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Abstract Frailty is a multidimensional syndrome associated with a decline in reserve capacity across multiple organ systems involving physical, psychological, and social aspects. Weakness is the earliest indicator of the frailty process. Multi‐morbidity is the state of presence of two or more chronic diseases. Frailty and chronic diseases are interlinked as frail individuals are more prone to develop chronic diseases and multi‐morbid individuals may present with frailty. They share common risk factors, pathogenesis, progression, and outcomes. Significant risk factors include obesity, smoking, aging, sedentary, and stressful lifestyle. Pathophysiological mechanisms involve high levels of circulating inflammatory cytokines as seen in individuals with frailty and chronic diseases such as hypertension, cardiovascular diseases, type 2 diabetes mellitus, chronic kidney disease, and anemia. Hence, frailty and chronic diseases go hand in hand and it is of utmost importance to identify them and intervene during early stages. Screening frailty and treating multi‐morbidity incorporate both pharmacological and majorly non‐ pharmacological measures, such as physical activities, nutrition, pro‐active care, minimizing polypharmacy and addressing reversible medical conditions. The purpose of this mini‐review is to highlight the interrelation of frailty and chronic diseases through the discussion of their predictors and outcomes and how timely interventions are essential to prevent the progression of one to the other.

Comprehensive Geriatric Assessment (CGA) is a process of care that involves a holistic, multidimensional, interdisciplinary assessment of an older individual and has been demonstrated to be the choice of management for frailty. By 2050, it is expected that 80 % of the aging population will be living in low and low-middle income countries (LMICs). The implementation of geriatric programs is scarce in LMICs. CGA based frailty clinics could help facilitate early screening for impairment in physical and psychological capacities among pre-frail and frail older individuals allowing for suggestions for targeted interventions. Creating a sound healthcare model which addresses issues of older adults living with frailty is the need of the hour, especially in LMICs. Establishing frailty clinics in low-middle income countries could thus help to create a sustainable age-friendly healthcare model for the vulnerable and poor aging population. It is now the time to act.

Introduction The burden of multimorbidity is recognised increasingly in low- and middle-income countries (LMICs), creating a strong emphasis on the need for effective evidence-based interventions. Core outcome sets (COS) appropriate for the study of multimorbidity in LMICs do not presently exist. These are required to standardise reporting and contribute to a consistent and cohesive evidence-base to inform policy and practice. We describe the development of two COS for intervention trials aimed at preventing and treating multimorbidity in adults in LMICs.Methods To generate a comprehensive list of relevant prevention and treatment outcomes, we conducted a systematic review and qualitative interviews with people with multimorbidity and their caregivers living in LMICs. We then used a modified two-round Delphi process to identify outcomes most important to four stakeholder groups (people with multimorbidity/caregivers, multimorbidity researchers, healthcare professionals and policymakers) with representation from 33 countries. Consensus meetings were used to reach agreement on the two final COS. Registration: https://www.comet-initiative.org/Studies/Details/1580.Results The systematic review and qualitative interviews identified 24 outcomes for prevention and 49 for treatment of multimorbidity. An additional 12 prevention and 6 treatment outcomes were added from Delphi round 1. Delphi round 2 surveys were completed by 95 of 132 round 1 participants (72.0%) for prevention and 95 of 133 (71.4%) participants for treatment outcomes. Consensus meetings agreed four outcomes for the prevention COS: (1) adverse events, (2) development of new comorbidity, (3) health risk behaviour and (4) quality of life; and four for the treatment COS: (1) adherence to treatment, (2) adverse events, (3) out-of-pocket expenditure and (4) quality of life.Conclusion Following established guidelines, we developed two COS for trials of interventions for multimorbidity prevention and treatment, specific to adults in LMIC contexts. We recommend their inclusion in future trials to meaningfully advance the field of multimorbidity research in LMICs.PROSPERO registration number CRD42020197293.

Objective: Rheumatic Heart Disease (RHD) remains a significant public health problem with high morbidity and mortality in children and young adults from lower-middle income countries like Nepal. However, a nation-wide database of the disease is lacking for designing effective future prevention and control programmes and strategies. The aim of our study is to estimate the prevalence of RHD in school-attending Nepalese children. Methods: We performed a cross-sectional descriptive analysis of a nationally representative database of Nepal Heart Foundation (NHF) national RHD screening programme which included school-attending Nepalese children between five and sixteen years of age. The screening was conducted between May 2015 and March 2020 in 236 schools, representing all seven provinces, across all three ecological zones of Nepal. Transthoracic two-dimensional echocardiography was performed in all eligible children with more than grade one murmur on cardiac auscultation. We estimated the prevalence of RHD among school-attending children as the number of RHD cases per 1000 school-attending children with a 95% confidence interval. Results: The database included a total of 107,340 children who were screened clinically, of whom 10,600 (9·9%) underwent transthoracic two-dimensional echocardiography. The overall prevalence of RHD was 2.22 cases per 1000 school-attending children (95% CI:1·94 - 2·50). The highest prevalence was observed among children living in the southern Terai ecological zone (2·89 per 1000, 95% CI (2·32–3·46)) of Nepal. Among the provinces, Karnali had the highest prevalence of RHD (3·45 per 1000, 95% CI (2·42–4·48)). Among the districts screened, Kalikot had the highest RHD prevalence (5.47 per 1000, 95% CI (3.02–7.92)). Conclusion: Primordial, primary and secondary prevention programmes should pay special attention to southern Terai zone, particularly the under-privileged children from remote districts.

This article details a correction to: Klassen, S.L., Okello, E., Ferrer, J.M.E., Alizadeh, F., Barango, P., Chillo, P., Chimalizeni, Y., Dagnaw, W.W., Eiselé, J.-L., Eberly, L., Gomanju, A., Gupta, N., Koirala, B., Kpodonu, J., Kwan, G.F., Mailosi, B.G.D., Mbau, L., Mutagaywa, R., Pfaff, C., Piñero, D., Pinto, F., Rusingiza, E., Sanni, U.A., Sanyahumbi, A., Shakya, U., Sharma, S.K., Sherpa, K., Sinabulya, I., Wroe, E.B., Bukhman, G. and Mocumbi, A. (2024) ‘Decentralization and Integration of Advanced Cardiac Care for the World’s Poorest Billion Through the PEN-Plus Strategy for Severe Chronic Non-Communicable Disease’, Global Heart. 2024; 19(1): 33. Available at: https://doi.org/10.5334/gh.1313.

Key Clinical Message Posterior reversible encephalopathy syndrome may occur secondary to abrupt cessation of antihypertensive therapy. A gradual reduction in blood pressure and counseling regarding medication adherence are crucial to prevent adverse consequences. Abstract Posterior reversible encephalopathy syndrome (PRES) is a reversible clinical radiographic syndrome with headache, hypertensive encephalopathy, seizures, and visual disturbances as common modes of presentation. PRES can be attributed to several risk factors. We reported the case of a 66‐year‐old Asian female with PRES following nonadherence to antihypertensive treatment. Initially, her computed tomography scan of the head was normal. After 48 h, we again ordered a head CT scan, which showed lesions suggestive of hypertensive encephalopathy. We immediately reduced 20%–25% of mean arterial pressure, followed by a gradual blood pressure lowering to avoid adverse consequences. We did a follow‐up CT scan of the head at 2 weeks, showing the resolution of early lesions. Hence, we made a diagnosis of PRES. In these patients, it is crucial to ensure medication adherence to avoid complications.

Rheumatic and congenital heart disease, cardiomyopathies, and hypertensive heart disease are major causes of suffering and death in low- and lower middle-income countries (LLMICs), where the world’s poorest billion people reside. Advanced cardiac care in these counties is still predominantly provided by specialists at urban tertiary centers, and is largely inaccessible to the rural poor. This situation is due to critical shortages in diagnostics, medications, and trained healthcare workers. The Package of Essential NCD Interventions – Plus (PEN-Plus) is an integrated care model for severe chronic noncommunicable diseases (NCDs) that aims to decentralize services and increase access. PEN-Plus strategies are being initiated by a growing number of LLMICs. We describe how PEN-Plus addresses the need for advanced cardiac care and discuss how a global group of cardiac organizations are working through the PEN-Plus Cardiac expert group to promote a shared operational strategy for management of severe cardiac disease in high-poverty settings.

Gastric antral vascular ectasia (GAVE) is a rare condition which accounts for 4% of the nonvariceal acute upper gastrointestinal (GI) bleeding. The mean age of diagnosis is 70 years. This condition is often misdiagnosed as hemorrhagic antral gastritis or portal hypertensive gastropathy. In this case report, we report the oldest person to date in the South Asian population with upper GI bleeding caused by GAVE. An 87-year-old, female, known case of chronic obstructive pulmonary disorder and systemic hypertension under medication for 2 years, current smoker, previous alcohol consumer presented to the emergency department with complaints of hematemesis, melena, and easy fatigability. On general physical examination, pallor was present. A provisional diagnosis of chronic anemia secondary to upper GI bleeding was made. Upper GI endoscopy revealed ectatic vessels radiating from the gastric antrum which was diagnosed as GAVE. Blood transfusion was done, and three sessions of argon plasma coagulation were done. In the oldest old, GAVE is an overlooked cause of GI bleeding and persistent severe anemia. It might also mimic the signs and symptoms of GI malignancy. However, the frail older adult and their caretakers must be counseled about its reversibility, good prognosis, and nonmalignant nature. Simple intervention can improve the quality of life in the frail oldest old.

Background: Effective treatments for COVID-19 are urgently needed, but conducting randomized trials during the pandemic has been challenging. Methods: The Anti-Coronavirus Therapy (ACT) trials are parallel factorial international trials that aimed to enroll 3500 outpatients and 2500 inpatients with symptomatic COVID-19. The outpatient trial is evaluating colchicine vs usual care, and aspirin vs usual care. The primary outcome for the colchicine randomization is hospitalization or death, and for the aspirin randomization, it is major thrombosis, hospitalization, or death. The inpatient trial is evaluating colchicine vs usual care, and the combination of rivaroxaban 2.5 mg twice daily and aspirin 100 mg once daily vs usual care. The primary outcome for the colchicine randomization is need for high-flow oxygen, need for mechanical ventilation, or death, and for the rivaroxaban plus aspirin randomization, it is major thrombotic events, need for high-flow oxygen, need for mechanical ventilation, or death. Results: At the completion of enrollment on February 10, 2022, the outpatient trial had enrolled 3917 patients, and the inpatient trial had enrolled 2611 patients. Challenges encountered included lack of preliminary data about the interventions under evaluation, uncertainties related to the expected event rates, delays in regulatory and ethics approvals, and in obtaining study interventions, as well as the changing pattern of the COVID-19 pandemic. Conclusions: The ACT trials will determine the efficacy of anti-inflammatory therapy with colchicine, and antithrombotic therapy with aspirin given alone or in combination with rivaroxaban, across the spectrum of mild, moderate, and severe COVID-19. Lessons learned from the conduct of these trials will inform planning of future trials. Résumé: Contexte: Il est urgent de mettre au point des traitements efficaces contre la COVID-19, mais il n’est pas facile de réaliser des essais à répartition aléatoire dans un contexte pandémique. Méthodologie: Les essais internationaux factoriels ACT (Anti-Coronavirus Therapy) avaient un objectif d’inscription de 3 500 patients externes et de 2 500 patients hospitalisés présentant une COVID-19 symptomatique. L’essai mené auprès de patients externes visait à évaluer la colchicine par rapport aux soins habituels, et l’aspirine par rapport aux soins habituels. Le paramètre d’évaluation principal au terme de la répartition aléatoire des patients était l’hospitalisation ou le décès dans le groupe traité par la colchicine, et la thrombose majeure, l’hospitalisation ou le décès dans le groupe traité par l’aspirine. L’essai mené auprès de patients hospitalisés visant à évaluer la colchicine par rapport aux soins habituels, et un traitement associant le rivaroxaban à 2,5 mg deux fois par jour et l’aspirine à 100 mg une fois par jour par rapport aux soins habituels. Le paramètre d’évaluation principal au terme de la répartition aléatoire des patients était le recours à l’oxygénothérapie à haut débit ou à la ventilation mécanique ou le décès dans le groupe traité par la colchicine, et la survenue de manifestations thrombotiques majeures, le recours à l’oxygénothérapie à haut débit ou à la ventilation mécanique ou le décès dans le groupe traité par l’association rivaroxaban-aspirine. Résultats: À la fin de la période d’inscription, le 10 février 2022, 3 917 patients externes et 2 611 patients hospitalisés formaient la population des essais. Certains aspects se sont révélés problématiques, notamment le manque de données préliminaires sur les interventions à évaluer, les incertitudes liées aux taux d’événements prévus, les retards touchant les approbations réglementaires et éthiques et les interventions de recherche, de même que l’évolution de la pandémie de COVID-19. Conclusions: Les essais ACT détermineront l’efficacité du traitement anti-inflammatoire par la colchicine et du traitement antithrombotique par l’aspirine, administrée seule ou en association avec le rivaroxaban, contre la COVID-19 légère, modérée ou sévère. Les leçons tirées de ces essais orienteront la planification d’essais ultérieurs.

Summary: Background: Snakebite envenoming is a neglected tropical disease that mainly affects poor populations in rural areas. In hyperendemic regions, prevention could partially reduce the constant risk, but the population still needs timely access to adequate treatment. In line with WHO's snakebite roadmap, we aim to understand snakebite vulnerability through modelling of risk and access to treatment, and propose plausible solutions to optimise resource allocation. Methods: We combined snakebite-risk distribution rasters with travel-time accessibility analyses for the Terai region of Nepal, considering three vehicle types, two seasons, two snakebite syndromes, and uncertainty intervals. We proposed localised and generalised optimisation scenarios to improve snakebite treatment coverage for the population, focusing on the neurotoxic syndrome. Findings: In the Terai, the neurotoxic syndrome is the main factor leading to high snakebite vulnerability. For the most common scenario of season, syndrome, and transport, an estimated 2.07 (15.3%) million rural people fall into the high vulnerability class. This ranges between 0.3 (2.29%) and 6.8 (50.43%) million people when considering the most optimistic and most pessimistic scenarios, respectively. If all health facilities treating snakebite envenoming could optimally treat both syndromes, treatment coverage of the rural population could increase from 65.93% to 93.74%, representing a difference of >3.8 million people. Interpretation: This study is the first high-resolution analysis of snakebite vulnerability, accounting for uncertainties in both risk and travel speed. The results can help identify populations highly vulnerable to snakebite envenoming, optimise resource allocation, and support WHO's snakebite roadmap efforts. Funding: Swiss National Science Foundation.

[This corrects the article DOI: 10.1371/journal.pntd.0009657.].

Abstract Most efforts to understand snakebite burden in Nepal have been localized to relatively small areas and focused on humans through epidemiological studies. We present the outcomes of a geospatial analysis of the factors influencing snakebite risk in humans and animals, based on both a national-scale multi-cluster random survey and, environmental, climatic, and socio-economic gridded data for the Terai region of Nepal. The resulting Integrated Nested Laplace Approximation models highlight the importance of poverty as a fundamental risk-increasing factor, augmenting the snakebite odds in humans by 63.9 times. For animals, the minimum temperature of the coldest month was the most influential covariate, increasing the snakebite odds 23.4 times. Several risk hotspots were identified along the Terai, helping to visualize at multiple administrative levels the estimated population numbers exposed to different probability risk thresholds in 1 year. These analyses and findings could be replicable in other countries and for other diseases.

Background: The COPCOV study (chloroquine/ hydroxychloroquine prevention of coronavirus disease), which started recruitment in April 2020, is a multi-country double-blind, randomised, placebo-controlled trial which is being conducted in healthcare facilities involved in COVID-19 case management. Participants are staff employed in facilities managing people with proven or suspected COVID-19. As part of the study, we conducted a series of engagement sessions. The aims were to assess the feasibility of the study, to identify context-specific ethical issues, to understand possible concerns, to fine tune research procedures and to refine the COPCOV information materials. Methods: The COPCOV study was approved by relevant institutional review boards. The sessions described in this paper were part of the study. We conducted a series of engagement sessions, each involving a short presentation of the study, a section where attendees were asked to express their willingness to participate in such a study, which information they would need to change their view and an open Q&A section. Answers were transcribed and coded into themes by two independent investigators. Themes were derived from the data. They complemented other site-specific engagement, communication, and public relation activities such as press releases and websites. Results and conclusions: From 16 th March 2020 to 20 th January 2021, 12 engagement sessions were conducted in Thailand, Laos, Vietnam, Nepal and the UK involving 213 attendees in total. Issues raised revolved around the social value and study rationale; safety of trial medications and risk-benefit balance; study design and commitments. These sessions helped us identify concerns people had, which helped us refine information materials as well as complement site feasibility assessments. Our experience strongly supports the use of participatory practices prior to conducting clinical trials.

Snakebite is an important public health issue around the world. In Nepal, it affects a huge number of people mostly belonging to low-income households who are involved in agriculture. Although snakebite has a serious impact on the Terai population, a few studies suggest that snakebite also occurs frequently in hills and mountains. In the absence of sufficient studies related to snakebites in these geographical regions, it is tough to sketch a true picture and estimate the magnitude of snakebites in those areas. Because of this, the healthcare system is probably not prepared enough to handle the victims of snakebites. This demands a proper study of the burden of the issue in these regions and appropriate initiatives for addressing it.

Introduction: A core outcome set (COS) is a minimal list of consensus outcomes that should be used in all intervention research in a specific domain. COS enhance the ability to undertake meaningful comparisons and to understand the benefits or harms of different treatments. A first step in developing a COS is to identify outcomes that have been used previously. We did this global systematic review to provide the foundation for development of a region-specific COS for snakebite envenomation. Methods: We searched 15 electronic databases, eight trial registries, and reference lists of included studies to identify reports of relevant trials, protocols, registry records and systematic reviews. We extracted verbatim data on outcomes, their definitions, measures, and time-points. Outcomes were classified as per an existing outcome taxonomy, and we identified unique outcomes based on similarities in the definition and measurement of the verbatim outcomes. Results: We included 107 records for 97 studies which met our inclusion criteria. These reported 538 outcomes, with a wide variety of outcome measures, definitions, and time points for measurement. We consolidated these into 88 unique outcomes, which we classified into core areas of mortality (1, 1.14 %), life impact (6, 6.82%), resource use (15, 17.05%), adverse events (7, 7.95%), physiological/clinical (51, 57.95%), and composite (8, 9.09%) outcomes. The types of outcomes varied by the type of intervention, and by geographic region. Only 15 of the 97 trials (17.04%) listed Patient Related Outcome Measures (PROMS). Conclusion: Trials evaluating interventions for snakebite demonstrate heterogeneity on outcomes and often omit important information related to outcome measurement (definitions, instruments, and time points). Developing high quality, region-specific COS for snakebite could inform the design of future trials and improve outcome reporting. Measurement of PROMS, resource use and life impact outcomes in trials on snakebite remains a gap.

Introduction: A core outcome set (COS) is a minimal list of consensus outcomes that should be used in all intervention research in a specific domain. COS enhance the ability to undertake meaningful comparisons and to understand the benefits or harms of different treatments. A first step in developing a COS is to identify outcomes that have been used previously. We did this global systematic review to provide the foundation for development of a region-specific COS for snakebite envenomation. Methods: We searched 15 electronic databases, eight trial registries, and reference lists of included studies to identify reports of relevant trials, protocols, registry records and systematic reviews. We extracted verbatim data on outcomes, their definitions, measures, and time-points. Outcomes were classified as per an existing outcome taxonomy, and we identified unique outcomes based on similarities in the definition and measurement of the verbatim outcomes. Results: We included 107 records for 97 studies which met our inclusion criteria. These reported 538 outcomes, with a wide variety of outcome measures, definitions, and time points for measurement. We consolidated these into 88 unique outcomes, which we classified into core areas of mortality (1, 1.14 %), life impact (6, 6.82%), resource use (15, 17.05%), adverse events (7, 7.95%), physiological/clinical (51, 57.95%), and composite (8, 9.09%) outcomes. The types of outcomes varied by the type of intervention, and by geographic region. Only 15 of the 97 trials (17.04%) listed Patient Related Outcome Measures (PROMS). Conclusion: Trials evaluating interventions for snakebite demonstrate heterogeneity on outcomes and often omit important information related to outcome measurement (definitions, instruments, and time points). Developing high quality, region-specific COS for snakebite could inform the design of future trials and improve outcome reporting. Measurement of PROMS, resource use and life impact outcomes in trials on snakebite remains a gap.

Objectives Rheumatic fever (RF) and rheumatic heart disease (RHD) remain among the major heart problems among children in Nepal. Although these conditions are preventable and treatable, the lack of proper knowledge and resources to diagnose and manage these conditions in rural health centres is a key concern. This study assessed the impact of educational sessions to improve the knowledge of healthcare workers in the early recognition, diagnosis, and management of RF and RHD in rural far-western Nepal.Design, setting and participants This study used a pretest and post-test interventional design and was conducted among 64 healthcare workers in two primary healthcare centres and a peripheral district-level hospital in Achham district in the far-western region of Nepal. A self-administered questionnaire was used before and after the educational sessions. Data were analysed using SPSS V.21.Results The overall test scores increased from 10 (SD=2.4) pre-intervention to 13.8 (SD=1.9) post-intervention (p

Objective This study aimed to determine population-based prevalence of chronic kidney disease (CKD) and its associated factors in Nepal.Study design The study was a nationwide population-based cross-sectional study.Setting and participants Cross-sectional survey conducted in a nationally representative sample of 12 109 Nepalese adult from 2016 to 2018 on selected chronic non-communicable diseases was examined. Multistage cluster sampling with a mix of probability proportionate to size and systematic random sampling was used for the selection of individuals aged 20 years and above.Primary and secondary outcome measures Primary outcome in this study was population-based prevalence of CKD in Nepal. A participant was considered to have CKD if the urine albumin-to-creatinine ratio was greater than or equal to 30 mg/g and/or estimated glomerular filtration rate is less than 60 mL/min/1.73 m2 at baseline and in follow-up using modification of diet in renal disease study equations. The secondary outcome measure was factors associated with CKD in Nepal. The covariate adjusted association of risk factors and CKD was calculated using multivariable binary logistic regression.Results The overall prevalence of CKD in Nepal was 6.0% (95% CI 5.5 to 6.6). Factors independently associated with CKD included older age (adjusted OR (AOR) 2.6, 95% CI 1.9 to 3.6), Dalit caste (AOR 1.6, 95% CI 1.1 to 2.3), hypertension (AOR 2.4, 95% CI 2.0 to 3.0), diabetes mellitus (AOR 3.2, 95% CI 2.5 to 4.1), raised total cholesterol (AOR 1.3, 95% CI 1.0 to 1.6) and increased waist-to-hip ratio (AOR 1.6, 95% CI 1.2 to 2.3).Conclusion This nationally representative study shows that the prevalence of CKD in the adult population of Nepal is substantial, and it is independently associated with several cardiometabolic traits. These findings warrant longitudinal studies to identify the causes of CKD in Nepal and effective strategies to prevent it.

Introduction: Amidst the chaos of COVID-19, health care practitioners are persistently providing services and experiencing many challenges. This study aimed to determine the perception of health care practitioners of government designated COVID-19 hospitals of Nepal towards the management of COVID-19 pandemic. Methods: A descriptive cross-sectional study was conducted among the frontline health care practitioners working in the government designated COVID-19 hospitals in Nepal from 21st June, 2020 to 15th August, 2020. Ethical approval was obtained from the Ethical Review Board of the Nepal Health Research Council (Reference number: 347/2020 P). A total of 252 health care practitioners (doctors, nurses, and paramedics) working at the forefront in the emergency ward, general wards, intensive care units, isolation centers, fever clinics, laboratory, quarantine centers, help desks, etc. in the designated hospitals who consented to participate were included in the study. Convenience sampling was used. The data was analyzed using Statistical Package for the Social Sciences version 16.0. Point estimate at 95% confidence interval was calculated along with frequency and proportion for binary data. Results: Only 41 (16.3%) (11.73-20.86 at 95% Confidence Interval) of the health care practitioners were found to have satisfactory perception towards the management of COVID-19 pandemic in Nepal. Conclusions: The satisfactory perception of the health care practitioners in our study towards the management of COVID-19 pandemic in Nepal is lower as compared to the other studies in Nepal and abroad.

BackgroundThe 20-minute whole blood clotting test (20WBCT) has been used to detect coagulopathy following snakebite for almost 50 years. A systematic review and meta-analysis of the 20WBCT was conducted to evaluate the accuracy of the 20WBCT to detect coagulopathy, indicative of systemic envenoming.Methods and findingsDatabases were searched from inception up to 09/12/2020 to identify studies that compared the 20WBCT and INR/fibrinogen on five or more subjects. Data was extracted from full-text articles by two reviewers using a predetermined form. Authors of 29 studies that lacked sufficient details in the manuscript were contacted and included if data meeting the inclusion criteria were provided. Included studies were evaluated for bias using a tailored QUADAS-2 checklist. The study protocol was prospectively registered on PROSPERO database (CRD42020168953). The searches identified 3,599 studies, 15 met the inclusion criteria and 12 were included in the meta-analysis. Data was reported from 6 countries and included a total of 2,270 patients. The aggregate weighted sensitivity of the 20WBCT at detecting INR >1.4 was 0.84 (CI 0.61 to 0.94), the specificity was 0.91 (0.76 to 0.97) and the SROC AUC was 0.94 (CI 0.91 to 0.96). The aggregate weighted sensitivity of the 20WBCT at detecting fibrinogen ConclusionsIn the absence of laboratory clotting assays, the 20WBCT remains a highly specific and fairly sensitive bedside test at detecting coagulopathy following snakebite. However, clinicians should be aware of the importance of operator training, standardized equipment and the lower sensitivity of the 20WBCT at detecting mild coagulopathy and resolution of coagulopathy following antivenom.

Snakebite envenoming is a life-threatening disease in humans and animals and a major public health issue in rural communities of South-East Asia and sub-Saharan Africa. Yet the impact of snakebite on domestic animals has been poorly studied. This study aimed to describe the context, clinical features, treatment, and outcomes of snakebite envenoming in domestic animals in Nepal and Cameroon. Primary data on snakebite in animals were recorded from a community-based nation-wide survey on human and animal snakebite in Nepal and Cameroon (Snake-byte project). Mobile teams collected data on snakebite in humans and animals in 13,879 and 10,798 households in Nepal and Cameroon respectively from December 2018 to June 2019. This study included 405 snakebite cases (73 in Nepal and 332 in Cameroon) in multiple types of animals. An interview with a structured questionnaire collected specific information about the animal victims.Snake bites in animals took place predominantly inside and around the house or farm in Nepal (92%) and Cameroon (71%). Other frequent locations in Cameroon were field or pasture (12%). A large diversity of clinical features was reported in all types of envenomed animals. They showed either a few clinical signs (e.g., local swelling, bleeding) or a combination of multiple clinical signs. Only 9% of animal victims, mainly cattle and buffaloes and less frequently goats, sheep, and dogs, received treatment, predominantly with traditional medicine. The overall mortality of snakebite was 85% in Nepal and 87% in Cameroon.Results from this nationwide study show an important impact of snakebite on animal health in Nepal and Cameroon. There is a need for cost-effective prevention control strategies and affordable snakebite therapies in the veterinary field to save animal lives and farmer livelihood in the poorest countries of the world. The WHO global strategy to prevent and control snakebite envenoming supports a One Health approach, which may help develop integrated solutions to the snakebite problem taking into account human and animal health.

Lupus nephritis (LN) is one of the common complications of systemic lupus erythematosus (SLE). Timely treatment will decrease progression to chronic kidney disease. Treatment varies with different stages for which biopsy is needed. Controversies still exist regarding its requirement in management. This is a retrospective study from September 2014 to August 2016 in B. P. Koirala Institute of Health Sciences, Dharan, Nepal among all patients with SLE and undergone renal biopsy. Of 92 patients, most were female 85 (92.4%) with a median age of 32 years. In this study, 80.4% had some clinical symptomatology. Of the clinical manifestations, 41.3% had polyarthritis, edema (20.7%), and malar rash (17.4%). Anti-nuclear antibody was positive in 80.4% and ds DNA in 70.7%. Renal biopsy showed more number of patients 27 (35%) had Stage IV LN, followed by Stage I, 19 (24%), and Stage II, 16 (20%) LN. Median urinary protein in Class I was 1.05 g, Class II (0.63 g), Class III (1.5 g), Class IV (2.44 g), Class V (3.99 g), and Class VI (4.7 g). Only Stage IV had Kappa of 0.269 {P = 0.003) showing agreement between proteinuria and histological staging which was statistically significant (P

BackgroundWorldwide, it is estimated that snakes bite 4.5-5.4 million people annually, 2.7 million of which are envenomed, and 81,000-138,000 die. The World Health Organization reported these estimates and recognized the scarcity of large-scale, community-based, epidemiological data. In this context, we developed the "Snake-Byte" project that aims at (i) quantifying and mapping the impact of snakebite on human and animal health, and on livelihoods, (ii) developing predictive models for medical, ecological and economic indicators, and (iii) analyzing geographic accessibility to healthcare. This paper exclusively describes the methodology we developed to collect large-scale primary data on snakebite in humans and animals in two hyper-endemic countries, Cameroon and Nepal.Methodology/principal findingsWe compared available methods on snakebite epidemiology and on multi-cluster survey development. Then, in line with those findings, we developed an original study methodology based on a multi-cluster random survey, enhanced by geospatial, One Health, and health economics components. Using a minimum hypothesized snakebite national incidence of 100/100,000/year and optimizing design effect, confidence level, and non-response margin, we calculated a sample of 61,000 people per country. This represented 11,700 households in Cameroon and 13,800 in Nepal. The random selection with probability proportional to size generated 250 clusters from all Cameroonian regions and all Nepalese Terai districts. Our household selection methodology combined spatial randomization and selection via high-resolution satellite images. After ethical approval in Switerland (CCER), Nepal (BPKIHS), and Cameroon (CNERSH), and informed written consent, our e-questionnaires included geolocated baseline demographic and socio-economic characteristics, snakebite clinical features and outcomes, healthcare expenditure, animal ownership, animal outcomes, snake identification, and service accessibility.Conclusions/significanceThis novel transdisciplinary survey methodology was subsequently used to collect countrywide snakebite envenoming data in Nepal and Cameroon. District-level incidence data should help health authorities to channel antivenom and healthcare allocation. This methodology, or parts thereof, could be easily adapted to other countries and to other Neglected Tropical Diseases.

BackgroundAcute kidney injury (AKI) is increasingly encountered in community settings and contributes to morbidity, mortality, and increased resource utilization worldwide. In low-resource settings, lack of awareness of and limited access to diagnostic and therapeutic interventions likely influence patient management. We evaluated the feasibility of the use of point-of-care (POC) serum creatinine and urine dipstick testing with an education and training program to optimize the identification and management of AKI in the community in 3 low-resource countries.Methods and findingsPatients presenting to healthcare centers (HCCs) from 1 October 2016 to 29 September 2017 in the cities Cochabamba, Bolivia; Dharan, Nepal; and Blantyre, Malawi, were assessed utilizing a symptom-based risk score to identify patients at moderate to high AKI risk. POC testing for serum creatinine and urine dipstick at enrollment were utilized to classify these patients as having chronic kidney disease (CKD), acute kidney disease (AKD), or no kidney disease (NKD). Patients were followed for a maximum of 6 months with repeat POC testing. AKI development was assessed at 7 days, kidney recovery at 1 month, and progression to CKD and mortality at 3 and 6 months. Following an observation phase to establish baseline data, care providers and physicians in the HCCs were trained with a standardized protocol utilizing POC tests to evaluate and manage patients, guided by physicians in referral hospitals connected via mobile digital technology. We evaluated 3,577 patients, and 2,101 were enrolled: 978 in the observation phase and 1,123 in the intervention phase. Due to the high number of patients attending the centers daily, it was not feasible to screen all patients to assess the actual incidence of AKI. Of enrolled patients, 1,825/2,101 (87%) were adults, 1,117/2,101 (53%) were females, 399/2,101 (19%) were from Bolivia, 813/2,101 (39%) were from Malawi, and 889/2,101 (42%) were from Nepal. The age of enrolled patients ranged from 1 month to 96 years, with a mean of 43 years (SD 21) and a median of 43 years (IQR 27-62). Hypertension was the most common comorbidity (418/2,101; 20%). At enrollment, 197/2,101 (9.4%) had CKD, and 1,199/2,101 (57%) had AKD. AKI developed in 30% within 7 days. By 1 month, 268/978 (27%) patients in the observation phase and 203/1,123 (18%) in the intervention phase were lost to follow-up. In the intervention phase, more patients received fluids (observation 714/978 [73%] versus intervention 874/1,123 [78%]; 95% CI 0.63, 0.94; p = 0.012), hospitalization was reduced (observation 578/978 [59%] versus intervention 548/1,123 [49%]; 95% CI 0.55, 0.79; p < 0.001), and admitted patients with severe AKI did not show a significantly lower mortality during follow-up (observation 27/135 [20%] versus intervention 21/178 [11.8%]; 95% CI 0.98, 3.52; p = 0.057). Of 504 patients with kidney function assessed during the 6-month follow-up, de novo CKD arose in 79/484 (16.3%), with no difference between the observation and intervention phase (95% CI 0.91, 2.47; p = 0.101). Overall mortality was 273/2,101 (13%) and was highest in those who had CKD (24/106; 23%), followed by those with AKD (128/760; 17%), AKI (85/628; 14%), and NKD (36/607; 6%). The main limitation of our study was the inability to determine the actual incidence of kidney dysfunction in the health centers as it was not feasible to screen all the patients due to the high numbers seen daily.ConclusionsThis multicenter, non-randomized feasibility study in low-resource settings demonstrates that it is feasible to implement a comprehensive program utilizing POC testing and protocol-based management to improve the recognition and management of AKI and AKD in high-risk patients in primary care.

Background. The microbiological and clinicoepidemiological profile of infective endocarditis (IE) has undergone significant change over time. The pattern of IE studied at local level provides broader vision in understanding the current scenario of this disease. This study aimed to depict the overall picture of IE and its changing profile by evaluating the microbiological and clinicoepidemiological features in the context of a tertiary care center of eastern Nepal. Methods. The descriptive study was conducted from September 2017 to August 2018 among IE patients presenting to B. P. Koirala Institute of Health Sciences, Nepal. Detailed history and clinical manifestations of patients were noted. Microorganisms isolated from the blood culture were processed for identification by standard microbiological methods, and susceptibility testings were done. Each patient was assessed daily during hospital stay. Results. Ten definite and 7 possible endocarditis cases were studied. The mean age was 41.4 ± 15.85 (17–70) years with predominance of male (4.7 : 1). Rheumatic heart disease (41.1%) was the most common underlying heart disease observed followed by injection drug user endocarditis (23.5%). All the cases had native valve endocarditis. Aortic valve was the most common valve involved (35.3%) followed by mitral, tricuspid, and pulmonary valves. Blood culture positivity was 53%. Staphylococcus aureus was the major causative agent responsible for 23.5% of the cases followed by Enterococcus faecium, Enterococcus faecalis, and Pseudomonas aeruginosa. Mortality of 2 cases (11.8%) was associated with S. aureus and P. aeruginosa. Majority of patients developed acute kidney injury (35.3%) and congestive cardiac failure (23.5%). Conclusion. IE patients in our center exhibited differences from the west in terms of age at presentation and predisposing factors but held similarity in terms of commonly isolated microorganisms. The changing patterns of IE, etiological agents, and their antimicrobial susceptibility observed in this study may be helpful for clinicians in formulating a new empirical antibiotic treatment protocol.

Background: Antiretroviral drugs are lifeline for patients living with HIV. Adverse drug reactions can compromise the compliance to antiretroviral therapy. The objectives of the study were to estimate the prevalence of adverse drug reactions and to assess its risk factors in patients living with HIV and receiving antiretroviral therapy. Methods: A prospective cohort study was conducted among 496 patients living with HIV at B.P. Koirala Institute of Health Sciences for a period of one year. Adverse drug reactions were evaluated based upon clinical history, clinical examination and investigations. Results: Majority of patients were of 31-45 year age group (58.1%) and on first-line antiretroviral therapy regimen (94.3%). Total of 240 adverse drug reactions were documented. Prevalence of adverse drug reaction was 34.7%. Skin rash, anemia and nausea and vomiting were the three most common adverse drug reactions. The adverse drug reactions were more common in patients having non-communicable diseases, chronic co-infections, taking more than 3 non-HIV drugs, second and third-line antiretroviral regimen and it was statistically significant (P-value < 0.05). Conclusions: Prevalence of adverse drug reaction was high in the patients living with HIV. Age, gender, co-infections, non-communicable diseases, taking more than three non-HIV drugs and second and third-line antiretroviral regimen were identified as possible risk factor for occurrence of adverse drug reactions and their prior identification is important to optimize the best suited antiretroviral regimen. Keywords: Adverse drug reactions; antiretroviral therapy; pharmacovigilance

Introduction In Nepal, approximately 31% of adult industrial employees have diabetes. While the prevention of type 2 diabetes through behavioural intervention has been disseminated, worksite could be an effective platform for the translation of this knowledge into action as employed adults spend most of their workday waking hours at workplaces.Methods and analysis We will conduct a randomised controlled trial to assess the effectiveness of a behavioural and a canteen intervention on diabetes risk reduction among those who are prediabetic at two worksites in eastern Nepal. We will recruit 162 adult full-time factory workers with haemoglobin A1c (HbA1c) of 5.7%–6.4% at baseline or fasting blood sugar of 100–125 mg/dL. The 8–14 months’ control period will be followed by the behavioural intervention where half of the participants will be randomised to receive the behavioural intervention and half will act as a control and will not receive any intervention. Then, all participants will receive the canteen intervention. The analysis will be intent-to-treat, comparing the difference in the change in HbA1c% between the behavioural intervention group and the control group using a two-sample t-test. The within-participant changes in HbA1c after 6 or more months on the canteen intervention among those not randomised to the behavioural intervention in the previous period will be assessed using the paired t-test.Ethics and dissemination Ethical approval was obtained from the Institutional Review Board at Yale School of Public Health, New Havens, USA and the Nepal Health Research Council.Trial registration number NCT04161937.

The clinical picture of infective endocarditis varies from the asymptomatic stage for a long duration to an acute fulminant course. A high index of suspicion is necessary whenever a patient presents with nonspecific symptoms and some peripheral clinical signs with a cardiac murmur. We report a case of sub-acute IE involving multiple left and right side cardiac valves with underlying rheumatic heart disease (RHD).

Introduction. Diabetes mellitus is a major cause of morbidity and mortality and places huge burden on public health funding. Diabetes affects quality of life through associated complications, comorbidity, and disease burden. Consequently, people have frequent healthcare visits. This study assessed quality of life and healthcare utilization patterns among type 2 diabetic populations in an urban area of eastern Nepal. Methods. A cross-sectional study was conducted among 270 participants of age ≥20 years with type 2 diabetes in Itahari using a semistructured questionnaire. A D-39 questionnaire was used to assess quality of life. Five wards were selected by systematic random sampling, and the population was proportionate according to the sample size. Multiple linear regressions were conducted to identify the factors associated with quality of life and its domains. Results. The highest mean score ± SD was found in the domain anxiety and worry (57.34 ± 11.08). About 18.5% of the participants perceived extremely affected quality of life. Hypertension (55.55%) was the most common comorbidity. Age, marital status, literacy, alcohol, disease duration, comorbidity, and complications were significantly associated with overall quality of life. In last 6 months of duration, 93.7% had hospital visits. Among them, 8.1% had emergency visit and 5.9% were admitted in the hospital. Conclusion. People with diabetes in this study were more affected in the domain anxiety and worry. The frequency of healthcare access and utilization in patients with type 2 diabetes was high. The quality of life among them could be improved by taking care on healthy behavior, comorbid conditions, and complications.

Background: The burden of non-communicable diseases has increased in the last few decades in low-and middle-income countries including in Nepal. There is limited data on population based prevalence of non-communicable diseases. Hence, this study aims to determine the nationwide prevalence of selected chronic non-communicable diseases in Nepal. Methods: A nationwide cross-sectional population-based study was conducted from 2016 to 2018. Data was collected electronically on android device inbuilt with research and monitoring software from 13200 eligible participants aged 20 years and above. Data was cleaned in SPSS version 20.0 and analyzed using Stata version 13.1. Results: The overall prevalence of selected non-communicable diseases was found to be chronic obstructive pulmonary disease 11.7% (95% CI: 10.5-12.9), diabetes mellitus 8.5% (95% CI: 7.8-9.3), chronic kidney disease 6.0% (95% CI: 5.5-6.6) and coronary artery disease 2.9% (95% CI: 2.4-3.4) in Nepal. Prevalence of non-communicable diseases varied across provinces. Higher prevalence of chronic obstructive pulmonary disease (25.1%, 95% CI: 18.1-33.8) in Karnali Province, diabetes (11.5%, 95% CI: 9.8-13.4) in Province 3, chronic kidney disease (6.8%, 95% CI: 5.6-8.1) in Gandaki Province and coronary artery disease in Gandaki (3.6%, 95% CI: 2.2-5.7) and Sudurpaschim Province (3.6%, 95% CI: 2.1-6.1) was observed. Conclusions: The study reported substantial proportion of adult population was found to have chronic non-communicable diseases in Nepal. The findings of this study may be useful for revising/updating multi-sectoral action plans on prevention and control of non-communicable diseases in Nepal. Keywords: Chronic kidney disease; chronic obstructive pulmonary disease; coronary artery disease; diabetes mellitus; non-communicable disease.

Introduction: Patients with heart failure (HF) have various co-morbidities that complicate management and may adversely affect outcomes. HF guidelines provide little discussion on this topic and evidence is sparse. Material and Methods: This is a descriptive cross-sectional study on 240 consecutive patients with HF admitted from September 2016 to July 2017 at B.P. Koirala Institute of Health Sciences (BPKIHS), Nepal. All patients admitted with diagnosis of HF with reduced or preserved ejection fraction (NYHA functional class III/IV) based on Framingham Criteria and echocardiography assessments were included. Pre-defined co-morbid conditions were assessed. Results: Mean age of patients was 53.5 years and 53% were female. Most patients were in NYHA class III or IV (25% and 75% respectively) and 28.3% had ischemia as a cause of HF. Among co-morbidities, 85% of patients with HF had at least one co-morbidity. Anemia (68.3%), coronary artery disease (30.4%), hypertension (26.6%), diabetes (18.7%) and chronic kidney disease (7.5%) were the co-morbidities with the highest prevalence. Chronic obstructive pulmonary disease (3.7%), sleep apnea (2.5%), hypothyroidism (2.5%) and stroke (2.5%) were less common. Of all patients, only 15% had no co-morbidity, 40% had one co-morbidity, 22% had two co-morbidities, and 13 % had three or more co-morbidities. Conclusion: Co-morbidities are common problems and anemia is the most common in our scenario which could be of multi-factorial etiology. Careful attention to the diagnosis and management of specific co-morbidities may help to improve outcomes in patients with HF. Journal of Nobel Medical College Volume 6, Number 2, Issue 11 (July-December, 2017) Page:35-41

Background: There have been very limited studies regarding health of the cement factory workers in Nepal. This study aimed to find out the prevalence of health problems and the factors associated with respiratory symptoms among the workers of Udayapur cement factory. Methods: This is a cross-sectional study conducted from March to August 2015 in Udayapur cement factory in eastern Nepal. All the workers working in the factory more than a year were included in the study. Thedata was collected by using a semi-structured questionnaire consisting of socio-demographic characteristics,type of work, reported health problems, use of personal protective measures.Chi-square test was used to determine the association of respiratory symptoms with related variables. Results: A total of 295 workers were included in this study with mean age of 45.9 years (SD=7.7). Majority 279 (94.6%) were males. The most common health problems were musculoskeletal pain (55.6%) followed by eye problems (33.2%). Among them, 17(21.1%) reported that they had at least one respiratory problem and chest tightness while running/climbing and wheeze were the most common. A total of 233 participants (79%) used at least one form of personal protective equipment. Low education, longer duration of work and smoking were found to be positively associated with respiratory symptoms. Conclusions: Respiratory problems were high among the workers of the cement factory. Proper use of PPEs and dust control measures should be promoted among the workers. Keywords: Cement factory; eastern Nepal; occupational health; respiratory problems.

Diagnosing and treating acute severe and recurrent antivenom-related anaphylaxis (ARA) is challenging and reported experience is limited. Herein, we describe our experience of severe ARA in patients with neurotoxic snakebite envenoming in Nepal. Patients were enrolled in a randomised, double-blind trial of high vs. low dose antivenom, given by intravenous (IV) push, followed by infusion. Training in ARA management emphasised stopping antivenom and giving intramuscular (IM) adrenaline, IV hydrocortisone, and IV chlorphenamine at the first sign/s of ARA. Later, IV adrenaline infusion (IVAI) was introduced for patients with antecedent ARA requiring additional antivenom infusions. Preantivenom subcutaneous adrenaline (SCAd) was introduced in the second study year (2012). Of 155 envenomed patients who received ≥ 1 antivenom dose, 13 (8.4%), three children (aged 5−11 years) and 10 adults (18−52 years), developed clinical features consistent with severe ARA, including six with overlapping signs of severe envenoming. Four and nine patients received low and high dose antivenom, respectively, and six had received SCAd. Principal signs of severe ARA were dyspnoea alone (n=5 patients), dyspnoea with wheezing (n=3), hypotension (n=3), shock (n=3), restlessness (n=3), respiratory/cardiorespiratory arrest (n=7), and early (n=1) and late laryngeal oedema (n=1); rash was associated with severe ARA in 10 patients. Four patients were given IVAI. Of the 8 (5.1%) deaths, three occurred in transit to hospital. Severe ARA was common and recurrent and had overlapping signs with severe neurotoxic envenoming. Optimising the management of ARA at different healthy system levels needs more research. This trial is registered with NCT01284855.

Background: Nepal is witnessing rise in non-communicable chronic diseases. Costs of the medicine, availability of the medicine for free in public health sectors and variation of price of medicines may play an important role in the management of chronic disease. The study was undertaken to find out the variation in price of drugs used for treating non communicable diseases among private pharmacies and availability of free essential medicines in public facilities. Methods: Randomly selected 33 public health centers and 13 pharmacies were included for the study. Availability of free essential medicines for treating selected chronic diseases was assessed in public health centers and percentage price variation in various branded drugs used for treating these diseases was assessed at the consumer level. Results: Out of 89 different formulations, variations between maximum and minimum priced brands of more than 100% were observed in 37 formulations and that of > 200% in 22 formulations. Thirty-seven formulations had more than 100% inter-pharmacy variation. The most commonly available free essential medicines was 4 mg salbutamol (88.57%) while the least available free essential drug was levothyroxine 5 mg (9.0%). Conclusions: Considerable variation in prices is seen among similar drugs and in prices of same drug in different pharmacies. These factors may have implications in the management of chronic disease in Nepal offsetting the government’s effort to control chronic diseases. Keywords: Chronic diseases; essential medicines; price variation.

Introduction: Muscle cramp is a common intradialytic complication observed in hemodialysis patients. Similarly Peripheral arterial disease is a common condition in the hemodialysis population. No study on intradialytic muscle cramp and its association with Peripheral arterial disease is yet reported from Nepal. Methods: Fifty patients with a diagnosis of End Stage Renal Disease who were on hemodialysis were studied over a period of one year. Muscle cramp was defined clinically as contractions of a large muscle group and Peripheral arterial disease was diagnosed on the basis of the ankle –brachial index. Chi square (X2) test was used to determine the association between Intradialytic Muscle cramps and Peripheral Arterial Disease. Results: A total of 50 End Stage Renal Disease patients were analyzed. The mean age of the patient was 49.81±12.63 years. The major causes of End Stage Renal Disease in the study population was Chronic Glomerulonephritis 40 % (n=20). Muscle cramps were present in 26% (n=13) cases. Peripheral arterial disease was present in 30% (n=15) of patients. However there was no statistically significant association between the presence of Intradialytic Muscle cramps and peripheral arterial disease (p value =0.18) Conclusions: Intradialytic Muscle cramps and peripheral arterial disease were common occurrence in end stage renal disease patients on hemodialysis patients, however there was no association between the presence of intradialytic Muscle cramps and peripheral arterial disease. Keywords: end stage renal disease; intradialytic muscle cramps; peripheral arterial disease.

BACKGROUND:Currently, there is inadequate evidence on which to base clinical management of neurotoxic snakebite envenoming, especially in the choice of initial antivenom dosage. This randomised controlled trial compared the effectiveness and safety of high versus low initial antivenom dosage in victims of neurotoxic envenoming. METHODOLOGY/ PRINCIPAL FINDINGS:This was a balanced, randomised, double-blind trial that was conducted in three health care centers located in the Terai plains of Nepal. Participants received either low (two vials) or high (10 vials) initial dosage of Indian polyvalent antivenom. The primary composite outcome consisted of death, the need for assisted ventilation and worsening/recurrence of neurotoxicity. Hourly evaluations followed antivenom treatment. Between April 2011 and October 2012, 157 snakebite victims were enrolled, of which 154 were analysed (76 in the low and 78 in the high initial dose group). Sixty-seven (43·5%) participants met the primary outcome definition. The proportions were similar in the low (37 or 48.7%) vs. high (30 or 38.5%) initial dose group (difference = 10·2%, 95%CI [-6·7 to 27·1], p = 0·264). The mean number of vials used was similar between treatment groups. Overall, patients bitten by kraits did worse than those bitten by cobras. The occurrence of treatment-related adverse events did not differ among treatment groups. A total of 19 serious adverse events occurred, including seven attributed to antivenom. CONCLUSIONS:This first robust trial investigating antivenom dosage for neurotoxic snakebite envenoming shows that the antivenom currently used in Nepal performs poorly. Although the high initial dose regimen is not more effective than the low initial dose, it offers the practical advantage of being a single dose, while not incurring higher consumption or enhanced risk of adverse reaction. The development of new and more effective antivenoms that better target the species responsible for bites in the region will help improve future patients' outcomes. TRIAL REGISTRATION:The study was registered on clinicaltrials.gov (NCT01284855) (GJ 5/1).

Introduction: Kidney Biopsy is an important diagnostic tool in Nephrology. It is useful in Nephrology in terms of diagnosis, prognosis and management. There is little information on renal biopsy data from central Nepal. We describe our center`s experience in kidney biopsy in term of histological patterns, complications and outcomes. Methods: We prospectively analyzed the biopsies data of patients over a period of one and half year. All kinds of kidney disease patients were included for kidney biopsy, irrespective of their clinical syndromes and underlying diagnosis. Results: A total of 75 biopsies were analyzed. Majority of them were females; 56% (n=42). Most of the biopsies; 84% (n=63) were from younger subjects ≤ 45 years and majority of them fell in the age group 11-20 years. Most common clinical renal syndrome to undergo biopsy was Sub Nephrotic range Proteinuria in 53.3% (n=40). Among comorbid conditions, 53.3% (n=40) had Hypertension. The most common histological pattern seen was Mesangial proliferative Glomerulonephritis (MesPGN) seen in 24% (n=18). Among complications associated with the procedure, macroscopic hematuria was seen in 6.7% (n=5) cases and clinically significant perinephric hematoma causing pain was seen in 5.3% (n=4). There was no mortality associated with biopsy procedure. Conclusions: Sub Nephrotic range Proteinuria was the commonest clinical renal Syndrome observed. In terms of renal histology, Mesangial Proliferative Glomerulonephritis (MesPGN) was the commonest histological pattern observed. Kidney biopsy is a safe procedure without any significant adverse events. Keywords: Kidney biopsy, sub nephrotic range proteinuria, mesangial proliferative glomerulonephritis