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

Patrones de forrajeo en dos especies de peces intermareales herbívoros de las costas de Chile: Efecto de la abundancia y composición química del alimento Foraging patterns of two species of intertidal herbivorous fishes: Effect of food abundance and chemical composition

Los peces herbívoros son organismos que deben suplir los requerimientos de su economía energética a partir de una fuente de alimento con un bajo contenido de nutrientes y energía. Dos de las interrogantes más importantes en relación con la herbivoría por peces son: i) ¿cuáles son los factores que influyen en la selección o rechazo de un determinado item dietario? y ii) ¿son capaces los peces herbívoros de extraer los nutrientes y energía necesarios para suplir sus requerimientos energéticos en base a una dieta de macroalgas?. En este trabajo se estudiaron en dos especies de peces herbívoros, Scartichthys viridis y Girella laevifrons, los patrones de selectividad dietaria en terreno y laboratorio, la eficiencia de asimilación y la relación entre los patrones encontrados con la composición química del alga. Los resultados obtenidos señalan que la dieta de estos organismos se compone en más del 90% de macroalgas bentónicas. En terreno ambas especies presentan una conducta trófica no selectiva en verano y selectiva en invierno, prefiriendo el consumo de algas verdes. En los experimentos de selección dietaria ambas especies presentan un patrón similar caracterizado por la preferencia de algas verdes y rojas por sobre algas pardas. Los resultados de los experimentos de asimilación, indican que Girella laevifrons presenta tasas de asimilación mayores que Scartichthys viridis, siendo en la primera las algas verde Ulva y Enteromorpha las que presentan una mayor eficiencia de asimilación. Los resultados sugieren una fuerte relación entre el patrón de selección trófica observado en estas especies y la relación entre composición del alimento y características digestivas<br>Herbivores are organisms that must meet their energy and nutrients requirements from a food source that typically has been characterized as having low nutritional value given their low concentration of nutrients and energy. Two of the most important questions in relation to fish herbivory are: i) which are the factors that determine the selection or rejection of a given algal item? and ii) are herbivorous fishes capable of extracting the nutrients and energy of a macroalgal diet? In this work, we studied in two species of herbivorous intertidal fishes, Scartichthys viridis and Girella laevifrons, the patterns of food selectivity in the field and in laboratory experiments, the assimilation efficiency for different dietary algal items, and the relationship between the observed patterns and the chemical composition of the algae. The results showed that more than 90% of the diet of these organisms consisted of benthic macroalgae. In the field both species present a non-selective trophic behavior in summer and selective one in winter, characterized by the consumption of green algae in the later season. Furthermore, in the experiments of food selection both species showed a similar pattern characterized by the preference of green and red algae. The results of the assimilation experiments, indicate that Girella laevifrons presents higher values of this parameter than Scartichthys viridis, being in the former the green algae Ulva and Enteromorpha, the items that present a higher efficiency of assimilation. Finally, the results obtained suggest in this herbivorous species a strong relationship among the patterns of food selection and the relationship between food composition and digestive characteristic

Efecto del parasitismo del isópodo bopírido Ionella agassizi (Isopoda: Epicaridea) (Bornnier, 1900) sobre la fisiología nutricional del nape Neotrypaea uncinata (M. Edwards, 1837) (Decapoda: Thalassinidea) Effects of parasitism in nutritional physiology of the ghost shrimp Neotrypaea uncinata parasitized by the isopod Ionella agassizi

El nape Neotrypaea uncinata se encuentra parasitado en sus branquias por el isópodo Ionella agassizi. Trabajos anteriores han señalado que I. agassizi provoca un efecto negativo en la biología reproductiva del nape, afectando significativamente tanto el desarrollo de los órganos reproductores como la expresión de las características sexuales secundarias. Lo anterior podría estar asociado a una disminución de las sustancias de reserva de N. uncinata, afectando de esta manera su metabolismo. En este trabajo se determinaron las concentraciones de metabolitos relacionados con el estado nutricional de N. uncinata (proteínas totales, hemocianina, lactato y glucosa); además se evaluó el porcentaje de lípidos en el tejido del hospedador. Los resultados obtenidos indican una mayor frecuencia de infección en machos adultos, lo que sugiere la existencia de mortalidad diferencial en el hospedador. Se determinó una menor masa corporal en los individuos parasitados en comparación con los no parasitados. En relación con la concentración de metabolitos: se determinó una disminución de los niveles de proteínas totales y de las concentraciones de hemocianina, lo que evidencia un efecto importante del parasitismo a nivel nutricional. Además, se encontró una concentración menor de lactato en individuos parasitados asociado a una alta concentración de glucosa, lo cual sugiere la utilización del lactato como sustrato para la síntesis de glucosa en presencia del parásito. Finalmente la reducción de los lípidos en individuos parasitados evidencia la carencia de sustancias de reserva.The ghost shrimp Neotrypaea uncinata is parasitized in the branchial chamber for the isopod Ionella agassizi. Previous works had indicated that the parasite causes a negative effect in the reproductive biology of the ghost shrimp, influencing seriously the development of reproductive organs and the expression of secondary sexual characteristics. This effect can be produced by a general reduction of the reserve substances of N. uncinata caused by the presence of the parasite. In order to evaluate the effect of the parasite on the nutritional status of the ghost shrimp we measured the concentration of some metabolites related to the nutritional physiology of N. uncinata. The results showed a greater frequency of infection in adult males, which suggests differential mortality by effect of the parasite through the host ontogeny. The parasitized individuals showed a reduction of the body mass and a diminution of both protein and haemocyanin levels. However, the measured lactate levels are smaller in parasitized individuals, but the levels of glucose were higher in this individuals, this relationships suggest the use of lactate as substrate for glucose synthesis. Finally the lipid reduction in parasitized ghost shrimps demonstrates the scarcity of the reserve substances in this specie

The impact of conversion on the risk of major complication following laparoscopic colonic surgery: an international, multicentre prospective audit.

This is the peer reviewed version of the following article: The and E. S. o. C. c. groups (2018). "The impact of conversion on the risk of major complication following laparoscopic colonic surgery: an international, multicentre prospective audit." Colorectal Disease 20(S6): 69-89., which has been published in final form at https://doi.org/10.1111/codi.14371. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.BACKGROUND: Laparoscopy has now been implemented as a standard of care for elective colonic resection around the world. During the adoption period, studies showed that conversion may be detrimental to patients, with poorer outcomes than both laparoscopic completed or planned open surgery. The primary aim of this study was to determine whether laparoscopic conversion was associated with a higher major complication rate than planned open surgery in contemporary, international practice. METHODS: Combined analysis of the European Society of Coloproctology 2017 and 2015 audits. Patients were included if they underwent elective resection of a colonic segment from the caecum to the rectosigmoid junction with primary anastomosis. The primary outcome measure was the 30-day major complication rate, defined as Clavien-Dindo grade III-V. RESULTS: Of 3980 patients, 64% (2561/3980) underwent laparoscopic surgery and a laparoscopic conversion rate of 14% (359/2561). The major complication rate was highest after open surgery (laparoscopic 7.4%, converted 9.7%, open 11.6%, P < 0.001). After case mix adjustment in a multilevel model, only planned open (and not laparoscopic converted) surgery was associated with increased major complications in comparison to laparoscopic surgery (OR 1.64, 1.27-2.11, P < 0.001). CONCLUSIONS: Appropriate laparoscopic conversion should not be considered a treatment failure in modern practice. Conversion does not appear to place patients at increased risk of complications vs planned open surgery, supporting broadening of selection criteria for attempted laparoscopy in elective colonic resection

Association of mechanical bowel preparation with oral antibiotics and anastomotic leak following left sided colorectal resection: an international, multi-centre, prospective audit.

This is the peer reviewed version of the following article: , (2018), Association of mechanical bowel preparation with oral antibiotics and anastomotic leak following left sided colorectal resection: an international, multi‐centre, prospective audit. Colorectal Dis, 20: 15-32. doi:10.1111/codi.14362, which has been published in final form at https://doi.org/10.1111/codi.14362. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived VersionsINTRODUCTION: The optimal bowel preparation strategy to minimise the risk of anastomotic leak is yet to be determined. This study aimed to determine whether oral antibiotics combined with mechanical bowel preparation (MBP+Abx) was associated with a reduced risk of anastomotic leak when compared to mechanical bowel preparation alone (MBP) or no bowel preparation (NBP). METHODS: A pre-planned analysis of the European Society of Coloproctology (ESCP) 2017 Left Sided Colorectal Resection audit was performed. Patients undergoing elective left sided colonic or rectal resection with primary anastomosis between 1 January 2017 and 15 March 2017 by any operative approach were included. The primary outcome measure was anastomotic leak. RESULTS: Of 3676 patients across 343 centres in 47 countries, 618 (16.8%) received MBP+ABx, 1945 MBP (52.9%) and 1099 patients NBP (29.9%). Patients undergoing MBP+ABx had the lowest overall rate of anastomotic leak (6.1%, 9.2%, 8.7% respectively) in unadjusted analysis. After case-mix adjustment using a mixed-effects multivariable regression model, MBP+Abx was associated with a lower risk of anastomotic leak (OR 0.52, 0.30-0.92, P = 0.02) but MBP was not (OR 0.92, 0.63-1.36, P = 0.69) compared to NBP. CONCLUSION: This non-randomised study adds 'real-world', contemporaneous, and prospective evidence of the beneficial effects of combined mechanical bowel preparation and oral antibiotics in the prevention of anastomotic leak following left sided colorectal resection across diverse settings. We have also demonstrated limited uptake of this strategy in current international colorectal practice

An international multicentre prospective audit of elective rectal cancer surgery; operative approach versus outcome, including transanal total mesorectal excision (TaTME)

IntroductionTransanal total mesorectal excision (TaTME) has rapidly emerged as a novel approach for rectal cancer surgery. Safety profiles are still emerging and more comparative data is urgently needed. This study aimed to compare indications and short-term outcomes of TaTME, open, laparoscopic, and robotic TME internationally.MethodsA pre-planned analysis of the European Society of Coloproctology (ESCP) 2017 audit was performed. Patients undergoing elective total mesorectal excision (TME) for malignancy between 1 January 2017 and 15 March 2017 by any operative approach were included. The primary outcome measure was anastomotic leak.ResultsOf 2579 included patients, 76.2% (1966/2579) underwent TME with restorative anastomosis of which 19.9% (312/1966) had a minimally invasive approach (laparoscopic or robotic) which included a transanal component (TaTME). Overall, 9.0% (175/1951, 15 missing outcome data) of patients suffered an anastomotic leak. On univariate analysis both laparoscopic TaTME (OR 1.61, 1.02-2.48, P=0.04) and robotic TaTME (OR 3.05, 1.10-7.34, P=0.02) were associated with a higher risk of anastomotic leak than non-transanal laparoscopic TME. However this association was lost in the mixed-effects model controlling for patient and disease factors (OR 1.23, 0.77-1.97, P=0.39 and OR 2.11, 0.79-5.62, P=0.14 respectively), whilst low rectal anastomosis (OR 2.72, 1.55-4.77, P<0.001) and male gender (OR 2.29, 1.52-3.44, P<0.001) remained strongly associated. The overall positive circumferential margin resection rate was 4.0%, which varied between operative approaches: laparoscopic 3.2%, transanal 3.8%, open 4.7%, robotic 1%.ConclusionThis contemporaneous international snapshot shows that uptake of the TaTME approach is widespread and is associated with surgically and pathologically acceptable results

Safety of primary anastomosis following emergency left sided colorectal resection: an international, multi-centre prospective audit.

This is the peer reviewed version of the following article: group, T. E. S. o. C. c. (2018). "Safety of primary anastomosis following emergency left sided colorectal resection: an international, multi-centre prospective audit." Colorectal Disease 20(S6): 47-57., which has been published in final form at https://doi.org/10.1111/codi.1437. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived VersionsINTRODUCTION: Some evidence suggests that primary anastomosis following left sided colorectal resection in the emergency setting may be safe in selected patients, and confer favourable outcomes to permanent enterostomy. The aim of this study was to compare the major postoperative complication rate in patients undergoing end stoma vs primary anastomosis following emergency left sided colorectal resection. METHODS: A pre-planned analysis of the European Society of Coloproctology 2017 audit. Adult patients (> 16 years) who underwent emergency (unplanned, within 24 h of hospital admission) left sided colonic or rectal resection were included. The primary endpoint was the 30-day major complication rate (Clavien-Dindo grade 3 to 5). RESULTS: From 591 patients, 455 (77%) received an end stoma, 103 a primary anastomosis (17%) and 33 primary anastomosis with defunctioning stoma (6%). In multivariable models, anastomosis was associated with a similar major complication rate to end stoma (adjusted odds ratio for end stoma 1.52, 95%CI 0.83-2.79, P = 0.173). Although a defunctioning stoma was not associated with reduced anastomotic leak (12% defunctioned [4/33] vs 13% not defunctioned [13/97], adjusted odds ratio 2.19, 95%CI 0.43-11.02, P = 0.343), it was associated with less severe complications (75% [3/4] with defunctioning stoma, 86.7% anastomosis only [13/15]), a lower mortality rate (0% [0/4] vs 20% [3/15]), and fewer reoperations (50% [2/4] vs 73% [11/15]) when a leak did occur. CONCLUSIONS: Primary anastomosis in selected patients appears safe after left sided emergency colorectal resection. A defunctioning stoma might mitigate against risk of subsequent complications