Mohammad H. Forouzanfar

Reliable and timely information on the leading causes of death in populations, and how these are changing, is a crucial input into health policy debates. In the Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010), we aimed to estimate annual deaths for the world and 21 regions between 1980 and 2010 for 235 causes, with uncertainty intervals (UIs), separately by age and sex.We attempted to identify all available data on causes of death for 187 countries from 1980 to 2010 from vital registration, verbal autopsy, mortality surveillance, censuses, surveys, hospitals, police records, and mortuaries. We assessed data quality for completeness, diagnostic accuracy, missing data, stochastic variations, and probable causes of death. We applied six different modelling strategies to estimate cause-specific mortality trends depending on the strength of the data. For 133 causes and three special aggregates we used the Cause of Death Ensemble model (CODEm) approach, which uses four families of statistical models testing a large set of different models using different permutations of covariates. Model ensembles were developed from these component models. We assessed model performance with rigorous out-of-sample testing of prediction error and the validity of 95% UIs. For 13 causes with low observed numbers of deaths, we developed negative binomial models with plausible covariates. For 27 causes for which death is rare, we modelled the higher level cause in the cause hierarchy of the GBD 2010 and then allocated deaths across component causes proportionately, estimated from all available data in the database. For selected causes (African trypanosomiasis, congenital syphilis, whooping cough, measles, typhoid and parathyroid, leishmaniasis, acute hepatitis E, and HIV/AIDS), we used natural history models based on information on incidence, prevalence, and case-fatality. We separately estimated cause fractions by aetiology for diarrhoea, lower respiratory infections, and meningitis, as well as disaggregations by subcause for chronic kidney disease, maternal disorders, cirrhosis, and liver cancer. For deaths due to collective violence and natural disasters, we used mortality shock regressions. For every cause, we estimated 95% UIs that captured both parameter estimation uncertainty and uncertainty due to model specification where CODEm was used. We constrained cause-specific fractions within every age-sex group to sum to total mortality based on draws from the uncertainty distributions.In 2010, there were 52·8 million deaths globally. At the most aggregate level, communicable, maternal, neonatal, and nutritional causes were 24·9% of deaths worldwide in 2010, down from 15·9 million (34·1%) of 46·5 million in 1990. This decrease was largely due to decreases in mortality from diarrhoeal disease (from 2·5 to 1·4 million), lower respiratory infections (from 3·4 to 2·8 million), neonatal disorders (from 3·1 to 2·2 million), measles (from 0·63 to 0·13 million), and tetanus (from 0·27 to 0·06 million). Deaths from HIV/AIDS increased from 0·30 million in 1990 to 1·5 million in 2010, reaching a peak of 1·7 million in 2006. Malaria mortality also rose by an estimated 19·9% since 1990 to 1·17 million deaths in 2010. Tuberculosis killed 1·2 million people in 2010. Deaths from non-communicable diseases rose by just under 8 million between 1990 and 2010, accounting for two of every three deaths (34·5 million) worldwide by 2010. 8 million people died from cancer in 2010, 38% more than two decades ago; of these, 1·5 million (19%) were from trachea, bronchus, and lung cancer. Ischaemic heart disease and stroke collectively killed 12·9 million people in 2010, or one in four deaths worldwide, compared with one in five in 1990; 1·3 million deaths were due to diabetes, twice as many as in 1990. The fraction of global deaths due to injuries (5·1 million deaths) was marginally higher in 2010 (9·6%) compared with two decades earlier (8·8%). This was driven by a 46% rise in deaths worldwide due to road traffic accidents (1·3 million in 2010) and a rise in deaths from falls. Ischaemic heart disease, stroke, chronic obstructive pulmonary disease (COPD), lower respiratory infections, lung cancer, and HIV/AIDS were the leading causes of death in 2010. Ischaemic heart disease, lower respiratory infections, stroke, diarrhoeal disease, malaria, and HIV/AIDS were the leading causes of years of life lost due to premature mortality (YLLs) in 2010, similar to what was estimated for 1990, except for HIV/AIDS and preterm birth complications. YLLs from lower respiratory infections and diarrhoea decreased by 45-54% since 1990; ischaemic heart disease and stroke YLLs increased by 17-28%. Regional variations in leading causes of death were substantial. Communicable, maternal, neonatal, and nutritional causes still accounted for 76% of premature mortality in sub-Saharan Africa in 2010. Age standardised death rates from some key disorders rose (HIV/AIDS, Alzheimer's disease, diabetes mellitus, and chronic kidney disease in particular), but for most diseases, death rates fell in the past two decades; including major vascular diseases, COPD, most forms of cancer, liver cirrhosis, and maternal disorders. For other conditions, notably malaria, prostate cancer, and injuries, little change was noted.Population growth, increased average age of the world's population, and largely decreasing age-specific, sex-specific, and cause-specific death rates combine to drive a broad shift from communicable, maternal, neonatal, and nutritional causes towards non-communicable diseases. Nevertheless, communicable, maternal, neonatal, and nutritional causes remain the dominant causes of YLLs in sub-Saharan Africa. Overlaid on this general pattern of the epidemiological transition, marked regional variation exists in many causes, such as interpersonal violence, suicide, liver cancer, diabetes, cirrhosis, Chagas disease, African trypanosomiasis, melanoma, and others. Regional heterogeneity highlights the importance of sound epidemiological assessments of the causes of death on a regular basis.Bill & Melinda Gates Foundation.

Background In 2010, overweight and obesity were estimated to cause 3·4 million deaths, 3·9% of years of life lost, and 3·8% of disability-adjusted life-years (DALYs) worldwide. The rise in obesity has led to widespread calls for regular monitoring of changes in overweight and obesity prevalence in all populations. Comparable, up-to-date information about levels and trends is essential to quantify population health effects and to prompt decision makers to prioritise action. We estimate the global, regional, and national prevalence of overweight and obesity in children and adults during 1980–2013. Methods We systematically identified surveys, reports, and published studies (n=1769) that included data for height and weight, both through physical measurements and self-reports. We used mixed effects linear regression to correct for bias in self-reports. We obtained data for prevalence of obesity and overweight by age, sex, country, and year (n=19 244) with a spatiotemporal Gaussian process regression model to estimate prevalence with 95% uncertainty intervals (UIs). Findings Worldwide, the proportion of adults with a body-mass index (BMI) of 25 kg/m2 or greater increased between 1980 and 2013 from 28·8% (95% UI 28·4–29·3) to 36·9% (36·3–37·4) in men, and from 29·8% (29·3–30·2) to 38·0% (37·5–38·5) in women. Prevalence has increased substantially in children and adolescents in developed countries; 23·8% (22·9–24·7) of boys and 22·6% (21·7–23·6) of girls were overweight or obese in 2013. The prevalence of overweight and obesity has also increased in children and adolescents in developing countries, from 8·1% (7·7–8·6) to 12·9% (12·3–13·5) in 2013 for boys and from 8·4% (8·1–8·8) to 13·4% (13·0–13·9) in girls. In adults, estimated prevalence of obesity exceeded 50% in men in Tonga and in women in Kuwait, Kiribati, Federated States of Micronesia, Libya, Qatar, Tonga, and Samoa. Since 2006, the increase in adult obesity in developed countries has slowed down. Interpretation Because of the established health risks and substantial increases in prevalence, obesity has become a major global health challenge. Not only is obesity increasing, but no national success stories have been reported in the past 33 years. Urgent global action and leadership is needed to help countries to more effectively intervene. Funding Bill & Melinda Gates Foundation.

Non-fatal outcomes of disease and injury increasingly detract from the ability of the world's population to live in full health, a trend largely attributable to an epidemiological transition in many countries from causes affecting children, to non-communicable diseases (NCDs) more common in adults. For the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015), we estimated the incidence, prevalence, and years lived with disability for diseases and injuries at the global, regional, and national scale over the period of 1990 to 2015.We estimated incidence and prevalence by age, sex, cause, year, and geography with a wide range of updated and standardised analytical procedures. Improvements from GBD 2013 included the addition of new data sources, updates to literature reviews for 85 causes, and the identification and inclusion of additional studies published up to November, 2015, to expand the database used for estimation of non-fatal outcomes to 60 900 unique data sources. Prevalence and incidence by cause and sequelae were determined with DisMod-MR 2.1, an improved version of the DisMod-MR Bayesian meta-regression tool first developed for GBD 2010 and GBD 2013. For some causes, we used alternative modelling strategies where the complexity of the disease was not suited to DisMod-MR 2.1 or where incidence and prevalence needed to be determined from other data. For GBD 2015 we created a summary indicator that combines measures of income per capita, educational attainment, and fertility (the Socio-demographic Index [SDI]) and used it to compare observed patterns of health loss to the expected pattern for countries or locations with similar SDI scores.We generated 9·3 billion estimates from the various combinations of prevalence, incidence, and YLDs for causes, sequelae, and impairments by age, sex, geography, and year. In 2015, two causes had acute incidences in excess of 1 billion: upper respiratory infections (17·2 billion, 95% uncertainty interval [UI] 15·4-19·2 billion) and diarrhoeal diseases (2·39 billion, 2·30-2·50 billion). Eight causes of chronic disease and injury each affected more than 10% of the world's population in 2015: permanent caries, tension-type headache, iron-deficiency anaemia, age-related and other hearing loss, migraine, genital herpes, refraction and accommodation disorders, and ascariasis. The impairment that affected the greatest number of people in 2015 was anaemia, with 2·36 billion (2·35-2·37 billion) individuals affected. The second and third leading impairments by number of individuals affected were hearing loss and vision loss, respectively. Between 2005 and 2015, there was little change in the leading causes of years lived with disability (YLDs) on a global basis. NCDs accounted for 18 of the leading 20 causes of age-standardised YLDs on a global scale. Where rates were decreasing, the rate of decrease for YLDs was slower than that of years of life lost (YLLs) for nearly every cause included in our analysis. For low SDI geographies, Group 1 causes typically accounted for 20-30% of total disability, largely attributable to nutritional deficiencies, malaria, neglected tropical diseases, HIV/AIDS, and tuberculosis. Lower back and neck pain was the leading global cause of disability in 2015 in most countries. The leading cause was sense organ disorders in 22 countries in Asia and Africa and one in central Latin America; diabetes in four countries in Oceania; HIV/AIDS in three southern sub-Saharan African countries; collective violence and legal intervention in two north African and Middle Eastern countries; iron-deficiency anaemia in Somalia and Venezuela; depression in Uganda; onchoceriasis in Liberia; and other neglected tropical diseases in the Democratic Republic of the Congo.Ageing of the world's population is increasing the number of people living with sequelae of diseases and injuries. Shifts in the epidemiological profile driven by socioeconomic change also contribute to the continued increase in years lived with disability (YLDs) as well as the rate of increase in YLDs. Despite limitations imposed by gaps in data availability and the variable quality of the data available, the standardised and comprehensive approach of the GBD study provides opportunities to examine broad trends, compare those trends between countries or subnational geographies, benchmark against locations at similar stages of development, and gauge the strength or weakness of the estimates available.Bill & Melinda Gates Foundation.

Background Improving survival and extending the longevity of life for all populations requires timely, robust evidence on local mortality levels and trends.The Global Burden of Disease 2015 Study (GBD 2015) provides a comprehensive assessment of all-cause and cause-specifi c mortality for 249 causes in 195 countries and territories from 1980 to 2015.These results informed an in-depth investigation of observed and expected mortality patterns based on sociodemographic measures. MethodsWe estimated all-cause mortality by age, sex, geography, and year using an improved analytical approach originally developed for GBD 2013 and GBD 2010.Improvements included refi nements to the estimation of child and adult mortality and corresponding uncertainty, parameter selection for under-5 mortality synthesis by spatiotemporal Gaussian process regression, and sibling history data processing.We also expanded the database of vital registration, survey, and census data to 14 294 geography-year datapoints.For GBD 2015, eight causes, including Ebola virus disease, were added to the previous GBD cause list for mortality.We used six modelling approaches to assess causespecifi c mortality, with the Cause of Death Ensemble Model (CODEm) generating estimates for most causes.We used a series of novel analyses to systematically quantify the drivers of trends in mortality across geographies.First, we assessed observed and expected levels and trends of cause-specifi c mortality as they relate to the Socio-demographic Index (SDI), a summary indicator derived from measures of income per capita, educational attainment, and fertility.Second, we examined factors aff ecting total mortality patterns through a series of counterfactual scenarios, testing the magnitude by which population growth, population age structures, and epidemiological changes contributed to shifts in mortality.Finally, we attributed changes in life expectancy to changes in cause of death.We documented each step of the GBD 2015 estimation processes, as well as data sources, in accordance with Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER). FindingsGlobally, life expectancy from birth increased from 61•7 years (95% uncertainty interval 61•4-61•9) in 1980 to 71•8 years (71•5-72•2) in 2015.Several countries in sub-Saharan Africa had very large gains in life expectancy from 2005 to 2015, rebounding from an era of exceedingly high loss of life due to HIV/AIDS.At the same time, many geographies saw life expectancy stagnate or decline, particularly for men and in countries with rising mortality from war or interpersonal violence.From 2005 to 2015, male life expectancy in Syria dropped by 11•3 years (3•7-17•4), to 62•6 years (56•5-70•2).Total deaths increased by 4•1% (2•6-5•6) from 2005 to 2015, rising to 55•8 million (54•9 million to 56•6 million) in 2015, but age-standardised death rates fell by 17•0% (15•8-18•1) during this time, underscoring changes in population growth and shifts in global age structures.The result was similar for noncommunicable diseases (NCDs), with total deaths from these causes increasing by 14•1% (12•6-16•0) to 39•8 million (39•2 million to 40•5 million) in 2015, whereas age-standardised rates decreased by 13•1% (11•9-14•3).Globally, this mortality pattern emerged for several NCDs, including several types of cancer, ischaemic heart disease, cirrhosis, and Alzheimer's disease and other dementias.By contrast, both total deaths and age-standardised death rates due to communicable, maternal, neonatal, and nutritional conditions signifi cantly declined from 2005 to 2015, gains largely attributable to decreases in mortality rates due to HIV/AIDS (42•1%, 39•1-44•6), malaria (43•1%, 34•7-51•8), neonatal preterm birth complications (29•8%, 24•8-34•9), and maternal disorders (29•1%, 19•3-37•1).Progress was slower for several causes, such as lower respiratory infections and nutritional defi ciencies, whereas deaths increased for others, including dengue and drug use disorders.Age-standardised death rates due to injuries signifi cantly declined from 2005 to 2015, yet interpersonal violence and war claimed increasingly more lives in some regions, particularly in the Middle East.In 2015, rotaviral enteritis (rotavirus) was the leading cause of under-5 deaths due to diarrhoea (146 000 deaths, 118 000-183 000) and pneumococcal pneumonia was the leading cause of under-5 deaths due to lower respiratory infections (393 000 deaths, 228 000-532 000), although pathogen-specifi c mortality varied by region.Globally, the eff ects of population growth, ageing, and changes in age-standardised death rates substantially diff ered by cause.Our analyses on the expected associations between cause-specifi c mortality and SDI show the regular shifts in cause of death composition and population age structure with rising SDI.Country patterns of

BackgroundThe Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context.MethodsWe used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI).FindingsBetween 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa.InterpretationDeclines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden.FundingBill & Melinda Gates Foundation.

Cancer is the second leading cause of death worldwide. Current estimates on the burden of cancer are needed for cancer control planning.To estimate mortality, incidence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) for 32 cancers in 195 countries and territories from 1990 to 2015.Cancer mortality was estimated using vital registration system data, cancer registry incidence data (transformed to mortality estimates using separately estimated mortality to incidence [MI] ratios), and verbal autopsy data. Cancer incidence was calculated by dividing mortality estimates through the modeled MI ratios. To calculate cancer prevalence, MI ratios were used to model survival. To calculate YLDs, prevalence estimates were multiplied by disability weights. The YLLs were estimated by multiplying age-specific cancer deaths by the reference life expectancy. DALYs were estimated as the sum of YLDs and YLLs. A sociodemographic index (SDI) was created for each location based on income per capita, educational attainment, and fertility. Countries were categorized by SDI quintiles to summarize results.In 2015, there were 17.5 million cancer cases worldwide and 8.7 million deaths. Between 2005 and 2015, cancer cases increased by 33%, with population aging contributing 16%, population growth 13%, and changes in age-specific rates contributing 4%. For men, the most common cancer globally was prostate cancer (1.6 million cases). Tracheal, bronchus, and lung cancer was the leading cause of cancer deaths and DALYs in men (1.2 million deaths and 25.9 million DALYs). For women, the most common cancer was breast cancer (2.4 million cases). Breast cancer was also the leading cause of cancer deaths and DALYs for women (523 000 deaths and 15.1 million DALYs). Overall, cancer caused 208.3 million DALYs worldwide in 2015 for both sexes combined. Between 2005 and 2015, age-standardized incidence rates for all cancers combined increased in 174 of 195 countries or territories. Age-standardized death rates (ASDRs) for all cancers combined decreased within that timeframe in 140 of 195 countries or territories. Countries with an increase in the ASDR due to all cancers were largely located on the African continent. Of all cancers, deaths between 2005 and 2015 decreased significantly for Hodgkin lymphoma (-6.1% [95% uncertainty interval (UI), -10.6% to -1.3%]). The number of deaths also decreased for esophageal cancer, stomach cancer, and chronic myeloid leukemia, although these results were not statistically significant.As part of the epidemiological transition, cancer incidence is expected to increase in the future, further straining limited health care resources. Appropriate allocation of resources for cancer prevention, early diagnosis, and curative and palliative care requires detailed knowledge of the local burden of cancer. The GBD 2015 study results demonstrate that progress is possible in the war against cancer. However, the major findings also highlight an unmet need for cancer prevention efforts, including tobacco control, vaccination, and the promotion of physical activity and a healthy diet.

<h2>Summary</h2><h3>Background</h3> Exposure to ambient air pollution increases morbidity and mortality, and is a leading contributor to global disease burden. We explored spatial and temporal trends in mortality and burden of disease attributable to ambient air pollution from 1990 to 2015 at global, regional, and country levels. <h3>Methods</h3> We estimated global population-weighted mean concentrations of particle mass with aerodynamic diameter less than 2·5 μm (PM_2·5) and ozone at an approximate 11 km × 11 km resolution with satellite-based estimates, chemical transport models, and ground-level measurements. Using integrated exposure–response functions for each cause of death, we estimated the relative risk of mortality from ischaemic heart disease, cerebrovascular disease, chronic obstructive pulmonary disease, lung cancer, and lower respiratory infections from epidemiological studies using non-linear exposure–response functions spanning the global range of exposure. <h3>Findings</h3> Ambient PM_2·5 was the fifth-ranking mortality risk factor in 2015. Exposure to PM_2·5 caused 4·2 million (95% uncertainty interval [UI] 3·7 million to 4·8 million) deaths and 103·1 million (90·8 million 115·1 million) disability-adjusted life-years (DALYs) in 2015, representing 7·6% of total global deaths and 4·2% of global DALYs, 59% of these in east and south Asia. Deaths attributable to ambient PM_2·5 increased from 3·5 million (95% UI 3·0 million to 4·0 million) in 1990 to 4·2 million (3·7 million to 4·8 million) in 2015. Exposure to ozone caused an additional 254 000 (95% UI 97 000–422 000) deaths and a loss of 4·1 million (1·6 million to 6·8 million) DALYs from chronic obstructive pulmonary disease in 2015. <h3>Interpretation</h3> Ambient air pollution contributed substantially to the global burden of disease in 2015, which increased over the past 25 years, due to population ageing, changes in non-communicable disease rates, and increasing air pollution in low-income and middle-income countries. Modest reductions in burden will occur in the most polluted countries unless PM_2·5 values are decreased substantially, but there is potential for substantial health benefits from exposure reduction. <h3>Funding</h3> Bill & Melinda Gates Foundation and Health Effects Institute.

Background— The global burden of atrial fibrillation (AF) is unknown. Methods and Results— We systematically reviewed population-based studies of AF published from 1980 to 2010 from the 21 Global Burden of Disease regions to estimate global/regional prevalence, incidence, and morbidity and mortality related to AF (DisModMR software). Of 377 potential studies identified, 184 met prespecified eligibility criteria. The estimated number of individuals with AF globally in 2010 was 33.5 million (20.9 million men [95% uncertainty interval (UI), 19.5–22.2 million] and 12.6 million women [95% UI, 12.0–13.7 million]). Burden associated with AF, measured as disability-adjusted life-years, increased by 18.8% (95% UI, 15.8–19.3) in men and 18.9% (95% UI, 15.8–23.5) in women from 1990 to 2010. In 1990, the estimated age-adjusted prevalence rates of AF (per 100 000 population) were 569.5 in men (95% UI, 532.8–612.7) and 359.9 in women (95% UI, 334.7–392.6); the estimated age-adjusted incidence rates were 60.7 per 100 000 person-years in men (95% UI, 49.2–78.5) and 43.8 in women (95% UI, 35.9–55.0). In 2010, the prevalence rates increased to 596.2 (95% UI, 558.4–636.7) in men and 373.1 (95% UI, 347.9–402.2) in women; the incidence rates increased to 77.5 (95% UI, 65.2–95.4) in men and 59.5 (95% UI, 49.9–74.9) in women. Mortality associated with AF was higher in women and increased by 2-fold (95% UI, 2.0–2.2) and 1.9-fold (95% UI, 1.8–2.0) in men and women, respectively, from 1990 to 2010. There was evidence of significant regional heterogeneity in AF estimations and availability of population-based data. Conclusions— These findings provide evidence of progressive increases in overall burden, incidence, prevalence, and AF-associated mortality between 1990 and 2010, with significant public health implications. Systematic, regional surveillance of AF is required to better direct prevention and treatment strategies.

Suboptimal diet is an important preventable risk factor for non-communicable diseases (NCDs); however, its impact on the burden of NCDs has not been systematically evaluated. This study aimed to evaluate the consumption of major foods and nutrients across 195 countries and to quantify the impact of their suboptimal intake on NCD mortality and morbidity.By use of a comparative risk assessment approach, we estimated the proportion of disease-specific burden attributable to each dietary risk factor (also referred to as population attributable fraction) among adults aged 25 years or older. The main inputs to this analysis included the intake of each dietary factor, the effect size of the dietary factor on disease endpoint, and the level of intake associated with the lowest risk of mortality. Then, by use of disease-specific population attributable fractions, mortality, and disability-adjusted life-years (DALYs), we calculated the number of deaths and DALYs attributable to diet for each disease outcome.In 2017, 11 million (95% uncertainty interval [UI] 10-12) deaths and 255 million (234-274) DALYs were attributable to dietary risk factors. High intake of sodium (3 million [1-5] deaths and 70 million [34-118] DALYs), low intake of whole grains (3 million [2-4] deaths and 82 million [59-109] DALYs), and low intake of fruits (2 million [1-4] deaths and 65 million [41-92] DALYs) were the leading dietary risk factors for deaths and DALYs globally and in many countries. Dietary data were from mixed sources and were not available for all countries, increasing the statistical uncertainty of our estimates.This study provides a comprehensive picture of the potential impact of suboptimal diet on NCD mortality and morbidity, highlighting the need for improving diet across nations. Our findings will inform implementation of evidence-based dietary interventions and provide a platform for evaluation of their impact on human health annually.Bill & Melinda Gates Foundation.

Although stroke is the second leading cause of death worldwide, no comprehensive and comparable assessment of incidence, prevalence, mortality, disability, and epidemiological trends has been estimated for most regions. We used data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010) to estimate the global and regional burden of stroke during 1990-2010.We searched Medline, Embase, LILACS, Scopus, PubMed, Science Direct, Global Health Database, the WHO library, and WHO regional databases from 1990 to 2012 to identify relevant studies published between 1990 and 2010.We applied the GBD 2010 analytical technique (DisMod-MR), based on disease-specific, pre-specified associations between incidence, prevalence, and mortality, to calculate regional and country-specific estimates of stroke incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) lost by age group (<75 years, ≥ 75 years, and in total)and country income level (high-income, and low-income and middle-income) for 1990, 2005, and 2010.We included 119 studies (58 from high-income countries and 61 from low-income and middle-income countries). From 1990 to 2010, the age-standardised incidence of stroke significantly decreased by 12% (95% CI 6-17)in high-income countries, and increased by 12% (-3 to 22) in low-income and middle-income countries, albeit nonsignificantly. Mortality rates decreased significantly in both high income (37%, 31-41) and low-income and middle income countries (20%, 15-30). In 2010, the absolute numbers of people with fi rst stroke (16・9 million), stroke survivors (33 million), stroke-related deaths (5・9 million), and DALYs lost (102 million) were high and had significantly increased since 1990 (68%, 84%, 26%, and 12% increase, respectively), with most of the burden (68・6% incident strokes, 52・2% prevalent strokes, 70・9% stroke deaths, and 77・7% DALYs lost) in low-income and middle-income countries. In 2010, 5・2 million (31%) strokes were in children (aged <20 years old) and young and middle-aged adults(20-64 years), to which children and young and middle-aged adults from low-income and middle-income countries contributed almost 74 000 (89%) and 4・0 million (78%), respectively, of the burden. Additionally, we noted significant geographical differences of between three and ten times in stroke burden between GBD regions and countries. More than 62% of new strokes, 69・8% of prevalent strokes, 45・5% of deaths from stroke, and 71・7% of DALYs lost because of stroke were in people younger than 75 years.Although age-standardised rates of stroke mortality have decreased worldwide in the past two decades,the absolute number of people who have a stroke every year, stroke survivors, related deaths, and the overall global burden of stroke (DALYs lost) are great and increasing. Further study is needed to improve understanding of stroke determinants and burden worldwide, and to establish causes of disparities and changes in trends in stroke burden between countries of different income levels.Bill & Melinda Gates Foundation.

Alcohol use is a leading risk factor for death and disability, but its overall association with health remains complex given the possible protective effects of moderate alcohol consumption on some conditions. With our comprehensive approach to health accounting within the Global Burden of Diseases, Injuries, and Risk Factors Study 2016, we generated improved estimates of alcohol use and alcohol-attributable deaths and disability-adjusted life-years (DALYs) for 195 locations from 1990 to 2016, for both sexes and for 5-year age groups between the ages of 15 years and 95 years and older.Using 694 data sources of individual and population-level alcohol consumption, along with 592 prospective and retrospective studies on the risk of alcohol use, we produced estimates of the prevalence of current drinking, abstention, the distribution of alcohol consumption among current drinkers in standard drinks daily (defined as 10 g of pure ethyl alcohol), and alcohol-attributable deaths and DALYs. We made several methodological improvements compared with previous estimates: first, we adjusted alcohol sales estimates to take into account tourist and unrecorded consumption; second, we did a new meta-analysis of relative risks for 23 health outcomes associated with alcohol use; and third, we developed a new method to quantify the level of alcohol consumption that minimises the overall risk to individual health.Globally, alcohol use was the seventh leading risk factor for both deaths and DALYs in 2016, accounting for 2·2% (95% uncertainty interval [UI] 1·5-3·0) of age-standardised female deaths and 6·8% (5·8-8·0) of age-standardised male deaths. Among the population aged 15-49 years, alcohol use was the leading risk factor globally in 2016, with 3·8% (95% UI 3·2-4·3) of female deaths and 12·2% (10·8-13·6) of male deaths attributable to alcohol use. For the population aged 15-49 years, female attributable DALYs were 2·3% (95% UI 2·0-2·6) and male attributable DALYs were 8·9% (7·8-9·9). The three leading causes of attributable deaths in this age group were tuberculosis (1·4% [95% UI 1·0-1·7] of total deaths), road injuries (1·2% [0·7-1·9]), and self-harm (1·1% [0·6-1·5]). For populations aged 50 years and older, cancers accounted for a large proportion of total alcohol-attributable deaths in 2016, constituting 27·1% (95% UI 21·2-33·3) of total alcohol-attributable female deaths and 18·9% (15·3-22·6) of male deaths. The level of alcohol consumption that minimised harm across health outcomes was zero (95% UI 0·0-0·8) standard drinks per week.Alcohol use is a leading risk factor for global disease burden and causes substantial health loss. We found that the risk of all-cause mortality, and of cancers specifically, rises with increasing levels of consumption, and the level of consumption that minimises health loss is zero. These results suggest that alcohol control policies might need to be revised worldwide, refocusing on efforts to lower overall population-level consumption.Bill & Melinda Gates Foundation.

BackgroundThe Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution.MethodsAttributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk–outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990–2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian meta-regression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol.FindingsAll risks combined account for 57·2% (95% uncertainty interval [UI] 55·8–58·5) of deaths and 41·6% (40·1–43·0) of DALYs. Risks quantified account for 87·9% (86·5–89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa.InterpretationBehavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks.FundingBill & Melinda Gates Foundation.

Healthy life expectancy (HALE) and disability-adjusted life-years (DALYs) provide summary measures of health across geographies and time that can inform assessments of epidemiological patterns and health system performance, help to prioritise investments in research and development, and monitor progress toward the Sustainable Development Goals (SDGs). We aimed to provide updated HALE and DALYs for geographies worldwide and evaluate how disease burden changes with development.We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2015. We calculated DALYs by summing years of life lost (YLLs) and years of life lived with disability (YLDs) for each geography, age group, sex, and year. We estimated HALE using the Sullivan method, which draws from age-specific death rates and YLDs per capita. We then assessed how observed levels of DALYs and HALE differed from expected trends calculated with the Socio-demographic Index (SDI), a composite indicator constructed from measures of income per capita, average years of schooling, and total fertility rate.Total global DALYs remained largely unchanged from 1990 to 2015, with decreases in communicable, neonatal, maternal, and nutritional (Group 1) disease DALYs offset by increased DALYs due to non-communicable diseases (NCDs). Much of this epidemiological transition was caused by changes in population growth and ageing, but it was accelerated by widespread improvements in SDI that also correlated strongly with the increasing importance of NCDs. Both total DALYs and age-standardised DALY rates due to most Group 1 causes significantly decreased by 2015, and although total burden climbed for the majority of NCDs, age-standardised DALY rates due to NCDs declined. Nonetheless, age-standardised DALY rates due to several high-burden NCDs (including osteoarthritis, drug use disorders, depression, diabetes, congenital birth defects, and skin, oral, and sense organ diseases) either increased or remained unchanged, leading to increases in their relative ranking in many geographies. From 2005 to 2015, HALE at birth increased by an average of 2·9 years (95% uncertainty interval 2·9-3·0) for men and 3·5 years (3·4-3·7) for women, while HALE at age 65 years improved by 0·85 years (0·78-0·92) and 1·2 years (1·1-1·3), respectively. Rising SDI was associated with consistently higher HALE and a somewhat smaller proportion of life spent with functional health loss; however, rising SDI was related to increases in total disability. Many countries and territories in central America and eastern sub-Saharan Africa had increasingly lower rates of disease burden than expected given their SDI. At the same time, a subset of geographies recorded a growing gap between observed and expected levels of DALYs, a trend driven mainly by rising burden due to war, interpersonal violence, and various NCDs.Health is improving globally, but this means more populations are spending more time with functional health loss, an absolute expansion of morbidity. The proportion of life spent in ill health decreases somewhat with increasing SDI, a relative compression of morbidity, which supports continued efforts to elevate personal income, improve education, and limit fertility. Our analysis of DALYs and HALE and their relationship to SDI represents a robust framework on which to benchmark geography-specific health performance and SDG progress. Country-specific drivers of disease burden, particularly for causes with higher-than-expected DALYs, should inform financial and research investments, prevention efforts, health policies, and health system improvement initiatives for all countries along the development continuum.Bill & Melinda Gates Foundation.

Elevated systolic blood (SBP) pressure is a leading global health risk. Quantifying the levels of SBP is important to guide prevention policies and interventions.To estimate the association between SBP of at least 110 to 115 mm Hg and SBP of 140 mm Hg or higher and the burden of different causes of death and disability by age and sex for 195 countries and territories, 1990-2015.A comparative risk assessment of health loss related to SBP. Estimated distribution of SBP was based on 844 studies from 154 countries (published 1980-2015) of 8.69 million participants. Spatiotemporal Gaussian process regression was used to generate estimates of mean SBP and adjusted variance for each age, sex, country, and year. Diseases with sufficient evidence for a causal relationship with high SBP (eg, ischemic heart disease, ischemic stroke, and hemorrhagic stroke) were included in the primary analysis.Mean SBP level, cause-specific deaths, and health burden related to SBP (≥110-115 mm Hg and also ≥140 mm Hg) by age, sex, country, and year.Between 1990-2015, the rate of SBP of at least 110 to 115 mm Hg increased from 73 119 (95% uncertainty interval [UI], 67 949-78 241) to 81 373 (95% UI, 76 814-85 770) per 100 000, and SBP of 140 mm Hg or higher increased from 17 307 (95% UI, 17 117-17 492) to 20 526 (95% UI, 20 283-20 746) per 100 000. The estimated annual death rate per 100 000 associated with SBP of at least 110 to 115 mm Hg increased from 135.6 (95% UI, 122.4-148.1) to 145.2 (95% UI 130.3-159.9) and the rate for SBP of 140 mm Hg or higher increased from 97.9 (95% UI, 87.5-108.1) to 106.3 (95% UI, 94.6-118.1). For loss of DALYs associated with systolic blood pressure of 140 mm Hg or higher, the loss increased from 95.9 million (95% uncertainty interval [UI], 87.0-104.9 million) to 143.0 million (95% UI, 130.2-157.0 million) [corrected], and for SBP of 140 mm Hg or higher, the loss increased from 5.2 million (95% UI, 4.6-5.7 million) to 7.8 million (95% UI, 7.0-8.7 million). The largest numbers of SBP-related deaths were caused by ischemic heart disease (4.9 million [95% UI, 4.0-5.7 million]; 54.5%), hemorrhagic stroke (2.0 million [95% UI, 1.6-2.3 million]; 58.3%), and ischemic stroke (1.5 million [95% UI, 1.2-1.8 million]; 50.0%). In 2015, China, India, Russia, Indonesia, and the United States accounted for more than half of the global DALYs related to SBP of at least 110 to 115 mm Hg.In international surveys, although there is uncertainty in some estimates, the rate of elevated SBP (≥110-115 and ≥140 mm Hg) increased substantially between 1990 and 2015, and DALYs and deaths associated with elevated SBP also increased. Projections based on this sample suggest that in 2015, an estimated 3.5 billion adults had SBP of at least 110 to 115 mm Hg and 874 million adults had SBP of 140 mm Hg or higher.

BackgroundLower respiratory infections are a leading cause of morbidity and mortality around the world. The Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study 2016, provides an up-to-date analysis of the burden of lower respiratory infections in 195 countries. This study assesses cases, deaths, and aetiologies spanning the past 26 years and shows how the burden of lower respiratory infection has changed in people of all ages.MethodsWe used three separate modelling strategies for lower respiratory infections in GBD 2016: a Bayesian hierarchical ensemble modelling platform (Cause of Death Ensemble model), which uses vital registration, verbal autopsy data, and surveillance system data to predict mortality due to lower respiratory infections; a compartmental meta-regression tool (DisMod-MR), which uses scientific literature, population representative surveys, and health-care data to predict incidence, prevalence, and mortality; and modelling of counterfactual estimates of the population attributable fraction of lower respiratory infection episodes due to Streptococcus pneumoniae, Haemophilus influenzae type b, influenza, and respiratory syncytial virus. We calculated each modelled estimate for each age, sex, year, and location. We modelled the exposure level in a population for a given risk factor using DisMod-MR and a spatio-temporal Gaussian process regression, and assessed the effectiveness of targeted interventions for each risk factor in children younger than 5 years. We also did a decomposition analysis of the change in LRI deaths from 2000–16 using the risk factors associated with LRI in GBD 2016.FindingsIn 2016, lower respiratory infections caused 652 572 deaths (95% uncertainty interval [UI] 586 475–720 612) in children younger than 5 years (under-5s), 1 080 958 deaths (943 749–1 170 638) in adults older than 70 years, and 2 377 697 deaths (2 145 584–2 512 809) in people of all ages, worldwide. Streptococcus pneumoniae was the leading cause of lower respiratory infection morbidity and mortality globally, contributing to more deaths than all other aetiologies combined in 2016 (1 189 937 deaths, 95% UI 690 445–1 770 660). Childhood wasting remains the leading risk factor for lower respiratory infection mortality among children younger than 5 years, responsible for 61·4% of lower respiratory infection deaths in 2016 (95% UI 45·7–69·6). Interventions to improve wasting, household air pollution, ambient particulate matter pollution, and expanded antibiotic use could avert one under-5 death due to lower respiratory infection for every 4000 children treated in the countries with the highest lower respiratory infection burden.InterpretationOur findings show substantial progress in the reduction of lower respiratory infection burden, but this progress has not been equal across locations, has been driven by decreases in several primary risk factors, and might require more effort among elderly adults. By highlighting regions and populations with the highest burden, and the risk factors that could have the greatest effect, funders, policy makers, and programme implementers can more effectively reduce lower respiratory infections among the world's most susceptible populations.FundingBill & Melinda Gates Foundation.

The contribution of modifiable risk factors to the increasing global and regional burden of stroke is unclear, but knowledge about this contribution is crucial for informing stroke prevention strategies. We used data from the Global Burden of Disease Study 2013 (GBD 2013) to estimate the population-attributable fraction (PAF) of stroke-related disability-adjusted life-years (DALYs) associated with potentially modifiable environmental, occupational, behavioural, physiological, and metabolic risk factors in different age and sex groups worldwide and in high-income countries and low-income and middle-income countries, from 1990 to 2013.We used data on stroke-related DALYs, risk factors, and PAF from the GBD 2013 Study to estimate the burden of stroke by age and sex (with corresponding 95% uncertainty intervals [UI]) in 188 countries, as measured with stroke-related DALYs in 1990 and 2013. We evaluated attributable DALYs for 17 risk factors (air pollution and environmental, dietary, physical activity, tobacco smoke, and physiological) and six clusters of risk factors by use of three inputs: risk factor exposure, relative risks, and the theoretical minimum risk exposure level. For most risk factors, we synthesised data for exposure with a Bayesian meta-regression method (DisMod-MR) or spatial-temporal Gaussian process regression. We based relative risks on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks, such as high body-mass index (BMI), through other risks, such as high systolic blood pressure (SBP) and high total cholesterol.Globally, 90·5% (95% UI 88·5-92·2) of the stroke burden (as measured in DALYs) was attributable to the modifiable risk factors analysed, including 74·2% (95% UI 70·7-76·7) due to behavioural factors (smoking, poor diet, and low physical activity). Clusters of metabolic factors (high SBP, high BMI, high fasting plasma glucose, high total cholesterol, and low glomerular filtration rate; 72·4%, 95% UI 70·2-73·5) and environmental factors (air pollution and lead exposure; 33·4%, 95% UI 32·4-34·3) were the second and third largest contributors to DALYs. Globally, 29·2% (95% UI 28·2-29·6) of the burden of stroke was attributed to air pollution. Although globally there were no significant differences between sexes in the proportion of stroke burden due to behavioural, environmental, and metabolic risk clusters, in the low-income and middle-income countries, the PAF of behavioural risk clusters in males was greater than in females. The PAF of all risk factors increased from 1990 to 2013 (except for second-hand smoking and household air pollution from solid fuels) and varied significantly between countries.Our results suggest that more than 90% of the stroke burden is attributable to modifiable risk factors, and achieving control of behavioural and metabolic risk factors could avert more than three-quarters of the global stroke burden. Air pollution has emerged as a significant contributor to global stroke burden, especially in low-income and middle-income countries, and therefore reducing exposure to air pollution should be one of the main priorities to reduce stroke burden in these countries.Bill & Melinda Gates Foundation, American Heart Association, US National Heart, Lung, and Blood Institute, Columbia University, Health Research Council of New Zealand, Brain Research New Zealand Centre of Research Excellence, and National Science Challenge, Ministry of Business, Innovation and Employment of New Zealand.

BackgroundThe burden of ischaemic and haemorrhagic stroke varies between regions and over time. With differences in prognosis, prevalence of risk factors, and treatment strategies, knowledge of stroke pathological type is important for targeted region-specific health-care planning for stroke and could inform priorities for type-specific prevention strategies. We used data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010) to estimate the global and regional burden of first-ever ischaemic and haemorrhagic stroke during 1990–2010.MethodsWe searched Medline, Embase, LILACS, Scopus, PubMed, Science Direct, Global Health Database, the WHO library, and regional databases from 1990 to 2012 to identify relevant studies published between 1990 and 2010. We applied the GBD 2010 analytical technique (DisMod-MR) to calculate regional and country-specific estimates for ischaemic and haemorrhagic stroke incidence, mortality, mortality-to-incidence ratio, and disability-adjusted life-years (DALYs) lost, by age group (aged <75 years, ≥75 years, and in total) and country income level (high-income and low-income and middle-income) for 1990, 2005, and 2010.FindingsWe included 119 studies (58 from high-income countries and 61 from low-income and middle-income countries). Worldwide, the burden of ischaemic and haemorrhagic stroke increased significantly between 1990 and 2010 in terms of the absolute number of people with incident ischaemic and haemorrhagic stroke (37% and 47% increase, respectively), number of deaths (21% and 20% increase), and DALYs lost (18% and 14% increase). In the past two decades in high-income countries, incidence of ischaemic stroke reduced significantly by 13% (95% CI 6–18), mortality by 37% (19–39), DALYs lost by 34% (16–36), and mortality-to-incidence ratios by 21% (10–27). For haemorrhagic stroke, incidence reduced significantly by 19% (1–15), mortality by 38% (32–43), DALYs lost by 39% (32–44), and mortality-to-incidence ratios by 27% (19–35). By contrast, in low-income and middle-income countries, we noted a significant increase of 22% (5–30) in incidence of haemorrhagic stroke and a 6% (–7 to 18) non-significant increase in the incidence of ischaemic stroke. Mortality rates for ischaemic stroke fell by 14% (9–19), DALYs lost by 17% (–11 to 21%), and mortality-to-incidence ratios by 16% (–12 to 22). For haemorrhagic stroke in low-income and middle-income countries, mortality rates reduced by 23% (–18 to 25%), DALYs lost by 25% (–21 to 28), and mortality-to-incidence ratios by 36% (–34 to 28).InterpretationAlthough age-standardised mortality rates for ischaemic and haemorrhagic stroke have decreased in the past two decades, the absolute number of people who have these stroke types annually, and the number with related deaths and DALYs lost, is increasing, with most of the burden in low-income and middle-income countries. Further study is needed in these countries to identify which subgroups of the population are at greatest risk and who could be targeted for preventive efforts.FundingBill & Melinda Gates Foundation.

Global stroke epidemiology is changing rapidly. Although age-standardized rates of stroke mortality have decreased worldwide in the past 2 decades, the absolute numbers of people who have a stroke every year, and live with the consequences of stroke or die from their stroke, are increasing. Regular updates on the current level of stroke burden are important for advancing our knowledge on stroke epidemiology and facilitate organization and planning of evidence-based stroke care.This study aims to estimate incidence, prevalence, mortality, disability-adjusted life years (DALYs) and years lived with disability (YLDs) and their trends for ischemic stroke (IS) and hemorrhagic stroke (HS) for 188 countries from 1990 to 2013.Stroke incidence, prevalence, mortality, DALYs and YLDs were estimated using all available data on mortality and stroke incidence, prevalence and excess mortality. Statistical models and country-level covariate data were employed, and all rates were age-standardized to a global population. All estimates were produced with 95% uncertainty intervals (UIs).In 2013, there were globally almost 25.7 million stroke survivors (71% with IS), 6.5 million deaths from stroke (51% died from IS), 113 million DALYs due to stroke (58% due to IS) and 10.3 million new strokes (67% IS). Over the 1990-2013 period, there was a significant increase in the absolute number of DALYs due to IS, and of deaths from IS and HS, survivors and incident events for both IS and HS. The preponderance of the burden of stroke continued to reside in developing countries, comprising 75.2% of deaths from stroke and 81.0% of stroke-related DALYs. Globally, the proportional contribution of stroke-related DALYs and deaths due to stroke compared to all diseases increased from 1990 (3.54% (95% UI 3.11-4.00) and 9.66% (95% UI 8.47-10.70), respectively) to 2013 (4.62% (95% UI 4.01-5.30) and 11.75% (95% UI 10.45-13.31), respectively), but there was a diverging trend in developed and developing countries with a significant increase in DALYs and deaths in developing countries, and no measurable change in the proportional contribution of DALYs and deaths from stroke in developed countries.Global stroke burden continues to increase globally. More efficient stroke prevention and management strategies are urgently needed to halt and eventually reverse the stroke pandemic, while universal access to organized stroke services should be a priority. © 2015 S. Karger AG, Basel.

Exposure to ambient air pollution is a major risk factor for global disease. Assessment of the impacts of air pollution on population health and evaluation of trends relative to other major risk factors requires regularly updated, accurate, spatially resolved exposure estimates. We combined satellite-based estimates, chemical transport model simulations, and ground measurements from 79 different countries to produce global estimates of annual average fine particle (PM2.5) and ozone concentrations at 0.1° × 0.1° spatial resolution for five-year intervals from 1990 to 2010 and the year 2013. These estimates were applied to assess population-weighted mean concentrations for 1990–2013 for each of 188 countries. In 2013, 87% of the world’s population lived in areas exceeding the World Health Organization Air Quality Guideline of 10 μg/m3 PM2.5 (annual average). Between 1990 and 2013, global population-weighted PM2.5 increased by 20.4% driven by trends in South Asia, Southeast Asia, and China. Decreases in population-weighted mean concentrations of PM2.5 were evident in most high income countries. Population-weighted mean concentrations of ozone increased globally by 8.9% from 1990–2013 with increases in most countries—except for modest decreases in North America, parts of Europe, and several countries in Southeast Asia.

The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 provides an up-to-date analysis of the burden of diarrhoea in 195 countries. This study assesses cases, deaths, and aetiologies in 1990-2016 and assesses how the burden of diarrhoea has changed in people of all ages.We modelled diarrhoea mortality with a Bayesian hierarchical modelling platform that evaluates a wide range of covariates and model types on the basis of vital registration and verbal autopsy data. We modelled diarrhoea incidence with a compartmental meta-regression tool that enforces an association between incidence and prevalence, and relies on scientific literature, population representative surveys, and health-care data. Diarrhoea deaths and episodes were attributed to 13 pathogens by use of a counterfactual population attributable fraction approach. Diarrhoea risk factors are also based on counterfactual estimates of risk exposure and the association between the risk and diarrhoea. Each modelled estimate accounted for uncertainty.In 2016, diarrhoea was the eighth leading cause of death among all ages (1 655 944 deaths, 95% uncertainty interval [UI] 1 244 073-2 366 552) and the fifth leading cause of death among children younger than 5 years (446 000 deaths, 390 894-504 613). Rotavirus was the leading aetiology for diarrhoea mortality among children younger than 5 years (128 515 deaths, 105 138-155 133) and among all ages (228 047 deaths, 183 526-292 737). Childhood wasting (low weight-for-height score), unsafe water, and unsafe sanitation were the leading risk factors for diarrhoea, responsible for 80·4% (95% UI 68·2-85·0), 72·1% (34·0-91·4), and 56·4% (49·3-62·7) of diarrhoea deaths in children younger than 5 years, respectively. Prevention of wasting in 1762 children (95% UI 1521-2170) could avert one death from diarrhoea.Substantial progress has been made globally in reducing the burden of diarrhoeal diseases, driven by decreases in several primary risk factors. However, this reduction has not been equal across locations, and burden among adults older than 70 years requires attention.Bill & Melinda Gates Foundation.

Global deaths from cardiovascular disease are increasing as a result of population growth, the aging of populations, and epidemiologic changes in disease. Disentangling the effects of these three drivers on trends in mortality is important for planning the future of the health care system and benchmarking progress toward the reduction of cardiovascular disease.We used mortality data from the Global Burden of Disease Study 2013, which includes data on 188 countries grouped into 21 world regions. We developed three counterfactual scenarios to represent the principal drivers of change in cardiovascular deaths (population growth alone, population growth and aging, and epidemiologic changes in disease) from 1990 to 2013. Secular trends and correlations with changes in national income were examined.Global deaths from cardiovascular disease increased by 41% between 1990 and 2013 despite a 39% decrease in age-specific death rates; this increase was driven by a 55% increase in mortality due to the aging of populations and a 25% increase due to population growth. The relative contributions of these drivers varied by region; only in Central Europe and Western Europe did the annual number of deaths from cardiovascular disease actually decline. Change in gross domestic product per capita was correlated with change in age-specific death rates only among upper-middle income countries, and this correlation was weak; there was no significant correlation elsewhere.The aging and growth of the population resulted in an increase in global cardiovascular deaths between 1990 and 2013, despite a decrease in age-specific death rates in most regions. Only Central and Western Europe had gains in cardiovascular health that were sufficient to offset these demographic forces. (Funded by the Bill and Melinda Gates Foundation and others.).

<b>Objective</b>&nbsp;To quantify the dose-response associations between total physical activity and risk of breast cancer, colon cancer, diabetes, ischemic heart disease, and ischemic stroke events. <b>Design</b>&nbsp;Systematic review and Bayesian dose-response meta-analysis. <b>Data sources</b>&nbsp;PubMed and Embase from 1980 to 27 February 2016, and references from relevant systematic reviews. Data from the Study on Global AGEing and Adult Health conducted in China, Ghana, India, Mexico, Russia, and South Africa from 2007 to 2010 and the US National Health and Nutrition Examination Surveys from 1999 to 2011 were used to map domain specific physical activity (reported in included studies) to total activity. <b>Eligibility criteria for selecting studies</b>&nbsp;Prospective cohort studies examining the associations between physical activity (any domain) and at least one of the five diseases studied. <b>Results</b>&nbsp;174 articles were identified: 35 for breast cancer, 19 for colon cancer, 55 for diabetes, 43 for ischemic heart disease, and 26 for ischemic stroke (some articles included multiple outcomes). Although higher levels of total physical activity were significantly associated with lower risk for all outcomes, major gains occurred at lower levels of activity (up to 3000-4000 metabolic equivalent (MET) minutes/week). For example, individuals with a total activity level of 600 MET minutes/week (the minimum recommended level) had a 2% lower risk of diabetes compared with those reporting no physical activity. An increase from 600 to 3600 MET minutes/week reduced the risk by an additional 19%. The same amount of increase yielded much smaller returns at higher levels of activity: an increase of total activity from 9000 to 12 000 MET minutes/week reduced the risk of diabetes by only 0.6%. Compared with insufficiently active individuals (total activity &lt;600 MET minutes/week), the risk reduction for those in the highly active category (≥8000 MET minutes/week) was 14% (relative risk 0.863, 95% uncertainty interval 0.829 to 0.900) for breast cancer; 21% (0.789, 0.735 to 0.850) for colon cancer; 28% (0.722, 0.678 to 0.768) for diabetes; 25% (0.754, 0.704 to 0.809) for ischemic heart disease; and 26% (0.736, 0.659 to 0.811) for ischemic stroke. <b>Conclusions</b>&nbsp;People who achieve total physical activity levels several times higher than the current recommended minimum level have a significant reduction in the risk of the five diseases studied. More studies with detailed quantification of total physical activity will help to find more precise relative risk estimates for different levels of activity.

BackgroundThe Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) provides an up-to-date analysis of the burden of diarrhoeal diseases. This study assesses cases, deaths, and aetiologies spanning the past 25 years and informs the changing picture of diarrhoeal disease worldwide.MethodsWe estimated diarrhoeal mortality by age, sex, geography, and year using the Cause of Death Ensemble Model (CODEm), a modelling platform shared across most causes of death in the GBD 2015 study. We modelled diarrhoeal morbidity, including incidence and prevalence, using a meta-regression platform called DisMod-MR. We estimated aetiologies for diarrhoeal diseases using a counterfactual approach that incorporates the aetiology-specific risk of diarrhoeal disease and the prevalence of the aetiology in diarrhoea episodes. We used the Socio-demographic Index, a summary indicator derived from measures of income per capita, educational attainment, and fertility, to assess trends in diarrhoeal mortality. The two leading risk factors for diarrhoea—childhood malnutrition and unsafe water, sanitation, and hygiene—were used in a decomposition analysis to establish the relative contribution of changes in diarrhoea disability-adjusted life-years (DALYs).FindingsGlobally, in 2015, we estimate that diarrhoea was a leading cause of death among all ages (1·31 million deaths, 95% uncertainty interval [95% UI] 1·23 million to 1·39 million), as well as a leading cause of DALYs because of its disproportionate impact on young children (71·59 million DALYs, 66·44 million to 77·21 million). Diarrhoea was a common cause of death among children under 5 years old (499 000 deaths, 95% UI 447 000–558 000). The number of deaths due to diarrhoea decreased by an estimated 20·8% (95% UI 15·4–26·1) from 2005 to 2015. Rotavirus was the leading cause of diarrhoea deaths (199 000, 95% UI 165 000–241 000), followed by Shigella spp (164 300, 85 000–278 700) and Salmonella spp (90 300, 95% UI 34 100–183 100). Among children under 5 years old, the three aetiologies responsible for the most deaths were rotavirus, Cryptosporidium spp, and Shigella spp. Improvements in safe water and sanitation have decreased diarrhoeal DALYs by 13·4%, and reductions in childhood undernutrition have decreased diarrhoeal DALYs by 10·0% between 2005 and 2015.InterpretationAt the global level, deaths due to diarrhoeal diseases have decreased substantially in the past 25 years, although progress has been faster in some countries than others. Diarrhoea remains a largely preventable disease and cause of death, and continued efforts to improve access to safe water, sanitation, and childhood nutrition will be important in reducing the global burden of diarrhoea.FundingBill & Melinda Gates Foundation.

Background Breast and cervical cancer are important causes of mortality in women aged ≥15 years. We undertook annual age-specific assessments of breast and cervical cancer in 187 countries. Methods We systematically collected cancer registry data on mortality and incidence, vital registration, and verbal autopsy data for the period 1980–2010. We modelled the mortality-to-incidence (MI) ratio using a hierarchical model. Vital registration and verbal autopsy were supplemented with incidence multiplied by the MI ratio to yield a comprehensive database of mortality rates. We used Gaussian process regression to develop estimates of mortality with uncertainty by age, sex, country, and year. We used out-of-sample predictive validity to select the final model. Estimates of incidence with uncertainty were also generated with mortality and MI ratios. Findings Global breast cancer incidence increased from 641 000 (95% uncertainty intervals 610 000–750 000) cases in 1980 to 1 643 000 (1 421 000–1 782 000) cases in 2010, an annual rate of increase of 3·1%. Global cervical cancer incidence increased from 378 000 (256 000–489 000) cases per year in 1980 to 454 000 (318 000–620 000) cases per year in 2010—a 0·6% annual rate of increase. Breast cancer killed 425 000 (359 000–453 000) women in 2010, of whom 68 000 (62 000–74 000) were aged 15–49 years in developing countries. Cervical cancer death rates have been decreasing but the disease still killed 200 000 (139 000–276 000) women in 2010, of whom 46 000 (33 000–64 000) were aged 15–49 years in developing countries. We recorded pronounced variation in the trend in breast cancer mortality across regions and countries. Interpretation More policy attention is needed to strengthen established health-system responses to reduce breast and cervical cancer, especially in developing countries. Funding Susan G Komen for the Cure and the Bill & Melinda Gates Foundation.

Young people's health has emerged as a neglected yet pressing issue in global development. Changing patterns of young people's health have the potential to undermine future population health as well as global economic development unless timely and effective strategies are put into place. We report the past, present, and anticipated burden of disease in young people aged 10-24 years from 1990 to 2013 using data on mortality, disability, injuries, and health risk factors.The Global Burden of Disease Study 2013 (GBD 2013) includes annual assessments for 188 countries from 1990 to 2013, covering 306 diseases and injuries, 1233 sequelae, and 79 risk factors. We used the comparative risk assessment approach to assess how much of the burden of disease reported in a given year can be attributed to past exposure to a risk. We estimated attributable burden by comparing observed health outcomes with those that would have been observed if an alternative or counterfactual level of exposure had occurred in the past. We applied the same method to previous years to allow comparisons from 1990 to 2013. We cross-tabulated the quantiles of disability-adjusted life-years (DALYs) by quintiles of DALYs annual increase from 1990 to 2013 to show rates of DALYs increase by burden. We used the GBD 2013 hierarchy of causes that organises 306 diseases and injuries into four levels of classification. Level one distinguishes three broad categories: first, communicable, maternal, neonatal, and nutritional disorders; second, non-communicable diseases; and third, injuries. Level two has 21 mutually exclusive and collectively exhaustive categories, level three has 163 categories, and level four has 254 categories.The leading causes of death in 2013 for young people aged 10-14 years were HIV/AIDS, road injuries, and drowning (25·2%), whereas transport injuries were the leading cause of death for ages 15-19 years (14·2%) and 20-24 years (15·6%). Maternal disorders were the highest cause of death for young women aged 20-24 years (17·1%) and the fourth highest for girls aged 15-19 years (11·5%) in 2013. Unsafe sex as a risk factor for DALYs increased from the 13th rank to the second for both sexes aged 15-19 years from 1990 to 2013. Alcohol misuse was the highest risk factor for DALYs (7·0% overall, 10·5% for males, and 2·7% for females) for young people aged 20-24 years, whereas drug use accounted for 2·7% (3·3% for males and 2·0% for females). The contribution of risk factors varied between and within countries. For example, for ages 20-24 years, drug use was highest in Qatar and accounted for 4·9% of DALYs, followed by 4·8% in the United Arab Emirates, whereas alcohol use was highest in Russia and accounted for 21·4%, followed by 21·0% in Belarus. Alcohol accounted for 9·0% (ranging from 4·2% in Hong Kong to 11·3% in Shandong) in China and 11·6% (ranging from 10·1% in Aguascalientes to 14·9% in Chihuahua) of DALYs in Mexico for young people aged 20-24 years. Alcohol and drug use in those aged 10-24 years had an annual rate of change of >1·0% from 1990 to 2013 and accounted for more than 3·1% of DALYs.Our findings call for increased efforts to improve health and reduce the burden of disease and risks for diseases in later life in young people. Moreover, because of the large variations between countries in risks and burden, a global approach to improve health during this important period of life will fail unless the particularities of each country are taken into account. Finally, our results call for a strategy to overcome the financial and technical barriers to adequately capture young people's health risk factors and their determinants in health information systems.Bill & Melinda Gates Foundation.

Remarkable financial and political efforts have been focused on the reduction of child mortality during the past few decades. Timely measurements of levels and trends in under-5 mortality are important to assess progress towards the Millennium Development Goal 4 (MDG 4) target of reduction of child mortality by two thirds from 1990 to 2015, and to identify models of success.We generated updated estimates of child mortality in early neonatal (age 0-6 days), late neonatal (7-28 days), postneonatal (29-364 days), childhood (1-4 years), and under-5 (0-4 years) age groups for 188 countries from 1970 to 2013, with more than 29,000 survey, census, vital registration, and sample registration datapoints. We used Gaussian process regression with adjustments for bias and non-sampling error to synthesise the data for under-5 mortality for each country, and a separate model to estimate mortality for more detailed age groups. We used explanatory mixed effects regression models to assess the association between under-5 mortality and income per person, maternal education, HIV child death rates, secular shifts, and other factors. To quantify the contribution of these different factors and birth numbers to the change in numbers of deaths in under-5 age groups from 1990 to 2013, we used Shapley decomposition. We used estimated rates of change between 2000 and 2013 to construct under-5 mortality rate scenarios out to 2030.We estimated that 6·3 million (95% UI 6·0-6·6) children under-5 died in 2013, a 64% reduction from 17·6 million (17·1-18·1) in 1970. In 2013, child mortality rates ranged from 152·5 per 1000 livebirths (130·6-177·4) in Guinea-Bissau to 2·3 (1·8-2·9) per 1000 in Singapore. The annualised rates of change from 1990 to 2013 ranged from -6·8% to 0·1%. 99 of 188 countries, including 43 of 48 countries in sub-Saharan Africa, had faster decreases in child mortality during 2000-13 than during 1990-2000. In 2013, neonatal deaths accounted for 41·6% of under-5 deaths compared with 37·4% in 1990. Compared with 1990, in 2013, rising numbers of births, especially in sub-Saharan Africa, led to 1·4 million more child deaths, and rising income per person and maternal education led to 0·9 million and 2·2 million fewer deaths, respectively. Changes in secular trends led to 4·2 million fewer deaths. Unexplained factors accounted for only -1% of the change in child deaths. In 30 developing countries, decreases since 2000 have been faster than predicted attributable to income, education, and secular shift alone.Only 27 developing countries are expected to achieve MDG 4. Decreases since 2000 in under-5 mortality rates are accelerating in many developing countries, especially in sub-Saharan Africa. The Millennium Declaration and increased development assistance for health might have been a factor in faster decreases in some developing countries. Without further accelerated progress, many countries in west and central Africa will still have high levels of under-5 mortality in 2030.Bill & Melinda Gates Foundation, US Agency for International Development.

The Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study 2015 provides an up-to-date analysis of the burden of lower respiratory tract infections (LRIs) in 195 countries. This study assesses cases, deaths, and aetiologies spanning the past 25 years and shows how the burden of LRI has changed in people of all ages.We estimated LRI mortality by age, sex, geography, and year using a modelling platform shared across most causes of death in the GBD 2015 study called the Cause of Death Ensemble model. We modelled LRI morbidity, including incidence and prevalence, using a meta-regression platform called DisMod-MR. We estimated aetiologies for LRI using two different counterfactual approaches, the first for viral pathogens, which incorporates the aetiology-specific risk of LRI and the prevalence of the aetiology in LRI episodes, and the second for bacterial pathogens, which uses a vaccine-probe approach. We used the Socio-demographic Index, which is a summary indicator derived from measures of income per capita, educational attainment, and fertility, to assess trends in LRI-related mortality. The two leading risk factors for LRI disability-adjusted life-years (DALYs), childhood undernutrition and air pollution, were used in a decomposition analysis to establish the relative contribution of changes in LRI DALYs.In 2015, we estimated that LRIs caused 2·74 million deaths (95% uncertainty interval [UI] 2·50 million to 2·86 million) and 103·0 million DALYs (95% UI 96·1 million to 109·1 million). LRIs have a disproportionate effect on children younger than 5 years, responsible for 704 000 deaths (95% UI 651 000-763 000) and 60.6 million DALYs (95ÙI 56·0-65·6). Between 2005 and 2015, the number of deaths due to LRI decreased by 36·9% (95% UI 31·6 to 42·0) in children younger than 5 years, and by 3·2% (95% UI -0·4 to 6·9) in all ages. Pneumococcal pneumonia caused 55·4% of LRI deaths in all ages, totalling 1 517 388 deaths (95% UI 857 940-2 183 791). Between 2005 and 2015, improvements in air pollution exposure were responsible for a 4·3% reduction in LRI DALYs and improvements in childhood undernutrition were responsible for an 8·9% reduction.LRIs are the leading infectious cause of death and the fifth-leading cause of death overall; they are the second-leading cause of DALYs. At the global level, the burden of LRIs has decreased dramatically in the last 10 years in children younger than 5 years, although the burden in people older than 70 years has increased in many regions. LRI remains a largely preventable disease and cause of death, and continued efforts to decrease indoor and ambient air pollution, improve childhood nutrition, and scale up the use of the pneumococcal conjugate vaccine in children and adults will be essential in reducing the global burden of LRI.Bill & Melinda Gates Foundation.

Background— Ischemic heart disease (IHD) burden consists of years of life lost from IHD deaths and years of disability lived with 3 nonfatal IHD sequelae: nonfatal acute myocardial infarction, angina pectoris, and ischemic heart failure. Our aim was to estimate the global and regional burden of IHD in 1990 and 2010. Methods and Results— Global and regional estimates of acute myocardial infarction incidence and angina and heart failure prevalence by age, sex, and world region in 1990 and 2010 were estimated based on data from a systematic review and nonlinear mixed-effects meta-regression methods. Age-standardized acute myocardial infarction incidence and angina prevalence decreased globally between 1990 and 2010; ischemic heart failure prevalence increased slightly. The global burden of IHD increased by 29 million disability-adjusted life-years (29% increase) between 1990 and 2010. About 32.4% of the growth in global IHD disability-adjusted life-years between 1990 and 2010 was attributable to aging of the world population, 22.1% was attributable to population growth, and total disability-adjusted life-years were attenuated by a 25.3% decrease in per capita IHD burden (decreased rate). The number of people living with nonfatal IHD increased more than the number of IHD deaths since 1990, but &gt;90% of IHD disability-adjusted life-years in 2010 were attributable to IHD deaths. Conclusions— Globally, age-standardized acute myocardial infarction incidence and angina prevalence have decreased, and ischemic heart failure prevalence has increased since 1990. Despite decreased age-standardized fatal and nonfatal IHD in most regions since 1990, population growth and aging led to a higher global burden of IHD in 2010.

The literature focuses on mortality among children younger than 5 years. Comparable information on nonfatal health outcomes among these children and the fatal and nonfatal burden of diseases and injuries among older children and adolescents is scarce.To determine levels and trends in the fatal and nonfatal burden of diseases and injuries among younger children (aged <5 years), older children (aged 5-9 years), and adolescents (aged 10-19 years) between 1990 and 2013 in 188 countries from the Global Burden of Disease (GBD) 2013 study.Data from vital registration, verbal autopsy studies, maternal and child death surveillance, and other sources covering 14,244 site-years (ie, years of cause of death data by geography) from 1980 through 2013 were used to estimate cause-specific mortality. Data from 35,620 epidemiological sources were used to estimate the prevalence of the diseases and sequelae in the GBD 2013 study. Cause-specific mortality for most causes was estimated using the Cause of Death Ensemble Model strategy. For some infectious diseases (eg, HIV infection/AIDS, measles, hepatitis B) where the disease process is complex or the cause of death data were insufficient or unavailable, we used natural history models. For most nonfatal health outcomes, DisMod-MR 2.0, a Bayesian metaregression tool, was used to meta-analyze the epidemiological data to generate prevalence estimates.Of the 7.7 (95% uncertainty interval [UI], 7.4-8.1) million deaths among children and adolescents globally in 2013, 6.28 million occurred among younger children, 0.48 million among older children, and 0.97 million among adolescents. In 2013, the leading causes of death were lower respiratory tract infections among younger children (905.059 deaths; 95% UI, 810,304-998,125), diarrheal diseases among older children (38,325 deaths; 95% UI, 30,365-47,678), and road injuries among adolescents (115,186 deaths; 95% UI, 105,185-124,870). Iron deficiency anemia was the leading cause of years lived with disability among children and adolescents, affecting 619 (95% UI, 618-621) million in 2013. Large between-country variations exist in mortality from leading causes among children and adolescents. Countries with rapid declines in all-cause mortality between 1990 and 2013 also experienced large declines in most leading causes of death, whereas countries with the slowest declines had stagnant or increasing trends in the leading causes of death. In 2013, Nigeria had a 12% global share of deaths from lower respiratory tract infections and a 38% global share of deaths from malaria. India had 33% of the world's deaths from neonatal encephalopathy. Half of the world's diarrheal deaths among children and adolescents occurred in just 5 countries: India, Democratic Republic of the Congo, Pakistan, Nigeria, and Ethiopia.Understanding the levels and trends of the leading causes of death and disability among children and adolescents is critical to guide investment and inform policies. Monitoring these trends over time is also key to understanding where interventions are having an impact. Proven interventions exist to prevent or treat the leading causes of unnecessary death and disability among children and adolescents. The findings presented here show that these are underused and give guidance to policy makers in countries where more attention is needed.

Ischemic heart disease (IHD) is the leading cause of death worldwide. The Global Burden of Diseases, Risk Factors and Injuries 2010 Study estimated global and regional IHD mortality from 1980 to 2010.Sources for IHD mortality estimates were country-level surveillance, verbal autopsy, and vital registration data. Regional income, metabolic and nutritional risk factors, and other covariates were estimated from surveys and a systematic review. An estimation and validation process led to an ensemble model of IHD mortality for 21 world regions. Globally, age-standardized IHD mortality has declined since the 1980s, and high-income regions (especially Australasia, Western Europe, and North America) experienced the most remarkable declines. Age-standardized IHD mortality increased in former Soviet Union countries and South Asia in the 1990s and attenuated after 2000. In 2010, Eastern Europe and Central Asia had the highest age-standardized IHD mortality rates. More IHD deaths occurred in South Asia in 2010 than in any other region. On average, IHD deaths in South Asia, North Africa and the Middle East, and sub-Saharan Africa occurred at younger ages in comparison with most other regions.In most world regions, particularly in high-income regions, age-standardized IHD mortality rates have declined significantly since 1980. High age-standardized IHD mortality in Eastern Europe, Central Asia, and South Asia point to the need to prevent and control established risk factors in those regions and to research the unique behavioral and environmental determinants of higher IHD mortality.

BackgroundIn September, 2015, the UN General Assembly established the Sustainable Development Goals (SDGs). The SDGs specify 17 universal goals, 169 targets, and 230 indicators leading up to 2030. We provide an analysis of 33 health-related SDG indicators based on the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015).MethodsWe applied statistical methods to systematically compiled data to estimate the performance of 33 health-related SDG indicators for 188 countries from 1990 to 2015. We rescaled each indicator on a scale from 0 (worst observed value between 1990 and 2015) to 100 (best observed). Indices representing all 33 health-related SDG indicators (health-related SDG index), health-related SDG indicators included in the Millennium Development Goals (MDG index), and health-related indicators not included in the MDGs (non-MDG index) were computed as the geometric mean of the rescaled indicators by SDG target. We used spline regressions to examine the relations between the Socio-demographic Index (SDI, a summary measure based on average income per person, educational attainment, and total fertility rate) and each of the health-related SDG indicators and indices.FindingsIn 2015, the median health-related SDG index was 59·3 (95% uncertainty interval 56·8–61·8) and varied widely by country, ranging from 85·5 (84·2–86·5) in Iceland to 20·4 (15·4–24·9) in Central African Republic. SDI was a good predictor of the health-related SDG index (r2=0·88) and the MDG index (r2=0·92), whereas the non-MDG index had a weaker relation with SDI (r2=0·79). Between 2000 and 2015, the health-related SDG index improved by a median of 7·9 (IQR 5·0–10·4), and gains on the MDG index (a median change of 10·0 [6·7–13·1]) exceeded that of the non-MDG index (a median change of 5·5 [2·1–8·9]). Since 2000, pronounced progress occurred for indicators such as met need with modern contraception, under-5 mortality, and neonatal mortality, as well as the indicator for universal health coverage tracer interventions. Moderate improvements were found for indicators such as HIV and tuberculosis incidence, minimal changes for hepatitis B incidence took place, and childhood overweight considerably worsened.InterpretationGBD provides an independent, comparable avenue for monitoring progress towards the health-related SDGs. Our analysis not only highlights the importance of income, education, and fertility as drivers of health improvement but also emphasises that investments in these areas alone will not be sufficient. Although considerable progress on the health-related MDG indicators has been made, these gains will need to be sustained and, in many cases, accelerated to achieve the ambitious SDG targets. The minimal improvement in or worsening of health-related indicators beyond the MDGs highlight the need for additional resources to effectively address the expanded scope of the health-related SDGs.FundingBill & Melinda Gates Foundation.

The purpose of this study was to provide the first national estimate on the prevalence of the metabolic syndrome and its components and the first ethnic-specific cutoff point for waist circumference in the Eastern Mediterranean Region.This national survey was conducted in 2007 on 3,024 Iranians aged 25-64 years living in urban and rural areas of all 30 provinces in Iran. The metabolic syndrome was defined by different criteria, namely the definition of the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III), the International Diabetes Federation (IDF) criteria, and the modified definition of the NCEP/ATP III (ATP III/American Heart Association [AHA]/National Heart, Lung, and Blood Institute [NHLBI]).The age-standardized prevalence of the metabolic syndrome was about 34.7% (95% CI 33.1-36.2) based on the ATP III criteria, 37.4% (35.9-39.0%) based on the IDF definition, and 41.6% (40.1-43.2%) based on the ATP III/AHA/NHLBI criteria. By all definitions, the prevalence of the metabolic syndrome was higher in women, in urban areas, and in the 55- to 64-year age-group compared with the prevalence in men, in rural areas, and in other age-groups, respectively. The metabolic syndrome was estimated to affect >11 million Iranians. The optimal cutoff point of waist circumference for predicting at least two other components of the metabolic syndrome as defined by the IDF was 89 cm for men and 91 cm for women.The high prevalence of the metabolic syndrome with its considerable burden on the middle-aged population mandates the implementation of national policies for its prevention, notably by tackling obesity. The waist circumference cutoff points obtained can be used in the region.

In the Global Burden of Disease Study 2013 (GBD 2013), knowledge about health and its determinants has been integrated into a comparable framework to inform health policy. Outputs of this analysis are relevant to current policy questions in England and elsewhere, particularly on health inequalities. We use GBD 2013 data on mortality and causes of death, and disease and injury incidence and prevalence to analyse the burden of disease and injury in England as a whole, in English regions, and within each English region by deprivation quintile. We also assess disease and injury burden in England attributable to potentially preventable risk factors. England and the English regions are compared with the remaining constituent countries of the UK and with comparable countries in the European Union (EU) and beyond.We extracted data from the GBD 2013 to compare mortality, causes of death, years of life lost (YLLs), years lived with a disability (YLDs), and disability-adjusted life-years (DALYs) in England, the UK, and 18 other countries (the first 15 EU members [apart from the UK] and Australia, Canada, Norway, and the USA [EU15+]). We extended elements of the analysis to English regions, and subregional areas defined by deprivation quintile (deprivation areas). We used data split by the nine English regions (corresponding to the European boundaries of the Nomenclature for Territorial Statistics level 1 [NUTS 1] regions), and by quintile groups within each English region according to deprivation, thereby making 45 regional deprivation areas. Deprivation quintiles were defined by area of residence ranked at national level by Index of Multiple Deprivation score, 2010. Burden due to various risk factors is described for England using new GBD methodology to estimate independent and overlapping attributable risk for five tiers of behavioural, metabolic, and environmental risk factors. We present results for 306 causes and 2337 sequelae, and 79 risks or risk clusters.Between 1990 and 2013, life expectancy from birth in England increased by 5·4 years (95% uncertainty interval 5·0-5·8) from 75·9 years (75·9-76·0) to 81·3 years (80·9-81·7); gains were greater for men than for women. Rates of age-standardised YLLs reduced by 41·1% (38·3-43·6), whereas DALYs were reduced by 23·8% (20·9-27·1), and YLDs by 1·4% (0·1-2·8). For these measures, England ranked better than the UK and the EU15+ means. Between 1990 and 2013, the range in life expectancy among 45 regional deprivation areas remained 8·2 years for men and decreased from 7·2 years in 1990 to 6·9 years in 2013 for women. In 2013, the leading cause of YLLs was ischaemic heart disease, and the leading cause of DALYs was low back and neck pain. Known risk factors accounted for 39·6% (37·7-41·7) of DALYs; leading behavioural risk factors were suboptimal diet (10·8% [9·1-12·7]) and tobacco (10·7% [9·4-12·0]).Health in England is improving although substantial opportunities exist for further reductions in the burden of preventable disease. The gap in mortality rates between men and women has reduced, but marked health inequalities between the least deprived and most deprived areas remain. Declines in mortality have not been matched by similar declines in morbidity, resulting in people living longer with diseases. Health policies must therefore address the causes of ill health as well as those of premature mortality. Systematic action locally and nationally is needed to reduce risk exposures, support healthy behaviours, alleviate the severity of chronic disabling disorders, and mitigate the effects of socioeconomic deprivation.Bill & Melinda Gates Foundation and Public Health England.

The Arab world has a set of historical, geopolitical, social, cultural, and economic characteristics and has been involved in several wars that have affected the burden of disease. Moreover, financial and human resources vary widely across the region. We aimed to examine the burden of diseases and injuries in the Arab world for 1990, 2005, and 2010 using data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010).We divided the 22 countries of the Arab League into three categories according to their gross national income: low-income countries (LICs; Comoros, Djibouti, Mauritania, Yemen, and Somalia), middle-income countries (MICs; Algeria, Egypt, Iraq, Jordan, Lebanon, Libya, Morocco, occupied Palestinian territory, Sudan, Syria, and Tunisia), and high-income countries (HICs; Bahrain, Kuwait, Oman, Qatar, Saudi Arabia, and the United Arab Emirates). For the whole Arab world, each income group, and each individual country, we estimated causes of death, disability-adjusted life years (DALYs), DALY-attributable risk factors, years of life lived with disability (YLDs), years of life lost due to premature mortality (YLLs), and life expectancy by age and sex for 1990, 2005, and 2010.Ischaemic heart disease was the top cause of death in the Arab world in 2010 (contributing to 14·3% of deaths), replacing lower respiratory infections, which were the leading cause of death in 1990 (11·0%). Lower respiratory infections contributed to the highest proportion of DALYs overall (6·0%), and in female indivduals (6·1%), but ischaemic heart disease was the leading cause of DALYs in male individuals (6·0%). DALYs from non-communicable diseases--especially ischaemic heart disease, mental disorders such as depression and anxiety, musculoskeletal disorders including low back pain and neck pain, diabetes, and cirrhosis--increased since 1990. Major depressive disorder was ranked first as a cause of YLDs in 1990, 2005, and 2010, and lower respiratory infections remained the leading cause of YLLs in 2010 (9·2%). The burden from HIV/AIDS also increased substantially, specifically in LICs and MICs, and road injuries continued to rank highly as a cause of death and DALYs, especially in HICs. Deaths due to suboptimal breastfeeding declined from sixth place in 1990 to tenth place in 2010, and childhood underweight declined from fifth to 11th place.Since 1990, premature death and disability caused by communicable, newborn, nutritional, and maternal disorders (with the exception of HIV/AIDS) has decreased in the Arab world--although these disorders do still persist in LICs--whereas the burden of non-communicable diseases and injuries has increased. The changes in the burden of disease will challenge already stretched human and financial resources because many Arab countries are now dealing with both non-communicable and infectious diseases. A road map for health in the Arab world is urgently needed.Bill & Melinda Gates Foundation.

Kidney, prostate, and bladder cancers increase with age and are influenced partly by modifiable risk factors. Urological cancer rates may increase substantially amid a growing, aging population. To describe kidney, bladder, and prostate cancer incidence, mortality, and risk factor-attributable bladder and kidney cancer deaths between 1990 and 2013, by age, sex, and development status. Cancer mortality data were derived from global vital registries. Incidence data from cancer registries were transformed to mortality estimates using separately estimated mortality incidence ratios. These sources served as input data for an ensemble modeling approach to estimate bladder, prostate, and kidney cancer mortality. Cause-specific mortality estimates were transformed into incidence estimates using mortality incidence ratios. In 2013, 2.1 million kidney, bladder, and prostate cancers cases occurred worldwide, increasing 2.5-fold since 1990. Mortality increased 1.6-fold between 1990 and 2013. Eight-two percent of new cases in 2013 occurred in individuals aged 60 yr and older. Men from developed countries had the highest age-standardized death rates among all three cancers. Smoking-attributable kidney cancer deaths decreased while obesity-related deaths rose, most prominently in women from developing countries. Smoking-related bladder cancer deaths increased among women from developed countries and decreased among men. Urologic cancer burden has increased globally amid population growth and aging. High income countries face the highest incidence and death rates; however, obesity-attributed kidney cancer deaths are increasing in developing countries. Efforts to expand the global oncologic workforce and reduce preventable factors may lessen cancer disparities in developing countries. We describe the impact of population growth, aging, and lifestyle factors such as smoking and obesity, on kidney, bladder, and prostate cancer rates worldwide. More new cancer cases and deaths occur in developed countries compared with developing countries. In addition to preventive efforts, healthcare systems must emphasize training of a urologic oncology workforce.

A comprehensive and systematic assessment of disability and mortality due to lower extremity peripheral artery disease (PAD) is lacking. Therefore, we estimated PAD deaths, disability-adjusted life years (DALYs), and years of life lost in 21 regions worldwide for 1990 and 2010. We used the GBD (Global Burden of Diseases 2010) study causes of death database, and the cause of death ensemble modeling approach to assess levels and trends of PAD deaths and years of life lost over time, by age, sex, and region. Assessment of DALYs employed estimates of PAD prevalence from systematic reviews of epidemiologic data using a Bayesian meta-regression method. In 1990, the age-specific PAD death rate per 100,000 population ranged from 0.05 (95% confidence interval [CI]: 0.03 to 0.09) among those 40 to 44 years old to 16.63 (95% CI: 10.47 to 25.31) among the 80+ years group. In 2010, the corresponding estimates were 0.07 (95% CI: 0.04 to 0.13) and 28.71 (95% CI: 18.3 to 43.06). Death rates increased consistently with age in 1990 and 2010, and the rates in 2010 were higher than they were in 1990 in all age categories. The largest relative change in median death rate of +6.03 per 100,000 (95% CI: 1.50 to 11.85) was noted in the Asia Pacific-High Income region and was largely driven by higher rates in women: +17.36 (95% CI: 1.79 to 32.01) versus +1.25 (95% CI: 0.13 to 2.39) in men. The overall relative change in median DALYs was larger in developing nations than in developed nations: 1.15 (95% CI: 0.80 to 1.66) versus 0.77 (95% CI: 0.55 to 1.08). Of note, the overall relative change in median DALYs was higher among both men and women in developing versus developed countries: men: 1.18 (95% CI: 0.82 to 1.65) versus 0.51 (95% CI: 0.30 to 0.81), and women: 1.11 (95% CI: 0.58 to 2.02) versus 1 (95% CI: 0.67 to 1.47). Within developed nations, the overall relative change in median DALY rates was larger in women than in men: +1.00 (95% CI: 0.67 to 1.47) versus +0.51 (95% CI: 0.3 to 0.81). Similarly, the overall relative change in median years of life lost rate in developed countries was larger in women than in men: +1.64 (95% CI: 1.17 to 2.34) versus +0.53 (95% CI: 0.24 to 0.94). The relative increases in median years lived with nonfatal disease disability (YLD) rates in men and women were larger in developing versus developed nations: men: 0.87 (95% CI: 0.59 to 1.2) versus 0.49 (95% CI: 0.29 to 0.73), and women: 0.75 (95% CI: 0.46 to 1.09) versus 0.49 (95% CI: 0.29 to 0.73). Disability and mortality associated with PAD has increased over the last 20 years, and this increase in burden has been greater among women than among men. In addition, the burden of PAD is no longer confined to the elderly population, but now involves young adults. Furthermore, the relative increase in PAD burden in developing regions of the world is striking and exceeds the increases in developed nations.

A comprehensive and systematic assessment of the global burden of aortic aneurysms (AA) has been lacking. Therefore, we estimated AA regional deaths and years of life lost (YLL) in 21 regions worldwide for 1990 and 2010. We used the GBD (Global Burden of Disease) 2010 study causes of death database and the cause of death ensemble modeling approach to assess levels and trends of AA deaths by age, sex, and GBD region. The global AA death rate per 100,000 population was 2.49 (95% CI: 1.78 to 3.27) in 1990 and 2.78 (95% CI: 2.04 to 3.62) in 2010. In 1990 and 2010, the highest mean death rates were in Australasia and Western Europe: 8.82 (95% CI: 6.96 to 10.79) and 7.69 (95% CI: 6.11 to 9.57) in 1990 and 8.38 (95% CI: 6.48 to 10.86) and 7.68 (95% CI: 6.13 to 9.54) in 2010. YLL rates by GBD region mirrored the mortality rate pattern. Overall, men had higher AA death rates than women: 2.86 (95% CI: 1.90 to 4.22) versus 2.12 (95% CI: 1.33 to 3.00) in 1990 and 3.40 (95% CI: 2.26 to 5.01) versus 2.15 (95% CI: 1.44 to 2.89) in 2010. The relative change in median death rate was +0.22 (95% CI: 0.10 to 0.33) in developed nations versus +0.71 (95% CI: 0.28 to 1.40) in developing nations. The smallest relative changes in median death rate were noted in North America high income, Central Europe, Western Europe, and Australasia, with estimates of +0.07 (95% CI: -0.26 to 0.37), +0.08 (95% CI: -0.02 to 0.23), +0.09 (95% CI: -0.02 to 0.21), and +0.22 (95% CI: -0.08 to 0.46), respectively. The largest increases were in Asia Pacific high income, Southeast Asia, Latin America tropical, Oceania, South Asia, and Central Sub-Saharan Africa. Women rather than men drove the increase in the Asia Pacific high-income region: the relative change in median rates was +2.92 (95% CI: 0.6 to 4.35) versus +1.05 (95% CI: 0.61 to 2.42). In contrast to high-income regions, the observed pattern in developing regions suggests increasing AA burden, which portends future health system challenges in these regions.

The burden of premature death and health loss from ESRD is well described. Less is known regarding the burden of cardiovascular disease attributable to reduced GFR. We estimated the prevalence of reduced GFR categories 3, 4, and 5 (not on RRT) for 188 countries at six time points from 1990 to 2013. Relative risks of cardiovascular outcomes by three categories of reduced GFR were calculated by pooled random effects meta-analysis. Results are presented as deaths for outcomes of cardiovascular disease and ESRD and as disability-adjusted life years for outcomes of cardiovascular disease, GFR categories 3, 4, and 5, and ESRD. In 2013, reduced GFR was associated with 4% of deaths worldwide, or 2.2 million deaths (95% uncertainty interval [95% UI], 2.0 to 2.4 million). More than half of these attributable deaths were cardiovascular deaths (1.2 million; 95% UI, 1.1 to 1.4 million), whereas 0.96 million (95% UI, 0.81 to 1.0 million) were ESRD-related deaths. Compared with metabolic risk factors, reduced GFR ranked below high systolic BP, high body mass index, and high fasting plasma glucose, and similarly with high total cholesterol as a risk factor for disability-adjusted life years in both developed and developing world regions. In conclusion, by 2013, cardiovascular deaths attributed to reduced GFR outnumbered ESRD deaths throughout the world. Studies are needed to evaluate the benefit of early detection of CKD and treatment to decrease these deaths.

The epidemiology of cardiovascular diseases in sub-Saharan Africa is unique among world regions, with about half of cardiovascular diseases (CVDs) due to causes other than atherosclerosis. CVD epidemiology data are sparse and of uneven quality in sub-Saharan Africa. Using the available data, the Global Burden of Diseases, Risk Factors, and Injuries (GBD) 2010 Study estimated CVD mortality and burden of disease in sub-Saharan Africa in 1990 and 2010. The leading CVD cause of death and disability in 2010 in sub-Saharan Africa was stroke; the largest relative increases in CVD burden between 1990 and 2010 were in atrial fibrillation and peripheral arterial disease. CVD deaths constituted only 8.8% of all deaths and 3.5% of all disability-adjusted life years (DALYs) in sub-Sahara Africa, less than a quarter of the proportion of deaths and burden attributed to CVD in high income regions. However, CVD deaths in sub-Saharan Africa occur at younger ages on average than in the rest of the world. It remains uncertain if increased urbanization and life expectancy in some parts of sub-Saharan African nations will transition the region to higher CVD burden in future years.

This report summarizes the findings of the GBD 2010 (Global Burden of Diseases, Injuries, and Risk Factors) study for hemorrhagic stroke (HS). Multiple databases were searched for relevant studies published between 1990 and 2010. The GBD 2010 study provided standardized estimates of the incidence, mortality, mortality-to-incidence ratios (MIR), and disability-adjusted life years (DALY) lost for HS (including intracerebral hemorrhage and subarachnoid hemorrhage) by age, sex, and income level (high-income countries [HIC]; low- and middle-income countries [LMIC]) for 21 GBD 2010 regions in 1990, 2005, and 2010. In 2010, there were 5.3 million cases of HS and over 3.0 million deaths due to HS. There was a 47% increase worldwide in the absolute number of HS cases. The largest proportion of HS incident cases (80%) and deaths (63%) occurred in LMIC countries. There were 62.8 million DALY lost (86% in LMIC) due to HS. The overall age-standardized incidence rate of HS per 100,000 person-years in 2010 was 48.41 (95% confidence interval [CI]: 45.44 to 52.13) in HIC and 99.43 (95% CI: 85.37 to 116.28) in LMIC, and 81.52 (95% CI: 72.27 to 92.82) globally. The age-standardized incidence of HS increased by 18.5% worldwide between 1990 and 2010. In HIC, there was a reduction in incidence of HS by 8% (95% CI: 1% to 15%), mortality by 38% (95% CI: 32% to 43%), DALY by 39% (95% CI: 32% to 44%), and MIR by 27% (95% CI: 19% to 35%) in the last 2 decades. In LMIC countries, there was a significant increase in the incidence of HS by 22% (95% CI: 5% to 30%), whereas there was a significant reduction in mortality rates of 23% (95% CI: -3% to 36%), DALY lost of 25% (95% CI: 7% to 38%), and MIR by 36% (95% CI: 16% to 49%). There were significant regional differences in incidence rates of HS, with the highest rates in LMIC regions such as sub-Saharan Africa and East Asia, and lowest rates in High Income North America and Western Europe. The worldwide burden of HS has increased over the last 2 decades in terms of absolute numbers of HS incident events. The majority of the burden of HS is borne by LMIC. Rates for HS incidence, mortality, and DALY lost, as well as MIR decreased in the past 2 decades in HIC, but increased significantly in LMIC countries, particularly in those patients ≤75 years. HS affected people at a younger age in LMIC than in HIC. The lowest incidence and mortality rates in 2010 were in High Income North America, Australasia, and Western Europe, whereas the highest rates were in Central Asia, Southeast Asia, and sub-Saharan Africa. These results suggest that reducing the burden of HS is a priority particularly in LMIC. The GBD 2010 findings may be a useful resource for planning strategies to reduce the global burden of HS.

Global Heart is the official and primary publication of the World Heart Federation, offering a platform for the dissemination of knowledge on research, developments, trends, solutions and public health programmes in the area of cardiovascular disease. Global Heart welcomes research results, points of view and educational material on the prevention, treatment and control of cardiovascular disease with a special focus on low and middle-income countries which are facing the brunt of epidemiological transition.Global Heart strongly encourages authors to adhere to CONSORT, STROBE, STARD, and PRISMA guidelines for reporting of clinical trials, observational studies, diagnostic test accuracy papers, and systematic reviews or meta-analyses. Authors are required for submission to download and complete the appropriate Equator Network checklist: http://www.equator-network.org/.

<h2>Summary</h2><h3>Background</h3> The eastern Mediterranean region is comprised of 22 countries: Afghanistan, Bahrain, Djibouti, Egypt, Iran, Iraq, Jordan, Kuwait, Lebanon, Libya, Morocco, Oman, Pakistan, Palestine, Qatar, Saudi Arabia, Somalia, Sudan, Syria, Tunisia, the United Arab Emirates, and Yemen. Since our Global Burden of Disease Study 2010 (GBD 2010), the region has faced unrest as a result of revolutions, wars, and the so-called Arab uprisings. The objective of this study was to present the burden of diseases, injuries, and risk factors in the eastern Mediterranean region as of 2013. <h3>Methods</h3> GBD 2013 includes an annual assessment covering 188 countries from 1990 to 2013. The study covers 306 diseases and injuries, 1233 sequelae, and 79 risk factors. Our GBD 2013 analyses included the addition of new data through updated systematic reviews and through the contribution of unpublished data sources from collaborators, an updated version of modelling software, and several improvements in our methods. In this systematic analysis, we use data from GBD 2013 to analyse the burden of disease and injuries in the eastern Mediterranean region specifically. <h3>Findings</h3> The leading cause of death in the region in 2013 was ischaemic heart disease (90·3 deaths per 100 000 people), which increased by 17·2% since 1990. However, diarrhoeal diseases were the leading cause of death in Somalia (186·7 deaths per 100 000 people) in 2013, which decreased by 26·9% since 1990. The leading cause of disability-adjusted life-years (DALYs) was ischaemic heart disease for males and lower respiratory infection for females. High blood pressure was the leading risk factor for DALYs in 2013, with an increase of 83·3% since 1990. Risk factors for DALYs varied by country. In low-income countries, childhood wasting was the leading cause of DALYs in Afghanistan, Somalia, and Yemen, whereas unsafe sex was the leading cause in Djibouti. Non-communicable risk factors were the leading cause of DALYs in high-income and middle-income countries in the region. DALY risk factors varied by age, with child and maternal malnutrition affecting the younger age groups (aged 28 days to 4 years), whereas high bodyweight and systolic blood pressure affected older people (aged 60–80 years). The proportion of DALYs attributed to high body-mass index increased from 3·7% to 7·5% between 1990 and 2013. Burden of mental health problems and drug use increased. Most increases in DALYs, especially from non-communicable diseases, were due to population growth. The crises in Egypt, Yemen, Libya, and Syria have resulted in a reduction in life expectancy; life expectancy in Syria would have been 5 years higher than that recorded for females and 6 years higher for males had the crisis not occurred. <h3>Interpretation</h3> Our study shows that the eastern Mediterranean region is going through a crucial health phase. The Arab uprisings and the wars that followed, coupled with ageing and population growth, will have a major impact on the region's health and resources. The region has historically seen improvements in life expectancy and other health indicators, even under stress. However, the current situation will cause deteriorating health conditions for many countries and for many years and will have an impact on the region and the rest of the world. Based on our findings, we call for increased investment in health in the region in addition to reducing the conflicts. <h3>Funding</h3> Bill & Melinda Gates Foundation.

United Nations member states have agreed to reduce premature cardiovascular disease (CVD) mortality 25% by 2025. Global CVD risk factor targets have been recommended. We produced estimates to show how selected risk factor reduction would affect CVD mortality for different regions and countries.We used mortality, risk factor, and relative risk data from the Global Burden of Disease, Risk Factors, and Injuries (GBD) 2013 study to project CVD mortality for 188 countries up to the year 2025. We disaggregated observed CVD mortality in 1990 and 2013 into deaths attributable and unattributable to hypertension, tobacco smoking, diabetes mellitus, and obesity using an age- and sex-specific population-attributable fraction. Risk factors were projected to 2025 assuming that current trends continue. Counterfactual scenarios were then constructed reflecting CVD premature mortality if United Nations risk factor targets are achieved in the year 2025, adjusting for joint effects of risk factors. We estimate 7.8 million premature CVD deaths in 2025 if current risk factor trends continue. Premature CVD deaths would be reduced to 5.7 million if these risk factors targets are achieved as a result of a 26% reduction for men and a 23% reduction for women in the global risk of premature CVD death. Globally, decreasing the prevalence of hypertension accounted for the largest risk reduction, followed by a reduction in tobacco smoking for men and obesity for women, but these results varied by region. The impact of meeting all risk factor targets on CVD mortality varied widely by region and sex.The United Nations target of a 25% reduction in premature CVD mortality by the year 2025 appears achievable for some countries, but more aggressive risk factor targets may be required if all regions are to reach this goal. Without these reductions in CVD risk factors, many countries will see no change or even an increase in premature CVD mortality.

Global Heart is the official and primary publication of the World Heart Federation, offering a platform for the dissemination of knowledge on research, developments, trends, solutions and public health programmes in the area of cardiovascular disease. Global Heart welcomes research results, points of view and educational material on the prevention, treatment and control of cardiovascular disease with a special focus on low and middle-income countries which are facing the brunt of epidemiological transition.Global Heart strongly encourages authors to adhere to CONSORT, STROBE, STARD, and PRISMA guidelines for reporting of clinical trials, observational studies, diagnostic test accuracy papers, and systematic reviews or meta-analyses. Authors are required for submission to download and complete the appropriate Equator Network checklist: http://www.equator-network.org/.

we aimed to recap and highlight the major results of the Global Burden of Diseases, Injuries, and Risk Factors Study 2010 by mortality and morbidity to clarify the current health priorities and challenges in Iran.We estimated Iran's mortality and burden of 289 diseases with 67 risk factors and 1160 sequelae, which were used to clinically present each disease and its disability or cause of death. We produced several measures to report health loss and status: all-cause mortality, cause-specific mortality, years of life lost due to death (YLL), healthy years of life lost due to disability (YLD), disability-adjusted life years (DALYs), life expectancy, and healthy life expectancy, for three time periods: 1990, 2005, and 2010.We found out that life expectancy at birth was 71.6 years in men and 77.8 years in women. Almost 350 thousand deaths occurred in both sexes and all age groups in 2010. In both males and females and all age groups, ischemic heart disease was the main cause of death, claiming about 90 thousand lives. The main contributors to DALYs were: ischemic heart disease (9.1%), low back pain (9.0%), road injuries (7.3%), and unipolar depressive disorders (6.3%). The main causes of death under 5 years of age included: congenital anomalies (22.4%), preterm birth complications (18.3%), and other neonatal disorders (13.5%). The main causes of death among 15 - 49 year olds in both sexes included: injuries (23.6%) and ischemic heart disease (12.7%) The highest rates of YLDs were observed among 70+ year olds for both sexes (27,365 per 100,000), mainly due to low back pain, osteoarthritis, diabetes, falls, and major depressive disorder. The main risk factors to which deaths were attributable among children under 5 years included: suboptimal breast feeding, ambient PM pollution, tobacco smoking, and underweight. The most important risk factors among 15 to 49 year olds were: dietary risks, high blood pressure, high body mass index, physical inactivity, smoking, and ambient PM pollution. The pattern was similar among 50+ year olds.Although non-communicable diseases had the greatest burden in 2010, the challenge of communicable and maternal diseases for health system is not over yet. Diet and physiological risk factors appear to be the most important targets for public health policy in Iran. Moreover, Iranians would greatly benefit from effective strategies to prevent injury and musculoskeletal disorders and expand mental care. Persistent improvement is possible by strengthening the health information system to monitor the population health and evaluate current programs.

To find the prevalence of musculoskeletal complaints and rheumatic disorders in Iran.Tehran, with one-ninth of the population of Iran and of mixed ethnic origins, was selected as the field. Subjects were randomly selected from the 22 districts. Interviews were conducted once a week, on the weekend. The 3 phases of stage 1 were done on the same day, in parallel, like the fast-track Community Oriented Program for Control of Rheumatic Diseases (COPCORD).Four thousand ninety-six houses were visited and 10,291 persons were interviewed. Musculoskeletal complaints during the past 7 days were detected in 41.9% of the interviewed subjects. The distribution was: shoulder 14.5%, wrist 10%, hands and fingers 9.4%, hip 7.1%, knee 25.5%, ankle 9.8%, toes 6.1%, cervical spine 13.4%, and dorsal and lumbar spine 21.7%. Degenerative joint diseases were detected in 16.6% of subjects: cervical spondylosis 1.8%, knee osteoarthritis (OA) 15.3%, hand OA 2.9%, and hip OA 0.32%. Low back pain was detected in 15.4% and soft tissue rheumatism in 4.6%. Inflammatory disorders were rheumatoid arthritis 0.33%, seronegative spondyloarthropathies 0.23%, ankylosing spondylitis 0.12%, systemic lupus erythematosus 0.04%, and Behçet's disease 0.08%. Fibromyalgia was detected in 0.69% and gout in 0.13% of the studied population.The large urban COPCORD study in Iran showed a high prevalence of rheumatic complaints in the population over the age of 15 years, 41.9%. Knee OA and low back pain were the most frequent complaints.

Child and maternal health outcomes have notably improved in Mexico since 1990, whereas rising adult mortality rates defy traditional epidemiological transition models in which decreased death rates occur across all ages. These trends suggest Mexico is experiencing a more complex, dissonant health transition than historically observed. Enduring inequalities between states further emphasise the need for more detailed health assessments over time. The Global Burden of Diseases, Injuries, and Risk Factors Study 2013 (GBD 2013) provides the comprehensive, comparable framework through which such national and subnational analyses can occur. This study offers a state-level quantification of disease burden and risk factor attribution in Mexico for the first time.We extracted data from GBD 2013 to assess mortality, causes of death, years of life lost (YLLs), years lived with disability (YLDs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) in Mexico and its 32 states, along with eight comparator countries in the Americas. States were grouped by Marginalisation Index scores to compare subnational burden along a socioeconomic dimension. We split extracted data by state and applied GBD methods to generate estimates of burden, and attributable burden due to behavioural, metabolic, and environmental or occupational risks. We present results for 306 causes, 2337 sequelae, and 79 risk factors.From 1990 to 2013, life expectancy from birth in Mexico increased by 3·4 years (95% uncertainty interval 3·1-3·8), from 72·1 years (71·8-72·3) to 75·5 years (75·3-75·7), and these gains were more pronounced in states with high marginalisation. Nationally, age-standardised death rates fell 13·3% (11·9-14·6%) since 1990, but state-level reductions for all-cause mortality varied and gaps between life expectancy and years lived in full health, as measured by HALE, widened in several states. Progress in women's life expectancy exceeded that of men, in whom negligible improvements were observed since 2000. For many states, this trend corresponded with rising YLL rates from interpersonal violence and chronic kidney disease. Nationally, age-standardised YLL rates for diarrhoeal diseases and protein-energy malnutrition markedly decreased, ranking Mexico well above comparator countries. However, amid Mexico's progress against communicable diseases, chronic kidney disease burden rapidly climbed, with age-standardised YLL and DALY rates increasing more than 130% by 2013. For women, DALY rates from breast cancer also increased since 1990, rising 12·1% (4·6-23·1%). In 2013, the leading five causes of DALYs were diabetes, ischaemic heart disease, chronic kidney disease, low back and neck pain, and depressive disorders; the latter three were not among the leading five causes in 1990, further underscoring Mexico's rapid epidemiological transition. Leading risk factors for disease burden in 1990, such as undernutrition, were replaced by high fasting plasma glucose and high body-mass index by 2013. Attributable burden due to dietary risks also increased, accounting for more than 10% of DALYs in 2013.Mexico achieved sizeable reductions in burden due to several causes, such as diarrhoeal diseases, and risks factors, such as undernutrition and poor sanitation, which were mainly associated with maternal and child health interventions. Yet rising adult mortality rates from chronic kidney disease, diabetes, cirrhosis, and, since 2000, interpersonal violence drove deteriorating health outcomes, particularly in men. Although state inequalities from communicable diseases narrowed over time, non-communicable diseases and injury burdens varied markedly at local levels. The dissonance with which Mexico and its 32 states are experiencing epidemiological transitions might strain health-system responsiveness and performance, which stresses the importance of timely, evidence-informed health policies and programmes linked to the health needs of each state.Bill & Melinda Gates Foundation, Instituto Nacional de Salud Pública.

BackgroundDiarrhoea is a leading cause of death and illness globally among children younger than 5 years. Mortality and short-term morbidity cause substantial burden of disease but probably underestimate the true effect of diarrhoea on population health. This underestimation is because diarrhoeal diseases can negatively affect early childhood growth, probably through enteric dysfunction and impaired uptake of macronutrients and micronutrients. We attempt to quantify the long-term sequelae associated with childhood growth impairment due to diarrhoea.MethodsWe used the Global Burden of Diseases, Injuries, and Risk Factors Study framework and leveraged existing estimates of diarrhoea incidence, childhood undernutrition, and infectious disease burden to estimate the effect of diarrhoeal diseases on physical growth, including weight and height, and subsequent disease among children younger than 5 years. The burden of diarrhoea was measured in disability-adjusted life-years (DALYs), a composite metric of mortality and morbidity. We hypothesised that diarrhoea is negatively associated with three common markers of growth: weight-for-age, weight-for-height, and height-for-age Z-scores. On the basis of these undernutrition exposures, we applied a counterfactual approach to quantify the relative risk of infectious disease (subsequent diarrhoea, lower respiratory infection, and measles) and protein energy malnutrition morbidity and mortality per day of diarrhoea and quantified the burden of diarrhoeal disease due to these outcomes caused by undernutrition.FindingsDiarrhoea episodes are significantly associated with childhood growth faltering. We found that each day of diarrhoea was associated with height-for-age Z-score (–0·0033 [95% CI −0·0024 to −0·0041]; p=4·43 × 10−14), weight-for-age Z-score (–0·0077 [–0·0058 to −0·0097]; p=3·19 × 10−15), and weight-for-height Z-score (–0·0096 [–0·0067 to −0·0125]; p=7·78 × 10−11). After addition of the DALYs due to the long-term sequelae as a consequence of undernutrition, the burden of diarrhoeal diseases increased by 39·0% (95% uncertainty interval [UI] 33·0–46·6) and was responsible for 55 778 000 DALYs (95% UI 49 125 400–62 396 200) among children younger than 5 years in 2016. Among the 15 652 300 DALYs (95% UI 12 951 300–18 806 100) associated with undernutrition due to diarrhoeal episodes, more than 84·7% are due to increased risk of infectious disease, whereas the remaining 15·3% of long-term DALYs are due to increased prevalence of protein energy malnutrition. The burden of diarrhoea has decreased substantially since 1990, but progress has been greater in long-term (78·7% reduction [95% UI 69·3–85·5]) than in acute (70·4% reduction [95% UI 61·7–76·5]) DALYs.InterpretationDiarrhoea represents an even larger burden of disease than was estimated in the Global Burden of Disease Study. In order to adequately address the burden of its long-term sequelae, a renewed emphasis on controlling the risk of diarrhoea incidence may be required. This renewed effort can help further prevent the potential lifelong cost on child health, growth, and overall potential.FundingBill & Melinda Gates Foundation.

Abstract. High concentration of fine particles (PM2.5), the primary concern about air quality in China, is believed to closely relate to China's large consumption of coal. In order to quantitatively identify the contributions of coal combustion in different sectors to ambient PM2. 5, we developed an emission inventory for the year 2013 using up-to-date information on energy consumption and emission controls, and we conducted standard and sensitivity simulations using the chemical transport model GEOS-Chem. According to the simulation, coal combustion contributes 22 µg m−3 (40 %) to the total PM2. 5 concentration at national level (averaged in 74 major cities) and up to 37 µg m−3 (50 %) in the Sichuan Basin. Among major coal-burning sectors, industrial coal burning is the dominant contributor, with a national average contribution of 10 µg m−3 (17 %), followed by coal combustion in power plants and the domestic sector. The national average contribution due to coal combustion is estimated to be 18 µg m−3 (46 %) in summer and 28 µg m−3 (35 %) in winter. While the contribution of domestic coal burning shows an obvious reduction from winter to summer, contributions of coal combustion in power plants and the industrial sector remain at relatively constant levels throughout the year.

The Eastern Mediterranean Region (EMR) is witnessing an increase in chronic disorders, including mental illness. With ongoing unrest, this is expected to rise. This is the first study to quantify the burden of mental disorders in the EMR. We used data from the Global Burden of Disease study (GBD) 2013. DALYs (disability-adjusted life years) allow assessment of both premature mortality (years of life lost-YLLs) and nonfatal outcomes (years lived with disability-YLDs). DALYs are computed by adding YLLs and YLDs for each age-sex-country group. In 2013, mental disorders contributed to 5.6% of the total disease burden in the EMR (1894 DALYS/100,000 population): 2519 DALYS/100,000 (2590/100,000 males, 2426/100,000 females) in high-income countries, 1884 DALYS/100,000 (1618/100,000 males, 2157/100,000 females) in middle-income countries, 1607 DALYS/100,000 (1500/100,000 males, 1717/100,000 females) in low-income countries. Females had a greater proportion of burden due to mental disorders than did males of equivalent ages, except for those under 15 years of age. The highest proportion of DALYs occurred in the 25-49 age group, with a peak in the 35-39 years age group (5344 DALYs/100,000). The burden of mental disorders in EMR increased from 1726 DALYs/100,000 in 1990 to 1912 DALYs/100,000 in 2013 (10.8% increase). Within the mental disorders group in EMR, depressive disorders accounted for most DALYs, followed by anxiety disorders. Among EMR countries, Palestine had the largest burden of mental disorders. Nearly all EMR countries had a higher mental disorder burden compared to the global level. Our findings call for EMR ministries of health to increase provision of mental health services and to address the stigma of mental illness. Moreover, our results showing the accelerating burden of mental health are alarming as the region is seeing an increased level of instability. Indeed, mental health problems, if not properly addressed, will lead to an increased burden of diseases in the region.

The effectiveness of regulatory actions designed to improve air quality is often assessed by predicting changes in public health resulting from their implementation. Risk of premature mortality from long-term exposure to ambient air pollution is the single most important contributor to such assessments and is estimated from observational studies generally assuming a log-linear, no-threshold association between ambient concentrations and death. There has been only limited assessment of this assumption in part because of a lack of methods to estimate the shape of the exposure-response function in very large study populations. In this paper, we propose a new class of variable coefficient risk functions capable of capturing a variety of potentially non-linear associations which are suitable for health impact assessment. We construct the class by defining transformations of concentration as the product of either a linear or log-linear function of concentration multiplied by a logistic weighting function. These risk functions can be estimated using hazard regression survival models with currently available computer software and can accommodate large population-based cohorts which are increasingly being used for this purpose. We illustrate our modeling approach with two large cohort studies of long-term concentrations of ambient air pollution and mortality: the American Cancer Society Cancer Prevention Study II (CPS II) cohort and the Canadian Census Health and Environment Cohort (CanCHEC). We then estimate the number of deaths attributable to changes in fine particulate matter concentrations over the 2000 to 2010 time period in both Canada and the USA using both linear and non-linear hazard function models.

Global Heart is the official and primary publication of the World Heart Federation, offering a platform for the dissemination of knowledge on research, developments, trends, solutions and public health programmes in the area of cardiovascular disease. Global Heart welcomes research results, points of view and educational material on the prevention, treatment and control of cardiovascular disease with a special focus on low and middle-income countries which are facing the brunt of epidemiological transition.Global Heart strongly encourages authors to adhere to CONSORT, STROBE, STARD, and PRISMA guidelines for reporting of clinical trials, observational studies, diagnostic test accuracy papers, and systematic reviews or meta-analyses. Authors are required for submission to download and complete the appropriate Equator Network checklist: http://www.equator-network.org/.

Objectives We used findings from the Global Burden of Disease Study 2013 to report the burden of musculoskeletal disorders in the Eastern Mediterranean Region (EMR). Methods The burden of musculoskeletal disorders was calculated for the EMR's 22 countries between 1990 and 2013. A systematic analysis was performed on mortality and morbidity data to estimate prevalence, death, years of live lost, years lived with disability and disability-adjusted life years (DALYs). Results For musculoskeletal disorders, the crude DALYs rate per 100 000 increased from 1297.1 (95% uncertainty interval (UI) 924.3–1703.4) in 1990 to 1606.0 (95% UI 1141.2–2130.4) in 2013. During 1990–2013, the total DALYs of musculoskeletal disorders increased by 105.2% in the EMR compared with a 58.0% increase in the rest of the world. The burden of musculoskeletal disorders as a proportion of total DALYs increased from 2.4% (95% UI 1.7–3.0) in 1990 to 4.7% (95% UI 3.6–5.8) in 2013. The range of point prevalence (per 1000) among the EMR countries was 28.2–136.0 for low back pain, 27.3–49.7 for neck pain, 9.7–37.3 for osteoarthritis (OA), 0.6–2.2 for rheumatoid arthritis and 0.1–0.8 for gout. Low back pain and neck pain had the highest burden in EMR countries. Conclusions This study shows a high burden of musculoskeletal disorders, with a faster increase in EMR compared with the rest of the world. The reasons for this faster increase need to be explored. Our findings call for incorporating prevention and control programmes that should include improving health data, addressing risk factors, providing evidence-based care and community programmes to increase awareness.

To investigate the impact of air pollutant control policies on future PM2.5 concentrations and their source contributions in China, we developed four future scenarios for 2030 based on a 2013 emission inventory, and conducted air quality simulations for each scenario using the chemical transport model GEOS-Chem (version 9.1.3). Two energy scenarios i.e., current legislation (CLE) and with additional measures (WAM), were developed to project future energy consumption, reflecting, respectively, existing legislation and implementation status as of the end of 2012, and new energy-saving policies that would be released and enforced more stringently. Two end-of-pipe control strategies, i.e., current control technologies (until 2017) and more stringent control technologies (until 2030), were also developed. The combinations of energy scenarios and end-of-pipe control strategies constitute four emission scenarios (2017-CLE, 2030-CLE, 2017-WAM, and 2030-WAM) evaluated in simulations. PM2.5 concentrations at national level were estimated to be 57 μg/m3 in the base year 2013, and 58 μg/m3, 42 μg/m3, 42 μg/m3, and 30 μg/m3 under the 2017-CLE, 2030-CLE, 2017-WAM, and 2030-WAM scenarios in 2030, respectively. Large PM2.5 reductions between 2013 and 2030 were estimated for heavily polluted regions (Sichuan Basin, Middle Yangtze River, North China). The energy-saving policies show similar effects to the end-of-pipe emission control measures, but the relative importance of these two groups of policies varies in different regions. Absolute contributions to PM2.5 concentrations from most major sources declined from 2017-CLE to 2030-WAM. With respect to fractional contributions, most coal-burning sectors (including power plant, industrial and residential coal burning) increased from 2017-CLE to 2030-WAM, due to larger reductions from non-coal sources, including transportation and biomass open burning. Residential combustion and open burning had much lower fractional contribution to ambient PM2.5 concentrations in the 2017-WAM/2030-WAM compared to the 2017-CLE/2030-CLE scenarios. Fractional contributions from transportation were reduced dramatically in 2030-CLE and 2030-WAM compared to 2017-CLE/2017-WAM, due to the enforcement of stringent end-of-pipe emission controls. Across all scenarios, coal combustion remained the single largest contributor to PM2.5 concentrations in 2030. Reducing PM2.5 emissions from coal combustion remains a strategic priority for air quality management in China.

Background: Health effects of air pollution have been studied in many different parts of the world. Although a fairly large number of studies have explored the cardiovascular impacts of air pollution, because of its unique location we studied the association between air pollutants and hospital admissions due to angina pectoris in Tehran for the first time. Methods: This is a retrospective time-series study. The variables of the study include the levels of five air pollutants—nitrogen dioxide (NO2), carbon monoxide (CO), ozone (O3), sulfur dioxide (SO2), and particulate matter <10 μm in aerodynamic diameter (PM10)—as independent variables; daily hospitalizations due to angina pectoris in 25 academic hospitals in Tehran as the dependent variable; and mean daily temperature and humidity, seasonality, time trend, and day of the week as potential confounders. All variables were measured during a 5-year period from 21 March 1996 to 20 March 2001. The data of mean daily levels of NO2, CO, O3, SO2, and PM10 were collected from one of the stations of Tehran's Air Quality Control Corp. Data were analyzed using Poisson regression models. Relative risks of angina pectoris admissions were calculated for an increase in 1 mg/m3 for CO and 10 μg/m3 for the other pollutants. Results: Daily admissions due to angina pectoris were significantly related to the CO level, after controlling for confounder effects. Each unit increase in the CO level caused a 1.00934 increase in the number of admissions (95% CI, 1.00359–1.01512). This association was verified with a lag of 1 day. There was no significant association between the other air pollutants and the number of daily admission due to angina pectoris. Conclusions: We found that with increasing levels of the pollutant CO, the number of admissions due to cardiac angina rose. Ischemic heart disease is the leading cause of death in Iran. Air pollution control will reduce the number of this preventable disease and resulting deaths.

Noninvasive markers for predicting significant fibrosis and inflammation have not yet been validated in an unselected group of chronic hepatitis B virus (HBV) carriers. The aim of this study was to create noninvasive models to predict significant fibrosis and inflammation in chronic HBV carriers.A total of 276 (229 HBeAg negative, 47 HBeAg positive) unselected consecutive treatment naïve patients chronically infected with HBV who attended our center over a 36-month period underwent liver biopsy. HBeAg negative patients were randomly divided into two cohorts: training group (N = 130) and validation group (N = 99). HBeAg positive patients were analyzed as a whole without separation. Thirteen parameters were analyzed separately in HBeAg negative and HBeAg positive patients to predict significant fibrosis (Ishak stage >or=3) and inflammation (Ishak grade >or=7).In HBeAg negative patients significant liver fibrosis was best predicted using the variables HBV DNA levels, alkaline phosphatase, albumin, and platelet counts with an area under ROC curve (AUC) of 0.91 for the training group and 0.85 for the validation group. Using the low cutoff probability of 4.72, significant fibrosis could be excluded with negative predictive value of 99% in the entire cohort, and liver biopsy would have been avoided in 52% of patients. The best model for predicting significant inflammation included the variables age, HBV DNA levels, AST, and albumin with an AUC of 0.93 in the training and 0.82 in the validation group. In HBeAg positive patients no factor could predict accurately stages of liver fibrosis, but the best factor for predicting significant inflammation was AST with an AUC of 0.87.Significant hepatic fibrosis and necroinflammation can reliably be predicted using routinely checked tests and HBV DNA levels.

Ischemic heart disease (IHD) was the leading cause of disease burden worldwide in 2010. The majority of IHD burden affected middle-income regions. We hypothesized IHD burden may vary among countries, even within the same broad geographic region.Disability-adjusted life years (DALYs) due to IHD were estimated at the region level for 7 “super-regions,” 21 regions, and 187 countries using geographically nested models for IHD mortality and prevalent nonfatal IHD (nonfatal acute myocardial infarction, angina pectoris, or ischemic heart failure). Acute myocardial infarction, angina, and heart failure disability weights were applied to prevalent cases. Absolute numbers of DALYs and age-standardized DALYs per 100,000 persons were estimated for each region and country in 1990 and 2010. IHD burden for world regions was analyzed by country, income, and age.About two-thirds of 2010 IHD DALYs affected middle-income countries. In the North Africa/Middle East and South Asia regions, which have high IHD burden, more than 29% of men and 24% of women struck by IHD were <50 years old. Age-standardized IHD DALYs decreased in most countries between 1990 and 2010, but increased in a number of countries in the Eastern Europe/Central Asia region (>1,000 per 100,000 increase) and South Asia region (>175 per 100,000). Age-standardized DALYs varied by up to 8-fold among countries, by about 9,000 per 100,000 among middle-income countries, about 7,400 among low-income countries, and about 4,300 among high-income countries.The majority of IHD burden in 2010 affected middle-income regions, where younger adults were more likely to develop IHD in regions such as South Asia and North Africa/Middle East. However, IHD burden varied substantially by country within regions, especially among middle-income countries. A global or regional approach to IHD prevention will not be sufficient; research and policy should focus on the highest burden countries within regions.

Ischemic heart disease (IHD) is the leading cause of death worldwide. The GBD (Global Burden of Disease, Injuries, and Risk Factors) study (GBD 2010 Study) conducted a systematic review of IHD epidemiology literature from 1980 to 2008 to inform estimates of the burden on IHD in 21 world regions in 1990 and 2010.The disease model of IHD for the GBD 2010 Study included IHD death and 3 sequelae: myocardial infarction, heart failure, and angina pectoris. Medline, EMBASE, and LILACS were searched for IHD epidemiology studies in GBD high-income and low- and middle-income regions published between 1980 and 2008 using a systematic protocol validated by regional IHD experts. Data from included studies were supplemented with unpublished data from selected high-quality surveillance and survey studies. The epidemiologic parameters of interest were incidence, prevalence, case fatality, and mortality.Literature searches yielded 40,205 unique papers, of which 1,801 met initial screening criteria. Upon detailed review of full text papers, 137 published studies were included. Unpublished data were obtained from 24 additional studies. Data were sufficient for high-income regions, but missing or sparse in many low- and middle-income regions, particularly Sub-Saharan Africa.A systematic review for the GBD 2010 Study provided IHD epidemiology estimates for most world regions, but highlighted the lack of information about IHD in Sub-Saharan Africa and other low-income regions. More complete knowledge of the global burden of IHD will require improved IHD surveillance programs in all world regions.

Background: A previous analysis of the Osteoarthritis Initiative study reported a dose-response relationship between physical activity and improved physical function in adults with knee osteoarthritis, using conventional statistical methods. These methods are subject to bias when confounders are affected by prior exposure. Methods: We used baseline and 1-, 2-, and 3-year follow-up data from the Osteoarthritis Initiative study of 2545 US adults with knee osteoarthritis recruited between 2004 and 2006 from 4 clinical sites. Physical activity was measured using the Physical Activity Scale for the Elderly, and outcomes were functional performance measured by the timed 20-meter walk test and self-reported knee pain measured by the Western Ontario and McMaster Universities Osteoarthritis Index. We estimated the effect of physical activity on each outcome using inverse probability-weighted (IPW) estimators of marginal structural models. For each outcome, we fitted 2 separate IPW models adjusting for concurrent or lagged confounders. Results: The mean differences in walking speed for the second, third, and fourth quartiles of physical activity relative to the first were 0.48 (95% confidence interval = −0.12 to 1.08), 0.45 (−0.23 to 1.13), and 0.46 (−0.29 to 1.22) meters/min based on the IPW model adjusting for concurrent confounders. When adjusting for lagged confounders, the results were 1.35 (0.64 to 2.07), 1.33 (0.54 to 2.14), and 1.26 (0.40 to 2.12). Both IPW models indicated that physical activity did not affect knee pain. Conclusions: Physical activity has no effect on knee pain and may have either a very small effect or no effect on functional performance in adults with knee osteoarthritis.

Exposure to air pollution is a major risk factor globally and particularly in Asia. A large portion of air pollutants result from residential combustion of solid biomass and coal fuel for cooking and heating. This study presents a regional modeling sensitivity analysis to estimate the impact of residential emissions from cooking and heating activities on the burden of disease at a provincial level in China. Model surface PM2.5 fields are shown to compare well when evaluated against surface air quality measurements. Scenarios run without residential sector and residential heating emissions are used in conjunction with the Global Burden of Disease 2013 framework to calculate the proportion of deaths and disability adjusted life years attributable to PM2.5 exposure from residential emissions. Overall, we estimate that 341 000 (306 000-370 000; 95% confidence interval) premature deaths in China are attributable to residential combustion emissions, approximately a third of the deaths attributable to all ambient PM2.5 pollution, with 159 000 (142 000-172 000) and 182 000 (163 000-197 000) premature deaths from heating and cooking emissions, respectively. Our findings emphasize the need to mitigate emissions from both residential heating and cooking sources to reduce the health impacts of ambient air pollution in China.

Drawing on the results of the country-level Global Burden of Diseases, Injuries, and Risk Factors 2010 Study, we attempted to investigate the drivers of change in the healthcare system in terms of mortality and morbidity due to diseases, injuries, and risk factors for the two decades from 1990 to 2010.We decomposed trends in mortality, cause of death, years of life lost due to disability, disability-adjusted life years (DALYs), life expectancy, health-adjusted life expectancy, and risk factors into the contribution of total increase in population size, aging of the population, and changes in age-specific and sex-specific rates.We observed a decrease in age-specific mortality rate for both sexes, with a higher rate for women. The ranking of causes of death and their corresponding number of years of life lost remained unchanged between 1990 and 2010. However, the percentages of change indicate patterns of reduction for most causes, such as ischemic and hemorrhagic stroke, hypertensive heart disease, stomach cancer, lower respiratory infections, and congenital anomalies. The number of years lost due to disability caused by diabetes and drug use disorders has significantly increased in the last two decades. Major causes of DALYs, such as injuries, interpersonal violence, and suicide, showed increasing trends, while rates of communicable diseases, neonatal disorders, and nutritional deficiencies have declined significantly. Life expectancy and health-adjusted life expectancy increased for both sexes by approximately 7 years, with the highest rate of increase pertaining to females over the age 30.Time trend information presented in this paper can be used to evaluate problems and policies specific to medical conditions or risk factors. Despite recent improvements, implementing policies to reduce the number of deaths and years of life lost due to road traffic injury remains the highest priority for Iranian policymakers. Immediate action by Iranian researchers is required to match Iran's decreasing mortality rate due to liver and stomach cancers to a rate comparable to the global level. Prevention and treatment plans for mental disorders, such as major depressive disorder, anxiety disorder, and particularly drug use disorders, should be considered in reforms of the health, education, and judiciary systems in Iran.

Despite the increasing availability of typhoid vaccine in many regions, global estimates of mortality attributable to enteric fever appear stable. While both Salmonella enterica serovar Typhi (S. Typhi) and serovar Paratyphi (S. Paratyphi) cause enteric fever, limited data exist estimating the burden of S. Paratyphi, particularly in Asia and Africa. We performed a systematic review of both English and Chinese-language databases to estimate the regional burden of paratyphoid within Africa and Asia. Distinct from previous reviews of the topic, we have presented two separate measures of burden; both incidence and proportion of enteric fever attributable to paratyphoid. Included articles reported laboratory-confirmed Salmonella serovar classification, provided clear methods on sampling strategy, defined the age range of participants, and specified the time period of the study. A total of 64 full-text articles satisfied inclusion criteria and were included in the qualitative synthesis. Paratyphoid A was commonly identified as a cause of enteric fever throughout Asia. The highest incidence estimates in Asia came from China; four studies estimated incidence rates of over 150 cases/100,000 person-years. Paratyphoid A burden estimates from Africa were extremely limited and with the exception of Nigeria, few population or hospital-based studies from Africa reported significant Paratyphoid A burden. While significant gaps exist in the existing population-level estimates of paratyphoid burden in Asia and Africa, available data suggest that paratyphoid A is a significant cause of enteric fever in Asia. The high variability in documented incidence and proportion estimates of paratyphoid suggest considerable geospatial variability in the burden of paratyphoid fever. Additional efforts to monitor enteric fever at the population level will be necessary in order to accurately quantify the public health threat posed by S. Paratyphi A, and to improve the prevention and treatment of enteric fever.

The prevalence of diabetes in the Eastern Mediterranean Region (EMR) is among the highest in the world. We used findings from the Global Burden of Disease 2013 study to calculate the burden of diabetes in the EMR.The burden of diabetes and burden attributable to high fasting plasma glucose (HFPG) were calculated for each of the 22 countries in the EMR between 1990 and 2013. A systematic analysis was performed on mortality and morbidity data to estimate prevalence, deaths, and disability-adjusted life years (DALYs).The diabetes death rate increased by 60.7%, from 12.1 per 100,000 population (95% uncertainty interval [UI]: 11.2-13.2) in 1990 to 19.5 per 100,000 population (95% UI: 17.4-21.5) in 2013. The diabetes DALY rate increased from 589.9 per 100,000 (95% UI: 498.0-698.0) in 1990 to 883.5 per 100,000 population (95% UI: 732.2-1,051.5) in 2013. In 2013, HFPG accounted for 4.9% (95% UI: 4.4-5.3) of DALYs from all causes. Total DALYs from diabetes increased by 148.6% during 1990-2013; population growth accounted for a 62.9% increase, and aging and increase in age-specific DALY rates accounted for 31.8% and 53.9%, respectively.Our findings show that diabetes causes a major burden in the EMR, which is increasing. Aging and population growth do not fully explain this increase in the diabetes burden. Programs and policies are urgently needed to reduce risk factors for diabetes, increase awareness of the disease, and improve diagnosis and control of diabetes to reduce its burden.

Objective Early detection of cancer is crucial for reducing the global burden of cancer, but effective screening tests for many cancers do not exist. This study aimed to develop a novel proteome-based multi-cancer screening test that can detect early-stage cancers with high accuracy. Methods and analysis We collected plasma samples from 440 individuals, healthy and diagnosed with 18 early-stage solid tumours. Using proximity extension assay, we measured more than 3000 high-abundance and low-abundance proteins in each sample. Then, using a multi-step statistical approach, we identified a limited set of sex-specific proteins that could detect early-stage cancers and their tissue of origin with high accuracy. Results Our sex-specific cancer detection panels consisting of 10 proteins showed high accuracy for both males (area under the curve (AUC): 0.98, 95% CI 0.96, 1) and females (AUC: 0.983, 95% CI 0.95, 1.00). At stage I and at the specificity of 99%, our panels were able to identify 93% (95% CI 79%, 100%) of cancers among males and 84% (95% CI 68%, 100%) of cancers among females. Our sex-specific localisation panels consisted of 150 proteins and were able to identify the tissue of origin of most cancers in more than 80% of cases. The analysis of the plasma concentrations of proteins selected showed that almost all the proteins were in the low-concentration part of the human plasma proteome. Conclusion The proteome-based screening test showed promising performance compared with other technologies and could be a starting point for developing a new generation of screening tests for the early detection of cancer.

<h3>Background</h3> Measuring the distribution of health is a part of assessing health system performance. This study aims to estimate health inequality between different socioeconomic groups and its determinants in Tehran, the capital of Iran. <h3>Methods</h3> Self-rated health (SRH) and demographic characteristics, including gender, age, marital status, educational years, and assets, were measured by structured interviews of 2464 residents of Tehran in 2008. A concentration index was calculated to measure health inequality by economic status. The association of potential determinants and SRH was assessed through multivariate logistic regression. The contribution to concentration index of level of education, marital status and other determining factors was assessed by decomposition. <h3>Results</h3> The mean age of respondents was 41.4 years (SD 17.7) and 49% of them were men. The mean score of SRH status was 3.72 (range: 1–5; SD 0.93). 282 respondents (11.5%) rated their health status as poor or very poor. The concentration index was −0.29 (SE 0.03; p&lt;0.001). Age, marital status, level of education and household economic status were significantly associated with SRH in both the crude and adjusted analyses. The main contributors to inequality in SRH were economic status (47.8%), level of education (29.2%) and age (23.0%). <h3>Conclusions</h3> Sub-optimal SRH was more in lower than in higher economic status. After controlling for age, the levels of education and household wealth have the greatest contributions to SRH inequality.

Pneumonia and diarrhea are leading causes of death for children under five (U5). It is challenging to estimate the total number of deaths and cause-specific mortality fractions. Two major efforts, one led by the Institute for Health Metrics and Evaluation (IHME) and the other led by the World Health Organization (WHO)/Child Health Epidemiology Reference Group (CHERG) created estimates for the burden of disease due to these two syndromes, yet their estimates differed greatly for 2010.This paper discusses three main drivers of the differences: data sources, data processing, and covariates used for modelling. The paper discusses differences in the model assumptions for etiology-specific estimates and presents recommendations for improving future models.IHME's Global Burden of Disease (GBD) 2010 study estimated 6.8 million U5 deaths compared to 7.6 million U5 deaths from CHERG. The proportional differences between the pneumonia and diarrhea burden estimates from the two groups are much larger; GBD 2010 estimated 0.847 million and CHERG estimated 1.396 million due to pneumonia. Compared to CHERG, GBD 2010 used broader inclusion criteria for verbal autopsy and vital registration data. GBD 2010 and CHERG used different data processing procedures and therefore attributed the causes of neonatal death differently. The major difference in pneumonia etiologies modeling approach was the inclusion of observational study data; GBD 2010 included observational studies. CHERG relied on vaccine efficacy studies.Greater transparency in modeling methods and more timely access to data sources are needed. In October 2013, the Bill & Melinda Gates Foundation (BMGF) hosted an expert meeting to examine possible approaches for better estimation. The group recommended examining the impact of data by systematically excluding sources in their models. GBD 2.0 will use a counterfactual approach for estimating mortality from pathogens due to specific etiologies to overcome bias of the methods used in GBD 2010 going forward.

The burden of non-communicable diseases (NCDs) has increased in sub-Saharan countries, including Ethiopia. The contribution of dietary behaviours to the NCD burden in Ethiopia has not been evaluated. This study, therefore, aimed to assess diet-related burden of disease in Ethiopia between 1990 and 2013. We used the 2013 Global Burden of Disease (GBD) data to estimate deaths, years of life lost (YLLs) and disability-adjusted life years (DALYs) related to eight food types, five nutrients and fibre intake. Dietary exposure was estimated using a Bayesian hierarchical meta-regression. The effect size of each diet-disease pair was obtained based on meta-analyses of prospective observational studies and randomized controlled trials. A comparative risk assessment approach was used to quantify the proportion of NCD burden associated with dietary risk factors. In 2013, dietary factors were responsible for 60,402 deaths (95% Uncertainty Interval [UI]: 44,943-74,898) in Ethiopia—almost a quarter (23.0%) of all NCD deaths. Nearly nine in every ten diet-related deaths (88.0%) were from cardiovascular diseases (CVD) and 44.0% of all CVD deaths were related to poor diet. Suboptimal diet accounted for 1,353,407 DALYs (95% UI: 1,010,433-1,672,828) and 1,291,703 YLLs (95% UI: 961,915-1,599,985). Low intake of fruits and vegetables and high intake of sodium were the most important dietary factors. The proportion of NCD deaths associated with low fruit consumption slightly increased (11.3% in 1990 and 11.9% in 2013). In these years, the rate of burden of disease related to poor diet slightly decreased; however, their contribution to NCDs remained stable. Dietary behaviour contributes significantly to the NCD burden in Ethiopia. Intakes of diet low in fruits and vegetables and high in sodium are the leading dietary risks. To effectively mitigate the oncoming NCD burden in Ethiopia, multisectoral interventions are required; and nutrition policies and dietary guidelines should be developed.

BackgroundSince 1990, health priorities in sub-Saharan Africa (SSAF) have been set primarily by epidemics of infectious diseases. For future global health efforts, it is important to understand the growing burden of non-communicable diseases (NCDs).MethodsFor ten major causes of NCDs, the burden of 357 diseases and sequelae was estimated. Cause-specific death rates were estimated by an ensemble method using vital registration and verbal autopsy data. The number of patients was estimated with DisMod III by mathematical modelling of epidemiological measures of each sequela. Disability weights were estimated by an open-access web-based survey, in addition to population-based surveys in Bangladesh, Indonesia, Peru, and the USA.FindingsIn 2010, more than 2·06 million deaths due to NCDs occurred in SSAF, a 46% (95% CI 41–59) increase from 1990. The risk in terms of age-standardised death rate has declined by about 12% (95% CI 8–14) from 1990 to 2010, with a negligible decline in central SSAF. The total burden of NCDs in terms of disability-adjusted life-years (DALYs) showed a similar pattern, with an increase of 45% (95% CI 41–52) in DALYs and a decrease of 9% (7–12) in standardised DALYs per capita. The fraction of burden of cancers remained at 8% in 2010, while cardiovascular and respiratory diseases decreased slightly from 16% and 12% in 1990 to 15% and 10% in 2010, respectively. Mental and behavioural disorders, musculoskeletal diseases, and diabetes and endocrine diseases increased by 3%, 2%, and 1% in 2010, respectively (from 12%, 9%, and 11% in 1990). In southern SSAF, the proportion of DALYs due to infectious diseases increased by 17% between 1990 and 2010, while the proportion of DALYs due to NCDs and injuries declined by about 20% and 15%, respectively. The decline in the burden of NCDs may be due to the pressure of competing infectious disease risks over this period.InterpretationAn increasing burden of NCDs in Africa shows a growing health iceberg hidden under epidemics of infectious diseases. The NCDs with an increasing burden of disease in SSAF are mental and behavioural conditions and musculoskeletal diseases.FundingBill & Melinda Gates Foundation.

Population health and disease profiles are diverse across Iran's neighboring countries. Borrowing the results of the country-level Global Burden of Diseases, Injuries, and Risk Factors 2010 Study (GBD 2010), we aim to compare Iran with 19 countries in terms of an important set of population health and disease metrics. These countries include those neighboring Iran and a few other countries from the Middle East and North Africa (MENA) region.We show the pattern of health transition across the comparator countries from 1990 through 2010. We use classic GBD metrics measured for the year 2010 to indicate the rank of Iran among these nations. The metrics include disability-adjusted life years (DALYs), years of life lost as a result of premature death (YLLs), years of life lost due to disability (YLDs), health-adjusted life expectancy (HALE), and age-standardized death rate (ASD).Considerable and uniform transition from communicable, maternal, neonatal, and nutritional (CMMN) conditions to non-communicable diseases (NCDs) was seen between 1990 and 2010. On average, ischemic heart disease, lower respiratory infections, and road injuries were the three principal causes of YLLs, while low back pain and major depressive disorders were the top causes of YLDs in these countries. Iran ranked 13th in HALE and 12th in ASD. The function of Iran's health care, measured by DALYs, was somewhat in the middle of the HALE spectrum for the comparator countries. This intermediate position becomes rather highlighted when Afghanistan, as outlier, is taken out of the comparison.Effective policies to reduce NCDs need to be formulated and implemented through an integrated health care system. Our comparison shows that Iran can learn from the experience of a number of these countries to devise and execute the required strategies.

The objective of this study was to compare ischaemic heart disease (IHD) mortality and risk factor burden across former Soviet Union (fSU) and satellite countries and regions in 1990 and 2015.The fSU and satellite countries were grouped into Central Asian, Central European and Eastern European regions. IHD mortality data for men and women of any age were gathered from national vital registration, and age, sex, country, year-specific IHD mortality rates were estimated in an ensemble model. IHD morbidity and mortality burden attributable to risk factors was estimated by comparative risk assessment using population attributable fractions.In 2015, age-standardised IHD death rates in Eastern European and Central Asian fSU countries were almost two times that of satellite states of Central Europe. Between 1990 and 2015, rates decreased substantially in Central Europe (men -43.5% (95% uncertainty interval -45.0%, -42.0%); women -42.9% (-44.0%, -41.0%)) but less in Eastern Europe (men -5.6% (-9.0, -3.0); women -12.2% (-15.5%, -9.0%)). Age-standardised IHD death rates also varied within regions: within Eastern Europe, rates decreased -51.7% in Estonian men (-54.0, -47.0) but increased +19.4% in Belarusian men (+12.0, +27.0). High blood pressure and cholesterol were leading risk factors for IHD burden, with smoking, body mass index, dietary factors and ambient air pollution also ranking high.Some fSU countries continue to experience a high IHD burden, while others have achieved remarkable reductions in IHD mortality. Control of blood pressure, cholesterol and smoking are IHD prevention priorities.

Diarrheal diseases (DD) are leading causes of disease burden, death, and disability, especially in children in low-income settings. DD can also impact a child's potential livelihood through stunted physical growth, cognitive impairment, and other sequelae. As part of the Global Burden of Disease Study, we estimated DD burden, and the burden attributable to specific risk factors and particular etiologies, in the Eastern Mediterranean Region (EMR) between 1990 and 2013. For both sexes and all ages, we calculated disability-adjusted life years (DALYs), which are the sum of years of life lost and years lived with disability. We estimate that over 125,000 deaths (3.6% of total deaths) were due to DD in the EMR in 2013, with a greater burden of DD in low- and middle-income countries. Diarrhea deaths per 100,000 children under 5 years of age ranged from one (95% uncertainty interval [UI] = 0-1) in Bahrain and Oman to 471 (95% UI = 245-763) in Somalia. The pattern for diarrhea DALYs among those under 5 years of age closely followed that for diarrheal deaths. DALYs per 100,000 ranged from 739 (95% UI = 520-989) in Syria to 40,869 (95% UI = 21,540-65,823) in Somalia. Our results highlighted a highly inequitable burden of DD in EMR, mainly driven by the lack of access to proper resources such as water and sanitation. Our findings will guide preventive and treatment interventions which are based on evidence and which follow the ultimate goal of reducing the DD burden.

AddictionVolume 111, Issue 10 p. 1806-1813 Research ReportOpen Access Alcohol-attributed disease burden in four Nordic countries: a comparison using the Global Burden of Disease, Injuries and Risk Factors 2013 study Emilie E. Agardh, Corresponding Author Emilie E. Agardh emilie.agardh@ki.se Department of Public Health Sciences, Karolinska Institutet, Stockholm, SwedenCorrespondence to: Emilie E. Agardh, Karolinska Institutet, Department of Public Health Sciences (PHS), SE-171 77 Stockholm, Sweden. E-mail: emilie.agardh@ki.seSearch for more papers by this authorAnna-Karin Danielsson, Anna-Karin Danielsson Department of Public Health Sciences, Karolinska Institutet, Stockholm, SwedenSearch for more papers by this authorMats Ramstedt, Mats Ramstedt Swedish Council for Information on Alcohol and Drugs (CAN), Stockholm, Sweden Department of Clinical Neurosciences, Karolinska Institutet, Stockholm, SwedenSearch for more papers by this authorAstrid Ledgaard Holm, Astrid Ledgaard Holm Department of Public Health Sciences, University of Copenhagen, Section of Social Medicine, Copenhagen, DenmarkSearch for more papers by this authorFinn Diderichsen, Finn Diderichsen Department of Public Health Sciences, University of Copenhagen, Section of Social Medicine, Copenhagen, DenmarkSearch for more papers by this authorKnud Juel, Knud Juel National Institute of Public Health, University of Southern Denmark, Odense, DenmarkSearch for more papers by this authorStein Emil Vollset, Stein Emil Vollset The Norwegian Institute of Public Health, Centre for Disease Burden, Oslo/Bergen, Norway Department of Global Public Health and Primary Care, University of Bergen, Bergen, NorwaySearch for more papers by this authorAnn Kristin Knudsen, Ann Kristin Knudsen The Norwegian Institute of Public Health, Centre for Disease Burden, Oslo/Bergen, Norway Department of Global Public Health and Primary Care, University of Bergen, Bergen, NorwaySearch for more papers by this authorJonas Minet Kinge, Jonas Minet Kinge Department of Health Statistics, The Norwegian Institute of Public Health, Oslo, Norway Department of Health Management and Health Economics, University of Oslo, Oslo, NorwaySearch for more papers by this authorRichard White, Richard White Department of Health Statistics, The Norwegian Institute of Public Health, Oslo, NorwaySearch for more papers by this authorVegard Skirbekk, Vegard Skirbekk The Norwegian Institute of Public Health, Centre for Disease Burden, Oslo/Bergen, Norway Columbia University, New York, NY, USASearch for more papers by this authorPia Mäkelä, Pia Mäkelä Alcohol and Drugs Unit, National Institute for Health and Welfare, Helsinki, FinlandSearch for more papers by this authorMohammad Hossein Forouzanfar, Mohammad Hossein Forouzanfar Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, USASearch for more papers by this authorMatthew M. Coates, Matthew M. Coates Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, USASearch for more papers by this authorDaniel C. Casey, Daniel C. Casey Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, USASearch for more papers by this authorMohesen Naghavi, Mohesen Naghavi Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, USASearch for more papers by this authorPeter Allebeck, Peter Allebeck Department of Public Health Sciences, Karolinska Institutet, Stockholm, SwedenSearch for more papers by this author Emilie E. Agardh, Corresponding Author Emilie E. Agardh emilie.agardh@ki.se Department of Public Health Sciences, Karolinska Institutet, Stockholm, SwedenCorrespondence to: Emilie E. Agardh, Karolinska Institutet, Department of Public Health Sciences (PHS), SE-171 77 Stockholm, Sweden. E-mail: emilie.agardh@ki.seSearch for more papers by this authorAnna-Karin Danielsson, Anna-Karin Danielsson Department of Public Health Sciences, Karolinska Institutet, Stockholm, SwedenSearch for more papers by this authorMats Ramstedt, Mats Ramstedt Swedish Council for Information on Alcohol and Drugs (CAN), Stockholm, Sweden Department of Clinical Neurosciences, Karolinska Institutet, Stockholm, SwedenSearch for more papers by this authorAstrid Ledgaard Holm, Astrid Ledgaard Holm Department of Public Health Sciences, University of Copenhagen, Section of Social Medicine, Copenhagen, DenmarkSearch for more papers by this authorFinn Diderichsen, Finn Diderichsen Department of Public Health Sciences, University of Copenhagen, Section of Social Medicine, Copenhagen, DenmarkSearch for more papers by this authorKnud Juel, Knud Juel National Institute of Public Health, University of Southern Denmark, Odense, DenmarkSearch for more papers by this authorStein Emil Vollset, Stein Emil Vollset The Norwegian Institute of Public Health, Centre for Disease Burden, Oslo/Bergen, Norway Department of Global Public Health and Primary Care, University of Bergen, Bergen, NorwaySearch for more papers by this authorAnn Kristin Knudsen, Ann Kristin Knudsen The Norwegian Institute of Public Health, Centre for Disease Burden, Oslo/Bergen, Norway Department of Global Public Health and Primary Care, University of Bergen, Bergen, NorwaySearch for more papers by this authorJonas Minet Kinge, Jonas Minet Kinge Department of Health Statistics, The Norwegian Institute of Public Health, Oslo, Norway Department of Health Management and Health Economics, University of Oslo, Oslo, NorwaySearch for more papers by this authorRichard White, Richard White Department of Health Statistics, The Norwegian Institute of Public Health, Oslo, NorwaySearch for more papers by this authorVegard Skirbekk, Vegard Skirbekk The Norwegian Institute of Public Health, Centre for Disease Burden, Oslo/Bergen, Norway Columbia University, New York, NY, USASearch for more papers by this authorPia Mäkelä, Pia Mäkelä Alcohol and Drugs Unit, National Institute for Health and Welfare, Helsinki, FinlandSearch for more papers by this authorMohammad Hossein Forouzanfar, Mohammad Hossein Forouzanfar Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, USASearch for more papers by this authorMatthew M. Coates, Matthew M. Coates Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, USASearch for more papers by this authorDaniel C. Casey, Daniel C. Casey Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, USASearch for more papers by this authorMohesen Naghavi, Mohesen Naghavi Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, USASearch for more papers by this authorPeter Allebeck, Peter Allebeck Department of Public Health Sciences, Karolinska Institutet, Stockholm, SwedenSearch for more papers by this author First published: 16 April 2016 https://doi.org/10.1111/add.13430Citations: 18AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Abstract Aims (1) To compare alcohol-attributed disease burden in four Nordic countries 1990–2013, by overall disability-adjusted life years (DALYs) and separated by premature mortality [years of life lost (YLL)] and health loss to non-fatal conditions [years lived with disability (YLD)]; (2) to examine whether changes in alcohol consumption informs alcohol-attributed disease burden; and (3) to compare the distribution of disease burden separated by causes. Design A comparative risk assessment approach. Setting Sweden, Norway, Denmark and Finland. Participants Male and female populations of each country. Measurements Age-standardized DALYs, YLLs and YLDs per 100 000 with 95% uncertainty intervals (UIs). Findings In Finland, with the highest burden over the study period, overall alcohol-attributed DALYs were 1616 per 100 000 in 2013, while in Norway, with the lowest burden, corresponding estimates were 634. DALYs in Denmark were 1246 and in Sweden 788. In Denmark and Finland, changes in consumption generally corresponded to changes in disease burden, but not to the same extent in Sweden and Norway. All countries had a similar disease pattern and the majority of DALYs were due to YLLs (62–76%), mainly from alcohol use disorder, cirrhosis, transport injuries, self-harm and violence. YLDs from alcohol use disorder accounted for 41% and 49% of DALYs in Denmark and Finland compared to 63 and 64% in Norway and Sweden 2013, respectively. Conclusions Finland and Denmark has a higher alcohol-attributed disease burden than Sweden and Norway in the period 1990–2013. Changes in consumption levels in general corresponded to changes in harm in Finland and Denmark, but not in Sweden and Norway for some years. All countries followed a similar pattern. The majority of disability-adjusted life years were due to premature mortality. Alcohol use disorder by non-fatal conditions accounted for a higher proportion of disability-adjusted life years in Norway and Sweden, compared with Finland and Denmark. Introduction Alcohol consumption is an important risk factor for mortality and morbidity 1, 2 and as part of public health monitoring, countries and regions often assess patterns of alcohol consumption and alcohol-related harm 3. Comparative studies play an important role in determining how well countries measure up against each other and can help to understand determinants influencing drinking behaviour and adverse health effects 4. Until now, alcohol-related mortality, and in particular cirrhosis mortality, has been used as the standard indicator due to its universal coverage and coding rules set up by the World Health Organization (WHO) 5. However, alcohol-related death does not estimate disease burden; that is, morbidity due to non-fatal conditions such as alcohol use disorder and injuries is not captured. An increasingly used measure to estimate overall disease burden in the population, combining premature death or years of life lost (YLL) and years lived with disability (YLD), is disability-adjusted life years (DALY) 6. DALY as a metric was developed in the 1990s 7 within the global burden of disease study (GBD). Results from the latest iteration of the GBD study were published in 2015, the so-called GBD 2013 8, 9. The analysis of risk factors for burden of disease have identified approximately 30 conditions attributed to alcohol which have been incorporated into the GBD 2013 1. The GBD estimates thus allow for a more comprehensive assessment of alcohol-attributed disease burden than previously. In the Nordic countries there has been a strong interest to follow and compare consumption and alcohol-related harm using cause of death data. Sweden, Norway, Denmark and Finland share important population, geographical and welfare characteristics, and alcohol consumption is deeply rooted in the culture of these countries 10. However, there are also notable differences with respect to alcohol policies and overall alcohol consumption over time. Sweden and Norway stand out historically as having restrictive alcohol policies, while Finland, although more lately, and especially Denmark, have a more liberal approach. As a consequence, the consumption levels in Denmark and Finland are higher than in Sweden and Norway, which also has been reflected in countrywise mortality rates from alcohol-related causes such as liver cirrhosis and injuries 11. At the same time, there is a geographical gradient in the effect of alcohol on mortality that in general is stronger in northern Europe compared to southern and central Europe 12. This supports the importance of drinking patterns. The Nordic countries have fairly similar drinking cultures 13, but report differences in levels of consumption and alcohol-related mortality. Important questions are thus how temporal and geographical patterns of alcohol-related harm are distributed across the Nordic countries when including non-fatal conditions, and also whether changes in harm over time reflects level of consumption when using the broader indicator of DALY. To quantify and compare overall harm and to identify key areas in which most of the harm occurs is crucial for laying a basis for specific policy measures, both in the field of prevention and treatment 13. In this study, we used the results from the Global Burden of Disease and Injuries and Risk Factors 2013 study to present new comparative estimates on the alcohol-attributed disease burden in the Nordic countries between 1990 and 2013. More specifically we aimed to: Compare the alcohol-attributed disease burden by overall DALYs, premature mortality (YLLs) and health loss from non-fatal conditions (YLDs); Examine whether changes in alcohol consumption informs alcohol-attributed disease burden; and Compare the distribution of alcohol-attributed disease burden separated by causes. Methods DALYs, YLLs and YLDs The GBD is currently the leading system to monitor overall disease burden as well as the contribution of risk factors. The latest iteration GBD 2013, which has been described in detail elsewhere 1, 8, 9, 14, has expanded in scope and comprises estimates of 306 diseases and injuries and 2337 sequelae (non-fatal health consequences of disease and injuries) for men and women in 20 age groups, and uses DALY as measure of population health. DALYs assess years of healthy life lost by different causes and are calculated by adding together YLLs and YLDs. The YLLs are based on 240 causes of death and are calculated by multiplying the number of deaths for each cause in each age group by a reference life expectancy at that age 8, 9. The reference life expectancy at birth is based on the lowest observed death rates for each age group across countries in 2013 15. The cause of death estimates are based on vital registration, i.e. the cause of death registers in the Nordic countries. The YLDs are based on two components, the prevalence of each of the 2337 sequelae, i.e. non-fatal health consequences of disease and injuries, and the disability weights 14. Disability weights are based on the general public's assessment of the severity of health loss associated with a health state, and is a number between zero (perfect health) and one (death) 16, 17. For example, mild alcohol use disorder has a disability weight of 0.235 and severe alcohol use disorder of 0.570. YLDs are calculated by multiplying the prevalence of each sequelae by its disability weight, and the number of YLDs for a specific disease or injury is the sum of the YLD from each sequelae arising from that cause, resulting in a total of 301 diseases and injuries 14. To obtain prevalence estimates for each sequel, available data on prevalence, incidence, remission, duration and excess mortality have been identified through a systematic search of published and unpublished sources 18. A modelling tool called DisMod-MR 2.0 (Disease Modeling–Metaregression) was used to generate the prevalence estimates from these data 14. Alcohol as a risk factor in GBD According to GBD 2013 estimates, alcohol was ranked to be the sixth leading risk factor to overall disease burden globally 1. The contribution of alcohol is estimated using a comparative risk assessment approach in which observed health outcomes are compared to those that would have been observed with a counterfactual set of exposure where no one is exposed 19. Calculations of the contribution of alcohol include several steps, as follows. Estimating the relative risk of alcohol for a given mortality or morbidity outcome; Alcohol has been causally related to approximately 30 diseases and injuries including harm to others, and relative risks in these exposure-outcome associations are estimated on the basis of systematic reviews and meta-analyses, usually giving a continuous risk function over average daily consumption amounts 20. Estimating the distribution of alcohol exposure in countries by age and sex; first, the average all-age consumption per capita is estimated using Food and Agriculture Organization of the United Nations (FAO) and WHO Global Information System on Alcohol and Health data. This all-age consumption estimate incorporates registered and unregistered consumption, se details in appendix of sources 1, 21, and is considered more reliable than survey data on consumption recall. Secondly, these all-age consumption estimates are split into 5-year age groups based on the consumption by age and sex estimated in DisMod-MR 2.0 using survey recall data, by taking the proportions of consumption in each age–sex group and applying those proportions to 80% total consumption to account for spillage, wastage and breakage; see details in the Supporting information of source 1. Other exposure data are also estimated using DisMod-MR 2.0: the proportions of the population that are drinkers, binge drinkers, former drinkers or never-drinkers (abstainers); and the frequency of binge events among binge drinkers 1, 21. The contribution of alcohol to disease burden is estimated by comparing the population risk of diseases or injuries under the current exposure distribution, to a theoretical counterfactual distribution, where no one is exposed, known as the population attributable fraction. Thus, for alcohol this is achieved by using the disease-specific relative risks (i.e. the risk of disease at different levels of alcohol consumption versus zero exposure to alcohol, i.e. never-drinkers or abstainers) from the meta-analyses described above and the estimated distribution of alcohol consumption in the population described above. The general approach for the calculation of this attributable fraction and some alcohol-specific methods are described elsewhere, the Supporting information in source 1. This fraction is then applied to the overall disease specific burden (DALYs, YLLs and YLDs) to gain the alcohol-attributable disease specific burden. Analytical strategy We used the results from GBD 2013 to present the age-standardized rates of DALYs, YLLs and YLDs per 100 000, with 95% uncertainty intervals (UIs) between 1990 and 2013 at a 5-year interval. Age-standardized rates adjust for total population and changes in age-specific population sizes over time, and allow comparison of alcohol-attributed health outcomes across countries. The following specific causes were included: alcohol use disorder, self-harm and violence, transport injuries, unintentional injuries, cirrhosis, neoplasms, cardiovascular diseases, diabetes, epilepsy, pancreatitis, lower respiratory infections and tuberculosis. Some of these are based on more detailed diagnoses such as, for example, type of transport injury or neoplasm (see Supporting information, Table S1). ICD codes for all included cases are available in the Supporting information, Table S3 of source 15. Results on consumption levels as well as estimates of alcohol-attributed disease burden were extracted from the IHME database. Results Alcohol-attributed disease burden (by overall DALYs, YLLs and YLDs) and population drinking Figure 1 shows the alcohol-attributed disease burden by overall DALYs, YLLs and YLDs per 100 000 and levels of population drinking between 1990 and 2013 in the four countries. In Finland, having the highest alcohol-attributed disease burden over the study period, overall DALYs decreased from 2060 (UI = 1790–2394) in 1990 to 1616 (UI = 1391–1859) in 2013, with a peak in 2005 with 2053 DALYs (95% UI = 1807–2294). Norway had the lowest burden and DALYs decreased from 715 (UI = 545–897) in 1990 to 634 (UI = 521–765) in 2013, with a peak in 2000 with 721 DALYs (95% UI = 577–872). Denmark's alcohol-attributed disease burden (1729: UI = 1463–2037 in 1990 and 1246: UI = 1053–1433 in 2013) was closer to the levels in Finland, while in Sweden (1101: UI = 918–1300 in 1990 and 788: UI = 655–938 in 2013) it was closer to Norway (see Supporting information, Table S2 for details). Figure 1Open in figure viewerPowerPoint Disease burden [age-standardized disability-adjusted life years (DALYs) by years of life lost (YLLs) and years lived with disability (YLDs) per 100 000] attributed to alcohol and consumption of alcohol (in litres of pure alcohol per person and year) in Nordic countries 1990–2013 The majority of the disease burden attributed to alcohol was due to premature mortality (YLLs) in all countries. In 1990 and 2013 overall YLLs accounted for approximately 73 and 69% of all DALYs in Finland, 78 and 76% in Denmark, 66 and 63% in Norway and 68 and 62% in Sweden (not shown). In Denmark and Finland changes in overall alcohol-attributed disease burden generally responded to changes in population drinking over the years. In Sweden and Norway, the consumption levels increased between 2000 and 2010, although not followed by a similar increase in disease burden. Alcohol-attributed disease burden (DALYs) distributed by causes Figure 2 shows the alcohol-attributed disease burden (age-standardized DALYs per 100 000) distributed by causes over time in all countries. Even if Finland and Denmark had higher levels of alcohol-attributed health problems, all countries followed a similar pattern, e.g. alcohol use disorder was the leading cause and accounted together with cirrhosis, transport and unintentional injuries, self-harm and violence and neoplasms for the majority of the alcohol-attributed disease burden as measured by DALYs. Figure 2Open in figure viewerPowerPoint Alcohol-attributed burden [age-standardized disability-adjusted life years (DALYs) per 100 000] distributed by causes in the Nordic countries 1990–2013 There are some discrepancies within and between countries over time. In Finland DALYs of cirrhosis, alcohol use disorders and injuries fluctuated over the years. Alcohol use disorders and cirrhosis were highest in 2005 with 617 DALYs (95% UI = 444–757) and 355 DALYs (95% UI = 317–386). At the same time, the burden of self-harm and violence decreased from 1990 to 2013 by 358 DALYs (95% UI = 302–408) to 205 DALYs (95% UI = 174–269) and transport injuries from 364 DALYs (95% UI = 318–415) to 162 DALYs (95% UI = 138–189). The relative contribution of neoplasms to DALYs was not as prominent in Finland as in the other three countries. Denmark and Sweden had a similar pattern as Finland for alcohol use disorder, being highest in Denmark in 2005 (498 DALYs, 95% UI = 352–601) and in 2000 in Sweden (324 DALYs, 95% UI = 250–414). In contrast, even if cirrhosis also made an important contribution to DALYs in Denmark, instead it decreased gradually between 1995 and 2013 (from 358 DALYs, 95% UI = 318–391 to 254 DALYs, 95% UI = 213–290), as did self-harm and violence, transport injuries and neoplasms. In Sweden and Norway, the burden of transport injuries, neoplasms, unintentional injuries, self-harm and violence and cirrhosis more or less shared the second place after alcohol use disorder from 2000 onwards, and all decreased slightly over time. Alcohol-attributed disease burden (by YLLs and YLDs) distributed by causes Figures 3 and 4 illustrate the alcohol-attributed burden by causes, separated by premature mortality (age-standardized YLLs per 100 000) and years lived with disability (age-standardized YLDs per 100 000) (see the Supporting information, Tables S3 and S4 for details). The causes by YLLs follow a similar pattern as for DALYs, largely because the majority of DALYs are caused by YLLs from alcohol use disorder, cirrhosis, transport injuries, self-harm and violence and neoplasms. One difference is that YLLs attributable to alcohol use disorder and unintentional injuries were less prominent compared to other causes. Instead, alcohol use disorder and unintentional injuries make an important contribution to DALYs through YLDs. Figure 3Open in figure viewerPowerPoint Alcohol-attributed disease burden [age-standardized years of life lost (YLLs) per 100 000] distributed by causes in the Nordic countries 1990–2013 Figure 4Open in figure viewerPowerPoint Alcohol-attributed disease burden [age-standardized years lived with disability (YLDs) per 100 000] distributed by causes in the Nordic countries 1990–2013 The YLDs did not follow a similar pattern to YLLs. For example, for alcohol use disorder, the largest contributor to YLDs in all countries, the gap in burden between Norway and Sweden compared to Finland was not as pronounced as for YLLs (Fig. 4). In 1990 and 2013, YLDs from alcohol use disorders accounted for 48 and 63% of DALYs in Norway and 55 and 64% in Sweden, while in Finland the corresponding contribution was 40–49% and 40–41% in Denmark (not shown). In Norway and Sweden YLDs by alcohol use disorder have been rather stable over time. Thus the decrease in DALYs of alcohol use disorder over time was due mainly to decreased YLLs. Discussion Our study shows that Finland and Denmark had a higher alcohol-attributed disease burden than Sweden and Norway in the period 1990–2013 and that changes in consumption levels in general corresponded to changes in harm in Finland and Denmark, but not for some years in Sweden and Norway. All countries followed a similar disease pattern. The majority of DALYs were due to YLLs from alcohol use disorder, cirrhosis, transport injuries, self-harm and violence and neoplasms that generally decreased over time. The exceptions were that YLLs of alcohol use disorder in Finland and Denmark and cirrhosis in Finland increased between 2000 and 2005. In contrast to YLLs, alcohol use disorder by YLDs accounted for a higher proportion of DALYs in Norway and Sweden, compared to Finland and Denmark. Finland and, to some extent, Denmark and Sweden also had a relatively high burden of non-fatal unintentional injuries. Our results on premature mortality correspond to other studies, showing higher mortality 3, 11 from cirrhosis, injuries and neoplasms in Finland and Denmark compared to Norway and Sweden. Moreover, it has been estimated that cirrhosis, injuries and neoplasm are responsible collectively for approximately 80% of alcohol-related deaths in the European Union (EU) 3. In our study premature mortality from alcohol use disorders also contributed significantly. Comparative studies assessing alcohol-related morbidity in the Nordic countries are lacking. Some studies have evaluated alcohol-related morbidity in relation to specific alcohol policy changes 22-26. These studies are based on different health outcomes and do not enable an overall comparison. The fact that YLDs accounted for a higher proportion of DALYs in Norway and Sweden compared to Finland and Denmark may be due to differences in treatment practices and improvement in survival rate from alcohol use disorders, or differences in underlying data. Further research is needed to understand this difference, but our results highlights the importance of including non-fatal harm when estimating the burden of alcohol-attributed adverse health effects. In general, the variation in alcohol-attributed disease burden over time corresponded to changes in levels of alcohol consumption in Denmark and Finland, although comparison to Finland's own statistical data suggests that the increase from 1990 to 2005 might have been somewhat underestimated 27. In Sweden and, to some extent, in Norway the burden of disease did not increase, although the GBD estimates show increased consumption during the past 10 years. However, there are also exceptions for Finland and Denmark when looking at specific causes of disease burden. For one thing, self-harm and violence decreased in Finland even if the overall consumption increased, as did premature mortality from alcohol use disorder in Norway. The importance of drinking patterns in the association between levels of alcohol consumption and alcohol-attributed mortality has been described previously 12, and some causes may be influenced more strongly by drinking patterns. This could also be due to differences in subgroups, such as sex, specific age groups or socio-economic groups 28. The separation of alcohol-attributed causes may give an indication of the consumption patterns and also have implications for specific policy measures, both in the field of prevention and treatment. The burden of alcohol use disorder in all countries and cirrhosis, especially in Finland and Denmark, may reflect a pattern of frequent and heavy chronic drinking 29, 30, while the burden of injuries implies risky single-occasion drinking 31. In the case of neoplasms, where the overall tissue exposure to alcohol has no lower threshold 20, 32, any level of drinking is important. The estimated beneficial effects of low to moderate alcohol consumption for cardiovascular outcomes and diabetes, resulting in negative DALYs, were seen mainly in Norway and Sweden, which may reflect a pattern of low to moderate drinking. Availability of alcohol and high taxes are effective policies 33 and these form the basis of the restrictive alcohol polices still in place, especially in Norway and Sweden, while in Finland since the mid-1990s the alcohol policies were liberalized considerably. In Denmark the high taxation of spirits was lowered in beginning of 2000. While several studies have analysed the effect of specific alcohol policy changes in relation to consumption and health outcomes in these countries 5, 22-26, these types of studies in general require more detailed time-specific data than provided herein. However, our findings, particularly regarding Finland, show that the variations in alcohol-attributed burden of disease follow variations in alcohol policy measures 34. Also, changes in alcohol-attributed disease burden in Sweden and Norway are related to policy changes as an effect of, for example, EU regulations, and the health effects in this study add to the ongoing debate on the consequences of these policy changes. There are limitations that need to be addressed. One is the quality and validity of data. Per-capita consumption is often underestimated. For this purpose a correction factor is used in the GBD calculation to account for unrecorded consumption 1. Moreover, even if estimates of levels of alcohol consumption in the GBD study largely match national surveys, there are data points where they differ. For example, contrary to the GBD estimates, Swedish data show that consumption levels actually increased from 1995 to 2000 and decreased between 2005 and 2010 35. This can be explained by the GBD methodology, in which multiple data sources are used. Furthermore, data on fatal outcomes are based on cause of death registers. Alcohol-attributed deaths tend to be under-reported in registers due to difficulties in making accurate diagnoses. Coding practices also differ across countries 36. The GBD study uses a general approach to assess causes of death from all countries. However, little is known about to what extent differences in coding affect the estimates. Another limitation concerns the relative risk estimates of the associations between alcohol and disease or mortality outcomes. These derive from meta-analyses which postulate comparability between countries. This is one of the assumptions inherited in the GBD methodology, and although plausible in view of biological pathways there could be unmeasured interactions between alcohol and other risk factors that differ between countries. Because the relative risk estimates from the meta-analyses derive mainly from high-income countries, the comparability between Sweden, Norway, Denmark and Finland should hardly be biased. A key strength with the GBD methodology is that disease burden due to alcohol is defined systematically and uniformly, also for non-fatal health outcomes, and thus estimates can be compared across countries over time. Data on non-fatal outcomes are based mainly on scientific studies reflecting the country prevalence of diseases. Even if Sweden, Norway, Denmark and Finland have comparatively high-quality records and registers, the underlying data are sometimes incomplete and not timely 18 and the results should be interpreted with caution. It should also be mentioned that the GBD methodology differs from many national studies in this area, and results are not always comparable with country-specific studies. In conclusion, we have shown a method to provide a comparative assessment of alcohol-attributed disease burden across four Nordic countries. The inclusion of alcohol-attributed non-fatal conditions, not only with regard to alcohol use disorder, but also injuries, makes an important contribution to the overall burden. As the GBD study will be shifting towards annual updating, these results may be used as a future regular monitoring system to assess and compare alcohol-attributed disease burden over time and across countries once new and updated data in this field become available. Declaration of interests None. Acknowledgements This study was supported from grants from the Alcohol Research Council of the Swedish Alcohol Retailing Monopoly (SRA). Supporting Information Table S1 Detailed diagnoses of causes. Table S2 Alcohol-attributed disease burden by agestandardized DALYs per 100 000 and (95% uncertainty intervals) distributed by causes in the Nordic countries. Table S3 Alcohol-attributed disease burden by age-standardized YLLs per 100 000 and (95% uncertainty intervals) distributed by causes in the Nordic countries. Table S4 Alcohol-attributed disease burden by age-standardized YLDs per 100 000 and (95% uncertainty intervals) distributed by causes in the Nordic countries. Filename Description add13430-sup-0001-Appendix.docxWord 2007 document , 97.9 KB Supporting info item Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. 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Citing Literature Volume111, Issue10October 2016Pages 1806-1813 FiguresReferencesRelatedInformation

BACKGROUND Gastrointestinal and liver diseases (GILDs) are major causes of death and disability in Middle East and North Africa (MENA). However, they have different patterns in countries with various geographical, cultural, and socio-economic status. We aimed to compare the burden of GILDs in Iran with its neighboring countries using the results of the Global Burden of Disease (GBD) Study in 2010. METHODS Classic metrics of GBD have been used including: age-standardized rates (ASRs) of death, years of life lost due to premature death (YLL), years of life lost due to disability (YLD), and disability adjusted life years (DALY). All countries neighboring Iran have been selected. In addition, all other countries classified in the MENA region were included. Five major groups of gastrointestinal and hepatic diseases were studied including: infections of gastrointestinal tract, gastrointestinal and pancreatobilliary cancers, acute hepatitis, cirrhosis, and other digestive diseases. RESULTS The overall burden of GILDs is highest in Afghanistan, Pakistan, and Egypt. Diarrheal diseases have been replaced by gastrointestinal cancers and cirrhosis in most countries in the region. However, in a number of countries including Afghanistan, Pakistan, Turkmenistan, Egypt, and Yemen, communicable GILDs are still among top causes of mortality and morbidity in addition to non-communicable GILDs and cancers. These countries are experiencing the double burden. In Iran, burden caused by cancers of stomach and esophagus are considerably higher than other countries. Diseases that are mainly diagnosed in outpatient settings have not been captured by GBD. CONCLUSION Improving the infrastructure of health care system including cancer registries and electronic recording of outpatient care is a necessity for better surveillance of GILDs in MENA. In contrast to expensive treatment, prevention of most GILDs is feasible and inexpensive. The health care systems in the region can be strengthened for prevention and control.

Abstract. This study focused on monitoring the water volume variations of the Doroudzan dam reservoir in Shiraz, Iran, using satellite observations. In particular, Sentinel-3 altimetry mission (SRAL) Level-1B and Level-2 data were employed to calculate water level changes, addressing the limitations in accuracy for inland and shallow waters. Re-tracking of returned waveforms was applied to improve the accuracy of Level-2 altimetry results. Additionally, Sentinel-2 optical images were utilized to monitor the water surface area of the dam reservoir. The results demonstrated that re-tracking the returned waveforms significantly improved the water level observations compared to Level-2 data. The analysis extended to comparing the time series of water surface area estimated from Sentinel-2 images with in-situ data, revealing a high accuracy of 5.39%. Combining optimum water level and surface area data in Heron's equation facilitated the calculation of water volume variations. A remarkable correlation of 95.27% was found when comparing the time series of estimated water volume variations and in-situ data. This study underscores the effectiveness of Copernicus satellites, particularly Sentinel-3 and Sentinel-2 missions, in monitoring inland water bodies and demonstrates the reliability of the techniques employed for tracking dam reservoir volume variations.

We are pleased to respond to Desmond O'Neill's comments on our paper about the global burden of stroke.1Feigin VL Forouzanfar MH Krishnamurthi R et al.Global and regional burden of stroke during 1990–2010: findings from the Global Burden of Disease Study 2010.Lancet. 2014; 383: 245-255Summary Full Text Full Text PDF PubMed Scopus (2588) Google Scholar We fully agree that the burden of stroke goes far beyond the reported data on incidence, prevalence, mortality, and disability-adjusted life-years. Stroke also has a large physical, psychological, and financial effect on patients, their families, the health-care system, and society.2Strong K Mathers C Bonita R Preventing stroke: saving lives around the world.Lancet Neurol. 2007; 6: 182-187Summary Full Text Full Text PDF PubMed Scopus (976) Google Scholar, 3Caro JJ Huybrechts KF Duchesne I Management patterns and costs of acute ischemic stroke : an international study.Stroke. 2000; 31: 582-590Crossref PubMed Scopus (134) Google Scholar Cognitive outcomes, occurring in nearly half of survivors, are important, but often ignored outcomes of stroke.4Dennis M O'Rourke S Lewis S Sharpe M Warlow C Emotional outcomes after stroke: factors associated with poor outcome.J Neurol Neurosurg Psychiatry. 2000; 68: 47-52Crossref PubMed Scopus (92) Google Scholar Additionally, as rightly emphasised by O'Neill, stroke is just one of the many manifestations (although the most catastrophic) of cerebrovascular disease, and there are clinically silent minor strokes and occult cerebrovascular disorders that contribute to the development of various non-fatal sequelae, including dementia, and mood and gait disorders. Consideration of these consequences of stroke is important, not only for a more accurate estimation of stroke burden, but also for addressing multiple risk factors to develop prevention strategies for all major consequences of stroke. We agree with O'Neill that current estimates of the global burden of stroke do underestimate the true stroke burden. The Global Burden of Diseases (GBD) analysis included calculating disability for over 300 causes including stroke. First, for example, dementia is a separate cause in the GBD analysis, and its burden is accounted for within this single cause example. Secondly, the dominant paradigm used in the GBD analysis is that of categorical attribution where mortality, morbidity, and eventually burden is attributed to only one cause, in this case stroke. An alternative is the counterfactual notion in which consequences relevant to stroke such as dementia,5Savva GM Stephan BCM Epidemiological studies of the effect of stroke on incident dementia: a systematic review.Stroke. 2010; 41: e41-e46Crossref PubMed Scopus (205) Google Scholar Parkinson's disease, and cognitive dysfunction are accounted for by calculating the total burden for a single cause. Although the idea of estimating effects by the counterfactual approach is very appealing, there are not much data for all aspects of interaction between different causes to make this possible. Therefore, estimating other aspects of the stroke burden was beyond the scope of our paper.1Feigin VL Forouzanfar MH Krishnamurthi R et al.Global and regional burden of stroke during 1990–2010: findings from the Global Burden of Disease Study 2010.Lancet. 2014; 383: 245-255Summary Full Text Full Text PDF PubMed Scopus (2588) Google Scholar We declare that we have no competing interests. The views expressed are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute, National Institutes of Health, or the US Department of Health and Human Services. Global burden of stroke: an underestimateThe global burden of stroke outlined by Valery Feigin and colleagues' Article (Jan 18, p 245)1 is likely to be a substantial underestimation in view of the consequences of stroke disease on conditions other than acute stroke, which substantially affect health and wellbeing.2 Overt and occult cerebrovascular disease, both large and small vessel, have been recognised to contribute to Alzheimer's disease and vascular dementia.3 Full-Text PDF Global and regional burden of stroke during 1990–2010: findings from the Global Burden of Disease Study 2010Although age-standardised rates of stroke mortality have decreased worldwide in the past two decades, the absolute number of people who have a stroke every year, stroke survivors, related deaths, and the overall global burden of stroke (DALYs lost) are great and increasing. Further study is needed to improve understanding of stroke determinants and burden worldwide, and to establish causes of disparities and changes in trends in stroke burden between countries of different income levels. Full-Text PDF

BACKGROUND Gastrointestinal and liver diseases (GILD) constitute a noteworthy portion of causes of death and disability in Iran. However, data on their prevalence and burden is sparse in Iran. The Global Burden of Disease (GBD) study in 2010 has provided invaluable comprehensive data on the burden of GILD in Iran. METHODS Estimations of death, years of life lost due to premature death (YLL), years of life lost due to disability (YLD), disability-adjusted life years (DALY), life expectancy, and healthy life expectancy have been reported for 291 diseases, 67 risk factors, 1160 sequelae, for both sexes and 19 age groups, form 1990 to 2010 for 187 countries. In the current paper, 5 major categories of gastrointestinal (GI) and liver diseases have been investigated as follows: GI infectious diseases, GI and liver cancers, liver infections, chronic end stage liver disease, and other digestive diseases. RESULTS Among women, 7.6% of all deaths and 3.9% of all DALYs were due to digestive and liver diseases in 2010. The respective figures in men were 7.8% of deaths and 4.6% of DALYs. The most important cause of death among children under 5 is diarrhea. Among adults between 15 to 49 years old, the main causes of death are GI and liver cancers and cirrhosis, while diarrhea still remains a major cause of DALY. Among adults 50 years and above, GI and liver cancers and cirrhosis are the main causes of both deaths and DALYs. Gastritis and duodenitis, diarrheal diseases, gall bladder and bile duct diseases, acute hepatitis A, peptic ulcer disease, appendicitis, and acute hepatitis A mainly cause disability rather than death. CONCLUSION GBD study provides invaluable source of data on burden of GILD in Iran. However, there exist limitations, namely overestimation of burden of liver cancer and underestimation of the burden of GI diseases that are usually diagnosed in outpatient settings. The collaboration of scientists across the world and specifically those from developing countries is necessary for improving the accuracy of future updates of GBD in these countries.

Heart failure has multiple causes and leads to significant health and economic burdens. Understanding heart failure prevalence by cause helps to design appropriate prevention strategies. Data from a systematic review of published literature and hospital discharge data were analyzed to estimate the

BACKGROUND The general pattern of epidemiologic transition from communicable to noncommunicable diseases is also observed for gastrointestinal and liver diseases (GILD), which constitute a heterogeneous array of causes of death and disability. We aimed to describe the trend of GILD in Iran based on the global burden of disease (GBD2010) study from 1990 to 2010. METHODS The trend of number of deaths, disability, adjusted life years (DALYs) and their age-standardized rates caused by 5 major GILD have been reported. The change in the rankings of major causes of death and DALY has been described as well. RESULTS The age standardized rates of death and DALYs in both sexes have decreased from 1990 to 2010 for most GILD. The most prominent decreases in death rates are observed for diarrheal diseases, gastritis and duodenitis, and peptic ulcer disease. Positive trends are observed for liver cancer, pancreatic cancer, and gall bladder cancer. Diarrheal diseases have retained their 1st rank among children under 5. Among adults, decreased ranks are observed for diarrheal diseases, appendicitis, gastritis and duodenitis, gall bladder diseases, pancreatitis, and all types of cirrhosis. The trends in age standardized rates of DALYs, deaths, and YLLs are negative for almost all GILD, and especially for diarrheal diseases. However, there is no upward or downward trend in rates of years lost due to disability (YLDs) for most diseases. Total numbers of DALYs and deaths due to acute hepatitis C, stomach cancer, and liver cancers are rising. The total DALYs due to overall digestive diseases except cirrhosis and DALYs due to cirrhosis are both somehow stable. No data has been reported for GILD that are mainly diagnosed in outpatient settings, including gastroesophageal reflux disease, irritable bowel syndrome, and non-alcoholic fatty liver disease. CONCLUSION The results of GBD 2010 demonstrate that the rates of most GILD are decreasing in Iran but total DALYs are somehow stable. However, as diseases detected in outpatient settings have not been captured, the burden of GILD seems to be underestimated. Population-based studies at national level are required for accurate reports.

Cardiovascular diseases (CVDs) are leading causes of death worldwide. However, comparable estimates of global and regional mortality and recent trends are not readily available. We assessed deaths from CVDs, including congenital heart disease (CoHD), by age and sex at the global level in 21 world

The threshold of thyroid-stimulating hormone (TSH) in current screening for congenital hypothyroidism (CH) from the heel prick test is 5 mU/l. This study uses cost-effective analysis to evaluate increasing the threshold to minimize false-positive results and recall rates.Cost of screening, diagnosis and treatment, education, and care of mentally retarded patients were gathered from the Ministry of Health State Welfare Organization and Department of Education in Tehran. Screening data were obtained from 34,007 neonates in the Central Health Laboratory of Tehran University of Medical Sciences in 2009. Sensitivity analysis and calculation of confidence interval for incremental costs and effects (gained disability adjusted life years - DALYs) and incremental cost-effectiveness ratios (ICER) were performed by Monte Carlo simulation with Ersatz software.ICER for screening programs with different TSH cut-off points versus no screening was similar, and approximately -4.5 ± 0.2 thousand US dollars per gained DALY. In the proposed cohort (10,000 neonates), gained DALYs were 316 ± 50 for a cut off point of 5 mU/l, 251 ± 40 for 10 mU/l, 146 ± 23 for 15 mU/l, and 113 ± 18 for a cut-off point of 20 mU/l. Sensitivity analysis showed that the model remained the same when the input parameters were changed.This study demonstrates that the current threshold of TSH in the national CH screening program in terms of cost-effectiveness is the most appropriate threshold. However, more studies are needed to examine new strategies and methods to reduce recall rates and related consequences such as repeated thyroid testing in neonates.

Introduction: To determine the prevalence of dyslipidaemia and the optimal cut-off points of body mass index (BMI) and waist circumference (WC) at which abnormal lipid levels can be identified with maximum sensitivity and specificity in a nationwide population-based sample for the first time in the Middle East. Material and methods: Using a probability proportional to size, multistage cluster sampling method, a sociodemographically representative sample of 3024 of the Iranian population aged 25-64 years living in urban and rural areas of all 30 provinces of the country was studied. Results: The mean age of participants was 41.3 (0.07) years. The receiver operating curve (ROC) analysis showed that the optimal cut-off value of BMI to identify with maximum sensitivity and specificity the detection of lipid disorders was 25 kg/m2 for males and 26-28 kg/m2 for females. Considering WC, among males this optimal cut-off value was 88-89 cm for high total cholesterol (T. Chol), low HDL-C and high triglycerides (TG), whereas it was lower (86 cm) for predicting high LDL-C. Among females, this cut-off value was 83-84 cm for predicting high T. Chol, high LDL-C and high TG, but it was higher (90 cm) for low HDL-C. The most prevalent type of abnormal lipid level was low HDL-C. Conclusions: The optimal cut-off points provided in the current study might serve as a public health action threshold in the Middle East population. The very high prevalence of high TG and low HDL-C suggest that current guidelines for screening lipid disorders that are based on total and LDL cholesterol should consider such ethnic differences.

Abstract. High concentration of fine particles (PM2.5), the primary concern about air quality in China, is believed to closely relate to China’s large consumption of coal. In order to quantitatively identify the contributions of coal combustion in different sectors to ambient PM2.5, we developed an emission inventory for the year 2013 using up-to-date information on energy consumption and emission controls, and conducted standard and sensitivity simulations using the chemical transport model GEOS-Chem. According to the simulation, coal combustion contributes 22 μg m−3 (40 %) to the total PM2.5 concentration at national level (averaged in 74 major cities), and up to 37 μg m−3 (50 %) in Sichuan Basin. Among major coal-burning sectors, industrial coal burning is the dominant contributor with a national average contribution of 10 μg m−3 (17 %), followed by coal combustion in power plants and domestic sector. The national average contribution due to coal combustion is estimated to be 18 μg m−3 (46 %) in summer and 28 μg m−3 (35 %) in winter. While the contribution of domestic coal burning shows an obvious reduction from winter to summer, contributions of coal combustion in power plants and industrial sector remain at relatively constant levels through out the year.

The harmful effects of urban air pollution on general population in terms of annoying symptoms are not adequately evaluated. This is in contrast to the hospital admissions and short term mortality. The present study protocol is designed to assess the association between the level of exposure to certain ambient air pollutants and a wide range of relevant symptoms. Awareness of the impact of pollution on the population at large will make our estimates of the pertinent covert burden imposed on the society more accurate.A cross sectional study with spatial analysis for the addresses of the participants was conducted. Data were collected via telephone interviews administered to a representative sample of civilians over age four in the city. Households were selected using random digit dialling procedures and randomization within each household was also performed to select the person to be interviewed. Levels of exposure are quantified by extrapolating the addresses of the study population over the air pollution matrix of the city at the time of the interview and also for different lag times. This information system uses the data from multiple air pollution monitoring stations in conjunction with meteorological data. General linear models are applied for statistical analysis.The important limitations of cross-sectional studies on acute effects of air pollution are personal confounders and measurement error for exposure. A wide range of confounders in this study are controlled for in the statistical analysis. Exposure error may be minimised by employing a validated geographical information system that provides accurate estimates and getting detailed information on locations of individual participants during the day. The widespread operation of open air conditioning systems in the target urban area which brings about excellent mixing of the outdoor and indoor air increases the validity of outdoor pollutants levels that are taken as exposure levels.

Primary cardiomyopathies affect individuals of all ages and ethnic groups in all regions of the world and are associated with significant morbidity and mortality. Though these conditions are globally prevalent, lack of rigorous epidemiological analysis on a worldwide scale has prevented accurate estimates of the burden of this subset of cardiac diseases on regional populations. The Global Burden of Diseases, Injuries and Risk Factors (GBD 2010) Study was designed to address such analytical shortfalls by delivering data-driven estimates of epidemiological parameters for nearly 200 diseases and injuries, including the primary cardiomyopathies. The methodology utilized to generate GBD 2010 disease burden estimates for the primary cardiomyopathies is described. Preliminary epidemiologic data for the study's 21 global regions is then presented and discussed, along with evaluation of challenges and future opportunities in addressing the burden of primary cardiomyopathies.

Mechanical complications following a myocardial infarction are uncommon, but with dramatic consequences and high mortality. The left ventricle is the most often affected cardiac chamber and complications can be classified according to the timing in early (from days to first weeks) or late complications (from weeks to years). Despite the decrease in the incidence of these complications thank to primary percutaneous coronary intervention programs —wherever this option is available—, the mortality is still significant and these infrequent complications are an emergent scenario and one of the most important causes of mortality at short term in patients with myocardial infarction. Mechanical circulatory support devices, especially if minimally invasive implantation is used avoiding thoracotomy, have improved the prognosis of these patients by providing stability until definitive treatment can be applied. On the other hand, the growing experience in transcatheter interventions for the treatment of ventricular septal rupture or acute mitral regurgitation has been associated to an improvement in their results, even though prospective clinical evidence is still missing.Las complicaciones mecánicas posteriores a un infarto agudo de miocardio no son comunes, pero tienen consecuencias dramáticas y potencialmente letales. El ventrículo izquierdo se ve afectado con mayor frecuencia y las complicaciones se clasifican, según su inicio después del evento primario, en tempranas (de días a semanas después) y tardías (de semanas hasta años). A pesar de que la incidencia de estas complicaciones se ha reducido en la era de la angioplastia primaria —allá donde está disponible—, la mortalidad sigue siendo significativa y, aunque estas complicaciones se consideran poco frecuentes, suponen una emergencia y son una importante causa de mortalidad a corto plazo. Los dispositivos de asistencia circulatoria mecánica, en especial implantados de forma mínimamente invasiva y sin necesidad de toracotomía, han mejorado el pronóstico de estos pacientes al facilitar su estabilidad hasta que se pueda aplicar el tratamiento definitivo. Por otro lado, la creciente experiencia en intervenciones percutáneas para el tratamiento de la rotura del septo interauricular y la insuficiencia mitral aguda se ha asociado con una aparente mejora en sus resultados que aún precisa de la obtención de evidencia prospectiva.

Background: Fluoxetine is frequently used to treat depression. There has not been any report for the effect of fluoxetine on hormonal axis of pituitary-gonad in rats. Several studies have also shown that antidepressants have interaction with sex hormones in both sexes and women are more likely to take antidepressants than men. This study aimed to examine the effect of fluoxetine on sexual hormones in female rats. Materials and Methods: In this experimental study, 40 female rats (180-200 g and 100-120 days of age) were divided into the five groups including control, sham and three experimental (fluoxetine 5, 10 and 20 mg/kg) groups. Fluoxetine was intraperitoneally injected during four weeks. Control group did not receive any drug, but the sham group was injected with distilled water (0.18-0.2 ml/kg body weight). Levels of FSH, LH, estrogen and progesterone were measured using a blood test. Results: Results of this study showed that fluoxetine (10 or 20mg/kg) considerably reduced the estrogen and FSH levels and also fluoxetine (20mg/kg) reduced the progesterone level. However, different doses of fluoxetine did not change the LH level. Conclusion: Fluoxetine can decrease the estrogen, progesterone, FSH levels and cause oogenic defects in rats.

Background Early detection of cancer is crucial for reducing the global burden of cancer and saving lives, but effective screening tests for many cancers do not exist. Genomics-based liquid biopsy tests for screening multiple cancers at once have been developed, but they have low sensitivity for early-stage cancers and are expensive. Recent advancements in measuring protein abundances in plasma offer new opportunities for developing multi-cancer screening tests. Methods We collected plasma samples from 440 individuals, healthy and diagnosed with 18 various types of early-stage solid tumours. Using Proximity Extension Assay, we measured more than 3000 high and low-abundance proteins in each sample. Then, using a multi-step statistical approach, we identified a limited set of proteins that could detect early-stage cancers and their tissue of origin with high diagnostic accuracy. Findings Our sex-specific cancer detection consisting of 10 proteins showed high accuracy for both males (AUC: 0.98) and females ((AUC: 0.983). At stage I and at the specificity of 99%, our detection panels were able to identify 89% of cancers among males and 75% of cancers among females. Our sex-specific localization panels consisted of 150 proteins and were able to identify the tissue of origin of most cancers in more than 80% of cases. The analysis of the plasma concentrations of proteins selected showed that almost all the proteins were in the low-concentration part of the human plasma proteome. Interpretation The proteome-based screening test showed promising performance compared with other technologies and could be a starting point for developing a new generation of screening tests for the early detection of cancer and potentially other chronic diseases. This new approach may provide a more accessible and cost-effective alternative to existing methods for cancer detection and may help reduce cancer mortality rates globally.

Abstract This study explores the application of deep proteomic profiling to extract disease-specific features from urine. Early detection of cancer and other chronic disorders is crucial for better outcomes, but traditional diagnostics as well as emerging genomic-based diagnostics are expensive and invasive. Our research reveals that a select group of urinary proteins can accurately detect early-stage diseases with high sensitivity, surpassing current tests. While urine-based protein panels could offer cost-effective and accurate alternatives to current screening methods, kidney factors and blood urine barrier pathologies could pose significant challenges. New diagnostic technologies may emerge because of these findings, ushering in an era of early detection for cancer and chronic diseases. One-Sentence Summary Urine-based protein panels show distinct patterns in early disease detection, promising opportunities for advancing diagnostic tests

I1 Introduction and aims of the workshop Christa Scheidt-Nave, Thomas Ziese, Judith Fuchs, Dietrich Plass S1 History, concept, and current results of GBD for Germany Tom Achoki, Katherine Leach-Kemon, Peter Speyer, William E. Heisel, Emmanuela Gakidou, Theo Vos S2 Methodology of the GBD 2013 Study–Mortality, Morbidity, Risk-Factors Mohammad Hossein Forouzanfar S3 National burden of disease surveillance examples of good practice: the case of Public Health England Jürgen C. Schmidt S4 Critical aspects of the burden of disease methodology and country-specific challenges Claudia E. Stein S5 Non-communicable disease surveillance in Germany – public health and data challenges Christa Scheidt-Nave, Elena von der Lippe, Benjamin Barnes, Markus Busch, Nina Buttmann-Schweiger, Judith Fuchs, Christin Heidemann, Klaus Kraywinkel, Enno Nowossadeck, Thomas Ziese S6 Different approaches in estimating the burden of communicable diseases using the examples of the healthcare associated infections and influenza Udo Buchholz, Matthias an der Heiden, Tim Eckmanns, Sebastian Haller S7 Behavioral and environmental attributable risk estimation Mohammad Hossein Forouzanfar S8 Environmental Burden of Disease (EBD) in Germany – past achievements and future perspectives Dietrich Plass, Myriam Tobollik, Dagmar Kallweit, Dirk Wintermeyer C1 Conclusions of the workshop Christa Scheidt-Nave, Thomas Ziese, Judith Fuchs, Dietrich Plass

Introduction: Reducing the health impacts of air pollution in highly polluted countries such as China requires understanding the relative impacts of specific source sectors. . Targeted air quality management can lead to substantial health benefits and reductions in climate-forcing emissions. Methods: We combined chemical transport model simulations with estimates of exposure to air pollution and the burden of disease to estimate deaths in China from major air pollution sources in 2013 and under four future scenarios for 2030. Scenarios included future energy mixes and pollution control measures. National and province-level estimates were developed. Results: In China ambient PM2.5 contributed to 916,102 premature deaths in 2013. Coal combustion was the most important contributor to ambient particle (PM2.5) pollution in China in 2013, responsible for 40% of population exposure. 366,000 deaths were attributed to coal combustion in 2013 in China. Industrial (coal and non-coal) emissions contributed 255,000 attributable deaths in 2013 with domestic combustion (biomass and coal) leading to 177,000 attributable deaths, more than the contribution from transportation (137,000), or coal combustion in power plants (86,500). Compared to 2013, deaths attributable to ambient PM2.5 in 2030 were increased by 8 – 38% under scenarios of pollution reduction where population-weighted exposure was decreased by 8 – 50%. These projected mortality increases were due to population aging and increases in ischemic heart disease, stroke, COPD and lung cancer in the Chinese population. Even under the most stringent energy use and pollution control scenario, coal remained the single largest contributor to ambient PM2.5 and attributable burden in 2030. Conclusions: These projections underscore the importance of population dynamics in determining future mortality due to ambient PM2.5. PM levels must be substantially lowered to stabilize or reduce burden given demographic trends.

BACKGROUND The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. METHODS We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors-the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). FINDINGS Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6-58·8) of global deaths and 41·2% (39·8-42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. INTERPRETATION Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. FUNDING Bill & Melinda Gates Foundation.

Background: Pump therapy (CSII) is offered as a safe and effective treatment for patients with type 1 Diabetes. We examined the efficacy and safety of continuous subcutaneous Insulin Infusion Therapy for six months as a before-after clinical trial study among type 1 diabetic patients. This is the first survey of this experience in Iranian patients. Methods: We recruited, type 1 diabetic patients without chronic complications of diabetes (retinopathy, nephropathy and etc.) and followed them for six months as a before-after clinical study with use of the pump. The efficacy of this way was assessed with HbA 1 C and fasting blood sugar measurements. Safety was estimated by frequency of clinical hypoglycemia episodes. Results: Our patients were 7 men and 2 women aged 15 - 39 years with past history of diabetes by ranging from 0.1 to 15 years. Mean level of HbA 1 C at the beginning of study and after six months follow-up were %8.6 and %7.1, respectively, with significant statistically difference between them (P= 0.02). During pump therapy the mean dose of insulin were decreased to 10 units with statistically significant difference to before investigation (P = 0.03). No case of hypoglycemia and weight loss was seen. One patient had 4 kg weight gain without any significant statistical effect. Conclusion: It seems CSII Therapy in Iranian patients with type 1 Diabetes mellitus was effective and safe. We can not conclude about possible side effects of pump based on this study.