World Health Organization - Italy

BACKGROUND: Epidemiologic studies show that high temperatures are related to mortality, but little is known about the exposure-response function and the lagged effect of heat. We report the associations between daily maximum apparent temperature and daily deaths during the warm season in 15 European cities. METHODS: The city-specific analyses were based on generalized estimating equations and the city-specific results were combined in a Bayesian random effects meta-analysis. We specified distributed lag models in studying the delayed effect of exposure. Time-varying coefficient models were used to check the assumption of a constant heat effect over the warm season. RESULTS: The city-specific exposure-response functions have a V shape, with a change-point that varied among cities. The meta-analytic estimate of the threshold was 29.4 degrees C for Mediterranean cities and 23.3 degrees C for north-continental cities. The estimated overall change in all natural mortality associated with a 1 degrees C increase in maximum apparent temperature above the city-specific threshold was 3.12% (95% credibility interval = 0.60% to 5.72%) in the Mediterranean region and 1.84% (0.06% to 3.64%) in the north-continental region. Stronger associations were found between heat and mortality from respiratory diseases, and with mortality in the elderly. CONCLUSIONS: There is an important mortality effect of heat across Europe. The effect is evident from June through August; it is limited to the first week following temperature excess, with evidence of mortality displacement. There is some suggestion of a higher effect of early season exposures. Acclimatization and individual susceptibility need further investigation as possible explanations for the observed heterogeneity among cities.

This paper describes an action framework for countries with low tuberculosis (TB) incidence (<100 TB cases per million population) that are striving for TB elimination. The framework sets out priority interventions required for these countries to progress first towards "pre-elimination" (<10 cases per million) and eventually the elimination of TB as a public health problem (less than one case per million). TB epidemiology in most low-incidence countries is characterised by a low rate of transmission in the general population, occasional outbreaks, a majority of TB cases generated from progression of latent TB infection (LTBI) rather than local transmission, concentration to certain vulnerable and hard-to-reach risk groups, and challenges posed by cross-border migration. Common health system challenges are that political commitment, funding, clinical expertise and general awareness of TB diminishes as TB incidence falls. The framework presents a tailored response to these challenges, grouped into eight priority action areas: 1) ensure political commitment, funding and stewardship for planning and essential services; 2) address the most vulnerable and hard-to-reach groups; 3) address special needs of migrants and cross-border issues; 4) undertake screening for active TB and LTBI in TB contacts and selected high-risk groups, and provide appropriate treatment; 5) optimise the prevention and care of drug-resistant TB; 6) ensure continued surveillance, programme monitoring and evaluation and case-based data management; 7) invest in research and new tools; and 8) support global TB prevention, care and control. The overall approach needs to be multisectorial, focusing on equitable access to high-quality diagnosis and care, and on addressing the social determinants of TB. Because of increasing globalisation and population mobility, the response needs to have both national and global dimensions.

OBJECTIVE: To estimate the global burden of congenital toxoplasmosis (CT), which results from infection of pregnant women with Toxoplasma gondii. METHODS: The authors systematically searched 9 major databases for published and unpublished sources and established direct contact with the authors of source materials. Searches were country-specific. To be included, studies had to report on the incidence of CT, on positivity to Toxoplasma-specific IgM in infants and pregnant women (including seroconversion results) or on positivity to Toxoplasma-specific IgG in the general population. Various modelling techniques were used, depending on the country-specific data available, to estimate the CT incidence and burden in each country. These data were then synthesized into an estimate of the global incidence of CT and of the global burden of CT in disability-adjusted life years (DALYs). FINDINGS: The global annual incidence of congenital toxoplasmosis was estimated to be 190,100 cases (95% credible interval, CI: 179,300-206,300). This was equivalent to a burden of 1.20 million DALYs (95% CI: 0.76-1.90). High burdens were seen in South America and in some Middle Eastern and low-income countries. CONCLUSION: Congenital toxoplasmosis poses a substantial burden of poor health globally. Toxoplasmosis should be included in future updates of the global burden of disease and the corresponding data should be used to support public health interventions to reduce disease burden.

BACKGROUND: The present study aimed at developing a standardized heat wave definition to estimate and compare the impact on mortality by gender, age and death causes in Europe during summers 1990-2004 and 2003, separately, accounting for heat wave duration and intensity. METHODS: Heat waves were defined considering both maximum apparent temperature and minimum temperature and classified by intensity, duration and timing during summer. The effect was estimated as percent increase in daily mortality during heat wave days compared to non heat wave days in people over 65 years. City specific and pooled estimates by gender, age and cause of death were calculated. RESULTS: The effect of heat waves showed great geographical heterogeneity among cities. Considering all years, except 2003, the increase in mortality during heat wave days ranged from + 7.6% in Munich to + 33.6% in Milan. The increase was up to 3-times greater during episodes of long duration and high intensity. Pooled results showed a greater impact in Mediterranean (+ 21.8% for total mortality) than in North Continental (+ 12.4%) cities. The highest effect was observed for respiratory diseases and among women aged 75-84 years. In 2003 the highest impact was observed in cities where heat wave episode was characterized by unusual meteorological conditions. CONCLUSIONS: Climate change scenarios indicate that extreme events are expected to increase in the future even in regions where heat waves are not frequent. Considering our results prevention programs should specifically target the elderly, women and those suffering from chronic respiratory disorders, thus reducing the impact on mortality.

We analyzed the results at 8 years of an international, randomized, prospective study carried out by the World Health Organization Melanoma Programme aimed at evaluating the efficacy of 1-cm-margin excision of primary melanomas not thicker than 2 mm. Data for 612 patients were assessable; 305 were randomized to receive 1-cm-margin excision and 307 to receive wide excision (margins of greater than or equal to 3 cm). The major prognostic criteria were similar in the two groups. Breslow thickness was 0.99 mm in the narrow excision group and 1.02 mm in the wide excision group. Disease-free and overall survival rates (mean follow-up period, 90 months) were similar in the two groups. Only four patients had a local recurrence as a first relapse. All underwent narrow excision, and each had primary melanomas thicker than 1 mm.

Periodontal diseases and dental caries are the most common diseases of humans and the main cause of tooth loss. Both diseases can lead to nutritional compromise and negative impacts upon self-esteem and quality of life. As complex chronic diseases, they share common risk factors, such as a requirement for a pathogenic plaque biofilm, yet they exhibit distinct pathophysiologies. Multiple exposures contribute to their causal pathways, and susceptibility involves risk factors that are inherited (e.g. genetic variants), and those that are acquired (e.g. socio-economic factors, biofilm load or composition, smoking, carbohydrate intake). Identification of these factors is crucial in the prevention of both diseases as well as in their management. AIM: To systematically appraise the scientific literature to identify potential risk factors for caries and periodontal diseases. METHODS: One systematic review (genetic risk factors), one narrative review (role of diet and nutrition) and reference documentation for modifiable acquired risk factors common to both disease groups, formed the basis of the report. RESULTS & CONCLUSIONS: There is moderately strong evidence for a genetic contribution to periodontal diseases and caries susceptibility, with an attributable risk estimated to be up to 50%. The genetics literature for periodontal disease is more substantial than for caries and genes associated with chronic periodontitis are the vitamin D receptor (VDR), Fc gamma receptor IIA (Fc-γRIIA) and Interleukin 10 (IL10) genes. For caries, genes involved in enamel formation (AMELX, AMBN, ENAM, TUFT, MMP20, and KLK4), salivary characteristics (AQP5), immune regulation and dietary preferences had the largest impact. No common genetic variants were found. Fermentable carbohydrates (sugars and starches) were the most relevant common dietary risk factor for both diseases, but associated mechanisms differed. In caries, the fermentation process leads to acid production and the generation of biofilm components such as Glucans. In periodontitis, glycaemia drives oxidative stress and advanced glycation end-products may also trigger a hyper inflammatory state. Micronutrient deficiencies, such as for vitamin C, vitamin D or vitamin B12, may be related to the onset and progression of both diseases. Functional foods or probiotics could be helpful in caries prevention and periodontal disease management, although evidence is limited and biological mechanisms not fully elucidated. Hyposalivation, rheumatoid arthritis, smoking/tobacco use, undiagnosed or sub-optimally controlled diabetes and obesity are common acquired risk factors for both caries and periodontal diseases.

A meta-analysis for response to treatment was undertaken using individual data of multidrug-resistant tuberculosis (MDR-TB) (resistance to isoniazid and rifampicin) patients from 26 centres. The analysis assessed the impact of additional resistance to fluoroquinolones and/or second-line injectable drugs on treatment outcome. Compared with treatment failure, relapse and death, treatment success was higher in MDR-TB patients infected with strains without additional resistance (n=4763; 64%, 95% CI 57-72%) or with resistance to second-line injectable drugs only (n=1130; 56%, 95% CI 45-66%), than in those having resistance to fluoroquinolones alone (n=426; 48%, 95% CI 36-60%) or to fluoroquinolones plus second-line injectable drugs (extensively drug resistant (XDR)-TB) (n=405; 40%, 95% CI 27-53%). In XDR-TB patients, treatment success was highest if at least six drugs were used in the intensive phase (adjusted OR 4.9, 95% CI 1.4-16.6; reference fewer than three drugs) and four in the continuation phase (OR 6.1, 95% CI 1.4-26.3). The odds of success in XDR-TB patients was maximised when the intensive phase reached 6.6-9.0 months duration and the total duration of treatment 20.1-25.0 months. In XDR-TB patients, regimens containing more drugs than those recommended in MDR-TB but given for a similar duration were associated with the highest odds of success. All data were from observational studies and methodologies varied between centres, therefore, the bias may be substantial. Better quality evidence is needed to optimise regimens.

The field of organizational learning (OL) has been characterized by a wide diversity of opinions, definitions, and conceptualizations. After discussing difficulties associated with previous conceptualizations of organizational learning, this paper suggests a broader conceptualization which is consistent with and integrates diverse perspectives in the field of OL. To the extent that organizations continuously act and enact their environments, cognitive processes associated with learning continually take place whether the organization recognizes it or not. OL cannot be understood without taking into account the continuous ongoing change of organizational cognitive structures. However, learning is only recognized when an observer identifies and contextualizes those changes. Thus, organizational learning can be interpreted as a social construction which transforms acquired cognition into accountable abstract knowledge. The paper concludes by discussing the implications of this conceptualization of learning on management practice and organizational research.

The risk of exposure, progression to active tuberculosis (TB) and then to cure is a process affected by several risk factors. Along with well known risk factors such as human immunodeficiency virus (HIV), use of immunosuppressive drugs and being of young age, emerging risk factors such socio-economic and behavioral aspects play a significant role in increasing the susceptibility to infection, and unsuccessful treatment outcomes. This paper summarizes the effects of these socio-economic determinants and co-morbidities (including HIV) on TB infection and disease.

Large studies on bedaquiline used to treat multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB) are lacking. This study aimed to evaluate the safety and effectiveness of bedaquiline-containing regimens in a large, retrospective, observational study conducted in 25 centres and 15 countries in five continents.428 culture-confirmed MDR-TB cases were analysed (61.5% male; 22.1% HIV-positive, 45.6% XDR-TB). MDR-TB cases were admitted to hospital for a median (interquartile range (IQR)) 179 (92-280) days and exposed to bedaquiline for 168 (86-180) days. Treatment regimens included, among others, linezolid, moxifloxacin, clofazimine and carbapenems (82.0%, 58.4%, 52.6% and 15.3% of cases, respectively).Sputum smear and culture conversion rates in MDR-TB cases were 63.6% and 30.1%, respectively at 30 days, 81.1% and 56.7%, respectively at 60 days; 85.5% and 80.5%, respectively at 90 days and 88.7% and 91.2%, respectively at the end of treatment. The median (IQR) time to smear and culture conversion was 34 (30-60) days and 60 (33-90) days. Out of 247 culture-confirmed MDR-TB cases completing treatment, 71.3% achieved success (62.4% cured; 8.9% completed treatment), 13.4% died, 7.3% defaulted and 7.7% failed. Bedaquiline was interrupted due to adverse events in 5.8% of cases. A single case died, having electrocardiographic abnormalities that were probably non-bedaquiline related.Bedaquiline-containing regimens achieved high conversion and success rates under different nonexperimental conditions.

Assessments of the potential human health impacts of climate change are needed to inform the development of adaptation strategies, policies, and measures to lessen projected adverse impacts. We developed methods for country-level assessments to help policy makers make evidence-based decisions to increase resilience to current and future climates, and to provide information for national communications to the United Nations Framework Convention on Climate Change. The steps in an assessment should include the following: a) determine the scope of the assessment; b) describe the current distribution and burden of climate-sensitive health determinants and outcomes; c) identify and describe current strategies, policies, and measures designed to reduce the burden of climate-sensitive health determinants and outcomes; d) review the health implications of the potential impacts of climate variability and change in other sectors; e) estimate the future potential health impacts using scenarios of future changes in climate, socioeconomic, and other factors; f) synthesize the results; and g) identify additional adaptation policies and measures to reduce potential negative health impacts. Key issues for ensuring that an assessment is informative, timely, and useful include stakeholder involvement, an adequate management structure, and a communication strategy.

Poor nutrition, foodborne disease and lack of secure access to good food make an important contribution to the burden of disease and death in the WHO European Region. Better diets, food safety and food security will not only reduce or prevent suffering to individuals and societies but also help cut costs to health care systems and bring social and economic benefits to countries. People's chances for a healthy diet depend less on individual choices than on what food is available and whether it is affordable. Policies to benefit health through good food and nutrition must extend beyond the health sector to include sectors ranging from agriculture and food processing, manufacturing and trade to transport, retailing, catering and advertising. Food and nutrition policies should be coordinated so that public health is given due priority in the making of food policies by non-health sectors. This publication discusses in depth the components of food and nutrition policies and the evidence supporting them. It describes food- and nutrition-related ill health and its costs, shows the need for action and describes the steps for decision-makers to take. This book highlights the urgent need for integrated, multisectoral food and nutrition policies to encourage the sustainable production of food, its safety and the provision of food of high nutritional quality for all.

BACKGROUND: Human alveolar echinococcosis (AE) is a severe zoonotic disease caused by the metacestode stage of Echinococcus multilocularis. AE is commonly associated with a long incubation period that may last for more than ten years. The objective of this systematic literature review was to identify and summarize the current knowledge on statistically relevant potential risk factors (PRFs) associated with AE in humans. METHODOLOGY/PRINCIPAL FINDINGS: Six bibliographic databases were searched, generating a total of 1,009 publications. Following the removal of duplicate records and the exclusion of papers that failed to meet the criteria of a previously agreed a priori protocol, 23 publications were retained; however, 6 of these did not contain data in a format that allowed their inclusion in the meta-analysis. The remaining 17 publications (6 case-control and 11 cross-sectional studies) were meta-analysed to investigate associations between AE and PRFs. Pooled odds ratios (OR) were used as a measure of effect and separately analysed for case-control and cross-sectional studies. In the case-control studies, the following PRFs for human AE showed higher odds of outcome: "dog ownership", "cat ownership", "have a kitchen garden", "occupation: farmer", "haymaking in meadows not adjacent to water", "went to forests for vocational reasons", "chewed grass" and "hunting / handling foxes". In the cross-sectional studies, the following PRFs showed higher odds of outcome: "dog ownership", "play with dogs", "gender: female", "age over 20 years", "ethnic group: Tibetan", "low income", "source of drinking water other than well or tap", "occupation: herding" and "low education". Our meta-analysis confirmed that the chance of AE transmission through ingestion of food and water contaminated with E. multilocularis eggs exists, but showed also that food- and water-borne PRFs do not significantly increase the risk of infection. CONCLUSIONS/SIGNIFICANCE: This systematic review analysed international peer-reviewed articles that have over the years contributed to our current understanding of the epidemiology of human AE. The identification of potential risk factors may help researchers and decision makers improve surveillance and/or preventive measures that aim at decreasing human infection with E. multilocularis. More primary studies are needed to confirm potential risk factors and their role in the epidemiology of human AE.

The broadest pattern of tuberculosis (TB) drug resistance for which a consensus definition exists is extensively drug-resistant (XDR)-TB. It is not known if additional drug resistance portends worsened patient outcomes. This study compares treatment outcomes of XDR-TB patients with and without additional resistance in order to explore the need for a new definition. Individual patient data on XDR-TB outcomes were included in a meta-analysis comparing outcomes between XDR alone and three nonmutually exclusive XDR-TB patient groups: XDR plus resistance to all the second-line injectables (sli) and capreomycin and kanamycin/amikacin (XDR+2sli) XDR plus resistance to second-line injectables and to more than one group 4 drug, i.e. ethionamide/protionamide, cycloserine/terizidone or para-aminosalicylic acid (XDR+sliG4) and XDR+sliG4 plus resistance to ethambutol and/or pyrazinamide (XDR+sliG4EZ). Of 405 XDR-TB cases, 301 were XDR alone, 68 XDR+2sli, 48 XDR+sliG4 and 42 XDR+sliG4EZ. In multivariate analysis, the odds of cure were significantly lower in XDR+2sli (adjusted OR 0.4, 95% CI 0.2-0.8) compared to XDR alone, while odds of failure and death were higher in all XDR patients with additional resistance (adjusted OR 2.6-2.8). Patients with additional resistance beyond XDR-TB showed poorer outcomes. Limitations in availability, accuracy and reproducibility of current drug susceptibility testing methods preclude the adoption of a useful definition beyond the one currently used for XDR-TB.

The report presents past and projected climate change and impacts in Europe by means of about 40 indicators and identifies sectors and regions most vulnerable with a high need for adaptation. The report covers the following indicator categories: atmosphere and climate, cryosphere, marine biodiversity and ecosystems, water quantity (including river floods and droughts), freshwater quality and biodiversity, terrestrial ecosystems and biodiversity, soil, agriculture and forestry, human health. Furthermore the report shows the need for adaptation actions at EU, national and regional level and the need for enhanced monitoring, data collection and exchange and reducing uncertainties in projections. The report is a joined effort of the European Environment Agency (EEA), the European Commission's Joint Research Centre (JRC-IES) and the World Health Organisation Europe (WHO)

Asthma is a chronic inflammatory airway disease resulting in airflow obstruction, which in part can become irreversible to conventional therapies, defining the concept of airway remodeling. The introduction of biologics in severe asthma has led in some patients to the complete normalization of previously considered irreversible airflow obstruction. This highlights the need to distinguish a "fixed" airflow obstruction due to structural changes unresponsive to current therapies, from a "reversible" one as demonstrated by lung function normalization during biological therapies not previously obtained even with high-dose systemic glucocorticoids. The mechanisms by which exposure to environmental factors initiates the inflammatory responses that trigger airway remodeling are still incompletely understood. Alarmins represent epithelial-derived cytokines that initiate immunologic events leading to inflammatory airway remodeling. Biological therapies can improve airflow obstruction by addressing these airway inflammatory changes. In addition, biologics might prevent and possibly even revert "fixed" remodeling due to structural changes. Hence, it appears clinically important to separate the therapeutic effects (early and late) of biologics as a new paradigm to evaluate the effects of these drugs and future treatments on airway remodeling in severe asthma.

Tuberculosis is an airborne infectious disease treated with combination therapeutic regimens. Adherence to long-term antituberculosis therapy is crucial for maintaining adequate blood drug level. The emergence and spread of drug-resistant Mycobacterium tuberculosis strains are mainly favored by the inadequate medical management of the patients. The therapeutic approach for drug-resistant tuberculosis is cumbersome, because of the poor, expensive, less-effective, and toxic alternatives to the first-line drugs. New antituberculosis drugs (bedaquiline and delamanid) have been recently approved by the health authorities, but they cannot represent the definitive solution to the clinical management of drug-resistant tuberculosis forms, particularly in intermediate economy settings where the prevalence of drug resistance is high (China, India, and former Soviet Union countries). New research and development activities are urgently needed. Public health policies are required to preserve the new and old therapeutic options.

BACKGROUND: In the last decades, a marked increased prevalence of differentiated thyroid cancer (DTC) has been observed worldwide. The aim of this study was to evaluate the changing features of DTC referred to our institution between 1969 and 2004. METHODS: Clinical and pathological features and prognostic factors were analyzed in 4187 DTC patients, subdivided into two groups: group 1 (n = 1215) and group 2 (n = 2972) diagnosed before and after 1990, respectively. RESULTS: Group 2 showed an increased proportion of micropapillary carcinoma and a concomitant decrease of follicular histotype. Male percentage was greater in group 2, whereas median age at diagnosis was unchanged. DTC of group 2 were more frequently associated with multinodular goiter or autoimmune thyroiditis, but many were unexpected findings. Features of aggressiveness were significantly less frequent in group 2, and the survival rate was greater (98.7 vs. 91.4%, P < 0.0001). Gender, age, histotype, tumor size, extrathyroidal macroinvasion, and lymph node and/or distant metastases were found to be poor prognostic factors in both groups using univariate analysis, but with multivariate analysis, only advanced age (odds ratio = 22.52 for older patients) and advanced stage (odds ratio = 53.54 for more advanced cases) were independently correlated with a lower survival. CONCLUSIONS: DTC patients diagnosed after 1990 have smaller tumors with less advanced stage and a better prognosis. The question of whether this is related to the finding of tumors with a low clinical penetrance or to the anticipation of diagnosis remains to be clarified. Despite these significant differences, both advanced stage and older age still represent the most important poor prognostic factors for survival.

BACKGROUND: Timely and comprehensive analyses of causes of death stratified by age, sex, and location are essential for shaping effective health policies aimed at reducing global mortality. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 provides cause-specific mortality estimates measured in counts, rates, and years of life lost (YLLs). GBD 2023 aimed to enhance our understanding of the relationship between age and cause of death by quantifying the probability of dying before age 70 years (70q0) and the mean age at death by cause and sex. This study enables comparisons of the impact of causes of death over time, offering a deeper understanding of how these causes affect global populations. METHODS: GBD 2023 produced estimates for 292 causes of death disaggregated by age-sex-location-year in 204 countries and territories and 660 subnational locations for each year from 1990 until 2023. We used a modelling tool developed for GBD, the Cause of Death Ensemble model (CODEm), to estimate cause-specific death rates for most causes. We computed YLLs as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. Probability of death was calculated as the chance of dying from a given cause in a specific age period, for a specific population. Mean age at death was calculated by first assigning the midpoint age of each age group for every death, followed by computing the mean of all midpoint ages across all deaths attributed to a given cause. We used GBD death estimates to calculate the observed mean age at death and to model the expected mean age across causes, sexes, years, and locations. The expected mean age reflects the expected mean age at death for individuals within a population, based on global mortality rates and the population's age structure. Comparatively, the observed mean age represents the actual mean age at death, influenced by all factors unique to a location-specific population, including its age structure. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 250-draw distribution for each metric. Findings are reported as counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2023 include a correction for the misclassification of deaths due to COVID-19, updates to the method used to estimate COVID-19, and updates to the CODEm modelling framework. This analysis used 55 761 data sources, including vital registration and verbal autopsy data as well as data from surveys, censuses, surveillance systems, and cancer registries, among others. For GBD 2023, there were 312 new country-years of vital registration cause-of-death data, 3 country-years of surveillance data, 51 country-years of verbal autopsy data, and 144 country-years of other data types that were added to those used in previous GBD rounds. FINDINGS: The initial years of the COVID-19 pandemic caused shifts in long-standing rankings of the leading causes of global deaths: it ranked as the number one age-standardised cause of death at Level 3 of the GBD cause classification hierarchy in 2021. By 2023, COVID-19 dropped to the 20th place among the leading global causes, returning the rankings of the leading two causes to those typical across the time series (ie, ischaemic heart disease and stroke). While ischaemic heart disease and stroke persist as leading causes of death, there has been progress in reducing their age-standardised mortality rates globally. Four other leading causes have also shown large declines in global age-standardised mortality rates across the study period: diarrhoeal diseases, tuberculosis, stomach cancer, and measles. Other causes of death showed disparate patterns between sexes, notably for deaths from conflict and terrorism in some locations. A large reduction in age-standardised rates of YLLs occurred for neonatal disorders. Despite this, neonatal disorders remained the leading cause of global YLLs over the period studied, except in 2021, when COVID-19 was temporarily the leading cause. Compared to 1990, there has been a considerable reduction in total YLLs in many vaccine-preventable diseases, most notably diphtheria, pertussis, tetanus, and measles. In addition, this study quantified the mean age at death for all-cause mortality and cause-specific mortality and found noticeable variation by sex and location. The global all-cause mean age at death increased from 46·8 years (95% UI 46·6-47·0) in 1990 to 63·4 years (63·1-63·7) in 2023. For males, mean age increased from 45·4 years (45·1-45·7) to 61·2 years (60·7-61·6), and for females it increased from 48·5 years (48·1-48·8) to 65·9 years (65·5-66·3), from 1990 to 2023. The highest all-cause mean age at death in 2023 was found in the high-income super-region, where the mean age for females reached 80·9 years (80·9-81·0) and for males 74·8 years (74·8-74·9). By comparison, the lowest all-cause mean age at death occurred in sub-Saharan Africa, where it was 38·0 years (37·5-38·4) for females and 35·6 years (35·2-35·9) for males in 2023. Lastly, our study found that all-cause 70q0 decreased across each GBD super-region and region from 2000 to 2023, although with large variability between them. For females, we found that 70q0 notably increased from drug use disorders and conflict and terrorism. Leading causes that increased 70q0 for males also included drug use disorders, as well as diabetes. In sub-Saharan Africa, there was an increase in 70q0 for many non-communicable diseases (NCDs). Additionally, the mean age at death from NCDs was lower than the expected mean age at death for this super-region. By comparison, there was an increase in 70q0 for drug use disorders in the high-income super-region, which also had an observed mean age at death lower than the expected value. INTERPRETATION: We examined global mortality patterns over the past three decades, highlighting-with enhanced estimation methods-the impacts of major events such as the COVID-19 pandemic, in addition to broader trends such as increasing NCDs in low-income regions that reflect ongoing shifts in the global epidemiological transition. This study also delves into premature mortality patterns, exploring the interplay between age and causes of death and deepening our understanding of where targeted resources could be applied to further reduce preventable sources of mortality. We provide essential insights into global and regional health disparities, identifying locations in need of targeted interventions to address both communicable and non-communicable diseases. There is an ever-present need for strengthened health-care systems that are resilient to future pandemics and the shifting burden of disease, particularly among ageing populations in regions with high mortality rates. Robust estimates of causes of death are increasingly essential to inform health priorities and guide efforts toward achieving global health equity. The need for global collaboration to reduce preventable mortality is more important than ever, as shifting burdens of disease are affecting all nations, albeit at different paces and scales. FUNDING: Gates Foundation.

BACKGROUND: High ambient summer temperatures have been shown to influence daily mortality in cities across Europe. Quantification of the population mortality burden attributable to heat is crucial to the development of adaptive approaches. The impact of summer heat on mortality for 15 European cities during the 1990s was evaluated, under hypothetical temperature scenarios warmer and cooler than the mean and under future scenarios derived from the Intergovernmental Panel on Climate Change Special Report on Emission Scenarios (SRES). METHODS: A Monte Carlo approach was used to estimate the number of deaths attributable to heat for each city. These estimates rely on the results of a Bayesian random-effects meta-analysis that combines city-specific heat-mortality functions. RESULTS: The number of heat-attributable deaths per summer ranged from 0 in Dublin to 423 in Paris. The mean attributable fraction of deaths was around 2%. The highest impact was in three Mediterranean cities (Barcelona, Rome and Valencia) and in two continental cities (Paris and Budapest). The largest impact was on persons over 75 years; however, in some cities, important proportions of heat-attributable deaths were also found for younger adults. Heat-attributable deaths markedly increased under warming scenarios. The impact under SRES scenarios was slightly lower or comparable to the impact during the observed hottest year. CONCLUSIONS: Current high summer ambient temperatures have an important impact on European population health. This impact is expected to increase in the future, according to the projected increase of mean ambient temperatures and frequency, intensity and duration of heat waves.