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

Improvement of EPID-based techniques for dosimetry and investigation of linac mechanical performance in advanced radiotherapy

Research Doctorate - Doctor of Philosophy (PhD)Advances in radiotherapy have increased the complexity of treatment delivery techniques. The complexity of plans, with dynamic variation of field shape, gantry speed and dose rate require highly accurate techniques for quality assurance of the treatment machines and dosimetric verification of the treatment plans. There has been a growing interest on the application of electronic portal imaging devices (EPIDs) for dosimetry applications and quality assurance testing of linear accelerators (linacs). The ultimate aim of this thesis is to develop methods to ensure more accurate treatment deliveries using EPID-based techniques. The project is divided into two parts. The first part is based on improvement of the accuracy of EPID dosimetry with Varian systems by either accounting for, or reduction of, the effect of backscattered radiation from the treatment room walls and the EPID support arm. The effect of backscatter from the treatment room walls was quantified for the first time using a number of measurement setups and comparisons with measurements in the presence of an independent portable wall. The Varian support arm backscatter was accounted for or reduced by three methods: (a) application of an experimentally derived backscatter kernel into an existing EPID dose prediction model, (b) insertion of lead sheets to reduce the non-uniform backscatter, and (c) insertion of a thicker piece of lead over the arm area and considering it as an arm component which could effectively reduce the backscatter effect. Application of the backscatter kernel measured with this lead shielded arm into the model was the most effective method to improve the accuracy of EPID dosimetry predictions. In the second part of the project, EPID-based measurement methods were used and new algorithms were developed for faster, easier, more robust, more accurate quantitative techniques for characterization of the linac components than existing methods. The results could be used for improvement of EPID dosimetry measurements and/or be included in the linac quality assurance program. The study includes: determination of the mechanical isocentre position with a level of accuracy suitable for stereotactic treatments; determination of the sag in EPID, gantry, jaws and MLC systems during arc deliveries; determination of gantry angle during rotation; and finally, a comprehensive investigation of MLC leaf positioning and dynamic performance in static and arc delivery modes. The proposed methods have been tested and are applicable for routine quality assurance of the linear accelerators used for advanced treatment techniques with all linacs, independent of their make and model

Burnout, Depression, and Anxiety in Teaching Professors of an Educational Hospital of Tehran University of Medical Sciences

Introduction: Burnout is prevalent in several physicians that may undermine the progress nad performance of physicians, reduced accessibility of patients to physicians, and patients’ safety. This study endeavored to determine burnout, anxiety, and depression in the specialists and attending physicians of one of the educational hospitals of Tehran University of Medical Sciences. Methods: This cross-sectional study conducted in the academic year 2018. One-hundred twenty-three physicians filled the Malach Burnout Inventory (MBI) questionnaire, Hospital Anxiety, and Depression Survey (HADS) questionnaires. Results: Forty-four physicians (35.8%) had some levels of burnout. Severe Emotional Exhaustion (EE) was seen in 18 physicians (14.6%). Likewise, severe Depersonalization (DP) in 12 physicians (9.8%), and severe dysfunction in Personal Accomplishment (PA) were seen in 33 physicians (26.8%). Four physicians (3%) had an abnormal level of anxiety, and 32 subjects (26%) were in the borderline zone. Four (3.2%) had abnormal depression, and 12 subjects (9.8%) had a borderline depression. There was a significant relationship between attending teacher type (i.e., educational, research, or treatment) and dysfunction of personal accomplishment (X2 = 12.24, p = 0.02). Moreover, anxiety was higher in non-married physicians (p = 0.046); anxiety was higher in part-time physicians as well (p = 0.03). Conclusion: Findings revealed that burnout is an essential issue in attending physicians of educational hospitals. Identifying and managing burnout and its adverse effects could eliminate further health complications for the physicians and under-treating patients

Root Canal Configuration of One-rooted Mandibular Canine in an Iranian Population:An In Vitro Study

<p><strong><em>Background and aims</em></strong><strong><em>. </em></strong>A<strong> </strong>perfect endodontic treatment necessitates proper understanding of the morphology of canal and pulpal variations.<strong> </strong>This in vitro study was conducted to demonstrate the internal anatomy of mandibular canine teeth in an Iranian population. </p> <p><strong><em>Materials and methods</em></strong><strong><em>.</em></strong><em> </em>The samples consisted of 100 extracted mandibular permanent canines. The roots of the teeth were molded in acrylic boxes. The crowns of the teeth were cut and 2 mm cross sections were made from CEJ to the apex. Sections were examined using stereomicroscope to reveal the number and location of root canals.</p> <p><strong><em>Results</em></strong><em>.</em><em> </em>From 100 evaluated teeth, 12 (12%) had 2 canals from which 5 had type II canal configuration and 7 (7%) had type III. 88% of the specimens had one canal and none were seen to be of type IV.</p> <p><strong><em>Conclusion.</em></strong><strong> </strong>The findings of this study emphasize the importance of dentist's knowledge of variations in root canal morphology, since leaving a canal untreated is one of the main reasons of endodontic failures. When treating mandibular canines, the existence of a second canal should be taken into consideration.</p&gt

Detection and correction for EPID and gantry sag during arc delivery using cine EPID imaging

Purpose: Electronic portal imaging devices(EPIDs) have been studied and used for pretreatment and in-vivo dosimetry applications for many years. The application of EPIDs for dosimetry in arc treatments requires accurate characterization of the mechanical sag of the EPID and gantry during rotation. Several studies have investigated the effects of gravity on the sag of these systems but each have limitations. In this study, an easy experiment setup and accurate algorithm have been introduced to characterize and correct for the effect of EPID and gantry sag during arc delivery. Methods: Three metallic ball bearings were used as markers in the beam: two of them fixed to the gantry head and the third positioned at the isocenter. EPIDimages were acquired during a 360° gantry rotation in cine imaging mode. The markers were tracked in EPIDimages and a robust in-house developedMATLAB code was used to analyse the images and find the EPID sag in three directions as well as the EPID + gantry sag by comparison to the reference gantry zero image. The algorithm results were then tested against independent methods. The method was applied to compare the effect in clockwise and counter clockwise gantry rotations and different source-to-detector distances (SDDs). The results were monitored for one linear accelerator over a course of 15 months and six other linear-accelerators from two treatment centers were also investigated using this method. The generalized shift patterns were derived from the data and used in an image registration algorithm to correct for the effect of the mechanical sag in the system. The Gamma evaluation (3%, 3 mm) technique was used to investigate the improvement in alignment of cine EPIDimages of a fixed field, by comparing both individual images and the sum of images in a series with the reference gantry zero image. Results: The mechanical sag during gantry rotation was dependent on the gantry angle and was larger in the in-plane direction, although the patterns were not identical for various linear-accelerators. The reproducibility of measurements was within 0.2 mm over a period of 15 months. The direction of gantry rotation and SDD did not affect the results by more than 0.3 mm. Results of independent tests agreed with the algorithm within the accuracy of the measurement tools. When comparing summed images, the percentage of points with Gamma index <1 increased from 85.4% to 94.1% after correcting for the EPID sag, and to 99.3% after correction for gantry + EPID sag. Conclusions: The measurement method and algorithms introduced in this study use cine-images, are highly accurate, simple, fast, and reproducible. It tests all gantry angles and provides a suitable automatic analysis and correction tool to improve EPIDdosimetry and perform comprehensive linac QA for arc treatments

Quality assurance of Cyberknife robotic stereotactic radiosurgery using an angularly independent silicon detector

Purpose: The aim of this work was to evaluate the use of an angularly independent silicon detector (edgeless diodes) developed for dosimetry in megavoltage radiotherapy for Cyberknife in a phantom and for patient quality assurance (QA). Method: The characterization of the edgeless diodes has been performed on Cyberknife with fixed and IRIS collimators. The edgeless diode probes were tested in terms of basic QA parameters such as measurements of tissue-phantom ratio (TPR), output factor and off-axis ratio. The measurements were performed in both water and water-equivalent phantoms. In addition, three patient-specific plans have been delivered to a lung phantom with and without motion and dose measurements have been performed to verify the ability of the diodes to work as patient-specific QA devices. The data obtained by the edgeless diodes have been compared to PTW 60016, SN edge, PinPoint ionization chamber, Gafchromic EBT3 film, and treatment planning system (TPS). Results: The TPR measurement performed by the edgeless diodes show agreement within 2.2% with data obtained with PTW 60016 diode for all the field sizes. Output factor agrees within 2.6% with that measured by SN EDGE diodes corrected for their field size dependence. The beam profiles\u27 measurements of edgeless diodes match SN EDGE diodes with a measured full width half maximum (FWHM) within 2.3% and penumbra widths within 0.148 mm. Patient-specific QA measurements demonstrate an agreement within 4.72% in comparison with TPS. Conclusion: The edgeless diodes have been proved to be an excellent candidate for machine and patient QA for Cyberknife reproducing commercial dosimetry device measurements without need of angular dependence corrections. However, further investigation is required to evaluate the effect of their dose rate dependence on complex brain cancer dose verification

Evaluation of argon plasma coagulation in healing of a solitary rectal ulcer in comparison with conventional therapy: a randomised controlled trial

Introduction: Argon plasma coagulation (APC) has been reported to be effective in the treatment of solitary rectal ulcer syndrome (SRUS). However, it has not appeared to be effective in healing ulcers. Aim : This study aimed at assessing the effectiveness of APC in controlling rectal ulcer-induced bleeding, and at examining the ultimate effect of this approach in healing these lesions. Material and methods : This randomised, controlled trial was conducted on 99 patients with SRUS. Patients were randomly enrolled into two groups of APC therapy (intervention) and conventional therapy (control). The control group (n = 58) received a high-fibre diet, laxatives, behaviour therapy, and sucralfate enemas, and the intervention group (n = 41) were treated with APC plus conventional therapy; in fact they received directed and focused argon gas in addition to a high-fibre diet and laxatives. Results: Responses to treatment in the control group and in the APC-receiving group were 29.3% and 75.6%, respectively. The continuation of ulcer healing after 3 months in the control group was 10.3%, and it was 70.7% in the APC-treated group. There was a significant statistical difference between the two groups (p < 0.004), i.e. bleeding was controlled more frequently in the group receiving APC plus conventional therapies than in the group receiving only the conventional therapies. However, the results showed no statistically significant difference between the two groups in terms of pain relief (p < 0.36). Conclusions : Argon plasma coagulation not only controlled bleeding in patients with SRUS, but also, in comparison with the conventional methods of treating SRUS, led to healing and continuation of healing of rectal ulcers