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.
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.
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.
Violence against women and against children are human rights violations with lasting harms to survivors and societies at large. Intimate partner violence (IPV) and sexual violence against children (SVAC) are two major forms of such abuse. Despite their wide-reaching effects on individual and community health, these risk factors have not been adequately prioritised as key drivers of global health burden. Comprehensive x§and reliable estimates of the comparative health burden of IPV and SVAC are urgently needed to inform investments in prevention and support for survivors at both national and global levels. We estimated the prevalence and attributable burden of IPV among females and SVAC among males and females for 204 countries and territories, by age and sex, from 1990 to 2023, as part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2023. We searched several global databases for data on self-reported exposure to IPV and SVAC and undertook a systematic review to identify the health outcomes associated with each of these risk factors. We modelled IPV and SVAC prevalence using spatiotemporal Gaussian process regression, applying data adjustments to account for measurement heterogeneity. We employed burden-of-proof methodology to estimate relative risks for outcomes associated with IPV and SVAC. These estimates informed the calculation of population attributable fractions, which were then used to quantify disability-adjusted life-years (DALYs) attributable to each risk factor. Globally, in 2023, we estimated that 608 million (95% uncertainty interval 518-724) females aged 15 years and older had ever been exposed to IPV, and 1·01 billion (0·764-1·48) individuals aged 15 years and older had experienced sexual violence during childhood. 18·5 million (8·74-30·0) DALYs were attributed to IPV among females and 32·2 million (16·4-52·5) DALYs were attributed to SVAC among males and females in 2023. IPV and SVAC were among the top contributors to the global disease burden in 2023, particularly among females aged 15-49 years, ranking as the fourth and fifth leading risk factors, respectively, for DALYs in this group. Among the eight health outcomes found to be associated with IPV, anxiety disorders and major depressive disorder were the leading causes of IPV-attributed DALYs, accounting for 5·43 million (-1·25 to 14·6) and 3·96 million (1·71 to 6·92) DALYs in 2023, respectively. SVAC was associated with 14 health outcomes, including mental health disorder, substance use disorder, and chronic and infectious disease outcomes. Self-harm and schizophrenia were the leading causes of SVAC-attributed burden, with SVAC accounting for 6·71 million (2·00 to 12·7) DALYs due to self-harm and 4·15 million (-1·92 to 13·1) DALYs due to schizophrenia in 2023. IPV and SVAC are substantial contributors to global health burden, and their health consequences span a variety of individual health outcomes. Importantly, mental health disorders account for the greatest share of disease burden among survivors. Investing in prevention of these avoidable risk factors has the potential to avert millions of DALYs and considerable premature mortality each year. Our findings represent strong evidence for global and national leaders to elevate IPV and SVAC among public health priorities. Sustained investments are needed to prevent IPV and SVAC and to implement interventions focused on supporting the complex social and health needs of survivors. Gates Foundation.
In Korea, the National Cancer Screening Program (NCSP) was implemented in 1999 and provides biennial endoscopy for adults aged ≥40 years. The NCSP has contributed to the early detection of gastric cancer and reduction of associated mortality in Korea. Helicobacter pylori is the main cause of gastric cancer. Screening for and eradication of H pylori reduces the incidence and mortality of gastric cancer. Previous studies have reported that screening for H pylori is a cost-saving intervention that can significantly decrease gastric cancer burden in areas with a high prevalence of H pylori infection. However, no study has examined whether incorporating H pylori screening into national endoscopic screening is cost effective. This study aims to evaluate the cost-effectiveness of incorporating H pylori screening into Korea's National Gastric Cancer Screening Program. We have developed a Markov model to compare two strategies: (1) endoscopy screening every 2 years starting at the age of 40 years (conventional screening), and (2) H pylori screening at the age of 40 years followed by continuous endoscopy screening every 2 years. We will also conduct a comparative analysis by varying the age at which the H pylori screening is performed. The primary outcome is the incremental cost-utility ratio (ICUR), calculated by dividing the incremental cost by the incremental quality-adjusted life-years (QALYs) between the two strategies. A probabilistic sensitivity analysis will be performed to test the uncertainty of the cost-effectiveness results. A sensitivity analysis will identify the most influential variables for cost-effectiveness. The primary outcome parameter is the cost-effectiveness of adding H pylori testing to the current NCSP, which is expressed as the ICUR. Costs and utilities are discounted at an annual rate of 4.5%. The ICUR threshold is set at KRW 50 million (US $36,719), which is the South Korean gross domestic product per capita. This research has been funded by a Patient-Centered Clinical Research Coordinating Center grant from the Ministry of Health & Welfare, Republic of Korea (grant RS-2024-00398474). This study will analyze and synthesize previously published information and is thus exempt from institutional review board approval. Data collection started in June 2024 and was completed in May 2025. Study results will be published in peer-reviewed journals and presented at national and international conferences throughout 2025. We will examine whether introducing H pylori testing and eradication therapy into the NCSP is a more cost-effective strategy for reducing gastric cancer risk than conventional endoscopy-based screening. Our study also examines the optimal age for H pylori screening, as well as the optimal screening frequency. DERR1-10.2196/72228.
The World Health Organization identified 13 critical threats to global health for the coming decade, including infectious disease prevention and antimicrobial resistance. Given the ongoing advancements in scientific evidence, it is imperative to discuss the Infectious Diseases training program. The aim of this study was to characterize and explore the respondents' perceptions regarding Infectious Diseases training and the clinical learning environment. A survey was developed to assess the clinical learning environment, targeting residents and young specialists who completed their training within the past five years. The questionnaire received 73 responses, 75.3% from residents. Most respondents agreed with the duration of Internal Medicine (83.5%), Microbiology (76.7%), and General Infectious Diseases (71.2%) rotations, but considered that the Intensive Care rotation should last less than six months. The areas of Infection Control/Antibiotic Stewardship and Immunosuppression/Infectious Risk were suggested as mandatory rotations by 84.9% and 65.8% of participants, respectively. Most respondents (67.1%) considered prolonged Internal Medicine Emergency rotations beyond the first year detrimental. In contrast, 84.6% of ARS Norte participants only performed this activity during the first year, whereas 86.8% of ARS LVT participants continued, at least, until the fourth year. Regarding clinical and scientific output, ARS Norte interns reported, on average, higher numbers of weekly assisted (21.7 vs 17.1) and performed (20.8 vs 17.7) appointments, as well as higher annual participation (3.7 vs 3.1) and presentations (2.8 vs 2.4) in scientific events, published articles (1.1 vs 0.6), and weekly study hours (7.4 vs 4.5), compared with ARS LVT. The main challenges reported were a lack of dedicated study time during working hours, scientific updates, and clinical practice in Internal Medicine Emergency rotations. Regarding the evaluation of the residency program, only 2.7% agreed completely with the current exam model and 1.37% with the current curriculum grid. The majority (64.4%) of participants considered themselves at least satisfied with the specialty. The results suggest a need to review the Infectious Diseases training program, include new areas of specialization, and discuss evaluation models throughout residency. Regional asymmetries were observed in emergency work, clinical and scientific output, which affect the equity and quality of training. Discussion of the Infectious Diseases training program is crucial for adapting the curriculum to current and future challenges. Introdução: A Organização Mundial de Saúde definiu as 13 mais importantes ameaças à Saúde Global da década, das quais se destacam a prevenção de doenças infeciosas e a resistência antimicrobiana. Dada a evolução célere da evidência científica e a necessidade de atualização, é imperativo discutir a formação em Doenças Infeciosas. Este estudo teve como objetivo caracterizar e explorar a perceção dos inquiridos relativamente à formação em Doenças Infeciosas e ao ambiente clínico de aprendizagem. Métodos: Foi desenvolvido um questionário sobre os ambientes clínicos de aprendizagem, dirigido a médicos internos e recém-especialistas que tenham concluído o seu programa de formação nos últimos cinco anos, inclusive. Resultados: O questionário obteve 73 respostas, 75,3% de médicos internos. A maioria concordou com a duração dos estágios de Medicina Interna (83,5%), Microbiologia (76,7%) e Infeciologia Geral (71,2%), mas considerou que o estágio de Medicina Intensiva deveria ter uma duração inferior a seis meses. Foi sugerido que as áreas de Controlo de Infeção/Prescrição Antibiótica e de Imunossupressão/Risco Infecioso tivessem estágios obrigatórios, por 84,9% e 65,8% dos participantes, respetivamente. A maioria (67,1%) dos inquiridos considerou prejudicial a realização de urgência externa de Medicina Interna para além do respetivo estágio, sendo que 84,6% dos participantes da ARS Norte realizaram esta atividade apenas durante o 1.º ano, em contraste com 86,8% da ARS LVT cuja atividade se prolongou pelo menos até ao 4.º ano. No que concerne à produção assistencial e científica, comparativamente aos médicos internos da ARS LVT, os da ARS Norte reportaram, em média, um maior número de consultas assistidas (21,7/17,1) e realizadas (20,8/17,7), semanalmente, assim como um maior número de participações (3,7/3,1) e apresentações (2,8/2,4) anuais em eventos científicos, artigos publicados (1,1/0,6) e horas de estudo semanais (7,4/4,5). As principais dificuldades reportadas foram a ausência de tempo de estudo dedicado no horário, a atualização científica e a realização de Urgência Externa de Medicina Interna. Sobre a avaliação do internato, apenas 2,7% concordaram totalmente com o modelo de exame atual e 1,37% com a grelha curricular atual. A maioria (64,4%) dos participantes consideraram-se, pelo menos, satisfeitos com a especialidade. Conclusão: Os resultados sugerem uma necessidade de rever o programa formativo, incluir novas áreas de especialização e discutir os modelos de avaliação ao longo do Internato. Verificam-se assimetrias regionais ao nível do exercício de funções em contexto de urgência externa de Medicina Interna e da produção assistencial e científica, o que condiciona a equidade e qualidade da formação. A discussão da formação em Doenças Infeciosas é crucial para a adaptação do programa formativo aos desafios atuais e futuros.
Seasonal influenza illness and acute respiratory infections can impose a substantial economic burden in low- and middle-income countries (LMICs). We assessed the cost of influenza illness and acute respiratory infections across household income strata. We conducted a secondary analysis of data from a prior systematic review of costs of influenza and other respiratory illnesses in LMICs and contacted authors to obtain data on cost of illness (COI) for laboratory-confirmed influenza-like illness and acute respiratory infection. We calculated the COI by household income strata and calculated the out-of-pocket (OOP) cost as a proportion of household income. We included 11 studies representing 11 LMICs. OOP expenses, as a proportion of annual household income, were highest among the lowest income quintile in 10 of 11 studies: in 4/4 studies among the general population, in 6/7 studies among children, 2/2 studies among older adults, and in the sole study for adults with chronic medical conditions. COI was generally higher for hospitalizations compared with outpatient illnesses; median OOP costs for hospitalizations exceeded 10% of annual household income among the general population and children in Kenya, as well as for older adults and adults with chronic medical conditions in China. The findings indicate that influenza and acute respiratory infections pose a considerable economic burden, particularly from hospitalizations, on the lowest income households in LMICs. Future evaluations could investigate specific drivers of COI in low-income household and identify interventions that may address these, including exploring household coping mechanisms. Cost-effectiveness analyses could incorporate health inequity analyses, in pursuit of health equity.
Early identification of hepatocellular carcinoma (HCC) is critical to reduce mortality. Diagnostic tools are limited for early disease. Intestinal microbiota may contribute to HCC risk directly and through metabolites, particularly bile acids (BAs), offering potential noninvasive biomarkers. This was a case-control study of patients with cirrhosis with or without early-stage HCC, matched based on liver disease severity. Comprehensive analyses of fecal microbiota composition and function were performed. There were 98 patients in the study (49 patients per group). Subjects with HCC were older (median 64 vs 60 years, P < 0.01) and more likely to have hepatitis C (78% vs 43%, P < 0.01). Alpha diversity, beta diversity, and genes and pathways related to BA metabolism did not differ between groups overall, but alpha diversity did differ within the subset of patients with metabolic-associated steatotic liver disease. There was differential abundance of multiple taxa between groups, including higher abundance of Klebsiella pneumoniae in cases. Increased concentration of secondary BA, which are microbiota-dependent, was associated with higher odds of HCC (adjusted odds ratio 2.4, P = 0.02); however, addition of microbial or BA features to a model with clinical data alone did not improve HCC prediction. When accounting for liver disease severity, there were limited differences in intestinal microbiota composition and BA metabolism between subjects with or without early-stage HCC. Promising areas for future study of microbiota-based HCC biomarkers were identified, including a focus on the subpopulation of patients with metabolic-associated steatotic liver disease.
The assembly of marine benthic communities has become a focal point in marine ecology. We address how the bottom layers of benthic communities (i.e., the microbes inhabiting the basal biofilm) influence the complex accumulation of eukaryotes that grow on top of them. Specifically, we discuss (a) what organisms make up benthic biofilms, what brings about their attachment to surfaces, and how they vary in space and time; (b) what eukaryotic organisms are in marine benthic communities, how they vary in space and time, and the nature of microbial cues that bring about their recruitment to particular benthic sites; (c) the roles of bacterial-animal symbiosis in the composition of benthic communities; (d) what is happening to biofilms and their roles as habitat engineers in the rapidly changing world; and (e) how the geological history of bacteria and microbial mats on the ocean floor powerfully influenced the evolution of larval-bacterial interactions.
The Centers for Disease Control and Prevention (CDC) estimates that Clostridioides difficile infection (CDI) results in 250,000 hospitalizations yearly in the U.S.A. an annual mortality of 12,800 and recurrence in 15-30% of patients. Consequently, new approaches and agents are needed to treat CDI. We review the current developmental pipeline for various categories of CDI therapies. We searched various data bases to identify relevant data. Ibezapolstat, CRS3123, and ridinilazole were identified with unique mechanisms of action and narrow spectrums of activity that result in gut microbiome preservation and reduced recurrent CDI (rCDI) rates. One cannot predict the potential efficacy of these new agents under study until further studies are done. Some may emerge as only supplemental therapies, while others may fail or be shelved and hopefully at least one will emerge as a primary CDI therapy and to prevent rCDI. Some have the ability to restore the microbiome (VE303) or preserve intestinal integrity (e.g. REC-3964, LMN-201, AQ). Regardless, patients and clinicians need new agents. CDI is a significant burden to the healthcare system and the quality of life for patients who suffer from CDI and rCDI. Further development of these investigational agents to prevent this cycle are of upmost importance.
Prevalent in marine and freshwater ecosystems, cyanophages compose a class of double-stranded DNA viruses that specifically infect cyanobacteria. During billions of years of coevolution, cyanophages and cyanobacteria have significantly contributed to the biogeochemical cycling and genetic diversity of aquatic ecosystems. As natural predators of cyanobacteria, cyanophages hold promise as eco-friendly agents against harmful cyanobacterial blooms. Recent technical advances in omics and cryo-electron microscopy have revealed the remarkable diversity of cyanophages in genome sequence and tail morphology. In this review, we summarize the genomic and metagenomic data, phylogenetic analyses, and diverse three-dimensional structures of cyanophages, in addition to their interplays with hosts. We also discuss the in vivo assembly processes of cyanophages, the exploration of uncultured cyanophages and host pairing, and the synthetic engineering and potential applications of cyanophages.
Most of our current knowledge about yeast is based on the workhorse Saccharomyces cerevisiae. However, can this yeast represent the vast array of natural yeast life-forms? This review discusses significant recent advances in the study of non-Saccharomyces yeasts, also known as non-conventional yeasts (NCYs). We (a) review recent literature on bioprospecting methodologies and on population genomics that have expanded our understanding of NCY diversity, (b) highlight critical species with industrial applications, and (c) offer insights into how NCYs' genetic diversity translates into phenotypic plasticity and adaptation to extreme environments. We assess the limitations that are delaying the widespread use of NCYs in biotechnology, including the need for ambitious bioprospecting efforts and robust genetic tools in the scaling up of NCY-based processes for industry. NCYs could offer novel sustainable solutions in the food, beverage, pharmaceutical, and bioenergy sectors and could open a new frontier of commercial opportunities.
Long-term clonal dynamics of Staphylococcus aureus remain incompletely characterized, particularly with respect to differences between methicillin-resistant (MRSA) and methicillin-susceptible (MSSA) populations. We analyzed the sequence type (ST) distribution of 800 S. aureus blood isolates collected in Korea between 1999 and 2018 using multilocus sequence typing. Temporal trends of ST72 were examined separately for MRSA and MSSA isolates and compared using interaction-based modeling and annual percent change (APC) analyses. The distribution of STs differed between MRSA and MSSA and changed over time. Among MRSA isolates, ST5 remained a predominant lineage throughout the study period. ST72 accounted for 16.9% of all isolates and increased over time in both MRSA and MSSA populations. ST72 emerged earlier and expanded more steadily among MRSA isolates, whereas its appearance among MSSA isolates showed a later onset and greater interannual variability. Although temporal slopes did not differ significantly between populations, APC estimates indicated a steeper increase of ST72 among MSSA isolates. These findings demonstrate the long-term establishment of ST72 within the Korean S. aureus population and highlight distinct population-level expansion patterns between MRSA and MSSA.
Marine bacteria display diverse lifestyles, many of which are shaped by close associations with microalgal partners. In the photic zone, where microalgae fix carbon through photosynthesis, bacteria consume algal-derived organic matter and often exhibit growth patterns that mirror algal activity and abundance. These interactions expose bacteria to strong fluctuations, with bursts of algal exudates during high productivity alternating with periods of scarcity. To cope, algal-associated bacteria have evolved strategies that balance rapid growth with the ability to endure starvation. This review highlights current knowledge and open questions in the physiology of algal-associated bacteria across three stages: the growth phase, supported by algal resources; the starvation phase, marked by storage strategies and a regulated decrease in cellular functions; and the transitions between these states, shaped by algal cues and corresponding bacterial responses. I hope this synthesis of our current understanding and the challenges ahead will inspire broader recognition of the importance and excitement of studying bacterial physiology in an environmental context.
The ability to synthesize lichen symbioses in vitro from pure cultures of transformable symbionts would be a game changer for experiments to identify the metabolic interplay that underpins the success of lichens. However, despite multiple reports of successful lichen resynthesis, no lichen lab model system exists today. We reviewed 150 years of in vitro lichen studies and found that the term resynthesis is applied to many types of fungal-photobiont cocultures that do not resemble lichens. Some of the most lichen-like results, for their part, were obtained from nonaxenic tissue culture. Only a few studies reported obtaining natural-looking lichens from axenic input cultures, but all appear to have been isolated successes obtained against the background of extensive contamination. We suggest revisiting resynthesis experiments in light of recent advances in our understanding of lichen microbial composition to test whether in vitro lichen morphogenesis requires microbial inputs beyond those of the canonical fungal and algal symbionts.
Cytochrome c (cyt c) is ubiquitous in nature, having evolved billions of years ago to function in respiration and photosynthesis. All c-type cytochromes require covalently attached heme, typically at a CXXCH motif. We highlight new studies from the past five years that address the structural and mechanistic bases for the three cyt c biogenesis pathways (Systems I-III). The solved structures of most of the proteins that comprise these systems provide insights into heme transport, the binding of heme, and the mechanism of apocytochrome c (apocyt c) interaction with the synthases. Detailed analyses of the active sites of each cyt c synthase have elucidated chemical mechanisms underlying cyt c biogenesis and their potential as novel antimicrobial targets. This potential is suggested from an evolutionary perspective, as bacteria use two pathways (Systems I and II) that are structurally and mechanistically distinct from the mitochondrial System III. Genomic analyses of bacteria's respiratory capacity, including their use of c-type cytochromes, reveal how the inhibition of cyt c biogenesis could attenuate growth.
BACKGROUND: Refraction disorders (RD), which includes myopia, hyperopia, astigmatism, and presbyopia, is the leading cause of visual impairment worldwide. Uncorrected RD is the leading cause of moderate and severe vision loss. However, existing studies have only analyzed the burden of RD at the global level, lacking analysis at the national level and specific populations. This study used data from the 2021 Global Burden of Disease (GBD) report to analyze regional differences and trends in the burden of RD among children, adolescents, and the elderly at the national level. METHODS: GBD 2021 data were used to examine RD burden in these groups, exploring associations with the Socio-demographic Index (SDI) and analyzing inequality trends. Decomposition analysis was applied, frontier analysis identified potential burden reductions, and Bayesian Age-Period-Cohort (BAPC) Models were used to forecast future trends. RESULTS: From 1990 to 2021, RD cases increased from 21.48 million to 24.45 million (a 13.8% increase) in children and adolescents, and from 29.26 million to 60.82 million (an increase of 107.87%) in the elderly. Decomposition analysis also revealed that population growth was the primary driver of the increased RD burden in both age groups. In regions with Middle, High-middle, and High SDI, the estimated annual percentage change (EAPC) of Age-Standardized Prevalence Rate (ASPR) in children and adolescents was positive, indicating an upward trend in the burden of RD. RD burden differed by age and region: higher SDI regions had a heavier burden in children and adolescents, while lower-income countries faced a greater burden in the elderly. Health inequalities became more evident in children and adolescents, while slightly lessened in the elderly. Overall, the RD burden was higher in the elderly compared to children and adolescents. By 2030, global RD cases are projected to reach 24.21 million in children and adolescents and 79.70 million in the elderly (31.05% increase expected), with countries like India, China, Oman, Paraguay, and Congo facing significant challenges. In addition, countries such as India, Spain, Bangladesh and others pay special attention to the male burden. CONCLUSION: The current RD burden is serious and requires targeted management strategies, especially in High SDI regions for children and adolescents and in Low-middle SDI regions for the elderly. The male burden in some high-burden areas cannot be ignored.
Bacteria of the phylum Actinomycetota are extremely diverse: They inhabit niches ranging from soils and ocean sediments to the normal human microbiota, and they cause tuberculosis, one of the most prevalent chronic bacterial infections. They display an accordingly wide range of adaptive traits that enable their persistence, including, in some clades, a vast repertoire of biologically active small molecules. While humans have capitalized on this trove of useful natural products (also called secondary or specialized metabolites), the utility of these molecules for their producers has been challenging to directly assess. In this review, we consider adaptations that may have paved the way for the evolution of the expansive specialized metabolisms present in certain clades of Actinomycetota. We also consider the evolutionary pressures that may have driven diversification of these metabolisms and document how these organisms use these molecules in microbial interactions.
Apicomplexan and trypanosomatid parasites cause important human diseases, including malaria, toxoplasmosis, Chagas disease, and human leishmaniasis. The mammalian-infective stages of these parasites colonize nutrient-rich, intracellular niches in a range of different host cells. These niches include specialized vacuoles (Plasmodium spp., Toxoplasma gondii), the mature lysosome of phagocytic cells (Leishmania), and the cytoplasm of nucleated host cells (Trypanosoma cruzi). Here, we review the different growth and metabolic strategies utilized by each of these protists to survive in these niches. Although all stages utilize sugars as preferred carbon sources, different species or developmental stages vary markedly in their dependence on aerobic fermentation versus respiratory metabolism and their co-utilization of other carbon sources. Stage-specific differences in glycolytic and mitochondrial respiratory capacity may be a hardwired feature of each stage and reflect the trade-off of achieving high growth rates at the expense of host range adaptability and establishing long-lived persistent infections.
Circadian clocks enable organisms to anticipate daily environmental changes. In fungi, Neurospora crassa has been the premier model for studying these rhythms, allowing the revelation of intricate phosphorylation dynamics, protein interactions, and the pivotal role of Casein Kinase 1 in clock regulation. FREQUENCY, an intrinsically disordered protein, plays a central role in the spatial and temporal control of N. crassa and coordinates interactions that define clock function at large. Recent findings highlight the extent of circadian regulation in N. crassa and span transcriptional and translational processes that dynamically reshape the daily proteome. Additionally, circadian control of metabolism and organismal interactions has emerged as a vibrant area of research, and multiple efforts have focused on uncovering circadian mechanisms in fungi other than Neurospora. And while the study of Neurospora will remain central to advancing the field, comparative studies across fungal systems offer unique perspectives on the evolution of clock mechanisms and further position fungi as a platform for unraveling the intricacies of complex eukaryotic systems.