Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015 : a systematic analysis for the Global Burden of Disease Study 2015

Background Improving survival and extending the longevity of life for all populations requires timely, robust evidence on local mortality levels and trends. The Global Burden of Disease 2015 Study (GBD 2015) provides a comprehensive assessment of all-cause and cause-specific mortality for 249 causes in 195 countries and territories from 1980 to 2015. These results informed an in-depth investigation of observed and expected mortality patterns based on sociodemographic measures. Methods We estimated all-cause mortality by age, sex, geography, and year using an improved analytical approach originally developed for GBD 2013 and GBD 2010. Improvements included refinements to the estimation of child and adult mortality and corresponding uncertainty, parameter selection for under-5 mortality synthesis by spatiotemporal Gaussian process regression, and sibling history data processing. We also expanded the database of vital registration, survey, and census data to 14 294 geography-year datapoints. For GBD 2015, eight causes, including Ebola virus disease, were added to the previous GBD cause list for mortality. We used six modelling approaches to assess cause-specific mortality, with the Cause of Death Ensemble Model (CODEm) generating estimates for most causes. We used a series of novel analyses to systematically quantify the drivers of trends in mortality across geographies. First, we assessed observed and expected levels and trends of cause-specific mortality as they relate to the Socio-demographic Index (SDI), a summary indicator derived from measures of income per capita, educational attainment, and fertility. Second, we examined factors affecting total mortality patterns through a series of counterfactual scenarios, testing the magnitude by which population growth, population age structures, and epidemiological changes contributed to shifts in mortality. Finally, we attributed changes in life expectancy to changes in cause of death. We documented each step of the GBD 2015 estimation processes, as well as data sources, in accordance with Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER). Findings Globally, life expectancy from birth increased from 61.7 years (95% uncertainty interval 61.4-61.9) in 1980 to 71.8 years (71.5-72.2) in 2015. Several countries in sub-Saharan Africa had very large gains in life expectancy from 2005 to 2015, rebounding from an era of exceedingly high loss of life due to HIV/AIDS. At the same time, many geographies saw life expectancy stagnate or decline, particularly for men and in countries with rising mortality from war or interpersonal violence. From 2005 to 2015, male life expectancy in Syria dropped by 11.3 years (3.7-17.4), to 62.6 years (56.5-70.2). Total deaths increased by 4.1% (2.6-5.6) from 2005 to 2015, rising to 55.8 million (54.9 million to 56.6 million) in 2015, but age-standardised death rates fell by 17.0% (15.8-18.1) during this time, underscoring changes in population growth and shifts in global age structures. The result was similar for non-communicable diseases (NCDs), with total deaths from these causes increasing by 14.1% (12.6-16.0) to 39.8 million (39.2 million to 40.5 million) in 2015, whereas age-standardised rates decreased by 13.1% (11.9-14.3). Globally, this mortality pattern emerged for several NCDs, including several types of cancer, ischaemic heart disease, cirrhosis, and Alzheimer's disease and other dementias. By contrast, both total deaths and age-standardised death rates due to communicable, maternal, neonatal, and nutritional conditions significantly declined from 2005 to 2015, gains largely attributable to decreases in mortality rates due to HIV/AIDS (42.1%, 39.1-44.6), malaria (43.1%, 34.7-51.8), neonatal preterm birth complications (29.8%, 24.8-34.9), and maternal disorders (29.1%, 19.3-37.1). Progress was slower for several causes, such as lower respiratory infections and nutritional deficiencies, whereas deaths increased for others, including dengue and drug use disorders. Age-standardised death rates due to injuries significantly declined from 2005 to 2015, yet interpersonal violence and war claimed increasingly more lives in some regions, particularly in the Middle East. In 2015, rotaviral enteritis (rotavirus) was the leading cause of under-5 deaths due to diarrhoea (146 000 deaths, 118 000-183 000) and pneumococcal pneumonia was the leading cause of under-5 deaths due to lower respiratory infections (393 000 deaths, 228 000-532 000), although pathogen-specific mortality varied by region. Globally, the effects of population growth, ageing, and changes in age-standardised death rates substantially differed by cause. Our analyses on the expected associations between cause-specific mortality and SDI show the regular shifts in cause of death composition and population age structure with rising SDI. Country patterns of premature mortality (measured as years of life lost [YLLs]) and how they differ from the level expected on the basis of SDI alone revealed distinct but highly heterogeneous patterns by region and country or territory. Ischaemic heart disease, stroke, and diabetes were among the leading causes of YLLs in most regions, but in many cases, intraregional results sharply diverged for ratios of observed and expected YLLs based on SDI. Communicable, maternal, neonatal, and nutritional diseases caused the most YLLs throughout sub-Saharan Africa, with observed YLLs far exceeding expected YLLs for countries in which malaria or HIV/AIDS remained the leading causes of early death. Interpretation At the global scale, age-specific mortality has steadily improved over the past 35 years; this pattern of general progress continued in the past decade. Progress has been faster in most countries than expected on the basis of development measured by the SDI. Against this background of progress, some countries have seen falls in life expectancy, and age-standardised death rates for some causes are increasing. Despite progress in reducing age-standardised death rates, population growth and ageing mean that the number of deaths from most non-communicable causes are increasing in most countries, putting increased demands on health systems. Copyright (C) The Author(s). Published by Elsevier Ltd.Peer reviewe

Systematic review and meta-analysis of efficacy and safety of hydroxychloroquine and chloroquine in the treatment of COVID-19

Repurposed drugs like hydroxycloroquine (HCQ) and chloroquine (CQ) are being tested for potential therapeutic role in COVID-19. We aimed to evaluate efficacy and safety of HCQ and CQ in COVID-19. Using PubMed, EMBASE, medRxiv, Google Scholar, clinicaltrials.gov, electronic search was carried out to identify relevant articles till June 2020 with re-evaluation in last week of November 2020. Observational and interventional clinical studies comparing efficacy of CQ or HCQ to standard management or other drug/s for SARS-CoV-2 infection patients were included. Cochrane review manager version 5.3 was used for synthesis of meta-analysis results. For randomized controlled trials, risk of bias was assessed using cochrane collaboration risk of bias assessment tool, version 2.0 (ROB-2). ROBINS-I was used for quality assessment of observational studies. Overall evidence quality generated by review was graded as per GRADE Recommendation. A total of 903 studies were screened. Nineteen studies were included in synthesis of meta-analysis with total of 4,693, 1,626, and 6,491 patients in HCQ/CQ, HCQ/CQ + AZ and control groups, respectively. HCQ/CQ treatment was associated with significantly increased rates of virological cure (OR = 2.08, 95%cI = 1.36–3.17; P = 0.0007) and radiological cure (OR = 3.89, 95%cI = 1.35 – 11.23; P = 0.01) compared to control. HCQ/CQ had no difference in unadjusted mortality rate (unadjusted OR = 0.98 95% cI = 0.70–1.37, P = 0.89, random effect model) and adjusted hazard ratio for mortality (adjusted HR = 1.05, 95%cI = 0.86--1.29; P = 0.64). However, a significant increase in odds of disease progression (OR = 1.77, 95%cI = 1.46–2.13; P < 0.00001) and QT prolongation (OR = 11.15, 95%cI = 3.95–31.44; P < 0.00001) was noted. The results with HCQ/CQ and azithromycin combination were similar to HCQ/CQ mono-therapy. In the light of contemporary evidence on effectiveness of HCQ/CQ, judicious and monitored use of HCQ/CQ for treatment of COVID-19 patients is recommended in low to middle income countries with emphasis on no mortality benefit. Registration number of Systematic review. Register in PROSPERO database: cRD4202018771

Neuroimaging Spectrum in COVID-19 Infection: A Single-Center Experience

Background and Purpose The ongoing coronavirus disease 2019 (COVID-19) pandemic is a multisystemic disease and involvement of the nervous system is well established. The neurological and neuroimaging features of the disease have been extensively evaluated. Our study aimed to elucidate the neuroradiological findings in COVID-19 infected patients admitted to our institute during the first and second waves of the pandemic in India. Methods This was a single-center retrospective study of all COVID-19 positive patients who underwent neuroimaging between March 2020 and May 2021. The presenting neurological complaints, the imaging findings in computed tomography (CT) imaging, and/or magnetic resonance imaging (MRI) were recorded. They recorded the findings in the subheadings of ischemic stroke, hemorrhagic stroke, parainfectious demyelination, acute encephalitis syndrome, and changes of global hypoxic changes. Patients with age-related, chronic, and incidental findings were excluded. Results The study comprised of 180 COVID-19 positive patients who underwent neuroimaging. CT scan was performed for 169 patients, MRI for 28, and a combination of both CT and MRI was performed for 17 patients. Seventy percent of patients were males, and median age was 61.5 years (interquartile range: 48.25–70.75). Out of the 180 patients, 66 patients had nonspecific findings that could not be attributed to COVID-19 infection. In the remaining 114 patients, 77 (42.7%) had ischemic findings, while 22 (12.2%) had hemorrhagic stroke. Hypoxic ischemic changes were noted in five patients. The rest of the patients had a spectrum of changes including, cerebellitis (3), tumefactive demyelination (1), COVID-19-associated encephalitis (1), hemorrhagic acute demyelinating encephalomyelitis (1), transverse myelitis (1), cytotoxic lesions of corpus callosum (1), Guillain-Barre syndrome (1), and COVID-19-associated microhemorrhages (1). Conclusion Neurological manifestations of COVID-19 infection are not uncommon, and our understanding of this topic is expanding. A complex interplay of neurotropism and direct central nervous system invasion, immune activation and cytokine storm, vasculitis, and parainfectious processes are implicated in the pathophysiology. While the most common imaging finding was ischemic stroke, followed by hemorrhagic stroke, a diverse range of parainfectious findings was also noted in our study

Practical guideline for setting up a comprehensive pediatric care unit for critical care delivery at district hospitals and medical colleges under ECRP-II

Pediatric critical care is highly sophisticated and precise and is possible only in specialized areas such as pediatric intensive care units (PICUs) or high dependency units equipped with round-the-clock monitoring facilities, skilled and trained staff, and treatment equipment. The need for critical care beds was sharply felt during the COVID-19 pandemic and the Government of India launched the COVID-19 emergency response and health system preparedness package: phase II (ECRP-II) with a hub and spoke model to strengthen pediatric critical care delivery at district level under the skilled supervision of state-level PICUs of the identified center of excellence (CoE). The CoEs will have well-equipped PICUs providing tele-ICU service, mentoring, and technical hand-holding to the district pediatric unit. This model was envisioned to be extended to critically ill children with nonCOVID illnesses after the pandemic abates. For achieving the proposed objectives under the ECRP-II scheme, this guideline aims to provide a practical framework for setting up comprehensive pediatric care units at district hospitals and medical colleges (spoke) well connected with a CoE (hub) for teleconsultation, knowledge exchange, referral, and back referral between hub and spokes

Epidemiology of Congenital Rubella Syndrome (CRS) in India, 2016-18, based on data from sentinel surveillance.

BACKGROUND:Government of India is committed to eliminate measles and control rubella/congenital rubella syndrome (CRS) by 2020. In 2016, CRS surveillance was established in five sentinel sites. We analyzed surveillance data to describe the epidemiology of CRS in India. METHODOLOGY/PRINCIPAL FINDINGS:We used case definitions adapted from the WHO-recommended standards for CRS surveillance. Suspected patients underwent complete clinical examination including cardiovascular system, ophthalmic examination and assessment for hearing impairment. Sera were tested for presence of IgM and IgG antibodies against rubella. Of the 645 suspected CRS patients enrolled during two years, 137 (21.2%) were classified as laboratory confirmed CRS and 8 (1.2%) as congenital rubella infection. The median age of laboratory confirmed CRS infants was 3 months. Common clinical features among laboratory confirmed CRS patients included structural heart defects in 108 (78.8%), one or more eye signs (cataract, glaucoma, pigmentary retinopathy) in 82 (59.9%) and hearing impairment in 51. (38.6%) Thirty-three (24.1%) laboratory confirmed CRS patients died over a period of 2 years. Surveillance met the quality indicators in terms of adequacy of investigation, adequacy of sample collection for serological diagnosis as well as virological confirmation. CONCLUSIONS/SIGNIFICANCE:About one fifth suspected CRS patients were laboratory confirmed, indicating significance of rubella as a persistent public health problem in India. Continued surveillance will generate data to monitor the progress made by the rubella control program in the country

Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980–2015: a systematic analysis for the Global Burden of Disease Study 2015

Background Improving survival and extending the longevity of life for all populations requires timely, robust evidence on local mortality levels and trends. The Global Burden of Disease 2015 Study (GBD 2015) provides a comprehensive assessment of all-cause and cause-specifi c mortality for 249 causes in 195 countries and territories from 1980 to 2015. These results informed an in-depth investigation of observed and expected mortality patterns based on sociodemographic measures. Methods We estimated all-cause mortality by age, sex, geography, and year using an improved analytical approach originally developed for GBD 2013 and GBD 2010. Improvements included refi nements to the estimation of child and adult mortality and corresponding uncertainty, parameter selection for under-5 mortality synthesis by spatiotemporal Gaussian process regression, and sibling history data processing. We also expanded the database of vital registration, survey, and census data to 14 294 geography–year datapoints. For GBD 2015, eight causes, including Ebola virus disease, were added to the previous GBD cause list for mortality. We used six modelling approaches to assess causespecific mortality, with the Cause of Death Ensemble Model (CODEm) generating estimates for most causes. We used a series of novel analyses to systematically quantify the drivers of trends in mortality across geographies. First, we assessed observed and expected levels and trends of cause-specifi c mortality as they relate to the Socio-demographic Index (SDI), a summary indicator derived from measures of income per capita, educational attainment, and fertility. Second, we examined factors aff ecting total mortality patterns through a series of counterfactual scenarios, testing the magnitude by which population growth, population age structures, and epidemiological changes contributed to shifts in mortality. Finally, we attributed changes in life expectancy to changes in cause of death. We documented each step of the GBD 2015 estimation processes, as well as data sources, in accordance with Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER). Findings Globally, life expectancy from birth increased from 61·7 years (95% uncertainty interval 61·4–61·9) in 1980 to 71·8 years (71·5–72·2) in 2015. Several countries in sub-Saharan Africa had very large gains in life expectancy from 2005 to 2015, rebounding from an era of exceedingly high loss of life due to HIV/AIDS. At the same time, many geographies saw life expectancy stagnate or decline, particularly for men and in countries with rising mortality from war or interpersonal violence. From 2005 to 2015, male life expectancy in Syria dropped by 11·3 years (3·7–17·4), to 62·6 years (56·5–70·2). Total deaths increased by 4·1% (2·6–5·6) from 2005 to 2015, rising to 55·8 million (54·9 million to 56·6 million) in 2015, but age-standardised death rates fell by 17·0% (15·8–18·1) during this time, underscoring changes in population growth and shifts in global age structures. The result was similar for noncommunicable diseases (NCDs), with total deaths from these causes increasing by 14·1% (12·6–16·0) to 39·8 million (39·2 million to 40·5 million) in 2015, whereas age-standardised rates decreased by 13·1% (11·9–14·3). Globally, this mortality pattern emerged for several NCDs, including several types of cancer, ischaemic heart disease, cirrhosis, and Alzheimer’s disease and other dementias. By contrast, both total deaths and age-standardised death rates due to communicable, maternal, neonatal, and nutritional conditions signifi cantly declined from 2005 to 2015, gains largely attributable to decreases in mortality rates due to HIV/AIDS (42·1%, 39·1–44·6), malaria (43·1%, 34·7–51·8), neonatal preterm birth complications (29·8%, 24·8–34·9), and maternal disorders (29·1%, 19·3–37·1). Progress was slower for several causes, such as lower respiratory infections and nutritional defi ciencies, whereas deaths increased for others, including dengue and drug use disorders. Age-standardised death rates due to injuries significantly declined from 2005 to 2015, yet interpersonal violence and war claimed increasingly more lives in some regions, particularly in the Middle East. In 2015, rotaviral enteritis (rotavirus) was the leading cause of under-5 deaths due to diarrhoea (146 000 deaths, 118 000–183 000) and pneumococcal pneumonia was the leading cause of under-5 deaths due to lower respiratory infections (393 000 deaths, 228 000–532 000), although pathogen-specifi c mortality varied by region. Globally, the eff ects of population growth, ageing, and changes in age-standardised death rates substantially diff ered by cause. Our analyses on the expected associations between cause-specifi c mortality and SDI show the regular shifts in cause of death composition and population age structure with rising SDI. Country patterns of premature mortality (measured as years of life lost [YLLs]) and how they diff er from the level expected on the basis of SDI alone revealed distinct but highly heterogeneous patterns by region and country or territory. Ischaemic heart disease, stroke, and diabetes were among the leading causes of YLLs in most regions, but in many cases, intraregional results sharply diverged for ratios of observed and expected YLLs based on SDI. Communicable, maternal, neonatal, and nutritional diseases caused the most YLLs throughout sub-Saharan Africa, with observed YLLs far exceeding expected YLLs for countries in which malaria or HIV/AIDS remained the leading causes of early death. Interpretation At the global scale, age-specifi c mortality has steadily improved over the past 35 years; this pattern of general progress continued in the past decade. Progress has been faster in most countries than expected on the basis of development measured by the SDI. Against this background of progress, some countries have seen falls in life expectancy, and age-standardised death rates for some causes are increasing. Despite progress in reducing agestandardised death rates, population growth and ageing mean that the number of deaths from most noncommunicable causes are increasing in most countries, putting increased demands on health systems