Efficacy and Safety of Colchicine in Post-acute Myocardial Infarction Patients : A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background: Inflammation plays a key role in atherosclerotic plaque destabilization and adverse cardiac remodeling. Recent evidence has shown a promising role of colchicine in patients with coronary artery disease. We evaluated the efficacy and safety of colchicine in post-acute myocardial infarction (MI) patients. Methods: We searched five electronic databases from inception to January 18, 2021, for randomized controlled trials (RCTs) evaluating colchicine in post-acute MI patients. Primary outcomes were cardiovascular mortality and recurrent MI. Secondary outcomes were all-cause mortality, stroke, urgent coronary revascularization, levels of follow-up high-sensitivity C-reactive protein (hs-CRP), and drug-related adverse events. All meta-analyses used inverse-variance random-effects models. Results: Six RCTs involving 6,005 patients were included. Colchicine did not significantly reduce cardiovascular mortality [risk ratio (RR), 0.91; 95% confidence interval (95% CI), 0.52-1.61; p = 0.64], recurrent MI (RR, 0.87; 95% CI, 0.62-1.22; p = 0.28), all-cause mortality (RR, 1.06; 95% CI, 0.61-1.85; p = 0.78), stroke (RR, 0.28; 95% CI, 0.07-1.09; p = 0.05), urgent coronary revascularization (RR, 0.46; 95% CI, 0.02-8.89; p = 0.19), or decreased levels of follow-up hs-CRP (mean difference, −1.95 mg/L; 95% CI, −12.88 to 8.98; p = 0.61) compared to the control group. There was no increase in any adverse events (RR, 0.97; 95% CI, 0.89-1.07; p = 0.34) or gastrointestinal adverse events (RR, 2.49; 95% CI, 0.48-12.99; p = 0.20). Subgroup analyses by colchicine dose (0.5 vs. 1 mg/day), time of follow-up (30 days) showed no changes in the overall findings. Conclusion: In post-acute MI patients, colchicine does not reduce cardiovascular or all-cause mortality, recurrent MI, or other cardiovascular outcomes. Also, colchicine did not increase drug-related adverse event

A novel role for the mineralocorticoid receptor in glucocorticoid driven vascular calcification

AbstractVascular calcification, which is common in the elderly and in patients with atherosclerosis, diabetes and chronic renal disease, increases the risk of cardiovascular morbidity and mortality. It is a complex, active and highly regulated cellular process that resembles physiological bone formation. It has previously been established that pharmacological doses of glucocorticoids facilitate arterial calcification. However, the consequences for vascular calcification of endogenous glucocorticoid elevation have yet to be established. Glucocorticoids (cortisol, corticosterone) are released from the adrenal gland, but can also be generated within cells from 11-keto metabolites of glucocorticoids (cortisone, 11-dehydrocorticosterone [11-DHC]) by the enzyme, 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). In the current study we hypothesized that endogenous glucocorticoids facilitate vascular smooth muscle cell (VSMC) calcification and investigated the receptor-mediated mechanism underpinning this process.In vitro studies revealed increased phosphate-induced calcification in mouse VSMCs following treatment for 7days with corticosterone (100nM; 7.98 fold; P<0.01), 11-DHC (100nM; 7.14 fold; P<0.05) and dexamethasone (10nM; 7.16 fold; P<0.05), a synthetic glucocorticoid used as a positive control. Inhibition of 11β-HSD isoenzymes by 10μM carbenoxolone reduced the calcification induced by 11-DHC (0.37 fold compared to treatment with 11-DHC alone; P<0.05). The glucocorticoid receptor (GR) antagonist mifepristone (10μM) had no effect on VSMC calcification in response to corticosterone or 11-DHC. In contrast, the mineralocorticoid receptor (MR) antagonist eplerenone (10μM) significantly decreased corticosterone- (0.81 fold compared to treatment with corticosterone alone; P<0.01) and 11-DHC-driven (0.64 fold compared to treatment with 11-DHC alone; P<0.01) VSMC calcification, suggesting this glucocorticoid effect is MR-driven and not GR-driven. Neither corticosterone nor 11-DHC altered the mRNA levels of the osteogenic markers PiT-1, Osx and Bmp2. However, DAPI staining of pyknotic nuclei and flow cytometry analysis of surface Annexin V expression showed that corticosterone induced apoptosis in VSMCs.This study suggests that in mouse VSMCs, corticosterone acts through the MR to induce pro-calcification effects, and identifies 11β-HSD-inhibition as a novel potential treatment for vascular calcification

Global, regional, and national burden of stroke, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016

© 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license Background: Stroke is a leading cause of mortality and disability worldwide and the economic costs of treatment and post-stroke care are substantial. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic, comparable method of quantifying health loss by disease, age, sex, year, and location to provide information to health systems and policy makers on more than 300 causes of disease and injury, including stroke. The results presented here are the estimates of burden due to overall stroke and ischaemic and haemorrhagic stroke from GBD 2016. Methods: We report estimates and corresponding uncertainty intervals (UIs), from 1990 to 2016, for incidence, prevalence, deaths, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs). DALYs were generated by summing YLLs and YLDs. Cause-specific mortality was estimated using an ensemble modelling process with vital registration and verbal autopsy data as inputs. Non-fatal estimates were generated using Bayesian meta-regression incorporating data from registries, scientific literature, administrative records, and surveys. The Socio-demographic Index (SDI), a summary indicator generated using educational attainment, lagged distributed income, and total fertility rate, was used to group countries into quintiles. Findings: In 2016, there were 5·5 million (95% UI 5·3 to 5·7) deaths and 116·4 million (111·4 to 121·4) DALYs due to stroke. The global age-standardised mortality rate decreased by 36·2% (−39·3 to −33·6) from 1990 to 2016, with decreases in all SDI quintiles. Over the same period, the global age-standardised DALY rate declined by 34·2% (−37·2 to −31·5), also with decreases in all SDI quintiles. There were 13·7 million (12·7 to 14·7) new stroke cases in 2016. Global age-standardised incidence declined by 8·1% (−10·7 to −5·5) from 1990 to 2016 and decreased in all SDI quintiles except the middle SDI group. There were 80·1 million (74·1 to 86·3) prevalent cases of stroke globally in 2016; 41·1 million (38·0 to 44·3) in women and 39·0 million (36·1 to 42·1) in men. Interpretation: Although age-standardised mortality rates have decreased sharply from 1990 to 2016, the decrease in age-standardised incidence has been less steep, indicating that the burden of stroke is likely to remain high. Planned updates to future GBD iterations include generating separate estimates for subarachnoid haemorrhage and intracerebral haemorrhage, generating estimates of transient ischaemic attack, and including atrial fibrillation as a risk factor. Funding: Bill & Melinda Gates Foundatio

Global mortality from dementia: Application of a newmethod and results from the global burden of disease study 2019

INTRODUCTION: Dementia is currently one of the leading causes of mortality globally, and mortality due to dementia will likely increase in the future along with corresponding increases in population growth and population aging. However, large inconsistencies in coding practices in vital registration systems over time and between countries complicate the estimation of global dementia mortality. METHODS: We meta-analyzed the excess risk of death in those with dementia and multiplied these estimates by the proportion of dementia deaths occurring in those with severe, end-stage disease to calculate the total number of deaths that could be attributed to dementia. RESULTS: We estimated that there were 1.62 million (95% uncertainty interval [UI]: 0.41–4.21) deaths globally due to dementia in 2019. More dementia deaths occurred in women (1.06 million [0.27–2.71]) than men (0.56 million [0.14–1.51]), largely but not entirely due to the higher life expectancy in women (age-standardized female-to-male ratio 1.19 [1.10–1.26]). Due to population aging, there was a large increase in all-age mortality rates from dementia between 1990 and 2019 (100.1% [89.1–117.5]). In 2019, deaths due to dementia ranked seventh globally in all ages and fourth among individuals 70 and older compared to deaths from other diseases estimated in the Global Burden of Disease (GBD) study. DISCUSSION: Mortality due to dementia represents a substantial global burden, and is expected to continue to grow into the future as an older, aging population expands globally

The 13th Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the SDSS-IV Survey Mapping Nearby Galaxies at Apache Point Observatory

The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) began observations in July 2014. It pursues three core programs: APOGEE-2,MaNGA, and eBOSS. In addition, eBOSS contains two major subprograms: TDSS and SPIDERS. This paper describes the first data release from SDSS-IV, Data Release 13 (DR13), which contains new data, reanalysis of existing data sets and, like all SDSS data releases, is inclusive of previously released data. DR13 makes publicly available 1390 spatially resolved integral field unit observations of nearby galaxies from MaNGA,the first data released from this survey. It includes new observations from eBOSS, completing SEQUELS. In addition to targeting galaxies and quasars, SEQUELS also targeted variability-selected objects from TDSS and X-ray selected objects from SPIDERS. DR13 includes new reductions ofthe SDSS-III BOSS data, improving the spectrophotometric calibration and redshift classification. DR13 releases new reductions of the APOGEE-1data from SDSS-III, with abundances of elements not previously included and improved stellar parameters for dwarf stars and cooler stars. For the SDSS imaging data, DR13 provides new, more robust and precise photometric calibrations. Several value-added catalogs are being released in tandem with DR13, in particular target catalogs relevant for eBOSS, TDSS, and SPIDERS, and an updated red-clump catalog for APOGEE.This paper describes the location and format of the data now publicly available, as well as providing references to the important technical papers that describe the targeting, observing, and data reduction. The SDSS website, http://www.sdss.org, provides links to the data, tutorials and examples of data access, and extensive documentation of the reduction and analysis procedures. DR13 is the first of a scheduled set that will contain new data and analyses from the planned ~6-year operations of SDSS-IV.PostprintPeer reviewe

The Fifteenth Data Release of the Sloan Digital Sky Surveys: First Release of MaNGA-derived Quantities, Data Visualization Tools, and Stellar Library

Twenty years have passed since first light for the Sloan Digital Sky Survey (SDSS). Here, we release data taken by the fourth phase of SDSS (SDSS-IV) across its first three years of operation (2014 July–2017 July). This is the third data release for SDSS-IV, and the 15th from SDSS (Data Release Fifteen; DR15). New data come from MaNGA—we release 4824 data cubes, as well as the first stellar spectra in the MaNGA Stellar Library (MaStar), the first set of survey-supported analysis products (e.g., stellar and gas kinematics, emission-line and other maps) from the MaNGA Data Analysis Pipeline, and a new data visualization and access tool we call "Marvin." The next data release, DR16, will include new data from both APOGEE-2 and eBOSS; those surveys release no new data here, but we document updates and corrections to their data processing pipelines. The release is cumulative; it also includes the most recent reductions and calibrations of all data taken by SDSS since first light. In this paper, we describe the location and format of the data and tools and cite technical references describing how it was obtained and processed. The SDSS website (www.sdss.org) has also been updated, providing links to data downloads, tutorials, and examples of data use. Although SDSS-IV will continue to collect astronomical data until 2020, and will be followed by SDSS-V (2020–2025), we end this paper by describing plans to ensure the sustainability of the SDSS data archive for many years beyond the collection of data

Global mortality from dementia : Application of a new method and results from the Global Burden of Disease Study 2019

Introduction Dementia is currently one of the leading causes of mortality globally, and mortality due to dementia will likely increase in the future along with corresponding increases in population growth and population aging. However, large inconsistencies in coding practices in vital registration systems over time and between countries complicate the estimation of global dementia mortality. Methods We meta-analyzed the excess risk of death in those with dementia and multiplied these estimates by the proportion of dementia deaths occurring in those with severe, end-stage disease to calculate the total number of deaths that could be attributed to dementia. Results We estimated that there were 1.62 million (95% uncertainty interval [UI]: 0.41-4.21) deaths globally due to dementia in 2019. More dementia deaths occurred in women (1.06 million [0.27-2.71]) than men (0.56 million [0.14-1.51]), largely but not entirely due to the higher life expectancy in women (age-standardized female-to-male ratio 1.19 [1.10-1.26]). Due to population aging, there was a large increase in all-age mortality rates from dementia between 1990 and 2019 (100.1% [89.1-117.5]). In 2019, deaths due to dementia ranked seventh globally in all ages and fourth among individuals 70 and older compared to deaths from other diseases estimated in the Global Burden of Disease (GBD) study. Discussion Mortality due to dementia represents a substantial global burden, and is expected to continue to grow into the future as an older, aging population expands globally.Peer reviewe

The 16th Data Release of the Sloan Digital Sky Surveys : First Release from the APOGEE-2 Southern Survey and Full Release of eBOSS Spectra

This paper documents the 16th data release (DR16) from the Sloan Digital Sky Surveys (SDSS), the fourth and penultimate from the fourth phase (SDSS-IV). This is the first release of data from the Southern Hemisphere survey of the Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2); new data from APOGEE-2 North are also included. DR16 is also notable as the final data release for the main cosmological program of the Extended Baryon Oscillation Spectroscopic Survey (eBOSS), and all raw and reduced spectra from that project are released here. DR16 also includes all the data from the Time Domain Spectroscopic Survey and new data from the SPectroscopic IDentification of ERosita Survey programs, both of which were co-observed on eBOSS plates. DR16 has no new data from the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey (or the MaNGA Stellar Library "MaStar"). We also preview future SDSS-V operations (due to start in 2020), and summarize plans for the final SDSS-IV data release (DR17).Peer reviewe