Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Pulmoner Aspergilloz: Aspergillus Fumigatus 'un Etken Olduğu Invaziv Aspergilloz Vakası

Aspergillus – a genus consisting of mold species widely distributed in the environment. The spectrum of pulmonary diseases includes invasive aspergillosis (IA), chronic pulmonary aspergillosis (CPA) and allergic bronchopulmonary aspergillosis (ABPA). We report a case of invasive aspergillosis caused by Aspergillus fumigatus in a 65-yearold patient admitted with complaints of shortness of breath, general weakness, and malaise. Diagnosis of “probable” aspergillosis was established based on microbiological and radiological investigations. During microbiological analysis A.fumigatus was isolated an identified based on cultural and morphological characteristics. Despite the medical treatment, the patient’s complaints worsened. He refused artificial lung ventilation apparatus. Probably, chronic obstructive pulmonary disease (COPD) together with late diagnosis and absence of appropriate treatment resulted in the development of IA and lethal outcome. CPA develops in immunocompetent patients, suffering from tuberculosis or other diseases accompanied by the formation of cavities in lungs. This case demonstrates the importance of reliable and timely diagnosis of aspergillosis in order to provide patients with adequate treatment. Taking into account difficulty of obtaining of punctate for histopathological examination and absence of radiological signs physicians should give more attention to the probability of aspergillosis in patients with chronic disease in order to apply adequate therapy and reduce the number of lethal outcomes.:Aspergillus, küf türlerinden oluşan ve çevrede yaygın olarak bulunan bir mantar türüdür. Akciğer hastalıkları spektrumuna invaziv aspergilloz (İA), kronik pulmoner aspergilloz (KPA) ve alerjik bronkopulmoner aspergilloz (ABPA) gibi hastalıklar dahildir. Nefes darlığı, genel halsizlik ve rahatsızlık yakınmaları ile başvuran 65 yaşındaki bir hastada Aspergillus fumigatus'un neden olduğu invaziv aspergilloz vakasını sunuyoruz. Mikrobiyolojik ve radyolojik araştırmalara dayanarak “olası” aspergilloz tanısı konuldu. Mikrobiyolojik incelemede A.fumigatus kültürel ve morfolojik özelliklerine göre tanımlandı. Tıbbi tedaviye rağmen hastanın durumu daha da kötüleşti. Hasta mekanik ventilasyon cihazını reddetti. Muhtemelen, kronik obstrüktif akciğer hastalığında (KOAH) geç tanı ve uygun tedavinin olmaması İA gelişimine ve letal sonluğa neden olmuştur. KPA, akciğerlerde kavite oluşumu ile sonuçlanan tüberküloz veya diğer hastalıklara maruz kalan immünokompetan hastalarda gelişir. Bu olgu, hastalara yeterli tedaviyi sağlamak için aspergilloz tanısının güvenilir ve zamanında konulmasının önemini göstermektedir. Histopatolojik inceleme için biyopsi alınmasının zorluğu ve radyolojik bulguların bulunmaması göz önünde bulundurularak, doktorlar yeterli tedaviyi uygulamak ve ölümcül sonuçların sayısını azaltmak için kronik hastalığı olan hastalarda aspergilloz olasılığına daha fazla dikkat etmelidir

The burden of serious fungal infections in Azerbaijan

BACKGROUND: Azerbaijan is an upper middle-income country in South Caucasus with an area of 86,600 km2 and a total population of 10 million people and gross domestic product of US $4480 per capita. The aim of this research is to estimate fungal infection burden and highlight the problem at national and international levels.METHODS: Fungal infection burden was estimated using data from epidemiological papers and population at risk and LIFE (Leading International Fungal Education) modelling.RESULTS: The number of people living with human immunodeficiency virus (PLHIV) in 2018 was 6193, 29% of them not receiving antiretroviral therapy. Based on 90% and 20% rates of oral and oesophageal candidiasis in patients with CD4 cell count &lt;200 µl-1 we estimate 808 and 579 patients with oral and oesophageal candidiasis, respectively. The annual incidences of cryptococcal meningitis and Pneumocystis pneumonia are 5 and 55 cases, respectively. We estimated 2307 cases of chronic pulmonary aspergillosis (CPA), 4927 patients with allergic bronchopulmonary aspergillosis (ABPA), and 6504 with severe asthma with fungal sensitization (SAFS). Using data on chronic obstructive pulmonary diseases (COPD), lung cancer, acute myeloid leukaemia rates, and number of transplantations, we estimated 693 cases of invasive aspergillosis following these conditions. Using a low-European rate for invasive candidiasis, we estimated 499 and 75 patients with candidemia and intra-abdominal candidiasis respectively. The number of adult women (15-55 years) in Azerbaijan is ~2,658,000, so it was estimated that 159,490 women suffer from recurrent vulvovaginal candidiasis (rVVC).DISCUSSION: In total, the estimated number of people suffering from fungal diseases in Azerbaijan is 225,974 (2.3% of the population). However, the fungal rate is underestimated due to lack of epidemiological data. The most imminent need is improvement in diagnostic capabilities. This aim should be achieved via establishing a reference laboratory and equipping major clinical centers with essential diagnostics assays.</p

The burden of serious fungal infections in Azerbaijan

Background: Azerbaijan is an upper middle-income country in South Caucasus with an area of 86,600 km2 and a total population of 10 million people and gross domestic product of US $4480 per capita. The aim of this research is to estimate fungal infection burden and highlight the problem at national and international levels. Methods: Fungal infection burden was estimated using data from epidemiological papers and population at risk and LIFE (Leading International Fungal Education) modelling. Results: The number of people living with human immunodeficiency virus (PLHIV) in 2018 was 6193, 29% of them not receiving antiretroviral therapy. Based on 90% and 20% rates of oral and oesophageal candidiasis in patients with CD4 cell count &lt;200 µl–1 we estimate 808 and 579 patients with oral and oesophageal candidiasis, respectively. The annual incidences of cryptococcal meningitis and Pneumocystis pneumonia are 5 and 55 cases, respectively. We estimated 2307 cases of chronic pulmonary aspergillosis (CPA), 4927 patients with allergic bronchopulmonary aspergillosis (ABPA), and 6504 with severe asthma with fungal sensitization (SAFS). Using data on chronic obstructive pulmonary diseases (COPD), lung cancer, acute myeloid leukaemia rates, and number of transplantations, we estimated 693 cases of invasive aspergillosis following these conditions. Using a low-European rate for invasive candidiasis, we estimated 499 and 75 patients with candidemia and intra-abdominal candidiasis respectively. The number of adult women (15–55 years) in Azerbaijan is ~2,658,000, so it was estimated that 159,490 women suffer from recurrent vulvovaginal candidiasis (rVVC). Discussion: In total, the estimated number of people suffering from fungal diseases in Azerbaijan is 225,974 (2.3% of the population). However, the fungal rate is underestimated due to lack of epidemiological data. The most imminent need is improvement in diagnostic capabilities. This aim should be achieved via establishing a reference laboratory and equipping major clinical centers with essential diagnostics assays. </jats:sec

Elevating fungal care: bridging Brazil’s healthcare practices to global standards

Brazil faces unique challenges in managing invasive fungal infections (IFIs) due to diverse ecosystems, a rural workforce, and prevalent health conditions. In Europe, IFIs are primarily associated with transplantation, intensive care, and chronic diseases. Inspired by initiatives in the Caribbean and Latin America in 2019, efforts to map global diagnostic and treatment resources expanded to Africa, Europe, and Asia/Pacific. This study conducts a comparative analysis, mainly drawing data from Brazil and Europe, to investigate IFI epidemiology and management. Data were collected through online surveys distributed to Brazilian and European institutions, with collaborations from scientific organizations. Surveys covered institutional profiles, IFI diagnoses, accessibil ity to diagnostic techniques, and antifungal drugs. A comparative survey involving 96 Brazilian and 388 European institutions revealed variations in the perception and practices related to fungal pathogens. Differences in ranking and prevalence were observed, along with variations in diagnostic procedures, fluorescence dye usage, culture practices, antifungal medication availability, and technological approaches. Europe exhibited higher utilization rates for molecular diagnostic approaches, including PCR tests, and therapeutic drug monitoring (TDM) was more widespread in Europe compared with Brazil, indicating substantial differences in understanding and managing fungal infections. Customized IFI management is crucial, considering regional differences and addressing technological gaps like underutilized PCR. The study advocates for increased international collaboration, targeted training, and enhanced resources to foster a unified global approach in preventing, diagnosing, and treating IFI

Search for Scalar Diphoton Resonances in the Mass Range 65−60065-600 GeV with the ATLAS Detector in pppp Collision Data at s\sqrt{s} = 8 TeVTeV

A search for scalar particles decaying via narrow resonances into two photons in the mass range 65–600 GeV is performed using $20.3\text{}\text{}{\mathrm{fb}}^{-1}$ of $\sqrt{s}=8\text{}\text{}\mathrm{TeV}$ $pp$ collision data collected with the ATLAS detector at the Large Hadron Collider. The recently discovered Higgs boson is treated as a background. No significant evidence for an additional signal is observed. The results are presented as limits at the 95% confidence level on the production cross section of a scalar boson times branching ratio into two photons, in a fiducial volume where the reconstruction efficiency is approximately independent of the event topology. The upper limits set extend over a considerably wider mass range than previous searches