Age-specifi c and sex-specifi c adult mortality risk in India in 2014: analysis of 0·27 million nationally surveyed deaths and demographic estimates from 597 districts

Background As child mortality decreases rapidly worldwide, premature adult mortality is becoming an increasingly important contributor to global mortality. Any possible worldwide reduction of premature adult mortality before the age of 70 years will depend on progress in India. Indian districts increasingly have responsibility for implementing public health programmes. We aimed to assess age-specifi c and sex-specifi c adult mortality risks in India at the district level. Methods We analysed data from fi ve national surveys of 0∙27 million adult deaths at an age of 15–69 years together with 2014 demographic data to estimate age-specifi c and sex-specifi c adult mortality risks for 597 districts. Cause of death data were drawn from the verbal autopsies in the Registrar General of India’s ongoing Million Death Study. Findings In 2014, about two-fi fths of India’s men aged 15–69 years lived in the 253 districts where the conditional probability of a man dying at these ages exceeded 50%, and more than a third of India’s women aged 15–69 years lived in the 222 districts where the conditional probability of a woman dying exceeded 40%. The probabilities of a man or woman dying by the age of 70 years in high-mortality districts was 62% and 54%, respectively, whereas the probability of a man or woman dying by the age of 70 years in low-mortality districts was 40% and 30%, respectively. The roughly 10-year survival gap between high-mortality and low-mortality districts was nearly as extreme as the survival gap between the entire Indian population and people living in high-income countries. Adult mortality risks at ages 15–69 years was highest in east India and lowest in west India, by contrast with the north–south divide for child mortality. Vascular disease, tuberculosis, malaria and other infections, and respiratory diseases accounted for about 60% of the absolute gap in adult mortality risk at ages 15–69 years between high-mortality and low-mortality districts. Most of the variation in adult mortality could not be explained by known determinants or risk factors for premature mortality. Interpretation India’s large variation in adult mortality by district, notably the higher death rates in eastern India, requires further aetiological research, particularly to explore whether high levels of adult mortality risks from infections and non-communicable diseases are a result of historical childhood malnutrition and infection. Such research can be complemented by an expanded coverage of known eff ective interventions to reduce adult mortality, especially in high-mortality district

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

A case of IgG4-related disease and Membranous Nephropathy associated with Thrombospondin type-1 Domain-containing 7A

BACKGROUND: IgG4-related disease (IgG4-RD) is a systemic multi-organ inflammatory disorder which affects the kidney 20% of the time. Patients with intrinsic IgG4-related kidney disease (IgG4-RKD) often have tubulointerstitial nephritis (TIN) whereas glomerular lesions like membranous nephropathy (MN) are less common. Antibodies to thrombospondin type-1 domain-containing 7A (THSD7A) have been described in primary MN, but never in association with IgG4-RKD. CASE REPORT: We report the first case of IgG4-MN associated with THSD7A antibodies in serum and positivity on glomerular staining, in a 57-year-old Caucasian male with IgG4-RD affecting the pancreas, liver, lacrimal glands, extraocular muscles, and kidneys. This patient presented initially with glomerular disease including significant proteinuria consistent with MN. Glomerular staining for THSD7A antigen and serum THSD7A antibody titres was positive. Treatment with corticosteroids and cyclophosphamide successfully induced remission with resolution of proteinuria, and improvement in renal function. However, despite maintenance azathioprine, the patient relapsed 39 months later. On relapse, there was minimal proteinuria but a significant rise in creatinine. Subsequent renal biopsy showed less glomerular disease and instead a TIN pattern. Subsequent treatment with Rituximab and corticosteroids successfully induced remission. CONCLUSION: The role of THSD7A autoantibodies in MN is emerging, and as both IgG4-MN and presence of THSD7A antibody are rare occurrences in themselves, we speculate that there may be an undiscovered association between THSD7A and IgG4-MN. Routine testing for THSD7A in IgG4-MN may help to identify the link

Are Global and Regional Improvements in Life Expectancy and in Child, Adult and Senior Survival Slowing?

<div><p>Improvements in life expectancy have been considerable over the past hundred years. Forecasters have taken to applying historical trends under an assumption of continuing improvements in life expectancy in the future. A linear mixed effects model was used to estimate the trends in global and regional rates of improvements in life expectancy, child, adult, and senior survival, in 166 countries between 1950 and 2010. Global improvements in life expectancy, including both child and adult survival rates, decelerated significantly over the study period. Overall life expectancy gains were estimated to have declined from 5.9 to 4.0 months per year for a mean deceleration of -0.07 months/year²; annual child survival gains declined from 4.4 to 1.6 deaths averted per 1000 for a mean deceleration of -0.06 deaths/1000/year²; adult survival gains were estimated to decline from 4.8 to 3.7 deaths averted per 1000 per year for a mean deceleration of -0.08 deaths/1000/year². Senior survival gains however increased from 2.4 to 4.2 deaths averted per 1000 per year for an acceleration of 0.03 deaths/1000/year². Regional variation in the four measures was substantial. The rates of global improvements in life expectancy, child survival, and adult survival have declined since 1950 despite an increase in the rate of improvements among seniors. We postulate that low-cost innovation, related to the last half-century progress in health–primarily devoted to children and middle age, is reaping diminishing returns on its investments. Trends are uneven across regions and measures, which may be due in part to the state of epidemiological transition between countries and regions and disparities in the diffusion of innovation, accessible only in high-income countries where life expectancy is already highest.</p></div

Mean rate of improvement in 1950–54 and the mean regional trends in improvements in life expectancy, child survival, adult and senior survival from 1950–2010.

<p>‘ indicates p ~ 0.10,</p><p>* indicates p < 0.05. S.E. (standard error) is in parentheses.</p><p>The rate of improvement in 1950–54 is in units of months per year or deaths per 1000 per year. The regional trends in improvement are in units of months per year² or deaths per 1000 per year².</p><p>Mean rate of improvement in 1950–54 and the mean regional trends in improvements in life expectancy, child survival, adult and senior survival from 1950–2010.</p

Mean regional trends in deceleration in life expectancy (months per year²), child survival, adult survival and senior survival (deaths per 1,000 per year²).

<p>Note: Size of marker is proportional to the region population size. Confidence intervals are indicated in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0124479#pone.0124479.t002" target="_blank">Table 2</a>. ME = Middle East; A = Asia; SSA = sub-Saharan Africa; LAMC = Latin American & the Caribbean; HI = High-income; EECA = Eastern Europe and Central Asia.</p

Regional changes in senior survival (deaths per 1000 per year), 1950–2010.

<p>Note: mean regional trends in changes in senior survival are indicated by the black dashed lines.</p