Mohsen Naghavi

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

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

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

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

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

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

Global malaria mortality between 1980 and 2010: a systematic analysis

BACKGROUND During the past decade, renewed global and national efforts to combat malaria have led to ambitious goals. We aimed to provide an accurate assessment of the levels and time trends in malaria mortality to aid assessment of progress towards these goals and the focusing of future efforts. METHODS We systematically collected all available data for malaria mortality for the period 1980-2010, correcting for misclassification bias. We developed a range of predictive models, including ensemble models, to estimate malaria mortality with uncertainty by age, sex, country, and year. We used key predictors of malaria mortality such as Plasmodium falciparum parasite prevalence, first-line antimalarial drug resistance, and vector control. We used out-of-sample predictive validity to select the final model. FINDINGS Global malaria deaths increased from 995,000 (95% uncertainty interval 711,000-1,412,000) in 1980 to a peak of 1,817,000 (1,430,000-2,366,000) in 2004, decreasing to 1,238,000 (929,000-1,685,000) in 2010. In Africa, malaria deaths increased from 493,000 (290,000-747,000) in 1980 to 1,613,000 (1,243,000-2,145,000) in 2004, decreasing by about 30% to 1,133,000 (848,000-1,591,000) in 2010. Outside of Africa, malaria deaths have steadily decreased from 502,000 (322,000-833,000) in 1980 to 104,000 (45,000-191,000) in 2010. We estimated more deaths in individuals aged 5 years or older than has been estimated in previous studies: 435,000 (307,000-658,000) deaths in Africa and 89,000 (33,000-177,000) deaths outside of Africa in 2010. INTERPRETATION Our findings show that the malaria mortality burden is larger than previously estimated, especially in adults. There has been a rapid decrease in malaria mortality in Africa because of the scaling up of control activities supported by international donors. Donor support, however, needs to be increased if malaria elimination and eradication and broader health and development goals are to be met. FUNDING The Bill & Melinda Gates Foundation.

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

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

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

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

Breast and cervical cancer in 187 countries between 1980 and 2010: a systematic analysis

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

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.

Global burden of diseases, injuries, and risk factors for young people's health during 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013.

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

Global and regional burden of first-ever ischaemic and haemorrhagic stroke during 1990–2010: findings from the Global Burden of Disease Study 2010

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