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ObjectiveWomen with heart failure with reduced ejection fraction (HFrEF) may reach optimal treatment effect at half of the guideline-recommended medication dose. This study investigates prescription practice and its relation with survival of patients with HF in daily care.MethodsElectronic health record data from 13 Dutch outpatient cardiology clinics were extracted for HF receiving at least one guideline-recommended HF medication. Dose changes over consecutive prescriptions were modelled using natural cubic splines. Inverse probability-weighted Cox regression was used to assess the relationship between dose (reference≥50% target dose) and all-cause mortality.ResultsThe study population comprised 561 women (29% HFrEF (ejection fraction (EF)ConclusionPatients with HF seen in outpatient cardiology clinics receive half of the guideline-recommended medication dose. Lower ACEI/ARB dose was associated with improved survival in women with HFrEF. These results underscore the importance of (re)defining optimal medical therapy for women with HFrEF.

ObjectiveIn the Netherlands, the threshold for offering active treatment for spontaneous birth was lowered from 25+0 to 24+0 weeks’ gestation in 2010. This study aimed to evaluate the impact of guideline implementation on survival and causes and timing of death in the years following implementation.DesignNational cohort study, using data from the Netherlands Perinatal Registry.PatientsThe study population included all 3312 stillborn and live born infants with a gestational age (GA) between 240/7 and 266/7 weeks born between January 2011 and December 2017. Infants with the same GA born between January 2007 and December 2009 (N=1400) were used as the reference group.Main outcome measuresSurvival to discharge, as well as cause and timing of death.ResultsAfter guideline implementation, there was a significant increase in neonatal intensive care unit (NICU) admission rate for live born infants born at 24 weeks’ GA (27%–69%, pConclusionsImplementation of the 2010 guideline resulted as expected in increased NICU admissions rate and postnatal survival of infants born at 24 weeks’ GA. In the years after implementation, a shift in cause of death was seen from respiratory insufficiency towards necrotising enterocolitis and sepsis.

BackgroundThe COVID-19 pandemic has resulted in a high death toll. We aimed to describe the place and cause of death during the COVID-19 pandemic.MethodsThis national death registry included all adult (aged ≥18 years) deaths in England and Wales between 1st January 2014 and 30th June 2020. Analyses were based upon ICD-10 codes corresponding to the underlying cause of death as stated on the Medical Certificate of Cause of Death. Daily deaths during COVID-19 pandemic were compared against the expected daily deaths estimated using Farrington surveillance algorithm for daily historical data between 2014 and 2020, by place and cause of death.FindingsBetween 2nd March and 30th June 2020, there was an excess mortality of 57,860 (a proportional increase of 35%) compared with the expected deaths, of which 50,603 (86.2%) were COVID-19 related. Almost half the excess deaths occurred in care homes (25,611 deaths) where deaths were 55% higher than expected. One fifth of the excess deaths occurred in hospital (15,938 deaths; a proportional increase of 21%) with the remainder occurring at home (16,190 deaths; a proportional increase of 39%). At home, only 14% of 16,190 excess deaths were related to COVID-19, with 5,963 deaths due to cancer and 2,485 deaths due to cardiac disease, very few of which involved COVID-19. In care homes or hospices, 61% of the 25,611 excess deaths were related to COVID-19, 5,539 of which were due to respiratory disease and most of these (4,315 deaths) involved COVID-19. In hospital, there were 16,174 fewer deaths than expected which did not involve COVID-19, and there were 4,088 fewer deaths due to cancer and 1,398 fewer deaths due to cardiac disease than expected.InterpretationThe COVID-19 pandemic has resulted in a substantial increase in the absolute numbers of deaths occurring at home and care homes. There was a huge burden of excess deaths occurring in care homes, which were poorly characterised, and were likely to be, at least in part, the result of undiagnosed COVID-19. There was a smaller but important and ongoing excess in deaths at home, particularly from cancer and cardiac disease, which suggests avoidance of hospital care for non-COVID-19 conditions.FundingThe study is unfunded.

BackgroundWe compared mortality inequalities by occupational class in Japan and South Korea with those in European countries, in order to determine whether patterns are similar.MethodsNational register-based data from Japan, South Korea and eight European countries (Finland, Denmark, England/Wales, France, Switzerland, Italy (Turin), Estonia, Lithuania) covering the period between 1990 and 2015 were collected and harmonised. We calculated age-standardised all-cause and cause-specific mortality among men aged 35–64 by occupational class and measured the magnitude of inequality with rate differences, rate ratios and the average inter-group difference.ResultsClear gradients in mortality were found in all European countries throughout the study period: manual workers had 1.6–2.5 times higher mortality than upper non-manual workers. However, in the most recent time-period, upper non-manual workers had higher mortality than manual workers in Japan and South Korea. This pattern emerged as a result of a rise in mortality among the upper non-manual group in Japan during the late 1990s, and in South Korea during the late 2000s, due to rising mortality from cancer and external causes (including suicide), in addition to strong mortality declines among lower non-manual and manual workers.ConclusionPatterns of mortality by occupational class are remarkably different between European countries and Japan and South Korea. The recently observed patterns in the latter two countries may be related to a larger impact on the higher occupational classes of the economic crisis of the late 1990s and the late 2000s, respectively, and show that a high socioeconomic position does not guarantee better health.

ObjectiveMost current cardiovascular disease (CVD) risk stratification tools are for people without CVD, but very few are for prevalent CVD. In this study, we developed and validated a CVD severity score in people with coronary heart disease (CHD) and evaluated the association between severity and adverse outcomes.MethodsPrimary and secondary care data for 213 088 people with CHD in 398 practices in England between 2007 and 2017 were used. The cohort was randomly divided into training and validation datasets (80%/20%) for the severity model. Using 20 clinical severity indicators (each assigned a weight=1), baseline and longitudinal CVD severity scores were calculated as the sum of indicators. Adjusted Cox and competing-risk regression models were used to estimate risks for all-cause and cause-specific hospitalisation and mortality.ResultsMean age was 64.5±12.7 years, 46% women, 16% from deprived areas, baseline severity score 1.5±1.2, with higher scores indicating a higher burden of disease. In the training dataset, 138 510 (81%) patients were hospitalised at least once, and 39 944 (23%) patients died. Each 1-unit increase in baseline severity was associated with 41% (95% CI 37% to 45%, area under the receiver operating characteristics (AUROC) curve=0.79) risk for 1 year for all-cause mortality; 59% (95% CI 52% to 67%, AUROC=0.80) for cardiovascular (CV)/diabetes mortality; 27% (95% CI 26% to 28%) for any-cause hospitalisation and 37% (95% CI 36% to 38%) for CV/diabetes hospitalisation. Findings were consistent in the validation dataset.ConclusionsHigher CVD severity score is associated with higher risks for any-cause and cause-specific hospital admissions and mortality in people with CHD. Our reproducible score based on routinely collected data can help practitioners better prioritise management of people with CHD in primary care.

Background Although previous studies have underscored some unique inequalities in occupational mortality in Japan, many of these trends have been dramatically altered during recent decades. We analyzed mortality data by occupation and industry in Japan, to determine whether differences remained by the mid-2010s for men in working-age population. Methods We calculated age-standardized all-cause and cause-specific mortality, according to occupation and industry, among men aged 25–64 years in the 2015 fiscal year (1 April 2015 to 31 March 2016). Occupational and industry-specific categories were defined using the Japan Standard Occupational Classification and Japan Standard Industrial Classification, respectively. Age-standardized mortality rates were computed using 5-year age intervals. Mortality rate ratios adjusted for age and 95% confidence intervals (CIs) were estimated using Poisson regression. Cause-specific deaths were classified into four broad groups (cancers [C00-D48], cardiovascular diseases [I00-I99], external causes [V01-Y98], and all other diseases) based on the International Statistical Classification of Diseases 10th Revision (ICD-10). Results Clear mortality differences were identified by both occupation and industry among Japanese males. All-cause mortality ranged from 53.7 (clerical workers) to 240.3 (service workers) per 100,000 population for occupation and from 54.3 (workers in education) to 1169.4 (workers in mining) for industry. In relative terms, service workers and agriculture, forestry, and fishing workers had 2.89 and 2.50 times higher all-cause mortality than sales workers. Administrative and managerial workers displayed higher mortality risk (1.86; 95% CI 1.76–1.97) than sales workers. Similar patterns of broad cause-specific mortality inequality were identified in terms of both absolute and relative measures, and all broad cause-specific deaths contributed to the differences in mortality by occupation and industry. Conclusions Substantial differences in mortality among Japanese male workers, according to occupation and industry, were still present in 2015.

BackgroundPeripheral arterial disease and vascular calcifications contribute significantly to the outcome of dialysis patients. The aim of this study was to evaluate the prognostic role of severity of abdominal aortic calcifications and peripheral arterial disease on outcome of peritoneal dialysis (PD) patients using methods easily available in everyday clinical practice.MethodsWe enrolled 249 PD patients (mean age 61 years, 67% male) in this prospective, observational, multicenter study from 2009 to 2013. The abdominal aortic calcification score (AACS) was assessed using lateral lumbar X ray, and the ankle-brachial index (ABI) using a Doppler device.ResultsThe median AACS was 11 (range 0 – 24). In 58% of the patients, all 4 segments of the abdominal aorta showed deposits, while 19% of patients had no visible deposits (AACS 0). Ankle-brachial index was normal in 49%, low (< 0.9) in 17%, and high (> 1.3) in 34% of patients. Altogether 91 patients (37%) died during the median follow-up of 46 months. Only 2 patients (5%) with AACS 0 died compared with 50% of the patients with AACS ≥ 7 ( p < 0.001). The adjusted hazard ratio for all-cause mortality was 4.85 (95% confidence interval [CI] 1.94 – 24.46) for aortic calcification (AACS ≥ 7), 2.14 for diabetes (yes/no), 0.93 for albumin (per 1 g/L), and 1.04 for age (per year). A low or high ABI were not independently associated with mortality.ConclusionsSevere aortic calcification was a strong predictor of all-cause mortality in PD patients. The evaluation of aortic calcifications by lateral X ray is a simple method that allows the identification of high-risk patients.

Aims: While heart failure with preserved (HFpEF) and reduced ejection fraction (HFrEF) are well described, determinants and outcomes of heart failure with mid-range ejection fraction (HFmrEF) remain unclear. We sought to examine clinical and biochemical predictors of incident HFmrEF in the community.Methods and results: We pooled data from four community-based longitudinal cohorts, with ascertainment of new heart failure (HF) classified into HFmrEF [ejection fraction (EF) 41-49%], HFpEF (EF ≥50%), and HFrEF (EF ≤40%). Predictors of incident HF subtypes were assessed using multivariable Cox models. Among 28 820 participants free of HF followed for a median of 12 years, there were 200 new HFmrEF cases, compared with 811 HFpEF and 1048 HFrEF. Clinical predictors of HFmrEF included age, male sex, systolic blood pressure, diabetes mellitus, and prior myocardial infarction (multivariable adjusted P ≤ 0.003 for all). Biomarkers that predicted HFmrEF included natriuretic peptides, cystatin-C, and high-sensitivity troponin (P ≤ 0.0004 for all). Natriuretic peptides were stronger predictors of HFrEF [hazard ratio (HR) 2.00 per 1 standard deviation increase, 95% confidence interval (CI) 1.81-2.20] than of HFmrEF (HR 1.51, 95% CI 1.20-1.90, P = 0.01 for difference), and did not differ in their association with incident HFmrEF and HFpEF (HR 1.56, 95% CI 1.41-1.73, P = 0.68 for difference). All-cause mortality following the onset of HFmrEF was worse than that of HFpEF (50 vs. 39 events per 1000 person-years, P = 0.02), but comparable to that of HFrEF (46 events per 1000 person-years, P = 0.78).Conclusions: We found overlap in predictors of incident HFmrEF with other HF subtypes. In contrast, mortality risk after HFmrEF was worse than HFpEF, and similar to HFrEF

BACKGROUND: An ischemic etiology of heart failure (HF) has been associated with reduced left ventricular reverse remodeling after cardiac resynchronization therapy (CRT). OBJECTIVE: The purpose of this study was to assess the relationship between the etiology of HF and reverse remodeling and outcome after CRT. METHODS: Consecutive patients undergoing CRT implantation between October 1, 2008 and August 14, 2015 were retrospectively evaluated. Coronary angiography classified ischemic vs nonischemic etiology. Reverse remodeling was defined as the changes in left ventricular ejection fraction (LVEF) after 6 months. Clinical outcome was assessed 1 year after implantation using a combined end point of all-cause mortality and HF readmission. RESULTS: A total of 685 patients were included (300/385 for ischemic/nonischemic etiology). Compared with patients with ischemic cardiomyopathy, patients with nonischemic cardiomyopathy exhibited a greater degree of improvement in LVEF (8.4% ± 10.4% vs 15.8% ± 12.3%; P < .001). After correcting for differences, an ischemic etiology of HF predicted less reverse remodeling (P < .001) and a higher rate of mortality or HF readmission (hazard ratio 1.63; 95% confidence interval [CI] 1.12-2.73; P = .011). Nevertheless, in comparison to a greater degree of improvement in LVEF, a lesser degree of improvement in LVEF (0%-5%) was associated with a higher risk of all-cause mortality and HF hospitalization in patients with nonischemic cardiomyopathy (odds ratio 9.78; 95% CI 1.95-49.04; P = .006) but not in patients with ischemic cardiomyopathy (odds ratio 3.58; 95% CI 0.85-15.18; P = .083). The most accurate cutoff for improvement in LVEF predicting good clinical outcome was 5.5% in ischemic cardiomyopathy vs 10.5% in nonischemic cardiomyopathy. CONCLUSION: CRT results in reverse remodeling in both patients with ischemic and nonischemic cardiomyopathy, but to a lesser extent in the former. Patients with an ischemic etiology are at an intrinsically higher risk of mortality and HF hospitalization, but derive benefit on outcome at a lesser degree of reverse remodeling.

Aims: While heart failure with preserved (HFpEF) and reduced ejection fraction (HFrEF) are well described, determinants and outcomes of heart failure with mid-range ejection fraction (HFmrEF) remain unclear. We sought to examine clinical and biochemical predictors of incident HFmrEF in the community. Methods and results: We pooled data from four community-based longitudinal cohorts, with ascertainment of new heart failure (HF) classified into HFmrEF [ejection fraction (EF) 41-49%], HFpEF (EF ≥50%), and HFrEF (EF ≤40%). Predictors of incident HF subtypes were assessed using multivariable Cox models. Among 28 820 participants free of HF followed for a median of 12 years, there were 200 new HFmrEF cases, compared with 811 HFpEF and 1048 HFrEF. Clinical predictors of HFmrEF included age, male sex, systolic blood pressure, diabetes mellitus, and prior myocardial infarction (multivariable adjusted P ≤ 0.003 for all). Biomarkers that predicted HFmrEF included natriuretic peptides, cystatin-C, and high-sensitivity troponin (P ≤ 0.0004 for all). Natriuretic peptides were stronger predictors of HFrEF [hazard ratio (HR) 2.00 per 1 standard deviation increase, 95% confidence interval (CI) 1.81-2.20] than of HFmrEF (HR 1.51, 95% CI 1.20-1.90, P = 0.01 for difference), and did not differ in their association with incident HFmrEF and HFpEF (HR 1.56, 95% CI 1.41-1.73, P = 0.68 for difference). All-cause mortality following the onset of HFmrEF was worse than that of HFpEF (50 vs. 39 events per 1000 person-years, P = 0.02), but comparable to that of HFrEF (46 events per 1000 person-years, P = 0.78). Conclusions: We found overlap in predictors of incident HFmrEF with other HF subtypes. In contrast, mortality risk after HFmrEF was worse than HFpEF, and similar to HFrEF

Background The effect of implantable cardioverter-defibrillator (ICD) therapy in patients with heart failure with reduced ejection fraction (HFrEF) and diabetes is not fully elucidated. Methods We examined the effect of ICD therapy on sudden cardiac death, cardiovascular death and all-cause mortality, according to diabetes status at baseline in the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT). The outcomes were analyzed by use of cumulative incidence curves and Cox regressions models. Results Of the 1676 patients randomized to an ICD or placebo, 540 (32%) had diabetes at baseline. Patients with diabetes were slightly older (61 vs 58 years) and were more often in NYHA class III (37% vs 28%). ICD therapy did not reduce the risk of sudden cardiac death in HFrEF patients with diabetes (HR = 0.85; 95% CI 0.52–1.40); even though these patients had a higher risk of sudden cardiac death compared to patients without diabetes (HR = 1.73 95% CI 1.22–2.47). By contrast, ICD therapy did reduce sudden cardiac death in HFrEF patients without diabetes (HR = 0.26; 95% CI 0.15–0.46); Pinteraction=0.002. The findings for cardiovascular and all-cause death were similar. Conclusion ICD therapy did not reduce the risk of sudden cardiac death (or, as a consequence, all-cause death) in HFrEF patients with diabetes. Conversely, an ICD reduced the risk of sudden death in patients without diabetes, irrespective of etiology. Electronic supplementary material The online version of this article (10.1007/s00392-019-01415-z) contains supplementary material, which is available to authorized users.

AIMS: We aimed to investigate major adverse cardiac events (MACE: defined as all-cause mortality, re-infarction, and stroke), length of hospital stays (LOS), and comorbidities following acute coronary syndrome (ACS) in a population with schizophrenia.METHODS AND RESULTS: This Danish register study included patients diagnosed with ACS in the period between 1995 and 2013 with a preceding diagnosis of schizophrenia (n = 726). Each patient was matched to a psychiatric healthy control 1:2 on sex, age, year of ACS diagnosis, and number of comorbidities (total n = 2178). After performing Cox regression and Kaplan-Meier analyses, we found that patients with schizophrenia had an increased risk of MACE [hazard ratio (HR) 1.62, 95% confidence interval (CI) 1.45-1.81], all-cause mortality (HR 2.54, 95% CI 2.22-2.90), and stroke (HR 1.51, 95% CI 1.15-1.99). No differences were found in the re-infarction rates and LOS between the populations. Patients with schizophrenia had higher prevalence's diabetes, anaemia, heart failure, cardiomyopathy, chronic obstructive lung disease, and stroke. Nonetheless, we found lower prevalence's of hypertension and hyperlipidaemia.CONCLUSION: Schizophrenia is associated with an increased risk of MACE despite a lower prevalence of some diagnosed traditional cardiac risk factors which may indicate underdiagnosing of these. Awareness of treatment bias may improve this increased risk. (Less)

OBJECTIVES: To use the estimates from the Global Burden of Disease Study 2016 to describe patterns of suicide mortality globally, regionally, and for 195 countries and territories by age, sex, and Socio-demographic index, and to describe temporal trends between 1990 and 2016. DESIGN: Systematic analysis. MAIN OUTCOME MEASURES: Crude and age standardised rates from suicide mortality and years of life lost were compared across regions and countries, and by age, sex, and Socio-demographic index (a composite measure of fertility, income, and education). RESULTS: The total number of deaths from suicide increased by 6.7% (95% uncertainty interval 0.4% to 15.6%) globally over the 27 year study period to 817 000 (762 000 to 884 000) deaths in 2016. However, the age standardised mortality rate for suicide decreased by 32.7% (27.2% to 36.6%) worldwide between 1990 and 2016, similar to the decline in the global age standardised mortality rate of 30.6%. Suicide was the leading cause of age standardised years of life lost in the Global Burden of Disease region of high income Asia Pacific and was among the top 10 leading causes in eastern Europe, central Europe, western Europe, central Asia, Australasia, southern Latin America, and high income North America. Rates for men were higher than for women across regions, countries, and age groups, except for the 15 to 19 age group. There was variation in the female to male ratio, with higher ratios at lower levels of Socio-demographic index. Women experienced greater decreases in mortality rates (49.0%, 95% uncertainty interval 42.6% to 54.6%) than men (23.8%, 15.6% to 32.7%). CONCLUSIONS: Age standardised mortality rates for suicide have greatly reduced since 1990, but suicide remains an important contributor to mortality worldwide. Suicide mortality was variable across locations, between sexes, and between age groups. Suicide prevention strategies can be targeted towards vulnerable populations if they are informed by variations in mortality rates.

OBJECTIVES: To use the estimates from the Global Burden of Disease Study 2016 to describe patterns of suicide mortality globally, regionally, and for 195 countries and territories by age, sex, and Socio-demographic index, and to describe temporal trends between 1990 and 2016.DESIGN: Systematic analysis.MAIN OUTCOME MEASURES: Crude and age standardised rates from suicide mortality and years of life lost were compared across regions and countries, and by age, sex, and Socio-demographic index (a composite measure of fertility, income, and education).RESULTS: The total number of deaths from suicide increased by 6.7% (95% uncertainty interval 0.4% to 15.6%) globally over the 27 year study period to 817 000 (762 000 to 884 000) deaths in 2016. However, the age standardised mortality rate for suicide decreased by 32.7% (27.2% to 36.6%) worldwide between 1990 and 2016, similar to the decline in the global age standardised mortality rate of 30.6%. Suicide was the leading cause of age standardised years of life lost in the Global Burden of Disease region of high income Asia Pacific and was among the top 10 leading causes in eastern Europe, central Europe, western Europe, central Asia, Australasia, southern Latin America, and high income North America. Rates for men were higher than for women across regions, countries, and age groups, except for the 15 to 19 age group. There was variation in the female to male ratio, with higher ratios at lower levels of Socio-demographic index. Women experienced greater decreases in mortality rates (49.0%, 95% uncertainty interval 42.6% to 54.6%) than men (23.8%, 15.6% to 32.7%).CONCLUSIONS: Age standardised mortality rates for suicide have greatly reduced since 1990, but suicide remains an important contributor to mortality worldwide. Suicide mortality was variable across locations, between sexes, and between age groups. Suicide prevention strategies can be targeted towards vulnerable populations if they are informed by variations in mortality rates.

OBJECTIVES: To use the estimates from the Global Burden of Disease Study 2016 to describe patterns of suicide mortality globally, regionally, and for 195 countries and territories by age, sex, and Socio-demographic index, and to describe temporal trends between 1990 and 2016. DESIGN: Systematic analysis. MAIN OUTCOME MEASURES: Crude and age standardised rates from suicide mortality and years of life lost were compared across regions and countries, and by age, sex, and Socio-demographic index (a composite measure of fertility, income, and education). RESULTS: The total number of deaths from suicide increased by 6.7% (95% uncertainty interval 0.4% to 15.6%) globally over the 27 year study period to 817 000 (762 000 to 884 000) deaths in 2016. However, the age standardised mortality rate for suicide decreased by 32.7% (27.2% to 36.6%) worldwide between 1990 and 2016, similar to the decline in the global age standardised mortality rate of 30.6%. Suicide was the leading cause of age standardised years of life lost in the Global Burden of Disease region of high income Asia Pacific and was among the top 10 leading causes in eastern Europe, central Europe, western Europe, central Asia, Australasia, southern Latin America, and high income North America. Rates for men were higher than for women across regions, countries, and age groups, except for the 15 to 19 age group. There was variation in the female to male ratio, with higher ratios at lower levels of Socio-demographic index. Women experienced greater decreases in mortality rates (49.0%, 95% uncertainty interval 42.6% to 54.6%) than men (23.8%, 15.6% to 32.7%). CONCLUSIONS: Age standardised mortality rates for suicide have greatly reduced since 1990, but suicide remains an important contributor to mortality worldwide. Suicide mortality was variable across locations, between sexes, and between age groups. Suicide prevention strategies can be targeted towards vulnerable populations if they are informed by variations in mortality rates.

Objectives To use the estimates from the Global Burden of Disease Study 2016 to describe patterns of suicide mortality globally, regionally, and for 195 countries and territories by age, sex, and Socio-demographic index, and to describe temporal trends between 1990 and 2016. Design Systematic analysis. Main outcome measures Crude and age standardised rates from suicide mortality and years of life lost were compared across regions and countries, and by age, sex, and Socio-demographic index (a composite measure of fertility, income, and education). Results The total number of deaths from suicide increased by 6.7% (95% uncertainty interval 0.4% to 15.6%) globally over the 27 year study period to 817 000 (762 000 to 884 000) deaths in 2016. However, the age standardised mortality rate for suicide decreased by 32.7% (27.2% to 36.6%) worldwide between 1990 and 2016, similar to the decline in the global age standardised mortality rate of 30.6%. Suicide was the leading cause of age standardised years of life lost in the Global Burden of Disease region of high income Asia Pacific and was among the top 10 leading causes in eastern Europe, central Europe, western Europe, central Asia, Australasia, southern Latin America, and high income North America. Rates for men were higher than for women across regions, countries, and age groups, except for the 15 to 19 age group. There was variation in the female to male ratio, with higher ratios at lower levels of Socio-demographic index. Women experienced greater decreases in mortality rates (49.0%, 95% uncertainty interval 42.6% to 54.6%) than men (23.8%, 15.6% to 32.7%). Conclusions Age standardised mortality rates for suicide have greatly reduced since 1990, but suicide remains an important contributor to mortality worldwide. Suicide mortality was variable across locations, between sexes, and between age groups. Suicide prevention strategies can be targeted towards vulnerable populations if they are informed by variations in mortality rates.

Publisher´s version (útgefin grein)., Background Neurological disorders are increasingly recognised as major causes of death and disability worldwide. The aim of this analysis from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 is to provide the most comprehensive and up-to-date estimates of the global, regional, and national burden from neurological disorders.Methods We estimated prevalence, incidence, deaths, and disability-adjusted life-years (DALYs; the sum of years of life lost [YLLs] and years lived with disability [YLDs]) by age and sex for 15 neurological disorder categories (tetanus, meningitis, encephalitis, stroke, brain and other CNS cancers, traumatic brain injury, spinal cord injury, Alzheimer’s disease and other dementias, Parkinson’s disease, multiple sclerosis, motor neuron diseases, idiopathic epilepsy, migraine, tension-type headache, and a residual category for other less common neurological disorders) in 195 countries from 1990 to 2016. DisMod-MR 2.1, a Bayesian meta-regression tool, was the main method of estimation of prevalence and incidence, and the Cause of Death Ensemble model (CODEm) was used for mortality estimation. We quantified the contribution of 84 risks and combinations of risk to the disease estimates for the 15 neurological disorder categories using the GBD comparative risk assessment approach.Findings Globally, in 2016, neurological disorders were the leading cause of DALYs (276 million [95% UI 247–308]) and second leading cause of deaths (9·0 million [8·8–9·4]). The absolute number of deaths and DALYs from all neurological disorders combined increased (deaths by 39% [34–44] and DALYs by 15% [9–21]) whereas their age-standardised rates decreased (deaths by 28% [26–30] and DALYs by 27% [24–31]) between 1990 and 2016. The only neurological disorders that had a decrease in rates and absolute numbers of deaths and DALYs were tetanus, meningitis, and encephalitis. The four largest contributors of neurological DALYs were stroke (42·2% [38·6–46·1]), migraine (16·3% [11·7–20·8]), Alzheimer’s and other dementias (10·4% [9·0–12·1]), and meningitis (7·9% [6·6–10·4]). For the combined neurological disorders, age-standardised DALY rates were significantly higher in males than in females (male-to-female ratio 1·12 [1·05–1·20]), but migraine, multiple sclerosis, and tension-type headache were more common and caused more burden in females, with male-to-female ratios of less than 0·7. The 84 risks quantified in GBD explain less than 10% of neurological disorder DALY burdens, except stroke, for which 88·8% (86·5–90·9) of DALYs are attributable to risk factors, and to a lesser extent Alzheimer’s disease and other dementias (22·3% [11·8–35·1] of DALYs are risk attributable) and idiopathic epilepsy (14·1% [10·8–17·5] of DALYs are risk attributable).Interpretation Globally, the burden of neurological disorders, as measured by the absolute number of DALYs, continues to increase. As populations are growing and ageing, and the prevalence of major disabling neurological disorders steeply increases with age, governments will face increasing demand for treatment, rehabilitation, and support services for neurological disorders. The scarcity of established modifiable risks for most of the neurological burden demonstrates that new knowledge is required to develop effective prevention and treatment strategies., ROA is funded by the National Institutes of Health (U01HG010273). SMA acknowledges the International Centre for Casemix and Clinical Coding, Faculty of Medicine, National University of Malaysia and Department of Health Policy and Management, Faculty of Public Health, Kuwait University for the approval and support to participate in this research project. AAw acknowledges funding support from Department of Science and Technology, Government of India, New Delhi, through INSPIRE Faculty scheme. TBA acknowledges partial funding from the Institute of Medical Research and Medicinal Plant Studies. ABa is supported by the Public Health Agency of Canada. TWB was supported by the Alexander von Humboldt Foundation through the Alexander von Humboldt Professor Award, funded by the Federal Ministry of Education and Research. MSBS acknowledges support from the Australian Government Research and Training Program scholarship for a PhD degree at the Australian National University, Australia. JJC is supported by the Swedish Heart and Lung Foundation. FCar is supported by the European Union (FEDER funds POCI/01/0145/FEDER/007728 and POCI/01/0145/FEDER/007265) and National Funds (FCT/MEC, Fundacao para a Ciencia e a Tecnologia and Ministerio da Educacao e Ciencia) under the Partnership Agreements PT2020 UID/MULTI/04378/2013 and PT2020UID/QUI/50006/2013. EC is supported by an Australian Research Council Future Fellowship (FT3 140100085). KD is supported by a Wellcome Trust [Grant Number 201900] as part of his International Intermediate Fellowship. EF is supported by the European Union (FEDER funds POCI/01/0145/FEDER/007728 and POCI/01/0145/FEDER/007265) and National Funds (FCT/MEC, Fundacao para a Ciencia e a Tecnologia and Ministerio da Educacao e Ciencia) under the Partnership Agreements PT2020 UID/MULTI/04378/2013 and PT2020UID/QUI/50006/2013. SMSI is funded by the Institute for Physical Activity and Nutrition (IPAN), Deakin University and received funding from High Blood Pressure Research Council of Australia. YKa is a DBT/Wellcome Trust India Alliance Fellow in Public Health. YJK is supported by the Office of Research and Innovation at Xiamen University Malaysia. BL acknowledges funding from the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre. WDL is supported in part by U10NS086484 NINDS. SLo is funded by the German Federal Ministry of Education and Research (nutriCARD, grant agreement number 01EA1411A). RML is supported by a National Health and Medical Research Council (NHMRC) of Australia Senior Research Fellowship. AMa and the Imperial College London are grateful for support from the NW London NIHR Collaboration for Leadership in Applied Health Research and Care. JJM is supported by the Danish National Research Foundation (Niels Bohr Professorship), and the John Cade Fellowship (APP1056929) from NHMRC. TMei acknowledges additional institutional support from the Competence Cluster for Nutrition and Cardiovascular Health (nutriCARD), Jena-Halle-Leipzig. IMV is supported by the Sistema Nacional de Investigacion (Panama). MOO is supported by SIREN U54 U54HG007479 and SIBS Genomics R01NS107900 grants. AMS was supported by a fellowship from the Egyptian Fulbright Mission Program. MMSM acknowledges the support from the Ministry of Education, Science and Technological Development, Republic of Serbia (contract no 175087). AShe is supported by Health Data Research UK. MBS' work on traumatic brain injury is supported by grants NIH U01 NS086090 (PI G Manley) from the National Institutes of Health (NIH) and DoD W81XWH-14-2-0176 (PI G Manley) from the United States Department of Defense. RTS is supported in part by grant number PROMETEOII/2015/021 from Generalitat Valenciana and the national grant PI17/00719 from ISCIIIFEDER. AGT was supported by a Fellowship from the NHMRC (Australia; 1042600. KBT acknowledges funding supports from the Maurice Wilkins Centre for Biodiscovery, Cancer Society of New Zealand, Health Research Council, Gut Cancer Foundation, and the University of Auckland. CY acknowledges support from the National Natural Science Foundation of China (grant number 81773552) and the Chinese NSFC International Cooperation and Exchange Program (grant number 71661167007)., "Peer Reviewed"

BACKGROUND: Since the mid-1990s, excess mortality has increased markedly for adults aged 25-44 years in the north compared with the south of England. We examined the underlying causes of this excess mortality and the contribution of socioeconomic deprivation.METHODS: Mortality data from the Office of National Statistics for adults aged 25-44 years were aggregated and compared between England's five most northern versus five most southern government office regions between Jan 1, 1981, and Dec 31, 2016. Poisson regression models, adjusted for age and sex, were used to quantify excess mortality in the north compared with the south by underlying cause of death (accidents, alcohol related, cardiovascular disease and diabetes, drug related, suicide, cancer, and other causes). The role of socioeconomic deprivation, as measured by the 2015 Index of Multiple Deprivation, in explaining the excess and regional variability was also explored.FINDINGS: A mortality divide between the north and south appeared in the mid-1990s and rapidly expanded thereafter for deaths attributed to accidents, alcohol misuse, and drug misuse. In the 2014-16 period, the northern excess was incidence rate ratio (IRR) 1·47 (95% CI 1·39-1·54) for cardiovascular reasons, 2·09 (1·94-2·25) for alcohol misuse, and 1·60 (1·51-1·70) for drug misuse, across both men and women aged 25-44 years. National mortality rates for cardiovascular deaths declined over the study period but a longstanding gap between north and south persisted (from 33·3 [95% CI 31·8-34·8] in 1981 to 15·0 [14·0-15·9] in 2016 in the north vs from 23·5 [22·3-24·8] to 9·9 [9·2-10·5] in the south). Between 2014 and 2016, estimated excess numbers of death in the north versus the south for those aged 25-44 years were 1881 (95% CI 726-2627) for women and 3530 (2216-4511) for men. Socioeconomic deprivation explained up to two-thirds of the excess mortality in the north (IRR for northern effect reduced from 1·15 [95% CI 1·14-1·15; unadjusted] to 1·05 [1·04-1·05; adjusted for Index of Multiple Deprivation]). By 2016, in addition to the persistent north-south gap, mortality rates in London were lower than in all other regions, with IRRs ranging from IRR 1·13 (95% CI 1·12-1·15) for the East England to 1·22 (1·20-1·24) for the North East, even after adjusting for deprivation.INTERPRETATION: Sharp relative rises in deaths from cardiovascular reasons, alcohol misuse and drug misuse in the north compared with the south seem to have created new health divisions between England's regions. This gap might be due to exacerbation of existing social and health inequalities that have been experienced for many years. These divisions might suggest increasing psychological distress, despair, and risk taking among young and middle-aged adults, particularly outside of London.FUNDING: Medical Research Council and Wellcome Trust.

Background The risk of infective endocarditis (IE) is markedly increased in patients receiving chronic hemodialysis compared with the general population, but outcome data are sparse. The present study investigated causes and risk factors of mortality in a hemodialysis-treated end-stage kidney disease- (ESKD) and a non-ESKD population with staphylococcus (S.) aureus endocarditis. Methods Hemodialysis-treated ESKD patients with S. aureus endocarditis were identified from Danish National Registries and Non-ESKD patients from The East Danish Database on Endocarditis. For establishing the cause of death The Danish Registry of Cause of Death was used. Independent risk factors of outcome were identified in multivariable Cox regression models. Results One hundred twenty-one hemodialysis patients and 190 non-ESKD patients with S. aureus endocarditis were included during 1996–2012 and 2002–2012, respectively. The all-cause in-hospital mortality was 22.3% in hemodialysis- and 24.7% in non-ESKD patients. One-year mortality, excluding in-hospital mortality, was 26.4% in hemodialysis patients and 15.2% in non-ESKD patients. The hazard ratio of all-cause mortality in hemodialysis was 2.64 (95% CI 1.70–4.10) at > 70 days after admission compared with non-ESKD. Age (HR 1.03 (95% CI 1.02–1.04)) and diabetes mellitus (HR 2.17 (95% CI 1.54–3.10)) were independent risk factors of all-cause mortality. The hazard ratio of cardiovascular death in hemodialysis was 3.20 (95% CI 1.78–5.77) at > 81 days after admission compared with non-ESKD. Age and diabetes mellitus were independently related to cardiovascular death. Conclusion All-cause in-hospital mortality rates were similar in hemodialysis and non-ESKD patients with S. aureus endocarditis whereas one-year mortality rates were significantly increased in the hemodialysis population. Electronic supplementary material The online version of this article (10.1186/s12882-018-1016-0) contains supplementary material, which is available to authorized users.

Background Early withdrawal of recommended antiplatelet treatment with clopidogrel adversely affects prognosis following percutaneous coronary interventions. Optimal antiplatelet treatment is essential following ST ‐segment elevation myocardial infarction ( STEMI ) given the increased risk of thrombotic complications. This study assessed the frequency, predictors, and clinical impact of early prasugrel cessation in patients with STEMI undergoing primary percutaneous coronary interventions. Methods and Results We pooled patients with STEMI discharged on prasugrel in 2 prospective registries (Bern PCI Registry [ NCT 02241291] and SPUM ‐ ACS (Inflammation and Acute Coronary Syndromes) [ NCT 01000701]) and 1 STEMI trial ( COMFORTABLE ‐ AMI (Comparison of Biomatrix Versus Gazelle in ST‐Elevation Myocardial Infarction) [ NCT 00962416]). Prasugrel treatment status at 1 year was categorized as no cessation; crossover to another P2Y 12 ‐inhibitor; physician‐recommended discontinuation; and disruption because of bleeding, side effects, or patient noncompliance. In time‐dependent analyses, we assessed the impact of prasugrel cessation on the primary end point, a composite of cardiac death, myocardial infarction, and stroke. Of all 1830 included patients (17% women, mean age 59 years), 83% were treated with new‐generation drug‐eluting stents. At 1 year, any prasugrel cessation had occurred in 13.8% of patients including crossover (7.2%), discontinuation (3.7%), and disruption (2.9%). Independent predictors of any prasugrel cessation included female sex, age, and history of cerebrovascular event. The primary end point occurred in 5.2% of patients and was more frequent following disruption (hazard ratio 3.04, 95% confidence interval,1.34–6.91; P =0.008), without significant impact of crossover or discontinuation. Consistent findings were observed for all‐cause death, myocardial infarction, and stent thrombosis following prasugrel disruption. Conclusions In this contemporary study of patients with STEMI , early prasugrel cessation was not uncommon and primarily involved change to another P2Y 12 ‐inhibitor. Disruption was the only type of early prasugrel cessation associated with statistically significant excess in ischemic risk within 1 year following primary percutaneous coronary interventions.

AIMS: While heart failure with preserved (HFpEF) and reduced ejection fraction (HFrEF) are well described, determinants and outcomes of heart failure with mid-range ejection fraction (HFmrEF) remain unclear. We sought to examine clinical and biochemical predictors of incident HFmrEF in the community. METHODS AND RESULTS: We pooled data from four community-based longitudinal cohorts, with ascertainment of new heart failure (HF) classified into HFmrEF [ejection fraction (EF) 41-49%], HFpEF (EF ≥50%), and HFrEF (EF ≤40%). Predictors of incident HF subtypes were assessed using multivariable Cox models. Among 28 820 participants free of HF followed for a median of 12 years, there were 200 new HFmrEF cases, compared with 811 HFpEF and 1048 HFrEF. Clinical predictors of HFmrEF included age, male sex, systolic blood pressure, diabetes mellitus, and prior myocardial infarction (multivariable adjusted P ≤ 0.003 for all). Biomarkers that predicted HFmrEF included natriuretic peptides, cystatin-C, and high-sensitivity troponin (P ≤ 0.0004 for all). Natriuretic peptides were stronger predictors of HFrEF [hazard ratio (HR) 2.00 per 1 standard deviation increase, 95% confidence interval (CI) 1.81-2.20] than of HFmrEF (HR 1.51, 95% CI 1.20-1.90, P = 0.01 for difference), and did not differ in their association with incident HFmrEF and HFpEF (HR 1.56, 95% CI 1.41-1.73, P = 0.68 for difference). All-cause mortality following the onset of HFmrEF was worse than that of HFpEF (50 vs. 39 events per 1000 person-years, P = 0.02), but comparable to that of HFrEF (46 events per 1000 person-years, P = 0.78). CONCLUSIONS: We found overlap in predictors of incident HFmrEF with other HF subtypes. In contrast, mortality risk after HFmrEF was worse than HFpEF, and similar to HFrEF.

BACKGROUND: This Danish study evaluated the association between psychiatric comorbidity and the course of chronic obstructive pulmonary disease (COPD), lung cancer and tuberculosis (TB) of an entire nation.METHODS: Data from the Danish National Patient Registry (1998-2009), material status, gender, educational level, comorbidities, age at diagnosis and death, medication, and causes of death were extracted from national databases. We identified 71,874 patients with COPD and found 32,282 with a pre-index psychiatric comorbidity, 20,787 patients with lung cancer and found 8406 with a pre-index psychiatric comorbidity, and 3495 patients with TB and found 797 with a pre-index psychiatric morbidity. Within the three groups we compared the patients with/without a pre-index psychiatric comorbidity.RESULTS: We found a reduced survival in patients with COPD or TB and a pre-existing psychiatric comorbidity. For all three pulmonary diseases, we found significantly higher age (p CONCLUSION: To our knowledge, this is the first epidemiological study investigating the influence of a psychiatric comorbidity on the course of COPD, lung cancer and TB at a national level. Our results emphasize the importance of detecting these major respiratory diseases in patients with psychiatric comorbidities and intensifying the treatment and follow up of these patients.

AIMS: To compare the hazard of all-cause, chronic obstructive pulmonary disease (COPD) and heart failure (HF) hospitalization in carvedilol vs. metoprolol/bisoprolol/nebivolol users with COPD and concurrent HF from 2009 to 2012, and to evaluate the use and persistence in treatment of these β-blockers, their impact on the risk of COPD-related hospitalization, and the factors important for their selection.METHODS AND RESULTS: Cox and logistic regression were used for both unadjusted and adjusted analyses. Carvedilol users had a higher hazard of being hospitalized for HF compared with metoprolol/bisoprolol/nebivolol users in both the unadjusted [hazard ratio (HR) 1.74; 95% confidence interval (CI) 1.65-1.83] and adjusted (HR 1.61; 95% CI 1.52-1.70) analyses. No significant differences were found for all-cause and COPD hospitalization between the two groups. Carvedilol users had a significant lower restricted mean persistence time than metoprolol/bisoprolol/nebivolol users. Patients exposed to carvedilol had an odds ratio (OR) of 1.38 (95% CI 1.23-1.56) for being hospitalized due to COPD within 60 days after redeeming the first carvedilol prescription, which was similar to that observed in metoprolol/bisoprolol/nebivolol users (OR 1.37; 95% CI 1.27-1.48). Patients with concurrent chronic kidney disease had a higher probability of receiving carvedilol (OR 1.16; 95% CI 1.04-1.29).CONCLUSION: Carvedilol prescription carried an increased hazard of HF hospitalization and lower restricted mean persistence time among patients with COPD and concurrent HF. Additionally, we found a widespread phenomenon of carvedilol prescription at variance with the European Society of Cardiology guidelines and potential for improving the proportion of patients treated with β-blockers.

AIMS: Quantification of systolic function in patients with atrial fibrillation (AF) is challenging. A novel approach, based on RR interval correction, to counteract the varying heart cycle lengths in AF has recently been proposed. Whether this method is superior in patients with systolic heart failure (HFrEF) with AF remains unknown. This study investigates the prognostic value of RR interval-corrected peak global longitudinal strain {GLSc = GLS/[RR^(1/2)]} in relation to all-cause mortality in HFrEF patients displaying AF during echocardiographic examination.METHODS AND RESULTS: Echocardiograms from 151 patients with HFrEF and AF during examination were analysed offline. Peak global longitudinal strain (GLS) was averaged from 18 myocardial segments obtained from three apical views. GLS was indexed with the square root of the RR interval {GLSc = GLS/[RR^(1/2)]}. Endpoint was all-cause mortality. During a median follow-up of 2.7 years, 40 patients (26.5%) died. Neither uncorrected GLS (P = 0.056) nor left ventricular ejection fraction (P = 0.053) was significantly associated with all-cause mortality. After RR^(1/2) indexation, GLSc became a significant predictor of all-cause mortality (hazard ratio 1.16, 95% confidence interval 1.02-1.22, P = 0.014, per %/s^(1/2) decrease). GLSc remained an independent predictor of mortality after multivariable adjustment (age, sex, mean heart rate, mean arterial blood pressure, left atrial volume index, and E/e') (hazard ratio 1.17, 95% confidence interval 1.05-1.31, P = 0.005 per %/s^(1/2) decrease).CONCLUSIONS: Decreasing {GLSc = GLS/[RR^(1/2)]}, but not uncorrected GLS nor left ventricular ejection fraction, was significantly associated with increased risk of all-cause mortality in HFrEF patients with AF and remained an independent predictor after multivariable adjustment.

Objective To compare all-cause and cause-specific mortality among 3 distinct groups: within-country, rural-to-urban migrants, and rural and urban dwellers in a longitudinal cohort in Peru. Methods The PERU MIGRANT Study, a longitudinal cohort study, used an age-stratified and sex-stratified random sample of urban dwellers in a shanty town community in the capital city of Peru, rural dwellers in the Andes, and migrants from the Andes to the shanty town community. Participants underwent a questionnaire and anthropomorphic measurements at a baseline evaluation in 2007–2008 and at a follow-up visit in 2012–2013. Mortality was determined by death certificate or family interview. Results Of the 989 participants evaluated at baseline, 928 (94%) were evaluated at follow-up (mean age 48 years; 53% female). The mean follow-up time was 5.1 years, totalling 4732.8 person-years. In a multivariable survival model, and relative to urban dwellers, rural participants had lower all-cause mortality (HR=0.27; 95% CI 0.07 to 0.98), and both the rural (HR=0.07; 95% CI 0.01 to 0.87) and migrant (HR=0.13; 95% CI 0.02 to 0.81) groups had lower cardiovascular mortality. Conclusions Cardiovascular mortality of migrants remains similar to that of the rural group, suggesting that rural-to-urban migrants do not appear to catch up with urban mortality in spite of having a more urban cardiovascular risk factor profile.

Background Detailed assessments of mortality patterns, particularly age-specific mortality, represent a crucial input that enables health systems to target interventions to specific populations. Understanding how all-cause mortality has changed with respect to development status can identify exemplars for best practice. To accomplish this, the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) estimated age-specific and sex-specific all-cause mortality between 1970 and 2016 for 195 countries and territories and at the subnational level for the five countries with a population greater than 200 million in 2016. Methods We have evaluated how well civil registration systems captured deaths using a set of demographic methods called death distribution methods for adults and from consideration of survey and census data for children younger than 5 years. We generated an overall assessment of completeness of registration of deaths by dividing registered deaths in each location-year by our estimate of all-age deaths generated from our overall estimation process. For 163 locations, including subnational units in countries with a population greater than 200 million with complete vital registration (VR) systems, our estimates were largely driven by the observed data, with corrections for small fluctuations in numbers and estimation for recent years where there were lags in data reporting (lags were variable by location, generally between 1 year and 6 years). For other locations, we took advantage of different data sources available to measure under-5 mortality rates (U5MR) using complete birth histories, summary birth histories, and incomplete VR with adjustments; we measured adult mortality rate (the probability of death in individuals aged 15–60 years) using adjusted incomplete VR, sibling histories, and household death recall. We used the U5MR and adult mortality rate, together with crude death rate due to HIV in the GBD model life table system, to estimate age-specific and sex-specific death rates for each location-year. Using various international databases, we identified fatal discontinuities, which we defined as increases in the death rate of more than one death per million, resulting from conflict and terrorism, natural disasters, major transport or technological accidents, and a subset of epidemic infectious diseases; these were added to estimates in the relevant years. In 47 countries with an identified peak adult prevalence for HIV/AIDS of more than 0·5% and where VR systems were less than 65% complete, we informed our estimates of age-sex-specific mortality using the Estimation and Projection Package (EPP)-Spectrum model fitted to national HIV/AIDS prevalence surveys and antenatal clinic serosurveillance systems. We estimated stillbirths, early neonatal, late neonatal, and childhood mortality using both survey and VR data in spatiotemporal Gaussian process regression models. We estimated abridged life tables for all location-years using age-specific death rates. We grouped locations into development quintiles based on the Socio-demographic Index (SDI) and analysed mortality trends by quintile. Using spline regression, we estimated the expected mortality rate for each age-sex group as a function of SDI. We identified countries with higher life expectancy than expected by comparing observed life expectancy to anticipated life expectancy on the basis of development status alone. Findings Completeness in the registration of deaths increased from 28% in 1970 to a peak of 45% in 2013; completeness was lower after 2013 because of lags in reporting. Total deaths in children younger than 5 years decreased from 1970 to 2016, and slower decreases occurred at ages 5–24 years. By contrast, numbers of adult deaths increased in each 5-year age bracket above the age of 25 years. The distribution of annualised rates of change in age-specific mortality rate differed over the period 2000 to 2016 compared with earlier decades: increasing annualised rates of change were less frequent, although rising annualised rates of change still occurred in some locations, particularly for adolescent and younger adult age groups. Rates of stillbirths and under-5 mortality both decreased globally from 1970. Evidence for global convergence of death rates was mixed; although the absolute difference between age-standardised death rates narrowed between countries at the lowest and highest levels of SDI, the ratio of these death rates—a measure of relative inequality—increased slightly. There was a strong shift between 1970 and 2016 toward higher life expectancy, most noticeably at higher levels of SDI. Among countries with populations greater than 1 million in 2016, life expectancy at birth was highest for women in Japan, at 86·9 years (95% UI 86·7–87·2), and for men in Singapore, at 81·3 years (78·8–83·7) in 2016. Male life expectancy was generally lower than female life expectancy between 1970 and 2016, and the gap between male and female life expectancy increased with progression to higher levels of SDI. Some countries with exceptional health performance in 1990 in terms of the difference in observed to expected life expectancy at birth had slower progress on the same measure in 2016. Interpretation Globally, mortality rates have decreased across all age groups over the past five decades, with the largest improvements occurring among children younger than 5 years. However, at the national level, considerable heterogeneity remains in terms of both level and rate of changes in age-specific mortality; increases in mortality for certain age groups occurred in some locations. We found evidence that the absolute gap between countries in age-specific death rates has declined, although the relative gap for some age-sex groups increased. Countries that now lead in terms of having higher observed life expectancy than that expected on the basis of development alone, or locations that have either increased this advantage or rapidly decreased the deficit from expected levels, could provide insight into the means to accelerate progress in nations where progress has stalled. Funding Bill & Melinda Gates Foundation, and the National Institute on Aging and the National Institute of Mental Health of the National Institutes of Health. Background Detailed assessments of mortality patterns, particularly age-specific mortality, represent a crucial input that enables health systems to target interventions to specific populations. Understanding how all-cause mortality has changed with respect to development status can identify exemplars for best practice. To accomplish this, the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) estimated age-specific and sex-specific all-cause mortality between 1970 and 2016 for 195 countries and territories and at the subnational level for the five countries with a population greater than 200 million in 2016. Methods We have evaluated how well civil registration systems captured deaths using a set of demographic methods called death distribution methods for adults and from consideration of survey and census data for children younger than 5 years. We generated an overall assessment of completeness of registration of deaths by dividing registered deaths in each location-year by our estimate of all-age deaths generated from our overall estimation process. For 163 locations, including subnational units in countries with a population greater than 200 million with complete vital registration (VR) systems, our estimates were largely driven by the observed data, with corrections for small fluctuations in numbers and estimation for recent years where there were lags in data reporting (lags were variable by location, generally between 1 year and 6 years). For other locations, we took advantage of different data sources available to measure under-5 mortality rates (U5MR) using complete birth histories, summary birth histories, and incomplete VR with adjustments; we measured adult mortality rate (the probability of death in individuals aged 15–60 years) using adjusted incomplete VR, sibling histories, and household death recall. We used the U5MR and adult mortality rate, together with crude death rate due to HIV in the GBD model life table system, to estimate age-specific and sex-specific death rates for each location-year. Using various international databases, we identified fatal discontinuities, which we defined as increases in the death rate of more than one death per million, resulting from conflict and terrorism, natural disasters, major transport or technological accidents, and a subset of epidemic infectious diseases; these were added to estimates in the relevant years. In 47 countries with an identified peak adult prevalence for HIV/AIDS of more than 0·5% and where VR systems were less than 65% complete, we informed our estimates of age-sex-specific mortality using the Estimation and Projection Package (EPP)-Spectrum model fitted to national HIV/AIDS prevalence surveys and antenatal clinic serosurveillance systems. We estimated stillbirths, early neonatal, late neonatal, and childhood mortality using both survey and VR data in spatiotemporal Gaussian process regression models. We estimated abridged life tables for all location-years using age-specific death rates. We grouped locations into development quintiles based on the Socio-demographic Index (SDI) and analysed mortality trends by quintile. Using spline regression, we estimated the expected mortality rate for each age-sex group as a function of SDI. We identified countries with higher life expectancy than expected by comparing observed life expectancy to anticipated life expectancy on the basis of development status alone. Findings Completeness in the registration of deaths increased from 28% in 1970 to a peak of 45% in 2013; completeness was lower after 2013 because of lags in reporting. Total deaths in children younger than 5 years decreased from 1970 to 2016, and slower decreases occurred at ages 5–24 years. By contrast, numbers of adult deaths increased in each 5-year age bracket above the age of 25 years. The distribution of annualised rates of change in age-specific mortality rate differed over the period 2000 to 2016 compared with earlier decades: increasing annualised rates of change were less frequent, although rising annualised rates of change still occurred in some locations, particularly for adolescent and younger adult age groups. Rates of stillbirths and under-5 mortality both decreased globally from 1970. Evidence for global convergence of death rates was mixed; although the absolute difference between age-standardised death rates narrowed between countries at the lowest and highest levels of SDI, the ratio of these death rates—a measure of relative inequality—increased slightly. There was a strong shift between 1970 and 2016 toward higher life expectancy, most noticeably at higher levels of SDI. Among countries with populations greater than 1 million in 2016, life expectancy at birth was highest for women in Japan, at 86·9 years (95% UI 86·7–87·2), and for men in Singapore, at 81·3 years (78·8–83·7) in 2016. Male life expectancy was generally lower than female life expectancy between 1970 and 2016, and the gap between male and female life expectancy increased with progression to higher levels of SDI. Some countries with exceptional health performance in 1990 in terms of the difference in observed to expected life expectancy at birth had slower progress on the same measure in 2016. Interpretation Globally, mortality rates have decreased across all age groups over the past five decades, with the largest improvements occurring among children younger than 5 years. However, at the national level, considerable heterogeneity remains in terms of both level and rate of changes in age-specific mortality; increases in mortality for certain age groups occurred in some locations. We found evidence that the absolute gap between countries in age-specific death rates has declined, although the relative gap for some age-sex groups increased. Countries that now lead in terms of having higher observed life expectancy than that expected on the basis of development alone, or locations that have either increased this advantage or rapidly decreased the deficit from expected levels, could provide insight into the means to accelerate progress in nations where progress has stalled. Funding Bill & Melinda Gates Foundation, and the National Institute on Aging and the National Institute of Mental Health of the National Institutes of Health.

Background Measurement of changes in health across locations is useful to compare and contrast changing epidemiological patterns against health system performance and identify specific needs for resource allocation in research, policy development, and programme decision making. Using the Global Burden of Diseases, Injuries, and Risk Factors Study 2016, we drew from two widely used summary measures to monitor such changes in population health: disability-adjusted life-years (DALYs) and healthy life expectancy (HALE). We used these measures to track trends and benchmark progress compared with expected trends on the basis of the Socio-demographic Index (SDI). Methods We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2016. We calculated DALYs by summing years of life lost and years of life lived with disability for each location, age group, sex, and year. We estimated HALE using age-specific death rates and years of life lived with disability per capita. We explored how DALYs and HALE differed from expected trends when compared with the SDI: the geometric mean of income per person, educational attainment in the population older than age 15 years, and total fertility rate. Findings The highest globally observed HALE at birth for both women and men was in Singapore, at 75·2 years (95% uncertainty interval 71·9–78·6) for females and 72·0 years (68·8–75·1) for males. The lowest for females was in the Central African Republic (45·6 years [42·0–49·5]) and for males was in Lesotho (41·5 years [39·0–44·0]). From 1990 to 2016, global HALE increased by an average of 6·24 years (5·97–6·48) for both sexes combined. Global HALE increased by 6·04 years (5·74–6·27) for males and 6·49 years (6·08–6·77) for females, whereas HALE at age 65 years increased by 1·78 years (1·61–1·93) for males and 1·96 years (1·69–2·13) for females. Total global DALYs remained largely unchanged from 1990 to 2016 (–2·3% [–5·9 to 0·9]), with decreases in communicable, maternal, neonatal, and nutritional (CMNN) disease DALYs offset by increased DALYs due to non-communicable diseases (NCDs). The exemplars, calculated as the five lowest ratios of observed to expected age-standardised DALY rates in 2016, were Nicaragua, Costa Rica, the Maldives, Peru, and Israel. The leading three causes of DALYs globally were ischaemic heart disease, cerebrovascular disease, and lower respiratory infections, comprising 16·1% of all DALYs. Total DALYs and age-standardised DALY rates due to most CMNN causes decreased from 1990 to 2016. Conversely, the total DALY burden rose for most NCDs; however, age-standardised DALY rates due to NCDs declined globally. Interpretation At a global level, DALYs and HALE continue to show improvements. At the same time, we observe that many populations are facing growing functional health loss. Rising SDI was associated with increases in cumulative years of life lived with disability and decreases in CMNN DALYs offset by increased NCD DALYs. Relative compression of morbidity highlights the importance of continued health interventions, which has changed in most locations in pace with the gross domestic product per person, education, and family planning. The analysis of DALYs and HALE and their relationship to SDI represents a robust framework with which to benchmark location-specific health performance. Country-specific drivers of disease burden, particularly for causes with higher-than-expected DALYs, should inform health policies, health system improvement initiatives, targeted prevention efforts, and development assistance for health, including financial and research investments for all countries, regardless of their level of sociodemographic development. The presence of countries that substantially outperform others suggests the need for increased scrutiny for proven examples of best practices, which can help to extend gains, whereas the presence of underperforming countries suggests the need for devotion of extra attention to health systems that need more robust support. Funding Bill & Melinda Gates Foundation. Background Measurement of changes in health across locations is useful to compare and contrast changing epidemiological patterns against health system performance and identify specific needs for resource allocation in research, policy development, and programme decision making. Using the Global Burden of Diseases, Injuries, and Risk Factors Study 2016, we drew from two widely used summary measures to monitor such changes in population health: disability-adjusted life-years (DALYs) and healthy life expectancy (HALE). We used these measures to track trends and benchmark progress compared with expected trends on the basis of the Socio-demographic Index (SDI). Methods We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2016. We calculated DALYs by summing years of life lost and years of life lived with disability for each location, age group, sex, and year. We estimated HALE using age-specific death rates and years of life lived with disability per capita. We explored how DALYs and HALE differed from expected trends when compared with the SDI: the geometric mean of income per person, educational attainment in the population older than age 15 years, and total fertility rate. Findings The highest globally observed HALE at birth for both women and men was in Singapore, at 75·2 years (95% uncertainty interval 71·9–78·6) for females and 72·0 years (68·8–75·1) for males. The lowest for females was in the Central African Republic (45·6 years [42·0–49·5]) and for males was in Lesotho (41·5 years [39·0–44·0]). From 1990 to 2016, global HALE increased by an average of 6·24 years (5·97–6·48) for both sexes combined. Global HALE increased by 6·04 years (5·74–6·27) for males and 6·49 years (6·08–6·77) for females, whereas HALE at age 65 years increased by 1·78 years (1·61–1·93) for males and 1·96 years (1·69–2·13) for females. Total global DALYs remained largely unchanged from 1990 to 2016 (–2·3% [–5·9 to 0·9]), with decreases in communicable, maternal, neonatal, and nutritional (CMNN) disease DALYs offset by increased DALYs due to non-communicable diseases (NCDs). The exemplars, calculated as the five lowest ratios of observed to expected age-standardised DALY rates in 2016, were Nicaragua, Costa Rica, the Maldives, Peru, and Israel. The leading three causes of DALYs globally were ischaemic heart disease, cerebrovascular disease, and lower respiratory infections, comprising 16·1% of all DALYs. Total DALYs and age-standardised DALY rates due to most CMNN causes decreased from 1990 to 2016. Conversely, the total DALY burden rose for most NCDs; however, age-standardised DALY rates due to NCDs declined globally. Interpretation At a global level, DALYs and HALE continue to show improvements. At the same time, we observe that many populations are facing growing functional health loss. Rising SDI was associated with increases in cumulative years of life lived with disability and decreases in CMNN DALYs offset by increased NCD DALYs. Relative compression of morbidity highlights the importance of continued health interventions, which has changed in most locations in pace with the gross domestic product per person, education, and family planning. The analysis of DALYs and HALE and their relationship to SDI represents a robust framework with which to benchmark location-specific health performance. Country-specific drivers of disease burden, particularly for causes with higher-than-expected DALYs, should inform health policies, health system improvement initiatives, targeted prevention efforts, and development assistance for health, including financial and research investments for all countries, regardless of their level of sociodemographic development. The presence of countries that substantially outperform others suggests the need for increased scrutiny for proven examples of best practices, which can help to extend gains, whereas the presence of underperforming countries suggests the need for devotion of extra attention to health systems that need more robust support. Funding Bill & Melinda Gates Foundation.

Background As mortality rates decline, life expectancy increases, and populations age, non-fatal outcomes of diseases and injuries are becoming a larger component of the global burden of disease. The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) provides a comprehensive assessment of prevalence, incidence, and years lived with disability (YLDs) for 328 causes in 195 countries and territories from 1990 to 2016. Methods We estimated prevalence and incidence for 328 diseases and injuries and 2982 sequelae, their non-fatal consequences. We used DisMod-MR 2.1, a Bayesian meta-regression tool, as the main method of estimation, ensuring consistency between incidence, prevalence, remission, and cause of death rates for each condition. For some causes, we used alternative modelling strategies if incidence or prevalence needed to be derived from other data. YLDs were estimated as the product of prevalence and a disability weight for all mutually exclusive sequelae, corrected for comorbidity and aggregated to cause level. We updated the Socio-demographic Index (SDI), a summary indicator of income per capita, years of schooling, and total fertility rate. GBD 2016 complies with the Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER). Findings Globally, low back pain, migraine, age-related and other hearing loss, iron-deficiency anaemia, and major depressive disorder were the five leading causes of YLDs in 2016, contributing 57·6 million (95% uncertainty interval [UI] 40·8–75·9 million [7·2%, 6·0–8·3]), 45·1 million (29·0–62·8 million [5·6%, 4·0–7·2]), 36·3 million (25·3–50·9 million [4·5%, 3·8–5·3]), 34·7 million (23·0–49·6 million [4·3%, 3·5–5·2]), and 34·1 million (23·5–46·0 million [4·2%, 3·2–5·3]) of total YLDs, respectively. Age-standardised rates of YLDs for all causes combined decreased between 1990 and 2016 by 2·7% (95% UI 2·3–3·1). Despite mostly stagnant age-standardised rates, the absolute number of YLDs from non-communicable diseases has been growing rapidly across all SDI quintiles, partly because of population growth, but also the ageing of populations. The largest absolute increases in total numbers of YLDs globally were between the ages of 40 and 69 years. Age-standardised YLD rates for all conditions combined were 10·4% (95% UI 9·0–11·8) higher in women than in men. Iron-deficiency anaemia, migraine, Alzheimer's disease and other dementias, major depressive disorder, anxiety, and all musculoskeletal disorders apart from gout were the main conditions contributing to higher YLD rates in women. Men had higher age-standardised rates of substance use disorders, diabetes, cardiovascular diseases, cancers, and all injuries apart from sexual violence. Globally, we noted much less geographical variation in disability than has been documented for premature mortality. In 2016, there was a less than two times difference in age-standardised YLD rates for all causes between the location with the lowest rate (China, 9201 YLDs per 100 000, 95% UI 6862–11943) and highest rate (Yemen, 14 774 YLDs per 100 000, 11 018–19 228). Interpretation The decrease in death rates since 1990 for most causes has not been matched by a similar decline in age-standardised YLD rates. For many large causes, YLD rates have either been stagnant or have increased for some causes, such as diabetes. As populations are ageing, and the prevalence of disabling disease generally increases steeply with age, health systems will face increasing demand for services that are generally costlier than the interventions that have led to declines in mortality in childhood or for the major causes of mortality in adults. Up-to-date information about the trends of disease and how this varies between countries is essential to plan for an adequate health-system response. Funding Bill & Melinda Gates Foundation, and the National Institute on Aging and the National Institute of Mental Health of the National Institutes of Health. Background As mortality rates decline, life expectancy increases, and populations age, non-fatal outcomes of diseases and injuries are becoming a larger component of the global burden of disease. The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) provides a comprehensive assessment of prevalence, incidence, and years lived with disability (YLDs) for 328 causes in 195 countries and territories from 1990 to 2016. Methods We estimated prevalence and incidence for 328 diseases and injuries and 2982 sequelae, their non-fatal consequences. We used DisMod-MR 2.1, a Bayesian meta-regression tool, as the main method of estimation, ensuring consistency between incidence, prevalence, remission, and cause of death rates for each condition. For some causes, we used alternative modelling strategies if incidence or prevalence needed to be derived from other data. YLDs were estimated as the product of prevalence and a disability weight for all mutually exclusive sequelae, corrected for comorbidity and aggregated to cause level. We updated the Socio-demographic Index (SDI), a summary indicator of income per capita, years of schooling, and total fertility rate. GBD 2016 complies with the Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER). Findings Globally, low back pain, migraine, age-related and other hearing loss, iron-deficiency anaemia, and major depressive disorder were the five leading causes of YLDs in 2016, contributing 57·6 million (95% uncertainty interval [UI] 40·8–75·9 million [7·2%, 6·0–8·3]), 45·1 million (29·0–62·8 million [5·6%, 4·0–7·2]), 36·3 million (25·3–50·9 million [4·5%, 3·8–5·3]), 34·7 million (23·0–49·6 million [4·3%, 3·5–5·2]), and 34·1 million (23·5–46·0 million [4·2%, 3·2–5·3]) of total YLDs, respectively. Age-standardised rates of YLDs for all causes combined decreased between 1990 and 2016 by 2·7% (95% UI 2·3–3·1). Despite mostly stagnant age-standardised rates, the absolute number of YLDs from non-communicable diseases has been growing rapidly across all SDI quintiles, partly because of population growth, but also the ageing of populations. The largest absolute increases in total numbers of YLDs globally were between the ages of 40 and 69 years. Age-standardised YLD rates for all conditions combined were 10·4% (95% UI 9·0–11·8) higher in women than in men. Iron-deficiency anaemia, migraine, Alzheimer's disease and other dementias, major depressive disorder, anxiety, and all musculoskeletal disorders apart from gout were the main conditions contributing to higher YLD rates in women. Men had higher age-standardised rates of substance use disorders, diabetes, cardiovascular diseases, cancers, and all injuries apart from sexual violence. Globally, we noted much less geographical variation in disability than has been documented for premature mortality. In 2016, there was a less than two times difference in age-standardised YLD rates for all causes between the location with the lowest rate (China, 9201 YLDs per 100 000, 95% UI 6862–11943) and highest rate (Yemen, 14 774 YLDs per 100 000, 11 018–19 228). Interpretation The decrease in death rates since 1990 for most causes has not been matched by a similar decline in age-standardised YLD rates. For many large causes, YLD rates have either been stagnant or have increased for some causes, such as diabetes. As populations are ageing, and the prevalence of disabling disease generally increases steeply with age, health systems will face increasing demand for services that are generally costlier than the interventions that have led to declines in mortality in childhood or for the major causes of mortality in adults. Up-to-date information about the trends of disease and how this varies between countries is essential to plan for an adequate health-system response. Funding Bill & Melinda Gates Foundation, and the National Institute on Aging and the National Institute of Mental Health of the National Institutes of Health.

Background The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) provides a comprehensive assessment of risk factor exposure and attributable burden of disease. By providing estimates over a long time series, this study can monitor risk exposure trends critical to health surveillance and inform policy debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2016. This study included 481 risk-outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk (RR) and exposure estimates from 22 717 randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources, according to the GBD 2016 source counting methods. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. Finally, we explored four drivers of trends in attributable burden: population growth, population ageing, trends in risk exposure, and all other factors combined. Findings Since 1990, exposure increased significantly for 30 risks, did not change significantly for four risks, and decreased significantly for 31 risks. Among risks that are leading causes of burden of disease, child growth failure and household air pollution showed the most significant declines, while metabolic risks, such as body-mass index and high fasting plasma glucose, showed significant increases. In 2016, at Level 3 of the hierarchy, the three leading risk factors in terms of attributable DALYs at the global level for men were smoking (124·1 million DALYs [95% UI 111·2 million to 137·0 million]), high systolic blood pressure (122·2 million DALYs [110·3 million to 133·3 million], and low birthweight and short gestation (83·0 million DALYs [78·3 million to 87·7 million]), and for women, were high systolic blood pressure (89·9 million DALYs [80·9 million to 98·2 million]), high body-mass index (64·8 million DALYs [44·4 million to 87·6 million]), and high fasting plasma glucose (63·8 million DALYs [53·2 million to 76·3 million]). In 2016 in 113 countries, the leading risk factor in terms of attributable DALYs was a metabolic risk factor. Smoking remained among the leading five risk factors for DALYs for 109 countries, while low birthweight and short gestation was the leading risk factor for DALYs in 38 countries, particularly in sub-Saharan Africa and South Asia. In terms of important drivers of change in trends of burden attributable to risk factors, between 2006 and 2016 exposure to risks explains an 9·3% (6·9–11·6) decline in deaths and a 10·8% (8·3–13·1) decrease in DALYs at the global level, while population ageing accounts for 14·9% (12·7–17·5) of deaths and 6·2% (3·9–8·7) of DALYs, and population growth for 12·4% (10·1–14·9) of deaths and 12·4% (10·1–14·9) of DALYs. The largest contribution of trends in risk exposure to disease burden is seen between ages 1 year and 4 years, where a decline of 27·3% (24·9–29·7) of the change in DALYs between 2006 and 2016 can be attributed to declines in exposure to risks. Interpretation Increasingly detailed understanding of the trends in risk exposure and the RRs for each risk-outcome pair provide insights into both the magnitude of health loss attributable to risks and how modification of risk exposure has contributed to health trends. Metabolic risks warrant particular policy attention, due to their large contribution to global disease burden, increasing trends, and variable patterns across countries at the same level of development. GBD 2016 findings show that, while it has huge potential to improve health, risk modification has played a relatively small part in the past decade. Funding The Bill & Melinda Gates Foundation, Bloomberg Philanthropies. Background The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) provides a comprehensive assessment of risk factor exposure and attributable burden of disease. By providing estimates over a long time series, this study can monitor risk exposure trends critical to health surveillance and inform policy debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2016. This study included 481 risk-outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk (RR) and exposure estimates from 22 717 randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources, according to the GBD 2016 source counting methods. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. Finally, we explored four drivers of trends in attributable burden: population growth, population ageing, trends in risk exposure, and all other factors combined. Findings Since 1990, exposure increased significantly for 30 risks, did not change significantly for four risks, and decreased significantly for 31 risks. Among risks that are leading causes of burden of disease, child growth failure and household air pollution showed the most significant declines, while metabolic risks, such as body-mass index and high fasting plasma glucose, showed significant increases. In 2016, at Level 3 of the hierarchy, the three leading risk factors in terms of attributable DALYs at the global level for men were smoking (124·1 million DALYs [95% UI 111·2 million to 137·0 million]), high systolic blood pressure (122·2 million DALYs [110·3 million to 133·3 million], and low birthweight and short gestation (83·0 million DALYs [78·3 million to 87·7 million]), and for women, were high systolic blood pressure (89·9 million DALYs [80·9 million to 98·2 million]), high body-mass index (64·8 million DALYs [44·4 million to 87·6 million]), and high fasting plasma glucose (63·8 million DALYs [53·2 million to 76·3 million]). In 2016 in 113 countries, the leading risk factor in terms of attributable DALYs was a metabolic risk factor. Smoking remained among the leading five risk factors for DALYs for 109 countries, while low birthweight and short gestation was the leading risk factor for DALYs in 38 countries, particularly in sub-Saharan Africa and South Asia. In terms of important drivers of change in trends of burden attributable to risk factors, between 2006 and 2016 exposure to risks explains an 9·3% (6·9–11·6) decline in deaths and a 10·8% (8·3–13·1) decrease in DALYs at the global level, while population ageing accounts for 14·9% (12·7–17·5) of deaths and 6·2% (3·9–8·7) of DALYs, and population growth for 12·4% (10·1–14·9) of deaths and 12·4% (10·1–14·9) of DALYs. The largest contribution of trends in risk exposure to disease burden is seen between ages 1 year and 4 years, where a decline of 27·3% (24·9–29·7) of the change in DALYs between 2006 and 2016 can be attributed to declines in exposure to risks. Interpretation Increasingly detailed understanding of the trends in risk exposure and the RRs for each risk-outcome pair provide insights into both the magnitude of health loss attributable to risks and how modification of risk exposure has contributed to health trends. Metabolic risks warrant particular policy attention, due to their large contribution to global disease burden, increasing trends, and variable patterns across countries at the same level of development. GBD 2016 findings show that, while it has huge potential to improve health, risk modification has played a relatively small part in the past decade. Funding The Bill & Melinda Gates Foundation, Bloomberg Philanthropies.

Background Monitoring levels and trends in premature mortality is crucial to understanding how societies can address prominent sources of early death. The Global Burden of Disease 2016 Study (GBD 2016) provides a comprehensive assessment of cause-specific mortality for 264 causes in 195 locations from 1980 to 2016. This assessment includes evaluation of the expected epidemiological transition with changes in development and where local patterns deviate from these trends. Methods We estimated cause-specific deaths and years of life lost (YLLs) by age, sex, geography, and year. YLLs were calculated from the sum of each death multiplied by the standard life expectancy at each age. We used the GBD cause of death database composed of: vital registration (VR) data corrected for under-registration and garbage coding; national and subnational verbal autopsy (VA) studies corrected for garbage coding; and other sources including surveys and surveillance systems for specific causes such as maternal mortality. To facilitate assessment of quality, we reported on the fraction of deaths assigned to GBD Level 1 or Level 2 causes that cannot be underlying causes of death (major garbage codes) by location and year. Based on completeness, garbage coding, cause list detail, and time periods covered, we provided an overall data quality rating for each location with scores ranging from 0 stars (worst) to 5 stars (best). We used robust statistical methods including the Cause of Death Ensemble model (CODEm) to generate estimates for each location, year, age, and sex. We assessed observed and expected levels and trends of cause-specific deaths in relation to the Socio-demographic Index (SDI), a summary indicator derived from measures of average income per capita, educational attainment, and total fertility, with locations grouped into quintiles by SDI. Relative to GBD 2015, we expanded the GBD cause hierarchy by 18 causes of death for GBD 2016. Findings The quality of available data varied by location. Data quality in 25 countries rated in the highest category (5 stars), while 48, 30, 21, and 44 countries were rated at each of the succeeding data quality levels. Vital registration or verbal autopsy data were not available in 27 countries, resulting in the assignment of a zero value for data quality. Deaths from non-communicable diseases (NCDs) represented 72·3% (95% uncertainty interval [UI] 71·2–73·2) of deaths in 2016 with 19·3% (18·5–20·4) of deaths in that year occurring from communicable, maternal, neonatal, and nutritional (CMNN) diseases and a further 8·43% (8·00–8·67) from injuries. Although age-standardised rates of death from NCDs decreased globally between 2006 and 2016, total numbers of these deaths increased; both numbers and age-standardised rates of death from CMNN causes decreased in the decade 2006–16—age-standardised rates of deaths from injuries decreased but total numbers varied little. In 2016, the three leading global causes of death in children under-5 were lower respiratory infections, neonatal preterm birth complications, and neonatal encephalopathy due to birth asphyxia and trauma, combined resulting in 1·80 million deaths (95% UI 1·59 million to 1·89 million). Between 1990 and 2016, a profound shift toward deaths at older ages occurred with a 178% (95% UI 176–181) increase in deaths in ages 90–94 years and a 210% (208–212) increase in deaths older than age 95 years. The ten leading causes by rates of age-standardised YLL significantly decreased from 2006 to 2016 (median annualised rate of change was a decrease of 2·89%); the median annualised rate of change for all other causes was lower (a decrease of 1·59%) during the same interval. Globally, the five leading causes of total YLLs in 2016 were cardiovascular diseases; diarrhoea, lower respiratory infections, and other common infectious diseases; neoplasms; neonatal disorders; and HIV/AIDS and tuberculosis. At a finer level of disaggregation within cause groupings, the ten leading causes of total YLLs in 2016 were ischaemic heart disease, cerebrovascular disease, lower respiratory infections, diarrhoeal diseases, road injuries, malaria, neonatal preterm birth complications, HIV/AIDS, chronic obstructive pulmonary disease, and neonatal encephalopathy due to birth asphyxia and trauma. Ischaemic heart disease was the leading cause of total YLLs in 113 countries for men and 97 countries for women. Comparisons of observed levels of YLLs by countries, relative to the level of YLLs expected on the basis of SDI alone, highlighted distinct regional patterns including the greater than expected level of YLLs from malaria and from HIV/AIDS across sub-Saharan Africa; diabetes mellitus, especially in Oceania; interpersonal violence, notably within Latin America and the Caribbean; and cardiomyopathy and myocarditis, particularly in eastern and central Europe. The level of YLLs from ischaemic heart disease was less than expected in 117 of 195 locations. Other leading causes of YLLs for which YLLs were notably lower than expected included neonatal preterm birth complications in many locations in both south Asia and southeast Asia, and cerebrovascular disease in western Europe. Interpretation The past 37 years have featured declining rates of communicable, maternal, neonatal, and nutritional diseases across all quintiles of SDI, with faster than expected gains for many locations relative to their SDI. A global shift towards deaths at older ages suggests success in reducing many causes of early death. YLLs have increased globally for causes such as diabetes mellitus or some neoplasms, and in some locations for causes such as drug use disorders, and conflict and terrorism. Increasing levels of YLLs might reflect outcomes from conditions that required high levels of care but for which effective treatments remain elusive, potentially increasing costs to health systems. Funding Bill & Melinda Gates Foundation. Background Monitoring levels and trends in premature mortality is crucial to understanding how societies can address prominent sources of early death. The Global Burden of Disease 2016 Study (GBD 2016) provides a comprehensive assessment of cause-specific mortality for 264 causes in 195 locations from 1980 to 2016. This assessment includes evaluation of the expected epidemiological transition with changes in development and where local patterns deviate from these trends. Methods We estimated cause-specific deaths and years of life lost (YLLs) by age, sex, geography, and year. YLLs were calculated from the sum of each death multiplied by the standard life expectancy at each age. We used the GBD cause of death database composed of: vital registration (VR) data corrected for under-registration and garbage coding; national and subnational verbal autopsy (VA) studies corrected for garbage coding; and other sources including surveys and surveillance systems for specific causes such as maternal mortality. To facilitate assessment of quality, we reported on the fraction of deaths assigned to GBD Level 1 or Level 2 causes that cannot be underlying causes of death (major garbage codes) by location and year. Based on completeness, garbage coding, cause list detail, and time periods covered, we provided an overall data quality rating for each location with scores ranging from 0 stars (worst) to 5 stars (best). We used robust statistical methods including the Cause of Death Ensemble model (CODEm) to generate estimates for each location, year, age, and sex. We assessed observed and expected levels and trends of cause-specific deaths in relation to the Socio-demographic Index (SDI), a summary indicator derived from measures of average income per capita, educational attainment, and total fertility, with locations grouped into quintiles by SDI. Relative to GBD 2015, we expanded the GBD cause hierarchy by 18 causes of death for GBD 2016. Findings The quality of available data varied by location. Data quality in 25 countries rated in the highest category (5 stars), while 48, 30, 21, and 44 countries were rated at each of the succeeding data quality levels. Vital registration or verbal autopsy data were not available in 27 countries, resulting in the assignment of a zero value for data quality. Deaths from non-communicable diseases (NCDs) represented 72·3% (95% uncertainty interval [UI] 71·2–73·2) of deaths in 2016 with 19·3% (18·5–20·4) of deaths in that year occurring from communicable, maternal, neonatal, and nutritional (CMNN) diseases and a further 8·43% (8·00–8·67) from injuries. Although age-standardised rates of death from NCDs decreased globally between 2006 and 2016, total numbers of these deaths increased; both numbers and age-standardised rates of death from CMNN causes decreased in the decade 2006–16—age-standardised rates of deaths from injuries decreased but total numbers varied little. In 2016, the three leading global causes of death in children under-5 were lower respiratory infections, neonatal preterm birth complications, and neonatal encephalopathy due to birth asphyxia and trauma, combined resulting in 1·80 million deaths (95% UI 1·59 million to 1·89 million). Between 1990 and 2016, a profound shift toward deaths at older ages occurred with a 178% (95% UI 176–181) increase in deaths in ages 90–94 years and a 210% (208–212) increase in deaths older than age 95 years. The ten leading causes by rates of age-standardised YLL significantly decreased from 2006 to 2016 (median annualised rate of change was a decrease of 2·89%); the median annualised rate of change for all other causes was lower (a decrease of 1·59%) during the same interval. Globally, the five leading causes of total YLLs in 2016 were cardiovascular diseases; diarrhoea, lower respiratory infections, and other common infectious diseases; neoplasms; neonatal disorders; and HIV/AIDS and tuberculosis. At a finer level of disaggregation within cause groupings, the ten leading causes of total YLLs in 2016 were ischaemic heart disease, cerebrovascular disease, lower respiratory infections, diarrhoeal diseases, road injuries, malaria, neonatal preterm birth complications, HIV/AIDS, chronic obstructive pulmonary disease, and neonatal encephalopathy due to birth asphyxia and trauma. Ischaemic heart disease was the leading cause of total YLLs in 113 countries for men and 97 countries for women. Comparisons of observed levels of YLLs by countries, relative to the level of YLLs expected on the basis of SDI alone, highlighted distinct regional patterns including the greater than expected level of YLLs from malaria and from HIV/AIDS across sub-Saharan Africa; diabetes mellitus, especially in Oceania; interpersonal violence, notably within Latin America and the Caribbean; and cardiomyopathy and myocarditis, particularly in eastern and central Europe. The level of YLLs from ischaemic heart disease was less than expected in 117 of 195 locations. Other leading causes of YLLs for which YLLs were notably lower than expected included neonatal preterm birth complications in many locations in both south Asia and southeast Asia, and cerebrovascular disease in western Europe. Interpretation The past 37 years have featured declining rates of communicable, maternal, neonatal, and nutritional diseases across all quintiles of SDI, with faster than expected gains for many locations relative to their SDI. A global shift towards deaths at older ages suggests success in reducing many causes of early death. YLLs have increased globally for causes such as diabetes mellitus or some neoplasms, and in some locations for causes such as drug use disorders, and conflict and terrorism. Increasing levels of YLLs might reflect outcomes from conditions that required high levels of care but for which effective treatments remain elusive, potentially increasing costs to health systems. Funding Bill & Melinda Gates Foundation.

BACKGROUND: Little information is available about the prevalence and impact on exercise capacity and outcome of iron deficiency in heart failure with mid-range (HFmrEF) and preserved (HFpEF) ejection fraction in comparison to heart failure with reduced ejection-fraction (HFrEF). Furthermore, no data is available about the progression of ID in patients without baseline anaemia. METHODS: We evaluated baseline iron and haemoglobin-status in a single-centre, prospective heart failure database. Baseline functional status, VO2max, echocardiography and clinical-outcome (all-cause mortality and heart failure admissions) were evaluated. ID, anaemia, HFrEF, HFmrEF and HFpEF were defined according to established criteria. RESULTS: A total of 1197 patients (71% male) were evaluated (HFrEF, n = 897; HFmrEF, n = 229; HFpEF, n = 72). The overall prevalence of ID was 53% (50% in HFrEF; 61% in HFmrEF; 64% in HFpEF) and 36% for anaemia. ID was associated with a lower VO2max in patients with HFrEF, HFmrEF and HFpEF (p

The mechanisms behind the increased mortality in patients with acute myocardial infarction and co-existing severe mental illness (SMI) compared with non-SMI patients remain unclear. We studied 12,102 patients with ST-elevation myocardial infarction treated with primary percutaneous coronary intervention, of whom 457 had SMI. The primary outcome was major adverse cardiac events (death, myocardial infarction, target vessel revascularization) at 30 days, 1 year, 2 years, and maximum follow-up. Patients with SMI were younger, more often women, had higher prevalence of active smoking and diabetes, and had a longer duration of symptoms than patients without SMI. There were no substantial differences in the in-hospital treatment of patients with and without SMI. Fewer SMI patients were treated with the recommended medications during follow up; however, the absolute differences were modest. Compared with non-SMI patients, the cumulative risks of major adverse cardiac events after 1 year, 2 years, and maximum follow-up were higher among SMI patients [hazard ratio 1.27 (1.02 to 1.57), hazard ratio 1.32 (1.09 to 1.60), and hazard ratio 1.43 (1.25 to 1.65), respectively]. Even after adjustment for differences in baseline characteristics, the differences in outcome persisted. In conclusion, compared with patients without SMI, primary percutaneous coronary intervention treated patients with SMI had a worse baseline risk profile. No differences in in-hospital treatments were found. Although the absolute differences were small, SMI patients were less likely to receive recommended medical treatment during follow up and they face a worse prognosis, even after adjustment for differences in risk profile. This indicates that SMI per se is likely to have an adverse effect on the prognosis following ST-elevation myocardial infarction.

BACKGROUND: Detailed assessments of mortality patterns, particularly age-specific mortality, represent a crucial input that enables health systems to target interventions to specific populations. Understanding how all-cause mortality has changed with respect to development status can identify exemplars for best practice. To accomplish this, the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) estimated age-specific and sex-specific all-cause mortality between 1970 and 2016 for 195 countries and territories and at the subnational level for the five countries with a population greater than 200 million in 2016.METHODS: We have evaluated how well civil registration systems captured deaths using a set of demographic methods called death distribution methods for adults and from consideration of survey and census data for children younger than 5 years. We generated an overall assessment of completeness of registration of deaths by dividing registered deaths in each location-year by our estimate of all-age deaths generated from our overall estimation process. For 163 locations, including subnational units in countries with a population greater than 200 million with complete vital registration (VR) systems, our estimates were largely driven by the observed data, with corrections for small fluctuations in numbers and estimation for recent years where there were lags in data reporting (lags were variable by location, generally between 1 year and 6 years). For other locations, we took advantage of different data sources available to measure under-5 mortality rates (U5MR) using complete birth histories, summary birth histories, and incomplete VR with adjustments; we measured adult mortality rate (the probability of death in individuals aged 15-60 years) using adjusted incomplete VR, sibling histories, and household death recall. We used the U5MR and adult mortality rate, together with crude death rate due to HIV in the GBD model life table system, to estimate age-specific and sex-specific death rates for each location-year. Using various international databases, we identified fatal discontinuities, which we defined as increases in the death rate of more than one death per million, resulting from conflict and terrorism, natural disasters, major transport or technological accidents, and a subset of epidemic infectious diseases; these were added to estimates in the relevant years. In 47 countries with an identified peak adult prevalence for HIV/AIDS of more than 0·5% and where VR systems were less than 65% complete, we informed our estimates of age-sex-specific mortality using the Estimation and Projection Package (EPP)-Spectrum model fitted to national HIV/AIDS prevalence surveys and antenatal clinic serosurveillance systems. We estimated stillbirths, early neonatal, late neonatal, and childhood mortality using both survey and VR data in spatiotemporal Gaussian process regression models. We estimated abridged life tables for all location-years using age-specific death rates. We grouped locations into development quintiles based on the Socio-demographic Index (SDI) and analysed mortality trends by quintile. Using spline regression, we estimated the expected mortality rate for each age-sex group as a function of SDI. We identified countries with higher life expectancy than expected by comparing observed life expectancy to anticipated life expectancy on the basis of development status alone.FINDINGS: Completeness in the registration of deaths increased from 28% in 1970 to a peak of 45% in 2013; completeness was lower after 2013 because of lags in reporting. Total deaths in children younger than 5 years decreased from 1970 to 2016, and slower decreases occurred at ages 5-24 years. By contrast, numbers of adult deaths increased in each 5-year age bracket above the age of 25 years. The distribution of annualised rates of change in age-specific mortality rate differed over the period 2000 to 2016 compared with earlier decades: increasing annualised rates of change were less frequent, although rising annualised rates of change still occurred in some locations, particularly for adolescent and younger adult age groups. Rates of stillbirths and under-5 mortality both decreased globally from 1970. Evidence for global convergence of death rates was mixed; although the absolute difference between age-standardised death rates narrowed between countries at the lowest and highest levels of SDI, the ratio of these death rates-a measure of relative inequality-increased slightly. There was a strong shift between 1970 and 2016 toward higher life expectancy, most noticeably at higher levels of SDI. Among countries with populations greater than 1 million in 2016, life expectancy at birth was highest for women in Japan, at 86·9 years (95% UI 86·7-87·2), and for men in Singapore, at 81·3 years (78·8-83·7) in 2016. Male life expectancy was generally lower than female life expectancy between 1970 and 2016, and the gap between male and female life expectancy increased with progression to higher levels of SDI. Some countries with exceptional health performance in 1990 in terms of the difference in observed to expected life expectancy at birth had slower progress on the same measure in 2016.INTERPRETATION: Globally, mortality rates have decreased across all age groups over the past five decades, with the largest improvements occurring among children younger than 5 years. However, at the national level, considerable heterogeneity remains in terms of both level and rate of changes in age-specific mortality; increases in mortality for certain age groups occurred in some locations. We found evidence that the absolute gap between countries in age-specific death rates has declined, although the relative gap for some age-sex groups increased. Countries that now lead in terms of having higher observed life expectancy than that expected on the basis of development alone, or locations that have either increased this advantage or rapidly decreased the deficit from expected levels, could provide insight into the means to accelerate progress in nations where progress has stalled.FUNDING: Bill & Melinda Gates Foundation, and the National Institute on Aging and the National Institute of Mental Health of the National Institutes of Health.

Background Patients with aortic stenosis ( AS ) often have concomitant hypertension. Antihypertensive treatment with a β‐blocker (Bbl) is frequently avoided because of fear of depression of left ventricular function. However, it remains unclear whether antihypertensive treatment with a Bbl is associated with increased risk of cardiovascular events in patients with asymptomatic mild to moderate AS . Methods and Results We did a post hoc analysis of 1873 asymptomatic patients with mild to moderate AS and preserved left ventricular ejection fraction in the SEAS (Simvastatin and Ezetimibe in Aortic Stenosis) study. Propensity‐matched Cox regression and competing risk analyses were used to assess risk ratios for all‐cause mortality, sudden cardiac death, and cardiovascular death. A total of 932 (50%) patients received Bbl at baseline. During a median follow‐up of 4.3±0.9 years, 545 underwent aortic valve replacement, and 205 died; of those, 101 were cardiovascular deaths, including 40 sudden cardiovascular deaths. In adjusted analyses, Bbl use was associated with lower risk of all‐cause mortality (hazard ratio 0.5, 95% confidence interval 0.3‐0.7, P P P =0.004). This was confirmed in competing risk analyses (all P AS severity (all P >0.1). Conclusions In post hoc analyses Bbl therapy did not increase the risk of all‐cause mortality, sudden cardiac death, or cardiovascular death in patients with asymptomatic mild to moderate AS . A prospective study may be warranted to determine if Bbl therapy is in fact beneficial. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 00092677.

BACKGROUND: The burden of cardiovascular diseases (CVDs) remains unclear in many regions of the world.OBJECTIVES: The GBD (Global Burden of Disease) 2015 study integrated data on disease incidence, prevalence, and mortality to produce consistent, up-to-date estimates for cardiovascular burden.METHODS: CVD mortality was estimated from vital registration and verbal autopsy data. CVD prevalence was estimated using modeling software and data from health surveys, prospective cohorts, health system administrative data, and registries. Years lived with disability (YLD) were estimated by multiplying prevalence by disability weights. Years of life lost (YLL) were estimated by multiplying age-specific CVD deaths by a reference life expectancy. A sociodemographic index (SDI) was created for each location based on income per capita, educational attainment, and fertility.RESULTS: In 2015, there were an estimated 422.7 million cases of CVD (95% uncertainty interval: 415.53 to 427.87 million cases) and 17.92 million CVD deaths (95% uncertainty interval: 17.59 to 18.28 million CVD deaths). Declines in the age-standardized CVD death rate occurred between 1990 and 2015 in all high-income and some middle-income countries. Ischemic heart disease was the leading cause of CVD health lost globally, as well as in each world region, followed by stroke. As SDI increased beyond 0.25, the highest CVD mortality shifted from women to men. CVD mortality decreased sharply for both sexes in countries with an SDI >0.75.CONCLUSIONS: CVDs remain a major cause of health loss for all regions of the world. Sociodemographic change over the past 25 years has been associated with dramatic declines in CVD in regions with very high SDI, but only a gradual decrease or no change in most regions. Future updates of the GBD study can be used to guide policymakers who are focused on reducing the overall burden of noncommunicable disease and achieving specific global health targets for CVD.

Mortality among HIV-infected persons is decreasing, and causes of death are changing. Classification of deaths is hampered because of low autopsy rates, frequent deaths outside of hospitals, and shortcomings of International Statistical Classification of Diseases and Related Health Problems (ICD-10) coding.We studied mortality among Swiss HIV Cohort Study (SHCS) participants (1988-2010) and causes of death using the Coding Causes of Death in HIV (CoDe) protocol (2005-2009). Furthermore, we linked the SHCS data to the Swiss National Cohort (SNC) cause of death registry.AIDS-related mortality peaked in 1992 [11.0/100 person-years (PY)] and decreased to 0.144/100 PY (2006); non-AIDS-related mortality ranged between 1.74 (1993) and 0.776/100 PY (2006); mortality of unknown cause ranged between 2.33 and 0.206/100 PY. From 2005 to 2009, 459 of 9053 participants (5.1%) died. Underlying causes of deaths were: non-AIDS malignancies [total, 85 (19%) of 446 deceased persons with known hepatitis C virus (HCV) status; HCV-negative persons, 59 (24%); HCV-coinfected persons, 26 (13%)]; AIDS [73 (16%); 50 (21%); 23 (11%)]; liver failure [67 (15%); 12 (5%); 55 (27%)]; non-AIDS infections [42 (9%); 13 (5%); 29 (14%)]; substance use [31 (7%); 9 (4%); 22 (11%)]; suicide [28 (6%); 17 (7%), 11 (6%)]; myocardial infarction [28 (6%); 24 (10%), 4 (2%)]. Characteristics of deceased persons differed in 2005 vs. 2009: median age (45 vs. 49 years, respectively); median CD4 count (257 vs. 321 cells/μL, respectively); the percentage of individuals who were antiretroviral therapy-naïve (13 vs. 5%, respectively); the percentage of deaths that were AIDS-related (23 vs. 9%, respectively); and the percentage of deaths from non-AIDS-related malignancies (13 vs. 24%, respectively). Concordance in the classification of deaths was 72% between CoDe and ICD-10 coding in the SHCS; and 60% between the SHCS and the SNC registry.Mortality in HIV-positive persons decreased to 1.33/100 PY in 2010. Hepatitis B or C virus coinfections increased the risk of death. Between 2005 and 2009, 84% of deaths were non-AIDS-related. Causes of deaths varied according to data source and coding system.

Funding: This project was funded as an Applied Health Research Question (AHRQ), a process by which government-funded research organisations are funded to answer questions from relevant knowledge users. The Institute for Clinical Evaluative Sciences (ICES), which is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care (MOHLTC), was funded to carry out this AHRQ research question on behalf of Public Health Ontario, Ontario's expert technical and scientific public health organisation. Background: Historically, women have lower all-cause mortality than men. It is less understood that sex differences have been converging, particularly among certain subgroups and causes. This has implications for public health and health system planning. Our objective was to analyse contemporary sex differences over a 20-year period. Methods: We analysed data from a population-based death registry, the Ontario Registrar's General Death file, which includes all deaths recorded in Canada's most populous province, from 1992 to 2012 (N=1 710 080 deaths). We calculated absolute and relative mortality sex differences for all-cause and cause-specific mortality, age-adjusted and age-specific, including the following causes: circulatory, cancers, respiratory and injuries. We used negative-binomial regression of mortality on socioeconomic status with direct age adjustment for the overall population. Results: In the 20-year period, age-adjusted mortality dropped 39.2% and 29.8%, respectively, among men and women. The age-adjusted male-to-female mortality ratio dropped 41.4%, falling from 1.47 to 1.28. From 2000 onwards, all-cause mortality rates of high-income men were lower than those seen among low-income women. Relative mortality declines were greater among men than women for cancer, respiratory and injury-related deaths. The absolute decline in circulatory deaths was greater among men, although relative deciles were similar to women. The largest absolute mortality gains were seen among men over the age of 85 years. Conclusions: The large decline in mortality sex ratios in a Canadian province with universal healthcare over two decades signals an important population shift. These narrowing trends varied according to cause of death and age. In addition, persistent social inequalities in mortality exist and differentially affect men and women. The observed change in sex ratios has implications for healthcare and social systems. Publisher PDF

Objective: The risk of premature mortality is increased in people with epilepsy. The reasons for this and how it may relate to epilepsy etiology remain unclear. Methods: The National General Practice Study of Epilepsy is a prospective, community-based cohort that includes 558 people with recurrent unprovoked seizures of whom 34% died during almost 25 years of follow-up. We assessed the underlying and immediate causes of death and their relationship to epilepsy etiology. Psychiatric and somatic comorbidities of epilepsy as predictors of mortality were scrutinized using adjusted Cox proportional hazards models. Results: The 3 most common underlying causes of death were noncerebral neoplasm, cardiovascular, and cerebrovascular disease, accounting for 59% (111/189) of deaths, while epilepsy-related causes (e.g., sudden unexplained death in epilepsy) accounted for 3% (6/189) of deaths. In 23% (43/189) of individuals, the underlying cause of death was directly related to the epilepsy etiology; this was significantly more likely if death occurred within 2 years of the index seizure (percent ratio 4.28 [95% confidence interval 2.63–6.97]). Specific comorbidities independently associated with increased risk of mortality were neoplasms (primary cerebral and noncerebral neoplasm), certain neurologic diseases, and substance abuse. Conclusions: Comorbid diseases are important causes of death, as well as predictors of premature mortality in epilepsy. There is an especially strong relationship between cause of death and epilepsy etiology in the first 2 years after the index seizure. Addressing these issues may help stem the tide of premature mortality in epilepsy.

BACKGROUND AND PURPOSE: Multiple sclerosis (MS) has been associated with increased mortality rates. However, influence of lifestyle parameters remains unknown, and inconsistencies exist regarding findings for causes of death. METHODS: We conducted a population-based cohort study using the General Practice Research Database, Hospital Episode Statistics, and national death certificates (January 2001 through March 2008). To each patient with MS (n = 1270), up to six referent subjects without MS were matched by age, gender, and practice. Cox proportional hazards models were used to estimate mortality rate ratios (HRs). RESULTS: Patients with MS had a 3.5-fold increased mortality rate for all-cause mortality, compared with referent subjects (HR 3.51, 95% CI 2.63-4.69). The rate further increased amongst current smokers (HR 6.72, 95% CI 4.16-10.87) (but not in ex-smokers) and subjects with a body mass index of

BACKGROUND AND PURPOSE: Multiple sclerosis (MS) has been associated with increased mortality rates. However, influence of lifestyle parameters remains unknown, and inconsistencies exist regarding findings for causes of death.METHODS: We conducted a population-based cohort study using the General Practice Research Database, Hospital Episode Statistics, and national death certificates (January 2001 through March 2008). To each patient with MS (n = 1270), up to six referent subjects without MS were matched by age, gender, and practice. Cox proportional hazards models were used to estimate mortality rate ratios (HRs).RESULTS: Patients with MS had a 3.5-fold increased mortality rate for all-cause mortality, compared with referent subjects (HR 3.51, 95% CI 2.63-4.69). The rate further increased amongst current smokers (HR 6.72, 95% CI 4.16-10.87) (but not in ex-smokers) and subjects with a body mass index of CONCLUSION: British patients with MS have a 3.5-fold increased mortality rate compared with the general population. Smoking and respiratory diseases are major (potentially preventable) factors related to increased mortality rate amongst patients with MS.

OBJECTIVE: This study investigated the impact of the increasing consumption of selective serotonin reuptake inhibitors (SSRIs) and newer anti-depressants on the following public health indicators: (1) suicide rates, (2) proportion of completed suicides by poisoning with solid or liquid substances, and (3) hospital admissions for depression and proportion of admissions for depression that were first admissions. METHOD: Data collected by IMS Health on antidepressants dispensed in Italy from 1983 to 2000 were obtained from the Italian Ministry of Health, while data on suicide deaths from 1955 to 2000 were obtained from the Italian National Institute of Statistics. RESULTS: In Italy from 1983 to 2000, the use of tricyclic antidepressants remained substantially stable, and the use of SSRIs and newer agents dramatically increased. In contrast, suicide rates for males decreased from 1955 to 1974 and subsequently increased, reaching a peak in 1985 and then declining. In females, suicide rates remained substantially stable until 1978. A subsequent increase occurred up to 1985, followed by a steady decline. Suicide by poisoning using solids or liquids dropped by nearly 50% from 1986 to 2000. Admissions to the hospital for depression showed an erratic pattern; however, no decline was observed. No change was observed in the rate of first admissions for depression. CONCLUSION: Despite a reduction in suicides by poisoning using solids or liquids, the analysis of long-term trends in suicide did not suggest that increases in antidepressant prescribing lie behind recent reductions in population suicides. Furthermore, in Italy, newer antidepressants had no impact on the total number of admissions for depression or on the proportion of all admissions that were first admissions.

ObjectiveChanges in mortality inequalities across socioeconomic groups have been a substantial public health concern worldwide. We investigated changes in absolute/relative mortality inequalities across occupations, and the contribution of different diseases to inequalities in tandem with the restructuring of the Japanese economy.MethodsUsing complete Japanese national death registries from 5 year intervals (1980–2010), all cause and cause specific age standardised mortality rates (ASMR per 100 000 people standardised using the Japanese standard population in 1985, aged 30–59 years) across 12 occupations were computed. Absolute and relative inequalities were measured in ASMR differences (RDs) and ASMR ratios (RRs) among occupations in comparison with manufacturing workers (reference). We also estimated the changing contribution of different diseases by calculating the differences in ASMR change between 1995 and 2010 for occupations and reference.ResultsAll cause ASMRs tended to decrease in both sexes over the three decades except for male managers (increased by 71% points, 1995–2010). RDs across occupations were reduced for both sexes (civil servants 233.5 to −1.9 for men; sales workers 63.3 to 4.5 for women) but RRs increased for some occupations (professional workers 1.38 to 1.70; service workers 2.35 to 3.73) for men and decreased for women from 1980 to 2010. Male relative inequalities widened among farmer, fishery and service workers, because the percentage declines were smaller in these occupations. Cerebrovascular disease and cancer were the main causes of the decrease in mortality inequalities among sexes but the incidence of suicide increased among men, thereby increasing sex related inequalities.ConclusionsAbsolute inequality trends in mortality across occupations decreased in both sexes, while relative inequality trends were heterogeneous in Japan. The main drivers of narrowing and widening mortality inequalities were cerebrovascular disease and suicide, respectively. Future public health efforts will benefit from eliminating residual inequalities in mortality by considering the contribution of the causes of death and socioeconomic status stratification.

BACKGROUND Preparticipation screening programs have been suggested to reduce the numbers of sports-related sudden cardiac deaths (SrSCD). OBJECTIVE The purpose of this study was to identify and characterize all SrSCD aged 12-49 years and to address the difference in incidence rates between competitive and noncompetitive athletes. METHODS All deaths among persons aged 12-49 years from 2007-2009 were included. Death certificates were reviewed. History of previous admissions to hospital was assessed, and discharge summaries and autopsy reports were read. Sudden cardiac deaths (SCDs) and SrSCD cases were identified. RESULTS In the 3-year period, there were 881 SCDs, of which we identified 44 SrSCD. In noncompetitive athletes aged 12-35 years, the incidence rate of SrSCD was 0.43 (95% confidence interval [CI] 0.160.94) per 100,000 athlete person-years vs 2.95 (95% CI 1.95-4.30) in noncompetitive athletes aged 36-49 years. In competitive athletes, the incidence rate of SrSCD was 0.47 (95% CI 0.10-1.14) and 6.64 (95% Cl 2.86-13.1) per 100,000 athlete person-years in those aged 12-35 years and 36-49 years, respectively. The incidence rate of SCD in the general population was 10.7 (95% CI 10.0-11.5) per 100.000 person-years. CONCLUSION The incidence rates of SrSCD in noncompetitive and competitive athletes are not different. The study showed an increase in the incidence rate of SrSCD in persons aged 36-49 years in both noncompetitive and competitive athletes compared to those aged 12-35 years. Importantly, SCD in the general population is much more prevalent than is SrSCD in all age groups. Background Preparticipation screening programs have been suggested to reduce the numbers of sports-related sudden cardiac deaths (SrSCD). Objective The purpose of this study was to identify and characterize all SrSCD aged 12-49 years and to address the difference in incidence rates between competitive and noncompetitive athletes. Methods All deaths among persons aged 12-49 years from 2007-2009 were included. Death certificates were reviewed. History of previous admissions to hospital was assessed, and discharge summaries and autopsy reports were read. Sudden cardiac deaths (SCDs) and SrSCD cases were identified. Results In the 3-year period, there were 881 SCDs, of which we identified 44 SrSCD. In noncompetitive athletes aged 12-35 years, the incidence rate of SrSCD was 0.43 (95% confidence interval [CI] 0.16-0.94) per 100,000 athlete person-years vs 2.95 (95% CI 1.95-4.30) in noncompetitive athletes aged 36-49 years. In competitive athletes, the incidence rate of SrSCD was 0.47 (95% CI 0.10-1.14) and 6.64 (95% CI 2.86-13.1) per 100,000 athlete person-years in those aged 12-35 years and 36-49 years, respectively. The incidence rate of SCD in the general population was 10.7 (95% CI 10.0-11.5) per 100.000 person-years. Conclusion The incidence rates of SrSCD in noncompetitive and competitive athletes are not different. The study showed an increase in the incidence rate of SrSCD in persons aged 36-49 years in both noncompetitive and competitive athletes compared to those aged 12-35 years. Importantly, SCD in the general population is much more prevalent than is SrSCD in all age groups.

Recurrence of syncope is a common event, but the influence of recurrent syncope on the risk of death has not previously been investigated on a large scale. We 'examined the prognostic impact of recurrent syncope in a nationwide cohort of patients with syncope. All patients (n = 70,819) hospitalized from 2001 to 2009 in Denmark with a first-time diagnosis of syncope aged from 15 to 90 years were identified from national registries. Recurrence of syncope was incorporated as a time-dependent variable in multivariable-adjusted Cox models on the outcomes of 30-day, 1-year, and long-term all-cause mortality and cardiovascular death. During a mean follow-up of 3.9 +/- 2.6 years, a total of 11,621 patients (16.4%) had at least 1 hospitalization for recurrent syncope, with a median time to recurrence of 251 days (33 to 364). A total of 14,270 patients died, and 3,204 deaths were preceded by a hospitalization for recurrent syncope. The long-term risk of all-cause death was significantly associated with recurrent syncope (hazard ratio 2.64, 95% confidence interval 2.54 to 2.75) compared with those with no recurrence. On 1-year mortality, recurrent syncope was associated with a 3.2-fold increase in risk and on 30-day mortality associated with a threefold increase. The increased mortality risk was consistent over age groups 15 to 39, 40 to 59, and 60 to 89 years, and a similar pattern of increase in both long-term and short-term risk of cardiovascular death was evident. In conclusion, recurrent syncope is independently associated with all-cause and cardiovascular mortality across all age groups exhibiting a high prognostic influence. Increased awareness on high short-and longterm risk of adverse events in subjects with recurrent syncope is warranted for future risk stratification. (C) 2014 Elsevier Inc. All rights reserved.

We describe changes in prostate cancer incidence, survival and mortality and the resulting impact in additional diagnoses and avoided deaths in European areas and the United States.Using data from 12 European cancer registries and the Surveillance, Epidemiology and End Results program, we describe changes in prostate cancer epidemiology between the beginning of the PSA era (USA: 1985-1989, Europe: 1990-1994) and 2002-2006 among patients aged 40-64, 65-74, and 75+. Additionally, we examine changes in yearly numbers of diagnoses and deaths and variation in male life expectancy.Incidence and survival, particularly among patients aged75, increased dramatically, yet both remain (with few exceptions in incidence) lower in Europe than in the United States. Mortality reductions, ongoing since the mid/late 1990 s, were more consistent in the United States, had a distressingly small absolute impact among patients aged 40-64 and the largest absolute impact among those aged 75+. Overall ratios of additional diagnoses/avoided deaths varied between 3.6 and 27.6, suggesting large differences in the actual impact of prostate cancer incidence and mortality changes. Ten years of remaining life expectancy was reached between 68 and 76 years.Policies reflecting variation in population life expectancy, testing preferences, decision aids and guidelines for surveillance-based management are urgently needed.

BACKGROUND AND PURPOSE: Multiple sclerosis (MS) has been associated with increased mortality rates. However, influence of lifestyle parameters remains unknown, and inconsistencies exist regarding findings for causes of death. METHODS: We conducted a population-based cohort study using the General Practice Research Database, Hospital Episode Statistics, and national death certificates (January 2001 through March 2008). To each patient with MS (n = 1270), up to six referent subjects without MS were matched by age, gender, and practice. Cox proportional hazards models were used to estimate mortality rate ratios (HRs). RESULTS: Patients with MS had a 3.5-fold increased mortality rate for all-cause mortality, compared with referent subjects (HR 3.51, 95% CI 2.63-4.69). The rate further increased amongst current smokers (HR 6.72, 95% CI 4.16-10.87) (but not in ex-smokers) and subjects with a body mass index of

Background Wartime stress has been associated with increased late-life mortality of all causes of death. We evaluated whether wounded Finnish World War II veterans who were alive at the age of 55 have increased long-term coronary heart disease (CHD) mortality. Methods Health survey data were recorded in 1980 from 667 men, aged 55 years. Of them 102 had been wounded or injured in action during 1939-1945. The remaining participants served as the comparison group. The death certificates during a 28-year follow-up were obtained from the national statistics centre. Statistical comparisons were done by Cox proportional hazard regression model. Results There were altogether 140 deaths from CHD. In men who had been wounded or injured in action the crude CHD mortality rate per 10,000 population was 2843, while in the comparison group the corresponding figure was 1961. Men who had been wounded or injured in action were 1.7 times (95% CI 1.1-2.5; p = 0.01) more likely to die from CHD than the comparison group. Conclusions Physical trauma at young adulthood may extend to lifelong effects on health. This study suggests that being physically wounded or injured in war may lead to increased CHD mortality in late adulthood in a Finnish population.

Summary Background Pronounced changes in patterns of health take place in adolescence and young adulthood, but the effects on mortality patterns worldwide have not been reported. We analysed worldwide rates and patterns of mortality between early adolescence and young adulthood. Methods We obtained data from the 2004 Global Burden of Disease Study, and used all-cause mortality estimates developed for the 2006 World Health Report , with adjustments for revisions in death from HIV/AIDS and from war and natural disasters. Data for cause of death were derived from national vital registration when available; for other countries we used sample registration data, verbal autopsy, and disease surveillance data to model causes of death. Worldwide rates and patterns of mortality were investigated by WHO region, income status, and cause in age-groups of 10–14 years, 15–19 years, and 20–24 years. Findings 2·6 million deaths occurred in people aged 10–24 years in 2004. 2·56 million (97%) of these deaths were in low-income and middle-income countries, and almost two thirds (1·67 million) were in sub-Saharan Africa and southeast Asia. Pronounced rises in mortality rates were recorded from early adolescence (10–14 years) to young adulthood (20–24 years), but reasons varied by region and sex. Maternal conditions were a leading cause of female deaths at 15%. HIV/AIDS and tuberculosis contributed to 11% of deaths. Traffic accidents were the largest cause and accounted for 14% of male and 5% of female deaths. Other prominent causes included violence (12% of male deaths) and suicide (6% of all deaths). Interpretation Present global priorities for adolescent health policy, which focus on HIV/AIDS and maternal mortality, are an important but insufficient response to prevent mortality in an age-group in which more than two in five deaths are due to intentional and unintentional injuries. Funding WHO and National Health and Medical Research Council.

Correction: Group Author(s): GBD 2016 Causes Death LANCET Volume: 390 Issue: 10106 Pages: E38-E38 Published: OCT 28 2017 Group Author(s): GBD 2016 Dis Injury Incidence LANCET Volume: 390 Issue: 10106 Pages: E38-E38 Published: OCT 28 2017, Background Monitoring levels and trends in premature mortality is crucial to understanding how societies can address prominent sources of early death. The Global Burden of Disease 2016 Study (GBD 2016) provides a comprehensive assessment of cause-specific mortality for 264 causes in 195 locations from 1980 to 2016. This assessment includes evaluation of the expected epidemiological transition with changes in development and where local patterns deviate from these trends. Methods We estimated cause-specific deaths and years of life lost (YLLs) by age, sex, geography, and year. YLLs were calculated from the sum of each death multiplied by the standard life expectancy at each age. We used the GBD cause of death database composed of: vital registration (VR) data corrected for under-registration and garbage coding; national and subnational verbal autopsy (VA) studies corrected for garbage coding; and other sources including surveys and surveillance systems for specific causes such as maternal mortality. To facilitate assessment of quality, we reported on the fraction of deaths assigned to GBD Level 1 or Level 2 causes that cannot be underlying causes of death (major garbage codes) by location and year. Based on completeness, garbage coding, cause list detail, and time periods covered, we provided an overall data quality rating for each location with scores ranging from 0 stars (worst) to 5 stars (best). We used robust statistical methods including the Cause of Death Ensemble model (CODEm) to generate estimates for each location, year, age, and sex. We assessed observed and expected levels and trends of cause-specific deaths in relation to the Socio-demographic Index (SDI), a summary indicator derived from measures of average income per capita, educational attainment, and total fertility, with locations grouped into quintiles by SDI. Relative to GBD 2015, we expanded the GBD cause hierarchy by 18 causes of death for GBD 2016. Findings The quality of available data varied by location. Data quality in 25 countries rated in the highest category (5 stars), while 48, 30, 21, and 44 countries were rated at each of the succeeding data quality levels. Vital registration or verbal autopsy data were not available in 27 countries, resulting in the assignment of a zero value for data quality. Deaths from non-communicable diseases (NCDs) represented 72.3% (95% uncertainty interval [UI] 71.2-73.2) of deaths in 2016 with 19.3% (18.5-20.4) of deaths in that year occurring from communicable, maternal, neonatal, and nutritional (CMNN) diseases and a further 8.43% (8.00-8.67) from injuries. Although age-standardised rates of death from NCDs decreased globally between 2006 and 2016, total numbers of these deaths increased; both numbers and age-standardised rates of death from CMNN causes decreased in the decade 2006-16-age-standardised rates of deaths from injuries decreased but total numbers varied little. In 2016, the three leading global causes of death in children under-5 were lower respiratory infections, neonatal preterm birth complications, and neonatal encephalopathy due to birth asphyxia and trauma, combined resulting in 1.80 million deaths (95% UI 1.59 million to 1.89 million). Between 1990 and 2016, a profound shift toward deaths at older ages occurred with a 178% (95% UI 176-181) increase in deaths in ages 90-94 years and a 210% (208-212) increase in deaths older than age 95 years. The ten leading causes by rates of age-standardised YLL significantly decreased from 2006 to 2016 (median annualised rate of change was a decrease of 2.89%); the median annualised rate of change for all other causes was lower (a decrease of 1.59%) during the same interval. Globally, the five leading causes of total YLLs in 2016 were cardiovascular diseases; diarrhoea, lower respiratory infections, and other common infectious diseases; neoplasms; neonatal disorders; and HIV/AIDS and tuberculosis. At a finer level of disaggregation within cause groupings, the ten leading causes of total YLLs in 2016 were ischaemic heart disease, cerebrovascular disease, lower respiratory infections, diarrhoeal diseases, road injuries, malaria, neonatal preterm birth complications, HIV/AIDS, chronic obstructive pulmonary disease, and neonatal encephalopathy due to birth asphyxia and trauma. Ischaemic heart disease was the leading cause of total YLLs in 113 countries for men and 97 countries for women. Comparisons of observed levels of YLLs by countries, relative to the level of YLLs expected on the basis of SDI alone, highlighted distinct regional patterns including the greater than expected level of YLLs from malaria and from HIV/AIDS across sub-Saharan Africa; diabetes mellitus, especially in Oceania; interpersonal violence, notably within Latin America and the Caribbean; and cardiomyopathy and myocarditis, particularly in eastern and central Europe. The level of YLLs from ischaemic heart disease was less than expected in 117 of 195 locations. Other leading causes of YLLs for which YLLs were notably lower than expected included neonatal preterm birth complications in many locations in both south Asia and southeast Asia, and cerebrovascular disease in western Europe. Interpretation The past 37 years have featured declining rates of communicable, maternal, neonatal, and nutritional diseases across all quintiles of SDI, with faster than expected gains for many locations relative to their SDI. A global shift towards deaths at older ages suggests success in reducing many causes of early death. YLLs have increased globally for causes such as diabetes mellitus or some neoplasms, and in some locations for causes such as drug use disorders, and conflict and terrorism. Increasing levels of YLLs might reflect outcomes from conditions that required high levels of care but for which effective treatments remain elusive, potentially increasing costs to health systems., Bill & Melinda Gates Foundation.

BACKGROUND: The SYNTAX score (SXscore), an angiographic score reflecting coronary lesion complexity, predicts clinical outcomes in patients with left main or multivessel disease, and in patients with ST-segment elevation myocardial infarction undergoing primary PCI. The clinical SXscore (CSS) integrates the SXscore and clinical variables (age, ejection fraction, serum creatinine) into a single score. We analyzed these scores in elderly patients with acute coronary syndrome (ACS) undergoing primary PCI. The purpose of this analysis was not to decide which patients should undergo PCI, but to predict clinical outcomes in this population. METHODS: The SXscore was determined in a consecutive series of 114 elderly patients (mean age, 79.6 ± 4.1 years) undergoing primary PCI for ACS. Outcomes were stratified according to SXscore tertiles: SXLOW ≤15 (n = 39), 15< SXMID