Core outcome set for intervention research on snakebite envenomation in South Asia.

BACKGROUND: The 2019 WHO strategy to reduce snakebite burden emphasises the need for fostering research on snakebite treatments. A core outcome set (COS) is a consensus minimal list of outcomes that should be measured in research on a particular condition. We aimed to develop a COS for snakebite research in South Asia, the region with the highest burden. METHODS: We used data from a systematic review of outcomes to develop a long list of outcomes which were rated in two rounds of online Delphi survey with healthcare providers, patients and the public, and potential COS users to develop a COS for intervention research on snakebite treatments in South Asia for five intervention groups. Subsequently, meetings, consultations and workshops were organised to reach further consensus. We defined the consensus criteria a priori. RESULTS: Overall, 72 and 61 people, including patients and the public, participated in round I and round II of the Delphi, respectively. Consensus COSs (including definition and time points) were developed for interventions that prevent adverse reaction to snake antivenom (three outcomes), specifically manage neurotoxic manifestations (five outcomes), specifically manage haematological manifestations (five outcomes) and those that act against snake venom (seven) outcomes. A priori criteria for inclusion in COS were not met for COS on interventions for management of the bitten part. CONCLUSION: The COS contributes to improving research efficiency by standardising outcome measurement in South Asia. It also provides methodological insights for future development of COS, beyond snakebite.

Frailty and chronic diseases: A bi-directional relationship.

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.

Evaluation of hydroxychloroquine or chloroquine for the prevention of COVID-19 (COPCOV): A double-blind, randomised, placebo-controlled trial.

BACKGROUND: Hydroxychloroquine (HCQ) has proved ineffective in treating patients hospitalised with Coronavirus Disease 2019 (COVID-19), but uncertainty remains over its safety and efficacy in chemoprevention. Previous chemoprevention randomised controlled trials (RCTs) did not individually show benefit of HCQ against COVID-19 and, although meta-analysis did suggest clinical benefit, guidelines recommend against its use. METHODS AND FINDINGS: Healthy adult participants from the healthcare setting, and later from the community, were enrolled in 26 centres in 11 countries to a double-blind, placebo-controlled, randomised trial of COVID-19 chemoprevention. HCQ was evaluated in Europe and Africa, and chloroquine (CQ) was evaluated in Asia, (both base equivalent of 155 mg once daily). The primary endpoint was symptomatic COVID-19, confirmed by PCR or seroconversion during the 3-month follow-up period. The secondary and tertiary endpoints were: asymptomatic laboratory-confirmed Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection; severity of COVID-19 symptoms; all-cause PCR-confirmed symptomatic acute respiratory illness (including SARS-CoV-2 infection); participant reported number of workdays lost; genetic and baseline biochemical markers associated with symptomatic COVID-19, respiratory illness and disease severity (not reported here); and health economic analyses of HCQ and CQ prophylaxis on costs and quality of life measures (not reported here). The primary and safety analyses were conducted in the intention-to-treat (ITT) population. Recruitment of 40,000 (20,000 HCQ arm, 20,000 CQ arm) participants was planned but was not possible because of protracted delays resulting from controversies over efficacy and adverse events with HCQ use, vaccine rollout in some countries, and other factors. Between 29 April 2020 and 10 March 2022, 4,652 participants (46% females) were enrolled (HCQ/CQ n = 2,320; placebo n = 2,332). The median (IQR) age was 29 (23 to 39) years. SARS-CoV-2 infections (symptomatic and asymptomatic) occurred in 1,071 (23%) participants. For the primary endpoint the incidence of symptomatic COVID-19 was 240/2,320 in the HCQ/CQ versus 284/2,332 in the placebo arms (risk ratio (RR) 0.85 [95% confidence interval, 0.72 to 1.00; p = 0.05]). For the secondary and tertiary outcomes asymptomatic SARS-CoV-2 infections occurred in 11.5% of HCQ/CQ recipients and 12.0% of placebo recipients: RR: 0.96 (95% CI, 0.82 to 1.12; p = 0.6). There were no differences in the severity of symptoms between the groups and no severe illnesses. HCQ/CQ chemoprevention was associated with fewer PCR-confirmed all-cause respiratory infections (predominantly SARS-CoV-2): RR 0.61 (95% CI, 0.42 to 0.88; p = 0.009) and fewer days lost to work because of illness: 104 days per 1,000 participants over 90 days (95% CI, 12 to 199 days; p < 0.001). The prespecified meta-analysis of all published pre-exposure RCTs indicates that HCQ/CQ prophylaxis provided a moderate protective benefit against symptomatic COVID-19: RR 0.80 (95% CI, 0.71 to 0.91). Both drugs were well tolerated with no drug-related serious adverse events (SAEs). Study limitations include the smaller than planned study size, the relatively low number of PCR-confirmed infections, and the lower comparative accuracy of serology endpoints (in particular, the adapted dried blood spot method) compared to the PCR endpoint. The COPCOV trial was registered with ClinicalTrials.gov; number NCT04303507. INTERPRETATION: In this large placebo-controlled, double-blind randomised trial, HCQ and CQ were safe and well tolerated in COVID-19 chemoprevention, and there was evidence of moderate protective benefit in a meta-analysis including this trial and similar RCTs. TRIAL REGISTRATION: ClinicalTrials.gov NCT04303507; ISRCTN Registry ISRCTN10207947.

Correction: Decentralization and Integration of Advanced Cardiac Care for the World's Poorest Billion Through the PEN-Plus Strategy for Severe Chronic Non-Communicable Disease.

[This corrects the article DOI: 10.5334/gh.1313.].

Mortality and Morbidity in Adults With Rheumatic Heart Disease.

Importance: Rheumatic heart disease (RHD) remains a public health issue in low- and middle-income countries (LMICs). However, there are few large studies enrolling individuals from multiple endemic countries. Objective: To assess the risk and predictors of major patient-important clinical outcomes in patients with clinical RHD. Design, Setting, and Participants: Multicenter, hospital-based, prospective observational study including 138 sites in 24 RHD-endemic LMICs. Main Outcomes and Measures: The primary outcome was all-cause mortality. Secondary outcomes were cause-specific mortality, heart failure (HF) hospitalization, stroke, recurrent rheumatic fever, and infective endocarditis. This study analyzed event rates by World Bank country income groups and determined the predictors of mortality using multivariable Cox models. Results: Between August 2016 and May 2022, a total of 13 696 patients were enrolled. The mean age was 43.2 years and 72% were women. Data on vital status were available for 12 967 participants (94.7%) at the end of follow-up. Over a median duration of 3.2 years (41 478 patient-years), 1943 patients died (15% overall; 4.7% per patient-year). Most deaths were due to vascular causes (1312 [67.5%]), mainly HF or sudden cardiac death. The number of patients undergoing valve surgery (604 [4.4%]) and HF hospitalization (2% per year) was low. Strokes were infrequent (0.6% per year) and recurrent rheumatic fever was rare. Markers of severe valve disease, such as congestive HF (HR, 1.58 [95% CI, 1.50-1.87]; P < .001), pulmonary hypertension (HR, 1.52 [95% CI, 1.37-1.69]; P < .001), and atrial fibrillation (HR, 1.30 [95% CI, 1.15-1.46]; P < .001) were associated with increased mortality. Treatment with surgery (HR, 0.23 [95% CI, 0.12-0.44]; P < .001) or valvuloplasty (HR, 0.24 [95% CI, 0.06-0.95]; P = .042) were associated with lower mortality. Higher country income level was associated with lower mortality after adjustment for patient-level factors. Conclusions and Relevance: Mortality in RHD is high and is correlated with the severity of valve disease. Valve surgery and valvuloplasty were associated with substantially lower mortality. Study findings suggest a greater need to improve access to surgical and interventional care, in addition to the current approaches focused on antibiotic prophylaxis and anticoagulation.

Decentralization and Integration of Advanced Cardiac Care for the World's Poorest Billion Through the PEN-Plus Strategy for Severe Chronic Non-Communicable Disease.

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.

Prevalence of multimorbidity and its associated risk factors among population of Mechinagar municipality of Nepal.

Background: Multimorbidity is a group of conditions, it has significant impact on the population as a whole, resulting in lower quality of life, higher mortality, frequent use of medical services, and consequently higher healthcare costs. The objective of this study is to document the prevalence of common multimorbidity and its associated risk factors among population of Mechinagar Municipality. Methods: Community-based cross-sectional study was conducted where selected multimorbidity were assessed in selected areas of Mechinagar municipality of Jhapa District . Systematic random sampling technique was used to select 590 adult participants from three pre-defined pocket areas. Pre-designed semi-structured multimorbidity assessment questionnaire for primary care (MAQ-PC)was used to assess prevalence of multimorbidity. Multiple logistic regression was conducted to identify the strongest determinants of multimorbidity. Results: The prevalence of multimorbidity was 22.4%.Hypertension, Diabetes mellitus and COPD was seen in 39.2%, 7.8.% and 4.4% of the participants respectively . Participants with advancing age i. e. 40-49yrs were 12.62 times (AOR) more likely to have multimorbidity compared to their counterparts who were 20-29yrs old( p=<0.01,CI3.01-15.28) after adjusting for occupation, physical activity and family history of kidney disease. Working individuals, Physical inactivity and positive family history of kidney disease were the strongest determinates of multimorbidity. Conclusions: The study revealed that participants with increasing age, working individuals, physical inactivity and family history of kidney disease were more vulnerable of having multimorbidity. The findings of our study indicate need of intervention strategies and community-based health promotion programs in reducing burden of chronic disease among adult population.

Posterior reversible encephalopathy syndrome due to nonadherence to antihypertensive treatment: A case report from Nepal.

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 heart disease in school-attending Nepalese children: A descriptive analysis of the national heart screening database.

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.

Vulnerability to snakebite envenoming and access to healthcare in the Terai region of Nepal: a geospatial analysis.

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.

Severe homozygous HbE disease: the first case report from Nepal.

Hemoglobin E (HbE) is the most prevalent hemoglobinopathy in the eastern Indian subcontinent. We presented the case of a 53-year-old male from Nepal with a history of multiple blood transfusions who presented with abdominal fullness for 15 years and easy fatigability for 2 months. He had pallor and massive splenomegaly. Laboratory parameters showed pancytopenia with microcytic anemia, indirect hyperbilirubinemia, target cells in the peripheral smear and iron overload. A computed tomography scan of the abdomen showed multiple splenic infarcts. Hemoglobin electrophoresis was suggestive of HbE homozygous disease. Based on these findings, we made a diagnosis of HbE homozygous disease. We provided symptomatic treatment and folic acid supplementation and counseled him for splenectomy and genetic screening. Our case highlighted the uncommon presentation of Hb E disease.

Global Variations in Heart Failure Etiology, Management, and Outcomes.

Importance: Most epidemiological studies of heart failure (HF) have been conducted in high-income countries with limited comparable data from middle- or low-income countries. Objective: To examine differences in HF etiology, treatment, and outcomes between groups of countries at different levels of economic development. Design, Setting, and Participants: Multinational HF registry of 23 341 participants in 40 high-income, upper-middle-income, lower-middle-income, and low-income countries, followed up for a median period of 2.0 years. Main Outcomes and Measures: HF cause, HF medication use, hospitalization, and death. Results: Mean (SD) age of participants was 63.1 (14.9) years, and 9119 (39.1%) were female. The most common cause of HF was ischemic heart disease (38.1%) followed by hypertension (20.2%). The proportion of participants with HF with reduced ejection fraction taking the combination of a ß-blocker, renin-angiotensin system inhibitor, and mineralocorticoid receptor antagonist was highest in upper-middle-income (61.9%) and high-income countries (51.1%), and it was lowest in low-income (45.7%) and lower-middle-income countries (39.5%) (P < .001). The age- and sex- standardized mortality rate per 100 person-years was lowest in high-income countries (7.8 [95% CI, 7.5-8.2]), 9.3 (95% CI, 8.8-9.9) in upper-middle-income countries, 15.7 (95% CI, 15.0-16.4) in lower-middle-income countries, and it was highest in low-income countries (19.1 [95% CI, 17.6-20.7]). Hospitalization rates were more frequent than death rates in high-income countries (ratio = 3.8) and in upper-middle-income countries (ratio = 2.4), similar in lower-middle-income countries (ratio = 1.1), and less frequent in low-income countries (ratio = 0.6). The 30-day case-fatality rate after first hospital admission was lowest in high-income countries (6.7%), followed by upper-middle-income countries (9.7%), then lower-middle-income countries (21.1%), and highest in low-income countries (31.6%). The proportional risk of death within 30 days of a first hospital admission was 3- to 5-fold higher in lower-middle-income countries and low-income countries compared with high-income countries after adjusting for patient characteristics and use of long-term HF therapies. Conclusions and Relevance: This study of HF patients from 40 different countries and derived from 4 different economic levels demonstrated differences in HF etiologies, management, and outcomes. These data may be useful in planning approaches to improve HF prevention and treatment globally.

Clinical manifestations of delayed reaction following mass hornet envenomation: a case report.

Delayed reaction following mass hornet envenomation is associated with various clinical manifestations. Case Presentation: The authors present a case of a 24-year-old male from eastern Nepal, who presented following mass envenomation by hornet stings. He had progressive yellowish discoloration of skin and sclera, myalgia, fever, and dizziness. He had passage of tea-coloured urine followed by anuria. Laboratory investigations suggested acute kidney injury, rhabdomyolysis, and acute liver injury. The authors managed the patient with supportive measures and haemodialysis. There was complete recovery of liver and renal function in the patient. Discussion: The findings in this patient were similar to other cases reported in the literature. These patients must be managed supportively, with few requiring renal replacement therapy. Most of these patients recover completely. In low-middle-income countries like Nepal, delay in seeking care and delay in reaching care is associated with severe clinical manifestations. Delayed presentation can lead to renal shutdown and mortality; hence, early intervention is simple, and, crucial. Conclusion: This case highlights the occurrence of delayed reaction following mass envenomation by hornets. Also, the authors show an approach to managing such patients, similar to managing any other case with acute kidney injury. In these cases, an early simple intervention can prevent mortality. It is crucial to train healthcare workers regarding toxin induced acute kidney injury and the importance of early identification and intervention.

Correction: The 20-minute whole blood clotting test (20WBCT) for snakebite coagulopathy-A systematic review and meta-analysis of diagnostic test accuracy.

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

Management of snake bite during third trimester of pregnancy with coagulopathy and delivery of a live baby in resource-limited setting in Nepal: a case report.

We reported a case of snakebite in an 18-year-old woman, Gravida 2 Para 1+0 in the third trimester of pregnancy who presented with pain and swelling over the left hand and forearm and vaginal spotting. The laboratory investigations revealed coagulopathy attributed to green pit viper envenomation. On the fourth day of admission, the patient developed sudden abdominal pain and massive per vaginal bleeding with haemorrhagic shock, most likely abruptio placentae. In Nepal, no anti-snake venom has been developed for green pit-viper. So, she was managed conservatively, including blood transfusion, and delivered a single live female baby without any foetal complications. The patient was discharged along with the baby after 8 days of hospitalization. This case demonstrated that vigilant observation and appropriate resuscitation with fluids and blood products could save mother and baby in pit viper envenomation cases in settings where specific anti-snake venom is unavailable.

Colchicine and aspirin in community patients with COVID-19 (ACT): an open-label, factorial, randomised, controlled trial.

BACKGROUND: The large number of patients worldwide infected with the SARS-CoV-2 virus has overwhelmed health-care systems globally. The Anti-Coronavirus Therapies (ACT) outpatient trial aimed to evaluate anti-inflammatory therapy with colchicine and antithrombotic therapy with aspirin for prevention of disease progression in community patients with COVID-19. METHODS: The ACT outpatient, open-label, 2 × 2 factorial, randomised, controlled trial, was done at 48 clinical sites in 11 countries. Patients in the community aged 30 years and older with symptomatic, laboratory confirmed COVID-19 who were within 7 days of diagnosis and at high risk of disease progression were randomly assigned (1:1) to receive colchicine 0·6 mg twice daily for 3 days and then 0·6 mg once daily for 25 days versus usual care, and in a second (1:1) randomisation to receive aspirin 100 mg once daily for 28 days versus usual care. Investigators and patients were not masked to treatment allocation. The primary outcome was assessed at 45 days in the intention-to-treat population; for the colchicine randomisation it was hospitalisation or death, and for the aspirin randomisation it was major thrombosis, hospitalisation, or death. The ACT outpatient trial is registered at ClinicalTrials.gov, NCT04324463 and is ongoing. FINDINGS: Between Aug 27, 2020, and Feb 10, 2022, 3917 patients were randomly assigned to colchicine or control and to aspirin or control; after excluding 36 patients due to administrative reasons 3881 individuals were included in the analysis (n=1939 colchicine vs n=1942 control; n=1945 aspirin vs 1936 control). Follow-up was more than 99% complete. Overall event rates were 5 (0·1%) of 3881 for major thrombosis, 123 (3·2%) of 3881 for hospitalisation, and 23 (0·6%) of 3881 for death; 66 (3·4%) of 1939 patients allocated to colchicine and 65 (3·3%) of 1942 patients allocated to control experienced hospitalisation or death (hazard ratio [HR] 1·02, 95% CI 0·72-1·43, p=0·93); and 59 (3·0%) of 1945 of patients allocated to aspirin and 73 (3·8%) of 1936 patients allocated to control experienced major thrombosis, hospitalisation, or death (HR 0·80, 95% CI 0·57-1·13, p=0·21). Results for the primary outcome were consistent in all prespecified subgroups, including according to baseline vaccination status, timing of randomisation in relation to onset of symptoms (post-hoc analysis), and timing of enrolment according to the phase of the pandemic (post-hoc analysis). There were more serious adverse events with colchicine than with control (34 patients [1·8%] of 1939 vs 27 [1·4%] of 1942) but none in either group that led to discontinuation of study interventions. There was no increase in serious adverse events with aspirin versus control (31 [1·6%] vs 31 [1·6%]) and none that led to discontinuation of study interventions. INTERPRETATION: The results provide no support for the use of colchicine or aspirin to prevent disease progression or death in outpatients with COVID-19. FUNDING: Canadian Institutes for Health Research, Bayer, Population Health Research Institute, Hamilton Health Sciences Research Institute, and Thistledown Foundation. TRANSLATIONS: For the Portuguese, Russian and Spanish translations of the abstract see Supplementary Materials section.

Outcomes in intervention research on snakebite envenomation: a systematic review.

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.

Corrigendum to "What is the impact of snakebite envenoming on domestic animals? A nation-wide community-based study in Nepal and Cameroon" [Toxicon: X 9 (2021) 100068].

[This corrects the article DOI: 10.1016/j.toxcx.2021.100068.].

Factors associated with health-related quality of life in heart failure in 23 000 patients from 40 countries: results of the G-CHF research programme.

AIMS: To examine clinical and social correlates of health-related quality of life (HRQL) in patients with heart failure (HF) from high- (HIC), upper middle- (UMIC), lower middle- (LMIC) and low-income (LIC) countries. METHODS AND RESULTS: Between 2017 and 2020, 23 292 patients with HF (32% inpatients, 61% men) from 40 countries were enrolled in the Global Congestive Heart Failure study. HRQL was recorded at baseline using the Kansas City Cardiomyopathy Questionnaire (KCCQ)-12. In a cross-sectional analysis, we compared age- and sex-adjusted mean KCCQ-12 summary scores (SS: 0-100, higher = better) between patients from different country income levels. We used multivariable linear regression examining correlations (estimated coefficients) of KCCQ-12-SS with sociodemographic, comorbidity, treatment and symptom covariates. The adjusted model (37 covariates) was informed by univariable findings, clinical importance and backward selection. Mean age was 63 years and 40% of patients were in New York Heart Association (NYHA) class III-IV. Average HRQL was 55 SD 27. It was 62.5 (95% confidence interval [CI] 62.0-63.1) in HIC, 56.8 (56.1-57.4) in UMIC, 48.6 (48.0-49.3) in LMIC, and 38.5 (37.3-39.7) in LICs (p < 0.0001). Strong correlates (estimated coefficient [95% CI]) of KCCQ-12-SS were NYHA class III versus class I/II (-12.1 [-12.8 to -11.4] and class IV versus class I/II (-16.5 [-17.7 to -15.3]), effort dyspnoea (-9.5 [-10.2 to -8.8]) and living in LIC versus HIC (-5.8 [-7.1 to -4.4]). Symptoms explained most of the KCCQ-12-SS variability (partial R2  = 0.32 of total adjusted R2  = 0.51), followed by sociodemographic factors (R2  = 0.12). Results were consistent in populations across income levels. CONCLUSION: The most important correlates of HRQL in HF patients relate to HF symptom severity, irrespective of country income level.