Abraham D. Flaxman

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

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

Global epidemiology of hepatitis C virus infection: new estimates of age-specific antibody to HCV seroprevalence.

In efforts to inform public health decision makers, the Global Burden of Diseases, Injuries, and Risk Factors 2010 (GBD2010) Study aims to estimate the burden of disease using available parameters. This study was conducted to collect and analyze available prevalence data to be used for estimating the hepatitis C virus (HCV) burden of disease. In this systematic review, antibody to HCV (anti‐HCV) seroprevalence data from 232 articles were pooled to estimate age‐specific seroprevalence curves in 1990 and 2005, and to produce age‐standardized prevalence estimates for each of 21 GBD regions using a model‐based meta‐analysis. This review finds that globally the prevalence and number of people with anti‐HCV has increased from 2.3% (95% uncertainty interval [UI]: 2.1%‐2.5%) to 2.8% (95% UI: 2.6%‐3.1%) and >122 million to >185 million between 1990 and 2005. Central and East Asia and North Africa/Middle East are estimated to have high prevalence (>3.5%); South and Southeast Asia, sub‐Saharan Africa, Andean, Central, and Southern Latin America, Caribbean, Oceania, Australasia, and Central, Eastern, and Western Europe have moderate prevalence (1.5%‐3.5%); whereas Asia Pacific, Tropical Latin America, and North America have low prevalence (<1.5%). Conclusion: The high prevalence of global HCV infection necessitates renewed efforts in primary prevention, including vaccine development, as well as new approaches to secondary and tertiary prevention to reduce the burden of chronic liver disease and to improve survival for those who already have evidence of liver disease. (HEPATOLOGY 2013)

Global distribution and prevalence of hepatitis C virus genotypes

Hepatitis C virus (HCV) exhibits high genetic diversity, characterized by regional variations in genotype prevalence. This poses a challenge to the improved development of vaccines and pan‐genotypic treatments, which require the consideration of global trends in HCV genotype prevalence. Here we provide the first comprehensive survey of these trends. To approximate national HCV genotype prevalence, studies published between 1989 and 2013 reporting HCV genotypes are reviewed and combined with overall HCV prevalence estimates from the Global Burden of Disease (GBD) project. We also generate regional and global genotype prevalence estimates, inferring data for countries lacking genotype information. We include 1,217 studies in our analysis, representing 117 countries and 90% of the global population. We calculate that HCV genotype 1 is the most prevalent worldwide, comprising 83.4 million cases (46.2% of all HCV cases), approximately one‐third of which are in East Asia. Genotype 3 is the next most prevalent globally (54.3 million, 30.1%); genotypes 2, 4, and 6 are responsible for a total 22.8% of all cases; genotype 5 comprises the remaining <1%. While genotypes 1 and 3 dominate in most countries irrespective of economic status, the largest proportions of genotypes 4 and 5 are in lower‐income countries. Conclusion: Although genotype 1 is most common worldwide, nongenotype 1 HCV cases—which are less well served by advances in vaccine and drug development—still comprise over half of all HCV cases. Relative genotype proportions are needed to inform healthcare models, which must be geographically tailored to specific countries or regions in order to improve access to new treatments. Genotype surveillance data are needed from many countries to improve estimates of unmet need. (Hepatology 2015;61:77–87)

Global Burden of Oral Conditions in 1990-2010 A Systematic Analysis

The Global Burden of Disease (GBD) 2010 Study produced comparable estimates of the burden of 291 diseases and injuries in 1990, 2005, and 2010. This article reports on the global burden of untreated caries, severe periodontitis, and severe tooth loss in 2010 and compares those figures with new estimates for 1990. We used disability-adjusted life-years (DALYs) and years lived with disability (YLDs) metrics to quantify burden. Oral conditions affected 3.9 billion people, and untreated caries in permanent teeth was the most prevalent condition evaluated for the entire GBD 2010 Study (global prevalence of 35% for all ages combined). Oral conditions combined accounted for 15 million DALYs globally (1.9% of all YLDs; 0.6% of all DALYs), implying an average health loss of 224 years per 100,000 population. DALYs due to oral conditions increased 20.8% between 1990 and 2010, mainly due to population growth and aging. While DALYs due to severe periodontitis and untreated caries increased, those due to severe tooth loss decreased. DALYs differed by age groups and regions, but not by genders. The findings highlight the challenge in responding to the diversity of urgent oral health needs worldwide, particularly in developing communities.

Healthy life expectancy for 187 countries, 1990–2010: a systematic analysis for the Global Burden Disease Study 2010

BACKGROUND Healthy life expectancy (HALE) summarises mortality and non-fatal outcomes in a single measure of average population health. It has been used to compare health between countries, or to measure changes over time. These comparisons can inform policy questions that depend on how morbidity changes as mortality decreases. We characterise current HALE and changes over the past two decades in 187 countries. METHODS Using inputs from the Global Burden of Disease Study (GBD) 2010, we assessed HALE for 1990 and 2010. We calculated HALE with life table methods, incorporating estimates of average health over each age interval. Inputs from GBD 2010 included age-specific information for mortality rates and prevalence of 1160 sequelae, and disability weights associated with 220 distinct health states relating to these sequelae. We computed estimates of average overall health for each age group, adjusting for comorbidity with a Monte Carlo simulation method to capture how multiple morbidities can combine in an individual. We incorporated these estimates in the life table by the Sullivan method to produce HALE estimates for each population defined by sex, country, and year. We estimated the contributions of changes in child mortality, adult mortality, and disability to overall change in population health between 1990 and 2010. FINDINGS In 2010, global male HALE at birth was 58·3 years (uncertainty interval 56·7-59·8) and global female HALE at birth was 61·8 years (60·1-63·4). HALE increased more slowly than did life expectancy over the past 20 years, with each 1-year increase in life expectancy at birth associated with a 0·8-year increase in HALE. Across countries in 2010, male HALE at birth ranged from 27·9 years (17·3-36·5) in Haiti, to 68·8 years (67·0-70·4) in Japan. Female HALE at birth ranged from 37·1 years (26·9-43·7) in Haiti, to 71·7 years (69·7-73·4) in Japan. Between 1990 and 2010, male HALE increased by 5 years or more in 42 countries compared with 37 countries for female HALE, while male HALE decreased in 21 countries and 11 for female HALE. Between countries and over time, life expectancy was strongly and positively related to number of years lost to disability. This relation was consistent between sexes, in cross-sectional and longitudinal analysis, and when assessed at birth, or at age 50 years. Changes in disability had small effects on changes in HALE compared with changes in mortality. INTERPRETATION HALE differs substantially between countries. As life expectancy has increased, the number of healthy years lost to disability has also increased in most countries, consistent with the expansion of morbidity hypothesis, which has implications for health planning and health-care expenditure. Compared with substantial progress in reduction of mortality over the past two decades, relatively little progress has been made in reduction of the overall effect of non-fatal disease and injury on population health. HALE is an attractive indicator for monitoring health post-2015. FUNDING The Bill & Melinda Gates Foundation.

UK health performance: findings of the Global Burden of Disease Study 2010

BACKGROUND The UK has had universal free health care and public health programmes for more than six decades. Several policy initiatives and structural reforms of the health system have been undertaken. Health expenditure has increased substantially since 1990, albeit from relatively low levels compared with other countries. We used data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010) to examine the patterns of health loss in the UK, the leading preventable risks that explain some of these patterns, and how UK outcomes compare with a set of comparable countries in the European Union and elsewhere in 1990 and 2010. METHODS We used results of GBD 2010 for 1990 and 2010 for the UK and 18 other comparator nations (the original 15 members of the European Union, Australia, Canada, Norway, and the USA; henceforth EU15+). We present analyses of trends and relative performance for mortality, causes of death, years of life lost (YLLs), years lived with disability (YLDs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE). We present results for 259 diseases and injuries and for 67 risk factors or clusters of risk factors relevant to the UK. We assessed the UKs rank for age-standardised YLLs and DALYs for their leading causes compared with EU15+ in 1990 and 2010. We estimated 95% uncertainty intervals (UIs) for all measures. FINDINGS For both mortality and disability, overall health has improved substantially in absolute terms in the UK from 1990 to 2010. Life expectancy in the UK increased by 4·2 years (95% UI 4·2-4·3) from 1990 to 2010. However, the UK performed significantly worse than the EU15+ for age-standardised death rates, age-standardised YLL rates, and life expectancy in 1990, and its relative position had worsened by 2010. Although in most age groups, there have been reductions in age-specific mortality, for men aged 30-34 years, mortality rates have hardly changed (reduction of 3·7%, 95% UI 2·7-4·9). In terms of premature mortality, worsening ranks are most notable for men and women aged 20-54 years. For all age groups, the contributions of Alzheimers disease (increase of 137%, 16-277), cirrhosis (65%, ?15 to 107), and drug use disorders (577%, 71-942) to premature mortality rose from 1990 to 2010. In 2010, compared with EU15+, the UK had significantly lower rates of age-standardised YLLs for road injury, diabetes, liver cancer, and chronic kidney disease, but significantly greater rates for ischaemic heart disease, chronic obstructive pulmonary disease, lower respiratory infections, breast cancer, other cardiovascular and circulatory disorders, oesophageal cancer, preterm birth complications, congenital anomalies, and aortic aneurysm. Because YLDs per person by age and sex have not changed substantially from 1990 to 2010 but age-specific mortality has been falling, the importance of chronic disability is rising. The major causes of YLDs in 2010 were mental and behavioural disorders (including substance abuse; 21·5% [95 UI 17·2-26·3] of YLDs), and musculoskeletal disorders (30·5% [25·5-35·7]). The leading risk factor in the UK was tobacco (11·8% [10·5-13·3] of DALYs), followed by increased blood pressure (9·0 % [7·5-10·5]), and high body-mass index (8·6% [7·4-9·8]). Diet and physical inactivity accounted for 14·3% (95% UI 12·8-15·9) of UK DALYs in 2010. INTERPRETATION The performance of the UK in terms of premature mortality is persistently and significantly below the mean of EU15+ and requires additional concerted action. Further progress in premature mortality from several major causes, such as cardiovascular diseases and cancers, will probably require improved public health, prevention, early intervention, and treatment activities. The growing burden of disability, particularly from mental disorders, substance use, musculoskeletal disorders, and falls deserves an integrated and strategic response. FUNDING Bill & Melinda Gates Foundation.

Global burden of disease attributable to illicit drug use and dependence: findings from the Global Burden of Disease Study 2010.

BACKGROUND No systematic attempts have been made to estimate the global and regional prevalence of amphetamine, cannabis, cocaine, and opioid dependence, and quantify their burden. We aimed to assess the prevalence and burden of drug dependence, as measured in years of life lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life years (DALYs). METHODS We conducted systematic reviews of the epidemiology of drug dependence, and analysed results with Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010) Bayesian meta-regression technique (DisMod-MR) to estimate population-level prevalence of dependence and use. GBD 2010 calculated new disability weights by use of representative community surveys and an internet-based survey. We combined estimates of dependence with disability weights to calculate prevalent YLDs, YLLs, and DALYs, and estimated YLDs, YLLs, and DALYs attributable to drug use as a risk factor for other health outcomes. FINDINGS Illicit drug dependence directly accounted for 20·0 million DALYs (95% UI 15·3-25·4 million) in 2010, accounting for 0·8% (0·6-1·0) of global all-cause DALYs. Worldwide, more people were dependent on opioids and amphetamines than other drugs. Opioid dependence was the largest contributor to the direct burden of DALYs (9·2 million, 95% UI 7·1-11·4). The proportion of all-cause DALYs attributed to drug dependence was 20 times higher in some regions than others, with an increased proportion of burden in countries with the highest incomes. Injecting drug use as a risk factor for HIV accounted for 2·1 million DALYs (95% UI 1·1-3·6 million) and as a risk factor for hepatitis C accounted for 502,000 DALYs (286,000-891,000). Suicide as a risk of amphetamine dependence accounted for 854,000 DALYs (291,000-1,791,000), as a risk of opioid dependence for 671,000 DALYs (329,000-1,730,000), and as a risk of cocaine dependence for 324,000 DALYs (109,000-682,000). Countries with the highest rate of burden (>650 DALYs per 100,000 population) included the USA, UK, Russia, and Australia. INTERPRETATION Illicit drug use is an important contributor to the global burden of disease. Efficient strategies to reduce disease burden of opioid dependence and injecting drug use, such as delivery of opioid substitution treatment and needle and syringe programmes, are needed to reduce this burden at a population scale. FUNDING Australian National Health and Medical Research Council, Australian Government Department of Health and Ageing, Bill & Melinda Gates Foundation.

The global burden of viral hepatitis from 1990 to 2013: findings from the Global Burden of Disease Study 2013

BACKGROUND With recent improvements in vaccines and treatments against viral hepatitis, an improved understanding of the burden of viral hepatitis is needed to inform global intervention strategies. We used data from the Global Burden of Disease (GBD) Study to estimate morbidity and mortality for acute viral hepatitis, and for cirrhosis and liver cancer caused by viral hepatitis, by age, sex, and country from 1990 to 2013. METHODS We estimated mortality using natural history models for acute hepatitis infections and GBDs cause-of-death ensemble model for cirrhosis and liver cancer. We used meta-regression to estimate total cirrhosis and total liver cancer prevalence, as well as the proportion of cirrhosis and liver cancer attributable to each cause. We then estimated cause-specific prevalence as the product of the total prevalence and the proportion attributable to a specific cause. Disability-adjusted life-years (DALYs) were calculated as the sum of years of life lost (YLLs) and years lived with disability (YLDs). FINDINGS Between 1990 and 2013, global viral hepatitis deaths increased from 0·89 million (95% uncertainty interval [UI] 0·86-0·94) to 1·45 million (1·38-1·54); YLLs from 31·0 million (29·6-32·6) to 41·6 million (39·1-44·7); YLDs from 0·65 million (0·45-0·89) to 0·87 million (0·61-1·18); and DALYs from 31·7 million (30·2-33·3) to 42·5 million (39·9-45·6). In 2013, viral hepatitis was the seventh (95% UI seventh to eighth) leading cause of death worldwide, compared with tenth (tenth to 12th) in 1990. INTERPRETATION Viral hepatitis is a leading cause of death and disability worldwide. Unlike most communicable diseases, the absolute burden and relative rank of viral hepatitis increased between 1990 and 2013. The enormous health loss attributable to viral hepatitis, and the availability of effective vaccines and treatments, suggests an important opportunity to improve public health. FUNDING Bill & Melinda Gates Foundation.

Trust-based recommendation systems: an axiomatic approach

High-quality, personalized recommendations are a key feature in many online systems. Since these systems often have explicit knowledge of social network structures, the recommendations may incorporate this information. This paper focuses on networks that represent trust and recommendation systems that incorporate these trust relationships. The goal of a trust-based recommendation system is to generate personalized recommendations by aggregating the opinions of other users in the trust network. In analogy to prior work on voting and ranking systems, we use the axiomatic approach from the theory of social choice. We develop a set of five natural axioms that a trust-based recommendation system might be expected to satisfy. Then, we show that no system can simultaneously satisfy all the axioms. However, for any subset of four of the five axioms we exhibit a recommendation system that satisfies those axioms. Next we consider various ways of weakening the axioms, one of which leads to a unique recommendation system based on random walks. We consider other recommendation systems, including systems based on personalized PageRank, majority of majorities, and minimum cuts, and search for alternative axiomatizations that uniquely characterize these systems. Finally, we determine which of these systems are incentive compatible, meaning that groups of agents interested in manipulating recommendations can not induce others to share their opinion by lying about their votes or modifying their trust links. This is an important property for systems deployed in a monetized environment.

The Global Burden of Ischemic Heart Disease in 1990 and 2010 The Global Burden of Disease 2010 Study

Background— Ischemic heart disease (IHD) burden consists of years of life lost from IHD deaths and years of disability lived with 3 nonfatal IHD sequelae: nonfatal acute myocardial infarction, angina pectoris, and ischemic heart failure. Our aim was to estimate the global and regional burden of IHD in 1990 and 2010. Methods and Results— Global and regional estimates of acute myocardial infarction incidence and angina and heart failure prevalence by age, sex, and world region in 1990 and 2010 were estimated based on data from a systematic review and nonlinear mixed-effects meta-regression methods. Age-standardized acute myocardial infarction incidence and angina prevalence decreased globally between 1990 and 2010; ischemic heart failure prevalence increased slightly. The global burden of IHD increased by 29 million disability-adjusted life-years (29% increase) between 1990 and 2010. About 32.4% of the growth in global IHD disability-adjusted life-years between 1990 and 2010 was attributable to aging of the world population, 22.1% was attributable to population growth, and total disability-adjusted life-years were attenuated by a 25.3% decrease in per capita IHD burden (decreased rate). The number of people living with nonfatal IHD increased more than the number of IHD deaths since 1990, but >90% of IHD disability-adjusted life-years in 2010 were attributable to IHD deaths. Conclusions— Globally, age-standardized acute myocardial infarction incidence and angina prevalence have decreased, and ischemic heart failure prevalence has increased since 1990. Despite decreased age-standardized fatal and nonfatal IHD in most regions since 1990, population growth and aging led to a higher global burden of IHD in 2010.Background— Ischemic heart disease (IHD) burden consists of years of life lost from IHD deaths and years of disability lived with 3 nonfatal IHD sequelae: nonfatal acute myocardial infarction, angina pectoris, and ischemic heart failure. Our aim was to estimate the global and regional burden of IHD in 1990 and 2010. Methods and Results— Global and regional estimates of acute myocardial infarction incidence and angina and heart failure prevalence by age, sex, and world region in 1990 and 2010 were estimated based on data from a systematic review and nonlinear mixed-effects meta-regression methods. Age-standardized acute myocardial infarction incidence and angina prevalence decreased globally between 1990 and 2010; ischemic heart failure prevalence increased slightly. The global burden of IHD increased by 29 million disability-adjusted life-years (29% increase) between 1990 and 2010. About 32.4% of the growth in global IHD disability-adjusted life-years between 1990 and 2010 was attributable to aging of the world population, 22.1% was attributable to population growth, and total disability-adjusted life-years were attenuated by a 25.3% decrease in per capita IHD burden (decreased rate). The number of people living with nonfatal IHD increased more than the number of IHD deaths since 1990, but >90% of IHD disability-adjusted life-years in 2010 were attributable to IHD deaths. Conclusions— Globally, age-standardized acute myocardial infarction incidence and angina prevalence have decreased, and ischemic heart failure prevalence has increased since 1990. Despite decreased age-standardized fatal and nonfatal IHD in most regions since 1990, population growth and aging led to a higher global burden of IHD in 2010. # CLINICAL PERSPECTIVE {#article-title-30}