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

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Molecular identification of heteroatomic and metal species related to hydrometallation and hydroconversion.

La présence d'hétéroatomes et métaux dans des fractions lourdes de pétrole brut peuvent entraîner la désactivation des catalyseurs d’hydrotraitement et d’hydrocraquage. Les composés contenant ces éléments sont connus pour être inclus dans des agrégats macromoléculaires d’asphaltènes, qui sont considérées comme les composants les plus problématiques des produits pétroliers. Ces travaux ont pour objectif d’apporter une meilleure compréhension de l’environnement chimique de ces espèces et des phénomènes d’agrégation pour optimiser les processus de raffinage. Des techniques de séparation comme la chromatographie de perméation de gel ou Gel Permeation Chromatography (GPC), Advanced Polymer chromatographie (APC) et la chromatographie sur couche mince d’haute performance ou High Performance Thin Layer Chromatography (HPTLC) ont été combinées avec des techniques d’analyse élémentaire comme la spectrométrie de masse à plasma à couplage inductif ou Inductively Coupled Plasma Mass Spectrometry (ICP-MS) et la spectrométrie de masse moléculaire d’haute résolution pour la caractérisation des fractions pétrolières lourdes. Les profils de distribution en taille d’espèces qui contiennent du vanadium, du nickel et du soufre, les hétéroatomes et métaux les plus abondants dans les produits pétroliers, ont été déterminés par GPC couplé à une détection élémentaire par ICP MS. Les paramètres ayant le plus d’impact sur la distribution en taille et l’évolution des agrégats dans les solutions de différentes coupes pétrolières ont été optimisés. Cela nous a permis de faire différentes comparaisons, entre de nombreuses charges et effluents de procédés, ainsi que d’autres séries d’échantillons ou de mélanges provenant d’unités-pilotes d’hydrotraitement. Les résultats obtenus ont pu être mis en regard de caractéristiques macroscopiques comme la viscosité. Le couplage du nouveau système APC avec l’ICP MS a été mis au point avec succès. Cette technique a permis de réaliser des cartographies d’échantillons pétroliers plus rapides qu’en GPC tout en consommant moins de solvant. Cependant, les différences des chromatogrammes APC obtenus par rapport aux profils GPC suggèrent des interactions indésirables avec la phase stationnaire, qui ont été l’objet d’une évaluation approfondie.Enfin, un dernier type de séparation a été évaluée. L’HPTLC, qui utilise des plaques à usage unique, peut être appliquée à la séparation de produits lourds par polarité, et ce sans étapes de déasphaltage préalable, contrairement aux colonnes de chromatographie liquide qui peuvent être détériorées à cause de l'adsorption irréversible et de la précipitation des asphaltènes. Différents types de plaques et éluants ont été testés afin de développer une méthode simple pour la séparation des fractions SAR (Saturés, Aromatiques et Résines) des échantillons de distillat sous vide ou Vacuum Gas Oil (VGO). Ce travail avait pour but des migrations en une seule étape et analyse UV qui pourrait être mis en œuvre pour l’analyse de routine dans les laboratoires de contrôle avec une adsorption irréversible réduite. Des résultats très prometteurs ont été obtenus avec l’utilisation de plaques de cellulose pour la séparation des familles de polarité différentes au sein des agrégats d’asphaltènes. Des tests sur l'analyse directe des plaques par Désorption-Ionisation par Électronébulisation (DESI) MS, l'analyse directe en temps réel ou Direct Analysis in Real Time (DART) MS et Ablation Laser (LA) ICP MS ont été effectués.The presence of heteroatoms and metals in heavy fractions of crude oil can cause the deactivation of hydrotreatment and hydrocracking catalysts. Compounds containing these elements are known to be included in macromolecular asphaltene aggregates, which are considered the most problematic components of heavy oil. This thesis aimed for a better understanding of the chemical environment of these species and on the aggregation phenomenon to optimize refining processes. Separation techniques such as Gel Permeation Chromatography (GPC), Advanced Polymer Chromatography (APC) and High Performance Thin Layer Chromatography (HPTLC) were combined with elementary analysis techniques such as Inductively Coupled Plasma Mass Spectrometry (ICP MS) or high-resolution molecular mass spectrometry for the characterization of heavy fractions of crude oil. Here, the size profiles of species that contain vanadium, nickel and sulfur, the most abundant heteroatoms and metals present in petroleum products, were determined by GPC online with elemental detection by ICP MS. The parameters having the most significant impact on size distribution and the evolution over time of aggregates from solutions of different petroleum cuts were optimized. This allowed the comparison between various feeds and effluents and other series of samples and mixtures from pilot units of refining processes by GPC ICP MS. Results obtained could be related to macroscopic characteristics such as viscosity. Hyphenation of the new APC System to ICP MS has been successfully completed. It allowed the mapping of petroleum samples faster than GPC, therefore with less solvent consumption. However, the differences of the APC chromatograms obtained with respect to the GPC profiles suggested significant unwanted interactions of the highly polar compounds of the petroleum samples with the stationary phase, which have been thoroughly studied. Finally, another type of separation was evaluated. HPTLC, of single-use plates, can be applied to the analysis of heavy petroleum products by polarity without prior deasphalting steps while chromatography columns can be deteriorated because of the irreversible adsorption and asphaltene precipitation. To this end, various types of plates and eluents were tested to develop straightforward SAR (Saturates, Aromatics and Resins) separations of Vacuum Gas Oil (VGO) samples. This method, based on single-step migrations with reduced irreversible adsorption and UV monitoring, could be implemented for routine analysis in control laboratories. Very promising results were obtained by the use of cellulose plates for the separation of different families within asphaltene aggregates. Tests on Desorption ElectroSpray Ionization (DESI) MS, Direct Analysis in Real Time (DART) MS and Laser Ablation (LA) ICP MS analyses of the plates have been performed

Molecular Fingerprints and Speciation of Crude Oils and Heavy Fractions Revealed by Molecular and Elemental Mass Spectrometry: Keystone between Petroleomics, Metallopetroleomics, and Petrointeractomics

International audiencePetroleum and its fractions are some of the most complex mixtures found in analytical chemistry. Mass spectrometry currently plays an increasing role in the characterization of these matrices. Since the last review on this topic in 2011, several new approaches have been introduced, and these approaches increasingly use sample fractionation by extraction and/or liquid chromatographic techniques. This review considers molecular mass spectrometry (with special emphasis on the use of ion mobility) and inorganic mass spectrometry. The combination of both techniques paves the way to "petrointeractomic" approaches, which are introduced as a novel, important part of "petroleomic" approaches