Global burden and strength of evidence for 88 risk factors in 204 countries and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background: Understanding the health consequences associated with exposure to risk factors is necessary to inform public health policy and practice. To systematically quantify the contributions of risk factor exposures to specific health outcomes, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 aims to provide comprehensive estimates of exposure levels, relative health risks, and attributable burden of disease for 88 risk factors in 204 countries and territories and 811 subnational locations, from 1990 to 2021. Methods: The GBD 2021 risk factor analysis used data from 54 561 total distinct sources to produce epidemiological estimates for 88 risk factors and their associated health outcomes for a total of 631 risk–outcome pairs. Pairs were included on the basis of data-driven determination of a risk–outcome association. Age-sex-location-year-specific estimates were generated at global, regional, and national levels. Our approach followed the comparative risk assessment framework predicated on a causal web of hierarchically organised, potentially combinative, modifiable risks. Relative risks (RRs) of a given outcome occurring as a function of risk factor exposure were estimated separately for each risk–outcome pair, and summary exposure values (SEVs), representing risk-weighted exposure prevalence, and theoretical minimum risk exposure levels (TMRELs) were estimated for each risk factor. These estimates were used to calculate the population attributable fraction (PAF; ie, the proportional change in health risk that would occur if exposure to a risk factor were reduced to the TMREL). The product of PAFs and disease burden associated with a given outcome, measured in disability-adjusted life-years (DALYs), yielded measures of attributable burden (ie, the proportion of total disease burden attributable to a particular risk factor or combination of risk factors). Adjustments for mediation were applied to account for relationships involving risk factors that act indirectly on outcomes via intermediate risks. Attributable burden estimates were stratified by Socio-demographic Index (SDI) quintile and presented as counts, age-standardised rates, and rankings. To complement estimates of RR and attributable burden, newly developed burden of proof risk function (BPRF) methods were applied to yield supplementary, conservative interpretations of risk–outcome associations based on the consistency of underlying evidence, accounting for unexplained heterogeneity between input data from different studies. Estimates reported represent the mean value across 500 draws from the estimate's distribution, with 95% uncertainty intervals (UIs) calculated as the 2·5th and 97·5th percentile values across the draws. Findings: Among the specific risk factors analysed for this study, particulate matter air pollution was the leading contributor to the global disease burden in 2021, contributing 8·0% (95% UI 6·7–9·4) of total DALYs, followed by high systolic blood pressure (SBP; 7·8% [6·4–9·2]), smoking (5·7% [4·7–6·8]), low birthweight and short gestation (5·6% [4·8–6·3]), and high fasting plasma glucose (FPG; 5·4% [4·8–6·0]). For younger demographics (ie, those aged 0–4 years and 5–14 years), risks such as low birthweight and short gestation and unsafe water, sanitation, and handwashing (WaSH) were among the leading risk factors, while for older age groups, metabolic risks such as high SBP, high body-mass index (BMI), high FPG, and high LDL cholesterol had a greater impact. From 2000 to 2021, there was an observable shift in global health challenges, marked by a decline in the number of all-age DALYs broadly attributable to behavioural risks (decrease of 20·7% [13·9–27·7]) and environmental and occupational risks (decrease of 22·0% [15·5–28·8]), coupled with a 49·4% (42·3–56·9) increase in DALYs attributable to metabolic risks, all reflecting ageing populations and changing lifestyles on a global scale. Age-standardised global DALY rates attributable to high BMI and high FPG rose considerably (15·7% [9·9–21·7] for high BMI and 7·9% [3·3–12·9] for high FPG) over this period, with exposure to these risks increasing annually at rates of 1·8% (1·6–1·9) for high BMI and 1·3% (1·1–1·5) for high FPG. By contrast, the global risk-attributable burden and exposure to many other risk factors declined, notably for risks such as child growth failure and unsafe water source, with age-standardised attributable DALYs decreasing by 71·5% (64·4–78·8) for child growth failure and 66·3% (60·2–72·0) for unsafe water source. We separated risk factors into three groups according to trajectory over time: those with a decreasing attributable burden, due largely to declining risk exposure (eg, diet high in trans-fat and household air pollution) but also to proportionally smaller child and youth populations (eg, child and maternal malnutrition); those for which the burden increased moderately in spite of declining risk exposure, due largely to population ageing (eg, smoking); and those for which the burden increased considerably due to both increasing risk exposure and population ageing (eg, ambient particulate matter air pollution, high BMI, high FPG, and high SBP). Interpretation: Substantial progress has been made in reducing the global disease burden attributable to a range of risk factors, particularly those related to maternal and child health, WaSH, and household air pollution. Maintaining efforts to minimise the impact of these risk factors, especially in low SDI locations, is necessary to sustain progress. Successes in moderating the smoking-related burden by reducing risk exposure highlight the need to advance policies that reduce exposure to other leading risk factors such as ambient particulate matter air pollution and high SBP. Troubling increases in high FPG, high BMI, and other risk factors related to obesity and metabolic syndrome indicate an urgent need to identify and implement interventions

Global, regional, and national burden of upper respiratory infections and otitis media, 1990–2021: a systematic analysis from the Global Burden of Disease Study 2021

Background: Upper respiratory infections (URIs) are the leading cause of acute disease incidence worldwide and contribute to a substantial health-care burden. Although acute otitis media is a common complication of URIs, the combined global burden of URIs and otitis media has not been studied comprehensively. We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2021 to explore the fatal and non-fatal burden of the two diseases across all age groups, including a granular analysis of children younger than 5 years, in 204 countries and territories from 1990 to 2021. Methods: Mortality due to URIs and otitis media was estimated with use of vital registration and sample-based vital registration data, which are used as inputs to the Cause of Death Ensemble model to separately model URIs and otitis media mortality by age and sex. Morbidity was modelled with a Bayesian meta-regression tool using data from published studies identified via systematic reviews, population-based survey data, and cause-specific URI and otitis media mortality estimates. Additionally, we assessed and compared the burden of otitis media as it relates to URIs and examined the collective burden and contributing risk factors of both diseases. Findings: The global number of new episodes of URIs was 12·8 billion (95% uncertainty interval 11·4 to 14·5) for all ages across males and females in 2021. The global all-age incidence rate of URIs decreased by 10·1% (–12·0 to –8·1) from 1990 to 2019. From 2019 to 2021, the global all-age incidence rate fell by 0·5% (–0·8 to –0·1). Globally, the incidence rate of URIs was 162 484·8 per 100 000 population (144 834·0 to 183 289·4) in 2021, a decrease of 10·5% (–12·4 to –8·4) from 1990, when the incidence rate was 181 552·5 per 100 000 population (160 827·4 to 206 214·7). The highest incidence rates of URIs were seen in children younger than 2 years in 2021, and the largest number of episodes was in children aged 5–9 years. The number of new episodes of otitis media globally for all ages was 391 million (292 to 525) in 2021. The global incidence rate of otitis media was 4958·9 per 100 000 (3705·4 to 6658·6) in 2021, a decrease of 16·3% (–18·1 to –14·0) from 1990, when the incidence rate was 5925·5 per 100 000 (4371·8 to 8097·9). The incidence rate of otitis media in 2021 was highest in children younger than 2 years, and the largest number of episodes was in children aged 2–4 years. The mortality rate of URIs in 2021 was 0·2 per 100 000 (0·1 to 0·5), a decrease of 64·2% (–84·6 to –43·4) from 1990, when the mortality rate was 0·7 per 100 000 (0·2 to 1·1). In both 1990 and 2021, the mortality rate of otitis media was less than 0·1 per 100 000. Together, the combined burden accounted for by URIs and otitis media in 2021 was 6·86 million (4·24 to 10·4) years lived with disability and 8·16 million (4·99 to 12·0) disability-adjusted life-years (DALYs) for all ages across males and females. Globally, the all-age DALY rate of URIs and otitis media combined in 2021 was 103 per 100 000 (63 to 152). Infants aged 1–5 months had the highest combined DALY rate in 2021 (647 per 100 000 [189 to 1412]), followed by early neonates (aged 0–6 days; 582 per 100 000 [176 to 1297]) and late neonates (aged 7–24 days; 482 per 100 000 [161 to 1052]). Interpretation: The findings of this study highlight the widespread burden posed by URIs and otitis media across all age groups and both sexes. There is a continued need for surveillance, prevention, and management to better understand and reduce the burden associated with URIs and otitis media, and research is needed to assess their impacts on individuals, communities, economies, and health-care systems worldwide. Funding: Bill & Melinda Gates Foundation

Burden of disease scenarios by state in the USA, 2022–50 : a forecasting analysis for the Global Burden of Disease Study 2021

DATA SHARING : To download the data used in these analyses, please visit the Global Health Data Exchange (https://ghdx.healthdata.org/gbd-2021/sources).AFFILIATIONS : See appendix 2 for collaborator affiliations.BACKGROUND : The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 provides a comprehensive assessment of health and risk factor trends at global, regional, national, and subnational levels. This study aims to examine the burden of diseases, injuries, and risk factors in the USA and highlight the disparities in health outcomes across different states. METHODS : GBD 2021 analysed trends in mortality, morbidity, and disability for 371 diseases and injuries and 88 risk factors in the USA between 1990 and 2021. We used several metrics to report sources of health and health loss related to specific diseases, injuries, and risk factors. GBD 2021 methods accounted for differences in data sources and biases. The analysis of levels and trends for causes and risk factors within the same computational framework enabled comparisons across states, years, age groups, and sex. GBD 2021 estimated years lived with disability (YLDs) and disability-adjusted life-years (DALYs; the sum of years of life lost to premature mortality and YLDs) for 371 diseases and injuries, years of life lost (YLLs) and mortality for 288 causes of death, and life expectancy and healthy life expectancy (HALE). We provided estimates for 88 risk factors in relation to 155 health outcomes for 631 risk–outcome pairs and produced risk-specific estimates of summary exposure value, relative health risk, population attributable fraction, and risk-attributable burden measured in DALYs and deaths. Estimates were produced by sex (male and female), age (25 age groups from birth to ≥95 years), and year (annually between 1990 and 2021). 95% uncertainty intervals (UIs) were generated for all final estimates as the 2·5th and 97·5th percentiles values of 500 draws (ie, 500 random samples from the estimate's distribution). Uncertainty was propagated at each step of the estimation process. FINDINGS : We found disparities in health outcomes and risk factors across US states. Our analysis of GBD 2021 highlighted the relative decline in life expectancy and HALE compared with other countries, as well as the impact of COVID-19 during the first 2 years of the pandemic. We found a decline in the USA's ranking of life expectancy from 1990 to 2021: in 1990, the USA ranked 35th of 204 countries and territories for males and 19th for females, but dropped to 46th for males and 47th for females in 2021. When comparing life expectancy in the best-performing and worst-performing US states against all 203 other countries and territories (excluding the USA as a whole), Hawaii (the best-ranked state in 1990 and 2021) dropped from sixth-highest life expectancy in the world for males and fourth for females in 1990 to 28th for males and 22nd for females in 2021. The worst-ranked state in 2021 ranked 107th for males (Mississippi) and 99th for females (West Virginia). 14 US states lost life expectancy over the study period, with West Virginia experiencing the greatest loss (2·7 years between 1990 and 2021). HALE ranking declines were even greater; in 1990, the USA was ranked 42nd for males and 32nd for females but dropped to 69th for males and 76th for females in 2021. When comparing HALE in the best-performing and worst-performing US states against all 203 other countries and territories, Hawaii ranked 14th highest HALE for males and fifth for females in 1990, dropping to 39th for males and 34th for females in 2021. In 2021, West Virginia—the lowest-ranked state that year—ranked 141st for males and 137th for females. Nationally, age-standardised mortality rates declined between 1990 and 2021 for many leading causes of death, most notably for ischaemic heart disease (56·1% [95% UI 55·1–57·2] decline), lung cancer (41·9% [39·7–44·6]), and breast cancer (40·9% [38·7–43·7]). Over the same period, age-standardised mortality rates increased for other causes, particularly drug use disorders (878·0% [770·1–1015·5]), chronic kidney disease (158·3% [149·6–167·9]), and falls (89·7% [79·8–95·8]). We found substantial variation in mortality rates between states, with Hawaii having the lowest age-standardised mortality rate (433·2 per 100 000 [380·6–493·4]) in 2021 and Mississippi having the highest (867·5 per 100 000 [772·6–975·7]). Hawaii had the lowest age-standardised mortality rates throughout the study period, whereas Washington, DC, experienced the most improvement (a 40·7% decline [33·2–47·3]). Only six countries had age-standardised rates of YLDs higher than the USA in 2021: Afghanistan, Lesotho, Liberia, Mozambique, South Africa, and the Central African Republic, largely because the impact of musculoskeletal disorders, mental disorders, and substance use disorders on age-standardised disability rates in the USA is so large. At the state level, eight US states had higher age-standardised YLD rates than any country in the world: West Virginia, Kentucky, Oklahoma, Pennsylvania, New Mexico, Ohio, Tennessee, and Arizona. Low back pain was the leading cause of YLDs in the USA in 1990 and 2021, although the age-standardised rate declined by 7·9% (1·8–13·0) from 1990. Depressive disorders (56·0% increase [48·2–64·3]) and drug use disorders (287·6% [247·9–329·8]) were the second-leading and third-leading causes of age-standardised YLDs in 2021. For females, mental health disorders had the highest age-standardised YLD rate, with an increase of 59·8% (50·6–68·5) between 1990 and 2021. Hawaii had the lowest age-standardised rates of YLDs for all sexes combined (12 085·3 per 100 000 [9090·8–15 557·1]), whereas West Virginia had the highest (14 832·9 per 100 000 [11 226·9–18 882·5]). At the national level, the leading GBD Level 2 risk factors for death for all sexes combined in 2021 were high systolic blood pressure, high fasting plasma glucose, and tobacco use. From 1990 to 2021, the age-standardised mortality rates attributable to high systolic blood pressure decreased by 47·8% (43·4–52·5) and for tobacco use by 5·1% (48·3%–54·1%), but rates increased for high fasting plasma glucose by 9·3% (0·4–18·7). The burden attributable to risk factors varied by age and sex. For example, for ages 15–49 years, the leading risk factors for death were drug use, high alcohol use, and dietary risks. By comparison, for ages 50–69 years, tobacco was the leading risk factor for death, followed by dietary risks and high BMI. INTERPRETATION : GBD 2021 provides valuable information for policy makers, health-care professionals, and researchers in the USA at the national and state levels to prioritise interventions, allocate resources effectively, and assess the effects of health policies and programmes. By addressing socioeconomic determinants, risk behaviours, environmental influences, and health disparities among minority populations, the USA can work towards improving health outcomes so that people can live longer and healthier lives.Bill & Melinda Gates Foundation.https://www.thelancet.com/journals/lancet/homehj2024School of Health Systems and Public Health (SHSPH)SDG-03:Good heatlh and well-bein

Forecasting the effects of smoking prevalence scenarios on years of life lost and life expectancy from 2022 to 2050: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundSmoking is the leading behavioural risk factor for mortality globally, accounting for more than 175 million deaths and nearly 4·30 billion years of life lost (YLLs) from 1990 to 2021. The pace of decline in smoking prevalence has slowed in recent years for many countries, and although strategies have recently been proposed to achieve tobacco-free generations, none have been implemented to date. Assessing what could happen if current trends in smoking prevalence persist, and what could happen if additional smoking prevalence reductions occur, is important for communicating the effect of potential smoking policies. MethodsIn this analysis, we use the Institute for Health Metrics and Evaluation's Future Health Scenarios platform to forecast the effects of three smoking prevalence scenarios on all-cause and cause-specific YLLs and life expectancy at birth until 2050. YLLs were computed for each scenario using the Global Burden of Disease Study 2021 reference life table and forecasts of cause-specific mortality under each scenario. The reference scenario forecasts what could occur if past smoking prevalence and other risk factor trends continue, the Tobacco Smoking Elimination as of 2023 (Elimination-2023) scenario quantifies the maximum potential future health benefits from assuming zero percent smoking prevalence from 2023 onwards, whereas the Tobacco Smoking Elimination by 2050 (Elimination-2050) scenario provides estimates for countries considering policies to steadily reduce smoking prevalence to 5%. Together, these scenarios underscore the magnitude of health benefits that could be reached by 2050 if countries take decisive action to eliminate smoking. The 95% uncertainty interval (UI) of estimates is based on the 2·5th and 97·5th percentile of draws that were carried through the multistage computational framework. FindingsGlobal age-standardised smoking prevalence was estimated to be 28·5% (95% UI 27·9–29·1) among males and 5·96% (5·76–6·21) among females in 2022. In the reference scenario, smoking prevalence declined by 25·9% (25·2–26·6) among males, and 30·0% (26·1–32·1) among females from 2022 to 2050. Under this scenario, we forecast a cumulative 29·3 billion (95% UI 26·8–32·4) overall YLLs among males and 22·2 billion (20·1–24·6) YLLs among females over this period. Life expectancy at birth under this scenario would increase from 73·6 years (95% UI 72·8–74·4) in 2022 to 78·3 years (75·9–80·3) in 2050. Under our Elimination-2023 scenario, we forecast 2·04 billion (95% UI 1·90–2·21) fewer cumulative YLLs by 2050 compared with the reference scenario, and life expectancy at birth would increase to 77·6 years (95% UI 75·1–79·6) among males and 81·0 years (78·5–83·1) among females. Under our Elimination-2050 scenario, we forecast 735 million (675–808) and 141 million (131–154) cumulative YLLs would be avoided among males and females, respectively. Life expectancy in 2050 would increase to 77·1 years (95% UI 74·6–79·0) among males and 80·8 years (78·3–82·9) among females. InterpretationExisting tobacco policies must be maintained if smoking prevalence is to continue to decline as forecast by the reference scenario. In addition, substantial smoking-attributable burden can be avoided by accelerating the pace of smoking elimination. Implementation of new tobacco control policies are crucial in avoiding additional smoking-attributable burden in the coming decades and to ensure that the gains won over the past three decades are not lost. FundingBloomberg Philanthropies and the Bill & Melinda Gates Foundation.Bloomberg Philanthropies and the Bill & Melinda Gates Foundation

PCSK9 Inhibitors: The Evolving Future

ABSTRACT Introduction PCSK9 inhibitors are a novel class of medications that lower LDL cholesterol (LDL‐C) by increasing LDL receptor activity, promoting clearance of LDL‐C from the bloodstream. Over the years, PCSK9 inhibitors have been explored as adjunct therapies to statins or as monotherapy in high‐risk cardiovascular patients. Aim This review aims to provide an updated perspective on PCSK9 inhibitors, assessing their clinical efficacy, safety, and significance, especially in light of recent clinical trials. Methods The review examines the role of PCSK9 in cholesterol regulation and summarizes the results of major cardiovascular trials, including FOURIER, SPIRE‐1, SPIRE‐2, and ODYSSEY Outcomes. It also discusses emerging treatments like small interfering RNA (siRNA) therapies and evaluates PCSK9 inhibitor effects on LDL‐C and lipoprotein(a) levels. Results Clinical trials have shown PCSK9 inhibitors reduce LDL‐C by up to 60%. In the FOURIER trial, evolocumab reduced LDL‐C by 59% and major cardiovascular events by 15%–20%. The SPIRE‐2 trial, despite early termination, showed a 21% risk reduction in the primary composite endpoint with bococizumab. The ODYSSEY Outcomes trial reported a 57% LDL‐C reduction with alirocumab, alongside a 15% reduction in adverse events. Emerging treatments like Inclisiran offer long‐term LDL‐C control with fewer doses. PCSK9 inhibitors are generally well‐tolerated, with the most common side effect being injection site reactions. Conclusion PCSK9 inhibitors significantly lower LDL‐C and reduce cardiovascular events, offering promising therapies for high‐risk patients, including those with familial hypercholesterolemia (FH) and those who cannot tolerate statins. Future research will focus on optimizing these inhibitors, integrating complementary therapies, and exploring gene‐editing technologies to improve patient outcomes

In-hospital and long-term clinical outcomes of spontaneous coronary artery dissection (SCAD): a meta-analysis of conservative versus revascularization approaches

Abstract Background The ideal treatment strategy for spontaneous coronary artery dissection (SCAD) remains unclear, with patients potentially treated with either conservative medical care or a revascularization approach. Methods We performed a systematic review and meta-analysis adhering to PRISMA 2020 guidelines. Inclusion criteria involved studies with confirmed SCAD diagnosis, reporting initial management strategies, and original research with ≥ 10 participants. Random-effect models were applied for insignificant heterogeneity with significance at p ≤ 0.05. Sensitivity analysis and funnel plots assessed potential publication bias. Results Our analysis found no significant differences in major adverse cardiac events (MACE) (OR = 0.61, p = 0.49), unstable angina pectoris (UAP) (OR = 1.04, p = 0.93), non-ST segment elevation myocardial infarction (NSTEMI) (OR = 1.16, p = 0.82), recurrent myocardial infarction (MI) (OR = 0.78, p = 0.56), stroke (OR = 0.35, p = 0.07), heart failure (OR = 0.41, p = 0.24), in-hospital mortality (OR = 0.35, p = 0.09), post-discharge mortality (OR = 1.66, p = 0.27), or ST segment elevation myocardial infarction (STEMI) (OR = 0.45, p = 0.23) between conservative management and revascularization procedures. However, sensitivity analysis reveals significant decreases in odds of inferior wall STEMI (OR = 0.41 [95% CI 0.17–0.97], p = 0.04) and heart failure (OR = 0.18 [95% CI 0.06–0.54], p = 0.002) in conservative treatment compared to revascularization group. Conclusion Conservative therapy significantly decreased inferior wall STEMI and heart failure as compared to revascularization in SCAD. Although no significant differences in cardiovascular outcomes, sensitivity analysis highlights potential benefits of conservative management

Global, regional, and national burden of upper respiratory infections and otitis media, 1990-2021: a systematic analysis from the Global Burden of Disease Study 2021

Background: Upper respiratory infections (URIs) are the leading cause of acute disease incidence worldwide and contribute to a substantial health-care burden. Although acute otitis media is a common complication of URIs, the combined global burden of URIs and otitis media has not been studied comprehensively. We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2021 to explore the fatal and non-fatal burden of the two diseases across all age groups, including a granular analysis of children younger than 5 years, in 204 countries and territories from 1990 to 2021. Methods: Mortality due to URIs and otitis media was estimated with use of vital registration and sample-based vital registration data, which are used as inputs to the Cause of Death Ensemble model to separately model URIs and otitis media mortality by age and sex. Morbidity was modelled with a Bayesian meta-regression tool using data from published studies identified via systematic reviews, population-based survey data, and cause-specific URI and otitis media mortality estimates. Additionally, we assessed and compared the burden of otitis media as it relates to URIs and examined the collective burden and contributing risk factors of both diseases. Findings: The global number of new episodes of URIs was 12·8 billion (95% uncertainty interval 11·4 to 14·5) for all ages across males and females in 2021. The global all-age incidence rate of URIs decreased by 10·1% (–12·0 to –8·1) from 1990 to 2019. From 2019 to 2021, the global all-age incidence rate fell by 0·5% (–0·8 to –0·1). Globally, the incidence rate of URIs was 162 484·8 per 100 000 population (144 834·0 to 183 289·4) in 2021, a decrease of 10·5% (–12·4 to –8·4) from 1990, when the incidence rate was 181 552·5 per 100 000 population (160 827·4 to 206 214·7). The highest incidence rates of URIs were seen in children younger than 2 years in 2021, and the largest number of episodes was in children aged 5–9 years. The number of new episodes of otitis media globally for all ages was 391 million (292 to 525) in 2021. The global incidence rate of otitis media was 4958·9 per 100 000 (3705·4 to 6658·6) in 2021, a decrease of 16·3% (–18·1 to –14·0) from 1990, when the incidence rate was 5925·5 per 100 000 (4371·8 to 8097·9). The incidence rate of otitis media in 2021 was highest in children younger than 2 years, and the largest number of episodes was in children aged 2–4 years. The mortality rate of URIs in 2021 was 0·2 per 100 000 (0·1 to 0·5), a decrease of 64·2% (–84·6 to –43·4) from 1990, when the mortality rate was 0·7 per 100 000 (0·2 to 1·1). In both 1990 and 2021, the mortality rate of otitis media was less than 0·1 per 100 000. Together, the combined burden accounted for by URIs and otitis media in 2021 was 6·86 million (4·24 to 10·4) years lived with disability and 8·16 million (4·99 to 12·0) disability-adjusted life-years (DALYs) for all ages across males and females. Globally, the all-age DALY rate of URIs and otitis media combined in 2021 was 103 per 100 000 (63 to 152). Infants aged 1–5 months had the highest combined DALY rate in 2021 (647 per 100 000 [189 to 1412]), followed by early neonates (aged 0–6 days; 582 per 100 000 [176 to 1297]) and late neonates (aged 7–24 days; 482 per 100 000 [161 to 1052]). Interpretation: The findings of this study highlight the widespread burden posed by URIs and otitis media across all age groups and both sexes. There is a continued need for surveillance, prevention, and management to better understand and reduce the burden associated with URIs and otitis media, and research is needed to assess their impacts on individuals, communities, economies, and health-care systems worldwide. Funding: Bill &amp; Melinda Gates Foundation.</p

Global, regional, and national burden of pulmonary arterial hypertension, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background Pulmonary arterial hypertension (PAH) is a vascular disease characterised by restricted flow and high pressure through the pulmonary arteries, leading to progressive right heart failure and death. This study reports the global burden of PAH, leveraging all available data and using methodology of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) to understand the epidemiology of this under-researched and morbid disease. Methods Prior to the current effort, the burden of PAH was included in GBD as a non-specific contributor to “other cardiovascular and circulatory disease” burden. In this study, PAH was distinguished as its own cause of death and disability in GBD, producing comparable and consistent estimates of PAH burden. We used epidemiological and vital registry data to estimate the non-fatal and fatal burden of PAH in 204 countries and territories from 1990 to 2021 using standard GBD modelling approaches. We specifically focused on PAH (group 1 pulmonary hypertension), and did not include pulmonary hypertension groups 2–5. Findings In 2021, there were an estimated 192 000 (95% uncertainty interval [UI] 155 000–236 000) prevalent cases of PAH globally. Of these, 119 000 (95 900–146 000) were in females (62%) and 73 100 (58 900–89 600) in males (38%). The age-standardised prevalence was 2·28 cases per 100 000 population (95% UI 1·85–2·80). Prevalence increased with age such that the highest prevalence was among individuals aged 75–79 years. In 2021, there were 22 000 deaths (18 200–25 400) attributed to PAH globally, with an age-standardised mortality rate of 0·27 deaths from PAH per 100 000 population (0·23–0·32). The burden of disease appears to be improving over time (38·2% improvement in age-standardised years of life lost [YLLs] in 2021 relative to 1990). YLLs attributed to PAH were similar to estimates for conditions such as chronic myeloid leukaemia, multiple sclerosis, and Crohn's disease. Interpretation PAH is a rare but fatal disease that accounts for a considerable health-associated burden worldwide. PAH is disproportionally diagnosed among females and older adults. Funding Cardiovascular Medical Research and Education Fund and the Bill & Melinda Gates Foundation

Global, regional, and national progress towards the 2030 global nutrition targets and forecasts to 2050: a systematic analysis for the Global Burden of Disease Study 2021

Background The six global nutrition targets (GNTs) related to low birthweight, exclusive breastfeeding, child growth (ie, wasting, stunting, and overweight), and anaemia among females of reproductive age were chosen by the World Health Assembly in 2012 as key indicators of maternal and child health, but there has yet to be a comprehensive report on progress for the period 2012 to 2021. We aimed to evaluate levels, trends, and observed-to-expected progress in prevalence and attributable burden from 2012 to 2021, with prevalence projections to 2050, in 204 countries and territories. Methods The prevalence and attributable burden of each target indicator were estimated by age group, sex, and year in 204 countries and territories from 2012 to 2021 in the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021, the most comprehensive assessment of causes of death, disability, and risk factors to date. Country-specific relative performance to date was evaluated with a Bayesian meta-regression model that compares prevalence to expected values based on Socio-demographic Index (SDI), a composite indicator of societal development status. Target progress was forecasted from 2021 up to 2050 by modelling past trends with meta-regression using a combination of key quantities and then extrapolating future projections of those quantities. Findings In 2021, a few countries had already met some of the GNTs: five for exclusive breastfeeding, four for stunting, 96 for child wasting, and three for child overweight, and none met the target for low birthweight or anaemia in females of reproductive age. Since 2012, the annualised rates of change (ARC) in the prevalence of child overweight increased in 201 countries and territories and ARC in the prevalence of anaemia in females of reproductive age decreased considerably in 26 countries. Between 2012 and 2021, SDI was strongly associated with indicator prevalence, apart from exclusive breastfeeding (vertical bar r-vertical bar=0.46-0.86). Many countries in sub-Saharan Africa had a decrease in the prevalence of multiple indicators that was more rapid than expected on the basis of SDI (the differences between observed and expected ARCs for child stunting and wasting were -0.5% and -1.3%, respectively). The ARC in the attributable burden of low birthweight, child stunting, and child wasting decreased faster than the ARC of the prevalence for each in most low-income and middle-income countries. In 2030, we project that 94 countries will meet one of the six targets, 21 countries will meet two targets, and 89 countries will not meet any targets. We project that seven countries will meet the target for exclusive breastfeeding, 28 for child stunting, and 101 for child wasting, and no countries will meet the targets for low birthweight, child overweight, and anaemia. In 2050, we project that seven additional countries will meet the target for exclusive breastfeeding, five for low birthweight, 96 for child stunting, nine for child wasting, and one for child overweight, and no countries are projected to meet the anaemia target. Interpretation Based on current levels and past trends, few GNTs will be met by 2030. Major reductions in attributable burden for exclusive breastfeeding and anthropometric indicators should be recognised as huge scientific and policy successes, but the comparative lack of progress in reducing the prevalence of each, along with stagnant anaemia in women of reproductive age and widespread increases in child overweight, suggests a tenuous status quo. Continued investment in preventive and treatment efforts for acute childhood illness is crucial to prevent backsliding. Parallel development of effective treatments, along with commitment to multisectoral, long-term policies to address the determinants and causes of suboptimal nutrition, are sorely needed to gain ground. Copyright (c) 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license

Burden of disease scenarios by state in the USA, 2022–50: a forecasting analysis for the Global Burden of Disease Study 2021

Background: The capacity to anticipate future health issues is important for both policy makers and practitioners in the USA, as such insights can facilitate effective planning, investment, and implementation strategies. Forecasting trends in disease and injury burden is not only crucial for policy makers but also garners substantial interest from the general populace and leads to a better-informed public. Through the integration of new data sources, the refinement of methodologies, and the inclusion of additional causes, we have improved our previous forecasting efforts within the scope of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) to produce forecasts at the state and national levels for the USA under various possible scenarios. Methods: We developed a comprehensive framework for forecasting life expectancy, healthy life expectancy (HALE), cause-specific mortality, and disability-adjusted life-years (DALYs) due to 359 causes of disease and injury burden from 2022 to 2050 for the USA and all 50 states and Washington, DC. Using the GBD 2021 Future Health Scenarios modelling framework, we forecasted drivers of disease, demographic drivers, risk factors, temperature and particulate matter, mortality and years of life lost (YLL), population, and non-fatal burden. In addition to a reference scenario (representing the most probable future trajectory), we explored various future scenarios and their potential impacts over the next several decades on human health. These alternative scenarios comprised four risk elimination scenarios (including safer environment, improved behavioural and metabolic risks, improved childhood nutrition and vaccination, and a combined scenario) and three USA-specific scenarios based on risk exposure or attributable burden in the best-performing US states (improved high adult BMI and high fasting plasma glucose [FPG], improved smoking, and improved drug use [encompassing opioids, cocaine, amphetamine, and others]). Findings: Life expectancy in the USA is projected to increase from 78·3 years (95% uncertainty interval 78·1–78·5) in 2022 to 79·9 years (79·5–80·2) in 2035, and to 80·4 years (79·8–81·0) in 2050 for all sexes combined. This increase is forecasted to be modest compared with that in other countries around the world, resulting in the USA declining in global rank over the 2022–50 forecasted period among the 204 countries and territories in GBD, from 49th to 66th. There is projected to be a decline in female life expectancy in West Virginia between 1990 and 2050, and little change in Arkansas and Oklahoma. Additionally, after 2023, we projected almost no change in female life expectancy in many states, notably in Oklahoma, South Dakota, Utah, Iowa, Maine, and Wisconsin. Female HALE is projected to decline between 1990 and 2050 in 20 states and to remain unchanged in three others. Drug use disorders and low back pain are projected to be the leading Level 3 causes of age-standardised DALYs in 2050. The age-standardised DALY rate due to drug use disorders is projected to increase considerably between 2022 and 2050 (19·5% [6·9–34·1]). Our combined risk elimination scenario shows that the USA could gain 3·8 additional years (3·6–4·0) of life expectancy and 4·1 additional years (3·9–4·3) of HALE in 2050 versus the reference scenario. Using our USA-specific scenarios, we forecasted that the USA could gain 0·4 additional years (0·3–0·6) of life expectancy and 0·6 additional years (0·5–0·8) of HALE in 2050 under the improved drug use scenario relative to the reference scenario. Life expectancy and HALE are likewise projected to be 0·4–0·5 years higher in 2050 under the improved adult BMI and FPG and improved smoking scenarios compared with the reference scenario. However, the increases in these scenarios would not substantially improve the USA's global ranking in 2050 (from 66th of 204 in life expectancy in the reference scenario to 63rd–64th in each of the three USA-specific scenarios), indicating that the USA's best-performing states are still lagging behind other countries in their rank throughout the forecasted period. Regardless, an estimated 12·4 million (11·3–13·5) deaths could be averted between 2022 and 2050 if the USA were to follow the combined scenario trajectory rather than the reference scenario. There would also be 1·4 million (0·7–2·2) fewer deaths over the 28-year forecasted period with improved adult BMI and FPG, 2·1 million (1·3–2·9) fewer deaths with improved exposure to smoking, and 1·2 million (0·9–1·5) fewer deaths with lower rates of drug use deaths. Interpretation: Our findings highlight the alarming trajectory of health challenges in the USA, which, if left unaddressed, could lead to a reversal of the health progress made over the past three decades for some US states and a decline in global health standing for all states. The evidence from our alternative scenarios along with other published studies suggests that through collaborative, evidence-based strategies, there are opportunities to change the trajectory of health outcomes in the USA, such as by investing in scientific innovation, health-care access, preventive health care, risk exposure reduction, and education. Our forecasts clearly show that the time to act is now, as the future of the country's health and wellbeing—as well as its prosperity and leadership position in science and innovation—are at stake. Funding: Bill &amp; Melinda Gates Foundation