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This study employed an interdisciplinary approach to assess the impact of agricultural production modifications and dietary changes on ammonia emissions, health outcomes and health inequalities. Statistical and econometric methods were applied to analyse agricultural emission trends and dietary patterns. Spatial data analysis and numerical modelling techniques were used to simulate the dispersion and transformation of atmospheric pollutants. Health impact modelling estimated mortality and morbidity outcomes under various policy scenarios, while cost-effectiveness and cost-benefit analyses supported decision-making. A participatory approach involving multistakeholder engagement was utilised to enhance policy relevance and implementation feasibility. A systematic scoping review of academic studies on agricultural-derived air pollution and clinically coded outcomes revealed very limited research on this topic, which presents an inconsistent picture as to whether agricultural-derived particulate matter affects health. Key findings indicate that dietary modifications have greater potential health benefits than direct reductions in particulate matter exposure from ammonia emissions. Small reductions in meat and dairy consumption, supported by taxation and subsidies, could help achieve environmental and health targets. A 20% meat and dairy tax, coupled with a 20% subsidy on fruits and vegetables, could reduce meat consumption by 21.5% and increase fruit and vegetable intake by up to 13.5%. These dietary shifts also significantly lower greenhouse gas emissions and water use. While ammonia's environmental effects are well documented, its direct health impacts remain uncertain. Epidemiological studies suggest a possible association between ammonium-derived particulate matter and increased mortality and cardiorespiratory diseases, though findings are inconsistent. Toxicological assessments indicate limited intrinsic toxicity of ammonium nitrate and sulfate. A 'high-ambition mitigation' scenario integrating ammonia reduction measures with dietary shifts could prevent 67,000 premature deaths and 270,000 cases of respiratory diseases over 30 years. Notably, older adults and lower-income populations would experience the greatest health benefits. Most farm-based ammonia reduction strategies demonstrated net economic benefits, with only a few measures having limited abatement potential. Additionally, reduced greenhouse gas emissions further amplified the benefits of each scenario. Despite robust modelling techniques and multistakeholder engagement, several limitations exist. The direct health effects of ammonia-derived particulate matter remain an area of uncertainty, necessitating further epidemiological research. Additionally, while economic and environmental benefits were quantified, behavioural responses to policy interventions - such as consumer acceptance of dietary changes - require further exploration. The study primarily focused on UK-specific data, limiting generalisability to other regions with different agricultural practices and policy landscapes. Finally, unintended consequences of dietary shifts on food security and cultural preferences were not fully explored, indicating the need for future research to refine policy recommendations. The Assessing Mitigation Pathways to Realise Public Health Benefits of Air Pollutant Emission Reductions from Agriculture project provides a comprehensive, interdisciplinary framework for evaluating integrated policy measures. It underscores the importance of sustainable agricultural and dietary transitions in achieving cobenefits for public health and environmental sustainability, while emphasising the need for continued research to address remaining uncertainties. More detailed spatial and temporal analyses are required to fully understand the potential importance of significant local sources on human health in specific areas/times of year. There is a need to better align evidence of studies, such as Assessing Mitigation Pathways to Realise Public Health Benefits of Air Pollutant Emission Reductions from Agriculture, with toxicological studies which suggest that (pure) ammonium nitrate and sulfate have only very modest toxicity. This study is registered as PROSPERO CRD42020172116. This award was funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme (NIHR award ref: NIHR129440) and is published in full in Public Health Research; Vol. 14, No. 3. See the NIHR Funding and Awards website for further award information. Agriculture is a main driver of air pollution in the United Kingdom and other countries. This is because it is responsible for emissions of ammonia and other nitrogen compounds into the atmosphere from livestock farming, fertiliser use and other activities. These chemicals contribute to air pollution and are harmful to health, leading to heart and lung disease, stroke, cancer, type 2 diabetes and early death. Solutions to reduce agricultural emissions and improve air quality and health can also support people’s efforts to eat healthier diets and reduce greenhouse gas emissions from food production. Such solutions were the focus of the Assessing Mitigation Pathways to Realise Public Health Benefits of Air Pollutant Emission Reductions from Agriculture project. Assessing Mitigation Pathways to Realise Public Health Benefits of Air Pollutant Emission Reductions from Agriculture evaluated the impact on health of past and future policy options. This was in order to see how policies could work together to: reduce agriculture-related air pollution to support healthy eating and act on climate change. It took account of the interconnections between how people eat, farming and agricultural production, and the social and economic consequences of policies. The project developed a list of existing and future policy actions and looked at different ways of improving agricultural technology, land-use management and other factors. It studied their impact on air pollution, United Kingdom diets and nutrition, and greenhouse gas emissions. Computer models calculated impacts on health arising from the effects of lower air pollution and better diets. Lastly, it compared the costs of policy interventions to the benefits they create. From the start, Assessing Mitigation Pathways to Realise Public Health Benefits of Air Pollutant Emission Reductions from Agriculture involved the public and other key stakeholders to give guidance to the project. We involved policy-makers, regulators, farmers, food producers, retailers, health professionals and food/environment advocates to help Assessing Mitigation Pathways to Realise Public Health Benefits of Air Pollutant Emission Reductions from Agriculture draw on many perspectives. We used this to craft research questions, analyse data and share results. The project found that agricultural technologies and changing land-use practices could reduce air pollution and improve health in the United Kingdom. However, combining these actions with policies that encourage people to eat healthier diets with less meat and more fruits and vegetables could result in much larger benefits for health. The evidence gathered by Assessing Mitigation Pathways to Realise Public Health Benefits of Air Pollutant Emission Reductions from Agriculture aims to shape policy. It will provide critical evidence for how efforts to reduce outdoor air pollution can play a lead role and support a holistic approach to human health.

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.

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.

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.

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.

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.

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.

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.

Background Sub-Saharan Africa's energy landscape is complex, with various factors influencing economic growth and development. Understanding the interplay between energy use, economic performance, and natural resources is crucial for sustainable development. This study investigates the relationships between energy use, GDP, low-carbon energy output, natural resources, and economic performance in Sub-Saharan Africa. Methods This study employed advanced econometric techniques, including generalized linear models, generalized method of moments, and vector error correction models. Data from the Global Economy Database spanning 1990-2024 were analyzed to uncover relationships between energy use, GDP, low-carbon energy output, and natural resources. Results The analysis showed significant variations in low-carbon energy output (mean = 68.86 units), natural gas profit margin (mean = $0.10), and oil operating surplus (mean = $3.50). The GLM and GMM estimates revealed significant relationships between energy use and GDP (7.419%), low-carbon energy output (6.079%), natural gas profit margin (67.377%), and oil operating surplus (4.575%). The analysis revealed significant variability in low-carbon energy production, natural gas profitability, and oil operating surpluses. Statistical models showed strong correlations between energy consumption and GDP growth, as well as low-carbon energy output and natural resource utilization. Conclusions The study finds complex dynamics between the variables, with both short-term and long-term effects. The research contributes to existing knowledge by providing empirical evidence of the relationships between energy use, GDP, low-carbon energy output, natural resources, and economic performance, offering valuable insights for policymakers and stakeholders seeking to promote sustainable energy use and economic development in Sub-Saharan Africa. This research provides novel insights into the intricate relationships governing Sub-Saharan Africa's energy sector and economic development. The findings offer valuable guidance for policymakers and stakeholders seeking to promote sustainable energy use, economic growth, and environmental stewardship in the region.

This study scrutinizes the effect of climate finance on inclusive growth in Africa. It further explores how regulatory quality dynamics impact the connection between climate finance and Africa's inclusive growth. Grounded on panel macroeconomic data straddling 54 African states from 2013 to 2023 and employing the two-step system generalized method of moments (2SYS-GMM) econometric estimation technique, the subsequent outcomes appeared. First, climate finance encourages inclusive growth in Africa, while the interactive terms of climate finance and regulatory quality have a shrinking effect. Before interacting with the regulatory quality, a 1% in increase in climate finance heightened Africa's inclusive growth by 0.3607% in the long run, while it was accompanying with a 0.1561% upsurge in the inclusive growth in the short run, all other factors remaining constant. Contrarily, the system GMM model publicized that in the long run, a one percent increase in the interactive terms of climate finance and regulatory quality of Africa signposts to a 0.775 percent diminution in inclusive growth, while it marks a 0.753 percent lessening in the short run, on average, and other things remaining constant. The study concludes that the feeble regulatory quality of Africa is harmful in both the long run and the short run. This suggests that negative regulatory quality dynamics completely shrink the positive effect of climate finance on the inclusive growth of Africa over the periods under this study. Further, the anticipated benefits of climate finance in fostering Africa's inclusive growth may persist elusive unless noteworthy progresses are made to Africa's currently existing regulatory frameworks.

Meningitis remains the leading infectious cause of neurological disabilities globally, disproportionately affecting children younger than 5 years and populations in the African meningitis belt. Whereas previous global estimates focused on ten pathogen categories, this study presents the most comprehensive analysis to date, assessing the meningitis burden attributable to 17 causative pathogens based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 framework. GBD is a systematic, scientific effort aimed at quantifying the comparative magnitude of health loss caused by diseases, injuries, and risk factors across age groups, sexes, and geographical locations over time. We estimated meningitis mortality using the Cause of Death Ensemble model (CODEm) and morbidity using DisMod-MR 2.1, incorporating data from vital registration, verbal autopsy, surveillance, hospital data, and systematic reviews. Aetiology-specific estimates were generated with pathogen-linked case-fatality ratios and splined binomial regression models. Risk factor attribution was based on established risk-outcome pairs and population attributable fractions. In 2023, there were 259 000 (95% uncertainty interval 202 000-335 000) global deaths and 2·54 million (2·20-2·93) incident cases of meningitis. Children younger than 5 years accounted for more than a third of deaths (86 600 [53 300-149 000]). Streptococcus pneumoniae, Neisseria meningitidis, non-polio enteroviruses, and other viruses were the leading causes of death, while non-polio enteroviruses caused the most cases. The four WHO-defined preventable meningitis pathogens of interest (S pneumoniae, N meningitidis, Haemophilus influenzae, and Group B streptococcus) contributed to 98 700 deaths (77 000-127 000) and 594 000 cases (514 000-686 000). Low birthweight, short gestation, and household air pollution were the top risk factors for meningitis-related mortality. Although mortality and incidence have declined significantly since 1990, progress is insufficient to meet WHO 2030 targets. Despite marked progress in reducing bacterial meningitis via global vaccination campaigns, a substantial meningitis burden persists, attributable both to common pathogens such as S pneumoniae and N meningitidis and to emerging non-bacterial pathogens such as Candida spp and drug-resistant fungi. Achieving WHO goals will require sustained investment in surveillance, vaccination, maternal screening, and health-system strengthening, especially in high-burden settings. Gates Foundation, Wellcome Trust, and UK Department of Health and Social Care.

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. 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. 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. 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. Gates Foundation, Wellcome, US National Kidney Foundation, and US National Institute of Diabetes and Digestive and Kidney Diseases.

The progress of the digital economy and low-carbon economy (hereinafter “both economies”) in China currently shows a digitalization trend and decarbonization urgency, and their intrinsic connections are becoming increasingly evident. Study on coordination of both economies is of crucial importance for China. In this study, an index system was constructed to measure the development level of both economies, and the entropy method was employed to calculate the index based on the data panel of China’s 282 prefecture-level cities during 2012–2021. Then, the coordinated development level of both economies (CDL) was assessed by the coupling coordination degree model. In addition, we conduct a sensitivity test on the weight setting of the composite index in the coupling coordination degree model to verify the robustness of CDL measurement to alternative weight specifications. Results indicate that CDL has steadily improved annually and is generally in the basic coordination stage. Cities in the basic maladjustment stage and the basic coordination stage still show considerable room for further improvement. The CDL across China’s four regions exhibits a pattern of “Eastern > Northeastern > Central > Western”. Next, the regional differences of CDL were decomposed by the Dagum Gini coefficient, revealing a decreasing trend in overall differences. Within-regional differences is the primary source of regional differences. More specifically, within-regional disparities rank from high to low as Western, Eastern, Northeastern, and Central; and the between-regional disparities, from high to low, are Western–Northeastern, Eastern–Western, Central–Western, Eastern–Central, Eastern–Northeastern, and Central–Northeastern. Accordingly, further empirical analysis using the spatial Durbin model identified several driving mechanisms for CDL. In the spatial econometric setting, we further perform robustness checks with alternative spatial weight matrices, including a geographic adjacency matrix, an economic distance matrix, and a gravity-model nested matrix, and we also report the decomposition of spatial effects. Moreover, we introduce a one-period lag of the dependent variable to estimate a dynamic spatial Durbin model, capturing path dependence in CDL and testing the robustness of the conclusions. Results demonstrate that government guidance, market regulation, technological innovation, and structural optimization mechanisms all promote CDL significantly, while the openness mechanism has a significant inhibiting effect. The direct effects are consistent with the above results, while the indirect effects indicate positive spatial spillovers from government guidance and market regulation, and a significant negative spatial spillover from openness; these findings remain broadly stable after replacing spatial weight matrices and after introducing the dynamic term, suggesting strong robustness in identifying the driving mechanisms. These findings can be interpreted through the technology–institution–structure analysis framework. Specifically, technological integration highlights digital technology empowering low-carbon technology innovation; institutional guarantee emphasizes synergy between government policies and market mechanisms; and structural transformation underscores the synergistic upgrading of industrial digitalization and low-carbonization.

This study explores the demographic and behavioral determinants of road traffic accident (RTA) severity in the context of the Dhaka metropolitan area, Bangladesh. Road crash data recorded by the Dhaka Metropolitan Police (DMP) were analyzed through ordered logistic regression and generalized ordered logistic regression. The results were interpreted using log odds ratios, odds ratios, predicted probabilities, and marginal effects. The findings reveal that young and middle-aged drivers exhibit significantly higher odds of severe crashes compared to underage drivers. Young-aged drivers are 14 percentage points more likely to cause fatal crashes when compared to old aged drivers in our ordered logit model. In addition, male drivers show higher odds of severe crashes than females. Factors such as overloading of vehicles, alcohol consumption while driving, and over-speeding were identified as the major contributors to increasing crash severity. Alcohol consumption had an odds ratio of 1.223 in the ordered logit model, and it had odds ratios of 2.418, 1.722, and 1.086 for the thresholds of motor collision, simple injury, and grievous injury, respectively, in the generalized ordered logit model. In contrast, the use of seatbelts, vehicle fitness maintenance, and drivers' licensing shows mitigating effects on crash severity, with significant odds ratios&#x2009;<&#x2009;1 in both the ordered logit and generalized ordered logit models. From the ordered logit model, we found that seat belt use, fitness certificate, and license decrease the likelihood of fatal crash by 10.7 percentage points, 8.2 percentage points, and 28.2 percentage points, respectively, whereas overspeed increases the likelihood of fatal crash by 13.5 percentage points. The results were reflected in the generalized ordered logit model, too. This research provides valuable insights for policymakers to design and implement effective policies and transport planning, including demographic driving regulations and behavioral control mechanisms to reduce road crash severity.

COVID-19 remains a substantial public health challenge in the Netherlands. Next-generation COVID-19 vaccine, mRNA-1283, is approved in the European Union, with potential for higher relative vaccine efficacy compared with originally licensed COVID-19 vaccines. The potential public health and economic impact of mRNA-1283 in adults &#x2265; 60 years and high-risk adults aged 18-59 years was modeled versus no vaccination and originally licensed mRNA-1273 and BNT162b2, adapting a published static Markov model with a 1-year time horizon. COVID-19 burden reflected two full post-pandemic seasons. Vaccine efficacy versus mRNA-1273 was based on pivotal phase 3 NextCOVE trial data; efficacy versus BNT162b2 was derived from an indirect treatment comparison. The economically justifiable price (EJP) of mRNA-1283 versus no vaccination and price premiums over existing vaccines were determined at a willingness-to-pay threshold of &#x20ac;50,000/quality-adjusted life-year (QALY) gained. Without COVID-19 vaccination, an estimated 460,000 infections, 23,800 hospitalizations, and 5300 deaths would occur. With current coverage, mRNA-1283 was estimated to prevent 68,000 infections, 5400 hospitalizations, and 1200 deaths, saving 9667 QALYs and over &#x20ac;66.5 million in treatment costs. The EJP was &#x20ac;238 versus no vaccination. Compared with mRNA-1273 and BNT162b2, mRNA-1283 was estimated to prevent additional burden (e.g., 1309 and 1679 hospitalizations, respectively) and was cost-effective at an incremental EJP of &#x20ac;62 versus mRNA-1273 and &#x20ac;80 versus BNT162b2. The results support continued COVID-19 vaccination to mitigate the ongoing health and societal burden of SARS-CoV-2 in the Netherlands. The comparative analyses indicate that mRNA-1283 may be associated with substantial health benefits over originally licensed mRNA vaccines; consequently, its use may further improve health outcomes and economic efficiency within COVID-19 vaccination programs.

This study examines aspects of women's empowerment related to the nutritional status of under-five children in Bangladesh, including their age-appropriate food intake and access to healthcare during acute respiratory tract infection (ARI). Three waves of the Bangladesh Demographic Health Survey (BDHS) data (2011, 2014 and 2017-2018) were pulled and utilised to construct three domains of the Survey-Based Women's Empowerment Index, such as social independence, intrinsic agency and instrumental agency. The height-for-age Z (HAZ), weight-for-age Z (WAZ) and weight-for-height Z (WHZ) scores were used to measure the nutritional status of offspring. Two variables were generated to measure age-appropriate food intake and treatment-seeking from medically trained providers (MTP) at the commencement of ARI. Generalised structural equation modelling was performed to develop pathways between women's empowerment and children's nutritional status. Data were collected from eight administrative divisions in Bangladesh. A total of 18 706 married women aged 15-45 years residing with their husbands and having at least one under-five child. Women's social independence was positively associated with HAZ (0&#xb7;25 (95 % CI: 0&#xb7;22, 0&#xb7;28)), WAZ (0&#xb7;21 (0&#xb7;18, 0&#xb7;24)) and WHZ (0&#xb7;06 (0&#xb7;02, 0&#xb7;09)). Intrinsic agency positively influenced HAZ (0&#xb7;03 (0&#xb7;02, 0&#xb7;04)) and WAZ (0&#xb7;02 (0&#xb7;01, 0&#xb7;02)). Both social independence and intrinsic agency promoted appropriate feeding, while instrumental agency had a negative effect on food consumption (-0&#xb7;0026 (-0&#xb7;005, -0&#xb7;0002)). Both age-appropriate food intake and seeking treatment from MTP during recent ARI episodes improved nutritional outcomes of offspring. Maternal social independence and intrinsic agency enhance the nutritional status, food consumption and healthcare access of offspring in Bangladesh.

Avoidable referral of children for outpatient pediatric general surgical evaluation creates inefficient healthcare utilization and unnecessary social and financial burdens for patients and families. We sought to characterize patient and referring provider characteristics associated with avoidable patient referrals for outpatient pediatric general surgical evaluation in a rural state. This is a multisite retrospective cohort study including patients <18 y referred for outpatient pediatric general surgical evaluation between November 2017 and July 2024. Avoidable referrals were defined as patients who attended pediatric general surgery clinic but did not require an in-clinic procedure, imaging, operation, or clinic follow-up within 1 y. Bivariate analysis and multivariable logistic regression were performed to evaluate for associations between patient and provider factors and avoidable referral. We included 5966 patients. One-quarter of referrals were identified as avoidable (n = 1402, 24%), with children 0-3 y more commonly identified as avoidable (P < 0.001). Umbilical hernia was the most common referral (n = 917); 39% of these were avoidable. Pectus excavatum was most likely to be avoidable (n = 188; 46% avoidable). Referrals for self-pay patients and those placed by emergency medicine providers were more likely to be avoidable [odds ratio 2.5, 95% Confidence Interval (CI) (1.5-4.1) P < 0.001; odds ratio 1.8, 95% CI (1.3-2.7) P < 0.001]. Avoidable referrals had a shorter average time from referral to outpatient pediatric general surgery clinic visit (34 versus 41 d, P < 0.001). Nearly one-quarter of referrals were identified as avoidable. Development of targeted screening prior to outpatient pediatric general surgical evaluation may improve access to pediatric specialty care for indicated referrals and appropriate healthcare utilization.

Pediatric pneumonia remains a major cause of morbidity and mortality in low- and middle-income countries (LMICs), imposing both health and financial burdens. While the clinical aspects of pediatric pneumonia are well-studied, less attention has been paid to its economic implications for households, particularly regarding out-of-pocket (OOP) expenditure. This paper synthesizes current evidence from Kenya, India, Bangladesh, and Vietnam and introduces a proposed econometric framework designed to identify cost determinants and model policy interventions. The framework integrates microeconomic data, identifies cost determinants, and models the effects of clinical and policy factors (e.g., intensive care, vaccination, insurance coverage) on household expenditures. Simulated results illustrate potential findings from such an approach. Existing studies show substantial variability in hospitalization costs, with OOP payments ranging from US$30 to US$250 per episode, often exceeding 20% of monthly household income. Econometric modeling using generalized linear models (GLMs) and difference-in-differences (DiD) can disentangle the impact of hospital practices, disease severity, and policy interventions. Simulated regression results demonstrate that length of stay, intensive care admission, and absence of insurance significantly increase household costs, while pneumococcal conjugate vaccine (PCV) introduction reduces both admissions and financial burden. Hospitalization for pediatric pneumonia imposes significant OOP costs on households in LMICs. An econometric framework provides rigorous tools to estimate cost drivers, evaluate policy impacts, and guide equitable health financing reforms.

Live-attenuated vaccines (LAVs) are typically contraindicated for immunocompromised patients and pregnant women, although the potential benefits of vaccination with LAV in these populations should not be overlooked. This systematic literature review was conducted to evaluate the safety of LAVs in immunocompromised patients and pregnant women. The searches were conducted across PubMed, Embase, and Cochrane databases. We included studies reporting on safety outcomes of LAV use in immunocompromised patients and pregnant women. A narrative synthesis was employed to present the primary findings. A total of 96 studies were included, reporting outcomes on 18 LAVs, mostly for varicella-zoster, measles-mumps-rubella, and influenza vaccines. Comparative studies revealed minor differences in adverse events (AEs) between immunocompromised LAV recipients and placebo recipients, and between immunocompromised and healthy vaccinated individuals. Severe AEs and fatalities were infrequent, primarily noted in oncology patients in case studies. Twelve studies addressed LAV safety in pregnant women, with no instances of vertical transmission reported, and no conclusive link found between LAVs and serious AEs. LAVs appeared generally safe and well-tolerated for immunocompromised patients and pregnant women. However, evidence is still limited, and more research is needed to address data gaps and support evidence-based decision-making.