Background Antimicrobial resistance (AMR) is an urgent global crisis and one of the world's most complex challenges. Although there is increasing evidence of its impact on human mortality and morbidity, precise burden estimation has many challenges, and thus far has been elusive for the Eastern Mediterranean Region. Here, we present a comprehensive time-trend analysis of regional and country-level AMR burden estimates in the WHO Eastern Mediterranean Region (EMR), between 1990 and 2021, with forecasts up to 2050. Methods We estimated deaths and disability-adjusted life-years (DALYs) attributable to and associated with AMR for 11 infectious syndromes, 22 bacterial pathogens, and 84 pathogen–drug combinations for the WHO EMR and each of its countries from 1990 to 2021. Data were obtained from mortality registries, surveillance systems, hospital records, systematic literature reviews, and other sources. We based our modelling approach on five broad components: the number of deaths in which 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 a given pathogen resistant to an antimicrobial drug of interest, and the excess risk of mortality (or duration of an infection) associated with this resistance. These components were then used to estimate the disease burden by using two counterfactual scenarios: deaths and DALYs attributable to AMR (considering an alternative scenario where drug-resistant infections are replaced with susceptible infections), and deaths and DALYs associated with AMR (considering an alternative scenario where infections would not occur at all). Predictive statistical modelling was applied to generate estimates of AMR burden for each country. We also generated AMR burden forecasts up to 2050. We generated 95% uncertainty intervals (UIs) for the final estimates by taking the 2·5th and 97·5th percentiles across 500 draws through the multistage computational pipeline, and models were cross-validated for out-of-sample predictive validity. Findings We estimated 380 000 deaths (95% UI 332 000–426 000) associated with bacterial AMR and 92 800 deaths (78 300–111 000) attributable to bacterial AMR in the EMR in 2021. In the past 31 years, there was considerable variation in AMR mortality trends across countries of the region and different age groups. Between 1990 and 2021, associated deaths among children younger than 5 years decreased by 50·0% (38·2–62·0), while those among adults aged 70 and older rose by over 85·7% (95% UI 57·0–115·7). Six pathogens were identified as the primary generators of burden: Streptococcus pneumoniae, Klebsiella pneumoniae, Escherichia coli, Staphylococcus aureus, Acinetobacter baumannii , and Pseudomonas aeruginosa . A substantial increase in the AMR burden due to S aureus was observed between 1990 (28 200 deaths [21 600–34 000]) and 2021 (49 500 deaths [43 100–56 200]); consequently, in 2021, methicillin-resistant S aureus was a leading pathogen–drug combination for most countries in the region for deaths and DALYs attributable to, and associated with AMR. Somalia had the highest age-standardised mortality rates in the region: for deaths attributable to and associated with AMR per 100 000 population in both 1990 and 2021; conversely, the country with the lowest burden in the EMR was Qatar. By 2050, the number of deaths attributable to AMR in region is forecasted to reach 187 000 (157 000–223 000) and deaths associated with AMR were projected to reach 752 000 (629 000–879 000). Interpretation Our study shows that bacterial AMR has been a serious public health threat in the EMR for more than 30 years, with a substantial fatal and non-fatal burden for priority bacterial pathogens and pathogen–drug combinations. The magnitude of this issue, future projects, and the inadequate response capacity in many countries underscore the need for more stringent regional leadership in this field. The insights gained from this study can direct targeted mitigation strategies for individual countries within the region, aiding in resource allocation and funding decisions, and emphasising the need for collaborative multisectoral endeavours among nations to address this issue. Funding Wellcome Trust, and the UK Department of Health and Social Care using aid funding managed by the Fleming Fund.

Background Violence against women and against children are human rights violations with lasting harms to survivors and societies at large. Intimate partner violence (IPV) and sexual violence against children (SVAC) are two major forms of such abuse. Despite their wide-reaching effects on individual and community health, these risk factors have not been adequately prioritised as key drivers of global health burden. Comprehensive x§and reliable estimates of the comparative health burden of IPV and SVAC are urgently needed to inform investments in prevention and support for survivors at both national and global levels. Methods We estimated the prevalence and attributable burden of IPV among females and SVAC among males and females for 204 countries and territories, by age and sex, from 1990 to 2023, as part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2023. We searched several global databases for data on self-reported exposure to IPV and SVAC and undertook a systematic review to identify the health outcomes associated with each of these risk factors. We modelled IPV and SVAC prevalence using spatiotemporal Gaussian process regression, applying data adjustments to account for measurement heterogeneity. We employed burden-of-proof methodology to estimate relative risks for outcomes associated with IPV and SVAC. These estimates informed the calculation of population attributable fractions, which were then used to quantify disability-adjusted life-years (DALYs) attributable to each risk factor. Findings Globally, in 2023, we estimated that 608 million (95% uncertainty interval 518–724) females aged 15 years and older had ever been exposed to IPV, and 1·01 billion (0·764–1·48) individuals aged 15 years and older had experienced sexual violence during childhood. 18·5 million (8·74–30·0) DALYs were attributed to IPV among females and 32·2 million (16·4–52·5) DALYs were attributed to SVAC among males and females in 2023. IPV and SVAC were among the top contributors to the global disease burden in 2023, particularly among females aged 15–49 years, ranking as the fourth and fifth leading risk factors, respectively, for DALYs in this group. Among the eight health outcomes found to be associated with IPV, anxiety disorders and major depressive disorder were the leading causes of IPV-attributed DALYs, accounting for 5·43 million (–1·25 to 14·6) and 3·96 million (1·71 to 6·92) DALYs in 2023, respectively. SVAC was associated with 14 health outcomes, including mental health disorder, substance use disorder, and chronic and infectious disease outcomes. Self-harm and schizophrenia were the leading causes of SVAC-attributed burden, with SVAC accounting for 6·71 million (2·00 to 12·7) DALYs due to self-harm and 4·15 million (–1·92 to 13·1) DALYs due to schizophrenia in 2023. Interpretation IPV and SVAC are substantial contributors to global health burden, and their health consequences span a variety of individual health outcomes. Importantly, mental health disorders account for the greatest share of disease burden among survivors. Investing in prevention of these avoidable risk factors has the potential to avert millions of DALYs and considerable premature mortality each year. Our findings represent strong evidence for global and national leaders to elevate IPV and SVAC among public health priorities. Sustained investments are needed to prevent IPV and SVAC and to implement interventions focused on supporting the complex social and health needs of survivors. Funding Gates Foundation.

Background Information on childhood cancer burden is crucial for effective cancer policy planning. Unfortunately, observed paediatric cancer data are not available in every country, and previous global burden estimates have not discretely reported several common cancers of childhood. We aimed to inform efforts to address childhood cancer burden globally by analysing results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023, which now include nine additional cancer causes compared with previous GBD analyses. Methods GBD 2023 data sources for cancer estimation included population-based cancer registries, vital registration systems, and verbal autopsies. For childhood cancers (defined as those occurring at ages 0–19 years), mortality was estimated using cancer-specific ensemble models and incidence was estimated using mortality estimates and modelled mortality-to-incidence ratios (MIRs). Years of life lost (YLLs) were estimated by multiplying age-specific cancer deaths by the standard life expectancy at the age of death. Prevalence was estimated using survival estimates modelled from MIRs and multiplied by sequelae-specific disability weights to estimate years lived with disability (YLDs). Disability-adjusted life-years (DALYs) were estimated as the sum of YLLs and YLDs. Estimates are presented globally and by geographical and resource groupings, and all estimates are presented with 95% uncertainty intervals (UIs). Findings Globally, in 2023, there were an estimated 377 000 incident childhood cancer cases (95% UI 288 000–489 000), 144 000 deaths (131 000–162 000), and 11·7 million (10·7–13·2) DALYs due to childhood cancer. Deaths due to childhood cancer decreased by 27·0% (15·5–36·1) globally, from 197 000 (173 000–218 000) in 1990, but increased in the WHO African region by 55·6% (25·5–92·4), from 31 500 (24 900–38 500) to 49 000 (42 600–58 200) between 1990 and 2023. In 2023, age-standardised YLLs due to childhood cancer were inversely correlated with country-level Socio-demographic Index. Childhood cancer was the eighth-leading cause of childhood deaths and the ninth-leading cause of DALYs among all cancers in 2023. The percentage of DALYs due to uncategorised childhood cancers was reduced from 26·5% (26·5–26·5) in GBD 2017 to 10·5% (8·1–13·1) with the addition of the nine new cancer causes. Target cancers for the WHO Global Initiative for Childhood Cancer (GICC) comprised 47·3% (42·2–52·0) of global childhood cancer deaths in 2023. Interpretation Global childhood cancer burden remains a substantial contributor to global childhood disease and cancer burden and is disproportionately weighted towards resource-limited settings. The estimation of additional cancer types relevant in childhood provides a step towards alignment with WHO GICC targets. Efforts to decrease global childhood cancer burden should focus on addressing the inequities in burden worldwide and support comprehensive improvements along the childhood cancer diagnosis and care continuum. Funding St Jude Children's Research Hospital, Gates Foundation, and St Baldrick's Foundation.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease, is one of the most prevalent liver diseases globally, contributing to both economic and health-related challenges. We aimed to evaluate the global, regional, and national burden of MASLD from 1990 to 2023, quantify the contribution of identified modifiable risk factors, and project future prevalence up to the year 2050. Methods: Estimates of MASLD prevalence and disability-adjusted life-years (DALYs) were produced by age, sex, region, Socio-demographic Index (SDI), and Healthcare Access and Quality (HAQ) index across 204 countries and territories from 1990 to 2023 as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023. The MASLD burden attributable to three risk factors (smoking, high BMI, and high fasting plasma glucose) was assessed as part of the GBD comparative risk assessment. As a secondary analysis, we used these estimates to forecast MASLD prevalence up to 2050 using fasting plasma glucose and mean BMI as predictors. Furthermore, to examine the relative contributions of population ageing, population growth, and changes in MASLD prevalence rate to the forecasted changes in case counts from 2023 to 2050, we conducted a decomposition analysis. Findings: In 2023, approximately 1·3 billion (95% uncertainty interval [UI] 1·2 to 1·4) individuals were estimated to be living with MASLD (ie, 16·1% of the global population), with an age-standardised prevalence rate of 14 429·3 (95% UI 13 268·3 to 15 990·6) per 100 000 population, representing a percentage increase of 142·7% (95% UI 139·2 to 146·7) in crude numbers from 1990 (0·5 billion [0·5 to 0·6]) and of 28·6% (27·8 to 29·5) in the rate (11 217·2 [10 276·8 to 12 467·0] per 100 000 in 1990). An estimated 3·6 million (2·8 to 4·5) total DALYs were attributable to MASLD worldwide in 2023, corresponding to an age-standardised DALY rate of 39·6 (31·2 to 49·9) per 100 000 population. Despite a 116·3% (93·3 to 139·4) increase in crude DALYs (from 1·7 million [1·3 to 2·1] in 1990), its age-standardised estimate remained consistent (1·8% [–8·6 to 12·8]) from 1990 (38·9 [30·1 to 49·8] per 100 000) to 2023. There was substantial variation in age-standardised estimates across regions. North Africa and the Middle East had the highest prevalence rate (29 246·1 [26 848·3 to 32 048·7] per 100 000) and Andean Latin America showed the highest DALY rate (152·3 [114·1 to 194·7] per 100 000). By contrast, the high-income Asia Pacific region had the lowest prevalence rate (8653·5 [7923·7 to 9592·8] per 100 000) and east Asia had the lowest DALY rate (16·3 [13·5 to 19·9] per 100 000) among all GBD regions. North Africa and the Middle East showed disproportionately higher prevalence rates relative to other regions with similar SDIs. Lower SDIs and HAQs were associated with higher age-standardised DALY rates. The age-standardised prevalence rate was consistently higher in males (15 616·4 [14 349·2 to 17 263·3] per 100 000 people in 2023) than in females (13 245·2 [12 132·0 to 14 692·6] per 100 000 people), and peaked at age 80–84 years in both sexes. The number of MASLD prevalent cases was the highest in younger adults, peaking at age 35–39 years for males and age 55–59 years for females. Among the risk factors for MASLD, high fasting plasma glucose presented the largest contribution to the age-standardised DALY rate of total MASLD in 2023 (2·2 [95% UI 1·6 to 3·1] per 100 000 people), followed by high BMI (1·4 [0·6 to 2·4] per 100 000 people) and smoking (1·0 [0·3 to 1·8] per 100 000 people). Our forecasting model estimates that 1·8 billion (95% UI 1·6 to 2·0) individuals are likely to have MASLD by 2050, representing a 42·0% increase from 2023. The age-standardised prevalence rate is expected to increase to 15 774·9 (95% UI 14 613·9 to 17 336·2) per 100 000 people in 2050, representing an average annual percentage change of 0·3% (95% UI 0·3–0·3). According to our decomposition analysis, this change will be primarily due to population growth, particularly in sub-Saharan Africa and North Africa and Middle East, and less by population ageing or epidemiological change. Interpretation: With a global prevalence of 16·1% and approximately 1·3 billion people already living with MASLD in 2023, the condition has and will continue to have substantial health and economic impacts worldwide. An inverse association between the HAQ Index and age-standardised DALY rates suggests that countries with lower health-care access and quality might be less well positioned to manage the growing MASLD burden, underscoring the need for strengthened health-system capacity in these settings. Funding: Gates Foundation.