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

Monitoring lung aeration during respiratory support in preterm infants at birth.

If infants fail to initiate spontaneous breathing, resuscitation guidelines recommend respiratory support with positive pressure ventilation (PPV). The purpose of PPV is to establish functional residual capacity and deliver an adequate tidal volume (VT) to achieve gas exchange.The aim of our pilot study was to measure changes in exhaled carbon dioxide (ECO2), VT, and rate of carbon dioxide elimination (VCO2) to assess lung aeration in preterm infants requiring respiratory support immediately after birth.A prospective observational study was performed between March and July 2013. Infants born at <37 weeks gestational age who received continuous positive airway pressure (CPAP) or PPV immediately after birth had VT delivery and ECO2 continuously recorded using a sensor attached to the facemask.Fifty-one preterm infants (mean (SD) gestational age 29 (3) weeks and birth weight 1425 (592 g)) receiving respiratory support in the delivery room were included. Infants in the CPAP group (n = 31) had higher ECO2 values during the first 10 min after birth compared to infants receiving PPV (n = 20) (ranging between 18-30 vs. 13-18 mmHg, p<0.05, respectively). At 10 min no significant difference in ECO2 values was observed. VT was lower in the CPAP group compared to the PPV group over the first 10 min ranging between 5.2-6.6 vs. and 7.2-11.3 mL/kg (p<0.05), respectively.Immediately after birth, spontaneously breathing preterm infants supported via CPAP achieved better lung aeration compared to infants requiring PPV. PPV guided by VT and ECO2 potentially optimize lung aeration without excessive VT administered

Values of exhaled CO₂ (ECO₂) and tidal volume (V_T) for infants supported with continuous positive airway pressure (+CPAP) and infants requiring positive pressure ventilation (+PPV).

<p>Data are presented as median (IQR) for ECO₂ and mean±SD for V_T.</p

Values of minute ventilation (MV) and rate of CO2 elimination (VCO₂) for infants supported with continuous positive airway pressure (+CPAP) and infants requiring positive pressure ventilation (+PPV).

<p>Data are presented as median (IQR) for MV and VCO_2.</p

Demographics of study infants.

<p>Data are presented as mean±SD unless indicated ^#median (IQR), *n (%), ^‡p<0.05.</p

Changes in oxygen saturation (SpO₂), heart rate (HR), fraction of inspired oxygen (FiO₂) and cerebral oxygenation (rSO₂) for infants supported with CPAP or PPV.

<p>Changes in oxygen saturation (SpO₂), heart rate (HR), fraction of inspired oxygen (FiO₂) and cerebral oxygenation (rSO₂) for infants supported with CPAP or PPV.</p

Tidal volume (V_T) and exhaled CO₂ (ECO₂) during positive pressure ventilation (PPV) and in infants who are supported with continuous positive airway pressure (CPAP).

<p>Tidal volume (V_T) and exhaled CO₂ (ECO₂) during positive pressure ventilation (PPV) and in infants who are supported with continuous positive airway pressure (CPAP).</p

Comparative genomics reveals mobile pathogenicity chromosomes in Fusarium

Fusarium species are among the most important phytopathogenic and toxigenic fungi. To understand the molecular underpinnings of pathogenicity in the genus Fusarium, we compared the genomes of three phenotypically diverse species: Fusarium graminearum, Fusarium verticillioides and Fusarium oxysporum f. sp. lycopersici. Our analysis revealed lineage-specific (LS) genomic regions in F. oxysporum that include four entire chromosomes and account for more than one-quarter of the genome. LS regions are rich in transposons and genes with distinct evolutionary profiles but related to pathogenicity, indicative of horizontal acquisition. Experimentally, we demonstrate the transfer of two LS chromosomes between strains of F. oxysporum, converting a non-pathogenic strain into a pathogen. Transfer of LS chromosomes between otherwise genetically isolated strains explains the polyphyletic origin of host specificity and the emergence of new pathogenic lineages in F. oxysporum. These findings put the evolution of fungal pathogenicity into a new perspective

Selenium speciation in framboidal and euhedral pyrites in shales.

The release of Se from shales is poorly understood because its occurrence, distribution, and speciation in the various components of shale are unknown. To address this gap we combined bulk characterization, sequential extractions, and spatially resolved μ-focus spectroscopic analyses and investigated the occurrence and distribution of Se and other associated elements (Fe, As, Cr, Ni, and Zn) and determined the Se speciation at the μ-scale in typical, low bulk Se containing shales. Our results revealed Se primarily correlated with the pyrite fraction with exact Se speciation highly dependent on pyrite morphology. In euhedral pyrites, we found Se(-II) substitutes for S in the mineral structure. However, we also demonstrate that Se is associated with framboidal pyrite grains as a discrete, independent FeSex phase. The presence of this FeSex species has major implications for Se release, because FeSex species oxidize much faster than Se substituted in the euhedral pyrite lattice. Thus, such an FeSex species will enhance and control the dynamics of Se weathering and release into the aqueous environment