The impact of body size, prior care quality, and weight gain on health care utilization during the COVID-19 pandemic.

The goal of this study was to ascertain the effect of patient body size on clinic- or patient-delayed health care during the COVID-19 pandemic and factors predicting delay. Primary survey data were collected in August 2021 from 3593 individuals living within the communities near Mayo Clinic facilities in Minnesota, Wisconsin, Arizona, and Florida. More people who identified with the higher-weight BMI categories reported having their care appointments cancelled (62.

Phylogenetics and population structure of the western North American endemic Pacific Laurasian clade of Isoëtes.

Premise: Isoëtes is a genus of small, semi-woody, hydrophilic, heterosporous lycophytes with a cosmopolitan, global distribution. However, local populations tend to be found in narrow, patchy, and highly fragmented mesic to aquatic habitats, many of which are currently under threat. In this study, we sought to uncover how this patchy distribution has affected the evolutionary history of one of the two lineages of Isoëtes found on the West Coast of North America-the Pacific Laurasian clade (PLC).

Impact of differences between interim and post-interim analysis populations on outcomes of a group sequential trial: Example of the MOVe-OUT study.

BackgroundPre-specified interim analyses allow for more timely evaluation of efficacy or futility, potentially accelerating decision-making on an investigational intervention. In such an analysis, the randomized, double-blind MOVe-OUT trial demonstrated superiority of molnupiravir over placebo for outpatient treatment of COVID-19 in high-risk patients. In the full analysis population, the point estimate of the treatment difference in the primary endpoint was notably lower than at the interim analysis.

Association of COVID-19 Vaccination With Risk of Medically Attended Postacute Sequelae of COVID-19 During the Ancestral, Alpha, Delta, and Omicron Variant Eras.

Background: Uncertainty exists regarding the effectiveness of COVID-19 vaccine to prevent postacute sequelae of COVID-19 (PASC) following a breakthrough infection. While most studies based on symptom surveys found an association between preinfection vaccination status and PASC symptoms, studies of medically attended PASC are less common and have reported conflicting findings.

Methods: In this retrospective cohort of patients with an initial SARS-CoV-2 infection who were continually empaneled for primary care in a large US health system, the electronic health record was queried for preinfection vaccination status, demographics, comorbidity index, and diagnosed conditions.

Genomic incongruence accompanies the evolution of flower symmetry in Eudicots: a case study in the poppy family (Papaveraceae, Ranunculales).

Reconstructing evolutionary trajectories and transitions that have shaped floral diversity relies heavily on the phylogenetic framework on which traits are modelled. In this study, we focus on the angiosperm order Ranunculales, sister to all other eudicots, to unravel higher-level relationships, especially those tied to evolutionary transitions in flower symmetry within the family Papaveraceae. This family presents an astonishing array of floral diversity, with actinomorphic, disymmetric (two perpendicular symmetry axes), and zygomorphic flowers.

Molnupiravir: Mechanism of action, clinical, and translational science.

Molnupiravir is an oral prodrug of the broadly active, antiviral ribonucleoside analog N-hydroxycytidine (NHC). The primary circulating metabolite NHC is taken up into cells and phosphorylated to NHC-triphosphate (NHC-TP). NHC-TP serves as a competitive substrate for viral RNA-dependent RNA polymerase (RdRp), which results in an accumulation of errors in the viral genome, rendering virus replication incompetent.

Respiratory virus coinfections during the COVID-19 pandemic: epidemiologic analysis and clinical outcomes from the Phase 2/3 molnupiravir trial (MOVe-OUT).

Unlabelled: This exploratory analysis assessed the incidence of respiratory viral coinfections and their impact on clinical outcomes in non-hospitalized adults with mild-to-moderate coronavirus disease-2019 (COVID-19) treated with molnupiravir versus placebo for 5 days in the Phase 2/3 MOVe-OUT trial (NCT04575597), which took place in October 2020 to January 2021 (Phase 2, = 302) and May 2021 to October 2021 (Phase 3, = 1,433). Among 1,735 total randomized participants, 1,674 had a baseline respiratory pathogen panel (NxTAG Respiratory Pathogen Panel for the Luminex MAGPIX instrument) performed and 69 (4.1%) were coinfected with at least one additional respiratory viral pathogen.

Virologic Outcomes with Molnupiravir in Non-hospitalized Adult Patients with COVID-19 from the Randomized, Placebo-Controlled MOVe-OUT Trial.

Introduction: The randomized, placebo-controlled, double-blind MOVe-OUT trial demonstrated molnupiravir (800 mg every 12 h for 5 days) as safe and effective for outpatient treatment of mild-to-moderate COVID-19, significantly reducing the risk of hospitalization/death in high-risk adults. At the time of that report, virologic assessments from the trial were partially incomplete as a result of their time-intensive nature. Here we present final results from all prespecified virology endpoints in MOVe-OUT based on the full trial dataset.

A phylogeny of the evening primrose family (Onagraceae) using a target enrichment approach with 303 nuclear loci.

Background: The evening primrose family (Onagraceae) includes 664 species (803 taxa) with a center of diversity in the Americas, especially western North America. Ongoing research in Onagraceae includes exploring striking variation in floral morphology, scent composition, and breeding system, as well as the role of these traits in driving diversity among plants and their interacting pollinators and herbivores. However, these efforts are limited by the lack of a comprehensive, well-resolved phylogeny.

The evolution of antimicrobial peptides in Chiroptera.

High viral tolerance coupled with an extraordinary regulation of the immune response makes bats a great model to study host-pathogen evolution. Although many immune-related gene gains and losses have been previously reported in bats, important gene families such as antimicrobial peptides (AMPs) remain understudied. We built an exhaustive bioinformatic pipeline targeting the major gene families of defensins and cathelicidins to explore AMP diversity and analyze their evolution and distribution across six bat families.

Population pharmacokinetics of molnupiravir in adults with COVID-19: Lack of clinically important exposure variation across individuals.

Effective antiviral treatments for coronavirus disease 2019 (COVID-19) are needed to reduce the morbidity and mortality associated with severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection, particularly in patients with risk factors for severe disease. Molnupiravir (MK-4482, EIDD-2801) is an orally administered, ribonucleoside prodrug of β-D-N4-hydroxycytidine (NHC) with submicromolar potency against SARS-CoV-2. A population pharmacokinetic (PopPK) analysis for molnupiravir exposure was conducted using 4202 NHC plasma concentrations collected in 1207 individuals from a phase I trial in healthy participants, a phase IIa trial in non-hospitalized participants with COVID-19, a phase II trial in hospitalized participants with COVID-19, and a phase II/III trial in non-hospitalized participants with COVID-19.

Frequent allopolyploidy with distant progenitors in the moss genera Physcomitrium and Entosthodon (Funariaceae) identified via subgenome phasing of targeted nuclear genes.

Allopolyploids represent a new frontier in species discovery among embryophytes. Within mosses, allopolyploid discovery is challenged by low morphological complexity. The rapid expansion of sequencing approaches in addition to computational developments to identifying genome merger and whole-genome duplication using variation among nuclear loci representing homeologs has allowed for increased allopolyploid discovery among mosses.

Subgroup analysis of phase 2 study of ceftolozane/tazobactam in neonates and young infants with pyelonephritis.

Ceftolozane/tazobactam is approved for the treatment of patients from birth to <18 y old with complicated urinary tract infections (cUTI). This post hoc analysis evaluated the safety, efficacy, and pharmacokinetics (PK) of ceftolozane/tazobactam compared with meropenem in neonates and young infants. NCT03230838 was a phase 2, randomized, active comparator-controlled, double-blind study of patients from birth to <18 y of age with cUTI, including pyelonephritis, given ceftolozane/tazobactam or meropenem in a 3:1 ratio.

Impact of Molnupiravir Treatment on Patient-Reported COVID-19 Symptoms in the Phase 3 MOVe-OUT Trial: A Randomized, Placebo-Controlled Trial.

Background: Molnupiravir is an orally administered antiviral authorized for COVID-19 treatment in adults at high risk of progression to severe disease. Here, we report secondary and post hoc analyses of participants' self-reported symptoms in the MOVe-OUT trial, which evaluated molnupiravir initiated within 5 days of symptom onset in nonhospitalized, unvaccinated adults with mild-to-moderate, laboratory-confirmed COVID-19.

Methods: Eligible participants completed a 15-item symptom diary daily from day 1 (randomization) through day 29, rating symptom severity as "none," "mild," "moderate," or "severe"; loss of smell and loss of taste were rated as "yes" or "no.

Hybrid Immunity Provides Protective Advantage Over Vaccination or Prior Remote Coronavirus Disease 2019 Alone.

Background: The protective efficacy of prior coronavirus disease 2019 (COVID-19) with or without vaccination remains unknown. This study sought to understand if 2 or more messenger RNA (mRNA) vaccine doses provide additional protection in patients with prior infection, or if infection alone provides comparable protection.

Methods: We conducted a retrospective cohort study of the risk of COVID-19 from 16 December 2020 through 15 March 2022, among vaccinated and unvaccinated patients of all ages with and without prior infection.

Insights into mammalian TE diversity through the curation of 248 genome assemblies.

We examined transposable element (TE) content of 248 placental mammal genome assemblies, the largest de novo TE curation effort in eukaryotes to date. We found that although mammals resemble one another in total TE content and diversity, they show substantial differences with regard to recent TE accumulation. This includes multiple recent expansion and quiescence events across the mammalian tree.

Safety and Efficacy of Ceftolozane/Tazobactam Plus Metronidazole Versus Meropenem From a Phase 2, Randomized Clinical Trial in Pediatric Participants With Complicated Intra-abdominal Infection.

Background: Ceftolozane/tazobactam, a cephalosporin-β-lactamase inhibitor combination, is approved for the treatment of complicated urinary tract infections and complicated intra-abdominal infections (cIAI). The safety and efficacy of ceftolozane/tazobactam in pediatric participants with cIAI were assessed.

Methods: This phase 2 study (NCT03217136) randomized participants to either ceftolozane/tazobactam+metronidazole or meropenem for treatment of cIAI in pediatric participants (<18 years).

Safety and Efficacy of Ceftolozane/Tazobactam Versus Meropenem in Neonates and Children With Complicated Urinary Tract Infection, Including Pyelonephritis: A Phase 2, Randomized Clinical Trial.

Background: Ceftolozane/tazobactam, a cephalosporin-β-lactamase inhibitor combination, active against multidrug-resistant Gram-negative pathogens, is approved for treatment of adults with complicated urinary tract infections (cUTI). Safety and efficacy of ceftolozane/tazobactam in pediatric participants with cUTI, including pyelonephritis, were assessed.

Methods: This phase 2 study (NCT03230838) compared ceftolozane/tazobactam with meropenem for treatment of cUTI in participants from birth to <18 years of age.

Molnupiravir for the treatment of COVID-19 in immunocompromised participants: efficacy, safety, and virology results from the phase 3 randomized, placebo-controlled MOVe-OUT trial.

Purpose: Immunocompromised patients have a potentially increased risk for progression to severe COVID-19 and prolonged replication of SARS-CoV-2. This post hoc analysis examined outcomes among immunocompromised participants in the MOVe-OUT trial.

Methods: In phase 3 of MOVe-OUT, non-hospitalized at-risk adults with mild-to-moderate COVID-19 were randomized to receive molnupiravir 800 mg or placebo twice daily for 5 days.

Key Stakeholder Perspectives of Community Engagement Efforts and the Impact of the Covid-19 Pandemic.

Introduction: The COVID-19 pandemic has disproportionally affected historically marginalized populations and their access to resources and healthcare. In times of crisis, authentic community engagement is more important than ever. This study was Phase 1 of a larger 3-phase study to conduct timely community-engaged research with community members to understand the disproportionate impact of COVID-19 on historically underserved communities.

Ceftolozane/Tazobactam Probability of Target Attainment in Patients With Hospital-Acquired or Ventilator-Associated Bacterial Pneumonia.

Probability of target attainment (PTA) analyses were conducted to support the recommended ceftolozane/tazobactam dosing regimens, adjusted for renal function, in patients with hospital-acquired/ventilator-associated bacterial pneumonia (HABP/VABP). Previously published population pharmacokinetic models describing the disposition of ceftolozane and tazobactam in plasma and epithelial lining fluid (ELF) in patients with HABP/VABP were used to simulate ceftolozane and tazobactam concentration-time profiles in plasma and ELF over the course of 14 days. The simulations were conducted for patients with normal renal function and for patients receiving adjusted doses for mild, moderate, and severe renal impairment.

A phase III, multicenter, double-blind, randomized clinical trial to evaluate the efficacy and safety of ceftolozane/tazobactam plus metronidazole versus meropenem in Chinese participants with complicated intra-abdominal infections.

Objectives: This study aimed to evaluate the efficacy and safety of ceftolozane/tazobactam (C/T) plus metronidazole versus meropenem plus placebo for the treatment of complicated intra-abdominal infection (cIAI) in Chinese adult participants.

Methods: In this phase III clinical trial (NCT03830333), Chinese adult participants with cIAI were randomized 1:1 to receive C/T plus metronidazole or meropenem plus placebo. The primary objective was to assess C/T plus metronidazole for noninferiority versus meropenem for clinical response rate at the test of cure (TOC; 28 ± 2 days after study start) visit in the clinically evaluable population.