Insights from semi-structured interviews on integrating artificial intelligence in clinical chemistry laboratory practices.

BACKGROUND: Artificial intelligence (AI) is gradually transforming the practises of healthcare providers. Over the last two decades, the advent of AI into numerous aspects of pathology has opened transformative possibilities in how we practise laboratory medicine. Objectives of this study were to explore how AI could impact the clinical practices of professionals working in Clinical Chemistry laboratories, while also identifying effective strategies in medical education to facilitate the required changes. METHODS: From March to August 2022, an exploratory qualitative study was conducted at the Section of Clinical Chemistry, Department of Pathology and Laboratory Medicine, Aga Khan University, Karachi, Pakistan, in collaboration with Keele University, Newcastle, United Kingdom. Semi-structured interviews were conducted to collect information from diverse group of professionals working in Clinical Chemistry laboratories. All interviews were audio recorded and transcribed verbatim. They were asked what changes AI would involve in the laboratory, what resources would be necessary, and how medical education would assist them in adapting to the change. A content analysis was conducted, resulting in the development of codes and themes based on the analyzed data. RESULTS: The interviews were analysed to identify three primary themes: perspectives and considerations for AI adoption, educational and curriculum adjustments, and implementation techniques. Although the use of diagnostic algorithms is currently limited in Pakistani Clinical Chemistry laboratories, the application of AI is expanding. All thirteen participants stated their reasons for being hesitant to use AI. Participants stressed the importance of critical aspects for effective AI deployment, the need of a collaborative integrative approach, and the need for constant horizon scanning to keep up with AI developments. CONCLUSIONS: Three primary themes related to AI adoption were identified: perspectives and considerations, educational and curriculum adjustments, and implementation techniques. The study's findings give a sound foundation for making suggestions to clinical laboratories, scientific bodies, and national and international Clinical Chemistry and laboratory medicine organisations on how to manage pathologists' shifting practises because of AI.

Developing and piloting an online course on osteoporosis using a multidisciplinary multi-institute approach- a cross-sectional qualitative study.

INTRODUCTION: Postgraduate medical trainees (PGs) in developing nations face various educational hurdles due to limited access to quality resources and training facilities. This study aimed to assess the effectiveness of e-learning, particularly Massive Open Online Courses (MOOCs), within postgraduate medical education. It involved the development of a customized online course focused on osteoporosis for PGs and an examination of their perspectives and preferences concerning online learning methods like Virtual Learning Environment (VLE) platforms. METHODS: The study was conducted from January 2018 to December 2020. A multi-institutional, multidisciplinary team was assembled to design an osteoporosis course on the VLE platform. PGs (n = 9) from diverse disciplines and institutions were selected with informed consent. Focus group discussions (FGDs) among these PGs identified their preferences for the online course, which subsequently guided the development of the MOOC. The modular MOOC comprised recorded micro-lectures, flashcards, videos, case challenges, and expert interviews. The educational impact of the VLE was assessed using pre- and post-module tests among the participants, and their perceptions of the PGs and course facilitators were gathered via an online survey. RESULTS: The study identified the involvement of PGs in the course design process as beneficial, as it allowed for content customization and boosted their motivation for peer-to-peer learning. During the FGDs, PGs expressed a strong preference for flexible learning formats, particularly short downloadable presentations, and micro-lectures. They also identified challenges related to technology, institutional support, and internet connectivity. In the subsequently customized MOOC course, 66% of PGs (n = 6) attempted the pre-test, achieving a mean score of 43.8%. Following the VLE module, all PGs (n = 9) successfully passed the end-of-module test, averaging a score of 96%, highlighting its impact on learning. The majority (n = 8, 88.9%) agreed that the course content could be applied in clinical practice, and 66.7% (n = 6) expressed extreme satisfaction with the learning objectives and content. Participants favoured end-of-module assessments and the use of best-choice questions for evaluation. CONCLUSION: This study highlights the importance of virtual learning, particularly MOOCs, in addressing the educational challenges faced by developing nations. It emphasizes the need for tailored online courses that cater to the preferences and requirements of PGs. The findings suggest that MOOCs can foster collaboration, networking, and opportunities for professional development, and interdisciplinary collaboration among faculty members can be a key strength in course development. This research provides valuable insights for educators, institutions, and e-learning developers seeking to enhance their teaching methodologies and establish accessible educational environments in the digital age.

Enhancing specimen collection skills for dried blood spots through an immersive virtual learning environment: a cross-sectional study.

OBJECTIVE: The quality of dried blood spot (DBS) specimens impacts newborn screening (NBS) results, hence proper training is crucial for DBS specimen collection. To address this, a training module for Allied Health Professionals (AHPs) and nurses was created on Moodle, a virtual learning environment (VLE). The purpose of this research was to determine the feasibility and effectiveness of this module. METHODOLOGY: Participants were trained on-site (March to December 2019), through online training sessions (January to June 2020), and the two training strategies were compared. Data analysis included the total number of participants, cost-effectiveness, trainer engagement, and the number of unacceptable samples collected by nurses/AHPs trained by the two strategies. RESULTS: A total of 55 nurses/AHPs were trained on-site, while 79 nurses/AHPs completed the online module and received certificates through online VLE-based training. The trainer engagement and cost were more for onsite training. After online training, the specimen rejection rate was reduced from 0.84% (44 rejected out of 5220 total specimens collected) to 0.38% (15/3920). CONCLUSIONS: This study shows that using VLE-based DBS specimen collection training is feasible and effective for training nurses and AHPs.

Sequence variants in the BTD underlying biotinidase deficiency in families of Pakistani origin.

BACKGROUND: Biotinidase deficiency (BTD) is a rare autosomal recessive metabolic disease, which develops neurological symptoms because of the impaired biotin recycling. Pathogenic mutations on BTD gene cause BTD deficiency. The clinical features and mutation analysis of Pakistani children with BTD deficiency have rarely been described. Herein, for the first time, we report the clinical features, BTD gene mutations and biochemical analysis of seven symptomatic children with BTD deficiency from Pakistan. METHODS: Seven suspected BTD-deficient patients who presented abnormal organic acid profiles and clinical features were subjected to Sanger sequencing to identify pathogenic mutations in the BTD gene. The results were analyzed by Mutation Surveyor Software. RESULTS: All seven patients exhibited common biotinidase deficiency symptoms including hypotonia, developmental delay and seizures. Biochemical analysis shows marked excretion of 3-hydroxy isovalerate in all cases, followed by 3-hydroxy propionate and methyl citrate. Sanger sequencing revealed one frame-shift mutation, c.98_104delinsTCC (p.Cys33Phefs), and two missense mutations, c.1612C>A (p.Arg538Ser) and c.1330G>C (p.Asp444His). All mutations were in the homozygous state and classified as pathogenic in published studies and mutation databases. CONCLUSIONS: This study has validated the BTD variants as the underlying cause of biotinidase deficiency in which molecular testing of BTD is supported by urinary organic acid analysis and clinical diagnosis. Secondly, the strength of the local availability of this test in Pakistan will paved the way for the neonatal screening of biotinidase deficiency.

Emphasising the Need for a National Fragility Fracture Network for Pakistan (FFN-Pak).

Null.

Assessing the knowledge, attitude and practice of osteoporosis among Pakistani women: A national social-media based survey.

BACKGROUND: There are numerous risk factors for osteoporosis and understanding and recognizing these risk factors is critical when deciding whether to take preventive measures. It is critical to reduce the healthcare expenditure burden of the Pakistani population by raising awareness and implementing osteoporosis-preventable measures. This survey aims to assess the knowledge, attitudes, and practices (KAP) of Pakistani women as well as their misconceptions about osteoporosis. METHODS: A cross-sectional survey was conducted from August 2021 to January 2022 by the Bone & Mineral Disease research group at Section of Chemical Pathology, Department of Pathology and Laboratory Medicine, Aga Khan University, Karachi, with exemption from the ethical review committee. Using snowball sampling, a validated Osteoporosis Prevention and Awareness Tool (OPAAT) was disseminated online via social media. With informed consent, 400 Pakistani women aged ≥ 18 years were included in the study. SPSS Statistics version 25.0 was used for data analysis. Chi-square test for association and Fisher-exact test were applied, and significance level was α<0.05. RESULTS: Based on the OPAAT scores of all (n = 400) participants, 22% (n = 88) had low knowledge, 44% (n = 176) had average knowledge, while 34% (n = 136) had good knowledge of osteoporosis. The most common misconceptions were about age-related risk, presentation of symptoms, radiation risk, associated risk factors like tooth loss, osteoarthritis, and knowledge about predictors of bone health. CONCLUSION: Adult Pakistani women have a fair understanding of osteoporosis, but the OPAAT tool clarifies some common misconceptions. There is a need to develop educational strategies to increase the knowledge of osteoporosis among Pakistani adults and to promote a bone-healthy lifestyle.

Factors Associated With Awareness Of Literate Mothers About Newborn Screening: A Cross-Sectional Study From A Low-Middle-Income Country.

Objectives: To explore the awarenesslevel of literate mothersregarding newborn screening programmes, and to evaluate the associated factors. METHODS: The descriptive, cross-sectional study was conducted at the Section of Chemical Pathology, Department of Pathology andLaboratoryMedicine,AgaKhanUniversity,Karachi,fromJanuary toSeptember 2021, andcomprisedmothers aged 18 years or more. Data was collected using a structured questionnaire about newborn screening, and the subjects were compared in terms of age, residential background, education and parity. Data was analysed using SPSS 23. RESULTS: Of the 1016 responses, 896(88.2%) were analysed. The mean age of the sample was 37.7±10.87 years. There were 470(52.4%) mothers aged 31-45 years, 859(95.87%) were from urban areas, 751(84%) had a graduate degree, 652(72.7%) weremultiparous andhad824(91.9%)hadhealthy children.Overall, 386 (43%)mothershadawarenessofnewbornscreening programmes. The main factors associated with awareness were age, education, primiparity, having healthy children, and province ofresidencebeing Sindh andPunjab(p<0.05),while the urban-ruraldividedwas not a significantfactor(p=0.737). Cost of healthcare 417(46.5%) and lack of awareness among physicians 356(39.7%) were identified asthe main challenges in establishing newborn screening servicesin the country. CONCLUSIONS: The awareness among mothers about new born screening programmes was generally low among the subjects studied.

A framework for implementing best laboratory practices for non-integrated point of care tests in low resource settings.

The method we respond to pandemics is still inadequate for dealing with the point of care testing (POCT) requirements of the next large epidemic. The proposed framework highlights the importance of having defined policies and procedures in place for non-integrated POCT to protect patient safety. In the absence of a pathology laboratory, this paradigm may help in the supply of diagnostic services to low-resource centers. A review of the literature was used to construct this POCT framework for non-integrated and/or unconnected devices. It also sought professional advice from the Chemical Pathology faculty, quality assurance laboratory experts and international POCT experts from the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC). Our concept presents a comprehensive integrated and networked approach to POCT with direct and indirect clinical laboratory supervision, particularly for outpatient and inpatient care in low-resource health care settings.

Interleukin-6 (IL-6) as a Predictor of Clinical Outcomes in Patients with COVID-19.

BACKGROUND: Interleukin-6 (IL-6) has been known to be involved in immune regulation, inflammatory response, and metabolism. It is also recognized as the major cause to underscore the pathology of severe COVID-19 patients. However, it remains to be seen if IL-6 is superior to other inflammatory biomarkers in ascertaining clinical severity and mortality rate for COVID-19. This study aimed to determine the value of IL-6 as a predictor of severity and mortality in COVID-19 patients and compare it with other pro-inflammatory biomarkers in the South Asian region. METHODS: An observational study was conducted, including all adult SARS-CoV-2 patients who had undergone IL-6 testing from December 2020 to June 2021. The patients' medical records were reviewed to collect demographic, clinical, and biochemical data. Other pro-inflammatory biomarkers apart from IL-6 included Neutrophils to Lymphocyte Ratio (NLR), D-dimer, C-reactive protein (CRP), ferritin, lactate dehydrogenase (LDH), and procal-citonin for analysis. SPSS version 22.0 was utilized. RESULTS: Out of the 393 patients who underwent IL-6 testing, 203 were included in the final analysis with a mean (SD) age of 61.9 years (12.9) and 70.9% (n = 144) were male. Fifty-six percent (n = 115) subjects had critical disease. IL-6 levels were elevated (> 7 pg/mL) in 160 (78.8%) patients. Levels of IL-6 significantly correlated with age, NLR, D-dimer, CRP, ferritin, LDH, length of stay, clinical severity, and mortality. All the inflammatory markers were significantly increased in critically ill and expired patients (p < 0.05). The receiver operator curve showed that IL-6 had the best area under the curve (0.898) compared to other pro-inflammatory biomarkers for mortality with comparable results for clinical severity. CONCLUSIONS: Study findings show that though IL-6 is an effective marker of inflammation and can be helpful for clinicians in recognizing patients with severe COVID-19. However, we still need further studies with larger sample size.

GRADE-ADOLOPMENT of clinical practice guideline for postmenopausal osteoporosis management-a Pakistani context.

Due to its high prevalence, we aimed to create postmenopausal osteoporosis clinical practice guideline via GRADE-ADOLOPMENT for Pakistan. We recommend a higher dose (2000-4000 IU) of vitamin D for osteoporotic patients who are old, have malabsorption, or are obese. The guideline will help standardize care provision and improve health care outcomes for osteoporosis. PURPOSE: Postmenopausal osteoporosis affects one in every five postmenopausal women in Pakistan. An evidence-based clinical practice guideline (CPG) is needed to standardize care provision to optimize health outcomes. Hence, we aimed to develop CPG for the management of postmenopausal osteoporosis in Pakistan. METHODS: The GRADE-ADOLOPMENT process was used to adopt (as is or with minor changes), exclude (omit), or adapt (modify based on local context) recommendations to the source guideline (SG)-clinical practice guidelines for the diagnosis and treatment of postmenopausal osteoporosis-2020 update from American Association of Clinical Endocrinology (AACE). RESULTS: The SG was "adoloped" to cater to the local context. The SG consisted of 51 recommendations. Forty-five recommendations were adopted as is. Due to unavailability of drugs, 4 recommendations were adopted with minor changes, and one was excluded, while one recommendation was adopted with the inclusion of use of a surrogate FRAX tool specific for Pakistan. One recommendation regarding vitamin D dosage was adapted to recommend a dose of 2000-4000 IU of vitamin D in patients with obesity, malabsorption, and old age. CONCLUSION: The developed Pakistani postmenopausal osteoporosis guideline consists of 50 recommendations. The guideline created recommends a higher dose (2000-4000 IU) of vitamin D for patients who are old, have malabsorption, or are obese, which is an adaptation from the SG by the AACE. This higher dose is justified as lower doses prove to be suboptimal in these groups and should be complemented with baseline vitamin D and calcium levels.

GRADE-ADOLOPMENT of clinical practice guideline for postmenopausal osteoporosis management-a Pakistani context

Due to its high prevalence, we aimed to create postmenopausal osteoporosis clinical practice guideline via GRADE-ADOLOPMENT for Pakistan. We recommend a higher dose (2000-4000 IU) of vitamin D for osteoporotic patients who are old, have malabsorption, or are obese. The guideline will help standardize care provision and improve health care outcomes for osteoporosis.Postmenopausal osteoporosis affects one in every five postmenopausal women in Pakistan. An evidence-based clinical practice guideline (CPG) is needed to standardize care provision to optimize health outcomes. Hence, we aimed to develop CPG for the management of postmenopausal osteoporosis in Pakistan.The GRADE-ADOLOPMENT process was used to adopt (as is or with minor changes), exclude (omit), or adapt (modify based on local context) recommendations to the source guideline (SG)-clinical practice guidelines for the diagnosis and treatment of postmenopausal osteoporosis-2020 update from American Association of Clinical Endocrinology (AACE). The SG was "adoloped" to cater to the local context. The SG consisted of 51 recommendations. Forty-five recommendations were adopted as is. Due to unavailability of drugs, 4 recommendations were adopted with minor changes, and one was excluded, while one recommendation was adopted with the inclusion of use of a surrogate FRAX tool specific for Pakistan. One recommendation regarding vitamin D dosage was adapted to recommend a dose of 2000-4000 IU of vitamin D in patients with obesity, malabsorption, and old age. The developed Pakistani postmenopausal osteoporosis guideline consists of 50 recommendations. The guideline created recommends a higher dose (2000-4000 IU) of vitamin D for patients who are old, have malabsorption, or are obese, which is an adaptation from the SG by the AACE. This higher dose is justified as lower doses prove to be suboptimal in these groups and should be complemented with baseline vitamin D and calcium levels.

Inappropriate supplementation of Vitamin D can result in toxicity: a crosssectional study of paediatrics population.

OBJECTIVE: To evaluate children with suspected or definite hypervitaminosis D with respect to prevalence, clinical manifestations and pharmacological aspects. METHODS: 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 <18 years with 25-hydroxyvitamin D levels >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.

Metabolomics of a neonatal cohort from the Alliance for Maternal and Newborn Health Improvement biorepository: Effect of preanalytical variables on reference intervals.

BACKGROUND: The study was conducted to determine reference interval (RI) and evaluate the effect of preanalytical variables on Dried blood spot (DBS)-amino acids, acylcarnitines and succinylacetone of neonates. METHODOLOGY: DBS samples were collected within 48-72 hours of life. Samples were analyzed for biochemical markers on tandem mass spectrometer at the University of Iowa. Comparison of RI across various categorical variables were performed. RESULTS: A total of 610 reference samples were selected based on exclusion criteria; 53.2% being females. Mean gestational age (GA) of mothers at the time of delivery was 38.7±1.6 weeks; 24.5% neonates were of low birth weight and 14.3% were preterm. Out of the total 610 neonates, 23.1% were small for GA. Reference intervals were generated for eleven amino acids, thirty-two acylcarnitines and succinylacetone concentrations. Markers were evaluated with respect to the influence of gender, GA, weight and time of sampling and statistically significant minimal differences were observed for some biomarkers. CONCLUSION: RI for amino acids, succinylacetone and acylcarnitine on DBS has been established for healthy neonates, which could be of use in the clinical practice. Clinically significant effect of GA, weight, gender and time of sampling on these markers were not identified.

Assessing Third-Year Medical Students' Perspective on Point of Care Testing Boot Camp: From Bench to Bedside.

Background: 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. Objectives: 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. Methodology: 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. Results: 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. Conclusion: 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.

Utilizing augmented artificial intelligence for aminoacidopathies using collaborative laboratory integrated reporting- A cross-sectional study.

Introduction: 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). Methods: 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 laboratory. Data was divided into reference and case data files after interpretation by a team of pathologists and technologists. All PAA samples were analyzed using ion-exchange high-performance chromatography. The CLIR application of Amino Acid in Plasma (AAQP) was used for statistical analysis for both data sets and post-analytical interpretive tools using a single condition tool was applied. Result: The 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. Conclusion: An agreement of >95% 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.

Reference Intervals of Serum TSH from Mixed Distributions Using Truncation Points and the Kolmogorov-Smirnov Distance.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Spectrum of Cystic Fibrosis Conductance Regulator Gene Mutations Reported in Pakistani Descent Cystic Fibrosis Patients.

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.

Publication dynamics: what can be done to eliminate barriers to publishing full manuscripts by the postgraduate trainees of a low-middle income country?

OBJECTIVES: This study aimed to determine the publication rate of free paper abstracts presented by the postgraduate (PG) trainees and determine the reasons for non-publication. A mixed methods study was conducted. PG trainees presenting free papers at the at the Pakistan Society of Chemical Pathologist conferences from 2012 to 2018 were included. Three databases were searched to identify if the abstracts were published or not. The PG trainee authors of abstracts not published as full manuscript, were surveyed to determine the barriers and challenges in publishing a manuscript. RESULTS: The average rate of full manuscript publication was 51.8% (n = 93/177) for the abstracts presented by the PG trainees. Publication rate was higher for oral (n = 73/119, 61.3%) compared to poster presentation (n = 20/58, 34.5%). Most of the manuscripts were published after two years of abstract presentation. The survey showed that the main challenges to publishing an abstract were lack of time, limited scientific writing or submission skills, lack of funding for publication fee, and negative or statistically non-significant results. This reflects a need to arrange workshops/symposia for the PG trainees of low-middle income country (LMIC) to enhance their writing and time management skills and improve the full manuscript publication rate from LMICs.

Disease activity correlates and functionality in patients with rheumatoid arthritis - real-world experience from a South Asian country.

Introduction: There is a lack of data assessing disease activity in patients with rheumatoid arthritis from Pakistan. We sought to determine the correlation between Disease Activity Score 28 (DAS28) and disease activity parameters and the modified Health Assessment Questionnaire (mHAQ). Secondarily, we evaluated the concordance of acute phase reactants with disease activity. Material and methods: We prospectively studied 132 patients with rheumatoid arthritis (RA) as per the 2010 American College of Rheumatology/European League Against Rheumatism criteria, not in clinical remission. Based on the DAS28 score, the patients were divided into low, moderate, and high activity groups. The patients were also categorized according to the elevation of acute phase reactants to determine concordance and discordance with DAS28-ESR and DAS28-CRP. Descriptive statistics and Pearson's correlation were computed. Results: Complete demographics was available for 132 participants. The mean age was 46.2 ±12.8 years; there were 85.6% (n = 113) females. The mean disease duration was 5.7 ±6.4 years. The (Rephrase as mean ±SD) DAS28 and mHAQ scores were 3.4 ±1.8 and 0.77 ±0.68, respectively. A significant correlation was observed between DAS28 and tender and swollen joint count (r = 0.64; p < 0.001); DAS28 and mHAQ (r = 0.47; p-value < 0.001), DAS28 and patient's global assessment (PGA) (r = 0.45; p-value < 0.001). A weak correlation was observed between mHAQ and CRP and ESR, with r = 0.242 and 0.225, respectively, p-value < 0.001. In comparison, no correlation of DAS28 with the rheumatoid factor (r = -0.035) or ACPA antibody (r = -0.094) was noted. A positive concordance between ESR and CRP was observed in severely active RA. Conclusions: From an outpatient setting in a South Asian country, DAS28-ESR emerged as the preferred choice for an accurate assessment of disease severity in RA when combined with the mHAQ. Acute phase reactants increase positively in concordance with severely active RA, although discordant in low to moderately active disease.

Biotin-responsive Multiple Carboxylase Deficiency (MCD).

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.