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

Near-field radiative heat transfer between irregularly shaped dielectric particles modeled with the discrete system Green's function method

Near-field radiative heat transfer (NFRHT) between irregularly shaped dielectric particles made of SiO2 and morphology characterized by Gaussian random spheres is studied. Particles are modeled with a new numerical method based on fluctuational electrodynamics, called the discrete system Green's function (DSGF) approach, that defines system interactions deterministically via a self-consistent Green's function equation and is applicable to finite, three-dimensional objects. The DSGF method is deemed suitable to model NFRHT between irregularly shaped particles after verification against the analytical solution for chains of two and three SiO2 spheres. The NFRHT results reveal that geometric irregularity in particles leads to a reduction of the total conductance from that of comparable perfect spheres at small separation distances where NFRHT is a surface phenomenon. At larger separation distances where NFRHT becomes a volumetric process, the total conductance between irregularly shaped particles converges to that of comparable perfect spheres. Spectral analysis reveals, however, that particle irregularity leads to damping and broadening of resonances at all separation distances, thereby highlighting the importance of the DSGF method for spectral engineering in the near field. The reduced spectral coherence when particle size is larger than the vacuum separation distance is attributed to coupling of surface phonon-polaritons within the randomly generated, distorted particle features. For particle size smaller than the vacuum separation distance, resonance broadening and damping is linked with the multiple localized surface phonon modes supported by the composite spherical harmonic morphologies of the Gaussian random spheres.Comment: 56 pages, 9 figures, 6 supplementary figure

Identifying barriers and facilitators towards implementing guidelines to reduce caesarean section rates in Quebec

OBJECTIVE: To investigate obstetricians’ perceptions of clinical practice guidelines targeting management of labour and vaginal birth after previous caesarean birth, and to identify the barriers to, facilitators of and obstetricians’ solutions for implementing these guidelines in practice. METHODS: This qualitative study was conducted in three hospitals in Montreal that represent around 10% of births in Quebec. Data was collected from 10 focus groups, followed by six semi-structured interviews. Two researchers jointly analysed the verbatim transcripts according to A manual for the use of focus groups. FINDINGS: The identified barriers to and facilitators of the implementation of guidelines can be classified into four categories: 1) the hospital level, including management and hospital policies; 2) the departmental level, including local policies, leadership, organizational factors, economic incentive, and availability of equipment and staff; 3) the health professionals’ motivations and attitudes, including medico-legal concerns, skill levels, acceptance of guidelines and strategies used to implement recommendations; and 4) patients’ motivations. CONCLUSION: Identifying the barriers to and facilitators of the adoption of recommendations is an important way to guide the development of efficient strategies. The findings of this study suggest that the adoption of guidelines may be improved if local health professionals’ perceptions are considered to make recommendations more acceptable and useful. Our findings also support the assumption that obstetricians seek to implement best practices, but require evidence tools and support to assess their practices and enhance their performance. In addition, peer review activities championed by opinion leaders have been identified by obstetricians as the most suitable strategy to improve the use of the guidelines in their practices

Profiling the polyadenylated transcriptome of extracellular vesicles with long-read nanopore sequencing

Abstract Background While numerous studies have described the transcriptomes of extracellular vesicles (EVs) in different cellular contexts, these efforts have typically relied on sequencing methods requiring RNA fragmentation, which limits interpretations on the integrity and isoform diversity of EV-targeted RNA populations. It has been assumed that mRNA signatures in EVs are likely to be fragmentation products of the cellular mRNA material, and the extent to which full-length mRNAs are present within EVs remains to be clarified. Results Using long-read nanopore RNA sequencing, we sought to characterize the full-length polyadenylated (poly-A) transcriptome of EVs released by human chronic myelogenous leukemia K562 cells. We detected 443 and 280 RNAs that were respectively enriched or depleted in EVs. EV-enriched poly-A transcripts consist of a variety of biotypes, including mRNAs, long non-coding RNAs, and pseudogenes. Our analysis revealed that 10.58% of all EV reads, and 18.67% of all cellular (WC) reads, corresponded to known full-length transcripts, with mRNAs representing the largest biotype for each group (EV = 58.13%, WC = 43.93%). We also observed that for many well-represented coding and non-coding genes, diverse full-length transcript isoforms were present in EV specimens, and these isoforms were reflective-of but often in different ratio compared to cellular samples. Conclusion This work provides novel insights into the compositional diversity of poly-A transcript isoforms enriched within EVs, while also underscoring the potential usefulness of nanopore sequencing to interrogate secreted RNA transcriptomes

Optical properties of spontaneous lateral composition modulations in AlAs/InAs short-period superlattices

The effect of lateral composition modulation, spontaneously generated during the epitaxial growth of a AlAs/InAs short-period superlattice, on the electronic band structure is investigated using photo-transmission and photoluminescence spectroscopy. Compared with uniform layers of similar average composition, the presence of the composition modulation considerably reduces the band gap energy and produces strongly polarized emission and absorption spectra. The authors demonstrate that the dominant polarization can selectively be aligned along the [{bar 1}10] or [010] crystallographic directions. In compressively strained samples, the use of (001) InP substrates slightly miscut toward [111]A or [101] resulted in modulation directions along [110] or [100], respectively, and dominant polarizations along a direction orthogonal to the respective composition modulation. Band gap reduction as high as 350 meV and 310 meV are obtained for samples with composition modulation along [110] and [100], respectively. Polarization ratios up to 26 are observed in transmission spectra