Addressing the burden of snakebite: analysing policy prioritisation, evaluating health systems, and fostering research on treatments

Introduction The World Health Organization (WHO) estimates 5.4 million snakebites annually. In 2019, WHO released a strategy to halve the burden of snakebite by 2030. This doctoral research aimed to generate practice and policy relevant evidence at three levels: globally, by understanding the prioritisation process in the WHO; nationally, in India, by evaluating the primary health care (PHC) system; and regionally, in South Asia, by fostering research on treatments. Methods To understand the global prioritisation of snakebite, I conducted a policy analysis, using interviews and documents as data sources. To evaluate health systems in India, I analysed secondary data for the first nationwide assessment of structural capacity and continuum of snakebite care. To understand health systems resilience, I used quantitative (analysis of facility-level data) and qualitative (interviews) approaches to understand the effects of COVID-19 and conducted an evidence synthesis on the effect of climate change. Through an overview of systematic reviews of treatments, I identified the need for a core outcome set (COS) on snakebite. I developed a COS for snakebite research in South Asia, by conducting a systematic review of outcomes and a Delphi survey. Results The policy analysis identified factors which enabled prioritisation of snakebite, and identified unaddressed challenges of sustaining legitimacy, and acceptance within the neglected tropical disease community. I identified structural limitations of the PHC system and gaps in referral pathways, in India. Relevant to the context, I report, how COVID-19 accentuated existing barriers, and identified that the choice of provider is a complex process with multiple factors interplaying. Evidence synthesis indicates the need to prepare health systems for possible geographic shifts in snakebite burden due to climate change. The overview of systematic reviews identified gaps in the evidence ecosystem. By developing a COS for future intervention research on snakebite treatments, I addressed the gap of non-standardised measurement of outcomes. Conclusion The findings of the thesis, provides contextually relevant evidence aligned with pillars of the WHO strategy, to practice and policy at global, national, sub-national, and program level. The policy analysis and COS work provides broader methodological insights, beyond snakebite

Diagnosis and management of preeclampsia in community settings in low and middle-income countries

Hypertensive disorders of pregnancy contribute significantly to maternal mortality and morbidity. Preeclampsia belongs to the spectrum of hypertensive disorders of pregnancy and if undiagnosed and/or untreated leads to fatal consequences for both the mother and the baby. Early detection and prevention of preeclampsia is limited by uncertainty in the knowledge about its etiopathogenesis. While much work has been done in establishing clinical guidelines for management of preeclampsia in the hospital or tertiary care settings, there is considerable lack of work in the domain of evidence-based guidelines for screening, identification and management of preeclampsia at the community-level. The article reviews these issues with special considerations and to challenges faced in low and middle-income countries. There is a need to focus on low-cost screening and interventions in the community to achieve a significant impact on preventable maternal and fetal mortality in order to control the burden of preeclampsia significantly as well as investing on more research at primary care level to improve the evidence base for community-level interventions

Cost-effectiveness of interventions to control cardiovascular diseases and diabetes mellitus in South Asia: a systematic review

OBJECTIVES: More than 80% of cardiovascular diseases (CVD) and diabetes mellitus (DM) burden now lies in low and middle-income countries. Hence, there is an urgent need to identify and implement the most cost-effective interventions, particularly in the resource-constraint South Asian settings. Thus, we aimed to systematically review the cost-effectiveness of individual-level, group-level and population-level interventions to control CVD and DM in South Asia. METHODS: We searched 14 electronic databases up to August 2016. The search strategy consisted of terms related to 'economic evaluation', 'CVD', 'DM' and 'South Asia'. Per protocol two reviewers assessed the eligibility and methodological quality of studies using standard checklists, and extracted incremental cost-effectiveness ratios of interventions. RESULTS: Of the 2949 identified studies, 42 met full inclusion criteria. Critical appraisal of studies revealed 15 excellent, 18 good and 9 poor quality studies. Most studies were from India (n=37), followed by Bangladesh (n=3), Pakistan (n=2) and Bhutan (n=1). The economic evaluations were based on observational studies (n=9), randomised trials (n=12) and decision models (n=21). Together, these studies evaluated 301 policy or clinical interventions or combination of both. We found a large number of interventions were cost-effective aimed at primordial prevention (tobacco taxation, salt reduction legislation, food labelling and food advertising regulation), and primary and secondary prevention (multidrug therapy for CVD in high-risk group, lifestyle modification and metformin treatment for diabetes prevention, and screening for diabetes complications every 2-5 years). Significant heterogeneity in analytical framework and outcome measures used in these studies restricted meta-analysis and direct ranking of the interventions by their degree of cost-effectiveness. CONCLUSIONS: The cost-effectiveness evidence for CVD and DM interventions in South Asia is growing, but most evidence is from India and limited to decision modelled outcomes. There is an urgent need for formal health technology assessment and policy evaluations in South Asia using local research data. PROSPERO REGISTRATION NUMBER: CRD42013006479

Cost-effectiveness of interventions to control cardiovascular diseases and type 2 diabetes mellitus in South Asia: protocol for a systematic review.

INTRODUCTION: While a number of strategies are being implemented to control cardiovascular diseases (CVDs) and type 2 diabetes mellitus (T2DM), the cost-effectiveness of these in the South Asian context has not been systematically evaluated. We aim to systematically review the economic (cost-effectiveness) evidence available on the individual-, group- and population-level interventions for control of CVD and T2DM in South Asia. METHODS AND ANALYSIS: This review will consider all relevant economic evaluations, either conducted alongside randomised controlled trials or based on decision modelling estimates. These studies must include participants at risk of developing CVD/T2DM or with established disease in one or more of the South Asian countries (India, Bangladesh, Pakistan, Sri Lanka, Nepal, Maldives, Bhutan and Afghanistan). We will identify relevant papers by systematically searching all major databases and registries. Selected articles will be screened by two independent researchers. Methodological quality of the studies will be assessed using a modified Drummond and a Phillips checklist. Cochrane guidelines will be followed for bias assessment in the effectiveness studies. RESULTS: Results will be presented in line with the PRISMA (Preferred Reporting Items for Systematic review and Meta-analysis) checklist, and overall quality of evidence will be presented as per the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) approach. ETHICS AND DISSEMINATION: The study has received ethics approval from the All India Institute of Medical Sciences, New Delhi, India. The results of this review will provide policy-relevant recommendations for the uptake of cost-effectiveness evidence in prioritising decisions on essential chronic disease care packages for South Asia. STUDY REGISTRATION NUMBER: PROSPERO CRD42013006479

School policies, built environment and practices for non-communicable disease (NCD) prevention and control in schools of Delhi, India.

OBJECTIVE: To assess school policies, built environment and practices for prevention and control of non-communicable diseases in schools of Delhi, India. METHODS: School built environments and policies were assessed using a structured observation checklist in 10 private and 9 government schools which were randomly selected from all 184 co-educational schools with primary to senior secondary level education in Delhi, India. A self-administered questionnaire was also completed by teachers from each school (n = 19) to capture information specific to school policies. Surveys were also conducted with parent of students in class II (aged 6-7 years; n = 574) and student in class XI (aged 15-16 years, n = 755) to understand school practices. RESULTS: The majority of government (88.9%; n = 8) and private (80%; n = 8) schools reported having comprehensive school health policy. In terms of specific health behaviours, policies related to diet and nutrition in government schools were mostly restricted to primary levels with provision of the mid-day meal programme. All schools had two physical education periods per week of about 45-50 minutes. Most schools were compliant with tobacco-free school guidelines (n = 15 out of 19) and had alcohol control policies (n = 13 out of 19). Parent and student reports of practices indicated that school policies were not consistently implemented. CONCLUSION: Most schools in Delhi have policies that address health behaviours in students, but there was considerable variation in the types and number of policies and school environments. Government schools are more likely to have policies in place than private schools. Further work is needed to evaluate how these policies are implemented and to assess their impact on health outcomes

Delays in hospital admissions in patients with fractures across 18 low-income and middle-income countries (INORMUS): a prospective observational study

© 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license Background: The Lancet Commission on Global Surgery established the Three Delays framework, categorising delays in accessing timely surgical care into delays in seeking care (First Delay), reaching care (Second Delay), and receiving care (Third Delay). Globally, knowledge gaps regarding delays for fracture care, and the lack of large prospective studies informed the rationale for our international observational study. We investigated delays in hospital admission as a surrogate for accessing timely fracture care and explored factors associated with delayed hospital admission. Methods: In this prospective observational substudy of the ongoing International Orthopaedic Multicenter Study in Fracture Care (INORMUS), we enrolled patients with fracture across 49 hospitals in 18 low-income and middle-income countries, categorised into the regions of China, Africa, India, south and east Asia, and Latin America. Eligible patients were aged 18 years or older and had been admitted to a hospital within 3 months of sustaining an orthopaedic trauma. We collected demographic injury data and time to hospital admission. Our primary outcome was the number of patients with open and closed fractures who were delayed in their admission to a treating hospital. Delays for patients with open fractures were defined as being more than 2 h from the time of injury (in accordance with the Lancet Commission on Global Surgery) and for those with closed fractures as being a delay of more than 24 h. Secondary outcomes were reasons for delay for all patients with either open or closed fractures who were delayed for more than 24 h. We did logistic regression analyses to identify risk factors of delays of more than 2 h in patients with open fractures and delays of more than 24 h in patients with closed fractures. Logistic regressions were adjusted for region, age, employment, urban living, health insurance, interfacility referral, method of transportation, number of fractures, mechanism of injury, and fracture location. We further calculated adjusted relative risk (RR) from adjusted odds ratios, adjusted for the same variables. This study was registered with ClinicalTrials.gov, NCT02150980, and is ongoing. Findings: Between April 3, 2014, and May 10, 2019, we enrolled 31 255 patients with fractures, with a median age of 45 years (IQR 31–62), of whom 19 937 (63·8%) were men, and 14 524 (46·5%) had lower limb fractures, making them the most common fractures. Of 5256 patients with open fractures, 3778 (71·9%) were not admitted to hospital within 2 h. Of 25 999 patients with closed fractures, 7141 (27·5%) were delayed by more than 24 h. Of all regions, Latin America had the greatest proportions of patients with delays (173 [88·7%] of 195 patients with open fractures; 426 [44·7%] of 952 with closed fractures). Among patients delayed by more than 24 h, the most common reason for delays were interfacility referrals (3755 [47·7%] of 7875) and Third Delays (cumulatively interfacility referral and delay in emergency department: 3974 [50·5%]), while Second Delays (delays in reaching care) were the least common (423 [5·4%]). Compared with other methods of transportation (eg, walking, rickshaw), ambulances led to delay in transporting patients with open fractures to a treating hospital (adjusted RR 0·66, 99% CI 0·46–0·93). Compared with patients with closed lower limb fractures, patients with closed spine (adjusted RR 2·47, 99% CI 2·17–2·81) and pelvic (1·35, 1·10–1·66) fractures were most likely to have delays of more than 24 h before admission to hospital. Interpretation: In low-income and middle-income countries, timely hospital admission remains largely inaccessible, especially among patients with open fractures. Reducing hospital-based delays in receiving care, and, in particular, improving interfacility referral systems are the most substantial tools for reducing delays in admissions to hospital. Funding: National Health and Medical Research Council of Australia, Canadian Institutes of Health Research, McMaster Surgical Associates, and Hamilton Health Sciences

Epidemiology of injuries from fire, heat and hot substances : global, regional and national morbidity and mortality estimates from the Global Burden of Disease 2017 study

Background Past research has shown how fires, heat and hot substances are important causes of health loss globally. Detailed estimates of the morbidity and mortality from these injuries could help drive preventative measures and improved access to care. Methods We used the Global Burden of Disease 2017 framework to produce three main results. First, we produced results on incidence, prevalence, years lived with disability, deaths, years of life lost and disability-adjusted life years from 1990 to 2017 for 195 countries and territories. Second, we analysed these results to measure mortality-to-incidence ratios by location. Third, we reported the measures above in terms of the cause of fire, heat and hot substances and the types of bodily injuries that result. Results Globally, there were 8 991 468 (7 481 218 to 10 740 897) new fire, heat and hot substance injuries in 2017 with 120 632 (101 630 to 129 383) deaths. At the global level, the age-standardised mortality caused by fire, heat and hot substances significantly declined from 1990 to 2017, but regionally there was variability in age-standardised incidence with some regions experiencing an increase (eg, Southern Latin America) and others experiencing a significant decrease (eg, High-income North America). Conclusions The incidence and mortality of injuries that result from fire, heat and hot substances affect every region of the world but are most concentrated in middle and lower income areas. More resources should be invested in measuring these injuries as well as in improving infrastructure, advancing safety measures and ensuring access to care.Peer reviewe

The burden of unintentional drowning : global, regional and national estimates of mortality from the Global Burden of Disease 2017 Study

Background Drowning is a leading cause of injury-related mortality globally. Unintentional drowning (International Classification of Diseases (ICD) 10 codes W65-74 and ICD9 E910) is one of the 30 mutually exclusive and collectively exhaustive causes of injury-related mortality in the Global Burden of Disease (GBD) study. This study's objective is to describe unintentional drowning using GBD estimates from 1990 to 2017. Methods Unintentional drowning from GBD 2017 was estimated for cause-specific mortality and years of life lost (YLLs), age, sex, country, region, Socio-demographic Index (SDI) quintile, and trends from 1990 to 2017. GBD 2017 used standard GBD methods for estimating mortality from drowning. Results Globally, unintentional drowning mortality decreased by 44.5% between 1990 and 2017, from 531 956 (uncertainty interval (UI): 484 107 to 572 854) to 295 210 (284 493 to 306 187) deaths. Global age-standardised mortality rates decreased 57.4%, from 9.3 (8.5 to 10.0) in 1990 to 4.0 (3.8 to 4.1) per 100 000 per annum in 2017. Unintentional drowning-associated mortality was generally higher in children, males and in low-SDI to middle-SDI countries. China, India, Pakistan and Bangladesh accounted for 51.2% of all drowning deaths in 2017. Oceania was the region with the highest rate of age-standardised YLLs in 2017, with 45 434 (40 850 to 50 539) YLLs per 100 000 across both sexes. Conclusions There has been a decline in global drowning rates. This study shows that the decline was not consistent across countries. The results reinforce the need for continued and improved policy, prevention and research efforts, with a focus on low- and middle-income countries.Peer reviewe

Population and fertility by age and sex for 195 countries and territories, 1950–2017: a systematic analysis for the Global Burden of Disease Study 2017

Background Population estimates underpin demographic and epidemiological research and are used to track progress on numerous international indicators of health and development. To date, internationally available estimates of population and fertility, although useful, have not been produced with transparent and replicable methods and do not use standardised estimates of mortality. We present single-calendar year and single-year of age estimates of fertility and population by sex with standardised and replicable methods. Methods We estimated population in 195 locations by single year of age and single calendar year from 1950 to 2017 with standardised and replicable methods. We based the estimates on the demographic balancing equation, with inputs of fertility, mortality, population, and migration data. Fertility data came from 7817 location-years of vital registration data, 429 surveys reporting complete birth histories, and 977 surveys and censuses reporting summary birth histories. We estimated age-specific fertility rates (ASFRs; the annual number of livebirths to women of a specified age group per 1000 women in that age group) by use of spatiotemporal Gaussian process regression and used the ASFRs to estimate total fertility rates (TFRs; the average number of children a woman would bear if she survived through the end of the reproductive age span [age 10–54 years] and experienced at each age a particular set of ASFRs observed in the year of interest). Because of sparse data, fertility at ages 10–14 years and 50–54 years was estimated from data on fertility in women aged 15–19 years and 45–49 years, through use of linear regression. Age-specific mortality data came from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 estimates. Data on population came from 1257 censuses and 761 population registry location-years and were adjusted for underenumeration and age misreporting with standard demographic methods. Migration was estimated with the GBD Bayesian demographic balancing model, after incorporating information about refugee migration into the model prior. Final population estimates used the cohort-component method of population projection, with inputs of fertility, mortality, and migration data. Population uncertainty was estimated by use of out-of-sample predictive validity testing. With these data, we estimated the trends in population by age and sex and in fertility by age between 1950 and 2017 in 195 countries and territories.Background Population estimates underpin demographic and epidemiological research and are used to track progress on numerous international indicators of health and development. To date, internationally available estimates of population and fertility, although useful, have not been produced with transparent and replicable methods and do not use standardised estimates of mortality. We present single-calendar year and single-year of age estimates of fertility and population by sex with standardised and replicable methods. Methods We estimated population in 195 locations by single year of age and single calendar year from 1950 to 2017 with standardised and replicable methods. We based the estimates on the demographic balancing equation, with inputs of fertility, mortality, population, and migration data. Fertility data came from 7817 location-years of vital registration data, 429 surveys reporting complete birth histories, and 977 surveys and censuses reporting summary birth histories. We estimated age-specific fertility rates (ASFRs; the annual number of livebirths to women of a specified age group per 1000 women in that age group) by use of spatiotemporal Gaussian process regression and used the ASFRs to estimate total fertility rates (TFRs; the average number of children a woman would bear if she survived through the end of the reproductive age span [age 10–54 years] and experienced at each age a particular set of ASFRs observed in the year of interest). Because of sparse data, fertility at ages 10–14 years and 50–54 years was estimated from data on fertility in women aged 15–19 years and 45–49 years, through use of linear regression. Age-specific mortality data came from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 estimates. Data on population came from 1257 censuses and 761 population registry location-years and were adjusted for underenumeration and age misreporting with standard demographic methods. Migration was estimated with the GBD Bayesian demographic balancing model, after incorporating information about refugee migration into the model prior. Final population estimates used the cohort-component method of population projection, with inputs of fertility, mortality, and migration data. Population uncertainty was estimated by use of out-of-sample predictive validity testing. With these data, we estimated the trends in population by age and sex and in fertility by age between 1950 and 2017 in 195 countries and territories