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 Chronic kidney disease (CKD) is common and ranks among the leading causes of mortality and morbidity. This analysis aimed to present global CKD estimates using the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 to inform evidence-based policies for CKD identification and treatment. Methods This analysis focused on adults aged 20 years and older over the period 1990 to 2023, from 204 countries and territories. Data sources used were published literature, vital registration systems, kidney failure treatment registries, and household surveys. Estimates of CKD burden, including deaths, incidence, prevalence, and disability-adjusted life-years (DALYs), were produced using a Cause of Death Ensemble model and a Bayesian meta-regression analytical tool. A comparative risk assessment approach estimated the proportion of cardiovascular deaths attributable to impaired kidney function and estimated risk factors for CKD. Findings Globally, in 2023, 788 million (95% uncertainty interval 743–843) people aged 20 years and older were estimated to have CKD, up from 378 million (354–407) in 1990. The global age-standardised prevalence of CKD in adults was 14·2% (13·4–15·2), a relative rise of 3·5% (2·7–4·1) from 1990. The region with the highest age-standardised prevalence was north Africa and the Middle East (18·0%; 16·9–19·4). Most people had stage 1–3 CKD, with a combined prevalence of 13·9% (13·1–15·0). In 2023, CKD was the ninth leading cause of death globally, accounting for 1·48 million (1·30–1·65) deaths, and the 12th leading cause of DALYs, with an age-standardised DALY rate of 769·2 (691·8–857·4) per 100 000. Impaired kidney function as a risk factor accounted for 11·5% (8·4–14·5) of cardiovascular deaths. High fasting plasma glucose, body-mass index, and systolic blood pressure were all leading risk factors for CKD DALYs. Interpretation CKD is a major global health issue, with rising prevalence and increasing importance as a cause of death and as a risk factor for cardiovascular death. A better understating of aetiology, appropriate screening, and implementation programmes are needed to translate advances in CKD treatment into improved patient outcomes. Funding Gates Foundation, Wellcome, US National Kidney Foundation, and US National Institute of Diabetes and Digestive and Kidney Diseases.

Background: The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 estimates health loss from migraine, tension-type headache, and medication-overuse headache. This study presents updated results on headache-attributed burden from 1990 to 2023, along with clinical and public health implications. Methods: Data on the prevalence, incidence, or remission of migraine, tension-type headache, and medication-overuse headache were extracted from published population-based studies. We used hierarchical Bayesian meta-regression modelling to estimate global, regional, and country-level prevalence of headache disorders. For the first time in GBD 2023, age-specific and sex-specific estimates of time in symptomatic state were applied by meta-analysing individual participant data from 41 653 individuals from the general populations of 18 countries from all parts of the world. Disability weights were applied to calculate years lived with disability (YLDs). Since medication-overuse headache is a sequela of a mistreated primary headache (due to medication overuse), its burden was reattributed to migraine or tension-type headache, informed by a meta-analysis of three longitudinal studies. Findings: In 2023, 2·9 billion individuals (95% uncertainty interval 2·6–3·1) were affected by headache disorders, with a global age-standardised prevalence of 34·6% (31·6–37·5) and a YLD rate of 541·9 (373·4–739·9) per 100 000 population, with 487·5 (323·0–678·8) per 100 000 population attributed to migraine. The prevalence rates of these headache disorders have remained stable over the past three decades. YLD rates due to headache disorders were more than twice as high in females (739·9 [511·2–1011·5] per 100 000) as in males (346·1 [240·4–481·8] per 100 000). Medication-overuse headache contributed 58·9% of the YLD estimates for tension-type headache in males and 56·1% in females, as well as 22·6% of the YLD estimates for migraines in males and 14·1% in females. Interpretation: Headache disorders, in particular migraine, continue to be a major global health challenge, emphasising the need for effective management and prevention strategies. Much headache-attributed burden could be averted or eliminated by avoiding overuse of medication (including over-the-counter medication), underscoring the importance of public education. 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.