A Second-Generation Oral SARS-CoV-2 Main Protease Inhibitor Clinical Candidate for the Treatment of COVID-19.

Despite the record-breaking discovery, development and approval of vaccines and antiviral therapeutics such as Paxlovid, coronavirus disease 2019 (COVID-19) remained the fourth leading cause of death in the world and third highest in the United States in 2022. Here, we report the discovery and characterization of PF-07817883, a second-generation, orally bioavailable, SARS-CoV-2 main protease inhibitor with improved metabolic stability versus nirmatrelvir, the antiviral component of the ritonavir-boosted therapy Paxlovid. We demonstrate the in vitro pan-human coronavirus antiviral activity and off-target selectivity profile of PF-07817883. PF-07817883 also demonstrated oral efficacy in a mouse-adapted SARS-CoV-2 model at plasma concentrations equivalent to nirmatrelvir. The preclinical in vivo pharmacokinetics and metabolism studies in human matrices are suggestive of improved oral pharmacokinetics for PF-07817883 in humans, relative to nirmatrelvir. In vitro inhibition/induction studies against major human drug metabolizing enzymes/transporters suggest a low potential for perpetrator drug-drug interactions upon single-agent use of PF-07817883.

Prenatal care in US birth centers: Midwives' perceptions of contributors to birthing People's confidence in physiologic birth.

OBJECTIVE: The purpose of this study was to describe US freestanding birth center models of prenatal care and to examine how the components of this care contribute to birthing people's confidence in their ability to have a physiologic birth. DESIGN: This was a qualitative descriptive study utilizing semi-structured interviews with birth center midwives. Data were analyzed using thematic analysis, constant comparative method and consensus coding to ensure rigor. SETTING AND PARTICIPANTS: Midwives from six urban and rural freestanding birth centers in a Midwestern US state were interviewed. Twelve birth center midwives participated. FINDINGS: Six themes emerged: the birth center physical space and organization of care, dimensions of midwifery care within the birth center, continuity of care and seamless service, the empowered birthing person, physiologic birth as normative, and the hospital paradigm and US cultures of birth. KEY CONCLUSIONS: We identified significant components of birth center models of prenatal care that midwives believe enhance birthing people's confidence for physiologic childbirth. These components may be considered for application to other settings and may improve perinatal care and outcomes.

Improved Self-Assessed Collaboration Through Interprofessional Education: Midwifery Students and Obstetrics and Gynecology Residents Learning Together.

INTRODUCTION: Research suggests that interprofessional education, bringing learners together to learn about, with, and from each other, improves health professions education and can improve health outcomes. Little research has measured outcomes of interprofessional education between midwifery students and obstetrics and gynecology residents. The purpose of this study was to examine self-assessed interprofessional and collaborative competencies among midwifery students and obstetrics and gynecology residents. METHODS: Baseline self-assessed interprofessional and collaborative competencies were compared with follow-up measurements to evaluate learners' experiences over an 11-month study period. Participants were midwifery students and obstetrics and gynecology residents who experienced interprofessional learning activities. The Interprofessional Education Collaborative Competency Self-Assessment Survey (IPEC Survey) and Interprofessional Collaborative Competency Attainment Survey (ICCAS) were used. RESULTS: Of 256 learners at 4 demonstration sites, 223 (87%) completed the baseline, and 121 of 237 eligible learners (51%) completed the follow-up surveys. The IPEC Survey total score (t = 2.31, P = .02) and interaction subscale (t = 2.85, P = .005) and ICCAS score (t = 4.04, P = .001) increased for midwifery students but not obstetrics and gynecology residents on the IPEC Survey (t = 0.32, P = .75) and ICCAS (t = -0.05, P = .96) measures. Midwifery students (87%) and residents (57%) reported improved overall ability to collaborate. Learners responding to 3 open-ended questions valued team-based experiences, including learning how to communicate with each other; appreciated learning each other's education and scope of practice; and recommended skills development including uncommon clinical events, case discussions, and direct clinical care. DISCUSSION: This study advanced knowledge about interprofessional education between midwifery students and obstetrics and gynecology residents. Midwifery students improved in self-assessed interprofessional and collaborative competencies. Most learners reported better interprofessional collaboration skills and were positive about future interprofessional learning. This evaluation approach is available for other programs implementing or extending interprofessional education.