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

A case report of primary aortoduodenal fistula: A forgotten cause of gastrointestinal bleeding

Aortoenteric fistula is one of the uncommon emergencies and is challenging to navigate for diagnostic testing. Here, we present a clinical case of an aortoduodenal fistula with primary etiology. A 73-year-old female patient with a history of hypertension was admitted to the hospital because of a 1-day history of melena. Ultrasound showed an abdominal aortic aneurysm sized (33 × 46) mm and a hematoma on the wall of the aorta. The patient underwent a gastrointestinal endoscopy with no bleeding point detected. However, the patient suddenly fell into a hemorrhagic shock on day 3 of admission. We rapidly performed fluid resuscitation, blood transfusion, a second gastrointestinal endoscopy, and a computed tomography scan of the abdomen with contrast injection that revealed a fistula from the abdominal aorta into the second segment of the duodenum. The patient was indicated for urgent endovascular aortic repair. Although this technique was successful with 3 abdominal aortic stents, the patient died due to multiorgan failure. Delayed diagnosis is the root cause of primary aortoduodenal fistula treatment failure, so it is important for clinicians to keep aortoduodenal fistula in mind as a possible cause of gastrointestinal bleeding in any patient

Deficiency of Natural Anticoagulants Involves in the Occurrence of Arterial Thrombosis

Background The role of natural anticoagulant deficiency in the development of arterial thrombosis (AT) is controversial. Objective Our objectives were to assess the deficiency of natural anticoagulants, including protein S (PS), protein C (PC), antithrombin III (AT III) and their involvement in the occurrence of AT. Design Retrospective cross-sectional study. Methods This study was conducted in 585 patients who were examined with PS, PC, and AT III tests. The activity of PC, PS (men, women), and ATIII under 70%, 75%, 60%, and 80% was recognized as a deficiency, respectively. Peripheral blood cell and coagulation tests were performed before starting treatment. Patients with previous AT, venous thromboembolism (VTE) or anticoagulant therapy were excluded. Results Patients without thrombosis were 222 (38%), patients with newly diagnosed VTE were 281 (48%), and patients with newly diagnosed AT were 82 (14%). The most common AT sites were in the lungs, brain, and lower extremities (31.2%, 20.8%, and 20.8%, respectively). Compared to the nonthrombosis group, the AT group had a lower PS activity (%) (82.77 ± 24.09 vs 91.31 ± 27.27), a higher fibrinogen (g/L) (4.25 ± 1.68 vs 3.74 ± 1.51), a higher D-dimer (mg/L FEU) (6.16 vs 1.95), and a higher neutrophil count (G/L) (8.57 vs 6.50) with P  < .05. Compared to the VTE group, the AT group had higher hemoglobin (g/L) (135.95 ± 23.75 vs 129.02 ± 25.22) and a higher neutrophil count (G/L) (8.57 vs 7.28) ( P  < .05). In the AT group, the frequencies of PC, PS, and AT III deficiency were 23.1%, 28%, and 17.1%, respectively. The AT group had a higher frequency of PS deficiency than the nonthrombosis group (28% vs 17.1%, P  = .035). Patients with PS deficiency had a higher risk of AT compared to those without PS deficiency (OR = 1.888, 95% CI [1.041-3.422], P  = .036). Conclusion PS deficiency may be considered a factor in increasing the risk of AT

Acute edematous pancreatitis caused by Fasciola hepatica infection: A rare case report

Acute edematous pancreatitis is a medical emergency characterized by a sudden pancreas inflammation. It can be caused by various factors, primarily gallstones, alcohol consumption, or medication. Acute edematous pancreatitis caused by Fasciola hepatica infection is exceptionally rare and could be overlooked. We report a case of a 24-year-old female patient who presented with onsets of clinical and paraclinical signs of acute pancreatitis (AP). The patient was diagnosed with Fasciola hepatica-induced edematous pancreatitis, a rare parasitic infection that can cause AP. This case highlights the importance of considering parasitic infections in the differential diagnosis of edematous pancreatitis, particularly in young patients with no significant medical history

Characteristics of Participants in Peripartum Interventional Research.

OBJECTIVE: To identify characteristics of pregnant women potentially influencing the decision to participate in peripartum interventional research. METHODS: Women screened as eligible to participate in two prospective interventional trials conducted in the labor and delivery unit at a single center were included. Characteristics of eligible women were compared based on their decision whether to participate or not. The best predictors of research participation were identified using multivariable logistic regression analyses. RESULTS: Of the 605 subjects who screened as eligible to participate, 363 (60%) agreed to participate and 242 (40%) declined. Women using a private obstetric provider or who had prior obstetrical complications were less likely to participate [aOR 0.6 (95% CI: 0.4-0.8)] and [aOR 0.6 (95% CI: 0.4-0.9)], respectively. A history of a mental health condition and a higher body mass index (BMI) were marginally more likely to participate [aOR 1.5 (95% CI: 1.0-2.3)] and [aOR 1.03 (95% CI: 1.0-1.1)], respectively. Overall logistic regression model R(2) was 0.23. CONCLUSIONS: There are differences between eligible subjects who decide to participate or not participate in prospective peripartum interventional research. There is a need to better understand non-participation in order to improve recruitment of representative populations that allow more generalizable research results