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

PER, CTX-M, TEM and SHV Beta-lactamases in Clinical Isolates of Klebsiella pneumoniae Isolated from Tehran, Iran

Objective(s)Different types of extended spectrum beta-lactamases (ESBLs) are encountered in the clinical settings worldwide. There are a few studies regarding the prevalence of ESBL genes among Klebsiella pneumoniae isolates at Tehran especially those of blaPER and blaCTX. The aim of this study was to determine the prevalence of blaSHV, blaTEM ,blaPER and blaCTX genes among clinical K. pneumoniae of different hospitals in Tehran.Materials and MethodsTwo hundred isolates of K. pneumoniae were received from different clinical specimens. The susceptibility of the isolates to 10 different antibiotics was examined by disk diffusion test. The MICs for ceftazidime were also determined using micro-broth dilution assay. Isolates showing MIC 4 μg/ml for ceftazidime were screened for ESBL production by phenotypic confirmatory test (PCT) and subjected to PCR for studied genes. Variation among four amplified genes was evaluated using PCR-RFLP.ResultsBy disk diffusion test, resistance to ceftazidime and cefotaxime were 34.7% and 33.5% respectively. However, all strains were susceptible to imipenem. Eighty isolates showed MICs≥ 4 μg/ml for ceftazidime of which 77 (96%) were positive for ESBL in PCT. The prevalence of blaSHV, blaCTX-M, blaTEM and blaPER among these isolates were 26%, 24.5%, 18% and 7.5%, respectively. No variation was detected in the genes by PCR-RFLP.ConclusionAs far as we know this is the first report of the blaPER-1 in K. pneumoniae in Iran. The blaCTX-M was the second most common gene detected among the ESBL positive isolates of K. pneumoniae. For rapid identification of ESBL producing isolates it was recommended that clinical laboratories adopt simple test based on CLSI recommendation for confirming ESBL production in enterobacterial species

A conceptual model for empowering faculty members of third-generation universities of medical sciences

الملخص: أهداف البحث: يجب أن تكون جامعات الجيل الثالث قادرة على أن تكون مستقلة وأن تعد طلابها لتلبية احتياجات المجتمع ودخول سوق العمل. في الواقع، الأداء المتوقع منهم هو تطبيق البحث في المجتمع. على الرغم من الدور الحاسم للموظفين وخاصة أعضاء هيئة التدريس في التحرك نحو جامعات الجيل الثالث، فضلا عن ضرورة تمكين الموظفين، إلا أنه تم إجراء عدد قليل من الدراسات حول تمكين أعضاء هيئة التدريس (أعضاء هيئة التدريس). هدفت هذه الدراسة إلى تصميم نموذج تصوري لتمكين أعضاء هيئة التدريس في جامعات العلوم الطبية وتسهيل الانتقال إلى جامعات الجيل الثالث. طرق البحث: تم اعتماد منهج النظرية المتجذرة لإجراء هذه الدراسة النوعية. تم اختيار ما مجموعه 11 من أعضاء هيئة التدريس من ذوي الخبرة في ريادة الأعمال كعينة باستخدام أخذ العينات الهادف. تم جمع البيانات باستخدام المقابلات شبه المنظمة، وتم إدخال البيانات التي تم الحصول عليها في برنامج حاسوبي مصمم للبيانات النوعية والمختلطة بمساعدة الكمبيوتر. النتائج: تم تلخيص المفاهيم المحددة في عملية الترميز وتصنيفها إلى خمس مجموعات وسبع فئات رئيسية. تم تصميم النموذج التصوري بعد ذلك بمجموعة من العوامل السببية (بما في ذلك هيكل نظام التعليم، والتوظيف، والتدريب، والاستثمار)، وعوامل الهيكل والسياق (بما في ذلك الهيكل والعلاقة)، والعوامل المتداخلة (بما في ذلك أنظمة الترقية والترتيب في الجامعات ونقص من الثقة المتبادلة بين الصناعة والجامعة)، فئة أساسية (خصائص أعضاء هيئة التدريس الأكفاء)، والنتيجة (جامعة الجيل الثالث). أخيرا، تم تطوير النموذج التصوري لتمكين أعضاء هيئة التدريس في جامعات الجيل الثالث من العلوم الطبية. الاستنتاجات: بناء على النموذج التصوري المصمم، فإن أهم قضية في التوجه نحو جامعات الجيل الثالث هي ''خصائص أعضاء هيئة التدريس القادرين''. تساعد النتائج الحالية صانعي السياسات على فهم العوامل الرئيسية التي تؤثر على تمكين أعضاء هيئة التدريس بشكل أفضل. Abstract: Background and objectives: Despite the crucial role of university staff and especially faculty members in moving towards third-generation universities, as well as the necessity of staff empowerment, only a handful of studies have been carried out on staff (especially faculty member) empowerment. This study designed a conceptual model for empowering faculty members of universities of medical sciences and facilitating transition to third-generation universities. Methods: The grounded theory approach was adopted to conduct this qualitative study. A total of 11 faculty members with entrepreneurial experience were selected as the sample using purposive sampling. The data were collected using semi-structured interviews, and the obtained data were entered into qualitative software (MAXQDA 10) for analysis. Results: The concepts identified in the coding process were summarized and classified into five groups and seven main categories. Then the conceptual model was designed with a set of causal factors (including structure of the education system, recruitment, training, and investment), structure and context factors (including structure and relationship), intervening factors (including promotion and ranking systems in universities and lack of mutual trust between industry and university), a core category (characteristics of capable faculty members), and an outcome (third-generation university). Finally, the conceptual model was developed to empower faculty members of third-generation universities of medical sciences. Conclusions: Based on the designed conceptual model, the most important issue in moving towards third-generation universities is “characteristics of capable faculty members.” The present findings will help policy makers better understand the major factors affecting faculty member empowerment

Chemoradiation therapy of 4T1 cancer cells with methotrexate conjugated platinum nanoparticles under X-Ray irradiation

© 2023 Elsevier B.V.Bovine serum albumin (BSA) coated platinum (Pt) nanoparticles (Pt@BSA NPs) were synthesized, followed by the conjugation of an anticancer drug (MTX) with the aim of chemoradiation therapy. The physical and chemical properties of Pt@BSA-MTX were evaluated by DLS, FESEM, STEM, UV–Vis and XRD. A release study was performed in the presence and absence of the proteinase K enzyme. In terms of morphology, nanoparticles appeared to be monodispersed and spherical. The size of nanoparticles was 7.4 ± 1.4 nm. Release behavior of Pt@BSA-MTX depended significantly on enzyme presence which accelerated and promoted the release of MTX. The improved chemoradiation was demonstrated in vitro using MTT, colony formation and apoptosis assays on mouse breast carcinoma cells (4T1). It was concluded that the combination of a nanoradiosensitizer with a chemotherapeutic agent resulted in superior anticancer activity after X-ray exposure

Targeted CuFe2O4 hybrid nanoradiosensitizers for synchronous chemoradiotherapy

© 2022 Elsevier B.V.Multifunctional nanoplatforms based on novel bimetallic nanoparticles have emerged as effective radiosensitizers owing to their potential capability in cancer cells radiosensitization. Implementation of chemotherapy along with radiotherapy, known as synchronous chemoradiotherapy, can augment the treatment efficacy. Herein, a tumor targeted nanoradiosensitizer with synchronous chemoradiotion properties, termed as CuFe2O4@BSA-FA-CUR, loaded with curcumin (CUR) and modified by bovine serum albumin (BSA) and folic acid (FA) was developed to enhance tumor accumulation and promote the anti-cancer activity while attenuating adverse effects. Both copper (Cu) and iron (Fe) were utilized in the construction of these submicron scale entities, therefore strong radiosensitization effect is anticipated by implementation of these two metals. The structure–function relationships between constituents of nanomaterials and their function led to the development of nanoscale materials with great radiosensitizing capacity and biosafety. BSA was used to anchor Fe and Cu ions but also to improve colloidal stability, blood circulation time, biocompatibility, and further functionalization. Moreover, to specifically target tumor sites and enhance cellular uptake, FA was conjugated onto the surface of hybrid bimetallic nanoparticles. Finally, CUR as a natural chemotherapeutic agent was encapsulated into the developed bimetallic nanoparticles. With incorporation of all abovementioned stages into one multifunctional nanoplatform, CuFe2O4@BSA-FA-CUR is produced for synergistic chemoradiotherapy with positive outcomes. In vitro investigation revealed that these nanoplatforms bear excellent biosafety, great tumor cell killing ability and radiosensitizing capacity. In addition, high cancer-suppression efficiency was observed through in vivo studies. It is worth mentioning that co-use of CuFe2O4@BSA-FA-CUR nanoplatforms and X-ray radiation led to complete tumor ablation in almost all of the treated mice. No mortality or radiation-induced normal tissue toxicity were observed following administration of CuFe2O4@BSA-FA-CUR nanoparticles which highlights the biosafety of these submicron scale entities. These results offer powerful evidence for the potential capability of CuFe2O4@BSA-FA-CUR in radiosensitization of malignant tumors and opens up a new avenue of research in this area

β-radiating radionuclides in cancer treatment, novel insight into promising approach.

Targeted radionuclide therapy, known as molecular radiotherapy is a novel therapeutic module in cancer medicine. β-radiating radionuclides have definite impact on target cells via interference in cell cycle and particular signalings that can lead to tumor regression with minimal off-target effects on the surrounding tissues. Radionuclides play a remarkable role not only in apoptosis induction and cell cycle arrest, but also in the amelioration of other characteristics of cancer cells. Recently, application of novel β-radiating radionuclides in cancer therapy has been emerged as a promising therapeutic modality. Several investigations are ongoing to understand the underlying molecular mechanisms of β-radiating elements in cancer medicine. Based on the radiation dose, exposure time and type of the β-radiating element, different results could be achieved in cancer cells. It has been shown that β-radiating radioisotopes block cancer cell proliferation by inducing apoptosis and cell cycle arrest. However, physical characteristics of the β-radiating element (half-life, tissue penetration range, and maximum energy) and treatment protocol determine whether tumor cells undergo cell cycle arrest, apoptosis or both and to which extent. In this review, we highlighted novel therapeutic effects of β-radiating radionuclides on cancer cells, particularly apoptosis induction and cell cycle arrest

Magnetite and bismuth sulfide Janus heterostructures as radiosensitizers for in vivo enhanced radiotherapy in breast cancer

Janus heterostructures based on bimetallic nanoparticles have emerged as effective radiosensitizers owing to their radiosensitization capabilities in cancer cells. In this context, this study aims at developing a novel bime-tallic nanoradiosensitizer, Bi2S3-Fe3O4, to enhance tumor accumulation and promote radiation-induced DNA damage while reducing adverse effects. Due to the presence of both iron oxide and bismuth sulfide metallic nanoparticles in these newly developed nanoparticle, strong radiosensitizing capacity is anticipated through the generation of reactive oxygen species (ROS) to induce DNA damage under X-Ray irradiation. To improve blood circulation time, biocompatibility, colloidal stability, and tuning surface functionalization, the surface of Bi2S3-Fe3O4 bimetallic nanoparticles was coated with bovine serum albumin (BSA). Moreover, to achieve higher cellular uptake and efficient tumor site specificity, folic acid (FA) as a targeting moiety was conjugated onto the bimetallic nanoparticles, termed Bi2S3@BSA-Fe3O4-FA. Biocompatibility, safety, radiation-induced DNA damage by ROS activation and generation, and radiosensitizing ability were confirmed via in vitro and in vivo assays. The administration of Bi2S3@BSA-Fe3O4-FA in 4T1 breast cancer murine model upon X-ray radiation revealed highly effective tumor eradication without causing any mortality or severe toxicity in healthy tissues. These findings offer compelling evidence for the potential capability of Bi2S3@BSA-Fe3O4-FA as an ideal nanoparticle for radiation-induced cancer therapy and open interesting avenues of future research in this area