Summary Background Up-to-date evidence on levels and trends for age-sex-specific all-cause and cause-specific mortality is essential for the formation of global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013) we estimated yearly deaths for 188 countries between 1990, and 2013. We used the results to assess whether there is epidemiological convergence across countries. Methods We estimated age-sex-specific all-cause mortality using the GBD 2010 methods with some refinements to improve accuracy applied to an updated database of vital registration, survey, and census data. We generally estimated cause of death as in the GBD 2010. Key improvements included the addition of more recent vital registration data for 72 countries, an updated verbal autopsy literature review, two new and detailed data systems for China, and more detail for Mexico, UK, Turkey, and Russia. We improved statistical models for garbage code redistribution. We used six different modelling strategies across the 240 causes; cause of death ensemble modelling (CODEm) was the dominant strategy for causes with sufficient information. Trends for Alzheimer's disease and other dementias were informed by meta-regression of prevalence studies. For pathogen-specific causes of diarrhoea and lower respiratory infections we used a counterfactual approach. We computed two measures of convergence (inequality) across countries: the average relative difference across all pairs of countries (Gini coefficient) and the average absolute difference across countries. To summarise broad findings, we used multiple decrement life-tables to decompose probabilities of death from birth to exact age 15 years, from exact age 15 years to exact age 50 years, and from exact age 50 years to exact age 75 years, and life expectancy at birth into major causes. For all quantities reported, we computed 95% uncertainty intervals (UIs). We constrained cause-specific fractions within each age-sex-country-year group to sum to all-cause mortality based on draws from the uncertainty distributions. Findings Global life expectancy for both sexes increased from 65·3 years (UI 65·0–65·6) in 1990, to 71·5 years (UI 71·0–71·9) in 2013, while the number of deaths increased from 47·5 million (UI 46·8–48·2) to 54·9 million (UI 53·6–56·3) over the same interval. Global progress masked variation by age and sex: for children, average absolute differences between countries decreased but relative differences increased. For women aged 25–39 years and older than 75 years and for men aged 20–49 years and 65 years and older, both absolute and relative differences increased. Decomposition of global and regional life expectancy showed the prominent role of reductions in age-standardised death rates for cardiovascular diseases and cancers in high-income regions, and reductions in child deaths from diarrhoea, lower respiratory infections, and neonatal causes in low-income regions. HIV/AIDS reduced life expectancy in southern sub-Saharan Africa. For most communicable causes of death both numbers of deaths and age-standardised death rates fell whereas for most non-communicable causes, demographic shifts have increased numbers of deaths but decreased age-standardised death rates. Global deaths from injury increased by 10·7%, from 4·3 million deaths in 1990 to 4·8 million in 2013; but age-standardised rates declined over the same period by 21%. For some causes of more than 100 000 deaths per year in 2013, age-standardised death rates increased between 1990 and 2013, including HIV/AIDS, pancreatic cancer, atrial fibrillation and flutter, drug use disorders, diabetes, chronic kidney disease, and sickle-cell anaemias. Diarrhoeal diseases, lower respiratory infections, neonatal causes, and malaria are still in the top five causes of death in children younger than 5 years. The most important pathogens are rotavirus for diarrhoea and pneumococcus for lower respiratory infections. Country-specific probabilities of death over three phases of life were substantially varied between and within regions. Interpretation For most countries, the general pattern of reductions in age-sex specific mortality has been associated with a progressive shift towards a larger share of the remaining deaths caused by non-communicable disease and injuries. Assessing epidemiological convergence across countries depends on whether an absolute or relative measure of inequality is used. Nevertheless, age-standardised death rates for seven substantial causes are increasing, suggesting the potential for reversals in some countries. Important gaps exist in the empirical data for cause of death estimates for some countries; for example, no national data for India are available for the past decade. Funding Bill & Melinda Gates Foundation.

Introduction 1 Institute for Health Metrics and Evaluation

GBD 2013 Protocol: global burden of diseases, injuries, and risk factors. The Global Burden of Disease (GBD) study provides a unique comprehensive framework to systematically assess national trends in age-specific and sex-specific all-cause and cause-specific mortality. Up-to-date and comprehensive evidence for levels and trends for each country is critical for informed priority setting. Trends quantify progress against explicit health targets, whether local, national, or global, and help to evaluate where programmes are working or not. Quantification across populations and over time using comparable definitions and methods can also enable benchmarking. Regular comprehensive updates about causes of death will identify emerging public health challenges. The GBD 2013 study provides the first GBD study to use a continuously updated approach to global health surveillance. 2 Wang H

Dwyer-Lindgren L

Lofgren KT

et al. Age-specific and sex-specific mortality in 187 countries, 1970–2010: a systematic analysis for the Global Burden of Disease Study 2010. , 3 Lozano R

Naghavi M

Foreman K

et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. , 4 Salomon JA

Wang H

Freeman MK

et al. Healthy life expectancy for 187 countries, 1990–2010: a systematic analysis for the Global Burden Disease Study 2010. , 5 Salomon JA

Vos T

Hogan DR

et al. Common values in assessing health outcomes from disease and injury: disability weights measurement study for the Global Burden of Disease Study 2010. , 6 Vos T

Flaxman AD

Naghavi M

et al. Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. , 7 Murray CJL

Vos T

Lozano R

et al. Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. , 8 Lim SS

Vos T

Flaxman AD

et al. A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. 9 Lozano R

Gómez-Dantés H

Garrido-Latorre F

et al. Burden of disease, injuries, risk factors and challenges for the health system in Mexico. , 10 Yang G

Wang Y

Zeng Y

et al. Rapid health transition in China, 1990–2010: findings from the Global Burden of Disease Study 2010. , 11 Murray C

Abraham J

Ali M The state of US health, 1990–2010: Burden of diseases, injuries, and risk factors. , 12 Murray CJ

Richards MA

Newton JN

et al. UK health performance: findings of the Global Burden of Disease Study 2010. , 13 Forouzanfar MH

Sepanlou SG

Shahraz S

et al. Evaluating causes of death and morbidity in Iran, global burden of diseases, injuries, and risk factors study 2010. , 14 Naghavi M

Shahraz S

Sepanlou SG

et al. Health transition in Iran toward chronic diseases based on results of Global Burden of Disease 2010. , 15 Shahraz S

Forouzanfar MH

Sepanlou SG

et al. Population health and burden of disease profile of Iran among 20 countries in the region: From Afghanistan to Qatar and Lebanon. , 16 USAID The GBD 2010 study, a collaboration of 488 investigators, showed important global and regional trends for all-cause and cause-specific mortality.The GBD 2010 reported substantial decreases in child mortality driven by reductions in diarrhoea, lower respiratory infections, and more recently, malaria. The lowest income regions had progressed in combating maternal mortality, HIV/AIDS, tuberculosis, and malaria. Nevertheless, much work remains to be done for these Millennium Development Goal-related diseases. Outside sub-Saharan Africa, 1990–2010 saw rapid shifts towards a larger share of death from non-communicable diseases and injuries and a rising mean age of death. Country analyses using the GBD 2010 database have been reported for China, Iran, Mexico, UK, and USA, taking advantage of the comparable methods and definitions of the GBD to benchmark these countries against their peers. 16 USAID 17 WHO

Roadmap for Childhood Tuberculosis. , 18 UNAIDS

2011–2015 Strategy: Getting to Zero. Joint United Nations Programme on HIV/AIDS. , 19 Treatment Action Group (TAG)

The Zero Declaration. July 22, 2012. New York, NY. , 20 Stop TB Partnership , 21 South Africa Info Reporter. South Africa's HIV/Aids battle plan. SouthAfrica.info, 2012. http://www.southafrica.info/about/health/aids-prevention.htm#.UxZ1nfldXg9 (accessed Nov 4, 2014). , 22 Ki-moon B , 23 Department for International Development

UKAID. Towards zero infections: the UK's position paper on HIV in the developing world. 24 Jamison DT

Summers LH

Alleyne G

et al. Global health 2035: a world converging within a generation. 25 WHO 24 Jamison DT

Summers LH

Alleyne G

et al. Global health 2035: a world converging within a generation. , 25 WHO , 26 The world we want

Health in the post-2015 agenda: report of the global thematic consultation on health. , 27 Atun R

Jaffar S

Nishtar S

et al. Improving responsiveness of health systems to non-communicable diseases. Much debate surrounds what should follow the Millennium Development Goals; objective, timely, and comprehensive evidence for the levels and trends in causes of death can be a useful input. Ambitious goals have been discussed,such as the elimination of preventable child and maternal mortality in a generation. Targets of zero disease have been formulated for HIV/AIDS, tuberculosis, and malaria by various groups.The Lancet Commission on Global health 2035: a world converging within a generationsuggested that a grand convergence in health can be achieved between poor and rich countries by 2035. Advocates for non-communicable disease programmes arguethat rapid epidemiological transitions in many regions of the world require broader health goals for the development community. Movements to focus on universal health coverage in the post-2015 health agenda emphasise the consequences of failure to meet basic health-care needs. Broad interest in the GBD 2010 has led to the expansion of the GBD collaboration to include more than 1000 investigators in 106 countries. The GBD 2013 not only incorporates newly published or released datasets, particularly from the past 5 years, but also expands the analysis in other ways. We included subnational assessments for provinces of China, states of Mexico, and regions of the UK. These subnational assessments will help national decision makers to identify inequalities and local variation in leading diseases, injuries, and risk factors. The list of causes has been expanded and many new and more detailed data sources incorporated. We report the new findings for the first time at the country-level for 1990–2013.

Discussion Main findings Panel Research in context Systematic review 83 International Agency for Research on Cancer

GLOBOCAN 2012: Estimated cancer incidence, mortality and prevalence worldwide in 2012. WHO: International Agency for Reserach on Cancer. 2 Wang H

Dwyer-Lindgren L

Lofgren KT

et al. Age-specific and sex-specific mortality in 187 countries, 1970–2010: a systematic analysis for the Global Burden of Disease Study 2010. , 3 Lozano R

Naghavi M

Foreman K

et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. , 4 Salomon JA

Wang H

Freeman MK

et al. Healthy life expectancy for 187 countries, 1990–2010: a systematic analysis for the Global Burden Disease Study 2010. , 5 Salomon JA

Vos T

Hogan DR

et al. Common values in assessing health outcomes from disease and injury: disability weights measurement study for the Global Burden of Disease Study 2010. , 6 Vos T

Flaxman AD

Naghavi M

et al. Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. , 7 Murray CJL

Vos T

Lozano R

et al. Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. , 8 Lim SS

Vos T

Flaxman AD

et al. A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. The GBD 2013 assessment of causes of death is a major improvement in the evidence base compared with GBD 2010 through the inclusion of new data from vital registration systems, verbal autopsy studies, maternal mortality surveillance, injury surveillance and other sources. Through the inclusion of sub-national data on China, Mexico, and UK the evidence base for causes of death has been greatly expanded. Redistribution algorithms for ill-defined causes of death used to enhance the comparability of data were based on new statistical models. GBD 2013 also benefits from several improvements in the methods used to estimate all-cause mortality and specific causes of death such as HIV/AIDS. GBD 2013 provides a more up-to-date and comprehensive assessment of causes of death than do other studies of cause of death in particular age groups ( CHERG ), for particular causes (GLOBOCAN),and previous GBD analyses (GBD 2010). Interpretation This study provides a comprehensive description of mortality levels and patterns worldwide, and provides the evidence to assess progress of global development goals, including control of non-communicable diseases, and priorities for further global health and development debates. Because the study provides a complete re-analysis of trends for each cause from 1990 to 2013, it supersedes the results of the GBD 2010 study. This is the first time that country-specific results for all 188 countries with populations of more than 50 000 people have been comprehensively published. Country-specific data provide the opportunity to examine the extent to which epidemiological convergence is occurring across countries. The GBD 2013 incorporates many new datasets for cause of death, particularly from China, and new data for 155 other countries. Compared with the GBD 2010, it provides the most comprehensive and up-to-date assessment of causes of death. The results for the GBD 2013 are based on re-estimation of all causes from 1990 to 2013, and thus supersede all previously published GBD time series ( panel ). Publication of country-level results provides many opportunities for comparing a country's performance with that of its peers. On the broadest level, our analysis of 240 causes of death for 188 countries confirms that global life expectancy at birth has continued to improve over the past 23 years and these improvements are driven largely by falls in diarrhoea, lower respiratory infections, and neonatal causes in low-income countries, and decreases in cardiovascular diseases and some cancers in middle-income and high-income countries. HIV/AIDS has had a large enough effect to negate progress made in other causes contributing to decreases in life expectancy, particularly in southern sub-Saharan Africa. This general progress masks enormous heterogeneity across countries and age groups. Even within regions, substantially different mortality, leading causes of death, and trends exist. Outside sub-Saharan Africa, premature mortality is dominated by relatively few causes including ischaemic heart disease, stroke, lower respiratory infections, road injury, diarrhoea, preterm birth complications, neonatal encephalopathy, congenital anomalies, tuberculosis, chronic obstructive pulmonary disease, cirrhosis, self-harm, and lung cancer. In addition to these common causes, great regional and country variation exists, such as the dominant role of interpersonal violence in most countries of central Latin America and Brazil. Our study points to extraordinary epidemiological progress: global age-standardised death rates fell significantly for 157 of 240 causes from 1990 to 2013. The largest decreases were for some of the major communicable diseases including diarrhoeal diseases, lower respiratory infections, tuberculosis, and measles. Age-standardised rates for many non-communicable causes are also falling. At the same time, numbers of deaths from 115 of these 240 causes, have increased, driven by both growth in population and shifts in the population age-structure towards older ages. For a further 58 causes, changes in the age-standardised death rate over the 23 year period were not statistically different from no change. For some of these causes, sparse data might have contributed to wide UIs and in other cases uncertainty might have arisen from inconsistent coding across countries. However, eight specific causes account for more than 100 000 deaths and their age-standardised death rates have increased significantly since 1990: HIV/AIDS, liver cancer caused by hepatitis C, pancreatic cancer, atrial fibrillation and flutter, drug use disorders, diabetes, chronic kidney disease, and sickle cell disorders. Of these causes, three (HIV/AIDS, diabetes, and chronic kidney disease) account for more than a half a million deaths each. HIV/AIDS, however, has been decreasing as a cause of death since 2005. These causes, which run counter to an extraordinary global trend towards lower age-standardised death rates, deserve special attention. The rise and subsequent fall of HIV/AIDS is well known as is the rise in diabetes. Increases for atrial fibrillation and flutter, pancreatic cancer, drug use disorders, and chronic kidney disease have received far less global attention. Drug use disorders and chronic kidney diseases cause many more deaths in some regions and countries than in others. Nevertheless, they are important emerging global challenges that show the potential adverse effects of some behaviours and socioeconomic developments. In view of the important behavioural component for some of these causes, there is potentially an important role for public health policy and resources to modify these causes of death. These diseases, particularly HIV/AIDS and drug use disorders are also subject to social stigmatisation, which adds an important challenge for effective policy interventions. Although global age-standardised death rates have increased for very few causes, there is remarkable and important variation in trends across countries such that causes with falling global age-standardised rates are increasing in some countries—for example, ischaemic heart disease in China. Convergence or divergence? 84 UNICEF , 85 USAID , 86 Bustreo F

Say L

Koblinsky M

Pullum TW

Temmerman M

Pablos-Méndez A Ending preventable maternal deaths: the time is now. 24 Jamison DT

Summers LH

Alleyne G

et al. Global health 2035: a world converging within a generation. 87 Quah DT Twin peaks: growth and convergence in models of distribution dynamics. , 88 Sala-i-Martin X The world distribution of income: falling poverty and…convergence, period. , 89 Ravallion M Why don't we see poverty convergence?. 90 Bloom DE

Canning D Mortality traps and the dynamics of health transitions. , 91 Clark R World health inequality: convergence, divergence, and development. , 92 Wilson C On the scale of global demographic convergence 1950–2000. 93 Vallin J

Meslé F Convergences and divergences in mortality. 94 Moser K

Shkolnikov V

Leon DA World mortality 1950–2000: divergence replaces convergence from the late 1980s. Ambitious goals have been set for maternal and child mortality,such as the end of preventable maternal and child death in a generation. The Lancet Commission Global health 2035: a world converging within a generation has argued that a grand convergence in health is possible between high-income, middle-income, and low-income countries.Trends in the past 23 years provide an important starting point for framing how great a challenge achieving these aspirations will be and the political will and financial resources required. Part of the answer depends on how the goals are framed—for example, what does convergence mean? In the development literature on economic convergence,convergence has been framed in terms of poverty rates or in terms of income inequality measured by the Gini coefficient or other measures of inequality. Work on convergence in life expectancy has tended to focus on measures of absolute differencerather than relative difference.We found unequivocal divergence in mortality rates for women aged 25–39 years and older than 80 years and for men aged 20–44 years and 65 years and older, similar to previous estimates of divergence of life expectancy at birth since the 1980s.In these age groups, both the Gini coefficient and the mean absolute difference in death rates are rising. In all other age groups, except girls aged 10–14 years, relative inequality is increasing but the absolute gap is narrowing. Framing a grand convergence as simply achieving a reduction in the differences in mortality rates across countries might not be sufficiently ambitious to meet the goals of many national policy makers. If mortality decreases in all countries by the same percent per year, absolute difference will decrease and relative differences will stay constant. For age groups in which global relative and absolute differences in death rates are diverging, extraordinary efforts will be needed to achieve laudable goals such as a grand convergence. If convergence includes reducing the ratio of the highest to lowest death rates, even for under-5 mortality, major new efforts will be needed to have faster percent decreases in countries with higher mortality. 24 Jamison DT

Summers LH

Alleyne G

et al. Global health 2035: a world converging within a generation. Arguments that convergence is technically and financially feasible are grounded on the rapid improvements of some countries.For example, from 1990 to 2013, 13 countries (all low-income), achieved increases in life expectancy greater than 10 years ( appendix pp 141–151 ). The real challenge is whether the strategies to decrease mortality used by these countries are generalisable or transferable to those countries who are making the least progress. The Lancet Commission on global health 2035 drew attention to the four Cs (Cuba, Costa Rica, Chile, and China). Life expectancy has improved faster than the global aggregate trend in China and Chile in the past 23 years. 95 Balabanova D

Mills A

Conteh L

et al. Good Health at Low Cost 25 years on: lessons for the future of health systems strengthening. 96 The good news is that some countries that were low-income in 1990 have achieved remarkable progress in the past 23 years—for example, in Nepal, life expectancy has increased by 12·16 years since 1990, reaching 70·64 years in 2013 for both sexes combined ( appendix pp 141–151 ). Other examples of improvements greater than 12 years for both sexes combined include Rwanda, Ethiopia, Niger, Maldives, Timor-Leste, and Iran. Because the Rwandan genocide occurred after 1990, the progress from the peak of mortality during the genocide until 2013 is even larger, 49·63 years. Studies have already assessed progress in Bangladesh, Ethiopia, and Niger, particularly in reducing child mortality.Further study of these countries might provide insights about how to achieve low mortality, including the role of development assistance for health, rapid economic growth, and addressing chronic challenges such as famines. Simple assessments built up from individual technology analyses, such as the Disease Control Priorities-2,assume a high-level of health system efficiency and contextual factors that enable technology to be delivered such as levels of maternal education. Plans to achieve a grand convergence in the face of diverging mortality will need to take into account low levels of health system efficiency and low levels of health system resourcing in some countries and the greater efforts needed to achieve high intervention coverage in low-income countries with inadequate primary health-care systems and low levels of educational attainment. The challenge of improving health system management, particularly locally, is a crucial component of the future plans. The analysis of average relative difference between countries and average absolute difference between countries by cause (data not shown) shows the general pattern that many communicable, maternal, and neonatal causes, along with war and natural disasters, are highly unequal across countries; almost all have average relative differences of more than 50%. Among the non-communicable disease categories, mental and substance use disorders is the only cause with a mean relative difference greater than 40%. Following the more stringent criteria for convergence—in which global rates and the Gini coefficient are both falling—only neoplasms and chronic respiratory diseases are converging. As more countries go through the epidemiological transition, it seems likely that cross-country inequalities or relative differences for communicable causes will rise and inequalities for non-communicable causes will narrow. Narrowing inequalities across countries will not necessarily narrow inequalities for non-communicable disease within countries. Because mortality exponentially rises with age, at least after age 50 years, relative differences at older ages, when mortality becomes concentrated, tend to be small. Causes such as diabetes, chronic kidney disease, and alcohol and drug use disorders—for which global death rates are rising and inequality is increasing—are exceptions to this general pattern. Non-communicable diseases Age-standardised death rates for cardiovascular and circulatory diseases have fallen in high-income and many middle-income countries since 1990. Rapid falls have occurred in some countries. For example, five countries (Israel, Denmark, Norway, South Korea, and UK), had at least a 65% decrease in age-standardised death rates for ischaemic heart disease. Many other countries have had decreases of 40–65%. Age-adjusted death rates caused by haemorrhagic stroke fell by three-quarters in South Korea. 97 Leon DA

Shkolnikov VM

McKee M

Kiryanov N

Andreev E Alcohol increases circulatory disease mortality in Russia: acute and chronic effects or misattribution of cause?. 97 Leon DA

Shkolnikov VM

McKee M

Kiryanov N

Andreev E Alcohol increases circulatory disease mortality in Russia: acute and chronic effects or misattribution of cause?. 98 AIWH: Field B The ageing and growth of populations has led to an increase in the total number of cardiovascular deaths, accounting for almost a third of all deaths globally in 2013. Ischaemic heart disease, ischaemic stroke, and haemorrhagic stroke continue to cause most cardiovascular and circulatory deaths in almost all countries. Some Balkan countries are an exception; cardiomyopathy was a leading cause of death, possibly as a result of alcohol exposure or local patterns of garbage codes.Additional studies are needed to establish whether this finding is driven by medical certification practices or is related to alcohol or some other factor.Age-standardised death rates for atrial fibrillation and flutter and peripheral vascular disease have increased, possibly because of increased awareness of these conditions or better survival from cardiovascular diseases that share the same risk factors. Much uncertainty remains for trends in mortality caused by rheumatic heart disease, partly because endemic populations are concentrated within poorer subnational regions where data collection is limited and rheumatic heart disease might not always be coded as the underlying cause of death.Efforts to benchmark changes in cardiovascular and circulatory diseases will benefit from increasing access to verbal autopsy in India and sub-Saharan Africa, household surveys focused on chronic diseases, and improvements in electronic health records. Generally, cancer deaths are increasing but age-standardised cancer death rates are falling. Some cancer-related risk factors, such as tobacco consumption, have decreased, but others, such as obesity, have increased. The substantial general fall in cancers require further explanation. Death rates for five cancers increased (non-Hodgkin lymphoma, mesothelioma, kidney cancer, pancreatic cancer, and multiple myeloma); some explanations, such as the potential link between the rise of diabetes and pancreatic cancer might account for some of these reversals. Because of different rates of decrease for other sites, the mix of cancers is steadily changing, particularly in low-income regions, such as the relative importance of breast cancer compared with cervical cancer. These local changes have important implications for the development of cancer care programmes and training. Because of the strong relation between cancer mortality and age, ageing of the world's population is the most important driver of the rising number of cancer deaths in most countries. Most countries can expect to have to deal with more patients who need diagnosis, treatment, and palliation in coming years. Alzheimer's disease and other dementias 99 Matthews FE

Arthur A

Barnes LE

et al. A two-decade comparison of prevalence of dementia in individuals aged 65 years and older from three geographical areas of England: results of the Cognitive Function and Ageing Study I and II. 100 United States Department of Health and Human Services We used a substantially different approach to estimate Alzheimer's disease and other dementia mortality in the GBD 2013 by focusing on studies of prevalence and using data from countries with the highest death to prevalence ratios in 2013 to estimate mortality in other regions and back in time. This change greatly lowers the increase compared with GBD 2010 in the age-standardised death rate for dementia although the numbers of dementia deaths nevertheless increased. Lower increases in the age-standardised rate were because the meta-regression of prevalence studies did not show a rapidly rising trend; one study, reported decreases in age-specific rates, although our overall assessment suggests a slight increase in age-specific rates.Even in high-income countries with complete medical certification of causes of death, we argue that dementia was systematically underestimated as a cause of death in earlier periods. Other studies, such as the National Mortality Followback Study in USA, support this idea.Dementia deaths might have been misclassified into categories such as senility. Our garbage code redistribution algorithms for this broad category might have under-allocated dementia deaths in earlier periods. For future research, we may want to more carefully trace to which garbage codes dementia deaths might have been assigned using hospital linkage or other approaches. The other effect of using this approach is that we estimated considerably more dementia deaths in middle-income countries than in the GBD 2010. Prevalence studies suggest dementia occurs in these countries although it is rarely recorded on a death certificate as a cause of death. Our overall conclusion is that dementia is more common worldwide and that numbers are increasing because of population ageing with only a small component of the increase caused by rising age-specific rates. The analysis of dementia will benefit from further population-based prevalence surveys, especially with repeated measurement over time using standardised definitions and methods. As further studies of this type become available and incorporated into the GBD, our estimates of dementia burden might be substantially revised. Trends in the category Alzheimer's disease and other dementias might mask upward trends in Alzheimer's and downward trends in vascular dementia; however, these disorders are difficult to tell apart in population-based prevalence studies and cause of death data. Nevertheless, our finding that the number of dementia deaths is increasing implies that governments should remain concerned about the rising demands for care that will come with population ageing even if future rates do not increase substantially. Diarrhoea and lower respiratory infections 57 Kotloff KL

Nataro JP

Blackwelder WC

et al. Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): a prospective, case-control study. We report that the distribution of the causes of diarrhoea is different around the world. The distribution of pathogens has also changed significantly since 1990—for example, almost 50% (20 343 [9054–41 216] deaths) of all cholera deaths in children occur in sub-Saharan Africa. Because we used GEMS data to estimate relative risks, it is perhaps not surprising that our results are comparable to their findings.The population attributable fraction for pathogens such as Campylobacter, Shigella, and Salmonella were not significant in some countries and some ages. Because of the nature of case notification data, we had to estimate all types of cholera and were unable to breakdown cholera into O1, non-O1, and O-139. 101 Nash TE

Herrington DA

Losonsky GA

Levine MM Experimental human infections with Giardia lamblia. , 102 Musher DM

Musher BL Contagious acute gastrointestinal infections. , 103 Rendtorff RC The experimental transmission of human intestinal protozoan parasites. II. Giardia lamblia cysts given in capsules. , 104 Yoder J, Harral C, Beach M, Division of Foodborne, Waterborne, and Environmental Diseases (proposed), National Center for Emerging and Zoonotic Infectious Diseases (proposed), CDC. Giardiasis Surveillance—United States, 2006–2008. Centers for Disease Control, 2010. , 105 Laishram S

Kang G

Ajjampur SSR Giardiasis: a review on assemblage distribution and epidemiology in India. In high-income countries, C difficile is an important threat that has increased during the past two decades. 65% (744 413 deaths) of unexplained diarrhoea in people older than 5 years is an important knowledge gap. Although the new counterfactual approach is successful for estimating attributable death empirically and adjusts for the overall pathogen load in the country, it still suffers from limitations such as the potential low sensitivity of diagnostic tests. Some pathogens are more prevalent in controls than in cases, which might present a distorted causal picture because of continuous shedding of pathogen long after the acute phase.These findings could also suggest a protective effect of infection from one or more pathogens against other pathogens or could be simply caused by a differential decrease in the sensitivity of diagnostic tests (for other pathogens) where diarrhoea presents assuming a single pathogen caused the diarrhoea. More sensitive diagnostic tests help to improve sensitivity but at the price of decreased specificity because of contamination and post-diarrhoea pathogen excretion. Follow-up studies with multiple measurements of pathogens in children during healthy and diarrhoea periods could help to elucidate the true causal associations. Better case definition and more strict criteria for pathogens such as excluding recent cases of diarrhoea could decrease exposure misclassifications. 63 Watt JP

Wolfson LJ

O'Brien KL

et al. Burden of disease caused by Haemophilus influenzae type b in children younger than 5 years: global estimates. , 64 O'Brien KL

Wolfson LJ

Watt JP

et al. Burden of disease caused by Streptococcus pneumoniae in children younger than 5 years: global estimates. , 106 Walker CLF

Rudan I

Liu L

et al. Global burden of childhood pneumonia and diarrhoea. , 107 Nair H

Nokes DJ

Gessner BD

et al. Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: a systematic review and meta-analysis. , 108 Nair H

Brooks WA

Katz M

et al. Global burden of respiratory infections due to seasonal influenza in young children: a systematic review and meta-analysis. Our estimates of the fraction of under-5 lower respiratory infection deaths attributable to the four causes of pneumonia (pneumococcus, H influenzae B, respiratory syncytial virus, and influenza) are much the same as previous estimates, with pneumococcus and H influenzae B the predominant causes.The large fraction of lower respiratory infection attributable to pneumococcus and H influenzae B, particularly in low-income regions where the absolute burden is highest, shows the potential benefit of continuing to scale up pneumococcal conjugate and H influenzae B vaccination. We calculated the contribution of each cause with a counterfactual approach. This approach means that they do not add up to 100% but also that there might be overlap; for example, death from lower respiratory infection might involve viral and bacterial co-infection. These results should also be interpreted with caution because of the data used to generate these estimates. Data for cause are sparse and prone to several biases, which is shown in the large UIs. 109 Pfizer

Pfizer presents detailed results from landmark community-acquired pneumonia immunization trial in adults (CAPiTA) evaluating efficacy of prevenar 13. New York, NY. Estimates of the mortality burden of pneumococcal pneumonia in children rely on data from vaccine probe studies, which showed that disease in infants fell after pneumococcal conjugate vaccination; there are no sensitive diagnostic tests to detect non-bacteraemic pneumococcal pneumonia in children. To calculate burden in the absence of a diagnostic assay, the pneumococcal conjugate vaccination probe studies assumed a vaccine efficacy against non-bacteraemic pneumonia caused by vaccine types equal to that of protection from vaccine type bacteraemia (75%). Data from a large randomised trial of pneumococcal conjugate vaccination in adults confirmed efficacy against bacteraemic pneumonia of 75%, but efficacy against non-bacteraemic pneumonia was only 45%.If similar efficacy estimates are applied to infants, then the contribution of the pneumococcus to pneumonia mortality in infants could be as high as 63% (166 324 deaths). Because data were sparse, we did not estimate the fraction of deaths caused by H influenzae B among people aged 5 years and older. The before-and-after vaccine efficacy studies used to estimate the burden of pneumococcus were limited to high-income settings. These types of studies might also be biased because of underlying temporal trends in hospital admissions for lower respiratory infection. Furthermore, the only variation included for pneumococcus and H influenzae B is a result of differences in vaccination coverage. 110 Levine OS

O'Brien KL

Deloria-Knoll M

et al. The pneumonia etiology research for child health project: a 21st century childhood pneumonia etiology study. The observational studies used for respiratory syncytial virus and influenza were based on case series data from predominantly tertiary-level hospitals, which might not be representative of the underlying population and are prone to varying case-definitions and diagnostic methods. Finally, hospital discharge data for the relative differences in case-fatality for respiratory syncytial virus and influenza compared with pneumococcus and H influenzae B were limited to high-income and middle-income countries. Several of these shortcomings are being addressed by the Pneumonia Etiological Research for Child Health project. Injuries Most global road traffic deaths occur in low-income and middle-income countries and are rapidly increasing because of the growth in motorisation. Mortality rates caused by traffic-related injuries are increasing in low-income and middle-income countries. Pedestrians are most often affected, followed by car occupants and motorcyclists. Conversely, traffic deaths are decreasing in high-income countries. We noted a similar divergence between low-income and high-income countries for occupational injuries: they generally fell in high-income countries (with the exception of deaths resulting from asbestos-related mesotheliomas), whereas occupational injury deaths have increased in low-income countries (data not shown). 111 Gunnell D

Eddleston M

Phillips MR

Konradsen F The global distribution of fatal pesticide self-poisoning: systematic review. Suicide continues to be a major public health problem in many regions. Half of all suicide deaths occur in China and India alone. However, the trends are in opposite directions, decreasing rapidly in China but rising in India between 1990 and 2013. Both countries have undergone economic growth and urbanisation, a key factor in limiting access to lethal pesticides, a common method of suicide by poisoning in both countries.Therefore, as yet unexplained reasons must exist for the divergence between the two countries. 112 Sahloul Z

Coutts A

Fouad FM

et al. Health response system for Syria: beyond official narrative. We recorded several sharp increases in mortality caused by war and disaster. Particularly, the 2010 Haiti earthquake, conflict in Syria over the past several years, the 2011 Tōhoku earthquake and tsunami in Japan, and conflict in Libya in 2011 have caused considerable loss of life. The war in Syria led to an estimated 29 947 deaths (19 392–54 903) in 2013, and about 10 504 deaths and 21 422 deaths in each of the preceding 2 years. Uncertainty around these estimates is large because several different estimates exist. These estimates are of the direct deaths attributable to armed conflicts and natural disasters and do not account for the full effects of mechanisms such as the breakdown of health systems or critical infrastructure. For example, the conflict in Syria has had a substantial effect on routine immunisation for polio, with coverage now as low as 50% in some areas.The estimation of direct deaths caused by war and natural disasters is one of the most challenging components of the GBD measurement. We depend on the work of various groups to collate combatant reports, newspaper reports, humanitarian agency assessments, and other direct accounts to approximate the number of deaths. Vital registration systems often do not function in war or conflict but might be more useful in countries with natural disasters as a way of measuring the number of deaths. More work is needed to better measure shock mortality. India India accounts for 19% of the world's deaths in 2013. Estimations of cause of death for India are important both for health policy in India and for global understanding of causes of death. India has had remarkable progress in reducing both child and adult mortality over the past 23 years. Average yearly rates of decline were 1·3% per year for adults and 3·7% for children. Unfortunately, less cause of death data were available for 2013 than for 1990 or 2000. The Medical Certification of Causes of Death system provided ongoing information about patterns of urban mortality with better completeness in some states than in others. In rural areas, the Survey of Causes of Death (Rural) routinely reported causes of death from verbal autopsy from 1980 to 1998. This survey was replaced with a verbal autopsy sample collected by the Registrar-General of India based on the ongoing Sample Registration Scheme. Data for 2002–04 have been reported but not in full detail—results were released in a series of articles spanning 2008–14 but even these have not provided the standard tabulation of deaths by International Classification of Diseases cause, age, and sex used by most countries. Verbal autopsies were collected after 2004 but no data have been analysed or released. Attempts to add verbal autopsy to other major data collection efforts of the Government of India, such as the Annual Health Survey and the latest round of the District Level Household Survey, have so far been unsuccessful. Small community studies continue to be published but there is a major gap in knowledge of rural cause of death. 113 Das S

Kolher RP

Mane BG

Singh JPN

Singh AP Chikungunya epidemic: global and Indian scenario. , 114 Kalantri SP

Joshi R

Riley LW Chikungunya epidemic: an Indian perspective. , 115 Raheel U

Faheem M

Riaz MN

et al. Dengue fever in the Indian subcontinent: an overview. , 116 Dhama K

Verma AK

Rajagunalan S

et al. Swine flu is back again: a review. In view of the rapid change in India, including decreases in child mortality and adult mortality, simple predictions based on the 2002–04 data are inadequate. Our modelling strategy takes into account trends for key covariates that explain some changes in age-specific rates for many causes; nevertheless, more recent national data would be helpful to develop more precise estimates of causes of death for India. Epidemics such as Chikungunya, dengue, and H1N1 influenza also point to the need for better ongoing surveillance of causes of death in India that does not suffer from long time lags. Comparing different global health estimates Comparison of the GBD 2013 results with GBD 2010 for 1990 or 2010 shows some important differences. The overall correlation coefficient of age-sex-country-cause rates was 0·998 in both 1990 and 2010 but some causes have changed substantially at the global level. The ten causes in terms of the largest change in the number of global deaths were Alzheimer's disease and other dementias, ischaemic heart disease, interstitial lung disease and pulmonary sarcoidosis, cerebrovascular disease, neonatal encephalopathy caused by birth asphyxia and trauma, lower respiratory infections, other cardiovascular and circulatory diseases, cirrhosis, malaria, and chronic kidney disease. These changes might be because of new data, modifications of garbage coding algorithms, and revised modelling strategies ( appendix ). Generally, the data used has substantially increased: from 8967 site-years to 14 244 site-years. 48 North AB

South CD Cancer incidence in Antarctica (2003–2007). Forman D, Bray F, Brewster DH, et al, eds. Cancer Incidence in Five Continents, Vol X (electronic version). Lyon, IARC. Some specific changes are worth noting. First, data for China has greatly increased. Given China's population, the incorporation of large amounts of new data for cause of death led to large changes in China and these affected even global estimates. The five largest changes for China in 2013 compared with the GBD 2010 were ischaemic heart disease, Alzheimer's disease and other dementias, cerebrovascular disease, interstitial lung disease and pulmonary sarcoidosis, and chronic obstructive pulmonary disease. Second, more detailed cause of death data covering 189 causes instead of 98 causes were available for Russia for the GBD 2013. This affected several smaller causes, such as those related to alcohol. Third, we included new vital registration data for Turkey for 2010–12. Fourth, we modelled India in two components, urban and rural, which enabled us to make much more use of some data sources such as the Survey of Causes of Death (Rural) for rural India. Because India is large, these changes have a global effect. Fifth, for cancers, we incorporated 1145 registry-years of new data, including 128 from the Cancer Incidence in Five Continents Volume X.Sixth, the change to use of a Bayesian noise reduction algorithm for smoothing has reduced the number of outliers, particularly in small verbal autopsy studies, some of which were included in the GBD 2010. Seventh, changes to garbage code redistribution algorithms, particularly the use of statistically derived algorithms that vary by region and country, has had effects on injuries, cancers, and cardiovascular diseases. Other changes included treating unspecified anaemia as a garbage code whereas in the GBD 2010 it was mapped to iron-deficiency anaemia, moving abdominal hernia from other digestive diseases to hernia, as well as moving deaths related to specific procedures to the category of adverse effects of medical treatment. In the GBD 2010, we included abdominal hernia, including umbilical hernia, ventral hernia, and diaphragmatic hernia in the category “other digestive diseases”. In the GBD 2013, we combined these with inguinal hernia and femoral hernia into one cause named “hernia”. Additionally, we moved some ill-defined causes from the other digestive diseases category to more specific causes, thereby reducing the number of deaths in other digestive and changing the distribution of all digestive deaths among its more disaggregated causes. Seventh, the assessment of all-cause mortality in the GBD 2013 benefited from both new data and improved approaches for assessment of the age pattern of mortality in the model life-table system. Finally, the more detailed analysis of HIV/AIDS led to major changes both for HIV/AIDS (particularly in countries with concentrated epidemics) and for other causes, particularly in the people of reproductive age and in countries with moderate-to-large epidemics. The International Agency for Research on Cancer produces cancer estimates by country, age, sex, and cancer site for 2008 and 2012 (GLOBOCAN). Our definitions and the GLOBOCAN definitions are compatible for 25 sites. For these cancer sites, the total estimated prevalence from GLOBOCAN was 6 848 204 cases in 2008 and 7 483 018 cases in 2012. By comparison, the GBD estimates were 6 930 377 for 2008, and 7 437 018 for 2012. Worldwide, the largest variation in estimates occurs for thyroid cancer, testicular cancer, and other pharynx cancers, with differences of 20–30%. The rough similarity of results at worldwide masks substantial national variation. Comparing age-standardised death rates for 2012, the correlation ranges from 0·94 for tracheal, bronchus, and lung cancer, to 0·20 for thyroid cancer. Five cancers have correlations below 0·5 (ovarian, non-Hodgkin lymphoma, testicular, Hodgkin lymphoma, and thyroid). A further six cancers have correlations of 0·5–0·7 (uterine, nasopharynx, lip and oral cavity, breast, leukaemia, and multiple myeloma). 83 International Agency for Research on Cancer

GLOBOCAN 2012: Estimated cancer incidence, mortality and prevalence worldwide in 2012. WHO: International Agency for Reserach on Cancer. , 117 Forouzanfar MH

Foreman KJ

Delossantos AM

et al. Breast and cervical cancer in 187 countries between 1980 and 2010: a systematic analysis. Because both GLOBOCAN and our estimates used population-based cancer registry data and vital registration data as inputs, the wide variation in results requires explanation. As with all comparisons of global health estimates, the differences stem from data, data processing, and model development. We included a wider range of registries than did GLOBOCAN, particularly in China, and we used of a broader database of vital registration data. Our redistribution of cancer of unknown primary was based on a statistical model. The most important differences, however, probably stem from the modelling strategy. For all cancer sites in all countries, we used CODEm. GLOBOCAN used nine different methods to estimate cancer mortality depending on the country.The choice of method can lead to surprising differences in estimated rates for neighbouring countries without data. For example, the age-standardised death rate for male thyroid cancer in Timor Leste is 250% higher than that for Indonesia; age-standardised death rates for testicular cancer differ by 1300% between Mali and Mauritania. The GLOBOCAN estimates have a substantial subjective component in the choice of which modelling strategy to use and do not provide any estimate of uncertainty. Empirical assessment of the validity of the GLOBOCAN methods—for example, through cross-validation—would help to understand the strength of the approach. Understanding causes of death begins with assessment of all-cause mortality. There are some notable differences between our assessment of global age-specific deaths and those produced by the United Nations Population Division in their World Population Prospects 2012 revision (WPP2012). For the three periods (1995–2000, 2000–05, and 2005–10) as defined in WPP2012, the total numbers of deaths were 2·4–3·6% higher (6·1 million–9·1 million deaths) than estimated by us. These differentials translate into a difference of 7·8 million deaths for the 5-year period between 2005 and 2010. The difference is greatest for younger age groups. For 2005–10, estimated under-5 deaths from WPP2012 are 10·7% higher (3·9 million more deaths) than for the GBD 2013. The WPP2012 global under-5 death estimates were also higher than those of UNICEF; part of this difference might be a result of the agencies releasing their estimates at different times. The biggest relative difference was for the adolescent age group (age 5–14 years). For 2005–10, the estimated deaths in adolescents from WPP2012 were 45·1% higher than in the GBD 2013, even though the absolute difference was about 2·2 million for a 5-year period, less than 1% (2·17 million of 264·7 million) of the total deaths for the same period. The differences are even greater at the GBD regional level. For 2005–10, the relative difference between WPP2012 and GBD 2013 ranged from 26·7% (122 800) lower in WPP2012 in Oceania, to 36·0% (1·9 million) higher in WPP2012 in central sub-Saharan Africa. WPP2012 tends to have high estimates of adolescent mortality compared with the GBD 2013 for all regions in sub-Saharan Africa, Andean Latin America, north Africa and Middle East, and southeast Asia. Overall, we find more differences in estimates for sub-Saharan Africa across all age group in both relative and absolute terms. 118 Hill K

Zimmerman L , 119 Gore FM

Bloem PJ

Patton GC

et al. Global burden of disease in young people aged 10–24 years: a systematic analysis. , 120 Patton GC

Coffey C

Sawyer SM

et al. Global patterns of mortality in young people: a systematic analysis of population health data. 5 q 5 (probability of death from age 5 years to age 10 years) and 5 q 10 (probability of death from age 10 years to age 15 years) to under-5 mortality, conflicting pictures arise: our GBD 2013 estimates are sometimes higher than one source and lower than the other. Further analysis is warranted to validate our approaches for estimating adolescent mortality in low-income and middle-income countries without working vital registration systems. In addition, efforts are needed to improve both data collection and method development to better estimate mortality for adolescents. Such discrepancy originates from different assessments of child mortality rates and the difference in model life-table systems, both of which used child mortality rate to generate age-specific mortality rates. Estimating mortality for the adolescent age group is important.As part of the background research for the GBD 2013, we assessed the Demographic Health Surveys complete birth history data for age groups 5–9 years and 10–14 years and compared this data in countries with almost complete vital registration or sample registration systems, such as India. We also systematically assessed estimates of adolescent mortality from sites of the health and demographic surveillance systems, a network known as INDEPTH . When we assessed the ratio of(probability of death from age 5 years to age 10 years) and(probability of death from age 10 years to age 15 years) to under-5 mortality, conflicting pictures arise: our GBD 2013 estimates are sometimes higher than one source and lower than the other. Further analysis is warranted to validate our approaches for estimating adolescent mortality in low-income and middle-income countries without working vital registration systems. In addition, efforts are needed to improve both data collection and method development to better estimate mortality for adolescents. Table 5 Comparison of GBD and CHERG estimated child deaths for select causes in 2010 CHERG GBD 2013 Neonates aged 0–27 days Congenital abnormalities 270 (207–366) 251 (221–291) Diarrhoea 50 (17–151) 52 (44–61) Pneumonia 325 (209–470) 213 (186–242) Intrapartum-related complications * * Compares GBD cause “Neonatal encephalopathy (birth asphyxia/trauma)” with CHERG cause “intrapartum-related complications”. 717 (610–876) 657 (532–770) Sepsis or meningitis 393 (252–552) 369 (237–504) Tetanus 58 (20–276) 34 (16–48) Other neonatal disorders 181 (115–284) 470 (411–557) All causes 3072 † † CHERG did not report uncertainty estimates for all-cause mortality in children. 2807 (2719–2898) Children aged 1–59 months Injury 354 (274–429) 350 (310–394) Diarrhoea 751 (538–1031) 536 (461–607) AIDS 159 (131–185) 102 (95–111) Pneumonia 1071 (977–1176) 772 (693–850) Malaria 564 (432–709) 699 (576–855) Measles 114 (92–176) 95 (52–166) Meningitis 180 (136–237) 129 (98–163) Other disorders 1356 (1112–1581) 1355 (1211–1524) All causes 4550 † † CHERG did not report uncertainty estimates for all-cause mortality in children. 4039 (3883–4207) Data are thousands of deaths (95% uncertainty interval). GBD=Global Burden of Disease Study. CHERG=Child Health Epidemiology Reference Group. As in the GBD 2010, we noted differences for causes of child death compared with those produced by the Child Health Epidemiology Reference Group (CHERG; table 5 ). Given the complexity of both approaches, it is difficult to isolate the reason for the differences. One reason might be the different studies used: we included 5039 site-years of vital registration and 358 of verbal autopsy data compared with 578 and 192 for CHERG. Our modelling strategy was founded on modelling each individual cause separately, using the most appropriate method for each cause, and then combining the different cause estimates into an overall assessment consistent with all-cause mortality using CoDCorrect. CHERG used separate modelling strategies for HIV/AIDS, measles, pertussis, and malaria outside of Africa, and four different models for the remainder of the child causes. Separate logistic models, each with subtly incomparable cause lists, were used for neonates and children older than 1 month, for low mortality countries excluding China, for high mortality countries excluding India, for India alone, and for China alone. This partition of the world into separate models was not justified statistically—for example, they have not shown statistically different relationships with covariates for their four sets of models. Additionally, post-estimation adjustments were applied to pneumonia, meningitis, and malaria to account for intervention effectiveness; pneumonia, sepsis, meningitis, and tetanus to account for the reliance on a combined severe infection cause in the primary model; and diarrhoea, neonatal sepsis, and sudden infant death syndrome in China to account for studies that report few causes. We used a more empirical approach. We quantified both the root-mean squared error and validity of the UIs through cross-validation; CHERG has not to date reported any cross-validation results. Given the possibility that different relationships might exist between covariates such as access to clean water or sanitation and diarrhoeal mortality in different parts of the world, we undertook a sensitivity analysis in which we excluded vital registration data from high-income regions from the models for lower respiratory infections and diarrhoea. We detected no substantial differences for estimated global cause of death patterns in these cases. Furthermore, in CHERG, neonatal causes were assumed to not cause deaths after 1 month although high quality vital registration systems routinely report deaths from these causes that extend into the second month of life. Challenges and limitations 121 Brown GD

Denning DW

Levitz SM Tackling human fungal infections. In the GBD 2013, we did not include several clinical pathways to death on the cause list, such as heart failure, sepsis, fungal infection, and acute kidney injury. These clinical entities following the underlying cause construct of the International Classification of Disease are treated as garbage codes and redistributed to the likely underlying cause. Although this approach is consistent with the idea of assigning each death uniquely to the underlying cause, it masks endpoints for clinical service delivery. For example, most fungal infections are relatively minor, but potentially millions of people contract invasive fungal diseasesthat can be important pathways to death. Similar assessments can be made for sepsis, acute kidney injury, and heart failure. In future iterations of the GBD, we will aim to quantify mortality that occurs through these intermediate causes. Such intermediate cause estimation cannot be presented in the same causes lists as underlying causes of death but can provide supplemental and important information that would otherwise go unrecognised in global epidemiology. 122 Vangen S

Ellingsen L

Andersgaard AB

et al. Maternal deaths in Norway 2005–2009. Even in high-income countries with complete vital registration systems, our results differ from official statistics.This difference is largely caused by the emphasis in the GBD on enhancing comparability through redistribution of deaths assigned to garbage codes. Country-specific data for cause of death show substantial national variation in coding practices. Generally, we used global or regional algorithms to redistribute deaths assigned to garbage codes. This approach is fairly coarse and does not capture local variation in certification practice or timing of implementation of coding rules. The GBD 2013 is the most detailed effort to date to try and systematically deal with garbage code redistribution. Some changes, such as the treatment of ill-defined cancers or heart failure using statistical approaches, altered the GBD 2013 results compared with the GBD 2010. We believe that the GBD results including the fraction of deaths assigned to different types of garbage codes can be useful for national statistical authorities' efforts to improve medical certification of causes of death. We also believe that through the extensive network of GBD collaborators, we can move in future research to more country-specific redistribution algorithms. To ensure comparability, however, these national variations will have to be grounded in a sound statistical approach and theory of measurement. 106 Walker CLF

Rudan I

Liu L

et al. Global burden of childhood pneumonia and diarrhoea. , 123 Roulson J

Benbow EW

Hasleton PS Discrepancies between clinical and autopsy diagnosis and the value of post mortem histology; a meta-analysis and review. , 124 Sonderegger-Iseli K

Burger S

Muntwyler J

Salomon F Diagnostic errors in three medical eras: a necropsy study. A study of this scope has many limitations. First is the quality of the underlying medical certification of causes of death and verbal autopsy data. Even medical certification of causes of death has limitations, which is shown by the need for garbage code redistribution.Moreover, verbal autopsy data vary substantially in terms of the instrument used and the training given to physicians assigning causes of death. These shortcomings might reduce the comparability of cause of death data between countries and of our estimates based on these data. Second, we did not incorporate uncertainty from garbage code redistribution into our estimation of UIs. Propagating such uncertainty into the CODEm models will require revision of the modelling strategy or an enormous increase in computational time. As evidenced by the change for some causes compared with the GBD 2010 as a result of changes in redistribution derived from statistical methods, this is an important area for future research. Third, the major expansion of data for China and the associated changes in the estimates for some but not all causes, shows that UIs cannot take into account data that have not been included in the analysis. 125 Murray CJL

Kulkarni SC

Ezzati M Understanding the coronary heart disease versus total cardiovascular mortality paradox a method to enhance the comparability of cardiovascular death statistics in the United States. 8 Lim SS

Vos T

Flaxman AD

et al. A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. Fourth, for some causes, CODEm produces larger UIs in high-income countries than might be expected. This difference is largely the result of heterogeneity across high-income countries for a cause that cannot be explained by the models. This effect is more notable for causes such as diabetes, for which there are reasons to believe that large variation in certification practice remains in high-income countries.Because diabetes or increased fasting plasma glucose is a risk factor for macrovascular outcomes, differences in how physicians interpret the meaning of underlying cause could explain such national variation in practice. In the GBD, the full consequences of high fasting plasma glucose are captured in the risk factor assessment;deaths caused by diabetes in our analysis were only those that were recorded on the death certificate to be the underlying cause. Fifth, although we tried to improve the comparability of cause of death data over time through mapping variants of the International Classification of Diseases and garbage-code redistribution, some time trends might be affected by changes in diagnostic technology. Some causes, such as cancers, might have been less likely to have been diagnosed in the 1980s and 1990s, when imaging and other diagnostic techniques were not widespread. Sixth, for chronic kidney disease, the breakdown into deaths from diabetes, hypertension, acute glomerulonephritis, and other depends on both detailed cause of death data and renal registry data. In clinical practice, assigning chronic kidney disease to a particular cause might be difficult for patients with both hypertension and diabetes. Seventh, in some unusual cases such as chronic respiratory diseases in India, the sum of modelled estimates for CoDCorrect level 2 causes are much smaller than the level 1 modelled estimate leading to very large corrections for the CoDCorrect step. Very large corrections for CoDCorrect suggests that the component models for these causes can be improved in the future with better data or methods. Eighth, for natural history models, most notably for HIV/AIDS, changes in parameter assumptions such as the death rate on or off antiretroviral therapy, can have a large effect on estimated mortality. We believe that progressive revision of these models improves the estimates but nevertheless, validation of natural history models is difficult. For CODEm, we were able to quantify with the cross-validation strategy model performance but this is not possible with the natural history models. Ninth, a strength of the GBD approach is that all estimates of cause-specific mortality must sum to all-cause mortality in a country-age-sex-year group. However, this means that estimates for a specific cause are affected by the estimates for all other causes. Causes of death such as malaria, that have very wide UIs are particularly affected by the estimates of other causes. Tenth, models used to generate estimates of all-cause mortality and cause-specific mortality make use of a long list of covariates. Uncertainty in these covariates, such as GDP per head, was not routinely quantified but nevertheless might be substantial. We were not able to propagate uncertainty in the independent variables used in the modelling stages into the final results. 95% UIs might therefore be under-estimated. However, when we have tested in a few cases the effect of propagating uncertainty in the independent variables in the case of the HIV crude death rate, the changes to UIs, were minor (data not shown). Eleventh, we made extraordinary efforts to propagate uncertainty throughout our all-cause mortality estimation process, which is not yet common practice in modern demographic research. However, uncertainty in covariates used in the first stage model of child and adult mortality rate was not included because of the complexity of added computation and the fact that these covariates have little effect on our final estimates, as indicated by our preliminary testing. Lastly, empirical age patterns of mortality, which are vital for the estimation of mortality for many low-income and middle-income countries, mostly come from high-income countries with great vital registration systems and some low-income and middle-income countries in the most recent period. Countries in the sub-Saharan African region are least represented in our empirical database of age pattern of mortality ( appendix pp 81–89 ). Propagating uncertainty from both under-5 and adult mortality rates (two key entry parameters for our new model life-table system), and from the standard life-table generation process has given our death estimates in sub-Saharan African countries substantial uncertainty; accurate documentation of age pattern of mortality in these countries are key for producing best all-cause mortality estimates in the future. Conclusion Global public policy to reduce premature death needs a detailed, up-to-date, and accurate understanding of progress (or lack thereof) of disease and injury control strategies. This understanding applies not just to diseases that have been the focus of global public health efforts for the past few decades, but increasingly, as we have shown, for newly recognised contributors to global health trends. Through the process of providing yearly updates, the GBD is transforming into a collective approach to global health surveillance. Ideally, it will aggregate data from all available sources and provide a coherent view of health levels and trends that is timely, valid, and local. To fully achieve a collective process of global health surveillance, the time lag will need to be shortened between data collection, reporting, and inclusion in the GBD. Public policy in countries will be much better informed if more frequent assessments are accompanied by less uncertainty around the estimates. Uncertainty will decrease not so much as a result of further methodological advances in disease modelling and data synthesis, but much more as a result of greater investment and awareness among countries and donors alike of the need to strengthen vital registration systems. Global collective action to reduce mortality from major communicable diseases such as diarrhoea, measles, tetanus, tuberculosis, and, more recently, HIV/AIDS and malaria, is working, but will require continued intervention efforts and resources and will probably be even more responsive if periodic assessments such as that reported here are available and used. While progress is being made to control several major non-communicable diseases of global concern, others have been largely neglected but are rising in importance, particularly drug use disorders, cirrhosis, diabetes, and chronic kidney disease. Greater prominence to reducing disease burden from these diseases, as well as continuing priority for injury control, is strongly suggested by our analysis. The findings on global, regional, and national trends in mortality from diseases should provide an important baseline for discussions about the next generation of health goals and targets after the Millennium Development Goals. Correspondence to: Prof Christopher J L Murray, 2301 5th Avenue, Suite 600, Seattle, WA 98121, USA [email protected] For interactive versions of figure 7 and figure appendices 1–3 , visit http://vizhub.healthdata.org/le

GBD 2013 Mortality and Causes of Death Collaborators

Mohsen Naghavi, Haidong Wang, Rafael Lozano, Adrian Davis, Xiaofeng Liang, Maigeng Zhou, Stein Emil Vollset, Ayse Abbasoglu Ozgoren*, Safa Abdalla*, Foad Abd-Allah*, Muna I Abdel Aziz*, Semaw Ferede Abera*, Victor Aboyans*, Biju Abraham*, Jerry P Abraham*, Katrina E Abuabara*, Ibrahim Abubakar*, Laith J Abu-Raddad*, Niveen ME Abu-Rmeileh*, Tom Achoki*, Ademola Adelekan*, Zanfina Ademi*, Koranteng Adofo*, Arséne Kouablan Adou*, José C Adsuar*, Johan Ärnlov*, Emilie Elisabet Agardh*, Dickens Akena*, Mazin J Al Khabouri*, Deena Alasfoor*, Mohammed Albittar*, Miguel Angel Alegretti*, Alicia V Aleman*, Zewdie Aderaw Alemu*, Rafael Alfonso-Cristancho*, Samia Alhabib*, Mohammed K Ali*, Raghib Ali*, Francois Alla*, Faris Al Lami*, Peter Allebeck*, Mohammad A AlMazroa*, Rustam Al-Shahi Salman*, Ubai Alsharif*, Elena Alvarez*, Nelson Alviz-Guzman*, Adansi A Amankwaa*, Azmeraw T Amare*, Omid Ameli*, Hassan Amini*, Walid Ammar*, H Ross Anderson*, Benjamin O Anderson*, Carl Abelardo T Antonio*, Palwasha Anwari*, Henry Apfel*, Solveig Argeseanu Cunningham*, Valentina S Arsic Arsenijevic*, Al Artaman*, Majed Masoud Asad*, Rana J Asghar*, Reza Assadi*, Lydia S Atkins*, Charles Atkinson*, Alaa Badawi*, Maria C Bahit*, Talal Bakfalouni*, Kalpana Balakrishnan*, Shivanthi Balalla*, Amitava Banerjee*, Ryan M Barber*, Suzanne L Barker-Collo*, Simon Barquera*, Lars Barregard*, Lope H Barrero*, Tonatiuh Barrientos-Gutierrez*, Arindam Basu*, Sanjay Basu*, Mohammed Omar Basulaiman*, Justin Beardsley*, Neeraj Bedi*, Ettore Beghi*, Tolesa Bekele*, Michelle L Bell*, Corina Benjet*, Derrick A Bennett*, Isabela M Bensenor*, Habib Benzian*, Amelia Bertozzi-Villa*, Tariku Jibat Beyene*, Neeraj Bhala*, Ashish Bhalla*, Zulfiqar A Bhutta*, Boris Bikbov*, Aref Bin Abdulhak*, Stan Biryukov*, Jed D Blore*, Fiona M Blyth*, Megan A Bohensky*, Guilherme Borges*, Dipan Bose*, Soufiane Boufous*, Rupert R Bourne*, Lindsay N Boyers*, Michael Brainin*, Michael Brauer*, Carol E G Brayne*, Alexandra Brazinova*, Nicholas Breitborde*, Hermann Brenner*, Adam D M Briggs*, Jonathan C Brown*, Traolach S Brugha*, Geoffrey C Buckle*, Linh Ngoc Bui*, Gene Bukhman*, Michael Burch*, Ismael Ricardo Campos Nonato*, Hélène Carabin*, Rosario Cárdenas*, Jonathan Carapetis*, David O Carpenter*, Valeria Caso*, Carlos A Castañeda-Orjuela*, Ruben Estanislao Castro*, Ferrán Catalá-López*, Fiorella Cavalleri*, Jung-Chen Chang*, Fiona C Charlson*, Xuan Che*, Honglei Chen*, Yingyao Chen*, Jian Sheng Chen*, Zhengming Chen*, Peggy Pei-Chia Chiang*, Odgerel Chimed-Ochir*, Rajiv Chowdhury*, Hanne Christensen*, Costas A Christophi*, Ting-Wu Chuang*, Sumeet S Chugh*, Massimo Cirillo*, Matthew M Coates*, Luc Edgar Coffeng*, Megan S Coggeshall*, Aaron Cohen*, Valentina Colistro*, Samantha M Colquhoun*, Mercedes Colomar*, Leslie Trumbull Cooper*, Cyrus Cooper*, Luis M Coppola*, Monica Cortinovis*, Karen Courville*, Benjamin C Cowie*, Michael H Criqui*, John A Crump*, Lucia Cuevas-Nasu*, Iuri da Costa Leite*, Kaustubh C Dabhadkar*, Lalit Dandona*, Rakhi Dandona*, Emily Dansereau*, Paul I Dargan*, Anand Dayama*, Vanessa De la Cruz-Góngora*, Shelley F de la Vega*, Diego De Leo*, Louisa Degenhardt*, Borja del Pozo-Cruz*, Robert P Dellavalle*, Kebede Deribe*, Don C Des Jarlais*, Muluken Dessalegn*, Gabrielle A deVeber*, Samath D Dharmaratne*, Mukesh Dherani*, Jose-Luis Diaz-Ortega*, Cesar Diaz-Torne*, Daniel Dicker*, Eric L Ding*, Klara Dokova*, E Ray Dorsey*, Tim R Driscoll*, Leilei Duan*, Herbert C Duber*, Adnan M Durrani*, Beth E Ebel*, Karen M Edmond*, Richard G Ellenbogen*, Yousef Elshrek*, Sergey Petrovich Ermakov*, Holly E Erskine*, Babak Eshrati*, Alireza Esteghamati*, Kara Estep*, Thomas Fürst*, Saman Fahimi*, Anna S Fahrion*, Emerito Jose A Faraon*, Farshad Farzadfar*, Derek FJ Fay*, Andrea B Feigl*, Valery L Feigin*, Manuela Mendonca Felicio*, Seyed-Mohammad Fereshtehnejad*, Jefferson G Fernandes*, Alize J Ferrari*, Thomas D Fleming*, Nataliya Foigt*, Kyle Foreman*, Mohammad H Forouzanfar*, F Gerry R Fowkes*, Urbano Fra Paleo*, Richard C Franklin*, Neal D Futran*, Lynne Gaffikin*, Ketevan Gambashidze*, Fortuné Gbètoho Gankpé*, Francisco Armando García-Guerra*, Ana Cristina Garcia*, Johanna M Geleijnse*, Bradford D Gessner*, Katherine B Gibney*, Richard F Gillum*, Stuart Gilmour*, Ibrahim Abdelmageem Mohamed Ginawi*, Maurice Giroud*, Elizabeth L Glaser*, Shifalika Goenka*, Hector Gomez Dantes*, Philimon Gona*, Diego Gonzalez-Medina*, Caterina Guinovart*, Rahul Gupta*, Rajeev Gupta*, Richard A Gosselin*, Carolyn C Gotay*, Atsushi Goto*, Hebe N Gouda*, Nicholas Graetz*, K Fern Greenwell*, Harish Chander Gugnani*, David Gunnell*, Reyna A Gutiérrez*, Juanita Haagsma*, Nima Hafezi-Nejad*, Holly Hagan*, Maria Hagstromer*, Yara A Halasa*, Randah Ribhi Hamadeh*, Hannah Hamavid*, Mouhanad Hammami*, Jamie Hancock*, Graeme J Hankey*, Gillian M Hansen*, Hilda L Harb*, Heather Harewood*, Josep Maria Haro*, Rasmus Havmoeller*, Roderick J Hay*, Simon I Hay*, Mohammad T Hedayati*, Ileana B Heredia Pi*, Kyle R Heuton*, Pouria Heydarpour*, Hideki Higashi*, Martha Hijar*, Hans W Hoek*, Howard J Hoffman*, John C Hornberger*, H Dean Hosgood*, Mazeda Hossain*, Peter J Hotez*, Damian G Hoy*, Mohamed Hsairi*, Guoqing Hu*, John J Huang*, Mark D Huffman*, Andrew J Hughes*, Abdullatif Husseini*, Chantal Huynh*, Marissa Iannarone*, Kim M Iburg*, Bulat T Idrisov*, Nayu Ikeda*, Kaire Innos*, Manami Inoue*, Farhad Islami*, Samaya Ismayilova*, Kathryn H Jacobsen*, Simerjot Jassal*, Sudha P Jayaraman*, Paul N Jensen*, Vivekanand Jha*, Guohong Jiang*, Ying Jiang*, Jost B Jonas*, Jonathan Joseph*, Knud Juel*, Edmond Kato Kabagambe*, Haidong Kan*, André Karch*, Chante Karimkhani*, Ganesan Karthikeyan*, Nicholas Kassebaum*, Anil Kaul*, Norito Kawakami*, Konstantin Kazanjan*, Dhruv S Kazi*, Andrew H Kemp*, Andre Pascal Kengne*, Andre Keren*, Maia Kereselidze*, Yousef Saleh Khader*, Shams Eldin Ali Hassan Khalifa*, Ejaz Ahmed Khan*, Gulfaraz Khan*, Young-Ho Khang*, Christian Kieling*, Yohannes Kinfu*, Jonas M Kinge*, Daniel Kim*, Sungroul Kim*, Miia Kivipelto*, Luke Knibbs*, Ann Kristin Knudsen*, Yoshihiro Kokubo*, Sowarta Kosen*, Meera Kotagal*, Michael A Kravchenko*, Sanjay Krishnaswami*, Hans Krueger*, Barthelemy Kuate Defo*, Ernst J Kuipers*, Burcu Kucuk Bicer*, Chanda Kulkarni*, Veena S Kulkarni*, Kaushalendra Kumar*, Ravi B Kumar*, Gene F Kwan*, Hmwe Kyu*, Taavi Lai*, Arjun Lakshmana Balaji*, Ratilal Lalloo*, Tea Lallukka*, Hilton Lam*, Qing Lan*, Van C Lansingh*, Heidi J Larson*, Anders Larsson*, Pablo M Lavados*, Alicia EB Lawrynowicz*, Janet L Leasher*, Jong-Tae Lee*, James Leigh*, Mall Leinsalu*, Ricky Leung*, Carly Levitz*, Bin Li*, Yichong Li*, Yongmei Li*, Chelsea Liddell*, Stephen S Lim*, Graça Maria Ferreira de Lima*, Maggie L Lind*, Steven E Lipshultz*, Shiwei Liu*, Yang Liu*, Belinda K Lloyd*, Katherine T Lofgren*, Giancarlo Logroscino*, Stephanie J London*, Joannie Lortet-Tieulent*, Paulo A Lotufo*, Robyn M Lucas*, Raimundas Lunevicius*, Ronan Anthony Lyons*, Stefan Ma*, Vasco Manuel Pedro Machado*, Michael F MacIntyre*, Mark T Mackay*, Jennifer H MacLachlan*, Carlos Magis-Rodriguez*, Abbas A Mahdi*, Marek Majdan*, Reza Malekzadeh*, Srikanth Mangalam*, Christopher Chabila Mapoma*, Marape Marape*, Wagner Marcenes*, Christopher Margono*, Guy B Marks*, Melvin Barrientos Marzan*, Joseph R Masci*, Mohammad Taufiq Mashal*, Felix Masiye*, Amanda J Mason-Jones*, Richard Matzopolous*, Bongani M Mayosi*, Tasara T Mazorodze*, John J McGrath*, Abigail C McKay*, Martin McKee*, Abigail McLain*, Peter A Meaney*, Man Mohan Mehndiratta*, Fabiola Mejia-Rodriguez*, Yohannes Adama Melaku*, Michele Meltzer*, Ziad A Memish*, Walter Mendoza*, George A Mensah*, Atte Meretoja*, Francis A Mhimbira*, Ted R Miller*, Edward J Mills*, Awoke Misganaw*, Santosh K Mishra*, Charles N Mock*, Terrie E Moffitt*, Norlinah Mohamed Ibrahim*, Karzan Abdulmuhsin Mohammad*, Ali H Mokdad*, Glen Liddell Mola*, Lorenzo Monasta*, Jonathan de la Cruz Monis*, Julio C Montañez Hernandez*, Marcella Montico*, Thomas J Montine*, Meghan D Mooney*, Ami R Moore*, Maziar Moradi-Lakeh*, Andrew E Moran*, Rintaro Mori*, Joanna Moschandreas*, Wilkister Nyaora Moturi*, Madeline L Moyer*, Dariush Mozaffarian*, Ulrich O Mueller*, Mitsuru Mukaigawara*, Erin C Mullany*, Joseph Murray*, Adetoun Mustapha*, Paria Naghavi*, Aliya Naheed*, Kovin S Naidoo*, Luigi Naldi*, Devina Nand*, Vinay Nangia*, KM Venkat Narayan*, Denis Nash*, Jamal Nasher*, Chakib Nejjari*, Robert G Nelson*, Marian Neuhouser*, Sudan Prasad Neupane*, Polly A Newcomb*, Lori Newman*, Charles R Newton*, Marie Ng*, Frida Namnyak Ngalesoni*, Grant Nguyen*, Nhung thi Trang Nguyen*, Muhammad Imran Nisar*, Sandra Nolte*, Ole F Norheim*, Rosana E Norman*, Bo Norrving*, Luke Nyakarahuka*, Shaun Odell*, Martin O'Donnell*, Takayoshi Ohkubo*, Summer Lockett Ohno*, Bolajoko O Olusanya*, Saad B Omer*, John Nelson Opio*, Orish Ebere Orisakwe*, Katrina F Ortblad*, Alberto Ortiz*, Maria Lourdes K Otayza*, Amanda W Pain*, Jeyaraj D Pandian*, Carlo Irwin Panelo*, Jeemon Panniyammakal*, Christina Papachristou*, Angel J Paternina Caicedo*, Scott B Patten*, George C Patton*, Vinod K Paul*, Boris Pavlin*, Neil Pearce*, Carlos A Pellegrini*, David M Pereira*, Sophie C Peresson*, Rogelio Perez-Padilla*, Fernando P Perez-Ruiz*, Norberto Perico*, Aslam Pervaiz*, Konrad Pesudovs*, Carrie B Peterson*, Max Petzold*, Bryan K Phillips*, David E Phillips*, Michael R Phillips*, Dietrich Plass*, Frédéric Bernard Piel*, Dan Poenaru*, Suzanne Polinder*, Svetlana Popova*, Richie G Poulton*, Farshad Pourmalek*, Dorairaj Prabhakaran*, Dima Qato*, Amado D Quezada*, D Alex Quistberg*, Felicia Rabito*, Anwar Rafay*, Kazem Rahimi*, Vafa Rahimi-Movaghar*, Sajjad UR Rahman*, Murugesan Raju*, Ivo Rakovac*, Saleem M Rana*, Amany Refaat*, Giuseppe Remuzzi*, Antonio L Ribeiro*, Stefano Ricci*, Patricia M Riccio*, Lee Richardson*, Jan Hendrik Richardus*, Bayard Roberts*, D Allen Roberts*, Margaret Robinson*, Anna Roca*, Alina Rodriguez*, David Rojas-Rueda*, Luca Ronfani*, Robin Room*, Gregory A Roth*, Dietrich Rothenbacher*, David H Rothstein*, Jane TF Rowley*, Nobhojit Roy*, George M Ruhago*, Lesley Rushton*, Sankar Sambandam*, Kjetil Søreide*, Mohammad Yahya Saeedi*, Sukanta Saha*, Ramesh Sahathevan*, Mohammad Ali Sahraian*, Berhe Weldearegawi Sahle*, Joshua A Salomon*, Deborah Salvo*, Genesis May J Samonte*, Uchechukwu Sampson*, Juan Ramon Sanabria*, Logan Sandar*, Itamar S Santos*, Maheswar Satpathy*, Monika Sawhney*, Mete Saylan*, Peter Scarborough*, Ben Schöttker*, Jürgen C Schmidt*, Ione JC Schneider*, Austin E Schumacher*, David C Schwebel*, James G Scott*, Sadaf G Sepanlou*, Edson E Servan-Mori*, Katya Shackelford*, Amira Shaheen*, Saeid Shahraz*, Marina Shakh-Nazarova*, Siyi Shangguan*, Jun She*, Sara Sheikhbahaei*, Donald S Shepard*, Kenji Shibuya*, Yukito Shinohara*, Kawkab Shishani*, Ivy Shiue*, Rupak Shivakoti*, Mark G Shrime*, Inga Dora Sigfusdottir*, Donald H Silberberg*, Andrea P Silva*, Edgar P Simard*, Shireen Sindi*, Jasvinder A Singh*, Lavanya Singh*, Edgar Sioson*, Vegard Skirbekk*, Karen Sliwa*, Samuel So*, Michael Soljak*, Samir Soneji*, Sergey S Soshnikov*, Luciano A Sposato*, Chandrashekhar T Sreeramareddy*, Jeffrey D Stanaway*, Vasiliki Kalliopi Stathopoulou*, Kyle Steenland*, Claudia Stein*, Caitlyn Steiner*, Antony Stevens*, Heidi Stöckl*, Kurt Straif*, Konstantinos Stroumpoulis*, Lela Sturua*, Bruno F Sunguya*, Soumya Swaminathan*, Mamta Swaroop*, Bryan L Sykes*, Karen M Tabb*, Ken Takahashi*, Roberto Tchio Talongwa*, Feng Tan*, David Tanne*, Marcel Tanner*, Mohammad Tavakkoli*, Braden Te Ao*, Carolina Maria Teixeira*, Tara Templin*, Eric Yeboah Tenkorang*, Abdullah Sulieman Terkawi*, Bernadette A Thomas*, Andrew L Thorne-Lyman*, Amanda G Thrift*, George D Thurston*, Taavi Tillmann*, David L Tirschwell*, Imad M Tleyjeh*, Marcello Tonelli*, Fotis Topouzis*, Jeffrey A Towbin*, Hideaki Toyoshima*, Jefferson Traebert*, Bach X Tran*, Thomas Truelsen*, Ulises Trujillo*, Matias Trillini*, Zacharie Tsala Dimbuene*, Miltiadis Tsilimbaris*, E Murat Tuzcu*, Clotilde Ubeda*, Uche S Uchendu*, Kingsley N Ukwaja*, Eduardo A Undurraga*, Andrew J Vallely*, Steven van de Vijver*, Coen H van Gool*, Yuri Y Varakin*, Tommi J Vasankari*, Ana Maria Nogales Vasconcelos*, Monica S Vavilala*, N Venketasubramanian*, Lakshmi Vijayakumar*, Salvador Villalpando*, Francesco S Violante*, Vasiliy Victorovich Vlassov*, Gregory R Wagner*, Stephen G Waller*, JianLi Wang*, Linhong Wang*, XiaoRong Wang*, Yanping Wang*, Tati Suryati Warouw*, Scott Weichenthal*, Elisabete Weiderpass*, Robert G Weintraub*, Wang Wenzhi*, Andrea Werdecker*, K Ryan R Wessells*, Ronny Westerman*, Harvey A Whiteford*, James D Wilkinson*, Thomas Neil Williams*, Solomon Meseret Woldeyohannes*, Charles DA Wolfe*, Timothy M Wolock*, Anthony D Woolf*, John Q Wong*, Jonathan L Wright*, Sarah Wulf*, Brittany Wurtz*, Gelin Xu*, Yang C Yang*, Yuichiro Yano*, Hiroshi Yatsuya*, Paul Yip*, Naohiro Yonemoto*, Seok-Jun Yoon*, Mustafa Younis*, Chuanhua Yu*, Kim Yun Jin*, Maysaa El Sayed Zaki*, Mohammed Fouad Zamakhshary*, Hajo Zeeb*, Yong Zhang*, Yong Zhao*, Yingfeng Zheng*, Jun Zhu*, Shankuan Zhu*, David Zonies*, Xiao Nong Zou*, Joseph R Zunt*, Theo Vos†, Alan D Lopez†, Christopher JL Murray†. *Authors listed alphabetically. †Joint senior authors.

Affiliations

Institute for Health Metrics and Evaluation (M Naghavi PhD, Wang H PhD, R Lozano PhD, S E Vollset MD, T Achoki MD, H Apfel BA, C Atkinson BS, R M Barber BS, A Bertozzi-Villa BS, S Biryukov BS, J C Brown MAIS, M M Coates BS, L E Coffeng PhD, M S Coggeshall BA, Prof L Dandona PhD, E Dansereau BA, D Dicker BS, H C Duber MD, K Estep MPA, T D Fleming BS, M H Forouzanfar PhD, D Gonzalez-Medina BA, N Graetz BS, J Haagsma PhD, H Hamavid BA, J Hancock MLS, G M Hansen MSW, K R Heuton BS, H Higashi PhD, C Huynh BA, M Iannarone MSc, J Joseph BS, N Kassebaum MD, H H Kyu PhD, C Levitz MPH, C Liddell BE, M L Lind BS, K T Lofgren MPH, M F MacIntyre MEd, C Margono BS, A McLain MA, A H Mokdad PhD, M D Mooney BS, M Moradi-Lakeh PhD, M Moyer BA, E C Mullany BA, P Naghavi BESc, M Ng PhD, G Nguyen BA, S Odell MPP, S L Ohno BA, K F Ortblad MPH, A W Pain MPH, D E Phillips BS, B K Phillips BA, L Richardson BS, D A Roberts BS, M Robinson BA, G A Roth MD, L Sandar BS, A E Schumacher BS, K Shackelford BA, L Singh BS, E Sioson MS, J Stanaway PhD, C Steiner MPH, A Stevens PhD, T Templin BA, B A Thomas MD, T M Wolock BA, S Wulf MPH, B Wurtz MPH, T Vos PhD, Prof A D Lopez PhD, Prof C J L Murray DPhil), School of Medicine (Prof R G Ellenbogen MD, J L Wright MD), Children's Hospital (N Kassebaum MD), Department of Neurology (D L Tirschwell MD), Harborview Injury Prevention and Research Center (B E Ebel MD), University of Washington, Seattle, WA, USA (R Alfonso-Cristancho PhD, Prof B O Anderson MD, Prof N D Futran MD, P N Jensen MPH, M Kotagal MD, Prof C N Mock PhD, T J Montine PhD, Prof C A Pellegrini MD, D A Quistberg PhD, M S Vavilala MD, Prof J R Zunt MD); National Institute of Public Health Mexico, Mexico City, Mexico (R Lozano, S Barquera PhD, T Barrientos-Gutierrez PhD, I R Campos Nonato PhD, Prof L Cuevas-Nasu MsC, V De la Cruz-Góngora MsC, J-L Diaz-Ortega MD, Prof F A García-Guerra MSc, H Gomez Dantes MC, I B Heredia Pi PhD, F Mejia-Rodriguez MD, J C Montañez Hernandez MsC, Prof R Perez-Padilla MD, A D Quezada MSc, D Salvo PhD, Prof E E Servan-Mori MSc, S Villalpando PhD); Public Health England, London (Prof A Davis PhD, D F J Fay MSc, J C Schmidt Dott.med.), Oxford, UK (A J Hughes MSc); National Center for Chronic and Noncommunicable Disease Control and Prevention (Prof M Zhou PhD, L Duan MD, Y Li MPH, S Liu PhD, Prof L Wang MD), National Institute of Occupational Health and Poison Control (Prof F Tan MD), China Centers for Disease Control and Prevention, Beijing, China (Prof X Liang PhD); Norwegian Institute of Public Health, Bergen (S E Vollset, A K Knudsen PhD), Oslo, Norway (J M Kinge PhD, Prof V Skirbekk PhD); University of Bergen, Bergen, Norway (S E Vollset, Prof O F Norheim PhD); Hacettepe University Institute of Population Studies, Ankara, Turkey (A Abbasoglu Ozgoren MA, B Kucuk Bicer MD); Sudanese Public Health Consultancy Group, Solihull, UK (S Abdalla MD); Faculty of Medicine, Cairo-University, Cairo, Egypt (Prof F Abd-Allah MD); Public Health Institute, Khartoum, Sudan (M I Abdel Aziz PhD); School of Public Health, College of Health Sciences (S F Abera MSc), Mekelle University, Mekelle, Tigray, Ethiopia (Y A Melaku MPH, B W Sahle MSc); Dupuytren University Hospital, Limoges, Limoges, France (Prof V Aboyans PhD); Oslo and Akershus University College of Applied Sciences (HiOA), Oslo, Norway (B Abraham M.Phil); University of Texas School of Medicine San Antonio, San Antonio, TX, USA (J P Abraham MD); University of Pennsylvania, Philadelphia, PA, USA (K E Abuabara MD, Prof D H Silberberg MD); Department of Epidemiology and Public Health (H Benzian PhD), University College London, London, UK (H Benzian PhD); Weill Cornell Medical College—Qatar, Doha, Qatar (L J Abu-Raddad PhD); Institute of Community and Public Health, Birzeti University, Ramallah, West Bank, Occupied Palestinian Territory (N M E Abu-Rmeileh PhD); Public Health Promotion Alliance, Osogbp, Nigeria (A Adelekan PHD); Beneral Practice and Primary Health Care Academic Centre (P P-C Chiang PhD), Centre for International Child Health (S M Colquhoun PhD), University of Melbourne, Melbourne, VIC, Australia (Z Ademi PhD, J D Blore PhD, M A Bohensky PhD, A Lakshmana Balaji MBBS, Prof G C Patton MD, R G Weintraub MB, Prof A D Lopez PhD); Kwame Nkrumah University of Science and Technology, Kumasi, Ashanti, Ghana (K Adofo MPH); Association Ivoirienne pour le Bien-Être Familial, Abidjan, Côte d'Ivoire, Côte d'Ivoire (A K Adou MD); University of Extremadura, Cáceres, Spain (Prof J C Adsuar PhD, U Fra. Paleo PhD); Uppsala University, Uppsala, Sweden (J Ärnlöv PhD, Prof A Larsson PhD); Institution of Public Health Sciences, Stockholm, Sweden (E E Agardh PhD); Makerere University, Kampala, Uganda (D Akena PhD, L Nyakarahuka MPH); Ministry of Health, Muscat, Oman (M J Al Khabouri PhD, D Alasfoor MSc); Baghdad College of Medicine, Baghdad, Baghdad, Iraq (F H Al Lami PhD); Independent, Damascus, Syria (M I Albittar BS); Grupo de Investigación en Ciencias de la Salud y Neurociencias (CISNEURO), Cartagena de Indias, Bolívar, Colombia (G Alcalá-Cerra MD); Universidad de la República, Facultad de Medicina, Departamento de Medicina Preventiva y Social, Montevideo, Uruguay (M A Alegretti MD, A V Aleman MD, F Cavalleri BS, V Colistro MSc); Debre Markos University, Debre Markos, Amhara, Ethiopia (Z A Alemu MPH); National Guard Health Affairs, Riyadh, Kingdom of Saudi Arabia (S Alhabib PhD); Rollins School of Public Health (E P Simard PhD, Prof K Steenland PhD), Emory University, Atlanta, GA, USA (M K Ali MBChB, S Argeseanu Cunningham PhD, K C Dabhadkar MPH, Prof Y Liu PhD, Prof K M V Narayan MD, S B Omer PhD, Prof M R Phillips MD); University of Oxford, Oxford, UK (R Ali MSc, D A Bennett PhD, A D M Briggs MSc, Prof Z Chen PhD, Prof S I Hay DSc, F B Piel PhD, K Rahimi DM, P Scarborough DPhil); School of Public Health, University of Lorraine, Nancy, France (Prof F Alla PhD); Department of Public Health Sciences (Prof P Allebeck PhD), Department of Neurobiology, Care Sciences, and Society (NVS) (S-M Fereshtehnejad MD), Aging Research Center (Prof M Kivipelto PhD), Department of Medical Epidemiology and Biostatistics, Stockholm, Sweden (Prof E Weiderpass PhD), Karolinska Institutet, Stockholm, Sweden (M Hagstromer PhD, R Havmoeller PhD, S Sindi PhD); Saudi Ministry of Health, Riyadh, Kingdom of Saudi Arabia (M A A AlMazroa MD, M O Basulaiman PhD, Prof Z A Memish MD, M Y Saeedi PhD); University of Edinburgh, Edinburgh, UK (Prof R Al-Shahi Salman PhD, Prof F G R Fowkes PhD); Charité—Universitätsmedizin Berlin, Berlin, Germany (U Alsharif DMD, S Nolte PhD, C Papachristou PhD); Government, Madrid, Spain (E Alvarez PhD); Universidad de Cartagena, Cartagena de Indias, Colombia (Prof N Alviz-Guzman PhD, A J Paternina Caicedo MSc); Albany State University, Albany, GA, USA (Prof A A Amankwaa PhD); Department of Epidemiology, University of Groningen, Groningen, The Netherlands (A T Amare MPH); College of Medicine and Health Sciences, Bahir Dar University, Bahir Dar, Ethiopia (A T Amare); Boston University, Boston, MA, USA (O Ameli MD); Kurdistan Environmental Health Research Center, Kurdistan University of Medical Sciences, Sanandaj, Kurdistan, Iran (H Amini MSPH); Department of Epidemiology and Public Health (H Amini), Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, Basel, Switzerland (Prof M Tanner PhD); Ministry of Public Health, Beirut, Lebanon (Prof W Ammar PhD, H L Harb MPH); St George's, University of London, London, UK (Prof H R Anderson MD); College of Public Health, University of the Philippines Manila, Manila, Philippines (C A T Antonio MD, E J A Faraon MD, C I A Panelo MA); UNFPA, Kabul, Afghanistan (P Anwari MSc); University of Belgrade, School of Medicine, Institute of Microbiology and Immunology, Belgrade, Serbia (Prof V S Arsic Arsenijevic PhD); Evidera Inc, Lexington, MA, USA (A Artaman PhD); Ministry of Health, Amman, Jordan (M M Asad PhD); South Asian Public Health Forum, Islamabad, Pakistan (R J Asghar MD); Mashhad University of Medical Sciences, Mashhad, Khorasan Razavi, Iran (R Assadi MD); Ministry Of Health, Wellness, Human Services and Gender Relations, Castries, St. Lucia (L S Atkins MPH); Public Health Agency of Canada, Toronto, ON, Canada (A Badawi PhD); INECO Neurociencias, Rosario, Santa Fe, Argentina (M C Bahit MD); Ministry of Health, Damascus, Syria (T Bakfalouni MD); Sri Ramachandra University, Chennai, Tamil Nadu, India (Prof K Balakrishnan PhD, S Sambandam PhD); National Institute for Stroke and Applied Neurosciences (S Balala MPH, Prof V L Feigin PhD), School of Psychology (S L Barker-Collo PhD), University of Auckland, Auckland, New Zealand (B del Pozo-Cruz PhD); University of Birmingham, Birmingham, UK (A Banerjee MA); Department of Occupational and Environmental Health, University of Gothenburg, Gothenburg, Sweden (Prof L Barregard PhD); Department of Industrial Engineering, Pontificia Universidad Javeriana, Bogota, Colombia (L H Barrero ScD); School of Health Sciences, University of Canterbury, Christchurch, Canterbury, New Zealand (A Basu PhD); Asian Liver Center, Palo Alto (Prof S So MBBS), School of Medicine, Stanford (L Gaffikin DrPH), Stanford University, Stanford, CA, USA (S Basu PhD); Oxford University, Ho Hi Minh City, Vietnam (J Beardsley MBChB); College of Public Health and Tropical Medicine, Jazan, Kingdom of Saudi Arabia (Prof N Bedi MD); IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milano (E Beghi MD), Bergamo, Italy (M Cortinovis BiotechD, N Perico MD, Prof G Remuzzi MD, M Trillini MD); Madawalabu University, Ethiopia, Bale Goba, Oromia, Ethiopia (T Bekele MPH); Yale University, New Haven, CT, USA (Prof M L Bell PhD, J J Huang MD); National Institute of Psychiatry Ramon de la Fuente, Mexico City, DF, Mexico (C Benjet PhD, R A Gutiérrez PhD); Hospital Universitário (I M Bensenor PhD, Prof A H Kemp PhD), University of Sao Paulo, Sao Paulo, Brazil (Prof P A Lotufo DrPH, Prof I S Santos PhD); Addis Ababa University, Debre Zeit, Ethiopia (T J Beyene DVM, K Deribe MPH); Wellington Hospital, Wellington, New Zealand (N Bhala Dphil); Post Graduate Institute of Medical Education and Research, Chandigarh, UT, India (Prof A Bhalla MD); Medical Center (Z A Bhutta PhD), Aga Khan University, Karachi, Pakistan (M I Nisar MSc); I.Evdokimov Moscow State University of Medicine and Dentistry, Moscow, Russia (B Bikbov MD); University of Missouri-Kansas City, Kansas City, MO, USA (A Bin Abdulhak MD); Woolcock Institute of Medical Research (Prof G B Marks PhD), Sydney School of Public Health (T R Driscoll PhD), University of Sydney, Sydney, NSW, Australia (F M Blyth PhD, J Leigh PhD); Instituto Nacional de Psiquiatria, Mexico, Mexico (Prof G Borges Doctor Science); World Bank, Washington DC, DC, USA (D Bose PhD); Transport and Road Safety (TARS) Research (S Boufous PhD), The Kirby Institute (A J Vallely PhD), University of New South Wales, Sydney, NSW, Australia (Prof L Degenhardt PhD, M Satpathy PhD); Vision & Eye Research Unit, Anglia Ruskin University, Cambridge, UK (Prof R R Bourne FRCOphth); Georgetown University School of Medicine, Washington, DC, USA (L N Boyers BA); Danube-University Krems, Krems, Austria (Prof M Brainin PhD); School of Population and Public Health (H Krueger PhD), University of British Columbia, British Columbia, Canada (M Brauer PhD, Prof C C Gotay PhD, F Pourmalek PhD); Cambridge Institute of Public Health, Cambridge, UK (Prof C E G Brayne MD); Trnava University, Faculty of Health Sciences and Social Work, Trnava, Slovakia (A Brazinova PhD, M Majdan PhD); University of Arizona, Tucson, AZ, USA (Prof N Breitborde PhD); German Cancer Research Center, Heidelberg, Germany (Prof H Brenner MD); University of Leicester, Leicester, UK (Prof T S Brugha MD); University of Massachusetts Medical School, Worcester, MA, USA (G C Buckle MPH, Prof P Gona PhD); Hanoi School of Public Health, Hanoi, Vietnam (L N Bui MIPH, N t T Nguyen MS); Harvard Medical School (G Bukhman PhD), Harvard School of Public Health (E L Ding ScD, S Fahimi PhD, S Shangguan MD), Harvard University (A B Feigl MPH, J A Salomon PhD, M G Shrime MD); Great Ormond Street Hospital for Children, London, UK (M Burch MD); Universidad Autonoma Metropolitana, Mexico, DF, Mexico (Prof R CÃ¡rdenas Sc.D.); Department of Biostatistics and Epidemiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA (Prof H Carabin PhD); Telethon Institute for Child Health Research, Subiaco, Western Australia, Australia (Prof J R Carapetis PhD); University at Albany, Rensselaer, NY, USA (Prof D O Carpenter MD); Stroke Unit, University of Perugia, Perugia, Italy (V Caso MD); Colombian National Health Observatory, Instituto Nacional de Salud, Bogota, Colombia (C A Castañeda-Orjuela MSc); Universidad Diego Portales, Santiago, Chile (Prof R E Castro PhD); Division of Pharmacoepidemiology and Pharmacovigilance, Spanish Medicines and Healthcare Products Agency (AEMPS), Ministry of Health, Madrid, Spain (F Catalá-López PhD); National Taiwan University, Taipei, Taiwan (Prof C-C Chang PhD); School of Population Health (D G Hoy PhD), The University of Queensland Centre for Clinical Research (J G Scott PhD), University of Queensland, Brisbane (F C Charlson MPH, H E Erskine BPsySc, A J Ferrari BPsySc, H N Gouda PhD, L Knibbs PhD, Prof J J McGrath MD, Prof H A Whiteford MD), Herston, QLD, Australia (R E Norman PhD); National Institute of Health, Bethesda, MD, USA (X Che PhD); Zhongshan Hospital (J She PhD), Fudan University, Shanghai, China (Prof Y Chen PhD, Prof H Kan MD); CTSU, Nuffield Dept. of Population Health, Oxford, UK (Prof Z Chen); Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, D