Vitamin D modulates systemic inflammation in patients with severe COVID-19

Aims The ability of vitamin D (VitD) to modulate immune responses in the clinical setting of COVID-19 infection is not well investigated. This study aimed to evaluate the ability of VitD to attenuate inflammatory responses in patients with severe COVID-19. Materials and methods Blood samples and nasopharyngeal swabs were obtained from patients with severe COVID-19 who had been treated (20 patients), or not (25 patients), with VitD, during their stay in the intensive care unit. Western blotting was used to evaluate the expressions of STAT3, JNK and AKT signaling pathways and ELISA was used to measure levels of IL-6, IL-17, and IL-1β in blood of these patients. Key findings Reduced levels of STAT3, JNK and AKT pathways and lower levels of proinflammatory cytokines such as IL-6, IL-17, and IL-1β were observed in VitD treated patients (50,000 IU of cholecalciferol weekly for 3 weeks), and in vitro following treatment of poly I:C stimulated PBMCs with VitD (50 nM of calcitriol). Moreover, lower circulatory levels of these proinflammatory cytokines following treatment with VitD were associated with lower serum levels of COVID-19-related severity markers such as D-dimer and C-reactive proteins (

Public health utility of cause of death data : applying empirical algorithms to improve data quality

Background: Accurate, comprehensive, cause-specific mortality estimates are crucial for informing public health decision making worldwide. Incorrectly or vaguely assigned deaths, defined as garbage-coded deaths, mask the true cause distribution. The Global Burden of Disease (GBD) study has developed methods to create comparable, timely, cause-specific mortality estimates; an impactful data processing method is the reallocation of garbage-coded deaths to a plausible underlying cause of death. We identify the pattern of garbage-coded deaths in the world and present the methods used to determine their redistribution to generate more plausible cause of death assignments. Methods: We describe the methods developed for the GBD 2019 study and subsequent iterations to redistribute garbage-coded deaths in vital registration data to plausible underlying causes. These methods include analysis of multiple cause data, negative correlation, impairment, and proportional redistribution. We classify garbage codes into classes according to the level of specificity of the reported cause of death (CoD) and capture trends in the global pattern of proportion of garbage-coded deaths, disaggregated by these classes, and the relationship between this proportion and the Socio-Demographic Index. We examine the relative importance of the top four garbage codes by age and sex and demonstrate the impact of redistribution on the annual GBD CoD rankings. Results: The proportion of least-specific (class 1 and 2) garbage-coded deaths ranged from 3.7% of all vital registration deaths to 67.3% in 2015, and the age-standardized proportion had an overall negative association with the Socio Demographic Index. When broken down by age and sex, the category for unspecified lower respiratory infections was responsible for nearly 30% of garbage-coded deaths in those under 1 year of age for both sexes, representing the largest proportion of garbage codes for that age group. We show how the cause distribution by number of deaths changes before and after redistribution for four countries: Brazil, the United States, Japan, and France, highlighting the necessity of accounting for garbage-coded deaths in the GBD

Neonatal, infant, and under-5 mortality and morbidity burden in the Eastern Mediterranean region: findings from the Global Burden of Disease 2015 study

Objectives Although substantial reductions in under-5 mortality have been observed during the past 35 years, progress in the Eastern Mediterranean Region (EMR) has been uneven. This paper provides an overview of child mortality and morbidity in the EMR based on the Global Burden of Disease (GBD) study. Methods We used GBD 2015 study results to explore under-5 mortality and morbidity in EMR countries. Results In 2015, 755,844 (95% uncertainty interval (UI) 712,064–801,565) children under 5 died in the EMR. In the early neonatal category, deaths in the EMR decreased by 22.4%, compared to 42.4% globally. The rate of years of life lost per 100,000 population under 5 decreased 54.38% from 177,537 (173,812–181,463) in 1990 to 80,985 (76,308–85,876) in 2015; the rate of years lived with disability decreased by 0.57% in the EMR compared to 9.97% globally. Conclusions Our findings call for accelerated action to decrease child morbidity and mortality in the EMR. Governments and organizations should coordinate efforts to address this burden. Political commitment is needed to ensure that child health receives the resources needed to end preventable deaths

Global, regional, and national incidence of six major immune-mediated inflammatory diseases: findings from the global burden of disease study 2019

BACKGROUND: The causes for immune-mediated inflammatory diseases (IMIDs) are diverse and the incidence trends of IMIDs from specific causes are rarely studied. The study aims to investigate the pattern and trend of IMIDs from 1990 to 2019. METHODS: We collected detailed information on six major causes of IMIDs, including asthma, inflammatory bowel disease, multiple sclerosis, rheumatoid arthritis, psoriasis, and atopic dermatitis, between 1990 and 2019, derived from the Global Burden of Disease study in 2019. The average annual percent change (AAPC) in number of incidents and age standardized incidence rate (ASR) on IMIDs, by sex, age, region, and causes, were calculated to quantify the temporal trends. FINDINGS: In 2019, rheumatoid arthritis, atopic dermatitis, asthma, multiple sclerosis, psoriasis, inflammatory bowel disease accounted 1.59%, 36.17%, 54.71%, 0.09%, 6.84%, 0.60% of overall new IMIDs cases, respectively. The ASR of IMIDs showed substantial regional and global variation with the highest in High SDI region, High-income North America, and United States of America. Throughout human lifespan, the age distribution of incident cases from six IMIDs was quite different. Globally, incident cases of IMIDs increased with an AAPC of 0.68 and the ASR decreased with an AAPC of −0.34 from 1990 to 2019. The incident cases increased across six IMIDs, the ASR of rheumatoid arthritis increased (0.21, 95% CI 0.18, 0.25), while the ASR of asthma (AAPC = −0.41), inflammatory bowel disease (AAPC = −0.72), multiple sclerosis (AAPC = −0.26), psoriasis (AAPC = −0.77), and atopic dermatitis (AAPC = −0.15) decreased. The ASR of overall and six individual IMID increased with SDI at regional and global level. Countries with higher ASR in 1990 experienced a more rapid decrease in ASR. INTERPRETATION: The incidence patterns of IMIDs varied considerably across the world. Innovative prevention and integrative management strategy are urgently needed to mitigate the increasing ASR of rheumatoid arthritis and upsurging new cases of other five IMIDs, respectively. FUNDING: The Global Burden of Disease Study is funded by the Bill and Melinda Gates Foundation. The project funded by Scientific Research Fund of Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital (2022QN38)

Mapping 123 million neonatal, infant and child deaths between 2000 and 2017

Since 2000, many countries have achieved considerable success in improving child survival, but localized progress remains unclear. To inform efforts towards United Nations Sustainable Development Goal 3.2—to end preventable child deaths by 2030—we need consistently estimated data at the subnational level regarding child mortality rates and trends. Here we quantified, for the period 2000–2017, the subnational variation in mortality rates and number of deaths of neonates, infants and children under 5 years of age within 99 low- and middle-income countries using a geostatistical survival model. We estimated that 32% of children under 5 in these countries lived in districts that had attained rates of 25 or fewer child deaths per 1,000 live births by 2017, and that 58% of child deaths between 2000 and 2017 in these countries could have been averted in the absence of geographical inequality. This study enables the identification of high-mortality clusters, patterns of progress and geographical inequalities to inform appropriate investments and implementations that will help to improve the health of all populations

Trends in HIV/AIDS morbidity and mortality in Eastern 3 Mediterranean countries, 1990–2015: findings from the Global 4 Burden of Disease 2015 study

Objectives We used the results of the Global Burden of Disease 2015 study to estimate trends of HIV/AIDS burden in Eastern Mediterranean Region (EMR) countries between 1990 and 2015. Methods Tailored estimation methods were used to produce final estimates of mortality. Years of life lost (YLLs) were calculated by multiplying the mortality rate by population by age-specific life expectancy. Years lived with disability (YLDs) were computed as the prevalence of a sequela multiplied by its disability weight. Results In 2015, the rate of HIV/AIDS deaths in the EMR was 1.8 (1.4–2.5) per 100,000 population, a 43% increase from 1990 (0.3; 0.2–0.8). Consequently, the rate of YLLs due to HIV/AIDS increased from 15.3 (7.6–36.2) per 100,000 in 1990 to 81.9 (65.3–114.4) in 2015. The rate of YLDs increased from 1.3 (0.6–3.1) in 1990 to 4.4 (2.7–6.6) in 2015. Conclusions HIV/AIDS morbidity and mortality increased in the EMR since 1990. To reverse this trend and achieve epidemic control, EMR countries should strengthen HIV surveillance,and scale up HIV antiretroviral therapy and comprehensive prevention services

Burden of cardiovascular diseases in the Eastern Mediterranean Region, 1990-2015 : findings from the Global Burden of Disease 2015 study

To report the burden of cardiovascular diseases (CVD) in the Eastern Mediterranean Region (EMR) during 1990-2015. We used the 2015 Global Burden of Disease study for estimates of mortality and disability-adjusted life years (DALYs) of different CVD in 22 countries of EMR. A total of 1.4 million CVD deaths (95% UI: 1.3-1.5) occurred in 2015 in the EMR, with the highest number of deaths in Pakistan (465,116) and the lowest number of deaths in Qatar (723). The age-standardized DALY rate per 100,000 decreased from 10,080 in 1990 to 8606 in 2015 (14.6% decrease). Afghanistan had the highest age-standardized DALY rate of CVD in both 1990 and 2015. Kuwait and Qatar had the lowest age-standardized DALY rates of CVD in 1990 and 2015, respectively. High blood pressure, high total cholesterol, and high body mass index were the leading risk factors for CVD. The age-standardized DALY rates in the EMR are considerably higher than the global average. These findings call for a comprehensive approach to prevent and control the burden of CVD in the region.Peer reviewe

Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-Adjusted life-years for 29 cancer groups, 1990 to 2017 : A systematic analysis for the global burden of disease study

Importance: Cancer and other noncommunicable diseases (NCDs) are now widely recognized as a threat to global development. The latest United Nations high-level meeting on NCDs reaffirmed this observation and also highlighted the slow progress in meeting the 2011 Political Declaration on the Prevention and Control of Noncommunicable Diseases and the third Sustainable Development Goal. Lack of situational analyses, priority setting, and budgeting have been identified as major obstacles in achieving these goals. All of these have in common that they require information on the local cancer epidemiology. The Global Burden of Disease (GBD) study is uniquely poised to provide these crucial data. Objective: To describe cancer burden for 29 cancer groups in 195 countries from 1990 through 2017 to provide data needed for cancer control planning. Evidence Review: We used the GBD study estimation methods to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-Adjusted life-years (DALYs). Results are presented at the national level as well as by Socio-demographic Index (SDI), a composite indicator of income, educational attainment, and total fertility rate. We also analyzed the influence of the epidemiological vs the demographic transition on cancer incidence. Findings: In 2017, there were 24.5 million incident cancer cases worldwide (16.8 million without nonmelanoma skin cancer [NMSC]) and 9.6 million cancer deaths. The majority of cancer DALYs came from years of life lost (97%), and only 3% came from years lived with disability. The odds of developing cancer were the lowest in the low SDI quintile (1 in 7) and the highest in the high SDI quintile (1 in 2) for both sexes. In 2017, the most common incident cancers in men were NMSC (4.3 million incident cases); tracheal, bronchus, and lung (TBL) cancer (1.5 million incident cases); and prostate cancer (1.3 million incident cases). The most common causes of cancer deaths and DALYs for men were TBL cancer (1.3 million deaths and 28.4 million DALYs), liver cancer (572000 deaths and 15.2 million DALYs), and stomach cancer (542000 deaths and 12.2 million DALYs). For women in 2017, the most common incident cancers were NMSC (3.3 million incident cases), breast cancer (1.9 million incident cases), and colorectal cancer (819000 incident cases). The leading causes of cancer deaths and DALYs for women were breast cancer (601000 deaths and 17.4 million DALYs), TBL cancer (596000 deaths and 12.6 million DALYs), and colorectal cancer (414000 deaths and 8.3 million DALYs). Conclusions and Relevance: The national epidemiological profiles of cancer burden in the GBD study show large heterogeneities, which are a reflection of different exposures to risk factors, economic settings, lifestyles, and access to care and screening. The GBD study can be used by policy makers and other stakeholders to develop and improve national and local cancer control in order to achieve the global targets and improve equity in cancer care. © 2019 American Medical Association. All rights reserved.Peer reviewe

Transport injuries and deaths in the Eastern Mediterranean Region : findings from the Global Burden of Disease 2015 Study

Transport injuries (TI) are ranked as one of the leading causes of death, disability, and property loss worldwide. This paper provides an overview of the burden of TI in the Eastern Mediterranean Region (EMR) by age and sex from 1990 to 2015. Transport injuries mortality in the EMR was estimated using the Global Burden of Disease mortality database, with corrections for ill-defined causes of death, using the cause of death ensemble modeling tool. Morbidity estimation was based on inpatient and outpatient datasets, 26 cause-of-injury and 47 nature-of-injury categories. In 2015, 152,855 (95% uncertainty interval: 137,900-168,100) people died from TI in the EMR countries. Between 1990 and 2015, the years of life lost (YLL) rate per 100,000 due to TI decreased by 15.5%, while the years lived with disability (YLD) rate decreased by 10%, and the age-standardized disability-adjusted life years (DALYs) rate decreased by 16%. Although the burden of TI mortality and morbidity decreased over the last two decades, there is still a considerable burden that needs to be addressed by increasing awareness, enforcing laws, and improving road conditions.Peer reviewe

Measuring routine childhood vaccination coverage in 204 countries and territories, 1980-2019 : a systematic analysis for the Global Burden of Disease Study 2020, Release 1

Background Measuring routine childhood vaccination is crucial to inform global vaccine policies and programme implementation, and to track progress towards targets set by the Global Vaccine Action Plan (GVAP) and Immunization Agenda 2030. Robust estimates of routine vaccine coverage are needed to identify past successes and persistent vulnerabilities. Drawing from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2020, Release 1, we did a systematic analysis of global, regional, and national vaccine coverage trends using a statistical framework, by vaccine and over time. Methods For this analysis we collated 55 326 country-specific, cohort-specific, year-specific, vaccine-specific, and dosespecific observations of routine childhood vaccination coverage between 1980 and 2019. Using spatiotemporal Gaussian process regression, we produced location-specific and year-specific estimates of 11 routine childhood vaccine coverage indicators for 204 countries and territories from 1980 to 2019, adjusting for biases in countryreported data and reflecting reported stockouts and supply disruptions. We analysed global and regional trends in coverage and numbers of zero-dose children (defined as those who never received a diphtheria-tetanus-pertussis [DTP] vaccine dose), progress towards GVAP targets, and the relationship between vaccine coverage and sociodemographic development. Findings By 2019, global coverage of third-dose DTP (DTP3; 81.6% [95% uncertainty interval 80.4-82 .7]) more than doubled from levels estimated in 1980 (39.9% [37.5-42.1]), as did global coverage of the first-dose measles-containing vaccine (MCV1; from 38.5% [35.4-41.3] in 1980 to 83.6% [82.3-84.8] in 2019). Third- dose polio vaccine (Pol3) coverage also increased, from 42.6% (41.4-44.1) in 1980 to 79.8% (78.4-81.1) in 2019, and global coverage of newer vaccines increased rapidly between 2000 and 2019. The global number of zero-dose children fell by nearly 75% between 1980 and 2019, from 56.8 million (52.6-60. 9) to 14.5 million (13.4-15.9). However, over the past decade, global vaccine coverage broadly plateaued; 94 countries and territories recorded decreasing DTP3 coverage since 2010. Only 11 countries and territories were estimated to have reached the national GVAP target of at least 90% coverage for all assessed vaccines in 2019. Interpretation After achieving large gains in childhood vaccine coverage worldwide, in much of the world this progress was stalled or reversed from 2010 to 2019. These findings underscore the importance of revisiting routine immunisation strategies and programmatic approaches, recentring service delivery around equity and underserved populations. Strengthening vaccine data and monitoring systems is crucial to these pursuits, now and through to 2030, to ensure that all children have access to, and can benefit from, lifesaving vaccines. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.Peer reviewe