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SummaryBackground18% of the world's population lives in India, and many states of India have populations similar to those of large countries. Action to effectively improve population health in India requires availability of reliable and comprehensive state-level estimates of disease burden and risk factors over time. Such comprehensive estimates have not been available so far for all major diseases and risk factors. Thus, we aimed to estimate the disease burden and risk factors in every state of India as part of the Global Burden of Disease (GBD) Study 2016.MethodsUsing all available data sources, the India State-level Disease Burden Initiative estimated burden (metrics were deaths, disability-adjusted life-years [DALYs], prevalence, incidence, and life expectancy) from 333 disease conditions and injuries and 84 risk factors for each state of India from 1990 to 2016 as part of GBD 2016. We divided the states of India into four epidemiological transition level (ETL) groups on the basis of the ratio of DALYs from communicable, maternal, neonatal, and nutritional diseases (CMNNDs) to those from non-communicable diseases (NCDs) and injuries combined in 2016. We assessed variations in the burden of diseases and risk factors between ETL state groups and between states to inform a more specific health-system response in the states and for India as a whole.FindingsDALYs due to NCDs and injuries exceeded those due to CMNNDs in 2003 for India, but this transition had a range of 24 years for the four ETL state groups. The age-standardised DALY rate dropped by 36·2% in India from 1990 to 2016. The numbers of DALYs and DALY rates dropped substantially for most CMNNDs between 1990 and 2016 across all ETL groups, but rates of reduction for CMNNDs were slowest in the low ETL state group. By contrast, numbers of DALYs increased substantially for NCDs in all ETL state groups, and increased significantly for injuries in all ETL state groups except the highest. The all-age prevalence of most leading NCDs increased substantially in India from 1990 to 2016, and a modest decrease was recorded in the age-standardised NCD DALY rates. The major risk factors for NCDs, including high systolic blood pressure, high fasting plasma glucose, high total cholesterol, and high body-mass index, increased from 1990 to 2016, with generally higher levels in higher ETL states; ambient air pollution also increased and was highest in the low ETL group. The incidence rate of the leading causes of injuries also increased from 1990 to 2016. The five leading individual causes of DALYs in India in 2016 were ischaemic heart disease, chronic obstructive pulmonary disease, diarrhoeal diseases, lower respiratory infections, and cerebrovascular disease; and the five leading risk factors for DALYs in 2016 were child and maternal malnutrition, air pollution, dietary risks, high systolic blood pressure, and high fasting plasma glucose. Behind these broad trends many variations existed between the ETL state groups and between states within the ETL groups. Of the ten le...

Clinical decisions should be based on the totality of the best evidence and not the results of individual studies. When clinicians apply the results of a systematic review or meta-analysis to patient care, they should start by evaluating the credibility of the methods of the systematic review, ie, the extent to which these methods have likely protected against misleading results. Credibility depends on whether the review addressed a sensible clinical question; included an exhaustive literature search; demonstrated reproducibility of the selection and assessment of studies; and presented results in a useful manner. For reviews that are sufficiently credible, clinicians must decide on the degree of confidence in the estimates that the evidence warrants (quality of evidence). Confidence depends on the risk of bias in the body of evidence; the precision and consistency of the results; whether the results directly apply to the patient of interest; and the likelihood of reporting bias. Shared decision making requires understanding of the estimates of magnitude of beneficial and harmful effects, and confidence in those estimates.

Background and Purpose-Pilot studies have suggested benefit from intravenous administration of bone marrow mononuclear stem cells (BMSCs) in stroke. We explored the efficacy and safety of autologous BMSCs in subacute ischemic stroke. Methods-This was a phase II, multicenter, parallel group, randomized trial with blinded outcome assessment that included 120 patients. Patients with subacute ischemic stroke were randomly assigned to the arm that received intravenous infusion of autologous BMSCs or to control arm. Coprimary clinical efficacy outcomes were Barthel Index score and modified Rankin scale at day 180. Secondary outcomes were change in infarct volume, National

SummaryBackgroundThe burden of cardiovascular diseases is increasing in India, but a systematic understanding of its distribution and time trends across all the states is not readily available. In this report, we present a detailed analysis of how the patterns of cardiovascular diseases and major risk factors have changed across the states of India between 1990 and 2016.MethodsWe analysed the prevalence and disability-adjusted life-years (DALYs) due to cardiovascular diseases and the major component causes in the states of India from 1990 to 2016, using all accessible data sources as part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2016. We placed states into four groups based on epidemiological transition level (ETL), defined using the ratio of DALYs from communicable diseases to those from non-communicable diseases and injuries combined, with a low ratio denoting high ETL and vice versa. We assessed heterogeneity in the burden of major cardiovascular diseases across the states of India, and the contribution of risk factors to cardiovascular diseases. We calculated 95% uncertainty intervals (UIs) for the point estimates.FindingsOverall, cardiovascular diseases contributed 28·1% (95% UI 26·5–29·1) of the total deaths and 14·1% (12·9–15·3) of the total DALYs in India in 2016, compared with 15·2% (13·7–16·2) and 6·9% (6·3–7·4), respectively, in 1990. In 2016, there was a nine times difference between states in the DALY rate for ischaemic heart disease, a six times difference for stroke, and a four times difference for rheumatic heart disease. 23·8 million (95% UI 22·6–25·0) prevalent cases of ischaemic heart disease were estimated in India in 2016, and 6·5 million (6·3–6·8) prevalent cases of stroke, a 2·3 times increase in both disorders from 1990. The age-standardised prevalence of both ischaemic heart disease and stroke increased in all ETL state groups between 1990 and 2016, whereas that of rheumatic heart disease decreased; the increase for ischaemic heart disease was highest in the low ETL state group. 53·4% (95% UI 52·6–54·6) of crude deaths due to cardiovascular diseases in India in 2016 were among people younger than 70 years, with a higher proportion in the low ETL state group. The leading overlapping risk factors for cardiovascular diseases in 2016 included dietary risks (56·4% [95% CI 48·5–63·9] of cardiovascular disease DALYs), high systolic blood pressure (54·6% [49·0–59·8]), air pollution (31·1% [29·0–33·4]), high total cholesterol (29·4% [24·3–34·8]), tobacco use (18·9% [16·6–21·3]), high fasting plasma glucose (16·7% [11·4–23·5]), and high body-mass index (14·7% [8·3–22·0]). The prevalence of high systolic blood pressure, high total cholesterol, and high fasting plasma glucose increased generally across all ETL state groups from 1990 to 2016, but this increase was variable across the states; the prevalence of smoking decreased during this period in all ETL state groups.InterpretationThe burden from the leading cardiovascular diseases in India—ischaemic heart disease and strok...

Background and Objectives:One year since the onset of the COVID-19 pandemic, we aimed to summarize the frequency of neurological manifestations reported in COVID-19 patients and investigate the association of these manifestations with disease severity and mortality.Methods:We searched PubMed, Medline, Cochrane library, clinicaltrials.gov and EMBASE from 31st December 2019 to 15th December 2020 for studies enrolling consecutive COVID-19 patients presenting with neurological manifestations. Risk of bias was examined using Joanna Briggs Institute (JBI) scale. A random-effects meta-analysis was performed, and pooled prevalence and 95% Confidence Intervals (CI) were calculated for neurological manifestations. Odds ratio (OR) and 95%CI were calculated to determine the association of neurological manifestations with disease severity and mortality. Presence of heterogeneity was assessed using I-square, meta-regression, and subgroup analyses. Statistical analyses were conducted in R version 3.6.2.Results:Of 2,455 citations, 350 studies were included in this review, providing data on 145,721 COVID-19 patients, 89% of whom were hospitalized. Forty-one neurological manifestations (24 symptoms and 17 diagnoses) were identified. Pooled prevalence of the most common neurological symptoms included: fatigue (32%), myalgia (20%), taste impairment (21%), smell impairment (19%) and headache (13%). A low risk of bias was observed in 85% of studies; studies with higher risk of bias yielded higher prevalence estimates. Stroke was the most common neurological diagnosis (pooled prevalence- 2%). In COVID-19 patients aged ≥60, the pooled prevalence of acute confusion/delirium was 34% and the presence of any neurological manifestations in this age group was associated with mortality (OR 1.80; 95%CI 1.11 to 2.91).Discussion:Up to one-third of COVID-19 patients analysed in this review experienced at least one neurological manifestation. One in 50 patients experienced stroke. In those over 60, more than one-third had acute confusion/delirium; the presence of neurological manifestations in this group was associated with near doubling of mortality. Results must be interpreted keeping in view the limitations of observational studies and associated bias.

Cochrane Database of Systematic Reviews groups in the incidence of adverse events, which included gastrointestinal bleeding, invasive bacterial infections, hyperglycaemia, and liver dysfunction. One trial followed up participants for five years. The e ect on death was no longer apparent at this time-point (RR 0.93, 95% CI 0.78 to 1.12; one trial, 545 participants, moderate quality evidence); and there was no di erence in disabling neurological deficit detected (RR 0.91, 95% CI 0.49 to 1.69; one trial, 545 participants, low quality evidence). One trial included human immunodeficiency virus (HIV)-positive people. The stratified analysis by HIV status in this trial showed no heterogeneity, with point estimates for death (RR 0.90, 95% CI 0.67 to 1.20; one trial, 98 participants) and disability (RR 1.23, 95% CI 0.08 to 19.07; one trial, 98 participants) similar to HIV-negative participants in the same trial. Authors' conclusions Corticosteroids reduce mortality from tuberculous meningitis, at least in the short term. Corticosteroids may have no e ect on the number of people who survive tuberculous meningitis with disabling neurological deficit, but this outcome is less common than death, and the CI for the relative e ect includes possible harm. However, this small possible harm is unlikely to be quantitatively important when compared to the reduction in mortality. The number of HIV-positive people included in the review is small, so we are not sure if the benefits in terms of reduced mortality are preserved in this group of patients.

Background Tuberculous meningitis is a serious form of tuberculosis (TB) that affects the meninges that cover a person's brain and spinal cord. It is associated with high death rates and with disability in people who survive. Corticosteroids have been used as an adjunct to antituberculous drugs to treat people with tuberculous meningitis, but their role has been controversial. Objectives To evaluate the effects of corticosteroids as an adjunct to antituberculous treatment on death and severe disability in people with tuberculous meningitis. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register up to the 18 March 2016; CENTRAL; MEDLINE; EMBASE; LILACS; and Current Controlled Trials. We also contacted researchers and organizations working in the field, and checked reference lists. Selection criteria Randomized controlled trials that compared corticosteroid plus antituberculous treatment with antituberculous treatment alone in people with clinically diagnosed tuberculous meningitis and included death or disability as outcome measures. Data collection and analysis We independently assessed search results and methodological quality, and extracted data from the included trials. We analysed the data using risk ratios (RR) with 95% confidence intervals (CIs) and used a fixed‐effect model. We performed an intention‐to‐treat analysis, where we included all participants randomized to treatment in the denominator. This analysis assumes that all participants who were lost to follow‐up have good outcomes. We carried out a sensitivity analysis to explore the impact of the missing data. Main results Nine trials that included 1337 participants (with 469 deaths) met the inclusion criteria. At follow‐up from three to 18 months, steroids reduce deaths by almost one quarter (RR 0.75, 95% CI 0.65 to 0.87; nine trials, 1337 participants, high quality evidence ). Disabling neurological deficit is not common in survivors, and steroids may have little or no effect on this outcome (RR 0.92, 95% CI 0.71 to 1.20; eight trials, 1314 participants, low quality evidence ). There was no difference between groups in the incidence of adverse events, which included gastrointestinal bleeding, invasive bacterial infections, hyperglycaemia, and liver dysfunction. One trial followed up participants for five years. The effect on death was no longer apparent at this time‐point (RR 0.93, 95% CI 0.78 to 1.12; one trial, 545 participants, moderate quality evidence); and there was no difference in disabling neurological deficit detected (RR 0.91, 95% CI 0.49 to 1.69; one trial, 545 participants, low quality evidence ). One trial included human immunodeficiency virus (HIV)‐positive people. The stratified a...