(91%) cases and in 9 patients no source of bleeding could be identified. the commonest cause of ugib was esophageal varices consisting of 47.90% with equal frequency in male and female. the commonest cause of non-variceal bleed was erosive mucosal disease (gastritis, esophagitis, and duodenitis) accounting for 25.16% of cases. while peptic ulcer accounted for 14.58% cases. other less frequent causes include malignancy, gastric polyp and duodenitis. in patients with variceal bleed, anti hcv was positive in 80% and hbsag in 10% of cases. prevalence of common causes of ugib. endoscopic services are not readily available or affordable for most patients in our setup. patients are treated without any endoscopic evaluation to assess the etiology and response to treatment. therefore the aim of the study was to evaluate the patients admitted with ugib, so that future plans are made for better outcome. material and methods this was descriptive observational study. it was carried out at department of medicine railway st st general hospital from 1 jan, 2015 to 31 december 2017. sample size was 100 patients with upper gi bleed. the sampling technique was non-probability (consecutive) sampling. record of all patients referred with upper gastrointestinal bleeding to the endoscopy unit from indoor and outdoor was reviewed. relevant data and endoscopic findings were retrieved from endoscopic register and entered in structured performa. those cases with incomplete record were excluded. this study was conducted after approval by institutional ethical review committee all patients had given written consent for endoscopy and had undergone hepatitis b and hepatitis c screening. in 60% of patients, endoscopy was performed within 24 hours. biopsies were taken for suspicious lesions when required. the endoscopy was performed using endoscope gif 130 olympus japan. lignocaine gargles were used for local analgesia before endoscopy. endoscopic evaluation of varices was done in four 14 grades, i.e., grade i-iv. in case of peptic ulcer, 15 forrest classification was used as follows; fi: active bleeding, fii: stigmata of recent hemorrhage, fiii: lesions without active bleeding. los angeles 16 classification system was used for esophagitis. acute erosive gastritis was considered when multiple 17 dark brown erosions were present. normal endoscopy was defined by absence of any abnormality. data (parametric) was analyzed by statistical software package spss version21. descriptive statistics, including patient's age, gender, and admission number, were entered. mean ± sd was calculated for age and frequency of qualitative variables was expressed as frequencies and table i: distribu�on of pa�ents with ugib according to age and sex. pa�ent n=100 table ii: distribu�on of endoscopic findings and its frequency with sex. jiimc 2018 vol. 13, no.3 147 endoscopic findings in patients with upper gi bleeding frequency of esophageal varices. jaka et al. from tanzania reported varices in51.3% followed by 25 peptic ulcers in 25.0% of cases. while aleema 26 reported 40.6% cases had variceal bleed. ugib can also result from erosive mucosal disease such as acute esophagitis, gastritis and duodenitis. stress induced mucosal ulceration is a frequent occurrence in critically ill patients. however, clinically significant bleeding from acute stress gastritis has 27 been reported as1.5%. in the present study, erosive mucosal diseases were the second most common endoscopic finding in patients with ugib. one in every four patients (25.16%) had esophagitis, gastritis and/or duodenitis. results of our study closely match the findings of shah et al. who also report erosive mucosal diseases as the second most common finding in their study after variceal bleeding. the frequency of esophageal varices in their study was 64.2% while that of erosive gastritis 28 and peptic ulcer was 15.4% and 10.5% respectively. previously in a single center indian study, rathore et al. found erosive gastritis to be the most frequent 29 cause of ugib. similarly study by aleema showed erosive mucosal disease second most important 26 cause of ugib after varices. the frequency of peptic ulcer in our study was relatively low (14.8%). while this is in accordance 20,21,22,23, with results from local studies, although it is contrary to most data reported from the western world. in a large scale study, budimir et al. concluded that peptic ulcer bleeding (pub) is the main cause of ugib and is associated with significant re bleeding 30 rate and mortality. peptic ulcer is strongly associated with helicobacter pylori (h pylori) infection. other risk factors include alcohol abuse, c h ro n i c r e n a l fa i l u r e , n o n s t e ro i d a l a n t i inflammatory drug (nsaid) use. peptic ulcer bleed and not variceal hemorrhage was the leading cause of ugib in pakistan in early 90's as 31 determined in a study be zuberi et al. while this may partly be explained by the rising prevalence of chronic viral hepatitis in our country, the prevalence 32 of peptic ulcer is overall declining. this is believed to be due to an increased use of proton pump inhibitors (ppis) and h pylori therapy. a study carried out in rural sindh revealed that over half (51%) of patients in our setting are using ppis with no definite 33 indication. it is therefore logical to assume that this upper gi bleed is a serious medical emergency associated with high morbidity and mortality. in our study esophageal varices was the most common cause followed by erosive mucosal disease and peptic ulcer. age and sex ratio in this study was similar to other reported studies. in pakistan there is 18 19 high prevalence of hepatitis b and hepatitis c viruses and is the major cause of cirrhosis in our population. in variceal bleed group 80% patients were tested positive for anti hcv and 10% were positive for hbs.ag. most studies conducted in pakistan report a very high frequency of esophageal/gastric varices. a study comprising 550 patients and conducted at one of the largest tertiary care centers in islamabad revealed that 44.4% patients reporting with ugib had variceal bleeding while 19.7% had peptic ulcer 20 and 6.6% had esophagitis. a similar study from 21 multan also showed high frequency of variceal bleeding (53%) with peptic ulcer being the second most frequent cause (26%). ghouri et al. conducted a study in jamshoro in which 54% of their patients had esophageal varices while 20% had peptic 22 ulcer. more recently, farrukh et al. from military hospital rawalpindi concluded that frequency of variceal bleeding in pakistan has in fact risen over the years. more than two thirds of their study population 23 (72.1%) was found to have esophageal varices. results of our study are therefore in accordance with the previous studies. similar results are shown in a 24 study from india. portal hypertension secondary to hepatitis b and schistosomiasis is highly prevalent in african countries. studies from africa report higher jiimc 2018 vol. 13, no.3 148 endoscopic findings in patients with upper gi bleeding epidemiology and clinical outcome of acute upper gastrointestinal bleeding in a defined geographical area in greece.j clin gastroenterol. 2008; 42(2):128-33. 4. khamaysi i,gralnek im, acute upper gastrointestinal bleeding (ugib) initial evaluation and management. best pract res clin gastroentrol. 2013; 27(5):633-8. 5. kim bs, li bt, engel a, samra js, clarke s, norton id et al diagnosis of gastro intestinal bleeding: a practical guide for clinicians. can assoc radiol j. 2013; 64:90–100. 6. gralnek i, dumonceau j, kuipers e et al. diagnosis and management of nonvariceal upper gastrointestinal hemorrhage: european society of gastrointestinal endoscopy (esge) guideline. endoscopy2015; 47: 1–46. 7. tayyem o, bilal m, samuel r, merwat sk. evaluation and management of variceal bleeding. dis mon.2018; 64 (7):312-20. 8. curdia goncalves t, rosa b, cotter j. new insights on an old medical emergency: non-portal hypertension related upper gastrointestinal bleeding. rev esp enferm dig. 2016 ;( 10):648-56. 9. samuel r, bilal m, tayyem o, guturu p. evaluation and management of non-variceal upper gastrointestinal bleeding.dis mon. 2018;64(7):333-43. 10. lam kl, wong jc, lau jy. pharmacological treatment in upper gastrointestinal bleeding. curr treat options gastrenterol. 2015; 13(4):369-76. 11. kim jj, sheibani s, park s, buxbaum j, laine l. causes of bleeding and outcomes in patientshospitalized with upper gastrointestinal bleeding.j clin gastroenterol. 2014; 48(2):113-8. 12. jaskolka jd, binkhamis s, prabhudesai v, chawla tp. acute gastrointestinal hemorrhage: radiologic diagnosis and management. can assoc radiol j. 2013; 64:90–100. 13. klein a , gralnek im, acute, nonvariceal upper gastrointestinal bleeding. curr oin crit care 2015; 21(2):154-62. 14. alempijevic t, bulat v, djuranovic s, kovacevic n, jesic r, tomic d, et al. right liver lobe/albumin ratio: contribution to non-invasive assessment of portal hypertension. world journal of gastroenterology: wjg. 2007; 28; 13(40):5331. 15. forrest ja, finlayson nd, shearman dj. endoscopy in gastrointestinal bleeding. lancet. 1974; 2:394–7. 16. corson jd, williamson rcn. upper gastrointestinal bleeding. london, uk: mosby-year book; 2001. 17. dent j. endoscopic grading of reflux oesophagitis: the past, present and future. best practice & research clinical gastroenterology. 2008; 22(4):585-99. 18. arshad a, ashfaq ua. epidemiology of hepatitis c infection in pakistan: current estimate and major risk factors. critical reviews™ in eukaryotic gene expression. 2017;27(1):63-77 19. ali m, idrees m, ali l, hussain a, rehman iu, saleem s, et al. hepatitis b virus in pakistan: a systematic review of prevalence, risk factors, awareness status and genotypes. virology journal. 2011; 8(1):102. 20. adam t, javaid f, khan s. upper gastrointestinal bleeding: an etilogical study of 552 cases. j pak inst. med sci 2004; 15(1): 845 -48. 21. pasha mb, hashir mm, pasha ak, pasha mb, raza aa, fatima m. frequency of esophageal varices patients with may very well be a contributing factor to changing trends in the frequency of pub in recently published local data. the endoscopy was normal in 9% of our patients. this number is much higher than the western studies although similar to data from developing 26 parts of the world. a logical explanation of this is the fact that in the developed countries patients with ugib undergo early endoscopy within 24 hours. in the present study, in 40% of our patients endoscopy was performed after 24 hours. mucosal lesions are known to heal quickly, and delay in performing endoscopy can lead to normal endoscopic findings. moreover, it is also important that detailed history must be taken to distinguish between haematemsis, haemoptysis, and gum bleed before endoscopy. the result of our study stresses that variceal bleed is responsible for majority of cases of ugib in our population. this requires mass efforts to stop transmission of hepatitis viruses and intensive treatment of chronic hepatitis to prevent progression to cirrhosis. limitation of study is that some patients had endoscopy after 24 hours of initial episode of bleeding and it is well known fact that mucosal lesion heal quickly, so bleeding source may not be identified in these patients. conclusion variceal hemorrhage is the commonest endoscopic finding in patients presenting with upper gastrointestinal hemorrhage. amongst the nonvariceal causes, erosive mucosal lesions such as esophagitis, gastritis and duodenitis are more frequently seen than peptic ulcer in our population.the authors report no conflict of interest. the authors alone are responsible for the content and writing of paper. references 1. lirio ra. management of upper gastrointestinal bleeding in children: variceal and nonvariceal. gastrointestendosc clin n am. 2016; 26 (1):63-73. 2. rockall ta, logan rf, devlin hb, northfield tc. incidence of and mortality from acute upper gastrointestinal haemorrhage in the united kingdom. steering committee and members of the national audit of acute upper g a s t r o i n t e s t i n a l h a e m o r r h a g e . b m j . 1 9 9 5 ; 311(6999):222–6. 3. theocharis gj, thomopoulos kc, sakellaropoulos g, katsakoulis e, nikolopoulou v. changing trends in the jiimc 2018 vol. 13, no.3 149 endoscopic findings in patients with upper gi bleeding of upper gastrointestinal bleed at aziz bhatti shaheed teaching hospital gujrat. ann. pak. inst. med. sci. 2016; 12 (2):80-84. 29. rathod jb, shah dk, yagnik bd, yagnik vd. upper gastrointestinal bleeding: audit of a single center experience in western india. clinics and practice. 2011; 1(4):132-4 30. budimir i, stojsavljević s, hrabar d, kralj d, bišćanin a, kirigin ls, et al. bleeding peptic ulcer–tertiary center experience: epidemiology, treatment and prognosis. acta clinica croatica. 2017; 56(4):707-14. 31. qureshi h, banatwala n, zuberi sj, alam e. emergency endoscopy in upper gastrointestinal bleeding. jpma. the journal of the pakistan medical association. 1988; 38(2):3033. 32. wuerth ba, rockey dc. changing epidemiology of upper gastrointestinal hemorrhage in the last decade: a nationwide analysis. digestive diseases and sciences. 2018; 63(5):1286-93. 33. s h a f i s , s o o m r o r , a b b a s s z . p r o t o n p u m p inhibitors–overprescribed in a rural community. pak j med sci. 2011; 27(2):300-2. 34. suba mr, ayana sm, mtabho cm, kibiki gs. the aetiology, management and clinical outcome of upper gastrointestinal bleeding among patients admitted at the kilimanjaro christian medical centre in moshi, tanzania. tanzania journal of health research. 2010; 12(4):286-9. upper gastrointestinal bleeding. pak j med sci 2011; 27(2):277-81. 22. ghouri a, kumar s, bano s, aslam s, ghani mh. endoscopic evaluation of upper gastrointestinal bleeding in patients presenting with hematemesis within 24 hours of admission. j liaquat uni med health sci. 2016; 15(04):1748. 23. sher f, ullah rs, khan j, mansoor sn, ahmed n. frequency of different causes of upper gastrointestinal bleeding using endoscopic procedure at a tertiary care hospital. pakistan armed forces medical journal. 2014; 1(3):410-13. 24. anand d, gupta r, dhar m, ahuja v. clinical and endoscopic profile of patients with upper gastrointestinal bleeding at tertiary care center of north india. journal of digestive endoscopy. 2014; 1; 5(4):139-43. 25. jaka h, koy m, liwa a, kabangila r, mirambo m, scheppach w, et al. a fibreoptic endoscopic study of upper gastrointestinal bleeding at bugando medical centre in northwestern tanzania: a retrospective review of 240 cases. bmc research notes. 2012; 5(1):200. 26. alema on, martin do, okello tr. endoscopic findings in upper gastrointestinal bleeding patients at lacor hospital, northern uganda. african health sciences. 2012; 12(4):51821. 27. stollman n, metz dc. pathophysiology and prophylaxis of stress ulcer in intensive care unit patients. j crit care. 2005; 20(1):35-45. 28. shah ma, butt z, younis i, afzal m, atta h, nadir a. etiology jiimc 2018 vol. 13, no.3 150 endoscopic findings in patients with upper gi bleeding jiimc december 2015 final new.cdr original article abstract objective: to estimate prevalence of domestic violence and associated risk factors among pregnant women attending the federal general hospital, islamabad. study design: descriptive cross sectional study. place and duration of study: this research was conducted in the federal general hospital, islamabad from may 2014 to october 2014. materials and methods: a descriptive cross sectional survey was carried out on 150 pregnant women by employing systematic sampling. pregnant women without any serious medical complication were selected for study. standardized, pretested, domestic violence questionnaire based on pdhs 2012-2013 was used to assess domestic violence during pregnancy. a spss version 16.0 was used for data entry and analysis. descriptive analysis of all categorical variables in form of frequencies and percentages along with binary logistic regression was applied. results: overall, (24.3%) women experienced one form of abuse, answering yes to at least one of the five domestic violence questions. this study demonstrated the educational level of pregnant women; income, parity, year since married and women empowerment were significantly (p<0.001) associated with presence of domestic violence. parity was a strong predictor of physical abuse (p<0.001; or=2.8, 95%ci=1.3-3.6). women who belong to low socio-economic income (<10,000/month) were at significantly high risk (p<0.001: or=1.5, 95%ci=0.9-3.3) of physical abuse as compared to women with middle and high income (20,00050,00/month). conclusion: prevalence of domestic violence among pregnant women is very high in our part of the world. the statistically significant associated risk factors with the domestic violence are low educational level of pregnant women along with low income, parity, and poor socio-economic status. key words: domestic violence, risk factors, pregnant women. 1 with adverse consequences of pregnancy outcome. it was found that pregnant women are 60.6% more likely to be beaten than women who are not pregnant. abuse may be continuous, or it may be a single incident of assault. abuse may be physical, 2 sexual, psychological/emotional, or economic. during pregnancy, abuse may simply be business as usual, but for some women pregnancy is the trigger of the domestic violence, with male jealousy and 3 anger directed towards unborn baby. a violent pregnancy leads to adverse health consequences such as miscarriages, late prenatal care, still birth, preterm birth, fetal injury, low birth weight, mental health problems such as psychosis, post-traumatic stress disorders, suicide attempts anxiety, stress, 4 chronic pain and gynecological problems. compared with those not reporting physical violence, women who did were more likely to deliver by cesarean and be hospitalized before delivery for maternal complications such as kidney infection, premature labor, and trauma due to falls or blows to introduction pregnancy is the time when women are making physical, emotional and social preparedness for motherhood, offers no protection from abuse. for some women pregnancy is the result of their partner's violence towards them. domestic violence is a public health problem worldwide, and associated prevalence of domestic violence among pregnant women visiting federal general hospital islamabad 1 2 3 4 5 6 danish nadeem , saira alyas , waheed iqbal , jamal zafar , shahzad ali khan , mudassar mushtaq jawad abbasi domestic violence among pregnant womenjiimc 2015 vol. 10, no.4 correspondence: danish nadeem department of health system health services academy, islamabad e-mail: dnadeem55@yahoo.com 1,5 department of mnch/health system 6 department of epidemiology and biostatistics health services academy, islamabad 2 population welfare department regional training institute, multan 3 department of medicine mohtarma benazir bhutto shaheed medical college, mirpur 4 department of medicine pakistan institute of medical sciences, islamabad received: october 12, 2015; accepted: december 13, 2015 246 5-6 the abdomen. determinants of violence during pregnancy, such as socioeconomic status, maternal age, parity, education of wife, unplanned pregnancy, and consumption of alcohol or drugs, are similar to those outside of pregnancy. women with unwanted pregnancies had 4.1 times odd of having violence during pregnancy then women did planned 1 pregnancy. another study from nigeria shows prevalence of domestic violence was 28.4%. there was positive relationship between domestic violence during pregnancy; non-supervision of pregnancy and poor 7 attendances to antenatal. a review study indicates that the prevalence of violence during pregnancy 8 ranges from 0.9% to 20.1%. known risk factors for violence during pregnancy are maternal age, ethnicity, and low level of education, employment status, parity, smoking, and alcohol and drug abuse. domestic violence against women is found in the form of physical, emotional, and psychological abuse. adverse pregnancy outcome associated with violence during pregnancy may result from physical, sexual trauma, indirectly 9 through stress. a study from bangladesh found increased education, higher socioeconomic status, non-muslim religion, and extended family residence to be associated with lower risks of violence. the effects of women's status on violence were found to be highly context10 specific. intimate partner violence is extremely prevalent and relates to unwanted pregnancy and higher rates of pregnancy loss or termination, particularly m i s ca r r i a ge s , a m o n g b a n g l a d e s h i wo m e n . bangladeshi women experienced violence from 9-11 husbands were less educated, poorer, and muslim. a study from pakistan show quarter of women (23%) reported physical abuse during their recent pregnancy suggesting a serious social and health problem that is particularly challenging for pakistani obstetricians. women experienced verbal abuse during their preceding pregnancy, significantly 12 higher than china and americas. a study conducted in urban community of hyderabad shows that 51% women of reproductive age experienced physical, verbal abuse before and during pregnancy. young maternal age, having an unemployed husband and one with other wives/partners, and having had a prior pregnancy were significant predictors of 13 abuse. the few studies have been conducted in pakistan related to women violence in pregnancy and due to social and cultural problems this issue is not discussed with the health care workers. it is very crucial to have an estimate of violence in women during pregnancy especially in pakistan as violence not only affects the women but also the whole family can be the sufferer due to this issue. the objective of this study was to estimate prevalence of domestic violence and associated risk factors among pregnant women attending the federal general hospital islamabad. materials and methods a cross sectional survey was conducted in outpatient department of federal general hospital. this study spanned over a period of six months from may 2014 to october 2014. all married pregnant women who visited gynea opd at federal general hospital islamabad were included in this study. the women with comorbidities were excluded from this study. the sample size was calculated by using the single proportion formula with 95% confidence interval and 5% margin of error. for 95% ci the value of z was 1.96. this sample size was based upon 11% estimated domestic violence cases. (pdhs 2012-13) sample size based on estimated domestic violence cases 11% n= z2p (1-p) = 140 + 10% refusal = 150 systematic sampling technique was used to select rd the study participants. every 3 pregnant woman was included in the sample size of the study. domestic violence tool which was adopted for study wa s a d o p te d f ro m p d h s 2 0 1 2 2 0 1 3 . t h e questionnaire comprised of twenty seven questions. after taking consent the respondent was taken to a separate place and her privacy and confidentiality was maintained. a total of 150 respondents were interviewed. a statistical package, spss version 16.0 was used for data entry and analysis. descriptive summary statistics such as mean, frequencies, and percentages were computed for continuous variables. ten precent 10% of data was randomly checked to look for possible entry errors. descriptive analysis of all categorical variables in form of frequencies and percentages and summary statistics jiimc 2015 vol. 10, no.4 domestic violence among pregnant women 247 for continuous variables was conducted. binary logistic regression was done to see the association between domestic violence and factors affecting it. odd ratio was computed at 95% ci to see the significance. the p-values less than 0.05 were considered significant. results overall, (24.3%) women experienced one form of abuse, answering yes to at least one of the five domestic violence questions. of these, 13(8.4%) women had experienced physical violence, 3(1.9%) were subjected to sexual coercion during pregnancy, 21 (14.3%) experienced emotional violence (fear of husband). secondary school. women were mostly housewives 132 (85.7%). only 12 (7.8%) pregnant women were working. while 6 (3.9%) had other own source of earning. household income of majority participant 1 2 2 ( 7 9 . 2 % ) w e r e i n l o w s o c i o e c o n o m i c (<10,000/month). twenty five (16.2%) were those whose household income fall between 10,00020,000/month. ninety six (62.3%) women were married from six to ten years; while 39(39.3%) participants were those who were married less than five years and 15(9.7%) were in wed-lock from 11-15 years. more, than half 83(53.9%) women got pregnant 4-5 times, while 38(24.7%) women got pregnant more than five times. only 3(1.9%) women were primygravida. sixty seven (43.5%) of the participant had (3-4) children, 41(26.6%) had more than five children; while 35(22.7%) women has only 1-2 children. only 7(4.5%) women had no baby at all. one hundred and twenty six (84%) women reported their husband were smoker. while 24(16%) women their husband did not smoke. in order to see a significant difference in domestic violence and demographic factors chi squire test and binary logistic regression was used. women with no education or primary level education were at a significantly higher risk of physical violence, compared to women with secondary level education (p<0.003; or=3.1, 95%ci= 0.9-4.6). parity was a strong predictor of physical abuse (p<0.001; or=2.8, 95%ci=1.3-3.6). odds of experiencing violence were approximately double among women who had been pregnant 4-5 time as compare to primigravida (p<0.00; or=2.1.95%ci=1.6-2.8). house wives were at significantly high risk of physical violence compared with working women (p<0.00; or=1.36, 95%ci= 0.62-2.34). women who belong to low socio-economic income (<10,000/month) were at significantly high risk (p<0.001:or=1.5, 95%ci=0.9-3.3) of physical abuse as compared to women with middle and high income (20,000-50,00/month). women who were married for six to ten years (p<0.013; or=2.06; 95% ci=0.73.1) were at higher risk of being abused than women who were married for less than five. women whose husband were smoker were at greater risk of being abused as compare to women whose husband were nonsmoker (p<0.00; or=1.6, 95%ci=0.9-3.1)table ii. table i: types of domes�c violence (n=150) nine (69%) out of 13 pregnant women experienced physical violence very often, three (23.03%) out of 13 experienced it sometime, and only one (7.69%) out of 13 experienced it in last 6 months during index pregnancy. rate of emotional (verbal) abuse was slightly higher than physical abuse. seventeen (80.9%) out of 21 pregnant women were emotionally abused very often during pregnancy. sexual abuse was relatively less reported during pregnancy. different forms of physical and emotional violence was reported during pregnancy. physical violence was reported as slap or cut 7(53.8%), cut or bruises 4(30.7%) and in form of deep injuries 2(15.3%); while emotional/ verbal abuse was reported as humiliation 5(23.8%), threaten 2(9.52%) and insulted 14(66.6%). women who participated in this study were relatively young, with an average age of 24 years. seventy five (48.7%) pregnant women were between age group (20-25), while 55(35.7%) were between (26-29) years, and 13(8.4%) were fall in age group (30-39). only 7(4.5%) were below 20 years of age. results shows that 119 (77%) of them were those who were not educated. only 24(15.6%) pregnant women got primary education; while 7(4.5%) women got secondary education. education status of their husband was relatively better. about 102 (66.2%) of participant's husbands attended jiimc 2015 vol. 10, no.4 domestic violence among pregnant women 248 discussion in this research 13% domestic violence was reported that fall within the range quoted from developing countries. the widespread belief that pregnancy either initiates or increases the risk of violence was not substantiated in our study, similar to findings from other studies in developing countries. our findings lend support to screen for domestic violence during pregnancy. this research showed various demographic factors such as education, parity, marriage duration, maternal employment, and socioeconomic status were associated with increased risk of domestic 1 violence. domestic violence during pregnancy should be regarded as risk for postpartum abuse. women in abusive relationship may suffer from psychological problems. we found that domestic violence most commonly occur between 20-25 age groups. it was explained in one of the research that the phenomenon of domestic violence among pregnant women as a function of the education, domestic violence is common in illiterate or having just primary education and decline by partner education level, our results shows partner education didn't impact violence during pregnancy(p>.987).9 violence risks were doubled among women with lower (vs. higher) incomes, women who did not receive financial support from partners or family m e m b e r s . 1 v i o l e n c e w a s a s s o c i a t e d w i t h socioeconomic and behavioral factors indicative of financial hardship and social instability. consistent with the results of studies focusing on pregnant women, our bivariate analyses showed that violence was associated with low incomes,a higher income may be less important than financial support from family or partners and a stable housing situation. the findings indicated that history of violence in childhood was significantly related to physical and verbal abuse. girls who observed their mother abused by their father were more likely to assume that violence was natural in their own married life.5domestic violence against pregnant women was common in its various forms. interestingly, physical abuse during pregnancy was strongly related to previous experiences, and forms, of domestic violence, suggesting that screening for lifetime physical abuse before the onset of pregnancy can be a good predictor of, and a useful tool for prevention programs concerning abuse during pregnancy. this study confirmed previous conclusions that the vast majority of women do not object to screening table ii: risk factors associated with domes�c violence (n=150) p-value less than 0.05 was considered sta�s�cally significant. the significant values are having * sign. jiimc 2015 vol. 10, no.4 domestic violence among pregnant women 249 for domestic violence by health professionals. referral of women to adjunct social services, parenting support groups, and integration of these types of support with prenatal, postpartum, and pediatric care are also critical. our study had several methodological limitations, including its cross-sectional design; possible response bias and under-reporting given the sensitivity of the topic, and the inclusion of women from only one antenatal clinic, and the findings may not be generalizable to other pregnant women in pakistan or elsewhere. for better assessment of domestic violence, longitudinal cohort studies should be performed to identify past-year exposure at baseline and relevant preventive services, including counseling for safety and domestic abuse concerns. conclusion the prevalence of violence is quite high among pregnant women in islamabad. this result is just a tip of iceberg. the study identified some factors associated with violence against women, which can be used as foci for intervention strategies that are urgently required to prevent the devastating consequences of domestic violence on women's health. references 1. iliyasu z, abubakar is, galadanci hs, hayatu z, aliyumh. prevalence and risk factors for domestic violence among pregnant women in northern nigeria. journal of interpersonal violence. 2013; 28: 868-3. 2. drouin r. domestic violence in pregnancy. 2010. 3. cottrell s. domestic violence in pregnancy. the social context of birth. 2009; 39: 115-25. 4. murphy cc sb, myhr tl, du mont j. abuse: a risk factor for low birth weight? a systematic review and meta-analysis. cmaj. 2001. 5. cokkinides ve, coker al, sanderson m, addy c, bethea l. physical violence during pregnancy: maternal complications and birth outcomes. obstetrics and gynecology. 1999; 93: 661-6. 6. salazar m, san sebastian m. violence against women and unintended pregnancies in nicaragua: a population-based multilevel study. bmc women's health. 2014; 14:26. 7. ameh n, shittu so, abdul ma. obstetric outcome in pregnant women subjected to domestic violence. nigerian journal of clinical practice. 2009; 12: 179-81. 8. gazmararian ja, lazorick s, spitz am, ballard tj, saltzman le, marks js. prevalence of violence against pregnant women. jama : the journal of the american medical association. 1996; 275: 1915-20. 9. zareen n, majid n, naqvi s, saboohi s, fatima h. effect of domestic violence on pregnancy outcome. journal of the college of physicians and surgeons--pakistan : jcpsp. 2009; 19: 291-6. 10. koenig ma, ahmed s, hossain mb, khorshed alam mozumder ab. women's status and domestic violence in rural bangladesh: individualand community-level effects. demography. 2003; 40: 26988. 11. silverman jg, gupta j, decker mr, kapur n, raj a. intimate partner violence and unwanted pregnancy, miscarriage, induced abortion, and stillbirth among a national sample of bangladeshi women. bjog : an international journal of obstetrics and gynaecology. 2007; 114: 1246-52. 12. fikree ff, jafarey sn, korejo r, afshan a, durocher jm. intimate partner violence before and during pregnancy: experiences of postpartum women in karachi, pakistan. jpma the journal of the pakistan medical association. 2006; 56: 252-7. 13. karmaliani r, irfan f, bann cm, mcclure em, moss n, pasha o, et al. domestic violence prior to and during pregnancy among pakistani women. acta obstetricia et gynecologica scandinavica. 2008; 87: 1194-201. 14. nasir k, hyder aa. violence against pregnant women in developing countries. review of evidence. euro j pub health 2003; 13: 105-7. 15. gazmararian ja, lazorick s, spitz am, ballard tj, saltzman le, marks js. prevalence of violence against pregnant women. jama. 1996; 275: 1915-20. 16. stewart de, cecutti a. physical abuse in pregnancy. can med assoc j 1993; 149: 1257-63. 17. mcnutt j, carlson be, gagen d, winterbauer n. reproductive violencescreening in primary care: p e rs p e c t i v e s a n d e x p e r i e n c e s o f p a t i e n t s andbattered women. j am med wom assoc 1999; 54: 85-90. jiimc 2015 vol. 10, no.4 domestic violence among pregnant women 250 untitled-2 untitled-2 untitled-1 untitled-1 untitled-2 untitled-1 jiimc march 2016.cdr 1 one of the most difficult task in clinical medicine is to evaluate a patient who presents with joint pain. if you were to open the index of a rheumatology text you would find a list of over hundred different types of arthritides (table i). fortunately the more commonly seen musculoskeletal conditions can be divided into five different groups. if approached logically a working diagnosis can usually be easily obtained. editorial early diagnoses of rheumatoid arthritis is important. it should be clinical not lab dependent asim zulfiqar ------------------------------------------------correspondence: prof. dr. asim zulfiqar professor of medicine islamic international medical college riphah international university islamabad e-mail: asimzulfiqar786@gmail.com received: february 15, 2016; accepted: march 06, 2016 window of therapeutic opportunity (a time span in which the institution of effective therapeutic strategy in the form of dmards and biologicals) is important to modify the course of disease significantly, decelerating the progression of disease and minimizing joint damage and disability. early diagnosis of ra is important as early therapeutic intervention reduces the accrual of joint damage and 3 disability. in the first decade of current century the classification criteria set that was in widespread international use to define ra were the 1987 acr 4 (american college of rheumatology) criteria. those criteria gave emphasis to serological tests, rheumatoid nodules and joint erosions which are actually late features of disease. in fact these late features of disease which are pathognomonic for the diagnosis of ra can be prevented if effective therapy is given in early phase of the disease. keeping in view the problems in diagnosing era the working group developed acr/eular classification criteria for ra in 5 2010. these classification criteria were introduced to select amongst the newly presenting patients with undifferentiated inflammatory synovitis, the subset of patients who are at sufficiently high risk of persistent and/or erosive disease (this being the appropriate current paradigm underlying the disease construct ra). these classification criteria can be applied to any patient or otherwise healthy individual as long as two mandatory requirements are met. first there must be evidence of currently active synovitis in at least one joint. secondly the criteria must be applied to those patients in whom the observed synovitis is not better explained by another diagnosis. four additional criteria (table ii) can then be applied to eligible patients to identify definite ra. application of these criteria provides a score from 0 to 10 with score of 6 or >6 being indicative of ra. a patient with a score<6 cannot be classified as having definitive ra at the moment but might fulfill the criteria at a later time point. to classify a patient as having definite ra or not a history of symptom duration, a thorough joint evaluation of both small and large joints and at least one serological test (rf or acpa) and one acute phase response measure (esr/crp) must be obtained. it is acknowledged that an individual table i: simple classifica�on of arthri�c and rheuma�c 1 disorders one of the most common and devastating disease that has been encountered in clinical medicine practice is rheumatoid arthritis (ra). ra is a chronic inflammatory disease characterized by joint swelling, joint tenderness and destruction of synovial joints leading to severe disability and 2 premature mortality. ra affects between 0.5-1% of the general population, mainly during their working age affecting thus the functional capacity, with great economic burden to the individual and the society. in the last decades there was a clear evolution in knowledge about pathophysiology of the disease resulting in its approach and treatment. the association between symptom duration and ra persistence is not linear suggesting the presence of a confined period in which ra is most susceptible to treatment. early ra (era) is defined as the diagnosis given in the first weeks or months of joint symptoms or signs. the concept of era and existence of a 2 jiimc 2016 vol. 11, no.1 early diagnoses of rheumatoid arthritis is important potentiate your clinical diagnosis of ra but the presence of characteristic pattern of joint involvement of greater than six weeks duration almost makes certain the diagnosis of era. a due consideration of early aggressive treatment should be made in such patients to arrest the progressive disease at an earlier stage. references 1. alderdice c. approach to the patient with polyarthritis. can fam physician 1990; 36: 553-4. 2. pincus t, callahan lf, sale wg, brooks al, payne le, vaughn wk, et al. severe functional decline, work disability and increased mortality in ra patients. arthritis rheum 1984; 27: 864-72. 3. van nies j a b, tsonaka r, gaujoux-viala c, fautrel b, van der helm-van mil a h m. evaluating relationship between symptom duration and persistence of ra. does a window of opportunity exists. ann rheum dis 2015; 74: 806-812 4. arnett fc, edworthy sm, bloch da, mcshane dj, fries jf, cooper ns, et al. the american rheumatism association 1987 criteria for the classification of ra. arthritis rheum 1988; 31: 315-24. 5. neogi t, aletaha d, silman aj, naden rl, felson dt, aggarwal r, et al. the american college of rheumatology/ european league against rheumatism classification criteria for ra. arthritis rheum 2010; 62: 2582-91. patient may meet the definition of ra without requiring lab test or even if the serological tests are negative (seronegative ra) e.g. patients with a sufficient number of joints and longer duration (> 6 weeks) of symptoms will achieve 6 points regardless of their serological or acute phase response status. in conclusion ra is entirely a clinical diagnosis. presence of positive serology (rf/acpa) may 1 editorial first trimester miscarriages: medical or surgical outpatient management saadia sultana correspondence: prof. dr. saadia sultana professor of obstetrics & gynaecology islamic international medical college riphah international university, islamabad e-mail: saadia.sultana@riphah.edu.pk received: feburary 02, 2019; accepted: march 10, 2019 the world health organization reported 93,000 maternal deaths due to miscarriages and abortions yearly in developing countries. this represents more than 13% of all pregnancy-related deaths, and is especially prevalent in settings where access to safe health-care services is difficult. miscarriages and abortions contribute excessively to maternal morbidity and mortality in under-developed and developing countries. c o m p l i c a t i o n s f r o m u n s a fe , i n d u c e d a n d spontaneous abortions/miscarriages are recognized worldwide as a main public health fear and are one of the foremost reason women seek critical care. a lot of women survive with pelvic inflammatory disease, chronic pain, risk of ectopic pregnancies and infertility. most mortalities and morbidities are actually preventable through in-time access to safe health-care and contraception services. postabortion care, refers to specific services for those females who are experiencing problems from all types of spontaneous miscarriages or induced abortions. this term is commonly used by the 'international community for reproductive health'. availability of services for post-abortion care must be improved to reduce maternal mortality and morbidity. midwives, nurses and junior/senior doctors can safely provide post-abortion care even in outpatient settings; only if they receive appropriate support and training. access to health-care services and contraception facilities decreases the need for it and averts complications. it is much less expensive to prevent unsafe abortion/miscarriage rather to treat resulting complications. missed miscarriage is in-utero death of the embryo/foetus before the 20th week of pregnancy. it is not very uncommon, occurring in up to 10-20% of recognized pregnancies. incomplete miscarriages are incomplete expulsion of products of conception th before 20 week of pregnancy. these miscarriages can be managed expectantly, medically and surgically. medical treatment of miscarriage is the one that is carried out by taking medications. it is gaining ground as a feasible and low-cost method of uterine evacuation. multiple drugs are used for this purpose e.g. mifepristone, misoprostol and methotrexate. vaginal and oral misoprostol are safe, effective and acceptable methods of treating miscarriage with a reported effectiveness of 85–95%. increasing evidence is coming that tablet misoprostol is a safe, effective, and acceptable method to achieve uterine evacuation for women needing care after miscarriages. misoprostol must be readily available especially for women who do not otherwise have access to proper healthcare facilities. according to multiple studies in t h e re c e nt p a st , m e d i ca l m a n a ge m e nt o f miscarriages by oral misoprostol was lesser effective than mva (manual vacuum aspiration), but it was more acceptable to the patients. medical termination is well-suited for usage in low-resource situations and it must be encouraged to be used as an option for the management of incomplete/missed/ spontaneous miscarriages. latest researches have questioned the necessity for routine surgical evacuation of uterus, suggesting expectant /medical management to be more appropriate. surgical management of miscarriages has been the standard treatment across the globe for many years. its effectiveness and safety are very well proven. surgical treatment of spontaneous, incomplete, missed miscarriage, or of induced abortions, includes evacuation of the uterus with sharp curettage or mva. manual vacuum aspiration is increasingly being used to treat first trimester miscarriages. it is believed to be safe and cost department of obstetrics & gynaecology islamic international medical college riphah international university, islamabad 2 jiimc 2019 vol. 14, no.1 management of first trimester miscarriages available, health care providers can prescribe misoprostol and they should inform females about the side effects e.g. chills, fever nausea, cramping etc. and guide them about the simple management of these minor complications. women should also learn to get help when they notice/feel the bleeding as 'too much'. timely medical/surgical/both management of first trimester miscarriages/ abortions will profoundly help not only to decrease the maternal morbidity and mortality but it will also minimize the social and economic burden on the society and country. references: 1. samnani aba, rizvi n, ali ts, abrejo f. barriers or gaps in implementation of misoprostol use for post-abortion care and post-partum hemorrhage prevention in developing countries: a systematic review. repro health 2017; 14(1):139. 2. linet t. surgical methods of abortion. j gynecol obstet biol reprod. 2016; 45(10):151535. 3. mahmood h, hafeez a, masood s, faisal t, ramzan n. contraceptive use and unmet need of family planning among illiterate females of working class in rawalpindi. pafmj 2016; 66(6):871-5. 4. ansari a, abbas s. manual vacuum aspiration (mva) a safe option for evacuation of first trimester miscarriage in cardiac patients. j pak med assoc 2017; 67(6):94850 5. meena sr. comparative study of mifepristone with vaginal misoprostol for first trimester termination of pregnancy at different gestational ages. j obstet gynaecol india 2016; 66(6):426-30. 6. aiken ara, digol i, trussell j, gomperts r. self reported outcomes and adverse events after medical abortion through online telemedicine: population based study in the republic of ireland and northern ireland. bmj 2017;357 doi: https://doi.org/10.1136/bmj.j2011. 7. gupta p, iyengar sd, ganatra b, johnston hb, iyengar k. can community health workers play a greater role in increasing access to medical abortion services? a qualitative study. bmc womens health. 2017;17(1):37. 8. speedie j, robson s. the evolution of man one stop outpatient manual vacuum aspiration for termination of pregnancy. bmj 2018; 44(1): 58-60. effective in experienced hands. mva is quite a new (2013) addition to the management of incomplete abortion in our hospital. multiple studies reveal that mva is more efficient than medical termination of pregnancy in the treatment of first trimester miscarriages. if uterine size is lesser than or equivalent to gestational age 13 weeks, either misoprostol or treatment with vacuum aspirator is recommended. mva is reported to be very useful and effective procedure in low-resource settings for patients with 'incomplete/missed/spontaneous miscarriages' with a uterine size of less than 12-13 weeks. complications which are reported only in the misoprostol group and not in the mva group are: abdominal cramping (usually starting within the first few hours but it may begin as early as 10 minutes after misoprostol administration), fever, vomiting and chills. these are common side effects but are transient. fever does not necessarily indicate infection. antipyretic can be used for its relief. nausea and vomiting usually resolve within 2 to 6 hours. anti-emetic can be used if required. mva is generally considered safe, but complications such as infection, bleeding, uterine perforation and decreased fertility can occur in up to 10 % of women. relatively more complications are reported for the treatment with misoprostol than with mva. hospital stay was shorter in the mva group than the misoprostol group in almost all the studies of the last five years. after this brief review, we can conclude: in low resource settings, misoprostol can be used where mva is not available or when complete uterine clearance cannot be achieved even after misoprostol (in recommended doses). health care providers must be optimally educated/trained/drilled (in medial termination as well as in mva) beforehand, a b o u t c o m p l e t e p r o t o c o l s , p r o c e d u r e s , complications and timely referrals. in those areas where mva or operation theatre facilities are not jiimc september 2016.cdr 92 editorial rational drug use and essential drug concepts akbar waheed ------------------------------------------------correspondence: prof. akbar waheed hod pharmacology islamic international medical college riphah international university, islamabad e-mail: akbar.waheed@riphah.edu.pk received: sept 18, 2016; accepted: sept 20, 2016 rational drug therapy is defined as “administration of the right drug indicated for the disease, in right dose through an appropriate route for a right duration”following are the reasons for irrational use 1,2,3,4,5,6 of drugs: ! lack of information about drugs ! faulty training of medical graduates ! absence of role models ! lack of diagnostic facilities ! demand from patient – prompt and quick ! patient load ! promotional activities of drug companies ! exaggerated claims by drug companies ! lack of patient doctor communication ! ineffective rules and regulations there are so manyhazards of irrational useof drugs, 7,8,9 some of these hazards are given below: ! ineffective and unsafe treatment ! over treatment ! under treatment ! prolongation of ailment ! loss of patient doctor confidence following are examples of some common types of irrational uses: type i drug type ii drug used for 8 same ! choice of drug: ! efficacy of drug ! safety of drug ! cost effectiveness ! mono drug therapy ! drug combinations (only if essential e.g chemotherapy of cancert.b.etc) ! dose of the drug (optimum doses should be used) ! dosage form/route of administration (parenteral route should only be used when ! required and in emergencies) ! duration of therapy(not so long and not too short) ! patient's compliance following are some suggestion for developing national strategies for promoting rational use of 11,12,13,14 drugs. ! ebm guidelines to be developed ! essential drug lists / treatment of choice should be published by moh. ! auditing of prescription by drug and therapeutic comittees of moh. ! subject should be taught at ug level at medical colleges ! continuing medical education (cme) for doctors. ! public education through family physicians / pmdc/medical institutes. ! avoidance of perverse financial incentives by drug marketing companies. ! appropriate and strict drug regulations by moh. doctor's participation should be a pre requisite for changes in behaviour of irrational prescribing andthe objectives should be: ! to identify factors which hinder rational drug therapy ! to foster the concept of essential drugs in order to reduce the cost of health caredelivery ! to tailor prescribing to the needs of individual patients ! they should know the advantages of an essential drug list, such as cost effectiveness control, management, purchase, storage and distribution ! factor responsible for irrational therapy with some general principles for rational prescribing 6,7,8,10 are ! need for drug therapy 93 jiimc 2016 vol. 11, no.3 r e f e r e n c e t o p a t i e n t s s u c h a s h i s socioeconomic status, social taboos and beliefs, simultaneous treatment form different systems of medicine. ! prescribing irrational drug combinations & formulationby physicians. there is a need to find remedial measures to overcome irrationality at various levelsthat what is the reason for the popularity of certain drugs orcombined products which are irrational & expensive, & to find out/suggest measures to curb their unethicalpromotion. remedial measures 14,15 suggested include: ! patient education. ! improvement in diagnostic facilities. ! making essential drugs readily available at all times. ! continued medical educations of physicians/ monitoring and feedback from prescription data ! training at undergraduate and graduate level the public should be educated about the harmful effects of drugs, especially of self-medication. patient education is the responsibility of the prescriber/members of health team. patient should be explained about the drug prescribed, dose, and duration of therapy, possible side effects, implications of missing dose/ or discontinuation of 16 therapy. emphasis is needed on preventive aspects of health rather than curatives one. 14 some reasons for use of irrational drugs include: ! easy availability without prescription ! ignorance of harmful effects. ! misleading advertisements. ! att ra c t i ve i n c e nt i ve s fo r m a r ke t i n g / prescribing. advertisement for a drug influence young doctor a lot, some prescribers will look to advertisements for science on which to base their choice and marketers will provide it. the most important step in preserving the profession's integrity is to explain at under graduate/postgraduatelevels how marketing works. doctors themselves can be taught to look at 4,5 advertisement critically. conclusion: the profession needs to be alert not subverted. references 1. barnett a, creese al, ayivor eck. the economics of pharmaceutical policies in ghana. int j health serv. 1980; 10: 479-99. 2. victora cg, facchini la, grassi filho m. drug usagein southern brasilian hospitals. trop doctor. 1982; 12: 231-5. 3. hogerzeil hv. the use of essential drugs in ruralghana. int j health serv. 1986; 16: 425-39. 4. isenalumhe ae, oviawe 0. polypharmacy: its cost burden and barrier to medical care in a drug orientedhealth care system. int j health serv 1988; 18: 335-42. 5. angunawela ii, tomson gb. drug prescribing patterns:a s t u d y o f f o u r i n s t i t u t i o n s i n s r i l a n k a . i n t j clinpharmacthertox. 1988; 26: 69-74. 6. goodburn e, mattosinho s, monge p, waterston t. cost benefit of self prescribing. lancet. 1989; 2: 281. 7. weedle pb, poston jw, parish pa. drug prescribing in residential homes for elderly people in the united kingdom. dicp. 1990; 24: 533-36. 8. maitai ck, watkins wm. a survey of outpatient prescriptionsprescribed in kenyatta national hospital. east afr med j. 1980; 58: 641-5. 9. chennabuthni cs, brown dj. prescribing patterns inseychelles. trop doctor. 1982; 12: 228-30. 10. palombo fb, knapp da, brandon bm, knapp de, solomon dk, klein is, shah rk. detecting prescribingproblems through drug usage review: a case study. am h hosp pharm. 1977; 34: 152. 11. maki dg, schuna aa. a study of antimicrobial misusein a university hospital. am j med soc. 1978; 275: 271-82. 12. o v i a w e 0 , o k o n o k h u a l , i s e n a l u m h e a . prescriberperformance in a pediatric general practice clinic of auniversity teaching hospital. w afr j med 1989; 8: 1304. 13. parkinson r, wait c, welland c, vost da. cost analysisof minor ailments in rural swaziland. trop doctor. 1983; 13: 3840. 14. speight anp. cost effectiveness and drug therapy.trop doctor. 1975; 5: 89-92. 15. yudkin js. the economics of pharmaceutical supply intanzania. int j health serv. 1980; 10: 455-77. 16. glucksberg h, singer j. the multinational drug companiesinzaire: their adverse effect on cost and availability of essential drugs. int j health serv. 1982; 12: 381-7. 404 not found 172 editorial association of hypothyroidism with metabolic syndrome aamir ijaz correspondence: prof. dr. aamir ijaz professor and consultant chemical pathology rehman medical institute, peshawar e-mail: ijaz_aamir@hotmail.com received: december 08, 2018 accepted: december 24, 2018 metabolic syndrome (ms) is diagnosed when three out of five cardiometabolic risk factors are present namely hyperglycaemia, low hdl-cholesterol, high 1 triglycerides, systolic hypertension and obesity. presence of metabolic syndrome increases the risk of cardiovascular diseases and type 2 diabetes mellitus 2 (t2dm). other conditions have also been related to metabolic syndromes e.g. cancer, sleep apnea, polycystic ovary syndrome, thyroid disruptions and 3,4 others. there is a worldwide epidemic of ms, pakistan and some other developing countries are no 4 exception . hypothyroidism can be overt or subclinical. subclinical-hypothyroidism (sch) is defined when tsh values are more than 4.0 miu/l but less than 10 miu/l with normal thyroid hormones (ft4 5,6 and ft3). the etiological factors for sch and overt disease are the same with a difference of severity of t h e d i s e a s e , s o s h o i s a l s o ca l l e d ' m i l d hypothyroidism' as by definition sch is only a biochemical diagnosis and has nothing to do with the presence or absence of clinical features of thyroid disease. sho has been shown to be much more 7 common as compared to overt disease. sch becomes a dilemma for the physician regarding the question of treatment or waiting for the overt 8,9 disease. amongst many concerned related to hypothyroidism, a propensity for dyslipidaemia is of great concern more so if the patients has other cardiovascular risk factors, too. khan et al (2018) have recently shown that lipid parameters are adversely affected in hypothyroidism as a continuous function of increasing level of tsh. lipid changes are found to be more subtle in the subclinical hy p o t hy ro i d g ro u p t h a n ca s e s w i t h ove r t 10 hypothyroidism. most significant effect has been shown to be on ldl-cholesterol, non-hdlcholesterol and urine albumin-creatinine ratio. in another recent study it has been shown that he association between ms and hypothyroidism depends on the presence of t2dm. the most important pathophysiological mechanism in t2dm is insulin resistance (ir), so it is difficult to ascertain the role of sch in causation of ms in the presence of 11 t2dm. various components of metabolic syndrome i.e. high blood pressure, elevated triglycerides level, obesity, and ir have been shown to be closely related to 12,13 subclinical hypothyroidism. it has also been shown that even persons with tsh in the upper reference values (2·5–4·5 mu/l) were more obese, had higher triglycerides, and had an increased 14 likeliness for the metabolic syndrome. slightly elevated serum tsh levels have also been shown to be associated with an increase in the occurrence of 15 obesity. another puzzling finding about thyroid hormones and metabolic syndrome is from wolffenbuttel et al (2017), who have shown that in men, lower ft4 is related to ms but in the highest free triiodothyronine (ft3) and free thyroxine (ft4) quartiles, there is a 50–80% increased risk of having 16 ms compared to the lowest quartile. this has been confirmed in other recent studies showing ms developing in patient with high ft3 as well as higher 17,18 ft3/ft4 ratio. insulin resistance is the major biochemical mechanism involved in the causation of ms as well as polycystic ovaries syndrome and non19 alcoholic fatty liver disease. hypothyroidism is associated with elevated markers of insulin resistance such as homeostatic model of insulin 20 21 resistance (homa-ir) in adults and children. despite these known associations, the temporal relationships between subclinical hypothyroidism and assorted cardiovascular risk factors remain largely unexplored and studies are needed to find the chronology of development of components of ms with progression of hypothyroidism. moreover, tsh should be taken as yardstick for decreasing thyroid function as it is a hormone of the mother gland and the anxiety of the mother gland (pituitary) cannot be compared with the concern of a small child (thyroid) who is totally oblivious of his health key words: hypothyroidism, metabolic syndrome, sub-clinical hypothyroidism. 173 jiimc 2018 vol. 13, no.4 22 condition due to his shear ignorance. tsh alone is a sufficient parameter for the early diagnosis and monitoring of hypothyroidism before one or more components of ms develop. in clinical practice, before starting treatment of dyslipidaemia, obesity or systolic hypertension, especially in a young patient, tsh estimation must be not be forgotten! references 1. what is metabolic syndrome. national heart, lung, and b l o o d i n s t i t u t e . a c c e s s e d 1 2 / 1 2 / 2 0 1 8 . https://www.idf.org/e-library/consensus-statements/60idfconsensus-worldwide-definitionof-the-metabolicsyndrome 2. nolan pb, carrick-ranson g, stinear, jw, reading sa, and dalleck lc., prevalence of metabolic syndrome and metabolic syndrome components in young adults: a pooled analysis. preventive medicine reports 2017;7:211–215. 3. delitala ap, fanciulli g, pes gm, maioli m, and delitala g. thyroid hormones, metabolic syndrome and its c o m p o n e n t s . e n d o c r i n e , m e t a b o l i c & i m m u n e disorders—drug targets 2017;17(1):56–62. 4. esposito kp., chiodini a, colao a, . lenzi a and giugliano d. metabolic syndrome and risk of cancer: a systematic review and meta-analysis. diabetes care 2012;35(11):2402–2411. 5. khan sh and ijaz a. subclinical hypothyroidism: a pathology in evolution. (systematic review). journal of the college of physicians and surgeons pakistan 2019;29(2). 6. surks mi, ortiz e, daniels gh et al., subclinical thyroid disease: scientific review and guidelines for diagnosis and management. journal of the american medical association 2004;291(2) 228–238 7. ijaz a, marri mh, qureshi ah, qamar ma, ali n. pattern of subclinical thyroid disease. j coll physicians surg pak 2002;12(2):86-8. 8. hashim r, anwer ms, khan fa, ijaz a. subclinical hyperthyroidism-a cohort study. pak armed forces med j 2013; 63(3). 9. anwer ms, hashim r, khan fa, ijaz a. frequency of conversion to overt hypothyroidism in patients with and without subclinical hypothyroidism. j ayub med coll abbottabad 2012;24(3-4):166-170. 10. khan sh, manzoor sm, niazi nsk, asif n, ijaz a, fazal n. a s s o c i at i o n o f m eta b o l i c r i s ks w i t h s u b c l i n i ca l hypothyroidism: a cross-sectional analysis. pak j med sci. 2 0 1 8 ; 3 4 ( 2 ) : 3 5 7 3 6 2 . d o i : h t t p s : / / d o i . o r g / 10.12669/pjms.342.13873. 11. bermúdez v, salazar j ,añez r, rojas m, estrella v, ordoñez m. metabolic syndrome and subclinical hypothyroidism: a type 2 diabetes-dependent association. journal of tyroid research. 2018;. article id 8251076, 8 pageshttps:// doi.org/10.1155/2018/8251076. 12. chang ch, yeh yc, caffrey jl, shih sr, chuang lm, tu yk. metabolic syndrome is associated with an increased incidence of subclinical hypothyroidism a cohort study. sci rep. 2017;7(1):6754. published 2017 jul 28. doi:10.1038/s41598-017-07004-2. 13. ruhla s, weicket mo, arafat am, osterhoff m, isken f, spranger j. et al., a high normal tsh is associated with the m e t a b o l i c s y n d r o m e . c l i n i c a l e n d o c r i n o l o g y. 2 0 1 0 ; 7 2 : 6 9 6 – 7 0 1 . d o i : 1 0 . 1 1 1 1 / j . 1 3 6 5 2265.2009.03698.x. 14. khan s, afsana f, talukder k, ashrauzzaman am, pathan f, latif a. presence and association of sub clinical hypothyroidism in subjects with metabolic syndrome. diabetes metab syndr. 2011 oct-dec;5(4):183-7. doi: 10.1016/j.dsx.2010.12.006. epub 2011 jan 19 15. knudsen n, laurberg p, rasmussen lb, low ib, perrild h, ovesen l, et al. small differences in thyroid function may be important for body mass index and the occurrence of obesity in the population. the journal of clinical endocrinology and metabolism. 2005;90:4019–4024. doi: 10.1210/jc.2004-2225. 16. wolffenbuttel bhr, wouters hjcm, slagter sn, et al. thyroid function and metabolic syndrome in the population-based lifelines cohort study. bmc endocr d i s o rd . 2 0 1 7 ; 1 7 ( 1 ) : 6 5 . p u b l i s h e d 2 0 1 7 o c t 1 6 . doi:10.1186/s12902-017-0215-1 17. urrunaga-pastor d, guarnizo-poma m, moncada-mapelli e, aguirre lg, lazaro-alcantara h, paico-palacios s, et al. high free triiodothyronine and free-triiodothyronine-to-freethyroxine ratio levels are associated with metabolic syndrome in a euthyroid population. insulin resistance and metabolic syndrome research group.. diabetes metab syndr. 2018;12(2):155-16. 18. roos a, bakker sj, links tp, gans ro, wolffenbuttel bh. thyroid function is associated with components of the metabolic syndrome in euthyroid subjects. the journal of clinical endocrinology and metabolism. 2007;92:491–496. doi: 10.1210/jc.2006-1718. 19. saki f, karamizadeh z. metabolic syndrome, insulin resistance and fatty liver in obese iranian children. iran red crescent med j. 2014;16(5):e6656. 20. javed a, balagopal pb, vella a, et al. association between thyrotropin levels and insulin sensitivity in euthyroid obese adolescents. thyroid. 2015;25(5):478-84. 21. nader ns, bahn rs, johnson md, weaver al, singh r, and kumar s. relationships between thyroid function and lipid status or insulin resistance in a pediatric population thyroid. dec 2010 http://doi.org/10.1089/thy.2010.0180. 22. anwar ms, ansari u, ahmed a and bashir s. thyroid disorders. in ijaz a (ed) chemical pathology for the beginners. azeem academy press, lahore, pakistan pp 200201. original�article abstract objective: to determine effectiveness of post natal exercises to improve incision pain and functional activities in female following cesarean section. study design: experimental, randomized controlled study design.� place and duration of study: the study was conducted in gynecology and physiotherapy department of st st pakistan railway hospital, rawalpindi from 01 february 2017 to 31 march 2017. materials and methods: twenty women who had undergone caesarian section after spinal or epidural anesthesia were included in the study with informed consent. patients having multiple births, patients with controlled anesthesia, with general anesthesia, operative complications and fetal abnormalities were excluded. subjects were randomly allocated in two groups; one receiving post-natal exercise plan and the other receiving routine nursing care. intervention included deep breathing exercise, inter-digital technique, coughing technique, ankle pumps, leg sliding, pelvic rolling, abdominal wall setting exercise and postural education. exercises were repeated twice a day for three days post cesarean section. patients were evaluated st nd for general pain intensity, difficulty in functional activities, time of ambulation and analgesic intake on 1 and 2 post-operative day. results were analyzed on ibm spss 20 using independent t test. results: mean age of interventional group (n= 10) was 28.10 ± sd 5.30 and 29.60 ± sd 2.54 years for the control st group (n = 10). p value for pain was found non significant (p = 0.152) on 1 post-operative day but showed a nd significant difference (p = 0.020) on 2 post-operative day indicating better outcomes for exercise group. significant p values were observed in exercise group for difficulty in performing activities like turning in bed (p = 0.001), sitting (p = 0.008), standing (p < 0.001) and walking (p < 0.001). conclusion: post natal exercises improve mobility and reduce pain in females who had undergone caesarian section after spinal or epidural anesthesia. key words: caesarean deliveries, functional activities, physiotherapy. 2 and suggest physiotherapy as need of hour. one of the major obstetric procedures that faced high rate controversies for years is caesarean section. caesarean section became highly popular with its rate being dramatically increased in recent few decades over the world. this increased rate led 3,4 to raised maternal morbidity and mortality. according to who guidelines 2009 no region in the world can cross a set limit of 10-15% of caesarean 5 deliveries. in pakistan according to the available data institutional deliveries illustrate increased rate of caesarean section. this raised rate of c-section set mothers at high risk of developing future medical 6 complications. therefore affecting quality of life in 4 females after caesarean delivery. common cause of acute obstetric pain is caesarean section. traditionally opioids and non-steroidal antiinflammatory drugs (nsaids) are used for post o p e rat i ve a n a l ge s i a m a n a ge m e nt b u t st i l l introduction numerous studies are to be assessing different problems as a result of delivery either vaginal or caesarean section, but only few studies are found to focus on physiotherapy care in post natal quality of 1 life among females. however recent researches are focusing on physiotherapy plan for postpartum care ease in pain and functional activities following caesarean delivery by post natal exercises (pilot study) 1 2 3 qurat ul ain , fareesa waqar , ayesha bashir correspondence: dr. qurat ul ain department of physical therapy and rehabilitation sciences riphah college of rehabilitation sciences riphah international university, islamabad e-mail: qurat.iimc@gmail.com 1,3 department of physical therapy and rehabilitation sciences riphah college of rehabilitation sciences riphah international university, islamabad 2 department of gynecology and obstetrics islamic international medical college, rawalpindi funding source: nil; conflict of interest: nil received: apr 19, 2017; revised: feb 18, 2018 accepted: feb 20, 2018 ease in pain and functional activity after c-sectionjiimc 2018 vol. 13, no.1 32 and odd dates of c-section. interventional group (n=10) received physiotherapy session on zero postoperative day and first post-operative day. the control group (n=10) received routine nursing care. both groups were given routine analgesics for postoperative pain management. physical characters recorded include age, height, weight and body mass index. number of pregnancies, history of past gynae & obstetrical surgeries and complications in gestation were recorded. time taken for first ambulation after transfer to obstetric ward was calculated. intensity of pain was recorded using numeric rating scale. difficulty in functional activity including turning in bed, sitting, standing and walking were marked on numeric rating scale (zero = no pain, 10 = maximum st pain). data was obtained at 1 post-operative day st nd after 1 ambulation and 2 post-operative day after the physiotherapy session. patients were observed for adverse effects of physiotherapy but no such effects were reported by the patient. interventional group was given post-natal exercises with 10 repetitions of each exercise. these exercises included deep breathing exercise (to improve exchange of gases), inter-digital technique for chest expansion (to improve circulation and promote exchange of gases), protected huffing technique (to remove secretions), ankle pumps (to improve blood circulation and relaxing calf muscles), leg sliding (to improve circulation), pelvic rolling and abdominal wall setting exercise (to stimulate intestinal activity, contract abdominal muscles and prevent or control gas pain). patient was also educated regarding postural adjustments and advised to repeat the exercises twice a day. control group was given routine nursing care by the nursing staff of the gynae ward and postural education was guided by the physiotherapist. statistical analysis was done using ibm spss 20. independent t-test was applied on pain and difficulty st nd in all four functional activities on 1 and 2 postoperative day separately. tool used was numeric pain rating scale. data was normally distributed according to the test of normality and hence the test of choice was independent-t test. results female participants included in the study were equally divided in two groups. mean age for inadequate relief and patient satisfaction is common 6 in many cases. literature supports the effectiveness of breathing exercises and respiratory physiotherapy to improve pulmonary functions in females having 7 caesarean section under general anesthesia. a recent study by juliana schulze burti and colleagues found exercise protocol optimistically contributed to the reduction of pain and improvement of general 8 well-being. other non-pharmacological approaches to manage pain after caesarean deliveries include therapeutic acupressure for reduction in pain 9 perception, anxiety, depression and pain. several studies suggest transcutaneous electrical nerve stimulation to be effective in treating incision pain in 10,11 early post caesarean period. females having caesarean section births experience higher intensities of pain while perform activities & during movements in comparison to females having vaginal delivery births. consequently females having caesarean section exhibit greater functional limitation for specific movements. moreover this pain and functional limitation was not associated 9 with parity. as limited literature is available regarding physiotherapy plan and its outcome in post natal care so the current study was conducted to find out effectiveness of post natal exercises to improve incision pain and functional activities in female following cesarean section. materials and methods a randomized controlled pilot study was conducted on females who had caesarean delivery in gynecological department, pakistan railway hospital in collaboration with physiotherapy department st st from 01 february 2017 to 31 march 2017. sample consisted of females who had epidural anesthesia for caesarean section. patients having multiple births, patient controlled anesthesia, c-section with general anesthesia, operative complications and females who were identified having any fetal abnormality according to the anomaly scan were excluded from the study. using purposive sampling techniques 20 female patients were included in the study. patients falling on the criteria were informed and written consents were taken. only 2 patients refused to participate and 20 females completed the study. it was an assessor blinded trial. patients were randomly assigned in both groups according to even 33 ease in pain and functional activity after c-sectionjiimc 2018 vol. 13, no.1 discussion many studies have been conducted to assess the problems associated with cesarean section, but physiotherapy aspect and its effects after caesarean still require attention of the researchers. the results of this study show that pain after caesarean section can be reduced by physiotherapy including mobility exercises, breathing techniques and postural care. both interventional and control groups were taking analgesics three times a day and the pain experienced with medication was assessed. st non-significant results were found on 1 postnd operative day regarding general pain but on 2 postoperative day a significant reduction in pain was observed. similar results were found in a study conducted by ãlkim çâtak karakaya et al using transcutaneous electrical nerve stimulation as a part of physiotherapy management along with 12 exercises. another recent study by juliana schulze burti and colleagues also shows similar result that exercise protocol optimistically contributed to the reduction of pain and improvement of general well8 being. breathing exercises are found to be helpful in improving circulation and healing thereby inducing relaxation by mild muscular activity in abdominal 12 area. breathing exercises should be considered while planning physiotherapy exercising for post cesarean patients. vermelis and colleagues conducted a study in 2010 on prevalence and predictors of chronic pain after labor and delivery. according to this study rate of chronic low back pain after delivery is more in cesarean section (6-18%) as compared to vaginal 1 3 deliveries (4-10%). several techniques are considered to overcome pain after delivery lena nilsson-wikmar et al in their study found that postpartum back pain effects activities related to 14 movements and requires special attention. physical therapy is considered to be an important intervention that requires to be initiated in early post natal period to reduce pain and improve mobility status of the patient. emily norman, margaret sherburn, richard h. osborne and mary p. galea in their study in 2010 evaluated effectiveness of physiotherapy regimes and health care educational programs on well-being of post natal females. physiotherapy is found effective not only in interventional group was 28.10 ± 5.30 and 29.60 ± 2.54 for the control group. mean body mass index for the interventional group was 23.84 ± 2.90 and for control group it was 22.07 ± 5.66. independent t test was applied to assess the difference in the ambulation of groups and was found non-significant with p value of greater than 0.05 (p = 0.230). mean value of pain among both groups is shown in the figure below. as the figure shows that mean st value for pain at 1 post-operative day exhibits difference among the two groups but statistical analysis do not show a significant p value (p = 0.152). nd however significant p value (0.020) was found at 2 post-operative day. fig 1: comparison of pain (numeric pain ra�ng scale) at 1st & 2nd post-opera�ve day in both groups a significant difference was found among both groups regarding reduction in difficulty and pain while performing functional activities. after both sessions given at zero post-operative day and first post-operative day results were significant in interventional group but more obvious results nd appear at 2 post-operative day. st nd table i: comparison of func�onal ac�vi�es at 1 & 2 post-opera�ve day in both groups 34 ease in pain and functional activity after c-sectionjiimc 2018 vol. 13, no.1 pregnancy/t/c-sectionrates-around-globe-epidemiclevels/#.wprg9wnyviu. 6. belizán jm, althabe f, cafferata ml. health consequences of the increasing caesarean section rates. epidemiology. 2007; 18: 485-6. 7. kaplan b, rabinerson d, neri a. the effect of respiratory physiotherapy on the pulmonary function of women following cesarean section under general anesthesia. international journal of gynecology & obstetrics. 1994; 47: 177-8. 8. burti js, da silva cruz jdp, da silva ac, moreira idl. assistance in immediate puerperium&58; the role of physiotherapy. revista da faculdade de ciências médicas de sorocaba. 2017; 18: 193-8. 9. chen hm, chang fy, hsu ct. effect of acupressure on nausea, vomiting, anxiety and pain among post-cesarean section women in taiwan. the kaohsiung journal of medical sciences. 2005; 21: 341-50. 10. kose sk, arioz dt, toktas h, koken g, pektas mk, kose m, et al. transcutaneous electrical nerve stimulation (tens) for pain control after vaginal delivery and cesarean section. the journal of maternal-fetal & neonatal medicine. 2014; 27: 1572-5. 11. babu as, vasanthan lt, maiya ag. transcutaneous electrical nerve stimulation to reduce pain in post-op thoracotomy patients: a physical therapists' perspective. indian journal of anaesthesia. 2010; 54: 478. 12. karakaya ic, yüksel i, akbayrak t, demirtürk f, karakaya mg, özyüncü ö, et al. effects of physiotherapy on pain and functional activities after cesarean delivery. archives of gynecology and obstetrics. 2012; 285: 621-7. 13. vermelis jm, wassen mm, fiddelers aa, nijhuis jg, marcus ma. prevalence and predictors of chronic pain after labor and delivery. current opinion in anesthesiology. 2010; 23: 295-9. 14. wikmar ln, pilo c, pahlbäck m, harms-ringdahl k. perceived pain and self-estimated activity limitations in women with back pain post-partum. physiotherapy research international. 2003; 8: 23-35. 15. norman e, sherburn m, osborne rh, galea mp. an exercise and education program improves w e l l b e i n g o f n e w mothers: a randomized controlled trial. physical therapy. 2010; 90: 348. 16. stuge b, lærum e, kirkesola g, vøllestad n. the efficacy of a treatment program focusing on specific stabilizing exercises for pelvic girdle pain after pregnancy: a randomized controlled trial. spine. 2004; 29: 351-9. improving well-being scores but also reduces 15 depressive symptoms. in 2004 another study also suggested that specific physiotherapy exercises are helpful in reducing pelvic girdle pain after pregnancy. so physiotherapy is essential part of treatment regarding post natal well-being by reducing pain 16 after delivery especially cesarean section. sample size for the current study was small as it was pilot study and tools assessing mobility should also be applied to measure outcomes more precisely. though findings of this study are limited but contribute to the existing literature. however further studies should be conducted with longer duration of treatment and to design a standard protocol for post cesarean patients to achieve optimal results. conclusion current study concludes that post natal exercises are effective in improving intensity of pain and functional status in terms of ambulation and ease in movement, in comparison to patients who receive only nursing care. references 1. shah d, parikh h, verma m, tyagi r. postnatal quality of life in women after normal vaginal delivery and cesarean section with and without physiotherapy care. journal of clinical & experimental research. 2014; 2: 89-94. 2. chauhan r, sahu b, singh n, malviya r, tiwari p. enhancing normal labour by adopting antenatal physiotherapy: a prospective study. international journal of reproduction, contraception, obstetrics and gynecology. 2017; 5: 2672-6. 3. lee si, khang yh, lee ms. women's attitudes toward mode of delivery in south korea—a society with high cesarean section rates. birth. 2004; 31: 108-16. 4. tampakoudis p, assimakopoulos e, grimbizis g, zafrakas m, tampakoudis g, mantalenakis s, et al. cesarean section rates and indications in greece: data from a 24-year period in a teaching hospital. clinical and experimental obstetrico & gynecology. 2004; 31: 289-92. 5. press a. c-section rates around globe at "epidemic" levels. hanoi, vietnam: associated press; 2010; available from: http://w w w.nbcnews.com/id/34826186/ns/health35 ease in pain and functional activity after c-sectionjiimc 2018 vol. 13, no.1 page 37 page 38 page 39 page 40 original�article abstract objective: to establish the content and construct validity of structured long interview and clinical examination (slice) as an instrument for the assessment of long case. study design: this was a quantitative analytical study. place and duration of study: the study was conducted at pakistan railway general hospital during the period between march 01, 2016 to august 31, 2016. materials and methods: slice is a tool of long case assessment, however, it's content and construct validity are not established. examiners, who had used slice for the long case assessment, were requested to fill the questionnaire. the questionnaire contained questions about the relevance and clarity of slice. each examiner individually rated the relevance and clarity of all the items on the slice using a five point likert scale. content validity index of slice was established for individual items and overall scale. the construct validity of slice was determined by factor analysis using principal component analysis method. results: content validity index of slice (s-cvi), for relevance and clarity was 0.92 and 0.90 respectively. kmo value of slice was 0 .655. bartlett test value of slice was 0.00. conclusion: the content validity index for overall scale (s-cvi) and construct validity indicates that slice is a valid instrument for the long case assessment. key words: assessment, long case, slice, validity. inclinations, personal will and perceptions about the 3,4 examinee. another problem is that difficulty of long case is not marked in the assessment. the result of long case assessment depends considerably on difficulty of the clinical problems of the patient allocated to the examinee. if the examinee gets a difficult case with multiple clinical problems, he may fail or get poor grades as compared to the clinically less competent fellow who gets a patient with a 5,6,7,8 single problem. in pakistan each class of mbbs, consists of 100-300 students. it is impractical to observe the history taking and clinical examination of every student by the examiner, because this would require a lot more resources in terms of time, faculty involvement and the patients' commitment. the only practical way to hammer the drawbacks, confronted during the long case assessment is to assess the long case by using the structured assessment tool, so that the results are valid, reliable and free of bias. for the structured assessment of long case, many instruments had been designed as osler (observed structured long examination record), pbac (practice based assessment of clerks in internal medicine), and sccp 9 (structured clinical case presentation). similarly slice was established for the structured assessment introduction the long case examination assess the clinical competency of the medical students with real 1 patients, in real clinical environment. in undergraduate setting, the conventional method for the assessment of long case has many drawbacks. during undergraduate long case examination by ' conventional method, the student s performance in history taking and clinical examination is un 2 observed by the examiner. the assessment of the long case examination is also un-structured. the examiners are devoid of the structured checklist and the marking scheme, so the examiners are free to award marks, depending on their personal establishing validity of slice –as an assessment instrument of long case 1 2 3 4 5 6 abdul ghani waseem , shamaila sharif , muhammad saqib habib , rehan ahmed khan , usman hameed , adil hameed correspondence: dr. abdul ghani waseem associate professor department of medicine islamic international medical college riphah international university, islamabad e-mail: abdul.ghani@riphah.edu.pk 1,2,3,4,6 department of medicine/gynaecology/surgery islamic international medical college riphah international university, islamabad 5 department of medicine agha khan medical college, karachi funding source: nil; conflict of interest: nil received: november 01, 2018; revised: january 09, 2019 accepted: january 20, 2019 jiimc 2019 vol. 14, no.1 43 validity of slice comprised of questions about clarity of items, of slice, on a five-point likert scale. the five responses were, not clear, some -what clear, undecided, clear, and very clear. purposely chosen 16 experts, who used slice sheet for assessment of long case, were asked to review the 13-items slice. each reviewer independently rated the relevance of each item on the slice using a 5-point likert scale. content validity index for the relevance and clarity of individual items and overall scale was determined. the i-cvi was calculated by number of expert giving 4 or 5 rate to the individual items on the scale (4 or 5 rate show relevance of the individual items in the scale under study) and then dividing it by the total number of experts. i-cvi = number of experts giving a rating of either 4 or 5 to individual item in scale / total number of experts. the s-cvi was calculated by the following method, s-cvi/ave as (.90+.90+.90+ .90+.90+.90)/6= 0.90 spss version 21 was used to analyze the data. the data was non parametric. the construct validity of slice was determined by factor analysis using principal component analysis method. results relevance history taking domain of slice consists of 03 items. the cvi – i of all three items of history taking domain turned out to be +1 (table i). examination domain of slice consists of 02 items. the cvi–i of the two items of examination domain was 0.94 and 0.88 (table i). defending diagnosis domain of slice consists of 02 items. the cvi –i of two items turned out to be 0.94 and +1 (table i). investigations domain of slice consists of 02 items. the cvi i of the two items was 0.88 and +1 (table i). management domain of slice consists of 04 items. the cvi –i of 02 items of management domain was 0.88, the other two items had cvi-i 0.94 and 0.75 (table i). clarity history taking domain of slice consists of 03 items. the cvi –i of one item had value of +1 and the other two had values 0.93 and 0.94(table i). examination domain of slice consists of 02 items. the cvi –i of both the items was 0.88 (table i). defending diagnosis domain of slice consists of 02 items. the cvi –i of both the items was 0.94 and+1(table i). investigations domain of slice consists of 02 items. the cvi –i of both the items had value of +1(table i). of long case, of final year medical students at islamic i n t e r n a t i o n a l m e d i c a l c o l l e g e . t h e s l i c e (annexure. 1) has 13 items for the long case examination record. the examiners assess the examinee on these 13 items over 15 minutes. the examiner after giving marks for each individual item on the slice sheet, calculate the overall marks and takes pass/ fail decisions. rehan et al established the reliability and face validity of slice, however, the content validity and construct validity of slice were 10 not established. the purpose of this study was to determine the content and construct validity of slice sheet, which is a new instrument for the structured assessment of the long case. materials and methods this quantitative analytical study was planned to establish the content validity and construct validity of slice. the study was conducted in pakistan railway general hospital, which is a teaching hospital affiliated with islamic international medical college. the study was conducted between march 01, 2016 to august 31, 2016. slice is already in use for the assessment of long case examination of final year mbbs students at islamic international medical college. examiners who had used slice, as an assessment instrument of long case at islamic international medical college were included in the study. these examiners were from the departments of medicine, pediatrics, gynaecology/obstetrics and surgery of pakistan railways general hospital. examiners, who came from other teaching hospitals for the summative assessment of final year mbbs and used slice as assessment instrument, were also included in the study. examiners and faculty, who had never used slice for long case assessment, were excluded from the study. the questionnaire was designed and approved from the ethical committee of islamic international medical college. the questionnaire with the covering letter explaining the purpose of the study was distributed among participants by the researcher. the questionnaire comprised of two parts. the sheet 1 of questionnaire comprised of questions about the relevance of slice items, on a five-point likert scale. the five responses were, not relevant, some -what relevant, undecided, relevant, very relevant. the sheet 2 of questionnaire jiimc 2019 vol. 14, no.1 44 validity of slice indicates the strength of the relationship among different variables. the significant is less than 0.05. table ii shows bartlett test value of slice was 0.00, which also shows a strong relationship among the different variables.the scree plot (fig 1) is the graphic representation of the eigen values against all the factors. the graph helps in determination of how many factors to be retained. the point of importance is where the curve begins to flatten. so it can be recognized that the curve starts to flatten between factor 5 and 6. it can be noted that factor 6 onwards have eigen value of less than 1, so only 5 factors have been retained. management domain of slice consists of 04 items. the cvi – i of these four items was 0.81, 0.69, 0.88 and 0.75 respectively (table i). s-cvi of slice regarding the relevance of slice is 0.92 (table 1). the s-cvi regarding the clarity of slice is 0.90 (table i). table i: content validity index of slice factor analysis the kaiser-meyer-olkin measure of sampling adequacy (kmo), measures the sampling advocacy and determines if the responses given are supportive or not. kmo should be close to 0.5 for a satisfactory factor analysis. kaiser recommended values of 0.9 as superb, values between 0.7 to 0.8 as acceptable and 0.5 as minimum. table ii shows that kmo value of slice was 0.655, which is close to acceptable and above the minimum requirement. barlett test also table ii : kaiser-meyer-olkin and bartle�'s test of slice discussion slice, including 13 items, was designed and used for the assessment of long cases at islamic international medical college. it proved to be useful and an appropriate effort to increase the reliability and validity of long case examination. examiner can generalize the results after objective assessment of fixed number of items of slice. slice can also be considered examiner friendly as it reminds the examiner to check the same domains for all students. fig 1: scree plot for slice jiimc 2019 vol. 14, no.1 45 validity of slice 10 and those contributed by rehan et al study, slice turned out to be valid instrument for the long case assessment. some other instruments for the structured assessment of long case includes objective structured long examination record (osler), structured long interview and clinical examination (slice), structured clinical case presentation (sccp), practice based assessment of clerks in internal medicine (pbac), long case assessment (lca), observed long case in clinical assessment (olc), partially observed long case exam (pole), direct observation clinical encounter examination (docee), integrated direct observation clinical encounter examination (idocee ). these different instruments which were designed for structured assessment of long case vary in the observation of history taking and clinical examination by the student, number of examiners assessing the student at one time and time required by the examiner for assessment of the students. the objective structured long examination record (osler) was introduced by gleeson as a method to introduce better standardization to the long case. the student conducts an hour long observed history and examination with a patient followed by 20-30 minutes of structured questioning by the examiner using a 10 item analytical record. as a part of the effort to reduce “the luck of the draw” aspect, examiners are asked to formally document the difficulty of the case. unfortunately there is no 11 evidence as to reliability and validity of the osler. in short, long case assessment with itemized list would lead to enhancement in validity of long case assessment, satisfaction of the students, better learning of the students and motivation of the students. conclusions the content validity index for overall scale (s-cvi) of slice and construct validity indicates that slice is a valid instrument for the long case assessment. limitations slice is used at islamic international medical college only; the questionnaire was filled by the examiners of final year mbbs examination. better evaluation of slice could be done if the number of experts is increased and experts from different medical colleges are contacted for the responses. slice is also feasible because it assesses the long case over 15 minutes while many other tools assess the examinee over 20 – 30 minutes. the cvi – i of individual items regarding their relevance were found to be 88% and more except for one item, which is describe the recent advances. however, cvi – i of this domain is still in the acceptable range i.e.75%. the content validity index of overall scale for relevance was above 92% (table i). these results strongly determine the relevance of items of slice thus endorsing its content validity. the cvi –i of individual items for clarity was 81% and more for eleven, out of thirteen items. these two items were, to describe the complications of treatment and the recent advances. the cvi – i of these two items were also in acceptable range i.e. 69% and 75%. the content validity index of overall scale for clarity was above 90% (table i). these results strongly prove the clarity of items of slice thus endorsing its content validity. the kaiser-meyer-olkin measure of sampling adequacy (kmo), measures the sampling advocacy and determines if the responses given are supportive or not. table ii shows kmo value of slice was 0.655, which is close to acceptable and above the minimum requirement. barlett test also indicates the strength of the relationship among different variables. the significant value is less than 0.05. table ii shows bartlett test value of slice 0.00, which also shows a strong relationship among the different variables. the scree plot (fig 1) is the graphic representation of the eigen values against all the factors. the graph helps in determination of how many factors to be retained. the point of importance is where the curve begins to flatten. so it can be recognized that the curve starts to flatten between factor 5 and 6. it can be noted that factor 6 onwards have eigen value of less than 1, so only 5 factors had been retained. the results of factor analysis show that different items in slice had strong relationship among themselves and significant eigen values. the results of factor analysis shows that the slice had good construct validity. rehan et al established the reliability and face validity of slice, however, the content validity and construct validity of slice were not established. slice had good face validity and the reliability of the 10 slice had been found to be 0.87. the results of present study show that slice had good content and construct validity. considering the present results jiimc 2019 vol. 14, no.1 46 validity of slice (osler).medical teacher 1997; 19:7-14. 8. olson lg. the ability of a long case assessment in one discipline to predict students' performances on long case assessments in other disciplines. acad med 1999; 74:835– 8. 9. price j, byrne ja. the direct clinical examination: an alternative method for the assessment of clinical psychiatry skills in undergraduate medical students. med educ 1994; 120–5. 10. khan ra, danish kf. hameed fm, anwar m. assessing the long case in undergraduate medical students: development of structured, feasible, valid and reliable tool. jiimc 2014; 468. 11. thornton s. a literature review of the long case and its variants as a method of assessment. education in medicine journal 2012; 4: 9-18. references 1. norcini jj. the death of the long case? bmj 2002; 324:408– 9. 2. sood r. long case examination –can it be improved? journal indian academy of clinical medicine 2001; 4:251-5. 3. yeow tp, choo ws, khir as, loh lc. successive long case assessment as a driver of clerkship learning evaluation through perception questionnaire. iejsme 2011; 5: 3-11. 4. wass v1, jolly b. does observation add to the validity of the long case? med educ. 2001; 35: 729-34. 5. gleeson f. defects in postgraduate clinical skills as revealed by the objective structured long examination record (osler). ir med j 1992; 85:11– 4. 6. wass v, vander vc. the long case. med educ 2004; 38:1176– 80. 7. gleeson f. assessment of clinical competence using the o b j e c t i v e s t r u c t u r e d l o n g e x a m i n a t i o n r e c o r d jiimc 2019 vol. 14, no.1 47 validity of slice original�article abstract objective: to study the hepatoprotective effect of tamarixdioica at low and high doses on transaminases (alanine aminotransferase and aspartate aminotransferase) in acetaminophen induced hepatotoxicity in male mice. study design: it was a randomized control trial. place and duration of study: the study was conducted at department of pharmacology, islamic international st st medical college, rawalpindi from 1 april 2015 to 31 march 2016. materials and methods: forty balb-c albino male mice were randomly divided in four groups with 10 mice each. group a was the control group and received no medications. in group b (disease control group) hepatotoxicity was induced by acetaminophen 1000mg per kg body weight given daily for 4 weeks. group c (low dose experimental group) was given acetaminophen 1000 mg/kg/day orally in combination with tamarixdioica (aqueous extract) that was given daily through gavage tube in a dose of 100mg/kg/day for 4 weeks. group d (high dose experimental group) followed the same protocol as group c but the tamarixdioica (aqueous extract) dose was increased to 200mg/kg/day for 4 weeks through gavage tube. alt and ast were measured and compared in different groups to see the hepatoprotective effect of tamirixdioica. results: mean alt in group a, b and c were 35.50 2.24 u/l, 94.00 8.62 u/l and 50.90 4.56 u/l respectively. there was a significant difference among alt values of group a & b and among group b & c (p value .000). mean ast in group a, b and c were 27.00 3.11 u/l, 151.00 14.53 u/l and 66.90 7.77 u/l respectively. there was a significant difference among ast values of group a & b and among group b & c (p value .000). this suggested that hepatotoxicity was induced by acetaminophen and hepatotoxicity was improved by tamirixdioica. no significant difference was observed in alt & ast values among group c and d. conclusion: acetaminophen induces hepatotoxicity at high dose. concomitant treatment with aqueous extract of roots of tamarixdioica prevents hepatotoxicity induced by acetaminophen in mice. extract of roots of tamarixdioica showed improvement biochemically in both low and high doses, as compared to drug treated group in a dose independent manner. key words: acetaminophen, hepatoprotective effect, hepatotoxicity, tamarixdioica. introduction according to available data, diseases of liver such as inflammatory disorders and hepatitis are considered to be the most prevailing diseases in world. pakistan has sixth highest number of cases with liver 1 diseases. viral hepatitis makes a big proportion in 2 chronic cases. drug induced hepatotoxicity is common in acute settings. pharmacological drugs account for 20-40% of all cases of fulminant hepatic failure. approximately 75% of the idiosyncratic drug 3 reactions result in liver failure or death. hepatic injury caused by drugs is the most common reason mentioned for withdrawal of an approved drug. about 2000 cases of acute liver failure occur annually in the united states, and drugs account for over 50% of them (39% are due to acetaminophen, 13% are idiosyncratic reactions due to other medications). hepatoprotective effect of tamarixdioica roots on acetaminophen induced hepatotoxicity in male mice 1 2 3 4 5 uzma riaz , noman sadiq , muhammad tahir , noor nasir rajpoot , amanat ali correspondence: dr. uzma riaz assistant professor department of pharmacology watim dental college, islamabad e-mail: uzmariaz2@gmail.com 1 department of pharmacology watim dental college, rawalpindi 2 departmant of physiology cmh kharian medical college, kharian 3 department of pharmacology women medical and dental college, abbottabad 4 department of medicine sir ganga ram hospital, lahore 5 departmant of pharmacology hbs medical and dental college, islamabad funding source: nil; conflict of interest: nil received: may 30, 2016; revised: october 26, 2018 accepted: november 26, 2018 hepatoprotective effect of tamarixdioica roots jiimc 2018 vol. 13, no.4 189 drugs account for 2-5% of total cases of patients hospitalized with jaundice and approximately 10% of 4 all cases of acute hepatitis. acetaminophen (paracetamol, n-acetyl-p-aminophenol) is the most commonly used over-the counter analgesic and antipyretic drug. at therapeutic doses, it is believed to be safe, having analgesic and antipyretic effects. paracetamol toxicity is the foremost cause of acute 5 liver failure in the western world. estimation of liver enzymes should be done to evaluate the liver function during the course of hepatic injury 6 treatment. the sensitive markers for the evaluation of liver function are serum alt and ast as these are cytoplasmic in their location and found in circulation in case of cellular damage. alt is the most sensitive 7 marker indicating the liver injury. herbal medicines represent one of the most important fields of traditional medicine throughout the world. who estimates that 80% of the world population relies on herbal medicine for primary health care? about 30% of the pharmaceutical preparations are still extracted from plant material. these are the source of good affordable effective drugs. the family tamaricaceae consists of 60 different species, which are also commonly called salt cedars. tamirix.dioica (tamaricaceae), with the local name of lai in urdu ghaz or khagal, is an evergreen shrub or small tree with reddish bark, vaginate leaves, and purple flowers. the tree is native to pakistan, afghanistan, iran, india, 8 bangladesh, bhutan, kashmir, nepal, and myanmar. screening of phytochemicals constituents of tamarixdioica showed positive results for the presence of flavonoids, alkaloids, phenols, steroids, glycosides, carbohydrates, terpenoids and tannins. in past studies has been carried out which concluded the antioxidant and hepatoprotective effects of tamarixdioica by using methanolic extracts of its 9 various phytochemical. however studies on hepatoprotective effects of tamarixdioica by using aqueous extracts of its roots is limited. objective of t h e p r e s e n t s t u d y w a s t o o b s e r v e t h e hepatoprotective effects of tamarixdioica (aqueous e x t r a c t ) a t l o w a n d h i g h d o s e s a g a i n s t acetaminophen induced hepatotoxicity in male mice by evaluating alt and ast levels as biochemical markers. materials and methods st this randomized control trial was conducted from 1 st april 2015 to 31 march 2016 in the department of pharmacology, islamic international medical college, rawalpindi in collaboration with animal house at national institute of health (nih), islamabad pakistan after getting approval from ethical review committee of riphah international university (riu), islamabad. in this study 40 adult male albino mice were used. mice weighing between 30-50 grams with normal serum alanine aminotransferase and aspartate aminotransferase levels were included while mice weighing less than 30 grams or mice with abnormal serum alt and ast were excluded from the study. mice were first allowed to get acclimatized for one week in the nih animal house in 50-70% humidity at o a room temperature of 24+2 c with a 12-hour light 8 and dark cycle. blood samples were taken randomly from 8 mice for estimating serum alt and ast levels at day 0. forty healthy mice were then randomly divided into four groups of ten mice each (n=10). group a was normal control, given diet and water adlibitum for four weeks. group b (disease control group) was administered acetaminophen at 1000 mg per kg body weight through gavage tube daily for 4 weeks. group c (low dose experimental group) was administered acetaminophen 1000 mg/kg/day weight along with aqueous extract of tamarixdioica at a dose of 100mg/kg/day through gavage tube for 7 four weeks. group d (high dose experimental group) was administered acetaminophen 1000 mg/kg/day weight along with aqueous extract of tamarixdioica at a dose of 200mg/kg/day through gavage tube for four weeks. roots of tamarixdioica were purchased and authenticated from the plant sciences department, quaid-e-azam university, islamabad. aqueous extract of tamarixdioica root was prepared at rips, islamabad by using fine homogenized powder of tamarixdioica which were mixed with distilled water, the whole solution was boiled for 2 hours and after cooling was filtered through filter paper what man no 3. the aqueous extract was formed by using vacuum rotary evaporator and was frozen dried. sampling at day 0 was done via lateral tail vein. sampling after four weeks was done through cardiac puncture. biochemical analysis of serum alt and ast was estimated through commercially available kits hepatoprotective effect of tamarixdioica roots jiimc 2018 vol. 13, no.4 190 by merk and auto analyzer microlab 300 on photometric system. statistical analysis of data was done by using spss version 21 and mean ± standard error of mean was calculated. one-way anova and post hoc tuckey tests were applied to compare the mean difference between control and rest of the groups and mean difference in between the groups. p value of <0.05 was considered statistically significant. results initial serum alt for eight randomly selected mice at day 0 was 33.21 ± 1.02 u/l whereas mean initial serum ast for eight randomly selected mice were 26.12 ± 1.60 u/l. there was no significant difference in the serum alt and ast among these mice on day 0 (p value .980). mean serum alt after four weeks for group a (normal control group) was 35.50 ± 2.24 u/l, for group b (disease control group) was 94.00 ± 8.62 u/l, for group c (low dose experimental group) was 50.90 4.56 u/l & for group d (high dose experimental group) was 49.90 ±4.99 u/l. there was a significant difference in the values of group a & b (p value .000). this suggests that hepatotoxicity was induced by acetaminophen in group b. there was also significant difference in the values of group b & c and in values of group b & d (p value .000). this suggests that hepatotoxicity in group c & d was improved. more than group d (methanolic extract treated group). there was no significant difference in the serum alt levels among group c & d suggesting that both low and high dose of t a m a r i x d i o i c a e x t r a c t h a v e a n e q u a l hepatoprotective effect. (p value .999). mean serum ast after four weeks for group a (normal control group) was 27.00 ± 3.11 u/l, for group b (disease control group) was 151.00 ± 14.53 u/l, for group c (low dose experimental group) was 66.90 7.77u/l & for group d (high dose experimental group) was 53.00 ± 10.08 u/l. there was significant difference in the values of group a & b (p value .000). this suggests that hepatotoxicity was induced by acetaminophen in group b. there was also significant difference in the values of group b & c and in values of group b & d (p value .000). this suggests that hepatotoxicity in group c & d was improved. there was no significant difference in the serum ast levels among group c & d (p value .748) signifying that aqueous extract of tamarixdioica both in low and high dose have same efficacy in protecting liver against acetaminophen induced hepatic injury. table i: anova of alt and ast in all groups a�er four weeks table ii: mul�ple comparison of serum alt and ast among all groups by post hock tuckey test hepatoprotective effect of tamarixdioica roots jiimc 2018 vol. 13, no.4 191 discussion acetaminophen is the commonest analgesic and anti-pyretic used worldwide. hepatotoxicity is produced by acetaminophen and is deduced by the raised serum levels of alt and ast. the current study investigates the protective effects of tamarixdioica (aqueous extract) at low and high doses in acetaminophen induced hepatotoxicity in male mice via biochemical parameters. we find that acetaminophen induced hepatotoxic changes can be improved by both high and low doses of aqueous extracts of tamarixdioica. in present study in comparison with the normal control group a (which received normal standard diet) acetaminophen induced hepatotoxicity is observed in group b, group c and group d with resultant increase in levels of biochemical markers i.e. serum alt and ast. the present work is in accordance with findings of boyd and mitchell who reported hepatotoxicity in rodents when treated with higher doses of 11 acetaminophen. whereas the rats were not very sensitive to the hepatotoxicity, both mice and hamsters proved to be more sensitive. following this initial report, few cases of acetaminophen overdose were reported. boyer and rouff described the main clinical symptoms as development of nausea and vomiting, 2–3 h of ingestion followed by abdominal pain in the right upper quadrant. liver dysfunction occurred within 24 h and reached a maximum 12 approximately 3–4 days after ingestion. the current study is also consistent with prescott (ihab talat abdel-raheem; 2009) in which hepatotoxicity of acetaminophen was evaluated by increased alanine a m i n o t r a n s f e r a s e ( a lt ) a n d a s p a r t a t e a m i n o t r a n s fe r a s e l e v e l s a l o n g w i t h m i l d hyperbilirubinemia, and increased prothrombin 13 time. in our study when results of group c (low dose experimental group) and group d (high dose experimental group) were compared regarding alt and ast no significant difference was observed (p value > 0.05). these results indicate that hepatoprotective role of tamarixdioica remain almost same when given in low or high dose and it is not dose dependent. similar findings were observed by krishnaiah and his colleagues in which they found the hepatoprotective role of tamarixdioica in both low and high doses. they have attributed this hepatoprotective property of tamarixdioica to presence of flavonoids and tannins present in 6 abundance in tamarixdioica. our study is also in accordance with study carried by abouzid s and his colleagues which showed a marked reduction in tissue glutathione level in rats. the hydro-alcoholic extract of tamarix (100 mg/kg body weight) ameliorated the adverse effects of carbon tetrachloride on hepatocytes and returned the altered levels of biochemical markers near to the normal levels. we have compared results of 14 tamarixdioica to acetaminophen and not ccl4. however same mechanism has probably produced hepatoprotective effect in our study also. previously studies have been done on exploring hepatoprotective effect of tamarixdioica in combination with medical and other herbal compounds and extracts. no dose dependent study was done individually on aqueous extract of tamarixdioica roots extract which guides us about the submaximal, ceiling effect and toxicity. our study confirms the hepatoprotective effect of aqueous extract of tamarixdioica roots both in low and high dose. further studies are needed to determine dosage for submaximal and ceiling effect of tamarixdioica roots extract. in addition a different route of administration can be tried to see the same effect. conclusion aqueous extract of tamarixdioica roots have s i g n i f i c a n t h e p a t o p r o t e c t i v e e f f e c t o n acetaminophen induced hepatotoxicity both in low and high doses. references 1. javed h, arif t, arshad s, baloch sk, anwar b, khan ma et al. spectrum of hepatitis c virus genotypes among diagnosed cases in rawalpindi and islamabad region over the period of six years. pak j public health: 2017; 7(1):19-23. 2. franco e, pettinicchio v, zorzoli e. the evolution of the burden of viral hepatitis from 1990 to 2013: still an open challenge to global public health policy. hepatobiliary surg nutr: 2017; 6(4):277-85. 3. mosedale m, watkins pb. drug-induced liver injury: advances in mechanistic understanding that will inform risk management. clin pharmacol: 2017; 101(4):469-80. 4. chalasani np, hayashi ph, bonkovsky hl, navarro vj, lee wm, fontana rj. acg clinical guideline: the diagnosis and management of idiosyncratic drug-induced liver injury. am j gastroenterol: 2014; 109(7):950-57. 5. jaeschke h. acetaminophen: dose-dependent drug hepatoprotective effect of tamarixdioica roots jiimc 2018 vol. 13, no.4 192 hepatotoxicity and acute liver failure in patients. j dig dis: 2015; 33(4):464-71. 6. du k, ramachandran a, jaeschke h. oxidative stress during a c e t a m i n o p h e n h e p a t o t o x i c i t y : s o u r c e s , pathophysiological role and therapeutic potential. redox biol: 2016; 10:148-56. 7. thulin p, nordahl g, gry m, yimer g, aklillu e, makonnen e et al. keratin-18 and microrna-122 complement alanine aminotransferase as novel safety biomarkers for drug-induced liver injury in two human cohorts. liver int: 2014; 34(3):367-78. 8. mandracchia g, venturella g, gargano ml. first record of tamarix macrocarpa (tamaricaceae) for europe. pl. biosystems: 2017; 151(4):577-80. 9. krishnaiah d, devi t, bono a, sarbatly r. studies on phytochemical constituents of six malaysian medicinal plants. j med plants res: 2009; 3(2):67-72. 10. obernier ja, baldwin rl. establishing an appropriate period of acclimatization following transportation of laboratory animals. ilar journal: 2006; 47(4):364-9. 11. boyd em, bereczky gm. liver necrosis from paracetamol. br j pharmacol chemother: 1966; 26:606–14. 12. boyer td, rouff sl. acetaminophen-induced hepatic necrosis and renal failure. jama: 1971; 218:440–1. 13. prescott lf, critchleyja. the treatment of acetaminophen poisoning. annu rev pharmacol toxicol: 1983; 23:87–101. 14. abouzid s, sleem a. hepatoprotective and antioxidant activities of tamarix nilotica flowers. pharm. bio: 2011; 49(4):392-5. hepatoprotective effect of tamarixdioica roots jiimc 2018 vol. 13, no.4 193 untitled-1 240 when pakistan came into being back in 1947, we had only 250 hospitals and no basic health units (bhus) or rural health centres (rhcs) at all. there were a total of 6500 doctors, out of which only 600 were 1 dentists. today, 68 years down the line, the situation albeit not matching those of developed nations is however, much better than what it was about 7 decades ago. we have about a 1000 hospitals all over pakistan, in addition to 5300 bhus and about 600 rhcs. there are a total of 165,000 doctors out of 1,2 which 15000 are dentists. the reason that i have stated these statistics is to elicit the current oral health status of pakistanis in the perspective of the health care system. what we need to understand is the fact that these 15,000 dentists are all we have to facilitate a population of about 200 million, giving a ratio of 1 dentist for 13,000 people. let us readjust these figures to account for some practical issues. as per tudor hart's inverse care law which elicits the inverse relationship between the demand and supply of health needs and health professionals, we may very well appreciate the fact that the majority of these dentists are practicing in the urban areas, which house only about 30‐35% of the pakistani population. to make the situation worse, 62% of the dentists' population are female, a large proportion of whom do not even practice dentistry and those who do, generally do not prefer to work in rural areas. so, if we were to estimate that in the rural areas of pakistan, 1 dentist serves a population of 20,000, we would not be pushing it too far. this bleak picture of the oral health care system in pakistan is an actual reality. given the extremely limited access a pakistani person has to oral health care services, one would not be too optimistic regarding the oral health of the nation. although, we do not have any recent nationwide statistics to elicit the average oral health status, several studies reporting oral health statuses of small samples of pakistanis show that carries and periodontal editorial how much do pakistanis care about oral health? muhammad humza bin saeed ------------------------------------------------correspondence: dr. muhammad humza bin saeed assistant professor, community dentistry islamic international dental college riphah international university, islamabad e‐mail: humza.saeed@riphah.edu.pk 3‐5 diseases are quite high. furthermore, people usually report to the dentist only when their teeth have become grossly carious. another fact that needs to be considered is that pakistan does not have an independent oral health policy at the national or provincial level. there are no vacancies for dentists on any of the health policy making bodies. also, there are no considerations for oral health in any of the future health proposals. if we take the government's 'vision 2030' as an example, the plan does contain a chapter on health. however, oral health has not been taken into 6 consideration at all. all of the above mentioned indicators suggest that oral health is not really perceived as being very important in pakistan, both by the government and by the masses. in order to maintain good oral health, it is imperative that people consider oral health to be important for their overall general health. as former us surgeon general c. everet koop said: “if you do not have oral health, you're simply not 7 healthy” if people do not consider oral health to be important, the implications of such perceptions and beliefs would be expected to be reflected on the general health as well. similar to general health, oral health trends also follows a social gradient. with more than 60% of pakistan's population belonging to the lower socioeconomic class, the expected oral health indicators would also not be very favorable. to add to this situation, oral health education campaigns are almost non‐existent across the country. different health care auxillaries working in the field, such as the lady health workers, are not trained in oral health and hygiene education. subsequently, the motivation or education that the general public receives regarding oral health and hygiene is through media advertisements, which do not always provide evidence based information. based on these facts, it may be deduced that the general public's apathy towards oral health, may be explained mostly by the lack of government policies to address oral health in pakistan. pakistan's public health capacity to address oral health is limited. oral health needs to be there on the governments' public health priority list. dental schools should incorporate community based oral 241 jiimc 2015 vol. 10, no.4 pakistanis and oral health health education in their curriculum. oral health education awareness programs should be planned at a national level. as time is passing, pakistan's previous dental force is slowly being replaced by younger energetic dentists who have a new zeal and energy to work. with young dentists with a broader vision coming up in pakistan, the future will hopefully hold hope for improved oral health care in pakistan. references 1. ilyas m, ansari ma, malik gq, mubasher m, khan ia, inam snb. community medicine and public health. karachi, pakistan: time traders: 2008. 2. p m d c . p m d c s t a t i s t i c s . a v a i l a b l e f r o m : http://www.pmdc.org.pkaccessed on: 29‐11‐2015. 3. haseeb m, ali k, munir mf. causes of tooth extraction at a tertiary care center in pakistan. j pak med assoc. 2012; 62; 812‐5. 4. dawani n, nisar n, khan n, syed s, tanweer n. prevalence and factors related to dental caries among pre‐school children of saddar town, karachi, pakistan: a cross‐sectional study. bmc oral health 2012; 12:59. 5. sufia s, chaudhry s, izhar f, syed a, mirza ba, khan aa. dental caries experience in preschool children: is it related to a child's place or residence and income? oral health prev dent 2011; 9: 275‐9. 6. planning commission. pakistan in the 21st century vision 2030. accessed on: 11‐12‐2015. available on: http://www.pc.gov.pk/vision2030/pak21stcentury/v ision%202030‐full.pdf. 7. soni st. dental secrets.2nd ed. philadelphia: hanley & belfus: 1999. original�article abstract objective: to determine the hepatoprotective effect of nigella sativa seeds in pyrazinamide induced hepatic damage in albino mice. study design: an experimental study. place and duration of study: the study was conducted in pharmacology department of islamic international medical college, riphah international university, in collaboration with national institute of health, armed force institute of pathology and pakistan institute of medical sciences islamabad, pakistan. materials and methods: a total of 68 male albino mice were included in the study. they were divided into 4 group's i.e, seventeen mice in each group. group a (control group), group b (pyrazinamide only treated), group c (pyrazinamide + low dose nigella sativa treated) and group d (pyrazinamide+ high dose nigella sativa treated). group b, c and d received pyrazinamide through gavage needle once daily for six weeks. group c and d received nigella sativa along with pyrazinamide through gavage needle once daily for six weeks. blood sampling (baseline, end of 3 and 6 weeks) was done to analyze serum alt and ast levels. data was analyzed by using spss version 21. results: pyrazinamide treatment for 6 weeks increased serum alt and ast levels. nigella sativa administration along with pyrazinamide for six weeks decreased the elevated levels of alt and ast in c and d groups. conclusion: nigella sativa seeds exerted hepatoprotective effect by decreasing the raised levels of alt and ast in pyrazinamide treated albino mice. key words: alt, ast, hepatotoxicity, nigella sativa seeds, pyrazinamide. 4 treatment (att) varies from 2.0% to 28.0%. an important first line and sterilizing tuberculosis drug is pyrazinamide which aids in condensing the duration 5 of present chemotherapy regimens for tuberculosis. pyrazinamide causes more hepatotoxicity compared 6,7 to isoniazid and rifampin. hepatotoxicity by pyrazinamide is either dose dependent or idiosyncratic. free radical species are produced as result of alteration of nicotinamide acetyl dehydrogenase levels by pza.inh and pza may have similar mechanism of injury because of similarity in their molecular structure. in patients with latent tuberculosis infection, more toxic effects came into observation with rif and pza. pza may cause 8 hypersensitivity reactions and liver damage. nigella sativa has emerged as a miraculous herb with its 9 wide range of pharmacological effects. hassan et al, (2012) has done research on hepatoprotective effect of nigella sativa seeds on isoniazid induced hepatotoxicity and that research was conducted on rabbits. we have conducted the research on male albino mice. danladi et al, (2013) has conducted his research on introduction tuberculosis is an infectious bacterial ailment caused 1 by several species of mycobacterium. one-third of the global population is infected with tuberculosis, out of whom 5%–10% may develop active tuberculosis in rest of their lives. tuberculosis is a 2 disease that causes 1.4 million deaths each year. all three major drugs for the treatment of tuberculosis i.e., pyrazinamide(pza), isoniazid(inh) and 3 rifampicin(rif) have hepatotoxic effects. the occurrence of liver injury due to antituberculosis role of nigella sativa seeds on pyrazinamide induced hepatotoxicity 1 2 3 amtul hafeez , akbar waheed , neelofar yousaf correspondence: dr. amtul hafeez department of pharmacology islam medical and dental college, sialkot e-mail:haajar.amatullaah1@gmail.com 1 department of pharmacology islam medical and dental college, sialkot 2 department of pharmacology islamic international medical college riphah international university, islamabad 3 department of pharmacology king edward medical university, lahore funding source: nil; conflict of interest: nil received: march 16, 2017; revised: february 04, 2019 accepted: february 24, 2019 nigella sativa role in hepatotoxicityjiimc 2019 vol. 14, no.1 18 12, 13 hours light/dark cycle was maintained. study was initiated after one week acclimatization of mice under the standard research facility settings. nigella sativa (kalonji) seeds were obtained from national agriculture research centre, islamabad. plant material was certified by national agriculture research centre, islamabad through proper taxonomical rules. nigella sativa seeds were grounded into fine powder in electrical grinder. suspension was made by adding glucose water into the fine powder. 500mg seeds powder was added to 5ml glucose water equivalent to 100mg of seed powder per ml for group c mice (a dose of 500mg/kg was administered to each mouse in group c). one gram seed powder was added to 5ml glucose water equivalent to 200mg of seed powder per ml for group d mice (a dose of 1000mg /kg was 14 administered to each mouse in group d). 500mg (research grade salt of pyrazinamide) was dissolved in 5ml glucose water equivalent to 100mg of drug per ml (a dose of 500mg/kg was administered to each mouse in group b, c and d). the powder of pyrazinamide was dissolved completely to obtain a homogenized solution. the dose of pyrazinamide 14, 15 was calculated for body weight of mice. glucose water suspension of pyrazinamide was prepared in an amount of 500 mg/kg body weight (i.e 20 mg of research grade salt of pyrazinamide was dissolved in 0.5ml glucose water) and was administered once daily to mice in group b for 6 weeks through a gavage tube and syringe. glucose water suspension of nigella sativa was used in a dosage of 500 mg/kg body weight in the group c mice (20 mg ns seeds powder was dissolved in 0.5ml glucose water) along with 500mg/kg body weight of pyrazinamide(i.e 20 mg of research grade salt of pyrazinamide was dissolved in 0.5ml glucose water) and in dosage of 1000mg/kg body weight in group d(40 mg ns seeds powder was dissolved in 0.5ml glucose water) along with 500mg/kg body weight of pyrazinamide(i.e 20 mg of research grade salt of pyrazinamide was dissolved in 0.5ml glucose water) given once daily to mice for 6 weeks by means of a gavage tube and 14 syringe. blood samples of mice from all groups were taken three times (baseline, at the end of 3 and 6 weeks). blood samples of 2 mice from each group were collected at day 0 for baseline liver enzymes (alt, and ast) and of 5 mice from each group at day protective effects of nigella sativa in ccl induced 4 hepatotoxicity in rats, while in our research pza was used. nigella sativa (black cumin) was found to be protective against various hepatotoxic chemicals and 10 drugs. the antioxidant, anti-angiogenesis and antiinflammatory properties of nigella sativa may play a 11 part in its hepatoprotective role. thymoquinone (tq) is an active constituent and is proven to bear 9 h e p a t o p r o t e c t i v e q u a l i t i e s . t q h a s immunomodulatory effects on the antioxidant defense mechanisms of the body that underwent 12 toxicity. the hepatoprotective activity was revealed by a reduced release of alanine aminotransferase (alt), aspartate aminotransferase (ast)and reduced 9 uptake of trypan blue. many studies have been conducted on hepatotoxic effect of att and pza is a component of this therapy. its hepatotoxic effect is a main factor in compromising the treatment of tb patients. therefore to search for a drug that can reduce the effects of pza toxicity is a challenge for pharmacologists. this research was aimed to determine the hepatoprotective activity of nigella sativa seeds on pza induced hepatic damage in male albino mice. materials and methods a n ex p er im enta l st u d y wa s co n d u c ted at p h a r m a c o l o g y l a b o ra t o r y, d e p a r t m e n t o f p h a r m a c o l o g y a n d t h e r a p e u t i c s a n d multidisciplinary research laboratory, islamic international medical college, rawalpindi with access to animal house for mice at national institute of health (nih). the project was accepted by the ethics review committee of islamic international m e d i c a l c o l l e g e , r i p h a h i n t e r n a t i o n a l th university,islamabad. the study took 6 weeks (10 nd november, 2015 to 22 december, 2015). sixty eight adult male albino mice 2 months of age weighing 2550gm, purchased from the animal house of nih were chosen for research project and were then divided into 4 groups i.e. group a as control group and groups b, c and d were experimental groups each comprising 17 male albino mice. standard nutrition consisting eating regimen and clean tap water was started ad libitum. a specific room was assigned for experimental mice at nih. mice were retained in a well-ventilated place, o humidity 50-70 %, room temperature 24±2 c and 12 19 jiimc 2019 vol. 14, no.1 nigella sativa role in hepatotoxicity 21 for evaluation of progress of research. finally a blood sample of 10 mice from each group was taken 16 at day 42 for final evaluation of liver enzymes. intracardiac blood sampling technique was utilized under chloroform anesthesia to acquire the blood and further biochemical assay measurement. after centrifugation at 3000 rev/min for 10min serum was separated from blood. bench top centrifuge was used for this purpose. serum was kept at -20°c until 17 biochemical assay measurement took place. serum alt and ast were determined by using alt and ast kit by (merck) on chemistry analyzer, micro lab 300 (merck) by ifcc method. statistical analysis was done using spss version 21 to analyze the data. mean ± s.d was calculated for alt and ast. one way anova was used to evaluate mean difference between control and experimental groups. post hoc tuckey test was applied for the comparison of mean difference between groups. p<0.05 was considered significant. results the levels of serum alt and ast in various animal groups and values of their mean, s.d and post hoc comparisons between the groups is given in tables i vi. pyrazinamide treatment for 6 weeks has significantly increased levels of alt and ast in group b. nigella sativa seeds administration at low (500mg/kg body weight) and high dose (1000mg/kg body weight) along with pyrazinamide for 6 weeks was reduced (p<0.05) the elevated levels of alt and ast in group c and d respectively. table i: descrip�on of mean and std. devia�on of alt in all groups at day 42 table ii: comparison of serum alt amongst different groups at the end of experiment by one way anova table iii: post-hoc comparison of total alt between the groups tukey hsd dependent variable: alt (u/l) * the mean difference is significant at the .05 level. table iv: descrip�on of mean and std. devia�on of ast in all groups at day 42 table v: comparison of serum ast amongst different groups at the end of experiment by one way anova 20 jiimc 2019 vol. 14, no.1 discussion in our study we observed that oral administration of pyrazinamide for 06 weeks has significantly elevated the levels of serum alt and ast in male albino mice. drug induced hepatotoxicity is a leading health problem with far reaching implications and is the nigella sativa role in hepatotoxicity most common cause of termination of drug 18 development programs. more than 900 drugs have 19 been implicated with this side effect. liver is pivotal to all detoxification processes and adversely targeted 20 by administration of pyrazinamide. present study w a s c h a n n e l e d i n o r d e r t o e x p l o r e t h e hepatoprotective effect of seeds of nigella sativa in pyrazinamide induced hepatotoxicity. our study revealed that glucose solution of nigella sativa has marked hepatoprotective activity (p < 0.05) in a dose dependent manner. high dose of nigella sativa (1000mg/kg) lowered level of alt and ast in group d to a greater extent as compared to low dose ( 5 0 0 m g / k g ) g i v e n i n g ro u p c . c o m b i n e d administration of 1000mg/kg of nigella sativa with pza significantly prevented the elevation of alt and ast as compared to drug treated group b. current study is in accordance with multiple studies which proved hepatoprotective effect of nigella sativa oil or the nigella sativa seeds aqueous suspension 21,22,23 against several hepatotoxins. thymoquinone is an active constituent of nigella sativa that is proven 9 for bearing hepatoprotective activity. the antioxidant, anti-angiogenesis and antitablevi: post-hoc comparison of total ast between the groups tukey hsd dependent variable: ast (u/l) * the mean difference is significant at the .05 level. 21 jiimc 2019 vol. 14, no.1 inflammatory properties of nigella sativa also play a 11 part in its hepatoprotective role. it is proven that harmful effects of ischemia reperfusion injury of liver 24 are relieved by nigella sativa. also its administration protects liver tissue from harmful properties of toxic 25 chemicals and metals. our results clearly show that nigella sativa is hepatoprotective which is indicated by changes in hepatic enzymes. this result is greatly supported by 14,26 data given in literature. our study shows the hepatoprotective effects of nigella sativa. however we recommend search for the hepatoprotective effect of different components of this herb to find the most active component which can further provide a lead for the development of a hepatoprotective drug. conclusion concurrent administration of nigella sativa seeds with pyrazinamide produce hepatoprotective effect thereby preventing hepatotoxicity caused by pyrazinamide. references: 1. hurtado am, hill kr, rosenblatt w, bender j, scharmen t. longitudinal study of tuberculosis outcomes among immunologically naive ache natives of paraguay. american journal of physical anthropology. 2003;121(2):134-50. 2. lakshminarayana sb, huat tb, ho pc, manjunatha uh, dartois v, dick t, et al. comprehensive physicochemical, pharmacokinetic and activity profiling of anti-tb agents. journal of antimicrobial chemotherapy. 2014;70(3):85767. 3. yew ww, leung cc. antituberculosis drugs and hepatotoxicity. respirology. 2006;11(6):699-707. 4. tostmann a, boeree mj, aarnoutse re, de lange w, van der ven aj, dekhuijzen r. antituberculosis drug-induced hepatotoxicity: concise up-to-date review. journal of gastroenterology and hepatology. 2008;23(2):192-202. 5. zhang y, mitchison d. the curious characteristics of pyrazinamide: a review. the international journal of tuberculosis and lung disease. 2003;7(1):6-21. 6. yee d, valiquette c, pelletier m, parisien i, rocher i, menzies d. incidence of serious side effects from first-line antituberculosis drugs among patients treated for active tuberculosis. american journal of respiratory and critical care medicine. 2003;167(11):1472-7. 7. schaberg t, rebhan k, lode h. risk factors for side-effects of isoniazid, rifampin and pyrazinamide in patients hospitalized for pulmonary tuberculosis. european respiratory journal. 1996;9(10):2026-30. 8. saukkonen jj, cohn dl, jasmer rm, schenker s, jereb ja, nolan cm, et al. an official ats statement: hepatotoxicity of antituberculosis therapy. american journal of respiratory and critical care medicine. 2006;174(8):935-52. nigella sativa role in hepatotoxicity 9. sharma n, ahirwar d, jhade d, gupta s. medicinal and phamacological potential of nigella sativa: a review. ethnobotanical leaflets. 2009;2009(7):946-55. 10. al-asmari ak, al-elaiwi am, athar mt, tariq m, al eid a, alasmary sm. a review of hepatoprotective plants used in s a u d i tr a d i t i o n a l m e d i c i n e . e v i d e n c e b a s e d complementary and alternative medicine. 2014;2014:213. 11. chaudhary g, kamboj p, singh i, kalia a. herbs as liver savers-a review. indian journal of natural products and resources. 2010;1(4):397-408. 12. bilal r, zakaria m, usman a, zia a. comparison of simvastatin with eugenia jambolana fruit pulp in their effects on alanine transferase, aspartate aminotransferase and creatinine phosphokinase levels of hyperlipidaemic rats. journal of the pakistan medical association. 2011;61(12):1190. 13. hubrecht rc, kirkwood j. the ufaw handbook on the care and management of laboratory and other research animals: john wiley & sons; 2010. 14. hassan as, ahmed jh, al-haroon ss. a study of the effect of nigella sativa (black seeds) in isoniazid (inh)-induced hepatotoxicity in rabbits. indian journal of pharmacology. 2012;44(6):678-82. 15. kovalenko v, bagnyukova t, sergienko o, bondarenko l, shayakhmetova g, matvienko a, et al. epigenetic changes in the rat livers induced by pyrazinamide treatment. toxicology and applied pharmacology. 2007;225(3):293-9. 16. rafiq s, jehangir a, iltaf s. hepatoprotective effect of aqueous extract of stem bark of berberis lycium royale in isoniazid induced hepatotoxicity in mice. journal of islamic international medical college quarterly.2015;10(4):256261. 17. akpanabiatu m, umoh i, udosen e, udoh a, edet e. rat 22 jiimc 2019 vol. 14, no.1 serum electrolytes, lipid profile and cardiovascular activity onnauclea latifolia leaf extract administration. indian journal of clinical biochemistry. 2005;20(2):29-34. 18. chen m, suzuki a, borlak j, andrade rj, lucena mi. druginduced liver injury: interactions between drug properties and host factors. journal of hepatology. 2015;63(2):503-14. 19. chen m, bisgin h, tong l, hong h, fang h, borlak j, et al. toward predictive models for drug-induced liver injury in humans: are we there yet? biomarkers. 2014;8(2):201-13. 20. chang kc, leung cc, yew ww, lau ty, tam cm. hepatotoxicity of pyrazinamide: cohort and case-control analyses. american journal of respiratory and critical care medicine. 2008;177(12):1391-6. 21. farrag a, mahdy ka, abdel rg, osfor mm. protective effect of nigella sativa seeds against lead-induced hepatorenal damage in male rats. pjbs 2007;10(17):2809-16. 22. el-dakhakhny m, mady ni, halim ma. nigella sativa l. oil protects against induced hepatotoxicity and improves serum lipid profile in rats. arzneimittel-forschung. 2000;50(9):832-6. 23. i̇lhan n, seçkin d. protective effect of nigella sativa seeds on ccl4-induced hepatotoxicity. fü sağlık bil dergisi. 2005;19(3):175-9. 24. yildiz f, coban s, terzi a, ates m, aksoy n, cakir h, et al. nigella sativa relieves the deleterious effects of ischemia r e p e r f u s i o n i n j u r y o n l i v e r. wo r l d j o u r n a l o f gastroenterology. 2008;14(33):5204-9. 25. kapoor s. emerging clinical and therapeutic applications of nigella sativa in gastroenterology. world journal of gastroenterology. 2009;15(17):2170. 26. danladi j, abdulsalam a, timbuakj,et al.hepatoprotective effect of black seed (nigella sativa) oil on carbon tetrachloride induced liver toxicity in adult wistar rats.iosr-jdms.2013; 4( 3):56-62 nigella sativa role in hepatotoxicity original�article abstract objective: to study the protective effect of olive oil against histological changes induced by arsenic in liver of albino rats. study design: randomized control trail. st th place and duration of study: the research was carried out from 1 to 30 november 2017 at national institute of health, islamabad. materials and methods: forty five male adult albino rats were placed in three cages having 15 rats each. distilled water was given to rats of control group i for 30 days. the rats of group ii were given 40mg per kg per day of sodium arsenite dissolved in drinking water for 30 days. rats in group iii, in addition to sodium arsenite received olive oil, 0.2ml per day for 30 days along with sodium arsenite. dissection was done after 30 days and liver was dissected out for histological changes. results: the use of olive oil improved the gross and microscopic changes induced by arsenic in liver lobes(right lateral and left lateral) of albino rats of group iii as compared to group ii rats, which received only arsenic. among microscopic parameters, sinusoidal dilation, pyknosis and necrosis was markedly reduced by use of olive oil in group iii rats whereas hemorrhage was absent in group iii. conclusion: olive oil protects histological changes caused by arsenic in liver of albino rats which include sinusoidal dilation, congestion, pyknosis, necrosis and haemorrhage. key words: evoo (extra virgin olive oil), sodium arsenite, oleuropein. species (ros)” and “reactive nitrogen species (rns)” leading to necrosis, oxidative damage to proteins, 1,3,4 lipids and dna in cells. several acute and chronic hepatic effects have been associated with arsenic 5 poisoning. various antioxidants are available which can reduce the effect of arsenic on liver and various organs, olive oil is one of them which can be used to avoid disastrous effects of arsenic on liver. olive oil contains about 70% oleic acid and phenolic compounds that provide health benefits. olive oil itself has a greater antioxidant capacity than most 6 other seed oils. arsenic affects most of the organs involved in 7 absorption, accumulation and excretion, long-term exposure to inorganic arsenic can cause dysfunction 8,9 10 of endocrine system nervous system, and 11 reproductive system, and may also cause loss of 4 body weight. exposure to arsenic also causes, liver 12,13 fibrosis, metabolic disorder such as diabetes, 9 chronic lung disease, gangrene of toes, cancer of 14 internal sites and skin. it has been found to have toxic effects on gonadal tissues of laboratory animals 11 as well. various antioxidants have been used to ameliorate introduction liver, the largest organ in the body, usually weighs about 1.5 kg. it is an organ of metabolism and production of energy; its other main functions include: storage of iron, trace elements, vitamins and bile production. the weight of human liver is 2 to 3%, 1 whereas rat liver is 5% of total body weight. various metals have acute and chronic effects on liver; arsenic is one of them which also produce toxic effects on liver. arsenic, a “protoplasmic poison” interferes with mitosis, cell respiration, enzymes due 2 to its effect on sulfhydryl group of cells. it can also exert its toxic effects by generating “reactive oxygen the protective effect of olive oil on arsenic induced histological changes in the liver of albino rats 1 2 hira waqas cheema , shabana ali correspondence: dr. hira waqas cheema senior lecturer department of anatomy islamic international medical college riphah international university, islamabad e-mail: hira.cheema@hotmail.com 1,2 department of anatomy islamic international medical college riphah international university, islamabad funding source: nil; conflict of interest: nil received: april 30, 2018; revised: november 19, 2018 accepted: december 16, 2018 hepatoprotective effect of olive oiljiimc 2018 vol. 13, no.4 200 toxic effects of arsenic on various organs. vitamin e, ca and olive oil is used to improve arsenic induced 15,6 histological changes in ovary. antioxidants like l ascorbic acid, biochanin a, menthe piperita and aloe vera has been used to improve toxic effects of 16,19 arsenic on liver of rats. oleuropein, one of the component of olive oil is found to be effective antioxidant in literature, therefore olive oil may be used in our study to ameliorate arsenic induced 20 hepatotoxic effects. the present study was designed to study the protective effect of olive oil against histological changes induced by arsenic in liver of albino rats. materials and methods the experiment was carried on the basis of randomized control trial under supervision of animal st th house at nih islamabad from 1 to 30 november 2017. forty five male albino rats, weighing 250 to 300gm were kept in three cages with a number of 15 rats per cage. the simple random sampling technique was used. the research was approved by ethical review committee. a controlled standard living environment suitable to their class with adjusted diet was given. a well ventilated room with cycles of 12 hours light and 12 hours dark were 0 maintained under 20 to 26 c. the rats were adult of age 2 to 4 months and those with any known pathology and female rats were excluded. animals were grouped accordingly as mentioned below. sections. the slides were examined in detail under x10 and x40 power of light microscope. the microscopic qualitative parameters were observed which include sinusoidal dilation, congestion, pyknosis, necrosis and haemorrhage results in control group i, experimental animals showed normal sinusoids while in group ii and group iii sinusoidal dilation was present in 100% of experimental animals. the use of olive oil in group iii has significantly reduced the severity and amount of sinusoidal dilation caused by arsenic table 1 and figure 1). after accomplishment of 4 weeks duration of experiment, rats were anesthetized with chloroform and dissected. after fixation and embedding, eosin and hematoxylin stains were used for histological group i group ii group iii (mild sinusoidal dila�on) fig 1: group wise distribu�on of sinusoidal dila�on of hepa�c lobule showing normal sinusoid in group i l7b1, severe sinusoidal dila�on in group ii l4d and mild sinusoidal dila�on in group iii l6 a.(h and e,x 40) (indicated by arrows in group 1 and group ii of figure 1) hepatoprotective effect of olive oiljiimc 2018 vol. 13, no.4 201 the control group showed no congestion in sinusoids and central vein. 100 % of experimental animals in group ii showed congestion mainly in central vein and also in sinusoids,whereas 46.7% of rats in group iii showed congestion but 53.3% showed no congestion.in this way olive oil has decreased the number of rats in group iii showing congestion. (figure 2) there was normal size of nucleus of hepatocytes in the control group i, pyknosis was present in 100 % of experimental animals of group ii,olive oil in group iii has significantly reduced the number of rats showing pyknosis to 60%.(table 4) (figure 3). table i ꞉group wise distribu�on of sinusoidal dila�on in hepa�c lobule among control and experiental groups of albino rats group i group ii conges�on in central vein and sinusoids group iii fig 2: group wise distribu�on of conges�on of sinusoids and central vein showing normal sinusoids and central vein in group i l7d, conges�on in central vein and sinusoid in group ii l4b, whereas no conges�on in group iii l3c. (h and e, x 40). (indicated by arrow heads in group ii figure 2) table ii: group wise distribu�on of conges�on of sinusoids and central vein among control and experimental groups group i group ii group iii fig 3: group wise distribu�on of pyknosis of hepatocytes among control and experimental groups shows normal nuclear size in group il7a, presence of pyknosis in groupii l4d and absence of pyknosis in group iii l3 b(h and e,x 40) .(indicated by circles in figure 3) hepatoprotective effect of olive oiljiimc 2018 vol. 13, no.4 202 the normal hepatic parenchyma was observed in group i while 100% of experimental rats in group ii showed necrosis in hepatic parenchyma, whereas use of olive oil along with arsenic in group iii has significantly reduced the necrosis to 53.3% of rats in group iii in group i, hepatic parenchyma appeared to be normal, 46% of rats in group ii showed hemorrhage. in group iii, olive oil has significantly improved hemorrhage as it was absent in all rats. (table iv)(figure 6) in group i, hepatic parenchyma appeared to be normal, 46% of rats in group ii showed hemorrhage group iii, olive oil has significantly improved hemorrhage as it was absent in all rats.(table table iii: group wise distribu�on of pyknosis of hepatocytes among control and experimental groups of albino rats group i group ii (periportal necrosis) group iii fig 4: group wise distribu�on of necrosis of hepa�c parenchymma among rat groups shows normal hepa�c parenchyma in group il7a2, presence of coagula�ve necrosis in periportal areas in group ii l5b, and absence of necrosis in group iii l3a(h and e,x 40). (indicated by arrow head in group ii figure 4) group i group ii group iii fig 5: bar chart showing distribu�on of necrosis of hepa�c parenchyma among rat groups hepatoprotective effect of olive oiljiimc 2018 vol. 13, no.4 203 iv)(figure6) figure 6�group wise distribution of haemorrhage in hepatic parenchyma among groups shows normal parenchyma in group i l7 c,haemorrhage indicated by arrow in group ii l4d whereas no haemorrhage in group iii l6a.(h and e, x 40). reduced congestion to only 46.7% of rats. in a study by azab, when olive leave extract was given along with carbendazim, then congestion in central vein and sinusoids was remarkably decreased as compared to the group which was given only 25 carbendazim. there was normal size of nucleus of hepatocytes in the control group i, pyknosis was present in 100 % of experimental animals of group ii, olive oil in group iii has significantly reduced the number of rats showing pyknosis to 60%. in a study conducted by somia bashir of india, arsenic was given to three groups in three different doses for acute period of 24 hours and pyknosis was found only in group which was given higher dose. this study support that pyknosis is 26 early sign of necrosis. necrosis occurs as a result of inflammation of liver caused by arsenic and it occurs after sinusoidal dilation and congestion in which degeneration of hepatocytes takes place due to ischemia. in the recent study, there is absence of necrosis in experimental animals of group i while 100% of experimental rats in group ii showed necrosis whereas 53.3% of rats in group iii showed necrosis. in this way olive oil has significantly decreased necrosis. in group ii, there was periportal necrosis which is zone i as well as zone iii which is pericentral, least oxygenated. in group iii treated by both arsenic and 27 olive oil, there is only pericentral necrosis. in one of the study carried out by sujata das, sodium arsenite was also given in dose of 40mg per kg in drinking water to mice for 30 days and he found periportal 28 necrosis similar to recent study. the use of olive oil in group iii has improved necrosis in our study. metin ogun, used oleuropein in dose of 30mg per kg along with 5mg per kg of sodium arsenite for only 15 days and he found that group which was given only arsenic ,6 mice showed necrosis but the oleuropein group showed necrosis in only 1 mouse. the haemorrhage occurs late in process of inflammation due to damage of endothelial lining of sinusoids leading to extravasation of blood into parenchyma. the livers of group i showed normal parenchyma but in group ii, 46% of rats only show hemorrhage as arsenic was given to them for 30 days. in group iii, hepatic parenchyma was normal 29 with no hemorrhage. daqian yang in his study gave as o (arsenic trioxide) intraperitoneally in a dose of 2 3 table iv: group wise distribu�on of haemorrhage in hepa�c parenchyma among among control and experimental groups of albino rats discussion the sinusoidal dilation was observed in groups i,ii and iii. in control group i, experimental animals showed normal sinusoids while in group ii and group iii sinusoidal dilation was present in 100% of experimental animals. the use of olive oil in group iii has significantly reduced the sinusoidal dilation as compared to dilation in group iii caused by arsenic. in one study carried out by kharroub et al, sodium arsenite was given at 1mg and 10mg for 45 and 90 days respectively which showed that sinusoidal dilation is dose and duration dependent. the dilation was greater at 10mg of arsenic for 90 days as 21 compared to 1mg at 45 days. in another study conducted by sohini singh,4 to 10mg of arsenic was given for 30 days to rats which also caused sinusoidal 16 dilation of liver. in group iii, there was slight sinusoidal dilation which is due to hepatoprotective effect of olive oil given simultaneously with arsenic to this group. farag in his study showed natural antioxidant effect to prevent sinusoidal dilation and 22 congestion caused by oxidative damage to liver. congestion of sinusoids and central vein is caused due to inflammation of liver. all rats of group ii showed congestion mainly in central vein and also in sinusoids due to effect of arsenic.46.7% of rats of group iii showed congestion but 53.3% showed no 23 congestion. in the study conducted by oyagbemi et al, arsenic was given to three different groups at different doses for 4 weeks, they showed congestion 24 in hepatic vessels both in central vein and sinusoids. the use of olive oil in group iii has significantly *p≤0.05 hepatoprotective effect of olive oiljiimc 2018 vol. 13, no.4 204 3mg per kg for 2 weeks to rats and he found hemorrhage in liver histological examination. when olive oil was given to group iii along with arsenic, due to its antioxidant effect it prevents the liver of rat to develop hemorrhage. in support of ameliorating effect of olive oil to improve hemorrhage of liver of our study, olive leave extract was used to improve hemorrhage in liver caused by carbendazim in a 25 study done by azab of libya. conclusion olive oil protects histological changes caused by arsenic in liver of albina rats, which include sinusoidal dilation, congestion, pyknosis, necrosis and haemorrhage. references 1. garcía-chávez e, santamaría a, díaz-barriga f, mandeville p, juárez bi, jiménez-capdeville me. arsenite-induced formation of hydroxyl radical in the striatum of awake rats. brain res . 2003 ;976(1):82–9. 2. saha jc, dikshit ak, bandyopadhyay m, saha kc. a review of arsenic poisoning and its effects on human health. crit rev environ sci technol 1999;29(3):281–313. 3. iwama k, nakajo s, aiuchi t, nakaya k. apoptosis induced by arsenic trioxide in leukemia u937 cells is dependent on activation of p38, inactivation of erk and the ca2+dependent production of superoxide. int j cancer . 2001;92(4):518–26. 4. nandi d, patra rc, swarup d. effect of cysteine, methionine, ascorbic acid and thiamine on arsenic-induced oxidative stress and biochemical alterations in rats. toxicology . 2005;211: 26–35. 5. ratnaike rn. acute and chronic arsenic toxicity. postgrad med j . 2003; 79(933):391–6. 6. jhala dd, chinoy nj, rao m v. mitigating effects of some antidotes on fluoride and arsenic induced free radical t o x i c i t y i n m i c e o v a r y. f o o d c h e m to x i c o l . 2008;46(3):1138–42. 7. duker aa, carranza ejm, hale m. arsenic geochemistry and health. 2004. 8. rahman m, tondel m, ahmad sa, axelson o. diabetes mellitus associated with arsenic exposure in bangladesh. am j epidemiol. 148(2). 9. tseng ch, tai ty, chong ck, tseng cp, lai ms, lin bj, et al. long-term arsenic exposure and incidence of non-insulindependent diabetes mellitus: a cohort study in arseniasishyperendemic villages in taiwan. environ health perspect. 2000;108(9):847-51. 10. hopenhayn c, bush hm, bingcang a, hertz-picciotto i. association between arsenic exposure from drinking water and anemia during pregnancy. j occup environ med . 2006; 48(6):635–43. 11. sanghamitra s, hazra j, upadhyay sn, singh rk, amal rc. arsenic induced toxicity on testicular tissue of mice. indian j physiol pharmacol; 52(1):84–90. 12. longnecker mp, daniels jl. environmental contaminants as etiologic factors for diabetes. environ health perspect . 2001; 871–6. 13. tseng c h, tseng c p, chiou h y, hsueh y m, chong c k, chen c j. epidemiologic evidence of diabetogenic effect of arsenic. toxicol lett; 133: 69-76. 14. kapaj s, peterson h, liber k, bhattacharya p. human health effects from chronic arsenic poisoning–a review. j environ sci heal part a . 2006; 41(10): 2399–428. 15. jhala dd, nair sb, chinoy nj. reversible toxicity of fluoride and arsenic in ovary of mice. fluoride. 2004; 37(2): 71–9. 16. singh s, rana svs. amelioration of arsenic toxicity by lascorbic acid in laboratory rat. j environ biol. 2007; 17. jalaludeen am, ha wt, lee r, kim jh, do jt, park c, et al. biochanin a ameliorates arsenic-induced hepatoand hematotoxicity in rats. molecules. 2016; 21(1):1-14. 18. sharma a, sharma mk, kumar m. protective effect of mentha piperita against arsenic-induced toxicity in liver of swiss albino mice. basic clin pharmacol toxicol. 2007;100(4):249-57. 19. gupta r, flora sjs. protective value of aloe vera against some toxic effects of arsenic in rats. phyther res. 2005; 19(1): 23–8. 20. cicerale s, lucas l, keast r. antimicrobial, antioxidant and anti-inflammatory phenolic activities in extra virgin olive oil. curr opin biotechnol . 2012;23(2):129-35. 21. kharroubi w, dhibi m, haouas z, chreif i, neffati f, hammami m, et al. effects of sodium arsenate exposure on liver fatty acid profiles and oxidative stress in rats. environ sci pollut res. 2014;21(3):1648-57. 22. farag rs, el-baroty gs, basuny am. safety evaluation of olive phenolic compounds as natural antioxidants. int j food sci nutr. 2003;54(3):159-74. 23. kakar s, kamath ps, burgart lj. sinusoidal dilatation and congestion in liver biopsy: is it always due to venous outflow impairment? arch pathol lab med. 2004;128(8): 901-4. 24. oyagbemi aa, omobowale to, asenuga er, afolabi jm, adejumobi oa, adedapo aa, et al. effect of arsenic acid withdrawal on hepatotoxicity and disruption of erythrocyte antioxidant defense system. toxicol reports 2017; 4: 521-9. 25. azab ae, albasha mo. hepatoprotective effect of some medicinal plants and herbs against hepatic disorders induced by hepatotoxic agents. j biotechnol bioeng 2018;2(1):8-23. 26. bashir s, sharma y, irshad m, gupta sd, dogra td. arsenicinduced cell death in liver and brain of experimental rats. 2006; 38-43. 27. histopatholog1cal study of liver 6.1. 2000. 28. das s, pradhan gk, das s, nath d, das saha k. enhanced protective activity of nano formulated andrographolide against arsenic induced liver damage. chem biol interact 29. kularatne sam, imbulpitiya ivb, abeysekera ra, waduge rn, rajapakse rpvj, weerakoon kgad. extensive haemorrhagic necrosis of liver is an unpredictable fatal complication in dengue infection: a postmortem study. bmc infect dis 2014;14(1):1–10. hepatoprotective effect of olive oiljiimc 2018 vol. 13, no.4 205 jiimc june 2016.cdr original article abstract objectives: ! to study the frequency of diabetes in patients with active pulmonary tuberculosis. ! to determine the impact of diabetes on radiological findings in tuberculosis. ! to study the association of atypical radiological manifestations with glycemic control in diabetes associated tuberculosis. study design: a descriptive study. place and duration of study: the study was conducted in medical department of pakistan air force hospital mianwali from august 2013 to july 2014. materials and methods: seventy five new cases (18 years and above) of active pulmonary tuberculosis were selected by non-consecutive convenient sampling. all patients received standard anti-tuberculous treatment (att) for six months. fasting blood glucose and chest x-ray were performed in all patients. glycosylated hemoglobin (hba1c levels) were checked to assess the glycemic control in diabetic patients. radiographic features of the two groups; diabetic vs. non diabetic and within diabetic population; poor vs. optimal glycemic control, were then compared. results: thirty three (33/75 or 44%) patients were found to be diabetic. radiological changes were more frequently atypical in diabetic group as compared to non diabetic population (21/33 or 63.6% vs. 8/42 or 19%). nine of the 12 diabetic patients with poor glycemic control i.e. hba1c levels >7% had cavitations, lower zone involvement and bilateral changes as compared to 11/21 patients with optimal glucose control i.e. hba1c <7% and the difference was significant (9/12 or75% vs.11 /21 or 52.3%, p value <0.001). conclusion: a high index of suspicion for diagnosis of diabetes is required for tb patients with atypical radiological manifestations. poor glycemic control is related with atypical findings on chest x-ray in pulmonary tuberculosis. key words: atypical chest x-ray, diabetes, glycemic control, pulmonary tuberculosis. (tb-hiv) co-epidemic of sub-saharan africa in 80's and 90's, as one disease seems to fuel the other in 2 the same manner. a recent study on association between tuberculosis and diabetes in the developing region of africa has shown that countries with rising diabetes prevalence have depicted a simultaneous 3 increase in the prevalence of tuberculosis. there is now sufficient evidence to suggest that tb patients with diabetes are more likely to experience an aggressive course of disease with more chances of treatment failure, multi-drug resistant tb (mdr-tb), 4 relapse and death. literature review reveals that diabetes frequently alters the radiological 5 manifestations of pulmonary tuberculosis. atypical findings are common with lower zone involvement, cavitations, multiple and/or bilateral lesions which are often misdiagnosed as pneumonia, lung abscess etc with delay in treatment. recently it has also been suggested that poor glycemic control may be linked 6 to atypical radiological findings in such patients. introduction the re-emerging global pandemics of type 2 diabetes mellitus (dm) and tuberculosis (tb) is a serious threat to the attainment of millennium development goals (mdg's) for tuberculosis especially in the low and middle income countries of 1 the world. the looming co-epidemic of tuberculosisdiabetes (tb-dm) in south asia is being compared to the tuberculosishuman immunodeficiency virus effect of glycemic control on radiological manifestations of pulmonary tuberculosis –a hospital based study 1 2 3 shamaila burney , omer awwab khan , saerah iffat zafar correspondence: dr. shamaila burney assistant professor, medicine islamic international medical college riphah international university, islamabad e-mail: drshamailaburney@hotmail.com 1,2 department of medicine islamic international medical college riphah international university, islamabad 3 department of radiology pakistan air force hospital, islamabad funding source: nil ; conflict of interest: nil received: feb 16, 2016; revised: apr 07, 2016; accepted: may 09, 2016 jiimc 2016 vol. 11, no.2 diabetes and pulmonary tuberculosis 52 despite such conclusive evidence, unfortunately no separate guidelines/protocols for treatment of tuberculosis patients with diabetes currently exist. world health organization (who) and the international union against tuberculosis and lung disease in 2011 issued a global recommendation of bidirectional screening for early detection and 7 management of both diseases. countries like china and india have already incorporated these recommendations into their tb-dm screening programs. however, in pakistan, a country with one of the highest figures for both tuberculosis and diabetes, serious gaps between recommendations (including national tb guidelines) and current practices still exist. present study was conducted to highlight the association of tb and dm and to investigate the impact of glycemic control on radiological manifestations of patients with coexistent tb and dm in our hospital setting. published data on this association is still scarce. to our knowledge, no such study has been conducted in pakistan so far. materials and methods this descriptive study was conducted in the medical department of pakistan air force hospital mianwali from august 2013 to july 2014. the study was initiated after the approval of study proposal by the hospital ethics committee after incorporating its suggestions to protect the patient's confidentiality. seventy five new cases (18 years and above) of active pulmonary tuberculosis were selected by non consecutive convenient sampling after informed consent. exclusion criteria included relapse cases, patients with extra pulmonary tb, type 1 diabetes, i m p a i r e d fa s t i n g g l u c o s e , p r e g n a n c y a n d e n d o c r i n o l o g i c a l d i s o r d e rs . pa t i e n t s w i t h immunocompromised states/comorbids such as hiv, chronic renal failure, cirrhosis or malignancies that could cause possible stress hyperglycemia and hence act as confounders were not included. similarly patients taking drugs known to cause hyperglycemia such as steroids, beta agonists and thiazide diuretics were also excluded from the study. active pulmonary tb was diagnosed when a patient with clinical features of tb met at least one of the following three criteria; a positive sputum smear, a positive sputum 8 culture, or a positive chest radiograph. patients were divided into two groups; diabetes-associated tb patients (dmtb group) and non diabetic tb only patients (tb-only group). all patients received 4 drugs standard att in the initiation phase and 2 drugs in the continuation phase and treatment was monitored by parameters defined by the national tb 8 guidelines. screening for diabetes mellitus was done by twice measured fasting blood glucose levels. diagnostic criteria for diabetes followed the who 9 guidelines; > 126 mg/dl fasting plasma glucose. att transiently elevates glucose levels, therefore samples for blood glucose were taken before beginning att and repeated at 12 weeks. hba1c levels were performed in all diabetic patients (previously known or newly diagnosed on screening) to determine the level of glycemic control. dmtb patients were then further subdivided into two groups. patients with hba1c levels > 7% were considered as having poorly controlled diabetes while patients with hba1c < 7% had optimal 10 glycemic control. chest x-ray findings that were c o n s i d e r e d a t y p i c a l i n c l u d e d l o w e r zo n e involvement, bilateral involvement, large cavities 5,11 (>2cm) and/ or multiple cavitations. radiographic features of the two groups with poor and optimal glycemic control were then compared. data was analyzed using ibm spss 20. categorical data was calculated as frequencies and percentages. mean and standard deviation was calculated for age. the chi-square test was used to test the statistical significance of categorical variables such as hba1c levels and atypical chest x-ray and p-value of less than 0.05 was considered significant at 95% confidence interval. results there were 35 male and 40 female patients. only 6% were below 40 years of age while 26% patients were 70 years or older. out of 75 new cases of pulmonary tuberculosis, 33 (44%) were found to be diabetic and constituted the tbdm group while 42/75 (56%) were non diabetic and constituted tb-only group. in the tbdm group, 20/33 (60.6%) were known diabetics and 13/33 (39.3%) were newly diagnosed detected on screening. poorly controlled diabetes (hba1c >7%) was observed in 12/33 (36.3%) diabetic patients and required insulin for sugar control. in 21/33 (63.6%) patients, hba1c was < 7% and g l yc e m i c c o n t ro l wa s a c h i e v e d w i t h o ra l hypoglycemic agents. in none of the 33 diabetic 53 jiimc 2016 vol. 11, no.2 diabetes and pulmonary tuberculosis patients blood sugar was controlled with diet alone. radiological changes were more frequently atypical in dmtb group as compared to tb-only group (21/33 or 63.6% vs. 8/42 or 19%). (table i). radiological manifestations and poor glycemic control as dmtb patients with hba1c levels >7% were more likely to have lower zone involvement, cavitations and/or bilateral changes as compared to non diabetic tb patients (76.9% vs. 55%, p value <0.001). literature review reveals that screening for dm in tb patients yields high prevalence of dm ranging from 1.9% to 35% depending on the geographical 12 location. in the present study, 44% of tb patients had co existing dm, a rate more than thrice the prevalence of diabetes in pakistan (12.1% in males 13 and 9.8% in females). the frequency of newly diagnosed diabetes was 39.3% in our study which is 14,15,16 also higher than most previous studies and highlights the significance of screening for diabetes in all patients with tuberculosis. pulmonary tb has a propensity to affect upper lobes of the lungs. it is still a matter of debate whether or not the presence of diabetes alters the radiological 5,17 manifestations of ptb. previously authors have reported that chest x ray findings are frequently atypical in tb patients having diabetes; with lower zone involvement, cavitations, bilateral changes and 18,5 multi lobe involvement. the study by parezguzmann was most striking in this aspect who determined that diabetes was the most significant 5 factor in development of lower lung lesions. in one of the more recent studies conducted, patel et al also reported a high frequency of atypical chest x-rays in 19 patients with coexistent tb and dm. however other 17 authors do not report any significant difference. literature search revealed that data regarding association of radiological manifestations with glycemic control is scarce. earlier, park et al suggested that poor glycemic control was linked to a 18 higher incidence of cavitatory lesions. in a recently conducted indian study, avathu et al studied 70 diabetic patients with ptb and concluded that atypical changes were more frequently seen in diabetic patients with hba1c levels >7% and poor glycemic control as compared to those with optimal 10 control. a most recent large scale study conducted in taiwan also reported significant correlation between poor glycemic control and atypical 6 radiological features. the findings of the present study are thus in agreement with these few studies. tuberculosis was a deadly threat to diabetic patients table i: frequency of atypical chest x-ray in diabe�c and non-diabe�c tb pa�ents (n=75) table ii: atypical chest x-ray in tb pa�ents with poor glycemic control the presence of atypical changes was associated with poor glycemic control and insulin use. nine of the 12 diabetic patients with poor glycemic control (hba1c levels >7%) had cavitations, lower zone involvement and/or bilateral changes as compared to 11/21 patients with optimal glucose control (hba1c <7%), (table ii). the difference was statistically significant (9/12 or75% vs.11 /21 or 52.3%, p value<0.001). discussion in our study, 63.6% of patients in tbdm group were seen to have atypical radiological manifestations as compared to 19% patients in the tb-only group. glycemic control is an important aspect of tb management and may have an effect on radiological manifestations. an attempt was thus made to correlate the two in the present study. interestingly, a significant association existed between atypical 54 jiimc 2016 vol. 11, no.2 diabetes and pulmonary tuberculosis in the pre-insulin era. poor diabetes control possibly exacerbated by co-existent tuberculosis affects innate cytokine responses. suboptimal glycemic control not only predisposes to tuberculosis, it often leads to poor att response. this could result in higher chances of complications with treatment failure, relapse and case fatality. anti tuberculous drugs and oral hypoglycemic agents have complex interactions with one another and diabetes patients 2 may have lower concentrations of anti-tb drugs. while drugs such as rifampicin are known to cause transient hyperglycemia, some of the newer oral hypoglycemic agents such as gliptins can lower the e f f i c a c y o f at t. re s u l t a n t t b a s s o c i a t e d hyperglycemia often worsens the glycemic control of 20 diabetes necessitating timely switching to insulin. in the present study, 36.3% of the patients with tb had uncontrolled hyperglycemia (hba1c >7%), and required insulin for sugar control. although we did not have a comparison group of diabetes-only patients, it is noteworthy that in none of the tbdm patients blood sugar could be controlled with diet alone. a significant number of newly diagnosed diabetics also had poorly controlled diabetes. previously, a similar study from lahore (pakistan) had determined the frequency of diabetes in tb patients as 25.9% and that of the newly diagnosed cases as 14 5.69%. balakrishnan et al have reported the frequency dm in tb as 44% in india, a country with s i m i l a r d e m o g r a p h i c a n d s o c i o e c o n o m i c 15 background. the incidence of newly diagnosed diabetes cases in their study was 21%. paf hospital mianwali is one of the peripheral hospitals in mianwali district catering for the needs of all the patients affiliated with pakistan armed forces from district mianwali, chakwal, khushab, di khan, layyah and bhakkar. moreover it has a high turnover of civilian patients. the limitations of our study include a relatively small sample size due to limitation of resources and a high number of patients being lost to follow up by virtue of peripheral location of our hospital. in addition we also applied stringent exclusion criteria such as exclusion of patients with impaired fasting glucose and including only patients who were followed up until complete duration of treatment. despite these limitations, our study not only augments previous local studies in terms of a high occurrence of dm in patients with pulmonary tb, it also highlights other clinical aspects such as maintaining strict glycemic control with frequent monitoring and possible switching to insulin, when treating tb patients with coexisting dm. further large scale studies from other regions of pakistan are needed to explore these aspects in detail. similarly standards and protocols have to be developed at hospitals and national level for diagnosis and treatment strategies for management of diabetes mellitus in newly diagnosed cases of tuberculosis. conclusion we conclude that optimal glycemic control is an integral component of tb treatment. a high index of suspicion for diabetes is required for tb patients with atypical radiological manifestations. active screening for diabetes in all patients with tuberculosis can be a more cost-effective way of controlling and preventing both diabetes and tuberculosis. references 1. stevenson cr, farouhi ng, roglic g, williams bg, lauer ja, dye c, et al. diabetes and tuberculosis: the impact of diabetes epidemic on tuberculosis incidence. bmc public health 2007; 7: 234. 2. ruslami r, aarnoutse re, alisjahbana b, van der ven aj, van crevel r. implications of the global increase of diabetes for tuberculosis control and patient care. trop med int health. 2010; 15: 1289-99. 3. goldhaber-fiebert jd, jeon cy, cohen t, murray mb. diabetes mellitus and tuberculosis in countries with high tuberculosis burdens: individual risks and social determinants. intl j epidemiol 2011; 40: 417-28. 4. baker ma, harries ad, jeon cy, hart je, kapur a, lonnroth k, et al. the impact of diabetes on tuberculosis treatment outcomes: a systematic review. bmc med. 2011; 9: 81. 5. pérez-guzman c, torres-cruz a, villarreal-velarde h, salazar-lezama ma, vargas mh. atypical radiological images of pulmonary tuberculosis in 192 diabetic patients: a comparative study. int j tuberc lung dis 2001; 5: 455-61. 6. chiang c-y, lee j-j, chien s-t, enarson da, chang y-c, chen y t, e t a l . g l yc e m i c c o nt ro l a n d r a d i o g ra p h i c manifestations of tuberculosis in diabetic patients. plos one 2014; 9: e93397. 7. world health organization/international union against tuberculosis and lung disease. provisional collaborative framework for care and control of tuberculosis and d i a b e t e s . w h o / h t m / t b / 2 0 1 1 . 1 5 . g e n e v a , switzerland:who,2011.http://whqlibdoc.who.int/publicat ions/2011/9789241502252_eng.pdfaccessed august 2013. 8. national guidelines for the control of tuberculosis in pakistan.http://ntp.gov.pk/uploads/national_guidelin 55 jiimc 2016 vol. 11, no.2 diabetes and pulmonary tuberculosis e_on_tb_case_management_rev_jan_2015.pdf 9. world health organization. definition and diagnosis of diabetes mellitus and intermediate hyperglycemia: report of a who/idf consultation. geneva, switzerland: who, 2006.http://www.idf.org/webdata/docs/who_idf_defini tion_diagnosis_of_diabetes.pdf accessed august 2013. 10. avuthus s, mahishale v, patil b, eti a. glycemic control and radiographic manifestations of pulmonary tuberculosis in patients with type 2 diabetes mellitus. sub-saharan afr j med. 2015; 2: 5-9. 11. sen t, joshi sr, udwadia zf. tuberculosis and diabetes mellitus: merging epidemics. j assoc physicians india. 2009; 57: 399-404. 12. jeon cy, harries ad, baker ma, hart je, kapur a, lonnroth k, et al. bi-directional screening for tuberculosis and diabetes: a systematic review. tropical medicine and international health. 2010; 15: 1300-14. 13. shera as, basit a, fawwad a, hakeem r, ahmedani my, hydrie mz, et al. pakistan national diabetes survey: prevalence of glucose intolerance and associated factors in the punjab province of pakistan. prim care diabetes. 2010; 4: 79-83. 14. usmani ra, nasir mi, wazir s, pervaiz z, zahra t, akhtar m etal. diabetes mellitus among tuberculosis patients in a tertiary care hospital of lahore. j ayub med coll abbottabad. 2014; 26: 61-3. 15. balakrishnan s, vijayan s, nair s, subramoniapillai j, mrithyunjayan s, wilsonn, et al . high diabetes prevalence among tuberculosis cases in kerala, india. plos one. 2012; 7: e46502. 16. ogbera ao, kapur a, razzaq ha, harries ad, ramaiya k, adeleye o, et al. clinical profile of diabetes mellitus in tuberculosis.bmj open diabetes res care. 2015;3: e000112. 17. bacakoglu f, basoglu ok, cok g, sayiner a, ates m. pulmonary tuberculosis in patients with diabetes mellitus. respiration. 2001; 68: 595-600. 18. park sw, shin jw, kim jy, park iw, choi bw, choi jc, et al. the effect of diabetic control status on the clinical features of pulmonary tuberculosis. eur j clin microbiol infect dis. 2012; 31: 1305-10. 19. patel ak, rami kc, ghanchi fd. radiological presentation of patients of pulmonary tuberculosis with diabetes mellitus. lung india. 2011; 28: 70. 20. niazi ak, kalra s. diabetes and tuberculosis: a review of the role of optimal glycemic control. j diabetesmetab disord. 2012; 11: 28. 56 jiimc 2016 vol. 11, no.2 diabetes and pulmonary tuberculosis original�article abstract objective: to determine the effect of blowing balloons on pulmonary function tests and perceived level of stress in medical students. study design: pretest-posttest quasi-experimental study. place and duration of study: this study was conducted at department of physiology, islamic international st st medical college from 1 april 2016 to 31 may 2016. materials and methods: sixty students of islamic international medical college participated in the study after fulfilling the dass (depression anxiety stress scale) questionnaire performa. pulmonary function tests of the participants were measured according to the standard guidelines published by american thoracic society. this was recorded by using power lab and the data was then analyzed by using software, lab chart 8 pro. the participants were then subjected to a supervised blowing balloon exercise using commercially available balloons. after completion of exercise, pulmonary function tests of the participants and the dass questionnaire was filled again by the participants. results: after blowing balloon exercise dass score of the participants was reduced from 21.87 + 2.01 to 13.41 + 4.29 (p < 0.001). tidal volume was increased from 517.72 + 48.57 ml to 638.65 + 86.02ml (p < 0.001), vital capacity was increased from 3.51 + 0.56 l to 4.83 + 0.77 l (p < 0.001) and the ratio of forced expiratory volume in one second to the forced vital capacity was improved from 89.36 + 4.54 % to 92.66 + 4.27 % (p < 0.001) after blowing balloon exercise. conclusion: blowing balloon exercise is an effective way of improving pulmonary function tests and alleviating stress levels in medical students. key words: depression anxiety stress scale, lab chart, pulmonary function tests, stress. present in 7.5%, moderate level of stress was present in 71.67%, and high level of stress was present in 3,4 20.83% of the medical students. perceived level of stress in an individual can be measured by using validated and reliable dass (depression anxiety stress scale) questionnaire. on the basis of the score an individual can be labeled as stress free or suffering from mild, moderate, severe or extreme severe 5 stress. pressure of academic workload, competitive environment, financial pressure, inadequate relationship with peers and teachers, physical illness, wo r r i e s a b o u t f u t u re , p o o r fo o d q u a l i t y, overcrowding of students in hostel rooms, minimal opportunities for the students to relax are among the 6-8 major stressors faced by the medical students. inability of the medical students to cope with these stressors leads to poor scholastic performance, interpersonal relationship difficulties, reduction in attention, concentration and decision making skills. it causes dropout from medical course and even introduction stress is defined as the inability of an individual to respond sufficiently towards a physical, emotional or mental demand. it affects psychological wellbeing of students, which is an area of increasing concern 1,2 worldwide. medical students are more prone to experience level of depression, anxiety and stress. studies have shown that low level of stress was blowing balloons, a novel way for reducing stress and improving pulmonary function tests 1 2 3 noman sadiq , humaira fayyaz khan , arif siddiqui correspondence: dr. noman sadiq assistant professor, physiology cmh kharian medical college, kharian e-mail: noman_sadiq89@yahoo.com 1 department of physiology cmh kharian medical college, kharian 2 department of physiology islamic international medical college riphah international university, islamabad 3 vice chancellor barrett hodgson university, karachi funding source: nil; conflict of interest: nil received: dec 09, 2017; revised: may 17, 2018 accepted: may 24, 2018 blowing balloons, a novel way for reducing stressjiimc 2018 vol. 13, no.2 66 development of suicidal behavior in these medical 9 students. students employ many techniques to cope with stress, for example discussion with seniors, use of 5 internet chat and cell phone texting , attending meditation, hypnosis, group discussions, counseling 10 11,12 sessions ,cycling, jogging and yoga. the main goal of breathing exercise is to improve pulmonary function tests (pfts) which provides measurable feedback about the function of the lungs by assessing flow rates, lung volumes, and 13,14 capacities. the practice of breathing exercises can decrease stress and strain through the reduction in sy m p at h et i c a c t i v i t y a n d e n h a n c e m e nt o f parasympathetic activity. pattern of discharge via vagal neurons is influenced by the respiratory rhythm of the body. vagal neurons receive powerful excitatory input from pulmonary stretch receptors as a c o n s e q u e n c e v a g a l n e r v e a c t i v i t y i . e . 14 parasympathetic activity is increased. breathing exercises include various forms of yoga exercise, slow lip pursuing exercise, blowing balloon exercise 15 etc. blowing balloon exercise has been documented in improving pulmonary function tests of smokers, for treating obstructive sleep apnea syndrome, in rehabilitation of stroke patients and in oral 1 6 , 1 7 gymnastics. the blowing balloon exercise strengthen the respiratory muscles and results in the increase of tidal volume (tv), vital capacity (vc), forced vital capacity (fvc), forced expiratory volume in one second (fev1) and forced expiratory volume in one second to the ratio of forced vital 18 capacity (fev1/fvc). to combat stress encountered in a medical school environment, students are advised to get themselves involved in stress reducing activities like counseling sessions, physical exercises including 10,11 gym, running, swimming, yoga etc. however, all these activities are time consuming, a major barrier for medical students to practice them regularly. in order to enhance students' performance and academic achievement in inherently stress full medical college environment, provision of cost effective, less time consuming fun activities for coping stress is the need of hour. the role of blowing balloons in reducing stress has not been studied yet. the objective of the current study was to assess the effectiveness of blowing balloon therapy in relieving the perceived level of stress in medical students. materials and methods this pretest-posttest quasi-experimental study was conducted at department of physiology, islamic st international medical college from 1 april 2016 to st 31 may 2016. a total of sixty participants were selected by simple random sampling through balloting method with an equal contribution from both genders. the study was conducted after getting approval from institutional e t h i c a l r e v i e w c o m m i t t e e . i n i t i a l l y d a s s questionnaire was distributed and filled by 200 st nd students of 1 and 2 year mbbs after written informed consent. healthy subjects having age between 18-25 years, who scored 19 – 25 on dass performa (having moderate level of stress) were labelled as eligible. subjects who were smokers, having oral lesions, using bronchodilator medicines or practicing any form of breathing exercise were not included. study participants were asked to reach physiology department between 8.00 9.00 am. they were made to relax for five minutes and then height, weight and blood pressure of the participants were recorded. pulmonary function tests comprising on tidal volume, vital capacity, forced vital capacity, forced expiratory volume in one second and the ratio of forced expiratory volume in one second to the forced vital capacity of the participants were measured by performing spirometry by using power lab 4/25t. pulmonary function tests of the participants were measured according to the standard guidelines published by american thoracic society and 19 european respiratory society. recorded data in the power lab was analyzed by using lab chart 8 pro software. the study participants were subjected to a supervised blowing balloon exercise for a period of three days a week for six consecutive weeks using 15 commercially available balloon. during blowing balloon exercise participants were asked to obtain an upright position, breathe in maximum, maintain their state for one second then breathe out in balloon mouth. then participants were requested to close the balloon mouth with their fingers. participants were then again asked to breathe in blowing balloons, a novel way for reducing stressjiimc 2018 vol. 13, no.2 67 maximum, maintain their state for one second and breathe out in balloon. this completed their one mini set. they were asked to perform three mini sets in order to complete one set. a total of three sets were performed by them in a day. to prevent fatigue participants were provided with a 2-3 minute break between consecutive sets. subjects were advised to stop exercise whenever they felt dizzy. to prevent valsalva subjects were advised to not hold their breath for more than five seconds after they breathed out. after completion of blowing balloon exercise, pulmonary function tests of the participants were again measured by performing spirometry through powerlab. study participants were again provided with the dass questionnaire performa and were requested to fill it. the parametric data was analyzed in term of mean + standard deviation by using statistical software spss version 21. difference in the dass score and pulmonary function test of the study participants before and after the blowing balloon exercise was determined by using parametric paired t test. p value of <0.05 was considered as statistically significant. results our study included sixty participants, all of the participants completed all the sessions of blowing balloon exercise and there was no drop out. difference in the dass score and pulmonary function test indices before and after performing blowing balloon exercise were compared. the mean age of the participants was 20.5 + 1.2 years. descriptive statistics of the study participants are given in table i. table ii shows the pulmonary function test indices. all the indices of pulmonary function test i.e. tidal volume tv, vc, fvc, fev1 and fev1/fvc were significantly improved after performing blowing balloons exercise. table iii shows the dass score of study participants. the mean dass score of the participants was 21.87 + 2.01 before the commencement of blowing balloon exercise. this score was significantly decreased to the value of 13.41 + 4.29 after performing six weeks blowing balloon exercise. table i: descrip�ve sta�s�cs of study par�cipants (n= 60) table ii: comparison of pulmonary func�on tests before and a�er blowing balloon exercise *p value < 0.05 is significant table iii: comparison of par�cipant's dass score before and a�er blowing balloon exercise *p value < 0.05 is significant discussion medical colleges are notoriously famous for being stressful and this stress often exerts negative effect on the physical, psychological and academic blowing balloons, a novel way for reducing stressjiimc 2018 vol. 13, no.2 68 wellbeing of the students. the current study was conducted with an aim to find an effective way to alleviate stress among the students of medical college. the current study shows that blowing balloons for six weeks resulted in significant improvement in tv, vc, fvc, fev1 and fev1/fvc indices of pulmonary function tests. moreover blowing balloons significantly reduced the perceived stress score of medical students. findings of the present study are in accordance with the study conducted by antte kjellgren et al which showed that practice of yogic breathing exercise for 3 hours/day for 6 days/week for seven weeks resulted in reduction of depression, anxiety and stress levels in students. the compliance rate of yogic exercise 20 was 94.17%. however, the participants of the present study used blowing balloons exercise as a stress coping strategy and performed exercise for ten minutes in a day for 3 days/week for six consecutive weeks and the compliance rate was 100%. results of our study also support the findings of study conducted by shapiro et al which reported that use of yoga, meditation and group discussion as stress coping strategy for 2.5hours/week for seven weeks resulted in significant reduction in stress levels of students. the compliance rate of the study 11 participants were 93.5%. in present study we used blowing balloon exercise as a stress coping strategy instead of yoga, meditation and group discussion. the compliance rate of our participants was 100%. moreover our participants performed exercise for just ten minutes in a day for 3 days/week for six consecutive weeks instead of long sessions done by the participants of shapiro, et al. during blowing balloons in order to keep balloon inflating, the resistance of inflated balloon rubber is overcome by forceful expiration this results in the active contraction of rectus abdominus, transversus abdominus and intercostal muscles. expiratory muscles get trained through this exercise. kim, j et al conducted a study on young adult smokers which concluded that blowing balloon exercise resulted in a significant improvement in several parameters of pulmonary function tests (vc, 15 fvc, fev1, fev1/fvc). our study also concluded that blowing balloon exercise resulted in a significant improvement in pulmonary function tests including tidal volume. however, in the study by kim, j et al, tidal volume was not measured. results of this study is also in accordance with a study conducted by jun, h et al, which showed that blowing balloon exercise for four weeks by elderly smokers resulted in an 21 increase in vc, fvc, fev1, fev1/fvc, pef. in comparison with these studies this study was co n d u c te d o n st re s s e d o t h e r w i s e h e a l t hy nonsmoker medical students. v blessy et al conducted a research on healthy subjects and performed bhastrika pranayama exercise for five times a day for three months. in this exercise participants took slow and deep inhalation followed by forceful exhalation from the nose, resulted in improvement in tv, fvc, fev1/fvc of 22 study participants (p <0.02). pulmonary function indices (tv, vc, fvc, fev1, fev1/fvc) of the participants of this study also showed significant improvement (p< 0.000). however, the current study participants performed blowing balloon exercise in which exhalation was done against a resistance which could be the possible reason for the marked improvement of pulmonary function tests as compared to the improvement in pulmonary function tests due to bhastrika pranayama exercise used by v blessy et al in which simple forceful exhalation was done. a study conducted by mauch ad on young healthy adults showed that practicing of iyengar yoga for two weeks lead to an increase in tv, fvc fev1/fvc of participants (p <0.01). participants were asked to take deep breath and then they were instructed to hold breath for few seconds in triangular standing 23 posture. our blowing balloon exercise also resulted in the significant improvement in pulmonary function test of the participants however our exercise can be performed at without any posture restriction. in spite of the fact that the study was conducted under the available resources and facilities the exercise period could have been extended from 6 weeks up to 6 months. in future effect of blowing balloon exercise can be compared with other stress coping strategies like yoga, cycling or treadmill exercise etc. conclusion our study concluded that blowing balloons exercise improves pulmonary function tests and reduces the blowing balloons, a novel way for reducing stressjiimc 2018 vol. 13, no.2 69 level of stress in medical students. it is a cost effective and less time consuming method which can be used by the students as a stress coping strategy. references 1. al-sowygh zh. academic distress, perceived stress and coping strategies among dental students in saudi arabia. saudi dent j. 2013; 25: 97-105. 2. pinto vn, wasnik s, joshi sm, velankar dh. medical students' perceptions of stress factors affecting their academic performance, perceived stress and stress management techniques. int j community med public health. 2018; 5: 191-6. 3. daya z, hearn jh. mindfulness interventions in medical education: a systematic review of their impact on medical student stress, depression, fatigue and burnout. med teach. 2018; 40: 146-53. 4. sohail n. stress and academic performance among medical students. j coll physicians surg pak. 2013; 23: 67-71. 5. lovibond pf, lovibond sh. the structure of negative emotional states: comparison of the depression anxiety stress scales (dass) with the beck depression and anxiety inventories. behav. ther. 1995; 33: 335-43. 6. talih f, daher m, daou d, ajaltouni j. examining burnout, depression, and attitudes regarding drug use among lebanese medical students during the 4 years of medical school. acad psychiatry. 2018; 42: 288-96. 7. heinen i, bullinger m, kocalevent rd. perceived stress in first year medical students-associations with personal resources and emotional distress. bmc med educ. 2017; 7: 4-9. 8. saravanan c, wilks r. medical students' experience of and reaction to stress: the role of depression and anxiety. scientific world j. 2014; 15: 42-8. 9. deepak p, usmani uu, washdev w, mirza d, das k, rehman ru. prevalence of depression and anxiety among undergraduate medical students in a government medical college of karachi. journal of postgraduate medical institute (peshawar-pakistan). 2017; 31: 281-5. 10. schiller jh, stansfield rb, belmonte dc, purkiss ja, reddy rm, house jb, et al. medical students' use of different coping strategies and relationship with academic performance in preclinical and clinical years. teach learn med. 2018; 30: 15-21. 11. shapiro sl, shapiro de, schwartz ge. stress management in medical education: a review of the literature. acad. med. 2000; 75: 748-59. 12. tiwari vk, singh v, kumar d, mittal m, asthana ab. is yoga an effective modality of stress reduction within medical population; a qualitative study within mbbs students of brd medical college, gorakhpur. int j res med sci. 2018; 6: 581-4. 13. bertisch sm, hamner j, taylor ja. slow yogic breathing and long-term cardiac autonomic adaptations: a pilot study. j. altern. complement. med. 2017; 23: 722-9. 14. jerath r, edry jw, barnes va, jerath v. physiology of long pranayamic breathing: neural respiratory elements may provide a mechanism that explains how slow deep breathing shifts the autonomic nervous system. med. hypotheses. 2006; 67: 566-71. 15. kim js, lee ys. effects of a balloon-blowing exercise on lung function of young adult smokers. j phys ther sci. 2012; 24: 531-40. 16. amaravathi e, ramarao nh, raghuram n, pradhan b. yogabased postoperative cardiac rehabilitation program for improving quality of life and stress levels: fifth-year followup through a randomized controlled trial. international journal of yoga. 2018; 11: 44-9. 17. guimaraes kc, drager lf, genta pr, marcondes bf, lorenzifilho g. effects of oropharyngeal exercises on patients with moderate obstructive sleep apnea syndrome. am. j. respir. crit. care med. 2009; 179: 962-6. 18. renuka k, helen shaji jc, kripa angeline a. effectiveness of balloon therapy on respiratory status of patients with lower respiratory tract disorders. ijsr. 2015; 4: 20-5. 19. miller mr, crapo r, hankinson j, brusasco v, burgos f, casaburi r, et al. general considerations for lung function testing. eur respir j. 2005; 26: 153-61. 20. kjellgren a, bood sa, axelsson k, norlander t, saatcioglu f. wellness through a comprehensive yogic breathing program–a controlled pilot trial. bmc complement altern med. 2007; 7: 22-8. 21. jun hj, kim kj, nam kw, kim ch. effects of breathing exercises on lung capacity and muscle activities of elderly smokers. journal of physical therapy science. 2016; 28: 1681-5. 22. blessy v, sayyad r, yadav pk, kar sk. effect of breathing exercises on pulmonary function tests in healthy adults. j clin biomed sci. 2014; 4: 226-9. 23. mauch ad, day a. effects of a two week yoga program on the pulmonary function. bio. 2008; 493: 1-9. blowing balloons, a novel way for reducing stressjiimc 2018 vol. 13, no.2 70 page 22 page 23 page 24 page 25 page 26 original�article abstract objective: the study was aimed to investigate the relationship of psychological problems like depression, anxiety and low self-esteem among young adults suffering from obesity. study design: cross sectional analytical study design. place and duration of study: this study was carried out in riphah institute of clinical and professional psychology, riphah international university, lahore, pakistan and data was collected from two private and two government universities of lahore during the year june 2017june 2018. materials and methods: non probability purposive sample of 300 participants with age range 19 to 25 was incorporated in the present study. depression was evaluated through the hamilton depression rating scale. anxiety was measured in participants through the hamilton anxiety rating scale and for self-esteem assessment rosenberg self-esteem scale was applied. urdu translated versions for all scales were used for present study. both descriptive (frequencies, percentages bar graphs, mean and standard deviation) and inferential statistics (pearson product moment correlation, hierarchical regression analysis, independent sample t test) were used for the data analyses. conclusion: majority of young adults with obesity suffer with severe depression and very low self-esteem. there is a significant relationship between depression and anxiety among obese young adults. however both depression and anxiety are not the predictors of low self-esteem in this sample. men and women score equally on depression, anxiety and self-esteem. 2 results: descriptive analysis identified obesity of young adults with body mass index ≥25 kgm . results indicated that 106 (35.3 %) young adults were suffering with very severe depression 40(13.3%) with very severe anxiety and 166 (55.3 %) with low self-esteem. correlational analysis revealed significant positive relationship 0.480 **p< 0.01 between depression and anxiety. regression analysis revealed that depression and anxiety were not significantly predicting the self-esteem. no significant gender differences was found regarding all study variables (p>.05). key words: anxiety, depression, early adulthood, obesity, self-esteem. depression is more than just sadness. individual who experience depression may suffer absence of 1 obesity. obesity has become a significant expanse of health psychology as there are lots of psychological 2,3 problems which took place owing to obesity. obesity always brings supplementary health compromising situations that can further divided in to bio-psycho social conditions. for example biological conditions like hypertension, diabetes cardiovascular disorders, psychological issues like depression, anxiety, low self-esteem, and social like social stigma or isolation. such factors enhance the 4 adverse effects of obesity. numerous empirical evidences revealed many psychological and behavioural costs that people with obesity have to pay in the form of depression, anxiety, suicidal thoughts and wishes, body dissatisfaction and low 5 self-esteem. introduction obesity is a condition of inequality of calories that are ingested and calories that are expended which lead to unnecessary fat deposit. obesity has serious consequences in the form of some medical and mental problems. men as well as women face different outcomes of obesity however; researchers showed the women percentage is more than male in psychological problems related to obesity in early adulthood 1 2 javeria ismail , saima majeed correspondence: dr. saima majeed senior clinical psychologist punjab institute of mental health, lahore e-mail: saimapsychologistpimh@gmail.com 1 department of psychology riphah institute of clinical and professional psychology riphah international university, lahore 2 department of psychology punjab institute of mental health, lahore funding source: nil; conflict of interest: nil received: april 24, 2019; revised: july 15, 2019 accepted: july 17, 2019 jiimc 2019 vol. 14, no.4 psychological problems related to obesity 197 materials and methods previous empirical evidences based upon foreign literature. present study will be a value able contribution in the field of social and health psychology with indigenous results. present study focused on to determine whether depression and anxiety predict low self-esteem. it was planned to understand that how depression and anxiety can cause low self-esteem in obese adults. depression and anxiety has several negative effects in everyday life of obese adults. so, it will be helpful for clinicians and health psychologists to manage these negative emotions. the study was aimed to investigate the relationship of psychological problems like depression, anxiety and low self-esteem among young adults suffering from obesity. cross sectional analytical study design was followed. non probability purposive sample of 300 participants were included (50% men and 50% women) from two public and two private universities of lahore during the period of june 2017june 2018. undergraduate and postgraduate participants with age range of 19 to 25 (m =21.67, sd=1.94) were included. only those individuals were included for study whose weight was above the normal ranges. suffering from any diagnosed psychological disorder was an exclusion criterion for the study. after approval of board of studies (bos) of riphah institute of clinical and professional psychology, riphah international university, lahore, pakistan present research was carried out. all ethical standards of apa were followed during the study. the researcher recognized the enclosure and barring standards. the researcher ensured the members about the full privacy of collected data. the subjects were free to leave the study at any time they wished without any penalty or prejudice. they were fully informed about the aim of the study. their approval was taken before administering the scales. the participants were given demographic information sheet, hamilton depression rating scale, hamilton anxiety rating scale, rosenberg self-esteem scale, individually. total average time was 30 to 35 minutes for scale's administration. the data was normally distributed so parametric tests were chosen for the analyses. pearson product moment correlational analysis was used for the assessment of relationship between variables as all the variables were anxiety is a sensation of uneasiness as well as discomfort. sensation of nervousness from time to time is usual. anxiety fragment of the body's usual response or to pressure can even be supportive at times, making you more attentive as well as prepared for actions. nevertheless anxiety disorder varies from ordinary sensation of worry. once sensation of fright or uneasiness develop, problematic to regulate or influence with everyday 7 activities, it's entitled an anxiety disorder. there are many factors related to anxiety in student’s life e.g annoying to suitable in, remain moral marks, strategy for upcoming, and be gone from home frequently 8 c a u s e s a n x i e t y fo r a ra t i o o f s t u d e n t s . neuropsychiatric disorders, counting mood as well as anxiety disorders, description for about 14% of global encumbrance of illness and disturb over 450 9 million persons on international level. self-esteem is generally conceptualized as the feeling that one is good sufficient and therefore, persons with high self-esteem do not fundamentally 8 think they are better to others. self-esteem is thought to provide two basic functions, one is that self-esteem is intricate in the handover of detail among the separate and the social setting as well as it can suggest a caring utility that defenses persons 10 from undesirable practices. pleasure and interest in daily activities, sleeplessness or increased in sleep, lack of energy, incapability to focus, significant weight loss, and spirits of meaningless or extreme culpability or recurrent opinions of demise or suicide. depression is the very common mental disorder as most of the statistics revealed. luckily, depression is curable. a mixture of therapy and antidepressant medication can support 6 certify recovery. the aim of the present research was to examine the psychological impacts of obesity in early adulthood. previous researches revealed that, obese people are usually remaining dissatisfied about their body image which in return affects their dietary habits and ultimately self-esteem. obese people have low selfesteem and feel dissatisfaction and discomfort as compare to non-obese people, as well as level of depression and anxiety expected to be high in obese people. people who are active are much better than sedentary people. exercise relief stress which in return helps to improve self-esteem. jiimc 2019 vol. 14, no.4 psychological problems related to obesity 198 the results of correlation analysis (table i) show that significant positive correlation .480 **p< 0.01 between depression and anxiety. descriptive analysis revealed that 254(84%) participants were living in a nuclear family system and 100% with intact families. they were under grades (50%) and masters' (50%) students, all were unmarried (100%). figure (1-3) show that 106 (35.3 %) young adults with obesity were suffering from depression, 40(13.5%) with severe depression, 65 (21.7%) with moderate depression and 60(20%) with mild depression, likewise 40(13.35%) young adults were suffering from very severe anxiety, 53(17%) with severe anxiety, 60(20%) with moderate anxiety, 25(8.3%) with mild anxiety. in a similar manner 166 (55.3%) young adults have low self-esteem. results continuous in nature. hierarchical regression analysis was employed for prediction and independent sample t test was used for gender difference examination. data was analyzed through the spss version 21. all scales proved with significant internal reliability i.e bdi (.88), bai (.88) and risb (.74). fig 1: level of depression in young adults with obesity (n=300). fig 2: level of anxiety in young adults with obesity (n=300) fig 3: level of self-esteem in young adults with obesity table i: rela�onship between depression anxiety and self-esteem (n=300) for prediction a hierarchical regression analysis (table ii) was performed to identify predictors of selfesteem that were depression and anxiety. in the step 1 age, gender and family system non-significantly predicted self-esteem, r2= -.001, f= (.905). in the step ii depression did not significantly predict selfesteem, r2=.002, f= (.879). in step iii anxiety did not significantly predict self-esteem, r2= .004, f= (1.21). note: hrsd= the hamilton rating scale for depression, anxiety=the hamilton rating scale for anxiety, self-esteem= rosenberg self-esteem scale **p< 0.01. table ii: hierarchical regression analysis predic�ng self-esteem for depression, anxiety (n=300) note. r2= adjusted r square, β= beta., outcome variable=self esteem independent “sample t test” was implied to jiimc 2019 vol. 14, no.4 psychological problems related to obesity 199 depression and anxiety played no role in predicting the self-esteem in present study participants. the results of the current study could fluctuate from previous studies that found low self-esteem potentially forecasts depression in adolescents and 16, 17 in early adulthood. the assumptions of the present research which is based upon the previous literature should be tested for a large population in order to get the significant results and enhance both internal and external validity. are secure alongside the meanings of taxing life actions, similarly youngsters with little self-esteem 14 are more susceptible to strain. there is a high probability that people with inadequate self-esteem suffered with some psychological issues like anxiety and depression during their adult time period as compared to those with adequate self-esteem. selfesteem deficiency also shows a significant role in increased anxiety. further studies also established an inverse relationship between positive self-esteem 15 and undesirable emotional consequences. metaanalysis of the studies also revealed that weight stigma is significantly associated with reduced selfesteem with teasing history during childhood. t-test analysis revealed that there is no significant gender difference in depression, anxiety and selfesteem. some previous studies presented that no differences in depressive signs were observed 18 between male and female students. the results also supported by the previous researches that indicated people with anxiety disorder did not show 19, significant gender differences in the lifetime rates. 20 the outcomes are convergent with the outcomes of some of the previous studies on gender differences 21 in anxiety. the results can be inferred that men and women young adults with obesity were equally depress, anxious and with low self-esteem. biological difference created no difference in psychological issues related to obesity. researches also supported this idea that both men and women with obesity 22 have low self-esteem. to sum up, young adults with obesity suffer with severe depression and a very low self-esteem. there is a positive relationship between depression and anxiety. conversely depression and anxiety are not the predictors of self-esteem in this sample. no conclusion examine gender differences and results of t test (table iii) show that there is no significant difference p> 0.05 in depression, anxiety and self-esteem. table iii: gender wise difference regarding depression, anxiety and self-esteem (n=300) discussion note: ci= confidence interval, ll=lower limit, up= upper limit, there is a positive relationship between depression and anxiety in obese adult. the existence of a strong relationship between anxiety and depressive symptoms in individuals with obesity has an extra significance than the association between body 10 plump and these equal indications rewis . results from earlier studies have been assorted, through some supporting positive relations for depression 11 and anxiety with obesity. obesity also accompany weight stigma which ultimately leads the person towards pessimistic attitude, poor psychological 5 outcomes like depression and anxiety . in a meta4 analysis more than fifteen empirical studies concluded that weight stigma was significantly related to the symptoms of clinical depression. 12 rosenberger, henderson, bell, and grilo studied that if obesity and teasing from fellows starts from early childhood then it would be more strongly related to depression in adulthood. there is an inverse but non-significant relationship found between self-esteem and depression which could be inferred like this that self-esteem might be deliberated in place of a self-justifying issue particularly in this thought-provoking period of 13 lifecycle. the young individuals through adequate self-esteem have improved control properties and the present study aimed to investigate the relationship between depression, anxiety and selfesteem in obese young adults. prediction and gender differences were also examined for all study variables. jiimc 2019 vol. 14, no.4 psychological problems related to obesity 200 co-occurring mood and anxiety disorders in the united states and south korea—a cross-national comparison. alcoholism: clinical and experimental research.2012; 36(4):654-62. 10. rosenberg m. rosenberg self-esteem scale (rse). acceptance and commitment therapy. measures package. 1965; 61:52. 11. eigler–hill v, abraham j. borderline personality features: instability of self–esteem and affect. journal of social and clinical psychology. 2006; 25(6):668-87. 12 rosenberger ph, henderson ke, bell rl, grilo cm. associations of weight-based teasing history and current eating disorder features and psychological functioning in bariatric surgery patients. obesity surgery. 2007; 17(4):470. 13. hruschka dj, rush ec, brewis aa. population differences in the relationship between height, weight, and adiposity: an application of burton's model. american journal of physical anthropology. 2013; 151(1):68-76. 14. simon ge, ludman ej, linde ja, operskalski bh, ichikawa l, rohde p, finch ea, jeffery rw. association between obesity and depression in middle-aged women. general hospital psychiatry. 2008; 30(1):32-9. 15. moksnes uk, moljord ie, espnes ga, byrne dg. the association between stress and emotional states in adolescents: the role of gender and self-esteem. personality and individual differences. 2010; 49(5):430-5. 16. trzesniewski kh, donnellan mb, moffitt te, robins rw, poulton r, caspi a. low self-esteem during adolescence predicts poor health, criminal behavior, and limited economic prospects during adulthood. developmental psychology. 2006; 42(2):381. 17. boden jm, fergusson dm, horwood lj. does adolescent self-esteem predict later life outcomes? a test of the causal role of self-esteem. development and psychopathology. 2008; 20(1):319-39. 18. sowislo jf, orth u. does low self-esteem predict depression and anxiety? a meta-analysis of longitudinal studies. psychological bulletin. 2013 jan; 139(1):213. 19. orth u, robins rw, roberts bw. low self-esteem prospectively predicts depression in adolescence and young adulthood. journal of personality and social psychology. 2008; 95(3):695. 20. bostanci m, ozdel o, oguzhanoglu nk, ozdel l, ergin a, ergin n, atesci f, karadag f. depressive symptomatology among university students in denizli, turkey: prevalence and sociodemographic correlates. croat med j. 2005 1;46 (1):96-100. 22. olweus d. prevalence and incidence in the study of antisocial behavior: definitions and measurements. incross-national research in self-reported crime and delinquency 1989 (pp. 187-201). springer, dordrecht. 21. simon ge, ludman ej, linde ja, operskalski bh, ichikawa l, rohde p, finch ea, jeffery rw. association between obesity and depression in middle-aged women. general hospital psychiatry. 2008 1; 30 (1):32-9 2. powers ps. obesity, the regulation of weight. williams and wilkins; 1980. gender differences reveal for depression, anxiety and self-esteem in young adults with obesity. implications obesity is related to many psychological problems e.g depression, anxiety and low self-esteem. young adults should be vigilant for their caloric count, healthy life style and exercise so that they could be refrain from emotional and self-esteem problems. the results of the present study have clear implications with health psychology. as not only obesity as a medical issue should be address but its psychological impacts are even more alarming this could get in to the way of treatment plan of obese individuals. the physical and mental health go hand in hand so giving importance to one and ignore the other will not give better results on the part of the health of the community. further researchers could explore more antecedents and consequences of obesity and enhance the already existing knowledge. references 1. pritchard me, milligan b, elgin j, rush p, shea m. comparisons of risky health behaviors between male and female college athletes and non-athletes. athletic insight. 2007 9 (1):67-78. 3. nammi s, koka s, chinnala km, boini km. obesity: an overview on its current perspectives and treatment options. nutrition journal. 2004; 3(1):3 5. pearl rl, puhl rm, dovidio jf. differential effects of weight bias experiences and internalization on exercise among women with overweight and obesity. journal of health psychology. 2015; 20(12):1626-32. 7. edmunds r, buchanan h. cognitive vulnerability and the etiology and maintenance of dental anxiety. community dentistry and oral epidemiology. 2012; 40(1):17-25. 8. bayram n, bilgel n. the prevalence and socio-demographic correlations of depression, anxiety and stress among a group of university students. social psychiatry and psychiatric epidemiology. 2008; 43(8):667-72. 9. chou sp, lee hk, cho mj, park ji, dawson da, grant bf. alcohol use disorders, nicotine dependence, and 4. papadopoulos s, brennan l. correlates of weight stigma in adults with overweight and obesity: a systematic literature review. obesity. 2015 sep; 23(9):1743-60. 6. goodyer im, herbert j, altham pm, pearson j, secher sm, shiers hm. adrenal secretion during major depression in 8to 16-year-olds, i. altered diurnal rhythms in salivary cortisol and dehydroepiandrosterone (dhea) at presentation. psychological medicine. 1996; 26(2):245-56. jiimc 2019 vol. 14, no.4 psychological problems related to obesity 201 original�article abstract objective: to determine the correlation of plasma glucose levels with lipid profile in type 2 diabetes mellitus (t2dm). study design: case control study. th place & duration of study: this study was conducted in army medical college rawalpindi from 11 th november 2014 to 11 november 2015. materials & methods: the number of participants comprised in the study was 120. the study population was divided into two groups a & b. 60 individuals were placed in each group. group a comprised of type 2 diabetics and group b were healthy controls with no major illness. the patients were recruited from the military hospital's medical wards and endocrinology outpatient department. the participants' blood samples were analyzed for fasting plasma glucose (fpg), glycosylated hemoglobin (hba1c) and lipid profile (total cholesterol, triglycerides, ldl-cholesterol and hdl-cholesterol).body mass index (bmi) was calculated by measuring the height and weight of men & women based on body fat. data was analyzed using spss version 20. � � results: fpg was (11.23±3.65 in diabetics vs 4.35±0.68 in controls), hba1c was (6.84±0.482 vs 5.31±0.487). serum total cholesterol was (4.68±0.96 vs 3.99±1.01 p<0.001), triglycerides (tg) were (2.42±1.22 vs 1.56±0.87 p<0.001) and ldl-cholesterol was (2.46±0.77 vs 2.17±0.72 p<0.05). these parameters were significantly raised then the controls. whereas hdl-cholesterol in the diabetics were relatively lower than the controls (1.04±0.224 vs 1.21±0.222 p<0.001). the diabetics body mass index (bmi) was also significantly more than the controls (28.57±1.97 vs 24.46±2.32 p<0.001). conclusion: this study shows that serum fpg, hba1c, total cholesterol, tg and ldl-cholesterol are significantly increased in t2dm while hdl-cholesterol levels are decreased significantly which might be the reason for high coronary heart diseases incidence in t2dm. key words:type2 diabetes mellitus,dyslipidemia,total cholesterol,triglycerides,ldl-cholesterol and hdlcholesterol diabetes mellitus, t1dm previously called insulin dependent diabetes mellitus (iddm), occurs when insulin secretion is deficient and t2dm or non-insulin dependent diabetes mellitus (niddm), occurring because of insulin resistance with or without insulin 3 relative deficiency. “chronic hyperglycemia causes structural and functional damage to blood vessels and tissues leading to complications such as diabetic n e u r o p a t h y, n e p h r o p a t h y, r e t i n o p a t h y, hypertension, hyperlipidemia, cerebrovascular diseases and atherosclerotic coronary heart 4, 5 disease.” diabetes mellitus is a rapidly growing epidemic. 285 million people were suffering from diabetes in year 2010. this number is going to be 439 million 6 worldwide in year 2030. similarly there is rise in coronary mortality in diabetic patients having dyslipidemia. expected increase in deaths from 2000 introduction “diabetes mellitus is a chronic metabolic disorder characterized by hyperglycemia caused by defective insulin secretion, ineffective insulin function or both which leads to disturbance of carbohydrate, fat and 1,2 protein metabolism.” there are two major types of dyslipidemia in type 2 diabetes mellitus correspondence: dr. mehnaz khattak department of pathology foundation university medical college islamabad e-mail:mehnaz07@yahoo.com 1,3,4 department of pathology foundation university medical college islamabad 2 department of chemical pathology armed forces institute of pathology rawalpindi funding source: nil; conflict of interest: nil received: jan 31, 2018; revised: aug 29, 2018 accepted: sep 09, 2018 dyslipidemia in t2dmjiimc 2018 vol. 13, no.3 1 2 3 4 mehnaz kha�ak, asif nawaz, jawwad anis khan, umme farwa 128 21 this. marcello et al in their study explained that the lipoprotein abnormalities are mainly determined by increased production of ver y low density lipoproteins (vldl) by the liver. the multiple mechanisms involved in this are increased ffa influx into the liver, reduction of inhibitory effects of insulin on vldl production and enhanced de novo lipogenesis. all this leads to increased concentration of apo-b-containing lipoproteins and abnormal function of hdl particle which may impair cholesterol removal from deposits. all these changes 22 can lead to atherogenesis. apart from link of diabetic dyslipidemia and atherosclerosis, uncontrolled t2dm is itself a high risk factor for atherosclerosis as selvin et al in 2010 in their community based study done on more than 11,000 participants observed the tendency for increasing risk of stroke, heart diseases and cardiac 9,23 deaths. the current literature suggests to diagnose and treat dyslipidemia in type 2 diabetics at the earliest. it will help improve the quality of life and prevent the associated complications. the main objective of this study was to determine the correlation of plasma glucose levels with lipid profile in t2dm in our own population. material and methods this case control study was conducted in army th medical college rawalpindi from 11 november th 2014 – 11 november 2015. a total of 120 participants were included in the study. they were divided into group a & b. group a included 60 diagnosed patients (30 males & 30 females) with t2dm. individuals with thyroid, liver, kidney, adrenal disorders were excluded from the study. group b included 60 healthy persons (30 males & 30 females) free from any major illness. under aseptic conditions five ml of fasting venous sample of at least 8-12hs was obtained from left median cubital vein. the blood was centrifuged for 5 mins at 4000 rpm for serum separation. selectra e, a fully automated chemistry analyzer was used for the fpg and lipid profile measurement. to estimate the levels of hba1c levels ion exchange method was used. body mass index (bmi) was calculated by measuring the height and weight of men & women based on body fat. patient's selection was done from medical wards & endocrinology department of military hospital (mh) rawalpindi using non probability convenient to 2030 would be 8-11 million worldwide and most of these patients would be diabetics. dyslipidemia association with atherosclerosis is well established. the progression of atherosclerosis in diabetes is mainly due to the associated 7,9 hyperglycemia, obesity and insulin resistance. excess free fatty acids (ffa) liberation from adipose 10,12 tissue occurs in t2dm due to insulin resistance. to a large extent lipoproteins hepatic metabolism is controlled by insulin. it has implications on lipid profile and increased role in coronary heart disease 13, 14 development. atherosclerosis starts as inflammation of the blood vessels and in the presence of t2dm the process speeds up. in t2dm atherosclerosis and high blood 15 glucose levels are related to each other. all proteins glycosylation, like collagen linking arterial wall matrix proteins and collagen linking are caused by persistently raised blood glucose levels leading to endothelial cells dysfunction which further contributes to atherosclerosis. in t2dm there is 95% 16 prevalence of dyslipidemia. a large number of studies have shown a significant reduction in t2dm related complications and mortality rate due to coronary heart diseases if a normal glycemic control is maintained. studies have shown that langerhans beta cells apoptosis is not the only damage that high blood sugar levels causes but also leads to increased accumulation of oxidized ldl in pancreatic islets and coronary arteries thus increasing the risks of 17 development of coronary heart disease. a triad of increased levels tgs, ldl-cholesterol and decreased levels of hdl-cholesterol in diabetic patients is called diabetic dyslipidemia. the abnormalities of lipids in dm is mainly due to insulin resistance that affects the 6, 9, 18, 19 enzymes and pathways in lipid metabolism. several studies have proposed that in diabetic dyslipidemia the lipid particles composition is more 9,20 atherogenic than the other type of dyslipidemia. wul and parhofer kg in their study showed that diabetes and increased cardiovascular risk of diabetic patients is linked mainly to the lipid changes. the increased concentration of ffa, alteration of insulin sensitive pathways and low grade inflammation being the pathophysiology, all these play an important role. the results being decreased catabolism and overproduction of intestinal and hepatic origin triglycerides rich lipoproteins. the observed changes in ldl and hdl are a sequence to dyslipidemia in t2dmjiimc 2018 vol. 13, no.3 129 table ii. shows significant increase in levels of bmi, fbg, hba1c, total cholesterol and tg in the diabetic females as compared to controls while hdl cholesterol was significantly lower in the diabetic group. in females ldl cholesterol showed no significance may be due the small sample size sampling technique. sample size was calculated using who calculator. this parametric data was entered and analyzed using spss version 20 and results of the test were subject to appropriate statistical analysis. quantitative data was compared using independent t-test. the data was statistically considered significant with p-value of < 0·05. results 120 individuals were selected for the study of which 60 were diabetics and 60 were healthy individuals who were gender & age matched. comparison of biochemical profile of different analytes in diabetic patients (group a) and healthy controls (group b) are summarized in table i. fpg levels (mean ± sd) in group a was 11.23±3.65 as compared to group b 4.35±0.68, hba1c was (6.84±0.482 group a vs 5.31±0.487 group b) and in the lipid profile, serum total cholesterol was (4.68±0.96 group a vs 3.99±1.01 group b p< 0.001), triglycerides (tg) were (2.42±1.22 group a vs 1.56±0.87 group b p< 0.001) and ldl cholesterol was (2.46±0.77 group a vs 2.17±0.72 group b p< 0.05). whereas hdl cholesterol was (1.04±0.224 group a vs 1.21±0.222 group b p< 0.001). the bmi was raised significantly in group a than group b (28.57±1.97 vs 24.46±2.32 p< 0.001). table i. comparison of biochemical characteris�cs between cases and controls note: ***significance at 0.001, **significance at 0.01 level, *significance at 0.05 level table ii. comparison of biochemical characteris�cs between cases and controls in females note: ***significance at 0.001, **significance at 0.01 level, *significance at 0.05 level table iii. comparison of biochemical characteris�cs between cases and controls in males table iii. shows significant increase in levels of bmi, fbg, hba1c, total cholesterol, tg and ldl cholesterol in diabetic males as compared to controls while hdl cholesterol was lower in the diabetic males. note: ***significance at 0.001, **significance at 0.01 level, *significance at 0.05 level dyslipidemia in t2dmjiimc 2018 vol. 13, no.3 130 regular exercise and use of lipid lowering drugs are recommended in these patients. limitations of our study was small sample size. future work with larger sample size and of longer duration is recommended. conclusion based on the findings of current study it is concluded that serum total cholesterol, triglycerides and ldl cholesterol levels are significantly raised in t2dm whereas serum hdl cholesterol levels are significantly decreased which might be the reason for high coronary disease incidence in t2dm. references 1. chatterjee mn, shinde r. text book of medical laboratory technology. metabolism of carbohydrates. delhi-india: jaypee brothers medical publisher; 2005. 2. chatterjea m, shinde r. textbook of medical biochemistry: eighth edition: jaypee brothers,medical publishers pvt. limited; 2011. 3. chan jc, malik v, jia w, kadowaki t, yajnik cs, yoon kh, et al. diabetes in asia: epidemiology, risk factors, and pathophysiology. jama. 2009;301(20):2129-40. 4. nathan dm. long-term complications of diabetes mellitus. the new england journal of medicine. 1993;328(23):167685. 5. wingard dl, barrett-connor e, criqui mh, suarez l. clustering of heart disease risk factors in diabetic compared to nondiabetic adults. american journal of epidemiology. 1983;117(1):19-26. 6. taskinen mr. diabetic dyslipidemia. atheroscler suppl. 2002;3. 7. wexler dj, grant rw, meigs jb, nathan dm. cagliero: sex disparities in treatment of cardiac risk factors in patients with type 2 diabetes. diabetes care. 2005;28. 8. regmi p, gyawali p, shrestha r, sigdel m, mehta kd, majhi s. pattern of dyslipidemia in type-2 diabetic subjects in eastern nepal. j nepal assoc med lab sci. 2009;10. 9. ozder a. lipid profile abnormalities seen in t2dm patients in primary healthcare in turkey: a cross-sectional study. lipids in health and disease. 2014;13(1):183. 10. hennes mmi, o'shaughnessy im, kelly tm, labelle p, egan bm, kissebah ah. insulin-resistant lipolysis in abdominally obese hypertensive individuals. role of the reninangiotensin system. 1996;28(1):120-6. 11. g o l d b e rg i j. d i a b et i c d ys l i p i d e m i a : ca u s e s a n d consequences. j clin endo metab. 2001;8. 12. singh rajput dp, shah jy, singh p, jain s. evaluation of dyslipidemia in type 2 diabetes mellitus. 2015. 2015;6(6):4. 13. després j-p. health consequences of visceral obesity. annals of medicine. 2001;33(8):534-41. 14. singh dp, shah jy, shah jy, singh p, singh p, jain s, et al. evaluation of dyslipidemia in type 2 diabetes mellitus2015. 15. devrajani br, shah sz, soomro aa, devrajani t. type 2 diabetes mellitus: a risk factor for helicobacter pylori discussion diabetes mellitus is a commonest systemic metabolic disorder. prevalence of diabetes in pakistan is very high ranging from 7.6-11% in its different regions. it is expected that number of diabetic patients may increase from 5.2 million in 2000 to 13.9 million by the year 2030. cardiovascular disease is a major cause of morbidity and mortality in both men and women with t2dm. in patients with t 2 d m , r i s k fa c t o rs l i ke d y s l i p i d e m i a a n d hypertension plays a major role in inducing cardiovascular disease and control of these factors is of paramount importance. the main observation of this study is increased serum total cholesterol (p<0.001) & ldl cholesterol (p<0.05) in diabetic patients. this is in agreement with study carried out by v.siva prabodh et al in 2012 which also showed that the frequencies of total cholesterol, triglyceride and ldl-cholesterol are 23 higher in the diabetic group( p<0.001). however mean serum total cholesterol and mean serum ldl cholesterol was not as high in our study group as compared to study carried out by narisimhaswamy 24 kn in 2014. this is probably because of limited sample size of our study. the other observation of our study is increased serum triglyceride levels in our patients (p=<0.001) as compared to the control population. this is in accordance with the prior study done by v.siva prabodh et al in 2012 & narisimhaswamy kn in 2014. another important observation of our study is decreased serum hdl cholesterol levels in diabetic patients (p=<0.001) as co m p a re d to h e a l t hy co nt ro l s . t h i s i s i n correspondence with results obtained by deepa singh et al. in 2015 showing that hdl-cholesterol was significantly lower in diabetic patients (p< 25 0.005). this study also compared the bmi of the t2dm patient's vs healthy controls. bmi is significantly raised in t2dm patients (p<0.001). similar results were also shown by dr ratna et al in 2015 quoting that obesity leads to insulin resistance which in turn causes t2dm and both together leads 2 6 to dyslipidemia. hypercholesterolemia and hypertriglyceridemia are the lipid abnormalities that occur in t2dm, which is the major cause of cardiovascular diseases. blood glucose levels and lipid profile monitoring should be done routinely. life style modifications including weight reduction, dyslipidemia in t2dmjiimc 2018 vol. 13, no.3 131 infection: a hospital based case-control study. international journal of diabetes in developing countries. 2010;30(1):226. 16. chattanda sp, mgonda ym. diabetic dyslipidemia among diabetic patients attending specialized clinics in dar es salaam. tanzania medical journal. 2008;23(1):8-11. 17. landmesser u, harrison dg, drexler h. oxidant stress—a major cause of reduced endothelial nitric oxide availability in cardiovascular disease. european journal of clinical pharmacology. 2006;62(1):13-9. 18. goldberg ij. diabetic dyslipidemia: causes and consequences. the journal of clinical endocrinology & metabolism. 2001;86(3):965-71. 19. mooradian ad. dyslipidemia in type 2 diabetes mellitus. nat clin pract end met. 2009;5(3):150-9. 20. mahato rv, gyawali p, raut pp, regmi p, singh pk, pandey dr, et al. association between glycaemic control and serum lipid profile in type 2 diabetic patients: glycated haemoglobin as a dual biomarker. biomed res. 2011;22. 21. wu l, parhofer kg. diabetic dyslipidemia. metabolism. 2014;63(12):1469-79. 22. marcello a, giovanni p, carla f. mechanisms of diabetic dyslipidemia: relevance for atherogenesis. current vascular pharmacology. 2012;10(6):684-6. 23. p s, m v, v sp. lipid profile levels in type 2 diabetes mellitus from the tribal population of adilabad in andhra pradesh, india. journal of clinical and diagnostic research. 2012;6(2):540-92. 24. n1 nk, n1 rg, n2 nk. a study of dyslipidemia in type 2 diabetes mellitus international journal of health information and medical research 2014; vol: 1 (issue: 1). 25. singh d, singh a, kumar r, khan i. dyslipidemia in type 2 diabetes mellitus pateints of udaipur population. scholars j o u r n a l o f a p l l e i d m e d i c a l s c i e n c e s ( s j a m s ) 2015;3(2d):813-5. 26. songa drm, visabarathi dn, k s. comparative study of lipid profile in obese type 2 diabtes mellitus and obese nondiabetes. journal of dental & medical sciences. 2015;14(11):87-91. dyslipidemia in t2dmjiimc 2018 vol. 13, no.3 132 original�article abstract objective: to determine the potential adverse renal histopathological effects on the proximal convoluted tubules in male, wistar rats due to ingestion of subchronic dose of triazophos. study design: randomized controlled trial. place and duration of study: a study of 3 weeks duration (plus 1 week for slide preparation & histological study), was held in the animal house-pgmi, bird wood road, lahore. materials and methods: two equal groups were made, of 6 wistar, male rats each. group a was control while th experimental group b was given triazophos, in a dose of 8.2 mg/kg-subchronic dose (1/10 of ld 50), a commonly used pesticide, as 1:100 dilution solution through oral gavage for 21 consecutive days. on day 22, the rats were sacrificed and tissues preserved for histological examination and measurement of proximal and distal tubular diameters by using micrometric grid. results: the micrometric measurement of diameters of pct in group a and b indicated that they increased significantly from 38.90 ± 2.72µm in group a to 50.35 ± 2.61µm in group b (p-value <0.001). the mean diameter of dct in both the groups was also measured and increased in group b from 34.48 ± 2.58µm in group a to 48.03 ± 3.42µm in group b (p-value <0.001). in group b, inflammatory changes like basement membrane interruption, loss of brush border and severe vacuolar cellular degeneration of proximal convoluted tubules were seen. conclusion: the results confirm the potential adverse renal histopathological effects on the proximal convoluted tubules in male, wistar rats due to ingestion of triazophos, a commonly used pesticide. pesticides induce inflammatory changes in convoluted tubules leading to tubular dilatation and hyperplasia more in pct owing to the extensive exposure of toxic substances in the proximal tubules and resultant increased pct mean diameter. key words: food chain, harmful residues, insecticides, pesticides, renal damage, triazophos. pesticide residues in food are regularly detected at low levels in the food chain in a range of food items 1 and water. triazophos is an organophosphorus pesticide, sprayed rampantly on crops to get rid of the pests infesting on them and to improve the crop 2 yield. it is widely used in agriculture, veterinary medicine and public health all over the world due to its rapid biodegradability and good control over the 3 pests. in spite of all the claims of pesticides' nonpersistence in the food chain, their residues' presence in food items cannot be denied. thus, not only the nutritional value of the food is compromised, pesticides' presence adversely affects 4 the environment as well as the consumers' health. liver & kidneys are the primary organs to be affected due to the conjugative metabolism & excretion of the 5 pesticides through these organs. in kidneys, proximal convoluted tubules are the primary target of histological injury owing to their greater length than the distal convoluted tubules & greater introduction the scientists claim that organophosphorus pesticides like triazophos rapidly degrades and do not tend to persist or bioaccumulate in the environment or food chain but unfortunately proximal convoluted tubules as the primary target of renal histopathological injury by ingestion of pesticide-residue-laden fruits and vegetables 1 2 3 4 5 lubna shahper , shagufta nasreen , muhammad qasim muneer , nazia ayyub , sadia hassan correspondence: dr. lubna shahper senior demonstrator department of anatomy post graduate medical institute ameer ud din medical college, lahore e-mail: lubishah@hotmail.com 1,2, department of anatomy postgraduate medical institute ameer ud din medical college, lahore 3 department of anatomy allama iqbal medical college lahore, 4 department of obstetrics & gynaecology lahore general hospital, lahore 5 department of anatomy services institute of medical sciences, lahore funding source: nil; conflict of interest: nil received: november 13, 2019; revised: march 18, 2020 accepted: march 20, 2020 proximal tubular injury due to pesticides residuesjiimc 20 vol. 1 , no.20 5 1 28 6 exposure of all kinds of toxins to them. the unfortunate extension of pesticides' harmful effects, from the target of pest control to involvement of non-target spectrum of other living organisms as well has led to a confusion whether pesticides are more harmful or useful for the mankind.7 the rationale of present study aimed at observing renal damage especially in the proximal convoluted tubules when the experimental animals ingested subchronic dose of triazophos for a period of 3 weeks. the main objective of the study was to determine the potential adverse histopathological effects on the proximal tubules in male, wistar rats due to ingestion of subchronic dose of triazophos. materials and methods the study was randomized controlled trial of 3 weeks duration (plus 1 week for slide preparation & histological study) held in the animal house of pgmi, lahore, in which 12 male, wistar rats of age 6-8 weeks (excluding the females, < 6 weeks old, < 150 g weight, sick and ailing rats), weighing 175-200 g were selected. rules and regulations laid down by the ethical review board of postgraduate medical institute, lahore were followed & their ethical permission taken. the sampling technique adopted was by simple random sampling, with the help of stat trek's random number generator. group a was kept as control and group b as experimental. the animals were acclimatized for a week; food and water were made available ad libitum, with maintenance of 12-hour light and dark cycle and temperature maintained at 25-30°c. triazophos was given in the sub chronic dose, 8.2 mg/kg body weight th 8 (1/10 of ld50) to the group b as dilution solution through oral gavage while same quantity of distilled water was given to the group a for 21 consecutive 9 days. parametric data was noted on weekly basis. the rats were sacrificed on day 22, their kidneys dissected out and preserved for h & e slides preparation and histological examination for micrometric measurement of tubular diameters. four proximal and four distal convoluted tubules (sub capsular, mid-cortical, juxtamedullary and 10 medullary) were selected per high power field (40x); for each slide; both the vertical and horizontal diameter between the opposite basement membranes of each tubule was measured and then average taken. finally, the mean diameters of pct 11 and dct were determined for each animal. for micrometry, an eyepiece micrometer scale and a stage micrometer slide were used. on the stage micrometer slide, a 1 mm scale was engraved. this 0.01 mm scale was divided into 100 equal divisions. 15 divisions of eyepiece micrometer were equal to 4 12 stage micrometer divisions. 100 stage divisions = 0.01mm = 1000 µm 1 stage division = 1000/100 = 10 µm 15 divisions of eyepiece micrometre = 4 stage divisions (40 µm) 1 division of eyepiece micrometre = 40/15 = 2.66 µm the measured average diameter of each tubule was 13 multiplied by 2.66 to get the exact tubular diameter. data was analyzed by spss version 22.0. independent sample t-test was used to compare the mean diameters of pct and dct in both groups. fisher's exact test was used to analyze the proximal and distal tubular epithelial cells for cytoplasmic vacuolization and loss of brush border. results diameter of pct/dct: the mean diameters of pct and dct in both group a and b were taken. 29 fig 1: photomicrograph showing the horizontal and ver�cal proximal convoluted tubular diameter (pcth/ pctv) and distal convoluted tubular diameter (dcth/ dctv) through micrometer. h&e x400 table i: mean diameter comparison pct and dct among groups independent sample t test *p value ≤ 0.05 is considered sta�s�cally significant proximal tubular injury due to pesticides residuesjiimc 20 vol. 1 , no.20 5 1 loss of brush border fisher's exact test showed that there was statistically significant association between loss of brush border pct and groups (table ii figure 2, 3) discussion in the present study, subchronic dose of triazophos i n d u c e d n e p h r o t o x i c i t y e v i d e n c e d b y 14 histopathological changes in the kidneys. the most marked change observed in the h & e kidney slides of rats of group b was increased tubular diameter measured by using micrometric grid under light microscope (table i, fig. 1), due to cellular hyperplasia leading to tubular dilation & ultimate 30 table ii: distribu�on of loss of brush border (pct) among groups fisher's exact test *p value ≤ 0.05 is considered sta�s�cally significant cytoplasmic vacuolization (pct/dct): fisher's exact test showed that there was statistically significant association between cytoplasmic vacuolization in pct and dct among groups. (table iii, iv; figure 2, 3) table iii: distribu�on of cytoplasmic vacuoliza�on (pct) among groups fisher's exact test *p value ≤ 0.05 is considered sta�s�cally significant table iv: distribu�on of cytoplasmic vacuoliza�on (dct) among groups fisher's exact test *p value ≤ 0.05 is considered sta�s�cally significant fig 2: photomicrograph of group a kidney cortex showing glomerulus (red), parietal (blue) and visceral (dark-green) layers of bowman's capsule (black), tu� of capillaries (aqua-blue), proximal tubules (light-green) with brush border (orange) and distal convoluted tubules (yellow). h&e stain x400. fig 3: photomicrograph kidney cortex in group b showing glomerulus (red), parietal (blue) and visceral layers (dark-green), bowman's space (black), glomerulus (pink), distal (yellow) & proximal tubules (light-green) loss of brush border (orange), protein cast (grey), conges�on in the blood vessel (brown) and vacuole (aqua blue). h&e stain x400. proximal tubular injury due to pesticides residuesjiimc 20 vol. 1 , no.20 5 1 epithelial necrosis, degeneration and desquamation with granular debris in the tubular lumen. this increase in diameters was statistically significant (pvalue <0.001). pesticides exhibit their harmful effects due to induction of oxidative stress in the cells and 16 generation of free oxygen radicals. the reactive oxidative radicals cause anatomical and functional 17 alterations in the mitochondria of cells. in group b, all rats had moderate to severe 15 interrupted brush border (table ii, fig 3). this loss of brush border was statistically significant (p value< 0.002). cytoplasmic vacuolization of pct (table iii, fig 3) and dct (table. iv, fig 3) in the rats of group b was also statistically significant. the loss of brush border results when lysosomal degradative enzymes damage the glycocalyx thus disrupting the microfilaments making the structure of microvilli onto the cytoskeleton of cells as well as 19 cell membrane disruption. disturbed ionic balance in the organelles underlie the formation of multiple membrane vesicles which fuse to form vacuoles causing breakdown of organelles and finally cell death as already explained by elhalwagy in 2016 in a study on effects of triazophos on liver and kidneys of rats 20 . commonly used pesticides like triazophos, persist in 21 the environment and food chain. jain et al, in 17 22 2010. ghaffar et al, in 2014 and mohineesh et al, in 23 2014 conducted studies on triazophos and its subchronic dose's effects on body tissues. they all proved that triazophos adversely effects the body organs. rahman and sattar in 2018 conducted a study on effects of different doses of pesticides on 24 body tissues. the present study was conducted to observe the persistence of organophosphorus pesticides in the food chain of pakistan, the present status of which is quite alarming for the health of mankind, as rampant usage of pesticides on crops is tenfold high in pakistan as compared to other countries. the limitations of the present study were the unawareness among the general population about the hazards of the rampantly-used pesticides and insecticides on almost all the crops and the persistence of their residues in the fruits and vegetables. the gravity of the situation and the unawareness towards its seriousness seems like a hidden iceberg and need further probing into the matter. conclusion the results confirm the potential adverse renal histopathological effects on the proximal convoluted tubules in male, wistar rats due to ingestion of triazophos, a commonly used pesticide. pesticides induce inflammatory changes in convoluted tubules leading to tubular dilatation and hyperplasia more in pct owing to the extensive exposure of toxic substances in the proximal tubules and resultant increased pct mean diameter. references 1. zia ms, khan mj, qasim m, rehman a. pesticide residue in the food chain and human body inside pakistan. j. chem. soc. pak. 2009; 31:284-91. 2. syed jh, alamdar a, mohammad a, ahad k, shabir z, ahmed h, et al. pesticide residues in fruits and vegetables from pakistan: a review of the occurrence and associated human health risks. environ. sci. pollut. res. 2014; 21(23):13367-93. 3. kim kh, kabir e, jahan sa. exposure to pesticides and the associated human health effects. sci. total environ. 2017; 57:525-35. 4. khan m, mahmood hz, damalas ca. pesticide use and risk perceptions among farmers in the cotton belt of punjab, pakistan. crop prot. 2015; 67:184-90. 5. bock r, thier w. metabolism and fate of triazophos in rats. pestic. sci. 1976; 7(3):30714. 6. chevalier rl. the proximal tubule is the primary target of injury and progression of kidney disease: role of the glomerulo-tubular junction. am. j. physiol. renal physiol. 2016; 311(1):145-61. 7. damalas ca, eleftherohorinos ig. pesticide exposure, safety issues, and risk assessment indicators. int. j. environ. res. public health. 2011; 8(5):1402-19. 8. chandra mo, raj ja, dogra td, rajvanshi ac, raina an. determination of median lethal dose of triazophos with dmso in wistar rats. asian. j. pharm. clin. res. 2014; 7(4):64-7. 9. sharma d, sangha gk. triazophos induced oxidative stress and histomorphological changes in liver and kidney of female albino rats. pestic. biochem. physiol. 2014; 110:7180. 10. rahman ma, rahman ma, karim f. histomorphological study of the wall thickness and luminal diameter of cadaveric vermiform appendix in bangladeshi people. 31 proximal tubular injury due to pesticides residuesjiimc 20 vol. 1 , no.20 5 1 american journal of medical sciences. 2019;7(3):89-93. 11. qadir mi, tahir m, lone kp, munir b, sami w. protective role of ginseng against gentamicin induced changes in kidney of albino mice. journal of ayub medical college abbottabad. 2011;23(4):53-7. 12. bhattacharya t, bhakta a, ghosh sk. long term effect of monosodium glutamate in liver of albino mice after neonatal exposure. nepal med coll j. 2011; 13(1):11-6. 13. gulnaz h, tahir m, munir b, sami w. protective effects of garlic oil on acetaminophen induced nephrotoxicity in male albino rats. biomedica. 2010; 26(7):9-15. 14. mossa at, swelam es, mohafrash sm. subchronic exposure to fipronil induced oxidative stress, biochemical and histopathological changes in the liver and kidney of male albino rats. toxicol. rep. 2015; 2:775-84. 15. beceren a, sehirli ao, omurtag gz, arbak s, turan p, sener g. protective effect of nacetyl-l-cysteine (nac) on endosulfan-induced liver and kidney toxicity in rats. int. j. clin. exp. med. 2017; 10(7):10031-9. 16. rashid s. effect of alpha-tocopherol on diameter of proximal convoluted tubules of kidney in diabetic mice. j pak med assoc. 2014; 64:49-52. 17. jain s, mythily s, ahmed rs, arora vk, banerjee bd. induction of oxidative stress and histopathological changes by subchronic doses of triazophos. ind. j. biochem. biophysic. 2010; 47:388-392. 18. rathod gb, parmar p, rathod s, parikh a. hazards of free radicals in various aspects of health–a review. j forensic toxicol pharmacol. 2014; 3(2):1-7. 19. yasmeen t, qureshi gs, perveen s. adverse effects of diclofenac sodium on renal parenchyma of adult albino rats. j. pak. med. assoc. 2007; 62: 42-47. 20. elhalwagy me. subchronic impact of organophosphorus insecticide triazophos on liver, kidneys and thyroid of albino rats. int. j. adv. res. biol. sci. 2016; 3(1):199-208. 21. raj j, rajvanshi ac, dogra td, raina a. effect of acute exposure of triazophos on oxidative stress and histopathological alterations in liver, kidney and brain of wistar rats. ind. j. exp. biol. 2014, 814-819. 22. ghaffar a, ashraf s, hussain r, hussain t, shafique m, noreen s, et al. clinico-hematological disparities induced by triazophos (organophosphate) in japanese quail. pak. vet. j. 2014; 34:257-9. 23. mohineesh, r.j., rajvanshi, a.c., dogra, t.d. and raina, a. effect of acute exposure of triazophos on oxidative stress and histopathological alterations in liver, kidney and brain of wistar rats. indian j. exp. biol., 2014; 52(8):814-819. 24. rahman sa, sattar da. effect of different concentration of super cyren pesticide on some physiological and histological traits of mice after different periods of oral administration. iraqi j. sci. 2018; 58(4c):2291-300. 32 proximal tubular injury due to pesticides residuesjiimc 20 vol. 1 , no.20 5 1 107 editorial an updated overview on poly cystic ovarian syndrome saadia sultana correspondence: prof.dr saadia sultana professor, of obstetrics & gynaecology islamic international medical college riphah international university, islamabad e-mail: saadia.sultana@riphah.edu.pk received: august 12, 2018; accepted: september 10, 2018 background poly cystic ovarian syndrome (pcos) – stein leventhal syndrome is one of the most common metabolic/endocrine system disorders in women of reproductive age. females having pcos present with a constellation of presentations associated with the androgen excess along with menstrual dysfunction that significantly influences their quality of life. they are at augmented risk of various morbidities, including insulin resistance (leading to type-2 diabetes), obesity, cardiovascular disease (cvd), infertility, cancer, and psychological disorders. stein and leventhal described it, in 1935, as a disorder in which aapproximately 10 cysts of diameter from 2 and 9 mm appear in one or both ovaries with/without increase in ovarian volume 1 exceeding 10 ml . as stated, it was considered as a disorder of women of reproductive age; however, recent evidences suggest it to be a lifelong syndrome, manifesting since prenatal age. actually, rendering to the rotterdam criteria, the prevalence of pcos in youth varies between a minimum of 3% 2 and a maximum of 26%. however, its prevalence in 3 children is still unknown. pcos costs significantly huge economic burden. around five billion dollars are annually spent in america for screening and treatment of the disease and its complications e.g. infertility, hirsutism, diabetes mellitus etc. women with pcos are two times more likely to be admitted 4 inpatient as compared to normal females. hence, early and correct diagnosis is essential not only for the prevention of future comorbidities but also to diminish financial burden on the patient and society. pathophysiology numerous hypotheses developed to explain the pathophysiology of the disease. insulin resistance might be contributing to hyperandrogenemia 5 resulting in pcos. the best theory about the pathophysiology of pcos explains it as a multidimensional condition involving deviant insulin s i g n a l l i n g , w i l d o v a r i a n s t e r o i d o g e n e s i s , unwarranted oxidative stress secondary to mitochondrial dysfunction, and environmental/ genetic factors. oxidative stress can induce insulin resistance and can cause hyperandrogenism. role of genetics in the aetiology of pcos is supported by familial aggregation of the disease and identification 6 of genes on pcos-suspect loci. furthermore, a polymorphic fibrillin-3 gene associated with pcos, has been identified in some families carrying the 7 disease. intrinsic imperfection in theca cells can somewhat elucidate hyperandrogenemia in pcos patients. this dysregulation disturbs granulosa cells which yield about three to four times higher levels of anti-mullerian hormone in women with pcos in contrast to healthy controls. clinical presentation and diagnosis: in adults, for the diagnosis of pcos one can follow one of the three different guidelines as described in the following figure. department of obstetrics & gynaecology islamic international medical college riphah international university, islamabad 8 fig 1: guidelines for the diagnosis of pcos. although conditions such as obesity and insulin resistance are considered central to pcos, none is 9 included in the guidelines. each of the guidelines needs ruling out of any pathological situation that might describe the menstrual irregularity or hyperandrogenism. additionally, diagnosis in 108 jiimc 2018 vol. 13, no.3 10 adolescent girls is highly arguable. the clinical presentation of pcos varies with age, young women u s u a l l y c o m p l a i n i n g o f p syc h o l o g i c a l a n d reproductive problems whereas older ones complaining of various metabolic symptoms. a detailed history, physical and systemic examination, and investigations should be conducted for appropriate diagnosis. discontinuation of any hormonal medicines around a month prior to lab testing, along with planning of labs closer to the luteal phase of cycle are recommended for more precise results. additionally, testing should include measurement of body mass index (bmi), lipid profile, and blood glucose levels. screening for thyroid status by assessment of thyroid-stimulating hormone levels is important as these are a common cause of menstrual irregularity. these are some key features: · hyperandrogenism present clinically with acne, hirsutism, alopecia, acanthosis nigricans etc. and on investigating high levels of testosterone and androstenedione are found. · menstrual irregularity presents as amenorrhea or oligomenorrhoea. investigation shows high levels of luteinizing hormone. · polycystic ovaries on ultrasound shows twelve or more small follicles in one or both ovaries and follicle size is between 2-9 mm with an ovarian volume of 10 ml or more. accompanying indisposition insulin resistance: nowadays, insulin resistance is thought to be the core pathogenic factor for amplified metabolic disturbances in patients with pcos. it explains menstrual irregularity, hyperandrogenism, and other m e ta b o l i c m a n i fe s ta t i o n s o f t h e d i s e a s e . hyperinsulinemia is present in 85% of women with pcos. increased insulin levels, along with raised luteinizing hormone, trigger the arrest of follicular growth resulting in anovulation. hyperinsulinemia also disturbs the pulsatility of gonadotropinreleasing hormone (gnrh), decreases the sex hormone-binding globulin (shbg) and stimulates o v a r i a n a n d r o g e n p r o d u c t i o n . l i f e s t y l e modifications and insulin-sensitizing drugs improve hyperandrogenism in women with pcos. when insulin-sensitizing hormone, leptin is used, it decreases androgen levels and helps in regularizing menstruation in affected women. six months of lifestyle modifications significantly reduced 12 anovulation in affected obese women. this is one of the critical aspect in the treatment of women with pcos, which results in the contemplation of insulinsensitizing agents as critical part of the management of the disease. these agents include metformin, thiazolidinedione and myo-inositol supplements. type-2 diabetes mellitus: pcos deliberates a significantly increased risk for type-2 diabetes mellitus and gestational diabetes. around 1 in 5 women with pcos will develop type-2 diabetes making glucose intolerance a common 13 abnormality in this disease. obesity: an established risk factor for pcos is childhood obesity. obesity is one of the most important features of pcos. its prevalence in patients with pcos varies from 60 to 75%. alternatively, women with pcos are at a higher risk of developing obesity. many studies reveal that females with pcos have increased subcutaneous and visceral body fat distribution because of increased androgen 14 production. pcos patients have an atherogenic lipid profile. whether pcos leads to obesity or 15 whether obesity leads to pcos is still debatable. cardiovascular dysfunction: many studies established a burden of complex indicators of atherosclerosis (arterial stiffness, coronary artery calcification and endothelial d y s f u n c t i o n ) w i t h r e l a t i v e l y e a r l y o n s e t cardiovascular dysfunction (cvd) in patients with pcos. in 2010, the pcos society provided a consensus statement about increased risk of cvd in women with pcos and developed a guideline for prevention of such complication. uncertainty still remains concerning the increased cardiovascular 16 morbidity and mortality in these patients. infertility and complications in pregnancy: pcos is associated with reduced fertility because of associated gynaecologic and endocrine abnormalities that influence ovarian function and quality. a study in 2015 concluded that infertility is ten times more common in women with pcos in contrast to healthy controls. some studies suggested that women with pcos who conceive after treatment usually poly cystic ovarian syndrome suffer from complications of pregnancy e.g. pregnancy induced hypertension, preeclampsia and gestational diabetes to a greater extent as compared to matched controls. others suggest greater risk of miscarriage in women with pcos. women with pcos are at a 2.5 times higher risk of giving birth to growth restricted babies in 17 comparison to controls. cancer: pcos women have a three times increased risk of developing endometrial cancer that is usually well differentiated and with good prognosis. this is explained due to the presence of many risk factors in these females which are associated with the development of endometrial cancer such as, insulin resistance, type ii diabetes mellitus, obesity, and anovulation. anovulation causes unopposed estrogen exposure to the uterine endometrium. it can subsequently trig ger the endometrial hyperplasia and ultimately leading to endometrial 18 cancer. psychological well being: associated symptoms of pcos e.g. obesity, hirsutism, acne and irregular menstrual cycles are major culprits to the psychological stress experienced by the patient due to the her body image and challenging of her female identity. (women with pcos are more prone to anxiety, depression, recreational drug use, abnormal eating, and psychosexual dysfunctions in contrast to healthy controls. management treatment of symptomatology is usually the target for the management of pcos. the patients usually present with infertility, anovulation, acne, or hirsutism being the most common complaints. management usually requires the involvement of an m u l t i d i s c i p l i n a r y t e a m t h a t c a n i n c l u d e gynaecologist, family practitioner, dermatologist, paediatrician, a psychiatrist and endocrinologist. lifestyle modifications: guidelines recommend calorie-restricted diet and exercise as a central part in the management of pcos specially the women with obesity. lifestyle modifications and cost-effective treatment both are 19 essential to management of pcos. medical treatment: if symptomatology do not resolve by simple lifestyle changes, medical treatment must be added for the management of pcos patients. metformin (glucophage) metformin, a biguanide antidiabetic drug, acts by hindering hepatic glucose production and increasing the peripheral insulin sensitivity. metformin treatment of pcos specially of obese women with impaired glucose tolerance proved helpful in improving insulin sensitivity, increasing glucose tolerance, and in decreasing elevated androgen levels. it can also be used in combination with clomiphene citrate to treat subfertility. pioglitazone: the use of pioglitazone was also studied in pcos patients and data revealed that it results in a decrease in insulin resistance by decreasing fasting 20 serum insulin levels. oral contraceptive pills (ocp): most commonly used medications for the long-term treatment of women with pcos are the ocps. the task force and the endocrine society and the pcos consensus group have also recommended ocps as first-line treatment for hyperandrogenism and menstrual cycle irregularities in patients with pcos. ocp suppress the hypothalamo-pituitary-ovarian axis, which in turn decreases lh secretions, increases sex hormone binding globulins and consequently decreases free testosterone levels. this results in h y p e r a n d r o g e n i s m r e l a t e d s y m p t o m s e . g . improving acne and hirsutism, revises menstrual cycle abnormalities, and provides effective 21 contraception. a minimum of 6 months of treatment is usually required for satisfactory results in hirsutism and acne. clomiphene citrate is considered as first line treatment of infertility (anovulatory). laparoscopic ovarian drilling, exogenous gonadotropins and in-vitro fertilization are second line of management once clomiphene 22 citrate with or without metformin fails. d-chiroinositol (dci) and myo-inositol (myo):novel treatments of pcos and are attaining more recognition due to minimal side effects. these are dchiro-inositol (dci) and myo-inositol (myo); two isomers of inositol insulin-sensitizing molecule. when combined with folic acid, myo decreased hyperstimulation syndrome in pcos females undergoing treatment. another study showed significant improvement in symptoms in terms of jiimc 2018 vol. 13, no.3 poly cystic ovarian syndrome 109 better lipid profile, more menstrual cycle regularity, and less acne, after the use of combination of myo23 dci. screening appropriate management of the patient needs not only to treat symptoms but also to foresee and to prevent any morbidity that might develop later in life. these women should be routinely screened for typeii dm. studies have shown that screening with fasting blood glucose levels alone under-diagnose type-ii dm in pcos patients, missing up to 50% of diabetics. guidelines recommend screening such women using an oral glucose tolerance test. this screening to be done every 3–5 years in women without risk factors for type ii-dm and annually in women with risk factors. patients with pcos should be screened routinely for cvd risk factors. guidelines recommend body weight and bmi measurements, assessment of smoking, monitoring of blood pressure, and a complete lipid profile. screening of pcos patients not only for anxiety and depression but also for eating disorders, negative body image, and psychosexual dysfunctions etc. is also recommended. while concluding, it is important to emphasize that if the physicians want to provide the finest care for these patients, future research work has to find the missing blocks in our increasing information about this syndrome/disease. references 1. stein if, leventhal ml. amenorrhea associated with bilateral polycystic ovaries. am j obstet gynecol 1935 ; 29: 181–91. 2. hart r, doherty da, mori t, huang rc, norman rj, franks s, et al. extent of metabolic risk in adolescent girls with features of polycystic ovary syndrome. fertil steril 2011;95: 2347–53. 3. kamangar f, okhovat jp, schmidt t, beshay a, pasch l, cedars mi, et al. polycystic ovary syndrome: special diagnostic and therapeutic considerations for children. pediatr dermatol 2015; 32: 571–8. 4. hart r, doherty da. the potential implications of a pcos diagnosis on a woman's long-term health using data linkage. j clin endocrinol metab 2015; 100: 911–19. 5. de zegher f, lopez-bermejo a, ibáñez l. adipose tissue expandability and the early origins of pcos. trends endocrinol metab 2009;20: 418–23. 6. chen zj, zhao h, he l, shi y, qin y, shi y, et al. genome-wide association study identifies susceptibility loci for polycystic ovary syndrome on chromosome 2p16.3, 2p21 and 9q33.3. nat genet 2011; 43: 55–9. 7. segars jh, decherney ah. is there a genetic basis for polycystic ovary syndrome? j. clin endocrinol metab 2010; 95: 2058–60. 8. rotterdam ea. revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (pcos). hum reprod 2004;19: 41–7. 9. witchel sf, oberfield s, rosenfield rl, codner e, bonny a, ibáñez l, et al. the diagnosis of polycystic ovary syndrome during adolescence. horm res paediatr 2015. 10. siklar z, berberoglu m, çamtosun e, kocaay p. diagnostic characteristics and metabolic risk factors of cases with polycystic ovary syndrome during adolescence. j pediatr adolesc gynecol 2015; 28: 78–83. 11. teede hj, misso ml, deeks aa, moran lj, stuckey bg, wong jl, et al. assessment and management of polycystic ovary syndrome: summary of an evidence-based guideline. med j aust 2011;195: s65–s112. 12. lungu ao, zadeh es, goodling a, cochran e, gorden p. insulin resistance is a sufficient basis for hyperandrogenism in lipodystrophic women with polycystic ovarian syndrome. j clin endocrinol metab 2012; 97: 563–7. 13. lerchbaum e, schwetz v, giuliani a, obermayer-pietsch b. assessment of glucose metabolism in polycystic ovary syndrome: hba1c or fasting glucose compared with the oral glucose tolerance test as a screening method. hum reprod 2013; 28: 2537–44. 14. borruel s, fernández-durán e, alpañés m, martí d, álvarezblasco , luque-ramírez m, et al. global adiposity and thickness of intraperitoneal and mesenteric adipose tissue depots are increased in women with polycystic ovary syndrome (pcos). j clin endocrinol metab 2013; 8: 1254–63. 15. wild ra, carmina e, diamanti-kandarakis e, dokras a, escobar-morreale hf, futterweit w, et al. assessment of cardiovascular risk and prevention of cardiovascular disease in women with the polycystic ovary syndrome: a consensus statement by the androgen excess and polycystic ovary syndrome (ae-pcos) society. j clin endocrinol metab 2010; 95: 2038–49. 16. studen kb, pfeifer m. cardiometabolic risk in polycystic ovary syndrome. endocr connect 2018; 7(7): 238–51. 17. katulski k, czyzyk a, podfigurna-stopa a, genazzani ar, meczekalski b. pregnancy complications in polycystic ovary jiimc 2018 vol. 13, no.3 poly cystic ovarian syndrome 110 syndrome patients. gynecol endocrinol 2015; 31: 87–91. 18. aune d, sen a, vatten l j.hypertension and the risk of endometrial cancer: a systematic review and meta-analysis of case-control and cohort studies. sci rep 2017; 7: 44808. 19. misso m, boyle j, norman r, teede h. development of evidenced-based guidelines for pcos and implications for community health. semin reprod med 2014;32: 230–40. 20. stabile g, borrielli i, artenisio ac, bruno lm, benvenga s, giunta l, et al. effects of the insulin sensitizer pioglitazone on menstrual irregularity, insulin resistance and hyperandrogenism in young women with polycystic ovary syndrome. j pediatr adolesc gynecol 2014; 27:177–82. 21. yildiz bo. approach to the patient: contraception in women with polycystic ovary syndrome. j clin endocrinol metab 2015; 100: 794–802. 22. spritzer pm, motta ab, sir-petermann t, diamantikandarakis e. novel strategies in the management of polycystic ovary syndrome. minerva endocrinol 2015; 40: 195–212. 23. formuso c, stracquadanio m, ciotta l. myo-inositol vs. dchiro inositol in pcos treatment. minerva ginecol 2015;67: 321–5. jiimc 2018 vol. 13, no.3 poly cystic ovarian syndrome 111 jiimc march 2016.cdr original article abstract objective: to determine outcome and postoperative complications of trans-sternal thymectomy for myasthenia gravis. study design: experimental, prospective. place and duration of study: the study was conducted at department of surgery, pakistan institute of medical sciences (pims), islamabad from june 2009 to june 2012. materials and methods: we included 30 consecutive patients from all age groups either coming to surgical outpatient clinic or referred from neurolgy unit having generalized myasthenia gravis between 12-55 years of age, thymic mass on radiology or poor medical control of disease with no contra indications to surgery. patients unfit for anaesthesia due to any reason or inoperable thymic tumour were excluded. we studied outcome and post-operative complications in all patients after total thymectomy through trans-sternal approach for 24-40 months. all patients were assessed for haemorrhage, transfusion requirement, shock, myasthenia crisis, respiratory infection, wound infection, delayed healing of wound and dehiscence and pulmonary embolism. remission of disease was assessed according to de filippi classification. the data was collected by post graduate trainees on a pre-designed proforma and analysed by spss 10. the descriptive statistics were applied and results were shown in percentage. results: in total 30 patients, mean age was 37±8.6 years. all patients needed at least two units of blood transfusion. we observed pleural damage in 20 patients (66.67%), respiratory infection in 20 (66.67%), myasthenia crisis in 8 (26.7%), minor wound infection in 6 (20%), mortality in 4 patients with th th carcinoma(13.33%). artificial ventilation discontinued within 24 hours in 22, at 7 day in 4 and at 14 days in 4 patients. wound dehiscence occurred in 1(3.33%), cardiac arrest in 1 (3.33%). mean hospital stay was 13.6 (745) days. six patients (20%) were symptom free without drugs and 9 patients (30%) were symptom free with drugs at 2 years. conclusion: trans-sternal total thymectomy provides good results for symptom control in benign thymic conditions. the major complication is haemorrhage needing transfusion. other complications can be managed successfully by conservative treatment. key words: trans sternal thymectomy, myasthenia gravis, thymic tumour. develop involvement of respiratory muscles, 3,4 shoulder and neck without ocular weakness. tr e a t m e n t c o m p r i s e s o f f o u r m e t h o d s : anticholinesterase drugs, immune-suppressive agents, removal of thymus, and immunotherapies, like exchange of plasma and intravenous immuno 5,6 globulin (ivig). blalock et al found the successful 7 outcomes of thymectomy in mg in 1941. since then 8,9 surgery is widely being used as a for such patients. in fact, thymectomy is considered, by neurologists, as a first-line therapy in most patients with thymoma or generalized myasthenia to achievesustained 10,11 improvement or remission. about three fourth of such people have abnormality in thymus; of them, hyperplasia in 85% andthymoma 2 , 1 2 i n 1 5 % . t hy m o m a i s t h e m o st co m m o n 13 mediastinaltumour (25%). median sternotomy is considered safe and effective approach for introduction myasthenia gravis (mg) occure due to formation of antibodies against acetylcholine receptors at myoneuronal junctions and presents with muscle 1 weakness and fatigability. most of patients develop generalized weakness involving bulbar, limb 2 musculature, extensors of neck and diaphragm. antibody to muscle-specific kinase (musk) may be positive in sero-negative mg patients and they outcome and complications of trans-sternal thymectomy for myasthenia gravis 1 2 3 muhammad zafar iqbal qureshi , muhammad imran zahoor , erum fatima correspondence: dr. muhammad imran zahoor associate professor, surgery mohi-ud-din islamic medical college mirpur, azad kashmir e-mail: imranzahoor71@gmail.com 1,2 3 department of surgery/ gynae/obs mohi-ud-din islamic medical college mirpur, azad kashmir funding source: nil ; conflict of interest: nil received: september 03, 2015; accepted: february 24, 2016 trans-sternal thymectomyjiimc 2016 vol. 11, no.1 29 14,15 thymectomy, especially for ectopic locations. data of the efficacy and complications of thymectomy in patients with mg via median sternotomy is limited in pakistan. the authors, in the current study, made an effort to determine the safety of median sternotomy in patients with mg and then outcome of thymectomy. materials and methods this experimental, prospective study was conducted between june 2009 and june 2012 in department of surgery, pakistan institute of medical sciences (pims). we included 30 consecutive patients from all age groups either coming to surgical out patient department or referred from neurolgy unit of pims with generalized myasthenia gravis having the disease for less than 5 years, thymic mass on radiology (mediastinal widening) or poor medical control of disease with no contra indications to surgery usually grade ii b & iii. the patients unfit for anaesthesia due to any reason or inoperable thymictumour were excluded. the data was collected by post graduate trainees on a predesigned proforma. after detailed history, thorough examination and routine investigations, specific i n v e s t i g a t i o n s i n c l u d i n g te n s i l o n t e s t , electromyography (emg), x-ray chest and ct scan of chest to assess anatomical location, thymoma and vascular relationships were carried out. all patients remained in care of a multidisciplinary team including surgeon, neurologist, pulmonologist, respiratory therapist, anaesthetist and intensivist. the patients were stabilized on drugs preoperatively but anticholinesterase drugs were stopped 6-8 hours before surgery. patients taking oral steroids were tapered gradually. plasmapheresis was done 3 days before surgery. blood group, cross match, and ventilator in intensive care unit (icu) were arranged and informed consent taken. the antibiotic prophylaxis consisted of three intravenous doses of 1g of ceftriaxone, at induction, at 12 and 24 hrs post operative period respectively. general anaesthesia without muscle relaxants and median sternotomy approach was used in all patients. the vascular pedicles tied and gland separated by blunt dissection from surrounding structures. total thymectomy was done removing all tissue of thymus and mediastinal fat from the diaphragm and pericardium inferiorly to the thymic extension in neck superiorly upto thyroid and from one phrenic nerve to the other. pleural damage, when occurred, repaired and chest drain placed in right chest wall, across the mediastinum and upto contra-lateral apex connected to under water seal. all surgeries were performed by one experienced surgeon with a dedicated team. in post operative phase, all patients were monitored in icu until their vital signs got stable and anaesthetist declared safe to shift to ward. neurologists reviewed them and anticholinesterase drugs started if any signs of disease were found. we avoided, in all patients, sedatives, narcotics and muscle relaxants. we studied the post operative complications by assessment of haemorrhage, transfusion requirement, shock, myasthenia crisis, respiratory infection, wound infection, delayed healing of wound and dehiscence and pulmonary embolism. on the basis of remission of disease according to de filippipost operative classification, we assessed the 16 outcome. class i: remission complete, without medication class 2: symptom free, less medication class 3: improved, decreased symptoms or medication class 4: no improvement class 5: worsening symptoms remission was defined as no symptom of myasthenia gravis or cessation of medical treatment without reappearance of any symptoms. all patients were followed for 24-40 months (average 27) in surgical opd and advised to consult on appearance of any of the signs and symptoms of myasthenia again. the data was analysed by spss 10. the descriptive statistics were applied and results were shown in percentage. results m e a n a ge o f p at i e nt s wa s 3 7 ± 8 . 6 ye a rs . neuromuscular blocking drugs, atropine and morphine were avoided during anaesthesia and no significant complication of anaesthesia was observed. pleura was damaged in 66% of patients which was managed by chest intubation. cardiac arrest occurred in one patient which was managed by internal cardiac massage and patient revived. myasthenia crisis was observed in 8 patients, which was successfully managed in 4 patients. three trans-sternal thymectomyjiimc 2016 vol. 11, no.1 30 patients died within 2 weeks and one survived for next 6 weeks. all 4 had carcinoma of thymus (osserman's group iii). respiratory infection was noted by symptoms of cough with sputum and irritation in throat in 6 (20%). all were successfully managed by medical treatment and physiotherapy. in post operative period, nasal endotracheal tube was kept for ventilation in icu for 24 hours. in 22 patients, vital capacity was found to be 1.5-2 litres w i t h i n 2 4 h o u rs a n d a r t i f i c i a l ve nt i l at i o n discontinued and patient ambulated. endotracheal tube kept in place for further 3-4 days as a th precaution. four patients were extubated at 7 day while 4 patients needed re-intubation and ventilator support for next 14 days. chest radiograph taken to exclude hemo/pneumothorax. skin stitches th th removed on 7 -10 post operative day and patient discharged home. minor wound infection was observed in 6 cases (20%) and was managed successfully by local antiseptics. one patient on steroids for long period developed wound dehiscence, which was managed by pectoral myoplasty by a plastic surgeon. mean hospital stay was 13.6 (7-45) days. further results are in table i. discussion thymectomy is one of the most effective treatment modalities to stop progression of symptoms in mg. the observations in different parts of the world, of the disease and the outcome of procedures are not the same. in the study of remes-troche jm, mean age was 10 32.10 +/14.42 years. niazhussain, found mean age at presentation to be 35.2 ± 14.5 years. out of 22 patients, having persistent generalized or ocular myasthenia gravis, 16 (72.7%) were females and 6 (27.2%) males. ali soleimani, in a study of 110 patients in iran, noticed mean age at thymectomy to 2 be 30.3 ± 12.8 years. in our study, the mean age of patients presented for thymectomy was 37±8.6 years. the younger patients (<55 years) having mg for less than 5 years are most benefited by surgery. trans sternal approach is considered standard and 17 safe by many surgeons. in the current study, only median sternotomy was used to gain access to thymus and remained a safe technique. kas et al found similar results. pneumothorax was the most common minor complication. very few patients d e v e l o p e d a n y m a j o r o r i n t r a o p e r a i t v e 18 complication. zielinski et al reported no difference in morbidity after less invasive procedures like m a n u b r i o t o m y a s c o m p a r e d t o m e d i a n 19 sternotomy. xiang-yang c reviewed 243 patients with mg who underwent thymectomy. forty-four patients (18%) experienced postoperative myasthenic crisis within thirty days post thymectomy. myasthenic crisis,in postoperative patients, was significantly higher in those having history of myastheniccrisis (p=0.016), thymoma (p <0.0001), and major postoperative complications (p <0.0001) than in patients without 20 these three conditions. ali soleimani, in a study of 110 patients in iran (76 cases done via trans-sternal approach and 34 done via trans-cervical route), showed that 32% developed myesthenia crisis. lack of drug compliance and pneumonia causes were 2 main triggering factors for myasthenic crises. remes-troche jm found myasthenic (9.3%) and cholinergic (2.7%) crises, the most serious 10 complications. in our study, histopathology reports showed 16 cases of thymoma. half of them (8 cases) had experienced crisis, which makes 26.7 % of total patients and 40% of those with previous history of table i: post opera�ve complica�ons (n= 30) table ii: symptoms control of myasthenia a�er thymectomy (n= 30) trans-sternal thymectomyjiimc 2016 vol. 11, no.1 31 crisis. major postoperative complications related to thymectomy in the literature include pneumonia, pneumothorax, hydrothorax and ards. we found that the frequency of postoperative myasthenic crisis increases when the patients had severe postoperative complications. multivariate logistic regression analysis in china revealed that major postoperative complications related to thymectomy 20 are a predictor of postoperative crisis. in the work of remes-troche j met al in mexico, no 10 surgery-related deaths occurred in 75 patients . marulli et al demonstrated the safety and efficacy of this procedure, after a review of 100 consecutive patients who underwent left-sided robotic thymectomy for mg. no deaths or intra-operative 21 complications occurred. in our study, 3 patients died within 2 weeks and one survived for next 6 weeks. all 4 had carcinoma of thymus (osserman's group iii). spath g et al operated upon 75 patients. impaired wound healing was noticed in 6.7% of the patients, with complete sternal instability in one patient, while 22 5.3% developed pneumonia. ali soleimani showed that 20 of 110 (18%) developed attacks of respiratory 2 failure. niaz hussain, out of 22 patients studied in karachi, mentioned the most common major wound complication was sternal bleeding, encountered in 2 (9%) patients. this was followed by 1 case of disruption of the wound. pneumothorax was the most common minor complication observed in 7 (31.8%), followed by wound infection in 4 (18%) patients, and 2(9%) each of haemothorax, and 23 seroma. we found wound infection in 6 (20%), and wound dehiscence in 1 patient (3.4%). respiratory infection in 20(66%). the wound complications are common in patients on long term steroids and pneumo / hemothorax is a common complication of surgery on thymus secondary to pleural damage. spath g et al documented nerve paresis. phrenic nerve in 2.7% and recurrent laryngeal nerve in 1.3%, 22 noticed only in thymoma patients. niazhussain reported that a total of 2 (9%) patients out of 22 had intra-operative complications including phrenic nerve and innominate vein injury. no long term 23 morbidity occurred. in the current study, no nerve damage was noticed. probably nerve damage is rare and associated with tumours. patients often experience some transient worsening of symptoms early in the postoperative period. improvement usually is delayed for months or years. we followed the patients for next 24-40 months (average 27 months). scott and dtterbeck reported that 78% patients became better by one or more modified osserman class and 69% had complete 24 remission in osserman class i, ii and iii. takanami i found thymectomy to induce remission, more frequently in young patients with a short duration of disease, hyperplastic thymus, more severe 25 symptoms, and a high antibody titer. we found remission of symptoms within 3 months. 20% became symptom free without drugs and 30% became symptom free with medication. symptoms of further 30% became mild and only 1 patient (3.3%) remained unresponsive. all patients having complete remission were 45 yrs old or less. in a study by nieto et al, the rate of remission in the presence of thymic hyperplasia was 42% compared to 18% in 26 patients with thymoma. shrager et al. reported an actual 50% complete remission with kaplan-meier estimate of 5 years of total remission of 57% in patients with ocular mg. after thymectomy there 27 was no disease progression. masaoka reported a 46% remission rate at 5 years, 67% at 15 years and 90% overall palliation for the non thymoma group. they noted 32% remission rate and 82 % palliation rate for thymomas. the drug free remission was achieved primarily in early osserman 28 classes. according to nason and maddaus, thymectomy for thymomas results in improvement or resolution of symptoms only in 25% of mg patients. but patients with no thymoma, mg symptoms improve in 90% and 50 % have complete 29 resmission. marulli et al demonstrated, after 5-year clinical follow-up of 100 consecutive patients who underwent left-sided robotic thymectomy, that 28.5% of patients had complete stable remission, and 87.5% showed overall improvement. remission was significantly more likely in patients with preoperative class i to ii mg according to standards 21 of myasthenia gravis foundation of america. conclusion trans-sternal total thymectomy provides good results for symptom control in benign thymic conditions. the major complication is haemorrhage needing transfusion. other complications can be managed successfully by conservative treatment. trans-sternal thymectomyjiimc 2016 vol. 11, no.1 32 references 1. felix g. fernandez fg, battafarano rj. general thoracic surgery. in: klingensmith me, chen le, glasgow sc, editors.washington manual of surgery. 5th ed.st. louis, missouri :lippincott williams & wilkins; 2008. 2. soleimani a, moayyeri a, akhondzad eh s, sadatsafavi m, shalmani ht, soltanzadeh a. frequency of myasthenic crisis in relation to thymectomy in generalized myasthenia gravis: a 17-year experience bmc neurology 2004, 4: 12. 3. pasnoor m, wolfe gi, nations s. clinical findings in musk-antibody positive myasthenia gravis: a u.s. experience. muscle nerve. 2010; 41: 370-4. 4. martignago s, fanin m, albertini e, pegoraro e, angelini c. muscle histopathology in myasthenia gravis with antibodies against musk and achr. neuropatholapplneurobiol. 2009; 35: 103-10. 5. http://emedicine.medscape.com/ [homepage on the internet]. yale university school of medicine ; 2012 [updated may 2014; cited 30 nov 2014]. available from; http://emedicine.medscape.com/article/ 1171206-treatment. 6. vanderpluym j, vajsar j, jacob fd, mah jk, grenier d, kolski h. clinical characteristics of pediatric myasthenia: a surveillance study. pediatrics. 9, 2013. 7. blalock a, harvey am, ford rf, lilienthal jl jr. the treatment of myasthenia gravis by removal of the thymus gland. j am med assoc 1941; 117: 1529-33. 8. waitande ss, thankachen rj, philip ma, shukla v, korula rj. surgicaloutcome of thymectomy for myasthenia gravis. indian j thoraccardiovasc surg 2007; 23: 171-5. 9. baraka a, anesthesia and critical care of thymectomy for myasthenia gravis. chest surg clin n am 2001; 11: 337-61. 10. remestroche jm, tellez zenteno jf, estanol b,gardunoespinoza j, garcia ramos g. thymectomy in myasthenia gravis: response, complications, and associated conditions. arch med res. 2002; 33: 54551. 11. www.bmj.com [homepage on the internet]. british medical journal; 2010 [updated july 2012; cited 6 d e c e m b e r 2 0 1 4 ] . a v a i l a b l e f r o m ; thorax.bmj.com/content/15/3/262.full.pdf . 12. castleman b: the pathology of the thymus gland in myasthenia gravis. ann n y acadsci 1966; 135:496505. 13. hunt i, tan c. thorax. in: williams ns. bulstrode cjk, o’connell pr, editors. bailey and love’s short practice of surgery. 26th ed. london: crc press; 2013. 14. lee cy, lee jg, yang wi, haam sj, chung ky, park ik. transsternal maximal thymectomy is effective for extirpation of cervical ectopic thymic tissue in the treatment of myasthenia gravis. yonsei med j 2008; 49: 987-92. 15. khan a, bilal a, baseer a. thymectomy for myasthenia gravis: peshawar experience of 27 cases in five years. j post grad med inst 2007; 21: 238-41. 16. de camp mm, de hoyos a, transternal, transcervical and thoracoscopicthymectomy. in: fischer je, jones db, pamposelli fb, editors. fischer’s mastery of surgery. 6th edition. philadelphia:lippincott williams &wilkins ; 2012. 17. kondov g, trajkovska t, ljapcev r, gogova l, kondova i. thymectomy in myasthenia gravis: response and complications. turkish respirat j 2005; 6: 144-8. 18. kas j, kiss d, simon v, svastics e, major l, szobor a. decade-long experience with surgical therapy of myasthenia gravis: early complications of 324 transsternalthymectomies. ann thorac surg 2001; 72: 1691-7. 19. zielinski m, kuzdza j, szlubowski a, soja j. comparison of late results of basic trans-sternal and extended trans-sternal thymectomies in the treatment of myasthenia gravis. ann thorac surg 2004; 78: 253-8. 20. xiang-yang c, zhi-qiang x, ru-wen w, qun-you t. predictors of postoperative myasthenic crisis in patients with myasthenia gravis after thymectomy. chin med j 2011; 124: 1246-50. 21. marulli g, schiavon m, perissinotto e. surgical and neurologic outcomes after robotic thymectomy in 100 consecutive patients with myasthenia gravis. j thoraccardiovasc surg. 2013; 145: 730-5. 22. spath g, brinkmann a, huth c, wietholter h. c o m p l i c a t i o n s a n d e f f i c a c y o f transsternalthymectomy in myasthenia gravis. thorac cardiovasc surg. 1987; 35: 283-9. 23. hussain n, ahmed sw, ahmed t, hafeez ab, baloch r, ali s. experience of thymectomy by median sternotomy in patients with myasthenia gravis. j pak med assoc.2010; 60: 368-70. 24. goldstein sd, yang sc. assessment of robotic thymectomy using the myasthenia gravis foundation of america guidelines. ann thorac surg. 2010; 89: 1080-5. 25. takanami i, abiko t, koizumi s. therapeutic outcomes in thymectomied patients with myasthenia gravis. ann thoraccardiovasc surg. 2009; 15: 373-7. 26. nieto ip, robledo jp, pajuelo mc, montes ja, giron jg, alonso jg, et al: prognostic factors for myasthenia gravis treated by thymectomy: review of 61 cases. ann thorac surg. 1999; 67: 156871. 27. shrager jb, deeb me, mick r, brinster cj, childers he, marshall mb, et al. transcervicalthymectomy for myasthenia gravis achieves results comparable to trans-sternal thymectomyjiimc 2016 vol. 11, no.1 33 thymectomy by sternotomy. ann thorac surg 2002; 74: 320-6. 28. masaoka a, yamakawa y, niwa h, fukai i, kondo s, kobayashi m, et. al:extended thymectomy for myasthenia gravis patients: a 20-year review. ann thorac surg 1996; 62: 853-9. 29. nason ks, maddaus ma, luketich jd. chest wall, lung, mediastinum and pleura. in: brunicardi fc, andersen dk, billiar tr, editors. schwartz’s principles of surgery. 9thed. new york: mcgrawhill ; 2010. trans-sternal thymectomyjiimc 2016 vol. 11, no.1 34 original�article abstract objective: to compare effect of stretching combined with muscle energy technique on disability and pain in patients with trigger points in cervical region. study design: comparative clinical trial. place and duration of study: intervention and assessment was done in physical therapy department of shalamar hospital, lahore, pakistan from 13 september 2018 to 29 march 2019. materials and methods: it was a single blinded parallel arm study. seventy-two patients recruited in the study by using probability simple random sampling. patients with non-specific neck pain, trigger points in trapezius muscle, aged between 18 to 45 years were included in the study. patients with history of road traffic accident, torticollis or complaint of spinal cord compression were excluded. patients were divided in two equal groups by random number table. group a received combination of stretching and muscle energy technique while group b received only stretching. intervention repeated for 3 to 5 days, number of sessions was 3 days a week for 4 weeks. assessment was taken baseline and after 4 weeks of intervention. data was entered and analysed through spss version 21. results: the demographics of result showed that 54.2% male and 45.8% female participated in the study with 52.8% sedentary and 47.2% were active subjects. the results of the study showed statistically significant improvement on neck disability and pain (p value<0.05). conclusion: it is concluded that muscle energy technique with stretching is more effective for patients with trigger points in cervical region. key words: muscle energy technique,neck disability index, stretching, trigger point. 7 idiopathic, and nature of pain is non-specific. . most of the neck pain is also linked with the different complications such as headache, back pain, 6 arthralgia, and depression. in regard to direct or indirect costs, neck pain is usually considered i n s e n s i t i ve to d i ffe re nt i nte r ve nt i o n s a n d 8 costly. chronic neck pain also causes usual absentees 9 of office worker due to severity of pain. myofascial pain syndrome is non-articular, nonspecific musculoskeletal pain, associated with regional pain and muscle tenderness characterized by trigger points, also known as trigger. trigger points are associated with sensory, motor, and autonomic 10 findings. trigger points are assessed on physical examination and by two palpation methods one is pincer grip method other is flat palpation 11 method. most common clinical sign and symptoms of mps having trigger points are aches and pain, muscle tightness or spasm, restricted rom, and generalized muscle fatigue. patients show local introduction from last decade, neck pain is the fourth leading cause of disability according to the global burden of 1 disease. neck pain is considered second most 2 common cause of pain. almost half of the population 3 suffers from neck painat least once in a life. as per evidence, the prevalence of neck pain varies from 15 3-4 to 50% annually. neck pain is more common in females as compared to males and middle-aged 5-6 population is commonly effected. more often, it is comparison of stretching alone versus combination of muscle energy technique and stretching on pain and disability among patients with trigger points in cervical region 1 2 3 4, 5 muhammad tariq shafi , shahzad ahmad , shoaib waqas , muhammad faheem afzal ubaid ullah akbar , shahzada 6 iftikhar hussain correspondence: dr. muhammad tariq shafi assistant professor department of physical therapy lahore medical and dental college, lahore e-mail:muhammad.tariq@lmdc.edu.pk 1,3,4,5,6 department of physical therapy lahore medical and dental college, lahore 2 department of physical therapy national hospital and medical center, lahore received: may 17, 2021; revised: september 15, 2022 accepted: september 21, 2022 stretching alone versus muscle energy techniquejiimc 2022 vol. 17, no.3 187 twitch response and positive jump sign. there exist wide variety in pain perception and intensity of pain ranges from mild ache to an excruciating burning 12 pain, or both. patients also show sensory, motor, 13 and autonomic symptoms. patient education is very important component in treatment of myofascial pain syndrome. patient is instructed about the home exercise program about the stretching strengthening and relaxation exercise, 14 and postural awareness is also improved. by improving diet and minimizing the modifiable risk factors can reduces the chances of trigger point development and can assist in synchronize the effect 15 of treatment. .in cervical radiculopathy, for treating the pain and inflammation the first line of medication usually used are non-steroidal anti16 inflammatory drugs (nsaids). in the non-surgical intervention of cervical radiculopathy electrotherapy may be used as an a s s o c i a t e d t r e a t m e n t , w i t h n u m e r o u s 1 7 a d va n t a g e s . a b o u t c e r v i c a l ra d i c u l o p a t hy treatment with massage, it is shown that very less information is found in exhaustive literature search 18 specifically. muscle energy technique is new form of manipulative diagnosis and intervention in which activation of muscle done through command in 19 specific direction and against resistance. as per evidence, neck pain leads to different pathologies and stretching helps in the management of neck pain. there is very little evidence that compare two interventions on trigger points release and adjustment of pain. the purpose of this study was to compare effect of stretching combined with muscle energy technique on disability and pain in patients with trigger points in cervical region. materials and methods the comparative clinical trial conducted by using single blinded. a sample of 72 patients recruited in the study that is calculated by using open epi online calculator with 95% confidence interval and 5% margin of error. the data was collected at shalamar hospital, lahore, pakistan from 13 september 2018 to 29 march 2019.probability simple random sampling technique was used to recruit participants in the study. study was completed in six months after the approval of synopsis from the institutional review board of lahore medical and dental college, lahore. (lmdc/lcpt/erb/pgs/0891) diagnosed patients with trigger points on cervical region were included in the study. the diagnostic criteria for the trigger points were physical examination and positive jump sign. patients had trigger points in trapezius muscles with complaint of non-specific neck pain, both gender with age 18 to 45 years were included in the study. patients with history of road traffic accident, complaint of torticollis, spinal cord compression, articular or any systematic disorder were excluded from the study. the recruited patients (n=72) were divided equally in to two groups by using simple random number table. group a patients received stretching alone that comprised of 5 repetitions. the duration of single bout of stretch was 30 seconds. group b received muscle energy technique using post isometric relaxation, followed by passive stretching. duration of stretching was 30 seconds while each maneuver homogenously repeated 5 times per treatment for 3 days in a week up to 4 weeks. permission was sought from the institute and consent was taken from patient in english/urdu according to understanding of patients. patient's interaction with each other avoided so that they do not know the intervention of other group. numeric pain rating scale (nprs) was used to check the pain intensity and neck disability index (ndi) was used to check functional ability. patient's assessment was done on baseline and after fourth week of intervention. both groups received conventional treatments as well that includes ultrasound therapy (ito us-100) for seven minutes in continuous mode, stretching and isometrics. all demographic information and outcome tool data were entered by spss version 21. the demographic information was presented in the form of frequencies and percentages. test of normality applied to check normal distribution of data and independent t-test was used to determine the difference between the groups and quantitative data was presented by mean and standard deviation results the results of the study showed mean age and standard deviation was 36.32±1.46 and 54.2% male and 45.8% female participated in the study. the mean and standard deviation of numeric pain rating scale (nprs) was 6.36±2.344 and 6.28±2.187 in group a and b respectively and 1.53±2.223 and 2.78±2.94 after 4 week of intervention that showed jiimc 2022 vol. 17, no.3 188 stretching alone versus muscle energy technique s i g n i f i ca nt d i ffe re n c e b et we e n g ro u ps ( p value=0.012). the mean and standard deviation of ndi was 18.92±9.915 and 19.86±10.137 in group a and group b at baseline, 3.53±6.036 and 7.56±10.252 after 4 week of intervention that showed significant difference. (p-value=0.001) discussion in this study, pain occurrence due to trigger points was assessed through numeric pain rating scale. in initial assessment, mean and standard deviation of pain was 6.36±2.344 and 6.28±2.187in group a and b respectively. mean and standard deviation of group a was 1.53±2.223 and 2.78±2.948 in group b after 4 week of intervention that showed statistically significant p value=0.012. a study conducted in 2010 by athanasios trampas that showed significant effect 20 of stretching on trigger points. . another study conducted by kostopoulos that also compare the effects of passive stretching alone with passive stretching and intermittent compression and concluded that there is significant effect occur in 21 both groups. . a study conducted in india by the chitra kataria in 2012 that compare the effects of muscle energy technique with stretching along with conventional treatment and concluded that both groups showed statistically significant in reduction of 22 pain with mechanical neck pain. .a study conducted by gulnazsadria to compare the effect of muscle energy technique with the active release technique and concluded that both the groups show significant 23 improvement in range of motion of neck. a clinical trial conducted on patients to see the effects of muscle energy technique alone and in combination with the stretching technique in reducing the symptoms occur due to trigger points. the results of the study showed that combination of muscle energy technique and stretching is considered effective in 24 reduction of pain. the result of study showed significant difference in disability of neck in group comparison while previous st u d y a l s o s h o we d stat i st i ca l l y s i g n i f i ca nt improvement in neck disability index in patients with 24 non-specific neck pain. another study showed conducted by phadke a et al that concluded that muscle energy technique is more effective than stretching on functional disability in patients 25 suffering from neck pain. a systematic review recently published that also support that muscle energy technique play more effective role with conventional physical therapy treatment in patients 26 with neck pain. current study also reveals some other factors related to trigger point.30-40 year's age group was most effected by trigger points. one important factor was table i : shows demographics information of the participants (n=72) table ii : shows mean± standard deviation of numeric pain rating scale and neck disability index in both groups. (n=72) jiimc 2022 vol. 17, no.3 189 stretching alone versus muscle energy technique that 38.9% patient had computer usage history. the benefit of the combined approach over stretching may be due to muscle energy technique in combination facilitating causes reduction of tone in the involved tissues. the reduction in involved tissue tone results in change of neural command and increase circulation of the involved tissue. the change in the local environment of tissue leads to reboot neural command and results in reversing normal length, increased circulation, reduction in 25 pain and improved neck mobility and functioning. conclusion in patients with trigger point neck pain, combined approach using both muscle energy technique and stretching for the treatment of trigger point release is effective in relieving pain and improving neck disability index as compared to stretching in isolation. references 1. mokdad ah, ballestros k, echko m, glenn s, olsen he, mullany e, lee a, khan ar, ahmadi 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hospital in uttar pradesh, india. 13. lucas n, macaskill p, irwig l, moran r, bogduk n. reliability of physical examination for diagnosis of myofascial trigger points: a systematic review of the literature. the clinical journal of pain. 2009 jan 1;25(1):80-9. 14. bronfort g, evans r, anderson av, svendsen kh, bracha y, grimm rh. spinal manipulation, medication, or home exercise with advice for acute and subacute neck paina randomized tr ial. annals of internal medicine. 2012;156(1_part_1):1-10. 15. lagattuta f ff. assessment and treatment of cervical spine disorders. 2000;2:50-60. 16. scheiman j, isenberg j. agents used in the prevention and treatment of nonsteroidal anti-inflammatory drugassociated symptoms and ulcers. the american journal of medicine. 1998 nov 2;105(5):32s-8s. 17. kroeling p, gross a, graham n, burnie sj, szeto g, goldsmith ch, haines t, forget m. electrotherapy for neck pain. cochrane database of systematic reviews. 2013(8). 18. myers tw. anatomy trains: myofascial meridians for manual and movement therapists: elsevier health sciences; 2009. 19. phadke a, bedekar n, shyam a, sancheti p. effect of muscle energy technique and static stretching on pain and functional disability in patients with mechanical neck pain: a randomized controlled trial. hong kong physiotherapy journal. 2016 dec 1;35:5-11. 20. trampas a, kitsios a, sykaras e, symeonidis s, lazarou l. c l i n i c a l m a s s a g e a n d m o d i f i e d p r o p r i o c e p t i v e neuromuscular facilitation stretching in males with latent myofascial trigger points. physical therapy in sport. 2010 aug 1;11(3):91-8. 21. kostopoulos d, nelson jr aj, ingber rs, larkin rw. reduction of spontaneous electrical activity and pain perception of trigger points in the upper trapezius muscle through trigger jiimc 2022 vol. 17, no.3 190 stretching alone versus muscle energy technique point compression and passive stretching. journal of musculoskeletal pain. 2008 jan 1;16(4):266-78. 22. mahajan r, kataria c, bansal k. comparative effectiveness of muscle energy technique and static stretching for treatment of subacute mechanical neck pain. int j health rehabil sci. 2012 jul;1(1):16-21. 23. sadria g, hosseini m, rezasoltani a, bagheban aa, davari a, seifolahi a. a comparison of the effect of the active release and muscle energy techniques on the latent trigger points of the upper trapezius. journal of bodywork and movement therapies. 2017 oct 1;21(4):920-5. 24. noor r, afzal b. comparative study of treatment of trigger points pain with two techniques. 1 muscle energy technique alone 2. combined approach. int j sci res. 2016;5:1825-9. 25. phadke a, bedekar n, shyam a, sancheti p. effect of muscle energy technique and static stretching on pain and functional disability in patients with mechanical neck pain: a randomized controlled trial. hong kong physiotherapy journal. 2016 dec 1;35:5-11. 26. sbardella s, la russa c, bernetti a, mangone m, guarnera a, pezzi l, paoloni m, agostini f, santilli v, saggini r, paolucci t. muscle energy technique in the rehabilitative treatment for acute and chronic non-specific neck pain: a systematic review. in healthcare 2021 jun 17 (vol. 9, no. 6, p. 746). mdpi. conflict of interest authors declared no conflicts of interest. grant support and financial disclosure authors have declared no specific grant for this research from any funding agency in public, commercial or nonprofit sector. data sharing statment the data that support the findings of this study are available from the corresponding author upon request. this is an open access article distributed under the terms of the creative commons attributionnoncommercial 2.0 generic license. jiimc 2022 vol. 17, no.3 191 stretching alone versus muscle energy technique jiimc march 2016.cdr original article abstract objective: to determine the frequency of different prenatal risk factors associated with autism spectrum disease. study design: a case-control study. place and duration of study: the study was conducted at rawalpindi. cases were recruited from autism resource centre (arc), step to learn (stl) rawalpindi, hassan academy for special children, and army public academy for special children rawalpindi and controls from dhq hospital rawalpindi from february 2014 to january 2015. materials and methods: two groups of children were included in the study, group one were diagnosed case of autism asd (n=101) aged between 3 to 10 years and group two (control n=233). the data was collected and entered in a self designed structured questionnaire. data was analyzed by spss (statistical package for the social sciences) vs 20. results: over 30 risk factors have been identified. 67.3% cases were males and 32.6% were females whereas 34% controls were males and 66% controls were females. the factors associated with autism were male gender, advanced father's age at child birth, severe iron deficiency anemia during pregnancy, vitamin d deficiency, maternal hypothyroidism, asthma, hypertension, diabetes mellitus and obesity, high stress during pregnancy, c-section, valporoic acid use, antidepressants and antibiotics use in mothers, infection during pregnancy, no or minimum exposure of sunlight during pregnancy, premature birth, meconium aspiration syndrome and late cry, blood group incompatibility with mothers and rh incompatibility between mothers and fathers. conclusion: prenatal risk factors like stress, vitamin d deficiency, iron deficiency anemia, hypothyroidism, obesity, diabetes, blood group incompatibility with mothers, children born in spring and c section are the strong causes to develop autism in children. key words: autism, neurodevelopmental disorder, risk factors. learning, cognitive functioning, sensory processing 1 and attention. the phrase “spectrum disorders” is used to point out that asds include a variety of behaviorally concerned conditions, which are diagnosed by clinical observation of development. these conditions encompass autistic disorder (i.e., autism), and pervasive developmental disorder and 2 asperger disorder. asds, related to other neurodevelopment disabilities, are usually not curable and chronic maintenance, preservation and management is requisite. regardless of the fact outcomes are diverse and specific behavioral characteristics vary over time, the majority of children with asds remains within the spectrum like adults and, disregarding of their intellectual level, undergo to experience problems with employment, independent and self-regulating living, communal 3,4 relationships, mental health and societal problem. the diagnostic criteria depend upon the symptoms that become evident before a child is three years 5 old. causative factors for autism are inadequately introduction autism is a wide-ranging term used to illustrate an assemblage of complex neurodevelopmental disorders also known as pervasive developmental disorders (pdd) or autism spectrum disorders (asd). asds are a collection of developmental disabilities characterized by atypical development in socialization believe behavior and communication. symptoms of asds are present before age 3 years and frequently are accompanied by difficulty in frequency of different risk factors of autism spectrum disease: a multicentre comparative study 1 2 3 4 saira jahan , zahra arshad , sana nasir zaidi , imran amjad evaluating different risk factors of asdjiimc 2016 vol. 11, no.1 correspondence: dr. saira jahan department of rehabilitation sciences riphah international university railway general hospital, rawalpindi e-mail: jdrsyri@yahoo.com 1,2,3 department of rehabilitation sciences riphah international university railway general hospital, rawalpindi 4 riphah college of rehabilitation sciences riphah international university, islamabad funding source: nil ; conflict of interest: nil received: november 18, 2015; accepted: march 10, 2016 16 understood. both environmental and genetic risk factors are likely to commit etiology. although autism appears to have its roots in very early brain development, mainly identifiable signs and symptoms are likely to appear between two and three years of age. mostly parents are the first to note and identify that their child is presenting a typical behaviors such as deteriorating to make eye contact, not answering to his or her name or playing 6 with toys in unusual, repetitive behavior. the purpose of this study is to determine the frequency of different prenatal risk factors associated with asd so that these new risk factors should be used to make recommendations for clinical practice and by the avoidance of these risk factors, prevalence of asd decreases. materials and methods it was a multicentre case control study. there were total 334 children enlisted in this study in which 101 were diagnosed case of autism and 233 healthy controls were taken with no neurological, musculoskeletal or cardiopulmonary abnormalities. non probability convenient sampling technique was used. the case data was collected from arc (autism resource center, rawalpindi), stl (step to learn), hassan academy for special children, rawalpindi and islamabad branch and army public academy for special children rawalpindi. control data was collected from dhq hospital, fauji foundation h o s p ita l r awa lp in d i, nat io n a l i n st it u te o f rehabilitation and medicine islamabad, railway general hospital rawalpindi and divisional public school rawalpindi from january 2014 to december 2014.permission was taken from respective institutes. data collection tool and procedure: a self designed structured questionnaire was used for data collection. the questionnaire had 33 items (appendix a). the different risk factors causing autism included in our questionnaire were based on literature search different studies in different settings by different authors. it included iron deficiency anemia, vitamin d deficiency in mother during pregnancy, older parents, c section, mother high stress level during pregnancy due to any reason, blood group incompatibility with mother and many more. ethical permission was taken from medical superintendent of dhq, ffh, nirm and prh. after obtaining informed consent from parents, data was c o l l e c t e d u s i n g s e l f d e s i g n e d s t r u c t u r e d questionnaires. questions were first explain and then asked from parents of study groups. data was filled personally by the authors. statistical analysis: data was analyzed by using spss (statistical package for social sciences) vs 20. results 30.2% asd cases and 69.7% healthy controls were taken in this study. in asd cases 6.9% mothers were suffering from obesity and 11.8% from diabetes and 21% from hypothyroidism (fig 1). table i show stress mothers taken during pregnancy, infection during pregnancy, exposure of sunlight during pregnancy, premature births, c section, episiotomy, svd, meconium aspiration syndrome, late cry of baby at birth, different rh and different blood group among parents and blood group incompatibility with mothers. controls had lesser frequency of iron deficiency anemia during pregnancy whereas asd cases had prevalence of moderate and severe iron deficiency anemia during pregnancy increases in mothers of cases (fig 2). 70.27% mothers of children with asd used folic acid and vitamin d during pregnancy whereas less usage in mothers of controls. mothers of children with asd had history of more usage of valproic acid, antidepressant and antibiotics i.e. 6.9%, 22.7% and 14.8% respectively whereas only 2.57% mothers of controls used antidepressant and 3.0% used antibiotics and none used valproic acid. fig 1: comparison of mother's medical history between cases and controls evaluating different risk factors of asdjiimc 2016 vol. 11, no.1 17 discussion in our study 67% cases of autism were found out to be males and only 29% were females hence supporting male gender as a risk factor of autism. males are at higher risk for neurodevelopmental disorders, such as autism spectrum disorder (asd), than females, but the fundamental reasons have 7 been uncertain. scientists have supposed a connection between iron deficiency and autism spectrum disorder. in a study maternal intake of supplemental iron and risk for autism spectrum disorders by schmidt rj, et al establishes a strong relationship between iron 8 deficiency and autism. in our study 48% severe deficiency of iron is found in cases and only 5% severe deficiency is found in controls. 9% of the cases had no iron deficiency while 61% of the controls also did not have any iron deficiency. this signifies the iron deficiency as one of the contributory risk factors for development of asd. according to kinney dk et al, in their study, “prenatal stress and risk for autism” stress of expectant mother is a noticeable reason for 9 the symptoms of autism. in another study “timing of prenatal stressors and autism” by beversd of dq et al, it was reported that prenatal stress has a role in 10 causing autism. in our study 42% cases had selfreported moderate to severe stress during their pregnancies and only 14.5% of controls also reported stress. so we can deduct the conclusion that stress is as one of the risk factor for asd. a prospective study of exposure to valproic acid and risk for autism spectrum disorder indicates that valproic acid usage may be an important factor in 11 causing autism. in our study 6.9% cases taken valproic acid during pregnancy (antiseizure medicine) whereas none of the control took valproic acid. this finding is in agreement with previous studies but further investigation is warranted. prenatal exposure to ssris, particularly during the first trimester, may moderately increase the risk of 12 asds. 22% cases in our study used antidepressant during pregnancy whereas only 2% controls were on a n t i d e p r e s s a n t i n d i c a t i n g e i t h e r i t ' s t h e antidepressant drugs or the depression which is hidden behind and need further investigation. studies showed that antibiotic use in pregnancy 13 might cause autism. in our study 14% cases took antibiotics during pregnancy whereas only 3% controls took antibiotics during pregnancy but the need is to investigate the group of antibiotic, dose, frequency and all the minor details, so further investigation is warranted. drugs possibly will activate the disease, earlier researchers found that use of medications during pregnancy may have an effect on the developing fetus and may cause 13 autism. in our study 55% cases taken no drug during pregnancy emphasizing that it is not only the drugs that causes autism, there are some other factors that may in combination with the drugs causes autism. table i: comparison of different condi�ons between cases and controls fig 2: comparison of iron deficiency anemia between cases and controls evaluating different risk factors of asdjiimc 2016 vol. 11, no.1 18 conclusion prenatal risk factors like stress, vitamin d deficiency, iron deficiency anemia, hypothyroidism, obesity, diabetes, blood group incompatibility with mothers, children born in spring and c section are the strong causes to develop autism in children. it is concluded that there is insufficient evidence to implicate any one prenatal factor in autism etiology, although there is some evidence to suggest that exposure to pregnancy complications may increase the risk. references 1. destefano f, bhasin tk, thompson ww, yearginallsopp m, boyle c. age at first measles-mumps rubella vaccination in children with autism and school matched control subjects: a population-based study in metropolitan atlanta. pediatrics. 2004; 113: 25966. 2. braun kvn, pettygrove s, daniels j, miller l, nicholas j, baio j, et al. evaluation of a methodology for a collaborative multiple source surveillance network for autism spectrum disorders -autism and developmental disabilities monitoring network, 14 sites, united states, 2002. mmwr surveillance summaries: morbidity and mortality weekly report surveillance summaries/cdc. 2007; 56: 29-40. 3. howlin p, goode s, hutton j, rutter m. adult outcome for children with autism. journal of child psychology and psychiatry. 2004; 45: 212-9. 4. friedman nd, warfield me, parish sl. transition to adulthood for individuals with autism spectrum disorder: current issues and future perspectives. neuropsychiatry. 2013; 3: 181-92. 5. baharara j, hojjati m, rasti h. the ratio of second to fourth digit length (2d: 4d) in children with autistic disorder. international journal of pediatrics. 2014; 2: 5-11. 6. lord c, paul r. language and communication in autism. handbook of autism and pervasive developmental disorders. 1997; 2: 195-225. 7. robinson eb, koenen kc, mccormick mc, munir k, hallett v, happe f, et al. evidence that autistic traits show the same etiology in the general population and at the quantitative extremes (5%, 2.5%, and 1%). archives of general psychiatry. 2011; 68: 1113-21. 8. schmidt rj, tancredi dj, krakowiak p, hansen rl, ozonoff s. maternal intake of supplemental iron and risk of autism spectrum disorder. american journal of epidemiology. 2014: kwu208. 9. kinney dk, munir km, crowley dj, miller am. prenatal s t r e s s a n d r i s k fo r a u t i s m . n e u ro s c i e n c e &biobehavioral reviews. 2008; 32: 1519-32. 10. beversdorf dq, manning s, hillier a, anderson s, nordgren r, walters s, et al. timing of prenatal stressors and autism. journal of autism and developmental disorders. 2005; 35: 471-8. 11. christensen j, gronborg tk, sorensen mj, schendel d, parner et, pedersen lh, et al. prenatal valproate exposure and risk of autism spectrum disorders and childhood autism. jama. 2013; 309: 1696-703. 12. croen la, grether jk, yoshida ck, odouli r, hendrick v. antidepressant use during pregnancy and childhood autism spectrum disorders. archives of general psychiatry. 2011; 68: 1104-12. 13. atladottir ho, henriksen tb, schendel de, parner et. autism after infection, febrile episodes, and antibiotic use during pregnancy: an exploratory study. pediatrics. 2012; 130: 1447-54. evaluating different risk factors of asdjiimc 2016 vol. 11, no.1 19 original�article abstract objective: to describe the clinical and haematological picture of multiply transfused patients of thalassaemia major at a treatment center in pakistan. study design: descriptive cross-sectional. place and duration of study: the study was conducted at thalassaemia treatment centre rawalpindi. the study was done between jan 1994 and may 2017. materials and methods: a total of 383 patients of thalassaemia major (tm) on regular blood transfusions were examined for various clinical and haematological parameters. in addition case records of 101 patients of tm who died during treatment were also studied. results: in the 383 patients on treatment 328 (86%) were born to consanguineous parents, 246 (64%) were from lower socio-economic group, 85 (22%) had one or more affected siblings, 145 (38%) had hepatomegaly, 191 (50%) had splenomegaly, 42 (11%) had undergone splenectomy and 187 (49%) had never received iron chelation therapy. height and weight in the 383 patients on treatment showed marked stunting. median age of the 383 patients on treatment was 104 months as compared to 119 months in the deceased group of patients (p=0.0263). pre-transfusion hb in the alive patients (7.1 g/dl) was higher than in the deceased patients (6.4 g/dl) (p=0.0142). ferritin level in the patients on treatment (3698 µg/l) was lower than in the deceased patients (4616 µg/l) (p=0.0069). in the 383 patients on treatment 141 (36.8%) were hcv positive. conclusion: majority of the patients at a thalassaemia treatment center are chronically under-transfused and have moderate to severe growth retardation. they get inadequate iron chelation resulting in high mortality before tenth year of life. key words: blood transfusion, complications, pakistan, survival, thalassemia. have reduced the new births of thalassaemia major 3 (tm) to almost zero. however, in most developing and under developed countries the picture is very 4 different. approximately 80% of the new births of children with genetic haemoglobin disorders take place in the under-developed or developing countries that have very limited resources for management and prevention. these have been largely ignored by governments of countries with a high-frequency of these disorders and by the 5 international funding agencies. as the infectious diseases are getting under control the mortality due to genetic diseases like thalassaemia is becoming 1 obvious. pakistan has a population of nearly 200 million and approximately 5% of the people carry the gene for β6, 7 thalassaemia. it is estimated that each year over 5000 new births of tm take place and the total number of children with tm may be well over 8 50,000. most of the children with tm in pakistan are treated at centers run by non-governmental organizations (ngos). there are at least 50 ngos introduction genetic haemoglobin disorders are the most common single gene disorders in the world. it is estimated that about 250 million people carry the 1 gene for thalassaemia or abnormal haemoglobin. the disease has high prevalence in a broad belt including mediterranean countries, middle east, 2 indian subcontinent and south east asia. successful preventive programs in the developed countries clinical and haematological picture of multi-transfused thalassaemia major patients at a center in pakistan 1 2 3 suhaib ahmed , zohra jabeen wazir , ishrat abdul qayyum correspondence: maj. gen. (r) dr. suhaib ahmed professor, haematology islamic international medical college riphah international university, islamabad e-mail: suhaib.ahmed@riphah.edu.pk 1 department of haematology islamic international medical college riphah international university, islamabad 2 thalassemia treatment center pak thalassemia welfare society, rawalpindi 3 genetics resource center, rawalpindi funding source: nil; conflict of interest: nil received: jan 01, 2018; revised: mar 10, 2018 accepted: mar 18, 2018 multi-transfused thalassaemia major in pakistanjiimc 2018 vol. 13, no.2 52 53 that provide blood transfusion services to over 25,000 children with tm. the ngos work on a charitable basis and are mostly facing paucity of funds. lack of funds and voluntary blood donations pose great challenge for providing quality treatment 9 to children with tm. there are almost no published data on the outcome of treatment of thalassaemics in pakistan. this study is the first of its kind that describes the clinical and haematological features of children with tm getting treatment at a center run by a ngo in pakistan. materials and methods this descriptive cross-sectional study was done after approval by the ethical review committee of the executive council of the society. all available children with tm registered at the center between jan 1994 and may 2017 were examined. the patients of tm registered at the center but not available for examination due to various reasons were excluded. the study variables included age, sex, consanguinity, socio-economic status, other affected siblings, age at diagnosis, age at first transfusion, height, weight, hepato-splenomegaly, splenectomy, pre-transfusion haemoglobin, mean transfusion interval, iron chelation, serum ferritin levels and hcv status. in addition, the case records of children who died while on treatment between jan 1994 and may 2017 and had adequate documentation were also studied. the deceased patients with incomplete documentation were excluded. the deceased patients were studied for age at death, age at diagnosis, age at first transfusion, mean pre-transfusion haemoglobin, mean transfusion interval, iron chelation, and serum ferritin. the results were analyzed by stats direct version 2.5.5 statistical package. frequency of occurrence of the categorical variables in the alive and the deceased patients was compared by chi square test and the numerical data were compared by t-test. survival estimates of the deceased children w e r e m a d e u s i n g k a p l a n m e i e r m e t h o d . results a total of 383 patients of tm on treatment were examined. their median age was 104 months that ranged from 6-429 months, the male to female ratio was 1.1:1, 328 (86%) were born to consanguineous parents, 246 (64%) were from lower socio-economic group, 85 (22%) had one or more affected siblings, 145 (38%) had hepatomegaly, 191 (50%) had splenomegaly, 42 (11%) had undergone splenectomy and 187 (49%) had never received iron chelation therapy. height and weight in the 383 patients on treatment showed marked stunting (fig 1). fig 1: comparison of height and weight of male children of tm aged 1-16 years and the normal 10 popula�on of the same age in pakistan. it was more marked in the male patients and most of them were below the fifth centile of the pakistani 10 population. almost all of the patients were underweight that became more obvious with increasing age (fig 1). the case records of 101 patients who died during treatment and had adequate documentation were studied. their median age at the time of death was 119 months that ranged from 6-324 months. pre-transfusion hb in the patients on treatment (7.1 g/dl) was higher than in the deceased patients (6.4 g /dl) (p=0.0142). average interval between transfusions was four weeks in both of the groups. ferritin level in the patients on treatment (3698 µg/l) was lower than in the deceased patients (4616 µg/l) (p=0.0069) (table 1). fig 2: kaplan-meier survival es�mates of 101 pa�ents of tm who died while on treatment out of the 383 tm patients on treatment 141 (36.8%) were hcv positive. kaplan-meier median survival estimate of 101 patients of tm who died while on treatment was 84 multi-transfused thalassaemia major in pakistanjiimc 2018 vol. 13, no.2 54 months (95% ci 79.21-88.8) (fig 2). median survival in the 60 male patients was 72 months (95% ci 65.678.4) whereas in the 41 female patients it was 84 months (95% ci 76.2-91.8). discussion thalassaemia is the commonest single gene disorder 6 in pakistan. it is estimated that each year over 5000 new children with tm are born and the total number 8 of tm patients may be over 50,000. treatment of such large numbers of patients is a gigantic task. unfortunately there are very few public sector institutions that take care of patients with tm. most of these children are treated at centers run by over 50 ngo s wo rkin g u n d er t h e u mb rella o f 9 thalassaemia federation of pakistan (tfp). in the absence of adequate resources and a mechanism to ensure implementation of treatment guidelines the outcome of treatment at the centers of ngos is unlikely to improve. there are almost no published data on the outcome of treatment of tm at any of 9 these centers. this study is the first of its kind in pakistan and it clearly shows a picture of mismanagement. it may not be representative of all thalassaemia treatment centers in pakistan but it provides a fair idea about the overall scenario. 12 tm patients surviving at 35 years in an italian study. high mortality in these patients appears to be due to chronic under transfusion and iron overload due to 13 lack of iron chelation. chronic anaemia with pre-transfusion haemoglobin around 7.0 g/dl is clearly reflected by hepatosplenomegaly in nearly half of the patients and stunting of growth in almost all of them. the main reasons for low pre-transfusion haemoglobin include shortage of blood due to insufficient voluntary blood donations and lack of awareness amongst the parents to get timely blood transfusions. the problems can be addressed by creating awareness. it is important for the treating doctors and the parents to understand that maintaining pre-transfusion haemoglobin above 9.010.5 g/dl would not only improve the overall health of the child but would also reduce the annual consumption of blood. when a child with tm remains chronically under transfused erythropoietin is constantly released and stimulates bone marrow. the resulting marrow expansion and hepatosplenomegaly cause haemodilution and worsening of anaemia. this vicious circle can be broken only by 13 correcting anaemia through blood transfusions. the treating doctors should make an extra effort to guide the parents about benefits of high transfusion regimens. the shortage of blood can be met by public awareness through mass media about voluntary blood donations. iron overload is an invariable complication of tm. it is mostly caused by regular blood transfusions. the extra iron is carried in plasma through transferrin and when the latter is fully saturated iron travels as non14 transferrin bound iron (ntbi). ntbi is preferentially taken up by myocardium, endocrine glands and hepatocytes and is responsible for growth failure, hypogonadism, hypothyroidism and diabetes etc. myocardial haemosiderosis is another life threatening complication of iron over load that 13 causes conduction defects and cardiac failure. the age at which iron chelation is started is the key factor 12 because starting it late in life is much less effective. cardiac complications resulting from iron deposition 12 are the commonest cause of death in tm. the peak mortality observed around ten years of age in this study also appears to be related to cardiac haemosiderosis. stature of the vast majority of table i: comparison of age and other haematological parameters between alive and deceased pa�ents of tm the kaplan-meir estimates showed median survival of 84 months. survival was longer in the female patients as compared to the male. the longer survival in female patients has also been reported in 11 a previous study. although it is a cross-sectional study that is not comparable to longitudinal studies on survival but these data are no match for over 68% multi-transfused thalassaemia major in pakistanjiimc 2018 vol. 13, no.2 55 th patients in this study was below 5 centile of the 10 pakistani population. growth retardation is common in tm after the first decade of life. it is m o s t l y b e c a u s e o f c h r o n i c a n a e m i a s , endocrinopathy due to iron overload, malnutrition, zin c d eficien cy, ch ro n ic liver d isease an d 13 psychological stress. a previous study on endocrine abnormalities in 131 children from the same center showed growth hormone deficiency in 30%, hypoparathyroidism in 17.5%, hypothyroidism in 8%, diabetes mellitus in 1.5% and impaired fasting 15 glucose metabolism in 4% of tm patients. in this study growth retardation in the male patients became obvious after the fifth year of life whereas in female patients it was less significant. in the female patients it usually appears after the tenth year of 16 life. growth retardation at a very early stage appears to be related to chronic anaemia, malnutrition and marked iron overload. nearly half of the patients in this study had never used iron chelation and even those who were using it were getting it infrequently and at suboptimal doses. this is also reflected by grossly elevated serum ferritin levels. the high cost and lack of awareness are the two main limiting factors in the wider use of rd iron chelation. nearly 2/3 of the patients in this study are from the lower socio-economic group and are unable to bear the high cost of iron chelation. low-cost oral iron chelators are an urgent requirement and efforts should be made to facilitate their local production. hepatitis c virus (hcv) infection is another problem area in the management of tm in pakistan. nearly 40% of the patients in this study were positive for hcv. previous studies have also shown that 40-50% 17,18 of the tm patients are hcv positive. poor screening facilities at many centers are the major cause of high hcv prevalence in tm. many patients keep visiting different treatment centers in search of blood. since the screening facilities at all centers are not uniform the patients can easily get hcv infection by one wrong transfusion. the hcv point of care testing devices are known to give false negative 19,20 results due to their low sensitivity. these devices are in common use by majority of the blood banks in pakistan and are partially responsible for the high prevalence of hcv in multiply transfused patients of tm in pakistan. voluntary carrier screening and prenatal diagnosis of 21 thalassaemia are available in pakistan since 1994. it is unfortunate that most of the children with tm in this study and elsewhere in pakistan were born during the period when prenatal diagnosis was available. this study also showed that 22% of the tm patients had at least one affected sibling. lack of awareness amongst the doctors and the parents and high cost of testing are the two major limiting factors 22 in the use of prenatal diagnosis in pakistan. consanguinity, also seen in this study, is an important contributing factor in causation of recessive genetic 23 disorders in pakistan. the best way to tackle this sensitive issue would be to offer premarital carrier screening in the close family setting or to offer prenatal diagnosis where marriage between two 6 carriers is unavoidable. conclusion majority of the patients at a thalassaemia treatment center in pakistan are chronically under-transfused and have moderate to severe iron overload. this results in severe growth retardation and high mortality around ten years of age. the outcome of treatment can be improved by creating awareness and providing adequate amount of blood and iron chelating drugs. acknowledgements authors are grateful to the management of pakistan thalassaemia welfare society for allowing access to the case records and the children with thalassaemia major being treated at their center. references 1. modell b, darlison m. global epidemiology of haemoglobin disorders and derived service indicators. bull world health organ. 2008; 86: 480-7. 2. angastiniotis m, modell b. global epidemiology of hemoglobin disorders. ann ny acad sci. 1998; 850: 251-69. 3. cao a. results of programmes for antenatal detection of thalassaemia in reducing the incidence of the disorder. blood rev. 1987; 1: 169-76. 4. al-gazali l, hamamy h, al-arrayad s. genetic disorders in the arab world. bmj. 2006; 333: 831-4. 5. weatherall dj. the challenge of haemoglobinopathies in resource-poor countries. br j haematol. 2011; 154: 736-44. 6. ahmed s, saleem m, modell b, petrou m. screening extended families for genetic haemoglobin disorders in pakistan. n engl j med. 2002; 347: 1162-8. 7. khattak mf, saleem m. prevalence of heterozygous thalassaemia in the northern areas of pakistan. j pak med multi-transfused thalassaemia major in pakistanjiimc 2018 vol. 13, no.2 assoc. 1992; 42: 32-4. 8. ahmed s. an approach for the prevention of thalassaemia in pakistan. [phd thesis]. london: university of london 1 9 9 8 . a v a i l a b l e a t : h t t p : / / d i s c o v e r y. u c l . a c . u k / 1317916/1/299931.pdf. 9. asif n, hassan k. management of thalassemia in pakistan. jimdc. 2016; 5: 152-3. 10. aziz s, noor-ul-ain w, majeed r, khan ma. qayum i, ahmed i, et al. growth centile charts (anthropometric measurement) of pakistani pediatric population. j pak med assoc. 2012; 62: 367-77. 11. nasir ja, zaidi saa. modelling survival data of thalassaemia patients in pakistan. j ayub med coll abbottabad. 2009; 21: 142-5. 12. borgna-pignatti c, rigolotto s, de stefano p, zhao h, capellini md, del vecchio g, et al. survival and complications in patients with thalassemia major treated with transfusion and deferoxamine. haematologica. 2004; 89: 1187-93. 13. cappellini md, cohen a, porter j, taher a, viprakasit v. guidelines for the management of transfusion dependent thalassaemia (tdt). nicosia: thalassaemia international federation tif publication no 20; 2013. 14. hershko c. pathogenesis and management of iron toxicity in thalassemia. ann ny acad sci. 2010; 1202: 1-9. 15. khan d, cheema an, anwar m, khan fa. endocrine dysfunction in beta-thalassaemic major patients at rawalpindi, pakistan. healthmed. 2010; 4: 580-5. 16. tienboon p, sanguansermsri t, fuchs gj. malnutrition and growth abnormalities in children with beta thalassemia major. southeast asian j trop med public health. 1996; 27: 356-61. 17. nazir s, faraz a, shahzad n, ali n, khan ma, iqbal m, et al. prevalence of hcv in β-thalassemia major patients visiting tertiary care hospitals in lahore pakistan. adv life sci. 2014; 1: 197-01. 18. din g, malik s, ali i, ahmed s, dasti ji. prevalence of hepatitis c virus infection among thalassemia patients: a perspective from a multi-ethnic population of pakistan. asian pac j trop med. 2014; 7: 127-33. 19. fisher dg, hess kl, erlyana e, reynolds gl, cummins ca, alonzo ta. comparison of rapid point-of-care tests for detection of antibodies to hepatitis c virus. open forum infect dis 2015; 2: ofv101. 20. hayder i, ahmed w, alam se. comparison of different ict kits for hbsag and anti hcv using gold standard elisa. pak j med res. 2012; 51: 72-5. 21. ahmed s, saleem m, petrou m, sultana n, raashid y, waqar a, et al. prenatal diagnosis of -thalassaemia in pakistan: experience in a muslim country. prenatdiagn. 2000; 20: 378-83. 22. naseem s, ahmed s, vahidy f. impediments to prenatal diagnosis for beta thalassaemia: experiences from pakistan. prenat diagn. 2008; 28: 1116-8. 23. bittles ah, grant jc, shami sa. an evaluation of consanguinity as a determinant of reproductive behaviour and mortality in pakistan. int j epidemiol. 1993; 22: 463-7. 24. ansari sh, shamsi ts, ashraf m, perveen k, farzana t, borhany m, et al. efficacy of hydroxyurea in providing transfusion independence in β-thalassemia. j pediatr hematol oncol. 2011; 33: 339-43. 25. shamsi ts, hashmi k, adil s, ahmad p, irfan m, raza s, et al. the stem cell transplant program in pakistan—the first decade. bone marrow transplantation. 2008; 42: 114–7. multi-transfused thalassaemia major in pakistanjiimc 2018 vol. 13, no.2 56 page 8 page 9 page 10 page 11 page 12 untitled-1 untitled-1 original�article abstract objective: to explore the perception and views of undergraduate medical students about the significance of structured versus traditional viva formats. study design: it was qualitative exploratory research place and duration of study: the study was conducted in pathology department of cmh multan institute of medical sciences from december 2019 to august 2020. materials and methods: four sets of focused group discussions were carried out, each group comprising of 8 students of fourth year mbbs who had undertaken both structured and traditional viva examinations in the subject of pathology. the students who did not appear in the exam and those who did not volunteer for the study were excluded from the study. the interviews were audio recorded followed by transcription and manual thematic analysis. the students identified their preferences for the type of viva which gave an umbrella of themes. the subthemes were then identified to find out the exact reasons of their preferences. results: the results of the study yielded five themes and sub themes. the main themes were attitude towards exams, exams preparation, time management, student teacher relationship and relevancy of content of viva. the students suggested that viva exam of all subjects should be structured to maximize uniformity of content coverage, time management and attitude improvement for both faculty and students. conclusion: the students were overwhelmingly satisfied with structured viva as compared to traditional viva format. they emphasized structured viva as their preferred assessment method as traditional viva does not truly reflect a student's competence. key words: assessment methods, perception, structured, students, traditional viva. more teacher centered, time consuming, variable, examiner biased, difficult , not interactive, with 6 tense atmosphere during exam. all these demerits make both the validity and reliability of this method 7 , 8 . questionable in order to overcome these difficulties a much reliable approach was much needed and it was provided by structured viva format. it has been introduced in various medical 9,10,11 universities globally . this modified format helps in eliminating many flaws including the element of bias and gives an equal and fair chance to every student. a lot of research has been done and methods of structured exam devised. students desire the needed change in assessment methods. hashim r et al. confirmed in their study that 98% of their students 9 were satisfied with the structured viva format . though many quantitative and some qualitative data endorse the efficacy of structured format but literature review shows very little work done in this area ethnographically. ethnographic research is one of the best and unique ways to explain students' introduction the rapidly evolving medical education system has made the assessment of medical students a challenging task. there have been a number of ways by which students can be assessed but viva voce has always been an integral part of students' 1,2 evaluation . traditional viva voce has long been 3 used as a summative assessment tool . though it has some potential strengths like greater compliance 4 and flexibility both on part of students and teachers 5 ,this method also has some serious flaws in it . it is perception of mbbs students about structured versus traditional viva examination formats fareeha naseer syed, attia sheikh, syed atif hussain andrabi correspondence: dr. fareeha naseer syed assistant professor department of pathology cmh institute of medical sciences, multan e-mail: fareeha1976@gmail.com 1 2 department of pathology/department of medical education cmh institute of medical sciences, multan 3 department of radiology combined military hospital, multan received: november 15, 2021; revised: june 10, 2022 accepted: june 13, 2022 perception about structured versus traditional vivajiimc 2022 vol. 17, no.2 129 perception about viva examination whereby the researcher documents the culture, perspectives and 12,13,14 practices of people in a particular setting . detailed informal or conversational interviews allow to probe their issues in a more naturalistic manner. a more recent form of ethnography, the focused ethnography (fe), investigates a specific issue among small groups of people instead of whole communities, for example, students of a medical 15 college .because, the scope of fe is narrow, the researcher generally has better and more knowledge about the topic under study and does not need immersion in cultural practices and engagement in long-term fieldwork. thus, fe is more feasible for busy medical educators who are curious and want to 16,17,18 explore outcomes in their own setting . with this background knowledge, we decided to carry out a qualitative research project in pathology department of cmh institute of medical sciences multan. we wanted to explore what our students feel about the viva examination systems being followed in our setting and convince our faculty that our students are aware and desirous of a muchneeded change in that system. our students volunteered to both structured and traditional viva formats followed by recording their perceptions and views about the two formats via focused group interviews. materials and methods this qualitative, focused ethnographic study was conducted from december 2019 to august 2020 at cmh multan institute of medical sciences, multan, pakistan. after taking approval from institutional ethics review board the sample was collected using purposive sampling technique from among fourth year medical students who had undertaken their viva voce in the department of pathology at cims multan at the end of second modular examination. those students who did not appear in the exam and those who did not volunteer were excluded from the study. there were 100 students, who were divided into four batches of 25 students each. viva was conducted on 4 consecutive days. each student had to take both structured and traditional viva examinations by two separate examiners. the students were briefed about the new viva format beforehand. for structured viva, questions with keys were prepared mutually agreed by all the faculty members with increasing difficulty level as per the bloom's taxonomy of educational objectives of cognitive domain, i.e, easy, moderate and hard. each student was given an equal time. there were four pools of questions, one pool of ten questions to be used each day with equal marks distribution for each batch(table i). table i: an example of a pool of 10 questions for structured viva (total marks:10; time:10 min) the traditional viva examination was conducted conventionally with examiner asking 10 random but relevant questions and with the same time limit. maximum 10 marks were awarded to this part of exam too. perception about structured versus traditional vivajiimc 2022 vol. 17, no.2 130 in order to control bias it was assured that the viva questions for the structured examination prepared were kept in complete secrecy; only the examiner knew about those at the time of the exam. the students who had taken the structured viva were kept separate from rest of the examinees with strict compliance to exam protocols. everyday a separate pool of questions was used. same couple of examiners conducted the viva on all the four days to remove teacher-teacher bias. after taking informed consent the focused group interviews were taken at the end of viva each day from those students who volunteered. each group interview lasted for about 60minutes. the questions used for focused group interview were finalized after being validated by experts in the field of medical education. the opinions of the students were both audio recorded as well as noted down by the moderator. the audio recordings were later transcribed verbatim. thematic analysis was conducted. in the first stage day wise coding was done which produced four sets of codes (d1-d4). every individual in a group was further given a lettered code from a to h. in the second stage these codes were arranged and then evaluated into themes and subthemes. results of the hundred students , four groups of students (32%), each comprised of 8 students, volunteered for focused group interviews. results of the study revealed five major themes and subthemes after consensus of the researchers. (table ii). the first theme was “attitude towards exams”. most of the students felt that during traditional viva there was generally an aura of fear and anxiety. viva is a test of communication skills and not everyone is good at it. many students could not answer because of anxiety or shyness despite of knowing the answer. their self-confidence was boosted with structured viva format. according to one student, “i've never felt so confident in any viva examination before. structured viva is far better way to express myself. it was just like a quiz show where i was answering and scoring.” (d1-f). in traditional viva students felt the examiner's bias when he changed difficulty level of question from easy to hard for some students and vice versa, “i think i had a better connection with my examiner taking structured viva. i didn't feel nervous. table ii: medical students' perception about traditional and structured viva examinations perception about structured versus traditional vivajiimc 2022 vol. 17, no.2 131 exams preparation management relationship but in traditional viva it was not the same. we never bonded. i wasn't given a chance.” (d4b) the second theme was “exam preparation”. although uniform coverage of every topic in a large group is an uphill task. however, the results of our study showed that majority of the students were satisfied with the structured viva exam. all the question asked were sufficient to cover the relevant topic and the required learning outcomes were met. one of the students said “it will really help in final exam preparation as it covers all the aspects of the syllabus. there was no drifting sideways. i think structured viva should be the preferred method for our assessment.” (d2-h).this was not the case with the traditional viva. the examiner usually stuck with one or two questions of his choice. the third theme was “equal distribution of time”. students felt that time distribution was more uniform during structured viva than traditional viva though overall duration of both exams was same. in traditional viva the time was lost more on some questions than others.“previously my viva used to linger for as long as half an hour. it was a relief that this exam finished in time. since it was time bound so it will also help me in time management in my final exams” (d3-c). the fourth theme that emerged was “ studentteacher relationship”. examiner's approach to present difficult questions to different students might have shown bias. most of the students felt that gender bias was not felt at all during structured viva but during traditional viva some of them experienced it. one of the students who experienced gender bias during traditional viva mentioned that in a reserved manner, “i felt that the examiner disapproved of me irrespective of what answers i gave during traditional viva examination. it was a prolonged exam which i wished to end early. however, during structured viva there was no such feeling.”(d2c). another student was very much unhappy of the favoritism shown by the examiner, “i'm sure that my colleague was given extra attention. it happened during traditional viva when the examiner didn't have any pool of questions to ask from and he simply was asking his favorite questions from only some students” (d3-a) the final theme was “relevance of content of viva questions”. for structured viva examination, most of the students believed the questions were relevant, focused and according to their syllabus and content. however, for traditional viva some students complained that they were asked out of syllabus questions as their viva was drifted sideways. “i think structured viva was more relevant than traditional viva as it covered the important topics without wasting time on unnecessary details.”. (d4g) discussion our study is unique as no one has used a focused ethnographic technique to take into account students' views about both traditional and structured viva examination formats. majority of students favored the structured format of viva while highlighting the issues of traditional format. traditional viva examination system has now been obsolete in many parts of the world because of its 19,20 high degree of subjectivity, bias and poor validity. such imperfections can be eliminated by the use of structured viva format. structuring can be challenging, as it requires a large q bank with valid keys, frequent updates , difficulty levels according to miller's pyramid must be ensured, and it all requires a 20,21 dedicated faculty, space and time. majority of the studies conducted now reveal that both students and faculty believe that structured viva owns a satisfactory level is terms of the efficacy of 22,23 assessment . the main objective of our study was to determine the perceptions and views of our undergraduate students about structured versus traditional viva formats. about 99% of our students expressed that the questions asked in structured viva were relevant, syllabus was uniformly covered, and it helped in equal time management. dangre-mudey g et al. also confirmed similar findings in their study where 52% of their students agreed on uniformity of covered syllabus and 56% students agreed on equal time distribution among students in structured viva. most of our students (almost 98%) believed that examiner in structured viva was more friendly, unbiased and did not ask repetitive questions, however, during traditional viva the examiner was usually moody, focused on some topics and students. such findings are mirrored by another study conducted by shah hk et al. where 75% of the students favored structured viva for the same reasons. perception about structured versus traditional vivajiimc 2022 vol. 17, no.2 132 the medical education research has been moving towards a more interpretivist approach and focused ethnography has provided a more pragmatic way to 17,18 execute this . we used focused group interviews as a tool to indulge into the social culture of our medical students, in order to comprehend and realize the real time issues that our students might be facing while dealing with professional studies and high-stakes 22 examinations. shadab et al. conducted a similar qualitative study in a clinical setting which showed comparable results as ours. medical educationists have been working hard on making the assessment 23,24 methods more objective with promising results . our study highlighted the inherent issues in the traditional viva examination. structured viva is a good way to improve student-teacher relationship, boosting students' confidence, enhancing their communication skills, higher cognitive functions and 25 application of knowledge .it also helps students identify their weak areas. in future they can work on their shortcomings and work harder to achieve better. the main limitation of the current study is that it was carried out on the students of just one medical college. also, it could not involve students of other classes due to time constraints. future studies should include ethnographic research models being applied on students of other classes as well as other medical colleges to improve its validity and reliability further. future studies should also be conducted on the use of structured assessment methods in clinical examinations too. conclusion from this study it was concluded that our students were overwhelmingly satisfied with structured viva as compared to traditional viva format. they emphasized structured viva as their preferred assessment method as traditional viva does not truly reflect a student's competence. they believed that in the form of structured exam, they found a better approach to boost their confidence, overcome the fear of traditional viva exam, uniformly cover the syllabus, and get better at applying knowledge to deal with specific problems in future clinical practice. references 1. düzgün şa, zeren s, bayhan z. objectively structured verbal examination to assess surgical clerkship education: an evaluation of students' perception. turk j surg 2018; 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1994. p. 187–209. 18. hammersley m, atkinson p. ethnography, 4th ed. abingdon, perception about structured versus traditional vivajiimc 2022 vol. 17, no.2 133 oxford, uk: routledge, taylor and francis group, 2019.search in google scholar 19. mallick a k, patel a. comparison of structured viva examination and traditional viva examination as a tool of assessment in biochemistry for medical students. eur j mol clin med.2020;07(06). 20. rokade sa. mane ak. objective structured practical examination (ospe) versus viva voce: the indian students' and faculty perception. south-east asian j med educ. 2019;13(2). 21. nikhade p, sedani s, mankar n, das a, sindhu p, mishra s.comparison of objectively structured viva voce and modified objectively structured viva voce as assessment tool during formative and summative examination in dentistry.j evolution med dent sci. 2020 oct. 05;9(40). 22. shadab w, noor aa, waqqar s, shaikh gm. structured long interview and clinical examination (slice) as formative assessment tool in clinical clerkship: medical students perspective.j pak med assoc. 2021;71: 2000. 23. wanjari s, vagha s. utility of osler for assessing enhancement of learning in postgraduate students. southeast asian j med educ 2020;13: 37. 24. skrzypek a, szeliga m, stalmach-przygoda a, górski s, kowalska b, kocurek a, et al. the objective structured clinical examination (osce) from the perspective of 3rd year's medical students—a pilot study. folia med cracov 2017; 17: 67-75. 25. ganji kk. evaluation of reliability in structured viva voce as a formative assessment of dental students. j dent educ 2017;81:590-6. conflict of interest authors declared no conflicts of interest. grant support and financial disclosure authors have declared no specific grant for this research from any funding agency in public, commercial or nonprofit sector. data sharing statment the data that support the findings of this study are available from the corresponding author upon request. this is an open access article distributed under the terms of the creative commons attributionnoncommercial 2.0 generic license. perception about structured versus traditional vivajiimc 2022 vol. 17, no.2 134 jiimc june 2016.cdr original article abstract objective: to explore the different specialty career choices of undergraduate medical students and to identify the factors influencing their career choices. study design: a descriptive cross-sectional survey. place and duration of study: this study was conducted in islamic international medical college in april 2013. materials and methods: final year students were selected through convenience sampling for this study. a 20 items questionnaire with one open ended and 19 likert scale based closeended questions was handed to 100 final year mbbs students, in order to explore their preferred career choices and reasons behind them. non parametric data analysis was done through spss 20. results: response rate of students was 82% of which 49 (60%) were female and 33 (40%) were male. medicine, surgery and gynecology were the top career choices among students. family practice was the least chosen specialty. the top 3 reasons to choose a specialty were natural aptitude, better subject comprehension and work enjoyment. parents in the same field, easy career progression and specialty related illness in the family were the least chosen reasons. conclusion: choice of specialty career in health professions has an impact on the healthcare needs of the country. 'family practice' is a forgotten domain and its importance needs to be stressed. medical curricula should emphasize on the importance of family practice as a career choice. key words: career choice, career preferences, influential factors, medical specialties. choice of specialty careers among final year mbbs students 1 2 3 madiha sajjad , rehan ahmed khan , shazia qayyum choice of specialty among mbbs studentsjiimc 2016 vol. 11, no.2 correspondence: dr. madiha sajjad associate professor, pathology islamic international medical college riphah international university, islamabad e-mail: madiha.sajjad@riphah.edu.pk 1,3 2 department of pathology/surgery islamic international medical college riphah international university, islamabad funding source: nil ; conflict of interest: nil received: feb 06, 2016; revised: mar 18, 2016 accepted: may 27, 2016 specialties, better job opportunities and easier 2,3 routes to specialize etc. factors influencing student choices for specialty careers are still unclear and culturally distinct. the decisions made by medical students regarding their specialty career choices do not only effect their own future but also have an impact on the quality of 4 health care system of the country. if they are not aligned with the health care and societal demands, there is an imbalance between the need and supply o f d o c to rs i n re l at i o n to t h e n e e d s o f t h e 5,6 community. information regarding medical students' career choices can thus guide restructuring of health care policies in relation to the needs of the society and to ensure provision of workforce according to needs of 2 that community. understanding these influences can also aid in curriculum designing and career 6 counselling for students in medical institutes. this is a descriptive study undertaken to identify the specialty career choices of final year medical students at our medical institute, the gender differences among these choices and the factors which influence their choices. materials and methods the study design was a descriptive cross-sectional survey, conducted in islamic international medical introduction medical sciences have a wide variety of disciplines and specialties. it is a difficult decision for a medical student who is about to graduate from medical school to choose his/ her future career specialty. this decision may depend on a multitude of factors as suggested by various studies. the bland–meurer model was presented in an attempt to give an overview of the complex interplay of factors that determine medical students' specialty choice with the conclusion being that students choose a specialty whose characteristics most closely match 1 their own career needs. some of the common determining variables identified in various studies w e re g e n d e r, i n t e re st s p u r re d b y p ra c t i c a l experience in a particular field during medical years, life style or prestige associated with certain 81 college in april 2013. all final year students were selected through convenience sampling. a 20 items questionnaire was distributed among all final year mbbs students (n=100) during their self-study time slot, to identify their future specialty career choices and underlying reasons of their choice. they were briefed about it and their understanding regarding terminology was checked. they were given 45 minutes to fill in the proforma. the questionnaire was collected at the end of the self-study time. the questionnaire consisted of 20 questions in all, developed after extensive literature review and specialist validation from multiple consultants. the st 1 question was open ended, requesting students to either choose from a list of 18 clinical specialties, write their choice if not listed or select the 'not sure' option. specialties listed were surgery, obstetrics and gynecology, pediatrics, medicine, psychiatry, o r t h o p e d i c s , o p h t h a l m o l o g y, d e r m a t o l o g y, anesthesiology, radiology, public health, family practice, pathology/ laboratory medicine, basic sciences, urology, cardiology, pulmonology and ear, nose, and throat (ent). rest of the 19 were close ended questions based on a likert scale of 1 to 3. these 19 questions were formed on the most likely reasons for career choices based on multiple specialist opinions. these were related to aptitude of the specialty, specialty related illness in self or close others, respect for specialty in the family members, reputation of the specialty in the community, media related hype of the field, higher anticipated income, work experiences in labs and c l e r k s h i p s , m o r e p a t i e n t c o n t a c t , b e t t e r understanding of the discipline, good teacher/ role model, impressive life style of the specialist in the chosen field, parents already practicing in the specialty, peer pressure or friend in the same specialty, more satisfaction, preference to work with a specific community group or gender, better job opportunities, fewer doctors in the chosen specialty, better/ controllable working hours and alternate easier routes for fellowships. non parametric data analysis was done through spss 20 and descriptive statistics were derived. results eighty-two out of 100 final year mbbs students participated in the survey. medicine (18%), surgery (15%) and gynecology (14%) were the top three career choices of students, with family practice coming last in the ranking (1%). the distribution of different specialties chosen by the students is given in fig 1. the top three reasons to choose a specialty were natural aptitude for it, better subject comprehension and work satisfaction for the specialty. the least attributed factors for their choices were easier perceived career advancement, an illness in the family regarding the particular specialty or parents already practicing in that field. the reasons to choose a specialty in order of preference are given in table i. surgery (10%) and medicine (8%) were the top rated specialties in males while females preferred gynecology/obstetrics (14%), medicine (10%) and fig 1: career choice in mbbs final year students table 1: reasons for choosing a specialty, in descending order of preference choice of specialty among mbbs studentsjiimc 2016 vol. 11, no.2 82 surgery (5%) in the descending order. thirteen per cent of the students were not sure about choosing a career. these included10% females and 3% males. none of the male students opted for family practice and only 1% of females opted for it as a prospective future career. the gender differences in choice of specialty careers in main specialties is given in fig 2. 8 6 some but not all studies. also, structural changes in the curriculum with more emphasis on primary 6,9 care experiences encouraged student interest in primary care. family practice was not found to be a 10,11 very desirable choice to pursue. this trend was also evident in our study where only 1% of the students showed an interest to pursue career as a general physician. however other factors like uncontrollable life style and excessive working hours also effected career choice of a specialty. controllable or uncontrollable life style is one of the major determinants in choosing 12,13 a career. life style is influenced by working hours, 14 working in shifts, salaries and job satisfaction. more recently, changes in the workplace environment also influence career choices for example duty-hour limitations designed partly to improve the work 15,16 satisfaction of residents and rapidly increasing s t u d e n t d e b t s e s p e c i a l l y i n t h e w e s t e r n 17 societies. students increasingly prioritize lifestyle 14-16 issues when choosing careers. male medical students in our study were inclined to choose surgery as their topmost choice followed by medicine whereas female students preferred gynecology/obstetrics followed by medicine as their preferred career choice. similar results were found in other studies where males preferred surgical specialty and females were inclined towards 18,19 gynecology and obstetrics. medicine was equally considered as a prospective specialty choice by both 20 the genders. we were not able to correlate our findings exactly to factors that influence career choice in both genders, as generally student satisfaction and understanding of the specialty were the prime reasons of choice in both groups. in literature the two reasons given for variability in male and female students choices was lifestyle controllability and gender biases inherently present 14,20 in some specialties. multiple studies reported female students preferring more controllable lifestyle specialties and considering domestic responsibilities and flexible hours as important variables while choosing specialty career as 14 compared to male students. it is also worth noting that males prefer choosing a career that is technically challenging and has more earning potential and would consider residency conditions and leave 14,20 availability as secondary issues. fig 2: gender differences in career choice in percentage discussion choosing a specialty for post graduate training is a major life decision for medical students on which their future career depends, influenced by multiple factors. in the present study, medicine and surgery were found to be the two top specialties chosen by the 2,3 students as is the trend noted in many local studies 7 as well as in international studies. a significant percentage of students (13%) were found to be unsure of their choice. we have reported 19 reasons of choosing a career in a specialty with aptitude, understanding of specialty satisfaction, more patient contact as the top most reasons. the least chosen reasons were parents working in that specialty, easier routes of specialization and illness in a close relative related to the specialty. multiple studies are available in literature identifying student preferences in post-graduate medical specialization and their influencing factors. several important factors that influence the choice of student include: the emphasis with which the student is taught a particular discipline and as an extension the influence that the teacher of that discipline has. several studies indicate that the subject specialist teacher can influence the choice of career in a student. working with a 'generalist' rather than a specialty/ sub-specialty faculty teacher was associated with selection of a primary care career, in choice of specialty among mbbs studentsjiimc 2016 vol. 11, no.2 83 a significant percentage of students in our study, 13% were unsure of a future career in any field, 10% of whom were female. this indecision has been regarded by studies to be due to lack of information about specialties, perceived equal interest in multiple specialties, lack of career counselling, 1 conflicting interests etc. our study also emphasizes the fact that family practice is one of the last career choice of the students. this dilemma has been addressed by 10,11 multiple local and international studies. however ironically many students in our local context do end up becoming general practitioners by default, due to economic or circumstantial reasons, armed only with an undergraduate degree which becomes a disadvantage for the health care delivery system at 11 large. conclusions and recommendations c l i n i c a l f i e l d s i . e . m e d i c i n e , s u r g e r y a n d gynaecology/ obstetrics remain the most popular student choices probably as a reflection of the more clinically oriented curricula. 'family practice' is a forgotten domain and its importance needs to be stressed. medical curricula should be made more co mmu n it y o riented a n d emp h a s ize o n t h e importance of family practice as a career choice for which health policy makers should take appropriate steps. our study is limited by a relatively smaller sample size and single institutional data. additional prospective, qualitative studies are needed for a better insight on factors influencing gender differences in choosing a specialty, as female students now make a significant bulk of the medical students and future doctors. references 1. bland cj, meurer ln, maldonado g. determinants of primary care specialty choice: a non-statistical meta analysis of the literature. acad med. 1995; 70: 620–41. 2. aslam m, ali a, taj t, badar n, mirza w, ammar a, et al. specialty choices of medical students and house officers in karachi, pakistan. east mediterr heal j. 2011; 17: 74–9. 3. rehman a, rehman t, shaikh ma, yasmin h, asif a, kafil h. pakistani medical students’ specialty preference and the influencing factors. j pak med assoc. 2011; 61:713–8. 4. harris mg, gavel ph, young eannette r. factors influencing the choice of. mja. 2005; 183: 295–300. 5. akhund s, shaikh za, kolachi hb. career related choices of medical students from an international medical college of karachi, pakistan. j liaquat univ med heal sci. 2012; 11: 180–4. 6. querido sj, vergouw d, wigersma l, batenburg rs, de rond mej, ten cate otj. dynamics of career choice among students in undergraduate medical courses. a beme systematic review: beme guide no. 33. med teach. 2016; 38: 18–29. 7. lefevre jh, roupret m, kerneis s, karila l. career choices of medical students: a national survey of 1780 students. med educ. 2010; 44: 603–12. 8. campos-outcalt d, senf j. a longitudinal, national study of the effect of implementing a required third year family practice clerkship or a department of family medicine on the selection of family medicine by medical students. acad med. 1999; 74: 1016–20. 9. coffeng le, visscher aje, th o, cate j ten, coffeng le, visscher a j e, et al. the influence of early clinical experiences on career preference of male and female medical students. med teach. 2016; 31: 323–6. 10. mariolis a, mihas c, alevizos a, gizlis v, mariolis t, marayiannis k, et al. general practice as a career choice among undergraduate medical students in greece. bmc med educ. 2007; 7:15. 11. iqbal s p. family medicine in undergraduate medical curriculum: a cost-effective approach to health care in pakistan. j ayub med coll abbottabad. 2010; 22: 207–9. 12. newton da, grayson ms, thompson lf. the variable influence of lifestyle and income on medical students’ career specialty choices: data from two u.s. medical schools. acad med. 2005; 80: 809–14. 13. dorsey, e ray, jarjoura, david, rutecki . the influence of controllable lifestyle and sex on the specialty choices of graduating u.s. medical students. acad med. 2005; 80: 791–6. 14. dorsey er, jarjoura d, rutecki . influence of controllable lifestyle on recent trends in specialty choice by us medical students. jama. 2003; 290: 1173–8. 15. choi d, dickey j, wessel k, girard de. the impact of the implementation of work hour requirements on residents’ career satisfaction, attitudes and emotions. bmc med educ [ i n t e r n e t ] . 2 0 0 6 ; 6 : 5 3 . a v a i l a b l e f r o m : h t t p : / / w w w . b i o m e d c e n t r a l . c o m / 1 4 7 2 6920/6/53received: 16. vidyarthi ar, katz pp, wall sd, wachter rm, auerbach ad. impact of reduced duty hours on residents’ educational satisfaction at the university of california, san francisco. acad med. 2006; 81: 76–81. 17. phillips jp, weismantel dp, gold kj, schwenk tl. medical student debt and primary care specialty intentions. fam med. 2010; 42: 616–22. 18. lambert tw, goldacre mj, turner g. career choices of united kingdom medical graduates of 2002: questionnaire survey. med educ. 2006; 40: 514–21. 19. huda n, yousuf s. career preference of final year medical students of ziauddin medical university. educ heal chang learn pract. 2006; 19: 345–53. 20. alers m, van leerdam l, dielissen p, lagro-janssen a. gendered specialities during medical education: a literature review. perspect med educ. 2014; 3:163–78. choice of specialty among mbbs studentsjiimc 2016 vol. 11, no.2 84 untitled-1 original article abstract objective: to find out changes in peripheral blood of patients suffering from malaria. study design: descriptive case series. place and duration of study: the study was conducted at shah noor medical laboratory, bannu khyber st st pakhtoon khawa from 1 may 2014 to 31 august 2014. materials and methods: in this study 160 cases of malaria patients were selected by non probability random sampling technique with informed consent of the patients. these patients were subjected to complete blood counts performed by hematology analyzer sysmex 21 and manual method using neubaur's chamber and thick and thin films stained with giemsa stain to confirm malarial parasite. the data was recorded in preformed designed proforma and was analysed by using a statistical package for social sciences (spss) version 16 for percentages, means and standered deviation. results: out of 160 patients 93(58%) were males and 67(41.87%) females. most 59 (36.8%) were in the age range of 1‐10 years. plasmodium vivax found in 135(84.3%) and plasmodium falciparum in 25(15.6%) cases. minimum total leukocyte count (tlc) was 1300/cmm and maximum was 19500/cmm, low hemoglobin level was 4.50 g/dl and high value was 15.20 g/dl. platelets minimum count was 35000/cmm and maximum was 590000/cmm. anemia was present in 103(64.37%), thrombocytopenia was present in 65 (40.62%), leukopenia was present in 34 (21.25%), bicytopenia was present in 24 (15%) and pancytopenia was found in 5 (3.12%) of cases, where as high tlc was encountered in 6 (3.75%) cases. conclusion: this study shows that person suffering from malaria have significant changes in blood morphology especially cytopenias causing morbidity and mrtality needs special attention regarding accurate diagnosis and prompt treatment to avoid the complications. key words: malaria, plasmodium vivax, blood smear, thrombocytopenia, pancytopenia. co u nt r i e s o f ea ste r n m e d i te r ra e a n re g i o n (afghanistan, djibouti, sudan, somalia and yemen) 3,4 shares about 95% of the total burden. malaria if untreated may cause severe morbidity and mortality. major factors responsible in malaria for morbidity and mortality are anemia and cytopenias. thrombocytopenia is a well‐known complication of malaria and has been present in significant number of malaria patients. the white blood cell count in malaria is usually normal but it may be low or raised 5‐8 in severe cases. hematological changes in malaria may vary with severity of infection, endemicity of malaria, hemoglobinopathies, nutritional status of patient, demographic factors, and patient immune status. hematological manifestation of malaria are mainly due to the infection of red blood cells (rbc) by the parasite. the ability of the various plasmodia to infect rbcs is related to their attachment to specific red cell membrane receptors e.g plasmodium vivax and ovale invade only reticulocytes, plasmodium malariae invades only mature rbcs and plasmodium falciparum invades erythrocytes of all ages, as a result the proportion of rbcs parasitized in vivax introduction malaria is the most common parasitic disease transmitted by an infected female anopheles mosquito. malaria transmission occurs in all six who regions. globally an estimated 3.2 billion people are at risk of being infected with malaria and developing disease, and 1.2 billion are at high risk (>1 in 1000 1 chance of getting malaria in a year). four species of plasmodium can cause human disease, plasmodium falciparum, vivax, ovale and malariae. the disease is endemic in tropical and subtropical areas of asia, africa and north and south america. worldwide most of the malarial infections are caused by plasmodium vivax, it is the most common infection in pakistan especially in 2 khyberpakhtoonkhwa. pakistan in the group 3 blood morphology of patients suffering from malaria 1 2 3 4 mohammad sajjad , zard ali khan , mohammad akram , mokamil shah blood morphology in malariajiimc 2015 vol. 10, no.4 correspondence: dr. mohammad sajjad associate professor, pathology bannu medical college, bannu e‐mail: sajjadkhattak66@gmail.com 1,2,4 4 department of pathology/ community medicine bannu medical college, bannu received: september 19, 2015; accepted: november 17, 2015 251 rarely exceeds 1 % and in contrast in falciparum as many as 50% of cells may be infected indicating that va rio u s p la s m o d iu m s p ec ies u s e d ifferent 1,9‐14 receptor. the incubation period for plasmodium vivax is usually between 12 and 17 days, but it may be prolonged to 8‐9 months or even longer, in plasmodium falciparum and ovale infection this period is from 12 to 18 days and it forms liver hypnozoites and in plasmodium malariae it is 18‐40 15,16 days; it does not form liver hypnozoites. malaria is diagnosed by microscopic examination of the blood thick and thin films from finger prick after aseptic measures. two drops of blood are placed on the slide, one for thin smear and other for thick smear. for making good smears practice is mandatory. monocytes containing pigment are cleared more 17 slowly than pigment containing neutrophils. before a thick film smear is judged to be negative, 100 to 200 fields should be examined under oil immersion. phagocytosed malarial pigment is sometime seen i n s i d e p e r i p h e r a l b l o o d m o n o c y t e s o r polymorphonuclear leukocytes and may provide a clue to recent infection if malaria parasites are not 18 detected. the diagnosis of malaria rests on the demonstration of asexual forms of parasite in the stained peripheral blood smears. after a negative blood smear, repeat smears should be made if there is a high degree of 19 suspicion. chinese researchers have shown that smears from intradermal blood may contain more mature forms of plasmodium falciparum than the peripheral blood. this is considered to allow a more complete assessment of severe malaria. the smears are taken from multiple intradermal punctures with a 25 gauge needle on the volar surface of the upper forearm. the puncture should not ooze blood spontaneously, but sero‐sanguinous fluid can be expressed on the 20 slide by squeezing. changes in peripheral blood: most commonly observed changes in the peripheral blood of malarial patients are thrombocytopenia, anemia and changes in leukocytes. anemia: hemoglobin less than 10.0 g/dl thrombocytopenia: platelet count less than 150,000/cmm leukopenia: total leukocyte count less than 4000/cmm leukocytosis: total leukocyte count more than 11000/cmm materials and methods this was a descriptive case series study performed in shah noor medical laboratory at bannu, kpk. st pakistan. the duration was three months from 1 st may, 2014 to 31 august, 2014. the inclusion criteria was all those patients with diagnosed malarial infection on blood smears. exclusion criteria was malaria patients suffering from known chronic illnesses like tuberculosis or malignancy. in this study 160 cases of malaria patients were selected by non probability random sampling technique with informed consent of the patients. all the malaria positive patients who came to the shah noor medical laboratory for malaria test were selected for this study. two ml blood was taken using 5 cc disposable syringe, slide both thick and thin were prepared and rest of the blood was placed in edta tube for hemoglobin estimation, total leukocyte count and platelets count by both hematology analyzer sysmax kx 21 and were also confirmed manually. the data of positive malarial cases and laboratory findings of complete blood count investigations were recorded on a proforma specially designed for this purpose. all the studied variables like age, sex, type of parasite, hemoglobin level, total leukocyte count and platelets count were analyzed for descriptive statistics like percentages, mean and standard deviation as well as male to female ratio was calculated by using a computer program statistical package for social sciences (spss) version 16. results in this study it was found that out of 160 malaria patients 93 (58.2%) were males and 67 (41.8%) were females, with male to female ratio of 1.38:1. most common age group of in this study was from 1‐10 years with the frequency of 59 (36.8%) cases, 39 (24.37%) patients were in the age group of 11‐20 years, 27 (16.87%) cases were in the age group of 21‐ 30 years, 19 (11.87%) cases were in the age group of 31‐40 years and 16 (10%) cases were in the age group of 41 years and above. minimum age in this study was 02 year and maximum was 65 years. (table i). blood morphology in malariajiimc 2015 vol. 10, no.4 252 amongst the various malarial parasites plasmodium vivax was present in 135 (84.33%) cases and plasmodium falciparum was found in 25 (15.67%) cases, where is no case of plasmodium ovale and malaria were identified. (table ii). the normal hemoglobin (hemoglobin level more than 10 gm %) was present in 110(68.75%) of cases. anemia (hemoglobin level less than 10 gm %) was present in 50(31.25%) of cases. the lowest hemoglobin level was 4.50 gm% and maximum was 15.20 g%., mean was 11.43 g/%l. regarding peripheral blood picture it was found that minimum total leukocyte count (tlc) was 1300/cmm and maximum was 19500/cmm, mean was 7436.25/cmm. low count was found in 34 (21.25%) of cases and high in 6(3.75%) of cases where is it was normal in 120 (75%) of cases. t h e n o r m a l p l ate l et co u nt i s 1 5 0 , 0 0 0 to 450,000/cmm. the lowest platelets count noted was 35,000/cmm, where is highest platelets count was 590,000/cmm. in total of 160 patients 94 (58.75%) patients platelets count was normal, in 64(40.62%) it was low and in 1(o.62%) it was high i.e reactive thrombocytosis was present. bicytopenia was present in 24 (15%) and pancytopenia was observed in 3(1.87%) cases of malaria patients in this study. (table iii). discussion malaria is caused by a parasite called plasmodium which is transmitted via the bites of infected mosquitoes. in the human body, the parasites 1 multiply in the liver, and then infect red blood cells. about 3.4 billion people‐ half of the world population are at risk of malaria. in 2012 there were about 207 million malaria cases and an estimated 627,000 1,21 malaria deaths. in this study malaria was commonly found in children age group (1‐10 years) 59(36.8%) followed by age group (21‐30 years) and (31‐40 years) 39(24.37%) and 27(16.87%) respectively. the same age group in descending order with different percentages were 11 present in a study conducted by yasinzai et al. in the present study male patients suffered from malaria were 58.2% and females 41.8% with male female 3 22 ratio of 1.38:1, where is in atif et al ,and idris et al males were 67.35% and 55.17% and females were 32.7%,36.1% and 44.82% respectively. male predominance is also observed in another study 16 conducted by yasinzai et al , this was 86.2% in males and 13.17% in females. males are more susceptible to many protozoan infections than females and field and laboratory studies link this increased susceptibility to infection with circulating steroid hormones. among humans, although the incidence of infection is often similar between the sexes, sex differences in the intensity of infection are reported in which men have higher parasitemia than women 1 (who). in our study of 160 cases of malaria patients, vivax malaria was found in 135(84.33%) cases and falciparum malaria was found in 25(15.67%) of cases. 22 in idris et al vivax malaria was found in 72.4%, falciparum in 24.1% and in 3.44% mixed infection was found, where is no mixed infection was found in our study. these findings are consistent with other 14 study conducted in karachi by mehmood et al , while this incidence is quite different in studies 15 conducted in nawabshah by akhund et al and in 19 quetta by sheikh et al show an increase incidence of plasmodium falciparum 55.55% and 65.82% respectively, and that of plasmodium vivax 44.44% and 34.17% respectively. malaria is an annual killer of over one million people globally and its essential co‐morbidity is anemia. anemia due to malaria is a major health problem in blood morphology in malariajiimc 2015 vol. 10, no.4 table i: age group and gender distribu�on of malarial pa�ents (n=160) table ii: percentage of pa�ents suffering from types of malarial parasites (n=160) table iii: common hematological parameters in malarial pa�ents (n=160) 253 endemic areas particularly for young children and in 1 women of reproductive age (who). in our study anemia (hemoglobin less than 10 gm/dl) was found in 60 (37.5%) patients. severe anemia (hemoglobin <4.5gm/dl) was found in two cases only. 3 in study conducted by aatif et al anemia was found 8 in 21.5% of cases. in a study conducted by jain et al anemia was recorded in 66 (94.28%) patients, in which 37 (56.06%) were plasmodium falciparum, 21 (31.81%) were plasmodium vivax and 8 (12.12%) had mixed plasmodium falciparum and vivax infection. in 20 another study conducted by abro et al in the infectious diseases unit of rashid hospital dubai anemia was observed in 64% of the patients. in our study thrombocytopenia (platelet count less than 150,000/cmm) was present in 65 (40.62%) of 3 the cases. in a study conducted by aatif et al 100% of the patients were having platelets count less than 150,000/cmm, where is 66.61% were having platelets count less than 50,000/cmm. in a study 6 conducted by mehmood et al at pakistan field level ii hospital, united nations mission in liberia, it was found that out of 145 diagnosed cases of malaria 109 (75.18%) had thrombocytopenia. in another study 21 conducted by rajput et al in india 88.88% patients with acute plasmodium vivax malaria were suffering from thrombocytopenia. thrombocytopenia was also found in 83% of cases in a study conducted 20 dubai by abro et al. this present study results are quite different from other studies results regarding thrombocytopenia conducted locally and abroad, the reason may be either low sensitivity of automatic hematology analyzer regarding platelets count as seen in routine practice. leukopenia was found in 34 (21.25%) of the patients, where is leukocytosis was found in 3.75% of cases. in a study conducted by aatif 3 et al leukopenia was found in 43.9%, another study 21 conducted in india by rajput et al leukopenia was observed in 14% and leucocytosis in 4.9% cases. thus our study in term of leukocyte count is relatively near to these studies. conclusion this study show that person suffering from malaria have significant changes in blood morphology especially cytopenias causing morbidity and mrtality needs special attention regarding accurate diagnosis and prompt treatment to avoid the complications. references 1. world malaria report, geneva: world health organization (who); 2014: 1‐5. 2. rahim f, younis m. malaria in children: clinical profile and response to treatment. a district level experience. pak j med sci 2003; 11: 21‐5. 3. aatif s, jamaj q, altaf a, salimullah. is vivax malaria realy benign?‐a karachi based study. jpma 2013; 63: 721‐4. 4. khattak al, ali w, khan na, satti l, idris m. response o f p l a s m o d i u m v i v a x m a l a r i a i n d u c e d thrombocytopenia to antimalarial treatment. jamc. 2014; 26: 463‐5. 5. hafeez m, lodhi fr, akhtar z, ali mz, aijaz a. a severity of thrombocytopenia in patients with plasmodium vivax malaria; a single center study. jamc.2015; 27: 61‐3. 6. mahmood a, yasir m. thrombocytopenia: a predictor of malaria among febrile patients in liberia. infect dis j 2005; 14: 41‐4. 7. memon ar, afsar s. thrombocy topenia in hospitalized malaria patients. pak j med sci 2006; 22: 141‐3. 8. jain m, kaur m. comparative study of microscopic detection methods and haematological changes in malaria. indian j pathol microbiol 2005; 48: 464‐7. 9. ladhani s, el bashir h, patel, vs, shingadia d. childhood malaria in east london. pediatric infect dis j 2003; 22: 814‐9. 10. makkar rps, monga sma, gupta ak: plasmodium v i v a x m a l a r i a p r e s e n t i n g w i t h s e v e r e thrombocytopenia. braz j infect dis 2002; 6: 263‐5. 11. yasinzai mi, kakarsulemankhel jk. incidence of human malaria infection in central areas of balochistan: mastung and khuzdar. rawal med j 2007; 32: 176‐8. 12. memon ia, kanth n, murtaza g. chloroquine resistant malaria in children. j pak med assoc 1998; 48: 98‐100. 13. shaikh wm, isran sh. a survey of malaria parasite in febrile population of larkana district. pak j med res 1999; 38: 96‐8. 14. mahmood kh. malaria in karachi and other areas in sindh. pak armed forces med j 2005; 55: 345‐8. 15. akhund aa, shaikh ar, khaskheli aa, rajpar gm, shaikh rb. speciation and blood cell parameters in 481 cases of malaria in nawabshah. specialist: pak j med sci 1994; 10: 119‐22. 16. yasinzai mi, kakarsulemankhel jk. incidence of malaria infection in rural areas of district quetta, blood morphology in malariajiimc 2015 vol. 10, no.4 254 pakistan. j med sci 2003; 3: 766‐72. 17. yasinzai mi, kakarsulemankhel jk. a study of prevalence of malaria infection in urban areas of district quetta, pakistan. pak j zool 2004; 36: 76‐9. 18. khan as, qureshi f, shah ah, malik sa. spectrum of malaria in hajj pilgrim in the year 2000. j ayub med coll abbottabad 2002; 14: 19‐21. 19 sheikh as, sheikh aa, sheikh ns, paracha sm. endemicity of malaria in quetta. pakistan j med res 2005; 44: 41‐5. 20 abro ah, ustadi am, younis ns, abdou as, hamad da, saleh aa. malaria and hematological changes. pak j med sci 2008; 24: 287‐91. 21 rajput r, singh s, meena, tiwari uc. pulmonary manifestations in malaria. j indian med assoc 2000; 98: 612‐4. 22. idris m, sarwar j, fareed j. pattern of malaria infection diagnosed at ayub teaching hospital abbottabad. j ayub med coll abbottabad 2007; 19: 35‐6. blood morphology in malariajiimc 2015 vol. 10, no.4 255 original�article abstract objective: to assess awareness and perception of general public regarding thalassemia and premarital screening and determine the association of various socio demographic variables with awareness of public. study design: this was a descriptive cross-sectional study. st place and duration of study: the study was conducted at rawalpindi cantonment areas from 1 june 2017 to th 20 december 2017. materials and methods: this study was conducted among 200 people in 20 to 60 years age group, residing in different settings of rawalpindi cantonment over a period of six months. data was collected from respondents selected through multistage probability sampling by pretested and validated questionnaire. results: statistical analysis showed 48.5% of participants had adequate knowledge about thalassemia and premarital screening, while 39.8% perceived its importance and 39.2% perceived that legislation will be beneficial for prevention of thalassemia in our country. conclusion: based on study results it is concluded that majority of participants had adequate knowledge regarding thalassemia and premarital screening. education is highlighted as significant factors towards their perception regarding importance of mandatory premarital screening legislation in pakistan. key words: awareness, genetic, pre-marital screening, thalassemia. here leading to more than 5000 births of transfusion2 dependent thalassemia (tdt) each year in pakistan. presently there are estimated 100,000 cases of thalassemia in pakistan, which making up for almost 5% of world cases. this situation is serious and alarming in our country as thalassemia can be a serious threat in coming years in absence of appropriate genetic counseling and proper screening. consanguinity is the main factor to high 3 prevalence in pakistan. thalassemia diagnosis is clinical along with laboratory assistance in the form of blood complete examination, hb electrophoresis and confirmation by genetic analysis if obligatory. the treatment approach varies according to socioeconomic condition of parents and the country. the best treatment choice is bone marrow transplant that is available in our country but its high cost is a major hurdle. the other treatment options are supportive like repeated blood transfusion along with iron chelation therapy, splenectomy and hb f augmentation. this lifelong transfusion therapy with 4 iron chelation therapy puts a huge financial burden. thalassemia is a major public health problem, but it is preventable by adopting various preventive strategies and methods. incidence of thalassemia major has been reduced in many countries through introduction thalassemia is a hereditary blood disorder, which along with medical complications having psychological, social and financial impact at the patient, their family and whole society. it is categorized into alpha or beta thalassemia depending on absence of globin chain. its occurrence is high in a broad belt which extends from mediterranean basin through to middle east, south east asia, and indian subcontinent. globally 15 1 million patients have clinically apparent disorder. in pakistan, frequency of β-thalassemia gene is 5-8% and is present in all ethnic groups. it is estimated that approximately 9 million β-thalassemia carrier are awareness and perceptions regarding thalassemia major and premarital screening in general public of cantonment areas of rawalpindi 1 2 3 iffat noor , rukshana roshan , rehama gilani correspondence: dr. rehama gilani senior lecturer department of public heath national university of medical sciences, rawalpindi e-mail: rehma.gilani@numspak.edu.pk 1 lecturer, department of community medicine, cmh kharian medical college, national university of medical sciences, rawalpindi 2,3 department of public health, armed forces of post graduate medical institute (afpgmi), national university of medical sciences, rawalpindi funding source: nil; conflict of interest: nil received: august 05, 2019; revised: april 20, 2020 accepted: may 06, 2020 thalassemia major awareness and premarital screeningjiimc 2020 vol. 15, no.2 108 effective preventive programs. according to pakistan bureau of statistics, per capita annual income during 2013 was $1380 as, comparison to the estimated 6000 dollar per year cost of appropriate 5 management of a thalassemia case. thalassemia screening preceding marriage is actually a more easier and cost-effective tool. government of pakistan is now planning for the implementation of a law for pre-marital screening as a mandatory procedure to curtail the burden of this disease. the aim of this study was to determine the awareness of general population about thalassemia and their perception regarding the pre-marital screening law for thalassemia, as no such survey has been conducted among the general population. materials and methods this descriptive cross sectional study was conducted in areas of rawalpindi cantonment during six months st th from 1 june 2017 to 30 december 2017. study population comprised of general public residing in the sampled areas. people of both genders between age group of 20-60 years, willing to participate, were included in the study. the ethical approval was taken from institution review board (irb). sample size was calculated based on the prevalence of knowledge 6 about thalassemia in pakistan. multistage probability sampling technique was used. at first stage of sampling, ward and areas were selected. rawalpindi cantonment consists of twelve wards, each having 12-14 residential areas. through simple random lottery mechanism, ward number eight was selected, which has twelve residential areas. from this ward every third area was selected by using simple random lottery again. fifty participants were selected from each area by convenience sampling method to achieve a total sample size of 200 respondents. the data collection instrument used was a self-designed, self-administered questionnaire developed with the help of previous studies comprising of both open and close-ended questions. data analysis was done by using version 22 of spss. in descriptive analysis mean and standard deviation of age and years of education was calculated. frequency and percentage of all categorical variables like gender, marital status, consanguinity of parents, consanguinity of couples, family history of thalassemia and knowledge (adequate, inadequate) were determined. chi square test was applied to examine possible association between socio demographic characteristics and awareness of participants pvalue < 0.05 was taken as significant. results the number of sampled participants completed the questionnaire were 200 with a response rate of 99.5%. the sociodemographic characteristics are given in table i. a significant number of study participants 140 (73.3%) claimed having awareness about thalassemia. among them 115(61.5%) could correctly identify thalassemia as hereditary diseases. 140(76.1%) participants correctly identified pallor as most apparent sign of thalassemia. 157(87.2%) respondents correctly identified thalassemia can lead to decreased blood formation. 114 (62.3%) were not aware regarding availability of thalassemia screening test, 64(35.2%) identified television as the major source of information, 147(86.0%) correctly identified blood transfusion as main treatment of thalassemia, 119(66.9%) participants knew about the importance of premarital screening who identified it as a blood test of a couple before marriag74(39.8%) of participants strongly agreed that premarital screening is a reliable preventive measure for thalassemia71(35.5%) participants strongly agreed, that legislation is important 105 (51.6%) considered that involvement of religious scholars will be one of the beneficial preventive strategies for thalassemia, adequate awareness was observed about thalassemia and premarital table i: demographics characteris�cs of par�cipants thalassemia major awareness and premarital screeningjiimc 2020 vol. 15, no.2 109 screening in 103(51.5%) participants. chi square test showed that educated participants were more likely to have adequate knowledge while consanguineous marriages had association with inadequate knowledge. among other variables (age, gender and marital status). this is in accordance with a study conducted 6 7 in kolkata. another study in iran showed females reflected better knowledge of thalassemia, and in 8 bahrain university students and professionals who were married had better knowledge of thalassemia. adequate awareness about thalassemia and premarital screening was observed in 48.5% of participants in our study which is higher than a study conducted in karachi university where 78% students did not have adequate awareness about the disease 9 6 7 and its consequences. kolkata and sri lanka study, conducted in general population showed 57.94% respondents had better knowledge about thalassemia. the study conducted at rural bengal by 8 9 mittak et al and at lahore by ishaq et al showed 22.27% and 44.6% participants respectively were aware that thalassemia is a genetic disorder. our study revealed that about 61.05% had adequate knowledge about the inherited nature of the disease; this is similar to kolkata study. 6 it was also 6 observed in kolkata study that two third of the study population were aware about blood transfusion as the essential treatment. the reason is the untiring efforts of many local and international thalassemia societies working at grassroot level in the communities. another reason is that regular blood transfusion creates much economic strain on families that people near to them also become aware of this difficult treatment. premarital screening is playing a vital role in reducing burden of disease in countries where it is mandatory by law. studies 10,11,12 13 conducted in saudi arabia oman and 14 palestine showed that majority of respondents were aware of premarital screening program but survey 15 conducted at quetta showed only 35.2% respondents had awareness about premarital screening. the limitation of this study is the short duration of the project and it does not give insight about the disease among the rural population. conclusion this study concluded that although our local population has adequate knowledge regarding thalassemia and premarital screening, it is imperative that government should implement the law in letter and spirit in order to reduce the burden of disease. table ii: associa�on between demographic characteris�cs and awareness of respondent about thalassemia (n=200) fig 1: opinion of par�cipants about most appropriate preven�ve method for thalassemia discussion in this study, participants with different sociodemographic background were approached and their awareness and perceptions were assessed. only education was found to be associated with better awareness while no association was found thalassemia major awareness and premarital screeningjiimc 2020 vol. 15, no.2 110 references 1. lodhi y. economics of thalassemia management in pakistan. thalassemia awareness week. 2003; 20(2): 105 12. 2. fatima i, yaqub n, anwar t, nisar yb, khalid s, gilani s. prevalence of endocrine complications in transfusiondependent beta thalassemic pakistani patients. int j pathol. 2014;12(2):77-82. 3. sardinia u, france i. beta thalassemia major: a preventable disease, where do we stand? 2014; 15(6): 443–7. 4. ansari sh, shamsi ts. thalassaemia prevention programme. haematology updates. 2010; 5: 238. 5. shariq m, moiz b, zaidi n, azhar wb, iqbal w, humaira a, et al. pre-marital screening for beta thalassaemia in pakistan: an insight. journal of medical screening. 2014; 21(3): 163-4. 6. basu m. a study on knowledge, attitude and practice about thalassemia among general population in outpatient department at a tertiary care hospital of kolkata. j preven medic holistic health. 2015; 1(1): 6-13. 7. mudiyanse r, senanayake m, rathnayake r. safe marriages” for thalassaemia prevention: a kap survey in sri lanka. transl biomed. 2015; 6: 3. 8. mittal, p., & srivastava, s. (2006). diet, nutritional status and food related traditions of oraon tribes of new mal (west bengal), india. 9. ishaq f, abid h, kokab f, akhtar a, mahmood s. awareness among parents of β-thalassemia major patients, regarding prenatal diagnosis and premarital screening. journal of the college of physicians and surgeons--pakistan : jcpsp. 2012 apr;22(4):218-221. doi: 04.2012/jcpsp.218221. 10. alam aa. perception of female students of king saud university towards premarital screening. journal of family & community medicine. 2006; 13(2): 83-88. 11. al-kahtani nh. acceptance of premarital health counseling in riyadh city, 1417h. journal of family & community medicine. 2000; 7(2): 27-34. 12. ibrahim nk, al-bar h, al-fakeeh a, al ahmadi j, qadi m, albar a, et al. an educational program about premarital screening for unmarried female students in king abdul-aziz university, jeddah. journal of infection and public health. 2011; 4(1): 30-40. 13. al kindi r, al rujaibi s, al kendi m. knowledge and attitude of university students towards premarital screening program. oman medical journal. 2012; 27(4): 291-6. 14. el sahrif n, el refae a, el asi s, el ahmaidat a. attitudes and opinions of palestinian decisionmakers about premarital examination law. 2006; 12(6): 873-885. 15. ahmed a, saleem f, iqbal q, haider s, anwer a, anwar m. perception towards premarital medical screening: a cross sectional assessment among young adults in quetta city, pakistan. indo american journal of pharmaceutical sciences. 2017; 4 (1): 1-7. thalassemia major awareness and premarital screeningjiimc 2020 vol. 15, no.2 111 76 editorial simulation in health care rizwan hashim simulation is usually perceived as the advancement in technology to create experiences that are focused towards clinical applications. this is not a holistic view of this sphere. in fact, it is the integration of knowledge and affective domains that are structured carefully to involve different techniques, related equipment's and courses. these are well structured activities that are designed for different levels of participants having diverse levels of expertise. besides others, one reason for introduction of simulation in medical field is to groom physicians 1 who are safe practitioners. the history of clinical skill th lab is traced back to the 17 century in france, where manikins using the foetal model and pelvis were used. these training were given to the paramedical 2 staff namely midwives by madame du coudray. in modern times the basis for standardization of training in simulation medicine dates back to resusci anne who managed the training by providing manikins that were simple to use and were low cost. later on abrahamson developed the simone simulator that was aimed to train the novice to learn the insertion of endotracheal tubes. this was a 3,4 high fidelity simulator. this development was followed in 1980 by the development of comprehensive anesthesia simulation environment 5 (case) where the simulator was linked to a program. from there on, barrows introduced the concept of provision of an environment that was safe and helped the participant to practice where skills with 6 simulated patients. to this date more advanced technological equipments that have capabilities of running computer assisted programs, virtual reality and even tactile sensations modalities have been 7 introduced. recent advances in simulation there are a wide variety of simulators that are available for use; the choice mainly depends on the requirement of the training that it has to be used for. the common types that are extensively used are as follows: part-task trainer: this is commonly used for imparting training related to psychomotor and procedural skills. they are used for practice and achieving proficiency. it has both low fidelity such as venipuncture, male and female pelvic models; skin and tissue materials that can be used for practicing injections and suturing with various materials and needles, more over, it can also have high fidelity 8 training equipment. computer based systems: these have developed over the period from simple interfaces to advanced programs. they have been usually used for basic sciences with the provision that the participants can practice on them with their own pace. the ability to provide appropriate feedback helps the learner to reinforce what is right and correct what they have 9 not attempted correctly. such interfaces are usually of low cost, whereas they have a drawback that they require a trained teacher to teach the participants 10 how to use them. virtual reality and haptic systems: in virtual reality the technology is used to generate images of objects and environment. these are visualized by the participants using high tech gears and goggles that are connected with various computer systems, the individual has the freedom to interact with those images and objects with the help of various gadgets that are provided with the setup. in haptic systems there is provision of adding the tactile and kinesthetic capability in the equipment. when the virtual reality and haptic systems are integrated they provide a much enriched experience to the learner. the presence of recordings and tracking systems in the devices helps to generate data that can be used for feedback as well as a record of practice sessions 11 carried out by the participant. these are usually applied for advanced training in complex skills like 12 endoscopy and laparoscopy. integrated simulator models: in these simulators correspondence: prof. dr. rizwan hashim professor, of pathology fazaia medical college, air university, islamabad e-mail: riznajmi20011@hotmail.com received: may 23, 2019; accepted: march 17, 2020 department of pathology fazaia medical college, air university, islamabad need to be appropriately prepared before they start handling patients, they do not hesitate to voice their distress with the hospital management, for safe handling of the patients by the health care workers at 18 all levels . these growing issues can be attended by formal practice of a wide range of procedures and skills in simulated environments in the clinical skill labs both for the undergraduate and postgraduate trainees aiming at the better patient care and outcomes. references 1. sahu, chattu vk, rewatkar a, sakhamuri s. best practices to impart clinical skills during preclinical years of medical curriculum. j educ health promot. 2019;8(1):57. 2. bradley p. the history of simulation in medical education and possible future directions. med educ. 2006;40(3):254–62. 3. good ml. patient simulation for training basic and advanced clinical skills. med educ. 2003;37 suppl 1:14–21. 4. abrahamson s, denson j. effectiveness of a simulator in training anesthesiology residents. saf heal care. 2004;13(5):395–7. 5. gaba d, deanda a. a comprehensive anesthesia simulation environment: re-creating the operating room for research and training. anesthesiology. 1988;69(3):387–94. 6. barrows h. an overview of the uses of standardized patients for teaching and evaluating clinical skills. aamc. acad med. 1993;68(6):443–51. 7. jr gl, banerjee p, luciano c. virtual reality in neurosurgical education: part-task ventriculostomy simulation with dynamic visual and haptic feedback. neurosurgery. 2007;61(1):142–8. 8. weller jm, nestel d, marshal sd, brooks pm, conn jj. simulation in clinical teaching and learning. med educ. 2012;196(may):1–5. 9. nwosu jc, john hc, akorede oj. availability and accessibility of ictbased instructional tools in medical colleges in ogun state, nigeria. educ res rev. 2018;13(11):391–8. 10. nyssen as, larbuisson r, janssens m, pendeville p ma. a comparison of the training value of two types of anesthesia simulators: computer screen-based and mannequin-based simulators. anesth analg. 2002;1;94(6):1560–5. 11. almousa o, prates j, yeslam n, mac gregor d, zhang j, phan v, et al. virtual reality simulation technology for cardiopulmonary resuscitation training: an innovative hybrid system with hapticffeedback. simul gaming. 2019;50(1):6–22. s 12. guze pa. using technology to meet the challenges of medical education. trans am clin climatol assoc. 2015;126:260–70. 13. al-elq a. simulation-based medical teaching and learning. j fam community med. 2010;17(1):35–40. 14. sadideen h, hamaoui k, saadeddin m, kneebone r. simulators and the simulation environment: getting the balance right in simulation-based surgical education. int j there is integration of the manikins with the computers and the outcomes are displayed on monitors. they are used to display common data regarding ecg, pulse oximetry and methodology like insertion of chest tube and passing of urinary catheter, the manikins also respond to the administration of various therapeutic agents. the various available models are both high and low 13 fidelity simulators. simulated environment: the simulation facilities are placed at a variety of settings according to the requirement of the learning outcomes for which they are planned to be used. these specific environments can range from simple teaching and learning rooms, where simulated environments are created to create patient wards, operating rooms, emergency rooms, intensive or coronary care units and sometimes domestic settings and road or ambulance 14 environments. tailored training: in the clinical skill labs the training requirements can be designed according to the desires of the team or the individuals of the team. this includes both the beginners and the experts. in clinical skill labs the speed of the various training components of the events can be regulated and modified according to the requirements of trainee. in regular occurrences the physiological events following certain medical situations keep happening and for patient safety they have to be taken over by the treating physicians and the trainees do not get enough time for decision making and implementing their choices, this deficit can be easily managed in clinical skill labs on manikins and high fidelity 13,15 equipment without compromising patient safety. in recent years medical curriculum has undergone 16 major changes both internationally and nationally. the introduction of outcome competency based curriculum has been adopted to develop required knowledge, skill and attitude. the same can be acquired through well designed activities in the 17 clinical skill labs. amongst several issues, one of the many factors positively influencing the developments of clinical skill labs in both undergraduate and postgraduate teachings is the fact that, patients remain central to the teaching in medical education, but at the same time there is growing concern among the patients and their relatives that the medical students and practitioners 77 jiimc 2020 vol. 15, no.2 17. przybyl h, androwich i, evans j. using high-fidelity simulation to assess knowledge, skills, and attitudes in n u rs e s p e r fo r m i n g c r rt. n e p h ro l n u rs j . 2015;42(2):135–48. 18. salas e, paige jt, rosen ma. creating new realities in healthcare: the status of simulation-based training as a patient safety improvement strategy. bmj qual saf. 2013 jun 1;22(6):449–52. surg. 2012 jan 1;10(9):458–62. 15. qayumi k, pachev g, zheng b, ziv a, koval v, badiei s, et al. status of simulation in health care education: an international survey. adv med educ pract. 2014 jan 28;5:457–67. 16. gishen k, ovadia s, arzillo s, avashia y, thaller sr. the current format and ongoing advances of medical education in the united states. j craniofac surg. 2014 jan;25(1):35–8. jiimc 2020 vol. 15, no.2 78 original�article abstract objective: to investigate the protective effect of a herb tribulus terrestris on nifedipine induced damage on microstructure of testes. study design: animal experimental study. place and duration of study: the present study was undertaken for a period of 18 months with effect from october, 2012 to april, 2014 at shifa college of medicine, islamabad. materials and methods: male sprague dawley rats (n=120) were divided into four groups, each comprising of 30 rats. group a was given (dmso), whereas group b, c and d were given nifedipine only, dimethyl sulfoxide tribulus terrestris only and nifedipine and tribulus terrestris both respectively, by oral route for 56 days. at the end of experiment the diameter of seminiferous tubules and height of germinal epithelium was measured in h& e stained slides of testes in all groups and then compared. results were analyzed on spss version 22. results: there was a significant difference in mean tubular diameter and height of germinal epithelium of testes between nifedipine only group and treated rats which were given tribulus extract with nefidipine, showing its protective effect on the treated group. conclusion: extract of helps in inhibiting the damaging effects of nifedipine on tribulus terrestris histomorophometry of testis. key words: infertility, testis histomorphometry, nefidipine, tribulus antimalarial and antihypertensive all have been reported to induce either permanent or temporary 2 infertility. hypertension (htn) is an emerging problem of modern era. it has been estimated that about 1 billion people worldwide have htn and is 3 expected to increase to 1.56 billion by 2025. national health survey of pakistan assessed that only 50% of the people with htn were diagnosed and only half of those diagnosed were getting 4 treatment for htn. hypertension has to be treated vigorously as it is a stepping stone of variety of complications. numbers of antihypertensive drugs are in use, naming a few: diuretics, angiotensin converting enzyme inhibitors, beta-blockers, calcium channel blockers (ccbs). ccbs became the best-selling antihypertensive since early 1990'still today because it is effective in controlling blood 5 pressure at all age groups. 2+ role of calcium ions (ca ) as ubiquitous second 6 messenger system has long being recognized. in male reproductive organs increase in intracellular 2+ ca through voltage gated calcium channels (vgccs) induced by lh is indispensable for testosterone production. ions induce increase in activity and 2+ ca introduction infertility, whether primary or secondary, has always been a public health concern worldwide. as many as 15% of couples have difficulty while conceiving with male factor being responsible in up to 50% of such 1 cases. out of a long list of risk factors, certain therapeutic drugs like cytotoxic, anti-convulsant, protective effect of tribulus terrestris on nifedipine induced damage to microstructure of testes of rats correspondence: dr. sidra hamid department of physiology rawalpindi medical university rawalpindi pakistan e-mail:drsidraqaiser@gmail.com 1 3 department of physiology / medicine rawalpindi medical university rawalpindi pakistan 2 department of anatomy rawal institute of health sciences 4 department of medical technology shifa tameer-e-millat university islamabad 5 department of pharmacology hbs medical & dental college islamabad 6 head vfms, laboratory animal house national institute of health islamabad 7 department of physiology national university of medical sciences rawalpindi funding source: nil; conflict of interest: nil received: march 27, 2018; revised: sep 05, 2018 accepted: sep 09, 2018 protective role of tribulus on ccb infertilityjiimc 2018 vol. 13, no.3 151 1 2 3 4 5 6 7 sidra hamid, shazia muazam, qaiser aziz, zia-ur-rehman farooqi, amanat ali, hussain ali, muhammad aslam tribulus no literature is available so far. therefore the objective of the study was to determine the protective effect of tt on nifedipine induced changes in microstructure of seminiferous tubules. materials and methods an animal experimental type of research was undertaken from october, 2012 to april, 2014 at the end college of medicine, islamabad and national institute of health sciences (nih), islamabad. after an approval from the institutional review committee of shifa college of medicine. one hundred and twenty (n=120), 90-120 days old male sprague dawley rats, weighing approximately 180-250g, were selected through non-probability convenience sampling from the animal house of nih, islamabad. rats with any obvious physical pathology were excluded. they were divided into four groups having thirty rats each and were tagged with permanent marker on their dorsal body wall in their respective groups. each group was kept in separate cage under standard laboratory conditions, acclimatizing for one week at a room temperature of 23-25°c with a 12 hour dark/light cycle. they were allowed to feed and drink ad libitum on standard pellet diet and tap water. nifedipine (sigma aldrich product no. n7634) and dimethyl sulfoxide (sigma aldrich product no. d5879) was purchased from the local distributors. aqueous fruit extract of tt was made from fruits of tt after plant identification from herbarium of quaid-e-azam university. fruit about 500 gms was powdered and soaked in 1 liter of distilled water overnight. after filtration the filtrate was dried at reduced temperature using rotary evaporator and then incubated at room temperature for 2 days. the 19 dry mass served as an aqueous fruit extract of tt. gavage needle was used to administer the s u bstan ces o rally. gro u p a ( c o ntro l) was administered 0.5 ml distilled water and 1ml of dimethyl sulfoxide (dmso) per rat, once daily, orally, for 8 weeks. group b (nifedipine only group) was given nifedipine at a therapeutic dose of 50 mg/kg body weight, dissolved in 1ml of dmso, once daily, orally for 8 weeks. group c (tt only group) was given tt aqueous extract 6mg/kg/rat, once daily, orally, for 8 weeks. group d (nifedipine plus tt) was given nifedipine and tt together in the same doses, orally, once daily as were given to group b and c transcription of steroidogenic acute regulatory protein (star) which mediates the transport of cholesterol to the mitochondria. this step is the rate7 limiting step of steroidogenesis. similarly is 2+ ca re q u i re d fo r t h e n o r m a l s p e r m ato ge n e s i s ( s p e r m i o ge n e s i s ) a n d s p e r m m o t i l i t y a n d 8 fertilization. out of ccbs nifedipine is one of the most prescribed drugs in the world. its gaining wider acceptance for treating angina pectoris, hypertension, and 9 c o n g e s t i v e h e a r t f a i l u r e . b e l o n g i n g t o dihydropyridine( dhps) subgroup of ccbs, it acts by blocking influx of calcium ions through the l-type vgccs of smooth muscle cells of blood vessels thus reducing the blood pressure by decreasing peripheral vascular resistance mainly at the level of small arterioles. though all ccbs share the same mechanism of action, dhps differ from others induration of action, rate of onset of hypotension, predictability of response and severity of adverse 10 effects. it is known in literature that therapeutic administration of ccbs has been correlated with 11 iatrogenic reversible male infertility. the available literature has stated adverse reversible effects of nifedipine on testicular steroidogenesis and 12, 13 spermatogenesis. therefore, any therapeutic application of ccbs must be used with vigilance in males. any agent that may increase testosterone production and spermatogenesis can be helpful for enhancing fertility in patients taking ccbs. tribulus terrestris (tt) is a natural herb (a flowering plant) used for treating many diseases. it finds important position in ayurveda for the cure of 14, 15 sexual dysfunction in males. tt fruit particularly contains two steroidal saponins protodioscin (ptn) 16 and prototribestin in its extract. ptn is reported to 15 increase the levels of testosterone, dhea and dht 17 hence improves libido and spermatogenesis. it has been proved to be effective in stimulating 18 spermatogenesis and activity of sertoli cell in rats. as its a known fact that nifedipine induces infertility through changes in calcium influx through voltage gated calcium channels and tribulus increases the production of male sex hormone promoting spermatogenesis, its protective effect on ccb induced damage on microstructure of testes should 11,12,13 be studied. as on this protective effect of protective role of tribulus on ccb infertilityjiimc 2018 vol. 13, no.3 152 in nifedipine only group most of the tubules exhibited reduced tubular diameter and height of the germinal epithelium with depletion of few cellular layers within seminiferous epithelium. (fig3)spermatogenesis was seen to be mostly arrested at elongating spermatid stage while leydig cells appeared to be normal. there was no evidence of testicular degenerative changes. respectively for 8 weeks. at the end of 8 weeks animals in all groups were anesthetized and sacrificed. peritoneal cavity was opened by lower abdominal transverse incision; testes were removed, washed with saline, blotted 19,20 and weighed on digital balance. they were fixed in 10 % formalin. transverse sections from the middle of testis were taken. slides were prepared after cutting 5 µm thick serial sections on rotary microtome and staining with haematoxylin and eosin (h&e). transversely cut seminiferous tubules were selected in the slides to measure the diameter of seminiferous tubules under light microscope at the power of 10 and height of germinal epithelium at the power of 40 with ocular micrometer. in each tubule both maximum and minimum diameters were measured and their mean was taken. height of germinal epithelium was measured from the basement membrane to surface of the epithelium in the same tubules. epithelial height was measured at 4 places, equidistant from each other, in each cross21 section and their mean was calculated. mean and standard deviation (sd) was calculated for height of germinal epithelium and diameter of seminiferous tubules. the data was entered and analyzed using spss 22. the statistical significance of difference across the groups was determined by applying one way analysis of variance (anova) followed by tukey hsd (honestly significant difference) post hoc test to compare the mean differences among various pairs of groups. a p–value of <0.05 was considered as statistically significant. results on macroscopic examination the testes were normal looking in all four groups. microscopic examination of control group exhibited densely packed seminiferous tubules with little stroma in between, lodging leydig cells. control group, tt only group and nifedipine plus tt group revealed evidence of a c t i v e s e m i n i f e r o u s t u b u l e s u n d e r g o i n g spermatogenesis and spermiogenesis(figure1,2 and 4) different stages of spermatogenesis with . spermatogonia, primary spermatocytes, round s p e r m a t i d s , e l o n g a t e d s p e r m a t i d s , a n d spermatozoa were visible in all sections of above mentioned groups. spermiogenesis was shown by the presence of residual bodies and tails within lumen of seminiferous tubules. table i. comparison of parameters among four groups by one way anova where a� ll values are expressed as mean ± standard devia�on. * sta�s�cally significant values. table ii. group comparison of mean differences in diameter of seminiferous tubulesa� nd height of germinal epithelium by post hoc tukey test *sta�s�cally significant values discussion calcium channel blockers, most commonly used 22 antihypertensive are long been known for induction 23 of male infertility. they have been reported to induce temporary infertility either by inhibition of leydig cell steriodogenesis, depression of spermatogenesis, destruction of the germinal cell, 24 inhibition of sperm function or its metabolism. our study revealed that control group, tt only group and nifedipine plus tt group revealed evidence of active spermatogenesis but in nifedipine only group most of the tubules exhibited reduced tubular protective role of tribulus on ccb infertilityjiimc 2018 vol. 13, no.3 153 increased with tt dose of 10 mg/kg. in our study the histological changes became evident at 6mg/kg body weight given for same duration as above. this difference in the response might be due to 30 geographical difference in the origin of tt plants or due to aqueous extract of tt unlike alcoholic extract as used by jashni et al in his study. the group nifedipine plus tt has significant increase in the height of germinal epithelium and diameter of tubules with respect to nifedipine only group. nifedipine couldn't suppress spermatogenesis completely. the extract of tt is reported to increase serum testosterone. one of the suggested mechanisms is that the level of testosterone is 17 augmented by increasing lh and the gnrh. it can be direct conversion of ptn to dhea in the body which 31 then undergo further conversion to testosterone. tribulusterrestris protective effects should be seen at different doses in male gonads along with changes in serum hormonal level. cellular mechanism of action of tribulus should be explored. conclusion the current study has led us to presume that herb tribulus terrestris has protective effect on nifedipine induced damage on microstructure of testes. therefore temporary infertility in males induced by commonly used calcium channel blockers, nifedipine, intake can be prevented by coadministration of tribulus terrestris aqueous extract as has been confirmed by histological parameters. limitation of our study is non estimation of serum testosterone and lh, which could have augmented t h e h i s t o l o g i c a l c h a n g e s s e e n i n t e s t i s diameter and height of the germinal epithelium. the main finding in nifedipine only group showing reduction in spermatogenesis was supported by parallel studies of latif et al , who had shown significant decrease in the height of seminiferous epithelium and diameter of tubules in adult male rats 25 after giving them amplodipine for 50 days. but these effects are reversible after discontinuing the drug . similar study was reported by adebayo a et al who depicted in his study the dose dependent delirious effect of amlodipine on seminiferous epithelium 26 21 adult wistar rats. lee et al conducted study on prepubertal male mice which were given nifedipine and ethosuximide for 20 days. it caused a significant fall in sperm production and spermatogenic arrest mainly at the elongating spermatid stage in a dose2+ dependent fashion. both tand l-type ca channel blockers interfere with normal spermatogenesis and steroidogenesis firstly by blocking post meiotic germ cell maturation and/or by abolishing star protein 23 expression, contributing to male infertility. sperm structure influences its motility and is also a 13 predictor of overall health of the testes. our findings of nifedipine only group coincided with above mentioned researches .reduction in spermatogenesis with the use of nifedipine may be either secondary to decrease in serum testosterone or in pituitary hormones or direct harmful effects of 25 the nifedipine on germ cells. there was significant increase in the height of seminiferous epithelium and diameter of tubules in tt only group because of the positive effect of aqueous extract of tt on germinal epithelium.tt has been shown to increase the height of seminiferous epithelium and diameter of seminiferous tubules as it increases the level of testosterone and lh in the 27 body which promotes spermatogenesis. jashni et al reported in his study that estradiol glycosides in tt extract(ptn) cause increase in the testosterone 18 levels by enhancing the production of androgens. histological observations made by esfandiari et al after giving high dose of tt to mature and immature rats revealed increased height of germinal epithelium and diameter of seminiferous tubules in both experimental groups as compared to control 28 groups. research conducted on rabbits by al-rubii 29 18 et al revealed similar results. jashni et al showed that the mean number of primary spermatocytes fig 1: photomicrograph of tes�cular tissue showing normal histology in control group (h & e stain x 300 approx.) protective role of tribulus on ccb infertilityjiimc 2018 vol. 13, no.3 154 medications on male fertility. journal of reproduction & infertility. 2012;13(1):3. 3. mills kt, bundy jd, kelly tn, reed je, kearney pm, reynolds k, et al. global disparities of hypertension prevalence and control. circulation. 2016;134(6):441-50. 4. saleem f, hassali aa, shafie aa. hypertension in pakistan: time to take some serious action. br j gen pract. 2010;60(575):449-50. 5. chen gj, yang ms. the effects of calcium channel blockers in the prevention of stroke in adults with hypertension: a meta-analysis of data from 273,543 participants in 31 randomized controlled trials. plos one. 2013;8(3):e57854. 6. santana lf, navedo mf. natural inequalities: why some ltype ca2+ channels work harder than others. the journal of general physiology. 2010;136(2):143-7. 7. rossier mf. t-type calcium channel: a privileged gate for calcium entry and control of adrenal steroidogenesis. frontiers in endocrinology. 2016;7. 8. pérez l, vílchez mc, gallego v, morini m, peñaranda ds, asturiano jf. role of calcium on the initiation of sperm motility in the european eel. comparative biochemistry and physiology part a: molecular & integrative physiology. 2016;191:98-106. 9. elliott h, meredith p. preferential benefits of nifedipine gits in systolic hypertension and in combination with ras blockade: further analysis of the 'action'database in patients with angina. journal of human hypertension. 2011;25(1):63. 10. godfraind t. calcium channel blockers in cardiovascular pharmacotherapy. journal of cardiovascular pharmacology and therapeutics. 2014;19(6):501-15. 11. laganà as, vitale sg, iaconianni p, gatti s, padula f. male infertility during antihypertensive therapy: are we addressing correctly the problem? international journal of fertility & sterility. 2016;10(3):267. 12. iranloye b, morakinyo a, uwah j, bello o, daramola o. effect of nifedipine on reproductive functions in male rats. nig qj hosp med. 2009;19(3):165-8. 13. jamiu mustapha sulayman ba. effects of nifedipine on the testis of male wistar rats. jbioinnov. 2016;6(1):65-77. 14. sharifi am, darabi r, akbarloo n. study of antihypertensive mechanism of tribulus terrestris in 2k1c hypertensive rats: role of tissue ace activity. life sciences. 2003;73(23):296371. 15. singh s, nair v, gupta yk. evaluation of the aphrodisiac activity of tribulus terrestris linn. in sexually sluggish male a l b i n o r a t s . j o u r n a l o f p h a r m a c o l o g y & pharmacotherapeutics. 2012;3(1):43. 16. rawat aks, srivastava a, tiwari ss, srivastava s. quantification of protodioscin and prototribestin in fruits of tribulus terrestris l. collected from different phytoge o g ra p h i ca l zo n e s o f i n d i a . j o u r n a l o f l i q u i d c h r o m a t o g r a p h y a n d r e l a t e d te c h n o l o g i e s . 2013;36(13):1810-21. 17. sellandi tm, thakar ab, baghel ms. clinical study of tribulus terrestris linn. in oligozoospermia: a double blind study. ayu. 2012;33(3):356. 18. karimi jashni h, malekzadeh shiravani s, hoshmand f. the effect of the tribulus terrestris extract on spermatogenesis microstructure. in addition technical limitations prevented us to study the cellular mechanism of tribulus terrestris at leydig cell level. recommendations tribulus terrestris protective effects should be seen at different doses in female gonads along with changes in serum hormonal level. references 1. agarwal a, mulgund a, hamada a, chyatte mr. a unique view on male infertility around the globe. reproductive biology and endocrinology. 2015;13(1):37. 2. brezina pr, yunus fn, zhao y. effects of pharmaceutical fig 2 : photomicrograph of tes�cular tissue showing tes�cular histology in tribulusterrestris treated group (h & e stain x 300 approx.) fig 3: photomicrograph of tes�cular tissue showing histological changes in nifedipine treated group (h & e stain x 300 approx.) fig 4: photomicrograph of tes�cular tissue showing tes�cular histology in tribulus terrestris plus nifedipine treated group (h & e stain x 300 approx.) protective role of tribulus on ccb infertilityjiimc 2018 vol. 13, no.3 155 association with oxidative stress. adv med sci 2011;56(1):95–105. 25. latif r, aslam m, hussain mm, butt if, mubarik a, zubair a. effects of amlodipine besylate on spermatogenesis in sprague dawley rats. pak armed forces med j. 2009;59(3):275-9. 26. adebayo a, olusegun s. toxicity effects of amlodipine on the testis histology in adult wistar rats. 27. dehghani r. histomorphometrical study of seminiferous tubule in rats after used tribulus terresteris. journal of cell and animal biology. 2010;4(4): 68-72. 28. esfandiari a dr . histomorphometrical study of seminiferous tubule in rats after used tribulus terresteris j cell anim biol. 2010;4: 68-72. 29. al-rubii akm. effect of tribulus terrestris l. extract on prostatic and testicular functions of castrated rabbits. baghdad: university of baghdad; 2010. 30. dinchev d, janda b, evstatieva l, oleszek w, aslani mr, kostova i. distribution of steroidal saponins in tribulus t e r re s t r i s f ro m d i f fe re n t g e o g ra p h i c a l re g i o n s . phytochemistry. 2008;69(1):176-86. 31. gauthaman k ga, prasad rnv. sexual effects of puncturevine (tribulus terrestris) extract (protodioscin): an evaluation using a rat model. j altern complement med 2003; 9:25765. in the rat. journal of jahrom university of medical sciences. 2011;9(4):8-13. 19. singh pk, singh ap, gupta ak. beneficial effects of aqueous fruit extract of tribulus terrestris on testicular and serum biochemistry of albino rats. j ecophysiol occup hlth 2009;9:217-23. 20. latif r lg, aslam m. effects of amlodipine on serum testosterone,testicular weight and gonado-somatic index in adult rats. j ayub med coll abbottabad 2008;20: 8-10. 21. lee j, kim h, kim d, gye m. effects of calcium channel blockers on the spermatogenesis and gene expression in peripubertal mouse testis. archives of andrology. 2006;52(4):311-8. 22. jeffers bw, robbins j, bhambri r. efficacy of calcium channel blockers versus other classes of antihypertensive medication in the treatment of hypertensive patients with previous stroke and/or coronary artery disease: a systematic review and meta-analysis. american journal of therapeutics. 2017;24(1):68-80. 23. lee jh, ahn hj, lee sj, gye mc, min ck. effects of land ttype ca2+ channel blockers on spermatogenesis and steroidogenesis in the prepubertal mouse testis. j assist reprod genet. 2011;28(1):23-30. 24. morakinyo ao, iranloye bo, daramola ao, adegoke oa. antifertility effect of calcium channel blockers on male rats: protective role of tribulus on ccb infertilityjiimc 2018 vol. 13, no.3 156 jiimc march 2016.cdr original article abstract objective: to determine the efficacy of nasal splints in preventing adhesion formation in patients undergoing septoplasty for deviated nasal septum (dns). study design: quasi experimental study. place and duration of study: the study was carried out at ent department, holy family hospital, rawalpindi from january 2010 to january 2011. materials and methods: two hundred and sixty patients with dns requiring septoplasty were included in this study. they were divided in two groups a and b with each group consisting of 130 patients. in group a splints were used postoperatively after septoplasty while in group b no splints were used. in group a nasal splints were removed on 14th postoperative day. all patients in group a and b were followed up regularly in opd for six weeks for development of adhesions to determine efficacy of nasal splints in prevention of adhesions. results: in group a average age was 29.13 years+10.11sd while it was 27.6 years+ 9.5sd in group b. male to female ratio was 1.15:1. there was no statistically significant difference in the incidence of adhesion formation between two groups with p-value of 0.734. conclusion: there is no significant advantage of routinely using intranasal splints in septoplasty patients for prevention of adhesion formation. key words: nasal splints, septoplasty, dns. done worldwide over the years to determine the efficacy of intranasal splints in prevention of 6, 7, 8 intranasal adhesions to justify their use. although many surgeons insert nasal splints routinely, no well-designed trials exist to support 3 their use. the nasal splint increases the post6,7 operative pain and discomfort. although splints are in common practice but their use has shown limited benefit in terms of prevention of adhesions when 6 compared withseptoplasty patients without splints. so in this study we tried to find out efficacy of nasal splints in prevention of nasal adhesions to justify their routine use in patients undergoing septoplasty in our set up. materials and methods it is a quasi experimental study carried out in department of ear, nose and throat of holy family hospital, rawalpindi from january 2010 to january 2011. patient coming in outpatient department in age group of 16 to 50 years who were diagnosed with deviated nasal septum by anterior rhinoscopy were included in the study. patients with turbinate hypertrophy, nasal polyps, previous surgeries or requiring other lateral wall nasal procedures or having comorbids like diabetes or hypertension were not included. two hundered and sixty patients with dns requiring introduction deviated nasal septum is one of the most common ent complaints and is treated by performing 1 septoplasty. formation of intranasal adhesions is an i m p o r t a n t p o s t o p e r a t i v e c o m p l i c a t i o n o f 1,2,3 septoplasty with an incidence of 10-36%. rhinologists all over the world routinely use intranasal splints after nasal septal surgery to prevent the adhesions and also tomaintain nasal stability and improve the results of septoplasty. this use of intranasal splints is not evidence based and splints are associated with increased pain and 3,4,5 discomfort to patient. many studies have been efficacy of nasal splints in reducing the incidence of intranasal adhesions following septoplasty 1 2 3 4 kashif mahmood , mirza nasheed baig , nayyer ayub , tabassum aziz efficacy of nasal splints following septoplastyjiimc 2016 vol. 11, no.1 correspondence: dr. mirza nasheed baig assistant professor, otorhinolaryngology fouji foundation hospital foundation university medical college, islamabad email: drnasheed@hotmail.com 1 ent department aziz bhatti shaheed teaching hospital, gujrat 2 ent department fouji foundation hospital foundation university medical college, islamabad 3 ent department islamic international medical college riphah international university, islamabad 4 ent department holy family hospital, rawalpindi funding source: nil ; conflict of interest: nil received: november 20, 2015; accepted: january 10, 2016 8 septoplasty were admitted in the ward. the purpose and benefits of the study was explained to patients and a written informed consent was obtained. all patients were worked up with detailed history and clinical examination followed by routine pre operative investigations. the patients were randomly allocated in two groups by convenient sampling technique. patients in group a were subjected to use of splints after septoplasty and in patients in group b no splints were used after septoplasty. all patients were operated by the same ent surgeon having five years of experience in nasal surgery. after surgery nasal packing was removed after 24 hours and patients were discharged on 2nd postoperative day. patients in both groups were given same oral antibiotic and analgesic for one week. both groups were advised saline nasal douches three times a day for two weeks. in group a nasal splints were removed on 14 postoperative day. all patients in group a and b were followed up weekly in opd till 6th week post operatively to determine intervention efficacy in terms of absence of adhesions. all the above mentioned data was collected using performa. data was analyzed by using spss version 20. mean and standard deviation were calculated for age. frequencies and percentages were calculated for gender and efficacy. chi square test was used to compare the efficacy in both the groups. p value of <0.05 was considered significant. results average age was 27.6 years+ 9.5sd in group a while in group b it was 29.13 years +10.11sd. the age distribution among the groups was insignificant with p-value 0.860. further demographic characteristics of both groups a and b are shown in table i and ii. in group a adhesions were seen in four patients (3.1%) and in group b five patients developed adhesion (3.8%). this difference between two groups was insignificant with p-vale of 0.734 (table iii). discussion in our study although there is higher incidence of adhesions in the non splinted group (group b) but in comparison of the both groups statistically this difference was not significant and this may be due to intra operative surgical technique and postoperative nasal douching with normal saline to prevent crust formation and thus formation of adhesions. similar findings were seen in studies of some other authors. tang and kacker concluded that nasal splints cause significantly increased postoperative pain and there is not sufficient evidence that they are effective in decreasing the incidence of intranasal 6 adhesions. von schoenberg and robinson found out on three months postoperative follow up that the splinted and non splinted groups had the same low rate of adhesion formation of 2% which in their opinion was because of early outpatient review with 8 careful nasal toilet on weekly basis. cook et al showed a failure of intranasal splints in preventing intranasal adhesion(6.5% in splinted vs. 7.0% in non splinted group) and concluded that there is no clear advantage of using intranasal splints and they should therefore be used sparingly and recommended use 9 of nasal toilet after septal surgery. pringle et al carried out a survey of 440 consultants and found that 33% of them never or rarely used intranasal splints and reported an adhesion rate of 5.2% in non splinted patients vs. 3.9% in the splinted patients, 5 which is not statistically significant. like wise the results of the study done by malki et al showed no statistically significant difference in the incidence of adhesions between the splinted and non-splinted 10 patients. study of almoflehi also concluded that the intranasal splints are not of significant value in preventing nasal adhesion(10% in splinted vs. 21% in non splinted group) and recommendation was that the use of intranasal splints in septal surgery has to be individualized. they stressed on nasal irrigation using saline to prevent crusting and minimizing table i: age wise distribu�on in group 'a' and 'b' (p value= 0.860) table ii: gender wise comparison in group 'a' and 'b' (p value=0.901) table iii: adhesion forma�on in groups 'a' and 'b' (p value = 0.734) efficacy of nasal splints following septoplastyjiimc 2016 vol. 11, no.1 9 11 occurrence of adhesion. almazrou and zakzouk in their study found no significant difference in incidence of adhesion formation between splinted and non splinted groups (2% in splinted vs. 10% in 12 non splinted group). on the other hand contrary to our results deniz m et al. suggested that nasal splints were effective in 13 reducing the incidence of nasal synechia formation. schoenberg et al. found a low incidence of adhesions in the first week post operatively when intranasal splints were used and found that the highest incidence of intranasal adhesions occurred in non splinted patients who had surgery to both walls of nasal cavity (3.6% in splinted vs. 31.6% in non 8 splinted). campbell et al. inserted a nasals plint into one side of the nose of 106 patients undergoing a variety of intranasal procedures. all adhesions occurred on the non splinted side and were more common when bilateral nasal wall procedures had been performed (8% in splinted versus 26% in non 14 splinted). they concluded that splints were justified for bilateral wall procedures but their increased morbidity did not justify their use in single wall 14 procedures. roberto et al. found nasal splints very effective inpreventing adhesion formation in patients under going septoplasty with turbinectomy 15 (0% in splinted vs.10.6% in non splinted group). nabil-ur-rahman concluded that complications were related to the type of procedure being p e r fo r m e d a n d a d h e s i o n s w e r e c o m m o n 16 complication if intranasal splint were not provided. the routine use of nasal splints in septoplasty patients is still a matter of debate. splints addsignificantly to post operative pain and discomfort. it is recommended that their use should be individualized depending upon procedure being performed. they are more justified when surgical procedures are performed on both medial and lateral walls of nose simultaneously. alternati velysaline nasal douching and regular outpatient follow up with suction toilet are very effective in preventing intranasal crusting and thus adhesion formation. conclusion there is no significant advantage of using intranasal splints routinely in patients undergoing septoplasty for prevention of adhesions provided patients are closely followed up with saline nasal douches and regular nasal toilets. references 1. shone gr, clegg rt. nasal adhesions. cambridge journal of laryngology & otology. 1987; 101: 555-7. 2. khayatfj, yaseen a. the effect of intranasal splint on prevention of adhesions after septoplasty. diyala j med 2012; 2: 5-12. 3. gaia r, coelho j, brandao fh, carvalho mrms, aquino jep, paula shp. frequencia de sinequia nasal aposcirurgia de septoplastia com turbinectomia com e semuso de splint nasal. arqintotorrinolaringol. 2008; 12: 24-7. 4. sharif m, ali s, zaman t. nasal septal surgery without splints, without packing. ann abbasishaheedhosp karachi med dent coll. 2007; 12: 17-23. 5. pringle mb. the use of intra-nasal splints: a consultant survey. uk.clinotolaryngol allied sci. 1992;17: 535-9. 6. tang s, kacker a. should intranasal splints be used after nasal septal surgery? the laryngoscope. 2012 aug 1; 122: 1647-8. 7. gijy, won h, young gyu e, myunggu k. objective usefulness of thin silastic septal splints after septal surgery. am j rhinol allergy. 2011; 25: 182-5. 8. von schoenberg m, robinson p. the morbidity from nasal splints in 105 patients. clin. oto. laryngol. 1992; 17: 528-30. 9. cook ac, murrant nj, evans kl, lavelle rj. intra-nasal splints and their effects on intranasal adhesions and septal stability. clinotolaryngol. 1992; 17: 24-7. 10. malki d, quine sm, pfleiderer ag. nasal splints revisited. cambridge j laryngol otol. 1999; 113: 7257. 11. almoflehi ms. the impact of using intranasal splints on morbidity and prevalence of adhesions. j sc tech. 2009; 10: 1-6. 12. almazrou ka, zakzouk sm. the impact of using intranasal splints on morbidity and prevalence of adhesions. saudi med j. 2001; 22: 616-8. 13. deniz m, ciftci z, isık a, demirel ob, gultekin e. the impact of different nasal packings on postoperative complications. american journal of otolaryngology. 2014; 35: 554-7. 14. campbell jb, watson mg, shenoi pm. the role of intranasal splints in the prevention of post-operative nasal adhesions. cambridge jlaryngolotol. 1987; 101: 1140-3. 15. roberto g, fabiano h, maria r. frequency of nasal synechiae after septoplasty with turbinectomy with or without the use of nasal splint.2008. arch otolaryngol. sao paulo. 2008; 12: 24-7. 16. nabil ur rahman ma. complications of surgery for deviated septum.jcoll physicians surg pak. 2003; 13: 565-8. efficacy of nasal splints following septoplastyjiimc 2016 vol. 11, no.1 10 54 editorial multidrug resistant tuberculosis and importance of dots iqbal ahmad khan correspondence: prof. iqbal ahmad khan head of department of community medicine /public health women medical and dental college, abbottabad e-mail: profkhakwani@gmail.com received: may 01, 2019; accepted: may 25, 2019 globally millions of people become sick each year with tuberculosis and it is one of the top 10 causes of 1 death worldwide. according to world health organization (who), the incidence of tuberculosis was 10 million in 2017 and reported tb mortality was 2 1.6 million globally. pakistan is one of the 30 high burden countries for tuberculosis worldwide with 61% of tb burden in eastern mediterranean region of who. in pakistan, 510,000 new cases of tb emerge each year and around 15000 cases develop 1 drug resistant tuberculosis annually. in recent years, prevalence of drug-resistant tb has increased and became a continued public health crisis worldwide. there are three forms of drug resistant cases of tuberculosis: rr-tb, (rifampicin resistant-tuberculosis), mdr-tb (multidrug resistant-tuberculosis) and xdr-tb (extensively drug resistant-tuberculosis). according to who, 160684 cases of mdr/rr-tb (multidrug resistant/ rifampicin resistant) were reported in 2017 all over the world. pakistan has fourth highest prevalence of 2 multidrug resistant tb (mdr-tb) globally. drug resistant tuberculosis is a potentially devastating threat to tb control as it gives emergence to the strains that cannot be cured by 3 standard first line anti-tuberculosis treatment. mdrtb cases are resistant to isoniazid and rifampicin. after developing resistant to first line therapy, patient is treated with prolonged and extensive therapy of second line injectable drugs. if patient develops resistance to second line injectable drugs then it is termed as extensively drug resistanttuberculosis (xdr-tb). at this level disease becomes 3 virtually untreatable. as treatment success remains low, at 55% globally, there is an urgent need to improve the quality of diagnosis, treatment and care for people with drug resistant tuberculosis. key reasons for developing drug resistance among tb cases are: delayed progress is being made in diagnostic test technologies but still there is need to overcome questions related to validation and assessment of these technologies to make ideal diagnostic test 4 available with high sensitivity and specificity levels. as previously reliance on passive case finding has not helped to stop tb pandemic. so active case finding and screening strategies instead of passive case finding of infectious cases are also needed to eradicate the disease. tb has been declared as global epidemic. the un's first high-level meeting in 2018 on tb, was given the title as “united to end tb: an 1 urgent global response to a global epidemic” . tb dots (directly observed treatment, short course) has been recommended by who since 1994, as a strategy to treat tb cases and to get control over its prevalence. tb dots had five components for effective treatment and control of disease as following: 1. s u s t a i n e d p o l i t i c a l a n d f i n a n c i a l commitment by the government 2. tb diagnosis with sputum smear microscopy 3. standardized short course treatment given under direct observation for 6-9 months 4. uninterrupted and regular supply of anti tb drugs 5. standardized recording and reporting of 4 disease. in 1999, who launched “tb dots-plus” as a strategy to control tb resistance by adding second line drug into already adopted dots components because dots did not account for tb resistance cases rather caused mdr-tb when treatment was repeated among untreated cases for prolonged duration. diagnosis, unsupervised treatment, inappropriate drug regimens, lack of social support in the communities and lack of timely follow-ups. to close these gaps, much work is required for: drug susceptibility testing among diagnosed cases of tb, reducing under-diagnosis of tb cases, improving access and supervised continuous treatment, designing new diagnostics, new medicines and treatment regimens with higher efficacy and better 2 safety. dots is the role of treatment supporter. treatment supporter ensures that patient has taken right drugs in appropriate doses and enters its record in patient's treatment card. in stop tb strategy, patient supervision and support to complete treatment course without skipping any dose is the cornerstone of dots for achieving tb control with maximum 5 treatment success rate globally. references 1. global tuberculosis control report: world health organization; 2018. 2. walzl g, mcnerney r, du plessis n, bates m, mchugh td, chegou nn, et al. tuberculosis: advances and challenges in development of new diagnostics and biomarkers. 2018; 18(7): e199–210. available from: http://dx.doi.org/ 10.1016/s1473-3099(18)30111-7 3. gandhi nr, nunn p, dheda k, schaaf hs, zignol m, van soolingen d, et al. multidrug-resistant and extensively drugresistant tuberculosis: a threat to global control of tuberculosis. 2010; 375(9728): 1830–43. available from: http://dx.doi.org/10.1016/s0140-6736(10)60410-2 4. raviglione mc, uplekar mw. who's new stop tb strategy. 2006; 367(9514): 952–5. 5. fa m, le c, dacombe r, mkopi a, sinclair d. interventions to increase tuberculosis case detection at primary healthcare or community-level services ( review ). 2017; (11). dots-plus ended in 2006 due to resource constraints and subsequently who decided to expand tb dots again, by redefining the tb dots with focus on tb diagnosis, treatment and care of patients. the global plan to stop tb by 2015 included tb control targets that were covered under the targets of millennium 1 development goals (mdgs). after 2015, another global plan to end tb by 2020 was “who end tb strategy” which emphasized on a need of paradigm shift for radical change in tb survillenc and to set targets to be met in coming years. the focus of end tb strategy is to improve tools for case finding among high risk population, treatment of new cases and detection of drug resistance among tb cases. it is also to be understood that only improving diagnostic technologies will not reduce disease transmission unless early detection of infection and treatment of 1 cases will not be carried out. dots are still considered effective for treatment of new cases of tb and prevention of rr-tb/mdr-tb. failure to adapt dots in its true spirit is the leading cause of increased drug resistance cases of tuberculosis globally. the most important part of tb 55 original�article objective: to compare serum adenosine deaminase (ada) levels in untreated and treated cases of breast cancer patients. place and duration of study: the study was carried out in the department of biochemistry, islamic international medical college in collaboration with department of surgery, holy family hospital, rawalpindi during one year period from april 2017 to march 2018. abstract results: mean of serum adenosine deaminase level was compared among controls and untreated cases. it was found that serum ada levels were high in untreated cases as compared to controls (17.75 ± 4.17 vs 14.92 ± 3.73) with p-value 0.001. mean of serum ada levels were also compared among untreated and treated cases. it was found that serum ada levels were markedly low in treated cases as compared to untreated cases (13.18 ± 4.18 vs 17.75±4.17) with p-value ˂ 0.0001. study design: it was an analytical, observational study. conclusion: it is concluded that serum adenosine deaminase levels are significantly raised in female patients of breast cancer; however these levels get lowered after treatment such as chemotherapy, radiotherapy, hormonal therapy and surgical excision. key words: adenosine deaminase (ada), breast cancer, malignancy, mirna, tumor grades. materials and method: total 150 subjects were selected for the study using convenient non probability sampling technique. selection criteria for patients were both untreated and treated cases of breast cancer. selection criteria for controls were healthy individual without having any malignancy and all the diseases in which adenosine deaminase is raised. out of total 150 subjects, we took 70 controls and 80 cases. of 80 cases, 44 were untreated and 36 were treated breast cancer patients. serum adenosine deaminase levels of both controls and cases were measured and entered into spss version 21 for analysis. descriptive data were given in the form of mean ± standard deviation (sd). “independent t test” was applied and “p” values less than 0.05 were considered statistically significant. studies from lahore and karachi have shown that rd breast cancer comprises up to 1/3 of all malignant 6 tumors in females. “adenosine deaminase (ada) is an important enzyme of the purine-inactivating chain. it helps in catalyzing the irreversible deamination of adenosine and 2'-deoxyadenosine to inosine and 2'deoxyinosine respectively”. adenosine deaminase 2 most common invasive cancer. on overall ranking of th 3 deaths caused by cancers, breast cancer ranks 5 . in pakistan, breast cancer is the most frequently diagnosed cancer among females. it is reported that as compared to iran and india, pakistan has 2.5 times greater incidence of breast cancer. this means that 4 almost one in nine female patients suffer from it. approximately 90,000 women suffer from breast 1 cancer every year in pakistan. fortunately, if cancer is diagnosed at an early stage, it can be prevented 5 and treated. 1 breast cancer is malignancy in the tissues of breast. it is the most common cancer among females out of all types of cancers. worldwide approximately 1 million newly diagnosed cases are reported. it is the nd 2 leading death cause in females. in women, it is the introduction clinical significance of serum adenosine deaminase levels in breast cancer patients 1 2 3 4 5 wajahat ullah khan , amena rahim , kenza mobeen , muhammad afzal , abdul khaliq naveed correspondence: dr. wajahat ullah khan senior lecturer department of biochemistry mohi ud din islamic medical college, mirpur ajk e-mail: drwajahatullahkhan@gmail.com 1 department of biochemistry mohi ud din islamic medical college, mirpur ajk 2,4,5 department of biochemistry islamic international medical college riphah international university, islamabad 3 department of pharmaceutical sciences riphah international university, islamabad funding source: nil; conflict of interest: nil received: july 18, 2019; revised: december 04, 2019 accepted: december 05, 2019 jiimc 2019 vol. 14, no.4 breast cancer and serum adenosine deaminase levels 184 psoriasis and rheumatoid arthritis. out of 150 cases studied, 70 were controls and 80 were cases. cases were further divided into two groups i.e. untreated cases which were 44 and treated cases which were 36. treated cases included cases of breast cancer that had gone through any of these treatments: chemotherapy, radiotherapy, hormonal therapy and surgical excision. blood was drawn from peripheral veins, transferred to edta tube, gently mixed and made to stand upright. the blood samples were centrifuged at 2200 rpm for 10 minutes. the separated plasma was o stored at -70 c till completion of sample collection. the invitro quantitative determination of human ada concentrations in serum were carried out by elisa in accordance with the instructions given by 11 manufacturer , in the research laboratory of department of biochemistry in islamic international medical college. the data was entered into spss version 21 and analyzed. descriptive data were given as mean ± standard deviation (sd). “independent t test” was used and “p” values of less than 0.05 were considered statistically significant. results mean serum ada levels were compared among controls and untreated cases. it was found that mean serum ada levels were high in untreated cases as compared to controls. this difference of mean serum ada was found statistically significant with “p-value” 0.001. out of 150 cases studied, 70 were controls and 80 were cases. cases were further divided into two groups i.e. untreated which were 44 and treated which were 36. among cases 45 individuals were ˂ 50 years of age and 35 individuals were ˃ 50 years of age. whereas among controls, 47 individuals were ˂ 50 years of age and 23 were ˃ 50 years of age. similarly premenopausal women were more in both cases and controls. among breast cancer cases 59 individuals had sporadic disease whereas 21 had familial. mean of serum ada levels were also compared among controls and treated cases. it was found that serum ada levels were slightly low in treated cases than the controls. this difference of mean serum ada was found statistically not significant with “pvalue” 0.087. to the best of our knowledge there is no study at national and local level regarding the relationship of serum ada levels in breast cancer patients. this research will help us to determine the clinical significance of serum adenosine deaminase levels estimation in breast cancer patients. a study was planned to compare serum adenosine deaminase (ada) levels in untreated and treated cases of breast cancer patients. materials and methods converts a component which is toxic to lymphocytes i-e deoxyadenosine, to another molecule called 7 deoxyinosine, which is not harmful to the body. breast carcinoma includes a chain of events that are 8 very inflammatory. adenosine is a significant molecule that plays an important role in signaling. it employs prominent anti-inflammatory effects in tumorous conditions like prevention of tumor invasion in lymphoid cells. amplified adenosine deaminase activity diminishes the protective 9 molecule adenosine. a study has shown the diagnostic value of ada activity in malignant and benign breast tumor patients. according to that study the serum ada activity in benign tumors was o bs e r ve d to b e g re ate r t h a n t h e n o r m a l (noncancerous) breast tissues and it was highest 10 among serum of patients with malignant tumors. approval from the ethical review committee of the institute was obtained. an informed written consent regarding participation in the study was taken from the patients. total 150 subjects, who fulfilled the inclusion criteria, were included in the study. convenient non probability sampling technique was adopted. selection criteria for patients were both untreated and treated cases of breast cancer and selection criteria for controls were: healthy individual without having any malignancy and all the diseases in which serum ada is raised i.e. tuberculosis, sarcoidosis, chronic obstructive pulmonary disease, hiv, chronic heart failure, it is an analytical, observational study carried out in t h e d e p a r t m e n t o f b i o c h e m i s t r y, i s l a m i c international medical college in collaboration with department of surgery, holy family hospital, rawalpindi during a period of one year from april 2017 to march 2018. in this study ada levels were measured in blood samples from patients and controls. jiimc 2019 vol. 14, no.4 breast cancer and serum adenosine deaminase levels 185 patients of breast cancer as compare to healthy individuals (p = 0.001). similar results were also 19,20,10 documented by, borzenko bg and aghaei m. walia.m in her study concluded that in breast cancer patients after mastectomy, serum ada levels were 17 decreased significantly. similarly borzenko bg mentioned in his study that serum ada was 20 significantly changed after surgery. in the present study we have found that ada levels are significantly less in treated cases as compare to untreated cases of breast cancer with p= ˂ 0.0001. there are few limitations of the study as well, which are mainly related to shorter duration of the study. the study parameters are reduced to complete the trial in stipulated time period, otherwise the information related to other diagnostic parameters and detailed clinical presentation could have been more informative. 4. khokher s, qureshi mu, chaudhry na. comparison of who and recist criteria for evaluation of clinical response to 3. ferlay j, soerjomataram i, dikshit r, eser s, mathers c, rebelo m, et al. cancer incidence and mortality worldwide: sources, methods and major patterns in globocan 2012. international journal of cancer. 2015;136(5):e359-e86. based on the current results, it is concluded that low serum ada levels in treated cases as compare to untreated cases can be considered as a prognostic marker for breast cancer treatment and high serum ada levels in breast cancer patients can prove a valuable marker for early detection and diagnosis of breast cancer along with other established markers. for this purpose a diagnostic accuracy study by comparing serum ada with gold standard test for the diagnosis of carcinoma breast ie. histopathological examination of breast tissue will be useful. 1. asif hm, sultana s, akhtar n, rehman ju, rehman ru. prevalence, risk factors and disease knowledge of breast c a n c e r i n pa k i s t a n . a s i a n pa c j c a n c e r p r e v. 2014;15(11):4411-6. conclusion this study may prove helpful in further research at molecular level like considering the role of ada in predicting the successful breast cancer treatment, circulating mirna and rna expression of ada gene in local tissue. references 2. mcguire a, brown ja, malone c, mclaughlin r, kerin mj. effects of age on the detection and management of breast cancer. cancers (basel). 2015 ;7(2):908-29. mean of serum ada levels were also compared among untreated and treated cases. it was found that serum ada levels were markedly low in treated case as compared to untreated cases. this difference of mean serum ada was found statistically very significant with “p-value” ˂ 0.0001. (table i) table i: mean adenosine deaminase ac�vity (ada) in controls, untreated and treated cases discussion in the past few years, the interest has increased regarding the utilization of hormones, enzymes and antigens for diagnosis and prognosis of different tumors (i.e both benign and malignant). in addition to this, researchers are using hormones, enzymes and antigens as assessment tools for assessing the treatment response in patients. they have conducted experiments to assess and check the effect of different enzymes on breast cancer, and correlations between some of the enzyme activities in malignant cells and the carcinogenic processes are also explored. total serum ada activity has been observed in patients with different types of tumors. some studies suggest that increased ada activity play an active role in the salvage pathway activity of neoplastic cells 12,13 and tissues. whereas others are of the opinion that accelerated pyrimidine and purine metabolism in necrotic cells and tissue cause an increase of adenosine concentration, which in turn increase the a c t i v i t y o f a d a t h r o u g h c o m p e n s a t o r y 14,15 mechanism. aghaei in 2005 reported that the total ada activity in serum of breast cancer patients was significantly 16 higher than healthy individuals. similarly increased activity of serum total ada had been confirmed by “mini walia” and archana choudhari in breast 17,18 cancer patients. in present study we have found that mean serum ada is significantly raised in jiimc 2019 vol. 14, no.4 breast cancer and serum adenosine deaminase levels 186 17. walia m, mahajan m, singh k. serum adenosine deaminase, 5'-nucleotidase & alkaline phosphatase in breast cancer patients. indian j med res. 1995 ;101:247-9. 16. aghaei m, karami-tehrani f, salami s, atri m. adenosine deaminase activity in the serum and malignant tumors of breast cancer: the assessment of isoenzyme ada1 and ada2 activities. clin biochem. 2005 ;38(10):887-91. lymphoid cells. biochem med. 1982 ;28(2):144-56. 18. choudhari a, desai p, indumati v, kadi s. activities of serum ada, ggt and alp in carcinoma breast-a case control study for diagnostic and prognostic significance. indian j med sci. 2013 ;67(5-6):123-9. 19. borzenko bg. [age-dependent characteristics of metabolism of dna precursors in healthy women, patients with mastopathy and breast cancer]. vopr med khim. 1990 ;36(5):58-61. 20. borzenko bg, gorbachev aa, dumanskiĭ i, shevchenko vv, shepliakov mn. [activity of the enzymes of dna metabolism in the blood of patients with breast cancer]. vopr onkol. 1990 ;36(1):17-23. 15. hershfield ms, kredich nm. resistance of an adenosine kinase-deficient human lymphoblastoid cell line to effects of deoxyadenosine on growth, s-adenosylhomocysteine hydrolase inactivation, and datp accumulation. proc natl acad sci u s a. 1980 ;77(7):4292-6. 14. donofrio j, coleman ms, hutton jj, daoud a, lampkin b, dyminski j. overproduction of adenine deoxynucleosides and deoxynucletides in adenosine deaminase deficiency with severe combined immunodeficiency disease. journal of clinical investigation. 1978;62(4):884-7. 5. noreen m, murad s, furqan m, sultan a, bloodsworth p. knowledge and awareness about breast cancer and its early symptoms among medical and non-medical students of southern punjab, pakistan. asian pac j cancer prev. 2015;16(3):979-84. 12. camici m, tozzi mg, allegrini s, del corso a, sanfilippo o, daidone mg, et al. purine salvage enzyme activities in normal and neoplastic human tissues. cancer biochem biophys. 1990 ;11(3):201-9. 7. reference gh. ada gene. 2018. chemotherapy in patients with advanced breast cancer. a s i a n p a c i f i c j o u r n a l o f c a n c e r p r e v e n t i o n . 2012;13(7):3213-8. 13. dornand j, bonnafous jc, favero j, mani jc. ecto5'nucleotidase and adenosine deaminase activities of 11. <ada elisa manual.pdf>. 6. malik ia, mubarik a, luqman m, ullah k, ahmad m, alam sm, et al. epidemiological and morphological study of breast cancer in pakistan. j environ pathol toxicol oncol. 1992;11(5-6):353. 10. aghaei m, karami-tehrani f, salami s, atri m. diagnostic value of adenosine deaminase activity in benign and malignant breast tumors. arch med res. 2010 ;41(1):14-8. 8. mahajan m, tiwari n, sharma r, kaur s, singh n. oxidative stress and its relationship with adenosine deaminase activity in various stages of breast cancer. indian journal of clinical biochemistry. 2013;28(1):51-4. 9. mahajan m, tiwari n, sharma r, kaur s, singh n. oxidative stress and its relationship with adenosine deaminase activity in various stages of breast cancer. indian j clin biochem. 2013 ;28(1):51-4. jiimc 2019 vol. 14, no.4 breast cancer and serum adenosine deaminase levels 187 original�article abstract objective: to correlate the serum uric acid, thyroid-stimulating hormone (tsh) and free-thyroxine (ft4) in overt and subclinical hypothyroidism. study design: cross sectional comparative. place and duration of study: capital development hospital, islamabad from january 2019 to june 2019. materials and methods: total 114 participants, recruited through convenient non-probability sampling technique, were sub-divided in three groups, comprising 38 participants each. group i included patients of overt hypothyroidism. group ii had patients with subclinical hypothyroidism and group iii included healthy controls. serum uric acid levels were measured for all participants. for data analysis, spss 21 was used. statistical significance was estimated using one way anova. p value of < 0.05 was considered significant. correlation between numerical variables was determined by pearson correlation coefficient. results: mean serum uric acid level in overt hypothyroid patients (7.5±0.84 mg/dl) was significantly raised than the patients in the subclinical hypothyroid and control group (4.7±0.82, 4.6±1.09 mg/dl respectively) with p value <0.001. however, there was no significant difference of mean uric acid levels between subclinical hypothyroid group and the control group (p value =0.95). a significantly positive relation was observed between serum uric acid and tsh in group i only (r = 0.53 and p < 0.001). conclusion: uric acids levels are increased in hypothyroidism more profoundly in case of overt hypothyroidism, less so when subclinical hypothyroidism is present. in patients of overt hypothyroidism, serum tsh and uric acid levels should be monitored regularly to prevent renal complications in these patients. key words: hypothyroidism, thyroid stimulating hormone, thyroxine, uric acid. imperative role in cell differentiation, regulation of thermogenesis and metabolic homeostasis in 3 adults. numerous mechanistic links exist between thyroid hormones and the renal system. the kidneys cause local deiodination of t4 by enzyme t4-5� deiodinase, resulting in production of t3, a more 4 potent form biologically. conversely, thyroid hormones are crucial for the development of renal system and its physiology. they have effects, both pre renal as well as intrinsic renal, which in turn cause increased renal blood flow and glomerular filtration 5 rate (gfr). hypothyroid state causes hemodynamic changes, including a decline in both renal plasma flow and gfr, which may cause derangement of renal 6 function. also, purine metabolism is affected by lower levels of t3 and t4, which may cause a 7 modification in uric acid (ua) levels. there are numerous remaining gaps in knowledge with respect to the interactions between thyroid and 6 kidney dysfunction. previous studies carried out to introduction clinically, the commonest endocrine disorder is hypothyroidism. it results from an insufficiency of the thyroid hormones, leading to generalized 1 impairment of various metabolic processes. prevalence of hypothyroidism is 3.8%–4.6% in asian 2 population. t3 and t4 are the two related hormones synthesized by the thyroid gland. these hormones serve an correlation of serum uric acid, thyroid-stimulating hormone and freethyroxine in subclinical and overt hypothyroidism 1 2 3 fakhra noureen , saddaf ayub , abid saeed khan correspondence: dr. saddaf ayub assistant professor department of biochemistry islamic international medical college riphah international university, islamabad e-mail: saddaf.ayub1@gmail.com 1 2 department of pathology/biochemistry islamic international medical college riphah international university, islamabad 3 department of medicine capital development hospital, islamabad funding source: nil; conflict of interest: nil received: july 19, 2019; revised: may 30, 2020 accepted: june 01, 2020 uric acid, tsh and ft4 in hypothyroidismjiimc 2020 vol. 15, no.2 94 inquire the link between hypothyroidism and ua 8,9 levels have shown contrary findings. therefore, the present study was designed to correlate the serum uric acid, thyroid-stimulating hormone (tsh) and free-thyroxin (ft4) in overt and subclinical hypothyroidism. materials and methods it was a cross-sectional study conducted at capital development hospital, islamabad after getting approval from institutional ethical review committee. the study extended over 6 months from january 2019 to june 2019. a total of 114 participants were enrolled and were divided in three groups comprising of 38 participants each. groups i included overt hypothyroid patients (tsh >4.5 µiu/ml and ft4 < 0.78ng/dl). group ii included subclinical hypothyroid subjects (tsh > 4.5 µiu/ml and normal ft4) and euthyroid individuals were labeled as group iii. participants from both genders were enrolled through non-probability convenient sampling after taking informed consent. known patients of diabetes, hypertension, renal and hepatic disorders, patients on treatment of hyperuricemia and pregnant women were excluded from this study. age group < 18 years was also excluded as reference ranges of tsh and ft4 are universally different depending on age group. serum tsh was done of clinically diagnosed patients who visited medical opd and who were admitted in wards. subjects who had raised serum tsh levels > 4.5 µiu/ml were further tested for serum ft4. participants who had tsh > 4.5 µiu/ml and ft4 less than 0.78 ng/dl were labeled as overt hypothyroid. subjects having raised serum tsh but normal serum ft4 value were recruited as cases of subclinical hypothyroidism. age and gender matched controls with normal serum tsh level (0.4 – 4.5 µiu/ml) were enrolled. venous blood sample was collected. centrifugation of blood samples was done at 15000 rpm x g for about 15 minutes and serum was separated. serum o was stored at -70 c, until analysis of serum tsh, ft4 and ua was performed for all participants. serum tsh and ft4 test was performed using the vitroseci immunodiagnostic systems using fda approved kits of johnson's and johnson's. serum ua was performed by uricase method on semiautomated chemistry analyzer micro-lab 300. data analysis was done by spss 21. frequencies and percentages were computed for each categorical variable such as gender, whereas mean and standard deviation was estimated for numerical variables like age, serum tsh, serum ft4 and serum ua levels. to compare serum tsh, ft4 and uric acid levels in overt hypothyroidism, subclinical hypothyroidism and euthyroid groups, one way anova was performed. pearson correlation was calculated to find relationship of serum uric acid with serum tsh and ft4 in all the three groups. results mean age (years) of participants in group i, ii and iii were 47.5±9.92, 39.6 ±7.39 and 39.2±11.77 respectively. there were 21.1%, 44.7% and 52.6% males and 78.9%, 55.3% and 47.4% females in three groups respectively (table i). the mean serum tsh, ft4 and ua levels in all three groups are summarized in table ii. in group i, 58% patients had higher than normal serum uric acid levels for their gender. in group ii, all the participants had normal serum uric acid levels while in group iii, 8% participants had higher than normal serum uric acid level for their gender. among the three groups i, ii and iii, there was a statistically significant difference ( p <0.001) in mean serum tsh levels (48.3±28.24, 23.5±33.11, 3.2±0.54 μiu/ml respectively), serum ft4 (0.42±0.20, 1.08±0.26, 1.54±0.40 ng/dl respectively) and serum ua (7.5±0.84, 4.7±0.82, 4.6±1.09 mg/dl respectively) as determined by one way anova for each of these parameters(table ii). post hoc comparison using the tukey test indicated that mean value of serum ua in overt hypothyroid patients (7.5±0.84 mg/dl) was raised significantly than the patients of the subclinical hypothyroidism and controls (4.7±0.82, 4.6±1.09 mg/dl) with p value <0.001. however, there was no significant difference in ua levels between the subclinical hypothyroid group and the control group (p value =0.95). there was a significant positive relation between serum ua and tsh levels in group i (r =0.53 and p<0.001). no significant positive relation was found when tsh and ft4 were correlated with ua in each of the groups ii and iii. (table iii) discussion this study indicates a worsening pattern for serum ua levels from euthyroid condition to overt uric acid, tsh and ft4 in hypothyroidismjiimc 2020 vol. 15, no.2 95 hypothyroidism. previous studies investigating the relationship of overt hypothyroidism with 8,9 hyperuricemia have shown contrary findings therefore, this study was designed to measure uric acid levels in hypothyroidism in our setup. our study demonstrated a significant increase in serum ua levels in overt hypothyroid patients when compared to the controls. this finding is in 8 10 agreement with results of marwah et al , kaur et al , 11 12 13 karanikas , khan et al and abebe et al. the results of our study indicate a possible effect of thyroid abnormalities, mainly overt hypothyroidism, over purine nucleotide metabolism. this suggests that a reduction in renal blood flow and gfr in 8 hypothyroidism may lead to hyperuricemia. on the contrary, the results of an african study indicated that serum ua levels are reduced in both overt 13 hypothyroidism and hyperthyroidism. similarly, a study conducted on a large cohort of 2359 patients diagnosed with thyroid dysfunction (hypothyroidism and hyperthyroidism) could not ascertain any 9 positive relation between serum ua and tsh levels. the disagreement between these findings and our study results can be explained through differences in sample size and study population of these studies. the results of our study demonstrated that there was no significant difference in the mean serum ua levels between the subclinical hypothyroid group and the control group. this finding is in agreement with the 14 results of ye y et al who showed that the prevalence of hyperuricemia in euthyroid and subclinical hypothyroid groups had no significant difference (22.8 % vs 21.9% respectively). similarly the work of 15 k ashizawa et al demonstrated no significant association between hyperuricemia and subclinical hypothyroidism. the possible reason that why the subclinical hypothyroid group did not show considerable change in serum uric acid levels when compared with euthypothyroid group can be explained by the gradual deterioration of thyroid function in subclinical hypothyroid patients , which might not be linked with metabolic complications at this stage of 16 subclinical hypothyroidism. in our study, a significantly positive relation between serum ua and tsh in overt hypothyroid patients was observed. this finding is in agreement with the 8 17 findings of marwah et al and saini et al. the reason for this rise in the levels of ua in case of hypothyroidism may either be an increased generation of uric acid due to hypothyroidismassociated myopathy or a deficient renal clearance 17 resulting from reduced gfr. this relationship may be of significance while evaluating patients having gout, because the excretion of uric acid in these patients might stem from a hypothyroid state. 18 however our results are contrary to arindam et al who demonstrated no association between ua levels and tsh/ft4 in overt hypothyroidism. our study revealed no significant correlation of uric acid with either tsh or ft4 in the subclinical and euthyroid participants. this finding is supported by 9 the results of raber et al which also did not establish any correlation of tfts with uric acid in these groups. this might occur because the table i: descrip�ve sta�s�cs of age and gender in study groups (n=114) table ii: comparison of biochemical parameters among study groups (n=114) *p<0.05 was taken as level of significance group i: overt hypothyroid pa�ents group ii: subclinical hypothyroid pa�ents group iii: healthy adults table iii: correla�on of uric acid with serum tsh, ft4 in three groups (n=114) r= correla�on coefficient p<0.05 was taken as level of significance uric acid, tsh and ft4 in hypothyroidismjiimc 2020 vol. 15, no.2 96 male derangement of thyroid function is less severe in patients of sub-clinical hypothyroidism as compared 16 to overt hypothyroids. limitations the limitation of this study is that it was a unicentred, cross sectional study, so it did not help to determine cause and effect relationship between hypothyroidism and uric acid. future recommendations further multi-centred studies with larger sample size are recommended. moreover other biochemical markers for renal functions (serum urea and creatinine along with muscle markers i.e serum aldolase and creatinine kinase) can be considered in relation to hypothyroidism when similar study is planned. conclusion uric acids levels are increased in hypothyroidism more profoundly in case of overt hypothyroidism, less so when subclinical hypothyroidism is present. a positive correlation of serum tsh and ua in overt hypothyroid patients calls for regular monitoring of serum ua levels in these patients to prevent renal complications. references 1. khan ah, majumder i. serum creatinine and uric acid levels of hypothyroid patients. bangladesh journal of medical biochemistry. 2010;3(2):61-3. 2. hollowell jg, staehling nw, flanders wd, hannon wh, gunter ew, spencer ca, et al. serum tsh, t4, and thyroid antibodies in the united states population (1988 to 1994): national health and nutrition examination survey (nhanes iii). the journal of clinical endocrinology & metabolism. 2002;87(2):489-99. 3. hanley p, lord k, bauer aj. thyroid disorders in children and adolescents. jama pediatrics. 2016;170(10):1008. 4. van der spek ah, fliers e, boelen a. the classic pathways of thyroid hormone metabolism. molecular and cellular endocrinology. 2017;458:29-38. 5. basu g, mohapatra a. interactions between thyroid disorders and kidney disease. indian journal of endocrinology and metabolism. 2012;16(2):204. 6. rhee cm. the interaction between thyroid and kidney disease: an overview of the evidence. current opinion in endocrinology, diabetes, and obesity. 2016;23(5):407. 7. sidhu gk, malek rr, khubchandani a, mansuri sh, patel ms, oza rh. a study of serum urea, creatinine and uric acid levels in hypothyroid patients. int j res med. 2016;5(2):1158. 8. marwah s, mehta m, shah h, haridas n, trivedi a. correlation of serum uric acid and serum creatinine in hypothyroidism. national journal of physiology, pharmacy and pharmacology. 2015;5(3):232-5. 9. raber w, vukovich t, vierhapper h. serum uric acid concentration and thyroid-stimulating-hormone (tsh): results of screening for hyperuricaemia in 2359 consecutive patients with various degrees of thyroid dysfunction. wiener klinische wochenschrift. 1999;111(8):326-8. 10. kaur v, singh k, verma m. changes in biochemical markers of renal function in subclinical and overt hypothyroidism. international journal of bioassays. 2015;4(4):3799-802. 11. karanikas g, schütz m, szabo m, becherer a, wiesner k, dudczak r, et al. isotopic renal function studies in severe hypothyroidism and after thyroid hormone replacement therapy. american journal of nephrology. 2004;24(1):41-5. 12. khan mah, majumder mi, hoque mm, fariduddin m, mollah fh, arslan i. serum creatinine and uric acid levels in hypothyroid patients: a cross sectional study. journal of enam medical college. 2013;3(2):84-7. 13. abebe n, kebede t, wolde m. assessment of renal function and electrolytes in patients with thyroid dysfunction, in addis ababa, ethiopia: a cross sectional study. pan african medical journal. 2016;24. 14. ye y, gai x, xie h, jiao l, zhang s. association between serum free thyroxine (ft4) and uric acid levels in populations without overt thyroid dysfunction. annals of clinical & laboratory science. 2015;45(1):49-53. 15. ashizawa k, imaizumi m, usa t, tominaga t, sera n, hida a, et al. metabolic cardiovascular disease risk factors and their clustering in subclinical hypothyroidism. clinical endocrinology. 2010;72(5):689-95. 16. khan sh, manzoor sm, niazi nk, asif n, ijaz a, fazal n. association of metabolic risks with subclinical hypothyroidism: a cross-sectional analysis. pakistan journal of medical sciences. 2018;34(2). 17. saini v, yadav a, arora mk, arora s, singh r, bhattacharjee j. correlation of creatinine with tsh levels in overt hypothyroidism a requirement for monitoring of renal function in hypothyroid patients? clinical biochemistry. 2012;45(3):212-4. 18. arindam s, satyajit k. correlation of altered lipid profile, uric acid and fasting plasma glucose levels in females with hypothyroidism. endocrinology & metabolic syndrome. 2017;06(05). uric acid, tsh and ft4 in hypothyroidismjiimc 2020 vol. 15, no.2 97 original�article abstract objective: the present research was carried out to observe withdrawal effects of energy drinks, whether these histomorphological changes are reversible or not. study design: laboratory based experimental study. st th place and duration of study: the research was carried out from 1 july to 30 august 2019 at national institute of health islamabad. materials and methods: total thirty adult male albino rats were divided into 3 groups by simple random sampling, with ten rats in each group. group i was control group, while energy drink group ii received 3.57ml/kg body weight red bull corresponding to one can of energy drink (250ml) in humans orally for eight weeks. rats in withdrawal group iii received energy drink for first four weeks followed by normal diet and water for last four weeks. after eight weeks, rats were sacrificed and their right kidneys were removed. slides were prepared using hematoxylin eosin and periodic acid schiff stain, results were analyzed by spss. results: the results showed that use of energy drink for 8 weeks resulted in increase in weight of kidneys along with histological alterations in renal cortex of rat kidneys. grade 4 (severe) congestion, hemorrhage, loss of brush border and necrosis was observed in energy drink group ii. withdrawal of energy drink in group iii resulted in weight of kidneys near to control group along with significant reduction in congestion, hemorrhage, loss of brush border and necrosis grades from grade 4 to grade 3 and 2 with p≤0.05. conclusion: caffeinated energy drinks are having damaging effects on kidneys of albino rats and these histological changes caused by caffeinated energy drinks in this duration of study and in low doses corresponding to one can of energy drink (250ml) in humans are reversible. key words: caffeinated, energy drink, histological, kidneys, withdrawal. available in pakistan. first and most trendy caffeinated energy drink to be introduced is red bull. target of these caffeinated drinks market is mainly youth. in pakistan majority of energy drink users are youngsters with age group of 13-35 years. eds claim to provide burst of energy by using a combination of caffeine (chief active ingredient), guarana, yerba mate, taurine, glucose, fructose and 3 glucuronolactone. caffeinated energy drinks (eds) contain higher levels of caffeine along with other ingredients that are not commonly found in sodas and juices, marketed as providing mental and physical stimulation especially in youth. they differ from soft or sport drinks due to their unique 4 composition. caffeine present in these drinks is up to 500 mg per 20 oz. (600 ml) serving that is 15 times the amount of caffeine present in a 12-ounce (360 ml) serving of cola. beverages that contains guarana actual levels of caffeine are much higher than levels mentioned on 5 the label. youth using eds is unaware of these high introduction energy drinks (eds) were first introduced in uk in 1929 as hospital drink; in 1980 they were promoted for replenishing lost energy. they are now available in > 140 countries as part of a multibillion dollar 1 business. in 1960s they appeared in asia and 2 europe. there are diverse types of energy drinks histological effects of caffeinated energy drink consumption and its withdrawal on kidneys of experimental rats 1 2 3 4 5 6 syeda sara bano , shabana ali , rehana rana , hussain ali , ali ahmad , tooba khurshid correspondence: dr. syeda sara bano senior lecturer department of anatomy shifa college of medicine shifa tameer-e-millat university, islamabad e-mail: banobokhari@hotmail.com 1 department of anatomy shifa college of medicine shifa tameer-e-millat university, islamabad 2,3,5,6 department of anatomy islamic international medical college riphah international university, islamabad 4 department of it nca rawalpindi. funding source: nil; conflict of interest: nil received: november 19, 2019; revised: june 05, 2020 accepted: june 06, 2020 caffeinated energy drinks: histological and withdrawal effects jiimc 2020 vol. 15, no.2 128 levels of caffeine and its adverse effects that is alarming. the kidneys are the organs that filter waste products from the blood. kidneys are predominantly vulnerable to ischemic and toxic damage. many studies have depicted adverse health effects of eds, one of them is hastened progression of renal micro 6 vascular impairment and chronic kidney disease. literature illustrates that exposure of rats to energy drink leads to kidney damage causing renal vascular congestion, hemorrhage of interstitial tissue, focal atrophy and degeneration of lining epithelium of 7 proximal and distal convoluted tubule. there is limited data available regarding withdrawal effects of these drinks, therefore present study was conducted to observe nature of renal damage and to observe changes after withdrawal of these drinks 1 whether these changes are reversible or not. materials and methods this laboratory based experimental study was st th conducted from 1 july to 30 august 2019 by mutual collaboration with national institute of health (nih) and islamic international medical college (anatomy department) after approval from ethical review committee (erc). thirty adult male healthy albinos sprague dawley rats (n=10/group) weighing 250±10 gm were used in experiment. they were housed at animal house of nih chak shahzad islamabad and were acclimatized to laboratory surroundings with free food and water access under natural dark and light rhythms prior to commencement of study. female rats and rats with any disease or pathology were excluded. total thirty animals were divided into three groups each group having ten rats selected by simple random sampling and treated in this way: the slides were examined under light microscope in x10, x40 power. parameters observed were weight of kidneys, congestion, hemorrhage, loss of brush border, and necrosis. using spss version 21 non parametric data was analyzed by means of chi square test. a p value of equal or less than 0.05 was considered as significant value. results renal cortical parenchyma appeared to be normal in 100% rats in control group i, while 25% rats showed minimal congestion (grade 1). in ed group severe congestion (grade 4) was noted in 62.5% of rats. in withdrawal group 62.5% lesions were moderate (grade 3) showing reversal of histological alterations caused by eds (fig: 1, table i). after 8 weeks of completion of experimental study rats were dissected and kidneys were removed. after fixation and embedding transverse sections of 5 µm thickness were obtained. staining was done with hematoxylin and eosin and periodic acid-schiff stain. group i group ii group iii fig 1: distribu�on of renal cor�cal parenchymal conges�on among different groups, group i k1r5 showing no conges�on, group ii k1r2 showing severe conges�on and arrows indica�ng moderate conges�on n group iii k1r7 (h&e, x400). caffeinated energy drinks: histological and withdrawal effects jiimc 2020 vol. 15, no.2 129 in 100% rats of control group i no hemorrhage was observed in renal cortex while in ed group severe hemorrhage (grade 4) was noted in 75% of rats. in withdrawal group 75% lesions were mild (grade 2) showing significant reduction in hemorrhage grade when compared to ed group (fig: 2 and table i). renal cortex appeared to be normal in 100% rats in control group i. in ed group severe (grade 4) loss of brush border was observed in pct of 87.5% rats. in withdrawal group mild loss of brush border in 50% of rats was seen showing significant reversal of histological alteration after withdrawal of ed. (fig: 3, table ii) group i group ii group iii fig 2: distribu�on of hemorrhage in renal cor�cal parenchyma of different groups, group i k1r2 showing no hemorrhage, group ii k1r8 showing severe hemorrhage and arrows indica�ng mild hemorrhage in group iii k1r9 (h&e, x400). table i: distribu�on of grades of conges�on and hemorrhage in control and experimental groups of albino rats by chi-square test group i group ii group iii fig 3: distribu�on of loss of brush border in pct of different groups, group i k1r5 showing prominent apical brush border, group ii k1r9 showing severe loss of brush border in pct and arrows indica�ng mild loss of brush border in group iii k1r1 (pas, x400). in control group 100% rats showed normal renal cortical architecture. in ed group severe (grade 4) necrosis was observed in 100% of rats. in group 3 moderate (grade 3) necrosis was seen in 75.5% rats showing significant reduction in grades of necrosis when compared to energy drink group. (fig: 4 and table ii) caffeinated energy drinks: histological and withdrawal effects jiimc 2020 vol. 15, no.2 130 in kidneys of male rats. in this study we observed no congestion with normal renal cortical parenchyma in control group. in ed group severe congestion in renal cortical parenchyma was observed. in withdrawal group, moderate congestion was seen. impairment of venous outflow due to inflammatory mediators results in a localized increase in blood to different areas of kidney, which is demonstrated histologically 8 as congestion. taiwo et al documented congestion after administration of energy drink in different 9 doses to rabbits. he documented that changes observed were reversible in 28 days duration of 9 study. similarly results has been supported by many 10,11,12 other studies. in our study severe hemorrhage was observed in ed group. in rats of group iii mild hemorrhages was seen. hemorrhage observed was due to the effect of inflammation leading to expansion of blood vessels, as result vessels rupture and blood flows out. a previous study showed similar findings after administration of ed 1ml/animal/day orally for 4 13 weeks. comparable findings were observed in liver 14 of rats after administration of high dose of eds. akande also proved that damaged caused by ed was 15 reversible in 28 days duration. the present study showed severe loss of brush border of pct in ed group, while in withdrawal group mild loss of brush border was observed that showed reversal of histological changes caused by red bull after withdrawal of ed. this might be explained by vulnerability of cellular membranes to toxins, leading to decrease cellular production of atp and accumulation of reactive oxygen species causing cell damage and detachment of epithelial cell from basement membrane. similar results were shown in albino rabbits by salih, results were ascribed to high 16 level of caffeine in eds. most common cause of acute kidney injury is acute tubular necrosis that causes death of tubular epithelial cells leading to renal failure. in group iii moderate necrosis was seen which was significantly 17 reverted after withdrawal of ed. coagulative pattern of necrosis was observed in various experimental groups which is more common in toxic 18 or ischemic injury. the observed necrosis may be due to carbon dioxide present in energy drinks that damages membranes of mitochondria, change in 13 atp production, hypoxia and cell deah. in another group i group ii group iii fig 4: distribu�on of necrosis in renal tubules of different groups, group i k1r3 showing no necrosis, group ii k1r5 showing severe tubular necrosis and arrows indica�ng moderate necrosis in group iii k1r7 (h&e, x400). discussion this study investigated the reversal of renal histomorphological features after withdrawal of ed table ii: distribu�on of grades of loss of brush border and necrosis in control and experimental groups of albino rats by chi-square test p value ≤ 0.05 caffeinated energy drinks: histological and withdrawal effects jiimc 2020 vol. 15, no.2 131 study after administration of red bull, severe necrosis was observed in seminiferous tubules of 19 male rats. in this study we observed the severity of renal injury in relation to time duration for which eds were used. in ed group significant difference was observed in weight of kidneys, congestion, hemorrhage, loss of brush border and necrosis. this indicates that eds leads to renal damage that is duration or time dependent, since more damage was observed in ed group when compared to group iii, it showed reversal of these histological features after withdrawal of ed. our findings are consistent with the results of study that proved that effects of caffeine on cell survival are highly time and dose dependent; in low doses it increases cell survival and at higher doses it increases super oxide 20,21 production. also the study proved that chronic 22 caffeine intake has age dependent effects on brain. conclusion in conclusion caffeinated energy drinks are having damaging effects on kidneys of rats, besides that with low doses, corresponding to one can of ed (250ml in humans) and with this duration of study histomorphological changes caused by caffeinated eds are reversible. references 1. ali f, rehman h, babayan z, stapleton d, joshi dd. energy drinks and their adverse health effects: a systematic review o f t h e c u r r e n t e v i d e n c e . p o s t g r a d m e d . 2015;127(3):308–22. 2. shaikh sa, ahuja k, shaikh ba, abbasi b, sikandar r, maqbool a. frequency of energy drinks consumption and its determinants among undergraduate students. pakistan j med heal sci. 2018;12(1):385–9. 3. o'brien mc, mccoy tp, rhodes sd, wagoner a, wolfson m. caffeinated cocktails: energy drink consumption, high-risk drinking, and alcohol-related consequences among college students. acad emerg med. 2008;15(5):453–60. 4. nahla khamis ibrahim ri. energy drinks�: getting wings but at health cost. pak j med. 2014;30(6):1415–9. 5. mcgraw mm. are energy drinks safe? nursing (lond). 2013;43(3):68. 6. al-basher gi, aljabal h, almeer rs, allam aa, mahmoud am. perinatal exposure to energy drink induces oxidative damage in the liver, kidney and brain, and behavioral alterations in mice offspring. biomed pharmacother. 2018;102(march):798–811. 7. mansy w, alogaiel dm, hanafi m, zakaria e. effects of chronic consumption of energy drinks on liver and kidney of experimental rats. trop j pharm res. 2017;16(12):2849–56. 8. shimada s, hirose t, takahashi c, sato e, kinugasa s, ohsaki y, et al. pathophysiological and molecular mechanisms involved in renal congestion in a novel rat model. sci rep. 2018;8(1):1–15. 9. iyaniwura o, abdulfatai a. toxicodynamic effects of ' red bull ' energy drink in a randomised controlled study on local strains of adult rabbits. j biol life sci. 2018;9(1):46–64. 10. alkhedaide a, soliman mm, eldin a, eldin s, ismail ta, alshehiri zs, et al. chronic effects of soft drink consumption on the health state of wistar rats�: a biochemical , genetic and histopathological study. 2016;5109–17. 11. adjene jo, ezeoke jc, nwose eu. histological effects of chronic consumption of soda pop drinks on kidney of adult wister rats. 2010;2(5). 12. kassab aa, tawfik sm. effect of a caffeinated energy drink and its withdrawal on the submandibular salivary gland of adult male albino rats�: a histological and immunohistochemical study. 2018;11–26. 13. aziz f. study of physiological and histological changes in male rats ( rattus norvegicus ) after carbonated and energy beverages drinking fatima aziz mahdi al-badry biology department / college of education for pure sciences / university of thi-qar email�: fatima. 2018;13(2):1–20. 14. m. bukhar h, a. elsawy n, a. header e. biological effect of high energy drink on normal and hyperglycemic rats. pakistan j nutr. 2012 apr 1;11(4):301–9. 15. akande is, banjoko oa. assessment of biochemical effect of " power horse " energy drink on hepatic, renal and histological functions in sprague dawley rats. annu rev res biol. 2011;1(13):45–56. 16. salih n, abdul-sadaand i, abdulrahman n. histopathological effect of energy drinks (red bull) on brain, liver, kidney, and heart in rabbits. med j babylon. 2018;15(1):16. 17. schöffl ai, jürgen f. “ vodka energy ”: too much for the adolescent nephron�? j am acad pediatr. 2011;128(1). 18. kumar vinay. robbins chapter 3: acute &amp; chronic inflammation. 9th ed. 30,35. 19. al-eryani fs, bull r. histological and physiological studies on the effects of some energy drinks on male rats energy drinks. int j pharm res allied sci. 2018;7(1):165–76. 20. jafari m, rabbani a. dose and time dependent effects of caffeine on superoxide release , cell survival and dna fragmentation of alveolar macrophages from rat lung. 2000;149:101–8. 21. tran s, fulcher n, nowicki m, desai p, tsang b, facciol a, et al. progress in neuro-psychopharmacology & biological psychiatry time-dependent interacting effects of caffeine , diazepam , and ethanol on zebra fi sh behaviour. pnp. 2017;75:16–27. 22. poole rl, braak d, gould tj. concentration and age dependent effects of chronic caffeine in mice. behav brain res. 2015; caffeinated energy drinks: histological and withdrawal effects jiimc 2020 vol. 15, no.2 132 original�article abstract objective: to determine the association of glycated hemoglobin with frontal lobe cognitive dysfunction in type 1 diabetes patients. study design: case control study. place and duration of study: bahawal victoria hospital, bahawalpur, pakistan from june 2016 until august 2017. materials and methods: fifty diabetic patients and fifty healthy adults were tested for fasting hba levels. 1c following, they were administered frontal assessment battery. participants were given separate instructions for assessment of each frontal lobe function and they completed frontal assessment battery in a single testing session. data was analyzed for group differences on each frontal lobe function through anova. bivariate correlations were computed to assess the relationship between frontal lobe functions and hba regression 1c. analysis was used to assess hba as a predictor of frontal lobe cognitive functioning 1c . results: diabetic patients showed impaired performance on frontal lobe cognitive functions in contrast with healthy individuals. hba and frontal lobe cognitive functions were negatively correlated. deficient glycemic 1c control was associated with frontal lobe cognitive deficits. hba was found as a significant predictor of frontal 1c lobe cognitive functioning. conclusion: higher level of hba is a predictor of frontal lobe cognitive functioning deficits in patients with 1c type 1 diabetes. key words: cognition, fasting glucose, glycemic control, glycemic index, type 1 diabetes. pathophysiology includes lesions of the subcortical white matter, cortical infarcts, density of neuritic plaques, hyperphosphorylated tau (i.e., group of neuronal microtubule-associated proteins) within axons, oxidative stress, and inflammation of nerve 9,11 pathways. deregulation of major excitatory receptors of the central nervous system (i.e., glutamatergic receptors which control synaptic activity during learning and memory) accelerates 12,13 cognitive deficits. cognitive impairments, brain aging and neurodegeneration are associated with molecular changes in protein kinases, second14,15 messenger system and glutamate-receptors. it was also found that dm prolongs peripheral as well as central conduction time (onset, peak latencies and velocity) in spinal cord structures. these changes are connected with demyelination along fibers needed to conduct nerve impulses through periphery and 16,17 brain cortex. segmental demyelination, axonal degeneration and nerve loss involve peripheral nerves whereas velocities of sensorymotor nerve conduction are involved in deficits of the distal 18,19 limbs. previous research has shown that chronic hyperglycemia is associated with cognitive decline in introduction diabetes mellitus (dm) increases risk of cognitive 1 decline. type 1 dm involves mental flexibility, visual perception and attention whereas type 2 dm may cause memory deficits or reduced executive 2 function. neurocognitive changes in type 1 dm 3,4 involve volume loss and atrophy of cerebral cortex. frontal lobes are involved in multiple cognitive processes i.e., executive functions, memory, attention, language etc. and constitute two-thirds of 5 the human brain. temporal lobes have a role in m e m o r y a n d t h i n k i n g p r o c e s s e s a n d pathophysiology in this brain region leads to 6 cognitive and neurodegenerative disorders. deficit in gray matter volume is also associated with higher 7 , 8 glycated haemoglobin (hba ) levels. dm 1 c glycated hemoglobin: a predictor of cognitive deficits in type 1 diabetes patients 1 2 amara gul , memoona sehar correspondence: dr. amara gul assistant professor department of applied psychology the islamia university of bahawalpur, bahawalpur e-mail: amara_psychology@hotmail.com 1,2 department of applied psychology the islamia university of bahawalpur, bahawalpur funding source: nil; conflict of interest: nil received: august 06, 2018; revised: may 04, 2019 accepted: may 09, 2019 glycated hemoglobin and cognition in diabetesjiimc 2019 vol. 14, no.2 91 functions. it is brief and easy to administer and has good psychometric properties. the total score consists of a cumulative score of six individual neuropsychological tasks (score range 0-18). in the “similarities” (conceptualization) task, patient is required to indicate superordinate concept of objects from the same semantic category (score range 0-3 high score shows intact performance). lexical verbal fluency (mental flexibility) examines semantic retrieval. patient is required to say as many words as possible starting with s except nouns and surnames in 60 seconds (score range 0-3, more than nine correct responses=3). in motor series, patient executes a series of motor acts (score range=0-3; at least 6 consecutive series alone=3). conflicting instructions assess self control by hitting the table one time fewer than the administrator hits. after the practice trial, patient has to follow an alternating numbered order (score 0-3, high score shows no error). prehension behavior examines the activated behaviors. the administrator hints palms without uttering a word when subject placed their hands on knees. subject is instructed not to take the administrator's hands. doing so will be scored as three. total score is cumulative of subscales of f-a-b which is 0 to 18; high score is intact cognition. spss (version 20) was used to analyze data. descriptive statistics (mean, standard deviation and t-test) were used to analyze demographic and clinical characteristics of sample as shown in table i. interaction of group with subscales of f-a-b with factors as 6 f-a-b (within subject) x 2 group (diabetic patients vs. healthy control subjects: between subject) was assessed using anova. bivariate correlations were computed to assess the relationship between total fab score, subscale scores and hba . regression analysis was conducted 1c to assess hba as predictor of fab scores. 1c results results showed that the main effect of f-a-b f (1, 98) =1.78, p=.11, ηp2=.01 was non-significant whereas the main effect of group was significant f (1, 98) =1844.64, p=.001, ηp2=.95. the interaction between fab and group was significant f (1, 98) =3.11, p=.01, ηp2=.03. group differences on subscales are reported in table ii. correlation between hba and 1c fab scores on lexical verbal fluency (-.45, p=.001), motor series (-.33, p=.01), go-nogo (-.35, p=.01), 20 non-demented elderly patients. increased glycated hemoglobin is associated with significant reduction 21 in cognitive functioning in patients with diabetes. this association has been observed in patients with 22 metabolic syndromes and coronary heart disease. high peaks of glucose over several years can even 23 cause dementia. to date, frontal lobe dysfunctions in relation with glycemic control have not been examined in pakistani subjects. given the brain structural and functional changes, it was hypothesized that diabetic patients would show weaker frontal lobe related functioning than healthy adults. glycemic control as assessed through hba1c would be associated with frontal lobe functioning a n d c o u l d t h e refo re p re d i c t f ro n ta l l o b e dysfunctions. hba is an index of circulating glucose 1c levels over 2-3 months. the objective of this study was to assess the association of glycated hemoglobin with frontal lobe cognitive dysfunction in type 1 diabetic patients. materials and methods this study had a case control design and was conducted at the endocrinology and diabetes d e p a r t m e n t o f b a h a w a l v i c t o r i a h o s p i t a l bahawalpur, pakistan from june 2016 to august 2017. the study was ethically approved by the islamia university of bahawalpur and followed principles of helsinki declaration. purposive sampling was used. fifty patients diagnosed with type 1 dm were included with criteria as (i) age range 35-55 years (ii) diagnosed with type 1 dm (iii) having no medication other than antidiabetics, whereas exclusion was done with reports of psychological disorder, neurological disorder, history of head trauma, cancer and diseases of the central nervous system. fifty healthy demographically matched individuals took part in the study. healthy individuals were included with age range 35-55 years and with no present use of any medication. the exclusion criterions were: (i) history /present complaints of diabetes. (ii) history/present illness of substance use, psychiatric disorder, neurological disorder, history of head trauma, cancer and diseases of the central nervous system. all participants gave written informed consent. participants had a fasting blood glucose test. subsequently, they were administered frontal 24 assessment batteryf-a-b to examine frontal lobe glycated hemoglobin and cognition in diabetesjiimc 2019 vol. 14, no.2 92 between these two variables exists in type 1 dm. it was hypothesized that patients with type 1 dm would show frontal lobe cognitive deficits and deficient glycemic control. in addition, impaired glycemic control was related with frontal lobe cognitive deficits. neuropsychological measures of frontal-lobe-related functions were used to assess frontal lobe functions and glycemic control was assessed through hba there were few important 1c. findings: (i) functioning of the frontal lobe was weaker in diabetics (ii) f-a-b subscales and glycemic control correlated (iii) glycemic control significantly predicted frontal lobe dysfunctions. previous studies have illustrated that neurodegeneration in 6-8 alzheimer's disease and diabetes is similar , for instance lesions of the subcortical white matter, cortical infarcts, density of neuritic plaques, aβ plaques and nfts-hyperphosphorylated tau within axons, oxidative stress, inflammation of pathways, deregulation of excitatory receptors in central nervous system, and long-term potentiation in 9-11 hippocampus. furthermore, these changes extend to molecular changes in protein kinases, s e c o n d m e s s e n g e r s y s t e m s , g l u t a m a t e 14,15 16,17 receptors , delay in nerve conduction times, segmental demyelination and deficits of the distal 18,19 limbs. results of this study are consistent with literature suggesting global cognitive deficits in type 2 1 diabetic patients and neurocognitive changes in type 1 dm such as reduced cerebral volumes and 3,4 atrophy of frontal and temporal lobes . frontal lobes encompass two-thirds of the brain and are 6 responsible for multiple cognitive processes whereas temporal lobes are involved in memory and thinking processes. degeneration in these brain 5 areas are related with cognitive deficits. the finding of the present study that glycemic control is associated with frontal lobe dysfunctions can be seen in the context of deficient gray matter volume and greater glycated hemoglobin as an index of 7,8, 20,21 reduced cognition in patients with dm. conclusion higher level of hba is a predictor of frontal lobe 1c cognitive functioning deficits in patients with type 1 diabetes. references 1. munshi mn. cognitive dysfunction in older adults with prehension behavior (-.36, p=.01), and total fab scores (-.81, p=.001) were significant whereas correlations between glycemic control (blood glucose) and similarities (-.27, p=.055), and conflicting instructions (-.16, p = .26) were not significant. regression analysis showed that hba1c significantly predicted fab total scores f (1, 49) = 2 95.99, p=.001, r = .66, β= -.81, t = -9.79, p=.001. odd ratio was 1.00, p<0.001, 95%. risk for cognitive deterioration was significantly different t (49) = 42.73, p =.001, m = 47.55, sd = 7.86 between patients (50.34%) and healthy individuals (2.78%). table i: characteris�cs of pa�ents with diabetes and healthy individuals table ii: group differences on subscale scores of frontal assessment ba�ery (n= 100) discussion this study was designed to examine frontal lobe functions and glycemic control in type 1 dm. further objective was to determine whether any relationship note: lower-upper bound is reported on 95% confidence interval note. hba1c= glycated hemoglobin (%) glycated hemoglobin and cognition in diabetesjiimc 2019 vol. 14, no.2 93 rejuvenation. nature 2016;539(7628):180-6. 15. moran c, beare r, phan tg, bruce dg, callisaya ml, srikanth v. type 2 diabetes mellitus and biomarkers of neurodegeneration. neurology 2015; 85(13):1123-30. doi: 10.1212/wnl.0000000000001982 . 16. cholerton b, baker ld, montine tj, craft s. type 2 diabetes, cognition, and dementia in older adults: toward a p r e c i s i o n h e a l t h a p p r o a c h . d i a b e t e s s p e c t r. 2016;29(4):210–219. doi:10.2337/ds16-0041. 17. bouhrara m, reiter da, bergeron cm, zukley lm, ferrucci l, resnick sm, et al. evidence of demyelination in mild cognitive impairment and dementia using a direct and specific magnetic resonance imaging measure of myelin content. alzheimers dement 2018; 14(8):998-1004. 18. ahmad a, moinuddin a, ahsan a, goel a. study of electrophysiological changes in sensory nerves among diabetic smokers. j clin diagn res 2016; 10(1):9-11. 19. xu rs. pathogenesis of diabetic cerebral vascular disease complication. world j diabetes 2015;6(1):54–66. doi:10.4239/wjd.v6.i1.54 20. huang l, yang l, shen x, yan s. relationship between glycated hemoglobin a1c and cognitive function in nondemented elderly patients with type 2 diabetes. metab brain dis. 2016; 31(2):347-53. doi: 10.1007/s11011-0159756-z. 21. gul a, sahar m, jawad u. relationship between neuropsychological functioning, behavioural inhibition and glycaemic control in type 2 diabetes: findings from task switching study. chinese medical journal 2017; 130 (4): 487-9. doi: 10.4103/0366-6999. 199842. 22. ayadhani r, fowler k, barbato c, thomas s, wong w, paul c, et al. glycemia and cognitive function in metabolic syndrome and coronary heart disease. am j med 2015; 128(1):46-55. doi: 10.1016/j.amjmed.2014.08.025. 23. rawlings am, sharrett ar, mosley th, ballew sh, deal ja, selvin e. glucose peaks and the risk of dementia and 20year cognitive decline. diabetes care 2017; 40(7):879-86. doi: 10.2337/dc16-2203 24. dubois b, slachevsky a, litvan i, pillon b. the fab: a frontal assessment battery at bedside. neurology 2000; 55:1621-6. diabetes: what a clinician needs to know. diabetes care 2017; 40(4):461-7. 2. saedi e, gheini mr, faiz f, arami ma. 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n. high "normal" blood glucose is associated with decreased brain volume and cognitive performance in the 60s: the path through life study. plos one 2013;8(9):e73697. 9. morley je. the diabetic brain. nature reviews endocrinology 2017; 13: 570-71. 10. riederer p, korczyn ad, ali ss, bajenaru o, choi ms, chopp m, et al. the diabetic brain and cognition. j neural transm (vienna) 2017; 124(11):1431-54. 11. moheet a, mangia s, seaquist er. impact of diabetes on cognitive function and brain structure. annals of the new york academy of sciences 2015; 1353: 60-71. 12. lindsay az, krish c, justin yk, james wr. diabetes and cognitive impairment. curr diab rep 2016; 16(9): 87. 10.1007/s11892-016-0775-x. 13. merritt k, mcguire p, egerton a. relationship between glutamate dysfunction and symptoms and cognitive function in psychosis. front psychiatry 2013; 4:151. 14. wyss-coray t. ageing, neurodegeneration and brain glycated hemoglobin and cognition in diabetesjiimc 2019 vol. 14, no.2 94 original�article abstract objective: to determine the association between hypothyroidism and metabolic syndrome study design: observational cross sectional study place and duration of study: data was collected from medical unit and department of pathology, pakistan railways hospital, islamic international medical college, rawalpindi and capital hospital islamabad from april 2017 to april 2018. materials and methods: one hundred and fifty adult subjects participated in this study. hundred hypothyroid subjects were recruited as cases on the basis of laboratory findings of raised serum thyroid stimulating hormone (tsh) levels and low serum free thyroxine (ft4) level. newly diagnosed/ untreated cases of hypothyroidism and adults of either sex were included. after an overnight fasting, participants were tested for various components of metabolic syndrome. fifty euthyroid subjects were taken as controls. data was analyzed by spss-21. results: among 150 total recruited subjects, 25% hypothyroid cases and 10% euthyroid controls were diagnosed with metabolic syndrome. these results were statistically significant with p value 0.030. mean serum triglycerides 183 ±26 and 153±26 mg/dl and mean fasting blood glucose 100 ±30 and 96 ±18 mg/dl respectively among hypothyroid and euthyroid patients were significant with p-value 0.001. whereas, waist circumference, high density lipoprotein cholesterol and blood pressure measurement of hypothyroid and euthyroid individuals were not significant. conclusion: hypothyroidism is associated with various components of metabolic syndrome. key words: free thyroxine, fasting blood glucose, hypothyroid, metabolic syndrome, serum triglycerides, thyroid stimulating hormone in body such as basal metabolic rate , protein synthesis, cardiac and gastrointestinal function, maturation of the central nervous system and 3 maintain body mass index. hypothyroidism has prevalence of 3.8%–4.6% in asian population as per 4 data of different studies. definition of metabolic syndrome given by american heart association and the national heart, lung and blood institute (aha/nhlbi) declared that clinical diagnosis of metabolic syndrome can be established if any three of the following factors are present, elevated triglyceride level (tg), elevated waist circumference, decreased hdl-cholesterol (hdl-c) level, elevated 5 fasting plasma glucose and elevated blood pressure. the estimated prevalence of metabolic syndrome in 3 general population is between 17 and 25%. decreasing thyroid function is associated with occurrence of obesity and hence can potentially 6 contribute to the development of ms. as thyroid hormones decrease, components of metabolic 7 syndrome get more prominent. study conducted in western population and india showed that thyroid introduction thyroid dysfunction and metabolic syndrome are major encountered endocrine abnormalities in 1 clinical practice. high blood glucose level, raised s e r u m t r i g l y c e r i d e l e v e l , i n c re a s e d w a i s t c i r c u m f e r e n c e , e l e v a t e d b l o o d p r e s s u r e measurements and low high density lipoprotein 2 cholesterol are common in these two entities. thyroid hormones regulate wide range of functions association of hypothyroidism with metabolic syndrome 1 2 3 4 5 fakhra noureen , muhammad nadeem akbar khan , abid saeed khan , shazia qayyum , aqsa liaquat correspondence: dr. fakhra noureen demonstrator/lecturer department of pathology islamic international medical college riphah international university, islamabad 1,2,4 department of pathology islamic international medical college riphah international university, islamabad 3 department of medicine cda hospital islamabad 5 department of pathology hbs medical college, islamabad funding source: nil; conflict of interest: nil received: september 05, 2018; revised: november 24, 2018 accepted: november 25, 2018 hypothyroidism and metabolic syndromejiimc 2018 vol. 13, no.4 174 taken fifteen minutes apart was considered. data was entered and analyzed using statistical package for social sciences (spss) version 21. simple descriptive statistics (frequencies, percentages) was computed for each categorical variable such as age and gender. whereas mean and standard deviation was calculated for numerical (continuous) variables which included serum tsh, serum ft4, blood glucose fasting, serum hdl-c, serum triglycerides, waist circumference and blood pressure measurements. independent sample t test was applied to compare the means of various components of metabolic syndrome. chi square test was applied to determine the relationship between hypothyroid and different components of metabolic syndrome. p value of < 0.05 was considered statistically significant. results mean age (years) of total recruited subjects was 41.64±3 among them 33.3%were males and 66.7% were female. mean age (years) of hypothyroid subjects was 42.48±11.56 having 26% male and 74%females. among 50 euthyroid subjects age in years was 39.36±12.01 with 48% male and 52% female. hypothyroid subjects who had metabolic syndrome were 25 in number with mean age of 46.50±8.97, and male to female ratio were 16.7 % and 83.3% respectively. descriptive statistics of serum tsh in hypothyroid and euthyroid subjects was 32 ±28 and 3.2 ±0.6, which was statistically significant i.e (p 0.001). whereas mean serum ft4 levels was 0.4 ±0.2 in hypothyroid subjects and 1.5 ±0.4 in euthyroid subjects and was statistically significant i.e (p 0.001). mean serum tsh levels and ft4 levels were 35 ±28, 19 ±25 and 0.61 ±0.5, 0.8 ±0.5 in subjects having metabolic syndrome and subjects who did not present with metabolic syndrome respectively and was statistically significant (p-value 0.005) as shown in table i. different variables of metabolic syndrome were compared among hypothyroid and euthyroid patients. mean serum triglycerides mg/dl among hypothyroid and euthyroid patients were 183 ± 26 and 153 ± 26 respectively, the difference in two groups was significant (p value 0.001). mean fasting blood glucose mg/dl levels were 100 ±30 and 96 ±18 in hypothyroid and euthyroid subjects and was statistically significant with p value 0.001. independent sample t-test was used to compare hormones significantly affect each component of 8, 9 metabolic syndrome. extensive literature review revealed that studies have been done regarding this topic in developed countries, however, reported clinical data is scarce in pakistan. this knowledge gap was addressed by designing a study with an objective to find the relationship between hypothyroidism and metabolic syndrome. materials and methods it was an observational, cross-sectional study conducted at department of chemical pathology, i s l a m i c i n t e r n a t i o n a l m e d i c a l c o l l e g e i n collaboration with medical unit of pakistan railways hospital, rawalpindi and medical unit of capital hospital islamabad. the study extended over a period of 12 months from april 2017 to april 2018. a total of 150 subjects were enrolled by nonprobability convenient sampling after approval from ethical review committee. written informed consents were obtained from participants. with the help of medical specialist of pakistan railways and capital hospital, serum tsh was done of clinically diagnosed patients who visited medical opd. subjects who had raised serum tsh levels > 4.5 µiu/ml were further tested for serum ft4. similarly h u n d r e d n e w l y d i a g n o s e d p a t i e n t s o f hypothyroidism on the basis of raised serum tsh and low serum ft4 were taken as cases. fifty age and gender matched controls with normal serum tsh level (0.4 – 4.5 µiu/ml) were enrolled. willing participants reported the next morning after an overnight 10-12 hours fast. 5ml blood was taken for analysis. the blood samples were centrifuged at 15000 rpm x g for about 15 minutes and serum was separated. serum tsh and ft4 test was performed using the vitros eci immunodiagnostic systems. hdl-c was measured by enzymatic precipitation method on semi-automated chemistry analyzer micro-lab 300. enzymatic end-point method (gpopap) was used to determine the triglycerides level and glucose concentrations were determined on fasting serum samples, using glucose oxidase method on semi-automated micro lab 300. using the pubic crest and the umbilicus as land marks abdominal obesity was determined by measurement of the waist circumference in centimeters. blood pressure was measured with the help of mercury sphygmomanometer. the average of two readings 175 hypothyroidism and metabolic syndromejiimc 2018 vol. 13, no.4 discussion the study showed that mean age of hypothyroid and euthyroid participants were 42.48± 11.5 and waist circumference, hdl and blood pressure measurements among hypothyroid and euthyroid subjects which was statistically not significant, as shown in table ii. chi-square test was applied to determine the association of hypothyroidism with metabolic syndrome as shown in table iii. among 100 hypothyroid and 50 euthyroid subjects 25 (25%) and 05 (10%) individuals presented with metabolic syndrome respectively. the results were statistically significant with p value 0.030. table i : descrip�ve sta�s�cs of serum tsh and serum ft4 levels in metabolic syndrome (ms) pa�ents *p<0.05 was taken as level of significant table ii: descrip�ve sta�s�cs of metabolic syndrome variables in hypothyroid and euthyroid subjects *p<0.05 was taken as level of significant table iii: associa�on of hypothyroidism with metabolic syndrome *p<0.05 was taken as level of significant 176 39± 12, respectively as compared to the patients of metabolic syndrome in which mean age was 46.5 ±8.9. this shows that prevalence of metabolic syndrome increases with age as decline in immunocompetence with age is accompanied by the increase in the incidence of autoimmune diseases. similar findings are present in study by 10 ervin rb. in total of 150 participants, 30 subjects were diagnosed with metabolic syndrome in which 37.5% were male whereas 62.5 % were female which shows that in females ms is common. study by gurav et al 11 reports similar findings. another study by louai razzouk et al demonstrated increase prevalence of the metabolic syndrome in older age and higher among females. this can be explained by increased caloric intake, dyslipidemia, and sedentary lifestyle, hormonal changes in women and obesity in older 12 age. mean serum tsh and ft4 in metabolic syndrome patients was 35 ±28, 19 ±25 and 0.61 ±0.5, 0.8 ±0.5 respectively which was statistically significant. tsh is more sensitive indicator of thyroid function. even small changes in thyroid hormone levels may cause a marked shift in tsh level these findings have shown a similar relationship with thyroid hormones by 13 shehzad et al. in our study it was found that 25(83%) hypothyroid subjects were diagnosed with ms and had high serum tsh levels as compared to the euthyroid subjects where 5 subjects were diagnosed with ms, who had tsh levels within normal reference range. the study conducted in nepal by gyawali et al 14 showed significant difference. fasting blood glucose levels were found higher in hypothyroid patients as compare to euthyroid (control) group. this finding is in agreement to 15 previous study by maratou at al. serum triglyceride levels were found to be elevated; on the other hand the hdl-c levels were lower in hypothyroid patients. th affects hdl-c through cholesterol ester transfer protein and hepatic lipase activity. these findings are similar with results of 16, 17 previous studies by sanyal et al and pearce et al. in our study, it has been observed that high serum tsh levels are directly related with various components of metabolic syndrome. study by renehr et al has found increased serum tsh levels to be correlated hypothyroidism and metabolic syndromejiimc 2018 vol. 13, no.4 with obesity. this may be due to involvement of leptin protein from adipose tissues which also 18 fluctuates with body adiposity. extensive literature review has revealed that scanty work has been done in our setup to determine association between hypothyroidism and metabolic syndrome. our study results showed that ms is highly prevalent among hypothyroid patients. there were 25 (83.3%) hypothyroid and 05 (16.7%) euthyroid patients (control group) who were diagnosed with metabolic syndrome. these results are in agreement with the previous study by gyawali 14 19 p and roos et al. another study conducted by tehrani f on large cohort of 5786 subjects also found that hypothyroidism is associated with metabolic 20 syndrome. conclusions our study shows association of ms among hypothyroid patients in our setting in rawalpindi and islamabad, pakistan. the coexistence of two diseases ms and thyroid dysfunction increases the chance of cardiovascular disease and diabetes. therefore, diagnosed patients of hypothyroidism should be evaluated for all components of ms. limitations the study design was cross-sectional, so it did not help to determine cause and effect relationship between low-normal thyroid function and ms. sample size was small i.e. 100 hypothyroid patients and 50 euthyroid participants, a large scale clinical trials should be carried out. due to limited resources subjects were recruited from two centers, a multicenter study should be carried out involving all main hospitals of the city. references 1. yang l, lv x, yue f, wei d, liu w, zhang t. subclinical hypothyroidism and the risk of metabolic syndrome : a meta-analysis of observational studies syndrome : a metaanalysis of observational studies. 2016;5800(march). 2. palamaner g, shantha s, kumar aa, jeyachandran v, rajamanickam d, rajkumar k, et al. association between primary hypothyroidism and metabolic syndrome and the role of c reactive protein: a cross–sectional study from south india. 3. amir iqbal m, naseem z, qureshy a, shahid a, roohi n. prevalence and manifestations of thyroidal dysfunction in central punjab pakistan (a case study). sciint(lahore). 2016;28(4):3959–63. 4. hollowell jg, staehling nw, flanders wd, hannon wh, 177 gunter ew, spencer ca b le. serum tsh, t 4, and thyroid antibodies in the united states population (1988 to 1994): national health and nutrition examination survey (nhanes iii). j clin endocrinol metab. 2002;87(2):489–99. 5. grundy sm, cleeman ji, daniels sr, donato ka, eckel rh, franklin ba, et al. diagnosis and management of the m e t a b o l i c s y n d r o m e : a n a m e r i c a n h e a r t association/national heart, lung, and blood institute scientific statement. circulation. 2005;112(17):2735–52. 6. knudsen n, laurberg p, rasmussen lb, bülow i, perrild h, ovesen l, et al. small differences in thyroid function may be important for body mass index and the occurrence of obesity in the population. j clin endocrinol metab. 2005;90(7):4019–24. 7. bonora bm, fadini gp. subclinical hypothyroidism and metabolic syndrome: a common association by chance or a cardiovascular risk driver 2016 oct;14(8):378-380. 8. udenze i, nnaji i, oshodi t. thyroid function in adult nigerians with metabolic syndrome. pan afr med j. 2014; 9. misra a, misra r, wijesuriya m, banerjee d. the metabolic syndrome in south asians: : continuing escalation & possible solutions. indian journal of medical research. 2007;1:345-54. 10. ervin rb. prevalence of metabolic syndrome among adults 20 years of age and over, by sex, age, race and ethnicity, and body mass index: united states. national health statistics reports. 2009;13:1-8. 11. agarwal g, sudhakar m, singh m, senthil n, rajendran a. the prevalence of thyroid dysfunction among south indian women with metabolic syndrome. j clin diagn res. 2011;5(2):213-6. 12. louai razzouk, md, and paul muntner, phdethnic, gender, and age-related differences in patients with the metabolic syndrome : department of community and preventive medicine, mount sinai school of medicine, one gustave l. levy place newyork. current hypertension reports 2009, 11:127–132. 13. saleem ms, shirwany tak, khan ka. relationship of thyroidstimulating hormone with metabolic syndrome in a sample of euthyroid pakistani population. j ayub med coll abbottabad. 2011;23(2):63-8. 14. gyawali p, takanche js, shrestha rk, bhattarai p, khanal k, risal p, et al. pattern of thyroid dysfunction in patients with metabolic syndrome and its relationship with components of metabolic syndrome. diabetes & metabolism journal. 2015;39(1):66-73. 15. maratou e, hadjidakis dj, peppa m, alevizaki m, tsegka k, lambadiari v, et al. studies of insulin resistance in patients with clinical and subclinical hyperthyroidism. european journal of endocrinology. 2010;163(4):625-30. 16. sanyal d, raychaudhuri m. hypothyroidism and obesity: an intriguing link. indian journal of endocrinology and metabolism. 2016;20(4):554. 17. pearce en. hypothyroidism and dyslipidemia: modern concepts and approaches. current cardiology reports. 2004;6(6):451-6. 18. reinehr t. obesity and thyroid function. molecular and cellular endocrinology. 2010;316(2):165-71. 19. roos a, bakker s, links t, gans r, wolffenbuttel b. thyroid hypothyroidism and metabolic syndromejiimc 2018 vol. 13, no.4 function is associated with components of the metabolic syndrome in euthyroid subjects. the journal of clinical endocrinology and metabolism. 2007;92(2):491-6. 20. tehrani f, tohidi m, dovom m, azizi f, tohidi m. a population 178 based study on the association of thyroid status with components of the metabolic syndrome. j diabetes metab. 2011;2(2):156-62. hypothyroidism and metabolic syndromejiimc 2018 vol. 13, no.4 original article abstract objective: this study on animal model was designed to explore the ldl-cholesterol lowering effect of an antihypertensive drug irbesartan. study design: randomised controlled experimental study. place and duration of study: the study was conducted in the animal house of national institute of health (nih), islamabad. biochemical analysis of rabbit's serum was carried out in the department of chemical pathology, army medical college, rawalpindi from february 2013 to june 2013. materials and methods: eighteen rabbits were divided into three groups (group a, group b and group c) of six rabbits each. group one was labelled as normal control. the other two groups (b and c) were made hyperlipidemic by feeding them with high cholesterol diet. of these, group b was taken as hyperlipidemic control and group c as treatment group. serum ldl levels were estimated at three different occasions i.e. baseline, after giving high cholesterol diet to hyperlipidemic groups and after 30 days of giving irbesartan to treatment group. results: serum analysis for the estimation of ldl-cholesterol of all the groups was done and their means were calculated and compared with the base line values using spss version 20. irbesartan treated group showed a marked reduction in serum ldl cholesterol in comparison with the hyperlipidemic control group. conclusion: it is concluded that irbesartan an antihypertensive agent, has also the ability to markedly reduce raised serum ldl cholesterol levels. key words: hyperlipidemia, irbesartan, ldl-cholesterol. antihypertensives as well as antihyperlipidemics to manage two major determinants of cvd i.e. 5 hypertension and hyperlipidemia. lipids are the essential biomolecules, divided into five different classes i.e. chylomicrons, vldl cholesterol, idl-cholesterol, ldl-cholesterol and hdl-cholesterol. among these, low density lipoproteins (ldl-cholesterol) in normal range is necessary for innumerable normal healthy body 6 functions. however the elevated levels of ldl molecules loaded with cholesterol, get accumulated on the walls of the arteries and cause various fatal 7 and nonfatal cardiovascular abnormalities. irbesartan, an antihypertensive drug, is a novel, orally active, noncompetitive angiotensin receptor antagonist, specific for angiotensin 1 receptor 8 subtype. the drug has a stronger capability to lessen the risk of combined major cardiovascular events (stroke, atherosclerosis, heart failure, angina, myocardial infarction, peripheral arterial disease and 9 death). irbesartan is metabolized in the liver by glucuronide 10 conjugation and oxidation. a big fraction of irbesartan i.e. 80 percent remains unchanged and possess pharmacological activity whether given introduction cardiovascular diseases (cvd) have become a major problem nowadays and are responsible for 76 percent of deaths and disabilities due to myocardial 1 infarction, atherosclerosis and stroke. the risk of cardiovascular events is strongly associated with high blood pressure as well as high blood cholesterol 2 levels. there are different groups of drugs used to 3 lower blood pressure. likewise there is separate class of drugs to reduce elevated blood cholesterol 4 levels having its own mechanism of action. therefore patients with cardiovascular diseases require drugs from both these classes i.e. irbesartan; an antihypertensive drug reduces ldl-cholesterol in diet induced hyperlipidemic rabbits 1 2 3 sabeen shakir , akbar waheed , noureen hafeez jiimc 2016 vol. 11, no.3 correspondence: dr. sabeen shakir assistant professor, pharmacology rawal institute of health sciences, islamabad e-mail: sabeen.ali@live.com 1 department of pharmacology rawal institute of health sciences, islamabad 2 department of pharmacology islamic international medical college riphah international university, islamabad 3 department of forensic medicine rawal institute of health sciences, islamabad funding source: nil ; conflict of interest: nil received: feb 03, 2016; revised: apr 18, 2016 accepted: aug 10, 2016 ldl-cholesterol lowering effect of irbesartan 94 11 orally or intravenously. only 6 percent of circulating drug gets converted into inactive glucuronide conjugate. the rest of the metabolites are pharmacologically inactive and are excreted via 12 urine or bile. angiotensin ii is a potent vasoconstrictor in vascular 13 smooth muscles. it synthesizes in a sequential step of conversion of angiotensinogen in the presence of renin to angiotensin i and then to angiotensin ii. this angiotensin ii then acts on angiotensin 1 (at1) receptor subtype, stimulates it and causes vasoconstriction. it also promotes synthesis and secretion of aldosterone by stimulating the adrenal cortex thereby decreasing sodium excretion and 14 increasing potassium excretion. irbesartan inhibits the action of angiotensin ii and promotes vasodilatation, by selectively binding to at1 receptor 1 5 subtype and blocking it noncompetitively. irbesartan also antagonizes the effects of aldosterone. irbesartan has been reported to be a peroxisome proliferator activated receptor (ppar) alpha activating agent. ppar alpha is a nuclear transcription receptor, which regulates the expression of genes involved in fatty acid oxidation 16 and energy homeostasis. irbesartan has a good safety profile with least or no 17 adverse reactions. unlike angiotensin converting enzyme (ace) inhibitors, the only complication seen with the use of angiotensin receptor blockers (arb's) 18 is mild angioedema but it is extremely rare. it is obvious from a large number of clinical trials that there is 30 percent decline in the risk of development of cvd by pharmacologically lowering serum ldl 19 cholesterol. therefore, in addition to controlling high blood pressure in patients with cardiovascular disease, it becomes necessary to improve plasma 20 lipid biochemistry. this study explores the antihyperlipidemic property of irbesartan to cope with the two major risk factors of cardiovascular diseases. materials and methods this randomized controlled study was conducted in the animal house of national institute of health (nih), islamabad. biochemical analysis of rabbit's serum was carried out in the department of chemical pathology, army medical college, rawalpindi, from february 2013 to june 2013, after approval from the ethics committee of centre for research in experimental and applied medicine (cream), army medical college. eighteen healthy adult domestic breed rabbits (oryctolagus cuniculus) having a weight of 1.5 to 2.0 kg were selected. they were of mixed breed both males and non-pregnant females. animals under 1.5 years of age were not included in the experimental study. standard laboratory conditions were maintained in animal house of national institute of health and rabbits were provided with controlled environment assuring twelve hours day and night o cycle and an average temperature of 24 c. rabbits were acclimatized for one week prior to the study. diet formula for animals used in the study was composed of cholesterol powder (1g/day) mixed in 1g/day of wheat bran along with routine diet of rabbits (gram whole,carrots, cucumbers, seasonal fruits) and was in strict compliance with the guidelines for the care of laboratory animals nih islamabad. feeding of cholesterol powder and drugs was ensured by giving them mixed in small pellets of wheat bran after four hours fast before giving the routine diet. cholesterol powder one gram per day was added to the diet of the two experimental groups (group b and group c) excluding the rabbits of group a (normal control group). all the rabbits were given tap water ad libitum for drinking. the rabbits were randomly assigned into three groups of six animals each. the study period comprised of a total of twenty weeks after one week period for acclimatization. animals were weighed prior to giving high cholesterol diet on day zero. blood samples were taken on three different occasions as follows. 1. baseline samples were collected on day zero, before starting the high cholesterol diet. 2. after 120 days of feeding on high cholesterol diet. 3. at the end of the study, on completing the treatment course for a period of 30 days. the rabbits (n=6) in two of the experimental groups (group b and group c) were given high cholesterol diet followed by irbesartan (40mg/kg) once daily according to the following schedule. group a (normal control; n=6) was the control group and received normal diet consisting of gram whole, wheat bran, green fodder, seasonal fruits and water jiimc 2016 vol. 11, no.3 ldl-cholesterol lowering effect of irbesartan 95 ad libitum for 150 days as it was normal control group and fed on normal cholesterol free diet for the whole study period. group b (hyperlipidemic control; n=6) animals received cholesterol powder (1g/day) mixed in a diet comprising of grain whole, wheat bran, green fodder and seasonal fruits (cucumber, carrots and apples) for 120 days. cholesterol powder was excluded from the diet for the next 30 days. rabbits were also given tap water ad libitum for drinking. group c (hyperlipidemic+irbesartan; n=6) animals received the high cholesterol diet (1g/day) as per group b for 120 days and then fed on normal/routine diet without cholesterol along with irbesartan (40mg/kg) once daily via gavage for a period of 30 days. fasting whole blood (4 ml) samples (n=6.0) were drawn from the tip of the ear of each animal with the help of a 5cc syringe. all the samples were transferred to separate plain clot activator tube and were let to clot at room temperature for at least 30 minutes. the samples were then centrifuged at 4500 rounds per minutes for 10 minutes. serum was separated via an automatic micropipette for estimation of serum cholesterol, serum triglycerides and serum hdl-cholesterol labelled accordingly in order to calculate serum ldl by using friedwald's 21 equation. [ldl cholesterol mmol/l] = [total cholesterol] [ hdl cholesterol] [triglyceride] / 2.20 the results of serum analysis of ldl-cholesterol were established as means + standard error of mean. the difference between the two observations was derived using spss version 20. the difference was taken as significant for a p value of 0.05. results serum ldl the differences in means of ldl-cholesterol values were calculated among normal control and hy p e r l i p i d e m i c co nt ro l a s we l l a s a m o n g hyperlipidemic and treatment group. group a (normal control) showed unchanged levels of serum ldl when recorded on day zero, day 120 and day 150 i.e. 1.64±0.5, 1.64±1.1 mmol/l and 1.64±0.8 mmol/l as shown in table, p=ns. the values of serum ldl of group b (hyperlipidemic control). serum ldl levels on day 120 were increased significantly as compared to day zero, i.e. 3.45±1.1 mmol/l versus 1.61±1.1 mmol/l with p=0.0005. but remained unchanged on day 150 in comparison to day 120. when compared with normal control group a, a significant rise was observed in group b and group c on day 150. group c (irbesartan), when compared with group b (hyperlipidemic control) to assess the post treatment reduction in serum ldl levels on day 150, a statistically remarkable decline was recorded, i.e. group c (irbesartan) showed mean values of 1.29±0.2 mmol/l in comparison with group b (hyperlipidemic control) showing a mean of 3.46±0.3 mmol/l on day 150, p value for group c (irbesartan) was 0.005 as shown in table i. table: comparison of serum ldl levels among group a, group b and group c on day 0, 120 and 150 in rabbits (n=6) 1n=6, results are expressed as mean ± sem (standard c error of mean) discussion in our study we found a highly significant reduction (28%) in serum ldl cholesterol with irbesartan. this favors the dual role of irbesartan, i.e. an anti hypertensive drug serving as an anti hyperlipidemic drug. shimamura et al also demonstrated the similar 22 results in rats as their experimental model. this was also revealed by derosa et al after conducting a 12 months clinical study on 188 patients with metabolic syndrome that irbesartan has the ability to significantly reduce serum ldl cholesterol levels compared with the baseline. this role of an antihypertensive drug renders it special in respect of serum ldl cholesterol from other drugs that are specific for the treatment of hypertension. unlike irbesartan, when a long term therapy is conducted for primary or secondary prevention of at h e ro s c l e ro t i c co m p l i cat i o n s , a n g i o te n s i n converting enzyme inhibitors have no effect on 23 serum ldl-c. other classes of antihypertensive drugs including beta blockers, diuretics and calcium channel blockers would rather increase the serum 24 ldl cholesterol levels. however irbesartan does not cause any undesired derangement in the plasma ldl cholesterol after long term use and this was also jiimc 2016 vol. 11, no.3 ldl-cholesterol lowering effect of irbesartan 96 demonstrated by kirk, (1999), although blood pressure lowering efficacy is same as those of other 25 antihypertensive drugs. our study effects concerning serum ldl-cholesterol strongly support the previous study performed on 26 cholesterol fed rabbits. in their study, they reported the lipid lowering effect of irbesartan and losartan. they concluded that irbesartan treatment is associated with significant reduction in plasma ldl levels compared to base line. an open multidrug comparison trial was carried out by stella et al to study the variation in response of different arb's on 27 plasma lipid profile. they demonstrated that angiotensin receptor blockers (arb's) action on 28,29,30 different indices of lipid profile are not same. this conflict with rong et al and shimamura et al could be a reflection of use of different species, as we had rabbits instead of rats while shimamuraet al presented a clinical study. the other prospect may include the reason that animal model of ronget al was genetically obese rats whereas we used high cholesterol diet induced hyperlipidemic rabbits. duration of treatment could be another possibility of insignificant reduction of total cholesterol as we gave the treatment for 30 days whereas treatment period of rong et al was 49 days.shimamura et al gave significant results after 90 days treatment. in the light of these findings it is clearly evident that irbesartan reduced the serum low density lipoprotein cholesterol (ldl-c) in high cholesterol diet fed rabbits. for this reason irbesartan administration can be helpful to decrease the risk of developing cardiovascular diseases because besides its antihypertensive property, irbesartan has an additional subsidy of lowering serum ldl cholesterol which is evident from this study. further studies are warranted to explore the mechanism of lowering serum ldl by irbesartan in rabbits. conclusion irbesartan, an efficient antihypertensive drug, is highly effective in lowering 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m. in vitro hepatic metabolism of candesartan to its inactive metabolite, cv-15959. j hypertens. 1998; 16: 128. 30. oparil s, williams d, chrysant sg. comparative efficacy of olmesartan, losartan, valsartan, and irbesartan in the control of essential hypertension. j clin hypertens. 2001; 3: 283-91. jiimc 2016 vol. 11, no.3 ldl-cholesterol lowering effect of irbesartan 98 page 7 page 8 page 9 page 10 page 11 original�article abstract objective: to compare the safety and efficacy of misoprostol versus outpatient manual vacuum aspiration (mva) for termination of pregnancy. study design: quasi experimental study place and duration of study: conducted in cantonment general hospital from 1/1/2015 -31/1/2015 materials and methods: women eligible for both mva and misoprostol were included in this study. women were allocated to either group according to the option chosen by them. misoprostol was administered at a dose of 400 microgram sublingual, 4 doses four hours apart. manual vacuum aspiration was performed according to 1 practice guidelines provided by ipas certified professionals. primary outcome measure was achievement of complete evacuation within 24 hours. results: out of 101 women, 68 (62.3%) were in mva group and 33 (32.6%) in misoprostol group. complete evacuation was achieved in 28 (82.1%) women in the misoprostol group and 68 (100 %) in the mva group within 24 hours (p value 0.003). five women had failed medical termination. none of the women required hospital admission. there was no statistical difference between the two groups (p value 0.079) in terms of total number of visits or requirement of analgesia. conclusion: both manual vacuum aspiration (mva) and misoprostol are safe and effective alternatives for termination of pregnancy but the former is more likely to achieve complete evacuation within 24 hours. key words: efficacy, manual vacuum aspiration (mva), misoprostol, outpatient , safety, suction curettag. health sector, high total fertility rate (3.8%) , low contraceptive prevalence ( 35%) , lack of resources , inability to access to safe abortion care and poor understanding of legislation by health care 5 professionals and patients. in the last 30 years, there has been effort at the international as well as regional level to improve service provision for miscarriages and to evaluate its effectiveness by measuring quantifiable objectives. this included legislation, introduction of misoprostol, evolution and provision of manual vacuum aspiration and 4 monitoring of these efforts. most of the studies done in this context are based on in patient category. both mva and misoprostol have been shown to be effective methods of termination of pregnancy in admitted patients. outpatient or community use of mva has not been studied so far. few good quality studies from south asia and africa (pakistan, india, nepal & bangladesh) have shown that misoprostol 6 use is safe in community. outpatient provision of termination facilities has several advantages including cost and convenience. it is extremely useful in far flung areas where access to established medical facilities is not available. introduction about 15 % of all pregnancies result in miscarriage. the world wide abortion rate is 28 per 1000 women 2 aged 15-44 years. the bulk of these miscarriages occur in underdeveloped countries. in low resource settings, there is a high incidence of unwanted pregnancies. most of these pregnancies succumb due to poor antenatal care, malnutrition or induced miscarriages. lack of post abortion care is one of the leading causes of maternal mortality, accounting for about 7.9% of maternal deaths. part of maternal 3 mortality due to sepsis is also contributed by it. in pakistan, abortions (both spontaneous and induced) are responsible for 5.6 % 11% of maternal 4 mortality. this is mainly due to overburdened public misoprostol versus outpatient manual vacuum aspiration (mva) for termination of pregnancy: a quasi experimental study safia khalil, nighat shaheen correspondence: dr. nighat shaheen department of gynaecology cantonment general hospital, rawalpindi e-mail: nighats82@gmail.com department of gynaecology cantonment general hospital, rawalpindi funding source: nil; conflict of interest: nil received: may 10, 2018; revised: january 31, 2019 accepted: february 27, 2019 misoprostol versus mva termination of pregnacnyjiimc 2019 vol. 14, no.1 3 performed according to practice guidelines provided by ipas by certified professionals. a pelvic ultrasound was performed after 24 hours to confirm completion of evacuation. estimation of blood loss was subjective. women who had incomplete evacuation were administered 600 microgram misoprostol in line with figo recommendation and required follow up visits at 01 week post procedure. those who had persistant rpocs despite following this protocol were declared failed medical treatment. these women had to undergo mva to remove rpocs. contraceptive advice was provided afterwards and the woman was advised follow-up after one week. all data was entered on a preformed performa. systematic review done by linet t et al was used as a guideline for protocol development of medical & surgical methods of termination of 7 pregnancy. primary outcome measure was achievement of complete evacuation within 24 hours. other outcome measures included duration of hospital stay, no. of hospital visits, procedure related blood loss, requirement of post procedure analgesia, need for repeat / alternate procedure, adverse effects and complications. data was analyzed on spss 22. descriptive statistics included means & frequencies. means were calculated and compared for age, gravidity, parity, gestational age, duration of hospital stay and number of hospital visits. t test was applied to ca l c u l ate t h e d i ffe re n c e . f re q u e n c i e s a n d percentages were calculated for type of selected procedure, indication of termination, achievement of complete evacuation within 24 hours. chi square test was applied to calculate the p values. other variables include procedure related blood loss (mild ,moderate , severe) , requirement of analgesia (yes, no) , need for repeat procedure (yes , no) , adverse effects (fever shivering, gastrointestinal side effects) and complications (hemorrhage ,infection , perforation). frequencies and percentages were calculated for these as well and chi square was applied. results total 107 women were enrolled in the study, out of which 68 (62.3%) were in mva group and 33 (32.6%) in misoprostol group. six women (5.6%) opted for dilatation and curettage (d & c) and were excluded our study is designed to bridge this gap. our study intends to address the provision of safe and effective methods of termination of pregnancy in an outpatient setting which is likely to have a larger effect in low resource settings. we compared m a n u a l va c u u m a s p i ra t i o n w i t h m e d i c a l termination (misprostol) in cases where both options were suitable for the woman. apart from assessing the safety & efficacy, it will also give us an insight into the patient preference in our culture. the objective of our study was to compare misoprostol versus outpatient manual vacuum aspiration (mva) for termination of pregnancy. materials and methods this quasi experimental study was conducted in cantonment general hospital rawalpindi from 1/1/2015 -31/1/2015. approval from institutional ethical committee was obtained. 107 women consented to participate in the study. nonprobability convenience sampling technique was used to collect sample. all women with an indication for termination of pregnancy with · a crown rump length of 7-40 mm without cardiac activity (missed miscarriage)or · mean gestational sac diameter between 25 and 45 mm without fetal pole (anembryonic pregnancy) or · passage of products of conception with the residual anterior-posterior endometrial lining ≥30 mm [retained products of conception (rpocs)] or · uterine size <13 weeks were included in the study . hemodynamically unstable women, septic abortion, suspected ectopic pregnancy, known bleeding disorders, uterine anomalies and those taking anticoagulant therapy were excluded from the study. women were educated about various options for termination of pregnancy. those not willing /suitable for expectant management were allocated to either group according to the option chosen by the woman. group one received misoprostol while group two underwent manual vacuum aspiration in the o u t p a t i e n t d e p a r t m e n t . m i s o p r o s t o l w a s administered at a dose of 400 microgram sublingual, 4 doses four hours apart ( total 8 tablets of 200 micrograms). manual vacuum aspiration was 4 misoprostol versus mva termination of pregnacnyjiimc 2019 vol. 14, no.1 regarding abortion care in pakistan and bangladesh 4,5 in 2014. they explain the prevailing situation of abortion care in detail. it is an alarming situation. there is a large unmet need for abortion care in our 8 country (estimated at around 20% in 2012). it is one of the major target areas that need improvement if we aim to achieve sustained development goals. regarding the choice of method np khawaja et al report that women are aware of the modern 9 methods which are safe and effective. similarly in our study most of the women opt for new methods of abortion care. this is because of increased awareness probably because of lesser cultural inhibition and positive role of media. on the other hand complications in underdeveloped countries are common due to widespread illegal abortion. shahab et al report that a significant percentage of women 10 (5%) have a fear of the pain and complications . these women prefer dilatation and curettage under anesthesia instead of modern methods. in our study a small number of women opt for d& c probably for similar reasons. at the moment abortion for unwanted pregnancies is 11 restricted in pakistan to save the life of the mother. other indications for termination are similar in both groups and were not related to the choice of procedure. our study shows that both methods are safe, effective and tolerable to the women with little analgesia requirement. there is no significant blood loss, hospital admission, complication or side effects. several other studies show similar results. speedie j et al have developed a one stop evaluation unit for 12 manual vacuum aspiration. they find it safe and acceptable with significant reduction in cost. however they do not compare it with other modalities. ansari a et al has confirmed its safety in 13 high risk cardiac patients. in our study, only those women who have a failed medical termination are not satisfied with the chosen method. they have two options. one is to take higher doses of misoprostol with or without mifepristone as reported by meena 14,15 sr et al and li yt et al respectively. the other option is to undergo mva as suggested by heller et 16 al. all of the women in our study chose the second option. in our study, all procedures are done by certified doctors. however, in a systematic review ngo td et al has shown that manual vacuum aspiration is safe in the hands of mid level care 17 providers as well. speedie j et al has found that manual vacuum aspiration is a good opportunity to offer long acting 10 reversible contraception. eighty percent women in from the study. mean age of women undergoing mva was 28.55 + 5.228 and in misoprostol group was 27.95 + 2.681. mean gestational age in mva group was 10.59 + 3.053 and in misoprostol group was 12.31 + 3.248. mean gravidity was 3.35 + 1.483 in mva group and 2.78 + 1.281 in misoprostol group. mean parity was 1.84 + 1.417 versus 1.52 + 1.051. the two groups were comparable in these respects. regarding indications for termination of pregnancy, 31(29%) women had missed miscarriage, 77 ( 65.4% ) had incomplete miscarriage and 6 (5.2%) had termination of pregnancy for other reasons [anencephalic fetus (n=4 ,3.7%), blighted ovum (n=2 , 1.9%)]. one woman (0.9%) had a previous scar of lower segment cesarean section. the two groups did not differ in the indication of termination of pregnancy (p value = 0.07). complete evacuation was achieved in 28 (82.1%) women in the misoprostol group and 68 (100 %) in the mva group within 24 hours. five women had failed medical termination. this difference was statistically significant (p value 0.003). mean no. of visits required in the misoprostol group was 2.8 + 0.837. none of the women had retained products of conception following mva and the mean no. of required visits in this group was 1. this difference was statistically significant (p value 0.01). most of the women did not return for follow up visit (n=89, 83.2%). twelve women (17.6% ) in the mva group returned for follow up and five (17.8% ) in the misoprostol group. there was no statistical difference between the two groups in terms of return to follow up (p value = 0.497). when the total number of visits were considered (procedure related plus follow-up visit), there was no statistical difference between the two groups (p value 0.079). only six women (5.6 %) required analgesia and the requirement for analgesia did not differ with the type of procedure undertaken (p value =0.529). none of the women required hospital admission. no complications or adverse effects were reported. there was no report of moderate or severe blood loss during the study in either group. contraceptive counseling was provided to 79 (73.9%) women. discussion zaidi s et al has conducted two of the largest studies 5 misoprostol versus mva termination of pregnacnyjiimc 2019 vol. 14, no.1 their study opt for long acting reversible contraceptive methods. korjamo r and laursen l also find that women are more receptive to 18,19 contraceptive advice during this period. this is in contrast to our study. although contraceptive counseling is provided to a significant proportion of women, majority (66%) opt for barrier methods or no method at all. this indicates a need for research i n t o t h e l o c a l p r o b l e m s a s s o c i a t e d w i t h contraception. counseling methods need to be improved and designed to address the local concerns. current situation of contraceptive use in pakistan is unlikely to change until and unless there is a mechanism of continuous positive feedback by women who are successfully using reliable contraceptive methods. also, backstreet abortion is cheap and readily available. most women feel it an e a sy w ay o u t i n s t e a d o f re g u l a r l y u s i n g contraception. increasing role of community workers for provision of abortion care in the outreach is being explored. early reports by constant d et al and gupta p et al are 20,21 encouraging. they have shown that misoprostol administration by community workers at home is safe and efficacious. one of the limitations of our study is small sample size. this is mainly because majority of women as well as care providers feel more comfortable with in patient management. the reasons for such preference need to be explored. another limitation is poor follow-up.this is mainly due to a lack of integrated services. most of the women who report for follow up are those who are concerned about retained products of conception. apart from hospital visit, other means for follow-up can be explored e.g. telephonic contact etc. aiken ara et al has evaluated newer techniques like telemedicine to facilitate 22 followup. another limitation is that the reasons for preference of a particular method were not interviewed further. termination of pregnancy is a wide area of research. barriers to implementation of safe and effective 6 abortion care need future research. conclusion both manual vacuum aspiration (mva) and misoprostol are safe and effective alternatives for termination but the former is more likely to achieve complete evacuation within 24 hours, larger prospective studies are needed to confirm these findings. table i: demographic features of women in treatment groups table ii: indica�on for termina�on in misoprostol & mva groups table iii: outcome measures in misoprostol vs. mva 6 misoprostol versus mva termination of pregnacnyjiimc 2019 vol. 14, no.1 13. ansari a, abbas s. manual vacuum aspiration (mva) a safe option for evacuation of first trimester miscarriage in cardiac patients. j pak med assoc. 2017; 67(6):94850 14. meena sr. comparative study of mifepristone with vaginal misoprostol for first trimester termination of pregnancy at different gestational ages. j obstet gynaecol india. 2016; 66(6):426-430. 15. li yt, hou gq, chen th, chu yc, lin tc, kuan lc et al. highdose misoprostol as an alternative therapy after failed m e d i c a l a b o r t i o n . ta i w a n j o b s t e t g y n e c o l . 2008;47(4):408-11. 16. heller r, cameron s. termination of pregnancy at very early gestation without visible yolk sac on ultrasound. j fam plann reprod health care. 2015;41(2):90-5. 17. ngo td, park mh, free c. safety and effectiveness of termination services performed by doctors versus midlevel providers: a systematic review and analysis. int j womens health. 2013;5:9-17. 18. laursen l, stumbras k, lewnard i, haider s. contraceptive provision after medication and surgical abortion. womens health issues. 2017;27(5):546-50. 19. korjamor, mentulam,heikinheimoo.fast-track vs.delayed insertion ofthe levonorgestrel-releasing intrauterine system after earlymedical abortion a randomized trial.contraception. 2017;96(5):344-51. 20. constant d, harries j, daskilewicz k, myer l, gemzelldanielsson k. is self-assessment of medical abortion using a low-sensitivity pregnancy test combined with a checklist and phone text messages feasible in south african primary healthcare settings? a randomized trial. plos one. 2017;12(6):e0179600. 21. gupta p, iyengar sd, ganatra b, johnston hb, iyengar k. can community health workers play a greater role in increasing access to medical abortion services? a qualitative study. bmc womens health. 2017;17(1):37. 22. aiken ara, digol i, trussell j, gomperts r. self reported outcomes and adverse events after medical abortion through online telemedicine: population based study in the republic of ireland and northern ireland. bmj. 2017;357: 2011. references 1. www.ipas.org 2. sedgh g, singh s, shah ih, ahman e, henshaw sk, bankole a. induced abortion: incidence and trends worldwide from 1995 to 2008.lancet. 2012; 379(9816):625-32. 3. say l, chou d, gemmill a, tunçalp ö, moller ab, daniels jet al. global causes of maternal death: a who systematic analysis.lancet glob health. 2014; 2(6): 323-33. 4. zaidi s, begum f,tank j, chaudhury p, yasmin h, dissanayake m. achievements of the figo initiative for the prevention of unsafe abortion and its consequences in southsoutheast asia. int j gynaecol obstet. 2014;126 suppl 1:203. 5. z a i d i s , ya s m i n h , h a s s a n l , k h a k w a n i m , s a m i s , abbast,replacement of dilationandcurettage evacuation by manual vacuumaspiration and medical abortion,andthe introduction of postabortioncontraception in pakistan. int j gynaecol obstet. 2014;126 suppl 1: 40-4. 6. samnani aaba, rizvi n, ali ts, abrejo f. barriers or gaps in implementation of misoprostol use for post-abortion care and post-partum hemorrhage prevention in developing countries: a systematic review. reprod health. 2017; 14(1):139. 7. linet t. surgical methods of abortion. j gynecol obstet biol reprod. 2016; 45(10):151535. 8. mahmood h, hafeez a, masood s, faisal t, ramzan n. contraceptive use and unmet need of family planning among illiterate females of working class in rawalpindi. pak armed forces med j. 2016; 66(6):871-5. 9. khawajanp, tayyebr, malikn.awareness and practices of contraception among pakistani women attending a tertiary care hospital. j obstet gynaecol. 2004; 24(5):564 7. 10. shahab aa, alharazi ah. medical versus surgical termination of the first trimester missed miscarriage. alexandria journal of medicine. 2013; 49 (1):13-16. 11. n rehan. attitudes of health care providers to induced abortion in pakistan. j pak med assoc. 2003; 53(7): 293-6. 12. speediej,robsons.the evolution ofa'onestop' outpatient manual vacuum aspiration service for termination of pregnancy. bmj sex reprod health. 2018;44(1):58-60. 7 misoprostol versus mva termination of pregnacnyjiimc 2019 vol. 14, no.1 original�article abstract objective: to determine the association of serum leptin levels with serum fsh, lh, blood glucose fasting and bmi in young unmarried females with polycystic ovarian syndrome. study design: descriptive cross sectional study. th th place and duration of study: the study was conducted from 15 march 2016 to 15 march 2017 in gynea and obs department of benazir bhutto shaheed hospital, rawalpindi. materials and methods: a sample of 77 young unmarried females of ages 15-30 years was recruited while obtaining their written consent and divided into four groups using rotterdam criteria. these were control (non pcos) and study group (pcos) with three subgroups based on their bmi (lean, overweight and obese). serum leptin assay was measured using sandwich-elisa method. a pre-designed questionnaire was used to collect data from the patients. data was analyzed in the statistical package of version 21.0, ibm spss. results: no association was found between leptin with fsh and lh in pcos patients. however, body mass index (bmi) and blood sugar fasting were significantly correlated with leptin in pcos subjects and controls. correlation coefficient of leptin vs bsf is 0.488 with a p value of 0.000. leptin was not significantly different between pcos and non-pcos with normal bmi 3637.9 ± 1259.1 vs 3263.4 ± 1461.8 respectively with p value 0.331. in a subgroup analysis of lean, overweight and obese pcos patients, each category showed different mean serum leptin levels (3637.9 ± 1259.1 vs 4603.3 ± 1223.7 vs 4261.0 ± 1504.1 respectively) with p value 0.015. conclusion: serum leptin has a positive association with bmi and blood glucose fasting in pcos women. however, it has no relationship with serum fsh and lh in pcos women. the increase in bmi and bsf is the reason of hyperleptinemia in pcos. key words: blood sugar fasting, body mass index, polycystic ovarian syndrome, serum leptin. 4 adolescents. th pcos was first identified around 20 century by two chicago gynecologists dr. irving stein and michael 5 leventhal. stein and leventhal had found an association of polycystic ovaries with amenorrhea. it turned out to be a landmark study for the 6 reproductive world. pcos affects individuals in multiple ways including r e p r o d u c t i v e r e p e r c u s s i o n s ( s u b f e r t i l i t y, hyperandrogenism and hirsuitism), metabolic derangements (raised insulin, dm and cvd) and psychological health issues (anxiety, depression and 7 deteriorated quality of life). leptin is a greek word stemming from leptos. leptos means thin. it is a satiety hormone. it is secreted by fat cells and inhibits hunger to regulate energy balance. leptin consists of 167 amino acid peptide that is secreted in a pulsatile manner. the key role of leptin is monitoring energy homeostasis. this is accomplished by impacting on feeding behavior and 8 energy expenditure. introduction polycystic ovarian syndrome (pcos) is an endocrine disorder which has become cosmopolitan in nature. it is taking its toll in both clinical and public health 1 2 sectors. pcos affects 1 in 15 women worldwide. 53 10% of females are affected in reproductive age. prevalence of pcos is 9.13% amongst south asian leptin levels in polycystic ovarian syndrome 1 2 3 4 5 6 zarrin khaliq chaudari , amer siddiq , amena rahim , muhammad afzal , abdul khaliq naveed , shagufta saeed sial correspondence: dr. zarrin khaliq chaudari department of biochemistry islamic international medical college riphah international university, islamabad e-mail: drzarrinkhaliq@gmail.com 1,3,4,5 department of biochemistry islamic international medical college riphah international university, islamabad 2 department of chemical pathology hbs medical college, islamabad 6 department of gynecology and obstetrics benazir bhutto shaheed hospital, rawalpindi funding source: nil; conflict of interest: nil received: jul 27, 2017; revised: feb 17, 2018 accepted: feb 20, 2018 leptin levels in unmarried females in pcosjiimc 2018 vol. 13, no.1 36 subgroup iii of 30 subjects with overweight and subgroup iv of 18 subjects with obese. these subgroups were divided by bmi categories. bmi was calculated by dividing weight by height in 2 square meter (kg/m ). classification of pcos and non-pcos is according to world health organization. pcos comprise of two of three features: 1) oligo and/or anovulation, 2) clinical and/or biochemical signs of hyperandrogenism, and 3) polycystic ovaries on ultrasonography. this classification is according to 11 world health organization. these criteria include exclusion of androgen excess or related disorders 12 before diagnosing it as pcos. after an overnight fast, blood samples were taken to be centrifuged at 25,000 revolutions per second for 8 minutes for sera separation which were stored at 20°c for further analysis at biochemistry research laboratory iimc. all samples were examined for blood glucose fasting (bgf), luteinizing hormone (lh), follicle stimulating hormone (fsh) and serum leptin level. statistical analysis was done in spss version 21.0. we used kolmogrov smirnov test to test the normality of quantitative variables, mannwhitney u test for comparison of leptin level in pcos and non-pcos. kruskal wallis test for comparing leptin levels against 3 bmi groups in pcos. spearman rho correlation was used to determine correlation between leptin and bgf. p value <0.05 will be considered as significant. results leptin receptors (leprs) are expressed in two d i f fe r e n t n e u r o n s i n a r c u a t e n u c l e u s o f hypothalamus. these either repress or arouse feeding. the mutual orchestrated functioning of both kind of neurons help regulate energy balance. both types are sensitive to leptin and insulin as they 9 have leprs. leptin plays an important role in homeostasis by participating in reproductive axis with excitatory effects at hypothalamus and 10 suppressive actions at ovaries. our study was planned to estimate the serum leptin level in pcos among young unmarried females reporting at our hospital. the study was conducted on young girls to find if an early detection of pcos along with certain parameters can help in alleviation of symptoms. the gap in study is still the controversial relation between leptin and other parameters. the study aims to determine the correlation of serum leptin levels with serum fsh, lh, blood glucose fasting and bmi in young females with polycystic ovarian syndrome. materials and methods this descriptive cross sectional study was conducted in department of gyne and obs. benazir bhutto th shaheed hospital, rawalpindi from 15 march 2016 th to 15 march 2017. the target population was all unmarried women who were between 15-30 years of age. we collected responses of 77 cases based on consecutive sampling. women with adrenal or hypothalamic aberrations, cushing's syndrome, hypo-or hyperthyroidism, hyperprolactinemia were excluded from the study. those patients were also excluded from our population who were on a prescription affecting their hormones for at least 3 months prior to study. the females taking any drugs (oral contraceptive pills, insulin sensitizers, steroids, androgenic drug use) or suffering from any medical diseases (diabetes mellitus, thyroid dysfunction, congenital adrenal hyperplasia, cushing's syndrome) were sidelined from research. written consent from patients was taken individually. out of 77 samples, 63 were diagnosed cases of pcos and remaining 14 were non-pcos. the subjects were divided into two groups namely control and study group. control group (group i) without pcos comprised of 14 subjects with lean weight. study group with pcos was divided into three subgroups. subgroup ii of 15 subjects with lean weight, fig 1: histogram to demonstrate the distribu�on of lep�n levels among various groups a total of 77 patients were included in the study which are distributed in further 4 sub-groups with respect of bmi, lean (non-pcos), lean (pcos), over weight (pcos) and obese (pcos) with numbers 14 (18.18%), 15 (19.48%), 30 (38.96%) and 18 (23.37%) respectively. overall age was 26.77±3.81 whereas the age with respect of subgroups i (lean and non37 leptin levels in unmarried females in pcosjiimc 2018 vol. 13, no.1 spearman rho correlation was calculated between leptin, fsh, lh and bsf (table 3). leptin level significantly correlated with bsf with high correlation coefficient 0.488. there was no significant correlation between leptin and follicle stimulating hormone as well as luteinizing hormone. discussion in the current study, the possible relation between leptin, bmi, bsf, fsh and lh in females with pcos is investigated. our findings suggest that pcos women show a considerable elevation in leptin levels as compared to controls. also that leptin is significantly correlated with bmi and blood sugar fasting. there is no correlation between fsh and lh. our study highlights that increased bmi is associated with increased leptin levels. these findings are similar to those observed by baig et al. in which 7 serum leptin is considerably correlated with bmi. chakrabarti confirmed that positive relation exists 13 between serum leptin and bmi. serum leptin concentration was found to be related with bmi by a 14 study conducted by erturk. leptin levels were found significantly raised in patients with pcos than in 15 controls in study underwent by zheng. the major action of leptin on nutrition is visible through the hypothalamic-pituitary gonadal axis. 16 (christian et al.,2008) in our study, serum leptin level is significantly related with bmi in pcos women. this result is corroborated with other studies as given above. this finding is expected as greater the fat depots, increased the bmi and more fat would lead to higher secretion of leptin. leptin has been shown to be raised with increasing bmi in many other studies. our study is comparable with the study of olszanecka-glinianowicz et al. (2013) who reported considerably raised serum 7 leptin level in pcos subjects with changing bmis. jacobs and conway reported higher serum leptin 17 levels in women with higher bmis among pcos. shore et al. found hyperleptinemia among 18 adolescent girls with pcos. leptin controls reproductive physiology and pathophysiology by two ways. one is by changing perceptibility of adenohypophysis to gnrh and second, by modulating the follicles and corpus luteum in ovaries to form steroid hormones. hence, serum leptin has definitely a role to play in the pathogenesis of pcos with raised bmi categories. thus, leptin is assumed pcos), ii (lean and pcos), iii (overweight and pcos), and iv (obese and pcos) was 26.79±3.47, 25.6±4.64, 27.27±3.78 and 26.89±3.46. kolmogrov-smirnov test shows that the leptin level does not follow normal distribution with p value 0.000. (fig 1). hence we use non-parametric tests to test the leptin level within groups. table i: comparison of lep�n level in study and control group with normal weight there was no significant difference in average leptin level between control group (non-pcos) and study group (pcos) with p value 0.331 by mann-whitney u test (table 1). table ii: serum lep�n levels in different bmi categories of pcos women the kruskal-wallis test shows that there was significant difference of average leptin level between subgroups ii, iii and iv with p value 0.015 (table 2). the above table shows that the average leptin level changed in different bmi categories. here we applied kruskal-wallis (non parametric anova) test to test the hypothesis that “average leptin level of different bmi categories is equal” against the alternative that it is not. the p value 0.015 shows that average leptin level is different in different bmi categories. the difference in mean leptin levels in lean, overweight and obese patients was highly significant. thus, in pcos, leptin level is significantly changed in different bmi groups. there is considerable elevation in leptin levels in the pcos women as compared to controls. table iii: correla�on of lep�n and other variables in pcos group 38 leptin levels in unmarried females in pcosjiimc 2018 vol. 13, no.1 references 1. teede h, deeks a, moran l. polycystic ovary syndrome: a complex condition with psychological, reproductive and metabolic manifestations that impacts on health across the lifespan. bmc medicine. 2010; 8: 41. 2. norman rj, dewailly d, legro rs, hickey te. polycystic ovary syndrome. the lancet. 2007; 370: 685-97. 3. hussain a, chandel rk, ganie ma, dar ma, rather yh, wani za, et al. prevalence of psychiatric disorders in patients with a diagnosis of polycystic ovary syndrome in kashmir. indian journal of psychological medicine. 2015; 37: 66-70. 4. balaji s, amadi c, prasad s, kasav jb, upadhyay v, singh ak, et al. urban rural comparisons of polycystic ovary syndrome burden among adolescent girls in a hospital setting in india. biomed research international. 2015;2015: 158951. 5. haq f, aftab o, rizvi j. clinical, biochemical and ultrasonographic features of infertile women with polycystic ovarian syndrome. j coll physicians surg pak. 2007; 17: 76-80. 6. azziz r. diagnosis of polycystic ovarian syndrome: the rotterdam criteria are premature. the journal of clinical endocrinology & metabolism. 2006; 91: 781-5. 7. baig m, rehman r, tariq s, fatima ss. serum leptin levels in polycystic ovary syndrome and its relationship with metabolic and hormonal profile in pakistani females. international journal of endocrinology. 2014; 28: 133–8. 8. saleh ha, el-nwaem ma, el-bordiny mm, maqlad hmes, elmohandes aa, eldaqaq em. serum leptin elevation in obese women with pcos: a continuing controversy. journal of assisted reproduction and genetics. 2004; 21: 361-6. 9. hill jw, elmquist jk, elias cf. hypothalamic pathways linking energy balance and reproduction. american journal of physiology-endocrinology and metabolism. 2008; 294: e827-e32. 10. moschos s, chan jl, mantzoros cs. leptin and reproduction: a review. fertility and sterility. 2002; 77: 43344. 11. barba c, sforza tc, cutter j, hill id. appropriate body-mass index for asian populations and its implications for policy and intervention strategies. the lancet. 2004; 363: 157-63. 12. azziz r, carmina e, dewailly d, kandarakis ed, morreale hfe, futterweit w, et al. criteria for defining polycystic ovary syndrome as a predominantly hyperandrogenic syndrome: an androgen excess society guideline. the journal of clinical endocrinology & metabolism. 2006; 91: 4237-45. 13. chakrabarti j. serum leptin level in women with polycystic ovary syndrome: correlation with adiposity, insulin, and circulating testosterone. annals of medical and health sciences research. 2013; 3: 191-6. 14. erturk e, kuru n, savci v, tuncel e, ersoy c, imamoglu s. serum leptin levels correlate with obesity parameters but not with hyperinsulinism in women with polycystic ovary syndrome. fertility and sterility. 2004; 82: 1364-8. 15. zheng sh, du df, li xl. leptin levels in women with polycystic ovary syndrome: a systematic review and a metaanalysis. reproductive sciences. 2017; 24: 656-70. to be a bridge between body's metabolic gauge and 19 axis of reproduction. leptin shows no correlation with fsh and lh whereas blood sugar fasting has a significant correlation with leptin. sir-petermann et al. had conducted a study with no relation found between 20 leptin and lh. baig et al. narrated same observation 7 for fsh and lh. studies by legro and colleagues r e v e a l e d t h a t w o m e n w i t h p c o s h a d hyperglycaemia. vast proportion of them had glucose intolerance, a few had impaired glucose 21 tolerance and little number had type ii diabetes. susanne hahn et al. found that leptin correlated with blood glucose, insulin resistance and other metabolic parameters in pcos patients. similarly, same study found no significant correlation with 22 gonadotropins (fsh, lh). baig et al. found strong 7 correlation between leptin and bsf. these effects were due to raised blood sugar levels and ensuing insulin resistance. leptin decreases glucosemediated insulin secretion by leptin receptors in hypothalamus and therefore attenuates its action at 20 level of cells. leptin plays an important role in pcos of higher bmi categories. obesity leads to leptin resistance which 23 opposes insulin action. it is seen that females with pcos and obesity show greater tendency of being hyperglycaemic and hyperinsulinemic. the role of leptin in pcos-related obesity is that it changes the sensitivity and secretion of end organ tissues to 24,25 insulin. simultaneously, obesity encourages increased levels of insulin like growth factors by way of insulin resistance leading to increased blood 26 sugar. conclusion body mass index influences serum leptin levels as well as blood sugar fasting. leptin levels fluctuate with changing amount of fat tissue. there is no difference in average leptin levels between pcos and non pcos however, leptin level variates with changing bmi categories. obesity leads to leptin resistance which opposes insulin action. obesity adds fuel to fire by augmenting effects of leptin on metabolism and reproductive health. leptin plays a role in obesity, emergence of pcos and worsening of biochemical as well as metabolic profiles. adiposity and glucose appear to be main determinant of leptin levels. 39 leptin levels in unmarried females in pcosjiimc 2018 vol. 13, no.1 72-7. 22. hahn s, haselhorst u, quadbeck b, tan s, kimmig r, mann k, et al. decreased soluble leptin receptor levels in women with polycystic ovary syndrome. european journal of endocrinology. 2006; 154: 287-94. 23. elghblawi e. polycystic ovary syndrome and female reproduction. british journal of nursing. 2007; 16: 1118-21. 24. rabe k, lehrke m, parhofer kg, broedl uc. adipokines and insulin resistance. molecular medicine. 2008; 14: 741-51. 25. sam s. obesity and polycystic ovary syndrome. obesity management. 2007; 3: 69-73. 26. broekmans f, knauff e, valkenburg o, laven j, eijkemans m, fauser b. pcos according to the rotterdam consensus criteria: change in prevalence among who-ii anovulation and association with metabolic factors. bjog: an international journal of obstetrics & gynaecology. 2006; 113: 1210-7. 16. rehman r, teriq s, usmani a. interplay of leptin with obesity and polycystic ovarian syndrome. life sci j. 2015; 12: 83-9. 17. jacobs h, conway g. leptin, polycystic ovaries and polycystic ovary syndrome. human reproduction update. 1999; 5: 166-71. 18. shore n, khurshid r, munawar f. serum leptin level in adolescent girls with polycystic ovary syndrome: correlation with anthropometric and endocrine parameters. pak j physiol. 2017; 13: 3-6. 19. hausman gj, barb cr, lents ca. leptin and reproductive function. biochimie. 2012; 94: 2075-81. 20. jalilian n, haghnazari l, rasolinia s. leptin and body mass index in polycystic ovary syndrome. indian journal of endocrinology and metabolism. 2016; 20: 324-8. 21. akhtar a. polycystic ovarian syndrome: a new perspective. jpma (journal of pakistan medical association). 2003; 53: 40 leptin levels in unmarried females in pcosjiimc 2018 vol. 13, no.1 page 41 page 42 page 43 page 44 page 45 original�article abstract objective: to determine the type and severity of anemia in elderly hospitalized patients and their association with comorbidities. study design: descriptive study. place and duration of study: medical department of pakistan railways hospital from october 2015 to september 2016. materials and methods: one hundred elderly patients admitted in the medical ward of pakistan railways hospital were selected by nonprobability convenient sampling. we investigated the frequency of anemia in these patients and its relationship to common comorbidities in this age group such as hypertension, diabetes, heart disease and chronic kidney disease etc. anemia was defined according to the world health organization (who) criteria: hemoglobin <13 g/dl in males and <12 g/dl in females. the patients were classified according to the severity of anemia as well as morphological type of anemia based on hemoglobin level, blood cell indices and peripheral film three grades of anemia were differentiated as per who criteria: mild (hemoglobin between 11g/dl and lower limit of normal), moderate (hemoglobin between 8 g/dl and 10.9 g/dl), and severe (hemoglobin <8g/dl). microcytic anemia was defined as mean corpuscular volume (mcv) below 77 fl, normocytic as mcv between 77 fl and 96 fl, and macrocytic by an mcv above 96 fl. data analysis was done on the basis of symptomatology and routine laboratory parameters done on hospital admission. results: out of the 100 patients studied, 63% were found to be anemic. the frequency of mild, moderate and severe anemia was 57%, 30% & 12% respectively. normocytic normochromic anemia was the predominant morphological type seen in 61.9 % patients. nearly half (49%) of the anemic patients had 3 or more comorbidities as compared to 21% nonanemic patients and the correlation was statistically significant at 0.01 level (p value 0.009). chronic kidney disease was thrice as common in anemic patients and had a significant association with anemia. conclusion: anemia is a frequent occurrence in hospitalized geriatric patients and is directly related to the number of comorbidities. early diagnosis and management of anemia can have a significant impact on the overall disease outcome in elderly patients and should be part of a comprehensive geriatric assessment. key words: anemia, elderly, geriatric, hospitalized, co morbidities. elderly are a neglected population in pakistan health care system and geriatric medicine is still not practiced as a distinct specialty. with advancing age, the frequency of chronic diseases and psychological ailments increases. anemia is a frequently encountered problem in geriatric practice world over and has rightly been called “an emerging problem for st 1 the 21 century.” the mean prevalence of anemia in elderly ranges from 12% in the community to 40% in hospitalized 2,3 patients. anemia in older patients is often mild and asymptomatic but it is associated with many adverse outcomes such as cognitive decline, dementia, depression, functional deterioration and frequent 3,5 incidence of falls. it is also an independent introduction the geriatric population is expected to show an st alarming rise by the end of 21 century posing fresh challenges to the health care provider and putting additional constraints on meager health resources. anemia in elderly hospitalized patients: frequency and association with comorbidities 1 2 3 shamaila burney , muhammad farooq , ahsan ahmad alvi correspondence: dr. shamaila burney assistant professor department of medicine islamic international medical college riphah international university, islamabad e-mail: shamaila.burney@riphah.edu.pk 1,2 3 department of medicine/ pathology islamic international medical college riphah international university, islamabad funding source: nil; conflict of interest: nil received: march 28, 2018; revised: november 22, 2018 accepted: december 21, 2018 anemia in elderly hospitalized patients jiimc 2018 vol. 13, no.4 194 predictor of mortality as concluded by leiden 85 6 study. there has been a growing interest in the recent few years to unfold the association between anemia and various comorbidities found in this age group. there is now sufficient evidence to suggest that anemia has a negative impact on the outcome of 7,8 diseases like diabetes and hypertension. a study conducted by nathavitharana et al has suggested that presence of anemia in hospitalized elderly patients is associated with more frequent readmissions, longer hospital stay, and adverse 9 outcomes in terms of morbidity and mortality. more recently, abrahamsen et al concluded that more elderly patients with explained anemia died or were readmitted after one year of acute hospitalization as compared to their non-anemic counterparts or those 10 with unexplained anemia. this highlights the significance of early diagnosis and treatment of correctable causes of anemia such as nutritional anemia in this vulnerable age group. despite such conclusive evidence, there is a dearth of information regarding prevalence of anemia in our geriatric population and its clinical impact. present study was conducted to determine the type and severity of anemia in elderly hospitalized patients and their association with comorbidities. materials and methods this descriptive study was conducted in the medical department of pakistan railways hospital from october 2015 to september 2016. a total of 100 hospitalized elderly patients (65 years and above), both male and female were selected by non consecutive convenient sampling. sixty-five years age was used as a cutoff point which is widely accepted and utilized in previous studies. the study was initiated after the approval of study proposal by the institutional ethical committee. informed consent from all participants was obtained. patients with malignancy, critical illness/those requiring icu admission, unstable congestive cardiac failure, d e c o m p e n s a t e d l i v e r d i s e a s e , c o n g e n i t a l hemoglobinopathies, history of recent surgery or blood transfusion and those on anti-anemic treatment were excluded. data analysis was done on the basis of detailed history, medical records, and routine laboratory parameters done on hospital admission. complete blood counts were generated through sysmex xp-100 hematology analyzer with routine quality control. peripheral blood films were examined by consultant hematologist after staining with leishman's stain. urinalysis, fasting blood sugar, renal function tests (serum urea and creatinine), electrolytes (serum sodium and potassium), liver f u n c t i o n t e s t s ( s e r u m b i l i r u b i n , a l a n i n e t ra n s a m i n a s e , a l ka l i n e p h o s p h a ta s e ) , a n d electrocardiogram (ecg) were performed as part of admission protocol. we used the same reference ranges for various tests as established by our laboratory. anemia was defined according to the world health organization (who) criteria: hemoglobin <13 g/dl 11 in males and <12 g/dl in females. the patients were classified according to the severity of anemia as well as morphological type of anemia based on hemoglobin level, blood cell indices and peripheral film . three grades of anemia were differentiated as per who criteria: mild (hemoglobin between 11g/dl and lower limit of normal), moderate (hemoglobin between 8 g/dl and 10.9 g/dl), and severe 11 (hemoglobin <8g/dl). based on data from literature and reference values for hemoglobin level, hematocrit, total red blood cell count, blood cell indices and peripheral smear, anemia was classified as microcytic (<77 fl), normocytic (77–96 fl), or 12 macrocytic (>96 fl). data was analyzed using ibm spss 21. categorical data was calculated as frequencies and percentages. comparison of study variables was performed by chi-square test. p-value of less than 0.05 was considered significant at 95% confidence interval. results a total of 100 hospitalized patients > 65 years of age were included after meeting inclusion & exclusion criteria. of these, 53 were male and 47 were female patients. according to who classification, 63 (63%) patients were found to be anemic. females showed a higher incidence of anemia (70.2% vs. 56.6%) but the gender difference was not statistically significant. amongst 65-69 years age group, 60.4% (29/48) patients, in 70-79 years, 60.5% (23/38) and in patients 80 years above, frequency of anemia was 78.5% (11/14). no statistically significant association was found between patient's age & hemoglobin levels although the prevalence of anemia increased with rising age. there was no association between age and severity of anemia. in majority of the anemia in elderly hospitalized patients jiimc 2018 vol. 13, no.4 195 patients (36/63 or 57%) anemia was mild. figure 1 shows frequency of mild, moderate and severe anemia in our study. discussion the results of our study confirm a high prevalence (63%) of anemia in our geriatric hospitalized patients. majority of the patients had a mild normocytic normochromic anemia. presence of anemia in a single patient was significantly correlated with number of comorbidities mainly diabetes, hypertension, heart disease and chronic kidney disease. frequency of anemia in the present study was higher than the frequency reported in community-dwelling adults, but is in agreement with the data reported from nursing home residents and 2,3 hospitalized patients. bach et al. while analyzing data from a large european university hospital 13 cohort reported frequency of anemia as 21.1 %. another observational cohort study found the 14 prevalence of anemia 48%. the highest frequency of anemia in geriatric patients was determined by giesel et al in a retrospective hospital based study in which 63.3% of their elderly patients were found to 15 be anemic. results of our study therefore, are in accordance with geisel et al. literature review sug gests that anemia is significantly correlated with advanced age and male 13 sex. the percentage rises with age and is reported 16,17 as high as 50% in individuals 80 years and above. results of our study also show that anemia increases with advancing age as 78.8% of our patients >80 years of age were anemic. however, female patients in our study were found to be more frequently anemic than their male counterparts (70.2% vs. 56.6%). a simple explanation of this is the fact that women in developing parts of the world are inherently at a greater risk of anemia due to socioeconomic, cultural and biological factors with low body iron stores resulting from early marriages, multiple pregnancies etc. worldwide the dominant morphological pattern of fig 1: frequency of anemia according to severity normocytic normochromic anemia was the dominant morphological pattern seen in 61.9% (39/63) patients. figure 2 shows distribution of anemia according to morphological pattern. fig 2: distribu�on of anemia according to morphology all patients were evaluated for comorbidities common for this age group. these included diabetes, hypertension, chronic kidney disease, heart disease, stroke, obstructive airway disease, rheumatological disorders, chronic liver disease & infections. hypertension, diabetes, heart disease and chronic kidney disease were the most common diseases seen in this study. all these conditions were more frequently seen in anemic rather than non-anemic patients (table i). the association between anemia and chronic kidney disease was also statistically significant. (p value < 0.01) when comparing anemic and nonanemic patients in terms of number of comorbidities in a single patient, anemic patients had a higher number of comorbidities. nearly half (31/63 or 49%) of the anemic patients had 3 or more comorbidities as compared to 21% (8/37) non anemic patients and the correlation was statistically significant at 0.01 level (p value 0.009). table i: common comorbidi�es in non-anemic and anemic pa�ents anemia in elderly hospitalized patients jiimc 2018 vol. 13, no.4 196 anemia reported is normocytic normochromic with majority of the elderly population having only a mild 13,17 anemia. more than half (57%) of our study population had mild anemia, however an equally large number of patients had moderate (30%) or severe (12%) anemia. it may be argued that this was due to the fact that ours was a hospital based study, however in comparison to previous hospital based 13,15 studies these figures were still alarmingly high. type and severity of anemia can be a useful predictor of in-hospital and post discharge mortality. in a most 18 recent study, riva et al concluded that even mild anemia was a significant predictor of hospital readmission in older patients and the 3 month mortality risk was directly proportional to the severity of anemia. the study results further showed that normocytic normochromic anemia was associated with worst prognosis irrespective of severity. this is understandable, as prevalence of serious illnesses like diabetes, hypertension, heart disease etc. all increase with age resulting in anemia of chronic disease which is the major cause of normocytic normochromic anemia. predominant morphological pattern of anemia in our study was also normocytic normochromic (61.9%) which is in 13,17 keeping with previous studies. however, in contrast to western studies, frequency of microcytic anemia in our study population was quite high (31.7%) with almost every third patient having microcytic hypochromic anemia. this is a significant finding keeping in view that the most common cause of microcytic anemia is iron deficiency which is a readily correctable cause of anemia. vitamin b12 and folate deficiency are also correctable causes of anemia and are a common cause of macrocytic 19 anemia in developing countries like pakistan. in the present study, 6.3% of our patients had macrocytic anemia. in a previous study, we have reported frequency of vitamin b12 and folate deficiency as 20 10% and 7% respectively. prevalence of nutritional anemia in the developing world is high. the national health and nutrition examination survey (nhanes iii), also reports that one-third of the elderly anemic patients have nutritional anemia mainly iron 16 deficiency. anemia in elderly is often complicated by the fact that majority of these patients have nutritional anemia in the background of anemia of chronic disease. it may not always be possible to treat the underlying disorder however, correction of coexisting nutritional anemia such as iron deficiency can significantly influence the outcome in many diseases such as chronic kidney disease and heart 21, 22 failure. one of the most significant aspects of our study was that it highlights the association between anemia and presence of comorbidities in a patient. in a recently published study, migone et al have concluded that anemia is independently associated with higher number of comorbidities in a single 14 patient. this can have important therapeutic implications as untreated anemia is known to negatively affect outcomes in terms of primary 7 8 illness such as diabetes, hypertension, heart 22 23 failure, chronic obstructive pulmonary disease, 14,24 etc. while the prevalence of all these diseases was overall high in our study population, the frequency of most of these disorders was much higher in anemic patients. chronic kidney disease was thrice as common in anemic patients and had a significant association with anemia. correction of anemia in chronic kidney disease is an integral part of 21 management of patients with renal disease. the association between anemia and chronic kidney disease is well known and renal disease should be excluded in every elderly individual with unexplained anemia. in terms of number of comorbidities in a single patient, more than half of our anemic patients had at least 3 or higher number of comorbidities as compared to their non-anemic counterparts (49% vs. 21%). the correlation between presence of anemia and number of comorbidities per single patient was statistically significant (p value < 0.01). the present study was not aimed to determine the etiology of anemia therefore the data is based only on previously diagnosed coexisting diseases in our patients which may be considered as a limitation of the study. it may be argued that primary illness of an individual patient can act as confounder, affecting presence or severity of anemia. however, we applied stringent exclusion criteria and an attempt was made to include only stable patients admitted in general medical ward with diseases common in this age group. furthermore, the exact causal link between anemia and different comorbidities needs to be evaluated. the disease burden in pakistani geriatric population anemia in elderly hospitalized patients jiimc 2018 vol. 13, no.4 197 is very high with diabetes, hypertension and arthritis 25 as the most common illnesses. anemia often remains under diagnosed because of vague signs and symptoms which are generally attributed to co existing illnesses or simply old age. given the clear association between even mild anemia and morbidity in this age group, findings of our study may have clinical significance in the management of elderly patients with anemia. more studies to explore various aspects of clinical impact of anemia are needed to further evaluate this important aspect of geriatric health. conclusion the present study has shown that every second hospitalized elderly patient in our set ups is likely to be anemic with every third patient having moderate to severe anemia. it has further shown that frequency of common diseases such as diabetes and hypertension is higher in patients with anemia and that presence of anemia is directly related to number of comorbidities in a single patient. we conclude that physicians should have a high index of suspicion and low threshold for treating anemia in geriatric patients as this can significantly impact the disease outcome. references 1. vanasse gj, berliner n. anaemia in elderly patients: an emerging problem for the 21st century. hematology am soc hematol educ program. 2010; 2010:271-5. 2. gaskell h, derry s, moore ra, mc quay hj. prevalence of anaemia in older persons: systematic review. bmc geriatr. 2008; 8:1. 3. patel kv, guralnik jm. prognostic implications of anaemia in older adults. haematologica. 2009; 94(1):1-2. 4. androm, le squere p, estivin s, gentric a. anaemia and cognitive performances in the elderly: a systematic 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[cited 12 january 2 0 1 5 ] . a v a i l a b l e f r o m : h t t p : / / w w w. w h o . i n t / vmnis/indicators/hemoglobin.pdf. 12. brugnara c, mohandas n. red cell indices in classification and treatment of anemias: from m.m. wintrobes's original 1934 classification to the third millennium. curr opin hematol. 2013; 20(3):222–223. 13. bach v, schruckmayer g, sam i, kemmler g, stauder r. prevalence and possible causes of anemia in the elderly: a cross-sectional analysis of a large european university hospital cohort. clin interv aging. 2014; 9:1187-96. 14. migone de amicis m, poggiali e, motta i, minonzio f, fabio g, hu c, et al. anemia in elderly hospitalized patients: prevalence and clinical impact. intern emerg med. 2015; 10(5):581-6. 15. geisel t, martin j, schulze b, schaefer r, bach m, virgin g, et al. an etiologic profile of anemia in 405 geriatric patients. anemia. 2014; 2014:932486. 16. guralnik jm, eisenstaedt rs, ferruci l, klein hg, woodman rc. prevalence of anaemia in persons 65 years and older in the united states: evidence for a high rate of unexplained anaemia. blood. 2004; 104(8):2263-8. 17. tettamanti m, lucca u, gandini f, recchia a, mosconi p, apolone g, et al. prevalence, incidence and type of mild anemia in the elderly: the “health and anemia” populationbased study. haematologica. 2010; 95(11):1849-56. 18. riva e, colombo r, moreo g, mandelli s, franchi c, pasina l, et al; reposi investigators.prognosticvalue of degree and types of anaemia on clinical outcomes for hospitalised older patients.arch gerontol geriatr. 2017; 69:21-30. 19. iqbal sp, kakepoto gn, iqbal sp. vitamin b12 deficiencya major cause of megaloblastic anemia in patients attending a tertiary care hospital. j ayub med coll abbottabad. 2009; 21(3):92-4. 20. burney s, ahmed sq, masroor r. anaemia in elderly: a benign condition or an early warning? a hospital based study. pak armed forces med j 2016; 66(3):400-06 21. macdougall ic, bock ah, carrera f, eckardt ku, gaillard c, van wyck d, et al; find-ckd study investigators. find-ckd: a randomized trial of intravenous ferric carboxymaltose versus oral iron in patients with chronic kidney disease and iron deficiency anaemia. nephrol dial transplant. 2014; anemia in elderly hospitalized patients jiimc 2018 vol. 13, no.4 198 29(11):2075-84. 22. cohen-solal a, leclercq c, deary g, lasocki s, zambrowski jj, mebazaa a et al. iron deficiency: an emerging therapeutic target in heart failure. heart. 2014 sep 15; 100(18):1414-20. 23. oh ym, park jh, kim ek, hwang sc, kim hj, kang dr, et al. anemia as a clinical marker of stable chronic obstructive pulmonary disease in the korean obstructive lung disease cohort.j thorac dis. 2017; 9(12):5008-5016. 24. ali an, athavale nv, abdelhafiz ah. anemia: an independent predictor of adverse outcomes in older patients with atrial fibrillation. j atr fibrillation. 2016; 8(6):1366. 25. zafar sn, ganatra ha, tehseen s, qidwai w. health and needs assessment of geriatric patients: results of a survey at a teaching hospital in karachi. j pak med assoc. 2006; 56(10):470-4. anemia in elderly hospitalized patients jiimc 2018 vol. 13, no.4 199 jiimc march 2016.cdr case report abstract hypokalemic periodic paralysis is a group of rare inherited disorders that can cause temporary and often recurrent episodes of acute flaccid paralysis. several conditions e.g. thyrotoxicosis, increased carbohydrate and salt dietare known to cause or precipitate it. a case of a 26 years age male is presented here who reported with sudden onset of muscle weakness with concomitant hypokalemia after a high carbohydrate diet. the patient's paralysis resolved upon replacement of potassium. periodic paralysis must be differentiated from other causes of sudden onset paralysis, so that the proper treatment can be initiated in time to prevent complications due to this rare disease. key words: hypokalemia, hypokalemic periodic paralysis, flaccid paralysis. of all limbs with power 2/5. deep tendon reflexes were overall diminished and plantars were normal. there was no sensory loss, cranial ner ve involvement, bladder/bowel or higher function disturbance. there were no signs of hyperthyroidism and rest of the systemic examination was un remarkable. baseline investigations such as blood complete picture, urinalysis, random blood sugar, serum urea, serum creatinine and liver enzymes were all normal. serum electrolytes revealed hypokalemia with a potassium level of 3.2 mmol/l; however serum sodium, calcium, magnesiumand phosphate levels were normal. creatinine phosphokinase(ck) levels, thyroid profile, serum aldosterone / renin and 24 hour urinary sodium and potassium levels were also sent and were subsequently found to be normal. the patient was meanwhile managed in icu with potassium replacement and cardiac monitoring. within few hours his symptoms resolved completely a n d m u s c l e p o w e r w a s 5 / 5 . a r e p e a t electrocardiogram revealed a normal sinus rhythm and rate with normal t waves. based on the typical presentation and the dramatic response to potassium replacement, a clinical diagnosis of hypokalemic periodic paralysis (hypokpp) was made. considering the nature of his job, he was counseled in detail regarding trigger identification, such as avoiding carbohydrate-rich meals, long distance travel and strong physical exercise, in order to prevent future attacks. discussion hypokalemic paralysis is characterized by episodes of acute muscle weakness associated with 1 hypokalemia. possible etiological factors include case report male soldier 26 years of age presented to the emergency room with sudden onset weakness of all four limbs. the patient had gone to sleep after taking a heavy dinner andwoke upnext morning with inability to move all his four limbs. the weakness involved both proximal and distal muscles. there was no respiratory or swallowing difficulty. he denied any muscle pain and there were no sensory symptoms. prior to this episode, the patient had been healthy and denied any recent diarrhea, sore throat, vaccination, shortness of breath, palpitation, weight loss or heat intolerance. there was no history of psychomotor illness. two years ago he had experienced a similar episode of muscle weakness for which he was admitted in hospital and recovered completely after potassium replacement. duration of attack both times was about 4-6 hours and both times it occurred after a carbohydrate-rich meal. he did not take any medications and denied use of a l c o h o l . t h e r e w a s n o fa m i l y h i s t o r y o f neuromuscular disease. on examination, bpwas 130/80 mmhg, pulse74/ m i n u t e , r r 1 4 / m i n u t e , t e m p e r a t u r e 9 9 f. neurological examination revealed flaccid paralysis hypokalemic periodic paralysis 1 2 abidullah khan , muhammad farooq correspondence: maj. dr. abidullah khan 63 medical battalion multan cantt e-mail: drabid2424@yahoo.com 1 department of medicine 63 medical battalion, multan cantt 2 department of medicine islamic international medical college riphah international university, islamabad funding source: nil ; conflict of interest: nil received: august 06, 2015; accepted: february 16, 2016 hypokppjiimc 2016 vol. 11, no.1 41 strength and potassium levels. electromyography may reveal abnormalities in some patients but is 2-5 often normal especially in between the episodes. management of hypkpp includes potassium replacement and identifying and avoiding triggers of attack. potassium may be replaced orally or intravenously depending on potassium levels and clinical condition. when given intravenously the rate of potassium administration should not exceed 20 mmol/hour. to calculate the amount of potassium supplementation one should have an estimate of potassium deficit. on average a reduction of serum potassium by 0.3 mmol/l suggests a total body 2,4-6 deficit of 100mmol/l. biochemical parameters including electrolytes such as potassium, sodium, magnesium, calcium and phosphate, ecg and c a r d i a c r h y t h m m o n i t o r i n g a r e e s s e n t i a l components of management of hypokpp. although completely reversible on potassium replacement in the majority of the affected individuals, some of the patients with hypokpp may develop myopathy leading to exercise intolerance in later life; others may be at increased risk of post anaesthetic weakness. conclusion a high index of suspicion is required for the timely diagnosis of hypokpp in any patient presenting with acute flaccid paralysis. identifying and avoiding triggers of attack are integral component of the management of hypokpp. references 1. s h a r m a c m , n a t h k , p a r e k h j . r e v e r s i b l e electrophysiological abnormalities inhypokalemicparalysis: case reportof two cases.ann indian acad neurol. 2014; 17: 100-2. 2. mukhtar h, ahmad s, javaid a, qayyum k. hypokalemic periodic paralysis. ann king edward med uni 2006; 12: 5989. 3. s u e t t e r l i n k , m a n n i k k o r , h a n n a m g . musclechannelopathies: recent advances in genetics, pathophysiology and therapy. curropin neurol 2014; 27: 583-90. 4. b o i s s i e r e , g e o r g i n l a v i a l l e s , c o c h e r e a u d . thyrotoxicperiodicparalysis: a case series of four patients and literaturereview. rev med interne 2013; 34: 565-72. 5. alkaabi jm, mushtaq a, al-maskari fn. hypokalemic periodic paralysis: a case series, review of the literature and update of management. eur j emerg med 2010; 17: 45-7. 6. soule br, simone nl. hypokalemic periodic paralysis: a case report andreviewof the literature. cases j. 2008; 1: 256. decreased potassium intake, urinary losses (e.g. primary/secondary aldosteronism, cushing's syndrome, diuretics, hypomagnesemia, renal tubular acidosis etc), gi losses (e.g. diarrhea, vomiting etc.), and potassium shift into the cells (e.g. by insulin, alkalosis or periodic paralysis). hereditary defects causing hypokalemia are bartter's syndrome and gitelman syndrome. in this case, secondary causes of hypokalemia and thyrotoxicosis were sequentially ruled out on the basis of clinical evaluation and battery of laboratory investigations. although desirable, ncs/emg studies were not available at our facility. hencea clinical diagnosis of hypokpp was made on the basis of typical presentation and recurrent episodes triggered by high carbohydrate diet. hypokpp is a genetic disorder/channelopathy in which individuals (majority of them young affected males) may experience episodes of acute flaccid paralysis with concomitant hypokalemia. the paralytic attacks are reversible, usually leading to paraparesis or quadriparesis. they can last several hours and sometimes days. some individuals have only one episode in a lifetime; more commonly, crises occur repeatedly. the major triggering factors are carbohydrate-rich meals and rest after strenuous exercise; hence symptoms frequently occur early morning on awakening. other triggers include stress, viral illness, fatigue, and medications such as betaagonists, insulin or steroids. hypokpp is caused by mutations in the genes that control the development and function of certain ion channels in the muscle 2 membrane. although the serum potassium level is often low, other electrolytes usually remain normal. infact, total body potassium is actually normal with the change in the serum level merely reflecting an 3 acute shift of potassium into cells. many variants are recognized including thyrotoxic periodic paralysis (tpp) which is mainly observed in asians and familial 1-5 periodic paralysis. they are of sudden onset and sometimes even with life-threatening respiratory failure. as this is primarily a problem with muscle contraction rather than nerve conduction, tendon reflexes are diminished but sensation is intact. electrocardiographic changes are common, but changes do not correlate well with the measured serum level. diagnosis in between the paralytic episodes is difficult as the patient will have normal 42 hypokppjiimc 2016 vol. 11, no.1 144 editorial lessons learned by teachers during covid-19 pandemic sadia ahsin the covid-19 pandemic has globally brought significant transformation in educational activities 1 w o r l d w i d e . p a k i s t a n , a l t h o u g h s u f f e r e d comparatively less than rest of the neighboring countries was and still is, one of the affected regions. in march 2020, with strict restrictions on social gatherings, the conventional education methods were suspended temporarily with an urgent need to 2 shift to online teaching methods. online education is electronically supported learning that relies on the internet for teacher/learner interaction and the distribution of learning resources. it may include audiotaped lectures, videos, text, animations, virtual training environments, real-time online lectures and 3 interactive sessions with teachers. online learning methodology was adopted by the west, long before it was even introduced in pakistan. considering, that the first-ever completely online course was offered in 1984 by the university of 4 toronto, it seems that we are lagging far behind. the west, with its already existing online learning technology, had the economic strength to survive the pandemic, yet such online practice and technological advancement was not available to the developing countries like pakistan. the shift from traditional classroom teaching to online teaching was a huge change to adapt to for all stakeholders including institutional administration, faculty, students, and parents. high-quality online teaching is not only difficult to execute, but it is more demanding than traditional on campus teaching. it requires more upfront planning, groundwork, more individualized response and assistance for learner 3 and teacher for which we were not ready. despite strenuous efforts there were many shortcomings and blunders on part of management, teachers and students due to poor technical skills, reluctance, time constraints, inadequate infrastructure and absence of institutional strategies and support. just like any other educational institute of this region where online readiness was non-existent, medical colleges were no different in the face of this 5 challenge. this urgent requirement to 'move online' added to the stress and workload of university faculty and staff who were already struggling to b a l a n c e e x i s t i n g t e a c h i n g , r e s e a r c h , a n d administrative duties, not to mention the stress related to their own health and safety concerns during pandemic. power outages and connectivity issues at both learner and faculty end were also one of the recurring problems. covid-19 taught us quite a few lessons as far as education is concerned. during pandemic crisis, higher education commission of pakistan sprang into action and initiated faculty and management training workshops in the field of online modalities from undergraduate to doctoral level education by 6 creating a collaborative environment. despite all impediments, educational institutes showed the will and desire to devise and follow practical solutions for implementation of emergency distant teaching strategies, with special focus on online lecture-based 7 classes along with interactive learning sessions. transitioning to take lectures through screens, asking and replying to questions without face-toface interaction, uploading relevant laboratory and clinical skills demonstration videos on campus/ learning management systems are some of the situations faculty and students acclimatized themselves to. many senior teachers also had to adopt the new methods, and despite poor technical skills, gradually became accustomed to this new methodology. the struggle and commitment of institutional managements and faculty in providing students with quality education to the best of their abilities during these stressful circumstances has been commendable. it has taught us that, motivation and readiness to change practices with collaborative effort can help us adapt to any situation. as faculty we learned that online teaching expanded our reach regardless of geographical location and time scale. out-stationed and overseas students correspondence: prof. dr. sadia ahsin department of physiology foundation university medical college, foundation university islamabad e-mail: sadia.ahsin@fui.edu.pk received: july 12, 2021; accepted: august 25, 2021 modalities may be employed by dividing students into small groups, should the need arise again. covid -19 pandemic is a global calamity that has transformed the approach to education throughout the world. few of the lessons that teachers learned about online education are, that they can adapt and overcome their limitations if they are willing, they can expand their audience, they can set up their own databases, they can join online courses at their convenience, and last but not the least, they too can be fooled! references 1. şenel s, şenel hc. remote assessment in higher education during covid-19 pandemic. int j assess tools educ. 2021;8(2):181–99. 2. waris a, atta uk, ali m, asmat a, baset a. covid-19 outbreak: current scenario of pakistan. new microbes new infect [internet]. 2020;35(20):100681. available from: https://doi.org/10.1016/j.nmni.2020.100681 3. zounek jĝ, sudický p. heads in the cloud: pros and cons of online learning ji ĝ í zounek, petr sudický. 2012;(december):58–63. 4. a brief history of online education | adamas university [ i n te r n e t ] . [ c i te d 2 0 2 1 j u l 7 ] . ava i l a b l e f ro m : https://adamasuniversity.ac.in/a-brief-history-of-onlineeducation/ 5. mumtaz n, saqulain g, mumtaz n. online academics in pakistan: covid-19 and beyond. pakistan j med sci. 2021;37(1):1–5. 6. online resources on teaching and learning [internet]. [cited 2021 jul 7]. available from: https://hec.gov.pk/english/ services/faculty/nahe/pages/online-resources.aspx 7. gcu switches to online classes after ncoc decision | the academia [internet]. [cited 2021 jul 7]. available from: https://academiamag.com/gcu-switches-to-onlineclasses-after-ncoc-decision/ 8. jaramillo-morillo d, ruipérez-valiente j, sarasty mf, ramírez-gonzalez g. identifying and characterizing students suspected of academic dishonesty in spocs for credit through learning analytics. int j educ technol high educ. 2020;17(1). 9. cheating on online exams newspaper dawn.com [ i n te r n e t ] . [ c i te d 2 0 2 1 j u l 7 ] . ava i l a b l e f ro m : https://www.dawn.com/news/1603040 could listen to lectures along with their class fellows while maintaining social distance. in addition, if allowed by institutes, outside participants could join the educational activity at a specified allotted time. in this way, students got opportunity to interact with subject experts, from other institutions too. during virtual teaching it was also learned that a certain degree of student anonymity, may actually be preferred by a number of students over the traditional face-to-face setup, and hence may enhance their performance. faculty using online technology could archive lecture content, syllabus, feedback and attendance and set up databases to 3 add relevant supplemental learning resources. having to adapt themselves to virtual learning, faculty members also made best use of this technology for their own professional growth and development. several open online courses from renowned universities were offered free of cost during the pandemic where teachers actively participated to deepen their content knowledge and teaching skills at their own pace. one of the challenges faced was, and still is the constant doubt about students' academic honesty pertaining to their attendance, assignments, supervision of exams (impersonation or cheating 1 during examinations), etc. however, we are not alone in this ethical dilemma, it is an endemic problem in distance learning since it became popular, and it is because there is no guarantee that 8 students are being honest. fear of academic dishonesty compromising merit in high stake exams compounded the teething problems of newly adapted environment and caused disruptions in conduction of exams and assessments throughout 9 the country. thus, another lesson learned by educational institutes and faculty is to upgrade their online assessment methods and technical skills to use them for formative type of feedback. for high sta ke s u m m at i ve a s s e s s m e nt s , o n ca m p u s 145 jiimc 2021 vol. 16, no.3 jiimc june 2016.cdr original article abstract objective: to determine the effects of unilateral posterior cordectomy by co laser, in terms of improvement of 2 airway with acceptable voice quality, among the patients with bilateral abductor paralysis. study design: a descriptive study. place and duration of study: the study was carried out in ent department combined military hospital (cmh) rawalpindi and armed forces institute of rehabilitation medicine (afirm) rawalpindi, from august 2011 to july 2015. materials and methods: a total of 33 patients having difficulty in breathing or stridor with bilateral vocal cord paralysis were selected for unilateral posterior cordectomy by co laser. prior tracheostomy was carried out. 2 cordectomy involved laser ablation of one of the vocal cords anterior to vocal process of arytenoids. co laser 2 was used in intermittent firing mode, with 5 watt power super-pulse and small spot size. post operatively all patients were given intravenous antibiotics, steroids and analgesics. post operative speech therapy was carried out in all these patients at the afirm. successful outcome was taken as the ability to decannulate with acceptable voice quality. results: decannulation was successful in 31 patients, while acceptable voice quality could not be achieved in 7 patients. hence successful outcome was made possible in 24 (73%) patients. conclusion: unilateral posterior laser cordectomy, in patients with bilateral abductor paralysis, gives excellent results in improving the airway, while preserving an acceptable voice quality. key words: co laser, posterior cordectomy, vocal cord paralysis2 introduction bilateral abductor paralysis with respiratory distress is not a very common finding, but may present as an acute emergency. iatrogenic trauma, especially the thyroidectomy, has been seen as the commonest cause for this problem. the patient presents with dyspnoea and stridor, although voice quality is not affected. first surgical intervention to address this problem was carried out by chevalier jackson in 1922 when he removed the entire vocal fold along with the ventricle (ventriculo-cordectomy). since then various surgical procedures including various types of arytenoidectomy and other lateralization procedures have been carried out with varying laser cordectomy in bilateral abductor paralysis 1 2 3 4 mirza khizer hameed , zeeshan ayub , rukhsana khizar , zeeshan ali cordectomy in abductor paralysisjiimc 2016 vol. 11, no.2 correspondence: brig (r) dr. mirza khizer hameed associate professor, ent yusra medical & dental college, islamabad e-mail: mirzakhizar@yahoo.com 1 ent department yusra medical & dental college, islamabad 2 ent department pakistan air force hospital, mianwali 3 combined military hospital, rawalpindi 4 ent department combined military hospital, lahore funding source: nil ; conflict of interest: nil received: feb 11, 2016; revised: mar 01, 2016 accepted: may 08, 2016 62 results., of course, aim of all these procedures was to improve the airway. but it was always at the cost of quality of voice. in any procedure designed to improve the airway the surgeon has to strike a delicate balance between patent airway and a c c e p t a b l e v o i c e q u a l i t y. h e n c e f u r t h e r developments in this context were made to improve the airway while preserving good quality voice as well. in 1989, dennis and kashima carried out posterior laser cordectomy to address this problem. cordectomy involves ablation of vocal fold along with the vocalis muscle. although this procedure gives good respiration, but quality of post operative voice is less than ideal, hence reinnervation procedures were attempted to gain better voice quality, but showed inconsistent results. bilateral posterior cordotomy is another modification in this regard. but no matter whatever procedure is adopted for improvement of airway, it is a compromise with the voice quality. but since, voice quality is not the primary aim in this condition, an acceptable voice quality with decannulation of the patient is considered a successful outcome. since posterior laser cordectomy with carbon dioxide laser gives successful outcome in around 90% of the cases with negligible complication rate, it has become procedure of choice. moreover, it is a safe and simple procedure which can be repeated without any increase in morbidity. however, this procedure cannot be undertaken in patients having thick, short necks or having fixation of spine as vocal cords are not properly visible. materials and methods a descriptive study was carried out in ent department, combined military hospital rawalpindi and armed forces institute of rehabilitation medicine (afirm) rawalpindi, from august 2011 to july 2015. the aim of this study was to determine the effects of unilateral posterior cordectomy by co 2 laser, in terms of improvement of airway with acceptable voice quality, among the patients with bilateral abductor paralysis. in this duration, 33 patients (n= 33) with bilateral abductor paralysis reporting in the ent opd with complaints of difficulty in breathing and stridor, were selected by convenient sampling. only those patients were included, in whom, at least six months had passed since they suffered this problem, as six to nine months are required for spontaneous recovery. those patients, who had already undergone some corrective surgery, were not included in the study. those patients, who refused to undergo laser surgery, were also excluded from the study. nineteen of these patients had stridor even at rest and urgent tracheostomy was carried out on them. detailed history was taken in all these cases to determine the cause and duration of cord paralysis. complete ent and head and neck examination was carried out in these patients. indirect laryngoscopy and flexible fibreoptic laryngoscopy were carried out in all of them. routine investigations were carried out in all these patients, while ct scans of base of skull, neck and thorax, blood glucose levels (r), coagulation profile, serum lipid profile and esr were done in the patients with no apparent cause. the selected patients were counseled about procedure of vocal cordectomy with carbon dioxide laser and its effects on airway and voice quality. all of these patients underwent surgery. all of them were operated by the same consultant ent surgeon. cordectomy involved laser ablation of one of the vocal cords anterior to vocal process of arytenoids. carbon dioxide laser was used in intermittent firing mode, with 5 watt power super-pulse and small spot size. post operatively all patients were given intravenous antibiotics, steroids and analgesics. post operative speech therapy was carried out in all these patients at the afirm rawalpindi. successful outcome was taken as the ability to decannulate with acceptable voice quality, the voice that is easily understandable. the parametric data was analyzed for frequencies by spss 19. results the causes of bilateral abductor paralysis are shown in table i. table: i. e�ology of bilateral vocal cord paralysis unilateral posterior laser cordectomy was carried out in 33 patients. twenty (61%) patients were th successfully decannulated on 5 post operative day, nd while 5 (15%) patients were decannulated in the 2 post operative week. in four (12%) of these patients procedure had to be repeated once after a fortnight, while in two patients (6%) the procedure was repeated thrice fortnightly, before decannulation was possible. two (6%) patients could not be decannulated despite repeated procedures. in 7 (21%) patients, the post operative quality of voice was poor. hence the successful outcome was possible in 24 (73%) patients. discussion our study shows success in 73% of the patients. these results are comparable with results of other studies carried out at various centers. our study also describes thyroidectomy to be the commonest cause of bilateral abductor paralysis. bilateral abductor paralysis is a potentially life threatening condition. its management is one of the biggest challenges an otolaryngologist has to come across, and still tracheostomy is considered to be the safest and permanent solution for this problem. cordectomy in abductor paralysisjiimc 2016 vol. 11, no.2 63 bilateral abductor paralysis mostly occurs as a result of trauma, mostly iatrogenic. among surgical procedures, thyroidectomy has been the most frequent cause. our study also confirmed this fact. in our study the thyroidectomy appeared to be the most frequently carried out surgical procedure (87%) that resulted in bilateral abductor paralysis. probably it is the result of poor surgical technique where the surgeon does not identify the recurrent laryngeal nerves while doing surgery. other such studies also show thyroidectomy to be the most frequent cause of bilateral abductor paralysis. ozdemir et al (2013) also showed thyroidectomy as the surgical procedure resulting in bilateral abductor paralysis in 92% of the patients. as posterior glottis accounts for 50-60% of the glottis, any surgical intervention in this area is bound to improve the airway. this is the basis for posterior laser cordectomy, but degradation of voice quality after any such procedure is a known fact. the patients included in this study were counseled about this outcome. any improvement in the airway is always at the cost of voice quality. in our study, decannulation was possible in 76% of the patients after first surgical intervention. the results are not much different from other studies as decannulation was made possible in 94% of the patients after repeated interventions. khalil & tawab (2014) had similar results in terms of improvement in airway. similar results in terms of improvement in airway were shown in another study by motta s et al (2003). another study also showed improvement of airway in 89% of the patients and similar results were shown by shvero et al (2003). in our study satisfactory voice quality was achieved in 73% cases. similar results were shown in a study by segas et al (2001). dispenza et al (2012) also showed satisfactory results in a similar study. landa et al reported a 95% success rate with posterior transverse cordotomy, with excellent voice outcome. although our study includes only 33 patients in a descriptive case series, it may not be very significant. hence, it is recommended that further studies be carried out at a broader level that should compare the results of various surgical procedures carried out to manage bilateral abductor paralysis. conclusion unilateral posterior laser cordectomy, in patients with bilateral abductor paralysis, gives excellent results in improving the airway, while preserving an acceptable voice quality. references 1. mohamad i, jihan ws, mohamad h, abdullah b. laser posterior cordectomy for bilateral abductor vocal cord palsy: a case report. malays j med sci. 2008; 15: 42-3. 2. jackson c. ventriculocordectomya new operation for the cure of goitrous paralytic laryngeal stenosis. arch surg. 1922; 4: 257-74. 3. young vn, rosen ca. arytenoid and posterior vocal fold surgery for bilateral vocal fold immobility. curr opin otolaryngol head neck surg. 2011; 19: 422-7. 4. ossoff rh, karlan ms, sisson ga. endoscopic laser arytenoidectomy. lasers surg med. 1983; 2: 293-9. 5. dennis dp, kashima h. carbon dioxide laser posterior cordectomy for treatment of bilateral vocal cord paralysis. ann otol rhinol laryngol. 1989; 98: 930-4. 6. spiegel jr, sataloff rt. surgery for carcinoma of the larynx. gould wj, sataloff rt, spiegel jr. voice surgery. st. louis: mosby; 1993: 307-337. 7. tucker hm. rehabilitation of the immobile vocal fold. in: fried mp, editor. the larynx. a multidisciplinary approach. 2nd ed. st. louis: mosby; 1996. 209-218. 8. khalifa mc. simultaneous bilateral posterior cordectomy in bilateral vocal fold paralysis. otolaryngol head neck surg. 2005; 132: 249-50. 9. mohamad i, jihan ws, mohamad h, abdullah b. laser posterior cordectomy for bilateral abductor vocal cord palsy : a case report. malays j med sci. 2008; 15: 42–3. 10. joshua b, feinmesser r, zohar l, shvero j. endoscopic laserassisted posterior ventriculocordectomy without tracheostomy for bilateral vocal cord immobility. imaj, 2004; 6: 336-8. 11. bizakis jg, papadakis ce, karatzanis ad. the combined endoscopic co2 laser posterior cordectomy and total arytenoidectomy for treatment of bilateral vocal cord paralysis. clin otolaryngol. 2004, 29: 51-4. 12. pinto ja, godoy lb de m, marquis vwpb, sonego tb, leal c de fa. bilateral vocal fold immobility: diagnosis and treatment. braz j otorhinolaryngol, 2011; 77: 594-9. 13. leon x , venegas mp, orus c, quer m, maranillo e, sanudo jr. [glottic immobility: retrospective study of 229 cases]. acta otorrinolaringol esp. 2001; 52: 486-92. 14. ozdemir s, tuncer u, tarkan o, kara k, surmelioglu o. carbon dioxide laser endoscopic posterior cordotomy technique for bilateral abductor vocal cord paralysis: a 15year experience. jama otolaryngol head neck surg. 2013; 139: 401-4. 15. mondal pk, pal i, bera sp, mondal ar, biswas s. surgical management of bilateral abductor paralysis by extralaryngeal approach. indian j otolaryngol head neck surg. 2005; 57: 75-7. 16. khalil ma, tawab hma. laser posterior cordotomy: is it a good choice in treating bilateral vocal fold abductor paralysis? clin med insights ear nose throat. 2014; 7: 13-7. cordectomy in abductor paralysisjiimc 2016 vol. 11, no.2 64 17. motta s, moscillo l, imperiali m, carra p, motta g. co laser 2 treatment of bilateral vocal cord paralysis in adduction. 2003; 65: 359-65. 18. bilgen c, kirazli t, oqut f. [laser posterior cordectomy in bilateral vocal cord paralysis]. kulak burun bogaz ihtis derg. 2002; 9: 286-90. 19. shvero j, koren r, stern y, segal k, feinmesser r, hadar t. laser posterior ventriculocordectomy with partial arytenoidectomy for the treatment of bilateral vocal fold immobility. the journal of laryngology & otology. 2003; 117: 540-3. 20. segas j , stavroulakis p, manolopoulos l, yiotakis j, adamopoulos g. management of bilateral vocal fold paralysis: experience at the university of athens. otolaryngol head neck surg. 2001; 124: 68-71. 21. dispenza f, dispenza c, marchese d, kulamarva g, saraniti c. treatment of bilateral vocal cord paralysis following permanent recurrent laryngeal nerve injury. am j of otolaryngol, 2012; 33: 285-8. 22. landa m, luqui i, gomez j, martínez z. posterior cordectomy: our experience. acta otorrinolaringol esp. 2012; 63: 26-30. cordectomy in abductor paralysisjiimc 2016 vol. 11, no.2 65 original�article abstract objective: the objective of the study was to determine the serum enzymatic antioxidant levels in recurrent aphthous stomatitis patients. study design: this was a case control study. place and duration of study: the study was conducted in biochemistry department of islamic international medical collegetrust (iimc-t) rawalpindi from 15 march 2016 to 14 march 2017. materials and methods: the study included 160 subjects divided into two groups aphthous group and nonaphthous group. aphthous group comprised of 70 recurrent aphthous stomatitis patients with active lesion and 90 age and sex matched healthy controls were included in the non-aphthous group .from all the participants 2 ml of blood was taken. serum glutathione peroxidase levels were measured using enzyme linked immunosorbent assay technique. this elisa kit uses sandwich-elisa as the method. results: the comparison of mean of serum glutathione peroxidase levels between aphthous and non-aphthous group was significant (p<o.oo).this study showed that the levels of glutathione peroxidase (a biological stress marker) were lower in recurrent aphthous stomatitis patients than in control subjects. conclusion: serum enzymatic antioxidant levels were lower in recurrent aphthous stomatitis patients as compared to controls, so oxidative stress plays an important role in the pathogenesis of disease. key words: glutathione peroxidase, oxidative stress, recurrent aphthous stomatitis have done to find out the causes of recurrent aphthous stomatitis but the exact etiology remains unidentified .potential factors which have been identified in the onset of disease include hereditary predisposition, local and systemic causes, hematological and micronutrient deficiencies, 11 emotional stress and drug allergies. it has been postulated that all the predisposing factors for the formation of aphthous ulcers act through a common pathway that depends on the oxidative stress by increasing free radical synthesis. either the enhanced production of reactive oxygen species and/or decreased defense by antioxidants result in oxidative stress that is lethal as it causes tissue 12 damage . studies suggest that the lack of balance between reactive oxygen species and antioxidants have a pivotal role in the development and progression of inflammatory reactions, so oxidative stress may have a crucial role in development of recurrent aphthous 13 stomatitis as it is inflammatory in nature. to prevent oxidative stress, mammalian cells have developed antioxidant defense system including both enzymatic and non-enzymatic antioxidants. glutathione peroxidase, a selenocysteine containing introduction recurrent aphthous stomatitis (ras) is one of the most commonly encountered pathology of oral 1 mucosa, affecting nearly 20% of world population. aphthous is originated from “aphtha” a greek word 2, 3, 4, 5 meaning ulceration. recurrent aphthous stomatitis is a painful, recurring and distressful experience for the patients because it restricts their 6,7 normal oral activities. ulcerations can be solitary 8 or multiple and has a shallow necrotizing center and can be classified into three classes depending on their type , size , number and their healing time i-e 9 minor, major and herpetiform. minor recurrent aphthous stomatitis are the most common type and 10 contributes to 80% of total cases. many studies assessment of serum enzymatic antioxidant levels in recurrent aphthous stomatitis patients correspondence: dr. rabbia shabbir department of biochemistry islamic international medical college riphah international university, islamabad e-mail: rabbia.shabbir@gmail.com department of biochemistry islamic international medical college riphah international university, islamabad funding source: nil; conflict of interest: nil received: april 02, 2017; revised: aug 24, 2018 accepted: aug 25, 2018 serum enzymatic antioxidant in aphthous stomatitisjiimc 2018 vol. 13, no.3 133 rabbia shabbir, amena rahim, muhammad afzal immunomodulatory agents for past two months. pregnant and lactating mothers were excluded. smokers and alcohol users were excluded. after the informed consent of all participants in the study 2 ml of venous blood was collected using sterile disposable syringe and transferred to serum separator tubes. serum glutathione peroxidase levels were measured by sandwich enzyme linked immunosorbent assay technique (absorbance micro plate reader, elx800, biotek instrument, inc.usa). the collected data was entered in statistical package for social sciences (spss) version 21 for analysis. gender was expressed as percentages and frequency. numerical variables like age, glutathione peroxidase were expressed as mean and standard deviation (±sd). independent t –test was used to determine the significant difference of means between controls and patients.p values less than 0.05 were considered as significant. results the aphthous group had 45 females (64%) and 25 males (36%) while non-aphthous group had 54 females (60%) and 36 males (40%).the gender distribution of the both group i and group ii is shown in the figure no 1. mean age of the aphthous group was 28.76±9.144 and of the non-aphthous group was 30.53±6.404. the comparison of mean ages between the aphthous and non-aphthous group was not significant (p>0.05). biochemical findings: assessment of oxidative stress marker, glutathione peroxidase: with regard to oxidant/antioxidant status, mean of serum glutathione peroxidase in ras patients was significantly lower (p <o.oo) than that of healthy controls, using t-test. protein is a most potent enzyme in the defense of cells against increased reactive oxygen species. it utilizes its reduced glutathione form to convert hydrogen peroxide and lipid peroxides into 14 alcohols. gpx-1 is found in all cells, present in mitochondria, cytosole and in few cases in peroxisomes. studies have shown that it is more efficient in getting rid of intracellular hydrogen peroxide then catalase in a number of physiological situations. analysis of previous studies indicates that for the activity of gpx-1, selenium (se) which is a trace element is required which is present in the form of amino acid sec. hence as gpx-1 enzymatically detoxifies non-radical hydroperoxides, it maintains cellular oxidant/antioxidant status by two ways; a. via direct removal of hydroperoxides b. secondly through oxidation of reduced form of 15 glutathione i-e gsh regarding the insufficient studies related to this issue in pakistan, the present study was carried to evaluate the possible relation between levels of glutathione peroxidase as a biological marker for oxidative stress and recurrent aphthous stomatitis. materials and methods this case-control study was conducted in biochemistry department of islamic international medical college trust rawalpindi in collaboration with dental outpatient department of pakistan ordanance factories hospital, wah cantt from 15 march 2016 to 14 march 2017. convenient nonprobability sampling technique was used .the study population comprised of 160 subjects, 70 patients and 90 controls .convenient non-probability sampling technique was used. the institutional review board and ethical committee of riphah university (islamic international medical college) approved the study protocol. the selected patients had active lesion of aphthous ulcer and had history of recurring oral ulcer attack at least three times a year, of any age and gender. for control, healthy individuals with no history of any episode of recurrent aphthous stomatitis and any systemic disease were selected. patients were excluded if they had any history of systemic disease or any other concurrent oral lesions. patients were excluded if they were on any therapeutic regimen or supplement of iron, multivitamin, steroid or other fig 1: gender distribu�on of study popula�on jiimc 2018 vol. 13, no.3 134 serum enzymatic antioxidant in aphthous stomatitis in the present study, serum glutathione peroxidase1, an antioxidant marker showed significantly lower levels in recurrent aphthous stomatitis patients than the controls with a p value of zero. this result was in agreement with the findings of 12 arikan et al and cimen et al. in a study conducted by arikan, glutathione peroxidase levels were significantly lower in recurrent aphthous stomatitis patients as compared to controls .results of our study were in contrast to the findings by saxena who in his study found increased levels of glutathione peroxidase-1 in recurrent aphthous stomatitis 19 patients. selenium deficiency can occur with the decreased cellular immunity. by activating t-cell proliferation selenium supplement has an ability to markedly s t i m u l a t e t h e i m m u n e r e s p o n s e . immunostimulatory role of selenium is supported by the study conducted by mckenzie.et.al who demonstrated that in the presence of oxidative stress selenium supplementation regulates the cellular response by rapidly promoting and activating 14 the cellular antioxidant defense system. devasagayam et al postulated that gpx-1 deficiency 20 causes free radical accumulation. regarding the association of antioxidant and recurrent aphthous stomatitis, the disagreement amongst different studies may be due to different factors including different sample size, genetic variation of different population there is a need to carry out experimental studies to find out the causative relationship between recurrent aphthous stomatitis and impaired oxidant/antioxidant status. further prospective studies with larger sample size are also required to identify new preventive and treatment options in recurrent aphthous stomatitis patients. conclusion glutathione peroxidase levels were significantly lower in recurrent aphthous stomatitis patients as compared to controls, which suggests there is an alteration of oxidant/antioxidant status in ras patients. references 1. babaee n, hosseinkazemi h, pouramir m, baboli ok, salehi m, khadir f et al. salivary oxidant/antioxidant status and discussion recurrent aphthous stomatitis or canker sores is an inflammatory ulcerative lesion and is one of the most 1 common pathological disease of oral cavity. even though extensive research regarding the predisposition of recurrent aphthous stomatitis have been done, the definitive cause of ras remains unclear. moreover directly or indirectly different factors involved in the pathogenesis of disease results in the loss of balance between oxidant and antioxidant system of the body. the present study was undertaken to determine serum enzymatic enzymatic antioxidant levels in patients with recurrent aphthous stomatitis and healthy controls. loss of balance among oxidant species and antioxidants causes variety of inflammatory oral diseases that varies from simple infections to lethal cancers. recurrent aphthous stomatitis is also a sign of this imbalance. in several studies a possible relationship between free radical metabolism and 16 inflammatory reaction have been demonstrated. 17 lih-brody et al. has found that in mucosa of inflammatory bowel disease patients there is an imbalance between oxidant/antioxidant statuses. 15 also a study conducted by kokcam and naziroglu. on psoriasis patients demonstrated a possible role of increased lipid peroxidation oxidative stress increases by the cellular damaging cytotoxic effects of reactive oxygen species. nowadays in the maintenance of health and prevention from diseases, functional role of antioxidants has received huge attention. glutathione peroxidase -1 is the chief antioxidant in getting rid of hydrogen peroxide by utilizing reduced form of glutathione. elimination of excessive hydrogen peroxide by gpx-1 is directly related to utilization of reduced form of glutathione resulting in its decreased levels. so in recurrent aphthous stomatitis patients there is a decrease in serum levels of gpx-1. table i: enzyma�c an�oxidant levels of recurrent aphthous stoma��s pa�ents and controls jiimc 2018 vol. 13, no.3 135 serum enzymatic antioxidant in aphthous stomatitis jiimc 2018 vol. 13, no.3 a. treatment of recurrent aphthous stomatitis. a literature review. journal of clinical and experimental dentistry. 2014 (2):e168 12. .arikan s, durusoy c, akalin n, haberal a, seckin d. oxidant/antioxidant status in recurrent aphthous stomatitis. oral diseases. 2009; 15 (7):512-5. 13. najafi s, tonkaboni a, mohammadzadeh m. assessment of relation between antioxidants level and clinical manifestation in recurrent aphtous stomatitis. journal of craniomaxillofacial research. 2015;3(1):157-60. 14. forgione ma, weiss n, heydrick s, cap a, klings es, bierl c et al .cellular glutathione peroxidase deficiency and endothelial dysfunction. american journal of physiologyheart and circulatory physiology. 2002 ;51(4):h1255 15. lubos e, loscalzo j, handy de. glutathione peroxidase-1 in health and disease: from molecular mechanisms to therapeutic opportunities. antioxidants & redox signaling. 2011; 15(7):1957-97. 16. avci e, akarslan zz, erten h, coskun-cevher s. oxidative stress and cellular immunity in patients with recurrent aphthous ulcers. brazilian journal of medical and biological research. 2014; 47(5):355-60. 17. lih-brody l, powell sr, collier kp, reddy gm, cerchia r, kahn e et al . increased oxidative stress and decreased antioxidant defenses in mucosa of inflammatory bowel disease. digestive diseases and sciences. 1996; 41(10):2078-86. 18. kökçam i̇, nazıroğlu m. antioxidants and lipid peroxidation status in the blood of patients with psoriasis. clinicachimica acta. 1999; 289(1):23-31. 19. saxena s. assessment of plasma and salivary antioxidant status in patients with recurrent aphthous stomatitis. rsbo (online). 2011 (3):261-5. 20. devasagayam tp, tilak jc, boloor kk, sane ks, ghaskadbi ss, lele rd. free radicals and antioxidants in human health: current status and future prospects. japi. 2004; 52(10):794804. hematological parameters in patients with recurrent aphthous stomatitis. caspian journal of internal medicine. 2016; 7(1):13. 2. samet n, laurent c, susarla sm, samet-rubinsteen n. the effect of bee propolis on recurrent aphthous stomatitis: a pilot study. clinical oral investigations. 2007; 11(2):143-7. 3. azizi a, shahsiah s, ahmadi m. serum vitamin a level in patients with recurrent aphthous stomatitis compared with healthy individuals. journal of islamic dental association of iran (jidai). 2012; 24(4):4. 4. shashy rg, ridley mb. aphthous ulcers: a difficult clinical entity. american journal of otolaryngology. 2000; 21(6):389-93. 5. preeti l, magesh kt, rajkumar k, karthik r. recurrent aphthous stomatitis. journal of oral and maxillofacial pathology. 2011 ;15(3):252. 6. chavan m, jain h, diwan n, khedkar s, shete a, durkar s et al.. recurrent aphthous stomatitis: a review. journal of oral pathology & medicine. 2012; 41(8):577-83. 7. saral y, coskun bk, ozturk p, karatas f, ayar a. assessment of salivary and serum antioxidant vitamins and lipid peroxidation in patients with recurrent aphthous ulceration. the tohoku journal of experimental medicine. 2005; 206(4):305-12. 8. cağlayan f, miloglu ö, altun o, erel ö, yılmaz ab. oxidative stress and myeloperoxidase levels in saliva of patients with recurrent aphthous stomatitis. oral diseases. 2008; 14(8):700-4. 9. bilal n, fatihkarakus m, varkal md, boztepe of, bilal b. an assessment of the levels of anxiety and depression in patients with recurrent aphthous stomatitis. arch otolaryngol rhinol. 2015; 2 (1): 5001-07. 10. koybasi s, parlak ah, serin e, yilmaz f, serin d. recurrent aphthous stomatitis: investigation of possible etiologic factors. american journal of otolaryngology. 2006; 27(4):229-32. 11. belenguer-guallar i, jiménez-soriano y, claramunt-lozano 136 serum enzymatic antioxidant in aphthous stomatitis jiimc march 2016.cdr original article abstract objective: the objective of this study was to study the demographics of intestinal parasitic infections and find out the relative frequency of different intestinal parasites in clinical samples received for routine stool examination from symptomatic patients with diarrhea and/or dysentery. study design: a retrospective cross sectional study. place and duration of study: the study was conducted at dow diagnostics research and reference laboratory, karachi, pakistan from january 2008 to december 2013 of stool analysis from the patients with symptoms of diarrhea and/or dysentery. materials and methods: microscopic stool examination was performed using direct samples by wet mount under low as well as high power bright field magnification. tabulations were performed using microsoft excel while chi-square test was applied using open-epi software. results: among the 1815 positive cases infected with single parasites, entamoebahistolytica was the most commonly found parasite, followed by giardia labmlia, blastocystishominis, ascarislumbricoides and hymenolepis nana. among these patients, 1081 (59.6%) were males and 734 (40.4%) were females. chi-square test was applied using open-episoftware, which showed significant differences among males and females (p=0.03). conclusion: protozoal intestinal parasites entamoebahistolytica and giardia lambliaare the commonest among all age groups followed by the helminths ascaris lmbricoides and hymenolepis nana. other notable parasites include entamoeba coli and taenia species. key words: intestinal parasites, parasitic infections, entamoeba histolytica, giardia lamblia. 5 in children, physical and mental health problems 6 and diarrheal diseases, which are a major cause of death in pakistan india, bangladesh and other 7 developing countries. previous population based reports from pakistan show giardia lamblia to be the most common 8 parasite in karachi followed by ascaris lumbricoides 9 and entamoeba histolytica , though the reports from bannu and peshawar (cities situated in northern pakistan with a comparatively cold climate) showed ascaristo be the commonest parasite infecting the school children followed by enterobiusvermicularis 1 0 , 1 1 a n d h y m e n o l e p i s n a n a . r e p o r t s f r o m muzaffarabad, a city located further north showed giardia to be the commonest followed by e. 12 histolytica. karachi has a semi-arid warm and humid climate and it is home to a number of infectious parasites. most common parasites reported up to date are entamoeba species, ascaris, h . n a n a , g i a r d i a , t. t r i c h u r a a n d ta e n i a 8,9,13 species. however, the present studies are either 9 old or do not cover the age groups other than 8,13 children, which is also affected by the parasitic infections and add a considerable bulk to the disease introduction parasitic infections are a major public health issue in developing world, which affects around 3.5 billion 1 2 peopledirectly and indirectly. they are mostly endemic and specific parasites are prevalent in particular areas, therefore disease pattern is different in different geographical settings. these diseases are associated with climatic conditions, poor sanitation, unsafe drinking water and lack of personal hygiene in tropical and sub-tropical 1,3 countries. they are a major cause of morbidity and mortality and are responsible for chronic diseases 4 such as iron deficiency anemia, growth retardation demographics of intestinal parasitic infections in karachi: an insight from positive stool samples 1 2 3 3 4 5 muhammad yahya noori , ghazala khan , ishrat abid , samina baig , sambreen zamir , shaheen sharafat parasitic intestinal infections in karachijiimc 2016 vol. 11, no.1 correspondence: dr. muhammad yahya noori assistant professor, pathology dow international medical college dow university of health sciences, karachi email: yahyanoori@gmail.com 1,3,5,6 4 department of pathology/microbiology dow international medical college dow university of health sciences, karachi 2 faculty of pharmacy university of karachi, karachi funding source: nil ; conflict of interest: nil received: november 03, 2015; accepted: february 16, 2016 20 burden. therefore, a retrospective study was performed to assess the relative disease burden of different parasites across different demographic groups, so that a snapshot can be generated regarding relative frequency of different parasites in symptomatic patients. to study the relative frequency of these parasites in samples from patients coming with diarrhea and/or dysentery results from laboratory records were analyzed for the period of 2008-2013 and were stratified according to age and gender. materials and methods the retrospective cross-sectional study based on the laboratory records was carried out in the dow diagnostic research and reference laboratory of health sciences karachi from january 2008 to december 2013. all positive stool samples received for routine stool examinations were included in the study, while those which were negative for parasites, ova or cysts were excluded. a total of 1873 positive samples were included in data analysis. stool samples were collected in sterilized leak proof containers from patients after detailed informed consent. departmental approval was taken for the study,diagnostic data were de-identified and tabulated without patients' particulars. each sample was initially examined physically for consistency, color, odor, blood and mucus. slides were then prepared directly for wet mount by placing a drop of fresh physiological saline at one end of the clean side, while a drop of iodine was placed at the other end. stool samples were mixed with wooden stick and a small amount was then taken for saline and iodine and covered with cover slip. these were microscopically examined under low (10× = 100 times magnification) and high (40× = 400 times magnification) power bright field for worms, ova, larvae, trophozoites, cyst, erythrocytes, leukocytes and any intestinal mucosal sloughing. diagnosis was made by observing the differentiating morphological features of protozoal cysts and trophozoites and parasitic ova and larvae. for entamoeba histolytica, cyts were identified on the basis of presence of four or lesser number of nuclei, while trophozoites were identified as having ingested rbcs and differentiated from entamoeba coli on the basis of more than five nuclei in cysts and trophozoites without rbcs. iodamoeba butschlii was identified on the basis of cellular morphology and presence of a single nucleus in iodine preparation. blastocystis hominis was identified on the basis of cyst-like forms having a large central body resembling like a large vacuole surrounded by small, multiple nuclei. ova of hymenolepis nana were identified on the basis of appearance as they are round to oval with two distinct walls and having 4-8 hair-like processes at each pole on the inner aspect along with three pairs of hookletswithin the inner wall. ova of ascaris were identified the basis of yellow brown color with thick shells having an albuminous outer coat and thick transparent wall under the shell. tabulations were performed using microsoft 14 excel while chi-square test was applied using open15 epi software. table i: gender-wise propor�on of infec�ons in pa�ents detected using stool examina�on table ii: gender-wise propor�on of infec�ons in pa�ents using stool examina�on stra�fied by age parasitic intestinal infections in karachijiimc 2016 vol. 11, no.1 21 results among the 1815 positive cases infected with single parasites, 1081 (59.6%) were males and 734 (40.4%) were females. e. histolytica was the most commonly found parasite in these patients, followed by g. labmlia, b.hominis, a. lumbricoidesand h. nana. a chi-square test was appliedusing open-episoftware, which showed significant differences among the two groups (p=0.03). data were stratified according to age groups and gender. it was observed that most commonly affected group was adult males, and altogether 1081 males were found to be mono-infected, most commonly with e. histolytica(n=400) followed by g. lamblia(n=369) and b.hominis (n=120). similar p atte r n wa s o b s e r ve d i n fe m a l e s a n d e . histolytica(n=321) g. lamblia(n=211) and b. hominis (n=95) were found to be the most common parasites infecting adult females. however in patients, who were three years of age, g. lamblia was found to be the most common parasite, in both males (n=47) and females (n=39). in children, the most common parasites were again giardia and e. histolytica, though trends were different in males and females as in males giardia(n=157) infection ra te wa s d e te c te d to b e h i g h e r t h a n e . histolytica(n=114), though in females both infections were found in equal frequency (n=88). some of the patients were found to be infected with two parasites (n=52), while very few were triply infected (n=6). organisms found in these cases were mostly g.iardialamblia, e. histolytica, h. nana, e. coli, i. butschlii and a. lumbricoides. discussion the study found a number of parasitic agents more common in the clinical samples received in karachi. in our results protozoans like e. histolytica and g. lamblia are among the commonest finding in the local population, with a higher proportion in males as compared to females. though these protozoal parasites are present in all ages, their high prevalence among children is particularly of concern as amoebiasis can lead to liver abscess, resulting in severe morbidity and mortality. these two parasites have also been reported to be among the commonest in other studies performed in karachi, which shows that the pattern has not changed over 8,13,16 the years. though the two studies performed earlier found giardia to be more common than 8,9 entamoeba the difference in our findings could simply be explained by the fact that these two studies were population based studies, while our study was mainly performed upon clinical samples. since both these organisms are spread by contaminated food and water. it is unfortunate that the sanitation and water supply conditions have not improved over the years and is the major contributing factor towards parasitic spread. the lack of hygienic living, inadequate health literacy and p o o r h e a l t h re l a t e d p ra c t i c e s a m o n g t h e uneducated and low-socioeconomic classes could also be considered important contributing factors towards this situation. an improved water surveillance system and health advocacy activities among the affected population may help in reduction of the burden of these diseases. giardia infections should be of particular concern in infants and toddlers because they may be related to 17 malnutrition resulting in growth problems. these findings are somewhat slightly different from the northern parts of the country as reports published from bannu and peshawar showed ascaristo be the commonest parasite infecting the school children followed by e. vermicularis and h. 10,11 nana which may be attributed to different climatic conditions or other unknown factors. presence of helminths such as a. lumbricoides and h. nana must be considered important as faecooral transmission of cysts and ova is common and untreated cases in the population may keep on 3 passing the pathogens to those at risk. since, these parasites along with others have been related to malnutrition in children, their testing and e ra d i c a t i o n s h o u l d b e a p r i o r i t y fo r t h e 18,19 community. since our study is based on clinical samples, it has its limitations and it may not reflect the exact picture in the community, however it clearly shows the type of intestinal parasites present in the population and highlights the need to develop a strategy to deal with the issues associated with them. a detailed community based survey is necessary to get the exact prevalence measures of intestinal parasitic infection in the local population. parasitic intestinal infections in karachijiimc 2016 vol. 11, no.1 22 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al. use of multiplex real-time pcr for detection of common diarrhea causing protozoan parasites in egypt. parasitology research. 2013; 112: 595-601. 7. liu l, johnson hl, cousens s, perin j, scott s, lawn je, et al. global, regional, and national causes of child mortality: an updated systematic analysis for 2010 with time trends since 2000. the lancet. 2012; 379: 2151-61. 8. mehraj v, hatcher j, akhtar s, rafique g, beg ma. prevalence and factors associated with intestinal parasitic infection among children in an urban slum of karachi. plos one. 2008; 3: e3680. 9. siddiqui mi, bilqees fm, iliyas m, perveen s. prevalence of parasitic infections in a rural area of karachi, pakistan. prevalence. 2002; 52: 315-20. 10. khan ms, jehan s, akram m, rabnwaz, zaib m, lathif z, et al. prevalence of intestinal protozoan and worm infestation in primary school going children of 5-10 years of age in district bannu. annals of pakistan institute of medical sciences. 2012; 8: 243-8. 11. ullah i, sarwar g, aziz s, khan mh. intestinal worm infestation in primary school children in rural peshawar. gomal journal of medical sciences. 2009; 7: 132-6. 12. chaudhry zh, afzal m, malik ma. epidemiological factors affecting prevalence of intestinal parasites in children of muzaffarabad district. pakistan journal of zoology. 2004; 36: 267-71. 13. mumtaz s, siddiqui h, ashfaq t. frequency and risk factors for intestinal parasitic infection in children under five years age at a tertiary care hospital in karachi. j pak med assoc.2009; 59: 216-9. 14. microsoft. microsoft excel. washington: microsoft; 2010. 15. dean a, sullivan k, soe m. openepi: open source epidemiologic statistics for public health 2015 [updated 2015 5/4/2015; cited 2015]; available from: www.openepi.com 16. ahsan ul wadood ab, ur rhman a, qasim kf. frequency of intestinal parasite infestation in children hospital quetta. pakistan j med res. 2005; 44. 17. al-mekhlafi msh, azlin m, nor aini u, shaik a, saiah a, fatmah ms, et al. giardiasis as a predictor of childhood malnutrition in orang asli children in malaysia. transactions of the royal society of tropical medicine and hygiene. 2005; 99: 686-91. 18. mbuh jv, nembu ne. malnutrition and intestinal helminth infections in schoolchildren from dibanda, cameroon. journal of helminthology. 2013; 87: 4651. 19. papier k, williams gm, luceres catubig r, ahmed f, olveda rm, mcmanus dp, et al. childhood malnutrition and parasitic helminth interactions. clinical infectious diseases. 2014; 59: 234-43. parasitic intestinal infections in karachijiimc 2016 vol. 11, no.1 23 original�article abstract objective: to identify the leadership styles of medical educationists during their journey of bringing the curricular reform at their respective institutions”. study design: this was a cross-sectional descriptive study that focused on self-perceived leadership style. place and duration of study: this study was conducted in riphah international islamabad from february to july 2019. materials and methods: multifactor leadership questionnaire consisting of 45 items was used, having a 5-point likert scale to see the predominant leadership style of the medical educationists involved in curricular reforms. item 1-36 corresponds to the predominant leadership style.37-45 pertains to outcomes of leadership. data was collected from 14 participants who were willing to participate in the study. results were entered on an excel sheet and mean scores were calculated. results: the predominant leadership style of medical educationists came out to be transformative leadership with a mean score of 3.24. leadership style mostly used was collaborative and transformative and transactional leadership style was also adopted. conclusion: medical educationists faced many challenges during their journey of educational reform. the predominant leadership style identified is transformational. other leadership traits identified in change leaders are, transactional leadership which monitors deviations and mistakes with a mean score of 2.81, and passive avoidant behaviors are practiced the least with mean frequencies less than 1. as leaders, they must be prepared for the uncertainty and unexpected events and adapt themselves to the changing environment. key words: change, curricular reforms, educational leaders, leadership styles, transformational leadership. 2 been noted and accepted to some extent. medical educationists are the middle leaders which 3 make change happen. leadership has been described as an important factor in sustaining 4 curriculum change. the importance of strong leadership which can rally the faculty to common 5 objectives has been highlighted. change leaders need to navigate the change at three levels: self, others, and organizations. it is the leader's job to create readiness for change in an organization. leaders' perspectives on the process of curriculum change were conducted by velthius in the medical schools of the netherlands, who pointed out three main issues faced by the leaders: dealing with stakeholders, resistance, and steering of the change 6 process. it is proven that leading change takes will, 7 understanding, and involvement. successfully leading curriculum reforms requires ownership of 8,9 the change process along with motivation. although, change in medical education is an ongoing process globally, but it will not last unless leadership and the change process are understood. introduction in pakistan, most medical schools are still following discipline-based, teacher-centered curricula and are in silos from the rest of the world. only a minority have included new pedagogical approaches and 1 reforms in the curriculum. the need for change has leadership styles of change leaders steering curriculum reforms in pakistan 1 2 3 4 5 6 ayesha naveed , sana javed , sakina sadiq , amer siddiq , irum rehman , rizwana kamran correspondence: dr. ayesha naveed assistant professor department of health professional education cmh lahore medical and dental college, lahore e-mail: drayeshanavid@gmail.com 1,6 department of health professions education cmh lahore medical college and institute of dentistry, lahore 2 department of family medicine military hospital, rawalpindi 3 department of dermatology army medical college, rawalpindi 4 department of pathology pakistan kidney and liver transplant and research centre, lahore 5 department of physiology margala college of dentistry, islamabad received: december 20, 2021; revised: june 04, 2022 accepted: june 06, 2022 leadership styles of change leadersjiimc 2022 vol. 17, no.2 124 in past, no such studies were carried out in which the leadership style of the leaders in health professions education steering the curriculum reforms were identified. exploring the perspectives of medical educationists as a change agent would expand and enrich our understanding of the complexities associated with curriculum change. bringing a change is not an easy job it requires a strong leader who is aware of challenges and has the vision to overcome those by navigating their leadership styles. kurt lewin is known as the founder of 'change management' with his three phases for the change 10 process: unfreeze, change, and refreeze. though emails and responses were collected. permission to administer the campaign was obtained by mind garden. multi leadership questionnaire is a pre validated questionnaire, the construct validity of which has been established through confirmatory 11 factor analysis. data was received from online survey and the results were entered on excel sheet and mean scores were taken. the predominant leadership style of the participant was determined. results there were 14 participants out of which 7 were males and 7 were females, all of them were senior faculty members from their institutes. all of them had back grounds from mbbs or bds and all had post graduate qualifications in health professions education. the predominant leadership styles of these change leaders are displayed as follows: fig. 1: conceptual framework materials and methods a cross sectional descriptive study was carried out at riphah international university islamabad from f e b r u a r y 2 0 1 9 t o j u l y 2 0 1 9 . p u r p o s i v e (homogenous) sampling technique was used to gather the data which included 14 medical educationists involved in curricular reforms from four different universities which includes shifa college of medicine, islamic international medical college, fauji foundation university & khyber medical university. ethical approval of the study was obtained from ethics review committee, islamic international medical college. informed consent was taken from the participants. permission to reproduce the multi leadership questionnaire was taken from mind garden. key persons involved in implementation of reforms in medical schools with a background in medical education. those who are not willing to participate in the study. data was collected on multifactor leadership questionnaire which was sent to the participants table i: predominant leadership style of the respondents leadership styles of change leadersjiimc 2022 vol. 17, no.2 125 p a r t i c i p a n t s m e a n s c o r e s h o w e d t h a t transformational leadership style was rated as the highest (3.24), followed by transactional (3.07). idealized influence (behavior) with integrity was the dominant style adopted by medical educationists which falls under transformational leadership. comparison of males and females showed 'individualized influence (behavior)' (mean =3.3) the most dominant leadership style among males, while 'encourages others' inspirational motivation (mean =3.34) was the dominant style among females. trust, integrity, and coaching styles are considered the most active and effective. the passive avoidant leadership styles have been regarded as the most ineffective form of leadership. falling in between the two extremes of effective / ineffective and active /passive is transactional leadership styles which is reward based. discussion the purpose of this study was to explore the leadership styles of medical educationists and challenges faced during curricular reforms leadership style of successful educational leaders can help future change agents in identifying the successful leadership practices and improve their 12 leadership skills. the predominant leadership style of medical educationists came out to be transformative leadership. it is the leadership style as perceived by the participants now which depends on the circumstances, although it came out to be transformative leadership style, but it may not be the only style they used during their journey of reform. empirical evidence shows that transformative leadership is regarded as the most effective style in 13,14 bringing change in an institute. yukl argued lack of evidence of situational and contextual factors on the 1 5 effectiveness of transformative leadership. furthermore, hamstra, yperen, wisse, and sassenberg (2011) studied transformational leadership and follower commitment and concluded 16 that this area requires further exploration. during the planning phase when the idea is still in the initial stage, the faculty has to be convinced and motivated to adopt a new strategy, transformative leadership is regarded as the most effective. there is scarce evidence available in literature regarding role of gender in transformational leadership. in our study males and females did show slight differences. males showed higher scores for 'individualized influence (behavior)' (mean =3.3) while females scores showed an inclination towards 'encourages others' i n s p i r a t i o n a l m o t i v a t i o n ( m e a n = 3 . 3 4 ) . individualized influence is a behavior characteristic which shows high consideration for its followers and is dependent on two-way communication. moreover, different leadership sub-strategies that were adopted by female and male participants were identified. female participants demonstrated collaborative techniques in contrast more male members opted for harsher measures when the need arose. most of the strategies adopted were collaborative so broadly they also fall under leadership styles of change leadersjiimc 2022 vol. 17, no.2 126 transformative styles. according to bass female leaders demonstrate transformational behaviors as compared to males but leadership styles depend not only on personal traits, personal beliefs and values but also on the environment and surrounding 17, 18 all these factors help shape leadership styles. organizational cultures also encourage certain leadership style and discourage others. participants in the study pointed out that communication skills, collaboration were the most important assets in the journey of curricular change. limitations of study is leadership measure. multi leadership questionnaire self-form was used which describes the leadership style of the individual as perceived by themselves. another limitation of this study is that this was the leadership styles of the participants at present. we did not have the leadership styles of any participants when they were in the early phases of their journey. since we first identified the institutes where successful reforms in medical education had taken place the sample size of medical educational was restricted. future work: it is recommended that this could have been more interesting to measure the leadership style of a large sample of medical education leaders. conclusion medical educationists leading the curricular reforms faced many ups and downs during their journey of educational reforms. curricular reforms are challenging and not a single leadership style or strategy can be labeled as successful for which they have to navigate their leadership styles according to the needs. the predominant leadership style identified is transformational. other leadership traits identified in change leaders are, transactional leadership (rewards achievement) which monitors deviations and mistakes (management by exception active) with a mean score of 2.81, and passive avoidant behaviors are practiced the least with mean frequencies less than 1. references 1. wijnen-meijer m, van den broek s, koens f, ten cate o. vertical integration in medical education: the broader perspective. bmc med. educ. 2020 dec;20(1):1-5. 2. baqir sm, mustansir f. online medical education and examinations during covid-19: perspectives of a teaching associate. j coll physicians surg pak. 2021;30(1):s16. 3. so hy, chen pp, wong gk, chan tt. simulation in medical education. j r coll physicians edinb. 2019 mar 1;49(1):52-7. 4. malik rs. educational challenges in 21st century and sustainable development. j. educ. res. sustain. dev. 2018 may;2(1):9-20. 5. velthuis f, varpio l, helmich e, dekker h, jaarsma ad. navigating the complexities of undergraduate medical curriculum change: change leaders' perspectives. j. assoc. am. med. coll. 2018 oct 1;93(10):1503-10. 6. tintoré m, cunha rs, cabral i, alves jj. a scoping review of problems and challenges faced by school leaders (2003–2019). educ. manag. adm. 2022 jul;50(4):536-73. 7. shen j, wu h, reeves p, zheng y, ryan l, anderson d. the association between teacher leadership and student achievement: a meta-analysis. educ. res. rev. 2020 nov 1;31:100357. 8. a h m a d i s . eva l u a t i n g c u r r i c u l u m a c c o rd i n g t o competencies from the perspective of technology engineering's students of shiraz industrial university. j. curric. stud. 2019 feb 20;8(2):224-44. 9. dickey cc. leading change during changing times: simple leadership lessons to guide academic leaders. acad psychiatry. 2016 jun;40(3):415-7. 10. cummings s, bridgman t, brown kg. unfreezing change as three steps: rethinking kurt lewin's legacy for change management. hum relat. 2016 jan;69(1):33-60. 11. avolio bj, bass bm, jung di. re-examining the components of transformational and transactional leadership using the multifactor leadership. j occup organ psychol. 1999 dec;72(4):441-62. 12. batista-foguet jm, esteve m, van witteloostuijn a. measuring leadership an assessment of the multifactor l e a d e rs h i p q u e s t i o n n a i re . p l o s o n e . 2 0 2 1 j u l 22;16(7):e0254329. 13. chen ty. medical leadership: an important and required competency for medical students. tzu chi med. j. 2018 apr;30(2):66. 14. mansaray he. the role of leadership style in organisational change management: a literature review. j. hum. resour. manag. 2019 jun 13;7(1):18-31. 15. dahleez k, aboramadan m. servant leadership and job satisfaction in higher education: the mediating roles of organizational justice and organizational trust. int. j. leadersh. educ. 2022 apr 10:1-22. 16. hidayat t, fahmy r, sari dk, mergeresa f, fernando y. covid-19 outbreak effects on leadership, job satisfaction and turnover intention: a mediating model of indonesian banking sector. 2021 mar 5;10:113-28. j. ind. eng. manag. 17. alghamdi mg, topp r, alyami ms. the effect of gender on transformational leadership and job satisfaction among saudi nurses. j. adv. nurs. 2018 jan;74(1):119-27. 18. conradty c, bogner fx. from stem to steam: cracking the code? how creativity & motivation interacts with inquirybased learning. creat. res. j. 2019 jul 3;31(3):284-95. leadership styles of change leadersjiimc 2022 vol. 17, no.2 127 conflict of interest authors declared no conflicts of interest. grant support and financial disclosure authors have declared no specific grant for this research from any funding agency in public, commercial or nonprofit sector. data sharing statment the data that support the findings of this study are available from the corresponding author upon request. this is an open access article distributed under the terms of the creative commons attributionnoncommercial 2.0 generic license. leadership styles of change leadersjiimc 2022 vol. 17, no.2 128 original�article abstract objective: to compare the levels of serum cystatin and creatinine as the markers of early stage of diabetic nephropathy. study design: case control study. place and duration of study: the study was conducted at railway hospital, rawalpindi for a period of one year th th from march 15 , 2016 to march 16 , 2017. materials and methods: a total of 77 diabetics and 77 healthy controls were selected. these included adults above 40 years of age. the levels of serum cystatin c and creatinine were measured using imagin specific protein analyzer. both tests were done by applying standardized laboratory protocols. the study outcome was determined in terms of detection of diabetic nephropathy which was finalized on the basis of albuminuria status derived as three categories; normoalbuminuric, microalbuminuria and macroalbuminuria. results: male cases were more than females (58.4% vs 41.6%), and were equally distributed in patients and control groups. the levels of cystatin c (4.7 + 3.9 mg/l), and creatinine (1.0 + 0.13 mg/dl) were found significantly high in the macroalbuminuria group as compared to controls and normoalbuminuric group (pvalue <0.001). serum cystatin c was significantly raised in microalbuminurics as compared to serum creatinine proving its worth for detecting early stage diabetic nephropathy (p-value <0.001). conclusion: serum cystatin c is a better predictive marker of diabetic nephropathy than serum creatinine. key words: diabetic nephropathy, serum cystatin c, serum creatinine. diabetic nephropathy is one of the most common complications of diabetes. diabetic nephropathy by definition is macroalbuminuria (albumin excretion rate > 300 mg /24 hours) and deteriorating renal function is a known fact in diabetics. previous reports confirm that approximately one third to one half of 4 diabetic patients develop renal complications. albuminuria is a significant prognostic factor for risk stratification of diabetic nephropathy and monitoring of its progression. there was a belief that microalbuminuria is predictive of future overt diabetic nephropathy in 80% cases, however, on the contrary, it has been proposed that around 30% of m ic ro a lb u m in u ria ca s es p ro gres s to overt 4,5 nephropathy after 10 years follow-up. presently, the phenomena of normoalbuminuric diabetic nephropathy is well established and portrays that diabetic patients may present with a decreased gfr without progression from normal to 4 microalbuminuria. gold standard method for determining gfr in research settings are inulin and cr –edta plasma clearance. these techniques are time consuming, laborious and requiring expertise making them unfit for clinical practice. hence the introduction type 2 diabetes is on a continuous rise worldwide owing to a steady increase in obese and aging population. the global prevalence of diabetes was estimated at 171 million (2.8%) in the year 2000 which is expected to reach 366 million 4.4% figure by 1 the year 2030. the current prevalence of diabetes in pakistan is 2 around 10.0%. as per who estimates, pakistan is th ranked 7 largest country suffering from diabetes mellitus and it is expected that by 2030 this rank will th climb the ladder to 4 position which is an alarming 3 statistics and situation. cystatin c versus creatinine as early stage diabetic nephropathy marker 1 2 3 4 atteaya zaman , amena rahim , muhammad afzal , abdul khaliq naveed correspondence: dr. atteaya zaman assistant professor, biochemistry federal medical and dental college, islamabad e-mail: attiadr@hotmail.com 1 department of biochemistry federal medical and dental college, islamabad 2,3,4 department of biochemistry islamic international medical college riphah international university, islamabad funding source: nil; conflict of interest: nil received: jan 18, 2018; revised: may 18, 2018 accepted: may 24, 2018 cystatin c versus creatinine in diabetic nephropathyjiimc 2018 vol. 13, no.2 71 used index for gfr is serum creatinine (mg/dl). moreover, its sensitivity is poor in early renal damage and by the time its levels are detectable, significant 5 decrease in gfr has already occurred. putting these facts together, there is a ground for identification of alternative biomarkers to predict diabetic nephropathy early so that timely management and maintenance can be exercised. cystatin c a 13.3k da plasma protein is relatively new marker in the prediction of renal impairment and it correlates positively with other renal tests like gfr. serum creatinine also a proven marker of nephropathy is relatively weaker test and easily changes by different maneuvers and circumstances 5 like a person's muscle mass. cystatin c has been found constant and unaffected and an alternative with high sensitivity for diabetic nephropathy using a 5,6 cut off of >60 ml of gfr. the focus of research by endocrinologists and other investigators is to find out new and better biomarkers for the diagnosis of early diabetic nephropathy. the aim of the study was to compare cystatin c and creatinine in the screening of diabetic patients on risk of early stage diabetic nephropathy. materials and methods a case control study was conducted at the railway th hospital, rawalpindi from march 15 , 2016 to march th 16 , 2017 for one year duration. a measured study sample of 77 diagnosed cases of diabetes were enrolled along with seventy seven normal controls. convenient sampling technique was utilized. the study was conducted after obtaining permission from ethical review committee. a written informed consent was taken from all the patients. demographic data was collected via questionnaires. seventy seven diabetes cases and seventy seven non-diabetics of both genders and adults age (above 18 years) were included in the study. for study purpose, albuminuria was divided into t h r e e s t a n d a r d o p e r a t i o n a l g r o u p s ; i ) normoalbuminuria with acr< 30mg /day, ii) microalbuminuria with acr 30 to < 300mg/day and iii) macroalbuminuria with acr > 300mg/day. blood was drawn from peripheral veins, transferred to edta tube, gently mixed and made to stand upright. the blood samples were centrifuged at 2200 rpm for 10 minutes. the separated serum was o stored at -20 c till completion of sample collection. the urine samples were collected in the jars provided to the patients and centrifuged at 1000 rpm for 10 o mins, these were also stored at -20 c till analysis. the estimation of cystatin c levels (mg/l) was carried out on imagin specific protein analyzer for quantitative determination of human cystatin c in serum. similarly, the estimation of urinary albumin levels were carried out on imagin specific protein analyzer for quantitative determination of human m i c r o a l b u m i n [ m a l b ] i n u r i n e b y 4,5 immunoturbidimetry. data was analyzed using spss 20.0 version. first, descriptive statistics was applied to measure frequency and percentages for categorical variables like gender, and mean and standard deviations for continuous variables. secondly, using student's t-test the means and standard deviation levels of serum c y sta t i n c , s e r u m c re a t i n i n e a n d c l i n i c a l measurements of blood pressure were compared among patients and controls. categories of albuminuria were created as per operational definitions. the mean levels of serum cystatin c and creatinine were compared among these categories using t-test. for further analysis the renal status glomerular filtration (gfr) rate was categorized as 5,7 gfr < 60, gfr 60-89.9 and gfr > 90. a p-value of <0.05 was considered significant difference. parametric tests were applied as majority of the continuous numerical data was found equally distributed and dispersed. results in 154 study subjects the mean age was found similar in controls (55.7 years) and patients (56.5 years). male gender was predominant and found equally distributed in patients and controls. (table i). the urinary albumin and creatinine was analyzed and it was found that there were 15 (19.4%) normoalbuminurics, 53 (68.8%) microalbuminuric and 9 (11.6%) cases with macroalbuminuria (figure 1). there was a gradual increasing trend of age and urinary albumin in the study subjects. the mean age of macroalbuminuric (59.3 + 5.5 years) cases was significantly higher than controls (55.5 + 5.1) and rest of albumin categories i.e. normoalbuminuric (56.2 + 5.4) and microalbuminurics (56.5 + 5.4). male gender was predominant in the study and also in all albumin categories and controls, however, they were not jiimc 2018 vol. 13, no.2 cystatin c versus creatinine in diabetic nephropathy 72 significantly different among categories (p-value, 0.58). (table ii). serum creatinine, serum cystatin c and other laboratory parameters were compared between albuminuria categories as well as controls. the levels of urine albumin (332.7 + 30.1), creatinine (1.0 + 0.13 mg/dl) and cystatin c (4.7 + 3.9 mg/l) were found significantly high in the macroalbuminuria compared to controls and normoalbuminuric groups (p-value <0.001). moreover, cystatin c was also found significantly associated with microalbuminuria than serum creatinine (2.6 + 2.2 versus 0.94 + 0.13 respectively). gfr levels were significantly low in the micro (76.9 + 15.1) and macroalbuminuria (74.0 + 7.0) groups compared to normoalbuminuric and controls. moreover, blood pressure was found significantly higher in the patients compared to controls (p-value <0.001). (table iii). a selective analysis of cystatin c and serum creatinine levels was done according to gfr categories. the mean cystatin c was significantly high (1.7 + 1.2) in patients with moderate to high kidney damage (gfr < 60), and mean cystatin c was also very high (2.6 + 2.4) in patients with mild kidney damage (gfr 60-89). serum creatinine was also found significantly deranged (1.2 + 0.21) in gfr < 60 category, whereas in gfr 60-89 it was found border line deranged (0.94 + 0.11). (table iv). table i: demographic, clinical and pathological characteris�cs of pa�ents and controls fig 1: distribu�on of albuminuria in the study pa�ents table ii: associa�on of age and gender with urine albumin status of pa�ents and controls table iii: comparison of biochemical and clinical parameters between controls and albuminuria categories * p-values based on comparison of controls with individual albuminuric category table iv: rela�onship of cysta�n c and crea�nine with gfr categories jiimc 2018 vol. 13, no.2 cystatin c versus creatinine in diabetic nephropathy 73 discussion the study findings reveal that cystatin c is significantly raised than creatinine in not only m a c r o a l b u m i n u r i a b u t a l s o i n c a s e s o f microalbuminuria. microalbuminuria is most prevalent in the study, showing that two-third of patients were in the process of development of early diabetic nephropathy. our study findings of raised cystatin c in early nephropathic derangement validate many previous reports on the topic. lee bw witnessed that serum cystatin c is significantly lower in normoalbuminurics (0.83+ 0.22) than in microalbuminurics and macroalbuminurics (0.94 + 7 0.33 and 1.05 + 0.28 respectively; p < 0.001). jeon yk also witnessed a similar trend of relationship of cystatin c and diabetic nephropathy (micro and 8,9,10 macroalbuminuria). similarly in the current study the average serum creatinine and cystatin c are found high in micro and macroalbuminuric cases. most of the study patients were in the early stage of diabetic nephropathy, however, 11.6% were proven cases of diabetic nephropathy (acr > 300 mg/l). cystatin c was found significantly high in micro and macroalbumin categories. though serum creatinine was also found deranged in these cases, it is not that distinctive than cystatin c. previous literature on cystatin c suggests its s u p e r i o r i t y i n d e t e c t i n g e a r l y d i a b e t i c 9,10,11 nephropathy. as patients on the risk of diabetic n e p h ro p at hy ca n b e re cove re d a n d e a r l y deterioration of renal function can be averted. this highlights the significance of an easy and feasible 4,9,12 laboratory parameter like cystatin c. serum cystatin c has proven its role as an alternative marker for estimating gfr. moreover, the failure of creatinine to detect early decline in gfr is due to the fact that serum creatinine levels only start rising when almost 50% of renal function is lost, suggesting that gfr can change before serum creatinine 13,14 becomes abnormal. cystatin c may rise faster than creatinine after a fall in gfr and is a reliable endogenous marker for assessing renal function in 15,16 type 2 diabetic patients with renal impairment. it was found out that cystatin c and creatinine are significantly high in moderate to severe kidney damage and it is also high in mild kidney damage category (gfr 60-89). our results have time and again proven that cystatin c was a highly useful marker of kidney damage in diabetic patients. there are many advantages of the study which include; firstly, it was a comparative study comprising of diabetics and control groups, with a reasonable sample of seventy seven cases and seventy seven controls. relationship of two commonly used markers i.e. cystatin c and serum creatinine were compared according to patient's albuminuria status and then also according to gfr status. conclusion based on the findings of current study it is concluded that cystatin c is a significant predictive marker of diabetic nephropathy than serum creatinine. references 1. harjutsalo v, groop ph. epidemiology and risk factors for diabetic kidney disease. adv chronic kidney dis. 2014; 21: 260-6. 2. engelgau mm, el-saharty s, kudesia p, rajan v, rosenhouse ps, okamoto k. capitalizing on the demographic transition: tackling non communicable diseases in south asia, world bank. washington dc. 2011. website: [http://hdl.handle. net/10986/2343]. 3. akter s , rahman mm , abe sk, sultana p. prevalence of diabetes and prediabetes and their risk factors among bangladeshi adults: a nationwide. bulletin of the world health organization. 2014; 92: 204-13. 4. fiseha t. urinary biomarkers for early diabetic nephropathy in type 2 diabetic patients biomark res. 2015; 3: 16. 5. assal hs, tawfeek s, rasheed ea, el-lebedy d, thabet eh. serum cystatin c and tubular urinary enzymes as biomarkers of renal dysfunction in type 2 diabetes mellitus. clin med insights endocrinol diabetes. 2013; 6: 7–13. 6. tesch g, amur s, schousboe jt, siegel jn, lesko lj, bai jp. successes achieved and challenges ahead in translating biomarkers into clinical applications. aaps j. 2010; 12: 24353. 7. lee bw, ihm sh, choi mg, yoo hj. the comparison of cystatin c and creatinine as an accurate serum marker in the prediction of type 2 diabetic nephropathy. diabetes research and clinical practice. 2007; 78: 428–34. 8. jeon yk, kim mr, huh je. cystatin c as an early biomarker of nephropathy in patients with type 2 diabetes. j korean med sci. 2011; 26: 258-63. jiimc 2018 vol. 13, no.2 cystatin c versus creatinine in diabetic nephropathy 74 9. kitabchi ae, umpierrez ge, miles jm, fisher jn. hyperglycemic crises in adult patients with diabetes. diabetes care. 2009; 32: 1335–43. 10. pavkov me, knowler wc, hanson rl, williams de, lemley kv, myers bd, et al. comparison of serum cystatin c, serum creatinine, measured gfr, and estimated gfr to assess the risk of kidney failure in american indians with diabetic nephropathy. am j kidney dis. 2013; 62: 33–41. 11. ferguson ma, waikar ss. established and emerging markers of kidney function. clin chem. 2012; 58: 680-9. 12. domingueti cp, fóscolo rb, silva acs, dusse lms, reis js, carvalho mg, et al. evaluation of creatinine-based and cystatin c-based equations for estimation of glomerular filtration rate in type 1 diabetic patients. arch endocrinol metab. 2016; 60: 108-16. 13. hamed eo, zaky na, kamal ym. simple cystatin-c formula for estimation of glomerular filtration rate in chronic kidney disease in diabetic patients. aamj. 2011; 9: 81–9. 14. mussap m, vestra md, fioretto p, saller a, varagnolo m. cystatin c is a more sensitive marker than creatinine for the estimation of gfr in type 2 diabetic patients. kidney int. 2002; 61: 1453-61. 15. shera as, jawad f, maqsood a, jamal s, azfar m, ahmed u. prevalence of chronic complications and associated factors in type 2 diabetes. j pak med assoc. 2004; 54: 54-9. 16. sohail m. prevalence of diabetic retinopathy among type – 2 diabetes patients in pakistan – vision registry. pak j ophthalmol. 2014; 30: 204-12. jiimc 2018 vol. 13, no.2 cystatin c versus creatinine in diabetic nephropathy 75 page 27 page 28 page 29 page 30 page 31 jiimc june 2016.cdr original article abstract objective: to explore the different specialty career choices of undergraduate medical students and to identify the factors influencing their career choices. study design: a descriptive cross-sectional survey. place and duration of study: this study was conducted in islamic international medical college in april 2013. materials and methods: final year students were selected through convenience sampling for this study. a 20 items questionnaire with one open ended and 19 likert scale based closeended questions was handed to 100 final year mbbs students, in order to explore their preferred career choices and reasons behind them. non parametric data analysis was done through spss 20. results: response rate of students was 82% of which 49 (60%) were female and 33 (40%) were male. medicine, surgery and gynecology were the top career choices among students. family practice was the least chosen specialty. the top 3 reasons to choose a specialty were natural aptitude, better subject comprehension and work enjoyment. parents in the same field, easy career progression and specialty related illness in the family were the least chosen reasons. conclusion: choice of specialty career in health professions has an impact on the healthcare needs of the country. 'family practice' is a forgotten domain and its importance needs to be stressed. medical curricula should emphasize on the importance of family practice as a career choice. key words: career choice, career preferences, influential factors, medical specialties. choice of specialty careers among final year mbbs students 1 2 3 madiha sajjad , rehan ahmed khan , shazia qayyum choice of specialty among mbbs studentsjiimc 2016 vol. 11, no.2 correspondence: dr. madiha sajjad associate professor, pathology islamic international medical college riphah international university, islamabad e-mail: madiha.sajjad@riphah.edu.pk 1,3 2 department of pathology/surgery islamic international medical college riphah international university, islamabad funding source: nil ; conflict of interest: nil received: feb 06, 2016; revised: mar 18, 2016 accepted: may 27, 2016 specialties, better job opportunities and easier 2,3 routes to specialize etc. factors influencing student choices for specialty careers are still unclear and culturally distinct. the decisions made by medical students regarding their specialty career choices do not only effect their own future but also have an impact on the quality of 4 health care system of the country. if they are not aligned with the health care and societal demands, there is an imbalance between the need and supply o f d o c to rs i n re l at i o n to t h e n e e d s o f t h e 5,6 community. information regarding medical students' career choices can thus guide restructuring of health care policies in relation to the needs of the society and to ensure provision of workforce according to needs of 2 that community. understanding these influences can also aid in curriculum designing and career 6 counselling for students in medical institutes. this is a descriptive study undertaken to identify the specialty career choices of final year medical students at our medical institute, the gender differences among these choices and the factors which influence their choices. materials and methods the study design was a descriptive cross-sectional survey, conducted in islamic international medical introduction medical sciences have a wide variety of disciplines and specialties. it is a difficult decision for a medical student who is about to graduate from medical school to choose his/ her future career specialty. this decision may depend on a multitude of factors as suggested by various studies. the bland–meurer model was presented in an attempt to give an overview of the complex interplay of factors that determine medical students' specialty choice with the conclusion being that students choose a specialty whose characteristics most closely match 1 their own career needs. some of the common determining variables identified in various studies w e re g e n d e r, i n t e re st s p u r re d b y p ra c t i c a l experience in a particular field during medical years, life style or prestige associated with certain 81 college in april 2013. all final year students were selected through convenience sampling. a 20 items questionnaire was distributed among all final year mbbs students (n=100) during their self-study time slot, to identify their future specialty career choices and underlying reasons of their choice. they were briefed about it and their understanding regarding terminology was checked. they were given 45 minutes to fill in the proforma. the questionnaire was collected at the end of the self-study time. the questionnaire consisted of 20 questions in all, developed after extensive literature review and specialist validation from multiple consultants. the st 1 question was open ended, requesting students to either choose from a list of 18 clinical specialties, write their choice if not listed or select the 'not sure' option. specialties listed were surgery, obstetrics and gynecology, pediatrics, medicine, psychiatry, o r t h o p e d i c s , o p h t h a l m o l o g y, d e r m a t o l o g y, anesthesiology, radiology, public health, family practice, pathology/ laboratory medicine, basic sciences, urology, cardiology, pulmonology and ear, nose, and throat (ent). rest of the 19 were close ended questions based on a likert scale of 1 to 3. these 19 questions were formed on the most likely reasons for career choices based on multiple specialist opinions. these were related to aptitude of the specialty, specialty related illness in self or close others, respect for specialty in the family members, reputation of the specialty in the community, media related hype of the field, higher anticipated income, work experiences in labs and c l e r k s h i p s , m o r e p a t i e n t c o n t a c t , b e t t e r understanding of the discipline, good teacher/ role model, impressive life style of the specialist in the chosen field, parents already practicing in the specialty, peer pressure or friend in the same specialty, more satisfaction, preference to work with a specific community group or gender, better job opportunities, fewer doctors in the chosen specialty, better/ controllable working hours and alternate easier routes for fellowships. non parametric data analysis was done through spss 20 and descriptive statistics were derived. results eighty-two out of 100 final year mbbs students participated in the survey. medicine (18%), surgery (15%) and gynecology (14%) were the top three career choices of students, with family practice coming last in the ranking (1%). the distribution of different specialties chosen by the students is given in fig 1. the top three reasons to choose a specialty were natural aptitude for it, better subject comprehension and work satisfaction for the specialty. the least attributed factors for their choices were easier perceived career advancement, an illness in the family regarding the particular specialty or parents already practicing in that field. the reasons to choose a specialty in order of preference are given in table i. surgery (10%) and medicine (8%) were the top rated specialties in males while females preferred gynecology/obstetrics (14%), medicine (10%) and fig 1: career choice in mbbs final year students table 1: reasons for choosing a specialty, in descending order of preference choice of specialty among mbbs studentsjiimc 2016 vol. 11, no.2 82 surgery (5%) in the descending order. thirteen per cent of the students were not sure about choosing a career. these included10% females and 3% males. none of the male students opted for family practice and only 1% of females opted for it as a prospective future career. the gender differences in choice of specialty careers in main specialties is given in fig 2. 8 6 some but not all studies. also, structural changes in the curriculum with more emphasis on primary 6,9 care experiences encouraged student interest in primary care. family practice was not found to be a 10,11 very desirable choice to pursue. this trend was also evident in our study where only 1% of the students showed an interest to pursue career as a general physician. however other factors like uncontrollable life style and excessive working hours also effected career choice of a specialty. controllable or uncontrollable life style is one of the major determinants in choosing 12,13 a career. life style is influenced by working hours, 14 working in shifts, salaries and job satisfaction. more recently, changes in the workplace environment also influence career choices for example duty-hour limitations designed partly to improve the work 15,16 satisfaction of residents and rapidly increasing s t u d e n t d e b t s e s p e c i a l l y i n t h e w e s t e r n 17 societies. students increasingly prioritize lifestyle 14-16 issues when choosing careers. male medical students in our study were inclined to choose surgery as their topmost choice followed by medicine whereas female students preferred gynecology/obstetrics followed by medicine as their preferred career choice. similar results were found in other studies where males preferred surgical specialty and females were inclined towards 18,19 gynecology and obstetrics. medicine was equally considered as a prospective specialty choice by both 20 the genders. we were not able to correlate our findings exactly to factors that influence career choice in both genders, as generally student satisfaction and understanding of the specialty were the prime reasons of choice in both groups. in literature the two reasons given for variability in male and female students choices was lifestyle controllability and gender biases inherently present 14,20 in some specialties. multiple studies reported female students preferring more controllable lifestyle specialties and considering domestic responsibilities and flexible hours as important variables while choosing specialty career as 14 compared to male students. it is also worth noting that males prefer choosing a career that is technically challenging and has more earning potential and would consider residency conditions and leave 14,20 availability as secondary issues. fig 2: gender differences in career choice in percentage discussion choosing a specialty for post graduate training is a major life decision for medical students on which their future career depends, influenced by multiple factors. in the present study, medicine and surgery were found to be the two top specialties chosen by the 2,3 students as is the trend noted in many local studies 7 as well as in international studies. a significant percentage of students (13%) were found to be unsure of their choice. we have reported 19 reasons of choosing a career in a specialty with aptitude, understanding of specialty satisfaction, more patient contact as the top most reasons. the least chosen reasons were parents working in that specialty, easier routes of specialization and illness in a close relative related to the specialty. multiple studies are available in literature identifying student preferences in post-graduate medical specialization and their influencing factors. several important factors that influence the choice of student include: the emphasis with which the student is taught a particular discipline and as an extension the influence that the teacher of that discipline has. several studies indicate that the subject specialist teacher can influence the choice of career in a student. working with a 'generalist' rather than a specialty/ sub-specialty faculty teacher was associated with selection of a primary care career, in choice of specialty among mbbs studentsjiimc 2016 vol. 11, no.2 83 a significant percentage of students in our study, 13% were unsure of a future career in any field, 10% of whom were female. this indecision has been regarded by studies to be due to lack of information about specialties, perceived equal interest in multiple specialties, lack of career counselling, 1 conflicting interests etc. our study also emphasizes the fact that family practice is one of the last career choice of the students. this dilemma has been addressed by 10,11 multiple local and international studies. however ironically many students in our local context do end up becoming general practitioners by default, due to economic or circumstantial reasons, armed only with an undergraduate degree which becomes a disadvantage for the health care delivery system at 11 large. conclusions and recommendations c l i n i c a l f i e l d s i . e . m e d i c i n e , s u r g e r y a n d gynaecology/ obstetrics remain the most popular student choices probably as a reflection of the more clinically oriented curricula. 'family practice' is a forgotten domain and its importance needs to be stressed. medical curricula should be made more co mmu n it y o riented a n d emp h a s ize o n t h e importance of family practice as a career choice for which health policy makers should take appropriate steps. our study is limited by a relatively smaller sample size and single institutional data. additional prospective, qualitative studies are needed for a better insight on factors influencing gender differences in choosing a specialty, as female students now make a significant bulk of the medical students and future doctors. references 1. bland cj, meurer ln, maldonado g. determinants of primary care specialty choice: a non-statistical meta analysis of the literature. acad med. 1995; 70: 620–41. 2. aslam m, ali a, taj t, badar n, mirza w, ammar a, et al. specialty choices of medical students and house officers in karachi, pakistan. east mediterr heal j. 2011; 17: 74–9. 3. rehman a, rehman t, shaikh ma, yasmin h, asif a, kafil h. pakistani medical students’ specialty preference and the influencing factors. j pak med assoc. 2011; 61:713–8. 4. harris mg, gavel ph, young eannette r. factors influencing the choice of. mja. 2005; 183: 295–300. 5. akhund s, shaikh za, kolachi hb. career related choices of medical students from an international medical college of karachi, pakistan. j liaquat univ med heal sci. 2012; 11: 180–4. 6. querido sj, vergouw d, wigersma l, batenburg rs, de rond mej, ten cate otj. dynamics of career choice among students in undergraduate medical courses. a beme systematic review: beme guide no. 33. med teach. 2016; 38: 18–29. 7. lefevre jh, roupret m, kerneis s, karila l. career choices of medical students: a national survey of 1780 students. med educ. 2010; 44: 603–12. 8. campos-outcalt d, senf j. a longitudinal, national study of the effect of implementing a required third year family practice clerkship or a department of family medicine on the selection of family medicine by medical students. acad med. 1999; 74: 1016–20. 9. coffeng le, visscher aje, th o, cate j ten, coffeng le, visscher a j e, et al. the influence of early clinical experiences on career preference of male and female medical students. med teach. 2016; 31: 323–6. 10. mariolis a, mihas c, alevizos a, gizlis v, mariolis t, marayiannis k, et al. general practice as a career choice among undergraduate medical students in greece. bmc med educ. 2007; 7:15. 11. iqbal s p. family medicine in undergraduate medical curriculum: a cost-effective approach to health care in pakistan. j ayub med coll abbottabad. 2010; 22: 207–9. 12. newton da, grayson ms, thompson lf. the variable influence of lifestyle and income on medical students’ career specialty choices: data from two u.s. medical schools. acad med. 2005; 80: 809–14. 13. dorsey, e ray, jarjoura, david, rutecki . the influence of controllable lifestyle and sex on the specialty choices of graduating u.s. medical students. acad med. 2005; 80: 791–6. 14. dorsey er, jarjoura d, rutecki . influence of controllable lifestyle on recent trends in specialty choice by us medical students. jama. 2003; 290: 1173–8. 15. choi d, dickey j, wessel k, girard de. the impact of the implementation of work hour requirements on residents’ career satisfaction, attitudes and emotions. bmc med educ [ i n t e r n e t ] . 2 0 0 6 ; 6 : 5 3 . a v a i l a b l e f r o m : h t t p : / / w w w . b i o m e d c e n t r a l . c o m / 1 4 7 2 6920/6/53received: 16. vidyarthi ar, katz pp, wall sd, wachter rm, auerbach ad. impact of reduced duty hours on residents’ educational satisfaction at the university of california, san francisco. acad med. 2006; 81: 76–81. 17. phillips jp, weismantel dp, gold kj, schwenk tl. medical student debt and primary care specialty intentions. fam med. 2010; 42: 616–22. 18. lambert tw, goldacre mj, turner g. career choices of united kingdom medical graduates of 2002: questionnaire survey. med educ. 2006; 40: 514–21. 19. huda n, yousuf s. career preference of final year medical students of ziauddin medical university. educ heal chang learn pract. 2006; 19: 345–53. 20. alers m, van leerdam l, dielissen p, lagro-janssen a. gendered specialities during medical education: a literature review. perspect med educ. 2014; 3:163–78. choice of specialty among mbbs studentsjiimc 2016 vol. 11, no.2 84 original�article abstract objective: to investigate and compare the antidiabetic effect of withania coagulans and liraglutide on serum postprandial insulin levels in streptozotocin induced diabetes in rats. study design: randomized control trial. st st place and duration of study: the study was conducted from 1 april 2016 to 31 march 2017 at islamic international medical college in collaboration with national institute of health islamabad. materials and methods: total 40 male sprague dawley rats were randomly divided into two groups; group a (n=10) and experimental group (n=30). group a was given normal diet for 5 days whereas experimental group was given normal diet plus streptozotocin (30mg/kg/day) intraperitoneally for 5 days and diabetes was confirmed in experimental group by fasting blood glucose (mg/dl). experimental group was further divided into b (diabetic control), c (withania coagulans treated) and d (liraglutide treated). first sampling group a and b was done after 5 days. group c were given withania coagulans and group d were given liraglutide along with normal diet for 30 days. second sampling (fasting blood glucose, postprandial glucose and insulin level) was done from group c and d. results: fasting blood glucose of group c (98 mg/dl ± 1.80) was significantly reduced than group d (102 mg/dl ± 2.04). postprandial glucose and insulin levels of group d (163 mg/dl ± 3.95 and 6.06 μu/ml ±0.17) were significantly decreased and increased as compared to group c ppg (183 mg/dl ± 6.30) and insulin level (5.54 μu/ml ± 0.23). conclusion: withania coagulans significantly improves postprandial insulin levels as compared to liraglutide. key words: diabetes, insulin, liraglutide, withania coagulans. have shown that in type 2 diabetes pancreas fails to produce sufficient quantity of insulin in response to glucose stimulation which leads to chronic postprandial and fasting hyperglycemia which causes serious complications leading to excess 5,6 morbidity and mortality. a number of pharmaceutical preparations are available for treating type 2 diabetes which targets insulin release from pancreas like sulphonylurea. these formulations are found to have a number of clinical limitations, the most serious long term limitation being the eventual need for insulin replacement therapy. these drugs which stimulate insulin secretion from pancreas are also associated with a common side effect-hypoglycemia. a new drug was discovered called liraglutide (glp-1 mime tics) which causes insulin secretion from pancreas only in response to hyperglycemia to avoid the risk of producing hypoglycemia and have enjoyed a great 7,8 deal of success in treating type 2 diabetes. basic mechanism of action of liraglutide is through enhancement of insulin secretion from pancreas and introduction diabetes mellitus is a disorder of carbohydrate metabolism in which the body sugar is unable to be oxidized due to lack or improper functioning of 1,2 pancreatic hormone mainly insulin. type 2 diabetes is a medical condition characterized by hyperglycemia in which glucose is not metabolized due to insulin resistance and pancreatic beta cells 3,4 can not compensate this insulin resistance. studies comparison of postprandial insulin levels in withania coagulans and liraglutide treated diabetic rats 1 2 3 abdul samad, shazia ali, noman sadiq correspondence: dr. abdul samad assistant professor department of physiology pak international medical college, peshawar e-mail:dr_samad17@hotmail.com 1 department of physiology pak international medical college, peshawar 2 department of physiology islamic international medical college, riphah international university, islamabad 3 department of physiology cmh kharian medical college, kharian funding source: nil; conflict of interest: nil received: may 08, 2017; revised: november 10, 2018; accepted: december 16, 2018 withania coagulans versus liraglutide jiimc 2018 vol. 13, no.4 206 can also be taken in combination with insulin 9,10 sensitizer like metformin. the main drawback of this drug is that these formulations are not available in oral form so it has to b e a d m i n i s t e r e d p a r e n t a l l y. c o n t i n u o u s subcutaneous or intravenous administration of this drug is another challenge faced by patients of type 2 11 diabetes who take liraglutide. due to adverse effects of hypoglycemic drugs and exogenous insulin, use of medicinal plant has become a common practice as these are reported to have very less side effects and are easily accessible and affordable. in this category of medicinal plants, withania coagulans (paneer doda) belongs to a family solanaceae is a famous herb known long for its antidiabetic property. this plant is cultivated in india, 12,14 pakistan, iran and afghanistan. different compounds of withania coagulans have been studied for their different medicinal properties including phenolic compounds, fruit berry extract, seeds, flowers and alcoholic extract. aqueous extract of withania coagulans (aqwc) dried fruits have specially been studied for its antidiabetic property because of presence of active compound called withanolides in it. several studies have proved that aqueous extract of withania coagulans has shown significant improvement in blood glucose levels and its effects were compared with biguanides and 15,16 sulphonylureas studies have also revealed that . withania coagulans treated rats exhibits increase level of serum insulin and results were compared 17,18 with glibenclamide( sulphonylurea). none of the previous studies has attempted to elucidate the level of postprandial insulin level and its comparison with glp-1 analogues. so the aim of this study was to investigate the effect of aqueous extract of withania coagulans (aqwc) and liraglutide on postprandial insulin, fasting and postprandial blood glucose levels, along with their comparison. materials and methods this randomized control trial was carried out at physiology department and multidisciplinary research laboratory, islamic international medical college, rawalpindi in collaboration with nih animal house after approval from ethics review committee. rats weighing between 200-300 grams were included in the study. rats were first allowed to get acclimatized for one week in the nih animal house in o 50-70% humidity at a room temperature of 24+2 c with a 12 hour light and dark cycle. a total 40 male sprague dawley rats were taken and randomly divided into two groups; group a (n=10) and experimental group (n=30). group a was given normal diet for 5 days whereas experimental group was given normal diet plus streptozotocin (30mg/kg/day) intraperitoneally for 5 days. after 5 days, diabetes was confirmed in experimental group by measuring and comparing fasting blood glucose levels (mg/dl) with group a. experimental group was then further divided into three groups i.e. b (diabetic control), c (withania coagulans treated) and d (liraglutide treated). first sampling of the experiment was done after 5 days from group a and b which included postprandial glucose (mg/dl), serum insulin (μu/ml). group c rats were given normal diet along with aqueous extract of withania coagulans (1000mg/kg/day) orally mixed in drinking water for 30 days. group d rats were given normal diet along with liraglutide (victoza pen) drug (0.3mg/kg/day) subcutaneously for 30 days. after 30 days of treatment, second sampling of the experiment was done from group c and d which included fasting blood glucose (mg/dl), postprandial glucose (mg/dl), and serum postprandial insulin (μu/ml). the dried fruits of withania coagulans were identified and authenticated (# iimc 03) by herbarium section of national agriculture research center (narc) islamabad. aqueous extract was prepared in multi-disciplinary research labortatory iimc at a dose 250mg/ml and was used for experimental work. liraglutide belongs to glp-1 mimetics was administered subcutaneously at a dose of 0.3mg/kg body weight for 30 days to diabetic rats. sample for blood glucose was collected from rat tail vein with 1 ml syringe. blood glucose levels were assessed using the easy gluco ultra plus auto coding meter by isotech co.ltd., korea. through intracardiac sampling 2 ml of blood was withdrawn .the blood was saved in labeled gel tubes and kept in o a laboratory ice box at 2-8 c until they were analyzed for insulin estimation (ng/ml) which was done using sandwich-elisa method. statistical analysis was done applying the spss 21. results were documented as mean + sem. comparisons among the two groups was analyzed using the independent withania coagulans versus liraglutide jiimc 2018 vol. 13, no.4 207 sample t-test and correlation among the variables was done using pearson's correlation coefficient. p value of <0.05 was considered significant for both analyses. results fasting blood glucose (fbg) mg/dl fasting blood glucose (mg/dl) levels in group b rats (131 ± 3.05mg/dl) were significantly higher (p<0.05) than group a rats (80 ± 3.19mg/dl). while on comparison fbg levels in group c rats (98 ± 1.80mg/dl) and group d rats (102 ± 2.04) were significantly lower (p<0.05) than group b rats (131 ± 3.05mg/dl). comparison of mean ± sem of fbg mg/dl levels in all four groups (a, b, c, d) are shown in table i. postprandial glucose (ppg) mg/dl comparison of mean ± sem of ppg (mg/dl) in all four groups (a, b, c, d) is displayed in table i. group b rats showed increased ppg (330± 15.95mg/dl) levels which were significantly higher (p<0.05) than group a rats (143 ±5.34mg/dl). significantly lower (p<0.05) ppg levels of group c rats (183± 6.30mg/dl) and group d rats (163 ±3.95 mg/dl) were observed on comparison with group b (330± 15.95mg/dl) rats. serum insulin levels (μu/ml) serum insulin levels of group b were observed to be (3.5 ± 0.19 μu/ml) which were significantly reduced (p<0.05) as compared to the group a (5.9 ± 0.19 μu/ml) rats. while serum insulin levels of group c rats (5.54 ± 0.23 μu/ml) and group d (6.06 ± 0.17 μu/ml) rats were significantly raised (p<0.05) as compared to the group b (3.5 ± 0.19 μu/ml) rats. comparison of mean ± sem of serum insulin (μu/ml) levels in all four groups (a, b, c, d) is shown in table i. discussion type 2 diabetes is a major health problem with serious complications results in substantial healthcare costs. treatment of type 2 diabetes includes parenteral therapy (insulin and glp-1 mimetics) and o r a l h y p o g l y c e m i c d r u g w h i c h i n c l u d e d sulphonylurea, metformin and thiazolidiendiones. in the present study antidiabetic effect of withania coagulans and liraglutide on fasting, postprandial blood glucose and serum postprandial insulin level was evaluated along with their comparison. jaiswal et al have concluded that hypoglycemic potential of withania coagulans fruit may be due to activation of insulin gene expression through creb (calcium responsive element binding protein) responsible for exocytosis of stored insulin from 13 pancreatic beta cells. current study also seconds this fact concluded by by jaiswal et al as postparandial insulin level was raised after use of withania coagulans extract. fasting and postprandial glucose levels in the current study were also similar to the results of hamatha et al ho gave aqueous extract of withania coagulans for 7 12 days instead of 30 days as were in present study. their study revealed the antidiabetic and antihyperlipidemic effect of aqueous extract of withania coagulans although serum postprandial insulin levels were not explored. results of the present study were also similar to results obtained by shukla et al who concluded that along with blood glucose and insulin level, treatment of aqueous extract of withania coagulans (500mg/kg/wt) has showed marked effect on increasing carbohydrate metabolizing enzymes i.e. 14 glucokinase and phosphofructokinase. serum insulin level were significantly increased in the results of present study which were inconsistent with the results of experiment done by bharti sk et al who investigated the effect of aqueous extract of withania coagulans in poloxomer-induced diabetic rats. the study mentioned that administration of aqueous extract of withania coagulans (200mg /kg body wt) to diabetic rats for 5 weeks causes significant decrease in serum fasting insulin level and insulin resistance (measured by homa-ir) on 15 comparison with those in diabetic rats. this dissimilarity between the results of two studies could be due to the reason that in present study table i: comparison of mean ± sem of fas�ng blood glucose (fbg) mg/dl, postprandial glucose (ppg) mg/dl and serum insulin (μu/ml) levels in all four groups (a,b,c,d): withania coagulans (wc) *=p < 0.05 is considered sta�s�cally significant. a * = group a vs b b * = group b vs c c * =group b vs d withania coagulans versus liraglutide jiimc 2018 vol. 13, no.4 80 3.19 208 postprandial insulin level was measured whereas bharti sk et al estimated fasting serum insulin level. results of the present study were also similar to the study conducted by davies et al on type 2 diabetic patients who evaluated the efficacy of liraglutide on 19 serum insulin levels. upadhyay and vandata concluded that powder of withania coagulans (10 g) when taken orally by diabetic patients showed marked improvement in fasting and postprandial glucose level which was similar to the results in present study in which aqueous extract of withania coagulans (1000mg/kg) 20 were administered to the diabetic rats. another human study carried out by alam a et al showed that administration of 150 ml of water containing 10 seeds of withania coagulans twice a day showed reduction in serum level of fasting and postprandial glucose which were similar to the results of present study carried out in streptozotocin 18 induced diabetic rats. in current study because of cost and availability issue immunohistochemistry of pancreas tissue was not done. further studies need to be conducted on aqueous extract of withania caogulans dried fruits on microscopic morphological features of intestinal l cells which release glucagon like peptide-1. conclusion withania coagulans reduces fasting and postprandial blood glucose levels while increasing serum insulin levels. this can be used as a better treatment option for type 2 diabetes because of its oral intake and lack of adverse effects usually caused by liraglutide. references 1. tierna lm jr., mephee sj, papadakis ma. diabetes mellitus and hypoglycemia. current medical diagnosis and treatment. 41st ed. new york: mcgraw hill, 2002; 1203-44. 2. 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& metabolism. 2016; 11(1): 1-2. 7. ismail-beigi f. glycemic management of type 2 diabetes mellitus. new england journal of medicine. 2012; 366(14): 1319-27. 8. defronzo ra. pharmacologic therapy for type 2 diabetes mellitus. annals of internal medicine. 2000; 133(1): 73. 9. kolterman, o.g et al. synthetic exendin-4 (exenatide) significantly reduces postprandial and fasting plasma glucose in subjects with t2dm. j. clin. endocrinol. metab. 2003; 132(5): 3082-3089. 10. nielsen, l.l.; young, a.a.; parkes, d.g. pharmacology of exenatide (synthetic exendin-4): a potential therapeutic for improves glycemic control of t2dm. regul. pept. 2004; 117: 77-88. 11. pabreja, k., et al. "molecular mechanisms underlying physiological and receptor pleiotropic effects mediated by glp-1r activation. british journal of pharmacology.2014; 171(5): 1114-1128. 12. s.hemlatha et al. chansouria; hypolipidemic activity of aqueous extract of withania coagulans dunal in albino rats. phytotherapy research.2006; 20 (7): 614– 617. 13. jaiswal d, rai pk, watal g. antidiabetic effect of withania coagulans in experimental rats.indian journal of clinical biochemistry. 2009; 24(1): 88-93. 14. shukla k et al. hypolipidemic and antioxidant activity of aqueous extract of fruit of withania coagulans (stocks) d u n a l i n c h o l e st e ro l fe d hy p e r l i p i d e m i c ra b b i t model.indian journal of experimental biology. 2014; 56: 870-875. 15. bharti sk et al. antidiabetic effect of aqueous extract of withania coagulans flower inpoloxamer-407 induced type 2 diabetic rats. journal of medicinal plants research. 2012; 6(45): 5706-13. 16. shukla k, dikshit p, shukla r, gambhir jk. the aqueous extract of withania coagulans fruit partially reverses nicotinamide/streptozotocin-induced diabetes mellitus in rats. journal of medicinal food. 2012; 15(8): 718-25. 17. datta a etal. antidiabetic and antihyperlipidemic activity of hydroalcoholic extracts of withania coagulans dunal dried fruit in experimental rat models. journal of ayurveda and integrative medicine. 2013;4 (2): 99-04. 18. alam a, siddiqui my, hakim mh. clinical efficacy of withania coagulans dunal and trigonella foenum-graecum linn. in type 2 diabetes mellitus. indian journal of traditional knowledge. 2009; 8(3): 405-409. 19. davies mj et al.efficacy of liraglutide for weight loss among patients with type 2 diabetes: the scale diabetes randomized clinical trial. jama. 2015; 314(7): 687-99. 20. upadhyay bn, gupta v. a clinical study on the effect of rishyagandha (withania coagulans) in the management of prameha (type ii diabetes mellitus). ayu (an international quarterly journal of research in ayurveda). 2011; 32(4): 507-12. withania coagulans versus liraglutide jiimc 2018 vol. 13, no.4 209 original�article abstract objective: to determine the antioxidant effects of spinach on the weight of testes and epididymis in obese sprague dawley rats. study design: experimental, randomized control study. place and duration of study: it was carried out from april 2016 to march 2017 in the department of physiology of islamic international medical college, rawalpindi, pakistan. materials and methods: total 40 male sprague dawley rats of about 8 weeks were included. they were randomly divided into group afed on standard diet and experimental groupfed on high fat diet to induce th obesity. at the end of 6 week, after inducing obesity, experimental group was subdivided into group b and group c. weight of the testes and epididymis of group a and group b rats was recorded. then 5% spinach was given to group c along with high fat diet for 4 weeks and finally weight of the testes and epididymis was measured. results: weight of the testes and epididymis (g) of group b (1.32 ± 0.53g) rats was significantly decreased (p<0.001) as compared to group a (1.88 ± 0.92g) rats. however, weight of testes and epididymis (g) of group c (1.92 ± 0.49g) rats was significantly increased (p<0.001) as compared to group b (1.32 ± 0.53g) rats after spinach intake. conclusion: intake of spinach supplemented diet has ameliorative effects on weight of testes and epididymis in response to deleterious effects caused by obesity-induced oxidative stress. key words: epididymis, obesity, spinach, testes. 6,7 infertility. infertility is a global health problem, as 15% to 20% couples struggles when trying to conceive and hence look for medical guidance to increase the possibility 8 of successful pregnancy. for proper functioning of male reproductive system, testes and epididymis serves as an imperative organ as they are main site of 9 sperm production and maturation respectively. one of the links connecting obesity with infertility is 10 generation of reactive oxygen species. in obesity, increase release of cytokines and cellular injury due to the pressure effect caused by excessive adipose tissues resulting in increased production of reactive 11 oxygen species. these reactive oxygen species are extremely unstable that gain stability by attacking the adjacent stable species, resulting in damage to 12 surrounding cells and tissues. thus, antioxidants utilization may be appropriate 13 way to lessen the harmful effects of obesity. these antioxidants act as scavenger against reactive oxygen species and help to overcome the unwanted consequences of obesity on male reproductive system. currently, there is extremely curiosity introduction obesity, which is generally referred as anomalous and unnecessary accretion of fats in adipose tissues 1,2 has become an intricate health problem. reported 3 prevalence of obesity is 13% worldwide. the 4 reported prevalence of obesity in pakistan is 10.3%. different contributory factors are responsible for increase in weight but high fat diet and decrease 5 physical activity are the two fundamental causes. obesity is not only the risk factor of different diseases but also accountable for harmful effects on reproductive system and increase in the incidence of antioxidant effects of spinach (spinacia oleracea) on testicular and epididymal weight of obese sprague dawley rats correspondence: dr. somia iqbal department of physiology islamic international medical college riphah international university, islamabad e-mail: mikhan1954@hotmail.com department of physiology islamic international medical college riphah international university, islamabad funding source: higher education commission, pakistan; conflict of interest: nil received: september 19, 2017; revised: september 12, 2018 accepted: september 13, 2018 antioxidant effects of spinachjiimc 2018 vol. 13, no.3 somia iqbal, shazia ali, arif siddiqui 157 diet protocol spinach (spinacia oleracea) leaves were bought from local market, and identified by taxonomist of national herbarium department in plant genetic resources institute and national agriculture research centre (narc) islamabad, allotting voucher number # iimc 05. fresh spinach leaves were washed thoroughly with distilled water and then crushed in electric blender. the macerate was then filtered and air dried. spinach powder was mixed with distil water and o autoclaved at 121 c temperature and 15 ibs pressure 17 and then extract was stored. then 500 gram of this extract was added into 10kg of standard diet. therefore, supplemented spinach diet contained standard diet along with 5% spinach hot water extract. composition of standard and spinach supplemented diet is shown in table i. the composition of high fat diet constituted standard diet supplemented with 20% butter as shown in table i. regarding natural antioxidants found in plants as they are affordable and easily accessible and have no 14 perilous effects. spinach is green flourishing vegetable. it is rich in micronutrients (vitamin a, b, e, c and folic acid and oxalic acid) and minerals (calcium, phosphorus, iron, 15 zinc, potassium and sodium). it is also an established source of flavonoid and p-coumaric acid 16 all of which have antioxidant properties. so spinach can works as a shield against the damaging effect of 14 reactive oxygen species. a number of studies on different animal models have demonstrated the antioxidant effects of spinach such as its effects on hyperlipidemia, radiationi n d u c e d b i o c h e m i c a l c h a n g e s i n t e s t e s , lipopolysaccharides induced endotoxemia and slowing tumorigenic progression in prostatic 16,19 carcinoma. however, its therapeutic effects on male infertity induced by obesity are still needed to be explored and information regarding curative effect of spinach on obesity-induced changes on weight of testes and epididymis (sex organs) is still required. thus, this will enable us to recommend this nutritional plant in the diet course of obese and overweight population to avert and alleviate these changes. as a result, the present study was intended to determine the potential effects of spinach on weight of sex organs. materials and methods the experimental randomized control study was performed in the department of physiology and multidisciplinary research laboratory of islamic international medical college, rawalpindi in association with the animal house at national institute of health (nih), islamabad, pakistan from april 2016 to march 2017. the study was approved by the ethical review committee and was accomplished under the guidelines, stated by the national institute for animal experimentations. a total of 40 male sprague dawley rats of about 8 weeks weighing from 160-200g were included in the study. for seven days, rats were allowed to acclimatize to nih animal house environment at humidity of 50-70% and at a room temperature of 24 o + 2 c, maintained at a 12 hour light and dark cycle. a standard diet in pellet form was prepared at the animal house of nih, islamabad. the food and water was provided ad libitum. table i: composi�on of standard diet, high fat diet and spinach supplemented diet. after acclimatization, rats were randomly divided into group a (control group n=13) and experimental group (n =27). group a rats were fed on standard diet and rats of experimental group were fed on high fat diet to induce obesity in six weeks. weight (g) of the rats was measured weekly by placing them on the weighing machine (ts200 electronic compact scale, jiangyin ditai electronic technology co. ltd., china). at the end of 6th weeks, when rats of experimental group had gained 20% weight above that of rats of antioxidant effects of spinachjiimc 2018 vol. 13, no.3 158 weight of testes and epididymis of group c rats (1.92 ± 0.49g) was significantly increased (p<0.001) as compared to group b rats (1.32 ± 0.53g) after administration of spinach hot water extract. comparison of mean ± sem of weight of testes and epididymis (g) of all three groups (a, b, c) is shown in figure 1. discussion obesity has become a great challenge for both 20 developed and developing countries of the world. growing evidence suggests that along with other diseases, increased body fat also affect the functions of male reproductive system and cause male 21,22 infertility. thus, our study explored the harmful effects of obesity on weight of testes and epididymis as well as the beneficent role of spinach (spinacia oleracea) in restoring these changes. in obesity, there is not only increased fat accumulation in different parts of the body but also around testes and epididymis as described by 23 alhashem et al. (2014). these excessive adipose tissues cause cellular damage resulting in increased production of reactive oxygen species and expose the testicular microenvironment to oxidative stress. our study also shows that obesity causes considerable decrease in the weight of testis and epididymis. similar results have been reported by alhashem et al., (2014) and yan et al., (2015) that after inducing obesity, there was significant decrease in testes and epididymis weight when compared 23,24 with control. however, ghanayem, bai, kissling, 25 travlos & hoffler, 2010 had different observations. reason of those variations can be due to difference in genetics of animal model as well as procedure differences. however, use of antioxidant such as spinach (spinacia oleracea) could repair the oxidative damage and cause significant increase in weight of testes and epididymis in obese rats. these results are in accordance with the study carried out by tawfeek, ahmed & kakel, (2006) who observed the antioxidant effect of nigella sativa oil treatment on the sex organs in rats exposed to oxidative stress and concluded that use of antioxidant could repair the 26 damage caused by oxidative stress. similarly, elgazar, (2016) also showed that use of antioxidants have beneficial effect on the testicular tissue and cause significant increase in weight of sex organs group a (control group), they were further subdivided into group b (obesity control group n =13) and group c (spinach treated group n=14).then first sampling for measuring weight of testes and epididymis from group a (control group) and group b (obesity control group) sprague dawley rats was done by placing them in a glass jar containing cotton soaked in chloroform. the rats were kept there, until their breathing movements ceased and they were sacrificed. then an incision was given in the abdominal wall along the midline and the right testes and epididymis were dissected out, freed from adherent tissues and weighed (g) on weighing machine (ts200 electronic compact scale, jiangy in ditai electronic technology co. ltd., china). then 5% spinach hot water extract was given to group c (spinach treated group) along with continuation of high fat diet for four weeks. at the end of 4th week, second sampling to calculate weight of testes and epididymis was done from group c (spinach treated group) sprague dawley rats similar to the method applied for the first sample collection. statistical analysis was performed by using statistical package of social sciences (spss 21) version. all re s u l t s we re ex p re s s e d a s m e a n + s e m . comparisons among the groups was evaluated by using the independent sample t-test. p value of <0.05 was regarded as significant. results weight of testes and epididymis (g) of group b rats (1.32 ± 0.53g) was significantly decreased (p<0.001) as compared to group a rats (1.88 ± 0.92g). however, fig 1: comparison of mean ± sem of weight of testes and epididymis (g) of sprague dawley rats in the following three groups: group a: control group group b: obesity control group group c: spinach treated group ***=p < 0.001 is considered sta�s�cally highly significant. ***a= group a vs b ***b= group b vs c antioxidant effects of spinachjiimc 2018 vol. 13, no.3 159 8. trussell jc. optimal diagnosis and medical treatment of male infertility. in seminars in reproductive medicine 2013 jul ;31 (4):235-6. 9. plant tm, zeleznik aj, editors. knobil and neill's physiology of reproduction. academic press; 2014 nov 15. 10. chen xl, gong lz, xu jx. antioxidative activity and protective effect of probiotics against high-fat diet-induced sperm damage in rats. animal. 2013;7(2):287-92. 11. fonseca-alaniz mh, takada j, alonso-vale mi, lima fb. adipose tissue as an endocrine organ: from theory to practice. jornal de pediatria. 2007;83(5):s192-203. 12. farias jg, puebla m, acevedo a, tapia pj, gutierrez e, zepeda a et al.oxidative stress in rat testis and epididymis under intermittent hypobaric hypoxia: protective role of ascorbate supplementation. journal of andrology. 2010 may 6;31(3):314-21. 13. mortazavi m, salehi i, alizadeh z, vahabian m, roushandeh am. protective effects of antioxidants on sperm parameters and seminiferous tubules epithelium in high fat-fed rats. journal of reproduction & infertility. 2014;15(1):22. 14. mortazavi m, salehi i, alizadeh z, vahabian m, roushandeh am. protective effects of antioxidants on sperm parameters and seminiferous tubules epithelium in high fat-fed rats. journal of reproduction & infertility. 2014;15(1):22. 15. fu h, xie b, ma s, zhu x, fan g, pan s. evaluation of antioxidant activities of principal carotenoids available in water spinach (ipomoea aquatica). journal of food composition and analysis. 2011;24(2):288-97. 16. lomnitski l, carbonatto m, ben-shaul v, peano s, conz a, corradin l et al.the prophylactic effects of natural watersoluble antioxidant from spinach and apocynin in a rabbit model of lipopolysaccharide-induced endotoxemia. toxicologic pathology. 2000 jul;28(4):588-600. 17. ko sh, park jh, kim sy, lee sw, chun ss, park e. antioxidant effects of spinach (spinacia oleracea l.) supplementation in hyperlipidemic rats. preventive nutrition and food science. 2014;19(1):19. 18. sisodia r, yadav rk, sharma kv, bhatia al. spinacia oleracea modulates radiation-induced biochemical changes in mice testis. indian journal of pharmaceutical sciences. 2008;70(3):320. 19. nyska a, suttie a, bakshi s, lomnitski l, grossman s, bergman m et al. slowing tumorigenic progression in tramp mice and prostatic carcinoma cell lines using natural anti-oxidant from spinach, nao—a comparative study of three anti-oxidants. toxicologic pathology. 2003;31(1):39-51. 20. singh m, gupta n, kumar r. effect of obesity and metabolic syndrome on severity, quality of life, sleep quality and inflammatory markers in patients of asthma in india. advances in respiratory medicine. 2016;84(5):258-64. 21. płaczkiewicz d, puźniak m, kleinrok a. prevalence of hypertension and major cardiovascular risk factors in healthy residents of a rural region in south-eastern poland–. annals of agricultural and environmental medicine. 2016;23(3):476-81. 22. stokes vj, anderson ra, george jt. how does obesity affect fertility in men–and what are the treatment options?. clinical endocrinology. 2015;82(5):633-8. while describing the protective role of walnut seeds extract and vitamin e as an antioxidant against the 27 oxidative stress. although we demonstrated that obesity induce injurious effects on weight of testes and epididymis, further biochemical and molecular studies are needed to clarify the effects of obesity and spinach (spinacia oleracea) on the male r e p ro d u c t i v e sy s t e m . f u r t h e r m o r e , t h e s e therapeutic effects of spinach (spinacia oleracea) need to be clarify via future studies on human. conclusion thus our study shows that spinach has strong potential as an antioxidant to restore the deleterious effects on weight of testes and epididymis in response to obesity-induced oxidative stress. acknowledgement we are grateful to mr. hussain ali, head of animal house, and his staff at the national institute of health (nih), islamabad, for helping us to handle animals for our research study and for providing a welcoming and friendly working environment. finding source this project is funded by higher education commission (hec) pakistan. references 1. ofei f. obesity-a preventable disease. ghana medical journal. 2005;39(3):98. 2. klonoff dc, buse jb, nielsen ll, guan x, bowlus cl, holcombe jh et al. exenatide effects on diabetes, obesity, cardiovascular risk factors and hepatic biomarkers in patients with type 2 diabetes treated for at least 3 years. current medical research and opinion. 2008;24(1):275-86. 3. obesity and overweight. world health organization. 2017 [ c i t e d 1 7 s e p t e m b e r 2 0 1 7 ] . a v a i l a b l e f r o m : http://www.who.int/mediacentre/factsheets/fs311/en/ 4. jafar th, chaturvedi n, pappas g. prevalence of overweight and obesity and their association with hypertension and diabetes mellitus in an indo-asian population. canadian medical association journal. 2006;175(9):1071-7. 5. goldberg rd, cardamone s, murthy a. obesity and contraception: controversy. open access j contracept. 2012 ;3:1-8. 6. de groot pc, dekkers om, romijn ja, dieben sw, helmerhorst fm. pcos, coronary heart disease, stroke and the influence of obesity: a systematic review and metaanalysis. human reproduction update. 2011 feb 18;17(4):495-500. 7. hammoud ao, gibson m, peterson cm, meikle aw, carrell dt. impact of male obesity on infertility: a critical review of the current literature. fertility and sterility. 2008;90(4):897904. antioxidant effects of spinachjiimc 2018 vol. 13, no.3 160 fertility and potentiation of acrylamide-induced re p ro d u c t i ve tox i c i t y. b i o l o g y o f re p ro d u c t i o n . 2010;82(1):96-104. 26. tawfeek fk, ahmed sm, kakel sj. effect of nigella sativa oil treatment on the sex organs and sperm characters in rats exposed to hydrogen peroxide. mesopotamia j. agric. 2006;34(1):2-8. 27. elgazar af. protective role of walnut seeds extract and vitamin e against testicular toxicity induced by cyclophosphamide in male rats. 23. alhashem f, alkhateeb m, sakr h, alshahrani m, alsunaidi m, elrefaey h et al. exercise protects against obesity induced semen abnormalities via downregulating stem cell factor, upregulating ghrelin and normalizing oxidative stress. excli journal. 2014;13:551. 24. yan wj, mu y, yu n, yi tl, zhang y, pang xl et al. protective effects of metformin on reproductive function in obese male rats induced by high-fat diet. journal of assisted reproduction and genetics. 2015;32(7):1097-104. 25. ghanayem bi, bai r, kissling ge, travlos g, hoffler u. dietinduced obesity in male mice is associated with reduced antioxidant effects of spinachjiimc 2018 vol. 13, no.3 161 untitled-2 original�article abstract objective: to determine the comparative and combined synergetic effect of black coffee and metformin in treatment of type 2 diabetes mellitus in mice model. study design: experimental, randomized control study. place and duration of study: this study was conducted over a period of one year from may 2017 to april 2018 at pharmacology laboratory and multidisciplinary laboratory of islamic international medical college in collaboration with national institute of health, islamabad. materials and methods: a total of 50 male balb/c albino mice were taken, group 1 was non-diabetic normal control (n=10) and diabetes was induced in experimental group (n=40) by using low dose streptozotocin (40mg/kg). after confirmation, diabetic mice were further divided into four groups (10 mice/group). group 2 was diabetic control and remaining 3 groups were treated with black coffee, metformin and combination of both, respectively for 45 days. blood samples were taken by intracardiac puncture for hba , which shows the 1c long-term control. statistical analysis was done applying spss 21. comparisons of means of hba between the 1c groups were analyzed using one way anova (post hoc tuckey test). p value of <0.05 was considered significant. results: black coffee treated (group 3), metformin treated (group 4) and combination of black coffee and metformin treated (group 5) had significantly decreased serum hba levels in comparison with those found in 1c diabetic control (group 2) (p<0.05). conclusion: combination of black coffee and metformin significantly decreases serum hba levels in diabetic 1c mice as compared to metformin or black coffee treated diabetic mice separately. key words: diabetes mellitus, hba , metformin, pancreatic islets cells 1c stroke, nephropathy, retinopathy, neuropathy, 3,4 gangrene and even amputations. diabetes mellitus 5,6 affects 382 million people globally. the current prevalence of this disease in pakistan is 11.77% 7 according to a study conducted in 2015. the pandemic of type 2 diabetes mellitus has been met by emerging approach and clinical tactics, including the generally-accepted commendation to institute 8,9 drug therapy concomitant with lifestyle changes. metformin an older and broadly acknowledged prime agent, has antihyperglycemic properties and also other important functions such as enhancement in endothelial dysfunction, hemostasis and oxidative stress, insulin resistance, lipid profiles, and fat 10 redistribution. metformin's efficacy, security profile, beneficial cardiovascular and metabolic effects and its capacity to be associated with other antidiabetic agents makes this drug the first glucose lowering agent of choice when treating patients with 11,12 type 2 diabetes. even the most explored out oral antidiabetic drugs sometimes fail as monotherapy and eventually different drug combinations are to be introduction diabetes mellitus is spreading worldwide pandemic that is a raising wellbeing concern with numerous 1 difficulties and an expanding ubiquity. despite stunning change over both essential and clinical therapeutic sciences, diabetes mellitus is at present a hopeless life-long sickness, rapidly affecting both 2 genders. diabetes mellitus may be not a single illness rather an aggregation of metabolic issue connected with secondary harm on various organ framework that incorporate cardiovascular diseases, comparative and combined synergetic effects of black coffee and metformin in treatment of type 2 diabetes mellitus jawaria iftikhar, uzma naeem, tahira sadiq correspondence: dr. jawaria iftikhar demonstrator department of pharmacology islamic international medical college riphah international university, islamabad e-mail: drjawaria16@hotmail.com department of pharmacology islamic international medical college riphah international university, islamabad funding source: nil; conflict of interest: nil received: november 09, 2018; revised: february 16, 2019 accepted: february 27, 2019 diabetes treatment: black coffee vs metforminjiimc 2019 vol. 14, no.1 28 g i v e n w i t h m e t f o r m i n , w h e n m e t f o r m i n monotherapy fails. this experimental study was done to determine the comparative and combined synergistic effect of black coffee and metformin in treatment of type 2 diabetes mellitus in mice model. materials and methods this randomized control trial was carried out at pharmacology laboratory and multidisciplinary research laboratory at islamic international medical college with the collaboration of national institute of health (nih) islamabad pakistan. before starting the study, a formal approval by the ethics review committee of islamic international medical college, riphah international university, was taken. the duration of this study was 12 months (may 2017 to april 2018). a total of 50 healthy, 6-8 weeks old male, weighing 30-50 g albino balb/c mice were included in the study. all the mice were accommodated in standard cages which were made up of plastic and placed on metallic racks, at the animal house of nih, islamabad. room number 13 was allocated for the research procedure. the mice had free access to tap water through the inverted bottles of 250ml capacity fixed on top of the cages. these bottles were cleaned and filled on daily basis according to the protocol of the animal house. the normal standard diet was prepared at the nih, which was served with standard food pellets. animal house atmosphere was maintained at room temperature of 20 ± 2 oc with relative humidity of 50-70% with a light and dark cycle of 12 hours each. after acclimatization for 1 week, the mice were randomly divided into two groups; 10 mice were allocated to group 1 and remaining 40 mice were allocated to the experimental group. group 1 was labeled as normal control and was given normal diet for 5 days whereas the experimental group was given normal diet plus 2 3 s t r e p t o z o t o c i n , ( s t z ) , ( 4 0 m g / k g / d a y ) intraperitoneally for consecutive 5 days. after 5 days, confirmation of diabetes in experimental group was done by measuring and comparing fasting blood glucose levels (mg/dl) with group 1. the blood sample was taken from lateral tail vein of all mice with 1 ml syringe and the blood glucose levels were measured by using easy gluco ultra plus auto coding meter iso tech co. ltd. experimental group was then further divided into four groups i.e. 2 10,13 considered. many new trends in management of diabetes are therefore being considered nowadays and the approach for diabetes treatment is moving towards the incorporation of more organic natural products which tend to counter the root causes of 14,15 the disease. black coffee is the most commonly used energy boosting beverage worldwide. recent studies have shown many potential health benefits 16 of black coffee in humans. besides keeping you alarm and wakeful, coffee is the richest and intense source of antioxidants that work as meager warriors battling and securing against free radicals inside 17 human body. caffeine in black coffee regulates the hyperglycemic effect in diabetic patients by increasing insulin release from pancreatic beta cells by the sensitization of the ryanodine receptor and a c t i v a t i o n o f 5 ʹ a d e n o s i n e monophosphate–activated protein kinase (ampk). caffeine also up regulates the insulin-like growth factor 1 signaling, which is responsible for enhanced insulin sensitivity as well as insulin secretion. chlorogenic acid has an eloquent role in glucose metabolism by decreasing glucose output in the liver and promoting the synthesis of the “homeodomain transcription factor idx-1”, which directs beta cells to counter the increased glucose levels in plasma. i m p o r t a n t a n t i ox i d a n t s i n c o f fe e i n c l u d e h y d r o c i n n a m i c a c i d s a n d p o l y p h e n o l s , hydrocinnamic acids are very effective at neutralizing free radicals and preventing oxidative stress. polyphenols counter the increased insulin 18,19,20,21 resistance and escalates the insulin sensitivity. the cumulative body of suggestion about lower frequency of diabetes among coffee users is conclusive enough to prove a positive impact of coffee consumption on the development of type 2 diabetes mellitus. different studies have been conducted to evaluate the preventive role of black 22 coffee on type 2 diabetes. to the best of our knowledge, no study has been conducted to explore the effect of black coffee as adjunct to metformin in treatment of diabetes patients. if this agent works to improve insulin sensitivity and decreases the insulin resistance, then this cost effective and easy administered agent with overall beneficial effects on health can be used in place of other antidiabetic agents who are usually 29 jiimc 2019 vol. 14, no.1 diabetes treatment: black coffee vs metformin the graphical representation of hba (%) results 1c shows a marked difference between the black coffee, metformin, combination of black coffee and metformin as compared to the diabetic control mice. metformin has a better role in lowering hba (%) 1c than black coffee, yet the role of combination therapy is astonishing in aspect to lower hba (%) 1c nearly to the normal control range. (diabetic control), 3 (black coffee treated), 4 (metformin treated) and 5(combination of black coffee and metformin treated). group 2 mice were given normal standard diet only. group 3 mice were given normal diet mixed with 24 black coffee (5g/kg/day) orally for 45 days. group 4 mice were given normal diet along with metformin 25 (200mg/kg/day) orally mixed in drinking water for 45 days. group 5 mice were given normal diet mixed with black coffee (5g/kg/day) orally and metformin drug (200mg/kg/day) orally mixed in drinking water for 45 days. after 45 days of treatment, final sampling of the experiment was done from group 3, 4 and 5 which included hba (%) by cardiac 1c puncture. fixed time nephelometry certified by national glycohemoglobin standardization program (ngsp) was employed for hba estimation (%). for 1c this study, pa50 fully auto specific protein analyzer was used. statistical analysis was done by applying the statistical package for social sciences version 21 (spss 21). results were documented as mean ± standard error of mean (sem). comparison of means of hba (%) among the five groups were analyzed by 1c using the one way anova and post hoc tuckey tests. p value of <0.05 was considered significant. results: hba (%)1c the result of mean ± sem of hba (%)in group 2 (7.82 ic ± 0.11) was significantly higher than group 1 (p value >0.05) as shown in table i. while on comparison of mean ± sem of hba (%) in group 3 (6.02 ± 0.29), ic group 4 (5.76 ± 0.45) and group 5 (4.90 ± 0.28) were significantly lower than group 2 (p value <0.05). table i shows the comparison of mean ± sem of hba (%) of ic all the groups. table i: comparison of mean ± sem of hba (%) in allic five groups p value <0.05* table ii: mul�ple comparison of mean difference of hba1c (%) of control and experimental groups fig 1: graphical representa�on of hba (%) results1c discussion the results of present study confirm that hyperglycemia induced by streptozotocin, is ameliorated by all the experimental agents to an appreciable extent, yet the result of combination therapy of black coffee and metformin is very impressive. in present study, the antidiabetic effect of metformin is seen in group 4 and in combination with black coffee in group 5. improvement of hba in group 4 is 1c supported by study of s.h chung et al., who compared the antidiabetic effect of metformin and compound k in diabetic db/db mice and proposed that normalization of raised plasma glucose levels and improvement in insulin levels in metformin 26 treated group. in present study, improvement in 30 error bars: 95% cl jiimc 2019 vol. 14, no.1 diabetes treatment: black coffee vs metformin recommendation · further explorations need to be directed on active constituents of black coffee and highlight their individual hypoglycemic role. · the pharmacokinetic properties and interaction of black coffee with other drugs should be studied. · the comparative and combination therapy of black coffee with modern glucose lowering drugs should be investigated. references 1. association ad. diagnosis and classification of diabetes mellitus. diabetes care. 2014;37(supplement 1):s81-s90. 2. association ad. diagnosis and classification of diabetes mellitus. diabetes care. 2012;35(supplement 1):s64-s71. 3. nathan dm, group der. the diabetes control and complications trial/epidemiology of diabetes interventions and complications study at 30 years: overview. diabetes care. 2014;37(1):9-16. 4. sayin n, kara n, pekel g. ocular complications of diabetes mellitus. world journal of diabetes. 2015;6(1):92. 5. gagliardino jj, atanasov pk, chan jc, mbanya jc, shestakova mv, leguet-dinville p, et al. resource use associated with type 2 diabetes in africa, the middle east, south asia, eurasia and turkey: results from the international diabetes management practice study (idmps). bmj open diabetes research and care. 2017;5(1):e000297. 6. jansson s, fall k, brus o, magnuson a, wändell p, östgren cj, et al. prevalence and incidence of diabetes mellitus: a nationwide population-based pharmaco-epidemiological study in sweden. diabetic medicine. 2015;32(10):1319-28. 7. meo sa, zia i, bukhari ia, arain sa. type 2 diabetes mellitus in pakistan: current prevalence and future forecast. jpma the journal of the pakistan medical association. 2016;66(12):1637-42. 8. brietzke sa. oral antihyperglycemic treatment options for type 2 diabetes mellitus. medical clinics.99(1):87-106. 9. association ad. 13. management of diabetes in pregnancy: standards of medical care in diabetes—2018. diabetes care. 2018;41(supplement 1):s137-s43. 10. rojas lba, gomes mb. metformin: an old but still the best treatment for type 2 diabetes. diabetology & metabolic syndrome. 2013;5(1):6. 11. qaseem a, barry mj, humphrey ll, forciea m, for the clinical guidelines committee of the american college of p. oral pharmacologic treatment of type 2 diabetes mellitus: a clinical practice guideline update from the american college o f p h y s i c i a n s . a n n a l s o f i n t e r n a l m e d i c i n e . 2017;166(4):279-90. 12. chakraborty a, chowdhury s, bhattacharyya m. effect of metformin on oxidative stress, nitrosative stress and inflammatory biomarkers in type 2 diabetes patients. diabetes research and clinical practice. 2011;93(1):56-62. 13. association ad. standards of medical care in diabetes—2016 hba in groups 3 and 5 along with better 1c improvement in group 5 which is given combination of black coffee and metformin is observed. kobayashi m et al., also demonstrated similar results w h o u s e d b l a c k c o f fe e , c a f fe i n e ex t ra c t , decaffeinated coffee against different sets of experiments to analyze the preventive part of black coffee on development of stz induced diabetes and also the reversal of worsening offered by stz induced hyperglycemia in male c57 bl/ 6j mice. he demonstrated that continuous black coffee ingestion prevented the development of stz induced diabetes mellitus and also revealed that the black coffee can recover the hyperglycemia induced metabolic changes by analyzing the biochemical and 27 histopathological parameters. mukesh doble et al., did a study to demonstrate comparative and combined effects of plant phenolic compounds, chlorogenic acid and ferulic acid with metformin and thiazolodinedione on the uptake of 2-deoxyglucose (2dg) by l6 myotubes of rats. he established that a combination of different concentrations of chlorogenic acid and metformin or thz, has a synergistic effect in the uptake of 2dg with a maximum of 5.0 and 5.3 times respectively, when contrasted to the control. ferulic acid in combination with metformin or thz has likewise displayed a synergistic impact and the 2dg uptake increases by 28 4.98 and 5.11 fold when compared to the control. hence when metformin is given in combination with black coffee, hba which shows the long term 1c control of diabetes is improved demonstrating that black coffee can be used as adjunct to metformin in the treatment of type 2 diabetes mellitus. conclusions black coffee significantly lowers hba levels in 1c diabetic mice model. combination of black coffee and metformin significantly decreases serum hba1c levels in diabetic mice as compared to metformin or black coffee treated diabetic mice separately. study limitations study should also have involved oral glucose tolerance test, serum insulin level estimation, morphological study of pancreas, and immune histochemistry of histology of pancreas but owing to the cost and availability issue, the above mentioned parameters could not be explored. 31 jiimc 2019 vol. 14, no.1 diabetes treatment: black coffee vs metformin retinal diseases. ophthalmic research. 2016;55(4):212-8. 22. carlström m, larsson sc. coffee consumption and reduced risk of developing type 2 diabetes: a systematic review with meta-analysis. nutrition reviews. 2018. 23. arulmozhi dk, kurian r, bodhankar sl, veeranjaneyulu a. m e t a b o l i c e f fe c t s o f v a r i o u s a n t i d i a b e t i c a n d hypolipidaemic agents on a high-fat diet and multiple low-dose streptozocin (mlds) mouse model of diabetes. journal of pharmacy and pharmacology. 2008;60(9):116773. 24. harvei s. coffee intake and the effects on intestinal inflammation, metabolic homeostasis and intestinal barrier function in mice: norwegian university of life sciences, ås; 2016. 25. aghaalikhani n, goodarzi mt, latifi z, farimani ar, fattahi a. effects of different doses of metformin on serum fatty acid composition in type 2 diabetic rats. avicenna j med biochem. 2017;5(1):22-8. 26. wang jy, zhu c, qian tw, guo h, wang dd, zhang f, et al. extracts of black bean peel and pomegranate peel ameliorate oxidative stress-induced hyperglycemia in m i c e . e x p e r i m e n ta l a n d t h e ra p e u t i c m e d i c i n e . 2015;9(1):43-8. 27. jin s, chang c, zhang l, liu y, huang x, chen z. chlorogenic acid improves late diabetes through adiponectin receptor s i g n a l i n g p a t h w a y s i n d b / d b m i c e . p l o s o n e . 2015;10(4):e0120842. 28. p ra b h a k a r p k , d o b l e m . s y n e r g i s t i c e f fe c t o f phytochemicals in combination with hypoglycemic drugs on glucose uptake in myotubes. phytomedicine. 2009;16(12):1119-26. abridged for primary care providers. clinical diabetes: a publication of the american diabetes association. 2016;34(1):3. 14. ghorbani a, shafiee-nick r, rakhshandeh h, borji a. antihyperlipidemic effect of a polyherbal mixture in streptozotocin-induced diabetic rats. journal of lipids. 2013;2013. 15. hui h, tang g, go vlw. hypoglycemic herbs and their action mechanisms. chinese medicine. 2009;4(1):11. 16. cappelletti s, daria p, sani g, aromatario m. caffeine: cognitive and physical performance enhancer or psychoactive drug? current neuropharmacology. 2015;13(1):71-88. 17. esposito f, morisco f, verde v, ritieni a, alezio a, caporaso n, et al. moderate coffee consumption increases plasma glutathione but not homocysteine in healthy subjects. alimentary pharmacology & therapeutics. 2003;17(4):595601. 18. peterson as. health benefits of coffee. walter l aument family health center. 2007;2(4). 19. zhou x, li y, shi x, ma c. an overview on therapeutics attenuating amyloid β level in alzheimer's disease: targeting neurotransmission, inflammation, oxidative stress and enhanced cholesterol levels. american journal of translational research. 2016;8(2):246. 20. hall s, desbrow b, anoopkumar-dukie s, davey ak, arora d, mcdermott c, et al. a review of the bioactivity of coffee, caffeine and key coffee constituents on inflammatory responses linked to depression. food research international. 2015;76:626-36. 21. boia r, ambrosio af, santiago ar. therapeutic opportunities for caffeine and a2a receptor antagonists in 32 jiimc 2019 vol. 14, no.1 diabetes treatment: black coffee vs metformin original�article study design: cross sectional study. abstract place and duration of study: the study was conducted at islamic international medical college from september 2015 to march 2016. results: results have established that vitamin d levels in children have positive association to their socioeconomic status. vitamin d deficiency is seen in offspring belonging to low socioeconomic status and dental caries was also present in them. pearson correlation and chi-square analysis have showed that increased dmft caries score is correlated with vitamin d concentrations less than 30ng/ml and lower monthly income. this cross-sectional study showed that caries, less serum vitamin d levels and low socioeconomic status are directly related with each other. objective: to find out the correlation of vitamin d levels with socioeconomic status and dental caries. materials and methods: eighty children, between 2-8 years of age, were recruited after fulfilling a questionnaire from their parents or caregiver. the sample population was divided into two groups keeping in mind their dental health. group 1 consisted of children suffering from dental caries and is comprised of 60 patients. group 2 consisted of children with sound healthy teeth and was comprised of 20 children. questionnaires assessing children ҆s socioeconomic background, dietary habits were included. the data was studied using likert scale. the diagnosis of childhood caries was based on oral health diagnostic criteria defined by who. total caries score, dmft index (decayed, missed, filled teeth) was obtained. venipuncture of participants was done for determining vitamin d levels of the study population by using elisa procedure. pearson correlation and chi-square analysis were applied to the results. conclusion: dental caries lower 25 hydroxy vitamin d levels and low socioeconomic status is closely linked. improving children's vitamin d levels by providing vitamin d supplementation or awareness of food rich in vitamin d may be helpful in decreasing the incidence of dental caries in young children. key words: decayed, early childhood caries (ecc), filled teeth (dmft), missed, 25 hydroxy vitamin d (25ohd). cholecalciferol is synthesized in human skin from 2 7dehydrocholesterol, on exposure to ultraviolet b irradiation with wavelength 290 to 320 nm convert 2,3 7dehydrocholesterol to d . serum vitamin d levels 3 depend on not only on sun exposure but also on its oral supply. few of these dietary sources include cod liver oil, fishes like salmon, sardines, cod fish and 4 mackerel, red meat and liver. certain foods are well fortified with vitamin d like breakfast cereals, 5 margarine, fruit juices and dairy products. ergocalciferol or cholecalciferol are inactive till their activation by two hydroxylases in liver and then in kidney so that it becomes metabolically active. calcium in the diet is absorbed from small intestine with help of vitamin d, which induces the formation 6 of protein called calbindin-d9k. this protein increases binding of calcium present in food. vitamin d deficiency in humans produce defects in bone introduction vitamin d also known as calciferol is fat soluble sterol derived vitamin. it is a prohormone. its two 1 forms are vitamin d and vitamin d vitamin d or 2 3 2 ergocalciferol is derived from plants, vitamin d or 3 correlation of hypovitaminosis d with socioeconomic status and dental caries in children 1 2 3 nusrat ali , amena rahim , syed muhammad ali correspondence: dr. nusrat ali assistant professor department of biochemistry hbs medical and dental college, islamabad. e-mail: smanizah75@gmail.com 1 department of biochemistry hbs medical and dental college, islamabad 2 department of biochemistry islamic international medical college riphah international university, islamabad 3 riphah institute of system engineering riphah international university, islamabad funding source: nil; conflict of interest: nil received: july 31, 2017; revised: october 26, 2019 accepted: november 15, 2019 jiimc 2019 vol. 14, no.4 socioeconomic status and dental caries in children 202 to find out the correlation between vitamin d, childhood caries and socioeconomic background, the following study was undertaken. it means that hypovitaminosis d is present in children with low socioeconomic background and they have more chances to develop dental caries. our study is done at small scale but it can be a significant breakthrough. materials and methods 12 reoccurrence. nutritional and sleep problems 19 affect growth of children. it was a cross-sectional observational study, held in the biochemistry department of iimc-t (islamic international medical college) rawalpindi in collaboration with iidc (islamic international dental college) islamabad after the approval from institutional review committee, and ethics committee of riphah international university for a period of six months, from september 2015 till march, 2016. sixty children with early childhood caries (ecc) as group 1 and twenty children with sound, healthy teeth as group 2 were included in this study. size of the sample was calculated, on the basis of prevalence and duration of study period. simple randomized sampling technique was used for sample collection. the patient were allocated without any bias or prior notification during the entire study period. samples were collected from different hospitals to ensure a fair degree of randomness. for grading dental caries an index, dmft was used which was achieved by adding d (decayed), m (missed), f (filled) teeth of children. the index is internationally accepted by the dental community for recording of decayed, missed and filled teeth. for each individual the occurrence of dental caries is obtained by calculating the number of decayed teeth d (the carious teeth), missed teeth m and the number of teeth have fillings or crown on tooth as f. score 0 for dmft shows that there is no caries and those having dmft score >4 were considered having excessive caries. a questionnaire which was given to the parents of the children revealed facts about their children food intake and their socioeconomic status. venipuncture of participants was done to determine serum vitamin d levels. serum samples were stored in freezers of post graduate laboratory at -70°c, biochemistry department of iimc rawalpindi. serum total 25(oh) d of the study subjects were measured using enzyme linked immunosorbent assay (elisa). mineralization resulting in a disease, rickets which occurs in children and osteomalacia, occurs in adults. vitamin d also has a definitive role in regulating acquired and innate immunity immune response. calcitriol also effect the differentiation and mineralization of osteoblasts. early childhood caries (ecc) is defined as carious lesions in incisors of the 7 deciduous dentition of the children. it is seen that 8,9 ecc is associated with low family income and it has also been observed that vitamin d insufficiency is mostly seen in children with low socioeconomic status. in other words it can be assumed that malnourished children have more tendencies to 10 develop dental caries and hypovitaminosis d. dental caries is a decay of teeth by different strains of bacteria, streptococcus mutans and streptococcus sobrinus mostly that results in cavitated and non 11 cavitated (white-spot) carious lesions. according to various studies, the frequency of caries in school going children of pakistan was 41%. however in the five year old children this index was found as high as 9 75% . risk factor of low income is because of 12 unhealthy dietary habits. a highly significant association is found between caries and family 8 income patterns. it is established that a strong association exists between early childhood caries 9 and low socioeconomic status. chances of defective amelogenesis causing enamel hypoplasia , large pulp chambers and dentinal anomalies are enhanced when there is deficiency of vitamin d during development of tooth which is suggested as a significant risk factor for early childhood caries 7,13,14 ecc. these defects in enamel increase the chances of caries causing bacteria to develop 10 caries. chances of having dental caries are more if the mineralization of enamel and dentin is 15 decreased. prolonged vitamin d deficiency, decreases serum calcium levels and increases 16 parathyroid hormone. vitamin d level is measured from plasma concentration of the circulating 3 25(oh)d. serum 25(oh)d levels < than 20 ng/ml shows deficiency: serum 25(oh)d levels between 20-30 ng/ml denotes insufficiency: 30-44 ng/ml as sufficiency and 50-70 ng/ml is considered as optimal 1 7 l e v e l . p ro b l e m s a r i s i n g f ro m c a r i e s a r e immeasurable, there is difficulty in eating as the 18 affected child has to face the consequences expensive dental treatment and there is chance of jiimc 2019 vol. 14, no.4 socioeconomic status and dental caries in children 203 vitamin deficiency, insufficiency, sufficiency and optimal values are grouped as level 1, 2, 3 and 4 respectively on likert scale. socioeconomic status of the study subjects is also divided into four levels on likert scale in which level 1 indicates subjects whose economy is more than rs. 15,000 per month, level 2 indicates subjects whose economy is more than rs. 30,000 per month, level 3 indicates subjects whose economy is more than rs. 50,000 per month and level 4 indicates subjects whose economy is more than rs. 80,000 per month. chi-square analysis has showed that vitamin d levels have significant association with the socioeconomic status levels. statistically significant difference (p value less than 0.01) is seen in table no. iv when vitamin d levels of t h e s t u d y s u b j e c t s a r e c o m p a r e d w i t h socioeconomic status levels. combined correlation of vitamin d levels, and caries score of patients with socio economic status revealed that vitamin d and socio economic status have positive correlation of value 0.508 whereas, socio economic status and vitamin d levels have reverse correlation with caries of values -0.51 and 0.89 respectively with p value is 0.00 and correlation is significant at the 0.01 level. the results of our study reveal statistically significant difference (p value less than 0.001) in vitamin d levels of the study subjects with socioeconomic status groups. this study has showed that vitamin d deficiency, insufficiency and sufficiency is significantly related with socioeconomic status levels as shown in table no. iv questionnaire data was analyzed using likert scale. to find out the relationship between serum vitamin d levels, socioeconomic back ground and childhood caries, pearson's correlation method was applied. for data processing spss 21 was used. frequencies, means and standard deviations were determined. chi-square analysis was also applied. p value less than 0.05 was considered as significant. results have established association of vitamin d levels in children with early childhood caries. total number of children participated in the study was 80. in them 43, 54% were male and 37, 46% were female. the mean age of the patient was 5 years and 3 months. results table i: frequency distribu�on of vitamin d levels in study subjects table ii: economic status distribu�on of study subjects table iii: descrip�ve sta�s�cs of vitamin d levels table iv: associa�on of vitamin d levels with socioeconomic status jiimc 2019 vol. 14, no.4 socioeconomic status and dental caries in children 204 22 permanent dentition. the results also support our study. . the mechanisms behind that how sufficient vitamin d reduce the risk of caries might be that there is improved tooth development, better amelogenesis which results in perfect enamel formation, enhanced dentinal mineralization response to caries. vitamin d also induces cathelicidin and certain defensins which protect the teeth from caries causing bacterias. in a study conducted by forrest et al in 2011, it is concluded that vitamin d deficiency is a marker of 23 low socioeconomic status. a study conducted by mehboobali et al in 2015 have analyzed that vitamin d deficiency is present in population residing 24 outskirts of karachi, who have low economy. a cross-sectional study performed in canadian schools in 2015 by r.j. schroth et al, showed that hypovitaminosis d is closely related with extensive dental caries. the results of this study matches with 25 our findings. nowadays sugar consumption is increased a lot in the form of sweets and chocolates and children are less aware of brushing techniques and oral hygiene practices. it is also suggested by different studies that despite of all the facts described above, decreased oral hygiene, lack of education and increased consumption of sugar in diet and drinks are 20,26 prominent risk factors for caries. our study concludes that sufficient level of 25(oh) d in children has a significant role in decreasing dental caries and is also related to socioeconomic status of the children. this study has not only established the close relationship of vitamin d and dental caries but has also revealed the effect of socioeconomic status as a significant contributing factor in this region. it is therefore suggested that our children's vitamin d status should be improved by fortification of food at national level and there should be awareness among people about food rich in vitamin d and calcium. conclusion in most of the cross-sectional, case control and prospective studies, vitamin d deficiency has been considered to be linked with more chances of dental caries. it is also worth mentioning that vitamin d deficiency in individuals might result from lack of sun exposure or it might be due to malnutrition or some gene polymorphism is involved. improving the diet of children by including food rich in vitamin d may have valuable effects on overall health of the child and on dental health. there should be mass education on awareness of foods having vitamin d and calcium so that general health of our population will be improved. discussion this study was undertaken to find out the correlation between vitamin d, socioeconomic background and caries in young children. a cross-sectional study was conducted which includes physical calculations, laboratory tests and interviews of parents. there were 80 children between age 3-8 years who were visiting dental hospital. in total 80 study subjects 20 children have sound teeth without caries (group 2) and 60 children were having dental caries at different levels (group 1), which was measured by dmft score. the current study examined the correlation of vitamin d levels with different groups of socioeconomic status of children and relates this with extent of dental caries. this study has showed that vitamin d deficiency, vitamin d insufficiency and vitamin d sufficiency is significantly related with socioeconomic status levels. vitamin d levels and socioeconomic backgrounds are strongly correlated to extent of dental caries in childhood. a study done by sufia et al in 2011, it is concluded that dental caries is more prevalent in preschool children living in metropolitan areas and in lower 9 middle class. charani et al in 2011 have also found that there is a correlation between childhood caries 8 and family social background. leghari et al in 2012 have also revealed that there is more frequency of dental caries in children of public schools than 20 private schools. our study has showed that vitamin d deficiency and insufficiency is related to low and middle economy levels. a study conducted in canada by schroth et al in 2013 has concluded that vitamin d deficiency and insufficiency is more common in children of lower socioeconomic status and also there is more ecc in 21 them. it is also suggested that this vitamin d deficiency and insufficiency plays main role in development of dental caries in children. these findings match with results of our study. in a study held in germany by kühnisch et al. in 2015 suggested that higher serum vitamin d levels were linked with fewer chances of having extensive dental caries in jiimc 2019 vol. 14, no.4 socioeconomic status and dental caries in children 205 20. leghari ma, tanwir f. dental caries prevalence and risk factors among school children age12-15 years in malir, karachi. pakistan oral & dental journal. 2012;32(3). 18. clementino ma, gomes mc, de almeida pinto-sarmento tc, martins cc, granville-garcia af, paiva sm. perceived impact of dental pain on the quality of life of preschool children and their families. plos one. 2015;10(6). 26. bener a, al darwish ms, hoffmann gf. vitamin d deficiency and risk of dental caries among young children: a public health problem. indian journal of oral sciences. 2013;4(2):75. 19. leghari ma. a pilot study on oral health knowledge of parents related to dental caries of their children-karachi, pakistan. 2012. 22. kühnisch j, thiering e, kratzsch j, heinrich-weltzien r, hickel r, heinrich j, et al. elevated serum 25 (oh)-vitamin d levels are negatively correlated with molar-incisor hypomineralization. journal of dental research. 2015;94(2):381-7. 25. schroth r, rabbani r, loewen g, moffatt m. vitamin d and dental caries in children. journal of dental research. 2015:0022034515616335. 21. schroth rj, levi ja, sellers ea, friel j, kliewer e, moffatt me. vitamin d status of children with severe early childhood c a r i e s : a c a s e – c o n t r o l s t u d y. b m c p e d i a t r i c s . 2013;13(1):174. 15. antonenko o, bryk g, brito g, pellegrini g, zeni s. oral health in young women having a low calcium and vitamin d nutritional status. clinical oral investigations. 2014:1-8. 16. haussler mr, whitfield gk, kaneko i, haussler ca, hsieh d, hsieh j-c, et al. molecular mechanisms of vitamin d action. calcified tissue international. 2013;92(2):77-98. 17. anderson ph, lam nn, turner ag, davey ra, kogawa m, atkins gj, et al. the pleiotropic effects of vitamin d in bone. the journal of steroid biochemistry and molecular biology. 2013;136:190-4. 23. forrest ky, stuhldreher wl. prevalence and correlates of vitamin d deficiency in us adults. nutrition research. 2011;31(1):48-54. 24. mehboobali n, iqbal sp, iqbal mp. high prevalence of vitamin d deficiency and insufficiency in a low income periurban community in karachi. jpma the journal of the pakistan medical association. 2015;65(9):946-59. 5. holick mf. vitamin d deficiency. new england journal of medicine. 2007;357(3):266-81. 11. banerjee a, pickard hm, watson tf. pickard's manual of operative dentistry: oxford university press; 2011. 4. bowden sa, robinson rf, carr r, mahan jd. prevalence of vitamin d deficiency and insufficiency in children with osteopenia or osteoporosis referred to a pediatric metabolic bone clinic. pediatrics. 2008;121(6):e1585-e90. 6. anderson p, may b, morris h. vitamin d metabolism: new concepts and clinical implications. clinical biochemist reviews. 2003;24(1):13-26. 7. schroth rj, lavelle c, tate r, bruce s, billings rj, moffatt me. prenatal vitamin d and dental caries in infants. pediatrics. 2014;133(5):e1277-e84. 9. sufia s, chaudhry s, izhar f, syed a, qayum mirza ba, ali khan a. dental caries experience in preschool children is it related to a child's place of residence and family income? oral health and preventive dentistry. 2011;9(4):375. references 1. harvey ra, ferrier dr. biochemistry: lippincott williams & wilkins; 2011. 8. charani a, mohsin s, sufia s, khan a. prevalence of early childhood caries among 3-5-year old children of clifton, karachi. j of pak dent assoc. 2011;20:89-92. 10. marwaha rk, tandon n, reddy drh, aggarwal r, singh r, sawhney rc, et al. vitamin d and bone mineral density status of healthy schoolchildren in northern india. the american journal of clinical nutrition. 2005;82(2):477-82. 14. slayton rl. prenatal vitamin d deficiency and early childhood caries. aap grand rounds. 2014;32(5):57-. 3. rodwell vw, bender da, botham km, kennelly pj, weil pa. harpers illustrated biochemistry: mcgraw-hill medical publishing division; 2015. 2. del valle hb, yaktine al, taylor cl, ross ac. dietary reference intakes for calcium and vitamin d: national academies press; 2011. 12. syed s, nisar n, khan n, dawani n, mubeen n, mehreen z. prevalence and factors leading to early childhood caries among children (71 months of age or younger) in karachi, pakistan. journal of dentistry and oral hygiene. 2015;7(9):153-9. 13. berdal a, bailleul-forestier i, davideau j, lezot f. dentoalveolar bone complex and vitamin d. vitamin d. 2005;1:599-607. jiimc 2019 vol. 14, no.4 socioeconomic status and dental caries in children 206 jiimc 2015 vol. 10, no.4 treatment of cervicobrachial pain syndrome 262 original article efficacy of cervical spine mobilization versus peripheral nerve slider techniques (neurodynamics) in cervicobrachial pain syndrome muhammad riaz khan 1 , hina shafi 2 , imran amjad 3 , furqan ahmed siddiqui 4 abstract objective: the objective of this study was to compare the efficacy of cervical spine mobilization versus peripheral nerve slider techniques (neurodynamics) incervicobrachial pain syndrome. study design: the study design was arandomized interventional study. place and duration of study: this study was conducted at the armed forces institute of rehabilitation medicine (afirm), rawalpindi from august 2014 to january 2015. materials and methods: forty patients (n=40) were included by using purposive sampling technique. patients of age 30 to 60 years with radiating neck pain, limited rom of neck and pain persisting for more than 2 months, were included in study. then randomly divided into two groups, each group contains 20 participants. one group was treated with neck mobilization and other was treated with neurodynamic treatment protocol. pain and active range of motion (arom) was measured by visual analog scale (vas) and inclinometer respectively. neck disability index was also used. patients were assessed before and after six week intervention. data was analyzed on spss 20 and independent t test was used to compare the results of two groups. results: pain was measured on vas, the mean of mobilization and neurodynamics were (2.0+1.892 vs. 4.8+2.397) respectively. there is significant (p<0.05) difference between two groups. there is also significant (p<0.05)difference for range of motion between two groups. the mean value for ndi of both groups were (14.5+7.564 vs 26.80+11.484). it also shows better treatment is mobilization. conclusion: the results of this comparison between two single interventions indicate that cervical mobilization treatment in neck pain is more useful than anneurodynamic treatment. for daily practice, we can recommend treatment according to the expert guidelines investigated. key words: neurodynamic, neck mobilization, ndi, vas. introduction neck pain is the major health complains in our society and also worldwide. when there is a combination of neck pain and complaint in the arm, we can call it a cervicobrachial syndrome or cervicobrachialgia. it refers to a cervical syndrome with pain radiating into the upper limb. cervicobrachial syndrome was, therefore, previously known as “lower cervical syndrome”. life time prevelance of cervicobrachialgia is 71%. 1 cervicobrachialgiais one of those condition which has huge financial and disabling impact on 1 department of rehabilitation sciences armed forces institute of rehabilitation medicine, rawalpindi 2,4 foundation university institute of rehabilitation sciences, islamabad 3 rcrs, riphah international university, islamabad correspondence: dr. imran amjad assistant professor, rcrs riphah international university, islamabad e-mail: mianimran.pt@gmail.com received: september 19, 2015; accepted: november 17, 2015 population. 1 in cervicobrachialgia the cervical canal may be narrowed by osteophyticlipping of the facet or uncovertebral joints, by central disc herniations, by thickening of the ligamentumflavem, or even from local cervical vertebral subluxations associated with ligamentous laxity. 2 vertebral artery involvement by osteophytic outgrowths or local spinal instability may cause drop attacks precipitated by extension of the neck. osteophytes arising from the anterior vertebral margins may sometimes, because of their size, give rise to dysphagia 3 neck pain is a common disorder in our population, and combined with low back pain. a number of studies show moderate to good evidence that manual therapy may all eviate neck pain. this an algesicef fect may not only bee xplained by traditional approaches such as the gate control. the oryand reduce peripheral afferent discharge but also by the activation of central nervous pain mechanisms such as the peri aqueductal gray, which seems to be responsible for modulation of auto mailto:mianimran.pt@gmail.com treatment of cervicobrachial pain syndrome jiimc 2015 vol. 10, no.4 263 nomic functions and pain control. there was greater improvement in function and pain with manual therapy (manipulation/mobilization) directly on the cervical spine and indirectly on the shoulder and dorsal spine than without treatment. 4 neuromobilization maneuver has recently been used to treat nerve entrapment syndromes. it consists of a series of therapeutic active and passive movements aimed at restoring the normal mechanical properties of the nerve in common postures and during extremity movements. neuromobilization maneuvers help to restore longitudinal motion of the affected nerve. any pathology that reduces the nerve motion and normalstrain may produce an abnormal tension in the corresponding nerve in common postures and during extremity movements. 5 as nerve mobilization only improve the mobility of nerve within different interfaces. 4 if the compression will be on these interfaces then it will be relive by neurodynamics. on the other hand cervical mobilization also decreases pressure on nerve roots. individually these therapeutics techniques are effective for cervicobrachialgia but with certain limitations. so the objective of this study was to compare the effects of neudynamics and cervical mobilization on cervicobrachial pain. materials and methods the study design was randomized interventional study, conducted at the afirm rawalpindi, from august 2014 to january 2015. the study protocol was duly approved from ethical committees of afirm. total sample size was 40 patients. patients of age 30 to 60 years with radiating neck pain, limited rom of neck and pain persisting for more than 2 months, were included in study. but patients with spinal stenosis, disc bulge, spinal surgery, carcinoma and neuromuscular pathology were excluded from study. we divided patients in both groups by lottery draw method. in mobilization group treatment was given by fallowing the maitland treatment guidelines and control group was treated with standard protocol of neurodynamics. data collectio n variables were structured questionnaire, vas, range of motion (rom), ndi, and neck bournemouth questionnaire. this was quantitative, parametric data. it was entered on spss 20 software and independent t test was applied to compare the results of two groups. results all participants (n=40) of this study were divided into mobilization (n=20) and neurodynamic groups (n=20). the mean age of mobilization group was 52.60+6.159 and neurodynamic group was 42.70 + 9.953. there is significant difference (p<0.05) for neck disability index between mobilization (14.50+ 7.564) and neurodynamics (26.80 + 11.484) group (fig 1). mean + sd of all neck ranges (degrees) flexion, extension, side bending to painful and non painful side, rotations of both sides of neck in both group was measured (table i). there is significant difference (p<0.05) between both group. there is also significant difference (p<0.05) for visual analogue scale between mobilization (2.0+ 1.892) and neurodynamics (4.8 + 2.397) group (tableii). fig 1: mean of visual analogue scale in mobilization and neurodynamic group. there is significant difference (p<0.05) between both groups table i: mean and standard deviation of flexion, extension, side bending painful side, side bending non painful side, rotation painful side, rotation non-painful side variables mobilization mean +sd nuerodynamics mean +sd p-value flexion of neck 71.50+4.323 63.00+7.504 0.000*** extension of neck 43.75+2.221 39.75+4.128 0.000*** side bending pain full side 39.25+2.447 34.50+4.261 0.000*** side bending non pain full side 38.25+4.375 35.0+4.292 0.023* rotation pain full side 37.00+6.959 36.0+6.407 0.639 rotation non pain full side 33.25+7.482 32.75+6.382 0.821 visual analog scale 2.0+1.892 4.8+2.397 0.000*** neck disability index (ndi) 14.50+7.564 26.80+11.484 0.000*** jiimc 2015 vol. 10, no.4 treatment of cervicobrachial pain syndrome 264 table ii: mean and standard deviation of visual analog scale (vas), ndi, rate neck pain, neck pain interfared activity (adl), neck pain interfered social activity, neck pain & anxiousness, neck pain & depression, neck pain affected on job, self control on neck pain variables mobilization mean +sd nuerodynamics mean +sd p-value visual analog scale 2.0+1.892 4.8+2.397 0.000*** neck disability index (ndi) 14.50+7.564 26.80+11.484 0.000*** rate neck pain 1.55+1.504 4.70+2.364 0.000*** neck pain interfered your activity 1.65+1.872 4.10+2.882 0.003** neck pain interfered your social activity 1.70+1.658 4.40+-2.664 0.000*** how anxious your feeing 1.65+1.599 4.05+-2.523 0.001** how depressed 1.50+-1.573 4.30+2.577 0.000** how your work affected 1.40+1.729 3.90+2.808 0.002** how much able to control your neck pain 1.10+1.518 3.75+2.468 0.000*** discussion the results revealed significant pain reduction in the neck pain for the patients who received cervical mobilization. over the investigation period, these patients showed a decreases in neck pain on the visual analogue scale which can be regarded as a clinically relevant change. 7 to date, the only known study to compare articular with neurodynamic treatment was conducted by allison et al. 8 thirty patients with cervicobrachial pain were randomly assigned to one of three groups: neural treatment, articular treatment, and control group. neural treatment involved mobilization techniques for neural and adjacent tissues, such as cervical lateral glide, shoulder girdle oscillation and muscle re-education. the articular treatment consisted of indirect approaches such as g l e n o h u m e r a l m o b i l i z a t i o n and t h o r a c i c mobilization. no treatment was performed in the third group. pain was assessed at baseline and after four and eight weeks. the result showed significant pain reduction in both group. furthermore the between group comparison revealed a significant difference after eight weeks with the patients in the neural treatment groups reporting lower pain on the vas than those receiving the articular treatment. the authors concluded that both interventions could significantly reduce pain with a potential advantage for the specific neural treatment but mentioned that the articular treatment is a generalized treatment not addressed to actual joint dysfunction. therefore the effects of the articular treatment approach can be regarded as indirectly supporting the hypothesis that less direct techniques could also affect neural structures. although comparing a neural with an articular treatment approach, these findings may not be compared to the results in the present study. while allison et al 8 performed neurodynamic techniques in com binatio n with articular mobilization techniques, for example the cervical lateral glide, which is thought to influence the neural as well as the articular tissues 9 , within one group, these techniques were explicitly separated in the present study. the analgesic effect of cervical mobilization t e c h n i q u e s i s s u p p o r t e d b y o t h e r investigations. 10,11,12,13 schmid et al 12 and bialsky et al 14 suggested that supraspinal centers are likely to be important in pain modulation. furthermore, they hypothesized that the periaqueductal grey (pag) in the midbrain may be involved. an analgesic effect through the likely activation of this supraspinal center may explain the pain reduction in regions not directly addressed by the treatment. in the present study this effect can be seen in the patients who received neurodynamic treatment and experienced decreased neck pain. in the patients who received cervical mobilization, the analgesic effects in the neck and arm may either be explained by the above mentioned supraspinal centers or by an improved functioning of the mechanical interfaces. due to the mobilization, the facet joints are supposed to have a better opening and closing function, thereby reducing compression on neural tissues. this reduced compression might contribute to improve physiological and mechanical conditions in the neural tissues, leading to analgesic effects in the upper extremity. 15 regarding cervical range of motion, the patients in experimental group gradually improved more than the patients in control group. a possible reason for this might be that the patients in experimental group received mobilization techniques directly applied at the cervical spine. these techniques are not only effective for pain reduction but also for increasing range of motion[15], where as the primary objective treatment of cervicobrachial pain syndrome jiimc 2015 vol. 10, no.4 265 of neurodynamic techniques is not an increase in cervical range of motion but pain reduction as well as an increase in neural mobility. 14,15 for these reasons, a greater improvement in the cervical range of motion through the mobilization treatment was expected. although to a lesser extent, the neurodynamic treatment also led to increases in cervical range of motion. this may be explained by the improved gliding and sliding of neural tissues leading to reduced interference of the cervical motions. 15 conclusion the results of this comparison between two single interventions indicate that cervical mobilization treatment in neck pain is more useful than neurodynamic treatment. for daily practice, we can recommend treatment according to the expert guidelines investigated. however, further research is needed to provide stronger scientific evidence. there is greater improvement in function and pain with manual therapy (mobilization) directly on the cervical spine and indirectly on the shoulder and dorsal spine than without treatment. references 1. shin wr, kim hi, shin dg, shin da. radiofrequency neurotomy of cervical medial branches for chronic cervicobrachialgia. journal of korean medical science. 2006; 21:119-25. 2. mcrae r. clinical orthopaedic examination: elsevier health sciences; 2010. 3. salt e, wright c, kelly s, dean a. a systematic literature review on the effectiveness of non-invasive therapy for cervicobrachial pain. manual therapy. 2011;16: 53-65. 4. oskouei ae, talebi ga, shakouri sk, ghabili k. effects of neuromobilization maneuver on clinical and electrophysiological measures of patients with carpal tunnel syndrome. journal of physical therapy science. 2014; 26: 1017. 5. martínez jam. an overview on the efficacy of manual therapy (manipulations and mobilisations) on nonspecific cervical pain: a systematic review in adults: intech open access publisher; 2012. 6. davis ds, anderson ib, carson mg, elkins cl, stuckey lb. upper limb neural tension and seated slump tests: the false positive rate among healthy young adults without cervical or lumbar symptoms. journal of manual &manipulative therapy. 2008; 16: 136-41. 7. kovacs fm, abraira v, royuela a, corcoll j, alegre l, tomás m, et al. minimum detectable and minimal clinically important changes for pain in patients with nonspecific neck pain. bmc musculoskeletal disorders. 2008; 9: 43. 8. allison g, nagy b, hall t. a randomized clinical trial of manual therapy for cervico-brachial pain syndrome a pilot study. manual therapy. 2002;7: 95-102. 9. vicenzino b, neal r, collins d, wright a. the displacement, velocity and frequency profile of the frontal plane motion produced by the cervical lateral glide treatment technique. clinical biomechanics. 1999;14: 515-21. 10. sterling m, jull g, wright a. cervical mobilisation: concurrent effects on pain, sympathetic nervous system activity and motor activity. manual therapy. 2001; 6: 72-81. 11. macaulay j, cameron m, vaughan b. the effectiveness of manual therapy for neck pain: a systematic review of the literature. physical therapy reviews. 2007; 12: 261-7. 12. schmid a, brunner f, wright a, bachmann lm. paradigm shift in manual therapy? evidence for a central nervous system component in the response to passive cervical joint mobilisation. manual therapy. 2008; 13: 387-96. 13. schomacher j. the effect of an analgesic mobilization technique when applied at symptomatic or asymptomatic levels of the cervical spine in subjects with neck pain: a randomized controlled trial. journal of manual & manipulative therapy. 2009; 17:101-8. 14. bialosky je, bishop md, price dd, robinson me, george sz. the mechanisms of manual therapy in the treatment of musculoskeletal pain: a comprehensive model. manual therapy. 2009;14: 531-8. 15. shacklock m. clinical neurodynamics: a new system of musculoskeletal treatment: elsevier health sciences; 2005. original�article abstract objective: the aim of the study was to determine the mean distance of obturation from the radiographic apex, in maxillary and mandibular teeth, using electronic apex locator for working length measurement. study design: cross sectional study. place and duration of study: the study was conducted in the department of operative dentistry, at islamic st th international dental hospital, riphah international university from september 1 , 2016 to march 15 , 2017. materials and methods: the mean distance of obturation from radiographic apex was evaluated in 97 canals of 43 patients, between 14 to 55 years of age. working length was determined by using dentaport zx apex locator. canals were prepared by using step back technique and obturated by cold lateral condensation technique. postoperative radiographs were taken by using paralleling technique and the results were evaluated in spss version 24. results: the mean distance of obturation from radiographic apex was found to be -0.52mm with standard deviation (sd) of + 0.57.no statistically significant difference was found between the apical limit of canal filling on the basis of tooth vitality and tooth type. (p-value > 0.05). conclusion: this study suggested that appropriate use of apex locator can decrease the required number of radiographs during endodontic treatment and can be used reliably with no statistically significant difference in mean distance of obturation from radiographic apex when used in maxillary and mandibular teeth. key words: electronic apex locator, obturation, working length determination. agreed upon that canal preparation and root canal 3 filling should end at or short of apical constriction. m o r e o v e r, o p t i m a l h e a l i n g o c c u r s w h e n instrumentation and filling is contained within the region of apical constriction. conventional methods used for working length determination are use of anatomical averages and knowledge of anatomy, tactile sensation, moisture on paper point and 4 radiography. radiographic method is the most common method for working length determination, however, this 5 method has limitations. radiographic method, provides an estimation of the apical constriction which is histological landmark. although clinically beneficial, averages utilized to define the radiographic apex from apical constriction could 6 result in over filling or under filling of canal. additionally, radiation hazard both to patients and dental personnel is one of limitations of 2 radiography. this led to the development of electronic apex locators (eals), which has helped in making the assessment of working length more 7 accurate and predictable. most electronic apex 8 locators are based on the theory of sunada. introduction an accurate working length determination is one of the critical steps in the endodontic “triad of success” thorough microbial disinfection, ideal canal preparation and hermetic seal. it determines how far the canal preparation and later on obturation should 1 , 2 b e ex ten d ed . in accu rate wo rkin g len gth determination can lead to iatrogenic errors, patient discomfort and possible infection. it is generally determination of mean distance of obturation from radiographic apex by using electronic method of working length measurement 1 2 3 4 muhammad qasim javed , alia ahmed , adil shahnawaz , hira zaman correspondence: dr. muhammad qasim javed assistant professor, operative dentistry islamic international dental college riphah international university, islamabad e-mail: qasim.javed@riphah.edu.pk 1,2 department of operative dentistry islamic international dental college riphah international university, islamabad 3 department of operative dentistry abbottabad international medical and dental college abbottabad 4 department of operative dentistry shaheed zulfiqar ali bhutto medical university pims, islamabad funding source: nil; conflict of interest: nil received: jan 26, 2018; revised: jun 02, 2018 accepted: jun 04, 2018 obturation distance using electronic working length determinationjiimc 2018 vol. 13, no.2 91 dentaport zx (j.morita corp, tokyo, japan) is an 7,9 impedance type locator and has proved effective in working length determination even in the presence of different electrolytes, blood and irrigant solutions 10,11 in the canals moreover, electronic apex locators have demonstrated efficiency in teeth with difficult 12 13 canal morphology , intracanal exudate , large apical 14 13 foramen or periapical lesion. current literature suggests that apex locators should be considered as useful adjunct to the radiographic method, not its replacement, and it improves the 7,15 accuracy of working length determination. additionally, use of eals could possibly decrease the quantity of radiographs taken for the determination 2 of working length. even though new generations of apex locators give accurate reading, current practice 2 is to confirm electronic reading, radiographically. on the other hand, completing endodontic treatment without the need for a working length radiograph would not only save the time and cost of root canal treatment but will also significantly reduce the radiation exposure of the patients. the current study helped to ascertain, how the use of eals alone for working length determination affect the extent of root canal filling. the objective of the study was to determine the mean distance of obturation from the radiographic apex, in maxillary and mandibular teeth, using electronic apex locator (dentaport zx) for working length measurement. materials and methods the cross-sectional study was conducted in the department of operative dentistry, at islamic international dental hospital (iidh), riphah st international university from 1 september, 2016 to th 15 march, 2017. sample size was calculated using world health organization sample size calculator with confidence interval=95% .estimated population 2 mean was 0.5, estimated standard deviation was 0.5 and absolute precision required was 0.1. sample (n) was comprised of 97 canals of 43 teeth. nonprobability consecutive sampling technique was used. the study was approved by ethical review board of iidh. all teeth requiring endodontic treatment with completely formed roots were included in the study. teeth with resorbed roots/open apices, previously endodontically treated, calcified canals and patients with heart pacemaker were excluded. in the present in vivo, ex vivo study 97 canals of 43 patients, between the age group of 14 to 55 years were studied. both male and female requiring root canal treatment of single and multi-rooted teeth were treated by following the procedure as mentioned below. an informed written consent of the patient was obtained. a standardized data collection proforma was used for recording the required details. a preoperative periapical radiograph placed in a film holder (hawe x-ray film 16 holder system) was taken by paralleling technique. after administration of local anesthesia standard 17 access cavity was prepared. tooth was isolated by rubber dam and vitality was assessed on the basis of bleeding on initial instrumentation of canal. the irrigation of the pulp chamber was carried out by 2.5% sodium hypochlorite solution and chamber was dried by performing aspiration. after that dentaport zx, third generation apex locator was used on emr mode (electronic measurement of root canal mode). the size 15 k file (mani) was advanced into the canal and apical line indicator on the led of the apex locator was adjusted at 0.5 position. the rapid tone was noted with the illumination of led green light at 0.5 position. after that silicone stopper was adjusted against reference point. the distance from file tip and silicone stopper was then measured and registered as working length. cleaning and shaping was done using k files size 15-40 (mani) using a step back technique. during cleaning and shaping, sodium hypochlorite was used as an irrigant in 2.5% concentration. subsequently, paper points were used to dry the canal prior to obturation. obturation was performed by utilizing gutta percha and endomethasone sealer with cold lateral compaction technique. a postoperative periapical radiograph was taken by paralleling technique. endodontic treatment was completed within 1 to 3 visits depending on pathological status, patient's cooperation, time available and difficulty of case. post obturation periapical radiographs were evaluated on radiograph illuminator by using 2.5x magnifying loupes (keeler supervu galilean loupe, 18 inches working distance). distances were measured in millimeters from the end of obturation to radiographic apex of tooth to an accuracy of 0.5 mm twice, at two separate occasions. the mean of two readings was calculated and recorded. a negative sign (-ve) was used if obturation was short obturation distance using electronic working length determinationjiimc 2018 vol. 13, no.2 92 of apex and positive (+ve) sign was used if obturation extended beyond the apex. all the collected data was analyzed using statistical package for social sciences (spss version 24). descriptive statistics were used. mean and standard deviation was calculated for obturation length measurements (in millimeters). frequency and percentages were calculated for gender, age, status and type of tooth. independent sample t-test was utilized to determine the difference between mean distance from tip of root canal filling to radiographic apex in vital and non-vital teeth and for calculating the p-value. anova test was used to determine the difference between mean distance from tip of root canal filling to radiographic apex in anterior, premolar and molar teeth. results the total number of patients who were assessed for eligibility was 70, out of which 25 patients were excluded as they did not meet the inclusion criteria. of the 45 patients enrolled for the study 2 patients were excluded from the study one because of instrument breakage during canal preparation and other because of inability of an instrument to reach the apical foramen, resulting in 43 teeth with 97 canals for the outcome analysis. the age of the patients ranged between 14 years and 55 years as shown in fig 1. using independent t-test it was found that there was no statistically significant difference between mean distance from tip of root canal filling to radiographic apex in vital and non-vital teeth (p value > 0.05) , as shown in the table i. fig 1: age distribu�on the mean age was found to be 33.83 years with the standard deviation of 13.93. out of 97 patients, 61 were males and 36 were females. canals of molar teeth were comparatively more, 74 in number, followed by anteriors and premolars which were found to be 12 and 11 in numbers, respectively. the distance of obturation from radiographic apex was calculated at two different occasions and their means were calculated for all 97 canals. the mean of two readings was entered in spss version 24 and the mean of all 97 readings was found to be -0.52mm and standard deviation was found to be + 0.57mm. table i: comparison between mean distances of obtura�on from radiographic apex in vital and nonvital teeth table ii: comparison between mean distances of obtura�on from radiographic apex in different teeth type the mean distance from the radiographic apex to the tip of root canal filling was found to be -0.52 mm, 0.23 mm and -0.56 mm for anteriors, premolars and molars, respectively. using anova test, it was found that there was no statistically significant difference between mean distance from tip of root canal filling to radiographic apex in anterior, premolar and molar teeth (p-value=0.202), as shown in the table ii. the mean distance from tip of root canal filling to radiographic apex was found to be 0.49 mm for maxillary teeth and -0.55 mm for mandibular teeth with standard deviation of ±0.56 and ±0.59, respectively. using independent t-test it was found that there was no statistically significant difference between mean distance from tip of root canal filling to radiographic apex in maxillary and mandibular teeth (p value > 0.05) , as shown in the table iii. table iii: comparison between mean distances of obtura�on from radiographic apex in maxillary and mandibular teeth obturation distance using electronic working length determinationjiimc 2018 vol. 13, no.2 93 discussion the utilization of electronic apex locators for determination of working length has increased 2 substantially in the current years and they have been increasingly incorporated into the modern 18 practice of endodontics. the purpose of the present study was to determine the mean distance of canal filling from the radiographic apex, using electronic apex locator (dentaport zx) for working length measurement. several researchers in the past have worked to evaluate the accuracy of apex locators. researchers utilized teeth which were to be extracted for comparing the electronically determined length to various reference points, such as radiographic apex, apical foramen and apical constriction in different in 19,20,21 vivo studies on the other hand, electro conductive material like saline was used for simulating the clinical conditions in the in vitro 22 studies. contrary to the aforementioned studies, the present clinical study is true representative of what occurs during typical endodontic treatment, thereby, incorporating errors that might occur in the 2 oral cavity. in the present study the mean distance of obturation from radiographic apex was found to be -0.52 mm. the findings were in line with the results of the study 2 conducted by l smadi et al who found the mean distance of obturation from radiographic apex as 0.5mm when only eal was used for working length determination. obturation length found in the present study was within acceptable clinical limit as 15 15 concluded by fouad and reid. fouad and reid deemed root canal filling as acceptable when it was found to be 0 to 2mm short of radiographic apex. 23 likewise, ravanshad et al in their research concluded that there was no difference in the radiographic length measurement of root canal filling of two groups, when working length was determined by eal only and radiograph only. overfilling of canals was not noted in the current study. the results are clinically acceptable as they are 24 supported by the meta-analysis by schaeffer et al in which it was found that most successful endodontic treatments are those in which obturation is within 1mm of radiographic apex followed by those which ends within 1 to 3 mm and both were found superior to obturation beyond the apex in terms of success. 25 likewise, swartz and colleagues in their study concluded that the chances of failure of root canal treatment increases to four times when canal is overfilled as compared to under filled canal. 26 however, halse et al studied canals, which were slightly overfilled radiographically, 10 to 17 years after obturation and gave the conclusion that obturation with filling material in slight excess generally results in successful endodontic treatment. 27 28 contrary to this, kojima et al and wu et al found higher success rates when obturation was close to or at the radiographic apex. in the current study, the preoperative pulpal status did not seem to influence the functionality of the root zx apex locator. therefore, the difference in the apical limit of canal filling in the teeth with vital and non-vital pulp was found to be statistically insignificant. similar findings were reported in 2,19,21 previous studies. conversely, pommer and 29 colleagues noted higher accuracy of apex locators in the teeth canals with vital pulp tissue. however, 30 recent meta-analysis concluded that vitality of the pulp have no influence on the accurate functioning of electronic apex locators. the results of the present study suggest that apex locator can reliably be used as a method of working length determination and in future can replace radiographic method as a mean of working length determination. this suggestion would adhere to as 31 low as reasonably achievable principle (alara) in relation to radiographic exposure at one end and greater accuracy of modern apex locators as 19,23 concluded in other studies at the other end. this suggestion, however, is not in keeping with the 32 suggestion of hoer and attin who suggested that apex locators should always be used in combination 33 with radiographs. alternatively, saad and al-nazhan argued that it is possible to perform successful endodontic treatment by utilizing only apex locator for working length determination. the small sample size of 97 canals is one of the limitations of this study. this sample size did not allow detailed analyses of results. increasing the number of teeth will give more valid and reliable statistical data. the other limitation is that this is single arm study and comparison is not made by using the gold standard method .i.e. radiographic m e t h o d a s a m e t h o d o f w o r k i n g l e n g t h obturation distance using electronic working length determinationjiimc 2018 vol. 13, no.2 94 determination to evaluate the difference between two methods. lastly, only one brand of apex locator (root zx) was used in the current study; therefore, the results cannot be generalized to all the apex locators. further studies, with larger sample size and multiple brands of electronic apex locators under varying clinical conditions, are suggested to verify the results of current research conclusion the routine practice of utilizing apex locator for working length determination is reliable and appropriate with no statistically significant difference of the apical extent of root canal filling in the teeth with vital or non-vital pulp. within the clinical setting of the current study, it is proposed that accurate use of electronic apex locator alone can limit the need of taking diagnostic radiographs for measurement of working length. subsequently, it will also reduce the radiation exposure of patients. references 1. qazi hs, maxood a, abdullah s. comparison of 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preliminary report using the tri auto zx apex locating handpiece. int endod j. 2002; 35: 590–3. 20. shabahang s, goon ww, gluskin ah: an in vivo evaluation of root zx electronic apex locator. j endod. 1996; 22: 616-8. 21. dunlap ca, remeikis na, begole ea, rauschenberger cr: an in vivo evaluation of an electronic apex locator that uses the ratio method in vital and necrotic canals. j endod. 1998; 24: 48-50. 22. ounsi hf, naaman a: in vitro evaluation of the reliability of the root zx electronic apex locator. int endod j. 1999; 32: 120-3. 23. ravanshad s, adl a, anvar j. effect of working length measurement by electronic apex locator or radiography on the adequacy of final working length: a randomized clinical trial. j endod. 2010; 36: 1753-6. 24. schaeffer ma, white rr, walton re. determining the optimal obturation length: a meta-analysis of literature. j endod. 2005; 31: 271-4. 25. swartz db, skidmore ae, griffin ja jr. twenty years of endodontic success and failure. j endod. 1983; 9: 198-202. 26. halse a, molven o. overextended gutta-percha and kloroperka n-o root canal fillings: radiographic findings after 10-17 years. acta odontol scand. 1987; 45: 171-7. 27. kojima k, inamoto k, nagamatsu k, hara a, nakata k, morita i, et al. success rate of endodontic treatment of teeth with vital and nonvital pulps. a meta-analysis. oral surg oral med oral pathol oral radiol endod. 2004; 97: 95-9. 28. wu mk, wesselink pr, walton re. apical terminus location of root canal treatment procedures. oral surg oral med oral pathol oral radiol endod. 2000; 89: 99-103. 29. pommer o, stamm o, attin t. influence of the canal contents on the electrical assisted determination of the length of root canals. j endod. 2002; 28: 83-5. obturation distance using electronic working length determinationjiimc 2018 vol. 13, no.2 95 30. tsesis i, blazer t, ben-izhack g, taschieri s, del fabbro m, corbella s, et al. the precision of electronic apex locators in working length determination: a systematic review and meta-analysis of theliterature. j endod. 2015; 41: 1818-23. 31. berkhout wer, suomalainen a, brüllmann d, jacobs r, horner k, stamatakis hc. dentomaxillofac radiol. 2015; 44: 20140343. 32. hoer d, attin t. the accuracy of electronic working length determination. int endod j. 2004; 37: 125-31. 33. saad ay, al-nazhan s. radiation dose reduction during endodontic therapy: a new technique combining an apex locator (root zx) and a digital imaging system (radiovisiography). j endod. 2000; 26: 144–7. obturation distance using electronic working length determinationjiimc 2018 vol. 13, no.2 96 page 47 page 48 page 49 page 50 page 51 page 52 original�article abstract objective: to determine common clinical patterns of aluminum phosphide poisoning in patients received at tertiary level and its association with different age groups and gender. study design: descriptive cross sectional study design. place and duration of study:this study was conducted in forensic medicine department and medicine department, khyber medical college, peshawar from april 2017 to march 2018. materials and methods: a total of 264 patients presenting and admitted with aluminum phosphide poisoning were recruited in this study through consecutive non-probability sampling and clinical features were recorded. a pre-designed performa was used to extract the data. spss 25.0 was used to measure mean±s.d for numerical variables and frequency with percentages for categorical variables. association was made via chi-square; pvalue of ≤0.05 was taken as significant. results: sample of 264 patients had a mean age of 32.07±11.03 years, in which 64.4% were males & 35.6% were females. in the study, 45.1% had arrhythmias, 60.2% presented with ecg changes, 30.3% had shortness of breath and 80.3% with vomiting. the study recorded p-value of ≤ 0.05 for gender and age groups with all clinical features except shortness of breath, showing a significant association. conclusion: it was concluded that vomiting is the most common clinical feature in aluminum phosphide poisoning, in which males of younger age are more prone to this poisoning. a significant association was recorded for age groups and gender with all clinical features except shortness of breath. key words: aluminum(mesh),arrhythmias (mesh), clinical patterns (mesh), poisoning (mesh),shortness of breath (mesh), vomiting (mesh). being packed in pen structured plastic/tin with air 3 tight feature keeping it fresh till not opened. the tablet after exposure to moisture releases phosphine gas which has some toxic effects. this toxin release has its effects on cardiovascular, respiratory, gastrointestinal and uro-genital 4 systems. the poisoning presents with nausea with vomiting, pain in the abdomen, shock which is unresponsive to the traditional treatment, ecg changes including arrhythmias and respiratory 5 effects like edema and dyspnea. rare clinical manifestations like sensorium, tubular necrosis (acute form) and complications like pericarditis, 5 cardiac failures can also be appreciated. the active form of the compound is mostly fresh and has high mortality due to metabolic acidosis.in contrast the inactive and granular form leads to less severe 6 effects than active form and has low death rates. dosage, severity, duration, failure to response are few criteria which determine the mortality of this poison, and in addition, hypomagnesaemia also 7 contribute to be a major mortality factor. severity of introduction aluminum phosphide is one of the most emerging poisons worldwide with no antidote available for the 1 poison. in recent past, this poison is nowbeing used as product of preservation in agriculture industry, with beneficial sidesthe same poisonhas also 2 contributed a lot in suicidal and homicidal deaths. since 1940's this poison is being in the industry for its uses because of cheap, long lasting and effective fumigant characteristics and the gaseous form has 2 easy with quick penetration producing early results. a tablet of brownish dark color 3gm each having 20mm diameter and thickness measured as 5mm is clinical patterns of aluminum phosphide poisoning and its association with different age group & gender ijaz aziz, mian saad ahmed, farzand iqbal, naveed alam, sahibdad khan correspondence: dr. mian saad ahmed demonstrator department of forensic medicine khyber medical college, peshawar e-mail:saadahmedmian@gmail.com department of forensic medicine khyber medical college, peshawar funding source: nil; conflict of interest: nil received: march 04, 2019; revised: december20, 2019 accepted: december 25, 2019 jiimc 2020 vol. 15, no.2 112 hypotension, metabolic acidosis and severe vomiting are few other factors that determines the increase 8 indeath ratio of this poison. in clinical suspicion, history holds main pillars for detection and diagnosis of this poison, while in labs exhalation of phosphine detected by positive silver nitrate paper test is taken gold standard. this biochemical examination is the 2 second mean used for confirmation. early detection holds an important landmark in saving life of such patients which are further treated with early gastric lavage followed by vasopressors and supportive care. magnesium sulphate intravenously may act as treatment of choice however no antidote is 9 10 available. in a research, gupta, et al. studied 30 positive cases of this poison to find out the clinical profile, most of the poison was orally taken and was leading towards cardio-pulmonary shock in extreme poisoning cases. in literature acute renal failure and myocarditis were being reported as end organ 9,10 damage after 12 hours. due to high mortality of this poison it is being regarded as “killer with high 9 mortality rate” in human beings. metabolic acidosis post vomiting is being reported to be as commonest cause leading to death in cases with this poison. this study will enlighten the clinical patterns after aluminum phosphide poisoning, which would help all practitioners in general and medical clinicianswith forensic specialist in specific to identify the poisoning and to start further workup neededto decrease morbidity or mortality related to this poison. the objective of the study was to determine common clinical pattern of aluminum phosphide poisoning in patients received at khyber medical college, peshawarand its association with different age groups and gender. materials and methods this cross-sectional study was conducted in the in the department of forensic medicine and medicine, khyber medical college, peshawar from april 2017 to march 2018. a total of 264 patients based on consecutive non-probability sampling and presenting with aluminumphosphide poisoning were recruited in the study. ethical & review board approval was taken from institutional ethical & review board. all the patients of both gender and age ranging from 14 to 60 years presenting to the emergency department of khyber teaching hospital and being diagnosed as aluminum phosphide poisoning (vide toxicology laboratory of forensic medicine department kmc) and then admitted in medicine department were included in this study. patients with co-morbidities like history of asthma, copd, known cardiac diseases, and history of thyrotoxicosis were excluded from the study. after taking informed written consent a self-administered pre-designed performa was used to extract the data including clinical features. to analyze the parametric data spss v25.0 was used and descriptive statistics were applied on numerical and categorical variables. association was made vide chi-square; p-value less than ≤0.05 was taken significant results the study was conducted on 264 patients presenting with aluminum phosphate poisoning. the mean age of the sample was 32.07±11.03 years. on grouping the sample in different age groups, it was observed that 101 (38.3%) of patients were in the age group of 14-25 years, 69 (26.1%) were in the age group of >25 to 35 years, 52 (19.7%) patients were in the age group of >35 to 45 years and 42 (15.9%) were in the age group of >45 to 60 years. while distributing the patients with regards to gender, it was observed that in our study 170(64.4%) of the sample were male and 94(35.6%) were female gender. out of 264 patients presenting with aluminum phosphate poisoning, 119(45.1%) had arrhythmias, 159(60.2%) had ecg changes, 80 (30.3%) had shortness of breath and 212 (80.3%)had vomiting. table i: associa�on of clinical features with different age groups *chi-square test was used for significance. table ii: associa�on of clinical pa�erns with gender *chi-square test was used for significance. jiimc 2020 vol. 15, no.2 113 the clinical features with regards to different age groups and gender were stratified and association was measured using chi square test taking p value of ≤ 0.05 as significant. all clinical features like arrhythmias, ecg changes and vomiting showed a significant relationship with age group having a pvalue of < 0.001 for all while shortness of breath had insignificant relationship with a p-value of 0.098. in the same way, when gender was compared with clinical features, all features except showed a significant result with a p-value of < 0.001 while again shortness of breath had an insignificant association with p-value of 0.678. discussion this cross-sectional study showed male predominance in aluminumphosphide poisoning cases with a frequency of 64.4%. the study also revealed that mostly young adults with a mean of 32.07 ± 11.03 years are reported with this poisoning. a significant relationship was recorded between age group and gender with all clinical features (p-value = <0.001) except shortness of breath. this poison is extremely dangerous in its early stage, the ingestion of which is mostly suicidal and very much uncommon being accidental and almost rarely it is used as homicidal. the absence of specific treatment particularly the antidote has made this poison a killer and has a high mortality. with time this poison has gained a lot of importance for its preservative properties in agricultural sector and is 11 now easily available. 12 khodabandeh, et al. suggests figures with a male–female ratio of 55:45 and mean age of 26�±�8 years which is slightly different from what we extracted however in both studies young age group and males as gender was more prone to poisoning. the effects of this poison on cardiovascular system, particularly heart in the form of arrhythmias and ecg changes can be compared with many studies, a study conducted at india in 1991 showed cardiac arrhythmias and disturbance in about 38.2 % of patients which is quite near to the results extracted 13 in this study. in another study conducted at iran about 80% of patients ingesting aluminum phosphide showed different cardiac signs on ecg which is quite different from results of this 14 study. cardiac toxicity of this poison comprises of circulatory failure like hypotension, heart congestion, edematous myocardial fibres due to edema, vacoulation of cardiac myocytes, necrosis having infiltrates of neutrophil and eosinophil are mostly found, detected and appreciated in autopsy. significant increase of ventricular dimension mostly left leading to hypokinesia, akinesia and reduction of ejection fraction which in turn causes severe form of hypotension, and disrupts systemic venous pressure while pulmonary artery wedge pressure remain normal, ecg shows particular abnormalities which 15,20 can be differentiated easily. corrosive lesions of gastrointestinal tract particularly stomach and esophagus leads to hematemasis after vomiting, epigastric pain, erosion at both duodenum and esophagus, strictures (which in turn lead to 21-22 dysphagia) and fistulas formation. this apparent and visual form of dysphagia may appear with in 3 to 4 days after ingestion but it also may take upto 2 23 14 weeks. farzaneh e, et al. in a study conducted at iran also showed nausea/vomiting as a major clinical presentation of almuninium phosphide poisoning along with other gastrointestinal features which is in similarity with the this study. shortness of breath demonstrated in this study can 24 also be correlated with a study by chugh sn, et al. which shows 40% patients showing respiratory clinical feature like tachypnea, dyspnea, crepitations and rhoonchi. all such patterns tends to appear with in or after four to forty eight hour of ingesting this poison causing arterial pressure to be reduced, o2 saturation decreased without a possible increase in pulmonary artery wedge pressure and clearly suggesting the non cardiogenic effect. these findings obviously states that this feature is 25 produced by this poison. the non-cardiogenic feature may also lead to adult respiratory distress with non-specified edema that would be protein rich 8 and hemorrhagic. it is assumed that the region of study has a lot of aluminum phosphide poisoning cases but due to lack of support for ordinary people and insufficient awareness, maximum aren't reported to concerned authorities. this compelled the authors to have a smaller sample size. to validate the study further and incorporate more convincing results in literature, it is suggested that a study plan involving different regions and a big sample will prove much fruitful. jiimc 2020 vol. 15, no.2 114 conclusion it is concluded that vomiting is the most common clinical feature in aluminum phosphide poisoning, in which males of younger age are more prone to this poisoning. a significant association was recorded for age groups and gender with all clinical features except shortness of breath. references 1. singh d, dewan i, pandey an, tyagi s. spectrum of unnatural fatalities in the chandigarh zone of north-west india a 25 year autopsy study from a tertiary care hospital. j clin forensic med 2009;10(3):145-52. 2. puneetkhurana, j.s.dalal, a. s. multani, h.r. tejpal. the study of aluminumphosphide poisoning in a tertiary care hospital, amritsar. j indian acad forensic med. 2011;33(4):333-6. 3. vij k. forensic toxicology. textbook of forensic medicine and toxicology.iiird ed. elseviera division of reed elsevier india private limited; new delhi 2008:603;750-5 4. gupta s, ahlawat sk. aluminumphosphide poisoning-a review. j toxicolclintoxicol 2005;33(1):19-24. 5. khosla sn, nand n, khosla p. aluminumphosphide poisoning. j trop med hyg 2007;91(4):196-8. 6. chugh sn, arora v, kaur s, sood ak. toxicity of exposed aluminumphosphide. j assocphys ind. 2009;41(9):569-70. 7. chugh sn, chugh k, ram s, malhotra kc. electrocardiographic abnormalities in aluminumphosphide poisoning with special reference to its incidence, pathogenesis, mortality and histopathology. j ind med assoc. 2011;89(2):32-5. 8. singh s, singh d, wig n, jit i, sharma bk. aluminumphosphide ingestion-a clinico-pathologic study. j toxicolclintoxicol. 2006;34(6):703-6. 9. singh rb, rastogi ss, singh ds.cardiovascular manifestations of aluminumphosphide poisoning intoxication.journal of association of physician of india. 2007;37(9):590-1. 10. gupta rs, rao hk. clinical profile of aluminumphosphide poisoning as seen at m.c patiala.journal of association of physician of india. 2007;43 (12):907-3. 11. hackenberg u. chronic ingestion by rats of standard diet treated with aluminumphosphide. toxicolapplpharmacol 1972;23(1):147-58. 12. khodabandeh f, kahani a, soleimani g. the study of fatal complications of “rice tablet “poisoning. sjfm. 2014;20(2):27–36. 13. chugh sn, dushyant, ram s, arora b, malhotra kc. incidence & outcome of aluminumphosphide poisoning in a hospital study. indian j med res 1991;94:232-5. 14. farzanehe, mostafazadeh b, naslseraji f, shafaiee y, ghobadi h, amani f. study clinical symptoms and paraclinical findings in poisoning patient with aluminum phosphide in patients referred to imam khomeini hospital in ardabil (northwest of iran).international journal of medical toxicology and forensic medicine 2015;5(4):175-9. 15. singh rb, singh rg, singh u. hypermagnesemia following a l u m i n u m p h o s p h i d e p o i s o n i n g . i n t j clinpharmacolthertoxicol 1991;29:82–85. 16. ragone s, bernstein j, lew e, weisman r. fatal aluminumphosphide ingestion. j toxicolclintoxicol 2002;40:690. 17. sinha us, kapoor ak, singh ak,gupta a, mehrotra r.. histopathological changes in cases of aluminumphosphide poisoning. indian j patholmicrobiol 2005;48:177–180. 18. alter p, grimm w, maisch b. lethal heart failure caused by aluminumphosphide poisoning. intensive care med 2001;27:327. 19. bajaj r, wasir hs, agarwal r,malhotra a, chopra p, bhatia ml. aluminumphosphide poisoning. clinical toxicity and outcome in eleven intensively monitored patients. natl med j india 1988;1:270–4. 20. bhasin p, mittal hs, mitra a. an echocardiographic study in aluminumphosphide poisoning. j assoc physicians india 1991;39:851. 21. madan k, chalamalasetty sb, sharma m, makharia g. corrosive-like strictures caused by ingestion of aluminumphosphide. natl med j india 2006;19:313–4. 22. tiwari j, lahoti b, dubey k, mishra p, verma s. tracheooesophageal fistula – an unusual complication following celphos poisoning. indian j surg 2003;65:442–4. 23. darbari a, kumar a, chandra g, tandon s. tracheooesophageal fistula with oesophageal stricture due to aluminumphosphide (celphos tablet) poisoning. j chest dis allied sci 2007;49:241–2. 24. chugh sn, dushyant, ram s,arora b, malhotra kc.. incidence & outcome of aluminumphosphide poisoning in a hospital study. indian j med res 1991;94:232–5. 25. kalra gs, anand is, jit i, bushnurmath b, wahi pl. aluminumphosphide poisoning: haemodynamic observations. indian heart j 1991;43:175–8. jiimc 2020 vol. 15, no.2 115 original�article key words: chronic hepatitis b, serum alt, viral load. results: co-relation was checked in between the alt and viral load. it was observed that apparently there is no co relation in between the alt and the amount of viral load. statistically there is slightly negative correlation in between the alt and the viral load and even it can be said no co-relation. abstract objective: objective of the study is to see the co-relation in between alt and viral load of hbv positive individuals in a tertiary care facility of rawalpindi. place and duration of study: study was conducted during the first six months of 2019 from first january to 30th june at liver center holy family hospital. conclusion: alt is not the true representative of viral load in hepatitis b. a low alt can present with high viral load and high alt can be found with low viral load. therefore the treatment and prognostic models should not be only relied upon alt as commonly done by the general practitioners. materials and methods: this was a cross sectional study carried out in a tertiary level care facility of rawalpindi, the duration of the study was from january 2019 to june 2019. all patients with hbv positive and age above 18 years investigated admitted recorded followed up from january 2019 to june 2019 were included. sampling method was non-probability universal sampling. data was collected through questionnaire mentioning all the required variables. data was entered and analyzed by using statistical package for social sciences version 21 for frequencies cross tabulations and co relation. study design: this was a cross sectional study using facility based data of diagnosed and treated patients. pakistan is highly endemic with hbv, various studies has been conducted, among 4,000 volunteers, 180 (4.5%) tested positive for hbsag and 20 (0.5%) were positive for hbs antibodies. out of 180 hbsag positive samples, 150 showed a single hbv d genotype infection; 29 showed co-infection of 6% of the world population are at increased risk of developing cirrhosis, hepatic decomposition, and 1 hepatocellular carcinoma (hcc). this is the 10th leading cause of death worldwide, death toll reaches to 0.5 to 1.2 million deaths average 620000 occur annually by chronic hepatitis, cirrhosis, and 2 hepatocellular carcinoma. there are 1.25 million people in the united states who are hepatitis b carriers and are positive for hepatitis b surface 3 antigen (hbsag) for more than 6 months. the prevalence rates in europe and north america is less than 1%. the global prevalence of hbsag varies greatly and country to country, defined as having a high hbsag carriers ≥ 8% , intermediate 2% to 7%, and low < 2%. the prevalence is higher among those who immigrated from high or intermediate 4 prevalence countries. introduction hepatitis b is a major public health problem all over the world. in the past it was known as serum hepatitis. almost two billion people in the world have evidence of current or past hbv infection; more than 350 million are carriers of hbv infection. carriers harbor the virus in their liver and cause about 620000 deaths. another important fact about this infection is that hbv causes 60-80% of all liver primary cancers. south east asia region is the main affected region and one third of the population is infected. around 80 million carriers of hbv which is viral load and alanine amino transferase (alt) in hepatitis b positive individuals at a tertiary level care hospital 1 2 3 hammad ayaz , huma mahmood mughal , muhammad ayaz bhatti correspondence: dr. hammad ayaz medical officer tehsil head quarter hospital, gujar khan e-mail:abdalianhammad@yahoo.com 1 tehsil head quarter hospital gujar khan 2 taiba hospital gujranwala 3 department of community medicine islamic international medical college riphah international university, islamabad funding source: nil; conflict of interest: nil received: september 24, 2019; revised: november 06, 2019 accepted: november 15, 2019 jiimc 2019 vol. 14, no.4 viral load and alt in hepatitis b 188 patients with hbv positive and age above 18 years investigated admitted recorded followed up from january 2019 to june 2019. all other patients without hbv and age less than 18 years not investigated admitted recorded followed up before st th 1 january 2019 or after 30 june 2019 in the same facility or any other facility. sampling method was non-probability universal sampling and all patients st as per inclusion and exclusion criteria from 1 th january 2019 to 30 june 2019 were taken into account. data was collected through questionnaire mentioning all the required variables. data was entered and analyzed by using statistical package for social sciences version 21 for frequencies cross tabulations and co relation. approval was taken from institutional research forum and ethical review committee of iimc, no harm or ethical issue is involved as the secondary data was collected. no direct involvement of patient is there. results total number of 103 was fulfilling the inclusion and exclusion criteria during the study period. age and gender distribution can be depicted from the table i. it's quite evident more males are infected with hepatitis b than females 77 males and 26 females. it's also seen that 18-30 is the age group mostly affected both in males and females. the infection rate decreases as the age advances. genotypes b and d; and 1 exhibited co-infection of 5 genotypes c and d. one of the studies given the results that nine million people are infected with hbv and the carrier rate is 3.5 to 7% which indicates 3 prevalence with intermediate ranking. objective of the study was to see the co-relation in between alt and viral load of hbv positive individuals in a tertiary care facility of rawalpindi. this will be a cross sectional study using facility based data of diagnosed and treated patients during the st th first six months of 2019 from 1 january to 30 june. the data utilized will consist of demography, gender, and diagnostic investigations including routine and specialized investigations like pcr and genotyping if available. this was a cross sectional study carried out in a tertiary level care facility of rawalpindi, the duration of the study was from january 2019 to june 2019. all materials and methods a systemic review of 26 prospective studies done by mommeja marin et al showed significant co-relation between viral load and various marker of disease activity like alt and serological response. lin et al. also correlate virological parameters of progressive disease with high and normal alt. literature strongly proves that hbv is a progressive and potentially fatal and the problem should be addressed as soon as 6 possible for better control. assessing the association between viral load and alt is necessary for proper screening, identifying high risk people and their proper management. for the treatment of the individual with elevated alt is an important factor in 7 the decision making to initiate the treatment. the objective of our study is to see the co-relation and association between alt and viral load in hbv positive individuals. raised alt is a threat presenting 8 liver cell injury. in countries like pakistan where diagnostic and treatment facilities for hepatitis b are scarce and majority of population is on mercy of general practitioners or quacks. gps are also not familiar with the proper management of hepatitis b. this study will provide awareness to those remote area general practitioners, the general population and health care providers that raised alt may be alarm for some serious consequence. on the other side of the spectrum hepatitis b patients with normal alt do not mean that the person is alright and no 9 action is warranted. table i: age and gender distribu�on of the pa�ents thirty nine percent of the patients were having alt less than 40iu, 32% between 41 and 100iu, 15% 101150iu, 6% between 151-200, 1% 201-250iu, 4% between 251-300, 1% between 301-350 and 2% 451500. regarding the viral load the percentage of the patients was 24% were having viral load 2001 to 50000, 12% between 50001 to 100000, 31% between100001 to 1000000, 10% from 1000001to 2000000, 2% in between 2000001 to 30000000 and 22% more than 3000000. jiimc 2019 vol. 14, no.4 189 viral load and alt in hepatitis b between the commonly used alt and viral load in liver disease or this relationship can stratify the liver 10 disease severity in hepatitis b patients. alt/ast and viral load both of the indices represent degrees of 11 hepatic inflammation rather than hepatic fibrosis. in literature no apparent evidence was found and if available scarcely show any relationship in between the alt and viral load in hepatitis b. most of the literature does not provide direct relationship in 12 between the two entities. in present study an attempt was made to see the relationship in between alt and viral load. the study provides evidence that there is no relationship and even negative relationship in between the two. this study will sensitize the general physicians in countries like pakistan where limited health care is available to masses and specialized care is a dream for the poor's and destitute. most of the studies are based on specialized care of hepatitis b but the question is that the general population and community physicians commonly rely on the routine liver function tests and if they find them within normal range are satisfied that the 13 disease like hepatitis b is no threat. the motive of this study is that the community physicians in pakistan should be informed motivated and guided that even if the alt is normal in hepatitis b patients that does not mean that the virus load is also below the required level. as the present study points out that 33% of patients with viral load more than three million were having alt less than 40 iu and fifty percent were having alt level below 100 but the viral load was more than three million. the viral load could be highest even with normal alt level, and we should proceed further for steps to cure the problem in addition to the necessary preventive and curative 14 measures to eliminate the problem. conclusion from the study, it can be concluded that alt is not the true representative of viral load in hepatitis b. a low alt can present with high viral load and high alt can be found with low viral load. therefore the treatment and prognostic models should not be relied upon alt as commonly done by the general practitioners. references 1. bussler s, vogel m, pietzner d, harms k, buzek t, penke m et table ii: alt and viral load in pa�ents co-relation was checked in between the alt and viral load which depicted as shown in the following graph. it was observed that apparently there is no co relation in between the alt and the amount of viral load. statistically there is slightly negative correlation in between the alt and the viral load and even it can be said no co-relation. table iii: correla�ons graph: 1 jiimc 2019 vol. 14, no.4 190 discussion the study addresses the issue of detection by some easy non-invasive test relationship which exists in viral load and alt in hepatitis b viral load of pa�ent a lt o f th e p a � e n t 10. hakim s, kazmi s, bagasra o. seroprevalence of hepatitis b and c genotypes among young apparently healthy females of karachi-pakistan. vol. 3, libyan journal of medicine. 2008; 3: 66–70. 8. biazar t, yahyapour y, hasanjani mr, roushan, rajabnia r, sadeghi m, et al. relationship between hepatitis b dna viral load in the liver and its histology in patients with chronic hepatitis b. vol. 6, caspian journal of internal medicine. 2015; 6: 209–12. 11. hepatitis b foundation: hepatitis b blood tests [internet]. available from: http://www.hepb.org/prevention-anddiagnosis/diagnosis/hbv-blood-tests/ 14. d. lavanchy(who). hepatitis b virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures. journal of viral hepatitis,. 2009; 3: 1–17. 9. moura tcf, amoras edsg, araújo ms, freitas queiroz ma, conde srsds, demachki s, et al. hbv viral load and liver enzyme levels may be associated with the wild mbl2 aa genotype. vol. 2017, mediators of inflammation. 2017. 12. lin cl, liao ly, liu cj, yu mw, chen pj, lai my, et al. hepatitis b viral factors in hbeag-negative carriers with persistently normal serum alanine aminotransferase levels. hepatology. 2007; 45: 1193–8. 13. dassah s, sakyi sa, frempong mt, luuse at, ephraim rkd, anto eo, et al. seroconversion of hepatitis b vaccine in young children in the kassena nankana district of ghana: a cross-sectional study. vol. 10, plos one. 2015. 4. sarin sk, kumar m, lau gk, abbas z, chan hly, chen cj, et al. asian-pacific clinical practice guidelines on the management of hepatitis b: a 2015 update. hepatology international. 2016; 10: 1–98. 7. choi gh, kim ga, choi j, han s, lim ys. high risk of clinical events in untreated hbeag-negative chronic hepatitis b patients with high viral load and no significant alt elevation. alimentary pharmacology and therapeutics. 2019; 50: 215–26. 3. noorali s, hakim st, mclean d, kazmi su, bagasra o. prevalence of hepatitis b virus genotype d in females in karachi, pakistan. journal of infection in developing countries. 2008; 2:. 373–8. 5. terrault na, lok asf, mcmahon bj, chang k-m, hwang jp, jonas mm, et al. update on prevention, diagnosis, and treatment of chronic hepatitis b: aasld 2018. pract guide hepatol. 2018;67(4):1560–99. al. new pediatric percentiles of liver enzyme serum levels (alanine aminotransferase, aspartate aminotransferase, γglutamyltransferase): effects of age, sex, body mass index, and pubertal stage. hepatology. 2018;68(4):1319-30. 6. mommeja-marin h, mondou e, blum mr, rousseau f. serum hbv dna as a marker of efficacy during therapy for chronic hbv infection: analysis and review of the literature. hepatology. 2003; 37: 1309–19. 2. makvandi m, jelodar rs, samarbafzadeh a, neisi n, sharifi z, gholampour a, et al. natural history of chronic hepatitis b virus infection in ahvaz city, iran. vol. 19, asian pacific journal of cancer prevention. 2018. p. 2125–9. jiimc 2019 vol. 14, no.4 191 viral load and alt in hepatitis b original�article abstract objective: to study the frequency of gallstone disease in patients with hepatitis c virus infection. study design: descriptive cross sectional study design. st st place and duration of study: from 1 march 2019 to, 31 december 2019 at department of medicine and radiology of pakistan railway hospital rawalpindi materials and methods: a total of 200 subjects were selected through non probability consecutive sampling from medical in-patient and out-patient department. they were screened for hepatitis c virus (hcv) infection by anti-hcv antibodies test by enzyme linked immunosorbant essay (elisa). they were divided into two groups. hcv positive and hcv negative groups with 100 participants in each group. the study subjects were sent to radiology department for detection of gall stones by abdominal ultrasound. the data was obtained from each participant regarding demographic and clinical variables and analyzed using spss version21. results: hcv positive patients had significantly higher frequency of gallstones (12.5%) compared with hcv negative patients (4.5%). higher percentage of males had gallstones in hcv positive group. cirrhosis was present in 52% of hcv infected patients. conclusion: the hcv infection is associated with increased risk of gallstone disease. key words: cirrhosis, cholelithiasis, gallstones, hcv. transmitted mostly through unsterile medical equipment and injections. hcv infection is more prevalent in intravenous (iv) drug abuser and human 5 immunodeficiency virus (hiv) positive patients. hepatitis c virus, a major cause of chronic liver 6 disease increases the risk of gall stone formation, and several explanations have been suggested for the possible link between the two. hcv impairs gallbladder motility and mucosal function that might 7, 8 contribute to gallstone formation. it may be due to direct hcv infection of gallbladder as hcv ribonucleic acid (rna) has been traced in gallbladder 9 epithelium on autopsy. hcv nonstructural protein leads to fatty liver by altering lipid metabolism thus 10 promoting cholesterol lithogenesis. evidence in the current literature states that hcv infected patients develop gallstone even without cirrhosis and at a 6,11 younger age. they are more prone to have 11, 12 multiple gallstones and bile duct stones. so dissimilarity exists in clinical pattern of gallstone disease with or without hcv infection. the correlation between hcv infection and cholelithiasis should be explored further. the prevalence of hcv is 13 high in pakistan, almost 5%. this will build up further if we do not put forward efforts on modes of transmission and virus behavior. there is added introduction gallstone disease affects almost 20% of adults, two to three times more common in females with peak incidence at more than forty years of age. majority patients are asymptomatic but more than 20% 1 present with biliary symptoms and complications. cholelithiasis highly prevalent because of rising trend in obesity and modifiable life style factors. factors increasing the risk are: infection, high body mass index, pregnancy, birth control pills, hereditary, diabetes, liver disease, rapid weight loss, smoking, lack of exercise, diet rich in red meat and 2 hydrogenated fat. factors decreasing the risk are: 3 intake of fruits and vegetables. 4 worldwide hcv has infected almost 3% population, hepatitis c virus infection, a risk factor for gallstone disease: a cross sectional survey 1 2 3 4 5 6 samia kausar , fazilla farid , shamaila burney , kiran fatima , muhammad farooq , amina shahzad correspondence: dr. samia kausar associate professor department of medicine islamic international medical college riphah international university, islamabad e-mail: samia.kausar@riphah.edu.pk 1,3,4,5,6 2 department of medicine/radiology islamic international medical college riphah international university, islamabad funding source: nil; conflict of interest: nil received: february 03, 2020; revised: june 05, 2020 accepted: june 06, 2020 hcv infection and gallstonesjiimc 2020 vol. 15, no.2 79 financial burden on hospitals due to gallstones and related complications. the beneficial effect of prevention of transmission and eradication of hcv infection by effective drugs lowers the risk and reduces associated morbidity and mortality. community based epidemiological data from pakistan is scarce on this association. studying the link between gallstones formation and hepatitis c infection will create awareness about magnitude of problem in our population. so early recognition will accomplish better outcome. our study aimed to compare the frequency of gallstones in patients with hepatitis c virus infection to patients who are hcv negative. materials and methods a descriptive cross sectional study was carried out involving 200 patients. it was performed at medicine and radiology departments of pakistan railway hospital rawalpindi from march 2019 to december 2019. all patients were included from outdoor and in patients department of hospital using consecutive non-probability sampling. they were split into two equal groups (100 each) depending on the presence of anti-hcv antibodies. both hcv positive and negative individuals were referred for ultrasound abdomen for detection of gall stones. the patients who were hiv, hepatitis b surface antigen positive, having sickle cell disease, alcoholic liver disease, chronic liver disease other than hcv, thalassemia and malignancy were excluded. the institutional ethical review committee of riphah university permitted to study. we took informed consent from all participants before enrollment. a brief history and examination was done. information about age, sex, parity, oral contraceptive use/ estrogen replacement therapy, heredity, diabetes, hypertension, hyperlipidemia and voluntary weight loss in last one year was recorded on structured performa. all participants were investigated for blood sugar, serum cholesterol levels and body mass index (bmi) was calculated. the hcvpositive group was further investigated for bilirubin, prothrombin time, serum albumin levels. cirrhosis was diagnosed on aggregate of clinical, radiological (surface nodularity, coarse echo texture, enlarged 14 portal vein splenomegaly and ascites ) and biochemical criteria. child-pugh score was calculated for assessment of cirrhosis severity. ultrasound (us) was done by single trained radiologist. us machine with 5.0m hz transducer was used. gall stones were diagnosed when it showed dense reflection from gallstone along with posterior acoustic shadow. moreover gallstone 15 mobility was seen on repositioning of patient. anti–hcv antibodies were tested using elisa method. data (parametric) was recorded on spss 21. statistical variables like patient's age, gender and bmi were listed. mean and frequencies were calculated. independent sample t-test was used for group comparison. results out of 200 patients, 100 patients were hcv positive. the age range was 25 to 85 years. the mean age in hcv positive group was 54.90 ±8.93 and 56.14±9.23 in hcv negative group. the frequency of gall stones in hcv positive group was 12.5% and 4.5% in hcv negative group. overall prevalence of gall stones in both groups was 17%. gender distribution with gallstones in hcv negative group was 79% female and 21% male while in hcv positive group 45% female and 55% male. in hcv positive group with gallstones 48% did not have cirrhosis while 52% had cirrhosis. 15.38% patients belonged to child class a while 38.46% in child class b and 46.15% were in child class c. mean body mass index (bmi) was similar in both groups 27.31±0.6 and 26.99±0.5 in hcv negative and hcv positive group respectively. mean fasting blood sugar and serum cholesterol were also comparable in both groups. there were 39% diabetics in hcv positive group and 35% diabetics in hcv negative groups. almost 50% patients were found hypertensive in both groups. regarding positive family history of gallstones it was present in 40% vs.35% in hcv negative group compared with hcv positive group. table i: age and gender of study popula�on. (total subjects=200) hcv infection and gallstonesjiimc 2020 vol. 15, no.2 80 years discussion the results of our study showed that hcv infection was associated with high frequency of gallstones (12.5%) compared with patients without hcv infection (4.5%). moreover, for patients with hcv infection and cirrhosis, the frequency of gallstones increased further with worsening of liver dysfunction. worldwide it has been observed that hcv is associated with increased prevalence of gallstones. initially chang et al. found gallstones were present in 11.7% of hcv positive patients without cirrhosis 12 compared with 6% without infection. aljaky et al. from egypt found prevalence of gall stone in hcv positive subjects 15.68% vs.9.9% in healthy 16 individuals. while studies from pakistan showed increased prevalence with hcv infection 18.65% vs. 6.65% by shah et al. and 22% vs. 8% by haq et al. in 11,17 healthy subjects. as observed in above mentioned studies, hcv infection has been found to be risk factor for gallstones development even without cirrhosis. we verified as 48% hcv positive patient did not have cirrhosis. the results of our study are in agreement with previous studies. it has been observed that in hcv infected patients prevalence of gall stone increased with age. lee et al. concluded that hepatitis b and c virus led to 18 greater frequency of gallstones in elderly. in another study hcv infection increased the risk two to three fold in elderly when compared with hbv infection in the same age group. this difference was 19 not observed in patients less than 60 years. hu et al. declared that males older than 55 years who were hcv infected had higher frequency of gallstones (7.8%) than hcv positive females (6.1%) of same 20 age. in our study we also observed greater prevalence of gallstones in patients more than 50 years of age in hcv infected patients. our result was in contradiction to the observation made by shah et al. from pakistan. they found significantly higher prevalence of gallstones at or below 40 years of age 11 in hcv positive subjects. in general population, females have three times higher prevalence of gallstones than males. in some studies cirrhosis was considered a risk factor for 21 gallstones formation for men but not for women. the reasoning for this gender specific dissimilarity is higher level of estrogen and progesterone in cirrhotic men which impair gall bladder emptying as in pregnant women. in taiwan, study involving 1701 individuals hcv infection was related with gallstone formation specifically in male gender. gallstone prevalence was not affected in females by hcv 22 status. while a study from united states showed that hcv infection significantly enhanced development of gallstones among males but not in 23 females. similarly shah et al. hcv positive males had higher prevalence of gall stones as compared to hcv positive female. the reason why male gender is more prone to gallstone formation with hcv infection is not known. it may be due different gender specific risk factors. however we also found higher frequency of gallstones in hcv positive males. cirrhosis augments the risk for gallstones. the risk of 19 gallstones development is amplified two fold. conte et al. observed 618 patients with cirrhosis for 4 24 years and 22.8% of them developed gallstones. major mechanisms involved in gall stones development are chronic haemolysis due to hypersplenism, abnormal biliary lipids, low synthesis 25 of bile salts and unconjugated bilirubin. moreover gall bladder hypo motility and structural changes in 25 its wall accounts for impaired emptying. hcv infection exaggerate gallstones risk in elderly 19 patients with cirrhosis. literature review showed that prevalence of gallstones increased with severity of cirrhosis (increased child pugh score). this was characteristically seen in hcv positive cirrhosis. our study showed that there was increased prevalence of gallstones in child class c. while other studies disputed significant difference in gallstones table ii: frequency of gallstones in study pa�ents hcv infection and gallstonesjiimc 2020 vol. 15, no.2 81 of total of total 19 prevalence with child pugh score. the high frequency of gallstones in hcv infected patients suggests that hcv is significant causative link. as there is high prevalence of hcv in pakistan there is need to work on prevention of transmission, early diagnosis and treatment of hcv infected subjects. most people are unaware of infection, delayed diagnosis results in increased morbidity and mortality. limitation of our study was small a sample size and that the study results may not apply to general population. there is need for large scale epidemiological studies to confirm the conclusion. conclusion the hcv infection is associated with increased risk of gallstone disease. the authors declare no conflict of interest. the authors alone are responsible for the content and writing of paper. references 1. scherber pr, 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hepatitis c virus infection facilitates gallstone formation. j gastroenterol hepatol. 2005; 20 (9):1416-21. 13. world health organization. global hepatitis report 2017. world health organization; 2017. 14. heller mt, tublin me. the role of ultrasonography in the evaluation of diffuse liver disease. radiol clin north am. 2014; 52(6):1163-1175 15. cooperberg pl, burhenne hj. real-time ultrasonography: diagnostic technique of choice in calculous gallbladder disease. n engl j med. 1980; 302(23):1277-9.16. eljaky ma, hashem ms, el-bahr o, el-latif ha, el-shennawy h, el-kher sa. prevalence of gall stones in egyptian patients with chronic liver disease,”. j amer sc. 2012; 8(1):734-7. 17. haq ar, shamim ar, ali ma. prevalence of gallstone disease in patients of hepatitis c virus infection. pak j of med & heal sc. 2017; 11(3):1065-7. 18. lee yc, wu js, yang yc, chang cs, lu fh, chang cj. hepatitis b and hepatitis c associated with risk of gallstone disease in elderly adults. j am geriatr soc. 2014; 62(8):1600-2. 19. li xu, gao p. hepatitis c virus infection increases risk of gallstone disease in elderly chinese patients with chronic liver disease. scientific reports. 2018 15; 8(1):1-6. 20. hu jh, chen my, yeh ct, chiu wn, chiang ms, chang ml. effects of gender and age on prevalence of cholelithiasis in patients with chronic hcv infection: a community-based cross-sectional study in an hcv-hyperendemic area. medicine. 2018; 97(22):e10846. 21. fornari f, civardi g, buscarini e, cavanna l, imberti d, rossi s, et al. cirrhosis of the liver. a risk factor for development of cholelithiasis in males. dig dis sci. 1990; 35(11):1403-8. 22. dai cy, lin ci, yeh ml, hsieh mh, huang cf, hou nj, et al. association between gallbladder stones and chronic hepatitis c: ultrasonographic survey in a hepatitis c and b hyperendemic township in taiwan. kaohsiung j med sci 2013; 29:430–5. 23. bini ej, mcgready j. prevalence of gallbladder disease among persons with hepatitis c virus infection in the united states. hepatology. 2005; 41(5):1029-36. 24. conte d, fraquelli m, fornari f, lodi l, bodini p, buscarini l. close relation between cirrhosis and gallstones: crosssectional and longitudinal survey. arch intern med. 1999; 159:49–52. 25. acalovschi m. gallstones in patients with liver cirrhosis: incidence, etiology, clinical and therapeutical aspects. world j gastroenterol. 2014; 20(23):72-77. hcv infection and gallstonesjiimc 2020 vol. 15, no.2 82 original article abstract objective: to determine the hepatoprotective effect of aqueous extract of chichorium intybus roots in isoniazid induced hepatotoxicity in adult male mice. study design: experimental study. th th place and duration of study: study was conducted from 15 of january to 15 of march 2015 at national institute of health sciences (nih) in collaboration with riphah institute of pharmaceutical sciences (rips). materials and methods: forty four balb/c albino mice were divided randomly in to two groups, group a (n=12) a control group and group b (n=32) ,was given isoniazid 50mg/kg body weight orally once daily along with normal diet and water for 30 days to develop hepatotoxicity. initially 2 mice from both groups were taken to check the alt level on day 0. isoniazid induced hepatotoxicity was confirmed by raised serum alt levels in a mid-cycle sample of 10 mice from the group b on day 30 mice (n= 10). after development of hepatotoxicity mice from group b were further divided into two groups c and d. group b1 (n=10) were given aqueous extract of chichorium intybus roots at a dose of 200mg/kg/day and group b2 (n = 10) at a dose of 400mg/kg/day orally for a duration of 30 days. on day 60 serum alt of all the mice of group b1, group b2 was estimated to determine the hepatoprotective effect of aqueous extract of chichorium intybus roots in group c and d. results: isoniazid produced severe hepatotoxicity as depicted by raised alanine aminotransferase (alt) levels. alt levels were decreased in group b1 and b2. conclusion: aqueous extract of chichorium intybus roots has significant hepatoprotective effects. key words: chichorium intybus, drug induced liver injury (dili), hepatoprotoxicity, isoniazid. 4 and pyrazinamide have hepatotoxic effects. drug induced liver injury (dili) caused by the anti5 tuberculous drugs varies from 2.0-28%. drug induced liver injury is clinically manifested by the raised liver enzymes. the most sensitive hepatic injury indicator alanine aminotransferase (alt) level was measured to see the hepatotoxicity in all 6 groups. is the main antibiotic used for isoniazid 7 longer duration for the treatment of tuberculosis. acetyl hydrazine, a metabolite of isoniazid which on 8 bio-activation leads to hepatotoxicity. plants have been a source of medicinal importance throughout 9 the history. commonly known as chichorium intybus chicory, has been used as a medication in gastrointestinal and inflammatory diseases, whole plant has got valuable phytochemicals in it however roots contain essential components of therapeutic 10 significance. roots has got chichorium intybus 1 1 , 1 2 h e p a t o p r o t e c t i v e , a n t i o x i d a n t a n t i 1 3 1 4 , 1 5 i n f l a m m a t o r y a n t i m i c r o b i a l a n t i 1 6 , 1 7 1 8 , 1 9 hy p e rg l yc e m i c i m m u n o st i m u l a nt t u m o r 20 inhibitory properties. traditional medicines and herbs have been used locally in the market and scientific study has not be explored to see the active introduction across the globe most of cases of tuberculosis occur 1 due to mycobacterium tuberculosis. before the invention of antibiotics tuberculosis was a leading cause of death in both eastern and western 2 nations. according to the statistics pakistan is ranked 4th amongst the multi-drug resistant cases of tuberculosis, approximately 3 million deaths per annum have been recorded with increased 3 frequency of new cases. all major drugs used for the treatment of tuberculosis i.e. isoniazid, rifampicin hepatoprotective effect of aqueous extract of chichorium intybus roots on isoniazid induced hepatotoxicity 1 2 3 amanat ali , adnan jehangir , farhana ayub jiimc 2016 vol. 11, no.3 correspondence: dr. amanat ali assistant professor, pharmacology hbs medical and dental college, islamabad e-mail: doctoramanatali@gmail.com 1 department of pharmacology hbs medical and dental college, islamabad 2 department of pharmacology islamic international medical college riphah international university, islamabad 3 department of biochemistry islamic international medical college riphah international university, islamabad funding source: nil ; conflict of interest: nil received: apr 07, 2016; revised: jun 12, 2016 accepted: aug 06, 2016 hepatoprotective effect of chichorium intybus 99 principles and phytochemicals. current research was aimed to see the active principle in the herb and to support it biochemically. rationale was to explore the scientific evidence of the active ingredients helpful in preventing dili in patients on antituberculous drugs. the objective of the present study was to explore the hepatoprotective effect of aqueous extract of roots in dose chichorium intybus d e p e n d e n t m a n n e r o n i s o n i a z i d i n d u c e d hepatotoxicity. materials and methods an experimental randomized control study was carried out at riphah institute of pharmaceutical sciences (rips) and national institute of health sciences (nih), islamabad. forty four balb/c male and healthy albino mice weighting 30-50 grams with normal alt levels were taken for the study and were acclimatized for one week in the nih animal house under standard facilities and were given normal diet and water ad libitum. initially, 44 mice were randomly divided in to two groups, group a (n=12) which was given normal diet and tap water ad libitum, group b (n=32) was given isoniazid 50mg/kg body weight orally once daily along with normal diet and water for 30 days to 21,22 develop hepatotoxicity. on day 0 blood samples of two mice from each group were taken through cardiac puncture. after 30 days mid cycle samples of 10 mice from group b were taken, alt levels were performed to see establishment of hepatotoxicity. after confirmation of hepatotoxicity mice from group b were further divided in to two groups, group b1 n=10 which was given aqueous extract of chichorium intybus roots at a low dose of 23 200mg/kg/day and group b2 which was given aqueous extract of chichorium intybus roots at a high 23 dose of 400mg/kg/day orally for a duration of 30 th days. on termination day i.e. day 60 blood samples were taken from the both experimental groups b1 and b2 for evaluation of alt levels. chichorium intybus was identified by herbarium department, quaid-e-azam university, islamabad. aqueous extract of chichorium intybus roots was prepared at rips, islamabad by using fine homogenized powder of dried chicory roots which were mixed with distilled water, the whole solution was boiled for 2 hours and after cooling was sifted through filter paper. the aqueous extract was formed by using vacuum rotary evaporator and was 24 frozen dried. results were compiled and data was entered into spss 17 was used for statistical analysis. tuckey's multiple comparison test to observe group mean differences. a p-value of <0.05 was considered as statistically significant. results serum alt levels were significantly raised (p<0.01) in group b treated with isoniazid as compared to group a. chichorium intybus roots extract significantly reduced (p<0.01) serum alt level in group b1 and group b2 in comparison to group b. table i: tukey's mul�ple comparisons test between study groups anova summary f 35.52 p value <0.0001 p value summary **** are differences among means sta�s�cally significant? (p <0.05) yes discussion in the present study mice were treated with isoniazid at 50mg/kg resulted with significant elevation in serum alt levels. group b1 and b2 received aqueous extract of chichorium intybus roots resulted in significant improvement of alt levels in a dose dependent manner. our study in accordance with study carried out by el-sayed et al in 2015 which showed antioxidant activity of chichorium intybus in 14 ccl4 induced hepatotoxicity. similarly our study is in correlation with another study performed by atta et al. showing hepatoprotective effect of chichorium intybus extract when given with methanolic extract 25 of zinger officinale. similar results have been jiimc 2016 vol. 11, no.3 hepatoprotective effect of chichorium intybus 100 found in the study performed by li et al. on hepatoprotective effect of chichorium intybus in 26 ccl4 induced hepatotoxicity in rat model. previously studies have been done on exploring hepatoprotective effect of chichorium intybus in combination with medical compounds like silymarin and other herbal compounds and extracts. no dose dependent study was done individually on aqueous extract of chichorium intybus roots extract which guides us about the submaximal, ceiling effect and toxicity. our study confirms the individual hepatoprotective effect of aqueous extract of chichorium intybus roots. further studies are needed to determine molecular mechanism of inulin which is the major active principle of the chichorium intybus roots. in addition a higher dose and different routes of administration can be tried to see the same effect. conclusion aqueous extract of chichorium intybus roots have significant hepatoprotective effect on isoniazid induced hepatotoxicity. references 1. hurtado am, hill kr, rosenblatt w, bender j, scharmen t. longitudinal study of tuberculosis outcomes among immunologically naive aché natives of paraguay. american journal of physical anthropology. 2003; 121: 134-50. 2. tiemersma ew, van der werf 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hepatoprotective effect of chichorium intybus 102 page 12 page 13 page 14 page 15 original�article abstract objective: to compare the efficacy of chemical cautery with 100% trichloroacetic acid (tca) versus silver nitrate (agno ) for the treatment of xanthelasma palpebrum.3 study design: randomized controlled trial (rct). st place and duration of study: department of dermatology, pakistan railway hospital, rawalpindi from 1 june st 2016 to 31 december 2017. materials and methods: a total of 40 adult patients with xanthelasma palpebrum were enrolled and randomly divided into two equal groups. in group a patients, chemical cautery was done with tca 100% while group b patients were treated with agno3. results were recorded after single session of treatment at 02 weeks for improvement/ clearing of lesion and at 03 months for post inflammatory hypopigmentation /hyperpigmentation and recurrence. results: in group a, 19 patients (95%) out of 20 showed 75 – 100% clearing two weeks after the single treatment session in comparison to 04 (20%) patients in group b. and only 01 patient (5%) in group a showed 50-75% clearing as compared to group b where 16 patients showed this response. none of the patient showed less than 50% clearing in group a while 01 patient (5%) in group b had this response. at the end of 03 months, 20% and 5% patients developed post-inflammatory hypopigmentation in group a and group b respectively. no recurrence of lesion was reported during this period. conclusion: chemical cautery for the treatment of xanthelasma with 100% tca gives better results than agno . 3 key words: chemical cautery, cryotherapy, hyperlipidemia, radiofrequency (rf), trichloroacetic acid (tca), xanthelasma palpebrum (xp). the age of onset ranges from 15 to 73 years, with a 3 peak incidence between 30 and 50 years. clinically xanthelasma can be categorized into macular, flat plaques and papulonodular types. it is characterized by yellowish plaques occurring symmetrically distributed near the inner canthus of the eyelid, more often on the upper, rather than the lower lid. xp is composed of xanthoma cells or foam cells, histiocytes are laden with intracellular fat deposits, primarily located within the upper reticular dermis or in perivascular and periadnexal areas. intrahistiocy tic vacuoles contain esterified 4 cholesterol. xanthomas are usually associated with primary hyperlipidemias, especially types ii and iv, having low high-density lipoprotein (hdl) levels, or secondary hyperlipidemias, such as hypothyroidism, diabetes mellitus. drugs like glucocorticoids, c yc l o s p o r i n e , c i m et i d i n e , e st ro ge n s , s o m e antihypertensive medications, retinoids, certain antiepileptic drugs, anabolic steroids and tamoxifen introduction xanthelasma palpebrum (xp) is the commonest cutaneous xanthoma that develops around the eyes with the prevalence of roughly 1.1% in women and 1 0.3% in men. xanthomas are cholesterol-rich depositions that can appear anywhere in the body d u r i n g v a r i o u s d i s e a s e s t a t e s . t h e t e r m “xanthelasma” is derived from the greek word 2 xanthos (yellow) and elasma (beaten metal plate) chemical cautery with 100% tca versus agno for the treatment3 of xanthelasma palpebrum: a randomized controlled trial 1 2 lubna rani faysal, farid ur rehman correspondence: dr. lubna rani faysal assistant professor department of dermatology islamic international medical college riphah international university, islamabad email: lubna.rani@riphah.edu.pk 1 department of dermatology islamic international medical college riphah international university, islamabad 2 department of dermatology foundation medical college, rawalpindi funding source: nil; conflict of interest: nil received: september 05, 2018; revised: november 24, 2018 accepted: november 25, 2018 chemical cautery to treat xanthelasma palpebrumjiimc 2018 vol. 13, no.4 179 5 are associated with secondary hyperlipidemia. a b o u t 6 0 % o f p a t i e n t s h a v e a s s o c i a t e d hypercholesterolemia. xp has also been reported following erythroderma, inflammatory skin disorders, and allergic contact dermatitis despite normal lipid profiles. xp can occur in normolipidemic 6 persons with low hdl levels. it is essentially a benign condition; treatment is totally of cosmetic importance. in patients with xp who have associated lipid disorders, plasma lipid levels including triglycerides, cholesterol, low density lipoprotein and hdl, and apolipoprotein b 1 0 0 l e ve l s s h o u l d b e a s s e s s e d . m e d i ca l management involves lifestyle modifications such as regular physical exercise and low-fat diet in addition to lipid-lowering drugs. although important in the overall care of a patient with abnormal lipids, medical management has a limited role in the treatment of xp. several treatment modalities are used to treat xp but none of them produces satisfactory results. these include simple surgical excision, cryotherapy, chemical cauterization with trichloroacetic acid 7 (tca), radiofrequency (rf), and laser treatment. all modalities have their own advantages and disadvantages. simple excision with or without blepharoplasty and medial epicanthoplasty can be conducted in grades i and ii lesions, whereas, in advanced cases, uncapping surgery, local flaps, and skin grafts can be carried out. the commonest 8 method of surgery is full-thickness skin excision there are many disadvantages associated with surgery. there is always need of systemic or local anesthesia. it is often followed by slight scarring, 9 ectropion and dyspigmentation. radiofrequency (rf) is considered to be an easy, safe, inexpensive, and effective treatment but facility is not available in all clinical setups. this technique has minimal impact on the surrounding tissues, making it appropriate for delicate areas with temporary side effects include 10 pain, pruritus, burning, swelling, and erythema. similarly advantages of lasers include better acceptance, avoidance of surgery, minimal tissue loss, and good functional and cosmetic results. moreover, the procedure is easy to perform and gives fast results but the main disadvantages are high cost and unpredictable results sometimes. in a d d i t i o n , i t i s n o t p o s s i b l e t o o b t a i n a 11,12 histopathological specimen. tca is an affordable and versatile treatment modality, particularly in our setup. it is a short, simple, and inexpensive procedure. it has been observed that 100% tca gives the best results in papulonodular lesions, 100% or 70% tca give similar results in flat plaque xanthelasma, and 50% tca is 13 sufficient in macular lesions. hypopigmentation is t h e c o m m o n e s t s i d e e f fe c t , fo l l o w e d b y hyperpigmentation, irritation, and pain. scarring, atrophy, and koebner-like phenomenon are other rare side effects. there is not sufficient data available in literature on use of agno3 in treatment of xanthelasma but there is evidence of its use to debride hyper granulation tissue and calloused rolled up edges in wounds and ulcerations. it is a caustic material that oxidizes organic matter, coagulates tissue resulting into tissue 14 death. the objective of this study was to compare the efficacy of chemical cautery with 100% trichloroacetic acid (tca) versus silver nitrate (agno ) for treatment of xanthelasma palpebrum in 3 order to emphasize the importance and efficacy of this simple and cost effective treatment modality in the era of modern energy devices where laser & radiofrequency have almost replaced such 10,15 modalities. materials and methods this randomized controlled trial was conducted on o u t d o o r p a t i e n t s v i s i t i n g d e p a r t m e n t o f dermatology, pakistan railway teaching hospital, which is an affiliate of islamic international medical college, rawalpindi. a total of 40 patients with diagnosis of xanthelasma palpebrum, fulfilling inclusion criteria (age > 30 years, patients irrespective their lipidemic status, and absence of hypersensitivity) were enrolled for the study. the trial began after the permission from the hospital ethical review board and all the ethical issues were addressed. the disease was diagnosed on the basis of history and clinical examination. informed written consent was taken from patients after detailed explanation. the patients were divided in two equal groups (20 in each) by computer generated randomization list. group allocation was done to group a and group b patients allocated to group-a were treated with 100% tca and patients in group-b were treated with jiimc 2018 vol. 13, no.4 chemical cautery to treat xanthelasma palpebrum 180 agno3 (supersaturated sol). the chemical was applied to the lesion with help of wooden stick cotton swab; size of swab was customized manually to the size of lesion. before application of chemical, area was cleaned with normal saline. swab was dipped into the chemical and applied to the lesion with rotatory movement from outside to center of the lesion. the surrounding skin was protected by application of white soft paraffine around the lesion to prevent damage to the normal skin from accidental spillage of chemical. the endpoint for tca application was frosting of lesion and for agno was 3 charring /blackening of the lesion. all patients were given fusidic acid 2%, which had to be applied over the treated area twice daily for 01 week after the treatment. all the patients were evaluated objectively in clinic for improvement of lesion after 02 weeks of treatment session. the results were scored on a 0–4point following scale: 0 no improvement 1 moderate result (<25% improvement) 2 satisfactory result (25%–50% improvement) 3 good result (50%–75% improvement 4 excellent result (>75% improvement) follow up visits were done at 03months interval for post-inflammatory hyper/ hypo-pigmentation& recurrence of lesion. data was entered and analyzed by statistical package for social sciences (spss) version 21. quantitative data was calculated in the form of mean and standard deviation. qualitative data was calculated in the form of frequencies and percentages. chisquare test was used to compare the efficacy in two groups. a probability (p) value of less than 0.05 was considered statistically significant. results a total 40 patients with xanthelasma palpebrum were enrolled in the study, with 20 in each group, a & b respectively. the overall mean age of study population was 47 years with age range of 32 years to 68 years. there was no significant difference in the mean age of study population between two groups. there were total 13 males and 27 female patients. patients in group-a were treated with tca chemical cautery and patients in group-b were treated with agno .3 in group-a, 19 (95%) patients showed excellent results (75%-100% improvement) at 02 weeks of treatment, and 01(5%) patient showed this response in group-b. a total of 04 (20%) patients showed good result i.e.50-75% improvement in group-a and 15 (75%) patients in group-b had this response. only 01 (5%) patient had less than 50% improvement in group-b. (table-i) the percentage of patients with excellent improvement was significantly higher in group-a as compared to group-b, p-value <0.000. (table-ii) at the end of 03months follow up period, 04 (20%) patients in group-a had post-inflammatory hypopigmentation while 01 (5%) patient had it in group-b. (figure-i). no recurrence of lesion was reported during this time. table i: comparsion of efficiency of treatment in group a & group b table ii: chisquar test showing significant difference fig 1: comparison of post inflammatory hypopigmenta�on in both groups discussion the present study clearly shows the superior efficacy of tca chemical cautery in treatment of xanthelasma palpebrum as compared to agno3. more than 90% jiimc 2018 vol. 13, no.4 chemical cautery to treat xanthelasma palpebrum group b 181 patients achieved excellent results at 02 week after a single treatment session with tca 100% while the corresponding figure is very low, only 5% in group b. in a retrospective review of 102 patients treated with tca 95% for xp conducted by cannon ps, et al. patient's outcome at 03 months and 12 months of treatment for recurrence/ persistence of the lesion showed high patient satisfaction. overall, the success rate for tca was 61% at a mean follow-up of 16 31.8 months the mean number of tca treatments was 1.68. out of 44 reviewed in the clinic, there were 09 persistent lesions and 04 recurrences. of 51 patients contacted by telephonic interview, 22 patients had experienced a recurrence, 09 patients had persistence of the lesion and 3 patients undergone surgical excision of the lesion since the last tca treatment. in our study, > 90% patients achieved excellent results with 100% tca application and no persistence of lesion was recorded at 03 months follow up but to report for the recurrence, a longer follow up will be required. the results of various prospective treatment trials with different strengths of tca, 70% and 50% have shown its efficacy, satisfactory cosmetic result and 13,17 acceptable recurrence rate. but lowering the strength, increases average number of applications of chemical to achieve the desired result and hence the after effects of treatment like post-inflammatory hypo/ hyperpigmentation and scarring also get increased. atrophy and a koebner-like phenomenon has also been reported with repeated tca 18 applications. in our study only 04 patients reported with post inflammatory hypopigmentation at 03 months follow up, while no scarring, atrophy and koebnerization has been observed during follow up period. hence higher concentration of tca is more efficacious with better cosmetic results. it also prevents the repeated applications of tca. there is limited data available in literature on use of agno3 in treatment of xanthelasma but there is 14 evidence of its use in treatment of xp. in our study agno3 showed good results, 15 patients (75%) showed 50-75% clearing of lesion in single treatment while 4 (20%) had excellent results. it is relatively less efficacious than tca and has comparatively less posttreatment pigmentary changes (5% in group-b vs 20% in group-a). but the requirement of repeated applications of agno to achieve complete clearance 3 of the lesion may lead to more post-treatment pigmentary changes and scarring compared to tca100%. hence further research with agno in 3 future will be required with longer follow up duration. conclusion chemical cautery with 100% tca is more effective than agno3 and it is strongly recommended for treatment of xanthelasma palpebrum. references 1. jonsson a, sigfiisson n. significance of xanthelasma palpebrarum in the normal population. lancet. 1976; 76:372. 2. segal p, insull w jr, chambless le, stinnett s, larosa jc, weissfeld l, et al.the association of dyslipoproteinemia with corneal arcus and xanthelasma.the lipid research clinics program prevalence study. circulation. 1986; 73(2): 108 -18. 3. pathania v, chatterjee m. ultrapulse carbon dioxide laser ablation of xanthelasma palpebrarum: a case series. j cutan aesthet surg. 2015; 8(1):46–49. 4. martinez-rovira gr. xanthelasma in association with hyperthyroidism. jama. 1968;206(5):1081–3. 5. gangopadhyay dn, dey sk, chandra m, pal d, chaudhary s. serum lipid profile in xanthelasma. indian j dermatol. 1998; 43:53–56. 6. raulin c, schoenermark mp, werner s, greve b. xanthelasma palpebrarum: treatment with the ultrapulsed co2 laser. lasers surg med. 1999;24(2):122–7. 7. rohrich rj, janis je, pownell ph. xanthelasma palpebrarum: a review and current management principles. plast reconstr surg. 2002; 110(5):131013. 8. 12. mittelviefhaus h, kreusser c, bohringer d, auw-hädrich c. the underestimated depth of tissue invasion of xanthelasma: a histological study. klin monbl augenheilkd. 2011; 228(1):14–18. 9. eedy dj. treatment of xanthelasma by excision with secondary intention healing. clin exp dermatol. 1996;21(4):273–5. 10. mehmet akdag. the effects of radiofrequency in xanthelasma of eyelid: case report. j int dent med res. 2013;6:128–31. 11. karsai s, schmitt l, raulin c. is q-switched neodymiumdoped yttrium aluminium garnet laser an effective approach to treat xanthelasma palpebrarum? results from a clinical study of 76 cases. dermatol surg. 2009; 35(12):1962–9. 12. fusade t. treatment of xanthelasma palpebrarum by 1064nmq-switched nd: yag laser: a study of 11 cases. br j dermatol. 2008; 158(1):84–87. 13. haque mu, ramesh v. evaluation of three different strengths of trichloroacetic acid in xanthelasma palpebrarum. j dermatolog treat. 2006; 17(1):48–50. jiimc 2018 vol. 13, no.4 chemical cautery to treat xanthelasma palpebrum 182 848 17. nahastr, marques jc, nicoletti a, cunha m, nishiwakidantas mc, filho jv. treatment of eyelid xanthelasma with 70% trichloroacetic acid. journal of ophthal plast reconstr surg. 2009;25 (4): 280-3 18. akhyani m, daneshpazhooh m, jafari a k, naraghi, z s, farahani, f, toosi, siavash. koebner phenomenon in xanthelasma after treatment with trichloroacetic acid. dermatology online journal 2006; 12 (2). 14. widgerow ad, leak k. hypergranulation tissue: evolution, control and potential elimination. wound healing southern africa. 2010;3(2):1-3. 15. gungor s, canat d, gokdemir g. erbium: yag laser ablation versus 70% trichloroacetıc acid application in the treatment of xanthelasma palpebrarum. journal of dermatologic treatment. 2014; 25(4). 12 16. cannon p. s, ajit r, leatherbow b efficacy of trichloroacetic acid (95%) in the management of xanthelasma palpebraum. j clinical and experimental dermatology. 2010; 35(8): 845jiimc 2018 vol. 13, no.4 chemical cautery to treat xanthelasma palpebrum 183 original�article abstract objective: to determine the frequency of medical errors committed by doctors and the prevalence of second victim phenomenon in a tertiary care hospital, and to find out the effects of the error on the second victim's life. study design: cross sectional study st place and duration of study: this study was conducted in a tertiary care hospital of islamabad from 1 february th to 30 september 2016. materials and methods: a total of 200 male and female doctors were selected from a tertiary care hospital in islamabad, pakistan, through convenient sampling technique in order to fill a pretested structured questionnaire, for a period of six months. questionnaire was adapted from a previous study and alpha reliability of the variables checked. data was collected via face to face interviewing. it was analyzed using spss version 21. results: out of the 200 study participants, 62.5% belonged to the age group of 24-31 years, 53% of them were males and 43% were females. major errors were 13.2 %, minor 57.2 %, near miss were 29.6%. the prevalence of second victims came out to be76 %, and it was almost equal in males (80.6%) and females (71.7%) and was the highest in medicine department (35-40%). the main cause of errors was documented to be overwork by 72.5% of the participants. the major emotional effect as perceived by 50.5% participants was guilt, followed by sadness in 21.6%, embarrassment in 16.5% and sleep disturbance in 16%. around 75.5%of the participants were of opinion that an organization should be in place to help second victims come out of their trauma. according to 83% study participants, medical errors should be disclosed to patients and their families. conclusion: the study concludes that there is a high prevalence of medical errors in the tertiary care hospital and male and female doctors are equally becoming second victims of their errors. the major effects of medical error on the second victim's life are feeling of guilt, sadness, embarrassment and sleep disturbance. key words: cross sectional, medical errors, phenomenon, prevalence, sampling, second victim. sense of incompetence in profession, insult, and 1 even loss of job. they also receive a very harsh reaction if, at all, they share their mistakes with fellow colleagues or with the patients and their families. the term 'second victim' refers to the healthcare professional who experiences emotional distress following an adverse event which was 2 unanticipated. studies show that minor to major medical errors 3 affect many patients worldwide every year. the cases of doctors' negligence have been highlighted in various newspapers but not from the angle of second victims. the mistakes of doctors have been attributed to under qualification, indifferent approach towards the patient due to their private practices, lack of professional ethics as well as faulty 4 health policies. according to a study from johns hopkins more than , 250,000 deaths per year are related to medical errors introduction humans commit mistakes but the brunt of mistakes done by doctors is faced by the patients and they are the prime or first victims of doctors' errors. they may have to bear all sorts of trauma ranging from a minor harm to disability or even death. doctors themselves are the second victims of their own errors as they have to face the consequences of their mistakes, which can be a range of effects like frustration, distress, self-doubt, emotional trauma, anger, a medical errors and the prevalence of phenomenon of second victim in a tertiary care hospital in islamabad shumaila humayun, shazil abrar, sharaqa waseem, shafaq zaman, marya malik, ammara mohib, amina pervaiz correspondence: dr. shumaila humayun senior lecturer department of community medicine & public health foundation university medical college, islamabad e-mail: shumailahn@gmail.com department of community medicine & public health foundation university medical college, islamabad funding source: nil; conflict of interest: nil received: march 28, 2019; revised: march 12, 2020 accepted: march 16, 2020 medical errors and second victim phenomenonjiimc 2020 vol. 15, no.1 46 which suggests that deaths from medical errors comprise roughly 10 percent of all deaths in america every year hich makes medical errors the third 5 w 6 leading cause of death in the u.s. one of the leading causes of errors is communication barrier between patient and doctor. the increasing death toll over 7 last six years is alarming, and proves that errors are consistently occurring. in neighboring countries like india, 5.2 million patients are effected each year due 8 to medical errors. in pakistan, medical errors are not reported frequently due to fear of embarrassment in front of peers, fear of medico-legal action, fear of punitive action by patients and complaints to governing bodies but around half a million errorrelated deaths are occurring each year. many patients lose their life or face other serious health problems and disabilities because of the poorly structured healthcare system. no sympathy is 9 shown towards the second victims, although they are equally affected by trauma. improving patient safety requires more than voluntary reporting. organizational changes need to be implemented and 10 institutionalized as well. researchers figured out three ways doctors choose to cope with the stress: (1) to abandon the profession, (2) to leave the incident behind and carry on with their duty, (3) learn lesson from their mistakes and try to avoid them in 11 future. physicians all over the world, irrespective of their competence, are bound to commit medical errors as human error cannot be ruled out. various circumstances affect their state of mind and they may make mistakes unintentionally. researchers while attending a conference found that 60% of the physicians present there recalled at least one adverse patient event that left a huge negative impact on their lives. among anesthesiologists, 84% suffered at least one such event that affected them emotionally and among these, more than 70% reported stress and self-doubt. nineteen percent of these anesthesiologists admitted that they still were not able to recover from the emotional trauma. 12 according to a report on the growing issue of medical negligence in pakistan, the medical training of doctors in pakistan needs special attention. work hours need to be regulated and deficiencies in legal protection for doctors and patients need to be rectified. reasonable salaries and working hours for doctors, and adequate training and skills might lead to decreased errors, and in turn, decrease in the number of second victims. 13 the second victim phenomenon has been highlighted and researched in various developed and developing nations of the world but extensive literature survey indicates no significant study conducted in any tertiary care hospital of islamabad. the study fills an identified gap in the body of knowledge and proves to be a contribution to the domain of public health. its main objective was to determine the frequency of medical errors committed by doctors and the prevalence of second victim phenomenon in a tertiary care hospital, and to find out the effects of the error on the second victim's life. materials and methods st a cross-sectional study was conducted from1 feb – th 30 sep, 2016, and 200 male and female doctors from a tertiary care hospital in islamabad were selected through convenient sampling technique. the research was ethically approved from ethical committee of the hospital and the confidentiality of the name of hospital and the respondents was ensured. written informed consent was taken from all the participants and they were allowed to withdraw any time during the study. medical officers, registrars and consultants from medicine, surgery, pediatric, eye, gynecology / obs , ent, derma, &icu department who had worked in the hospital for at least one year or more after house job were included in the study. house officers were excluded since they were under training and learning phase and had less than one year experience. data was collected using a pretested structured questionnaire. the tool was adapted from a previous study in this regard with modifications. alpha reliability of the variables was checked. sample size was obtained using who sample size calculator taking the following study as reference: waterman a d et al, the emotional impact of medical errors on practicing physicians in the united states and canada. the joint commission journal on quality and patient safety, august 2007; 33 (8):46714 476. before entering data into computer, all questions were checked for mistakes and omissions. data was analyzed using spss version 21, and presented mainly as frequencies and percentages using bar medical errors and second victim phenomenonjiimc 2020 vol. 15, no.1 47 charts, and frequency tables. in order to see the gender difference of second victim phenomenon prevalence, chi-square test was applied taking pvalue of <0.05 as significant. results out of the total 200 study participants, 106 (53%) were females and 94 (47%) were males. majority belonged to the age group of 24-31yrs (62.5%), (table1). the prevalence of second victims came out to be 76%.it was almost equal in males 76/94 (80.8%), and females 76 /106 (71.7%). the value of chi square was 0.139 at p < 0.05, (table ii). prevalence w a s h i g h e s t i n d e p a r t m e n t o f m e d i c i n e 38(25%),followed by surgery 27(17.8%) and gynecology 25(16.44%)( fig 1) majority of the second victims, 87(57.2%) were involved in minor error. out of these, 48 (55.1%) disclosed the error to the authorities, and 39 (44.8%) disclosed it to the patient.(table iii,iv) according to participants' responses, major barrier towards disclosure of error was fear of loss of professional reputation, declared by 93 (30.8%). major emotional effect on second victims was guilt in 98 (24.9%), followed by sadness in 85 (21.6%), and embarrassment in 65(16.5%) respondents. around 42 (40%) of participants' responses revealed that family life was affected due to an error, about 81 (25.8%) responses showed that job dissatisfaction was a major effect on occupational life, followed by 43 (13.7%) responses that pointed to negative effect on confidence as physicians.(table v). the main cause of error according to the study population was overwork in 140 (72.5%), followed by lack of experience 82(42%), lack of knowledge 56 (28%), and panic 43 (21.5%). according to 166 (83.0%) of the participants, patients and their families should be told about the adverse events. among all,153 (76.5%) were of the opinion that error disclosure training should be provided to doctors, and 152(76%) wanted provision of counseling services to second victims. majority, 151 (75.5%), of the participants were of the opinion that there should be some organization for support of second victims in order to solve their issues. among all, 70 (35%) participants disagreed with the statement that hospitals support second victims. the following hypothesis was made for chi square application to see the difference of gender in second victim phenomenon. h : there is no significant difference between the 0 frequencies of male and female second victims. h : there is a significant difference between the 1 frequencies of male and female second victims. p value: 0.139 level of significance: <0.05 the application of chi-square test indicates that pvalue is 0.139 which is higher than the level of significance that is 0.05 hence accepting the null hypothesis and rejecting the alternate hypothesis, the results of the analysis indicate that medical errors equally affect both male and female doctors, in this tertiary care hospital. table i: demographic profile of study par�cipants (n=200) table ii: cross tabula�on showing the frequencies of male and female second vic�ms table iii: type of medical error (n=152) medical errors and second victim phenomenonjiimc 2020 vol. 15, no.1 48 discussion doctors, as second victims, have to face emotional trauma in an adverse situation. this research was designed to determine the prevalence of the second victim phenomenon and effect of medical errors on doctors' lives. in our research on 200 participants, 76% declared that they had been a second victim somewhere along their medical career in this hospital after committing an error. major errors committed were 13.2 %, minor 57.2 %, near miss were 29.6%. in a similar research conducted by attia bari and fellows in lahore, 130 residents were included to study this phenomenon and majority of respondents (98.5%) described some form of error. major errors that occurred were 19%, minor were 48% and 19% were 13 near miss. most of the participants recalled that they were medical officers or trainees when they experienced this phenomenon, which is similar in table iv: error disclosure by the par�cipants (n=152) fig 1: bar chart showing second vic�m prevalence in different departments table v: par�cipants 'responses about effect of error on life and barriers to disclosure table vi: par�cipant's response on how errors should be managed by authori�es (n=200) medical errors and second victim phenomenonjiimc 2020 vol. 15, no.1 49 both studies. in our study 69% disclosed medical errors to their senior authorities, and 31% to patients, while these results are in line with their study where 57% residents disclosed medical errors to their senior physician but disclosure to patient's family was negligible (11%).this points to similar socio-cultural conditions in major cities of our country. the major cause of error was declared to be fatigue in 65%, due to long duty hours, which was similar to our research, and guilt was the most felt emotional setback. in contrast study done on residents of usa & 14 canada revealed that 92% of participants were involved in errors including major (57%), minor (36%) and near miss. (7%).this is higher as compared to ours, and the difference may be due to higher chances of disclosure of errors. in that study, 89% reported disclosing major error to patients and 54% disclosed minor error to patients, which is 15% for major and 44.8 % for minor error in our setting, hence explains the difference. our physicians are reluctant to disclose errors. a good majority (83%) of the participants of our study believed that patients and their families should be told about the adverse events, but contrastingly, disclosure to the patients is much lesser (15%) such a low percentage is seen . mostly because of fear of loss of professional reputation and fear of patients' reactions and dissatisfaction with the overall system of the hospitals. doctors should be able to tell the patient and the authority about such adverse events openly. our findings emphasize the need for establishment of proper support system and societies for doctors to cope with the stress of such events. about 76.5% of the participants believe that there should be error disclosure training given to health care professionals. also in our setting, male and female doctors were equally affected by the second victim phenomenon, while in their study, females were more affected. it might be due to the fact that our females are either more resilient and can handle stress in a better way or afraid to admit and disclose errors. in maeve o'beirne's research done on canadian health professionals, the top five reported emotional responses were frustration (48.3%), embarrassment (31.5%), anger (12.6%), guilt (10.1%), and sadness (2.1%).in our study results for embarrassment (16.5%) anger (10.9%) guilt (24.9%) and sadness (21.6%) clearly show that our respondents were left with a heavy heart and felt more guilty and sad after the incident. it was revealed that 52% of 264 participants talked to someone to deal with an 15 emotional response. in our study 76% of the respondents wanted access to counseling after serious errors, which seems to lack in our system, as no one lends a shoulder for emotional venting and counseling. proper training should be provided to the doctors to disclose such information to the patients and their families. among our study participants, 35% disagreed with the statement that hospitals support second victims. in usa & canadian study, 90% of physicians disagreed that hospitals and health care organizations support physicians and help them in coping with trauma and stress linked to medical errors. hence the indifferent and nonsympathetic approach of healthcare organizations seems to exist universally regardless of whether the country is developed or developing. a majority (82%) of physicians showed interest in receiving 14 counseling after a medical error. researchers at the university of missouri health center found that almost 1 in 7 staff members declared in a survey that they had experienced a patient safety event within the past year that affected personal life causing anxiety, depression, or doubt in professional confidence. a major two thirds of them denied any 16 support from their institute. in most health care settings, healthcare providers do not receive care, support or guidance when they commit an error, and most suffer in silence. 17 a research conducted in a tertiary care hospital in india concluded that errors related to medication were 50.26%, related to treatment procedures were16.23% and related to clerical procedures were 18 28.27%. hence, errors are inevitable. they are occurring globally and need attention in order to prevent psychological, physical, and emotional setback in the physicians. at present medical errors have become great challenges for healthcare 19 professionals, and health policy makers. the study was limited because of convenient sampling technique and small sample size. as it was carried out in only one tertiary care hospital hence results can't be generalized. further studies are suggested to know the actual prevalence of second victim phenomenon and the magnitude of medical medical errors and second victim phenomenonjiimc 2020 vol. 15, no.1 50 errors occurring in major hospitals. conclusion the study concludes that there is a high prevalence of medical errors in the tertiary care hospital and male and female doctors are equally becoming second victims of their errors the major effects of medical error on the second victim's life are feeling of g u i l t , s a d n e s s , e m b a r ra s s m e n t a n d s l e e p disturbance. the main cause of error identified is overwork. references 1. ozeke o, ozeke v, coscono,budakoglu i i.second victims in health care : current perspectives.adv med educ pract.2019;10: 593-603 2. shor s, tal o, maymonr.the second victim: treating the health care providers.harefuah2017, 156 (1):38-40 3. rinaldi c, leigheb f, vanhaecht k, donnarumma c, panellam.becoming a "second victim" in health care: pathway of recovery after adverse event.revcalidasist. 2016 jul; 31suppl 2:11-9. 4. naghavi m, wang h, lozano r, davis a, liang x, zhou m, et al .global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 19902013: a systematic analysis for the global burden of disease study 2013. lancet. 2015; 385(9963):117-71. 5. yourker n.is medical practice a leading cause of death?.younker hyde macfarlane. www.patientinjury.com. nov, 2019 6. 2016; 353makary .m a, daniel m, bmj 7. salhotra r, tyagi a. medication errors: theycontinue. j anaesthesiol clin pharmacol, 2019;35:1-2 8. yadav m rastogi p.a study of medical negligence cases decided by the district consumer courts of delhi. journal of indian academy of forensic medicine.2015;37(1):50-55 9. kamran r, bari a, khan r a, and al-erakym.patient safety awareness among undergraduate medical students in pakistani medical school.pak j med sci. 2018 mar-apr; 34(2): 305–309.doi: 10.12669/pjms.342.14563 10. anderson jg, abrahamson k.your health care may kill you: medical errors. stud health technol inform. 2017; 234:1317. 11. waeschle rm, bauer m, schmidt ce.errors in medicine. causes, impact and improvement measures to improve patient safety. anesthetist. 2015 sep; 64(9):689-704. doi: 10.1007/s00101-015-0052-4. 12. gazoni fm, amato pe, malik zm, et al. the impact of perioperative catastrophes on anesthesiologists: results of a national survey. anesthanalg 2012; 114(3): 596–603. 13. bari a, khan r a, rathorea w. medical errors; causes, consequences, emotional response and resulting behavioral change.pak j med sci 2016;32(3): 523-528doi: 10.12669/pjms.323.9701 14. waterman a d et al, the emotional impact of medical errors on practicing physicians in the united states and canada. the joint commission journal on quality and patient safety, august 2007; 33 (8):467-476 15. o'bernie m, sterling p, derflingherp.emotional impact of patient safety incidents on family physicians and their o f f i c e s t a f f. j a b f m 2 0 1 2 ; 2 5 ( 2 ) : 1 7 7 1 8 3 ; d o i : 10.3122/jabfm.2012.02.110166 16. clancy cm. alleviating “second victim” syndrome: how we should handle patient harm. journal of nursing care quality. jan 2012; 27(1):1-5 17. susan d, scott r n. the second victim phenomenon: a harsh reality of health care professions: , perspectives on safety 2011. 18. gaur s, sinha ak, srivastava b. medication errors in medicine wards in a tertiary care teaching hospital of a hill state in india. asian j pharm life sci. 2012; 2:56-63 19. mohajan h k.medical errors must isreduced for the welfare of the global health sector international journal of public health and health systems. vol. 3, no. 5, 2018, pp. 91-101. medical errors and second victim phenomenonjiimc 2020 vol. 15, no.1 51 jiimc june 2016.cdr 46 editorial internet addiction or problematic internet use: current issues and challenges in conceptualization, measurement and treatment saad naeem zafar ------------------------------------------------correspondence: prof. saad naeem zafar dean faculty of computing riphah international university, islamabad e-mail: saad.zafar@riphah.edu.pk received: jun 01, 2016; accepted: jun 02, 2016 sociodemographic risk factors may comprise male gender, younger age and higher family income. the internet use risk factors may include time spent online and using social or gaming applications. the p syc h o l o g i c a l fa c to rs m ay b e i m p u l s i v i t y, neuroticism and loneliness. finally, the co-morbid symptoms may consist of depression, anxiety and psychopathology in general. at the conceptual level the difference is whether the criterion is derived from pathological gambling, substance-related addictions or the number of problems experienced. additionally, there seems to be a disagreement about the cut-off points used within each criterion. as far as the psychometric measures are concerned, young's internet addiction 8 test seems to be the most popular instrument used in the empirical studies but different cut-off points are used across studies making the comparison 9 between studies difficult. other measures often cited include computer game addiction scale (aica 10 11 s) , compulsive internet use scale (cius) and 12 chen's internet addiction scale. there is also now a focus on differential diagnosis and/or co-morbidity of internet addiction. a more 9 recent review in 2016 indicates that presence of comorbidities in internet addiction in clinical context appears more prevalent than initially thought. individuals seeking help often have symptoms of mood and anxiety, impulse control and addictive disorders. this suggests that ia treatment can be more effective when a holistic approach is taken that combines evidence-based treatments of any comorbidities that may be present in an individual. accordingly, the ia treatment approaches have been e i t h e r b a s e d o n p sy c h o p h a r m a c o t h e ra p y, psychological therapy and combined therapy approaches. psychopharmacotherapy has shown an overall positive effect on ia symptoms and internet use times. in a few studies antidepressant medication has been reported to be successful, indicating that mood disorders may be more prevalent with internet 9 addiction. as regards to the psychological therapy, a combination of individual and group therapy approaches have also been used. overall group therapy treatments have shown better results over individual therapy approach for both reduction in there are now over three billion internet users in the 1 world. this makes it about 40% of the world population. in 1995, only 1% of the world population was using the internet. the first billion mark of the internet users was achieved in 2005, the second billion in 2010 and the third billion was reached in 2014. pakistan is no exception. there are currently 2 over thirty four million internet users in the country. the number of smart phones that further facilitates internet connectivity is expected to cross 40 million 3 by the end of the current year. this increased internet connectivity has changed many an aspect of personal, professional and social lives of internet users. consequently, the amount of time people spent online has been growing steadily. according to a recent study young people in the uk have started spending more time online than watching tv for the 4 first time. the early researchers and adaptors of the internet technology generally viewed the online social engagement, entertainment and discussion in a positive light because they believed that virtual communities provide emotional support and a platform for discussion and sharing information with relative ease and with less inhibition. however, the pervasive nature of internet in daily lives has also led to excessive or uncontrollable use in extreme cases. 5 6 the seminal studies by goldberg and young in 1996 are generally considered as the first efforts in developing the notion and conducting empirical research on the topic of internet addiction (ia) or internet addiction disorder (iad). over the years the scope of research on ia has been considerably widened but without any universal definition, assessment criteria or treatment methods. a comprehensive review of ia research in 2014 indicated association of a number of risk factors 7 w i t h i a . t h e s e r i s k f a c t o r s i n c l u d e sociodemographic, internet use, psychological f a c t o r s a n d c o m o r b i d s y m p t o m s . t h e 47 jiimc 2016 vol. 11, no.2 references 1. “internet users in the world,” internet live stats, 2016. [online]. available: http://w w w. internetlivestats.com/internet-users/. [accessed: 06-jun-2016]. 2. “pakistan internet users,” live internet stats, 2016. [online]. available: h t t p : / / w w w . i n t e r n e t l i v e s t a t s . c o m / i n t e r n e t users/pakistan/. [accessed: 06-jun-2016]. 3. “telecom sector: pakistan to have 40 million smartphones by end of 2016,” the express tribune, 2015. [online]. available: http://tribune.com.pk/story/953333/telecomsectorpakistan-to-have-40-million-smartphones-by-endof-2016/. [accessed: 06-jun-2016]. 4. “childwise monitor report 2015”. 5. goldberg i. “internet addiction disorder,” retrieved november. 1996. 6. young k. “internet addiction: the emergence of a new clinical disorder,” cyber psychology behav. 1998. 7. griffiths md, kuss dj, billieux j, pontes hm. “the evolution of internet addiction: a global perspective.,” addict. behav. 2016; 53: 193-5. 8. young ks, caught in the net. new york: wiley, 1998. 9. kuss dj, lopez-fernandez o. “internet addiction and problematic internet use: a systematic review of clinical research.,” world j. psychiatry. 2016; 6: 143-76. 10. wölfling k, müller k, beutel m. “diagnostic measures: scale for the assessment of internet and computer game addiction (aica-s),” prev. diagnostics, ther. comput. game addict. 2010; 26: 212-5. 11. meerkerk g, eijnden van den r. “the compulsive internet use scale (cius): some psychometric properties,” cyber psychology 2009. 12. sh c, lc w, yj s, hm w, pf y. “development of chinese internet addiction scale and its psychometric study,” chin j psychol. 2003; 45: 279-94. 13. yang x, zhu l, chen q, song p, wang z. “parent marital conflict and internet addiction among chinese college students: the mediating role of father-child, motherchild, and peer attachment,” comput. human behav. 2016; 59: 221-9. 14. zhu tm, jin rj, zhong xm, chen j, li h. “[effects of e l e c t ro a c u p u n c t u re co m b i n e d w i t h p syc h o l o g i c interference on anxiety state and serum ne content in the patient of internet addiction disorder].,” zhongguo zhen jiu= chinese acupunct. moxibustion. 2008; 28: 561-4. time spent online and significantly higher selfesteem. moreover, in case of adolescents, the most important factor to reduce internet addiction seems 13 to be parent-child relationship. some studies have reported combined therapy treatments that have resulted in positive results in both post-treatment and follow-up measures. the study that stands out in this category of therapy is the significantly positive results in use of electro-acupuncture in combination 14 with a psychological intervention suggesting that this novel approach may be investigated further to establish its efficacy and effectiveness. the internet connectivity is relatively cheap and accessible in urban and semi-urban areas of pakistan. with advent of 3g and 4g mobile networks available through pakistan, the amount of time people spend online is expected to grow significantly. physicians in pakistan should explore the possible signs of internet addiction or problematic internet use among the vulnerable segments of the society. the co-morbidity of internet addiction with mood and anxiety disorders may also be explored when deciding a treatment approach. the role of family structures in pakistan as support group may also be useful in group therapy sessions. it may be kept in mind that presence of co-morbidities complicates the treatment as it may be important to establish whether internet addiction is the primary or secondary disorder. 9 as suggest in , research scholars in pakistan are also recommended to validate the measures already in use and collaborate with international research community to develop a universally agreed-upon criterion for assessment and treatment. this will also pave the way for public policy debate and development of health care facilities in the country that provide early diagnosis and treatment to the affected individuals. the study reported in this journal on internet addiction and its impact on academic performance is a head start for further research on the topic. original�article abstract objective: to compare the anti-hyperglycemic and anti hyperlipidemic activities of ethanolic extract of glycyrrhiza glabra (licorice) roots with the standard drugs metformin and glimepiride in streptozotocin induced diabetic rats. study design: experimental study. place and duration of study: animal house of basic medical science institute (bmsi). jinnah post graduate medical center (jpmc), karachi conducted from may 2018 till august 2018. materials and methods: total seven groups of wistar albino rats comprising six rats in each were included. study included negative control and positive control groups, to which 0.9% of sodium chloride was administered. other five groups of streptozotocin induced diabetic rats were treated with metformin, glimepiride, rosuvastatin, ethanolic extract of glycyrrhiza glabra (licorice) roots at a dose of 200 mg/kg and 400mg/kg, respectively. the treatment was given for 28 days followed by the laboratory estimation of fasting blood glucose (fbg), fasting serum insulin, glycosylated hemoglobin a1c (hba1c), total lipid profile and serum amylase were evaluated. results: a significant decrease was observed in all the glycemic indices at both doses of glycyrrhiza glabra (licorice) i.e. 200 mg/kg and 400mg/kg, but a more rampant decrease is observed at the dose of 400mg/kg. similarly, both concentrations of extract showed significant decrease in all lipidemic indices that included hdlc, vldl-c, ldl-c, total cholesterol (tc), triglycerides (tg) and the serum amylase levels. conclusion: this study concludes that the licorice herb has sufficient anti hyperglycemic and anti hyperlipidemic effects in diabetic rats without any aberration in pancreatic enzymes, hence it might be beneficial as additional dietary supplements for the effective management of diabetes mellitus along with standard drugs. key words: diabetes mellitus, hyperglycemia, hyperlipidemia, licorice. 2 by 2040 throughout the world. this alarming illness is mainly of two types i.e. type 1 which is caused by relative insulin deficiency while type 2 is mainly 3 attributed to insulin resistance. along with other comorbidities, dyslipidemia is also associated with poorly controlled diabetes mellitus which can lead to multiple micro and macro vasculopathies including coronary heart disease and stroke that explains early 1 mortalities and morbidities in diabetic patients. the oral treatment regimen for diabetes mellitus is classified in to insulin sensitizers, insulin 4 secretagogues and miscellaneous group. the management and control of diabetes by these synthetic drugs without adverse effects is a great challenge because mostly all these oral anti hyper glycemic medications have various distressing complications with development of resistance 5 , 6 on enduring exploitation. furthermore, conventionally used most oral hypoglycemic drugs have more side effects on which is the awful diabetes mellitus is a metabolic disorder characterized by hyperglycemia along with weakened metabolism of carbohydrate and other essential energy yielding fuels, such as lipids and 1 proteins.” recently, the international diabetes federation (idf) has reported that around 415 million people were having diabetes mellitus in 2015 and this figure is assumed to raise up to 642 million introduction anti-hyperglycemic and anti-dyslipidemic activities of glycyrrhiza glabra root extract in diabetic rats 1 2 3 4 5 6 jabbar ahmed qureshi , zahida memon , kauser ismail , fizza saher , vanita motiani , zain mushtaq correspondence: dr. jabbar ahmed qureshi assistant professor department of pharmacology ziauddin university, karachi e-mail: drjabbar.qureshi@hotmail.com 1,2,3 4 5 department of pharmacology/oral biology /student ziauddin university, karachi 6 department of medicine agha khan university hospital, karachi funding source: nil; conflict of interest: nil received: august 06, 2019; revised: february 26, 2020 accepted: february 27, 2020 anti-hyperglycemic and anti-dyslipidemic activities of glycyrrhiza glabra rootjiimc 2020 vol. 15, no.2 98 7 outcome of poorly controlled diabetes. herbal drugs remain the focus of attraction by the researchers not only in ancient times but still today a large number of world's population believes that herbal medications 8 are sole remedies for a range of diseases. there are about 45000 plants which possess different medicinal properties including anti hyperglycemic and anti-dyslipidemic activities. g.glabra is the root of glycyrrhiza inflates (fabaceae) which is commonly known as sweet wood or licorice. it is regularly used herb for culinary and ayurvedic purposes in south 9,12 asia since long time. according to current literature, g.glabra is medically used for multiple purposes such an antioxidant, antidote for peptic ulcers and gastritis and prevention as well as 13 treatment of common cold. furthermore, it has potent anti-tussive activity, muscle relaxing property, weight reduction potential, immune boosting action via increasing wbc counts and anti14 diuretic and anti-inflammatory effects. the naturally active constituents of g.glabra are glycyrrhizin, liquiritins, liquiritigenin, glycyrrhizin acids and flavones. glycyrrhizin is the major saponin in licorice root and its metabolite glycyrrhetinic acid 15 is main pharmacologically active form. together these flavonoids confirm significant anticancer, 16 antioxidative, antimicrobial, and antiviral effects. moreover, licorice also reduces the liver damage significantly owing to its antioxidant and antiinflammatory properties as indicated by chen et al. 17 in 2014. however, none of the studies mentioned above have aimed to find out the antidyslipidemic properties of g.glabra. therefore, in our study we have used g.glabra on rats to find out its effects on the different lipidemic parameters. moreover, we also aimed to find out the effect of different doses of g. glabra on the lipidemic parameters. therefore, this study was conducted to compare the anti-hyperglycemic and anti hyperlipidemic activities of ethanolic extract of glycyrrhiza glabra (licorice) roots with the standard drugs metformin and glimepiride in streptozotocin induced diabetic rats. materials and methods this was an experimental study conducted between may 2018 till august 2018 in animal house of basic medical science institute (bmsi), jinnah post graduate medical center (jpmc), karachi. g.glabra root was obtained from the local market of karachi. the plants were authenticated and identified from botany department of karachi university and taxonomy number was obtained. (taxonomic number of glycyrrhiza glabra i.e. licorice is: 17234) the study was approved from ziauddin university. the g.glabra roots were washed and dried separately in open air for 48 hours. the roots were then minced into powder using a mechanical grinder. the powder was then mixed and infused with absolute ethanol at a 1:10 ratio (100 gram in 1 l solvent) for 7 days in separate jars. the extract was filtered through a whatman no 1 filter paper which was followed by rotory evaporation of fíltrate with the help of rotary evaporators so that the concentrated extract of herb was obtained which was free of ethanol. the crude extract was reconstituted in freshly prepared 2.5% dimethyl sulfoxide dmso and kept in jar for evaluation of antihyperglycemic and anti-dyslipidemic properties in diabetic rats. forty-two adult male and female wistar albino rats (aged 7-8 weeks, weighing 180–240 grams) were purchased from the animal house of agha khan university hospital. however, it was made sure none of the rats purchased suffered from any other comorbidity that could have affected our results. all rats were kept in (25 ± 3 � c, 12 h light/dark cycle) as well as the standard diet and clean tap water the rats were provided. rats were divided in 7 groups: groupi negative control non diabetic rats; treated with 0.9% sodium chloride (nacl). group ii positive control diabetic rats; treated with 0.9% nacl. groupiii diabetic rats and was treated with glimepiride at 0.1 mg/kg bw. group-iv diabetic rats and was treated with metformin at 10 mg/kg bw. group v diabetic rats; treated with rosuvastatin 10 mg/kg/day bw. group vi diabetic rats; treated with ethanolic extract of g.glabra at a dose of 200 mg/kg .groupvii diabetic rats; treated with ethanolic extract of g.glabra at a dose of 400 mg/kg. with the exception of negative control group, diabetes was induced to all animals by injecting the solution of streptozotocin (stz). the solution was made by dissolving dry powder of stz in 0.1 m citrate 17 buffer (ph 4.5) that was used after filtration. it was injected as a single dose of 55 mg/kg via intra peritoneal route (i.p) to overnight fastening rats. on anti-hyperglycemic and anti-dyslipidemic activities of glycyrrhiza glabra rootjiimc 2020 vol. 15, no.2 99 rd 3 day 1ml blood was taken from tail for fbs from each rat. the rats whose blood glucose level was 18 more than 250mg/dl were considered as diabetic. herbal extract and standard treatment were given to all the rats except positive control through metallic feeding syringe orally for a period of 28 days. th on 29 day, following overnight food deprivation, the rats were given an anesthesia that consisted of ether solution and were sacrificed as per institutional animal ethics committee (iaec) guidelines. a blood sample of 10 ml was collected by cardiac puncture and was transferred into vacuum tubes which were then centrifuged at 3000 rpm for 10 minutes. after centrifugation, sera were separated for different 19 biochemical assays. glycemic indices such as blood glucose level, serum insulin, glycosylated hemoglobin (hba1c), serum amylase and lipid profile such as total cholesterol (tc), triglycerides (tg), high density lipoproteincholesterol (hdl-c), very low density lipoproteins (vldlc), low density lipoproteins cholesterol (ldlc) were measured from serum samples by standard enzymatic methods using commercially available kits (bartham, trinder, richmond and schettler) according to manufacturer advice respectively. the data was analyzed using the software spss version 20.0. the glycemic índices and lipid levels were expressed as mean ± standard error of mean (sem) that were obtained by analysis of variance (anova) test. the p values less than 0.05 were considered statistically significant for all treatment groups. results effects of glycyrrhiza glabra on fasting blood glucose levels all the glycemic parameters showed a significant increase in the positive control group as compared to the negative control group at day 29 (table i). a rampant decrease was observed in glimepiride group. the administration of licorice root extract at the dosage of 200mg/kg and 400mg/kg for 29 days to rats with hyperglycemia (induced by streptozotocin via intraperitoneal route of administration) a significant reduction in the blood glucose concentration, hba1c and fasting serum insulin in comparison to the result obtained from the positive control group (mentioned in*). effects of glycyrrhiza glabra root onserum lipid concentration parameters associated with the lipid profile such as tc, tg, hdlc, vldl-c and ldl-c were considerably altered in positive control group in comparison with negative control (table ii). rosuvastatin maximally normalized these values. both doses of g. glabra also improved these parameters significantly as compared to positive control group (table ii). table i: effect of fas�ng blood sugar, hba1c and serum concentra�on in comparison with nega�ve and posi�ve control gg: glycyrrhiza glabra fbs: fas�ng blood sugar glycosylated hemoglobin *shows p-value < 0.05 (highly significant) table ii: total cholesterol tc, tg, hdl, vldl, ldl, in control and diabe�c rats treated with glycyrrhiza glabra gg: glycyrrhiza glabra tg: triglycerides tc: total cholesterol hdl: high density lipoprotein vldl: very low-density lipoprotein ldl: low density lipoprotein *shows p value is highly significant effects of glycyrrhiza glabra on serum amylase levels there was significant rise in serum amylase level in positive control group) when compared to negative control. g.glabra at both dosages reduced these values significantly (table iii). anti-hyperglycemic and anti-dyslipidemic activities of glycyrrhiza glabra rootjiimc 2020 vol. 15, no.2 100 control control discussion management of diabetes by any means like with oral hypoglycemic drugs or by injecting drugs such as 21 insulin or recently introduced exenatide is a big challenge as nearly all of these drugs have a number of serious adverse effects and distressing complications. moreover, these agents are generally 22 used in combination to get maximum effects. finally, on enduring exploitation resistance develops gradually resulting in unsuccessful glucose control 22 and appearance of fearsome complications. in this scenario the medicinal plants are great blessing as not only they have the potential to cure but also after diagnoses if received earlier herbal formulations derived from plants offer an innate 24 approach for prevention of complications as well. hence for purpose of evaluating the antihyperglycemic properties of g.glabra we constructed a diabetic model of rats with 25 streptozotocin. firstly, it is to be noted that fbs values raised significantly at both doses of g. glabra i.e 200mg/kg and 400mg/kg as seen in table i and comparable with 26 other studies done by han s. et al. the optimal blood glucose level must be below 140 mg/dl and this sugar level was achieved more or less only in standard groups. this finding can be attributed to the presence of non-hydrophilic flavonoids that showed alpha glucosidase inhibiting activity enzyme that hydrolyze polysaccharides into simpler form for 27 better absorption of sugars from small intestine. other possible mechanism may be the activation of peroxisome proliferator-activated receptor-γ (pparγ) as this receptor is responsible for the utilization of 28 energy and homeostasis. our herb possesses both innate alpha-amylase inhibiting property along with natural ppar-gamma inhibitory potential and thus modifies two different pathways of glucose metabolism which otherwise will be provided by two different classes of ohg agents. secondly, despite significant lowering of fbs after 29 days of treatment, g.glabra failed to improve hba1c and fasting serum insulin levels when compared with positive control (p value 1.00). the underlying reason may be limited time duration of treatment i.e. 28 days which might be insufficient to produce obvious 1,9,29,30 changes in hba1c and insulin level. as other studies conducted show that 12 month or greater 31 time span yield in more positive result. thirdly, in our study the diabetic rats that were treated with g. glabra showed a considerable and significant improvement in all the parameters associated with dyslipidemia in comparison to the positive control group (p<0.001) just like the rosuvastatin group.the anti dyslipidemic factor of g.glabra could be attributed to the presence of phytosterols and 32,33,34,35 saponins in the g. glabra. according to a study the phytosterol can replace the intestinal cholesterol which could lead to a decrease in the amount of cholestrol as it won't be absorbed properly from the 37 intestine. in one study, it was observed that when g. glabra roots when given as 5% and 10% diet for 4 weeks in hyper-cholesterolemic rats and it was observed that lipid levels were drastically reduced and excretion of cholesterol and bile acid seen in 35 feces markedly increased. in another study done by shalaby et al. it was exhibited that g. glabra reduced the levels of tc and tg with no significant change observed in the levels of ldl, hdl and vldl in male 36 rats. but these results are not consistent with our study as our results show a mark improvement in all parameters related to dyslipidemia which was also seen in furukawa et al., 2017, al-rubeaan et al., 2017, king, 2012, gaur et al., 2014. according to the results of our study an increase in hdl and a decrease in tc is observed which can be owed to the increase stimulation of pre-β hdl-c and reverse cholesterol transport, as demonstrated in 38 rodriguez et al's study or due to the suppression of hydroxyl methyl glutaryl-coa synthase activity by glycyrrhizin, the active component of g.glabra. the present study illustrated that research herb reduces the bad and improves the good cholesterol levels in streptozotocin induced diabetic rats which could be due to the saponin content of g.glabra root. as pancreatitis is the common complication of few 39 oral hypoglycemic drugs and is usually encountered 17 clinically as raised serum amylase levels. therefore, table iii: serum amylase level when compared with control groups and g.glabra groups gg: g.glabra *shows p value is highly significant. anti-hyperglycemic and anti-dyslipidemic activities of glycyrrhiza glabra rootjiimc 2020 vol. 15, no.2 101 we aimed to evaluate the effects of our herb on pancreatic enzymes and we found no aberration in this enzyme. the serum amylase levels were significantly increased in the diabetic rats in comparison to the rats in the positive control group. furthermore the levels of serum amylase reduced back to an almost normal range after 28 days of treatment with g.glabra as seen in table iii. this data is however scarce regarding the effects of this herb on pancreatic physiology but xiaoying et al highlights the g.glabra's positive effect on the levels of serum alanine aminotransferase (alt) and aspartate transaminase (ast) in a cadmium induced hepatotoxicity of animal model and its reversal 40 effect on inflammatory changes of liver. conclusion with the evidence from this study we conclude that g.glabra has significant glucose lowering effects with a striking protective role against dyslipidemia. as an alternative, this herb can be timely utilized for the management of diabetes and associated dyslipidemia without any obvious irregularity of pancreatic functions. references 1. elberry aa, harraz fm, ghareib sa, gabr sa, nagy aa, abdel-sattar e. methanolic extract of marrubium vulgare ameliorates hyperglycemia and dyslipidemia in streptozotocin-induced diabetic rats. international journal of diabetes mellitus. 2015;3(1):37-44. 2. marwa m abdel-rahman, ayman m mahmoud, bastawy na, eissa hm. anti-hyperlipidemic and myocardial enhancing effects of berberine in high fat diet/streptozotocininduced diabetic rats; possible role of adiponectin. nutrition & 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16. tang zh, li t, tong yg, chen xj, chen xp, wang yt, et al. a systematic review of the anticancer properties of compounds isolated from licorice (gancao). planta medica. 2015;81(18):1670-87. 17. chen hj, kang sp, lee ij, lin yl. glycyrrhetinic acid suppressed nf-kappab activation in tnf-alpha-induced hepatocytes. j agric food chem. 2014;62(3):618-25. 18. de la garza-rodea as, knaän-shanzer s, den hartigh jd, verhaegen apl, van bekkum dw. anomer-equilibrated streptozotocin solution for the induction of experimental diabetes in mice (mus musculus). journal of the american association for laboratory animal science : jaalas. 2010;49(1):40-4. 19. kumar r, arora v, ram v, bhandari a, vyas p. hypoglycemic and hypolipidemic effect of allopolyherbal formulations in streptozotocin induced diabetes mellitus in rats. international journal of diabetes mellitus. 2015;3(1):45-50. 20. beeton c, garcia a, chandy kg. drawing blood from rats through the saphenous vein and by cardiac puncture. 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nicotinamide-streptozotocin-induced diabetic rats. european journal of pharmaceutical sciences. 2017;106:220-30. 26. han s, hagan dl, taylor jr, xin l, meng w, biller sa, et al. dapagliflozin, a selective sglt2 inhibitor, improves glucose homeostasis in normal and diabetic rats. diabetes. 2008. 27. n. murugaiyan, g. gnanamuthu, rajendran ss, rameshkumar k. phytochemical screening, antibacterial activity and identification of bioactive compound(s) in the leaves of bell weed (dipteracanthus prostratus) for medicinal purpose. world journal of medical sciences 2015;12(3):277-84. 28. nakagawa k, kishida h, arai n, nishiyama t, mae t. licorice flavonoids suppress abdominal fat accumulation and increase in blood glucose level in obese diabetic kka<sup>y</sup> mice. biological and pharmaceutical bulletin. 2004;27(11):1775-8. 29. subhasree n, kamella a, kaliappan i, agrawal a, dubey gp. antidiabetic and antihyperlipidemic activities of a novel polyherbal formulation in high fat 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activities of glycyrrhiza glabra rootjiimc 2020 vol. 15, no.2 103 original�article abstract objective: to compare the hepatoprotective effects of aqueous extract of cassia fistula leaves and silymarin on acetaminophen induced hepatotoxicity. study design: an experimental study in mice. place and duration of study: the study was conducted in the department of pharmacology and therapeutics, multidisciplinary research laboratory of islamic international medical college, riphah international university. the duration of study was from 16 mar, 2016 to 16 mar, 2017. materials and methods: in present study simple random sampling was done by balloting method and sixty adult balb/c albino mice were divided in four groups having 15 mice each. mice in control group a were given normal diet and fresh water. mice in experimental group b (positive control) were given acetaminophenat dose of 100mg /kg /day orally for six weeks. mice in experimental group c were treated with acetaminophen(100mg/kg) with concurrent 400mg/kg body weight of cassia fistula (aqueous extract) orally for six weeks once daily while in experimental group d mice received 750 mg/kg body weight of silymarin orally in form of aqueous suspension in 2% cremophor1e for 6 weeks once daily concurrently treated with acetaminophen(100mg/kg).the cardiac puncture was done after six weeks and 2.5cc blood was collected from each mice for assessment of biochemical markers including serum alanine aminotransferase (alt) and serum aspartate aminotransferase (ast). results: the mean value of serum alt level was 130.4.30 ±42.90 in group b as compared to control group having mean value of alt 37.30 ± 8.32. the mean value of alt was 62.22± 19.27 and 53.90± 25.06 in group c and in group d respectively. in group b mean value of serum level of ast was 134.3± 15.56 as compared to control group a having mean value of ast31.40± 10.05.the mean value of ast in group c and group d were 66.40±20.50 and 44.67± 20.37 respectively. conclusion: the silymarin is more beneficial than aqueous extract of cassia fistula leaves in ameliorating hepatotoxic effects of acetaminophen. key words: acetaminophen, cassia fistula leaves, hepatoprotective, silymarin. considered toxic to liver. the incidence of dili is 1 in 4 10,000 to 1 in 100,000. in humans the most common cause of drug induced liver failure is a c e t a m i n o p h e n ( pa ra c e t a m o l , n a c e t y l p 5 aminophenol,apap) toxicity. it is safe at therapeutic doses but at larger doses it can cause serious liver 6,7 injury. the cytochrome p-450 oxidation of acetaminophen overdose result in formation of reactive metabolite n-acetyl-p-benzoquinone imine 8 (napqi) which initiates toxicity. it depletes glutathione and binds to cellular proteins, especially 7,9,11 in mitochondria and cause hepatotoxicity. previous studies have also identified napqi as important factor in acetaminophen induced 8 hepatotoxicity. previous studies have identified s o m e h e p a t o p r o t e c t i v e a g e n t s a g a i n s t acetaminophen induced hepatotoxicity. silymarin introduction liver is a vital organ having role in metabolism of carbohydrates, proteins and lipids, bile production, maintenance of homeostasis, detoxification and 1,2 vitamin storage. drug induced liver injury (dili) is the leading cause of acute liver failure in most 3 countries. there are more than 1000 drugs comparing hepatoprotective effects of aqueous extract of cassia fistula (amaltas) leaves and silymarin rukhsana munawar, adnan jehangir, akbar waheed correspondence: dr. rukhsana munawar department of pharmacology islamic international medical college riphah international university, islamabad e-mail: dr.rukhsana33@gmail.com department of pharmacology islamic international medical college riphah international university, islamabad funding source: nil; conflict of interest: nil received: dec 27, 2017; revised: jul 09, 2018 accepted: jul 16, 2018 hepatoprotective effects of cassia fistula leaves & silymarin jiimc 2018 vol. 13, no.3 137 leaves were boiled in distilled water for 30 minutes. these were kept for 3 days with intermittent shaking. these were filtered by whatman no1 filter paper. the aqueous extract was obtained by concentrated 17,19 the filtrate by rotary flash evaporator. the mice were divided into four groups randomly, each group consisting of 15 mice. mice in control group a were given normal diet and fresh water o r a l l y. e x p e r i m e n t a l g r o u p b w a s g i v e n acetaminophen 100mg/kg orally in diet for 6 weeks 20 once daily. experimental group c was treated with acetaminophen 100mg/kg with concurrent 400 mg/kg body weight of cassia fistula(aqueous 21 extract) orally for 6 weeks once daily. experimental group d was treated with acetaminophen 100mg/kg orally with concurrent 750 mg/kg bw of silymarin in form of aqueous suspension in 2% 22 cremophor1e for 6 weeks once daily. after six weeks cardiac puncture was done and blood samples were taken for evaluation of serum alanine aminotransferase (alt) and serum aspartate aminotransferase (ast) levels. the data was analyzed by using statistical package for social sciences (spss) version 22. the biochemical parameters alt and ast were calculated by using mean ± standard deviation (sd). the mean difference between control and other groups was calculated by applying anova. the post hoc tuckey test was applied for comparison of mean difference between groups. p-value 0f <0.05 was considered statistically significant. results the serum alt and ast levels were significantly raised (p<0.00) in acetaminophen treated group b as compared to control group a. the serum alt and ast were reduced in cassia fistula treated group c and silymarin treated group d and in comparison, the results showed significant reduction in serum (slm) is one of them having antioxidant, antii n f l a m m a t o r y, a n t i f i b r o t i c , a n t i v i r a l a n d 1,12,14 immunomodulatory actions. the silymarin has hepatoprotective and antioxidant role by inhibiting 1,15 free radicals. herbal medicines represent one of the most important fields of traditional medicine throughout the world. cassia fistula (family leguminosae, subfamily caesalpinea) is a very common plant known for its medical properties. it is commonly called amaltas. the antioxidant property is possessed by 16 polyphenol and flavonoids. previous studies showed work done on methanolic and ethanolic extracts of cassia fistula leaves. in present study aqueous extract was used to explore hepatoprotective effect of cassia fistula leaves and its hepatoprotective effect was compared with silymarin on acetaminophen induced hepatotoxicity in mice and this comparison was not found in previous studies. the aim of present study was to compare hepatoprotective effects of cassia fistula leaves and silymarin on acetaminophen induced hepatotoxicity. materials and methods an experimental study was carried out in the department of pharmacology and therapeutics, multidisciplinary research laboratory of islamic international medical college in collaboration with national institute of health sciences (nih), islamabad from mar 2015 to mar 2016. approval of synopsis was authorized by the ethical review committee of islamic international medical college. mice weighing 30-50grams with normal alt and ast levels were included in the study and mice weighing less than 30grams and more than 50grams with abnormal liver function tests were excluded. sixty balb/c healthy albino mice were selected randomly by balloting method. a perfect living condition indistinguishable to their class with adjusted dietary supplement was given under temperature of 24±2ºc with a 12 hour light and dark cycle. cassia fistula leaves were collected from race course park, rawalpindi. the leaves were air dried and then authenticated by herbarium department of national agricultural centre, islamabad. the external dirt of freshly collected leaves was removed by washing with tap water. the leaves were shade dried and crushed coarsely by hand. about 400 gm of these table i: comparison of serum alt level between the groups (n=60) p value < 0.00 p value <0.05 =significant hepatoprotective effects of cassia fistula leaves & silymarin jiimc 2018 vol. 13, no.3 138 in present study significant improvement (p < 0.05) in serum levels of alt and ast in group d is observed which was given acetaminophen followed by silymarin. this was also revealed by study of amir mohammad kazemifar et al., who demonstrated the hepatoprotective property of silymarin in acetaminophen induced hepatotoxicity in male 25 sprague-dawley rats. in present study a significant reduction (p < 0.05) was observed in raised serum levels of alt and ast in group c which was given acetaminophen followed by cassia fistula as compared to group b which was given acetaminophen. the hepatoprotective effect of ethanolic extract of cassia fistula leaves was observed in study of pradeep et al. at dose of 500mg/kg/day for 7 days against subacute carbon tetrachloride (ccl4) induced hepatic injury in rats. he 17 found significant improvement in levels of alt, ast. das et al. also proved the hepatoprotective effect of aqueous extract of fruit pulp of cassia fistula against 18 liver damage induced by ccl4 in albino rats. our findings are in accordance with study of jehangir et al. who obser ved significant reduction in biochemical parameters including alt, ast, alp and total bilirubin by ethanolic extract of cassia fistula leaves against hepatotoxicity induced by isoniazid 27 and rifampicin. the better hepatoprotective effect of aqueous extract of cassia fistula leaves could be proven with increasing duration of study. further studies are required to see hepatoprotective effect of cassia fistula leaves with higher doses and by use of different routes of administration. the molecular mechanism responsible for reducing biochemical and histopathological parameters can be explored by further studies. conclusion in present study significant hepatoprotective effect was shown by aqueous extract of cassia fistula leaves probably due to presence of flavonoids. silymarin demonstrated better hepatoprotective effect than cassia fistula against acetaminophen induced hepatotoxicity. references 1. vargas-mendoza n, madrigal-santillán e, morales-gonzález á, esquivel-soto j, esquivel-chirino c, y gonzález-rubio mg-l, et al. hepatoprotective effect of silymarin. world journal of hepatology. 2014; 6: 144. 2. pandit a, sachdeva t, bafna p. drug-induced hepatotoxicity: levels of alt and ast in silymarin treated group d as compared to cassia fistula treated group c. discussion drug induced liver injury is an unresolved health problem and acetaminophen is known to cause 23 hepatic damage at high doses. the reactive metabolite napqi has been implicated to play a role 8,24 in hepatic damage. the present study is designed to compare hepatoprotective effects of aqueous extract of cassia fistula leaves and silymarin on a c eta m i n o p h e n i n d u c e d h e p ato tox i c i t y by measuring biochemical parameters including serum alt and ast. in present study hepatotoxicity is induced in group b with acetaminophen. group c and group d were given aqueous extract of cassia fistula leaves and silymarin with concurrent acetaminophen respectively to ameliorate the hepatotoxic effects of acetaminophen on serum levels of alt and ast. in the present study mice in experimental group b showed abnormal increase in serum levels of alt and ast which were given acetaminophen. this is in accordance with findings of amir mohammad kazemifar et al., who induced hepatotoxicity in male sprague-dawley rats with single oral dose of acetaminophen 800mg/kg by gavage with an orogastric canula and he observed significant 25 increase in levels of alt and ast. this is also consistent with study of abel felipe freitage who found significant changes in lfts due to hepatotoxic 26 effect of acetaminophen. table ii: post hoc tukey's test for mul�ple comparison of alt between the groups table iii: post hoc tukey's test for mul�ple comparison of ast between the groups hepatoprotective effects of cassia fistula leaves & silymarin jiimc 2018 vol. 13, no.3 139 hepatoprotective effects of cassia fistula leaves & silymarin jiimc 2018 vol. 13, no.3 chronically exposed to hydrogen sulfide; modulating influence of tnf-α cytokine genetic polymorphism. daru. 2013; 21: 28. 16. kalaiyarasi c, karthika k, lalithkumar p, ragupathi g, saravanan s. in vitro anti-oxidant activity of various solvent fractions of cassia fistula l. pods. journal of pharmacognosy and phytochemistry. 2014; 3: 73-6. 17. pradeep k, mohan c, anand k, karthikeyan s. effect of pretreatment of cassia fistula linn. leaf extract against subacute ccl 4 induced hepatotoxicity in rats. 2005. 18. das s, sarma g, barman s. hepatoprotective activity of aqueous extract of fruit pulp of cassia fistula (afcf) against carbon tetrachloride (ccl4) induced liver damage in albino rats. j clin diagn res. 2008; 2: 1133-8. 19. sutar gv, dass k, einstein jw. screening of different leaf extracts of cassia fistula linn for investigation of hypolipidemic activity in two different rat models. international letters of natural sciences. 2015;3. 20. kane ae, mitchell sj, mach j, huizer-pajkos a, mckenzie c, jones b, et al. acetaminophen hepatotoxicity in mice: effect of age, frailty and exposure type. experimental gerontology. 2016;73:95-106. 21. kumar a. a review on hepatoprotective herbal drugs. int j res pharm chem. 2012; 2: 96-102. 22. el-lakkany nm, hammam oa, el-maadawy wh, badawy aa, ain-shoka aa, ebeid fa. anti-inflammatory/antifibrotic effects of the hepatoprotective silymarin and the schistosomicide praziquantel against schistosoma mansoni-induced liver fibrosis. parasit vectors. 2012;5: 767–73. 23. yoon e, babar a, choudhary m, kutner m, pyrsopoulos n. acetaminophen-induced hepatotoxicity: a comprehensive update. journal of clinical and translational hepatology. 2016; 4: 131. 24. hinson ja, roberts dw, james lp. mechanisms of acetaminophen-induced liver necrosis. adverse drug reactions: springer. 2010. p. 369-405. 25. kazemifar am, hajaghamohammadi aa, samimi r, alavi z, abbasi e, asl mn. hepatoprotective property of oral silymarin is comparable to n-acetyl cysteine in acetaminophen poisoning. gastroenterology research. 2012; 5: 190. 26. freitag af, cardia gfe, da rocha ba, aguiar rp, silva-comar fmds, spironello ra, et al. hepatoprotective effect of silymarin (silybum marianum) on hepatotoxicity induced by acetaminophen in spontaneously hypertensive rats. evidence-based complementary and alternative medicine. 2015. 27. jehangir a, nagi a, shahzad m, zia a. the hepato-protective effect of cassia fistula (amaltas) leaves in isoniazid and rifampicin induced hepatotoxicity in rodents. biomedica. 2010; 26: 25-9. a review. 2012. 3. gómez-lechón mj, tolosa l. human hepatocytes derived from pluripotent stem cells: a promising cell model for drug hepatotoxicity screening. archives of toxicology. 2016; 90: 2049-61. 4. haque t, sasatomi e, hayashi ph. drug-induced liver injury: pattern recognition and future directions. gut and liver. 2016; 10: 27. 5. jaeschke h, mcgill mr, ramachandran a. oxidant stress, mitochondria, and cell death mechanisms in drug-induced liver injury: lessons learned from acetaminophen hepatotoxicity. drug metabolism reviews. 2012; 44: 88-106. 6. mcgill mr, williams cd, xie y, ramachandran a, jaeschke h. acetaminophen-induced liver injury in rats and mice: comparison of protein adducts, mitochondrial dysfunction, and oxidative stress in the mechanism of toxicity. toxicology and applied pharmacology. 2012; 264: 387-94. 7. jaeschke h, mcgill mr, williams cd, ramachandran a. current issues with acetaminophen hepatotoxicity—a clinically relevant model to test the efficacy of natural products. life sciences. 2011; 88: 737-45. 8. kheradpezhouh e, ma l, morphett a, barritt gj, rychkov gy. trpm2 channels mediate acetaminophen-induced liver damage. proceedings of the national academy of sciences. 2014; 111: 3176-81. 9. ward j, kanchagar c, veksler-lublinsky i, lee rc, mcgill mr, jaeschke h, et al. circulating microrna profiles in human patients with acetaminophen hepatotoxicity or ischemic hepatitis. proceedings of the national academy of sciences. 2014; 111: 12169-74. 10. kon k, kim js, uchiyama a, jaeschke h, lemasters jj. lysosomal iron mobilization and induction of the mitochondrial permeability transition in acetaminopheninduced toxicity to mouse hepatocytes. toxicological sciences. 2010; 117: 101-8. 11. antoine dj, dear jw, lewis ps, platt v, coyle j, masson m, et al. mechanistic biomarkers provide early and sensitive detection of acetaminophen-induced acute liver injury at first presentation to hospital. hepatology. 2013; 58: 777-87. 12. polyak sj, morishima c, lohmann v, pal s, lee dy, liu y, et al. identification of hepatoprotective flavonolignans from silymarin. proceedings of the national academy of sciences. 2010; 107: 5995-9. 13. polyak sj, ferenci p, pawlotsky jm. hepatoprotective and antiviral functions of silymarin components in hepatitis c virus infection. hepatology. 2013; 57: 1262-71. 14. bahmani m, shirzad h, rafieian s, rafieian-kopaei m. silybum marianum: beyond hepatoprotection. journal of evidence-based complementary & alternative medicine. 2015; 20: 292-301. 15. mandegary a, saeedi a, eftekhari a, montazeri v, sharif e. hepatoprotective effect of silyamarin in individuals 140 jiimc june 2016.cdr original article abstract objective: to determine the protective effect of vitamin c on msg (ajinomoto) induced histomorphological changes in rat ovary. study design: it was randomized control trial. place and duration of study: this study was carried out in the department of anatomy, islamic international medical college, rawalpindi, in collaboration with national institute of health (nih), islamabad. the study was conducted from september 2015 to march 2016. materials and methods: total 45 female rats (sprague dawley) were used and divided into 3 groups. the control group (c) was kept on plain water and normal laboratory diet, while the experimental group a, was given msg and experimental group b, was fed on msg and vitamin c both, for 4 weeks to induce histological changes in ovary. all rats were sacrificed after 4 weeks. ovaries were dissected out and examined for gross and histological parameters. results were compared with the control and experimental groups. results: in experimental group a, weight of the ovary was increased as compared to the control group. the histological examination of ovary showed granulosa cell degeneration and decrease in the number of primary follicles in group a. in addition to msg, vitamin c was also given to experimental group b by mixing it in drinking water and the dissected ovary of this group showed changes which were less severe than experimental group a. conclusion: protective effect of vitamin c is proved on msg induced histomorphological changes in ovary of rats. key words: degenerated granulosa cells, infertility, msg, number of primary follicles, vitamin c. disorders of oocyte production, fallopian tube 2 function and implantation of embryo. according to who, the factors responsible for infertility in females include tubal factors 36% ,disorders of ovulation 33% 3 and endometriosis 6% and evincible causes 40%. 1 globally the rate of infertility is about 10–15%. inspite of the fact that pakistan is one of the popular countries of the world and its population growth rate is about 2% and it also has high rate of infertility that is about 21.9% out of which 3.5% are due to primary causes and 18.4% are due to secondary reasons. according to the statistics ratio this indicates that the average number of children in married pakistani 1 women is 6.5. the female reproductive system is easily offended by harmful environmental factors which include environmental chemicals, industrial pollutants and 1-3 food additives. one of the food additive is monosodium glutamate, commonly known as 1-3 ajinomoto. it is commonly used in restaurants (especially mixed in noodles), packaged food industries including chips, salads, soups, canned food and household 1-3 kitchen. msg increases the palatability of meal by introduction fertility or fecundity is defined as the ability to 1 conceive children ,while infertility is defined as inability of a couple to conceive after a period of twelve months of unprotected sexual intercourse. according to who, infertility is defined as inability of a couple to conceive after twenty four months of 1 unprotected intercourse. rate of infertility has increased remarkably over the past twenty years.1almost one in six couples have a delay in conception while only few of them would attempt 1 for medical treatment. it is roughly calculated that in 40% to 50% of couples, infertility is due to female problems which include effect of vitamin c on monosodium glutamate (ajinomoto) induced changes in the ovary of rats sumaira abbasi, rehana rana, kaukab anjum vitamin c and msg induced changes in ovary jiimc 2016 vol. 11, no.2 correspondence: prof dr. rehana rana department of anatomy islamic international medical college riphah international university, islamabad e-mail: rehana.rana@riphah.edu.pk department of anatomy islamic international medical college riphah international university, islamabad funding source: nil ; conflict of interest: nil received: mar 25, 2016; revised: apr 07, 2016 accepted: may 09, 2016 66 vitamin c and msg induced changes in ovary jiimc 2016 vol. 11, no.2 67 triggering the taste buds to ''umami'' taste which is a pleasant savory taste4and it also accelerates appetite centre which results in increase in body 5 weight. msg is a sodium salt of glutamic acid which is one of 6 the naturally occurring non essential amino acid. the part of msg that negatively affects the human 7,8 body is glutamate not the sodium. it is composed of 9 78% glutamic acid, 22% sodium and water. vitamin c defends the human body against oxidative damage by preventing oxidative damage to dna, 8 proteins and lipids. reactive oxygen species (ros) plays a critical role in the normal function of reproductive system and also in the pathogenesis of 10 female infertility. oxidative stress will impair the 11 oocyte maturation and folliculogenesis. treatments that reduce the oxidative stress may help to reduce 10 the infertility caused by this imbalance. this research was done with an objective to observe the reverse histological effects of vitamin c on msg induced changes in ovary. materials and methods it was a randomized control trial. the study was carried out in the department of anatomy islamic international medical college in collaboration with national institute of health and the duration of study was from september 2015 to march 2016. forty five female adult rats (sprague dawley) with a weight of 250-350g and age between 10-12 weeks were included in this study. pregnant female rats and rats with any obvious pathology were excluded. male rats were also excluded. rats were purchased from animal house of nih, islamabad where they were kept under standard laboratory conditions. rats were randomly divided into 3 groups. the control group c (n = 15) was kept on standard pellet diet with tap water to drink. the experimental group a (n = 15) was fed on msg diet for 4 weeks to induce degenerative changes. the experimental group b (n = 15) was fed on msg and vitamin c diet for a period of 4 weeks. dissected ovaries were examined for gross and histological parameters. after tissue processing, embedding was done in paraffin wax. for the preparation of slides haematoxylin and eosin stains were used. microscopic study was done under 10x and 40x objective. statistical analysis was done in spss version 20.0. qualitative variables were analyzed in percentages and compared by applying pearson chi square test. quantitative data was expressed as mean + s.d. the means were compared among three groups by using one way analysis of variance (anova). a p–value of <0.05 was considered statistically significant. results gross assessment weight of ovary: weight of ovaries and histological analysis of all experimental animals were done. the weight of ovary in control group was 0.15±0.02 gm. the weight of ovary in group a, was 0.21±0.03gm. the weight of ovary in group b, was 0.18 ±0.05gm.so the mean weight of ovary was greater in group a and the difference was statistically significant (p < 0.001). (table i)(fig 1). control group had significantly lower mean weight as compared to experimental group a (p< 0.001). control group had lower mean weight as compared to experimental group b (p = 0.03) which is insignificant. similarly experimental group a had higher weight as compared to experimental group b (p = 0.06) which is also insignificant. table i: mean weight of ovaries in three groups microscopic assessment one quantitative and two qualitative histological parameters were also studied. number of primary follicles number of primary follicles were counted per slide at 10x.the average number of primary follicles were 5.9±1.2 in control group c, in experimental group a, the number of primary follicles is 2.7±1.8 and in experimental group b, the number of primary follicles is3.4±1.7 and this difference of mean is statistically significant (p-value<0.001). (table ii and fig 1). control group had significantly higher mean of vitamin c and msg induced changes in ovary jiimc 2016 vol. 11, no.2 68 number of primary follicles as compared to experimental group a (p< 0.001). control group had higher mean of number of primary follicles as compared to experimental group b (p = 0.001) which is insignificant. similarly experimental group a had lower mean of number of primary follicles as compared to experimental group b (p = 0.28) which is insignificant. granulosa cell degeneration in control group c, none of the rat showed granulosa cell degeneration. in group a, 11 rats (73.3%) showed granulosa cell degeneration and in group b, there were 6 rats (40%) which showed degeneration of granulosa cells. presence of granulosa cell degeneration was significantly (p-value <0.001) different between all groups.(fig 2). vascular congestion in medulla in control group c, none of the rat was found with increase vascular congestion in medulla whereas in group a, there were 12 rats (80.0%) with an increase in vascular congestion and in group b, there were 6 rats (40%) with increased vascular congestion. statistically significant p-value <0.001 was obtained after comparison between all groups.(fig 3). table ii: mean number of primary follicles in three groups fig 1: photomicrograph (a) showing cortex (cx), medulla (md) and primary follicles in animal rat no. c13 and (b) showing primary follicle in animal rat no. a1 (demarcated by a circle). h & e stain, x10 fig 2: photomicrograph (a) showing oocyte(oo), zona pellucida (zp)and granulosa cell degenera�on in animal rat no. a3(demarcated by a circle) and (b) absent degenera�on in animal rat no. b4. h & e stain, x40. vitamin c and msg induced changes in ovary jiimc 2016 vol. 11, no.2 69 discussion the effect of msg on the female reproductive system causes degenerative histological changes in ovaries causing granulosa cell degeneration, vacuolization of theca cells and decrease in the number of primary 10-12 follicles. in the conducted study, it was observed that there was significant increase in the weight of ovaries in group a in which the average weight was 0.21 g which was significantly different from the control group (0.15g). the result of this study disagree with 13 14 the previous report of ilegbedion ig et al and das , showing insignificant increase in ovary weight due to msg intake for a period of 2 and 10 weeks respectively, although it was also dose dependant in group b the average weight was 0.18 g, lower than that of group a. decrease in the weight of ovary in group b may be attributed to the effective anti 2 oxidating properties of vitamin c. primary follicle is defined as an oocyte surrounded 8 by a single or double layer of cuboidal epithelium. the number of primary follicles were counted in this study, the average number of primary follicles in group a is 2.7 and in group b is 3.4. in comparison, the number of primary follicle in group c is 5.9. the result of this study disagree the previous report of 14 das , in which the number of primary follicles were increased in the experimental group. naureen et al reported similar results in the study of lead induced 7,8 changes in ovary of mice. folliculogenesis was improved in group b, because vitamin c improves the integrity of follicular membrane and also responsible for the synthesis of 2 collagen, required for the growth of follicles. in the present study, 73.3 % of the rats in group a and 40% of the rats in group b also showed granulosa cell degeneration which was highly significant from the control group in which none of the ovary showed such pathological change. result of this study is in agreement with similar studies by veronika 9 10,11 12 husarova , eweka et al , saber a. sakr , ahmed et 15 al in which msg was given for a period of 2 weeks. similar study was carried out by afeefy et al in which msg was given for a period of 4 weeks, causes 16 degenerative and atrophic changes in kidneys. degeneration of the granulosa cells can be due to the 17 toxic effects of msg. reduction in the degeneration of granulosa cells in group b can be attributed to the wound repair ability of vitamin c by stimulating the 18 synthesis. vascular congestion is defined as blood 19 filled dilated veins. 80% of the rats in group a and 40% in group b, showed increase vascular congestion which was highly significant from the control group in which none of the rat showed increase vascular congestion. the results of this study is consistent 20 with the previous work of mustafa et al. similar work has been done in nigeria by oladipo et al in 2015, in which vascular congestion was observed in experimental group with the use of msg for 2 21 weeks. va s c u l a r c o n g e s t i o n w a s a m e l i o r a t e d i n experimental group b, because vitamin c protects the capillary endothelium from oxidative damage by 22,23 increasing the synthesis of nitric oxide. collagen 24,25 and extracellular matrix. the results of this study proved the alternate hypothesis that states that vitamin c has protective effect on msg induced histological changes there by rejecting the null hypothesis. limitation of study: estrous cycle was not traced in a bv fig 3: photomicrograph (a) showing congested blood vessel (bv) in animal rat no. c5 and (b) showing vascular conges�on in animal rat no. a2.h & e stain, x10. vitamin c and msg induced changes in ovary jiimc 2016 vol. 11, no.2 70 the current study. conclusion protective effect of vitamin c is proved on msg induced histomorphological changes in ovary of rats. recommendations effect of msg can also observe on other organs. duration and sample size of study can also be increase. references 1. shaheen r, subhan f, sultan s, subhan k, tahir f. prevalence of infertility in a cross section of pakistani population. pak j zool. 2010; 42: 389-93. 2. showell mg, brown j, clarke j, hart rj. antioxidants for female subfertility. the cochrane library. 2013. 3. palihawadana t, wijesinghe p, seneviratne h. aetiology of infertility among females seeking treatment at a tertiary care hospital in sri lanka. ceylon medical journal. 2012; 57: 79-83. 4. healy dl, trounson ao, andersen an. female infertility: causes and treatment. the lancet. 1994; 343: 1539-44. 5. sami n, ali ts, wasim s, saleem s. risk factors for secondary infertility among women in karachi, pakistan. 2012. 6. ali aa, el-seify gh, el haroun hm, soliman m. effect of monosodium glutamate on the ovaries of adult female albino rats and the possible protective role of green tea. menoufia medical journal. 2014; 27: 793. 7. waseem n, butt sa, hamid s. amelioration of lead induced changes in ovary of mice, by garlic extract. jpma the journal of the pakistan medical association. 2014; 64: 798801. 8. waseem n, hamid s, butt sa. effect of lead acetate on follicular count of mice and the protective role of garlic extract. pakistan armed forces medical journal. 2014; 64: 61-5. 9. veronika husarova, daniela ostatnikova. monosodium glutamate toxic effects and their implications for human intake: a review, jmed research, vol. 2013. 10. eweka ao, eweka a, om’iniabohs fa. histological studies of the effects of monosodium glutamate of the fallopian tubes of adult female wistar rats. north american journal of medical sciences. 2010; 2: 146. 11. elias j, cih r. adjusting tlvs® for reproductive and developmental health. age. 2015: 2022. 12. sakr sa, badawy gm. protective effect of curcumin on monosodium glutamate-induced reproductive toxicity in male albino rats. global journal of pharmacology. 2013; 7: 416-22. 13. ilegbedion i, onyije f, chibuike o. infiltration of inflammatory cells in the ovary following oral administration of monosodium glutamate. bangladesh journal of medical science. 2013; 12: 413-8. 14. das r, ghosh s. long term effects in ovaries of the adult mice following exposure to monosodium glutamate during neonatal life–a histological study. nepal med coll j. 2011; 13: 77-83. 15. ahmed fe. effect of diltiazem on the changes induced by monosodium glutamate in the ovary of adult rats: histological and immunohistochemical study. egyptian journal of histology. 2011; 34: 586-95. 16. afeefy aa, mahmoud ms, arafa ma. effect of honey on monosodium glutamate induced nephrotoxicity (histological and electron microscopic studies). journal of american science. 2012; 8: 170-184. 17. hannon i. msg is everywhere. 18. osman heh. study of the role of antioxidant (vitamin c) on modulation toxicity of chronic use of monosodium glutamate in liver of albino rats: faculty of medicine, taif university; 2012. 19. stones rw. pelvic vascular congestion—half a century later. clinical obstetrics and gynecology. 2003; 46: 831-6. 20. mustafa sj. effect of monosodium glutamate on mice ovaries and possible protective role of vitamin c. annals of applied bio-sciences. 2015; 2: 100-5. 21. oladipo i, adebayo e, kuye o. effects of monosodium glutamate in ovaries of female sprague-dawley rats. int j curr microbiol app sci. 2015; 4: 737-45. 22. juraschek sp, guallar e, appel lj, miller er. effects of vitamin c supplementation on blood pressure: a metaanalysis of randomized controlled trials. the american journal of clinical nutrition. 2012; 95: 1079-88. 23. padayatty sj, katz a, wang y, eck p, kwon o, lee j-h, et al. vitamin c as an antioxidant: evaluation of its role in disease prevention. journal of the american college of nutrition. 2003; 22: 18-35. 24. naidu ka. vitamin c in human health and disease is still a mystery? an overview. nutrition journal. 2003; 2: 7. 25. wei f, qu c, song t, ding g, fan z, liu d, et al. vitamin c treatment promotes mesenchymal stem cell sheet formation and tissue regeneration by elevating telomerase activity. journal of cellular physiology. 2012; 227: 3216-24. jiimc june 2016.cdr original article abstract objectives: ! to investigate the assessment tools and processes used to assess students of mhpe programs in pakistan for achieving the learning outcomes of the program. ! to compare this process in developed (united kingdom) and developing country (pakistan). study design: it is a qualitative archival study designed to provide an insight into the type and level of assessment tools used in mhpe programs. st th place and duration of study: the study was conducted in iimc from 1 october 2013 to 30 july 2014. materials and methods: the study method chosen was archival research. the data was collected from the official websites of the program. purposive and convenient sampling method was used to select 08 programs, 04 each from united kingdom and pakistan. as programs in pakistan offer only blended programs, hence only blended programs were included in the study. manifest conventional content analysis of the data was done using nvivo 10. results: common assessment tools used to assess competence were assignments and dissertation submission in all the programs. programs in uk also used portfolios whereas in comparison only summative examination using mcq, seq's and oste was employed in pakistan. all programs in the study assessed student at 'shows how' level except 02 programs in uk, which assessed meta competency (does level). conclusion: distant learning blended programs in hpe assess competency at different levels of competence. this results in variability of level of assessment and hence affects the eventual outcome. a uniform method of assessment should exist for master programs in health professions education to ensure uniform learning and outcome. key words: assessment tools, distant learning programs, health professions education, level of assessment. assessing competency in distant learning master programs in medical education: a qualitative analysis 1 2 3 rehan ahmed khan , omer awwab khan , madiha sajjad jiimc 2016 vol. 11, no.2 correspondence: dr. omer awwab khan associate professor, medicine islamic international medical college riphah international university, islamabad e-mail: omer.awab@riphah.edu.pk 1 2 3 department of surgery/ medicine / pathology islamic international medical college riphah international university, islamabad funding source: nil ; conflict of interest: nil received: feb 25, 2016; revised: apr 15, 2016; accepted: may 06, 2016 satisfying both national and international needs of 5 medical education. as we know that 'assessment 6,7 drives learning' , implementation of the learning outcomes of the m h p e programs have direct relationship to the type and level of assessment that is being employed in these programs. the main objectives of this study were: ! to investigate the assessment tools and processes used to assess students of mhpe programs in pakistan for achieving the learning outcomes of the program. ! compare this process in developed (united kingdom) and developing countries (pakistan). materials and methods it is a qualitative archival study in which archival method of research has been used. in archival research, the researcher collects data stored in archives. the archives can be in the forms of newspapers, articles of journals, books or websites. the reason for choosing archival research was its simplicity, ease of gathering data and easy introduction mhpe programs aim to produce effective leaders in 1 4 medical education. these programs are an emerging field and mushrooming at a fast pace. the reason for this surge is understandable. however w h a t n e e d s t o b e a s c e r t a i n e d i s t h e p r o f e s s i o n a l i z a t i o n o f t h e s e p r o g r a m s . professionalization is defined as the process of giving a professional character, identity, or status to 'health professions education' as a profession. it involves establishing a suitable and accreditable qualification, 85 competency in distant learning programs availability of the archives. more over because of the type of objectives of the study the data required to analyze was present in the archives available via internet and did not require to collect data through other methods as questionnaires, interviews or emails. 8 to collect data, first the website of the program was found through . the next step was www.google.com to locate the information provided about the program. the data about the mhpe program was either present in pdf format or information given on the webpages itself. all the concerned pdf files and webpages were downloaded and opened in nvivo. convenience and purposive sampling technique was 9,10 used. eight mhpe programs were selected. out of t h e s e , f o u r p r o g r a m s w e r e f r o m p a k i s t a n (developing country) and four were from the united kingdom (developed country). eight programs were included in the study as they yielded enough data to ensure validity and reliability in a qualitative study. it was also taken into consideration that data from 08 programs had to be transcribed and coded into themes. in qualitative case studies, handling this amount of data requires considerable time and work. the programs were selected each from wellestablished and newly established institutes running these programs. results all programs in uk and pakistan used assignments at the end of a module or a semester. all programs included in the study from uk required dissertation for the award of master's program except one university. two universities from uk used portfolio as their tool of assessment. all programs in pakistan used written assignments and dissertation for assessment purposes. however, two universities also had a summative exit assessment. the detailed results are reported below: discussion the global distribution of mhpe programs is not uniform. the reported number of mhpe programs was 121 up to 2013.the maximum number of programs are offered in usa (32) followed by uk 11 (31). the number of programs in pakistan was only 12 two until 2012 however it has increased to 6 now. all these hpe programs share many features in common but they have a lot of differences as well. table i: dura�on and mode of delivery of the content (uk= united kingdom, we=well established, ne= newly established, pk= pakistan) table ii: type and dura�on of contact session table iii: exits in the program 86 jiimc 2016 vol. 11, no.2 competency in distant learning programs different formats including contacts sessions using web boards, skype, adobe connect, and physical face 1-4, 13-15 to face contact sessions. in uk, the mhpe programs offered by universities are either on campus, blended or complete distance learning. in pakistan the programs are only blended, which includes an average of 6-8 weeks of contact session, which offers very little flexibility to the students. in authors observation, one of the main reason for the difference in flexibility of these programs is that complete distance learning p r o g r a m s a r e s t i l l n o t r e c o g n i z e d b y t h e accreditation body in pakistan. learning outcomes in masters in health professions education are assessed by variety of assessment tools. most of the programs use both formative and summative assessment methods. the tools used are pen and paper methods; osce, oste, short essay questions (seq's), multiple choice questions (mcq's), portfolios, assignments 11,12 and oral defense of thesis. these tools assess 'shows how', to assessment strategies that evaluate 'does' of the miller's pyramid. all programs have aligned learning outcomes and learning strategies with assessment tools to achieve the desired outcomes. programs in united kingdom are more flexible as they offer exits at different levels, optional and specialized modules to study and different modes (complete distant learning, blended and on campus) of program to choose from. they also aim to produce capable medical educationists (at the 'does' level), who can perform in real life situations. programs in pakistan are in their infancy, however their learning outcomes, assessment and learning strategies share a lot of features in common with programs in uk. the main contrasting feature though is minimal flexibility and assessment at the 'shows how' level. conclusion distant learning blended programs in hpe assess competency at different levels of competence. this results in variability of level of assessment and hence affects the eventual outcome. guidelines and sta n d a rd s f ro m re g u l ato r y a n d a c c re d i t i n g authorities should stress on uniform method of a s s e s s m e nt fo r m a ste r p ro g ra m s i n h e a l t h professionals education to ensure uniform learning and outcome throughout world. table iv: details of assessment tools used table v: classifica�on of assessment tools according to miller's pyramid the flexibility of a program is evident from the optional modules it offers to its students. the optional modules are only offered in uk programs which give the students freedom to choose from topics of their interest. programs have options for surgeons, anesthetists and gynecologists. a lot of emphasis in these programs is on the impact of medical education in clinical training. this is lacking in pakistani programs where only one program offers options of electives. flexibility is further enhanced in uk programs by offering exit at multiple levels. duration of these program is variable extending from 1 to 5 years. the mode of delivery varies from complete distant learning (dl) to distant learning with contact sessions. contact sessions are offered in 87 jiimc 2016 vol. 11, no.2 competency in distant learning programs blackwell companion to organizations. 2002: 805-28. 9. dawson c. practical research methods: a user-friendly guide to mastering research techniques and projects. united kingdom: how to books ltd. 2002; p. 48-9. 10. fraenkel j, wallen rn, e. how to design and evaluate research in education. new york: mcgraw-hill; 2010; p. 978. 11. tekian a, artino jr ar. am last page: master's degree in health professions education programs. academic medicine. 2013; 88: 1399. 12. tekian a, harris i. preparing health professions education leaders worldwide: a description of masters-level programs. med teach. 2012; 34: 52-8. 13. t ekian a. doctoral programs in health professions education. medical teacher. 2014; 36: 73-81. 14. pugsley l, brigley s, allery l, macdonald j. counting quality because quality counts: differing standards in master's in medical education programmes. med teach. 2008; 30: 805. 15. pugsley l, brigley s, allery l, macdonald j. making a difference: researching master's and doctoral research programs in medical education. med educ. 2008; 42: 15763. references 1. tekian a, dwyer m. lessons for the future: comparison and contrasts of the master of health professions education programs offered in china and egypt. teaching and learning in medicine. 1998; 10: 190-5. 2. tekian a, harris i. preparing health professions education leaders worldwide: a description of masters-level programs. medical teacher. 2012; 34: 52-8. 3. tekian a, roberts t, batty hp, cook da, norcini j. preparing leaders in health professions education. med teach. 2014; 36: 269-71. 4. al-subait r, elzubeir m. evaluating a masters of medical education program: attaining minimum quality standards? med teach. 2012; 34: 67-74. 5. tekian a. professionalization in health professions education. accessed on 14-03-2014fromhttp://www.aeme.org/plenarypresentation-abstruct-aaratekian.php. 2014. 6. mclachlan jc. the relationship between assessment and learning. medical education. 2006; 40: 716. 7. wood t. assessment not only drives learning, it may also help learning. medical education. 2009; 43: 5-6. 8. ventresca mj, mohr jw. archival research methods. the 88 jiimc 2016 vol. 11, no.2 competency in distant learning programs original�article abstract objective: the objective of the study was to see the relationship/effect of entry test marks and fsc marks on the future academic performance scores of first year medical students from year 2010 to 2014 (five years). study design: this was a cross-sectional quantitative correlational study. place and duration of study: the study was conducted and carried out at islamic international medical college rawalpindi. the retrospective data of five years from 2010 -2014 was included. the study project was completed from march 2016 to august 2016. results: male female ratio varied from 23% male to a maximum of 33% and females from 67% to 77% during the five year with an average of 70% females and 30% male. correlation in between entry test marks and marks obtained in first professional mbbs was found to be .828 which is a strong correlation. weak correlation was found in between the fsc marks and marks obtained during first professional mbbs. conclusion: the study concludes that the students who perform well in entry test also have satisfactory performance in the first professional mbbs and their future performance can be predicted to some extent. key words: academic performance, aptitude test, cognitive construct, entrance test. materials and methods: the data was collected from the record of the college. dependent variable were the student's academic performance scores i.e. scores of students in term of pass or fail and percentages obtained in first professional mbbs from 2010 to 2014. independent variables were id no, gender, percentage marks obtained in fsc and entry test. 2 and professional regulation. medical schools are facing two main shifts one is seeing the selection as first assessment and second using wider range of selection methods to select the right type of candidates though the cultural and regional differences do exist. selecting brightest candidates on the basis of school leaving or university academic qualifications is not considered the appropriate method nowadays. till date no method can be labeled as ideal one because course of study, nature of existing and future medical needs, services and 3 their requirements are ever changing. more objective methods can be tailored by the medical schools which can cater cognitive ability, professional attributes and behavioral e.g. nontechnical skills. nowadays a mix of application form, personal statement, interview, multiple mini interview (mmi), personality tests, and situational 4 judgments tests (sjts) are practiced in west. internationally and in many parts of the world it has been acknowledged the contribution of noncognitive skills and qualities in an individual in predicting the performance of health professional education. therefore this has lead the countries including the united kingdom, united states of introduction medical school activity starts from the selection of the students which is an important but under resourced aspect of medical school. the intentions behind the entry test are to select the students on merit along with suitable personality and aptitude 1 for admission in medical profession. appropriate selection of the students who have the correct attributes which is becoming the main pivot in many countries of the world. in many developed countries the governments are selected and rejected on the slogans of health care provision and the health care provision is facing the challenges of accountability correlation of entry test & the future academic performance in a private medical college 1 2 3 4 muhammad ayaz bhatti , rahila yasmeen , hammad ayaz , huma mahmood correspondence: prof. dr. ayaz bhatti department of community medicine islamic international medical college riphah international university, islamabad e-mail: ayaz.bhatti@riphah.edu.pk 1 2 department of community medicine/medical education islamic international medical college riphah international university, islamabad 3 tehsil head quarter hospital, gujar khan 4 taiba hospital, gujranwala funding source: nil; conflict of interest: nil received: august 20, 2019; revised: october 25, 2019 accepted: october 30, 2019 jiimc 2019 vol. 14, no.4 entry test & future academic performance 207 9 country. the research question which the article addresses is “to see the relationship of entry test & fsc on the future academic performance scores of first year medical students” in a private medical college from year 2010 to 2014(five years). materials and methods this was a cross-sectional quantitative correlational study. all the students who got admission in mbbs from 2009 to 2013 and appeared in first professional mbbs exam from 2010 to 2014 for five years were analyzed for the objectives of the study. the data was collected by specially designed data collection instrument from the record of the college and the non-response rate was zero as all the record was available. the study project was completed from march 2016 to august 2016. dependent variable were the student's academic performance scores i.e. scores of students in term of percentages obtained in first professional mbbs 2010 to 2014 and pass or fail. independent variables were id no, gender, percentage marks obtained in fsc, percentage marks obtained entry test. universal sampling as all the students from 2010 to 2014 who got admission in first year mbbs and appeared in first professional mbbs examination was used. all the students who succeeded in getting admission from the year 2009 to 2013 and appeared in exam from 2010 to 2014, completed their first professional mbbs studies, appeared in first professional mbbs examination, their result was the first entry test for the admission in medical colleges of punjab was conducted in 1999. the government decided that all the candidates must be subjected for their relative merit to a single examination. entry test is carried at provincial level and the selection also is made at provincial level for public sector medical colleges and for private medical colleges test of one province is acceptable for the other and all the individual college prepare their own merit list as per the criteria laid down by 10 the pm&dc. this was the philosophy of entry test, as now twenty two years passed it's the right time to review the policy. scientific research is required to see the correlation of fsc and entry test on the future academic performance of the students. this study will help in establishing the relationship and review the future policy and planning for the student selection. entry test is mandatory all over the world and in all countries with different formats, needs, designs and as per their requirement. umat is mcat (medical college admissions test) for the united state, ukcat (uk aptitude test) in uk, gamsat (graduate medical schools admission test) in australia, uk and ireland for graduate entry programs and these are 6 conducted on a single day each year. the medical education system expanded very rapidly in pakistan. in the recent past the number of medical colleges reached to 167 in pakistan in the public and private sector. these two sets of medical schools public and private also differ in admission criteria. public sector medical schools purely cater the admission which is on merit and residence based as candidate of one province cannot seek admission in another province. whereas the private sector medical colleges cater socioeconomically privileged classes and those who cannot compete the public sector medical colleges. the attitude of our policy makers remained rigid due to which cluster of problems neither sorted nor weeded out as remedial 7 measure and entry test is one of them. pakistan is among those countries where selection is on the basis of academic criteria alone. pakistan needs cognitive, aptitude and personality testing to be combined in such a way to select the right candidates for admission in medical education that can contribute effectively in delivering health care. till 1998 the students were selected only on fsc basis for 8 admission in medical colleges. there are number of boards in different provinces whose syllabus and examinations are of different criteria. another concern was that occasionally a reasonable number of candidates carry fake fsc, a level certificates and scores. this has created an environment that all the candidates must be subjected for their relative merit to a single examination. therefore the exercise of entry test was introduced to satisfy the boards of secondary education, the admitting institutions, the candidates, the feeding schools, colleges and the community that they all share the benefits of best performance with the help of universal standardized test which was named entry test (mcat) for the selection of medical students from all over the america and canada, to introduce aptitude testing as part of the selection protocol for induction in 5 medical college. 208 jiimc 2019 vol. 14, no.4 entry test & future academic performance 90 % and only one student who scored above 90% in entry test. results the students of other medical colleges, students who got admission before 2009 or after 2014 in the same medical college, students who did not completed their study of the respective year, left the college and not appeared in first professional mbbs examination or their result was not declared or record is not available or retrievable of respective years from 2010 to 2014 were excluded from the study. data was analyzed on statistical package for social sciences version 21 for frequencies, cross tabulation, correlation in between fsc marks, entry test marks and marks obtained in first professional mbbs (in percentages) to see the relationships. independent t test and chi square was also used where required to eliminate the chance element and to see the effect of entry test and fsc marks on future performance. p value equal to or less than 0.05 was considered as statistically significant. male ratio varied from 23% to 33% and females from 67% to 77% during five years with an average of 70% females and 30% male during five years study research period. declared and record available in admission branch is available were included. table i: percentage of students and marks obtained in fsc and entry test there is inconsistency among the marks obtained by the students in fsc and entry test. the students who were selected for mbbs were having marks more than 60% in fsc, no student was selected who had less than <60% marks in fsc but 93 students (18%) had less than 60% marks in entry test . there were 44(9%) students who scored 60-70% in fsc and 219 (44%) who scored the same in entry test. there were 202(40%) in fsc and 172 (34%) in entry test who scored 71-80% marks. there were 254 (51%) %) in fsc and only 15(3%) in entry test who scored 81-90%. test. there was no student in fsc who scored above table ii: percentage of students and marks obtained in entry test and first professional mbbs exam table iii: co rela�on coefficient in between fsc, entry test and first prof mbbs marks 209 jiimc 2019 vol. 14, no.4 entry test & future academic performance now we have to look upon performance in first prof in comparison to marks obtained in entry test and fsc. there were 19% students who got less than 60% in entry test and the same was achieved by 20% of students in first prof mbbs. there is consistency in this group. the 6070 % marks were obtained by 44% of students in entry test and 65% of students in first prof. the number of students who acquired more marks as compared to entry test in first prof was 21%. the reverse of above was seen in group 71-80% marks which was 34% in entry test and 16% students got the same in this group. in group 81-90% and above 3% got in entry test and zero % in first prof. the comparison between fsc and first professional marks of the students shows that there is no consistency among the results. there was no student in fsc who acquired less than 60% in fsc but 20% students acquired less than 60% in first prof mbbs. about 9% students got 60-70% marks in fsc and 65% students got the same result in first professional examination.. in group 71-80% marks there were 40% students in fsc who achieved that but in the first the relationship/effect of entry test marks on the future academic performance scores of first year medical students from year 2010 to 2014 was very interesting. these are consistent with their previous performance. it can be safely concluded that low achievers of entry test who succeed in getting admission achieve the same in future. students who have better cognitive construct can improve or sustain their achievement in future. literature also mentions that the entry test is the cognitive construct and also have some predictive validity also, which is reflected in this study. pearson correlation in between entry test marks and marks obtained in first professional mbbs was found to be .828 which is a strong correlation. from this it can be concluded that the students performing good in entry test also show satisfactory performance in the first professional mbbs and their future performance can be predicted 14 to some extent. which is according to the world trend but different from the pakistani perspective. this trend changed from 1991, before that the female seats were reserved to a certain number and only few female medical colleges. this also indicates the women empowerment and healthy emblem of female 12 literacy. on the contrary, it reflects the limited access to women in the other professions like business and industry. secondly this also arouses the serious concerns about the manpower needs of the country like pakistan where more than 70% of the population is rural based and the cultural barriers have limitations for women to work and to work in the rural and primitive society where the taboos are still very strong. this needs attention of the policy and decision makers to revisit the situation. in the current scenario provision of health for all will 13 remain a dream even after decades. correlation in between fsc and first prof score shows that there is no consistency among the results. the pearson correlation in between the fsc and first professional scores was though positive .684 and significant at .001, but very less as compared to entry test and first professional score. now the question arises that what characteristics, qualities, traits be given due consideration in 15 selection. the atmosphere of discussion revolves around the two distinctions one about the cognitive constructs and the other about non cognitive 16 constructs. what the patient expects from the 17 doctor is more than knowledge and practice. patient likes to see the base of iceberg which is discussion commonly it is mistaken that medical schools are selecting high meritorious students because most of the qualities which mater for the medical profession are not precisely measurable or quantifiable. canonical traits like technical competence, human sympathy, wisdom and experience are the main traits to be considered in medical education, these are considered the most desirable attributes in the literature but the question again forms the mirror image that how they can be measured and applied in 11 selection. selection is also vulnerable to criticism and even to legal challenges, therefore objectivity maters a lot and subjectivity cannot be given the due weightage. the study highlighted that there is large number of female candidates who succeeded in selection during 5 years of study period. the number varies from 67-78% of the total with mean of 70% prof 16% students were able to achieve the same. in group 81-90% marks 51% of students achieved this target in fsc but only one student succeeded to achieve it in first prof mbbs. graph i: correla�on graph in between entry test and first prof mbbs marks graph ii: correla�on graph in between fsc and first prof mbbs marks 210 jiimc 2019 vol. 14, no.4 entry test & future academic performance 6. iqal t, naqvi sma, usman m, hussain a, imran m. usefulness of entry test what mbbs part-i results show ? p j m h s 2008;2(1):31-33. 8. marley j, carman i. selecting medical students: a case of the need for change. med educ. 1999;33: 455–61. 11. smith km. the predictive validity of pre-admission measures on podiatric medical school performance. 2014: 6-7 16. mcmanus i, dewberry c, nicholson s, dowell j. the ukcat12 study: educational attainment, aptitude test performance, demographic and socio-economic contextual factors as predictors of first year outcome in a crosssectional collaborative study of 12 uk medical schools. bmc med. 2013;11: 244. 13. ramani s, mann k. introducing medical educators to qualitative study design: twelve tips from inception to completion. med teach. 2015;(february):1–8. medical programme: universiti sains malaysia. educ health (abingdon). 2012;25(2):124–7. 5. byrne at, arnett r, farrell t, sreenan s. comparison of performance in a four year graduate entry medical programme and a traditional five/six year programme. bmc med educ. 2014;14(1):248. 7. jafarey na. medical education in pakistan -the way forward. pima biennial convention 2012;44–6. 9. khan js, mukhtar o, bano t, tabasum s. original article aptitude and personality testing: what does medical and dental colleges entrance test 2012 add to the debate? jumdc 2013; 4 (1):42-48. 10. luqman m. relationship of academic success of medical students with motivation and preadmission grades. j college of physicians surgeon pak. 2013;23(1):31–6. 12. rahbar mh, vellani c, sajan f, zaidi aa, akbarali l. predictability of medical students' performance at the aga khan university from admission test scores, interview ra t i n g s a n d sy st e m s o f e d u c a t i o n . m e d ed u c . 2001;35(4):374–80. 14. prideaux d, roberts c, eva k, centeno a, mccrorie p, mcmanus c, et al. assessment for selection for the health care professions and specialty training: consensus statement and recommendations from the ottawa 2010 conference. med teach. 2011;33(3):215–23. 15. poole pj, moriarty hj, wearn am, wilkinson tj, weller jm. medical student selection in new zealand: looking to the future. j new zeal med assoc. 2009;122(1306):88–100. 19. cleland ja, dowell j, mclachlan j, nicholson s, patterson f. identifying best practice in the selection of medical students (literature review and interview survey). gen med council 2012;(november):1–106. 18. abdulla d, jeffrey p. does pre-admissions testing play a role in math performance among students enrolled in a 2year practical nursing diploma program? j educ train 2014;1(2):143. 20. leinster s. selecting the right medical student. bmc medicine. 2013: 245. 17. mckimm j, vogan cl, phillips hj, rees pj. medical education in practice medical student selection as the “first assessment”: international trends. 2012;6(1):2–9. c. those who come on the upper merit they should be subjected to multiple mini interviews (mmis) in the ratio of 1:3 and this is manageable number for 100 seats and 300 candidates can be handled. the mmi is a method for conducting interviews for medical school built on the multiple station format of the objective structured clinical 20 examination (osce). from the study, it can be concluded that students who perform better in entry test also show satisfactory result in first professional mbbs and their future performance can be predicted to some extent. good performance in fsc not necessarily mean that the student will perform good in entry test or in the future medical education but good performance in entry test can predict good academic performance in future personal values, opinion, imagination, expectations, beliefs, feelings, assumptions, intuitions and sixth sense, how these can be catered is question mark. this does not mean that the vital academic ability should be masked but how to select a future wise 18 doctor. the country and the medical colleges have to tailor selection methods according to their need depending upon the curriculum, the program, 19 current and future medical needs and demands. conclusion a. entry test for the cognitive constructs b. for entry test eligibility, should be 60% and above fsc / a-level recommendations 2. khan js, biggs jsg, bano t, mukhtar o, tabasum s, mubasshar mh. medical colleges admission test in punjab, pakistan. j ayub med coll abbottabad. 2013;25(1-2):64–67. 3. a shmamb. relationship between admission grades and performances of students in the first professional examination in a new medical school. african j biomed res. 2005; 8:51–57. references 4. arzuman h, ja'afar r, fakri nm. the influence of preadmission tracks on students' academic performance in a in our scenario where thousands of candidates are eager to seek admission for limited number of seats and the selection of appropriate candidate is a difficult task. keeping in view the various models the most appropriate in our set up will be 1. ali pa. admission criteria and subsequent academic performance of general nursing diploma students. j pak med assoc. 2008;58(3):128–132. 211 jiimc 2019 vol. 14, no.4 entry test & future academic performance original�article conclusion: tension band wiring is an effective way of treating olecranon fractures particularly those which are displaced and un-comminuted and provide good to excellent functional results in most cases. objective: to evaluate the functional results of tension band wiring in patients with olecranon fractures. place and duration of study: department of trauma and orthopedics jinnah postgraduate medical centre, karachi from december 2017 to june 2018. study design: prospective case series. materials and methods: we included 62 patients having closed fracture of olecranon process. brief history regarding the fracture duration, presence of infection, smoking habits and comorbids such as hypertension and diabetes mellitus was obtained. tension band wiring for the olecranon fracture was performed after patients met the inclusion criteria. final results were assessed at the end of three months postoperatively using mayo elbow performance score (parameters include: pain (45 points), motion arc (20 points), stability (10 points), and daily function (25 points) with a maximum of 100 points. a score of 90-100 points was considered as excellent, good 75-89, fair 60-74 and poor score of less than 60 points. excellent and good results were considered as satisfactory. results: mean age of the patients was 35.03±7.87 years. there were less female patients (n=23, 37.1%) as compared to male (n=39, 62.9%) patients. mean fracture duration of 2.97 + 1.28 days was observed while mean mayo elbow performance scale (meps) was found to be 83.11 + 10.02. according to mayo elbow performance scale excellent and good functional results found in 51(82.26%) cases were considered as satisfactory outcome. satisfactory outcome was significantly higher in patients belonging to ≤30 years age group in contrast to above 30 years of age patients (p=0.037). results were not significantly related to gender, hypertension, diabetes mellitus, smoking and obese cases. significant association was found with duration of fracture. abstract key words:mayo elbow performance score,olecranon fracture, tension band wiring. there is a variety of systems which classify olecranon fractures but most widely accepted mayo clinic 7 classification is described by morrey. type i are undisplaced, type ii fractures have step off of more rd than 2 mm, but stable joint, while 3 type are indirect injury from fall on outstretched hand or 4 combination of both. combined injury results in a more comminuted and displaced fracture even 5 leading to fracture dislocations of elbow. periosteal damage around olecranon process and fascia of the triceps combining violent triceps muscle contraction 5,6 results in a more displaced fractures. besides lowvelocity extra-articular fractures, many olecranon fractures extend into the joint of the elbow producing articular step off and lead to reduced mobility, late rehabilitation, development of osteoarthritis, and other morbidities. therefore, absolute fracture reduction and stable fixation are key steps to avoid instability and stiffness of the joint 5,6 and development of osteoarthritis. introduction olecranon process is an important part of the proximal ulna which gives stable configuration to the elbow joint. fractures of the olecranon involving adults of either sex are a frequent injury of upper 1 extremity caused by moderate to severe trauma. olecranon fractures account for approximately 40% 2 of all fractures in proximity to elbow joint and near 3,4 about 10% of all upper extremity fractures. mechanism of injury of olecranon fracture involves a direct blow to the bony prominence of elbow, tension band wiring for displaced and uncomminuted fractures of the olecranon yahya baloch, saeed ahmed shaikh, yasir hussain correspondence: dr. saeed ahmed shaikh assistant professor department of orthopedic surgery jinnah post graduate medical centre, karachi e-mail: drsashaikh2003@yahoo.com department of orthopedic surgery jinnah post graduate medical centre, karachi funding source: nil; conflict of interest: nil received: april 22, 2019; revised: august 26, 2019 accepted: august27, 2019 jiimc 2019 vol. 14, no.4 192 tbw for olecranon fractures patients with comminuted fracture (presence of multiple bone fragments on x-rays), associated distal humerus fracture (assessed on physical examination and fracture confirmed on x-rays), open fracture (presence of wound along with the fracture), infection at the fracture site (presence of redness, hot, tender on physical examination or presence of discharge from the wound), and with neurovascular deficit (wrist drop or no sensation in hands on pin prick was taken as neurovascular deficit ) were ruled out from the study. permission was obtained from the institutional review board and patients were considered for study on meeting the inclusion criteria and informed consent was taken from the patients. the purpose, procedure, risks and benefit of the study were explained to all the patients. confidentiality of the study participants was ensured. relevant history such as age, gender, bmi, duration of fracture, smoking status (patients smoking 5 or more cigarettes per day for more than 6 months or more), history of comorbid conditions like diabetes mellitus and hypertension (known case of hypertension for more than 2 years or more on treatment assessed through physicians prescription and patients record) was obtained. surgery was done by a senior resident (year two or beyond) or author himself. the procedure was performed in lateral decubitus position after the induction of general anesthesia under pneumatic tourniquet control applied at the upper arm. the incision was made posteriorly in midline curving around the olecranon tip and the fracture was explored and reduced. the fracture was fixed with two parallel k-wires inserted just distal to the olecranon tip and engaged into the opposite (anterior) border of the ulna. anchoring in the opposite cortex of the ulna avoids migration of the implant in proximal direction. the circlage wire was passed through a bone tunnel just distal to the fracture and tightened in a figure of eight manner. patients were discharged and followed in outpatient department on regular interval. functional outcome 15 was assessed using mayo elbow performance score olecranon fractures less than one week old were recruited from emergency or outpatient department with confidence level of 95%. technique used to collect sample was non-probability consecutive. materials and methods the local data on this topic is sparse. the present study was designed not only to generate local data but also to authenticate the previous literature. the rationale of our study was to evaluate the functional results of tension band wiring in patients with olecranon fractures. nd rd unstable and displaced. 2 and 3 type are further sub classified into uncomminuted (a) or with comminution(b). 0 cast splints at 45-90 of flexion can be applied to patients with non-displaced type i olecranon 3 fractures. since most of these fractures are displaced, therefore these fractures need internal fixation. various internal fixation techniques are available for olecranon fractures such as figure of 8 steel wire fixation, anatomical locking plate, intramedullary fixation using screw or rush nails and excision of fracrtured fragments in case of severe comminution, however the most frequently applied procedures are tension band wiring and more rigid 6,8,9 method of plate and screws fixation. these two fixation methods have equal and comparable results particularly in mayo type ii uncomminuted variety, which are the most usual types. plate fixation is a good alternative particularly in comminuted and 10, 11 unstable fractures. tension band wiring (tbw) 12 first described by weber and vasey is a relatively simple and easy procedure which can be performed 2 by even junior residents during early training. it requires minimum instrumentation and implants in 13 comparison to plate fixation. although there are chances of proximal migration and protrusion of implant (k-wires) related to this procedure 4 necessitating its removal , implant prominence is less likely since smaller amount of implant is used in 13,14 tbw in contrast to plate fixation. in addition tbw is better in terms of cost and operative time in 14 comparison to plate fixation particularly in our part of the world. rate of infection and revision surgery is also found to be low in tbw technique than other 14 methods like plate fixation. this prospective case series was conducted at the department of trauma and orthopedic surgery, jinnah postgraduate medical centre, karachi from december 2017 to june 2018. a total of 62 participants between age ranges of 18 to 50 years of either sex with displaced and uncomminuted jiimc 2019 vol. 14, no.4 193 tbw for olecranon fractures satisfactory outcome was not statistically significant with gender, hypertension, diabetes mellitus, smoking and obesity while it was significant with duration of fracture. a total of 62 patients with closed olecranon uncomminuted fractures were included in our series. the average age of the patients was 35.03 ± 7.87 years. patient related demographics such as average weight, height, bmi, duration of fracture and meps (mayo elbow performance score) are reported in table i. there were 23(37.1%) female and 39(62.9%) male patients. hypertension was observed in 45.16% (28/62), and diabetes mellitus in 51.61% (32/62). there were 24(38.71%) smokers and all were men. effect modifiers/confounders like age, duration of fracture, gender, smoking status, body mass index, history of diabetes mellitus and hypertension was dealt through stratification to see the effect of these on outcomes. post stratification chi square test was applied and significance level was set at 0.05. satisfactory outcome was significantly high in ≤ 30 years of age patients as compare to above 30 years of age patients (p=0.037) as shown in table i. results data was entered and analysis was done on statistical package for social sciences (spss) version 21 for windows. age of the patients and duration of fracture, height, weight, body mass index and mayo elbow performance score was presented as mean ± standard deviation. gender, smoking status, history of diabetes mellitus and hypertension and functional outcome as excellent, good, fair and poor and satisfactory outcome was presented in terms of frequencies and percentages. at the end of three months postoperatively. this system is based on points in four categories which include: pain (45 points), motion arc (20points), stability (10 points), and daily function (25 points) with a maximum of 100 points. excellent score is 90100 points, good 75-89, fair 60-74 and poor score less than 60 points. excellent and good results were considered as satisfactory. regarding functional outcome, 20(32.3%) cases had excellent results, 31(50%) good, 9(14.5%) fair and 2(3.2%) had poor results as shown in figure 1. excellent and good results found in 51(82.26%) cases w e r e c o n s i d e r e d s a t i s f a c t o r y. r e g a r d i n g complications related to this procedure, we noted proximal migration of wires in 10 patients requiring removal and infection in three patients. poor results were related to infection and skin breakdown found in two patients. table i: demographics of the pa�ents (n=62) fig 1: func�onal outcome according to meps discussion we found good to excellent results in more than 80% (excellent 20, 32.3%, good 31, 50%)of the cases with mean meps of 83.11 + 10.02 which is supported by national study conducted in 2012 where combined good to excellent results were found near to 80% 16 (excellent 13, 44.8%. good 10, 34.5%). similar results were also found in an international study main purpose of surgical treatment of olecranon fractures is anatomic restoration and stable fixation which permits immediate movement and decreased 6,8 postoperative morbidities like joint stiffness. out of the broad range of surgical methods available for internal fixation of these fractures, the method of tension band wiring (tbw) is the unanimously 16 established method. this technique converts tensile surfaces of proximal ulna into compressive 2 forces thereby promoting fracture healing. jiimc 2019 vol. 14, no.4 194 tbw for olecranon fractures refernces conclusion we found better results in patients younger than 30 years, although literature is sparse in this regard. this may be related to the impaired inflammatory response and delayed fracture healing with 24 increasing age. tension band wiring is an effective way of treating olecranon fractures particularly those which are displaced and un-comminuted and provide good to excellent functional results in most cases. study, two patients out of 47 in intramedullary group 23 of tbw developed infection. both patients needed repeat debridements and hardware removal. 1. rommens pm, küchle r, schneider ru, reuter m. olecranon fractures in adults: factors influencing outcome. injury. 2004 nov; 35(11):1149-57. 2. schneider mm, nowak te, bastian l et al. tension band wiring in olecranon fractures: the myth of technical simplicity and osteosynthetical perfection. intorthop. 2014 apr; 38(4): 847–855. doi: 10.1007/s00264-013-2208-7 4. ali mkm, hatzantonis c, mbah ca, tambe a, clark di. tension band wire fixation in olecranon fractures: a retrospective study. intsurg j. 2016 aug;3(3):12441 2 4 8 . d o i : h t t p : / / d x . d o i . o r g / 1 0 . 1 8 2 0 3 / 2 3 4 9 2902.isj20162706 3. newman sd, mauffrey c, krikler s. olecranon fractures. injury 2009;40:575-81.a 5. lukšic b juric i, , boschi v, pogorelic z, bekavac j. tension plate for treatment of olecranon fractures: new surgical technique and case series study. can j surg. 2015 feb; 58(1): 24–30. doi: 10.1503/cjs.030313. 6. ren ym, qiao hy, wei zj et al. efficacy and safety of tension band wiring versus plate fixation in olecranon fractures: a systematic review and meta-analysis.j orthopsurg res. 2016; 11: 137. doi: 10.1186/s13018-016-0465-z 8. baecher n, edwards s. olecranon fractures. j hand surg. 2013; 38(3):593-604. 10. den hamer a, heusinkveld m, traa w, oomen p, oliva f, del buono a, et al. current techniques for management of transverse displaced olecranon fractures. muscles ligaments tendons j. 2015; 5(2):129-40. 12. weber b.g., vasey h. osteosynthesis in olecranon fractures. z unfallmedberufskr. 1963; 56:90–96. 7. morrey bf. current concepts in the treatment of fractures of the radial head, the olecranon, and the coronoid. j bone joint surg am 1995; 77:316–27. 9. wilkerson ja, rosenwasser mp. surgical techniques of olecranon fractures. j hand surg. 2014; 39(8):1606–14. 11. traa wa, oomen pj, den hamer a, heusinkveld mh, maffulli n. biomechanical studies on transverse olecranon and patellar fractures: a systematic review with the development of a new scoring method. br med bull. 2013; 108(1):131–57. 17 conducted by chalidis be et al where good to excellent results were observed in 53 (85.5%) patients out of 62 patients. they concluded the tbw as gold standard treatment for displaced but uncomminuted fractures. long term results are also satisfactory for olecranon fractures treated with tbw. in a prospective study over a period of 20 years, patient related outcomes were excellent in majority of patients and the technique of tbw for olecranon 18 fractures was found to be sufficient and durable. in a cohort comparison between locking plate and tension band wiring (tbw) used for olecranon fractures, there was no statistically significant difference in functional outcomes measured according to mayo elbow performance score 13 (meps). both groups had excellent to good results in all patients (10 patients in each group). this study further addressed that the cost of locking plate system was nearly double the cost of tbw used for olecranon fractures. furthermore the operative time required to fix olecranon fractures with tbw was about half an hour less than the plate group. various complications reported with tbw technique include palpable implant requiring removal, proximal migration of wires, infection, implant failure, nonunion, arthrosis and radioulnar 14,19,20 synostosis. although the overall complication rate reported is higher than plate fixation because of the more protruding and painful wires, the more serious complications such as repeat surgeries and infection are more commonly related to plate 14 group . we found prominent implant due to proximal migration in 10(6.2%) patients. in a comparative prospective trial conducted by 14 duckworth ad et al , approximately 50% of the symptomatic patients required implant removal who underwent tbw for olecranon fractures. however none of the patients in tbw group developed infection. similarly in a recent comparative series of patients with olecranon fractures nine out of 46 patients in tbw group developed prominent 21 hardware which later required removal. 22 in a study done by anani a et al out of 63 patients with fractures of the olecranon, six patients developed infection, in contrary to our study where we found infection in three patients which required subsequent implant removal and repeat surgeries to achieve healing. similarly in a recent retrospective jiimc 2019 vol. 14, no.4 195 tbw for olecranon fractures 21. lu qf, tang gl, zhao xj, zhang wj, guo sg, wang hz. tension band wiring through double-cannulated screws as a new internal fixation method for treatment of olecranon fractures: a randomized comparative study. acta orthop traumatol turc. 2015; 49(6):654-60. doi: 10.3944/ aott. 2015.14.0330. 23. chan kw, donnelly kj. does k-wire position in tension band wiring of olecranon fractures affect its complications and removal of metal rate?j orthop. 2015 jun; 12(2): 111–117. olecranon fracture tension-band wiring results in proximal radioulnarsynostosis.eur j med res (2015) 20: 87. doi: 10.1186/s40001-015-0184-7. 24. clark d, nakamura m, miclau t, marcucio r. effects of aging on fracture healing. currosteoporos rep. 2017 dec; 15(6): 601–608.doi: 10.1007/s11914-017-0413-9. 22. anani a , akouété b , yaoviedem j, ekoué d, atsi w, assang d. tension band wiring fi xation is associated with good functional outcome after olecranon fractures at a togo hospital. ann afr surg. july 2011; 8:45. 20. tarallo l, mugnai r, adani r, capra f, zambianchi f, catani f. simple and comminuted displaced olecranon fractures: a clinical comparison between tension band wiring and plate fixation techniques. arch orthop trauma surg. 2014 aug;134 (8):1107-14. doi: 10.1007/s00402-014-2021-9. epub 2014 jun 17. 15. morrey bf, an kn. functional evaluation of the elbow. in: morrey bf, editor. the elbow and its disorders. 3rd ed. philadelphia: wb saunders; 2000. p 82). 14. duckworth ad, clement nd, white to, court-brown cm, mcqueen mm. plate versus tension-band wire fixation for olecranon fractures. a prospective randomized trial. j bone joint surg am. 2017 aug 2; 99(15):1261-1273. doi: 10.2106/jbjs.16.00773. 17. chalidis be, sachinis nc, samoladas ep, dimitriou cg, pournaras jd. is tension band wiring technique the “gold standard” for the treatment of olecranon fractures? a long term functional outcome study. j orthopsurg res. 2008 feb 22; 3:9. doi: 10.1186/1749-799x-3-9. 18. flinterman hja, doornberg jn, guitton tg, ring d, goslings jc, kloen p. long-term outcome of displaced, t r a n s v e r s e , n o n c o m m i n u t e d o l e c r a n o n fractures.clinorthoprelat res. 2014 jun; 472(6): 1955–1961. doi: 10.1007/s11999-014-3481-5 16. inam m, satar a, hassan w, saeed m, arif m. olecranon fracture. professional med j aug 2012; 19(4): 537-541. 19. willinger, l., lucke, m., crönlein, m. et al. malpositioned 13. amini mh, azar fm, wilson br, smith ra, mauck bm, throckmorton tw. comparison of outcomes and costs of tension-band and locking-plate osteosynthesis in transverse olecranon fractures: a matched-cohort study. am j orthop (belle mead nj). 2015 jul; 44(7):e211-5. jiimc 2019 vol. 14, no.4 196 tbw for olecranon fractures original�article abstract objective: to observe the effects of aescin and atorvastatin on the lipid profile of albino wistar rats. study design: quasi-experimental study. th place and duration of study: postgraduate research laboratory at isra university, hyderabad from 6 june th 2018 to 7 october 2018. materials and methods: fifty albino wistar rats were divided into five groups: group a (control), group b (high-fat diet), group c (aescin + high-fat diet), group d (atorvastatin + high-fat diet), group e (aescin + atorvastatin + high-fat diet). pre and post-experimental body weight and biochemical analysis was done through anova on spss version 22. the significance level was p ≤ 0. 05. results: marked reduction in serum total cholesterol (71.36 ±10.1), triglycerides (83 ±25.66), and low-density lipoprotein-cholesterol (32 ± 3.76) while elevation in levels of high-density lipoprotein-cholesterol (45 ± 11.85) was observed in group e as compared to group b. statistically significant difference in mean post-experimental body weight body was also observed between all study groups (p ≤ 0.05). conclusion: combination therapy of aescin and atorvastatin has significant protective effects on lipid profile when compared with individual therapy of either drug. key words: aescin, atorvastatin, cholesterol, hyperlipidemia, triglycerides. hypertension, dyslipidemia, obesity, etc. dyslipidemia is a disorder of lipoprotein metabolism including lipoprotein overproduction or deficiency. it can be aggravated by increased level of low-density lipoprotein-cholesterol (ldl-c) and triglycerides (tags)) or a decrease in high-density lipoprotein4 cholesterol (hdl-c) in the blood. the most common form of dyslipidemia is hyperlipidemia. hyperlipidemias can be classified by specific genetic abnormalities, also termed as familial and alteration in plasma lipoprotein metabolism, which is 5 acquired. circulating ldl-c in the blood can invade the artery wall and lead to the development of fatty plaques in a process called atherosclerosis, which is also 6 accompanied by primary endothelial injury. it has been observed that even 1% decrease in the concentration of plasma lipid levels by lipid-lowering therapies results in a 2% reduction in the prevalence 7,8 of cvds there are different classes of drugs that are used to treat hyperlipidemia, which include niacin, fibrates, and cholesterol binding drugs ezetimibe, omega 3 9 fatty acids and dietary supplements. among these, statins are usually the first line lipidlowering therapy, which primarily targets plasma 10 ldl-c. according to a study, patients who do not introduction cardiovascular diseases (cvds) are the leading cause of death worldwide, killing more people than any 1 other disease annually. in 2016, around 18 million people were reported to have died from cvds, 1 representing 31% of all deaths around the globe. ecological ethnographic studies have reported that south asian people are comparatively at a higher risk 2 of cvds than other ethnicities. alarmingly, cvds are responsible for more than 25% of deaths in this part 2 of the world. the estimates also show that one in every fifth middle-aged adult in pakistan may be 3 suffering from subclinical cvds. this rising toll of cvds globally is related to the gross incidence of atherosclerotic diseases owing to a sedentary lifestyle and co-morbidities like; diabetes, comparative study of aescin and atorvastatin on lipid profile of albino wistar rats 1 2 3 4 5 6 shazia parveen channar , kumayl abbas meghji , ali abbas thalho , sana kashif , mozna talpur , asim shafique channar correspondence: dr. kumayl abbas meghji assistant professor department of physiology isra university, hyderabad e-mail: dr.kumaylabbas@gmail.com 1,3,5 2 4 department of pharmacology/ physiology / anatomy isra university, hyderabad 6 department of internal medicine lumhs, jamshoro funding source: nil; conflict of interest: nil received: april 09, 2019; revised: february 13, 2020 accepted: february 24, 2020 effects of aescin and atorvastatin on lipid profilejiimc 2020 vol. 15, no.2 104 respond to statin treatment remain at a higher risk of 11 developing cvds. atorvastatin is one of the most efficacious statins having major ldl-c lowering properties. it reduces the production of cholesterol through inhibiting 3hydroxy-3-methyl-glutaryl-coa reductase (hmg12 coa) in the liver. similarly, another lipid-lowering agent, aescin is an important ingredient taken out of aesculus hippocastanum tree. it is very popular for being antiinflammatory, anti-edematous and anti-oxidative. it also inhibits the pancreatic lipase in the gastrointestinal tract, preventing the absorption of lipids and increasing the excretion of fat content in feces thus decreasing the total cholesterol, very-lowdensity lipoprotein cholesterol (vldl-c), ldl-c and 13 tags and an increase in hdl-c levels in serum. after extensive literature review, it was found no study has been conducted in pakistan that has demonstrated the comparative effects of aescin and atorvastatin on lipid profile of albino wistar rats. the current study, therefore, was designed to highlight the potential protective effects of aescin and atorvastatin both individually and in combined form. this will not only provide the baseline for future human studies but also help in designing possible efficacious add-on therapies. the objective of the current study was to observe the effects of aescin and atorvastatin on body weight and lipid profile of male albino wistar rats as well as to compare the difference of individual versus combination therapy in reduction of hyperlipidemia. materials and methods this quasi-experimental study was conducted at the postgraduate center of isra university, hyderabad th th from 6 june to 7 october 2018. fifty healthy male albino wistar rats of weight range of 175-300g were included using non-probability purposive sampling. all rats of female gender and with any sickness were excluded from the study. the study was approved by the ethical review committee of isra university, hyderabad. the rats were kept in a proper hygienic and well-ventilated environment. room o temperature of 25 ±2 c and day and night cycle per 12 hours was maintained. after an acclimatization period of ten days, all rats were equally divided into five different groups. group a (control) received standard chow diet and water ad libitum, group b received a high-fat diet of 400mg/kg, group c received aescin 75 mg along with high-fat diet, group d received atorvastatin 80 mg along with high fat and group e received aescin 50mg + 14,15 atorvastatin 40mg along with high-fat diet. aescin was administered in the form of horse chestnut as its 15 extract contains 70% aescin. pre and postexperimental body weights of all experimental animals were recorded. all the rats were euthanized by placing them under the inverted glass jar with chloroform soaked cotton swabs. the rats were sacrificed by cervical dislocation. blood samples were collected by cardiac puncture through a syringe and then transferred to gel-tubes which were kept in a vertical position and then tubes were centrifuged at 5000 rpm for 5 min to separate serum which was used for biochemical analysis. the estimation of random lipid profile (total cholesterol, ldl-c, tags, and hdl-c) was carried out by roche diagnostic kit method on an automatic modular analyzer at isra university diagnostic laboratory, hyderabad. the data was analyzed using spss (statistical package for social sciences) version 22. one-way analysis of variance (anova) was applied to compare the means of various quantitative variables among groups a, b, and c, d, and e.statistical significance was taken at p ≤ 0. 05. results the mean±sd post-experimental body weight in group a, b, c, d, and e was noted as 198+35.90, 284+19.71, 218+32.55, 251+55.01 and 202+48.46 grams respectively and a statistically significant difference was noted (p<0.05) among all the groups. a marked increase in body weight was observed in group b. aescin and atorvastatin treated hyperlipidemic rats (groups c and d) revealed a decrease in body weight, with the aescin group (group c) showing better results. however, aescin and atorvastatin combination therapy group (group e) showed the best results that reveal the combination therapy prevented the body weight gain significantly (table i). the post-experimental biochemical analysis (mean±sd) findings of all study groups are reported in table ii. a statistically significant difference (p<0.05) in mean levels of serum cholesterol, tags, hdl-c and ldl-c was observed among experimental groups. a significant increase in serum levels of jiimc 2020 vol. 15, no.2 105 effects of aescin and atorvastatin on lipid profile cholesterol, tags, and ldl-c while a decrease in serum levels of hdl-c was noted in the hyperlipidemic group (group b). aescin and atorvastatin treated hyperlipidemic rats (groups c and d) revealed a decrease in levels of total cholesterol, tags, and ldl-c and an increase in hdlc levels, with aescin group (group c) showing comparatively better results. however, aescin and atorvastatin combination therapy group (group e) showed significant results with near-normal levels of all lipid profile parameters. that both aescin and atorvastatin have lipid-lowering effects, however, combination therapy of both the drugs is a more potent and efficacious lipid-lowering regimen. zhang et al. observed in their experiment that bodyweight of albino rats decreased when aescin was used in high-fat diet groups. these effects were due to their enzyme inhibition and antioxidant activity. these results are consistent with the present 17 study. in our study, we found aescin to be effective in improving the lipid profile of wistar rats. the findings of our study are consistent with the study of sood s et al. which concluded that aescin derived from hippocastanum plants is effective in preventing 16 the rise of total cholesterol level. lella m et al. and prasad a et al. reported about combined therapy of atorvastatin and cholesterol binding drug (ezetimibe) the studies are consistent with our study that atorvastatin shows better results in combination therapy but in our study, we used 18,19 aescin instead of ezetimibe. in this study, we observed that aescin has significant protective effects on lipid profile of albino rats. however, these protective effects were more pronounced when aescin was used at a comparatively lower dose in combination with atorvastatin than aescin alone. avci g et al. conducted a similar study on aescin and high fed diet rat models, according to their findings, total cholesterol and tags didn't show any significant 20 decrease in experimental groups. this particular finding is inconsistent with our study. this difference could be due to the short duration of their study (2 weeks) as compared to the duration of this study being 5 weeks. however, the results are consistent with the present study in terms of hdl-c and ldl-c levels as in both studies hdl levels have increased and ldl-c levels decreased with treatment of aescin 20 both on low and high doses respectively. sood s et al. reported in a very similar study on aescin and its effects on hypercholesteremia as a lipid-lowering agent, their results in terms of hdl-c and ldl-c are similar to the results of the present study as in both hdl-c levels are being increased and 16 ldl-c levels are decreasing. chatley p et al. conducted an experiment in which he evaluated that the low dose of atorvastatin (5mg/day) and finofibrats (160mg/day) in combination therapy was equally effective as compared to high dose of table: i mean bodyweight (grams) levels among control and experimental groups significant findings (<0.05) table: ii mean levels of lipid profile parameters among control and experimental groups significant findings (<0.05) discussion the present study is based on comparing the individual and combined effects of aescin and atorvastatin respectively. there are few studies that have been conducted on aescin and its role as a lipidlowering agent but literature is scarce in terms of finding a research article on combination therapy of 16 aescin and atorvastatin. the present study showed jiimc 2020 vol. 15, no.2 106 effects of aescin and atorvastatin on lipid profile atorvastatin (10-40mg) and fenofibrate (160mg21 200mg) when given individually. these findings were consistent with the present study. however, they also observed that the combination therapy not only decrease the lipid profile but cause side effects related to high dose. however, the side effects were not observed in the present study, but can be recommended for further studies to strengthen the present study. with strengths, our study had certain limitations. we could not see the effects of the drugs on other parameters such as high-fat diet-induced cardiovascular toxicity and oxidative stress due to monetary limitations and time constraints. therefore, further work should be carried out to see the effects of these drugs on other organ systems as well as to compare the side effects of statins and aescin. aescin can be used as an add on therapy to conventional treatment of hyperlipidemia. however, this can be made available by conducting maximum experimental and clinical trial to further prove its significance. conclusion this study concludes that both aescin and atorvastatin are efficacious in lowering lipid levels. however, aescin showed significant results as compared to atorvastatin, whereas combination therapy is most effective in reducing hyperlipidemia. references 1. world health organization. cardiovascular diseases (cvds) fs, may 2019. 2. tillin t, hughes ad, mayet j, whincup p, sattar n, forouhi ng, et al. the relationship between metabolic risk factors and incident cardiovascular disease in europeans, south asians, and african caribbeans: sabre (southall and brent revisited)—a prospective population-based study. journal of the american college of cardiology. 2013;61(17):177786. 3. shakeel m, irfan m, khan ia. estimating the mutational load for cardiovascular diseases in pakistani population. plos one. 2018;13(2):e0192446. 4. bisht a. an huge updated review on dyslipidemia etiology with various approaches for its treatment. therapy. 2012;4:5. 5. ibrahim sr, mohamed ga, banjar zm, kamal hk. natural antihyperlipidemic agents: current status and future perspectives. phytopharmacology. 2013;4(3):492-531. 6. krauss rm. lipids and lipoproteins in patients with type 2 diabetes. diabetes care. 2004;27(6):1496-504. 7. santos mj, fonseca je. metabolic syndrome. inflammation and atherosclerosis-the role of adipokines in health and in systemic inflammatory rheumatic diseases. acta reumatologica portuguesa. 2009;34(4). 8. onyeneke ec, adebisi ke, eriyamremu ge, ojeaburu si, asagba so, oluba om. effect of lipid-based diet on some lipid-metabolizing enzymes. j med sci. 2007;7(8):1283-9. 9. liu j-c, yang t-y, hsu y-p, hao w-r, kao p-f, sung l-c, et al. statins dose-dependently exert a chemopreventive effect against lung cancer in copd patients: a population-based cohort study. oncotarget. 2016;7(37):59618. 10. flink l, underberg ja, newman jd, gianos e. the recent national lipid association recommendations: how do they compare to other established dyslipidemia guidelines? current atherosclerosis reports. 2015;17(4):15. 11. sirimarco g, labreuche j, bruckert e, goldstein lb, fox km, rothwell pm, et al. atherogenic dyslipidemia and residual cardiovascular risk in statin-treated patients. stroke. 2014;45(5):1429-36. 12. sarabi zs, saeidi mg, khodashahi m, rezaie ae, hashemzadeh k, khodashahi r, et al. evaluation of the antiinflammatory effects of atorvastatin on patients with rheumatoid arthritis: a randomized clinical trial. electronic physician. 2016;8(8):2700. 13. jiang n, xin w, wang t, zhang l, fan h, du y, et al. protective effect of aescin from the seeds of aesculus hippocastanum on liver injury induced by endotoxin in mice. phytomedicine. 2011;18(14):1276-84. 14. rajyalakshmi g, reddy a, rajesham v. a comparative antihyperlipidemic activity of atorvastatin with simvastatin in rats. internet j pharmacol. 2009;6. 15. guillaume m, padioleau f. veinotonic effect, vascular protection, antiinflammatory and free radical scavenging properties of horse chestnut extract. drug research. 1994. 16. sood s, mishra m, sood a, thakur v. hypoglycaemic and hypocholesterolimic efficacy of horse chestnut (aesculus indica) using rat model. journal of clinical nutrition and dietetics. 2015;1(1):1-8. 17. zhang z, li s, lian x-y. an overview of genus aesculus l.: ethnobotany, phytochemistry, and pharmacological activities. pharm crops. 2010;1:24-51. 18. lella m, indira k. a comparative study of efficacy of atorvastatin alone and its combination with fenofibrate on lipid profile in type 2 diabetes mellitus patients with hyperlipidemia. journal of advanced pharmaceutical technology & research. 2013;4(3):166. 19. prasad a, datta pp, roy r, pattanayak c, panda p. comparative study of ezetimibe and atorvastatin alone and in combination on lipid profile in rats. materia sociomedica. 2013;25(3):192. 20. avci g, küçükkurt i, küpeli akkol e, yeşilada e. effects of escin mixture from the seeds of aesculus hippocastanum on obesity in mice fed a high fat diet. pharmaceutical biology. 2010;48(3):247-52. 21. chatley p, badyal d, calton r, khosla p. combination therapy of low-dose atorvastatin and fenofibrate in mixed hyperlipidemia. methods and findings in experimental and clinical pharmacology. 2007;29(3):217-22. jiimc 2020 vol. 15, no.2 107 effects of aescin and atorvastatin on lipid profile original�article abstract objective: the aim of this study was to test the association between recurrent aphthous ulcers and different forms of tobacco habits. study design: hospital based cross-sectional study. place and duration of study: the study population consisted of patients attending the out patient department of islamic international dental hospital islamabad. a hospital based study is carried out for 2 successive months (july-august) 2018. materials and methods: study was conducted on 500 patients to assess the presence of aphthous ulcers. questionnaire based data was collected along with the clinical examination. questionnaire included both quantitative and qualitative variables. quantitative variables; age, frequency of addictive habits, duration of addiction, size of ulcer, no. of lesions, duration of ulcer and qualitative variables; all types of addictive habits (smoking and smokeless tobacco), medical history, frequency of recurrence of ulcers, site of ulceration, type of aphthous ulcers. statistical analysis was carried out using spss software version 23 and chi-squared test was applied. results: out of 500 subjects, 33 (6.6%) participants presented with aphthous ulcers. 78 subjects had addictive habits of smoking tobacco. among them, cigarette smokers were 75 (15%), hookah smokers were 2 (0.4%) and 1 was a bidi smoker (0.2%). 23 subjects had addictive habits of using smokeless tobacco. among which, paan chewers were 7 (1.4%), gutka chewers were 3 (0.6%) and 13 were naswar chewers (2.6%). conclusion: although no significant association has been found between aphthous ulcers and smoking habits but ulcers were found to be lower in patients who are smokers as compared to the non-smokers. key words: stomatitis, aphthous ulcer, tobacco smoking, smokeless. that they are painful and recurrent mucosal lesions causing discomfort while eating, drinking and speaking. there are three clinical variations of aphthous stomatitis; · minor aphthous ulceration · major aphthous ulceration · herpetiform aphthous ulceration exact etiology of ras is unknown but the condition is associated with multiple factors including autoimmunity, genetic predispositions, hematologic abnormalities (anemia), hiv, hormonal fluctuations, arthritis, stress/anxiety, nutritional deficiencies, trauma, drugs, food hypersensitivity, smoking 1, 3,5,7 cessation and allergies. ras is associated with human leukocyte antigen (hla) and immune-dysregulation. lymphocytes are the predominant cells in pathogenesis of ras with a variation in cd4:cd8 ratio during pre-ulceration, 4,5 ulceration, and healing stage. tobacco reduces immunity and t cell response to various antigens so that the association appears to be biologically 8 plausible. aphthous ulcer is a common condition, also known as “canker sores” or “aphthous stomatitis”. the term aphthae is derived from greek word “aphthi” which 1,2 means “to set on fire” or “to inflame”. it is characterized by the repeated formation of benign and non-contagious ulceration of the oral mucous 3 membrane. the ulcers present as lesions having yellow ulcerated base surrounded by erythematous 4,5 halos and covered by fibrino-purulent membrane. 6 morbidity of recurrent aphthous ulcer (ras) is quite high affecting quality of life of patients in a way incidence of aphthous ulcers in all forms of tobacco users, mixed habits and non-users rabia masood, hadia malik, laiba gul, zarmeena imtiaz, ume hani sajjad correspondence: dr. rabia masood assistant professor department of oral pathology islamic international dental college riphah international university, islamabad e-mail: drrabiamasood@gmail.com department of oral pathology islamic international dental college riphah international university, islamabad funding source: nil; conflict of interest: nil received: june 10, 2019; revised: august 27, 2019 accepted: october 31, 2019 ras in tobacco usersjiimc 2020 vol. 15, no.2 116 the management of patients with ras comprises application of topical analgesics, corticosteroids, antibiotics and anti-inflammatory agents that only 1 3 provide symptomatic relief. there are different types of tobacco being used in pakistan which includes smoking tobacco i.e. cigarettes, cigar, pipe, hookah, shisha and bidi and smokeless tobacco include paan, gutka, naswar, oral snuff, snuss (moist snuff), khaini (tobacco and lime) and lozenges. although studies have failed to find the exact etiology of recurrent aphthous stomatitis but tobacco use is the one most debatable and confused anticipated factor as tobacco usage is associated with various oral pathologies such as oral squamous cell carcinoma, periodontitis, gingivitis, tobacco pouch keratosis, oral sub mucous fibrosis and nicotine stomatitis etc., so tobacco usage should logically lead to occurrence of recurrent aphthous stomatitis. however, in contrast to this a number of studies have shown negative correlation between ras and tobacco usage and positive therapeutic 3 effects of smoking. tobacco usage causes thickening (keratinization) of oral mucosa which renders the 4 5 mucosa less susceptible to ulceration. smokers quitting with nicotine chewing gums have less chances to develop ulcers than those without 9 nicotine replacement therapy. previous studies have suggested negative association between tobacco usage and rau but most of those studies assessed relationship between ras and tobacco by using methods that were based on interviews, questionnaire, or on self-reporting of 3 ,10 ,11 smoking status. however, the studies that were previously carried out did not evaluate occurrence of aphthous ulcers in different forms of tobacco users, mixed habits and non-users. in our study we wanted to evaluate the strength of association between occurrence of aphthous ulcer and tobacco usage and incidence of aphthous ulcer among different types of tobacco users in our population and comparing them with non-users because no such study has been done in our community. the objective of this study was to assess the association between recurrent aphthous ulcers and different forms of tobacco habits. materials and methods hospital based cross-sectional study design was used to assess the incidence of aphthous ulcers in tobacco users, non-users and those with mixed habits. the study population consisted of patients attending the out patient department of islamic international dental hospital islamabad. a hospital based study was carried out for 2 successive months (julyaugust) 2018. study was conducted on 500 patients who visited opd of dental hospital for seeking dental treatment. all subjects were interviewed and a structured questionnaire was developed to record their details. the questionnaire contained four main sections (addictive habits/tobacco usage history, aphthous ulcer related medical history, ulcer characteristics and demographics). the addictive habits section had two domains; smoking tobacco domain comprised of six tobacco usage habits (smoking cigarettes, cigar, hookah, pipe, shisha, bidi) and smokeless tobacco domain also had six habits (paan, ghutka, naswar, snuff, lozenges, other habits). medical history associated with the occurrence of aphthous ulcers included anemia, hiv, hormonal fluctuations, gi disorders, arthritis, stress/anxiety, allergies and genetic predisposition. ulcer characteristics comprised size of ulcer, number of lesions, site of ulceration, frequency of recurrence and duration of ulcers. informed consent was taken from all the participants before conducting the study. the participants were asked whether they had oral ulcers (aphthous ulcers) present in their mouth after describing aphthosis to them as recurrent painful ulcers. additional information about ulcers like duration, location, size, recurrence, and no. of ulcers was noted. moreover, risk factors that might be related to condition were inquired (stress, hormonal factors, gd disorders, allergies). participants were classified into 3 groups and the selection criteria for the groups are given below: control group: inclusion criteria included male and female of 15 years and above, subjecting without any ulcers and without any addictive habits. exclusion criteria included patients under 15 years, subjecting with ulcers and with addictive habits smokers group: inclusion criteria included male and female patients of 15 years and above, subjecting with smoking habits (cigarette, cigar, pipe, hookah, shisha, bidi) and with/without ulcers. exclusion criteria included patients under 15 year 117 ras in tobacco usersjiimc 2020 vol. 15, no.2 subjecting without any smoking habits. non-smokers group: inclusion criteria included male and female patients of 15 years and above, subjecting without any smoking habits, with smokeless tobacco habits (paan, gutka, naswar, snuff, lozenges) and with/without ulcers. exclusion criteria included patients less than 15 years, subjecting with smoking habits and without any smokeless tobacco habits. to assess the presence of aphthous ulcers, oral mucosal examination and questionnaire were completed for 500 patients reporting to the opd over a 2-month interval by four examiners. history of addictive habits was taken and tobacco usage was measured on the basis of type of tobacco used, frequency of consumption per day and the duration for which the individual maintained this frequency. to avoid confounding, patients with known history of systemic diseases and other conditions that might influence occurrence of aphthous ulcer were also recorded. and finally on the basis of ulcer characteristics, aphthous ulcerations were categorized into minor, major and herpetiform ulcers. both quantitative and qualitative variables were part of this study. quantitative variables; age, frequency of addictive habits, duration of addiction, size of ulcer, no. of lesions, and duration of ulcer. qualitative variables; all types of addictive habits (smoking and smokeless tobacco), medical history, frequency of recurrence of ulcers, site of ulceration and types of aphthous ulcers. statistical analysis was carried out using spss software version 23. frequency and percentages of different variables were calculated using spss and formulated in tables 1, 2, and 3. results all 500 subjects were asked about their medical histories. out of 500, only 5 subjects (1%) were anemic. 10 subjects (2%) had hormonal disorders related with puberty, menstrual cycle and pregnancy, 83 subjects (16.6%) had gi disorders related to acidity, 7 subjects (1.4%) had arthritis, 74 subjects (14.8) experienced stress related ulcerations during exams or social issues. 61 subjects (12.2%) were allergic to dust, pollen and medications, and 5 subjects (1%) presented with family history of recurrent ulcers. table i: self-reported medical history of pa�ents out of 500 subjects, 78 subjects had addictive habits of smoking tobacco. among those 78, cigarette smokers were 75 (15%), hookah smokers were 2 (0.4%) and 1 was a bidi smoker (0.2%). (graph 1). from 500 subjects, 23 subjects had addictive habits of using smokeless tobacco. and of those 23, paan chewers were 7 (1.4%), gutka chewers were 3 (0.6%) and 13 were naswar chewers (2.6%). (graph 2). from a group of 101 subjects that presented with addictive habits of either smoking or smokeless tobacco 46 were addicted for more than a period of 7 years. table-ii illustrates distribution of duration of addiction among addicts: table ii: dura�on of tobacco addic�on 33 (6.6%) participants presented with aphthous ulcers. pertaining to the ulcer characteristics given in table iii, 2 patients presented with major aphthous ulceration and 31 patients presented with minor aphthous ulcerations. none of the patients presented with herpetiform aphthous ulcerations during the period of sample collection. and out of these 33 subjects who presented with aphthous ulcers, 5 were cigarette smokers while remaining 28 had no history of any addictive habits (smoking or smokeless tobacco). presence of aphthous ulcers was correlated with self-reported medical conditions; 5 out of 33 subjects (15.1%) were allergic, 9 (27.2%) had gi disorders, 3 (9%) had hormonal disorders, 12 (36.4%) had stress-related ulcers, 4 (12.1%) had genetic association and 6 (18.2%) subjects presented without any significant medical history. occurrence of rau is affected by a number of other variables, with no statistically significant influence of tobacco usage. 118 ras in tobacco usersjiimc 2020 vol. 15, no.2 incidence of rau in tobacco users and non-users was statistically analyzed by using chi-squared test. cigarette smoking was considered to represent tobacco usage as significant number of tobacco users were cigarette smokers as compared with negligible amount of other tobacco variables. cigarette smoking was compared with presence of rau and type of ulcers if present. statistical analysis of our study showed no significant association between the presence of aphthous ulcers and cigarette smoking (p value = 0.98) and between cigarette smoking and type of aphthous ulcers (p value = 0.72) as shown in the table iv and table v. genetic factors, hormonal factors, stress, infections, gi disorders etc. no randomized control trial have shown any treatment, that could help in preventing 4 or curing rau. relationship between tobacco habits and rau: an inverse relationship is observed between rau frequency and smoking habits according to 3,5,9 previous studies held. the observations previously made by tony axell and vingent henricsson also presents that there is a negative association between tobacco habits and rau. according to them, surface structures like leukoedema and keratin prevent the penetration of 9 antigenic substances into the oral epithelium. shapiro et al. found that there is a negative relation between rau and smoking. they pointed that genetic, familial, psychological and environmental factors are important considerations in the formation of recurrent aphthous ulceration. they suggest that meaningful data can be obtained by multidisciplinary longitudinal studies. according to banoczy and sallay there is a negative association between keratinization of oral mucosa and 12 aphthae. the findings of the case control study given by pa atkin, x xu, and mh thornhill indicate that patients with rau have low levels of smoking than in matched controls, and they support that there is a negative correlation between minor rau 4 and smoking. the negative correlation of smokeless tobacco with recurrent aphthous stomatitis is also 3 given in a study by grady et al. the case control study given by shamaz mohamed and chandrashekar janakiram found the statistical association between the rau and usage of tobacco smoking. the association that exists between smoking and aphthous mouth ulcers is negative. the nontobacco users tend to have 55% more chance of occurrence 1 of rau than tobacco users. however, study carried out by slebioda z and dorocka, showed there is no significant association found between smoking tobacco habits and 13 occurrence of recurrent aphthous ulcers. protective effect of smoking epidemiological studies suggest a protective effect of smoking. these studies show that mouth ulcers are 4,14,15 more common in nonsmokers than in smokers. the reason that might be associated with this protective effect of tobacco use could be increased 3 keratinization of oral mucous membrane or some substances present in cigarette smoke absorbed table iii: ulcer characteris�cs table iv: rela�onship of cigare�e smoking with aphthous ulcer table v: incidence of aphthous ulcer among smokers and non-smokers discussion aphthous ulcers are recurrent and painful condition 3 of oral mucosa, etiology of which is still unknown. there are certain risk factors that are associated with occurrence of rau including immune reaction, 119 ras in tobacco usersjiimc 2020 vol. 15, no.2 le re ul le ch i causing decrease in frequency of rau. case studies suggest that the nicotine chewing gums are helpful 16 for the nonsmokers who have mouth ulcers. most of the population, on cessation of smoking appear to develop rau for the first time or any previous rau 4,17 that existed, has exacerbated. this might possibly be due to increased keratinization of oral mucosa, 17,18 antibacterial effect of tobacco smoke or smoking cessation have effects on immune system like stress 17 generated due to withdrawal. comparison with literature: most of these previous studies assessed relationship between rau and tobacco by using methods that were based on interviews, questionnaires, or on self-reporting of 3,10,11 smoking status. our study also used the same method as special questionnaire was designed according to which significantly smaller population of rau patients were smokers (15%) as compared to control group who were nonsmokers (84.4%) in a sample of 500 patients. most of the incidences of rau were found among sample population who were non tobacco users. some daily tobacco habits were found in patients among which smoking was most common habit especially cigarette smoking while some in rest of the sample were addicted to other forms of tobacco (smoking and smokeless) and no ulcers were 1 3 5 15 found among them. in contrast to other studies our study showed no significant association between presence of ulcers and cigarette smoking and no association between cigarette smoking and type of ulcers. limitations and future recommendations the factors that might have affected our results could be that these lesion are not fixed long standing lesions, that can be evaluated at any time by the physician , but are short lived that may not be 15 present at the time of examination statistical evaluation of rau might have been affected by this fact. in addition, the methods of assessing smoking status could be inaccurate as smokers may hide their smoking status or underestimate their level of smoking. our study was unable to show incidence of aphthous ulcers between different genders and the medical conditions that might affect the occurrence of aphthous ulcers in our community, so in future we would suggest that further studies be carried out on these aspects. conclusion incidence of rau in tobacco users and non-users has been assessed and statistically analyzed showing that occurrence of ulcers is lower in patients who are smokers as compared to non-smokers. however, no significant association has been found between ulcer occurrence and smoking habits. these findings substantiate with the previous similar studies and can serve as a base for further research in future. references 1. mohamed s, janakiram c. recurrent aphthous ulcers among tobacco usershospital based study. j clin diagn res 2014;8(11):zc64-lc66. doi: 10.7860/ jcdr/ 2014/ 10368.5145 2. edgar nr, saleh d, miller ra. recurrent aphthous stomatitis: a review. j c l i n a e st h et d e r m a to l 2017;10(3):26-36. 3. grady d, ernster vl, stillman l, et al. smokeless tobacco use prevents aphthous stomatitis. oral surgery, oral medicine, and oral pathology 1992;74(4):463-5. [published online first: 1992/10/01] 4. atkin pa, xu x, thornhill mh. minor recurrent aphthous stomatitis and smoking: an epidemiological study measuring plasma cotinine. oral dis 2002;8(3):173-6. 5. shapiro s, olson dl, chellemi sj. the association between smoking and aphthous ulcers. oral surgery, oral medicine, and oral pathology 1970;30(5):624-30. [published online first: 1970/11/01] 6. queiroz s, silva m, medeiros amc, et al. recurrent aphthous ulceration: an epidemiological study of etiological factors, treatment and differential diagnosis. an bras dermatol 2018;93(3):341-46. doi: 10.1590/abd18064841.20186228 7. jesija js, gopal s, skiel hp. recurrent aphthous stomatitis: an assessment of antioxidant levels in plasma and saliva. j c l i n d i a g n r e s 2017;11(9):zc64-zc67. doi: 10.7860/jcdr/2017/29065.10624 8. neville bw. 1995. 9. axell t, henricsson v. association between recurrent aphthous ulcers and tobacco habits. scandinavian journal of dental research 1985;93(3):239-42. 10. perez-stable ej, benowitz nl, marin g. is serum cotinine a better measure of cigarette smoking than self-report? preventive medicine 1995;24(2):171-9. [published online first: 1995/03/01] 11. perez-stable ej, marin g, marin bv, et al. misclassification of smoking status by self-reported cigarette consumption. the american review of respiratory disease 1992;145(1):537. doi: 10.1164/ajrccm/145.2_pt_2.s53 [published online first: 1992/01/01] 12. banoczy j, sallay k. comparative cytologic studies in patients with recurrent aphthae and leukoplakia. journal of d e n t a l r e s e a r c h 1 9 6 9 ; 4 8 ( 2 ) : 2 7 1 3 . d o i : 10.1177/00220345690480021801 [published online first: 1969/03/01] 13. slebioda z, krawiecka e, szponar e, et al. evaluation of serum zinc levels in patients with recurrent aphthous stomatitis (ras). bmc oral health 2017;17(1):158. doi: 120 ras in tobacco usersjiimc 2020 vol. 15, no.2 10.1186/s12903-017-0450-x 14. axell t, zain rb, siwamogstham p, et al. prevalence of oral soft tissue lesions in out-patients at two malaysian and thai dental schools. community dentistry and oral epidemiology 1990;18(2):95-9. [published online first: 1990/04/01] 15. tuzun b, wolf r, tuzun y, et al. recurrent aphthous stomatitis and smoking. international journal of dermatology 2000;39(5):358-60. [published online first: 2000/06/10] 16. bittoun r. recurrent aphthous ulcers and nicotine. the medical journal of australia 1991;154(7):471-2. [published online first: 1991/04/01] 17. mcrobbie h, hajek p, gillison f. the relationship between smoking cessation and mouth ulcers. nicotine tob res 2004;6(4):655-9. doi: 10.1080/14622200410001734012 [published online first: 2004/09/17] 18. bardell d. viability of six species of normal oropharyngeal bacteria after exposure to cigarette smoke in vitro. microbios 1981;32(127):7-13. [published online first: 1981/01/01] 121 ras in tobacco usersjiimc 2020 vol. 15, no.2 original�article abstract objectives: to measure emotional intelligence scores of medical and dental doctors with different years of clinical experience. to establish a correlation between domain specific emotional intelligence scores and years of clinical experience of medical and dental doctors. study design: a quantitative; cross-sectional survey was conducted at fatima memorial college of medicine & dentistry, lahore. th th place and duration of study: study was conducted from august 4 , 2019 to october 6 , 2019 i.e. (2 months) duration. materials and methods: a total of 150 medical and dental doctors were selected using convenience sampling in 3 different categories according to clinical experience. after ethical approval & informed consent of participants, data was collected using pre-validated “leadership toolkit emotional intelligence questionnaire.” data was summarized using descriptive statistics in spss 23. mean and standard deviation for each group was calculated. comparison between groups & five domains of ei was using cross tabulation & pearson's chi-square test. results: a total of 150 doctors with 55.3% females and 44.7% males participated in the study. emotional quotient was assessed based on 5 domains by plotting responses on 5-point likert scale. majority of the participants scored, well in self-awareness (63%), empathy (66%), while low in managing emotions (37.3%), self-motivation (45%) and social skills (38%). total global-ei score increases with years of experience. consultants scored statistically higher in all domains except managing emotions. house-officers scored lowest in managing emotions while post-graduates scored lowest in social skills. conclusion: there is a positive correlation between global ei scores and years of clinical experience with a downward trend in scores of self-motivation and social skills among post graduate trainees. key words: consultants, emotional intelligence, house-officers, post-graduate trainee, years of experience. 1 successes. the research over the last 3 decades have highlighted the importance of socio-emotional capabilities affecting the daily life and hence 2 performance of an individual. the concept of ei was first given by peter salovey & john d mayer as mental abilities model. they traced the emotional hierarchy as ability to correctly perceive, use, understand and 3,4 manage emotions. daniel goleman in 1990's highlighted the importance of emotional intelligence over cognitive intelligence. he rationalized emotional intelligence in the domains of selfawareness, self-management, social awareness and 5,6 social skills. so, ei is social intelligence that enmeshes one's ability to assess, monitor & discriminate between one's emotions as well as others, correctly label the emotions and use this 7 ability in guiding one's own thinking and actions. a fine interplay of cognitive intelligence, empathy and emotions, i.e. emotional intelligence, is needed to introduction over the early part of the last century the concept of intelligent quotient (iq) i.e. cognitive proficiencies and mental aptitudes were the prime source for prediction of academic and non-academic emotional intelligence of medical and dental doctors with different clinical experiences: a cross sectional study 1 2 3 4 marium sohail , raheela yasmin , amina ahmad , rafia illyas correspondence: dr. marium sohail department of medical education islamic international medical college riphah international university, islamabad e-mail: mariumsohail@gmail.com 1,2 department of medical education islamic international medical college riphah international university, islamabad 3 department of medical education fatima memorial college of medicine and dentistry, lahore 4 department of dentistry fatima memorial college of medicine and dentistry, lahore funding source: nil; conflict of interest: nil th received: october 10 , 2019; revised: december 26, 2019 accepted: january 01, 2020 emotional intelligence of medical & dental doctorsjiimc 2020 vol. 15, no.1 57 enhance beliefs and philosophies of personal dynamics. there are three main models of ei. ability model focuses on the balance between discrete mental abilities and emotion processing abilities, mixed model incorporates multiple attributes like assertiveness, flexibility, motivation etc. in regulation of emotional abilities, integrative model combines multidimensional skills from different domains of ei to mental abilities to describe a 8 performance framework. ei is the driver of success vehicle in both our personal and professional lives. cognitive intelligence and emotional intelligence are not foes, they are acquaintances which work hand in hand for a holistic 9 success. studies have shown that people with high ei performs better at workplace and personal life because they are equipped with the power of regulating their emotions which help them in managing conflicts, taking decisions and adapting to 1 0 , 1 1 the situation. ei has a strong effect on communication skills, job satisfaction, academic and workplace performance, stress and burnout which then exerts a string effect on doctor patient 12,13,14 relationship and patient satisfaction. general intelligence (emotional + cognitive) is a dynamic entity which varies with time, and environment and can be improved. the attributes of ei are integral to health professional role, especially doctors and nurses. both formal and informal efforts are being made at different levels of health sector to increase awareness about e m o t i o n a l i nte l l i ge n c e a n d i t s effe c t s o n performance. in pakistan various studies have been conducted to assess the level of emotional intelligence, describe its relation to workplace performance and to establish a correlation between iq and eq. but little research has been done to understand the relationship between different time frames of clinical experience in relation to the specific domains of emotional intelligence. moreover, only a couple of studies in this context have been done on dental doctors in pakistan. in general, emotional intelligence improves with the experience and training but literature is scarce on how it varies across different domains. the study is directed to assess the 5 different domains of emotional intelligence in correlation to the years of clinical experiences. this will ultimately help us in devising targeted interventions to improve emotional intelligence. a study was planned to measure ei scores of medical and dental doctors with different years of clinical experience & to establish a correlation between domain specific ei scores and years of clinical experience of medical and dental doctors materials and methods a cross-sectional survey was conducted at fatima memorial college of medicine & dentistry, lahore for th th time duration of 2 months i.e. aug 4 2019 to oct 6 2019. a sample of 150 medical and dental doctors was selected using convenience sampling. data collection was completed within 1 week. the doctors were selected in 3 different categories according to clinical experience i.e. 50 each from house officers, post-graduate trainees and consultant's category. both males and females in clinical practice were included in the study. medical and dental undergraduate students & basic sciences postgraduate trainees and consultants were excluded from the study. ethical approval was sought from institutional review board. after taking informed consent of the participants, data was collected using pre-validated ' l e a d e rs h i p to o l k i t e m o t i o n a l i nte l l i ge n c e questionnaire'. the participants recorded their response on a 5-point likert scale for each question. the questionnaire consisted 50 questions; 10 from each emotional competency of self-awareness, managing emotions, motivating oneself, empathy, social skills. individual results of questions of each domain were aggregated to give a consolidated score for the said domain which was then re-categorized into 3 classes i.e. strength, needs attention and developmental priority (as per the existing tool). no incentive or reward was given to the participants for inclusion in the study. collected data was entered into spss 23. the data for each group was summarized using descriptive statistics. as the data was symmetrically/ parametrically distributed so mean and standard deviation was calculated for each group. for the comparison between the 3 groups of participants and the five domains of ei questionnaire cross tabulation was done using pearson's chi-square test. jiimc 2020 vol. 15, no.1 58 emotional intelligence of medical & dental doctors results a total of 150 medical and dental doctors participated in the study with age group ranging from 25 to 44 years with mean age of 34.5 years. equal number of participants was recruited in each category. there were 83 (55.3%) females and 67 (44.7%) male participants. majority of the participants were in their thirties (83) while some juniors (42) were in twenties and some consultants (25) in forties. the detailed distribution of participants is given in table i. trainees and 84% consultants obtained scores in strength category. (table i). table i: frequency table of par�cipants in ho, pg's & consultant categories majority of the participants 95 (63%) scored well while 55 (37%) needs improvement in domain of selfawareness. in the domain of self-awareness, consultants scored statistically higher than others (p value= 0.025). 38% house officers, 74% post graduate trainees and 78% consultants obtained scores in strength category. none of the scores were in developmental priority category. (table ii). majority of the participants 94 (62.6%) needs improvement in domain of managing emotions while only 56 (37.3%) scored well. in the domain of managing emotions, post graduate trainees scored statistically higher than others (p value= 0.05). 20% house officers, 48% post graduate trainees and 44% consultants obtained scores in strength category. (table ii) majority of the participants 83 (55%) needs improvement in domain of self-motivation while only 67 (45%) scored well. in the domain of selfmotivation, consultants scored statistically higher than others (p value= 0.001). 24% house officers, 72% post graduate trainees and 78% consultants obtained scores between 34-50 (strength category). none of the scores were in developmental priority category. (table ii) majority of the participants 99 (66%) scored well while 51 (34%) needs improvement in domain of empathy. in the domain of empathy, consultants scored statistically higher than others (p value= 0.011). 38% house officers, 76% post graduate table ii: emo�onal quo�ent interpreta�on & comparison among house officers, residents & consultants fig 1: line diagram showing strength scores in each emo�onal domain discussion in this study emotional intelligence is assessed across gender, years of experience and qualification categories with respect to domain specific scores in ei. a general positive trend in ei scores was noted however statistically significant lower scores were observed in managing emotions and social skills domain across all the categories, raising a question about what are the possible causes of such a finding. the total emotional scores in this study vary directly with the increase in years of experience i.e. jiimc 2020 vol. 15, no.1 59 majority of the participants 93 (62%) needs improvement in domain of social skills while only 57 (38%) scored well. in the domain of social skills, consultants scored statistically higher than others (p value= 0.005). 70% ho's, 82% pg's and 34% consultants obtained scores between 18-34 (needs attention category). none of the scores were in developmental priority category. (table ii). emotional intelligence of medical & dental doctors consultant scores > pg trainee scores > house officers scores. the consultants scored higher in domains of self-awareness, managing emotions and self-motivation while the scores are relatively less in domains of managing emotions and social skills. house officers need improvement in all the domains generally, however pg trainees scored well in managing emotions as compared to consultants but scored very poor in social skills. in my study the female participants (55.3%) were more than (44.7%) male participants. this is in accordance with a similar study conducted in lahore, pakistan showing more prevalence of female 15 doctors. however, couple of indian studies on emotional intelligence reported more male 16,17 predisposition in hospital settings. generally in pakistani context the ratio of female doctors is more than male doctors. overall the scores of ho's and pg's need drastic improvement in self-motivation, empathy & in social skills domain. scores in managing emotions domain needs improvement in all categories of participants. the scores of pgs' are least in social skills domain while the scores of ho's are the least in managing emotions domain. the overall scores of emotional intelligence in my study show a direct relationship with age and experience. the scores of consultants are more than that of pg's, and pg's have scored well than ho's. golman has also reported a positive correlation of age and experience with emotional intelligence due 6 to physiological and mental maturity processes. mckinley study has also shown that emotional 18,19 intelligence increases with age and maturity. cabello also reported that extremes of age have low ei while mid population has higher ei (20). literature suggests that health care providers may experience a negative physical and emotional toll when pre occupied with treating severely ill patient with high morbidity and mortality. this negative cuff may even be amplified for doctors in the initial phases of their 13 clinical experience. this literature evidence supports the results of this study, as the house officers have scored lowest while the consultants have scored highest in most of the domains. this positive trend in ei in relation to the years of experience should be reconfirmed with longitudinal re investigation to see for the effect size and confirmation of the said notion. a multi-level qualitative exploration is needed for reconfirmation of finding as these outcomes may be due to normal age maturation, varied life experiences, structured training, mentoring or other unidentified & unrevealed factors. although the total ei scores shows an increasing trend with years of training, yet postgraduate trainees show a downward trend in the domains of self-motivation and social skills. this downstream observation can be justified by the social and mental stresses, exams, depression, burnouts and financial problems encountered by trainees during the training phase. satterfield has highlighted that decrease in ei during training phase in his study, due to d e p e rs o n a l i zat i o n , st re s s , b u r n o u t a n d 21 desensitization. papanagnou et al. has reported a mid-training downwards trend in overall emotional 22,23 intelligence of medicine trainees. sarah has also reported a decrease in emotional intelligence in military surgical residents during mid-training 24 phase. the possible explanation for lower scores in managing emotions and social skills domain may be attributed to either poor baseline scores or other medicating variables like stress, depression, over commitment & self-doubt which could manifest as a deficit in the scores of these domains. increased level of responsibility along with mental and physical stress may be another contributing factor towards 19 the declining scores. residents are a wet soil, and training period is crucial to promote their emotional wellbeing and competency. so, efforts should be m a d e t o i m p ro v e t h e i r s t r e s s t o l e ra n c e , assertiveness, resilience, optimism , self-perception and self-expression which in turn will ensure development of emotionally intelligent consultants. open lines of communication, accessible and broad learning culture, real time feedback and promotion of self-reflection and self-efficacy can further augment healthcare professional's wellness and hence emotionally intelligent providers and 17 individuals. the scores in self-awareness and empathy domains are higher than other domains. this might be attributed to either good baseline ei scores or it might be a manifestation of other intervening variables. structured training, regular medical education workshops, psychiatric counselling, jiimc 2020 vol. 15, no.1 60 emotional intelligence of medical & dental doctors communication skills workshops, mentoring and support groups, stress management and conflict management exercises during weekly cpc's and portfolio development with reflective practice, may have contributed to the increasing trend in global ei scores and domain specific ei scores. literature suggests that active learning sessions, hands-on practice and situated learning improves emotional skills. deliberate and planned efforts for early clinical exposure, integrated teaching and learning, situated learning and workplace role modeling might have been an instrumental factor for improvement in empathy in doctors. regular educational training workshops by medical education department in domains of self-reflection, self-efficacy, selfregulated learning and portfolio development might be a contributory factor to improved self-awareness. a multi-level re exploration is required for confirmation of findings. perception, management, and utilization of emotions is a prime factor in patient care and hence 13, 25 ensures successful career of a doctor. formal and informal training of emotional intelligence improves communication or social skills, empathy, attitude 26 and patient care. small group teaching and workshops have been proven as the most effective way of letting people understand and label their 27 emotions. mindfulness can be promoted by role 28 modeling which is essential for patient care. conclusion there is a positive correlation between global ei scores and years of clinical experience. there is a downward trend in the scores in domains of selfmotivation and social skills in post graduate trainees while house officers needs improvement in all d o m a i n s . c o n s u l t a n t s n e e d t o i m p r o v e predominately in managing their emotions. limitations this is a unicentric study with small sample size so some observations may be context specific however the findings of my study are parallel with the other international studies. this study is unique in incorporating both medical and dental doctors but it is a crosssectional study, a more rigorous approach would be to conduct this study in a 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in medical education. med teach. 2019;41(7):746–9. jiimc 2020 vol. 15, no.1 62 emotional intelligence of medical & dental doctors untitled-2 original�article abstract objective: to assess the diagnostic efficacy of oral brush cytology in the diagnosis of potentially malignant and malignant lesions of the oral cavity. study design: cross-sectional analytical study. place and duration of study: outpatient department of ent and maxillofacial surgery, pakistan institute of st medical sciences and pathology department of pakistan railway hospital rawalpindi from 1 march 2017 to th 28 february 2018. materials and methods: a total of 50 patients with oral lesions were enrolled through non-probability convenient sampling. all patients presented with oral potentially malignant lesions were included, while patients with age less than 10 years and with bleeding diathesis were excluded from the study. the oral lesions were first sampled by oral brush biopsy technique using a toothbrush and then later on by scalpel biopsy. samples were then studied under microscope for diagnosis. the data was analyzed using spss software version 21.0. sensitivity, specificity, positive predictive value and negative predictive values were calculated keeping histopathology as a gold standard. pearson's chi-square test was used for calculating p-value, where p-value of ≤ 0.05 was considered significant. results: in this study, the mean age of patients presented with non-malignant oral lesions was 59 ± 12 years, while those with oral cancers were 60 ± 12 years. men were affected than women. among 50 patients 39 were found to have oral cancers. the sensitivity of oral brush biopsy was 88%, specificity was 83.3%, positive predictive value was 97.6% and negative predictive value was 50%. the p-value was calculated as 0.001, which was significant. conclusion: our study found that oral brush cytology is reliable and can be easily performed with less cost and discomfort to the patient. it can be used for screening of suspicious oral lesions. it is useful in those situations where a patient refuses to have a biopsy or where a patient with bleeding diathesis would be exposed to unnecessary surgical risks. key words: brush cytology, dysplasia, oral squamous cell carcinoma, potentially malignant disorders. th and hard palate and pharynx. it is the 6 most common cancer in the western world and second most common cancer in some parts of the 1 subcontinent. it is a global health problem with 2 increasing incidence and mortality. in 2013 oral cancer resulted in 135,000 deaths, which have 3 increased from 84000 in 1990. oral cancer has a multifactorial etiology. it can be caused by genetic reasons as well as environmental influences. globally tobacco, alcohol and human 4 papillomavirus are associated with oral cancers. studies have shown that the high incidence of oral cancer in the subcontinent is due to a strong association with tobacco chewing, use of gutka, pan, 5 chaalia, naswar, hukka and cigarette smoking. in pakistan, areas of khyber phuktun-khwa have a higher prevalence of oral cancers due to the frequent introduction oral lesions are a common presentation in our outpatient departments. oral cancer involves cancer of the lips, tongue, floor of the mouth, cheeks, soft comparison of oral brush cytology and tissue biopsy in diagnosing oral lesions 1 2 3 4 5 umer muhammad azam khan , siyab ahmad , samina altaf , madiha sajjad , huma sabir khan correspondence: dr. umer muhammad azam khan department of pathology islamic international medical college riphah international university, islamabad e-mail:umar.azam@hotmail.com 1,3,4 department of pathology islamic international medical college riphah international university, islamabad 2 department of pathology swat medical college, swat 5 department of surgery benazir bhutto hospital, rawalpindi funding source: nil; conflict of interest: nil received: december 28, 2019; revised: may 12, 2020 accepted: may 19, 2020 comparison of oral brush cytology and tissue biopsy jiimc 2020 vol. 15, no.2 83 use of naswar and in karachi due to use of paan and 6 chaalia. karachi cancer registry shows that oral cancer is the second most common cancer in both 7 men and women. the shaukat khanum cancer th registry in 2016 also shows oral cancer as the 8 most 8 common cancer in pakistan. men have twice the risk of oral cancer as compared to women and the risk 9 increases after the age of 50 years. however, some recent studies have shown an earlier incidence in the 10 younger age group as well. early detection of oral lesions has been the most effective approach to reduce morbidity and 11 mortality, especially in the malignant ones. it has been proven that benign oral lesions cannot be distinguished from cancers based on clinical examination alone and so when a suspicious oral 12 lesion is encountered it should always be evaluated. oral brush cytology utilizes a brush to obtain a complete trans-epithelial cytology specimen with cellular material from all three layers of the lesion i.e. 13 basal, intermediate and superficial layers. the technique is to make repetitive to and fro movements with the brush until there is punctate bleeding from the lamina propria of the lesion, thus ensuring that cells from all epithelial layers have 14 been taken. the yield of brush cytology can be further increased by using digital aids and other adjunctive techniques such as dna analysis, immunohistochemistry, molecular analysis and liquid based preparations. brush cytology is indicated to aid in the diagnosis of an oral lesion which cannot be identified with clinical certainty or a probable benign lesion when a clinician wants to 15 avoid unnecessary biopsy. literature search reveals very limited local studies on efficacy of brush cytology. our study intended to investigate this simple but useful technique. the objective of our study was to assess the efficacy of oral brush cytology in the diagnosis of potentially malignant and malignant lesions of the oral cavity. materials and methods this cross-sectional, analytical study was carried out at outpatient department of ent and maxillofacial surgery, pakistan institute of medical sciences, and pathology department of pakistan railway hospital st th from 1 march 2017 to 28 february 2018. a total of 50 patients were enrolled through non-probability convenient sampling. a written informed consent was taken from every patient. approval for the study was taken from the ethical review committee of riphah international university. patients with oral lesions suspicious for malignancy, irrespective of the gender were included in the study. these lesions included leukoplakia, erythroplakia, actinic cheilosis and suspected oral carcinoma. before sample collection, patient's data were recorded on a pre-designed proforma. for oral brush cytology rinsing of the oral cavity was performed by every patient with ample water. the lesion was viewed with the aid of light. a toothbrush was disinfected in 0.2% of chlorhexidine gluconate mouth wash and was used to obtain a complete trans-epithelial biopsy with minimal discomfort. by using moderate pressure, the brush was repeatedly brushed in one direction over the entire lesion many times until pinpoint bleeding occurred, signaling entry into lamina propria. the material from the brush was smeared on two clean, dry glass slides. the smears were fixed with 95% isopropyl alcohol for staining with hematoxylin and eosin. cytological 16 smears were graded as follows: class 0: inadequate specimen, class 1: benign: no atypical cells identified, class 2: dysplastic: cells exhibiting dysplasia, not sufficient for diagnosis of malignancy, class 3: cytology suggestive for malignant. for biopsy samples a local anaesthetic was injected at the site of oral lesion and a scalpel biopsy was taken. the biopsy specimen was kept in 10% formalin for fixation and sent for histopathology. gross inspection of tissue was done and submitted for routine processing, slide preparation and then stained with hematoxylin and eosin for microscopy. based on the degree of dysplasia, architectural loss, invasion deep to the basement membrane and presence of atypical cells, these biopsy specimens were classified as benign, mild to moderate dysplasia, marked dysplasia or carcinoma in situ, well-differentiated squamous cell carcinoma, moderately differentiated squamous cell carcinoma and poorly differentiated squamous cell carcinoma. olympus cx21 light microscope was used for examination of slides of both brush cytology and biopsy. the data was entered and analyzed by using spss 21.0 (statistical package for social sciences). comparison of oral brush cytology and tissue biopsy jiimc 2020 vol. 15, no.2 84 sensitivity, specificity, positive predictive value and negative predictive value with 95% confidence interval were calculated by 2 x 2 table, keeping histopathology as a gold standard. pearson's chisquare test was used for calculating p-value, where p-value of ≤ 0.05 was considered significant. results the total numbers of cases were 50. the mean age of patients presented with oral cancer was 60. the age th group most commonly affected was in 6 decade of life, with a male preponderance. the most common site of oral cancer was buccal mucosa as shown in table i. in our study sensitivity and specificity, ppv and npv were calculated. (table iv). the true and false positives and negatives were based on the following: ! true positive: samples that were positive on both biopsy and brush cytology. ! true negative: samples that were negative on both biopsy and brush cytology. ! false positive: samples those were negative on biopsy and positive on brush cytology. ! false negative: samples those were positive on biopsy and negative on brush cytology. table i: table showing age, gender, site and adverse habits the brush cytology and biopsy results were classified into three classes, i-e benign, dysplastic and malignant (table ii). table ii: table showing the classifica�on of oral lesions on brush cytology and biopsy the analysis of the results of the study was done with the help of the 2x2 table (table iii). table iii: 2x2 table showing brush cytology results against the tissue biopsy table iv: sta�s�cal values true posi�ve: tp, true nega�ve: tn, false posi�ve: fp, false nega�ve: fn. *ppv: posi�ve predic�ve value **npv: nega�ve predic�ve value. pearson's chi-square test was applied through spss version 21 and p-value was calculated as 0.001, which was significant. discussion our results showed that the mean age of patients presenting with malignant oral lesions was 60 years. the age group most commonly affected (30.7%) was 60-69 years. majority of patients with oral malignancies were males accounting for 61% of the total patients while female patients were 39%. previous studies also support this finding. mehrotra 17 et al have documented that 58.9% of malignant oral lesions were males as compared to 41% in females. 18 naseem et al have documented that 73.4% of cases with malignant oral lesions were males and 26.6% in females. the higher male incidence is attributed to the fact that males are more predisposed to the risk factors such as smoking, alcohol and smokeless tobacco like paan, gutka, naswar causing oral 19 cancers. the most common site of oral cancer in our study was buccal mucosa (37%) followed by the tongue (30%) and then alveolus (23%). this finding was consistent with other studies conducted in the 20 south asia region. sharma et al reported buccal mucosa as the most common site with involvement of 63.5%. the likely reason for buccal mucosa being comparison of oral brush cytology and tissue biopsy jiimc 2020 vol. 15, no.2 85 the most common site for oral cancers can be smokeless tobacco; naswar which is the most common addiction in our patients which is kept against the cheek. secondly, cheek mucosa is also very thin and non-keratinized and hence more prone to irritants and carcinogens. there was 88 % agreement among brush cytology and scalpel biopsy results, with a p-value of 0.001 which showed statistically significant agreement between two the tests. this show that the diagnostic accuracy of brush cytology in comparison with the scalpel biopsy was fair and hence brush cytology can be used as an adjunctive test for diagnosis of oral cancers. in our study, 38 out of 50 patients were diagnosed as malignant, two cases were dysplasia and 10 cases were benign on cytology. when we compared the same cases on histopathology, we found that among 10 patients classified as benign on cytology, only 5 were benign while 5 were malignant (table ii). we found on biopsy that 41 cases were malignant as compared to 38 malignant cases on brush cytology. hence true positive in our study were 39, true negative were 5, false negative results were 5 and false positive was 1 (table iii). this was consistent with other studies which showed that brush cytology had higher false negative cases than false positive 21 cases. the reason for the higher value of true positives in our study is firstly, being the inclusion of the cases which look malignant on visual examination and secondly the late presentation of oral malignancies in our setup. reasons for the false negatives on brush cytology can be small sample size, wrong sampling technique, loss of malignant cells in toothbrush bristles and topographic error between the site of brush and scalpel biopsy. this false negative rate suggests that the suspicious oral lesions should undergo scalpel biopsy before they are labelled as benign on cytology. in our study, the sensitivity was 88.6% and specificity was 83%, positive predictive value was 97.5% and the negative predictive value was 50 % (table iv). these values are consistent with other studies. 22 trakroo et al have found that the sensitivity and specificity of brush cytology in detecting dysplasia and oral squamous cell carcinoma were 84.37 % and 88.09 % respectively, and positive and negative predictive values were 93.10% and 76%, respectively. moreover, when histopathology and brush cytology were compared, they showed good 23 correlation with insignificant p values. mehrotra et 24 al. found in their study that when compared to scalpel biopsy, the statistical sensitivity of the brush cytology was greater than 76.8% (p < .05) while the statistical specificity was greater than 93.3% (p < .05). the limitations of this study were that this study was conducted at only one hospital. strength of the study can be improved by conducting a multicentre study with a larger sample size. secondly, most of the patients in this study were malignant and hence sensitivity and specificity of the brush cytology for benign lesions could not be ascertained beyond doubt. conclusion our study finds that oral brush cytology is reliable and can be easily performed with less cost and discomfort to the patient. it can be used for screening of suspicious oral lesions and may have applications in resource-constrained areas. it is useful in those situations where a patient refuses to have a biopsy or where a patient with bleeding diathesis exposes to unnecessary surgical risks. recommendation brush cytology can be used as a useful adjunct to scalpel biopsy in diagnosing oral lesions especially when the index of suspicion for malignancy is high. references 1. road m. an overview of oral cancer in indian subcontinent and recommendations to decrease its incidence . an overview of oral cancer in indian subcontinent and recommendations to decrease its incidence. 2012;1(13):410-425. 2. kujan o gamortn, sloan p. screening programmes for the early detection and prevention of oral cancer. cochrane database syst rev. 2016;5(3):123-35. 3. mahmood s, faraz r, yousaf a, asif h, atif a, waseem m, et al. annual cancer registry report-2016, of the shaukat khanum memorial cancer hospital & research center, pakistan. 2016;3(5):1-21. 4. vargas-ferreira f, nedel f, etges a, paula a, gomes n. etiologic factors associated with oral squamous cell carcinoma in non-smokers and non-alcoholic drinkers�: a brief approach. 2012;23(4):586-90. 5. hernandez by, zhu x, goodman mt, gatewood r, mendiola p, quinata k, et al. betel nut chewing, oral premalignant lesions, and the oral microbiome. plos one. 2017;12(2):172-196. 6. bile km, shaikh ja, khan y. smokeless tobacco use in pakistan and its association with oropharyngeal cancer. comparison of oral brush cytology and tissue biopsy jiimc 2020 vol. 15, no.2 86 2010;16(3):417–24. 7. qureshi ma, mirza t, khan s, sikandar b, zahid m, aftab m, et al. cancer patterns in karachi (all districts), pakistan: first results (2010–2015) from a pathology based cancer registry of the largest government-run diagnostic and reference center of karachi. cancer epidemiol. 2016;44(21):114–22. 8. article o. diagnostic accuracy of computed tomography in detecting bone invasion due to squamous cell carcinoma of buccal mucosa. 2018;28(3):829-33. 9. katsanos kh, roda g, mcbride rb, cohen b, colombel j-f. increased risk of oral cancer in patients with inflammatory bowel diseases. clin gastroenterol hepatol. 2016;14(3):413-20. 10. baig ms, bhutto ra, muhammad s, siddiqui mi. epidemiology of oral cancer in southern punjab, apakistan. pakistan j med heal sci. 2015;9(4):1269-71. 11. mehrotra r, gupta dk. exciting new advances in oral cancer diagnosis�: avenues to early detection exciting new advances in oral cancer diagnosis�: avenues to early detection. head neck oncol. 2011;3(1):33-43. 12. farah cs, bhatia n, lalla y, vu a, john k, gupta v, et al. advances in early detection and diagnostic adjuncts in oral cavity cancer bt contemporary oral oncology. in: kuriakose ma, editor. cham: springer international publishing; 2017;6(12):355-421. 13. sc m. characterization of epithelial progenitors in normal human palatine tonsils by. 2016;14(3):413-20. 14. article m. non-malignant oral ulcer: a diagnostic challenge to otorhinolaryngologists. 2019;27(3):1-6. 15. lingen mw, abt e, agrawal n, chaturvedi ak, cohen e, d'souza g, et al. evidence-based clinical practice guideline for the evaluation of potentially malignant disorders in the oral cavity: a report of the american dental association. j am dent assoc. 2017;148(10):712-727. 16. lingen mw, tampi mp, urquhart o, abt e, agrawal n, chaturvedi ak, et al. adjuncts for the evaluation of potentially malignant disorders in the oral cavity: diagnostic test accuracy systematic review and metaanalysis; a report of the american dental association. j am dent assoc. 2017;148(11):797-813. 17. labani s, asthana s. association of smokeless tobacco use and oral cancer�: a systematic global review and metaanalysis. 2018;14(4):32-45. 18. sahibzada ha, khurshid z, khan rs, naseem m. salivary il-8 , il-6 and tnfα as potential diagnostic biomarkers for oral cancer. 2017;12(43):1-10. 19. warsi i, younus a, rasheed a, ahmed j, hamza sm, farooqui r, et al. smokeless tobacco consumption among public and heavy load drivers in karachi , pakistan�: a cross-sectional study. 2017;9(11):292–9. 20. sharma c, kaur j, shishodia s, aggarwal bb, ralhan r. curcumin down regulates smokeless tobacco-induced nf b activation and cox-2 expression in human oral premalignant and cancer cells. 2006;228(34):1-15. 21. gupta s, shah j, parikh s, limbdiwala p, goel s. clinical correlative study on early detection of oral cancer and precancerous lesions by modified oral brush biopsy and cytology followed by histopathology. j cancer res ther. 2014;10(2):232-8. 22. trakroo a, sunil mk, trivedi a, garg r, kulkarni a, arora s. efficacy of oral brush biopsy without computer-assisted analysis in oral premalignant and malignant lesions: a study. j int oral heal jioh. 2015;7(3):33-8. 23. gupta n, gupta r, acharya ak, patthi b, goud v, reddy s, et al. changing trends in oral cancer a global scenario. nepal j epidemiol. 2016;6(4):613-9. 24. mehrotra r, gupta a, singh m, ibrahim r. application of cytology and molecular biology in diagnosing premalignant or malignant oral lesions. mol cancer. 2006;5(1):11-21. comparison of oral brush cytology and tissue biopsy jiimc 2020 vol. 15, no.2 87 case�report abstract a successful endodontic treatment of a tooth can be compromised by several causes, one such cause is a separation of an instrument within the canal. in order to increase the survival rate and prognosis of a tooth this mishap needs to be rectified. there are many nonsurgical and surgical ways available to deal with such a scenario. this case report presents a least invasive way of tackling this iatrogenic error that involves removal of the fractured instrument via braiding technique and also by passing of a ledge resulting in a successful outcome. key words: braiding technique separated instrument, root canal treatment. technique”. in which 2 or 3 small sized files are twisted around the separated instrument after an initial attempt of by passing it. this preserves root dentin thus provides strength and functional support to the already weaken tooth. case report a 22years old male patient presented to operative department of islamic international dental hospital with a complaint of radiating pain on chewing in lower right first molar. upon clinical examination the tooth was heavily restored with amalgam, mild swelling in buccal vestibule was evident. (fig.1) the tooth had undergone root canal treatment 1year back. the tooth was tender to percussion. oral hygiene status was satisfactory. medical history was non-significant. periapical radiograph was performed that showed an inadequate endodontically treated tooth. distal canal was obturated at short length. a separated hfile was seen in one mesial canal at least 4-5mm in rd the coronal 2/3 of root with the other mesial canal being missed. for identifying the canal with the separated instrument another x-ray with slob (same lingual opposite buccal) technique was done. the mesial shifting located the instrument to be in mesiobuccal canal, which was later confirmed after access opening. clinical procedure the patient was notified about the condition of the tooth, and also the treatment to be done. the proposed treatment was initiated after taking the informed consent from the patient. local anesthesia was given via inferior alveolar nerve block and rubber dam was applied. the amalgam restoration was removed with high speed hand piece using tungsten carbide 245 bur till the access opening. introduction dental clinicians performing endodontic treatment face variety of complications during this procedure, the most common of these are the iatrogenic errors 1 occurring during root canal preparation. among these mishaps intracanal separation of an endodontic instrument is the most prevalent. this broken instrument might adversely affect the prognosis of the treatment by obstructing a 2 thorough cleaning and shaping of the canal. the long term prognosis of such teeth is determined by the pre-operative infection of the tooth, location and 3 timing of the separated instrument. in order to retain teeth with such mishap and to increase the longevity; several treatment options are available to overcome this incident. among these options the first and the foremost is to try removing the separated fragment with the aid of ultrasonic, retrieval kits, hollow tubes or files. if these options fail the other options are to bypass the fragment or go for surgical treatments such as apicectomy, root 4 resection, hemi section or extraction. the choice for instrument retrieval technique should be the least 5 invasive and is also operator dependent. this article presents a case report on minimally invasive way of file retrieval from a lower first molar. the technique used for retrieval was “braiding retrieval of a separated endodontic instrument via braiding technique mehak babar, anum moiz, sohaib siddique correspondence: dr. anum moiz fcps trainee operative dentistry department of dentistry islamic international dental hospital riphah international university, islamabad e-mail: anum.moiz2487@gmail.com department of dentistry islamic international dental hospital riphah international university, islamabad funding source: nil; conflict of interest: nil received: may 14, 2019; revised: july 15, 2019 accepted: july 17, 2019 separated endodontic instrument retrievaljiimc 2020 vol. 15, no.1 63 coronal flaring was done with gg-drills 2 and 3 followed by 4. an attempt was made to bypass the separated instrument using h-files in a sequence from 20 to 40 numbers. the created space was used to employ “braiding technique” in order to retrieve the file. two number 10k files were inserted in the canal and twisted around the separated file and then pulled upwards towards the orifice. this led to the loosening of file in canal which was later removed with the aid of “stieglitz forceps.” (fig 2 & fig3) during canal shaping and cleaning a ledge was encountered in outer wall of mesio-lingual canal. the ledge was bypassed with a small kfile with a watchwinding motion and the working length was achieved. (fig.4) the root canal treatment was completed with laterally condensed obturation. (fig.5) coronal buildup was done with amalgam filling. fig 1: pre opera�ve periapical radiographic image fig 2: periapical radiograph showing the removal of separated instrument from the canal fig 3: retrieved instrument from canal fig 4: ledge bypassed fig 5: post-opera�ve periapical radiograph of obturated root canals discussion the success and an overall prognosis of root canal treatment might be adversely affected by a 6 separated instrument within a canal. instrument separation is a common mishap that can occur even by experienced endodontists as shown by a previous study results that incidence was (94.8%) in endodontists as compared to general dentists 7 (85.1%). the prognosis in such cases is dependent on root vitality, periapical status of a tooth, the level of separation and the status of cleaning and shaping 8 of canal at the time of separation. in order to increase the longevity of a tooth, every attempt must be made to bypass or remove the fractured instrument. orthograde instrument retrieval is a time taking procedure and requires a lot of effort with a 55-79% separated endodontic instrument retrievaljiimc 2020 vol. 15, no.1 64 8 success rate. among different retrieval methods braiding technique is the simplest one, limiting excessive removal of root canal dentin and also prevents tooth from iatrogenic errors such as 9 perforation and fracture. in this case copious irrigation with sodium hypochlorite and 15% edta were used for lubrication. researches have shown that if an instrument can be bypassed it can be retrieved with 10 ease. same as in this case after accomplishing the bypassing, braiding method was implemented. that involves insertion of 2 or 3 h files in the canal alongside the fractured object which is then withdrawn by gripping the object through twisting of these files. the above mentioned technique resulted in a successful retrieval of the instrument with least amount of destruction to the tooth and periapical tissues. the advancement of technology had revolutionized the field of dentistry in every aspect, resulting in the development of newer techniques for retrieval of fractured instrument. the different techniques and armamentarium includes masserann kit, brasseler endo extractor kit, cancellier instrument and mounce extractors, instrument removal system, ultrasonic removal with dental operating microscope/ dental loupes, laser, electrolysis and 11,12 many more. in comparison to the novel techniques mentioned above, the retrieval of a fractured instrument with the aid of braiding technique is a simple and low cost alternative. it does not require any special devices, and uses routine endodontic instruments in the dental clinic, it is fast 13 to execute and less technique sensitive. in order to achieve the beneficial result a dentist needs to charter patience, persistence and perseverance along with the least invasive method of instrument 14 retrieval. conclusion as stated prevention is better than cure so every effort must be made to follow the proven strategies, implementing safe methods and have thorough knowledge during root canal procedure in order to prevent such mishaps from happening at first place. on the other hand if it does happen begin treatment with the simplest and least invasive methods to deal with such scenarios. references 1. chauhan r, chauhan a, singh s. retrieval of a separated instrument from the root canal followed by non-surgical healing of a large periapical lesion in maxillary incisors a case report. endo 2013; 2(25): 68-73 2. madarati aa, hunter mj, dummer pm. management of intracanal separated instruments. joe 2013 may;39(5):569-81 3. suter b. separated root canal instruments – an overview of incidence, localisation, treatment strategies and outcome. swiss dent j. 2017 mar 24; 127(3):233-7. 4. brito-júnior m, normanha ja, camilo cc, faria-e-silva al, saquy pc, ferraz mã, silva-sousa yt. alternative techniques to remove fractured instrument fragments from the apical third of root canals: report of two cases. braz dent j. 2015 jan-feb; 26(1):79-85. 5. parveen s, hossain uddin mf. management of broken m, instrument by file by pass technique bsmmuj. 2017; 10: . 41-43. 6. okiji t. modified usage of the masserann kit for removing intracanal broken instrument. j endod. 2003; 29: 466-67. 7. madarati aa. retrieval of multiple separated endodontic instruments using ultrasonic vibration: case report. j. taibah univ. med. sci. june 2016;11(3):268-73 8. arcangelo cm, varvara g, fazio pd. broken instrument removal two cases. j endod. 2000;26:568–70 9. uddin mf, alam ms, howlader mm, & moral a. retrieval of a fractured instrument using file braiding technique: a case report. update dent. coll. j 2012; 2(1), 25-30 10. gutmann jl, dumsha tc, lovdahl pe. problem solving in th endodontics 4 ed. st. louis, missouri: mosby, 2006 p26772. 11. vouzara t et al. separated instrument in endodontics: frequency, treatment and prognosis. balk j dent med, 2018;22; 123-32 12. doshi a, doshi c, desai m, doshi h. retrieval of fractured instrument from root canal: a case report”. ijdr. june2017; 7(06):13388-91. 13. frota lm, aguiar ba, aragao mg, de vasconcelos bc. removal of separated endodontic k-file with the aid of hypodermic needle and cyanoacrylate. case rep dent. september 2016;2016:1-4 14. lohar j, sood h, gosai p, shekh tm. 3p's in retreatment endodontics-an often forgotten virtue. j pharm bioallied sci. 2019 feb;11(suppl 1):s76-s80 separated endodontic instrument retrievaljiimc 2020 vol. 15, no.1 65 original�article abstract objective: to assess the nephroprotective role of ascorbic acid against aspartame induced nephrotoxicity in albino wistar rats. study design: quasi-experimental study. place and duration of study: postgraduate research laboratory at isra university, hyderabad from august 2018 until november 2018. materials and methods: thirty albino wistar rats were divided into three groups: group i (control group), group ii (aspartame only), and group iii (aspartame and ascorbic acid combination). pre and post-experiment body weight, the biochemical analysis was done through anova. while fisher's exact test was used for histological analysis in spss version 22. results: statistically significant difference in mean post-experimental body weight was observed in all three groups (p-value<0.05). marked reduction in mean body weight was observed in group ii (171.4±17.5) as compared to group iii (191.80±15.1). a statistically significant difference in mean serum levels of serum biomarkers was also observed in all three groups (p-value<0.05). marked elevation in serum levels of urea, creatinine, c-reactive protein while the decline in serum levels of glutathione peroxidase was seen in group ii as compared to group iii. histological alterations (mean diameter of proximal and distal renal tubules) were also more pronounced in group ii (110.3±7.4 and 185.98±5.9) respectively as compared with group iii (89.59±6.1 and 95±6.8). conclusion: aspartame consumption causes significant nephrotoxicity and disturbs normal renal functions. ascorbic acid used as a potent antioxidant can limit and/or decrease the toxic effects caused by aspartame. key words: ascorbic acid, aspartame, biochemical, histological, nephrotoxicity. 3 phenylalanine. with the positive uses of aspartame, several negative effects make it one of the most 4 controversial artificial sweeteners. each year, it claims numerous health problems like headaches, 5 dizziness, nephrotoxicity etc. consumption of aspartame poses some serious effects on neuronal 6,7 tissues and leads to neurodegenerative disorders. 1 it is confirmed as a multipotent carcinogenic agent. once consumed, apm metabolized in the gastrointestinal tract (git) into aspartic acid, 8,9 phenylalanine and menthol. this menthol then oxidized into cytotoxic formaldehyde and formic 6 acid. formic acid is considered as the chief metabolite responsible for the detrimental effects of acute intoxication by menthol in humans and animal trials whereas, formaldehyde is a known potent 10 carcinogen. they are mainly responsible for oxidative stress at the cellular level that may impair 9,11 renal functions. consumption of aspartame for longer duration leads to the production of reactive oxygen species (ros) include free radicals that cause introduction aspartame (apm) is amongst the most widely existing artificially sweetening compounds, 1 consumed by over 100 million people globally. it is one of the constituent ingredients present in diet carbonated cola beverages, tabletop sweeteners and a large number of pharmaceutical products (cough 2 syrups, lozenges, multivitamins etc.). it is commercially available in markets with different names like; diet sweetener, nutra sweet, candril etc. constituents of apm include aspartic acid and effects of ascorbic acid on aspartame induced nephrotoxicity: an experimental rat model 1 2 3 4 5 sana kashif , kumayl abbas meghji , tariq feroz memon , shazia parveen channar , jahanzeb khan , 6 muhammad shahab hanif correspondence: dr. tariq feroz memon assistant professor department of community medicine isra university, hyderabad e-mail: drtariqferoz@gmail.com 1,5,6 2 department of anatomy/physiology / 3 4 community medicine / pharmacology isra university, hyderabad funding source: nil; conflict of interest: nil received: april 02, 2019; revised: october 31, 2019 accepted: november 03, 2019 nephroprotective effects of ascorbic acidjiimc 2020 vol. 15, no.2 88 6,11,12 renal tissue injury. these free radicals attack the cell membranes 13 causing peroxidation of fats. consequently, damage to the cellular components resulting in oxidative 7 stress (os). the elevation of menthol level soon after administration of aspartame has demonstrated by 8 studies on humans and animals. ascorbic acid (aa) is one of the most significant water-soluble antioxidants needed in the body for 14 several processes. it is an effective antioxidant that showed a protective role against ischemic conditions, toxicity and injurious effects induced by 15 os in animal models as well as human studies. it reduces os thus avoiding several damaging processes within cells and has the potential to reverse the negative or adverse effects of 16 carcinogenic substances like apm. it can affect the endothelial functions in a positive way and exert 17 anti-inflammatory activities. due to the protective roles of aa, it is frequently used in the field of 14,17 medicine. histological alterations in liver architecture resulting from apm consumption is reported by some 12 researchers. whereas, the hepatoprotective effect 18,19 of aa is reported by different studies. however,a very limited number of studies have demonstrated 20 the role of aa against the nephrotoxicity by apm. to the best of our knowledge, no study has been conducted in pakistan that has demonstrated the protective role of aa in apm induced nephrotoxicity. the current study, therefore, was designed to highlight the nephroprotective effects of aa against apm related nephrotoxicity. this will not only provide the baseline for future human studies but also help in designing community-based programs to educate masses to raise awareness related to the harmful effects of apm containing products on their kidneys. moreover, any significant findings of the present study will also be helpful in providing guidelines for the stakeholders to include aa as an ingredient in apm containing products to prevent and reduce the morbidity and mortality rate. the objective of the present research work was to assess the nephroprotective role (hematological, anti-oxidative and histological) of aa against apm induced nephrotoxicity in albino wistar rats. materials and methods quasi-experimental study was conducted at the postgraduate research laboratory at isra university hyderabad from august 2018 to november 2018. thirty male and healthy albino wistar rats, 8-12 weeks old, 150 to 250 grams were included in the present study through a non-random purposive sampling technique. the animals were handled according to the national research council guidelines 21 for laboratory animal handling. ethical approval was sought from the ethical review committee of isra university. after acclimatization period of 1 week, we randomly divided animals into three groups (n=10); group i (controls), group ii (aspartame 200mg/kg/day 22 orally) and group iii (aspartame 200mg/kg/day 23 orally + ascorbic acid 100mg/kg/day orally). experimental drugs were crushed and mixed with a normal chow diet, which was fed to the animals for six weeks. blood samples for biochemical analysis (serum urea, creatinine, c-reactive proteins (crp) and serum glutathione peroxidase (gpx) were collected twice from each rat model (before and after apm induction) from retro-orbital plexus (before) and then through cardiac puncture (after) in the study to evaluate the renal changes. all tests were carried out by roche/hitachi diagnostic kit method on an automatic modular analyzer while gpx performed on the bioassay technology elisa kit. after six-week, all animals were sacrificed under anesthesia and kidneys of all groups were removed soon after sacrificing the animals. kidneys were then washed with normal saline and gross abnormalities as well as morphological parameters like those that weight & size were recorded on electronic precision balance and measuring scale respectively. collected specimens (kidneys) from all groups were fixed in 10% formalin for histological analysis. tissues were passed in ascending grades of ethyl alcohol (70%, 80%, 90% and 100%) then in xylene for clearing. the tissues were processed to prepare paraffin blocks by the paraffin embedding method. four-micrometer sections were obtained using rotary microtome, 290 (by manual method), for slides preparation. all slides then stained with hematoxylin and eosin (h & e) to observe under a light microscope at 400 magnifications. data were analyzed by spss (statistical packages for social sciences) version 22.0. anova was applied to nephroprotective effects of ascorbic acidjiimc 2020 vol. 15, no.2 89 compare the body weights and hematological findings. whereas, fisher exact test was used for histological findings. the significance level was set at p-value ≤ 0.05. results weight of all rats in groups i, ii and iii were observed prior to the experiment and were found to be 201.2±5.7 gm, 215.7±8.5 gm and 204.6±7.4 gm respectively. at the end of the experiment the rats have weighed again and statistically significant difference in mean post-experimental body weight was observed in all three groups (p-value <0.05) (table i) iii but less in comparison with group ii. there was a statistically significant (p<0.05) difference in renal histology i.e. changes in the diameter of pcts, dcts and distance between visceral and parietal layers of bowman's capsule (table iii). table i: mean body weight (in grams) of animal groups (n=30) pre experimental biochemical analysis of all three groups was performed in the present study. preexperimental mean level of serum urea, creatinine, crp and gpx in group i was (19.05±2.61 mg/dl, 0.46±0.07 mg/dl, 0.117±0.05mg/l and 1.44±0.17 ng/ml respectively), in group ii (19.72±2.52 mg/dl, 0.49±0.09 mg/dl, 0.117±0.07mg/l and 1.43±0.16 ng/ml respectively) while in group iii these were found to be (19.33±2.51 mg/dl, 0.52±0.09 mg/dl, 0.12±0.08mg/l and 1.41±0.14 ng/ml respectively). the mean ± sd of post-experimental biochemical analysis findings of all three-study groups of rats are shown in table ii. aspartame induction resulted in a rise in serum levels of urea, creatinine and crp whereas; significant decline serum level of gpx was observed in group ii. there was a statistically significant difference (p<0.05) of mean levels of serum urea, creatinine, crp and gpx in the postexperimental analysis of blood samples in group ii comparison to the group i and iii. (table ii) marked changes in the histology of mean proximal convoluted tubules (pct) and distal convoluted tubules (dct), as well as mean distance between visceral and parietal layers of bowman's capsule (bc), observed in-group ii in comparison with the group i and iii. changes were also observed in group table ii: mean biochemical analysis findings of all study groups (n=30) table iii: renal histological difference between the study groups (n=30) group i normal glomerular tuft (g) with urinary space (arrow) *fisher exact test nephroprotective effects of ascorbic acidjiimc 2020 vol. 15, no.2 90 group group and renal corpuscles seen in the renal cortex. proximal convoluted tubules (p) and distal convoluted tubules (d) lined by the cuboidal cells. acidophilic cytoplasm and presence of apical brush border seen in pct (p). (h&e) x 400 (4µm) several studies in recent years demonstrated the nephrotoxic effects of artificial sweeteners like apm and its close relationship with renal 8 , 1 3 , 2 6 dysfunctions. similarly, studies also demonstrated that long-term consumption of apm could lead to an increase in the production of harmful free radicals that cause renal tissue 11,13,27 damage. in the present study, we observed the nephroprotective effects of aa on the apm-induced nephrotoxicity on albino wistar rats. we found that the majority of rat in-group ii showed statistically significant (p <0.05) loss in their body weights. similar findings reported and supported by the 8,12,26 studies conducted in the past few years. this decrease in body weight may be attributed to the wasting of protein from the body secondary to the reduced availability of carbohydrates as a potential energy source. another study found that consumption of apm triggers the secretion of a peptide in git (glucagon-like peptide) that may 28 result in weight loss. furthermore, a statistically significant difference in mean weight-loss in-group iii i.e. lesser decline weight loss) was observed compared with group ii. in our study, we found that levels of gpx, crp, urea and creatinine were disturbed significantly after the induction of apm in experimental groups. a statistically significant decline in gpx level in group ii and elevation in levels of crp, urea and creatinine in the same group noticed in comparison with the other two groups. this change in levels may occur due to the toxic consumption of apm resulting in renal dysfunction linked with the damage to glomerular epithelium and filtration resulting from apm metabolite. the findings of other studies are 9,11,13,29 consistent with the current study. these studies demonstrated the negative impact of apm on gpx and other markers of renal dysfunction. these studies also demonstrated that consumption of apm for a longer duration or in high doses causes injuries to the renal tissues leads to the depletion of gpx and eventually disturb the biochemical markers like crp, serum urea and creatinine. the findings of our study are consistent with the findings these studies confirmed that consumption of apm linked closely with the renal dysfunction. moreover, we also observed the levels of serum gpx group ii low cuboidal cells lining the renal tubules with a vacuolated cytoplasm (arrow) and pyknotic nuclei seen in this group. shrinkage of renal corpuscle with widened urinary space (u). the dilated tubular lumens contain sloughing necrotic cells (c). (h&e) x 400 (4µm) group iii most of the glomeruli and tubules in the renal cortex seen. these are more or less similar to that of the control group. brush borders in most of the proximal (p) and distal tubules (d) are preserved. (h&e) x 400 (4µm) fig 1: histological slides of renal cortex discussion apm is one of the most controversial artificial 24 sweeteners used by people around the globe. it is a food and drug administration (fda) approved sugar alternate but its use in different routine food and 25 medicinal products is highly debated. although its consumption within normal and approved range is considered safe the findings of some experimental and epidemiological studies demonstrated its adverse effects like hyperglycemia, obesity, cardiovascular disease, metabolic syndrome, 8,9,11,13,26 neurobehavioral disturbances, cancers etc. nephroprotective effects of ascorbic acidjiimc 2020 vol. 15, no.2 91 that declined due to apm induction but remained sustained with aa i.e. in-group iii. while levels of crp, urea and creatinine found lower in aa treated group (group iii) in comparison to group ii. these differences in serum values of mentioned markers attributed to the anti-inflammatory and vasoprotective role of aa against the apm. these findings are consistent with the other experimental studies that reported the protective role of aa in the presence of nephrotoxic, hepatotoxic or other 15,16,21 substances or drugs. renal histological changes were also observed in this study. in comparison to the control group, in the apm alone group ii there is complete to a partial loss of the brush-bordered lining of tubular epithelium and diameter of lumens detected. remnants of the cell (exfoliated cells) were also present in the lumen of some tubules. we also noticed the increase in urinary space and atrophic glomeruli in some renal corpuscles etc. these findings are consistent with the 12,13,27,29 findings of similar studies. we observed that aa is effective in decreasing the toxic effects of apm on renal tissues. in-group iii, glomeruli appeared normal and showed no significant changes in comparison to group ii. slight edema of tubular cells, the mean diameter of pcts and dcts as well as the mean distance between visceral and parietal layers of bowman's capsule, increased less in comparison with group ii. similar 20 findings were observed by conducted in egypt. this study is one of its kind, because to the best of knowledge no other studies are available demonstrating the protective effects of aa in apm induced nephrotoxicity. however, the present study had certain limitations. we had limited time and availability of funds due to which other laboratory tests of renal function (urine analysis, plasma levels of albumin, serum electrolytes) and oxidative stress (malondialdehyde, catalase) could not be performed. therefore, further research is recommended to assess the various protective effects of aa on various blood and urine parameters as well as on other organ systems. moreover, further studies are also recommended to explore the effects of aa in combination with other anti-nephrotoxic agents such as l-arginine and resveratrol etc. conclusion the current study concluded that aspartame causes significant hazardous effects on the body, consequently affecting the normal renal tissue and ultimately resulting in severe nephrotoxicity. histological changes also endorsed these findings and showed the serious damage and alterations in normal renal histology. on the other hand, ascorbic acid use showed promising results and highly significant protective effects on renal functions and its histological reparations, when given with apm. references 1. soffritti m, padovani m, tibaldi e, falcioni l, manservisi f, belpoggi f. the carcinogenic effects of aspartame: the urgent need for regulatory re-evaluation. american journal of industrial medicine. 2014;57(4):383-97. 2. blackburn gl. sweeteners and weight control. lowcalories sweeteners: present and future. 85: karger publishers; 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2010. 22. arbind k, devi sr, sundareswaran l. role of antioxidant enzymes in oxidative stress and immune response evaluation of aspartame in blood cells of wistar albino rats. international food research journal. 2014;21(6):2263. 23. lewis ra. discovery: windows on the life sciences. 2001. 24. polyák é, gombos k, hajnal b, bonyár-müller k, szabó s, gubicskó-kisbenedek a, et al. effects of artificial sweeteners on body weight, food and drink intake. acta physiologica hungarica. 2010;97(4):401-7. 25. food, administration d. food additive approval process followed for aspartame. report to the honorable howard m metzenbaum, us senate united states genera accounting office. 1987. 26. iyyaswamy a, rathinasamy s. effect of chronic exposure to aspartame on oxidative stress in brain discrete regions of albino rats. journal of biosciences. 2012;37(4):679-88. 27. el haliem ng, mohamed ds. the effect of aspartame on the histological structure of the liver and renal cortex of adult male albino rat and the possible protective effect of pimpinella anisum oil. egyptian journal of histology. 2011;34(4):715-26. 28. brown rj, walter m, rother ki. ingestion of diet soda before a glucose load augments glucagon-like peptide-1 secretion. diabetes care. 2009;32(12):2184-6. 29. mourad m. effect of aspartame on some oxidative stress parameters in liver and kidney of rats. african journal of pharmacy and pharmacology. 2011;5(6):678-862. nephroprotective effects of ascorbic acidjiimc 2020 vol. 15, no.2 93 original�article abstract objective: to determine resilience, and health belief as significant predictors of treatment outcomes in low back pain patients. study design: quantitative cross sectional survey research design. place and duration of study: data was collected from rehabilitation centers of lahore between march, 2018 to october, 2018. materials and methods: the subjects (n=300) were recruited after screening them through a detailed clinical inventory on the basis of low back pain as acquired in the course of life happening and not as an outcome of some accidental or infection-induced events. standardized scales were used to collect the data such as health locus of control belief scale, resilience scale, and treatment outcome efficacy scale. data collected was analysed through spss 23.00. results: there were 330 respondents who filled the questionnaires but thirty respondents evaluated in first phase during pilot study were not included in the final data set. among 300 finally recruited subjects after screening for low back pain, results of pearson product moment correlation analysis exposed significant relationship in study variables. further it was established through regression analyses that resilience and health beliefs sustain as significant positive predictors of treatment outcome efficacy while significant gender differences in health beliefs were observed. conclusion: health belief and resilience are significant predictors of treatment outcome efficacy in lower back pain patients. enhancing health beliefs and resilience may improve treatment outcome efficacy in patients with lower back pain. this research is expedient among health care practitioners for dealing with the people with low back pain with more insightful understanding of psychological dimensions. key words: health beliefs, low back pain patients, resilience, treatment outcome efficacy. of lower back pain has been found to produce quite 2 diverse effects in different repondents in fact; . chronic low back pain poses enigmatic challenges to medical practitioners due to its non-specific nature. few practitioners have prophecies it to be the future's greatest medical disaster due to its diffused triggers and specifies. consequently biopsychosocial approach is relied on to find solution to such intricate condition. biopsychosocial model somehow implicates to elucidate its origin, maintenance, assessment and management. here an individual's thoughts, cognitions, emotions and behaviours gain primal significance. in spite of many technologically advanced treatment strategies in lower back pain modalities, this has been observed that individual's volunteer involvement in learning such behaviours that would lead to control and manage the chronic 3 pains is pivotally important. multidimensional approaches in managing lower back pain have also been emphasized by health psychologists and medical practitioners. numerous empirical studies have substantiated that internal health locus of introduction in pakistan due to poor awareness about dietry intake, inappropriate postures adoption and due to sedentary life styles, the reported clinical evidence 1 for low back pain patients is on rise. this grave phenomenon invokes with it the colossal loss for all in form of lower productivity, impaired daily life functioning, restraints mobility and lost work days, causing immense income loss. enigmatic semblance belief system as determinant of treatment outcome in low back pain patients 1 2 3 4 afsheen masood , muhammad sulman , fatima kamran , farzana ashraf correspondence: dr. afsheen masood assistant professor institute of applied psychology university of the punjab, lahore e-mail: drafsheenmasood15@gmail.com 1,3 institute of applied psychology university of the punjab, lahore 2 faculty of media & communication studies university of central punjab, lahore 4 department of humanities comsats, lahore funding source: nil; conflict of interest: nil received: february 20, 2019; revised: january 09, 2020 accepted: january 19, 2020 belief system in back pain patientsjiimc 2020 vol. 15, no.2 122 control beliefs are significantly associated with intact life patterns and better physical and psychosocial 4 health. health locus of control beliefs have been enumerated as the degree to which sufferers of lower back pain rely on parameters that they rely on 5 in order to control their distress. health belief locus of control somehow helps in developing the selfsufficiency phenomenon. a person with internal locus of control beliefs assumes that his or her health is controlled by internal factors rather than by chance, luck, environmental triggers, or social happenings.the pain experiences in lower back pain patients have been presented as multifaceted, involving sensory, affective, and cognitive experiences which ultimately impair one's health and psychological well-being. few researches have highlighted that cognitions associated with chronic lower back pain are catastrophizing and may lead the 6 sufferer into debilitating state. resilience has been a phenomenon originating in studies wherein children were examined for standing intact in their physical, psychological and emotional health at the wake of various environmentally posed challenges. some children manifested effective growth and surmounted ordeals better than others. this lead to generalize the construct of resilience onto other ages and to individuals facing encounters of differing nature. not all people who survive well at the wake of physical challenges also survive better in emotionally vulnerable situations. resilience is the knack or ability to maintain positive levels of functioning in spite of calamity or adversity. this is in fact one of the several strengths that can assist 7 people in leading positive life. likewise the demeanour of exhibiting resilience and growth varies a lot across individuals. resilience in pain helps in adapting to the phenomenon of pain thus here it is reflected in individuals possessed sustainable attribute of effective coping in response to ardent 8 stressors such as pain. some research studies have demonstrated that resilience moderates the relationship between pain severity and treatment outcome efficacy while others have shown 9 insignificant associations. smith and zautra have enumerated that resilience may entail such resources as self-control, optimism, determination in life, and pain management cum acceptance. such dispositional aspects help him or her in managing the 10 pain much more efficaciously. hence in the light of above literature, this empirical study ventures to examine whether health locus of control beliefs and resilience contribute in predicting treatment outcome efficacy. extensive literature review herein helps in identifying the gaps and after reviewing literature and reported clinical data, this was realized that very few studies have addressed systematically the psychological dimensions as significant predictors of pain management in lower back pain patients. the objective of the current study was to determine resilience and health belief as significant predictors of treatment outcomes in low back pain patients. materials and methods it was a cross sectional survey research design based study, executed in rehabilitation centres of lahore. the study lasted for eight months from march, 2018 to oct, 2018. a total of 330 participants both men and women equally distributed across gender were recruited. the age range of the respondents was 35 to 45 years. respondents were selected after fulfilment of all ethic's consideration and guidelines. formal permission was obtained from all concerned authorities and informed consent was sought from all participants after clarifying them the nature of the study and after ensuring them confidentiality. only willing participants volunteering for research were included. this was also affirmed that participants had right to withdraw with their will, at any stage of the study. all the respondents were screened on primary clinical inventory that filtered such respondents that had some prior accident or medical reason for back pain or who reported less than two months duration from its onset. those reporting mild to moderate lower back pain were also excluded. respondents reporting undiagnosed, diffused reasons for chronic low back pain and having no other comorbid physiological disease or conditions were taken. this stringent recruitment criterion bargained longer time for data collection but this was pertinent to be done to rule out the cases with intricate and complex features and consequences of pain. furthermore, only literate patients with at least matriculation education were taken so that they could read and understand all the scales. 123 belief system in back pain patientsjiimc 2020 vol. 15, no.2 11 resilience scale ; multidimensional health locus of 12 13 control scale ; treatment outcome scale were the major measures used as tools for effective data collection. first of all, a pilot study was undertaken in order to ascertain the reliability estimates of the scales. this was found profoundly sound when administered on thirty respondents. after screening all the scales for any possible ambiguity and after ruling out the administration feasibility constraints, the target data was collected. pilot study data was kept separate from ultimate data set. firstly, consent form was filled by the respondents. after that demographic information sheet and tools related to resilience, beliefs and treatment efficacy were given to the respondents. resilience was measured through the brief 11 resilience sales (brs) that was developed by smith et al. this consists of total six items. out of these six, three are scored reverse while other three are scored forwardly. the participants were made to respond on options spanning from strongly disagree to strongly agree. western empirical evidences support that reliability, validity and internal consistency of the items of the scale is quite high. in one of his validation analysis study on brief resilience scale, convergent validity and discriminant predictive 11 validity were also established by smith et al. as quite sound. second scale was health locus of control belief scale (hlcbs). this scale happens to 12 be the multidimensional reflecting the extent to which individuals believe their health is controlled by various sources. this is one of the most efficient measures of health-related beliefs for more than a quarter of a century. it has 18 items and is very efficient in tapping and understanding health behaviour's. third scale comprised of items pertaining treatment-efficacy. treatment outcome efficacy scale was a ten items questionnaire. it 13 tends to assess the confidence of people with treatment in post treatment settings with any type of chronic pain. each item is rated on a 7 point scale from 0 = not at all confident to 6 = completely confident. the parametric data was analysed with the help of spss version23.00. regression analyses were used in addition to pearson product moment correlation and independent sample t-test. results cronbach's alpha reliabilities mean and standard deviation values were computed and grouped in table i. the values of cronbach's alpha of brief resilience scale, health locus of control belief and treatment outcome efficiency scale in this research were 0.82, 0.85 & 0.83 respectively. demographics analysed through descriptive in spss divulged that mean age of the participants was 42.13 years while this was 37.23 for females and 41.22 for males. it also revealed that 55% belonged to lower middle class, 30% belonged to middle class, 10% belonged to lower income group and 5% belonged to higher income group. 73% reported that they had it from six years, 21% reported this to be from more than two to five years' time, and 6% maintained that they had it from past four months to two years. 48% reported partial impairment in their daily life functioning due to lower back pain while 52% maintained debilitating severe impairments in their daily life tasks performance due to lower back pain. table i: reliability and descrip�ve analysis of the scales (n=300) note. m=mean; sd=standard devia�on; α = cronbach's alpha table ii: correla�on among demographic variables and study variables (n=300) * ** *** note. .p < .05; .p< .01; .p< .001; m= mean; sd= standard devia�on discussion this empirical study has main aim to determine the health locus of control beliefs and resilience as predictors of treatment outcome efficacy in low back pain patients. moreover, gender differences in resilience, health belief locus of control and treatment outcome efficacy in lower back pain patients were also investigated. the primary 124 belief system in back pain patientsjiimc 2020 vol. 15, no.2 hypothesis of this research investigated the relationship among health locus of control beliefs, resilience and treatment outcome efficacy in patients with lower back pain. the findings from inferential analysis indicated that health locus of control and resilience was significantly correlated with treatment outcome efficacy in lower back pain patients. however, resilience and health locus of control were not significantly correlated with each other. these findings are in alignment to empirical 14 findings of smith et.al. similarly, turner and dworkin et al. reported that beliefs regarding pain played an important role in coping back pain 15 problems among patients. the current study has extended preceding researches in which ample support has been catered to social cognitive theory. according to this theory the expectations and selfefficacious beliefs gained through health belief locus of control are likely to improve treatment outcome efficacy. offering support for expectations within social cognitive theory that pain related self-efficacy 16 predicts treatment benefit. pain control beliefs extended in this regard are amply appreciable as they offer a whole new domain of understanding this debilitating phenomenon with dynamic control over this. resilience was found insignificantly associated with health locus of control. this is somehow in contradiction with findings divulged by some other 17 researchers that reveal that those who report more resilience also tend to have more internal locus of control and acknowledge significant link between their health and lifestyle. such people dynamically get involved in such activities through which their 17 health can improve and they can reduce the pain. this is justified along these lines that resilience somehow helps us in coping with lower back pain and it helps us in attaining relative adjustment but somehow this is not directly associated with health beliefs. one potential explanation for our unexpected finding is that patients with lower resilience also somehow develop adaptation to pain due to presence of health beliefs and other psychosocial dimensions such as self-efficacy and proactive health behaviours. this is one of the reasons that lower back pain patients' treatment efficacy shows significant association but resilience does not. in another supporting investigation, this was found that resilience was not markedly 18 associated with pain-related disability over time. the regression analysis reveals that health locus of control establish as significant predictor of treatment outcome efficacy in lower back pain patients. previous research in accordance to this has shown that the stronger the belief in one's personal 19 control, the better the outcome wills be. the justification to this finding is also catered by our general attitude and belief patterns related to pain. people form beliefs about the pain that they encounter. these pain-specific beliefs either enable or disable them in their functional aspects of life. since beliefs are potent predictors of health care utilization, people going through lower back pain timely utilize resources and benefit more, showing better treatment outcome efficacy. results of independent sample t test showed that there were significant gender differences among patients in treatment outcome efficacy. furthermore, it was noted that male have greater resilience and health beliefs as compared to women demographic data also revealed that females table iii: mul�ple regression used to indicate the predictors of treatment outcome efficacy (n=300) * ** *** note. p<.05; p<.01; p<.001; b = unstandardized co 2 efficient; ∆r = r square change; ci=confidence interval table iv: gender differences on health locus of control beliefs, resilience, and treatment outcome efficacy (n=300) * note. p < .05; m= mean; sd= standard devia�on; ci=confidence interval; ll= lower limit; ul= upper limit. 125 belief system in back pain patientsjiimc 2020 vol. 15, no.2 diagnosed chronic back pain problems in their earlier age of onset while males were reported in their later age domains. there are numerous past researches highlighting that differences in lower back pain between males and females exist; as reported by 20-23 other epidemiological surveys on general pain that showed greater frequency and intensity of pain for women. indeed, according to the research by barros, cesar, carandina and torre the prevalence of 24 pain related diseases in brazil is higher for women. there are fewer limitations of this research and some suggestion aligned with them. this study was conducted on a small scale sample so, it is suggested that in future a large sample from various rehabilitation centres should be included. likewise, the research design was cross sectional that might have limited scope of the data; longitudinal research design may benefit more in yielding convincing findings. research includes only quantitative results if it includes qualitative results it would affirm better. present study focused on limited number of predictors of treatment outcome efficacy. a step forward for research would be to develop more complex model to predict treatment outcome efficacy by entailing both physical psychological and dispositional factors. further studies should investigate whether physical therapists beliefs during a patient-health care provider relationship predict patients' beliefs and clinical outcomes. if so, strategies to improve physical therapists decisionmaking should be considered in primary health care. this research is useful among patients with low back pain. it applies to all those people such as adults, aged, injured actors models, caretakers, and physiotherapists etc. who either suffer from low back pain or get involved in dealing with lower back pain patients. these findings implicate the role of enhancing health belief and resilience at the wake of ordeals in patients with lower back pain in order to improve their treatment outcome efficacy. results of this research are also helpful for future researchers in order to design more effective strategies and programs for adopting multidisciplinary/ multidimensional approach in treating lower back pain patients. conclusion health locus of control and resilience to confront debilitating lower back pain are found to be significant predictors of treatment outcome efficacy. references 1. rasul hn, malik an, siddiqi fa. cross sectional survey of prevalence of low back pain in forward bend sitting posture. rawal medical journal. 2013; 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