The burden of antimicrobial resistance in the Americas in 2019: a cross-country systematic analysis

Background Antimicrobial resistance (AMR) is an urgent global health challenge and a critical threat to modern health care. Quantifying its burden in the WHO Region of the Americas has been elusive—despite the region’s long history of resistance surveillance. This study provides comprehensive estimates of AMR burden in the Americas to assess this growing health threat. Methods We estimated deaths and disability-adjusted life-years (DALYs) attributable to and associated with AMR for 23 bacterial pathogens and 88 pathogen–drug combinations for countries in the WHO Region of the Americas in 2019. We obtained data from mortality registries, surveillance systems, hospital systems, systematic literature reviews, and other sources, and applied predictive statistical modelling to produce estimates of AMR burden for all countries in the Americas. Five broad components were the backbone of our approach: the number of deaths where infection had a role, the proportion of infectious deaths attributable to a given infectious syndrome, the proportion of infectious syndrome deaths attributable to a given pathogen, the percentage of pathogens resistant to an antibiotic class, and the excess risk of mortality (or duration of an infection) associated with this resistance. We then used these components to estimate the disease burden by applying two counterfactual scenarios: deaths attributable to AMR (compared to an alternative scenario where resistant infections are replaced with susceptible ones), and deaths associated with AMR (compared to an alternative scenario where resistant infections would not occur at all). We generated 95% uncertainty intervals (UIs) for final estimates as the 25th and 975th ordered values across 1000 posterior draws, and models were cross-validated for out-of-sample predictive validity. Findings We estimated 569,000 deaths (95% UI 406,000–771,000) associated with bacterial AMR and 141,000 deaths (99,900–196,000) attributable to bacterial AMR among the 35 countries in the WHO Region of the Americas in 2019. Lower respiratory and thorax infections, as a syndrome, were responsible for the largest fatal burden of AMR in the region, with 189,000 deaths (149,000–241,000) associated with resistance, followed by bloodstream infections (169,000 deaths [94,200–278,000]) and peritoneal/intra-abdominal infections (118,000 deaths [78,600–168,000]). The six leading pathogens (by order of number of deaths associated with resistance) were Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Streptococcus pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii. Together, these pathogens were responsible for 452,000 deaths (326,000–608,000) associated with AMR. Methicillin-resistant S. aureus predominated as the leading pathogen–drug combination in 34 countries for deaths attributable to AMR, while aminopenicillin-resistant E. coli was the leading pathogen–drug combination in 15 countries for deaths associated with AMR. Interpretation Given the burden across different countries, infectious syndromes, and pathogen–drug combinations, AMR represents a substantial health threat in the Americas. Countries with low access to antibiotics and basic health-care services often face the largest age-standardised mortality rates associated with and attributable to AMR in the region, implicating specific policy interventions. Evidence from this study can guide mitigation efforts that are tailored to the needs of each country in the region while informing decisions regarding funding and resource allocation. Multisectoral and joint cooperative efforts among countries will be a key to success in tackling AMR in the Americas.publishedVersio

Burden of Stroke in Europe:An Analysis of the Global Burden of Disease Study Findings From 2010 to 2019

BACKGROUND:While most European Regions perform well in global comparisons, large discrepancies within stroke epidemiological parameters exist across Europe. The objective of this analysis was to evaluate the stroke burden across European regions and countries in 2019 and its difference to 2010.METHODS:The GBD 2019 analytical tools were used to evaluate regional and country-specific estimates of incidence, prevalence, deaths, and disability-adjusted life years of stroke for the European Region as defined by the World Health Organization, with its 53 member countries (EU-53) and for European Union as defined in 2019, with its 28 member countries (EU-28), between 2010 and 2019. Results were analyzed at a regional, subregional, and country level.RESULTS:In EU-53, the absolute number of incident and prevalent strokes increased by 2% (uncertainty interval [UI], 0%–4%), from 1 767 280 to 1 802 559 new cases, and by 4% (UI, 3%–5%) between 2010 and 2019, respectively. In EU-28, the absolute number of prevalent strokes and stroke-related deaths increased by 4% (UI, 2%–5%) and by 6% (UI, 1%–10%), respectively. All-stroke age-standardized mortality rates, however, decreased by 18% (UI, −22% to −14%), from 82 to 67 per 100 000 people in the EU-53, and by 15% (UI, −18% to −11%), from 49.3 to 42.0 per 100 000 people in EU-28. Despite most countries presenting reductions in age-adjusted incidence, prevalence, mortality, and disability-adjusted life year rates, these rates remained 1.4×, 1.2×, 1.6×, and 1.7× higher in EU-53 in comparison to the EU-28.CONCLUSIONS:EU-53 showed a 2% increase in incident strokes, while they remained stable in EU-28. Age-standardized rates were consistently lower for all-stroke burden parameters in EU-28 in comparison to EU-53, and huge discrepancies in incidence, prevalence, mortality, and disability-adjusted life-year rates were observed between individual countries.<br/

Global mortality from dementia: Application of a newmethod and results from the global burden of disease study 2019

INTRODUCTION: Dementia is currently one of the leading causes of mortality globally, and mortality due to dementia will likely increase in the future along with corresponding increases in population growth and population aging. However, large inconsistencies in coding practices in vital registration systems over time and between countries complicate the estimation of global dementia mortality. METHODS: We meta-analyzed the excess risk of death in those with dementia and multiplied these estimates by the proportion of dementia deaths occurring in those with severe, end-stage disease to calculate the total number of deaths that could be attributed to dementia. RESULTS: We estimated that there were 1.62 million (95% uncertainty interval [UI]: 0.41–4.21) deaths globally due to dementia in 2019. More dementia deaths occurred in women (1.06 million [0.27–2.71]) than men (0.56 million [0.14–1.51]), largely but not entirely due to the higher life expectancy in women (age-standardized female-to-male ratio 1.19 [1.10–1.26]). Due to population aging, there was a large increase in all-age mortality rates from dementia between 1990 and 2019 (100.1% [89.1–117.5]). In 2019, deaths due to dementia ranked seventh globally in all ages and fourth among individuals 70 and older compared to deaths from other diseases estimated in the Global Burden of Disease (GBD) study. DISCUSSION: Mortality due to dementia represents a substantial global burden, and is expected to continue to grow into the future as an older, aging population expands globally

Global, regional, and national prevalence and mortality burden of sickle cell disease, 2000–2021: a systematic analysis from the Global Burden of Disease Study 2021

Background Previous global analyses, with known underdiagnosis and single cause per death attribution systems, provide only a small insight into the suspected high population health effect of sickle cell disease. Completed as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021, this study delivers a comprehensive global assessment of prevalence of sickle cell disease and mortality burden by age and sex for 204 countries and territories from 2000 to 2021. Methods We estimated cause-specific sickle cell disease mortality using standardised GBD approaches, in which each death is assigned to a single underlying cause, to estimate mortality rates from the International Classification of Diseases (ICD)-coded vital registration, surveillance, and verbal autopsy data. In parallel, our goal was to estimate a more accurate account of sickle cell disease health burden using four types of epidemiological data on sickle cell disease: birth incidence, age-specific prevalence, with-condition mortality (total deaths), and excess mortality (excess deaths). Systematic reviews, supplemented with ICD-coded hospital discharge and insurance claims data, informed this modelling approach. We employed DisMod-MR 2.1 to triangulate between these measures—borrowing strength from predictive covariates and across age, time, and geography—and generated internally consistent estimates of incidence, prevalence, and mortality for three distinct genotypes of sickle cell disease: homozygous sickle cell disease and severe sickle cell β-thalassaemia, sickle-haemoglobin C disease, and mild sickle cell β-thalassaemia. Summing the three models yielded final estimates of incidence at birth, prevalence by age and sex, and total sickle cell disease mortality, the latter of which was compared directly against cause-specific mortality estimates to evaluate differences in mortality burden assessment and implications for the Sustainable Development Goals (SDGs). Findings Between 2000 and 2021, national incidence rates of sickle cell disease were relatively stable, but total births of babies with sickle cell disease increased globally by 13·7% (95% uncertainty interval 11·1–16·5), to 515 000 (425 000–614 000), primarily due to population growth in the Caribbean and western and central sub-Saharan Africa. The number of people living with sickle cell disease globally increased by 41·4% (38·3–44·9), from 5·46 million (4·62–6·45) in 2000 to 7·74 million (6·51–9·2) in 2021. We estimated 34 400 (25 000–45 200) cause-specific all-age deaths globally in 2021, but total sickle cell disease mortality burden was nearly 11-times higher at 376 000 (303 000–467 000). In children younger than 5 years, there were 81 100 (58 800–108 000) deaths, ranking total sickle cell disease mortality as 12th (compared to 40th for cause-specific sickle cell disease mortality) across all causes estimated by the GBD in 2021. Interpretation Our findings show a strikingly high contribution of sickle cell disease to all-cause mortality that is not apparent when each death is assigned to only a single cause. Sickle cell disease mortality burden is highest in children, especially in countries with the greatest under-5 mortality rates. Without comprehensive strategies to address morbidity and mortality associated with sickle cell disease, attainment of SDG 3.1, 3.2, and 3.4 is uncertain. Widespread data gaps and correspondingly high uncertainty in the estimates highlight the urgent need for routine and sustained surveillance efforts, further research to assess the contribution of conditions associated with sickle cell disease, and widespread deployment of evidence-based prevention and treatment for those with sickle cell disease.publishedVersio

The burden of mental disorders, substance use disorders and self-harm among young people in Europe, 1990–2019: Findings from the Global Burden of Disease Study 2019

Summary Background Mental health is a public health issue for European young people, with great heterogeneity in resource allocation. Representative population-based studies are needed. The Global Burden of Disease (GBD) Study 2019 provides internationally comparable information on trends in the health status of populations and changes in the leading causes of disease burden over time. Methods Prevalence, incidence, Years Lived with Disability (YLDs) and Years of Life Lost (YLLs) from mental disorders (MDs), substance use disorders (SUDs) and self-harm were estimated for young people aged 10-24 years in 31 European countries. Rates per 100,000 population, percentage changes in 1990-2019, 95% Uncertainty Intervals (UIs), and correlations with Sociodemographic Index (SDI), were estimated. Findings In 2019, rates per 100,000 population were 16,983 (95% UI 12,823 – 21,630) for MDs, 3,891 (3,020 - 4,905) for SUDs, and 89·1 (63·8 - 123·1) for self-harm. In terms of disability, anxiety contributed to 647·3 (432–912·3) YLDs, while in terms of premature death, self-harm contributed to 319·6 (248·9–412·8) YLLs, per 100,000 population. Over the 30 years studied, YLDs increased in eating disorders (14·9%;9·4-20·1) and drug use disorders (16·9%;8·9-26·3), and decreased in idiopathic developmental intellectual disability (–29·1%;23·8-38·5). YLLs decreased in self-harm (–27·9%;38·3-18·7). Variations were found by sex, age-group and country. The burden of SUDs and self-harm was higher in countries with lower SDI, MDs were associated with SUDs. Interpretation Mental health conditions represent an important burden among young people living in Europe. National policies should strengthen mental health, with a specific focus on young people.publishedVersio

Population-level risks of alcohol consumption by amount, geography, age, sex, and year: a systematic analysis for the Global Burden of Disease Study 2020

Background: The health risks associated with moderate alcohol consumption continue to be debated. Small amounts of alcohol might lower the risk of some health outcomes but increase the risk of others, suggesting that the overall risk depends, in part, on background disease rates, which vary by region, age, sex, and year. Methods: For this analysis, we constructed burden-weighted dose–response relative risk curves across 22 health outcomes to estimate the theoretical minimum risk exposure level (TMREL) and non-drinker equivalence (NDE), the consumption level at which the health risk is equivalent to that of a non-drinker, using disease rates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2020 for 21 regions, including 204 countries and territories, by 5-year age group, sex, and year for individuals aged 15–95 years and older from 1990 to 2020. Based on the NDE, we quantified the population consuming harmful amounts of alcohol. Findings: The burden-weighted relative risk curves for alcohol use varied by region and age. Among individuals aged 15–39 years in 2020, the TMREL varied between 0 (95% uncertainty interval 0–0) and 0·603 (0·400–1·00) standard drinks per day, and the NDE varied between 0·002 (0–0) and 1·75 (0·698–4·30) standard drinks per day. Among individuals aged 40 years and older, the burden-weighted relative risk curve was J-shaped for all regions, with a 2020 TMREL that ranged from 0·114 (0–0·403) to 1·87 (0·500–3·30) standard drinks per day and an NDE that ranged between 0·193 (0–0·900) and 6·94 (3·40–8·30) standard drinks per day. Among individuals consuming harmful amounts of alcohol in 2020, 59·1% (54·3–65·4) were aged 15–39 years and 76·9% (73·0–81·3) were male. Interpretation: There is strong evidence to support recommendations on alcohol consumption varying by age and location. Stronger interventions, particularly those tailored towards younger individuals, are needed to reduce the substantial global health loss attributable to alcohol. Funding: Bill & Melinda Gates Foundation

Spatial, temporal, and demographic patterns in prevalence of chewing tobacco use in 204 countries and territories, 1990-2019: A systematic analysis from the Global Burden of Disease Study 2019

Background: Chewing tobacco and other types of smokeless tobacco use have had less attention from the global health community than smoked tobacco use. However, the practice is popular in many parts of the world and has been linked to several adverse health outcomes. Understanding trends in prevalence with age, over time, and by location and sex is important for policy setting and in relation to monitoring and assessing commitment to the WHO Framework Convention on Tobacco Control. Methods: We estimated prevalence of chewing tobacco use as part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2019 using a modelling strategy that used information on multiple types of smokeless tobacco products. We generated a time series of prevalence of chewing tobacco use among individuals aged 15 years and older from 1990 to 2019 in 204 countries and territories, including age-sex specific estimates. We also compared these trends to those of smoked tobacco over the same time period. Findings: In 2019, 273·9 million (95% uncertainty interval 258·5 to 290·9) people aged 15 years and older used chewing tobacco, and the global age-standardised prevalence of chewing tobacco use was 4·72% (4·46 to 5·01). 228·2 million (213·6 to 244·7; 83·29% [82·15 to 84·42]) chewing tobacco users lived in the south Asia region. Prevalence among young people aged 15–19 years was over 10% in seven locations in 2019. Although global age-standardised prevalence of smoking tobacco use decreased significantly between 1990 and 2019 (annualised rate of change: –1·21% [–1·26 to –1·16]), similar progress was not observed for chewing tobacco (0·46% [0·13 to 0·79]). Among the 12 highest prevalence countries (Bangladesh, Bhutan, Cambodia, India, Madagascar, Marshall Islands, Myanmar, Nepal, Pakistan, Palau, Sri Lanka, and Yemen), only Yemen had a significant decrease in the prevalence of chewing tobacco use, which was among males between 1990 and 2019 (−0·94% [–1·72 to –0·14]), compared with nine of 12 countries that had significant decreases in the prevalence of smoking tobacco. Among females, none of these 12 countries had significant decreases in prevalence of chewing tobacco use, whereas seven of 12 countries had a significant decrease in the prevalence of tobacco smoking use for the period. Interpretation: Chewing tobacco remains a substantial public health problem in several regions of the world, and predominantly in south Asia. We found little change in the prevalence of chewing tobacco use between 1990 and 2019, and that control efforts have had much larger effects on the prevalence of smoking tobacco use than on chewing tobacco use in some countries. Mitigating the health effects of chewing tobacco requires stronger regulations and policies that specifically target use of chewing tobacco, especially in countries with high prevalence. Funding: Bloomberg Philanthropies and the Bill & Melinda Gates Foundation

The burden of mental disorders, substance use disorders and self-harm among young people in Europe, 1990-2019 : Findings from the Global Burden of Disease Study 2019

Background Mental health is a public health issue for European young people, with great heterogeneity in resource allocation. Representative population-based studies are needed. The Global Burden of Disease (GBD) Study 2019 provides internationally comparable information on trends in the health status of populations and changes in the leading causes of disease burden over time. Methods Prevalence, incidence, Years Lived with Disability (YLDs) and Years of Life Lost (YLLs) from mental disorders (MDs), substance use disorders (SUDs) and self-harm were estimated for young people aged 10-24 years in 31 European countries. Rates per 100,000 population, percentage changes in 1990-2019, 95% Uncertainty Intervals (UIs), and correlations with Sociodemographic Index (SDI), were estimated. Findings In 2019, rates per 100,000 population were 16,983 (95% UI 12,823 - 21,630) for MDs, 3,891 (3,020 4,905) for SUDs, and 89.1 (63.8 - 123.1) for self-harm. In terms of disability, anxiety contributed to 647.3 (432 -912.3) YLDs, while in terms of premature death, self-harm contributed to 319.6 (248.9-412.8) YLLs, per 100,000 population. Over the 30 years studied, YLDs increased in eating disorders (14.9%;9.4-20.1) and drug use disorders (16.9%;8.9-26.3), and decreased in idiopathic developmental intellectual disability (-29.1%;23.8-38.5). YLLs decreased in self-harm (-27.9%;38.3-18.7). Variations were found by sex, age-group and country. The burden of SUDs and self-harm was higher in countries with lower SDI, MDs were associated with SUDs. Interpretation Mental health conditions represent an important burden among young people living in Europe. National policies should strengthen mental health, with a specific focus on young people. Funding The Bill and Melinda Gates Foundation Copyright (C) 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)Peer reviewe

Spatial, temporal, and demographic patterns in prevalence of smoking tobacco use and attributable disease burden in 204 countries and territories, 1990-2019: a systematic analysis from the Global Burden of Disease Study 2019

Background: Ending the global tobacco epidemic is a defining challenge in global health. Timely and comprehensive estimates of the prevalence of smoking tobacco use and attributable disease burden are needed to guide tobacco control efforts nationally and globally. Methods: We estimated the prevalence of smoking tobacco use and attributable disease burden for 204 countries and territories, by age and sex, from 1990 to 2019 as part of the Global Burden of Diseases, Injuries, and Risk Factors Study. We modelled multiple smoking-related indicators from 3625 nationally representative surveys. We completed systematic reviews and did Bayesian meta-regressions for 36 causally linked health outcomes to estimate non-linear dose-response risk curves for current and former smokers. We used a direct estimation approach to estimate attributable burden, providing more comprehensive estimates of the health effects of smoking than previously available. Findings: Globally in 2019, 1·14 billion (95% uncertainty interval 1·13–1·16) individuals were current smokers, who consumed 7·41 trillion (7·11–7·74) cigarette-equivalents of tobacco in 2019. Although prevalence of smoking had decreased significantly since 1990 among both males (27·5% [26·5–28·5] reduction) and females (37·7% [35·4–39·9] reduction) aged 15 years and older, population growth has led to a significant increase in the total number of smokers from 0·99 billion (0·98–1·00) in 1990. Globally in 2019, smoking tobacco use accounted for 7·69 million (7·16–8·20) deaths and 200 million (185–214) disability-adjusted life-years, and was the leading risk factor for death among males (20·2% [19·3–21·1] of male deaths). 6·68 million [86·9%] of 7·69 million deaths attributable to smoking tobacco use were among current smokers. Interpretation: In the absence of intervention, the annual toll of 7·69 million deaths and 200 million disability-adjusted life-years attributable to smoking will increase over the coming decades. Substantial progress in reducing the prevalence of smoking tobacco use has been observed in countries from all regions and at all stages of development, but a large implementation gap remains for tobacco control. Countries have a clear and urgent opportunity to pass strong, evidence-based policies to accelerate reductions in the prevalence of smoking and reap massive health benefits for their citizens. Funding: Bloomberg Philanthropies and the Bill & Melinda Gates Foundation

Global, regional and national burden of bladder cancer and its attributable risk factors in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease study 2019

Introduction The current study determined the level and trends associated with the incidence, death and disability rates for bladder cancer and its attributable risk factors in 204 countries and territories, from 1990 to 2019, by age, sex and sociodemographic index (SDI; a composite measure of sociodemographic factors). Methods Various data sources from different countries, including vital registration and cancer registries were used to generate estimates. Mortality data and incidence data transformed to mortality estimates using the mortality to incidence ratio (MIR) were used in a cause of death ensemble model to estimate mortality. Mortality estimates were divided by the MIR to produce incidence estimates. Prevalence was calculated using incidence and MIR-based survival estimates. Age-specific mortality and standardised life expectancy were used to estimate years of life lost (YLLs). Prevalence was multiplied by disability weights to estimate years lived with disability (YLDs), while disability-adjusted life years (DALYs) are the sum of the YLLs and YLDs. All estimates were presented as counts and age-standardised rates per 100 000 population. Results Globally, there were 524 000 bladder cancer incident cases (95% uncertainty interval 476 000 to 569 000) and 229 000 bladder cancer deaths (211 000 to 243 000) in 2019. Age-standardised death rate decreased by 15.7% (8.6 to 21.0), during the period 1990–2019. Bladder cancer accounted for 4.39 million (4.09 to 4.70) DALYs in 2019, and the age-standardised DALY rate decreased significantly by 18.6% (11.2 to 24.3) during the period 1990–2019. In 2019, Monaco had the highest age-standardised incidence rate (31.9 cases (23.3 to 56.9) per 100 000), while Lebanon had the highest age-standardised death rate (10.4 (8.1 to 13.7)). Cabo Verde had the highest increase in age-standardised incidence (284.2% (214.1 to 362.8)) and death rates (190.3% (139.3 to 251.1)) between 1990 and 2019. In 2019, the global age-standardised incidence and death rates were higher among males than females, across all age groups and peaked in the 95+ age group. Globally, 36.8% (28.5 to 44.0) of bladder cancer DALYs were attributable to smoking, more so in males than females (43.7% (34.0 to 51.8) vs 15.2% (10.9 to 19.4)). In addition, 9.1% (1.9 to 19.6) of the DALYs were attributable to elevated fasting plasma glucose (FPG) (males 9.3% (1.6 to 20.9); females 8.4% (1.6 to 19.1)). Conclusions There was considerable variation in the burden of bladder cancer between countries during the period 1990–2019. Although there was a clear global decrease in the age-standardised death, and DALY rates, some countries experienced an increase in these rates. National policy makers should learn from these differences, and allocate resources for preventative measures, based on their country-specific estimates. In addition, smoking and elevated FPG play an important role in the burden of bladder cancer and need to be addressed with prevention programmes.publishedVersio