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[This corrects the article DOI: 10.1055/a-2692-6661.][This corrects the article DOI: 10.1055/a-2699-8104.].
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. 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. 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. 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. Gates Foundation.
The majority of respiratory syncytial virus (RSV) infections in young children are managed in primary care, however, the disease burden in this setting remains poorly defined. We did a prospective cohort study in primary care settings in Belgium, Italy, Spain, the Netherlands, and the UK during the RSV seasons of 2020-21 (UK only; from Jan 1, 2021), 2021-22, and 2022-23. Children aged younger than 5 years presenting to their general practitioner or primary care paediatrician with symptoms of an acute respiratory tract infection were eligible for RSV testing. Children who tested positive for RSV were consented and followed up for 30 days via a physician clinical report (initial primary care visit on day 1) and two parent-report questionnaires (days 14 and 30). We assessed the burden of RSV in terms of clinical course (symptoms, illness duration, and complications), health-care resource utilisation (primary care visits, emergency department visits, hospitalisation rate, and medication use), and societal impact (daycare or school absence and parental work absence) for the 30-day follow-up period. Among 3414 tested children, 1124 (32·9%; 95% CI 31·3-34·5) tested positive for RSV. Among children with data on age, RSV positivity rate was 38·9% (36·1-41·7; n=466 of 1198) in children younger than 1 year and 25·9% (24·0-27·9; n=513 of 1979) in those aged 1 to <5 years. Of the 1124 RSV-positive children, 878 (78·1%) were enrolled and had day 1 data collected (median age 11·1 months [IQR 6·0-22·0]; 446 [50·9%] boys and 431 [49·1%] girls [N=877]). RSV illness lasted a mean of 11·7 days (95% CI 11·2-12·2; n=794). At day 14 and day 30, any remaining symptoms were reported in 451 of 804 (56·1% [95% CI 52·6-59·6]) and 261 of 724 (36·0% [32·6-39·7]) children. The mean number of primary care visits per child ranged from 1·4 (95% CI 1·2-1·6; the Netherlands) to 3·0 (2·8-3·3; Spain), and was higher in children younger than 1 year (2·7 visits [2·4-2·9]) than in those aged 1 to <5 years (2·1 [1·9-2·2]). Prescribed medication use varied, from 25 of 96 children (26·0% [95% CI 17·6-36·0]; the UK) to 228 of 297 children (76·8% [71·5-81·5]; Italy), with bronchodilators and antibiotics being the most commonly prescribed medicines across all countries. Prescribed medication use was reported in 258 of 418 children aged 1 to <5 years (61·7% [56·9-66·4]) and 196 of 394 children younger than 1 year (49·7% [44·7-54·8]). Missed working days by parents due to their child's RSV illness were reported in 340 of 744 cases (45·7% [42·1-49·4]); the mean number of missed workdays ranged from 1·3 days (95% CI 0·5-2·2) in Spain to 4·1 days (3·3-5·0) in Belgium. RSV infections in children younger than 5 years in primary care are associated with substantial symptomatology, health-care utilisation, and parental work absence. Notable differences in RSV burden existed across countries, likely due to differences in primary health-care systems, clinical practice, and health-care-seeking behaviour. This study emphasises the importance of considering country-specific primary care burden estimates when considering the implementation of RSV immunisations programmes. Sanofi and AstraZeneca.
For more than three decades, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) has provided a framework to quantify health loss due to diseases, injuries, and associated risk factors. This paper presents GBD 2023 findings on disease and injury burden and risk-attributable health loss, offering a global audit of the state of world health to inform public health priorities. This work captures the evolving landscape of health metrics across age groups, sexes, and locations, while reflecting on the remaining post-COVID-19 challenges to achieving our collective global health ambitions. The GBD 2023 combined analysis estimated years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) for 375 diseases and injuries, and risk-attributable burden associated with 88 modifiable risk factors. Of the more than 310 000 total data sources used for all GBD 2023 (about 30% of which were new to this estimation round), more than 120 000 sources were used for estimation of disease and injury burden and 59 000 for risk factor estimation, and included vital registration systems, surveys, disease registries, and published scientific literature. Data were analysed using previously established modelling approaches, such as disease modelling meta-regression version 2.1 (DisMod-MR 2.1) and comparative risk assessment methods. Diseases and injuries were categorised into four levels on the basis of the established GBD cause hierarchy, as were risk factors using the GBD risk hierarchy. Estimates stratified by age, sex, location, and year from 1990 to 2023 were focused on disease-specific time trends over the 2010-23 period and presented as counts (to three significant figures) and age-standardised rates per 100 000 person-years (to one decimal place). For each measure, 95% uncertainty intervals [UIs] were calculated with the 2·5th and 97·5th percentile ordered values from a 250-draw distribution. Total numbers of global DALYs grew 6·1% (95% UI 4·0-8·1), from 2·64 billion (2·46-2·86) in 2010 to 2·80 billion (2·57-3·08) in 2023, but age-standardised DALY rates, which account for population growth and ageing, decreased by 12·6% (11·0-14·1), revealing large long-term health improvements. Non-communicable diseases (NCDs) contributed 1·45 billion (1·31-1·61) global DALYs in 2010, increasing to 1·80 billion (1·63-2·03) in 2023, alongside a concurrent 4·1% (1·9-6·3) reduction in age-standardised rates. Based on DALY counts, the leading level 3 NCDs in 2023 were ischaemic heart disease (193 million [176-209] DALYs), stroke (157 million [141-172]), and diabetes (90·2 million [75·2-107]), with the largest increases in age-standardised rates since 2010 occurring for anxiety disorders (62·8% [34·0-107·5]), depressive disorders (26·3% [11·6-42·9]), and diabetes (14·9% [7·5-25·6]). Remarkable health gains were made for communicable, maternal, neonatal, and nutritional (CMNN) diseases, with DALYs falling from 874 million (837-917) in 2010 to 681 million (642-736) in 2023, and a 25·8% (22·6-28·7) reduction in age-standardised DALY rates. During the COVID-19 pandemic, DALYs due to CMNN diseases rose but returned to pre-pandemic levels by 2023. From 2010 to 2023, decreases in age-standardised rates for CMNN diseases were led by rate decreases of 49·1% (32·7-61·0) for diarrhoeal diseases, 42·9% (38·0-48·0) for HIV/AIDS, and 42·2% (23·6-56·6) for tuberculosis. Neonatal disorders and lower respiratory infections remained the leading level 3 CMNN causes globally in 2023, although both showed notable rate decreases from 2010, declining by 16·5% (10·6-22·0) and 24·8% (7·4-36·7), respectively. Injury-related age-standardised DALY rates decreased by 15·6% (10·7-19·8) over the same period. Differences in burden due to NCDs, CMNN diseases, and injuries persisted across age, sex, time, and location. Based on our risk analysis, nearly 50% (1·27 billion [1·18-1·38]) of the roughly 2·80 billion total global DALYs in 2023 were attributable to the 88 risk factors analysed in GBD. Globally, the five level 3 risk factors contributing the highest proportion of risk-attributable DALYs were high systolic blood pressure (SBP), particulate matter pollution, high fasting plasma glucose (FPG), smoking, and low birthweight and short gestation-with high SBP accounting for 8·4% (6·9-10·0) of total DALYs. Of the three overarching level 1 GBD risk factor categories-behavioural, metabolic, and environmental and occupational-risk-attributable DALYs rose between 2010 and 2023 only for metabolic risks, increasing by 30·7% (24·8-37·3); however, age-standardised DALY rates attributable to metabolic risks decreased by 6·7% (2·0-11·0) over the same period. For all but three of the 25 leading level 3 risk factors, age-standardised rates dropped between 2010 and 2023-eg, declining by 54·4% (38·7-65·3) for unsafe sanitation, 50·5% (33·3-63·1) for unsafe water source, and 45·2% (25·6-72·0) for no access to handwashing facility, and by 44·9% (37·3-53·5) for child growth failure. The three leading level 3 risk factors for which age-standardised attributable DALY rates rose were high BMI (10·5% [0·1 to 20·9]), drug use (8·4% [2·6 to 15·3]), and high FPG (6·2% [-2·7 to 15·6]; non-significant). Our findings underscore the complex and dynamic nature of global health challenges. Since 2010, there have been large decreases in burden due to CMNN diseases and many environmental and behavioural risk factors, juxtaposed with sizeable increases in DALYs attributable to metabolic risk factors and NCDs in growing and ageing populations. This long-observed consequence of the global epidemiological transition was only temporarily interrupted by the COVID-19 pandemic. The substantially decreasing CMNN disease burden, despite the 2008 global financial crisis and pandemic-related disruptions, is one of the greatest collective public health successes known. However, these achievements are at risk of being reversed due to major cuts to development assistance for health globally, the effects of which will hit low-income countries with high burden the hardest. Without sustained investment in evidence-based interventions and policies, progress could stall or reverse, leading to widespread human costs and geopolitical instability. Moreover, the rising NCD burden necessitates intensified efforts to mitigate exposure to leading risk factors-eg, air pollution, smoking, and metabolic risks, such as high SBP, BMI, and FPG-including policies that promote food security, healthier diets, physical activity, and equitable and expanded access to potential treatments, such as GLP-1 receptor agonists. Decisive, coordinated action is needed to address long-standing yet growing health challenges, including depressive and anxiety disorders. Yet this can be only part of the solution. Our response to the NCD syndemic-the complex interaction of multiple health risks, social determinants, and systemic challenges-will define the future landscape of global health. To ensure human wellbeing, economic stability, and social equity, global action to sustain and advance health gains must prioritise reducing disparities by addressing socioeconomic and demographic determinants, ensuring equitable health-care access, tackling malnutrition, strengthening health systems, and improving vaccination coverage. We live in times of great opportunity. Gates Foundation and Bloomberg Philanthropies.
The 2023 iteration of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) estimated prevalence, incidence, and health burden for 375 diseases and injuries, including 12 mental disorders. We assess past, current, and emerging trends in the prevalence and burden of mental disorders across sexes and age groups, for 21 regions, 204 countries and territories, and by Socio-demographic Index (SDI) quintile, from 1990 to 2023. Mental disorders included in GBD 2023 were anxiety disorders, major depressive disorder, dysthymia, bipolar disorder, schizophrenia, autism spectrum disorders, conduct disorder, attention-deficit hyperactivity disorder, anorexia nervosa, bulimia nervosa, idiopathic developmental intellectual disability, and a residual category of other mental disorders. A literature review identified epidemiological data for each disorder. These were analysed via a Bayesian meta-regression to estimate prevalence by disorder, sex, age, location, and year. Disorder-specific prevalence was multiplied by disability weights representing the severity of health loss associated with each disorder to estimate years lived with disability (YLDs). Deaths due to anorexia nervosa were assessed with a Cause of Death Ensemble modelling strategy to estimate deaths by sex, age, location, and year, and then multiplied by the standard life expectancy at age of death to estimate years of life lost (YLLs). YLDs equalled disability-adjusted life-years (DALYs) for all mental disorders except anorexia nervosa (the only mental disorder considered as an underlying cause of death in GBD), for which DALYs represented the sum of YLDs and YLLs. We presented prevalence, deaths, YLDs, YLLs, and DALYs as counts, age-specific rates per 100 000 population, and age-standardised rates per 100 000 population. We estimated 1·17 billion (95% uncertainty interval 1·06-1·31) prevalent cases of mental disorders globally in 2023, equivalent to an age-standardised prevalence rate of 14 210·7 cases (12 849·5-15 940·1) per 100 000 population. These estimates represented a 95·5% (75·0-121·2) increase in prevalent cases and 24·2% (11·4-41·4) increase in age-standardised prevalence rate between 1990 and 2023. All mental disorders showed increases in prevalent cases between 1990 and 2023, while notable increases were seen in age-standardised prevalence rates for anxiety disorders, major depressive disorder, dysthymia, anorexia nervosa, bulimia nervosa, schizophrenia, and conduct disorder. There were an estimated 171 million (127-228) DALYs due to mental disorders globally across sex and age in 2023, equivalent to an age-standardised DALY rate of 2070·5 DALYs (1519·1-2750·5) per 100 000 population. Mental disorders contributed to 6·1% (4·8-7·6) of all-cause DALYs in 2023, making them the fifth leading cause of global DALYs (up from 12th in 1990). DALYs were almost entirely composed of YLDs. Mental disorders were the leading cause of YLDs in 2023 (up from second in 1990), explaining 17·3% (14·8-20·6) of all-cause global YLDs. Leading causes of mental disorder DALYs were anxiety disorders (ranked 11th among the 304 diseases and injuries at Level 4 of the GBD cause hierarchy), major depressive disorder (15th), and schizophrenia (41st). Globally in 2023, mental disorder age-standardised DALY rates were higher among females (2239·6 [1643·7-3014·1] per 100 000) than among males (1900·2 [1399·8-2510·8] per 100 000), and peaked in the 15-19 years age group (2617·3 [1850·6-3696·8] per 100 000). All locations showed increased mental disorder DALY rates in 2023 compared with 1990, ranging across countries and territories from 1302·4 (952·7-1683·7) per 100 000 in Viet Nam to 3555·8 (2661·9-4715·0) per 100 000 in the Netherlands. Across SDI quintiles, DALY rates ranged from 1853·0 (1352·1-2469·3) per 100 000 for middle SDI to 2184·1 (1606·1-2890·3) per 100 000 for high SDI. A significant health burden was imposed by mental disorders in all countries and territories in 2023, irrespective of the health resources available. In some instances, this burden has increased over time and is unevenly distributed across populations. Stronger surveillance systems, particularly in low-income and middle-income countries, are required. Additionally, we need more coordinated and inclusive policies to reduce the burden through early treatment and prevention, tailored to sex and age differences across locations. Responding to the mental health needs of our global population, especially those most vulnerable, is an obligation, not a choice. Gates Foundation, Queensland Health, and University of Queensland.
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. 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. 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. 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. Gates Foundation.
Cancer is a leading cause of death globally. Accurate cancer burden information is crucial for policy planning, but many countries do not have up-to-date cancer surveillance data. To inform global cancer-control efforts, we used the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 framework to generate and analyse estimates of cancer burden for 47 cancer types or groupings by age, sex, and 204 countries and territories from 1990 to 2023, cancer burden attributable to selected risk factors from 1990 to 2023, and forecasted cancer burden up to 2050. Cancer estimation in GBD 2023 used data from population-based cancer registration systems, vital registration systems, and verbal autopsies. Cancer mortality was estimated using ensemble models, with incidence informed by mortality estimates and mortality-to-incidence ratios (MIRs). Prevalence estimates were generated from modelled survival estimates, then multiplied by disability weights to estimate years lived with disability (YLDs). Years of life lost (YLLs) were estimated by multiplying age-specific cancer deaths by the GBD standard life expectancy at the age of death. Disability-adjusted life-years (DALYs) were calculated as the sum of YLLs and YLDs. We used the GBD 2023 comparative risk assessment framework to estimate cancer burden attributable to 44 behavioural, environmental and occupational, and metabolic risk factors. To forecast cancer burden from 2024 to 2050, we used the GBD 2023 forecasting framework, which included forecasts of relevant risk factor exposures and used Socio-demographic Index as a covariate for forecasting the proportion of each cancer not affected by these risk factors. Progress towards the UN Sustainable Development Goal (SDG) target 3.4 aim to reduce non-communicable disease mortality by a third between 2015 and 2030 was estimated for cancer. In 2023, excluding non-melanoma skin cancers, there were 18·5 million (95% uncertainty interval 16·4 to 20·7) incident cases of cancer and 10·4 million (9·65 to 10·9) deaths, contributing to 271 million (255 to 285) DALYs globally. Of these, 57·9% (56·1 to 59·8) of incident cases and 65·8% (64·3 to 67·6) of cancer deaths occurred in low-income to upper-middle-income countries based on World Bank income group classifications. Cancer was the second leading cause of deaths globally in 2023 after cardiovascular diseases. There were 4·33 million (3·85 to 4·78) risk-attributable cancer deaths globally in 2023, comprising 41·7% (37·8 to 45·4) of all cancer deaths. Risk-attributable cancer deaths increased by 72·3% (57·1 to 86·8) from 1990 to 2023, whereas overall global cancer deaths increased by 74·3% (62·2 to 86·2) over the same period. The reference forecasts (the most likely future) estimate that in 2050 there will be 30·5 million (22·9 to 38·9) cases and 18·6 million (15·6 to 21·5) deaths from cancer globally, 60·7% (41·9 to 80·6) and 74·5% (50·1 to 104·2) increases from 2024, respectively. These forecasted increases in deaths are greater in low-income and middle-income countries (90·6% [61·0 to 127·0]) compared with high-income countries (42·8% [28·3 to 58·6]). Most of these increases are likely due to demographic changes, as age-standardised death rates are forecast to change by -5·6% (-12·8 to 4·6) between 2024 and 2050 globally. Between 2015 and 2030, the probability of dying due to cancer between the ages of 30 years and 70 years was forecasted to have a relative decrease of 6·5% (3·2 to 10·3). Cancer is a major contributor to global disease burden, with increasing numbers of cases and deaths forecasted up to 2050 and a disproportionate growth in burden in countries with scarce resources. The decline in age-standardised mortality rates from cancer is encouraging but insufficient to meet the SDG target set for 2030. Effectively and sustainably addressing cancer burden globally will require comprehensive national and international efforts that consider health systems and context in the development and implementation of cancer-control strategies across the continuum of prevention, diagnosis, and treatment. Gates Foundation, St Jude Children's Research Hospital, and St Baldrick's Foundation.
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. 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. 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. 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. Gates Foundation.
Neuroblastoma, the most common extracranial solid tumor in children, requires meticulous surgical interventions due to its complex anatomical location and proximity to vital structures. Emerging technologies, such as virtual reality (VR) and indocyanine green (ICG) fluorescence-guided imaging, offer promising solutions to enhance surgical precision and outcomes. Despite their potential, their use in pediatric oncology remains underexplored. This case report highlights the integration of VR and ICG fluorescence imaging in the surgical treatment of neuroblastoma, emphasizing their benefits, limitations, and the need for further advancements. A 12-month-old female with a prenatal diagnosis of cloacal malformation, Müllerian anomalies, and a horseshoe kidney was under care at our center for the management of her complex urogenital anomalies. During preoperative imaging to plan her reconstructive surgery, an abdominal MRI revealed a solid retroperitoneal mass, later confirmed as a right adrenal neuroblastoma. After six cycles of chemotherapy, metaiodobenzylguanidine (mIBG) scans indicated persistent uptake, suggesting the possible presence of tumor viability. Consequently, a definitive surgical resection was scheduled. The procedure incorporated VR for navigation and ICG fluorescence for real-time vascular mapping, facilitating precise dissection and preservation of critical structures. The patient's postoperative recovery was uneventful, and she was discharged in stable condition. Follow-up evaluations (i.e., MRI, mIBG) showed no evidence of residual macroscopic disease. VR and ICG fluorescence imaging hold promise for enhancing surgical precision and safety in pediatric neuroblastoma. While current limitations include the lack of real-time image overlay and inadequate visualization of tumor margins, future advancements in navigation systems and targeted probes may overcome these barriers and significantly improve oncologic outcomes.
Concurrent rupture of hepatic hydatid cysts into the biliary tree and into the pleural cavity is a very rare complication in echinococcosis and can pose diagnostic and treatment challenges. We present the case of a 15-year-old female patient with recurrent abdominal pain, chest pain, fever, vomiting, jaundice, and cholangitis. Ultrasound, X-rays, computed tomography of the abdomen and thorax and cholangio-magnetic resonance imaging revealed a hepatic hydatid cyst with rupture into the main biliary duct causing obstruction, gallbladder microlithiasis, rupture of the right hemidiaphragm, and pleural hydatidosis. Echinococcus serology tests were positive. Endoscopic retrograde cholangiopancreatography (ERCP) could not resolve the obstructive jaundice. A laparotomy with choledochotomy, removal of hydatid structures, choledochal drainage with Kehr tube, cholecystectomy, Lagrot partial pericystectomy, partial pleural resection, suturing of the diaphragm, and triple drainage (right pleural cavity, cystic cavity, and Douglas pouch) was performed. Perioperative albendazole and antibiotic therapy was administered. The patient had an uneventful postoperative course. Follow-up at 1, 6, 12, and 24 months showed a favorable evolution without relapse of the hydatidosis. The very rare complications of cholangiohydatidosis and concomitant hepatothoracic transit lead to a severe condition, which needs adequate surgical treatment. Clinical presentation and laboratory findings are not specific and may simulate an obstructive jaundice and acute cholangitis of other etiology. ERCP with endoscopic papillotomy offers the advantage of a minimally invasive surgery, but it does not allow a definitive treatment of the whole problem and may be useful as a bridge procedure to drain the bile duct while awaiting definitive surgery.
Healthcare professionals face significant challenges when deciding whether to continue or withdraw Extracorporeal Life Support (ECLS) in pediatric patients, which may cause moral distress. The ENd-of-life deciSion-making dURing ECLS (ENSURE) survey investigates the perspectives of European healthcare professionals on ECLS discontinuation in pediatric patients considering the potential impact of cultural, religious, and regional factors. A 23-item mixed-method questionnaire survey was conducted across 21 European countries in different languages, assessing respondent demographics, ethical viewpoints, and institutional practices. The analysis focused on differences in decision-making based on geographic region, profession, and religion. A total of 192 healthcare professionals participated, with 68% from ELSO centers. Most respondents (77%) agreed that ethics consultations would benefit patients and families when ECLS fails to meet treatment goals. Preferences for discontinuing ECLS varied regionally, with practitioners from Northern and Western Europe more likely to favor the discontinuation of ECLS with comfort care (62-68%) compared to those from Southern and Eastern Europe (34-50%). Religious beliefs might influence decisions, with Christian and agnostic/atheist participants more likely to support ECLS discontinuation.  Decision-making surrounding ECLS discontinuation in pediatric patients is influenced by regional, cultural, and possibly religious factors. There is a need for standardized guidelines and expanded access to ethics consultations to support healthcare professionals and reduce moral distress in these complex cases. Addressing discordance in clinical teams and enhancing palliative care access may improve the decision-making process and patient care outcomes. •Decisions about ECLS withdrawal in pediatric patients are ordinarily made in close consultation with families, who are particularly influenced by emotional factors. •There is a scarcity of literature related to the ethics of ECLS initiation, continuation, and termination in children, providing minimal, specific ethical recommendations. •The ENSURE study evaluates current viewpoints of ECLS professionals across Europe and investigates influencing respondent or institutional characteristics. •Guidelines for managing ECLS patients considering regional, religious, and cultural factors could reduce variability in treatment and mental distress in decision-making.
Breast cancer is a leading cause of mortality and morbidity among females worldwide. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023, we provided an updated comprehensive assessment of the epidemiological trends, disease burden, and risk factors associated with breast cancer globally, regionally, and nationally from 1990 to 2023. Breast cancer incidence, mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) were estimated by age and sex for 204 countries and territories from 1990 to 2023. Mortality estimates were generated using GBD Cause of Death Ensemble models, leveraging data from population-based cancer registration systems, vital registration systems, and verbal autopsies. Mortality-to-incidence ratios were calculated to derive both mortality and incidence estimates. Prevalence was calculated by combining incidence and modelled survival estimates. YLLs were established by multiplying age-specific deaths with the GBD standard life expectancy at the age of death. YLDs were estimated by applying disability weights to prevalence estimates. The sum of YLLs and YLDs equalled the number of DALYs. Breast cancer burden attributable to seven risk factors was examined through the comparative risk assessment framework. The GBD forecasting framework was used to forecast breast cancer incidence and mortality from 2024 to 2050. Age-standardised rates were calculated for each metric using the GBD 2023 world standard population. In 2023, there were an estimated 2·30 million (95% uncertainty interval [UI] 2·01 to 2·61) breast cancer incident cases, 764 000 deaths (672 000 to 854 000), and 24·1 million (21·3 to 27·5) DALYs among females globally. In the World Bank low-income group, where a low age-standardised incidence rate (ASIR) was estimated (44·2 per 100 000 person-years [31·2 to 58·4]), the age-standardised mortality rate (ASMR) was the highest (24·1 per 100 000 [16·8 to 31·9]). The highest ASIR was in the high-income group (75·7 per 100 000 [67·1 to 84·0]), and the lowest ASMR was in the upper-middle-income group (11·2 per 100 000 [10·2 to 12·3]). Between 1990 and 2023, the ASIR in the low-income group increased by 147·2% (38·1 to 271·7), compared with a 1·2% (-11·5 to 17·2) change in the high-income group. The ASMR decreased in the high-income group, changing by -29·9% (-33·6 to -25·9), but increased by 99·3% (12·5 to 202·9) in the low-income group. The increase in age-standardised DALY rates followed that of ASMRs. Risk factors such as dietary risks, tobacco use, and high fasting plasma glucose contributed to 28·3% (16·6 to 38·9) of breast cancer DALYs in 2023. The risk factors with a decrease in attributable DALYs between 1990 and 2023 were high alcohol use and tobacco. By 2050, the global incident cases of breast cancer among females were forecast to reach 3·56 million (2·29 to 4·83), with 1·37 million (0·841 to 2·02) deaths. The stable incidence and declining mortality rates of female breast cancer in high-income nations reflect success in screening, diagnosis, and treatment. In contrast, the concurrent rise in incidence and mortality in other regions signals health system deficits. Without effective interventions, many countries will fall short of the WHO Global Breast Cancer Initiative's ambitious target of achieving an annual reduction of 2·5% in age-standardised mortality rates by 2040. The mounting breast cancer burden, disproportionately affecting some of the world's most vulnerable populations, will further exacerbate health inequalities across the globe without decisive immediate action. Gates Foundation, St Jude Children's Research Hospital.
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. 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. 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. 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. Gates Foundation.
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. 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]). 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. 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. Bill & Melinda Gates Foundation.
INTRODUCTION: Low health literacy (HL) can impair decision-making in emergencies. Extending our preceding adult study, this preregistered observational study examined whether parental HL affects accuracy of severity assessments in the pediatric emergency department (PED) and whether the validity of children’s self-reports is age dependent. METHODS: This single-center prospective cross-sectional study enrolled 182 pediatric patients and parents presenting to a German university hospital PED. Subjective and independent emergency condition severity assessments were obtained from patients, parents, and medical staff. Parental HL was measured using the 16-item European Health Literacy Survey questionnaire (HLS-EU-Q16). Reference standard severity assessment was retrospectively collected by specialists (retrospective chart-based chase assessment). Analyses compared assessment accuracy across three parental HL level groups (adequate, problematic, inadequate). Assessments were adjusted for covariates except for regression analyses, which we performed using unadjusted values. RESULTS: Parental HL showed no measurable effect on assessment accuracy, discrepancy or concordance with medical team’s evaluations. Children’s self-reported anxiety emerged as a stronger predictor of actual clinical severity than HL measurements, with this relationship becoming significant at 8 years of age. Children’s severity assessment (OR = 1.38 [1.20, 1.57], p < .001) and less distinctly anxiety (OR = 1.15, 95% CI [1.01, 1.31], p = .037) predicted severe outcome, while the interaction between age and anxiety (B = 0.071, SE = 0.031, p = .022) showed that anxiety becomes a reliable indicator at around early school age. Concordance with the team’s assessment likewise emerged at school age (ρ ≈ 0.30, p < .05). Direct children’s self-assessment provided clinically meaningful information across all HL groups. Nursing assessments remained the strongest predictor of severe outcomes (OR = 1.95, 95% CI [1.37, 2.67], p < .001), followed by physicians (OR = 1.62, 95% CI [1.20, 2.19], p < .001). Parents were in our study not able to predict severe outcome (p = .22). Parental underestimation relative to specialists was consistently linked to severe outcomes (26–33%), regardless of HL level. CONCLUSION: Contrary to common assumptions, parental HL neither impaired nor improved recognition of pediatric emergency severity, and HL did not systematically shift discrepancy patterns. Instead, developmental maturity and professional observation are relevant for severity assessment. From early school age (7–8 years), children’s anxiety appears to provide an increasingly valid, dose-responsive signal of severity. Nurses’ assessments provided the highest predictive accuracy, underscoring their central role in triage. Age-appropriate use of pediatric patients’ self-assessments could further support risk stratification in the PED. CLINICAL TRIALS REGISTRATION: This observational study was preregistered in the German Clinical Trials Register (DRKS): DRKS00034108, Registration Date: 30th January 2025.
Congenital esophageal stenosis is a rare and heterogenous malformation often associated with esophageal atresia (EA). Failure of conservative endoscopic treatment leads to surgery. Transthoracic approach is rarely advocated due to the peridiaphragmatic localization of the stricture. Robotic-assisted thoracoscopic surgery (RATS) may offer enhanced precision in confined spaces; its application in patients under 10 kg is still considered a challenge. We report the first description of RATS resection of cartilaginous congenital stenosis and esophagoesophagostomy in a 9.5 kg patient. A female patient with a history of EA type III was corrected via videothoracoscopy, two cardiac surgeries via sternotomy, and laparoscopic treatment of duodenal atresia. During weaning, she did not tolerate thickened food, and endoscopy revealed a patent anastomosis but a distal esophageal stricture. A course of pneumatic dilation was attempted. Persistent clinical and radiological findings indicated the need for surgery. At 15 months, the patient underwent three-trocar thoracoscopy with the da Vinci Xi system. Esophagoscopy helped the identification of the stricture. A longitudinal incision exposed a 2-cm segment of thickened esophageal wall requiring complete excision. A tension-free end-to-end anastomosis was performed using 4/0 PDS. Tracheobronchial remnants were confirmed at histopathologIcal finding. Esophageal contrastography demonstrated a good diameter anastomosis. One month after the operation, she was able to swallow solid food. Surgery for congenital stenosis is indicated when endoscopic management fails. RATS for esophageal diseases in patients under 10 kg is feasible, and peridiahragmatic esophagus particularly suits to this technique. Previous accesses to the thorax seems not to be a limitation.
Child growth failure (CGF), which includes underweight, wasting, and stunting, is among the factors most strongly associated with mortality and morbidity in children younger than 5 years worldwide. Poor height and bodyweight gain arise from a variety of biological and sociodemographic factors and are associated with increased vulnerability to infectious diseases. We used data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 to estimate CGF prevalence, the risk of infectious diseases associated with CGF, and the disease mortality, morbidity, and overall burden associated with CGF. In this analysis we estimated the all-cause and cause-specific (diarrhoea, lower respiratory tract infections, malaria, and measles) disability-adjusted life-years (DALYs) lost and mortality associated with stunting, wasting, underweight, and CGF in aggregate. We combined the burden associated with mild, moderate, and severe forms of CGF: stunting was defined as height-for-age Z scores (HAZ) less than -1, underweight was defined as weight-for-age Z scores (WAZ) less than -1, and wasting was defined as weight-for-height Z scores (WHZ) less than -1, according to WHO Child Growth Standards. Population-level continuous distributions of HAZ, WAZ, and WHZ were estimated for 2000 to 2023 using data from surveys, literature, and individual-level study data. The risk of incidence of, and mortality due to, diarrhoea, lower respiratory infections, malaria, and measles was separately estimated in a meta-regression framework from longitudinal cohort data for Z scores less than -1. Finally, fatal outcomes associated with these diseases were estimated with vital registration, verbal autopsy, and case-fatality data, while non-fatal outcomes were estimated with surveys as well as health-care utilisation and case reporting data. The exposure prevalence and relative risk estimates were from continuous distributions, allowing for direct assessment of the attributable fractions for mild, moderate, and severe stunting, underweight, wasting, and the combined impact of child growth failure within populations. All estimates were age-specific, sex-specific, geography-specific, and year-specific. We estimated that, in children younger than 5 years in 2023, CGF was associated with 79·4 million (95% uncertainty interval [UI] 47·0-106) DALYs lost and 880 000 (517 000-1 170 000) deaths. This represented 17·9% (10·6-23·8) of 444 million (434-457) total under-5 DALYs and 18·8% (11·1-25·0) of all 4·67 million (4·59-4·75) under-5 deaths. Compared to stunting (33·0 million [24·1-42·2] DALYs, 373 000 [272 000-477 000] deaths) and wasting (39·2 million [23·8-53·0] DALYs, 428 000 [256 000-583 000] deaths), childhood underweight was associated with the largest share of CGF-related disease burden: 52·2 million (21·9-75·1) DALYs and 573 000 (236 000-824 000) deaths in children younger than 5 years in 2023. CGF remains a leading factor associated with death and disability in children younger than 5 years, despite global attention and focused interventions to reduce the prevalence of associated CGF indicators. Our findings underscore the need for policies, strategies, and interventions that focus on all indicators of CGF to reduce its associated health burden. Gates Foundation.
Arterio-ureteral fistula (AUF) is a rare condition affecting nearby adult-only patients. Patients usually present with hematuria, often starting as intermittent hematuria which frequently increases, and may lead to hemorrhagic shock. Without rapid diagnosis and prompt treatment, AUF can be lethal. Risk factors for developing an AUF include a history of pelvic surgery mainly due to cancer, a history of pelvic radiation, a history of vascular surgery, or chronic indwelling ureteral stents (CIUS). Imaging to confirm diagnosis includes angiography, computed tomography (CT) scan, or retrograde pyelography, although AUF may be missed. Therefore, even if imaging is negative, the presence of hematuria of unexplained origin in combination with mentioned risk factors is highly suspicious for AUF and must be excluded. We report the case of a 16-year-old male patient who presented with a new onset of intermittent hematuria to our emergency room. The patient's history included previous pelvic surgery for resection of ganglioneuroma 6 years ago with bilateral replacement of the iliac artery and postoperative acute kidney failure with reconstruction of both ureters and CIUS. After the initial uneventful postoperative follow-up over 5 years, another Double J (DJ) catheter had to be placed into the right ureter due to hydronephrosis. Six weeks later, the patient presented with intermittent hematuria. Despite negative imaging, we performed immediate surgical exploration confirming the diagnosis of AUF. To the best of our knowledge, this is the first case of AUF under the age of 18 years reported in the literature. In conclusion, in patients with macrohematuria and a history of the abovementioned risk factors, AUF has to be kept in mind and must be reliably excluded.
The global burden of sepsis, a life-threatening dysregulated host response to infection leading to organ dysfunction, remains challenging to quantify. We aimed to comprehensively estimate the global, regional, and national burden of sepsis, including the impact of the COVID-19 pandemic and underlying causes of sepsis-related deaths with co-occurring infectious syndromes. We used multiple cause-of-death, hospital, minimally invasive tissue sampling, and linked death certificate and hospital record data representing 149 million deaths, covering 4290 location-years with mortality estimates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 to capture explicit and implicit sepsis cases and deaths. We estimated age-location-sex-specific fractions of sepsis-related deaths from 195 underlying causes of death and 22 infectious syndromes from 1990 to 2021 using binomial logistic regression models, and estimated sepsis-related deaths using GBD cause-specific mortality estimates. Using 250 million hospital admissions and 7·82 million deaths from hospital data, representing 1310 location-years, we modelled case fatality rates by use of binomial logistic regression, applied to sepsis death estimates to estimate sepsis incidence by age, location, and year. In 2021, we estimated 166 million (95% uncertainty interval 135-201) sepsis cases and 21·4 million (20·3-22·5) all-cause sepsis-related deaths globally, representing 31·5% of total global deaths. Sepsis-related deaths decreased between 1990 and 2019, followed by a surge in 2020 and 2021. As of 2021, individuals aged 15 years and older experienced increases across incidence (230%) and mortality (26·3%) since 1990. Those aged 70 years and older had the highest sepsis-related mortality in 2021 (9·28 million [8·74-9·86] deaths). Sepsis-related deaths from infectious underlying causes decreased from 11·8 million (11·1-12·5) in 1990 to 8·34 million (7·72-9·01) in 2019, then increased by 86·4% to 15·5 million (14·7-16·4) in 2021. Sepsis-related mortality due to non-infectious underlying causes of death increased from 4·69 million (4·35-5·05) in 1990 to 5·81 million (5·40-6·25) in 2021; the leading non-infectious underlying causes of death with sepsis were stroke, chronic obstructive pulmonary disease, and cirrhosis. In 2021, bloodstream infections inclusive of HIV and malaria (3·08 million [2·83-3·35]) and lower respiratory infections inclusive of COVID-19 (11·33 million [1·20-1·47]) were the most prominent infectious syndromes complicating sepsis-related deaths from non-infectious underlying causes, representing a consistent trend since 1990. The global burden of sepsis increased in 2020 and 2021, reversing progress from 1990. Sepsis incidence and mortality increased in people aged 15 years and older, especially those aged 70 years and older, and as a complication of non-infectious underlying causes of death such as stroke, primarily through bloodstream infections and lower respiratory infections. The global burden of sepsis is substantial, and sepsis is increasingly a complication of non-infectious causes of death. Gates Foundation, Wellcome Trust, and Department of Health and Social Care using UK aid funding managed by the Fleming Fund.
Minimally invasive surgery (MIS) has improved patient outcomes by reducing surgical trauma and recovery times. Robotic-assisted surgery (RAS) advances MIS with superior precision, visualisation and ergonomics. These advantages are especially critical in paediatric procedures. The Senhance Surgical System (SSS) is a CE-marked robotic platform that enables RAS in children using 3 mm and 5 mm instruments. While RAS is routinely established in many adult procedures, its adoption and documentation in paediatric surgery are lagging. To address this disparity, the MiniTrust registry will generate real-world evidence on the safety and performance of the SSS in paediatric procedures. This multicentre, observational post-market clinical follow-up (PMCF) registry study includes both prospective and retrospective cases of paediatric patients undergoing RAS in urology, gynaecology or general surgery. If the underlying diagnosis is suitable for treatment with RAS, patients under 18 years of age and weighing ≥10 kg are eligible. Primary outcomes include procedure-related adverse events (AEs) classified as Clavien-Dindo >grade III within 30 days, and serious AEs within 3 months. Secondary endpoints include length of hospital stay, unplanned conversion rates and patient-reported pain outcomes. Data are collected via standardised case report forms and analysed descriptively, with results benchmarked against conventional paediatric laparoscopy literature. This study was approved in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Maastricht (2024-0425) and by the Ethics Committee of Munich (2024-0589). Results will be disseminated through peer-reviewed publications, scientific conferences and regulatory reports. This registry will contribute essential evidence to support the broader integration of RAS into paediatric surgical care. NCT07081828.