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Objective: To evaluate children with suspected or definite hypervitaminosis D with respect to prevalence, clinical manifestations and pharmacological aspects. Method: The retrospective cross-sectional study was conducted at the Aga Khan University Hospital, Karachi, and comprised medical records from January 1 to December 31, 2018, of children aged 50ng/ml. Clinical and pharmacological data was retrieved. Data was analysed using SPSS 23. Results: Of the 118,149 subjects visiting the clinical laboratory during the study period, children tested for serum 25-hydroxyvitamin D levels were 16,316(13.8%) who had a median age of 9.78 years (interquartile range: 10.2 years). Children who registered for consultation were 2720(16.6%), and, out of them, 602(22%) had serum 25-hydroxyvitamin D >50ng/ml. The median 25-hydroxyvitamin D levels and age were 70.1ng/ml (interquartile range: 100ng/ml) and 3.1 years (interquartile range: 17.93 years), respectively, and 345(57.3%) of them were boys. Children supplemented with vitamin D were 197(33.1%) and 193(97.9%) of them were prescribed by physicians. Mega-doses were taken by 68(34.17%), while the remaining had used various combinations in syrup or tablet forms. Commonly prescribed mega-doses were 600,000IU 30((44.1%) and 200,000IU 31(45.5%) injections of vitamin D. The primary indications were pains/aches in 51(25.8%) cases, developmental delay 50(25.3%), and vitamin D deficiency 49(24.8%). The main symptoms of hypervitaminosis D or toxicity were abdominal pain 27(13.7%) and constipation 31(15.7%). Conclusions: Children should be given vitamin D supplements with caution as prolonged supplementation and repeated mega-doses can result in toxicity which may cause serious consequences. Key Words: Vitamin D deficiency, Vitamin D supplements, Hypervitaminosis D, Vitamin D toxicity.

Objective: The dried blood spot (DBS) specimen quality affects the newborn screening (NBS) results. For accurate newborn screening, a properly collected dried blood spot (DBS) specimen is required, hence, proper training for specimen collection is essential. We created a training module on Moodle, a virtual learning environment, to train allied health professionals (AHPs) on how to collect DBS samples. The purpose of this study was to determine the acceptability and viability of a virtual learning environment (VLE) for collecting DBS specimens. A VLE module for AHPs and nurses was created on Moodle. Participants were enrolled, and upon completion, certificates were distributed. Data analysis included the total number of participants enrolled, participants who passed assessments, and unacceptable samples collected between March and December 2019 (onsite training) and January and June 2020 (offsite/online training). Results: 55 nurses were trained on-site, while 116 nurses and AHPs completed the module and received certificates through online VLE-based training. The specimen rejection rate was reduced from 0.85% (43 rejected out of 5075 total specimens collected) to 0.5% (15/2375) after online training. This study shows that by using a virtual learning environment, DBS specimen collection training can be provided to allied health professionals.

BACKGROUND To meet the changing needs of students, teaching methods have evolved over time. Online and technology-augmented teaching is becoming more common in the digital age to increase student engagement. The COVID-19 pandemic has accelerated this shift towards online education, necessitating research into its effects on medical students' academic performance and the modification of medical curricula to meet the needs of future generations. OBJECTIVE Based on summative scores, we aimed to compare the academic performance of undergraduate students in online modules compared to traditional face-to-face education and to assess the perceptions of medical students and faculty regarding online education. METHODS A cross-sectional study was carried out at Aga Khan University's Medical College in Karachi, Pakistan. Summative exam scores were reviewed before and after the implementation of online education for year II medical students. Medical students and faculty members were also surveyed to understand their perspectives on the challenges and success factors of online education and a SWOC analysis was done. RESULTS The mean (SD) scores were 76.93 (7.53) and 75.13 (7.15) before and after the implementation of online education respectively. Online education was welcomed by 66.15% of the student population, whereas face-to-face lectures were favored by 61.54% of the faculty. However, conventional face-to-face Problem-Based Learning (PBL) was favored by both students (55.38%) and faculty (53.58%) over online PBLs. In the future, 52.3% and 76.9% of students and faculty, respectively, supported the notion of blended learning. CONCLUSIONS Students in this study were satisfied with online education, although faculty preferred conventional lectures; nonetheless, no difference in cognitive results was seen.

Point-of-care testing (POCT), which is also known as bed side-testing, has been integrated into the healthcare system, offering faster results that can lead to improved patient outcomes. POCT was missing from the medical education curriculum in our institute.The primary objective of this study was to describe the development and introduce POCT training for medical students in a medical college in Pakistan.Secondary objectives were to evaluate student performance on POCT content and to assess the impact of POCT training via students' feedback.The boot camp experience was devised, directed, and facilitated by team constituting of Chemical Pathology faculty members, laboratory technologists and teaching assistants. The program included presentations, demonstrations of POCT instrument handling, supervised hands-on individual performance on glucometer using quality control specimens, competency assessment and sign off followed by interactive case-based discussions. A knowledge quiz via Kahoot was administered at the beginning and end of the experience and scores were compared statistically. Online evaluation and feedback were designed via virtual learning environment based on 10 questions regarding the program and methodology using on a five-point Likert Scale. Frequencies were generated and t-tests were employed to determine pre-post differences.The boot camp was spread over 2 days and ran three hours each day with the third-year medical students class split into two groups (n=80). On knowledge evaluation, the mean group pre and post test scores were 45% and 95% respectively (p-value =0.05). On documented structured competency assessment form a score of 95 was achieved by 100% participants. Positive feedback of 4 or more was recorded on the Likert's scale by 100% respondents.This POCT boot camp experience can be used by other institutions and can be applied at different times during the medical school curriculum and other professional education programs. This bootcamp will be helpful to educate medical students, postgraduate trainees and field workers working in rural areas and in low resource settings to deliver reliable POC tests results. Future research should examine these students' competence in achieving POCT skills when they enter in clinical practice.

Plasma amino acids profiling can aid in the screening and diagnosis of aminoacidopathies. The goal of the current study was to analyze and report the metabolic profiles of plasma amino acid (PAA) and additionally to compare PAA-reference intervals (RI) from Pakistan with more countries utilizing Clinical Laboratory Integrated Reports (CLIR).This was a cross sectional prospective single center study. Twenty-two amino acids were analyzed in each sample received for one year at the clinical laboratoryThe majority of 92% (n = 1913) of PAA profiles out of the total 2081 tests run were non-diagnostic; the PAA values were within the age-specific RI. The PAA median was in close comparison close to the 50th percentile of reference data available in CLIR software. Out of the total 2081 tests run, one hundred and sixty-eight had abnormal PAA levels; 27.38% were labeled as non-fasting samples, and the main aminoacidopathies identified were Phenylketonuria and Maple Syrup Urine Disorder.An agreement of95% was observed between the reporting done by the pathologists and technologists' team and then after the application of CLIR. Augmented artificial intelligence using CLIR can improve the accuracy of reporting rare aminoacidopathies in a developing country like ours.

ObjectiveNewborn screening for congenital hypothyroidism (CH) at our hospital during this study was by measurement of thyroid stimulating hormone (TSH) in serum samples. This audit was conducted over a 2 year period, to determine the compliance of reporting of results greater than the screening cutoffs for serum TSH. Gaps of non-compliance were identified, and re-audit was undertaken after the corrective actions were taken.ResultsThe critical limit was defined as serum TSH (≥ 20 µIU/ml) following consultation with a pediatric endocrinologist. All results above this limit were reported urgently to physicians. During the audit period, 27,407 tests were performed, 0.7% had a value of ≥ 20 µIU/ml, of those only 62% were reported to the general paediatrician or neonatologist. Reasons for not reporting results included non-availability of contact information, lack of policy awareness by technologists, critical results not highlighted on the computer display, and absence of regular monitoring. Corrective measures were taken, and re-audit was done. During the re-audit period, a total of 22,985 tests was performed, 0.6% had a value of ≥ 20 µIU/ml. Of these, 77% were reported to the general paediatrician or neonatologist. Critical result reporting was improved after the audit, and further enhanced the laboratory service of CH screening.

Background The evaluation of 24 h urinary oxalate excretion is the gold standard for diagnosing hyperoxaluria in patients with recurrent urolithiasis. However, 24 h urine sample collection is cumbersome. Therefore we aim to see if oxalate to creatinine ratio in random urine sample can be used as an alternative. Materials and methods A cross-sectional study was conducted at Section of Chemical Pathology, Department of Pathology and Laboratory Medicine Aga Khan University Karachi from 1st February to December 31, 2019. A total of 62 adult patients, 18–60 years of age with history of kidney stones presenting to the clinical laboratory for 24 h urine oxalate estimation were invited to participate in the study after informed consent. Clinical details were recorded on a structured questionnaire and patients were guided to submit 24 h urine and a random spot urine sample. Urinary oxalate was measured on Micro lab 300 using a kit based on oxalate oxidase principle by Trinity Biotech plc, Wicklow, Ireland following standard operating procedures. Urinary creatinine was measured on ADVIA 1800 by Siemens, US using kinetic Jaffe reaction according to the manufacturer's instructions. The data was analyzed on SPSS. Results In a period of ten months, a total of 62 subjects were recruited; mean age was 32.4 ± 2.6 years. Males were 49 (79.0%) and females were 13 (20.9%). Correlation was found to be (r = 0.289) by Spearman correlation (p value, Highlights • Oxalate to creatinine ratio is proposed as an alternative to 24 h urine. • Sensitivity & specificity of spot ox:cr ratio was 83.3% and 17.8% respectively. • PPV and NPV of spot ox:cr ratio was 9.8% and 90.9% respectively. • Studies taking diet and molecular testing into consideration are needed.

Newborn screening aims at detecting treatable disorders early so that the treatment can be initiated to prevent mortality and morbidity. Such programmes are well established in most developed countries, and all newborns are screened for selected metabolic, endocrine and other disorders based on disease epidemiology, testing and treatment availability, efficiency and cost-effectiveness. Even in developing countries, such screening programmes are initiated using heel prick capillary blood collected on filter paper. The current narrative was planned to provide a perspective with evidence in favour of starting newborn screened for different disorders. The programme project should be initiated nationwide, taking one disorder, congenital hypothyroidism, as the prototype and a newborn screening panel can then be extended to include other disorders. A task force should be set up to recommend disorders to be included in the panel, develop the national plan policies, and define procedures to strengthen the testing.

Serum TSH reference intervals (RIs) are methodology, population, and age specific. However, the ethical and practical challenges restrict the establishment of pediatric RIs using conventional approaches and advocates the use of indirect data mining-based algorithms. This study was carried out to estimate the reference interval of neonatal serum TSH in Pakistani population using an indirect approach.A data mining of serum TSH results of neonates (≤ 1 month of age) from 2013 - 2018 was done. Two subgroups on the basis of age from birth to 5 days and 6 - 30 days were assessed. The German study group's pre-validated indirect algorithm 'KOSMIC' was utilized for the statistical analysis.A total of non-duplicate 82,299 neonatal serum TSH tests were retrieved over a period of 6 years, including 88% (n = 70,788) aged 0 - 5 days and 12% (n = 11,511) ranging from 6 days to 1 month. The estimated RIs for the first age partition was 0.7 (90% CI 0.6 - 0.8) to 15.5 (90% CI 12.9 - 16.2) and for the second group 0.7 (90% CI 0.5 - 0.9) to 7.8 (90% CI 6.1 - 9.9) µIU/mL.This study revealed age related trends in serum TSH. The study advocates the need for population specific RIs owing to the significant variations noted on comparison with previously published literature. Precise RIs become vital particularly when serum TSH is undertaken as a confirmatory test for presumptive positive results on newborn screening for congenital hypothyroidism.

This study aimed to determine the clinical spectrum and biochemical findings on urine organic acids (UOA) in Biotin-responsive multiple carboxylase deficiency (MCD) patients presenting to the biochemical genetics laboratory (BGL). Patients reported as MCD, from January 2013-December 2020 were included. The UOA was analysed by gas chromatography mass spectrometer. Demographic, clinical, and biochemical details were extracted from the BGL history form. Two hundred and two patients were reported to have biotin responsive MCD with 111(55%) males and a median (Q3-Q1) age of 7 months (13-4). Of these 71.7% (n=145) patients presented in infantile period. Parental consanguinity was observed in 80% (n=161) and another 32.6% (n=66) cases grandparents were cousins. The main presenting features were seizures, developmental delay, and lethargy. The common peaks were determined on UOA 3OHIVA, MC and MCC. MCD is not rare in Pakistani population; it is recommended to include this disorder in newborn screening programs. Key Words: Biotin responsive multiple carboxylase deficiency, Organic acids, Amino acids, Pakistan, Inborn errors of metabolism.

Background Diagnosis of autism spectrum disorder (ASD) is generally made phenotypically and the hunt for ASD-biomarkers continues. The purpose of this study was to compare urine organic acids profiles of ASD versus typically developing (TD) children to identify potential biomarkers for diagnosis and exploration of ASD etiology. Methods This case control study was performed in the Department of Pathology and Laboratory Medicine in collaboration with the Department of Pediatrics and Child Health, Aga Khan University, Pakistan. Midstream urine was collected in the first half of the day time before noon from the children with ASD diagnosed by a pediatric neurologist based on DSM-5 criteria and TD healthy controls from August 2019 to June 2021. The urine organic acids were analyzed by Gas Chromatography-Mass Spectrometry. To identify potential biomarkers for ASD canonical linear discriminant analysis was carried out for the organic acids, quantified in comparison to an internal standard. Results A total of 85 subjects were enrolled in the current study. The mean age of the ASD (n = 65) and TD groups (n = 20) was 4.5 ± 2.3 and 6.4 ± 2.2 years respectively with 72.3% males in the ASD group and 50% males in the TD group. Parental consanguinity was 47.7 and 30% in ASD and TD groups, respectively. The common clinical signs noted in children with ASD were developmental delay (70.8%), delayed language skills (66.2%), and inability to articulate sentences (56.9%). Discriminant analysis showed that 3-hydroxyisovalericc, homovanillic acid, adipic acid, suberic acid, and indole acetic were significantly different between ASD and TD groups. The biochemical classification results reveal that 88.2% of cases were classified correctly into ASD& TD groups based on the urine organic acid profiles. Conclusion 3-hydroxy isovaleric acid, homovanillic acid, adipic acid, suberic acid, and indole acetic were good discriminators between the two groups. The discovered potential biomarkers could be valuable for future research in children with ASD.

Objective: This study was done to determine the factors responsible for non-treatment of inherited metabolic disorders (IMDs) requiring food for special medical purposes (FSMPs) in Pakistan. Methods: A descriptive cross-sectional study was conducted by Departments of Pediatrics & Child Health and Pathology & Laboratory Medicine, Aga Khan University. Patients diagnosed with IMDs from January 2013 to December 2016 requiring FSMPs were surveyed after a year of initial diagnosis to collect the details of treatment advised, mortality status, and reasons of non-treatment, including not prescribed by physician, non-acceptance by family, non-availability or non-affordability. Results: Over four years period, 311 patients were identified with IMDs; Median age of patients was 1.0 yrs (0.0.2-3.65) with 54% (n=168) being male. Of the total 38.2% (n=119) required FSMPs, 9% (n=28) patients were excluded due to unavailability of diagnostics information. Parents of 58 patients requiring FSMPs out of 119 participated in survey. The leading causes of non-treatment were, FSMPs not prescribed by physicians (n= 30, 51.7%) followed by non-affordability (n=23, 39.6%), families’ unacceptance in (n=9, 18%) patients, non-availability of FSMPs (n=2, 3.4%) and early death of patient (n=1, 1.7%). Conclusion: The main factors responsible for non-treatment of FSMPs requiring IMDs were non-prescription by physician and non-affordability. doi: https://doi.org/10.12669/pjms.37.7.3887 How to cite this:Majid H, Jafri L, Ali ZZ, Afroze B. Is diagnosing patients with Organic Acidurias and Aminoacidopathies enough? Conundrums of a low middle-income country. Pak J Med Sci. 2021;37(7):---------. doi: https://doi.org/10.12669/pjms.37.7.3887 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Introduction Hypoparathyroidism is a rare complication of iron overload in patients with transfusion dependent β thalassemia major (β-TM). We aim to determine the prevalence of parathyroid dysfunction in patients with β-TM. Methods Diagnosed cases of transfusion dependent β-TM between 5 and 17 years of age were recruited from outpatient clinics of a non-profit organization in Karachi, Pakistan. Blood and urine samples were collected in fasting to determine Ca, P, Alb, Mg, Cr 25OHD and iPTH. Patients were grouped on the basis of upper and lower levels of Ca, 25OHD and iPTH for assessing parathyroid dysfunction into primary hypoparathyroidism [low calcium (Ca) & intact parathyroid hormone (iPTH)], sub-clinical hypoparathyroidism [low iPTH and 25 hydroxy vitamin D (25OHD), low/normal Ca], normal functioning parathyroid gland [Normal Ca, iPTH and 25OHD] and secondary hyperparathyroidism [high iPTH, low/normal Ca and/or 25OHD]. Using PTH nomogram subject specific expected PTH (maxPTH) was calculated. Difference between maxPTH and measured iPTH was determined to assess the utility of nomogram in identifying parathyroid gland dysfunction. The statistical analysis was performed using the Statistical Package of Social Sciences (SPSS) version 20. Results Median age of patients was 11 years (13–7) with males being 54.2% (n = 205). Based on Ca, 25OHD and iPTH, primary hypoparathyroidism was identified in 3.4% (n = 13) [median iPTH 11.3 pg/ml (12.6–7)], 52.3% (n = 192) had subclinical hypoparathyroidism [iPTH 40.4 pg/ml (52.7–28.7)], and 34% (n = 125) were identified as secondary hyperparathyroidism [iPTH 88.6 pg/ml (116–74.7)]. Normal response to Ca & 25OHD was seen in 10.6% (n = 39) [iPTH 44.2 pg/ml (53.8–33.4)] patients. High phosphorous was present in all groups. Difference between maxPTH & iPTH was highest in primary hypoparathyroidism, followed by subclinical and secondary hyperparathyroidism. Conclusion Nomogram by Harvey et al. identify low secretion capacity of parathyroid gland that correlated with biochemical classification of patients. It requires clinical validation before using in clinical practice for assessing parathyroid dysfunction.

Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. This study aims to determine the genotypic and phenotypic spectrum of the CFTR gene mutations reported in the literature for Pakistani-origin CF patients. Databases were searched for such studies from 1947-2019 for sample size, method of diagnosis, and CFTR gene mutations. The authors identified 12 studies reporting 33 CFTR gene mutations, both intronic as well as exonic in Pakistani origin patients. The most widely tested mutation was D508 with a frequency of 17%-60%. No hotspot zone was identified and not all reported mutations were causing disease. There is a need to identify common mutations in the Pakistani population to develop population-specific CFTR mutations panel. This will enable the researchers to perform phenotype-genotype correlation studies to improve the CF detection rate. Key Words: Cystic fibrosis, Pakistan, Mutations, CFTR.

Introduction Reference intervals (RIs) of thyroid-stimulating hormone (TSH) and free thyroxine (FT4) are age, assay and population specific. Currently, the age and assay-specific RIs for TSH are not available for children under two years of age. This study aimed to establish reference intervals for serum concentrations of TSH and FT4 in healthy children aged 1–24 months as per CLSI C28-A3 guidelines. Methods This prospective cross-sectional study was conducted in children from 1 to 24 months visiting the clinical laboratory for serum vitamin D testing but without any recent illness, hospitalization, medication and history of maternal thyroid diseases from August 2018 to March 2019 were invited to participate in the study. Serum TSH and FT4 were measured on ADVIA Centaur (Siemens Diagnostics, US), using chemiluminescence immunoassay. Kolmogorov–Smirnov test assessed normality of the data and RIs based on central 95% of the population were established using the non-parametric approach. Results After excluding one subject with confirmed congenital hypothyroidism, a total of 131 children were included in the study. The median (IQR) age of the study subjects was 12 months (11), and majority 78 (59.5%) were boys. The RIs were established using non-parametric approach as the data was not normally distributed. Reference interval for TSH was 0.73–4.94 μIU/mL and for FT4 was 0.81–1.51 ng/dl. Conclusion We established assay-specific RIs for serum TSH and FT4 in children aged 1–24 months in our population. The RIs were slightly lower from RIs developed on other platforms in different population., Highlights • Reference intervals (RIs) of TSH and FT4 are age, assay and population specific. • RIs of TSH & FT4 for

Introduction Hepatic osteodystrophy is an osteoporotic bone disease that occurs in chronic liver disease patients. The global prevalence of osteoporosis in patients with chronic liver disease is 30% to 40%. The pathogenesis of hepatic bone disease is not clear, but it occurs due to unstable bone remodeling with increased bone resorption and decreases bone formation. There has been an interest in determining the clinical utility of bone turnover markers (BTMs) in the assessment of osteoporosis in chronic liver patients. Methods This was a cross-sectional study conducted in patients with chronic liver disease at the section of chemical pathology, department of pathology and laboratory medicine, Aga Khan University (AKU). A total of 50 patients with age >8 years and a history of liver disease >6 months were recruited from January to October 2019. Liver function tests, i.e. aspartate aminotransferase (AST), alanine transaminase (ALT), albumin, and bilirubin, along with clinical signs of liver disease chronicity, were noted. The samples for BTMs, i.e. total serum alkaline phosphatase (ALP) and serum C-terminal telopeptide of type-1 collagen (CTX) were withdrawn and analyzed on Microlab (ELItech Group, Puteaux, France) and ADVIA Centaur (Siemens Diagnostics, NY), respectively. Results The majority of patients were males (n=34, 68%). Twenty-four (48%) patients suffered from fibrosis while 26 (52%) were without fibrosis. Median platelet count (68×109/L (102.5-50)) and median cholesterol levels (102.5 mg/dl (147-99.5)) were decreased, whereas gamma-glutamyl transferase (GGT) levels were higher in the fibrosis group as compared to the non-fibrosis group. The median levels of total ALP were 91.5 IU/L (103-82), and the median levels of CTX were 0.24 pg/ml (0.34-0.21). Conclusion In the present study, no significant difference was found in the BTMs of patients with and without chronic liver disease (CLD). However, there was a positive and significant correlation of BTMs, particularly CTX with age, bilirubin levels, and hepatomegaly.

Introduction Liver cirrhosis is an irreversible and end-stage disease. It results from chronic liver damage characterized by the replacement of normal liver tissue by fibrosis, leading to the progressive loss of liver function. Making an early diagnosis of cirrhosis is important for patients with chronic hepatitis because early antiviral therapy can prevent the progression of cirrhosis and even induce regression. There have been efforts to develop surrogate markers for liver cirrhosis as the biopsy is invasive, costly, and difficult to standardize. Methods This was a cross-sectional study conducted at the Section of Chemical Pathology, the Department of Pathology and Laboratory Medicine in Collaboration with the Section of Gastroenterology, Department of Medicine, the Aga Khan University, from January to December 2018. A total of 90 patients (>18 years of age) with a history of chronic viral hepatitis, who were attending the FibroScan® (Echosens, Paris, France) clinic were included. Patients with a history of autoimmune liver diseases and hepatocellular carcinoma were excluded from the study. Blood samples withdrawn were analyzed on ADVIA Centaur® (Siemens Healthineers, Erlangen, Germany), and Forns scores were calculated based on the following four parameters: patient age, total cholesterol, gamma-glutamyl transferase (GGT), and platelet count. Results The median age of the patients was 38.5 years [interquartile range (IQR): 21]. Among the study population, 59 (65.6%) were males and 31 (34.4%) were females; 26 patients showed reactivity for hepatitis B surface antigen (HBsAg), and 63 patients were found chronic with hepatitis C virus (HCV). The proportion of HCV was observed to be higher as compared with that of Hepatitis B virus (HBV). Nineteen patients were found to have jaundice and only one patient had ascites. An Area Under the Receiver Operating Curve (AUROC) was generated to determine the diagnostic accuracy of the Forns score. It was observed that the Forn score value of >7.110 had an AUROC of 0.9928 (95% CI: 0.9821-1.003, p-value

Background The gold standard screening method of hyperoxaluria in children is using 24-hour urine collection. Urine collection may be cumbersome and challenging for children. Reference intervals (RI) of oxalate for the Pakistani population are not readily available. Therefore we aimed to determine the oxalate to creatinine ratio (Ox: Cr) for Pakistani children 0.05). It was significantly different in group I to V which was 0.25 (IQR: 0.06), 0.19 (IQR: 0.11), 0.15 (IQR: 0.04), 0.11 (IQR: 0.06) and 0.08 (IQR: 0.04) respectively (pvalue, Highlights • Reference intervals (RI) of oxalate for the Pakistani population are not readily available. • Established RIs of Ox: Cr ratio was 0.05–0.34 (90% CI) in children under 6 years. • Ox: Cr ratio showed a declining trend with age.

Introduction Distinguishing between inflammatory bowel disease (IBD) and functional gastrointestinal disorders is a diagnostic challenge. The need for non-invasive biomarker as a diagnostic tool in the assessment of gastrointestinal symptoms is required. The objectives of current study were to determine the spectrum of clinical features in patients tested for fecal calprotectin presenting with high levels and to compare calprotectin levels among already diagnosed patients known to have IBD as per biopsy findings and documented on patients' file with newly presenting patients who were being investigated and did not have a diagnosis. Methods This retrospective cross-sectional study was conducted in the Department of Pathology and Laboratory Medicine and Department of Medicine, Aga Khan University, Karachi, Pakistan from January 2017 to December 2019. Subjects tested for fecal calprotectin who had elevated fecal calprotectin levels (n = 150) were included in the current study. Each patient deposited a random stool sample in an airtight container for calprotectin analysis. Biochemical analysis of calprotectin was performed by enzyme-linked immunosorbent assay using epitope calprotectin test kit (Epitope Diagnostics, Italy) on ETI-Max 3000 immunoassay analyzer (DiaSorin, Italy). A structured history form was used for data collection. Results: One hundred and fifty patients were available for inclusion in the final analysis. Majority of the patients (n = 117, 78%) were adults (>18 years of age), and 52.7% (n = 79) were females. Median fecal calprotectin (IQR) was 317.3 μg/g (549.10 - 239.2 μg/g) in children (n = 33) and 305 μg/g (609.9 - 201.6 μg/g) in adults; the difference was statistically non-significant (p value > 0.05). On categorization according to disease, fecal calprotectin levels were significantly elevated (p value = 0.033) in IBD patients compared to normal subjects, 644 μg/g (644 - 587.8 μg/g) vs 308.5 μg/g (505.4 - 233.8 μg/g), respectively. Diarrhea (n = 13, 38.4%), abdominal cramps (n = 12, 36.4%), and weight loss (n = 11, 33.3%) were the most common complaints noted in children with high fecal calprotectin levels, whereas in adults, abdominal cramps (n = 60, 51.3%), diarrhea (n = 59, 50.4%), and weight loss (n = 46, 39.3%) were the common complaints. The median fecal calprotectin levels in children already known to have IBD (n = 3) were higher than the levels noted in children with no diagnosis (n = 30); p value > 0.05. Similarly, median fecal calprotectin levels in adults with IBD (n = 28) were higher than the levels noted in patients with no specific diagnosis (n = 91), 400.7 μg/g (656.6 - 244.3 μg/g) vs 302.7 μg/g (564.6 - 206 μg/g); p value > 0.05. Conclusion Current study affirms that the fecal calprotectin test can be used in identifying IBD patients in all age groups.

Corona Virus Disease 2019 (COVID-19) pandemic is the defining global health crisis of our time. Compared with its neighbors China and Iran, which were rated as epi-centers of the outbreak, Pakistan has lower standards of health care, unstable economy and dearth of financial resources to tackle the outbreak. Like other institutes and industries in the country, clinical laboratories were succumbed to a variety of challenges. This article is based on the experience and adapted workflow measures from the Clinical Chemistry laboratory at the Aga Khan University Hospital (AKUH), Karachi, which serves as a national referral center with its widespread network of satellite laboratories and phlebotomy centers across the country. It highlights the challenges faced and the appropriate responses to ensure the provision of diagnostic facilities during the COVID-19 outbreak. Furthermore, the lessons acquired and necessary preparations for the post crisis situation are also incorporated., Highlights • Coronavirus disease (COVID-19) pandemic is the defining global health crisis of our time. • Like other institutes and industries in the country, clinical laboratories were succumbed to a variety of challenges. • The challenges the appropriate actions on ad hoc basis by a Clinical Chemistry laboratory, in Pakistan are emphasized. • The lessons acquired and necessary preparations for the post crisis situation are also discussed.

BackgroundThe principle of workplace based assessment (WBA) is to assess trainees at work with feedback integrated into the program simultaneously. A student driven WBA model was introduced and perception evaluation of this teaching method was done subsequently by taking feedback from the faculty as well as the postgraduate trainees (PGs) of a residency program.MethodsDescriptive multimethod study was conducted. A WBA program was designed for PGs in Chemical Pathology on Moodle and forms utilized were case-based discussion (CBD), direct observation of practical skills (DOPS) and evaluation of clinical events (ECE). Consented assessors and PGs were trained on WBA through a workshop. Pretest and posttest to assess PGs knowledge before and after WBA were conducted. Every time a WBA form was filled, perception of PGs and assessors towards WBA, time taken to conduct single WBA and feedback were recorded. Faculty and PGs qualitative feedback on perception of WBA was taken via interviews. WBA tools data and qualitative feedback were used to evaluate the acceptability and feasibility of the new tools.ResultsSix eligible PGs and seventeen assessors participated in this study. A total of 79 CBDs (assessorsn = 7 and PGsn = 6), 12 ECEs (assessors n = 6 and PGsn = 5), and 20 DOPS (assessors n = 6 and PGs n = 6) were documented. PGs average pretest score was 55.6%, which was improved to 96.4% in posttest;pvalueConclusionBoth assessors and fellows were satisfied with introduction and implementation of WBA. It gave the fellows opportunity to interact with assessors more often and learn from their rich experience. Gain in knowledge of PGs was identified from the statistically significant improvement in PGs’ assessment scores after WBA implementation.

Malnutrition in hospitalized patients, contributes to poor outcomes. Biomarker serum prealbumin, can prevent the complications by commencement of nutritional support to improve clinical outcomes. This study was designed to assess the association between low serum prealbumin level (18 mg/dl), with length of stay and all cause intensive care unit mortality.This cross-sectional study was conducted from July 2016 to July 2017 at Aga Khan University Hospital Karachi Pakistan. All consecutive patients, aged between 18 to 70 years, admitted in medical or surgical intensive care unit were included. Demographic, clinical history and blood samples for analysing serum prealbumin were obtained on first day of admission. Patients were categorized into two groups based on their serum prealbumin level (taking18 mg/dl as low).A total of 139 patients were included in this study; 95 (68.3%) were male. Median (Q3-Q1) prealbumin level of 12.3 mg/dl (18.8-8.7) was observed with low prealbumin level (18 mg/dl) in 100 (71.9%) patients. All-cause mortality was observed in 26 (26.0%) patients, mortality rate was significantly higher in patients with low prealbumin level (26.0% vs. 17.9%), p-value =0.31). Hospital and intensive care unit length of stay were statistically insignificantly different between the two groups with p-values of 0.27 and 0.44 respectively.We did not find association of low serum prealbumin with length of stay and mortality. Further research is warranted for the assessment of prealbumin as independent predictor of ICU mortality.

To assess the clinical and biochemical features as well as outcome of hyperphenylalaninemia patients.The descriptive retrospective study was conducted at the Aga Khan University Hospital, Karachi, and comprised data from January 2013 to February 2017 of plasma amino acid analysed at the Biochemical Genetic Laboratory of patients with phenylalanine levels120 umol/L. Medical charts of patients registered with the Metabolic Clinics were reviewed, while outside referrals were contacted by telephone to collect data on a pre-structured questionnaire. Data was analysed using SPSS 21.Of the 18 patients, 13(72%) were males. Overall median age was 606 days (interquartile range: 761) and median phenylalanine levels were 1280 (interquartile range: 935) umol/L. Phenylalanine hydroxylase deficiency was present in 5(28%) patients while 3(16.6%) had defects in the metabolism or regeneration of tetrahydrobiopterin. The most common clinical features was intellectual deficit and seizures 14(78%) each, followed by lighter hair colour 10(55.5%) and hypotonia 11(61%). High treatment cost was the leading reason for cessation of therapy in 7(39%) followed by refusal by patient's family 5(28%).Most hyperphenylalaninemia cases were diagnosed late when intellectual disability had already developed.

To determine the frequency of disorders leading to methylmalonic acidurias.This cross-sectional study was conducted from January 2013 to April 2016 at the Aga Khan University Hospital, Karachi, and comprised patients diagnosed with methylmalonic acidurias based on urine organic acid analysis. Clinical history and biochemical data was collected from the biochemical genetics laboratory requisition forms. Organic acid chromatograms of all the subjects were critically reviewed by a biochemical pathologist and a metabolic physician. For assessing the clinical outcome, medical charts of the patients were reviewed. SPSS 19 was used for data analysis.Of the 1,778 patients 50(2.81%) were detected with methylmalonic acidurias. After excluding patients with non-significant peaks of methylmalonic acidemia, 41(2.31%) were included in the final analysis. Of these, 20(48.7%) were females, while the overall median age was 11.5 months (interquartile range: 6-41.5). On stratification by type of disorders leading to methylmalonic acidurias, 9(22%) had methylmalonic acidemia, 12(29%) had Cobalamin-related remethylation disorders, nonspecific methylmalonic acidurias in 16(39%), while 2(5%) each had succinyl coenzyme A synthetase and Vitamin B12 deficiency. respectively.Screening tests, including urine organic acid, provided valuable clues to the aetiology of methylmalonic acidurias.

A cross-sectional survey was done at the Section of Chemical Pathology, Department of Pathology and Laboratory Medicine, AKUH, Karachi, to determine frequency of Zn deficiency, the second major micronutrient deficiency in developing countries, in subjects coming for investigations. Data of plasma Zn, from Jan 2013 to Dec 2014 was analyzed and deficiency was labeled at65ug/dl. Total 469 subjects were tested for plasma Zn levels over the period of 24 months and complete information was available for 422 subjects, included in final analysis. Median age of subjects was 13 yrs (IQR 7-35) and 57% were male. Mean plasma Zn levels of the total subjects were 105±42.6ug/dl. Out of the total subjects 13.5% (n=57) had Zn deficiency (mean plasma Zn 52±11 ug/dl), and most of them were of age group 6-16yrs. These findings advocate that diet of Pakistani children should be revised in order to provide sufficient amounts of Zn.

This article was migrated. The article was marked as recommended. IntroductionThe study investigated students' perception of introducing blended learning strategies to engage and motivate them towards lecture halls and Problem Based Learning (PBL) sessions for improving the quality of the overall students' learning experience.MethodsA prospective study was conducted at the Aga Khan University Medical College involving a total of one hundred four (104) year II medical students for the Endocrine and Reproduction module in the academic year 2018. This module ran for six weeks. Modifications in teaching methods were made for this module introduced after approval from Endocrine & Reproduction module, year II and curriculum committees. Written informed consent was obtained from facilitators and students. To assess the effectiveness of modifications introduced, students' feedback was taken on a Likert's scale of 1-5, at the end of the module. Data were analyzed by SPSS version 20.ResultsTotal 94 (90%) students participated in the written feedback. Forty percent medical students (n=38) responded that videos were useful, 54% (n=51) acknowledged that post-PBL activities like crossword puzzles and Kahoot games, created significant discussions amongst students in a fun yet intellectual manner. Seventy percent of students (n=66) agreed that access to Kahoot was easy and no connectivity issues were faced. Twenty percent students (n=20) endorsed that flipped lectures enhanced understanding of topics, 87% students (n=82) felt that recorded lecture was very helpful and flash cards were found helpful by 14% students (n=12).ConclusionStudent engagement is an important issue in medical schools in this era. Results showed that blended learning and educational activities enhanced students' learning motivation and interest.

To assess the utility of HOMA-IR in assessing insulin resistance in patients with polycystic ovary syndrome (PCOS) and compare it with fasting insulin for assessing insulin resistance (IR).Observational study.Section of Clinical Chemistry, Department of Pathology and Laboratory Medicine, The Aga Khan University Hospital, Karachi, from January 2009 to September 2012.Medical chart review of all women diagnosed with PCOS was performed. Of the 400 PCOS women reviewed, 91 met the inclusion criteria. Insulin resistance was assessed by calculating HOMA-IR using the formula (fasting glucose x fasting insulin)/405, taking normal value2 in adults and hyperinsulinemia based on fasting insulin levels ≥12 µIU/ml.A total of 91 premenopausal women diagnosed with PCOS were included. Mean age was 30 ±5.5 years. Mean HOMA-IR of women was 3.1 ±1.7, respectively with IR in 69% (n=63) women, while hyperinsulinemia was present in 60% (n=55) women (fasting Insulin 18.5 ±5.8 µIU/ml). Hyperandrogenism was present in 53.8% (n=49), whereas 38.5% (n=35) women had primary infertility or subfertility, while 65.9% (n=60) had menstrual irregularities; and higher frequencies were observed in women with IR. Eight subjects with IR and endocrine abnormalities were missed by fasting insulin.Insulin resistance is common in PCOS and it is likely a pathogenic factor for development of PCOS. HOMAIR model performed better than hyperinsulinemia alone for diagnosing IR.

To evaluate the frequency of subclinical lead toxicity.Cross-sectional study.Department of Pathology and Laboratory Medicine, The Aga Khan University Hospital, Karachi, from January 2011 to December 2014.Analysis of laboratory data for blood lead levels (BLL) was performed. Lead was tested by atomic absorption spectrometer. For all subjects, only initial test results were included while the results of repeated testing were excluded. Exemption was sought from institutional ethical review committee. BLL of 2-10 ug/dl and 10-70 ug/dl in children and adults, respectively were taken as subclinical lead toxicity.Amongst the total number of subjects tested (n=524), 26.5% (n=139) were children (16 years) while rest were adults. Overall median BLLs was 6.4 ug/dl (20.9-3.1). The median BLL was 4 ug/dl (6.7-2.6) in children and 8.3 ug/dl (27.9-3.4) in adults, respectively. The BLL increased with age; higher levels were observed in age range 21-30 years of subjects [median lead level 16.9 ug/dl (36.1-4)] and lower level [4.2 ug/dl (6.8-2.6)] in children with10 years of age. Only 16% (n=22) children had desirable lead levels while most had either subclinical (76%, n=106) or toxic lead levels (8%, n=11). In adults, (55%, n=212) subjects had desired lead levels, and 40% (n=154) and 4.99% (n=19) had subclinical and toxic lead levels.Presence of subclinical lead poisoning even after phasing out of lead petroleum in Pakistanis is alarming, especially in children. A national population-based study to determine the lead status and targeted intervention to identify potential sources is need of the time.