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

Teacher evaluation in the Kingdom of Saudi Arabia's (KSA) schools - moving forward

The aim of this optimization study was to minimize the acquisition time of 68Ga-HBED-CC-PSMA positron emission tomography/magnetic resonance imaging (PET/MRI) in patients with local and metastatic prostate cancer (PCa) to obtain a sufficient image quality and quantification accuracy without any appreciable loss.Twenty patients with PCa were administered intravenously with the 68Ga-HBED-CC-PSMA ligand (mean activity 99 MBq/patient, range 76-148 MBq) and subsequently underwent PET/MRI at, on average, 168 min (range 77-320 min) after injection. PET and MR imaging data were acquired simultaneously. PET acquisition was performed in list mode and PET images were reconstructed at different time intervals (1, 2, 4, 6, 8, and 10 min). Data were analyzed regarding radiotracer uptake in tumors and muscle tissue and PET image quality. Tumor uptake was quantified in terms of the maximum and mean standardized uptake value (SUVmax, SUVmean) within a spherical volume of interest (VOI). Reference VOIs were drawn in the gluteus maximus muscle on the right side. PET image quality was evaluated by experienced nuclear physicians/radiologists using a five-point ordinal scale from 5-1 (excellent-insufficient).Lesion detectability linearly increased with increasing acquisition times, reaching its maximum at PET acquisition times of 4 min. At this image acquisition time, tumor lesions in 19/20 (95%) patients were detected. PET image quality showed a positive correlation with increasing acquisition time, reaching a plateau at 4-6 min image acquisition. Both SUVmax and SUVmean correlated inversely with acquisition time and reached a plateau at acquisition times after 4 min.In the applied image acquisition settings, the optimal acquisition time of 68Ga-PSMA-ligand PET/MRI in patients with local and metastatic PCa was identified to be 4 min per bed position. At this acquisition time, PET image quality and lesion detectability reach a maximum while SUVmax and SUVmean do not change significantly beyond this time point

Impact of Different Metal Artifact Reduction Techniques on Attenuation Correction of Normal Organs in 18F-FDG-PET/CT

Purpose: To evaluate the impact of different metal artifact reduction algorithms on Hounsfield units (HU) and the standardized uptake value (SUV) in normal organs in patients with different metal implants. Methods: This study prospectively included 66 patients (mean age of 66.02 ± 13.1 years) with 87 different metal implants. CT image reconstructions were performed using weighted filtered back projection (WFBP) as the standard method, metal artifact reduction in image space (MARIS), and an iterative metal artifacts reduction (iMAR) algorithm for large implants. These datasets were used for PET attenuation correction. HU and SUV measurements were performed in nine predefined anatomical locations: liver, lower lung lobes, descending aorta, thoracic vertebral body, autochthonous back muscles, pectoral muscles, and internal jugular vein. Differences between HU and SUV measurements were compared using paired t-tests. The significance level was determined as p = 0.017 using Bonferroni correction. Results: No significant differences were observed between reconstructed images using iMAR and WFBP concerning HU and SUV measurements in liver (HU: p = 0.055; SUVmax: p = 0.586), lung (HU: p = 0.276; SUVmax: p = 1.0 for the right side and HU: p = 0.630; SUVmax: p = 0.109 for the left side), descending aorta (HU: p = 0.333; SUVmax: p = 0.083), thoracic vertebral body (HU: p = 0.725; SUVmax: p = 0.392), autochthonous back muscles (HU: p = 0.281; SUVmax: p = 0.839), pectoral muscles (HU: p = 0.481; SUVmax: p = 0.277 for the right side and HU: p = 0.313; SUVmax: p = 0.859 for the left side), or the internal jugular vein (HU: p = 0.343; SUVmax: p = 0.194). Conclusion: Metal artifact reduction algorithms such as iMAR do not alter the data information of normal organs not affected by artifacts

Utility of Integrated PET/MRI for the Primary Diagnostic Work-Up of Patients with Ewing Sarcoma: Preliminary Results

Background: This study was conducted to evaluate the clinical applicability of integrated PET/MRI for staging and monitoring the effectiveness of neoadjuvant chemotherapy in Ewing sarcoma patients. Methods: A total of 11 juvenile patients with confirmed Ewing sarcoma, scheduled for induction polychemotherapy, were prospectively enrolled for a PET/MR examination before, during and after the end of treatment. Two experienced physicians analysed the imaging datasets. They were asked to perform a whole-body staging in all three examinations and to define treatment response according to the RECIST1.1 and PERCIST criteria for each patient. Results: In eight patients lymph node and/or distant metastases were detected at initial diagnosis. According to the reference standard, three patients achieved complete response, six patients partial response, and one patient showed stable disease while another patient showed progressive disease. RECIST1.1 categorized the response to treatment in 5/11 patients correctly and showed a tendency to underestimate the response to treatment in the remaining six patients. PERCIST defined response to treatment in 9/11 patients correctly and misclassified two patients with a PR as CR. Conclusion: PET/MRI may serve as a valuable imaging tool for primary staging and response assessment of juvenile patients with Ewing sarcoma to induction chemotherapy, accompanied by a reasonable radiation dose for the patient

Streamlining Patient Management of Suspected COVID-19 Patients in the Emergency Department: Incorporation of Pulmonary CT Angiography into the Triaging Algorithm

Purpose: To evaluate the use of pulmonary computed tomography (CT) angiography during initial admission at an emergency department (ED), to identify COVID-19 patients with accompanying pulmonary embolism (PE) and its impact on clinical management. Methods: We performed a retrospective analysis of COVID-19 patients that underwent pulmonary CT angiography at the ED. CT scans were evaluated for the presence and extent of PE and for imaging changes suspicious of COVID-19. Patients were subdivided into two groups: (1) Group A consisted of patients with proven COVID-19 based on real-time polymerase chain reaction (RT-PCR), and (2) Group B of patients suspected for COVID-19, comprising patients positive on RT-PCR and/or COVID-19-suspicious CT findings. To assess the differences between patients with and without pulmonary embolism, Fisher’s exact test was used. Results: A total of 308 patients were admitted to the ED for diagnostic work-up of dyspnea and suspected COVID-19, and 95 patients underwent pulmonary CT angiography. PE was detected in 13.6% (3/22) of patients in Group A and 20.7% (6/29) in Group B. No significant differences were observed between patients with and without PE concerning hospitalization (Group B: 100% (6/6) vs. 91.3% (21/23)), the necessity of oxygen therapy (Group B: 66% (4/6) vs. 43.5% (10/23)), and death (Group B: 33% (2/6) vs. 4.3% (1/23) p > 0.05, respectively). Conclusions: In 20.7% of COVID-19 patients, PE was detected upon admission to the ED. Although the incorporation of early pulmonary CT angiography in patients suspicious of COVID-19 may be beneficial to identify concomitant PE, further studies are necessary to corroborate these findings

Evaluation of the Predictive Potential of 18F-FDG PET and DWI Data Sets for Relevant Prognostic Parameters of Primary Soft-Tissue Sarcomas

Background: To evaluate the potential of simultaneously acquired 18F-FDG PET- and MR-derived quantitative imaging data sets of primary soft-tissue sarcomas for the prediction of neoadjuvant treatment response, the metastatic status and tumor grade. Methods: A total of 52 patients with a high-risk soft-tissue sarcoma underwent a 18F-FDG PET/MR examination within one week before the start of neoadjuvant treatment. For each patient, the maximum tumor size, metabolic activity (SUVs), and diffusion-restriction (ADC values) of the tumor manifestations were determined. A Mann–Whitney-U test was used, and ROC analysis was performed to evaluate the potential to predict histopathological treatment response, the metastatic status or tumor grade. The results from the histopathological analysis served as reference standard. Results: Soft-tissue sarcomas with a histopathological treatment response revealed a significantly higher metabolic activity than tumors in the non-responder group. In addition, grade 3 tumors showed a significant higher 18F-FDG uptake than grade 2 tumors. Furthermore, no significant correlation between the different outcome variables and tumor size or calculated ADC-values could be identified. Conclusion: Measurements of the metabolic activity of primary and untreated soft-tissue sarcomas could non-invasively deliver relevant information that may be used for treatment planning and risk-stratification of high-risk sarcoma patients in a pretherapeutic setting

Patient characteristics.

<p>Patient characteristics.</p

MR imaging sequence parameters.

<p>MR imaging sequence parameters.</p

PET images of a patient (age: 66 years, serum PSA: 2.3 ng/ml) with recurrent PCa in two iliacal lymph nodes obtained with the PET/MR hybrid imaging system at 134 min after intravenous injection of ⁶⁸Ga-HBED-CC-PSMA (146 MBq).

<p>a) Scatter und attenuation corrected PET images with intense ‘halo artifact’ showing only one iliacal lymph node. b) Non-scatter and attenuation corrected PET image showing both lymph nodes that were seen on PET/CT as well.</p

Image quality of ⁶⁸Ga-HBED-CC-PSMA PET/MRI of a patient with recurrent PCa in an ilical lymph node.

<p>Images were acquired at 3 h p.i.. Left panel: PET/MR fusion image, right panel: PET image of the PET/MR hybrid imaging system. Acquisition times were a) 1 min, b) 2 min, c) 3 min, d) 4 min, e) 6 min, f) 8 min, and g) 10 min. PET image quality rises with increasing acquisition times and reaches a plateau at an acquisition time of 4 min. The halo artifact first occurs at image acquisition times of 4 min.</p