Christopher J L Murray

Worldwide Epidemiology of Atrial Fibrillation A Global Burden of Disease 2010 Study

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.

Global burden of disease attributable to mental and substance use disorders: findings from the Global Burden of Disease Study 2010

BACKGROUND We used data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010) to estimate the burden of disease attributable to mental and substance use disorders in terms of disability-adjusted life years (DALYs), years of life lost to premature mortality (YLLs), and years lived with disability (YLDs). METHODS For each of the 20 mental and substance use disorders included in GBD 2010, we systematically reviewed epidemiological data and used a Bayesian meta-regression tool, DisMod-MR, to model prevalence by age, sex, country, region, and year. We obtained disability weights from representative community surveys and an internet-based survey to calculate YLDs. We calculated premature mortality as YLLs from cause of death estimates for 1980-2010 for 20 age groups, both sexes, and 187 countries. We derived DALYs from the sum of YLDs and YLLs. We adjusted burden estimates for comorbidity and present them with 95% uncertainty intervals. FINDINGS In 2010, mental and substance use disorders accounted for 183·9 million DALYs (95% UI 153·5 million-216·7 million), or 7·4% (6·2-8·6) of all DALYs worldwide. Such disorders accounted for 8·6 million YLLs (6·5 million-12·1 million; 0·5% [0·4-0·7] of all YLLs) and 175·3 million YLDs (144·5 million-207·8 million; 22·9% [18·6-27·2] of all YLDs). Mental and substance use disorders were the leading cause of YLDs worldwide. Depressive disorders accounted for 40·5% (31·7-49·2) of DALYs caused by mental and substance use disorders, with anxiety disorders accounting for 14·6% (11·2-18·4), illicit drug use disorders for 10·9% (8·9-13·2), alcohol use disorders for 9·6% (7·7-11·8), schizophrenia for 7·4% (5·0-9·8), bipolar disorder for 7·0% (4·4-10·3), pervasive developmental disorders for 4·2% (3·2-5·3), childhood behavioural disorders for 3·4% (2·2-4·7), and eating disorders for 1·2% (0·9-1·5). DALYs varied by age and sex, with the highest proportion of total DALYs occurring in people aged 10-29 years. The burden of mental and substance use disorders increased by 37·6% between 1990 and 2010, which for most disorders was driven by population growth and ageing. INTERPRETATION Despite the apparently small contribution of YLLs--with deaths in people with mental disorders coded to the physical cause of death and suicide coded to the category of injuries under self-harm--our findings show the striking and growing challenge that these disorders pose for health systems in developed and developing regions. In view of the magnitude of their contribution, improvement in population health is only possible if countries make the prevention and treatment of mental and substance use disorders a public health priority. FUNDING Queensland Department of Health, National Health and Medical Research Council of Australia, National Drug and Alcohol Research Centre-University of New South Wales, Bill & Melinda Gates Foundation, University of Toronto, Technische Universität, Ontario Ministry of Health and Long Term Care, and the US National Institute of Alcohol Abuse and Alcoholism.

Global Burden of Disease and Risk Factors

This volume is a single up-to-date source on the entire global epidemiology of diseases, injuries and risk factors with a comprehensive statement of methods and a complete presentation of results. It includes refined methods to assess data, ensure epidemiological consistency, and summarize the disease burden. Global Burden of Disease and Risk Factors examines the comparative importance of diseases, injuries, and risk factors; it incorporates a range of new data sources to develop consistent estimates of incidence, prevalence, severity and duration, and mortality for 136 major diseases and injuries. Drawing from more than 8,500 data sources that include epidemiological studies, disease registers, and notifications systems, this book incorporates information from more than 10,000 datasets relating to population health and mortality, representing one of the largest syntheses of global information on population health to date.Epidemiological studies report confidence or uncertainty intervals around their estimates. Estimates of the burden of diseases and risk factors are subject to a broader range of uncertainty because of the combination of multiple data sources and value choices. Sensitivity analysis can be used to examine the effects of social values that have been incorporated into the design of the disability–adjusted life year (DALY). Age weight, where a year of healthy life lived at one age is valued differently from at another age, is the most controversial value built into the DALY. The discount rate, which addresses the difference in value of current versus future health benefits, also has been criticized. The distribution of the global disease burden and rankings of various conditions are largely insensitive to alternate assumptions about the discount rate and age weighting. The major effects of discounting and age weighting are to enhance the importance of neuropsychiatric conditions and sexually transmitted infections. The Global Burden of Disease study also has been criticized for estimating mortality and disease burden for regions using incomplete and uncertain data. Including uncertain results, with uncertainty quantified to the extent possible, is preferable, however, to leaving blank cells in tables intended to provide policy makers with an overall assessment of burden of disease. No estimate is generally interpreted as no problem. Greater investment in getting the descriptive epidemiology of diseases and injuries correct in poor countries will do vastly more to reduce uncertainty in disease burden assessments than a philosophical debate about the appropriateness of social valueDetailed descriptions of the level and distribution of diseases and injuries and their causes are important inputs into strategies for improving population health. A substantial body of work has focused on quantifying causes of mortality and, more recently, the burden of disease (Murray and Lopez 1997; Preston, 1976; see also chapter 3 in this volume). Data on disease or injury outcomes alone, such as death or hospitalization, tend to focus on the need for curative or palliative services. Reliable and comparable analyses of risks to health are critical for preventing disease and injury. Investigators have frequently analyzed morbidity and mortality due to risk factors in the context of methodological traditions of individual risk factors and for selected populations (Kunzli and others 2000; Leigh and others 1999; McGinnis and Foege 1993; Peto and others 1992; Single and others 1999; Smith 2000; Smith, Corvalan, and Kjellstrom 1999; Willet 2002). As a result, most estimates have been affected by the following shortcomings, which limit comparability:

Maternal mortality for 181 countries, 1980–2008: a systematic analysis of progress towards Millennium Development Goal 5

BACKGROUND Maternal mortality remains a major challenge to health systems worldwide. Reliable information about the rates and trends in maternal mortality is essential for resource mobilisation, and for planning and assessment of progress towards Millennium Development Goal 5 (MDG 5), the target for which is a 75% reduction in the maternal mortality ratio (MMR) from 1990 to 2015. We assessed levels and trends in maternal mortality for 181 countries. METHODS We constructed a database of 2651 observations of maternal mortality for 181 countries for 1980-2008, from vital registration data, censuses, surveys, and verbal autopsy studies. We used robust analytical methods to generate estimates of maternal deaths and the MMR for each year between 1980 and 2008. We explored the sensitivity of our data to model specification and show the out-of-sample predictive validity of our methods. FINDINGS We estimated that there were 342,900 (uncertainty interval 302,100-394,300) maternal deaths worldwide in 2008, down from 526,300 (446,400-629,600) in 1980. The global MMR decreased from 422 (358-505) in 1980 to 320 (272-388) in 1990, and was 251 (221-289) per 100,000 livebirths in 2008. The yearly rate of decline of the global MMR since 1990 was 1.3% (1.0-1.5). During 1990-2008, rates of yearly decline in the MMR varied between countries, from 8.8% (8.7-14.1) in the Maldives to an increase of 5.5% (5.2-5.6) in Zimbabwe. More than 50% of all maternal deaths were in only six countries in 2008 (India, Nigeria, Pakistan, Afghanistan, Ethiopia, and the Democratic Republic of the Congo). In the absence of HIV, there would have been 281 500 (243,900-327,900) maternal deaths worldwide in 2008. INTERPRETATION Substantial, albeit varied, progress has been made towards MDG 5. Although only 23 countries are on track to achieve a 75% decrease in MMR by 2015, countries such as Egypt, China, Ecuador, and Bolivia have been achieving accelerated progress. FUNDING Bill & Melinda Gates Foundation.

Global and regional burden of stroke during 1990–2010: findings from the Global Burden of Disease Study 2010

BACKGROUND 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. METHODS 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. FINDINGS 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. INTERPRETATION 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. FUNDING Bill & Melinda Gates Foundation.

The global burden of disease, 1990-2020

The authors discuss the Global Burden of Disease Study and its role in setting priorities for improving international public health into the next century*.

The preventable causes of death in the United States: comparative risk assessment of dietary, lifestyle, and metabolic risk factors.

Majid Ezzati and colleagues examine US data on risk factor exposures and disease-specific mortality and find that smoking and hypertension, which both have effective interventions, are responsible for the largest number of deaths.

Tuberculosis: Commentary on a Reemergent Killer

Tuberculosis remains the leading cause of death in the world from a single infectious disease, although there is little knowledge of the mechanisms of its pathogenesis and protection from it. After a century of decline in the United States, tuberculosis is increasing, and strains resistant to multiple antibiotics have emerged. This excess of cases is attributable to changes in the social structure in cities, the human immunodeficiency virus epidemic, and a failure in certain major cities to improve public treatment programs. The economic costs of not adequately addressing the problem of tuberculosis in this country are estimated from an epidemiological model.

Rapid health transition in China, 1990-2010: findings from the Global Burden of Disease Study 2010.

Summary Background China has undergone rapid demographic and epidemiological changes in the past few decades, including striking declines in fertility and child mortality and increases in life expectancy at birth. Popular discontent with the health system has led to major reforms. To help inform these reforms, we did a comprehensive assessment of disease burden in China, how it changed between 1990 and 2010, and how Chinas health burden compares with other nations. Methods We used results of the Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010) for 1990 and 2010 for China and 18 other countries in the G20 to assess rates and trends in mortality, causes of death, years of life lost (YLLs), years lived with disability (YLDs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE). We present results for 231 diseases and injuries and for 67 risk factors or clusters of risk factors relevant to China. We assessed relative performance of China against G20 countries (significantly better, worse, or indistinguishable from the G20 mean) with age-standardised rates and 95% uncertainty intervals. Findings The leading causes of death in China in 2010 were stroke (1·7 million deaths, 95% UI 1·5–1·8 million), ischaemic heart disease (948 700 deaths, 774 500–1 024 600), and chronic obstructive pulmonary disease (934 000 deaths, 846 600–1 032 300). Age-standardised YLLs in China were lower in 2010 than all emerging economies in the G20, and only slightly higher than noted in the USA. China had the lowest age-standardised YLD rate in the G20 in 2010. China also ranked tenth (95% UI eighth to tenth) for HALE and 12th (11th to 13th) for life expectancy. YLLs from neonatal causes, infectious diseases, and injuries in children declined substantially between 1990 and 2010. Mental and behavioural disorders, substance use disorders, and musculoskeletal disorders were responsible for almost half of all YLDs. The fraction of DALYs from YLDs rose from 28·1% (95% UI 24·2–32·5) in 1990 to 39·4% (34·9–43·8) in 2010. Leading causes of DALYs in 2010 were cardiovascular diseases (stroke and ischaemic heart disease), cancers (lung and liver cancer), low back pain, and depression. Dietary risk factors, high blood pressure, and tobacco exposure are the risk factors that constituted the largest number of attributable DALYs in China. Ambient air pollution ranked fourth (third to fifth; the second highest in the G20) and household air pollution ranked fifth (fourth to sixth; the third highest in the G20) in terms of the age-standardised DALY rate in 2010. Interpretation The rapid rise of non-communicable diseases driven by urbanisation, rising incomes, and ageing poses major challenges for Chinas health system, as does a shift to chronic disability. Reduction of population exposures from poor diet, high blood pressure, tobacco use, cholesterol, and fasting blood glucose are public policy priorities for China, as are the control of ambient and household air pollution. These changes will require an integrated government response to improve primary care and undertake required multisectoral action to tackle key risks. Analyses of disease burden provide a useful framework to guide policy responses to the changing disease spectrum in China. Funding Bill & Melinda Gates Foundation.

Progress towards Millennium Development Goals 4 and 5 on maternal and child mortality: an updated systematic analysis

BACKGROUND With 4 years until 2015, it is essential to monitor progress towards Millennium Development Goals (MDGs) 4 and 5. Although estimates of maternal and child mortality were published in 2010, an update of estimates is timely in view of additional data sources that have become available and new methods developed. Our aim was to update previous estimates of maternal and child mortality using better data and more robust methods to provide the best available evidence for tracking progress on MDGs 4 and 5. METHODS We update the analyses of the progress towards MDGs 4 and 5 from 2010 with additional surveys, censuses, vital registration, and verbal autopsy data. For children, we estimate early neonatal (0-6 days), late neonatal (7-28 days), postneonatal (29-364 days), childhood (ages 1-4 years), and under-5 mortality. We use an improved model for estimating mortality by age under 5 years. For maternal mortality, our updated analysis includes greater than 1000 additional site-years of data. We tested a large set of alternative models for maternal mortality; we used an ensemble model based on the models with the best out-of-sample predictive validity to generate new estimates from 1990 to 2011. FINDINGS Under-5 deaths have continued to decline, reaching 7·2 million in 2011 of which 2·2 million were early neonatal, 0·7 million late neonatal, 2·1 million postneonatal, and 2·2 million during childhood (ages 1-4 years). Comparing rates of decline from 1990 to 2000 with 2000 to 2011 shows that 106 countries have accelerated declines in the child mortality rate in the past decade. Maternal mortality has also continued to decline from 409,100 (uncertainty interval 382,900-437,900) in 1990 to 273,500 (256,300-291,700) deaths in 2011. We estimate that 56,100 maternal deaths in 2011 were HIV-related deaths during pregnancy. Based on recent trends in developing countries, 31 countries will achieve MDG 4, 13 countries MDG 5, and nine countries will achieve both. INTERPRETATION Even though progress on reducing maternal and child mortality in most countries is accelerating, most developing countries will take many years past 2015 to achieve the targets of the MDGs 4 and 5. Similarly, although there continues to be progress on maternal mortality the pace is slow, without any overall evidence of acceleration. Immediate concerted action is needed for a large number of countries to achieve MDG 4 and MDG 5. FUNDING Bill & Melinda Gates Foundation.