Prescription rebate guarantees: employer insights.

Objectives: To describe (1) rebate arrangements for specialty drugs, (2) the use and influence of benefits brokers and consultants, and (3) the importance of rebate-related factors when selecting a pharmacy benefits manager (PBM) among a sample of employers with self-funded pharmacy benefits.

Study Design: A national survey of employer drug benefit decision makers (N = 110) for organizations with self-insured pharmacy benefits.

Methods: We summarized respondents' current rebate agreements for specialty drugs and their perspectives on the importance of rebates and rebate guarantees overall as well as by type of rebate agreement and by the person or entity identified as most influential in rebate strategy.

Subsequent Indications in Oncology Drugs: Pathways, Timelines, and the Inflation Reduction Act.

Introduction: Recent research has raised questions about potential unintended consequences of the Inflation Reduction Act's Drug Price Negotiation Program (DPNP), suggesting that the timelines introduced by the law may reduce manufacturer incentives to invest in post-approval research towards additional indications. Given the role of multiple indications in expanding treatment options in patients with cancer, IRA-related changes to development incentives are especially relevant in oncology. This study aimed to describe heterogeneous drug-level trajectories and timelines of subsequent indications in a cohort of recently approved, multi-indication oncology drugs, including overall, across subgroups of drugs characterized by the timing and pace of additional indications, and by drug type (i.

The accelerated approval program for oncology drugs: celebrating more than 250,000 life-years gained and counting.

This commentary explores how 2 recently published studies evaluating the clinical benefit of the FDA's accelerated approval program for oncology drugs came to different conclusions.

Unintended consequences of the Inflation Reduction Act: clinical development toward subsequent indications.

Objectives: To describe the clinical development landscape for high-spend Medicare Part D small molecule drugs and illustrate the potential impact of the Inflation Reduction Act of 2022 (IRA) on research and development investments toward subsequent indications.

Study Design: Descriptive analysis of research and development time lines of small molecule drugs in the top 50 of 2020 Medicare Part D spending using publicly available dates when pivotal clinical trials were first posted to ClinicalTrials.gov and FDA approval dates for initial and subsequent indications.

Association of Elevated Serum Aldosterone Concentrations in Pregnancy with Hypertension.

Emerging evidence indicates a previously unrecognized, clinically relevant spectrum of abnormal aldosterone secretion associated with hypertension severity. It is not known whether excess aldosterone secretion contributes to hypertension during pregnancy. We quantified aldosterone concentrations and angiotensin peptides in serum (using liquid chromatography with tandem mass spectrometry) in a cohort of 128 pregnant women recruited from a high-risk obstetrics clinic and followed prospectively for the development of gestational hypertension, pre-eclampsia, superimposed pre-eclampsia, chronic hypertension, or remaining normotensive.

Good health policy requires high-quality evidence. let's remember that with drug pricing.

In the health spending debate, what policy makers need most is an honest, realistic, and evidence-based discussion. Unfortunately, many studies in the public arena fall far short.

Modeling demersal fish and benthic invertebrate assemblages in support of marine conservation planning.

Marine classification schemes based on abiotic surrogates often inform regional marine conservation planning in lieu of detailed biological data. However, these schemes may poorly represent ecologically relevant biological patterns required for effective design and management strategies. We used a community-level modeling approach to characterize and delineate representative mesoscale (tens to thousands of kilometers) assemblages of demersal fish and benthic invertebrates in the Northwest Atlantic.

Rural residency as a risk factor for severe maternal morbidity.

Purpose: The goal of this study was to evaluate how rural/urban status and other risk factors alter women's odds of severe maternal morbidity (SMM) at delivery.

Methods: This study used 48,608 Kentucky resident delivery hospitalization records from 2017. We used multiple logistic regression with interaction terms to evaluate the moderating effect of rural/urban residence with other risk factors.

Smoking during pregnancy increases chemerin expression in neonatal tissue.

New Findings: What is the central question of this study? Is chemerin, an adipokine implicated in obesity, increased in neonates following in utero cigarette smoke exposure. What is the main finding and its importance? Chemerin mRNA expression was increased and chemerin DNA methylation was decreased in babies born to mothers who smoked during pregnancy. These data provide a potential mechanism that may be mediating the increased obesity risk in individuals that are born to mothers who smoked during pregnancy.

Vaginal progesterone is as effective as cervical cerclage to prevent preterm birth in women with a singleton gestation, previous spontaneous preterm birth, and a short cervix: updated indirect comparison meta-analysis.

Background: An indirect comparison meta-analysis published in 2013 reported that both vaginal progesterone and cerclage are equally efficacious for preventing preterm birth and adverse perinatal outcomes in women with a singleton gestation, previous spontaneous preterm birth, and a sonographic short cervix. The efficacy of vaginal progesterone has been challenged after publication of the OPPTIMUM study. However, this has been resolved by an individual patient-data meta-analysis (Am J Obstet Gynecol.

Vaginal progesterone for preventing preterm birth and adverse perinatal outcomes in singleton gestations with a short cervix: a meta-analysis of individual patient data.

Background: The efficacy of vaginal progesterone for preventing preterm birth and adverse perinatal outcomes in singleton gestations with a short cervix has been questioned after publication of the OPPTIMUM study.

Objective: To determine whether vaginal progesterone prevents preterm birth and improves perinatal outcomes in asymptomatic women with a singleton gestation and a midtrimester sonographic short cervix.

Study Design: We searched MEDLINE, EMBASE, LILACS, and CINAHL (from their inception to September 2017); Cochrane databases; bibliographies; and conference proceedings for randomized controlled trials comparing vaginal progesterone vs placebo/no treatment in women with a singleton gestation and a midtrimester sonographic cervical length ≤25 mm.

Nipped in the bud: mesograzer feeding preference contributes to kelp decline.

Small invertebrate grazers can disproportionately reduce plant fitness by discriminately consuming valuable tissues, but the context and attendant consequences of this activity at higher levels of ecological organization rarely are considered. To assess the impact of a gastropod mesograzer Lacuna vincta on fecundity and potential reproductive output of the habitat-forming kelp Saccharina latissima, we measured the intensity and distribution of grazing damage on kelp blades at five sites of varying kelp density, during the annual reproductive peak (October-November) in Nova Scotia. We found most grazing damage on reproductive individuals consisted of superficial excavations, and was concentrated on the central sorus (region where sporangia develop) compared to the vegetative blade margins.

Prevention of preterm birth with vaginal progesterone or 17-alpha-hydroxyprogesterone caproate: a critical examination of efficacy and safety.

Progestogens are the first drugs to demonstrate reproducibly a reduction in the rate of early preterm birth. The efficacy and safety of progestogens are related to individual pharmacologic properties of each drug within this class of medication and characteristics of the population that is treated. The synthetic 17-hydroxyprogesterone caproate and natural progesterone have been studied with the use of a prophylactic strategy in women with a history of preterm birth and in women with a multiple gestation.

The use of digital peripheral artery tonometry to detect endothelial dysfunction in pregnant women who smoke.

Objective: We hypothesized that, as has been shown outside of pregnancy, endothelial dysfunction would be seen in a dose-dependent fashion among women who smoke in the midtrimester of pregnancy.

Study Design: Endothelial function in women with singleton pregnancies between 16 and 23 weeks was analyzed utilizing the Endo-PAT2000 device (Itamar Medical Ltd., Caesarea, Israel) and expressed as a reactive hyperemia ratio (RHI).

Up-regulation of oxytocin receptor expression at term is related to maternal body mass index.

Background: The likelihood of cesarean is in part related to maternal body mass index (BMI). Myometrial changes may be responsible.

Methods: Myometrial biopsies were collected from the upper edge of the hysterotomy from women undergoing scheduled cesarean with term, singleton gestations.

Vaginal progesterone vs. cervical cerclage for the prevention of preterm birth in women with a sonographic short cervix, previous preterm birth, and singleton gestation: a systematic review and indirect comparison metaanalysis.

Objective: No randomized controlled trial has compared vaginal progesterone and cervical cerclage directly for the prevention of preterm birth in women with a sonographic short cervix in the mid trimester, singleton gestation, and previous spontaneous preterm birth. We performed an indirect comparison of vaginal progesterone vs cerclage using placebo/no cerclage as the common comparator.

Study Design: Adjusted indirect metaanalysis of randomized controlled trials.

The safety of progesterone and 17-hydroxyprogesterone caproate administration for the prevention of preterm birth: an evidence-based assessment.

The safety of supplemental progestin therapy during pregnancy reflects whether an agent exclusively promotes or potentially inhibits progestational cellular functions and whether treatment incites a metabolic derangement or other pathophysiology to initiate rare untoward events. No safety signal has been identified from intravaginal administration of natural progesterone from phase III clinical trials. The Food and Drug Administration has identified a legitimate safety signal regarding second-trimester miscarriage and stillbirth with exposure to 17-hydroxyprogesterone caproate (17-OHPC).

Vaginal progesterone in women with an asymptomatic sonographic short cervix in the midtrimester decreases preterm delivery and neonatal morbidity: a systematic review and metaanalysis of individual patient data.

Objective: To determine whether the use of vaginal progesterone in asymptomatic women with a sonographic short cervix (≤ 25 mm) in the midtrimester reduces the risk of preterm birth and improves neonatal morbidity and mortality.

Study Design: Individual patient data metaanalysis of randomized controlled trials.

Results: Five trials of high quality were included with a total of 775 women and 827 infants.

Augmenting myometrial healing after cesarean delivery: use of an adjuvant biologic graft placement in an ovine model.

We sought to reduce long-term complications after cesarean delivery by improving myometrial healing. Eight sheep (three with twins) underwent cesarean delivery. Hysterotomy sites were repaired in equal parts by suture alone or suture with a juxtaposed graft (Cook Medical, Bloomington, IN).