Elmonem, M. A., "Global burden of lower respiratory infections and aetiologies, 1990-2023: a systematic analysis for the Global Burden of Disease Study 2023.", The Lancet. Infectious diseases, 2025 Dec 15. Abstract

BACKGROUND: Lower respiratory infections (LRIs) remain the world's leading infectious cause of death. This analysis from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 provides global, regional, and national estimates of LRI incidence, mortality, and disability-adjusted life-years (DALYs), with attribution to 26 pathogens, including 11 newly modelled pathogens, across 204 countries and territories from 1990 to 2023. With new data and revised modelling techniques, these estimates serve as an update and expansion to GBD 2021. Through these estimates, we also aimed to assess progress towards the 2025 Global Action Plan for the Prevention and Control of Pneumonia and Diarrhoea (GAPPD) target for pneumonia mortality in children younger than 5 years.

METHODS: Mortality from LRIs, defined as physician-diagnosed pneumonia or bronchiolitis, was estimated using the Cause of Death Ensemble model with data from vital registration, verbal autopsy, surveillance, and minimally invasive tissue sampling. The Bayesian meta-regression tool DisMod-MR 2.1 was used to model overall morbidity due to LRIs. DALYs were calculated as the sum of years of life lost (YLLs) and years lived with disability (YLDs) for all locations, years, age groups, and sexes. We modelled pathogen-specific case-fatality ratios (CFRs) for each age group and location using splined binomial regression to create internally consistent estimates of incidence and mortality proportions attributable to viral, fungal, parasitic, and bacterial pathogens. Progress was assessed towards the GAPPD target of less than three deaths from pneumonia per 1000 livebirths, which is roughly equivalent to a mortality rate of less than 60 deaths per 100 000 children younger than 5 years.

FINDINGS: In 2023, LRIs were responsible for 2·50 million (95% uncertainty interval [UI] 2·24-2·81) deaths and 98·7 million (87·7-112) DALYs, with children younger than 5 years and adults aged 70 years and older carrying the highest burden. LRI mortality in children younger than 5 years fell by 33·4% (10·4-47·4) since 2010, with a global mortality rate of 94·8 (75·6-116·4) per 100 000 person-years in 2023. Among adults aged 70 years and older, the burden remained substantial with only marginal declines since 2010. A mortality rate of less than 60 deaths per 100 000 for children younger than 5 years was met by 129 of the 204 modelled countries in 2023. At a super-regional level, sub-Saharan Africa had an aggregate mortality rate in children younger than 5 years (hereafter referred to as under-5 mortality rate) furthest from the GAPPD target. Streptococcus pneumoniae continued to account for the largest number of LRI deaths globally (634 000 [95% UI 565 000-721 000] deaths or 25·3% [24·5-26·1] of all LRI deaths), followed by Staphylococcus aureus (271 000 [243 000-298 000] deaths or 10·9% [10·3-11·3]), and Klebsiella pneumoniae (228 000 [204 000-261 000] deaths or 9·1% [8·8-9·5]). Among pathogens newly modelled in this study, non-tuberculous mycobacteria (responsible for 177 000 [95% UI 155 000-201 000] deaths) and Aspergillus spp (responsible for 67 800 [59 900-75 900] deaths) emerged as important contributors. Altogether, the 11 newly modelled pathogens accounted for approximately 22% of LRI deaths.

INTERPRETATION: This comprehensive analysis underscores both the gains achieved through vaccination and the challenges that remain in controlling the LRI burden globally. Furthermore, it demonstrates persistent disparities in disease burden, with the highest mortality rates concentrated in countries in sub-Saharan Africa. Globally, as well as in these high-burden locations, the under-5 LRI mortality rate remains well above the GAPPD target. Progress towards this target requires equitable access to vaccines and preventive therapies-including newer interventions such as respiratory syncytial virus monoclonal antibodies-and health systems capable of early diagnosis and treatment. Expanding surveillance of emerging pathogens, strengthening adult immunisation programmes, and combating vaccine hesitancy are also crucial. As the global population ages, the dual challenge of sustaining gains in child survival while addressing the rising vulnerability in older adults will shape future pneumonia control strategies.

FUNDING: Gates Foundation.

Huysentruyt, K., S. M. Vandriel, M. Roelants, D. A. Piccoli, K. M. Loomes, E. B. Rand, N. H. Ebel, J. A. Feinstein, I. Jankowska, P. Czubkowski, et al., "Condition-Specific Growth Charts for Children With Alagille Syndrome.", JAMA network open, vol. 8, issue 11, pp. e2545294, 2025 Nov 03. Abstract

IMPORTANCE: Different degrees of growth delay have been reported in children with Alagille syndrome (ALGS), yet these patients are routinely evaluated using standard growth charts.

OBJECTIVE: To develop condition-specific growth charts for ALGS using modern statistical approaches.

DESIGN, SETTING, AND PARTICIPANTS: This case series used data from the international, multicenter Global Alagille Alliance (GALA) study accrued between May 14, 2018, and March 20, 2023. Children born at full term between January 1, 1997, and August 31, 2019, with a clinically and/or genetically confirmed ALGS diagnosis and their native liver were included. Data from children with a known history of prematurity were excluded for the development of the growth charts. Data were analyzed from March 25, 2023, to December 30, 2024.

EXPOSURE: Growth of children with Alagille syndrome.

MAIN OUTCOMES AND MEASURES: Generalized additive models for location scale and shape were fitted to generate percentile plots for weight and height relative to age and superimposed on US Centers for Disease Control and Prevention (CDC) growth charts to illustrate differences in growth patterns compared with children with typical development.

RESULTS: Data from 1204 children with ALGS in overlapping cohorts (median [IQR] gestational age, 38 [37-39] weeks) were analyzed (1204 in the weight cohort; 695 boys [57.7%]; 9855 weight observations; 995 with neonatal cholestasis [82.6%]; 306 receiving a liver transplant [25.4%]; 98 deaths [8.1%] and 1106 in the height cohort, 635 boys [57.4%]; 8464 height observations; 906 with neonatal cholestasis [81.9%]; 287 receiving a liver transplant [25.9%]; 86 deaths [7.8%]) were included for the modeling of the weight-for-age and height-for-age charts, respectively. The median birth weight was 2.8 kg (IQR, 2.5-3.0 kg) for boys and 2.6 kg (IQR, 2.4-2.9 kg) for girls. The median birth length was 48.0 cm (IQR, 46.0-50.0 cm) for boys and 47.0 cm (IQR, 45.0-49.0 cm) for girls. The weight-for-age and height-for-age growth charts for boys and girls with AGLS differed significantly from CDC growth charts. The estimated height at age 18 years corresponded to the 50th percentile was 171.5 cm for boys and 156.5 cm for girls on the condition-specific charts vs 176 cm and 163 cm, respectively, on the CDC growth charts.

CONCLUSIONS AND RELEVANCE: These findings suggest that condition-specific growth charts for ALGS may provide a crucial tool for clinicians to evaluate growth and aid in decision-making around listing children for liver transplant.

Perez, C. F. M., S. M. Vandriel, E. M. Gonzales, J. - S. Wang, L. - T. Li, H. She, I. Jankowska, P. Czubkowski, D. Gliwicz-Miedzińska, E. Jacquemin, et al., "Elevated Serum Bile Acids Predict Poor Liver Outcomes in Children With Alagille Syndrome: Results From the GALA Study Group.", Liver international : official journal of the International Association for the Study of the Liver, vol. 45, issue 12, pp. e70423, 2025 Dec. Abstract

BACKGROUND AND AIM: Alagille syndrome (ALGS) is a rare disorder characterised by cholestasis and extrahepatic manifestations. Given the current era of ileal bile acid transporter (IBAT) inhibitor therapies that reduce serum bile acid (SBA) levels, we evaluated whether SBA predicts liver disease outcomes in ALGS.

METHODS: Patients were ascertained from the Global ALagille Alliance (GALA) cohort. A prognostic threshold of SBA 102 μmol/L was assessed as a time-dependent covariate in Cox regression analyses for native liver survival (NLS) and event-free survival (EFS), while adjusting for total bilirubin (TB) levels.

RESULTS: 570 GALA patients were included (348 [61%] male). There was a moderate positive correlation between SBA and TB (Pearson correlation = 0.47, p < 0.001). SBA below 102 μmol/L was a significant predictor of outcomes (NLS: HR = 3.78, 95% CI 2.39-5.99, p < 0.001; EFS: HR = 3.44, 95% CI 2.35-5.04, p < 0.001). SBA remained a significant predictor for improved EFS after adjusting for TB clearance at 1 year (TB < 2 mg/dL; HR = 2.00, 95% CI 1.10-3.65, p = 0.02). Median SBA in the first year of life above 102 μmol/L, predicted lower NLS (67.2% vs. 83.5% at 7 years p = 0.05) and EFS (63.4% vs. 80.9% at 7 years, p = 0.02).

CONCLUSION: Lower SBA in children with ALGS liver disease predicts improved NLS and EFS. SBA is also associated with NLS in children with ALGS who clear their bilirubin, that is, those with anicteric cholestasis. Although the patients studied here did not receive IBAT inhibition, these data suggest that lowering SBA may improve important clinical outcomes.

Elmonem, M. A., "Global, regional, and national burden of chronic kidney disease in adults, 1990-2023, and its attributable risk factors: a systematic analysis for the Global Burden of Disease Study 2023.", Lancet (London, England), vol. 406, issue 10518, pp. 2461-2482, 2025 Nov 22. Abstract

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.

El-Karaksy, H., E. A. Mogahed, sherif Baroudy, H. Ghita, A. Enayet, M. A. R. W. A. EL-SHARKAWY, N. A. Radwan, H. Hosny, and M. A. Elmonem, "Unfolding the genetic map of monogenic liver diseases in Egypt.", Human genetics, vol. 144, issue 11-12, pp. 1053-1070, 2025 Dec. Abstract

UNLABELLED: Monogenic liver disorders constitute a major disease burden in pediatric patients presenting with manifestations of liver disease. This is particularly significant in countries with high rates of consanguinity as in Egypt. We recruited 228 infants and children suffering from various forms of liver disease with suspected monogenic background and no conclusive biochemical diagnosis. They presented to the Pediatric Hepatology Unit at Cairo-University-Children’s-Hospital, Egypt, over the period April 2017-June 2023 and were referred for genetic diagnosis by various next-generation-sequencing technologies. One-hundred and eighty-five children (81.1%) had a significant genetic finding. Those included 88 children with a main presentation of organomegaly, 83 with cholestasis, 8 with acute liver failure and 6 with hyperbilirubinemic syndromes. One-hundred seventy-five disease-causing variants (51 pathogenic, 86 likely-pathogenic and 38 of uncertain-significance) in 72 different genes were detected in our cohort, including 85 novel variants in 49 different genes. Variants in (Glycogen storage disease type-III; GSD3), (Progressive familial intrahepatic cholestasis type-III; PFIC3) and (PFIC2) genes were the most common affecting 19, 14 and 13 children, respectively. This study is the first to provide the landscape of pediatric monogenic liver diseases in a homogenous population from the Middle East and Africa, an area notoriously known to be poorly represented in genetic database and literature. Furthermore, our presented data are extremely important for genetic counseling and prenatal diagnosis and will further guide national health care policy makers to prevent or mitigate the effects of such disorders in the future.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00439-025-02776-4.

Elmonem, M. A., "Global burden of 292 causes of death in 204 countries and territories and 660 subnational locations, 1990-2023: a systematic analysis for the Global Burden of Disease Study 2023.", Lancet (London, England), vol. 406, issue 10513, pp. 1811-1872, 2025 Oct 18. Abstract

BACKGROUND: Timely and comprehensive analyses of causes of death stratified by age, sex, and location are essential for shaping effective health policies aimed at reducing global mortality. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 provides cause-specific mortality estimates measured in counts, rates, and years of life lost (YLLs). GBD 2023 aimed to enhance our understanding of the relationship between age and cause of death by quantifying the probability of dying before age 70 years (70q0) and the mean age at death by cause and sex. This study enables comparisons of the impact of causes of death over time, offering a deeper understanding of how these causes affect global populations.

METHODS: GBD 2023 produced estimates for 292 causes of death disaggregated by age-sex-location-year in 204 countries and territories and 660 subnational locations for each year from 1990 until 2023. We used a modelling tool developed for GBD, the Cause of Death Ensemble model (CODEm), to estimate cause-specific death rates for most causes. We computed YLLs as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. Probability of death was calculated as the chance of dying from a given cause in a specific age period, for a specific population. Mean age at death was calculated by first assigning the midpoint age of each age group for every death, followed by computing the mean of all midpoint ages across all deaths attributed to a given cause. We used GBD death estimates to calculate the observed mean age at death and to model the expected mean age across causes, sexes, years, and locations. The expected mean age reflects the expected mean age at death for individuals within a population, based on global mortality rates and the population's age structure. Comparatively, the observed mean age represents the actual mean age at death, influenced by all factors unique to a location-specific population, including its age structure. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 250-draw distribution for each metric. Findings are reported as counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2023 include a correction for the misclassification of deaths due to COVID-19, updates to the method used to estimate COVID-19, and updates to the CODEm modelling framework. This analysis used 55 761 data sources, including vital registration and verbal autopsy data as well as data from surveys, censuses, surveillance systems, and cancer registries, among others. For GBD 2023, there were 312 new country-years of vital registration cause-of-death data, 3 country-years of surveillance data, 51 country-years of verbal autopsy data, and 144 country-years of other data types that were added to those used in previous GBD rounds.

FINDINGS: The initial years of the COVID-19 pandemic caused shifts in long-standing rankings of the leading causes of global deaths: it ranked as the number one age-standardised cause of death at Level 3 of the GBD cause classification hierarchy in 2021. By 2023, COVID-19 dropped to the 20th place among the leading global causes, returning the rankings of the leading two causes to those typical across the time series (ie, ischaemic heart disease and stroke). While ischaemic heart disease and stroke persist as leading causes of death, there has been progress in reducing their age-standardised mortality rates globally. Four other leading causes have also shown large declines in global age-standardised mortality rates across the study period: diarrhoeal diseases, tuberculosis, stomach cancer, and measles. Other causes of death showed disparate patterns between sexes, notably for deaths from conflict and terrorism in some locations. A large reduction in age-standardised rates of YLLs occurred for neonatal disorders. Despite this, neonatal disorders remained the leading cause of global YLLs over the period studied, except in 2021, when COVID-19 was temporarily the leading cause. Compared to 1990, there has been a considerable reduction in total YLLs in many vaccine-preventable diseases, most notably diphtheria, pertussis, tetanus, and measles. In addition, this study quantified the mean age at death for all-cause mortality and cause-specific mortality and found noticeable variation by sex and location. The global all-cause mean age at death increased from 46·8 years (95% UI 46·6-47·0) in 1990 to 63·4 years (63·1-63·7) in 2023. For males, mean age increased from 45·4 years (45·1-45·7) to 61·2 years (60·7-61·6), and for females it increased from 48·5 years (48·1-48·8) to 65·9 years (65·5-66·3), from 1990 to 2023. The highest all-cause mean age at death in 2023 was found in the high-income super-region, where the mean age for females reached 80·9 years (80·9-81·0) and for males 74·8 years (74·8-74·9). By comparison, the lowest all-cause mean age at death occurred in sub-Saharan Africa, where it was 38·0 years (37·5-38·4) for females and 35·6 years (35·2-35·9) for males in 2023. Lastly, our study found that all-cause 70q0 decreased across each GBD super-region and region from 2000 to 2023, although with large variability between them. For females, we found that 70q0 notably increased from drug use disorders and conflict and terrorism. Leading causes that increased 70q0 for males also included drug use disorders, as well as diabetes. In sub-Saharan Africa, there was an increase in 70q0 for many non-communicable diseases (NCDs). Additionally, the mean age at death from NCDs was lower than the expected mean age at death for this super-region. By comparison, there was an increase in 70q0 for drug use disorders in the high-income super-region, which also had an observed mean age at death lower than the expected value.

INTERPRETATION: We examined global mortality patterns over the past three decades, highlighting-with enhanced estimation methods-the impacts of major events such as the COVID-19 pandemic, in addition to broader trends such as increasing NCDs in low-income regions that reflect ongoing shifts in the global epidemiological transition. This study also delves into premature mortality patterns, exploring the interplay between age and causes of death and deepening our understanding of where targeted resources could be applied to further reduce preventable sources of mortality. We provide essential insights into global and regional health disparities, identifying locations in need of targeted interventions to address both communicable and non-communicable diseases. There is an ever-present need for strengthened health-care systems that are resilient to future pandemics and the shifting burden of disease, particularly among ageing populations in regions with high mortality rates. Robust estimates of causes of death are increasingly essential to inform health priorities and guide efforts toward achieving global health equity. The need for global collaboration to reduce preventable mortality is more important than ever, as shifting burdens of disease are affecting all nations, albeit at different paces and scales.

FUNDING: Gates Foundation.

Elmonem, M. A., "Global age-sex-specific all-cause mortality and life expectancy estimates for 204 countries and territories and 660 subnational locations, 1950-2023: a demographic analysis for the Global Burden of Disease Study 2023.", Lancet (London, England), vol. 406, issue 10513, pp. 1731-1810, 2025 Oct 18. Abstract

BACKGROUND: Comprehensive, comparable, and timely estimates of demographic metrics-including life expectancy and age-specific mortality-are essential for evaluating, understanding, and addressing trends in population health. The COVID-19 pandemic highlighted the importance of timely and all-cause mortality estimates for being able to respond to changing trends in health outcomes, showing a strong need for demographic analysis tools that can produce all-cause mortality estimates more rapidly with more readily available all-age vital registration (VR) data. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) is an ongoing research effort that quantifies human health by estimating a range of epidemiological quantities of interest across time, age, sex, location, cause, and risk. This study-part of the latest GBD release, GBD 2023-aims to provide new and updated estimates of all-cause mortality and life expectancy for 1950 to 2023 using a novel statistical model that accounts for complex correlation structures in demographic data across age and time.

METHODS: We used 24 025 data sources from VR, sample registration, surveys, censuses, and other sources to estimate all-cause mortality for males, females, and all sexes combined across 25 age groups in 204 countries and territories as well as 660 subnational units in 20 countries and territories, for the years 1950-2023. For the first time, we used complete birth history data for ages 5-14 years, age-specific sibling history data for ages 15-49 years, and age-specific mortality data from Health and Demographic Surveillance Systems. We developed a single statistical model that incorporates both parametric and non-parametric methods, referred to as OneMod, to produce estimates of all-cause mortality for each age-sex-location group. OneMod includes two main steps: a detailed regression analysis with a generalised linear modelling tool that accounts for age-specific covariate effects such as the Socio-demographic Index (SDI) and a population attributable fraction (PAF) for all risk factors combined; and a non-parametric analysis of residuals using a multivariate kernel regression model that smooths across age and time to adaptably follow trends in the data without overfitting. We calibrated asymptotic uncertainty estimates using Pearson residuals to produce 95% uncertainty intervals (UIs) and corresponding 1000 draws. Life expectancy was calculated from age-specific mortality rates with standard demographic methods. For each measure, 95% UIs were calculated with the 25th and 975th ordered values from a 1000-draw posterior distribution.

FINDINGS: In 2023, 60·1 million (95% UI 59·0-61·1) deaths occurred globally, of which 4·67 million (4·59-4·75) were in children younger than 5 years. Due to considerable population growth and ageing since 1950, the number of annual deaths globally increased by 35·2% (32·2-38·4) over the 1950-2023 study period, during which the global age-standardised all-cause mortality rate declined by 66·6% (65·8-67·3). Trends in age-specific mortality rates between 2011 and 2023 varied by age group and location, with the largest decline in under-5 mortality occurring in east Asia (67·7% decrease); the largest increases in mortality for those aged 5-14 years, 25-29 years, and 30-39 years occurring in high-income North America (11·5%, 31·7%, and 49·9%, respectively); and the largest increases in mortality for those aged 15-19 years and 20-24 years occurring in Eastern Europe (53·9% and 40·1%, respectively). We also identified higher than previously estimated mortality rates in sub-Saharan Africa for all sexes combined aged 5-14 years (87·3% higher in GBD 2023 than GBD 2021 on average across countries and territories over the 1950-2021 period) and for females aged 15-29 years (61·2% higher), as well as lower than previously estimated mortality rates in sub-Saharan Africa for all sexes combined aged 50 years and older (13·2% lower), reflecting advances in our modelling approach. Global life expectancy followed three distinct trends over the study period. First, between 1950 and 2019, there were considerable improvements, from 51·2 (50·6-51·7) years for females and 47·9 (47·4-48·4) years for males in 1950 to 76·3 (76·2-76·4) years for females and 71·4 (71·3-71·5) years for males in 2019. Second, this period was followed by a decrease in life expectancy during the COVID-19 pandemic, to 74·7 (74·6-74·8) years for females and 69·3 (69·2-69·4) years for males in 2021. Finally, the world experienced a period of post-pandemic recovery in 2022 and 2023, wherein life expectancy generally returned to pre-pandemic (2019) levels in 2023 (76·3 [76·0-76·6] years for females and 71·5 [71·2-71·8] years for males). 194 (95·1%) of 204 countries and territories experienced at least partial post-pandemic recovery in age-standardised mortality rates by 2023, with 61·8% (126 of 204) recovering to or falling below pre-pandemic levels. There were several mortality trajectories during and following the pandemic across countries and territories. Long-term mortality trends also varied considerably between age groups and locations, demonstrating the diverse landscape of health outcomes globally.

INTERPRETATION: This analysis identified several key differences in mortality trends from previous estimates, including higher rates of adolescent mortality, higher rates of young adult mortality in females, and lower rates of mortality in older age groups in much of sub-Saharan Africa. The findings also highlight stark differences across countries and territories in the timing and scale of changes in all-cause mortality trends during and following the COVID-19 pandemic (2020-23). Our estimates of evolving trends in mortality and life expectancy across locations, ages, sexes, and SDI levels in recent years as well as over the entire 1950-2023 study period provide crucial information for governments, policy makers, and the public to ensure that health-care systems, economies, and societies are prepared to address the world's health needs, particularly in populations with higher rates of mortality than previously known. The estimates from this study provide a robust framework for GBD and a valuable foundation for policy development, implementation, and evaluation around the world.

FUNDING: Gates Foundation.

Elmonem, M. A., "Global, Regional, and National Burden of Cardiovascular Diseases and Risk Factors in 204 Countries and Territories, 1990-2023.", Journal of the American College of Cardiology, vol. 86, issue 22, pp. 2167-2243, 2025 Dec 02. Abstract

BACKGROUND: Cardiovascular diseases (CVDs) are the leading cause of mortality and are among the foremost causes of disability globally. CVD burden has continued to increase in most countries since 1990, with trends driven by changing exposures to harmful risk factors, population growth, and population aging.

OBJECTIVES: We report estimates of global, national, and subnational CVD burden, including 18 subdiseases and 12 associated modifiable risk factors. We analyzed change in CVD burden from 1990 to 2023 and identified drivers of change including population growth, population aging, and risk factor exposure.

METHODS: The Global Burden of Disease (GBD) 2023 study, a multinational collaborative research study, quantified burden due to 375 diseases including CVD burden and identified drivers of change from 1990 to 2023 using all available data and statistical models. GBD 2023 estimated the population-level burden of diseases in 204 countries and territories from 1990 to 2023.

RESULTS: CVDs were the leading cause of disability-adjusted life years (DALYs) and deaths estimated in the GBD. As of 2023, there were 437 million (95% UI: 401 to 465 million) CVD DALYs globally, a 1.4-fold increase from the number in 1990 of 320 million (292 to 344 million). Ischemic heart disease, intracerebral hemorrhage, ischemic stroke, and hypertensive heart disease were the leading cardiovascular causes of DALYs in 2023 globally. As of 2023, age-standardized CVD DALY rates were highest in low and low-middle Socio-demographic Index (SDI) settings and lowest in high SDI settings. The number of CVD deaths increased globally from 13.1 million (95% UI: 12.2 to 14.0 million) in 1990 to 19.2 million (95% UI: 17.4 to 20.4 million) in 2023. The number of prevalent cases of CVD more than doubled since 1990, with 311 million (95% UI: 294 to 333 million) prevalent cases of CVD in 1990 and 626 million (95% UI: 591 to 672 million) prevalent cases in 2023 globally. A total of 79.6% (95% UI: 75.7% to 82.5%) of CVD burden is attributable to modifiable risk factors 347 million [95% UI: 318 to 373 million] DALYs in 2023). Globally, high systolic blood pressure, dietary risks, high low-density lipoprotein cholesterol, and air pollution were the modifiable risks responsible for most attributable CVD burden in 2023. Since 1990, changes in exposure to modifiable risk factors have had mixed effects on CVD burden, with increases in high body mass index, high fasting plasma glucose, and low physical activity leading to higher burden, while reductions in tobacco usage have mitigated some of these increases. Population growth and population aging were the main drivers of the increasing burden since 1990, adding 128 million (95% UI: 115 to 139 million) and 139 million (95% UI: 126 to 151 million) CVD DALYs to the increase in CVD burden since 1990.

CONCLUSIONS: CVD remains the leading cause of disease burden and death worldwide with the greatest burden in low, low-middle, and middle SDI regions. Large variation exists in CVD burden even for countries at similar levels of development, a gap explained substantially by known, modifiable risk factors that are inadequately controlled. The decades-long increase in CVD burden was the result of population growth, population aging, and increased exposure to a subset of risk factors led by metabolic risks. Countries will need to adopt effective health system and public health strategies if they are to progress in achieving global goals to reduce the burden of CVD.

Elmonem, M. A., "The global, regional, and national burden attributable to low bone mineral density, 1990-2020: an analysis of a modifiable risk factor from the Global Burden of Disease Study 2021.", The Lancet. Rheumatology, vol. 7, issue 12, pp. e873-e894, 2025 Dec. Abstract

BACKGROUND: Fractures related to osteoporosis and low bone mineral density lead to substantial morbidity, mortality, and cost to individuals and health systems. Here we present the most up-to-date global, regional, and national estimates of the contribution of low bone mineral density to the burden of fractures from falls and additional categories of injuries from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021.

METHODS: The burden of low bone mineral density was estimated from 1990 to 2020 in terms of years lived with disability (YLDs), disability-adjusted life years (DALYs), and deaths, for individuals aged 40 years and older, using data from population-based studies from 48 countries or territories (169 unique sources). Mean standardised femoral neck bone mineral density values were estimated by GBD location, age, and sex by meta-regression. Based on a separate meta-analysis of population-based studies from nine countries (12 unique sources), we also estimated the pooled relative risk of fractures per unit decrease in bone mineral density (g/cm). The population-attributable fraction for low bone mineral density was calculated by comparing the observed distributions of standardised femoral neck bone mineral density to an age-specific and sex-specific counterfactual distribution, defined as the 99th percentile of five rounds of the National Health and Nutrition Examination Survey in the USA, by 5-year age group and sex. Hospital and emergency department data were used to derive the incidence of fractures for six categories of injury (road injuries, other transport injuries, falls, non-venomous animal contact, exposure to mechanical forces, and physical interpersonal violence) using ICD codes. Deaths due to fractures were estimated as the proportion of in-hospital deaths due to the specified injury causes for which a fracture (nature of injury code) was more severe than the cause of injury code. YLDs and DALYs attributable to low bone mineral density by cause of injury were also determined according to previous GBD methods.

FINDINGS: In 2020, 8·32 million (95% UI 5·58-10·84) YLDs, 17·2 million (14·1-20·2) DALYs, and 477 000 (411 000-536 000) deaths were attributable to low bone mineral density globally in individuals aged 40 years and older. Between 1990 and 2020, global YLDs, DALYs, and deaths attributable to low bone mineral density increased by 91·8% (88·5-95·1), 89·8% (81·5-99·0), and 127·1% (108·5-144·5), respectively. Over this period, the age-standardised global rates of YLDs, DALYs, and deaths attributable to low bone mineral density showed modest decreases. In 2020, falls accounted for 76·2% (95% UI 74·2-78·3) of YLDs, 65·2% (62·9-67·6) of DALYs, and 71·0% (67·4-72·8) of deaths attributable to low bone mineral density, and road injuries largely accounted for the remaining amount: 12·4% (11·1-13·6) of YLDs, 24·6% (22·5-27·1) of DALYs, and 23·1% (21·6-26·2) of deaths. As a proportion of all fall-related burden, low bone mineral density accounted for 26·6% (23·2-28·7) of YLDs, 25·6% (22·1-27·4) of DALYs, and 40·6% (35·4-44·0) of deaths in 2020. Of all road injury-related burden, 12·6% (10·8-13·5) of YLDs, 6·3% (5·4-6·9) of DALYs, and 8·9% (7·6-9·6) of deaths were attributable to low bone mineral density. In men, road injuries accounted for the largest proportion of DALYs attributable to low bone mineral density in those aged 40-59 years and the largest proportion of deaths in those aged 40-64 years. In women, road injuries were the leading cause of DALYs attributable to low bone mineral density in those aged 40-44 years and the leading cause of deaths attributable to low bone mineral density in those aged 40-54 years. In older age groups among both men and women, falls were the leading cause of the burden attributable to low bone mineral density.

INTERPRETATION: Low bone mineral density is a crucial modifiable risk factor for fractures, which are an important cause of morbidity and mortality particularly in ageing populations. This analysis highlights low bone mineral density as a cause of health loss not just from falls, but also from road injuries.

FUNDING: Gates Foundation.

Elmonem, M. A., "Global, regional, and national prevalence of kidney failure with replacement therapy and associated aetiologies, 1990-2023: a systematic analysis for the Global Burden of Disease Study 2023.", The Lancet. Global health, vol. 13, issue 8, pp. e1378-e1395, 2025 Aug. Abstract

BACKGROUND: Kidney failure with replacement therapy (KFRT) such as dialysis or transplantation represents a severe stage of chronic kidney disease (CKD) and poses a major global health burden. Although many CKD cases are diagnosed in the earlier stages, the greatest risk occurs when CKD progresses to KFRT. Despite its considerable financial and imposing impact on public health, there is a notable gap in international policies addressing CKD and KFRT. To bridge this gap and help policy makers and health systems effectively tackle the public health challenge of KFRT, a better understanding of the disease burden is essential. Thus, this analysis aims to provide a detailed overview of the global prevalence of KFRT and its associated aetiologies with estimates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) from 1990 to 2023.

METHODS: This study defined KFRT as individuals on maintenance dialysis for 90 days or more or those who have undergone a kidney transplant, aligning with the Kidney Disease: Improving Global Outcomes (KDIGO) 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Renal registries served as the primary data sources. Prevalence and underlying aetiology estimates (type 1 diabetes, type 2 diabetes, hypertension, glomerulonephritis, and other causes) were generated with DisMod-MR 2.1, an epidemiological Bayesian mixed-effects meta-regression modelling tool. Both all-age and age-standardised estimates were reported and accompanied with 95% uncertainty intervals (UIs).

FINDINGS: In 2023, the number of global cases of KFRT was 4·59 million (95% UI 4·17-5·08) for both sexes and all ages, with an age-standardised prevalence of 50·7 (46·1-56·0) per 100 000 population. Over the past three decades, there has been a steady increase in KFRT prevalence globally. The highest prevalence was found in the GBD high-income regions, while the lowest was observed in sub-Saharan Africa. KFRT prevalence was generally higher in countries classified within the World Bank's high-income and upper-middle-income groups, while lower prevalence was more common in countries within the World Bank's low-income and lower-middle-income groups. Additionally, a pronounced sex disparity was identified, where male dialysis and transplant prevalence estimates were consistently higher than those for females in most countries. Type 2 diabetes and hypertension were among the leading associated aetiologies of KFRT globally. From 1990 to 2023, the all-age and age-standardised prevalence estimates across the ascribed aetiologies increased for KFRT, with the largest increases associated with type 2 diabetes and hypertension.

INTERPRETATION: KFRT affects approximately 5 million people globally, with high treatment and mortality costs. Our study unveiled considerable geographical variation in KFRT prevalence, which should be seen as indicators of health-care system opportunities. As the prevalence of the leading aetiologies of KFRT-type 2 diabetes and hypertension-continues to rise, there is a crucial need to prioritise the development and implementation of cost-effective strategies aimed at preventing CKD and its progression to KFRT, particularly in low-resource settings. These preventive efforts must happen in tandem with efforts to expand capacity for dialysis and transplant services.

FUNDING: Gates Foundation.