Early and extended erythropoietin monotherapy after hypoxic ischaemic encephalopathy:a multicentre double-blind pilot randomised controlled trial

Objective: To examine the feasibility of early and extended erythropoietin monotherapy after hypoxic ischaemic encephalopathy (HIE). Design: Double-blind pilot randomised controlled trial.Setting: Eight neonatal units in South Asia. Patients: Neonates (≥36 weeks) with moderate or severe HIE admitted between 31 December 2022 and 3 May 2023. Interventions: Erythropoietin (500 U/kg daily) or to the placebo (sham injections using a screen) within 6 hours of birth and continued for 9 days. MRI at 2 weeks of age. Main outcomes and measures: Feasibility of randomisation, drug administration and assessment of brain injury using MRI. Results: Of the 154 neonates screened, 56 were eligible; 6 declined consent and 50 were recruited; 43 (86%) were inborn. Mean (SD) age at first dose was 4.4 (1.2) hours in erythropoietin and 4.1 (1.0) hours in placebo. Overall mortality at hospital discharge occurred in 5 (19%) vs 11 (46%) (p=0.06), and 3 (13%) vs 9 (40.9%) (p=0.04) among those with moderate encephalopathy in the erythropoietin and placebo groups. Moderate or severe injury to basal ganglia, white matter and cortex occurred in 5 (25%) vs 5 (38.5%); 14 (70%) vs 11 (85%); and 6 (30%) vs 2 (15.4%) in the erythropoietin and placebo group, respectively. Sinus venous thrombosis was seen in two (10%) neonates in the erythropoietin group and none in the control group. Conclusions: Brain injury and mortality after moderate or severe HIE are high in South Asia. Evaluation of erythropoietin monotherapy using MRI to examine treatment effects is feasible in these settings. Trial registration number: NCT05395195

Nations within a nation: variations in epidemiological transition across the states of India, 1990–2016 in the Global Burden of Disease Study

18% of the world's population lives in India, and many states of India have populations similar to those of large countries. Action to effectively improve population health in India requires availability of reliable and comprehensive state-level estimates of disease burden and risk factors over time. Such comprehensive estimates have not been available so far for all major diseases and risk factors. Thus, we aimed to estimate the disease burden and risk factors in every state of India as part of the Global Burden of Disease (GBD) Study 2016

Gender differentials and state variations in suicide deaths in India: the Global Burden of Disease Study 1990–2016

Summary: Background: A systematic understanding of suicide mortality trends over time at the subnational level for India's 1·3 billion people, 18% of the global population, is not readily available. Thus, we aimed to report time trends of suicide deaths, and the heterogeneity in its distribution between the states of India from 1990 to 2016. Methods: As part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016, we estimated suicide death rates (SDRs) for both sexes in each state of India from 1990 to 2016. We used various data sources for estimating cause-specific mortality in India. For suicide mortality in India before 2000, estimates were based largely on GBD covariates. For each state, we calculated the ratio of the observed SDR to the rate expected in geographies globally with similar GBD Socio-demographic Index in 2016 (ie, the observed-to-expected ratio); and assessed the age distribution of suicide deaths, and the men-to-women ratio of SDR over time. Finally, we assessed the probability for India and the states of reaching the Sustainable Development Goal (SDG) target of a one-third reduction in SDR from 2015 to 2030, using location-wise trends of the age-standardised SDR from 1990 to 2016. We calculated 95% uncertainty intervals (UIs) for the point estimates. Findings: There were 230 314 (95% UI 194 058–250 260) suicide deaths in India in 2016. India's contribution to global suicide deaths increased from 25·3% in 1990 to 36·6% in 2016 among women, and from 18·7% to 24·3% among men. Age-standardised SDR among women in India reduced by 26·7% from 20·0 (95% UI 16·5–23·5) in 1990 to 14·7 (13·1–16·2) per 100 000 in 2016, but the age-standardised SDR among men was the same in 1990 (22·3 [95% UI 14·4–27·4] per 100 000) and 2016 (21·2 [14·6–23·6] per 100 000). SDR in women was 2·1 times higher in India than the global average in 2016, and the observed-to-expected ratio was 2·74, ranging from 0·45 to 4·54 between the states. SDR in men was 1·4 times higher in India than the global average in 2016, with an observed-to-expected ratio of 1·31, ranging from 0·40 to 2·42 between the states. There was a ten-fold variation between the states in the SDR for women and six-fold variation for men in 2016. The men-to-women ratio of SDR for India was 1·34 in 2016, ranging from 0·97 to 4·11 between the states. The highest age-specific SDRs among women in 2016 were for ages 15–29 years and 75 years or older, and among men for ages 75 years or older. Suicide was the leading cause of death in India in 2016 for those aged 15–39 years; 71·2% of the suicide deaths among women and 57·7% among men were in this age group. If the trends observed up to 2016 continue, the probability of India achieving the SDG SDR reduction target in 2030 is zero, and the majority of the states with 81·3% of India's population have less than 10% probability, three states have a probability of 10·3–15·0%, and six have a probability of 25·1–36·7%. Interpretation: India's proportional contribution to global suicide deaths is high and increasing. SDR in India is higher than expected for its Socio-Demographic Index level, especially for women, with substantial variations in the magnitude and men-to-women ratio between the states. India must develop a suicide prevention strategy that takes into account these variations in order to address this major public health problem. Funding: Bill & Melinda Gates Foundation; and Indian Council of Medical Research, Department of Health Research, Ministry of Health and Family Welfare, Government of India

Early and extended erythropoietin monotherapy after hypoxic ischaemic encephalopathy:a multicentre double-blind pilot randomised controlled trial

Objective: To examine the feasibility of early and extended erythropoietin monotherapy after hypoxic ischaemic encephalopathy (HIE). Design: Double-blind pilot randomised controlled trial.Setting: Eight neonatal units in South Asia. Patients: Neonates (≥36 weeks) with moderate or severe HIE admitted between 31 December 2022 and 3 May 2023. Interventions: Erythropoietin (500 U/kg daily) or to the placebo (sham injections using a screen) within 6 hours of birth and continued for 9 days. MRI at 2 weeks of age. Main outcomes and measures: Feasibility of randomisation, drug administration and assessment of brain injury using MRI. Results: Of the 154 neonates screened, 56 were eligible; 6 declined consent and 50 were recruited; 43 (86%) were inborn. Mean (SD) age at first dose was 4.4 (1.2) hours in erythropoietin and 4.1 (1.0) hours in placebo. Overall mortality at hospital discharge occurred in 5 (19%) vs 11 (46%) (p=0.06), and 3 (13%) vs 9 (40.9%) (p=0.04) among those with moderate encephalopathy in the erythropoietin and placebo groups. Moderate or severe injury to basal ganglia, white matter and cortex occurred in 5 (25%) vs 5 (38.5%); 14 (70%) vs 11 (85%); and 6 (30%) vs 2 (15.4%) in the erythropoietin and placebo group, respectively. Sinus venous thrombosis was seen in two (10%) neonates in the erythropoietin group and none in the control group. Conclusions: Brain injury and mortality after moderate or severe HIE are high in South Asia. Evaluation of erythropoietin monotherapy using MRI to examine treatment effects is feasible in these settings. Trial registration number: NCT05395195

The burden of chronic respiratory diseases and their heterogeneity across the states of India: the Global Burden of Disease Study 1990–2016

Summary: Background: India has 18% of the global population and an increasing burden of chronic respiratory diseases. However, a systematic understanding of the distribution of chronic respiratory diseases and their trends over time is not readily available for all of the states of India. Our aim was to report the trends in the burden of chronic respiratory diseases and the heterogeneity in their distribution in all states of India between 1990 and 2016. Methods: Using all accessible data from multiple sources, we estimated the prevalence of major chronic respiratory diseases and the deaths and disability-adjusted life-years (DALYs) caused by them for every state of India from 1990 to 2016 as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016. We assessed heterogeneity in the burden of chronic obstructive pulmonary disease (COPD) and asthma across the states of India. The states were categorised into four groups based on their epidemiological transition level (ETL). ETL was defined as the ratio of DALYs from communicable diseases to those from non-communicable diseases and injuries combined, with a low ratio denoting high ETL and vice versa. We also assessed the contribution of risk factors to DALYs due to COPD. We compared the burden of chronic respiratory diseases in India against the global average in GBD 2016. We calculated 95% uncertainty intervals (UIs) for the point estimates. Findings: The contribution of chronic respiratory diseases to the total DALYs in India increased from 4·5% (95% UI 4·0–4·9) in 1990 to 6·4% (5·8–7·0) in 2016. Of the total global DALYs due to chronic respiratory diseases in 2016, 32·0% occurred in India. COPD and asthma were responsible for 75·6% and 20·0% of the chronic respiratory disease DALYs, respectively, in India in 2016. The number of cases of COPD in India increased from 28·1 million (27·0–29·2) in 1990 to 55·3 million (53·1–57·6) in 2016, an increase in prevalence from 3·3% (3·1–3·4) to 4·2% (4·0–4·4). The age-standardised COPD prevalence and DALY rates in 2016 were highest in the less developed low ETL state group. There were 37·9 million (35·7–40·2) cases of asthma in India in 2016, with similar prevalence in the four ETL state groups, but the highest DALY rate was in the low ETL state group. The highest DALY rates for both COPD and asthma in 2016 were in the low ETL states of Rajasthan and Uttar Pradesh. The DALYs per case of COPD and asthma were 1·7 and 2·4 times higher in India than the global average in 2016, respectively; most states had higher rates compared with other locations worldwide at similar levels of Socio-demographic Index. Of the DALYs due to COPD in India in 2016, 53·7% (43·1–65·0) were attributable to air pollution, 25·4% (19·5–31·7) to tobacco use, and 16·5% (14·1–19·2) to occupational risks, making these the leading risk factors for COPD. Interpretation: India has a disproportionately high burden of chronic respiratory diseases. The increasing contribution of these diseases to the overall disease burden across India and the high rate of health loss from them, especially in the less developed low ETL states, highlights the need for focused policy interventions to address this significant cause of disease burden in India. Funding: Bill & Melinda Gates Foundation; and Indian Council of Medical Research, Department of Health Research, Ministry of Health and Family Welfare, Government of India

The increasing burden of diabetes and variations among the states of India: the Global Burden of Disease Study 1990–2016

Summary: Background: The burden of diabetes is increasing rapidly in India but a systematic understanding of its distribution and time trends is not available for every state of India. We present a comprehensive analysis of the time trends and heterogeneity in the distribution of diabetes burden across all states of India between 1990 and 2016. Methods: We analysed the prevalence and disability-adjusted life-years (DALYs) of diabetes in the states of India from 1990 to 2016 using all available data sources that could be accessed as part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2016, and assessed heterogeneity across the states. The states were placed in four groups based on epidemiological transition level (ETL), defined on the basis of the ratio of DALYs from communicable diseases to those from non-communicable diseases and injuries combined, with a low ratio denoting high ETL and vice versa. We assessed the contribution of risk factors to diabetes DALYs and the relation of overweight (body-mass index 25 kg/m2 or more) with diabetes prevalence. We calculated 95% uncertainty intervals (UIs) for the point estimates. Findings: The number of people with diabetes in India increased from 26·0 million (95% UI 23·4–28·6) in 1990 to 65·0 million (58·7–71·1) in 2016. The prevalence of diabetes in adults aged 20 years or older in India increased from 5·5% (4·9–6·1) in 1990 to 7·7% (6·9–8·4) in 2016. The prevalence in 2016 was highest in Tamil Nadu and Kerala (high ETL) and Delhi (higher-middle ETL), followed by Punjab and Goa (high ETL) and Karnataka (higher-middle ETL). The age-standardised DALY rate for diabetes increased in India by 39·6% (32·1–46·7) from 1990 to 2016, which was the highest increase among major non-communicable diseases. The age-standardised diabetes prevalence and DALYs increased in every state, with the percentage increase among the highest in several states in the low and lower-middle ETL state groups. The most important risk factor for diabetes in India was overweight to which 36·0% (22·6–49·2) of the diabetes DALYs in 2016 could be attributed. The prevalence of overweight in adults in India increased from 9·0% (8·7–9·3) in 1990 to 20·4% (19·9–20·8) in 2016; this prevalence increased in every state of the country. For every 100 overweight adults aged 20 years or older in India, there were 38 adults (34–42) with diabetes, compared with the global average of 19 adults (17–21) in 2016. Interpretation: The increase in health loss from diabetes since 1990 in India is the highest among major non-communicable diseases. With this increase observed in every state of the country, and the relative rate of increase highest in several less developed low ETL states, policy action that takes these state-level differences into account is needed urgently to control this potentially explosive public health situation. Funding: Bill & Melinda Gates Foundation; and Indian Council of Medical Research, Department of Health Research, Ministry of Health and Family Welfare, Government of India

The changing patterns of cardiovascular diseases and their risk factors in the states of India: the Global Burden of Disease Study 1990–2016

Summary: Background: The burden of cardiovascular diseases is increasing in India, but a systematic understanding of its distribution and time trends across all the states is not readily available. In this report, we present a detailed analysis of how the patterns of cardiovascular diseases and major risk factors have changed across the states of India between 1990 and 2016. Methods: We analysed the prevalence and disability-adjusted life-years (DALYs) due to cardiovascular diseases and the major component causes in the states of India from 1990 to 2016, using all accessible data sources as part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2016. We placed states into four groups based on epidemiological transition level (ETL), defined using the ratio of DALYs from communicable diseases to those from non-communicable diseases and injuries combined, with a low ratio denoting high ETL and vice versa. We assessed heterogeneity in the burden of major cardiovascular diseases across the states of India, and the contribution of risk factors to cardiovascular diseases. We calculated 95% uncertainty intervals (UIs) for the point estimates. Findings: Overall, cardiovascular diseases contributed 28·1% (95% UI 26·5–29·1) of the total deaths and 14·1% (12·9–15·3) of the total DALYs in India in 2016, compared with 15·2% (13·7–16·2) and 6·9% (6·3–7·4), respectively, in 1990. In 2016, there was a nine times difference between states in the DALY rate for ischaemic heart disease, a six times difference for stroke, and a four times difference for rheumatic heart disease. 23·8 million (95% UI 22·6–25·0) prevalent cases of ischaemic heart disease were estimated in India in 2016, and 6·5 million (6·3–6·8) prevalent cases of stroke, a 2·3 times increase in both disorders from 1990. The age-standardised prevalence of both ischaemic heart disease and stroke increased in all ETL state groups between 1990 and 2016, whereas that of rheumatic heart disease decreased; the increase for ischaemic heart disease was highest in the low ETL state group. 53·4% (95% UI 52·6–54·6) of crude deaths due to cardiovascular diseases in India in 2016 were among people younger than 70 years, with a higher proportion in the low ETL state group. The leading overlapping risk factors for cardiovascular diseases in 2016 included dietary risks (56·4% [95% CI 48·5–63·9] of cardiovascular disease DALYs), high systolic blood pressure (54·6% [49·0–59·8]), air pollution (31·1% [29·0–33·4]), high total cholesterol (29·4% [24·3–34·8]), tobacco use (18·9% [16·6–21·3]), high fasting plasma glucose (16·7% [11·4–23·5]), and high body-mass index (14·7% [8·3–22·0]). The prevalence of high systolic blood pressure, high total cholesterol, and high fasting plasma glucose increased generally across all ETL state groups from 1990 to 2016, but this increase was variable across the states; the prevalence of smoking decreased during this period in all ETL state groups. Interpretation: The burden from the leading cardiovascular diseases in India—ischaemic heart disease and stroke—varies widely between the states. Their increasing prevalence and that of several major risk factors in every part of India, especially the highest increase in the prevalence of ischaemic heart disease in the less developed low ETL states, indicates the need for urgent policy and health system response appropriate for the situation in each state. Funding: Bill & Melinda Gates Foundation; and Indian Council of Medical Research, Department of Health Research, Ministry of Health and Family Welfare, Government of India

The impact of air pollution on deaths, disease burden, and life expectancy across the states of India: the Global Burden of Disease Study 2017

Summary: Background: Air pollution is a major planetary health risk, with India estimated to have some of the worst levels globally. To inform action at subnational levels in India, we estimated the exposure to air pollution and its impact on deaths, disease burden, and life expectancy in every state of India in 2017. Methods: We estimated exposure to air pollution, including ambient particulate matter pollution, defined as the annual average gridded concentration of PM2.5, and household air pollution, defined as percentage of households using solid cooking fuels and the corresponding exposure to PM2.5, across the states of India using accessible data from multiple sources as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017. The states were categorised into three Socio-demographic Index (SDI) levels as calculated by GBD 2017 on the basis of lag-distributed per-capita income, mean education in people aged 15 years or older, and total fertility rate in people younger than 25 years. We estimated deaths and disability-adjusted life-years (DALYs) attributable to air pollution exposure, on the basis of exposure–response relationships from the published literature, as assessed in GBD 2017; the proportion of total global air pollution DALYs in India; and what the life expectancy would have been in each state of India if air pollution levels had been less than the minimum level causing health loss. Findings: The annual population-weighted mean exposure to ambient particulate matter PM2·5 in India was 89·9 μg/m3 (95% uncertainty interval [UI] 67·0–112·0) in 2017. Most states, and 76·8% of the population of India, were exposed to annual population-weighted mean PM2·5 greater than 40 μg/m3, which is the limit recommended by the National Ambient Air Quality Standards in India. Delhi had the highest annual population-weighted mean PM2·5 in 2017, followed by Uttar Pradesh, Bihar, and Haryana in north India, all with mean values greater than 125 μg/m3. The proportion of population using solid fuels in India was 55·5% (54·8–56·2) in 2017, which exceeded 75% in the low SDI states of Bihar, Jharkhand, and Odisha. 1·24 million (1·09–1·39) deaths in India in 2017, which were 12·5% of the total deaths, were attributable to air pollution, including 0·67 million (0·55–0·79) from ambient particulate matter pollution and 0·48 million (0·39–0·58) from household air pollution. Of these deaths attributable to air pollution, 51·4% were in people younger than 70 years. India contributed 18·1% of the global population but had 26·2% of the global air pollution DALYs in 2017. The ambient particulate matter pollution DALY rate was highest in the north Indian states of Uttar Pradesh, Haryana, Delhi, Punjab, and Rajasthan, spread across the three SDI state groups, and the household air pollution DALY rate was highest in the low SDI states of Chhattisgarh, Rajasthan, Madhya Pradesh, and Assam in north and northeast India. We estimated that if the air pollution level in India were less than the minimum causing health loss, the average life expectancy in 2017 would have been higher by 1·7 years (1·6–1·9), with this increase exceeding 2 years in the north Indian states of Rajasthan, Uttar Pradesh, and Haryana. Interpretation: India has disproportionately high mortality and disease burden due to air pollution. This burden is generally highest in the low SDI states of north India. Reducing the substantial avoidable deaths and disease burden from this major environmental risk is dependent on rapid deployment of effective multisectoral policies throughout India that are commensurate with the magnitude of air pollution in each state. Funding: Bill & Melinda Gates Foundation; and Indian Council of Medical Research, Department of Health Research, Ministry of Health and Family Welfare, Government of India

Hypothermia for moderate or severe neonatal encephalopathy in low-income and middle-income countries (HELIX): a randomised controlled trial in India, Sri Lanka, and Bangladesh

Copyright (c) 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license