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

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

Database study of turbulent electron temperature fluctuation measurements at ASDEX Upgrade

In this work, an automated method for the analysis of data from the correlation electron cyclotron emission (CECE) diagnostic is applied to discharges in the ASDEX Upgrade (AUG) tokamak. This recently developed, automated method provides an efficient means of accurately analysing large quantities of experimental turbulence data, enabling the development of the largest database of CECE measurements of tokamak plasmas to-date. The turbulence database provides the opportunity to search for large-scale trends in experimental data to improve our understanding of transport-relevant plasma turbulence. The results of physics-based investigations utilizing this turbulence database will be reported on separately from this work

Advances in turbulence measurements using new Correlation ECE and nT-phase diagnostics at ASDEX Upgrade

Guided by predictions from nonlinear gyrokinetic simulations, two new turbulence diagnostics were designed and installed at ASDEX Upgrade (AUG) to probe the fundamentals of ion-scale turbulent electron heat transport. The first, a 30-channel correlation ECE (CECE) radiometer (105-128 GHz, 2nd harmonic X-mode), introduces a novel channel comb arrangement. This allows measurements of high radial resolution profiles (0:5 < r/a < 0:8) of low-k (k⍬⍴s < 0:3) temperature fluctuation amplitudes, frequency spectra and radial correlation length profiles in unprecedented detail. The second diagnostic is formed by the addition of two W-band and one V-band X-mode reflectometers on the same line of sight as the CECE to enable measurements of the phase angle between turbulent density and temperature fluctuations. Historically, the radial alignment between reflectometer and radiometer has been a challenge due to the requirement that alignment is achieved within a radial correlation length (< 5 10 mm). This challenge is significantly alleviated by using the CECE channel comb arrangement and the maximal coherence between reflectometer and radiometer can be unambiguously captured. Measurements of these quantities have been made in an AUG L-mode plasma, at the same radial location and have provided simultaneous quantitative constraints on realistic gyrokinetic simulations [Physics of Plasmas 25, 055903 (2018)] using the gyrokinetic code GENE. Here we present diagnostic detail for this study

Advances in turbulence measurements using new Correlation ECE and nT-phase diagnostics at ASDEX Upgrade

Guided by predictions from nonlinear gyrokinetic simulations, two new turbulence diagnostics were designed and installed at ASDEX Upgrade (AUG) to probe the fundamentals of ion-scale turbulent electron heat transport. The first, a 30-channel correlation ECE (CECE) radiometer (105-128 GHz, 2nd harmonic X-mode), introduces a novel channel comb arrangement. This allows measurements of high radial resolution profiles (0:5 < r/a < 0:8) of low-k (k⍬⍴s < 0:3) temperature fluctuation amplitudes, frequency spectra and radial correlation length profiles in unprecedented detail. The second diagnostic is formed by the addition of two W-band and one V-band X-mode reflectometers on the same line of sight as the CECE to enable measurements of the phase angle between turbulent density and temperature fluctuations. Historically, the radial alignment between reflectometer and radiometer has been a challenge due to the requirement that alignment is achieved within a radial correlation length (< 5 10 mm). This challenge is significantly alleviated by using the CECE channel comb arrangement and the maximal coherence between reflectometer and radiometer can be unambiguously captured. Measurements of these quantities have been made in an AUG L-mode plasma, at the same radial location and have provided simultaneous quantitative constraints on realistic gyrokinetic simulations [Physics of Plasmas 25, 055903 (2018)] using the gyrokinetic code GENE. Here we present diagnostic detail for this study

Electron temperature fluctuation measurements with Correlation Electron Cyclotron Emission in L-mode and I-mode plasmas at ASDEX Upgrade

The Correlation Electron Cyclotron Emission (CECE) diagnostic at ASDEX Upgrade (AUG) is used to investigate the features of outer core and pedestal (ρpol = 0.85-1.0) turbulence across confinement regime transitions. The I-mode confinement regime is a promising operational scenario for future fusion reactors because it features high energy confinement without high particle confinement, but the nature of the edge and pedestal turbulence in I-mode plasmas is still under investigation. The edge Weakly Coherent Mode (WCM) appears in the I-mode pedestal and may play a role in transport. In this work we explore electron temperature (Te) fluctuations in the plasma outer core and pedestal using a 24-channel high radial resolution CECE radiometer. CECE measurements provide turbulence information including the Te fluctuation amplitude, turbulent spectra, and radial localization of turbulent features. With CECE measurements we show that the WCM is localized in the pedestal region in both L-mode and I-mode and is measured in optically thick plasmas with a Te fluctuation amplitude of 2.3%. Broadband drift wave turbulence is measured in the outer core with a Te fluctuation amplitude of <1%. A second CECE system recently installed at AUG allowed for non-standard fluctuation measurements during L-mode and I-mode experiments. The second CECE system was toroidally separated from the primary system, allowing measurements of the long-range toroidal correlation of the WCM indicating its low toroidal mode number. A reflectometer sharing a line of sight with the second CECE system enabled density-temperature cross-phase (αne Te ) measurements. The WCM αne Te changes between L-mode and I-mode as the Te gradient steepens