Childhood Cancer Mortality in India: Direct Estimates From a Nationally Representative Survey of Childhood Deaths.

PURPOSE: Although most children with cancer live in low- and middle-income countries, measurements of childhood cancer burden in such countries have been restricted to incidence rates from a few subnational cancer registries and mortality rates from vital statistics. We aimed to provide alternative burden estimates by using nationally representative longitudinal survey-derived mortality rates. METHODS: We examined cancer deaths in childhood (1 month to 14 years of age) in the Million Death Study, a cohort of > 27,000 pediatric deaths in India on the basis of enhanced verbal autopsies. All deaths potentially due to childhood cancer were identified. Two pediatric specialists independently categorized deaths as definite, probable, possible, or unlikely cancer related. From definite and probable deaths, we estimated national and regional mortality rates attributable to childhood malignancies. Data on symptoms and health care-seeking behavior were abstracted from closed-ended questions and caregiver narratives. RESULTS: Of 700 included deaths, 189 were classified as definite or possibly cancer related. The κ-statistic between reviewers was 0.75 (95% CI, 0.71 to 0.78). From these deaths, we estimated that in 2010, 13,700 were a result of childhood cancer in India, which led to a mortality rate of 37 (95% CI, 31 to 42) per million population per year, which exceeds many prior estimates of mortality and even some estimates of incidence. Disparities between mortality estimates were widest in northeast India and for brain tumors. A preponderance of male deaths was seen (male:female ratio, 1.6:1). CONCLUSION: The burden of childhood cancer in India is substantially higher than previously suggested. This information will aid advocacy for national strategies aimed at improving outcomes for Indian children with cancer

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

Performance criteria for verbal autopsy-based systems to estimate national causes of death: development and application to the Indian Million Death Study.

BACKGROUND: Verbal autopsy (VA) has been proposed to determine the cause of death (COD) distributions in settings where most deaths occur without medical attention or certification. We develop performance criteria for VA-based COD systems and apply these to the Registrar General of India's ongoing, nationally-representative Indian Million Death Study (MDS). METHODS: Performance criteria include a low ill-defined proportion of deaths before old age; reproducibility, including consistency of COD distributions with independent resampling; differences in COD distribution of hospital, home, urban or rural deaths; age-, sex- and time-specific plausibility of specific diseases; stability and repeatability of dual physician coding; and the ability of the mortality classification system to capture a wide range of conditions. RESULTS: The introduction of the MDS in India reduced the proportion of ill-defined deaths before age 70 years from 13% to 4%. The cause-specific mortality fractions (CSMFs) at ages 5 to 69 years for independently resampled deaths and the MDS were very similar across 19 disease categories. By contrast, CSMFs at these ages differed between hospital and home deaths and between urban and rural deaths. Thus, reliance mostly on urban or hospital data can distort national estimates of CODs. Age-, sex- and time-specific patterns for various diseases were plausible. Initial physician agreement on COD occurred about two-thirds of the time. The MDS COD classification system was able to capture more eligible records than alternative classification systems. By these metrics, the Indian MDS performs well for deaths prior to age 70 years. The key implication for low- and middle-income countries where medical certification of death remains uncommon is to implement COD surveys that randomly sample all deaths, use simple but high-quality field work with built-in resampling, and use electronic rather than paper systems to expedite field work and coding. CONCLUSIONS: Simple criteria can evaluate the performance of VA-based COD systems. Despite the misclassification of VA, the MDS demonstrates that national surveys of CODs using VA are an order of magnitude better than the limited COD data previously available

Vangstadviezen voor snoekbaars, baars, blankvoorn en brasem in het IJsselmeer en Markermeer

Het ministerie wil in het kader van de visserijwet en de Kaderrichtlijn Water komen tot wetenschappelijk onderbouwd beheer van de belangrijkste commerciële schubvisbestanden. In 2013 zijn vangstadviezen gegeven voor vier schubvissoorten in het IJsselmeer en Markermeer; snoekbaars, baars, brasem en blankvoorn. In het huidige rapport worden voor het visseizoen 2015/2016 opnieuw vangstadviezen gegeven. De doelstelling is aangescherpt van ‘voorkomen van achteruitgang’ naar ‘herstel’ van de bestanden. Bovendien zijn vanaf juli 2014 sterke vangstbeperkingen voor deze soorten.

HIV mortality and infection in India: estimates from nationally representative mortality survey of 1.1 million homes

Objective To determine the rates of death and infection from HIV in India

Divergent trends in ischaemic heart disease and stroke mortality in India from 2000 to 2015: a nationally representative mortality study.

INTRODUCTION: India accounts for about a fifth of cardiovascular deaths globally, but nationally representative data on mortality trends are not yet available. In this nationwide mortality study, we aimed to assess the trends in ischaemic heart disease and stroke mortality over 15 years using the Million Death Study. METHODS: We determined national and subnational cardiovascular mortality rates and trends by sex and birth cohort using cause of death ascertained by verbal autopsy from 2001 to 2013 among 2·4 million households. We derived mortality rates for ischaemic heart disease and stroke by applying mortality proportions to UN mortality estimates for India and projected the rates from 2000 to 2015. FINDINGS: Cardiovascular disease caused more than 2·1 million deaths in India in 2015 at all ages, or more than a quarter of all deaths. At ages 30-69 years, of 1·3 million cardiovascular deaths, 0·9 million (68·4%) were caused by ischaemic heart disease and 0·4 million (28·0%) by stroke. At these ages, the probability of dying from ischaemic heart disease increased during 2000-15, from 10·4% to 13·1% in men and 4·8% to 6·6% in women. Ischaemic heart disease mortality rates in rural areas increased rapidly and surpassed those in urban areas. By contrast, the probability of dying from stroke decreased from 5·7% to 5·0% in men and 5·0% to 3·9% in women. A third of premature stroke deaths occurred in the northeastern states, inhabited by a sixth of India's population, where rates increased significantly and were three times higher than the national average. The increased mortality rates of ischaemic heart disease nationally and stroke in the northeastern states were higher in the cohorts of adults born in the 1970s onwards, than in earlier decades. A large and growing proportion of the ischaemic heart disease nationally and stroke deaths in high-burden states reported earlier diagnosis of cardiovascular disease, but low medication use. INTERPRETATION: The unexpectedly diverse patterns of cardiovascular mortality require investigation to identify the role of established and new cardiovascular risk factors. Secondary prevention with effective and inexpensive long-term treatment and adult smoking cessation could prevent substantial numbers of premature deaths. Without progress against the control of cardiovascular disease in India, global goals to reduce non-communicable diseases by 2030 will be difficult to achieve. FUNDING: Fogarty International Center of the US National Institutes of Health, Dalla Lana School of Public Health, University of Toronto, Indian Council of Medical Research, and the Disease Control Priorities

Diarrhea, Pneumonia, and Infectious Disease Mortality in Children Aged 5 to 14 Years in India

Background: Little is known about the causes of death in children in India after age five years. The objective of this study is to provide the first ever direct national and sub-national estimates of infectious disease mortality in Indian children aged 5 to 14 years. Methods: A verbal autopsy based assessment of 3 855 deaths is children aged 5 to 14 years from a nationally representative survey of deaths occurring in 2001–03 in 1?1 million homes in India. Results: Infectious diseases accounted for 58 % of all deaths among children aged 5 to 14 years. About 18 % of deaths were due to diarrheal diseases, 10 % due to pneumonia, 8 % due to central nervous system infections, 4 % due to measles, and 12 % due to other infectious diseases. Nationally, in 2005 about 59 000 and 34 000 children aged 5 to 14 years died from diarrheal diseases and pneumonia, corresponding to mortality of 24?1 and 13?9 per 100 000 respectively. Mortality was nearly 50 % higher in girls than in boys for both diarrheal diseases and pneumonia. Conclusions: Approximately 60 % of all deaths in this age group are due to infectious diseases and nearly half of these deaths are due to diarrheal diseases and pneumonia. Mortality in this age group from infectious diseases, and diarrhea i

Snakebite Mortality in India: A Nationally Representative Mortality Survey

Earlier hospital based reports estimate about 1,300 to 50,000 annual deaths from snakebites per year in India. Here, we present the first ever direct estimates from a national mortality survey of 1.1 million homes in 2001–03. Full-time, non-medical field workers interviewed living respondents about all deaths. The underlying causes were independently coded by two of 130 trained physicians. The study found 562 deaths (0.47% of total deaths) were assigned to snakebites, mostly in rural areas, and more commonly among males than females and peaking at ages 15–29. Snakebites also occurred more often during the rainy monsoon season. This proportion represents about 45,900 annual snakebite deaths nationally (99% CI 40,900 to 50,900) or an annual age-standardised rate of 4.1/100,000 (99% CI 3.6–4.5), with higher rates in rural areas (5.4) and with the highest rate in the state of Andhra Pradesh (6.2). Annual snakebite deaths were greatest in the states of Uttar Pradesh (8,700), Andhra Pradesh (5,200), and Bihar (4,500). Thus, snakebite remains an underestimated cause of accidental death in modern India, causing about one death for every two HIV-related deaths. Because a large proportion of global totals of snakebites arise from India, global snakebite totals might also be underestimated. Effective interventions involving education and antivenom provision would reduce snakebite deaths in India

More than two decades of Apc modeling in rodents

Mutation of tumor suppressor gene adenomatous polyposis coli (APC) is an initiating step in most colon cancers. This review summarizes Apc models in mice and rats, with particular concentration on those most recently developed, phenotypic variation among different models, and genotype/phenotype correlations

Oxr1 Is Essential for Protection against Oxidative Stress-Induced Neurodegeneration

Oxidative stress is a common etiological feature of neurological disorders, although the pathways that govern defence against reactive oxygen species (ROS) in neurodegeneration remain unclear. We have identified the role of oxidation resistance 1 (Oxr1) as a vital protein that controls the sensitivity of neuronal cells to oxidative stress; mice lacking Oxr1 display cerebellar neurodegeneration, and neurons are less susceptible to exogenous stress when the gene is over-expressed. A conserved short isoform of Oxr1 is also sufficient to confer this neuroprotective property both in vitro and in vivo. In addition, biochemical assays indicate that Oxr1 itself is susceptible to cysteine-mediated oxidation. Finally we show up-regulation of Oxr1 in both human and pre-symptomatic mouse models of amyotrophic lateral sclerosis, indicating that Oxr1 is potentially a novel neuroprotective factor in neurodegenerative disease