Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients.

Background: New treatments are needed to reduce the risk of progression of coronavirus disease 2019 (Covid-19). Molnupiravir is an oral, small-molecule antiviral prodrug that is active against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Methods: We conducted a phase 3, double-blind, randomized, placebo-controlled trial to evaluate the efficacy and safety of treatment with molnupiravir started within 5 days after the onset of signs or symptoms in nonhospitalized, unvaccinated adults with mild-to-moderate, laboratory-confirmed Covid-19 and at least one risk factor for severe Covid-19 illness.

A Randomized, Double-blind, Multicenter Trial Comparing Efficacy and Safety of Imipenem/Cilastatin/Relebactam Versus Piperacillin/Tazobactam in Adults With Hospital-acquired or Ventilator-associated Bacterial Pneumonia (RESTORE-IMI 2 Study).

Background: Imipenem combined with the β-lactamase inhibitor relebactam has broad antibacterial activity, including against carbapenem-resistant gram-negative pathogens. We evaluated efficacy and safety of imipenem/cilastatin/relebactam in treating hospital-acquired/ventilator-associated bacterial pneumonia (HABP/VABP).

Methods: This was a randomized, controlled, double-blind phase 3 trial.

Efficacy of Bezlotoxumab in Participants Receiving Metronidazole, Vancomycin, or Fidaxomicin for Treatment of () Infection.

Background: In phase 3 MODIFY I/II trials, bezlotoxumab significantly reduced recurrence of () infection (rCDI) over 12 weeks. Choice of CDI antibacterial treatment may affect CDI-related outcomes; therefore, this prespecified analysis assessed if the magnitude of bezlotoxumab-induced rCDI reduction was influenced by the antibiotic administered.

Methods: In MODIFY I/II (NCT01241552/NCT01513239), participants received a single infusion of bezlotoxumab (10 mg/kg) or placebo during anti-CDI treatment.

Evaluation of Renal Safety Between Imipenem/Relebactam and Colistin Plus Imipenem in Patients With Imipenem-Nonsusceptible Bacterial Infections in the Randomized, Phase 3 RESTORE-IMI 1 Study.

Background: In the randomized controlled RESTORE-IMI 1 clinical trial (NCT02452047), imipenem/cilastatin (IMI) with relebactam (IMI/REL) was as effective as colistin plus IMI for the treatment of imipenem-nonsusceptible gram-negative infections. Differences in nephrotoxicity were observed between treatment arms. As there is no standard definition of nephrotoxicity used in clinical trials, we conducted analyses to further understand the renal safety profile of both treatments.

Comparison of Treatment Outcomes between Analysis Populations in the RESTORE-IMI 1 Phase 3 Trial of Imipenem-Cilastatin-Relebactam versus Colistin plus Imipenem-Cilastatin in Patients with Imipenem-Nonsusceptible Bacterial Infections.

The RESTORE-IMI 1 phase 3 trial demonstrated the efficacy and safety of imipenem-cilastatin (IMI) combined with relebactam (REL) for treating imipenem-nonsusceptible infections. The objective of this analysis was to compare the outcomes among patients meeting eligibility requirements based on central laboratory susceptibility versus local laboratory susceptibility. Patients with serious infections caused by imipenem-nonsusceptible, colistin-susceptible, and imipenem-REL-susceptible pathogens were randomized 2:1 to IMI-REL plus placebo or colistin plus IMI for 5 to 21 days.

RESTORE-IMI 1: A Multicenter, Randomized, Double-blind Trial Comparing Efficacy and Safety of Imipenem/Relebactam vs Colistin Plus Imipenem in Patients With Imipenem-nonsusceptible Bacterial Infections.

Background: The β-lactamase inhibitor relebactam can restore imipenem activity against imipenem-nonsusceptible gram-negative pathogens. We evaluated imipenem/relebactam for treating imipenem-nonsusceptible infections.

Methods: Randomized, controlled, double-blind, phase 3 trial.

Equalization of four cardiovascular risk algorithms after systematic recalibration: individual-participant meta-analysis of 86 prospective studies.

Aims: There is debate about the optimum algorithm for cardiovascular disease (CVD) risk estimation. We conducted head-to-head comparisons of four algorithms recommended by primary prevention guidelines, before and after 'recalibration', a method that adapts risk algorithms to take account of differences in the risk characteristics of the populations being studied.

Methods And Results: Using individual-participant data on 360 737 participants without CVD at baseline in 86 prospective studies from 22 countries, we compared the Framingham risk score (FRS), Systematic COronary Risk Evaluation (SCORE), pooled cohort equations (PCE), and Reynolds risk score (RRS).

VIBRATIONAL DEPENDENCE OF LINE COUPLING AND LINE MIXING IN SELF-BROADENED PARALLEL BANDS OF NH.

Line coupling and line mixing effects have been calculated for several self-broadened NH lines in parallel bands involving an excited mode. It is well known that once the mode is excited, the inversion splitting quickly increases as this quantum number increases. In the present study, we have shown that the dependence of the inversion splitting plays a dominant role in the calculated line-shape parameters.

Use of Repeated Blood Pressure and Cholesterol Measurements to Improve Cardiovascular Disease Risk Prediction: An Individual-Participant-Data Meta-Analysis.

The added value of incorporating information from repeated blood pressure and cholesterol measurements to predict cardiovascular disease (CVD) risk has not been rigorously assessed. We used data on 191,445 adults from the Emerging Risk Factors Collaboration (38 cohorts from 17 countries with data encompassing 1962-2014) with more than 1 million measurements of systolic blood pressure, total cholesterol, and high-density lipoprotein cholesterol. Over a median 12 years of follow-up, 21,170 CVD events occurred.

Relaxation matrix for symmetric tops with inversion symmetry: Line coupling and line mixing effects on NH lines in the 𝝂 band.

Line shape parameters including the half-widths and the off-diagonal elements of the relaxation matrix have been calculated for self-broadened NH lines in the perpendicular ν band. As in the pure rotational and the parallel ν bands, the small inversion splitting in this band causes a complete failure of the isolated line approximation. As a result, one has to use formalisms not relying on this approximation.

Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection.

Background: Clostridium difficile is the most common cause of infectious diarrhea in hospitalized patients. Recurrences are common after antibiotic therapy. Actoxumab and bezlotoxumab are human monoclonal antibodies against C.

Line mixing in parallel and perpendicular bands of CO2: A further test of the refined Robert-Bonamy formalism.

Starting from the refined Robert-Bonamy formalism [Q. Ma, C. Boulet, and R.

Effects on calculated half-widths and shifts from the line coupling for asymmetric-top molecules.

The refinement of the Robert-Bonamy formalism by considering the line coupling for linear molecules developed in our previous studies [Q. Ma, C. Boulet, and R.

Two dimensional symmetric correlation functions of the Ŝ operator and two dimensional Fourier transforms: considering the line coupling for P and R lines of linear molecules.

The refinement of the Robert-Bonamy (RB) formalism by considering the line coupling for isotropic Raman Q lines of linear molecules developed in our previous study [Q. Ma, C. Boulet, and R.

Refinement of the Robert-Bonamy formalism: considering effects from the line coupling.

Since it was developed in 1979, the Robert-Bonamy (RB) formalism has been widely used in calculating pressure broadened half-widths and induced shifts for many molecular systems. However, this formalism contains several approximations whose applicability has not been thoroughly justified. One of them is that lines of interest are well isolated.

C-reactive protein, fibrinogen, and cardiovascular disease prediction.

Background: There is debate about the value of assessing levels of C-reactive protein (CRP) and other biomarkers of inflammation for the prediction of first cardiovascular events.

Methods: We analyzed data from 52 prospective studies that included 246,669 participants without a history of cardiovascular disease to investigate the value of adding CRP or fibrinogen levels to conventional risk factors for the prediction of cardiovascular risk. We calculated measures of discrimination and reclassification during follow-up and modeled the clinical implications of initiation of statin therapy after the assessment of CRP or fibrinogen.

Lipid-related markers and cardiovascular disease prediction.

Context: The value of assessing various emerging lipid-related markers for prediction of first cardiovascular events is debated.

Objective: To determine whether adding information on apolipoprotein B and apolipoprotein A-I, lipoprotein(a), or lipoprotein-associated phospholipase A2 to total cholesterol and high-density lipoprotein cholesterol (HDL-C) improves cardiovascular disease (CVD) risk prediction.

Design, Setting, And Participants: Individual records were available for 165,544 participants without baseline CVD in 37 prospective cohorts (calendar years of recruitment: 1968-2007) with up to 15,126 incident fatal or nonfatal CVD outcomes (10,132 CHD and 4994 stroke outcomes) during a median follow-up of 10.

Temperature dependences of mechanisms responsible for the water-vapor continuum absorption. II. Dimers and collision-induced absorption.

We investigated the magnitude and temperature dependence (T dependence) of the dimer absorption in the region of 0-600 cm(-1) and the collision-induced absorption (CIA) in the region of 0-1150 cm(-1). Together with our previous study of the self water-vapor continuum contributions resulting from far-wing line shapes of the allowed H(2)O lines in the infrared window between 800 and 1150 cm(-1), we find that the three mechanisms have completely different T dependence behaviors. The dimer absorption has the strongest negative T dependence and the continuum absorption from far wings of the allowed lines has a moderately strong negative one.

Critical Care Air Support Teams and deployed intensive care.

The evacuation of injured patients by air has been going on in one form or another for nearly 100 years. This paper presents some of the history behind Aeromedical Evacuation (AE), the current situation and looks to the future of this vital component in the chain of care from point of wounding to rehabilitation.

Temperature dependences of mechanisms responsible for the water-vapor continuum absorption. I. Far wings of allowed lines.

It is well known that the water-vapor continuum plays an important role in the radiative balance in the Earth's atmosphere. This was first discovered by Elsasser almost 70 years ago, and since that time there has been a large body of work, both experimental and theoretical, on this topic. It has been experimentally shown that for ambient atmospheric conditions, the continuum absorption scales quadratically with the H(2)O number density and has a strong, negative temperature dependence (T dependence).

Theoretical far-wing line shape and absorption for high-temperature CO2.

Theoretical results for the far-wing line shapes and corresponding absorption coefficients in the high-frequency wing of the nu(3) fundamental band of self-broadened CO(2) are presented for a number of temperatures between 218 and 751 K. These first-principles calculations are made assuming binary collisions within the framework of a quasi-static theory with a more accurate interaction potential than in previous calculations. The theoretical results are compared with existing laboratory data and are in good agreement for all the temperatures considered.

The Emerging Risk Factors Collaboration: analysis of individual data on lipid, inflammatory and other markers in over 1.1 million participants in 104 prospective studies of cardiovascular diseases.

Many long-term prospective studies have reported on associations of cardiovascular diseases with circulating lipid markers and/or inflammatory markers. Studies have not, however, generally been designed to provide reliable estimates under different circumstances and to correct for within-person variability. The Emerging Risk Factors Collaboration has established a central database on over 1.

Irreducible correlation functions of the S matrix in the coordinate representation: application in calculating Lorentzian half-widths and shifts.

By introducing the coordinate representation, the derivation of the perturbation expansion of the Liouville S matrix is formulated in terms of classically behaved autocorrelation functions. Because these functions are characterized by a pair of irreducible tensors, their number is limited to a few. They represent how the overlaps of the potential components change with a time displacement, and under normal conditions, their magnitudes decrease by several orders of magnitude when the displacement reaches several picoseconds.

Frequency of myopathy in patients receiving lovastatin.

Lovastatin (Mevacor) 20 mg is being considered for nonprescription availability. Because the most severe untoward consequence of therapy with any statin is rhabdomyolysis, the clinical data for lovastatin pertaining to this adverse event were reviewed. Evidence to date, based on almost 2 decades of experience, points to an extremely low risk for myopathy and rhabdomyolysis associated with lovastatin.