Response to Single Agent Cyclosporin in Patients with Non-Severe Aplastic Anaemia.

OBJECTIVE: To determine the effectiveness of cyclosporin A (CSA) monotherapy in treating patients with non-severe aplastic anaemia (NSAA). STUDY DESIGN: A cross-sectional observational study. Place and Duration of the Study: Department of Clinical Haematology, Armed Forces Bone Marrow Transplant Center, Rawalpindi, Pakistan, from January 2022 till December 2023. METHODOLOGY: A total of 51 patients of NSAA, classified as aplastic anaemia not satisfying criteria for severe and very severe disease as per Modified Camitta Criteria, were included. Results were evaluated in terms of survival rate (OS) and responses. Responses were assessed as complete response (CR), partial response (PR), overall response (ORR), and no response (NR) by using standard British Committee for standard Haematology (BCSH) response criteria at 3, 6, and 12 months. RESULTS: Out of 51 patients, 34 (67%) were males and 17 (33%) were females. Median age at the time of diagnosis was 25 (IQR 26) years. At follow-up of 12 months, OS was 86.3%. Overall response rates to cyclosporin monotherapy at 3, 6, and 12 months were 49%, 57%, and 59%, respectively. Baseline haemoglobin was associated with responses at 6 and 12 months and a significant association was found between transfusion dependency at 3, 6, and 12 months with overall survival (p = 0.01, 0.005, and 0.04, respectively). Responses at time-defined points also had significant impact on OS (3 months Plog-rank = 0.046, 6 months Plog-rank = 0.01, and 12 months Plog-rank = 0.008). CONCLUSION: Overall response rates at 3, 6, and 12 months indicate the potential of CSA as a viable treatment option, particularly in resource-constrained settings. Despite some patients experiencing treatment-related complications, CSA demonstrated a generally tolerable safety profile. KEY WORDS: Cyclosporin A, Non-severe aplastic anaemia, Survival rate, Response rate, Complete response, Partial response.

Diagnostic Accuracy of Polymerase Chain Reaction Against Giemsa Staining on Tissue Biopsy for Cutaneous Leishmaniasis.

OBJECTIVE: To evaluate the diagnostic accuracy of a commercial real-time polymerase chain reaction (PCR) kit targeting 18S rRNA against Giemsa-stained tissue slides in patients clinically suspected of cutaneous leishmaniasis (CL). STUDY DESIGN: Cross-sectional analytical study. Place and Duration of the Study: Department of Microbiology, Armed Forces Institute of Pathology / National University of Medical Sciences, Rawalpindi, Pakistan, from July to December 2022. METHODOLOGY: Samples of skin tissue in 98 patients suspected of CL were evaluated. These samples were subjected to Giemsa-staining for microscopy and real-time PCR. Sensitivity, specificity, and accuracy of the PCR were calculated keeping Giemsa-stained tissue slide microscopy as gold standard. RESULTS: Out of the 98 tissue samples, 37 were found positive for leishmaniasis on PCR while 13 were found Leishmania positive on microscopy of Giemsa-stained slides. The sensitivity, specificity, and accuracy of the PCR for the detection of Leishmania species were 100%, 71.8%, and 91.8%, respectively with 100% negative predictive value. CONCLUSION: This study demonstrates that the commercial PCR is a reliable diagnostic test for the diagnosis of CL. The ease, rapidity, and reliability of the PCR make it a dependable tool in diagnostic repertoire of CL. KEY WORDS: Giemsa stain, Leishmania spp., Polymerase chain reaction, Viasure.

Early Detection of Vascular Obstruction in Microvascular Flaps using Thermographic Camera.

OBJECTIVE: To evaluate the early detection of vascular obstruction in microvascular flaps using a thermographic camera. STUDY DESIGN: A cross-sectional study. Place and Duration of the Study: Department of Plastic Surgery, Jinnah Burn and Reconstructive Surgery Centre, Lahore, Pakistan, from July to December 2023. METHODOLOGY: Microvascular flaps with cutaneous islands were monitored postoperatively with a thermographic camera in addition to conventional clinical methods. The decision to re-explore was based on conventional methods, and confirmation was achieved through intraoperative findings of vascular obstruction during re-exploration. RESULTS: Thirty-one patients who underwent microvascular surgery were monitored postoperatively with a thermographic camera. There were 20 (64.5%) anterolateral thigh flaps, 4 (12.9%) radial forearm flaps, 3 (9.7%) scapular-parascapular flaps, 1 (3.2%) medial plantar flap, 1 (3.2%) myocutaneous gracilis flap, 1 (3.2%) latissimus dorsi (LD) flap, and 1 (3.2%) chimeric adductor longus and gracilis flap. Three (9.7%) flaps developed postoperative vascular obstruction. The thermographic camera detected complications two to four hours earlier than conventional methods, with a statistically significant difference (p >0.109). CONCLUSION: A thermographic camera is a valuable, non-invasive, and simple tool for monitoring microvascular flaps. It can detect complications several hours earlier and has the potential to be a practice-changing modality. KEY WORDS: Microvascular flaps, Thermographic camera, Vascular obstruction.

Comparison Between Pregabalin and Sertraline for Treatment of Uraemic Pruritus in Patients on Maintenance Haemodialysis: A Single-Centric Study.

OBJECTIVE: To compare oral pregabalin with oral sertraline for treatment of uraemic pruritus. STUDY DESIGN: Randomised controlled trial. Place and Duration of the Study: Department of Nephrology, Pak Emirates Military Hospital Rawalpindi, Pakistan, from October 2023 to January 2024. METHODOLOGY: Patients with end-stage renal disease having pruritus for at least 6 weeks were included. Exclusion criteria comprised other dermatological or systemic diseases associated with pruritus, mental health issues, thrice-a-week haemodialysis schedule, and use of other treatments for uraemic pruritus. They were randomised to receive either pregabalin 75mg daily or sertraline 50mg daily for six weeks using computer-generated sequences. The Urdu version of the 5-D Itch scale was used to document the severity of pruritus at the baseline and at the end of therapy. Side effects to the treatment were also monitored. RESULTS: There were 8 (16.67%) females and 40 (83.33%) males, with a mean age of 52.19 ± 12.19 years. The baseline 5-D Itch scale scores were equal in both groups. Mean improvement in 5-D Itch scale scores was 3.75 ± 1.26 and 2.08 ± 1.18 with pregabalin and sertraline, respectively (p <0.001). Side effects were reported by 2 (8.33%) patients on pregabalin and none using sertraline (p = 0.489). CONCLUSION: Pregabalin was found to be more effective than sertraline in treating uraemic pruritus, though with a statistically insignificant trend towards a higher frequency of side effects. KEY WORDS: Chronic renal failure, Pruritus, Renal dialysis, Selective serotonin reuptake inhibitors, Uraemia.

Impact of Teaching Methods on Clinical Reasoning in Forensic Medicine: A Quasi-Experimental Study.

OBJECTIVE: To compare the effectiveness of flipped classroom and video-assisted learning techniques with didactic lectures in promoting clinical reasoning skills in Forensic Medicine. STUDY DESIGN: Quasi-experimental study. Place and Duration of the Study: Department of Forensic Medicine, Dow International Medical College and Dow University of Health Sciences, Karachi, Pakistan, from May to October 2023. METHODOLOGY: The study included 114 third-year medical students divided into three predefined tutorial groups. Over four weeks, within the Forensic Medicine respiratory module, each group was taught one topic per week using a distinct teaching strategy: Traditional lectures (TL) for the first group, flipped classroom (FC) method for the second group, and video-assisted teaching (VAT) for the third group. Students' learning achievements and clinical reasoning skills were assessed through a pre-test, post-test, and revision post-test. RESULTS: Pre-test scores showed no significant differences among the groups (p = 0.655). However, post-test scores differed significantly (F2:111 = 11.93, p <0.001). Tukiye's test indicated that the mean score for the FC group was significantly different from the TL group (p = 0.003) and the VAT group (p <0.001), but there was no significant difference between the TL and VAT groups (p = 0.422). The revision post-test indicated a significant decrease in mean scores across all groups, regardless of the instructional approach (p <0.001). CONCLUSION: The FC approach for teaching clinical reasoning in Forensic Medicine shows promising results, effectively improving student performance and learning experience. KEY WORDS: Flipped classroom, Video-assisted teaching, Clinical reasoning, Forensic Medicine teaching.

Frequency of Phenotypes and their Clinical and Hormonal Characteristics of Polycystic Ovarian Syndrome.

OBJECTIVE: To determine the frequency of phenotypes of polycystic ovarian syndrome (PCOS) in patients presenting with sub-fertility, and to compare the clinical and hormonal characteristics among them. STUDY DESIGN: Descriptive cross-sectional study. Place and Duration of the Study: Department of Obstetrics and Gynaecology, Forest View Specialist Clinic, Peshawar, Pakistan, from August 2022 to January 2023. METHODOLOGY: The study included 662 female patients presenting with menstrual irregularities, hyperandrogenism, and infertility to the clinic. PCOS was diagnosed on the basis of the Rotterdam criterion and clinical features and classified into different phenotypes on the basis of the National Institute of Health (NIH) panel criteria. Data were entered and analysed by IBM SPSS VERSION 23.0. The frequency of four phenotypes was calculated and phenotypes were compared for age, weight, hormonal profiles, and history of miscarriages. A p <0.05 was considered statistically significant. RESULTS: Frequency of PCOS in patients with infertility was 59.76%. Phenotype A was seen in 58.2%, phenotype D in 23.3%, phenotype C in 16.9%, and phenotype B in 1.7% of cases. The LH/FSH ratio was statistically significant in phenotype A as compared to other phenotypes, while other parameters were non-significant. CONCLUSION: The frequency of PCOS is high in patients with infertility. Phenotype A is the most common variant and is associated with significant impairment of the LH/FSH ratio. KEY WORDS: Polycystic ovarian syndrome, Subfertility, Phenotypes of PCOS, Hyperandrogenism, Anovulation, R-C1.

Metabolomics in Pakistan: A Comprehensive Analysis of Availability, Practices, and Challenges in Clinical Laboratories.

OBJECTIVE: To comprehensively analyse the current state of metabolomics in clinical laboratories across Pakistan. STUDY DESIGN: Cross-sectional survey. Place and Duration of the Study: Section of Chemical Pathology, Department of Pathology and Laboratory Medicine, The Aga Khan University, Karachi, Pakistan, from June to November 2022. METHODOLOGY: This survey assessed metabolomics availability, computational methods, and resources in Pakistani clinical laboratories. The survey questionnaire was distributed within the chemical pathology community via Google Forms, and responses were garnered from 44 chemical pathologists across 17 laboratories in 10 cities. RESULTS: Among respondents, 11 had formal metabolomics training, with three having less than 1 year, five more than 1 year, and 33 lacking any experience. Primary clinical applications included inherited metabolic disorders, bio-informatics, microbiology, therapeutic drug monitoring, toxicology, and nutritional and environmental science. Thirty-three labs reported no omics-related technology; LC-MS and GC-MS were present in eight labs and capillary spectroscopy, direct infusion mass spectroscopy, and Fourier transform infrared-spectroscopy were predominantly used for metabolite identification. Challenges identified in implementing metabolomics included lack of awareness, limited expertise, low volume, restricted applicability, high instrument costs, and insufficient funding. CONCLUSION: Metabolomics in Pakistan faces limitations, but the chemical pathology community expresses strong interest, emphasising the need for intensified efforts in education and training in this emerging field. KEY WORDS: Metabolomics, Chemical pathology, Pakistan, Clinical laboratories, Genetics, Survey.

Unchecked Antibiotic Access: A Looming Crisis in Pakistan.

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The need for economic evaluations for neuro-oncology in low- and middleincome: the Pakistan perspective.

The incidence and prevalence of brain tumours have steadily increased within low- and middle-income countries, similar to patterns seen in high-income countries. In addition to the epidemiological landscape of brain tumours in Pakistan, it is important to consider the economics of brain tumour diagnosis and management to inform policy on neuro-oncological healthcare service delivery. The challenges associated with conducting economic evaluations in LMICs include the ability to receive funding for country-specific estimates, dearth of existing data and methodological development, and the need for investment in economic evaluations of health. Economic evaluations are most useful when funding support is given to country-specific initiatives to allocate resources. Cost and cost components must also be meticulously collected to enable accurate calculations of economic evidence for the decision-making process. To put neuro-oncological care at the forefront of the national health agenda, it is crucial for vigorous epidemiological and economic evidence to be available for policymakers.

Protocol: revolutionizing central nervous system tumour diagnosis in low- and middle-income countries: an innovative observational study on intraoperative smear and deep learning.

OBJECTIVE: The aim of this study is to assess the feasibility and implementation of a novel approach for intraoperative brain smears within the operating room, which is augmented with deep learning technology. Materials and methods: This study is designed as an observational to evaluate the feasibility and implementation of using an innovative approach to intraoperative brain smears within the operating room, augmented with deep learning technology. The study will be conducted at Aga Khan University Hospital in Karachi, Pakistan, from May 2024 to July 2026, with an estimated sample size of 258. A neurosurgical trainee, trained by the study neuropathologist, will prepare and examine the smears under a microscope in the operating room. The findings of the trainee will be documented and compared to routine intraoperative consultations (smear and/or frozen section) and final histopathology results obtained from the pathology department. Additionally, the study will incorporate artificial intelligence tools to assist with the interpretation of smear and a telepathology interface to enable consultation from an off-site neuropathologist. CONCLUSIONS: The results of this study will hold significant potential to revolutionise neurosurgery practices in lowand middle-income countries by introducing a cost-effective, efficient, and high-quality intraoperative consultation method to settings that currently lack the necessary infrastructure and expertise. The implementation of this innovative approach has the potential to improve patient outcomes and increase access to intraoperative diagnosis, thereby addressing a significant unmet need in LMICs.

Global neuro-oncology: what lies ahead for low- and middle-income countries?

Over the past few decades, the global healthcare community has achieved remarkable success in controlling many communicable diseases across various regions. However, non-communicable diseases now constitute a significant portion of disease morbidity and mortality, particularly in low- and middle-income countries (LMICs). Among these, cancer, in particular, is witnessing a notable increase in incidence in many LMICs. Among cancers, neurological tumours bear significant impact in terms of long-term disability, escalating costs of comprehensive multidisciplinary care, and often encounter resource-related and systemic delays in care leading to worse outcomes. This opinion paper discusses key concepts in developing global neuro-oncology care, with specific case examples from Pakistan to illustrate methods for improving care in these underserved regions. Additionally, it outlines strategic approaches and potential solutions to address these challenges, aiming to provide a roadmap for enhancing neuro-oncology care in LMICs.

Consensus guidelines for the management of vestibular schwannoma for lowand middle-income countries.

Vestibular Schwannoma (VS), previously known as acoustic neuroma, constitutes the majority of tumours found in the cerebellopontine angle (CPA). Most guidelines for managing CPA tumours have been developed by high-income countries (HICs). However, these guidelines often fall short in addressing the unique challenges encountered in low- and middle-income countries (LMICs), such as Pakistan. In LMICs, issues related to a limited healthcare workforce, inadequate infrastructure, and constrained financial resources hinder the effective implementation of these HIC-derived guidelines. Additionally, it has been observed that VS tends to present at a larger size in LMICs compared to HICs. Given that VS is the predominant type of CPA tumour and other types are covered under separate guidelines, this article aims to provide practical, contextspecific recommendations for the screening, diagnosis, and management of Vestibular Schwannoma in LMIC settings. Our focus is to bridge the gap in care strategies and adapt them to the resource constraints and clinical realities of LMICs.

Consensus guidelines for the management of pediatric medulloblastoma in low and middle-income countries.

The management of medulloblastoma, a pediatric brain tumor, has evolved significantly with the advent of genomic subgrouping, yet morbidity and mortality remain high in LMICs like Pakistan due to inadequate multidisciplinary care infrastructure. This paper aims to establish evidence-based guidelines tailored to the constraints of such countries. An expert panel comprising neuro-oncologists, neurosurgeons, radiologists, radiation oncologists, neuropathologists, and pediatricians collaborated to develop these guidelines, considering the specific challenges of pediatric brain tumor care in Pakistan. The recommendations cover various aspects of medulloblastoma treatment, including pre-surgical workup, neurosurgery, neuropathology, chemotherapy, radiation therapy, and supportive care. They offer both minimum required and additional optional protocols for more advanced centers, ensuring comprehensive patient management with attention to complications and complexities encountered in Pakistan. The paper's consensus guidelines strive for uniformity in healthcare delivery and address significant gaps in diagnosis, treatment, and follow-up of pediatric medulloblastoma patients.

Consensus guidelines for the management of adult high-grade gliomas for low and middle-income countries.

High-grade glioma (HGG), a formidable and often incurable disease, presents an even greater challenge in low- and middle-income countries (LMICs) where resources and medical expertise are scarce. This scarcity not only exacerbates the suffering of patients but also contributes to poorer clinical outcomes. Particularly in LMICs, the underrepresentation of the population in clinical trials and the additional hurdles posed by financial constraints underscore an urgent need for contextspecific management strategies. In response, we have rigorously evaluated recent guidelines from leading medical societies, adapting them to suit the specific needs and limitations of the local context in Pakistan. This effort, undertaken in collaboration with local physicians, aims to provide a comprehensive, standardised approach to diagnose, treat, and follow-up with HGG patients. By focussing on the best available clinical evidence and judicious use of limited resources, we strive to improve patient care and outcomes in these challenging settings.

Consensus guidelines for the management of intracranial ependymoma for low- and middle-income countries.

This paper presents comprehensive consensus guidelines for the management of intracranial ependymoma, neoplasms arising from ependymal cells in the central nervous system's ventricular system, in low- and middleincome countries (LMICs). Acknowledging the distinct epidemiological patterns of ependymomas, notably their higher incidence in paediatric patients, and variable survival rates, these guidelines emphasize tailored management approaches for different age groups. An expert panel, comprising specialists in neuro-oncology, convened to address gaps in diagnosis and management within LMICs, considering the varying clinical presentation based on tumour size and location. Emphasizing surgical intervention as the cornerstone of treatment, the guidelines also address challenges such as intraoperative bleeding and tumour location impacting complete resection. The role of molecular subgrouping in stratifying treatment and predicting prognosis is highlighted, alongside a careful consideration of radiotherapy timing, dose, and volume based on risk factors. Chemotherapy's role, especially in paediatric cases, is explored. The paper synthesizes current research and expert opinions, including the need for standardisation, genetic testing, and exploration of less invasive treatment modalities, to address the unique healthcare infrastructure challenges in LMICs. The guidelines also emphasize multidisciplinary teams, aiming to bridge the care gap between high-income countries and LMICs, and improve survival rates and quality of life for patients with intracranial ependymoma. This article serves as a valuable resource for clinicians, researchers, and policymakers in Pakistan and beyond, facilitating the development of evidence-based strategies in diverse healthcare settings.

Judicious and evidence-based use of radiosurgery - recommendations for low-middle income countries.

Surgical removal remains the primary treatment for most brain tumours. However, radiosurgery presents an effective, less invasive alternative or additional treatment for certain types. Our goal was to explore radiosurgery's roles in treating various brain tumours, focussing on its application in low- and middle-income countries (LMICs). We reviewed all relevant systematic reviews, metaanalyses, and guidelines to determine the most effective radiosurgical approaches. Additionally, we consulted a panel of experts with over ten years of experience in LMICs, such as Pakistan. For brain tumours, stereotactic radiosurgery should generally follow a confirmed histopathological diagnosis. Exceptions include tumours identified through Magnetic Resonance Imaging (MRI), like Vestibular Schwannoma (VS), pre-diagnosed Neurofibromatosis type 2 (NF2), multiple typical meningiomas, and metastases with a known histology from another site. While radiosurgery is gaining traction as a primary and adjunct treatment in some LMICs, the lack of regional guidelines, trained personnel, and collaboration among specialists hinders its wider adoption. Addressing these gaps is crucial for expanding radiosurgical care in these regions.

Comparative assessment of phytoremediation potential of four Ficus spp. under Semi-arid environmental conditions.

Heavy metals have been recognized as a prominent hazard in today's world, causing pollution in the air environment. Woody tree species can play a significant role in the extraction and remediation of metal pollutants from the air, therefore promoting the air quality index. This study investigated the potential of four species of the Ficus genus (F. benjamina, F. microcarpa, F. religiosa, and F. virens) to remediate varying levels of heavy metal contamination in industrial, residential, and highway areas of Faisalabad City, Pakistan. For this purpose, six heavy metals (cadmium, chromium, copper, lead, zinc, and manganese) were assessed in young leaves (YL) as well as old leaves (OL) of subjected tree species at selected study sites. Eight fully expanded leaves were selected from each tree species: two from each cardinal direction from the shoot of the current year (young leaves, YL), as well as from the shoot of the previous year (old leaves, OL). The results showed that the same genus has different capabilities to accumulate different heavy metals, and the overall trend was in the following order: F. virens > F. religiosa > F. benjamina > F. microcarpa at all study sites. The heavy metal contents in both YL and OL of selected tree species decreased in the order of Manganese (Mn)> Zinc (Zn)> Copper (Cu) > Chromium (Cr) > Lead (Pb) > Cadmium (Cd) at all study sites. The metal accumulation index (MAI) values ranged between 2.14-5.42 for F. benjamina, 2.09-3.89 for F. microcarpa, 3.61-7.01 for F. religiosa and 4.77-6.48 for F. virens across all study sites. Among the studied  tree species, it has been determined that F. virens and F. religiosa are well-suited for urban areas with significant heavy metal contamination and can be strategically planted in barrier areas to effectively combat atmospheric pollution.

Protocol of digital decision support system (DDSS) embedded within a tele-primary healthcare platform in Pakistan: an assessment of usability, acceptability, effectiveness and perceived quality of care in a resource-constrained setting.

BACKGROUND: A digital decision support system in healthcare is a digital health intervention that assists healthcare professionals in decision-making by providing treatment recommendations and enhancing diagnostic accuracy and quality of care. This will be the first study in Pakistan to assess the system's usability, acceptability and effectiveness in improving healthcare outcomes while also evaluating the perceived quality of care. This comprehensive assessment will inform policy development in areas such as the scale-up of digital health interventions, data privacy and technology interoperability. Measures of effectiveness will include changes in clinical outcomes through a patient exit feedback survey. This study aims to evaluate the role of digital decision support systems in healthcare decision-making, which may be integrated into Pakistan's tele-primary healthcare system. METHODS: The study will employ a multimethod approach. The data collection tools are adapted from the WHO's digital health intervention monitoring and evaluation framework and include a technology assessment, healthcare provider surveys, patient exit interviews and focus group discussions with healthcare providers. Purposive sampling will be used for qualitative interviews with providers (doctors) and patients. Government stakeholders, private sectors, multilateral, academia and policymakers will be engaged through a consultative meeting. We will also conduct a literature review, as well as a comprehensive analysis of existing studies, documents and data relevant to digital decision support systems and digital health interventions implemented globally, and assess the performance, challenges and opportunities. ETHICS AND DISSEMINATION: The study has been approved by the Ethics Review Committee at The Aga Khan University (2023-8514-26533). The dissemination of study findings through scientific publications and seminars will enable programme managers and policymakers to design tools to improve the quality of care provided through telemedicine platforms. This will contribute to efficient decision-making, access and quality of care for primary healthcare in low-income and middle-income countries. This study will also inform policy regarding the scale-up of decision support systems in primary care settings, data privacy and technology interoperability.

Uncovering the hidden health burden: a systematic review and meta-analysis of iron deficiency anemia among adolescents, and pregnant women in Pakistan.

INTRODUCTION: Iron deficiency anemia (IDA) is the most prevalent diet-related disorder and mainly affects women and children. To determine the trend of anemia incidence in Pakistan, a current review was carried out. This review aimed to estimate the prevalence of anemia among pregnant women and adult/adolescent nonpregnant women in Pakistan and to provide a 15-year trend analysis. MATERIALS AND METHODS: Studies were identified by searching PubMed, Google Scholar, Scopus, and Science Direct, complementing this digital exploration, and a manual review of reference lists from previously published prevalence studies was performed to enhance the scope of relevant articles. A total of twenty-seven population-based anemia studies on adolescent/adult females and pregnant women published in Pakistan from January 1st-2007 until December 2021 were included. Systematic data extraction was facilitated through the implementation of a standardized and rigorously pretested data extraction checklist. For the subsequent analysis, the sophisticated capabilities of R statistical software were harnessed. The I2 test was used to assess heterogeneity among studies, and the pooled prevalence of anemia was calculated. RESULTS: The final analysis included 27 research articles as well as two extensive National Nutrition survey reports, NNS 2011 and NNS 2018. The forest plot of sixteen studies on pregnant women revealed that the overall pooled prevalence of anemia among pregnant females in Pakistan was 70.4% (95% CI: 0.619, 0.789), and the forest plot of eleven studies on non-pregnant adolescent and adult females reported the pooled prevalence was 54.6% (95% CI: 0.422, 0.669). Subgroup analysis among pregnant women based on region, trimester and socioeconomic status revealed that the highest anemia incidence was observed in Punjab (77.4%). Similarly, females in the second trimester reported a higher prevalence of anemia 78% (95% CI, 0.556 1.015), and the status-wise group with a mixed background reported a higher prevalence 72.8% (95% CI, 0.620 0.835). According to the subgroup analysis, eleven studies of adult nonpregnant groups of mixed socioeconomic status reported a higher prevalence of 56.9% (95% CI, 0.292 0.845). CONCLUSION: In Pakistan, anemia, is widespread among pregnant women and nonpregnant adolescent/adult females. A deeper understanding of anemia in Pakistani women is necessary for targeted interventions and policy decisions to predict demographic shifts.

NOTCH3 p.Arg1231Cys is markedly enriched in South Asians and associated with stroke.

The genetic factors of stroke in South Asians are largely unexplored. Exome-wide sequencing and association analysis (ExWAS) in 75 K Pakistanis identified NM_000435.3(NOTCH3):c.3691 C > T, encoding the missense amino acid substitution p.Arg1231Cys, enriched in South Asians (alternate allele frequency = 0.58% compared to 0.019% in Western Europeans), and associated with subcortical hemorrhagic stroke [odds ratio (OR) = 3.39, 95% confidence interval (CI) = [2.26, 5.10], p = 3.87 × 10-9), and all strokes (OR [CI] = 2.30 [1.77, 3.01], p = 7.79 × 10-10). NOTCH3 p.Arg231Cys was strongly associated with white matter hyperintensity on MRI in United Kingdom Biobank (UKB) participants (effect [95% CI] in SD units = 1.1 [0.61, 1.5], p = 3.0 × 10-6). The variant is attributable for approximately 2.0% of hemorrhagic strokes and 1.1% of all strokes in South Asians. These findings highlight the value of diversity in genetic studies and have major implications for genomic medicine and therapeutic development in South Asian populations.