59 research outputs found

    Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

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    IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

    Multiyear Measurements of Flame Retardants and Organochlorine Pesticides in Air in Canada’s Western Sub-Arctic

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    Fourteen polybrominated diphenyl ethers (PBDEs), 14 non-BDE flame retardants (FRs), and 25 organochlorine pesticides (OCPs) were analyzed in air samples collected at Little Fox Lake (LFL) in Canada’s Yukon Territory from August 2011 to December 2014. LFL is a long-term monitoring station operated under the Northern Contaminants Program (NCP) and one of only a few stations that contribute to the assessment of air pollution levels and pathways to the sub-Arctic region. BDE-47 was the most abundant congener among the 14 PBDEs, followed by BDE-99. Non-BDE FRs pentabromotoluene (PBT) and dechlorane plus (DP) were detected in all the samples. Dechlorane 602, 2,3-dibromopropyl-2,4,6-tribromophenyl ether (DPTE), hexabromobenzene (HBB), and 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (EH-TBB) were also detected in >75% of all samples. PBDEs have shown a decreasing tendency as of 2013, which may reflect the phase-out of penta- and octa-BDE mixtures has led to significant decline in the atmosphere. The highest concentrations of OCPs were observed for hexachlorobenzene (HCB), with a median concentration of 61 pg/m<sup>3</sup>, followed by α-hexachlorocyclohexane (α-HCH) and α-endosulfan. Potential source contribution function (PSCF) highlights Northern Canada, Pacific, and East Asia as potential sources in warm seasons; whereas in cold seasons, the chemicals mainly came from the Pacific Rim

    Guideline for herbal medicine research

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    Herbal medicine is widely used in Traditional and Complementary Medicine (T&CM) practices. With its increasing use within the Malaysian community, there needs to be more specific guidance on the requirements for herbal medicine research to produce evidence-based herbal medicine products with therapeutic claims. Therefore, the pathway of herbal product development involving preclinical and clinical research must be well outlined in tandem with the ‘Guideline on Natural Products with Therapeutic Claim’ from the regulators. The primary purpose of this guideline is to provide structured guidance to be utilised by researchers, academicians, clinicians, T&CM practitioners, and relevant stakeholders of the herbal industry. This guideline outlines a concise yet informative description of the prerequisites and processes involved in planning and conducting herbal medicine-related research in the Malaysian context. This guideline will bridge the gap often associated with the population's demand for other treatment options besides conventional medicine. This effort will also help accommodate the growing interest in herbal medicine research and spur the discovery of herbal products with therapeutic claims in Malaysia

    SN 2018agk:a prototypical type Ia supernova with a smooth power-law rise in Kepler (K2)

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    We present the 30-min cadence Kepler/K2 light curve of the Type Ia supernova (SN Ia) SN 2018agk, covering approximately one week before explosion, the full rise phase and the decline until 40 days after peak. We additionally present ground-based observations in multiple bands within the same time range, including the 1-day cadence DECam observations within the first \sim5 days after the first light. The Kepler early light curve is fully consistent with a single power-law rise, without evidence of any bump feature. We compare SN 2018agk with a sample of other SNe~Ia without early excess flux from the literature. We find that SNe Ia without excess flux have slowly-evolving early colors in a narrow range (gi0.20±0.20g-i\approx -0.20\pm0.20 mag) within the first 10\sim 10 days. On the other hand, among SNe Ia detected with excess, SN 2017cbv and SN 2018oh tend to be bluer, while iPTF16abc's evolution is similar to normal SNe Ia without excess in gig-i. We further compare the Kepler light curve of SN 2018agk with companion-interaction models, and rule out the existence of a typical non-degenerate companion undergoing Roche-lobe overflow at viewing angles smaller than 4545^{\circ}.Comment: 20 pages, 14 figures, 5 tables. Published in Ap

    Search for CPCP violation in D0^0\to KS0^0_\mathrm{S}KS0^0_\mathrm{S} decays in proton-proton collisions at s\sqrt{s} = 13 TeV

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    International audienceA search is reported for charge-parity D0^0\to KS0^0_\mathrm{S}KS0^0_\mathrm{S}CPCP violation in D0^0\to KS0^0_\mathrm{S}KS0^0_\mathrm{S} decays, using data collected in proton-proton collisions at s\sqrt{s} = 13 TeV recorded by the CMS experiment in 2018. The analysis uses a dedicated data set that corresponds to an integrated luminosity of 41.6 fb1^{-1}, which consists of about 10 billion events containing a pair of ẖadrons, nearly all of which decay to charm hadrons. The flavor of the neutral D meson is determined by the pion charge in the reconstructed decays D+^{*+}\to D0π+^0\pi^+ and D^{*-}\to D0π^0\pi^-. The D0^0\to KS0^0_\mathrm{S}KS0^0_\mathrm{S}CPCP asymmetry in D0^0\to KS0^0_\mathrm{S}KS0^0_\mathrm{S} is measured to be ACPA_{CP}( KS0^0_\mathrm{S}KS0^0_\mathrm{S}) = (6.2 ±\pm 3.0 ±\pm 0.2 ±\pm 0.8)%, where the three uncertainties represent the statistical uncertainty, the systematic uncertainty, and the uncertainty in the measurement of the D0^0 \to KS0^0_\mathrm{S}KS0^0_\mathrm{S} CPCP asymmetry in the D0^0 \to KS0π+π^0_\mathrm{S}\pi^+\pi^- decay. This is the first D0^0 \to KS0^0_\mathrm{S}KS0^0_\mathrm{S} CPCP asymmetry measurement by CMS in the charm sector as well as the first to utilize a fully hadronic final state
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