Testing the effect of the non-selective opioid PPL-138 in a model of alcohol relapse in the context of PTSD.

Alcohol use disorder (AUD) is a frequent comorbidity in patients suffering from post-traumatic stress disorder (PTSD). Few therapeutic options are available for the individual disorders, and there are currently no drugs specifically shown to treat AUD in patients with comorbid PTSD. As PTSD has been associated with dysregulation of the brain's opioid system, our study aimed to examine the effects of a non-selective opioid compound, PPL-138, for use in co-morbid PTSD and AUD.

The opioid partial agonist PPL-138 reduces alcohol self-administration in rats susceptible to post-traumatic stress disorder.

Background And Purpose: Post-traumatic stress disorder (PTSD) is a significant challenge in the military population and civilians exposed to danger and violence. Alcohol use disorder (AUD) and pain are common PTSD comorbidities, with a higher incidence in PTSD patients than the general population. Approved pharmacotherapies for these disorders are often ineffective and adverse effect potential limits use.

Extended Caffeine for Apnea in Moderately Preterm Infants: The MoCHA Randomized Clinical Trial.

Importance: Hospitalization of moderately preterm infants may be prolonged while waiting for apnea of prematurity to resolve after discontinuing caffeine.

Objective: To evaluate whether extending caffeine treatment reduces the duration of hospitalization.

Design, Setting, And Participants: From February 2019 to December 2022, this randomized clinical trial in 29 US hospitals enrolled infants born at 29 to 33 weeks' gestation who at 33 to 35 weeks' postmenstrual age were receiving caffeine treatment with plans to discontinue it plus receiving full feeds (≥120 mL/kg/d).

Impact of Bowel Diary Completion and Education on Fecal Incontinence Severity.

Objective: This study aimed to determine the effect of a run-in period on fecal incontinence (FI) symptom severity.

Study Design: This study conducted a planned secondary analysis of the run-in period to a study evaluating the effect of 12-week treatment with percutaneous tibial nerve stimulation versus sham in reducing FI severity in women. All participants completed a 4-week run-in period designed to exclude from randomization women whose symptoms reduced below the eligibility threshold after receiving education on FI and completing bowel diaries.

Dietary Intake and Symptom Severity in Women with Fecal Incontinence.

Introduction And Hypothesis: The goal of this study was to determine whether dietary fat/fiber intake was associated with fecal incontinence (FI) severity.

Methods: Planned supplemental analysis of a randomized clinical trial evaluating the impact of 12-week treatment with percutaneous tibial nerve stimulation versus sham in reducing FI severity in women. All subjects completed a food screener questionnaire at baseline.

Social distancing and extremely preterm births in the initial COVID-19 pandemic period.

Hypothesis: Increased social distancing was associated with a lower incidence of extremely preterm live births (EPLB) during the initial COVID-19 pandemic period.

Study Design: Prospective study at the NICHD Neonatal Research Network sites comparing EPLB (22-28 weeks) and extremely preterm intrapartum stillbirths (EPIS) rates during the pandemic period (March-July, weeks 9-30 of 2020) with the reference period (same weeks in 2018 and 2019), correlating with state-specific social distancing index (SDI).

Results: EPLB and EPIS percentages did not significantly decrease (1.

Correlation Between Mobile-Application Electronic Bowel Diary and Validated Questionnaires in Women with Fecal Incontinence.

Introduction And Hypothesis: Despite growing interest in a mobile-app bowel diary to assess fecal incontinence (FI) symptoms, data are limited regarding the correlation between mobile-app diary and questionnaire-based outcomes. The primary aim is to determine whether percentage reduction in FI episodes (FIEs)/week recorded on a mobile-app diary correlates with changes in scores of validated FI-symptom measures from baseline to 12 weeks in women with FI undergoing percutaneous tibial nerve stimulation (PTNS) versus sham.

Methods: This is a planned secondary analysis of a multicenter randomized trial in which women with FI underwent PTNS or sham.

Secular Trends in Patent Ductus Arteriosus Management in Infants Born Preterm in the National Institute of Child Health and Human Development Neonatal Research Network.

We evaluated changes in patent ductus arteriosus (PDA) diagnosis and treatment from 2012 through 2021 in a network of US academic hospitals. PDA treatment decreased among infants born at 26-28 weeks but not among infants born at 22-25 weeks. Rates of indomethacin use and PDA ligation decreased while acetaminophen use and transcatheter PDA closure increased.

Vaginal morphology and position associated with prolapse recurrence after vaginal surgery: A secondary analysis of the DEMAND study.

Objective: To identify vaginal morphology and position factors associated with prolapse recurrence following vaginal surgery.

Design: Secondary analysis of magnetic resonance images (MRI) of the Defining Mechanisms of Anterior Vaginal Wall Descent cross-sectional study.

Setting: Eight clinical sites in the US Pelvic Floor Disorders Network.

Characteristics associated with subjective and objective measures of treatment success in women undergoing percutaneous tibial nerve stimulation vs sham for accidental bowel leakage.

Introduction And Hypothesis: In randomized trials both percutaneous tibial nerve stimulation (PTNS) and sham result in clinically significant improvements in accidental bowel leakage (ABL). We aimed to identify subgroups who may preferentially benefit from PTNS in women enrolled in a multicenter randomized trial.

Methods: This planned secondary analysis explored factors associated with success for PTNS vs sham using various definitions: treatment responder using three cutoff points for St.

FKBP5 inhibitors modulate alcohol drinking and trauma-related behaviors in a model of comorbid post-traumatic stress and alcohol use disorder.

Post-traumatic stress disorder (PTSD) leads to enhanced alcohol drinking and development of alcohol use disorder (AUD). Identifying shared neural mechanisms might help discover new therapies for PTSD/AUD. Here, we employed a rat model of comorbid PTSD/AUD to evaluate compounds that inhibit FK506-binding protein 51 (FKBP5), a co-chaperone modulator of glucocorticoid receptors implicated in stress-related disorders.

Effect of the glucocorticoid receptor antagonist PT150 on acquisition and escalation of fentanyl self-administration following early-life stress.

There is comorbidity between posttraumatic stress disorder (PTSD) and opioid use disorder (OUD), perhaps because PTSD-like stressful experiences early in life alter the hypothalamic-pituitary-adrenal stress axis to increase the risk for OUD. The present study determined if the glucocorticoid receptor antagonist PT150 reduces the escalation of fentanyl intake in rats exposed to a "two-hit" model of early-life stress (isolation rearing and acute stress). Male and female rats were raised during adolescence in either isolated or social housing and then were given either a single acute stress (restraint and cold-water swim) or control treatment in young adulthood.

Placental protein levels in maternal serum are associated with adverse pregnancy outcomes in nulliparous patients.

Background: The Eunice Kennedy Shriver National Institute of Child Health and Human Development Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be was established to investigate the underlying causes and pathophysiological pathways associated with adverse pregnancy outcomes in nulliparous gravidas.

Objective: This study aimed to study placental physiology and identify novel biomarkers concerning adverse pregnancy outcomes, including preterm birth (medically indicated and spontaneous), preeclampsia, small-for-gestational-age neonates, and stillbirth. We measured levels of placental proteins in the maternal circulation in the first 2 trimesters of pregnancy.

Percutaneous Tibial Nerve Stimulation vs Sham Stimulation for Fecal Incontinence in Women: NeurOmodulaTion for Accidental Bowel Leakage Randomized Clinical Trial.

Introduction: To determine whether percutaneous tibial nerve stimulation (PTNS) is superior to sham stimulation for the treatment of fecal incontinence (FI) in women refractory to first-line treatments.

Methods: Women aged 18 years or older with ≥3 months of moderate-to-severe FI that persisted after a 4-week run-in phase were randomized 2:1 (PTNS:sham stimulation) to 12 weekly 30-minute sessions in this multicenter, single-masked, controlled superiority trial. The primary outcome was change from baseline FI severity measured by St.

Duration of noninvasive respiratory support and risk for bronchopulmonary dysplasia or death.

Objective: To determine whether the duration of noninvasive respiratory support exposure is associated with bronchopulmonary dysplasia (BPD) or death in preterm infants.

Methods: Multicenter, retrospective study of infants born at <29 weeks' gestation. The association between days on noninvasive respiratory support and BPD or death was determined using instrumental variable techniques and generalized propensity score matching to account for potential confounding by illness severity.

Characteristics Associated With Treatment Failure 1 Year After Midurethral Sling in Women With Mixed Urinary Incontinence.

Objective: To evaluate characteristics associated with treatment failure 1 year after midurethral sling in women with mixed urinary incontinence.

Methods: Four-hundred three women who participated in a randomized trial that compared midurethral sling and behavioral and pelvic floor muscle therapy (combined group) compared with midurethral sling alone for mixed incontinence with 1-year follow-up data were eligible for this planned secondary analysis. Overall treatment failure was defined as meeting criteria for subjective or objective failure or both.

The GABA receptor positive allosteric modulator ASP8062 reduces operant alcohol self-administration in male and female Sprague Dawley rats.

Rationale: Pre-clinical evidence implicates the GABAergic system in mediating the reinforcing effects of alcohol and offers a therapeutic target for alcohol use disorder (AUD). The orthosteric GABA receptor agonist baclofen decreases alcohol self-administration in animals and alcohol use in humans; however side effects limit its utility. Pre-clinical evidence shows positive allosteric GABA receptor modulators also decrease alcohol self-administration without untoward side effects.

Effects of the glucocorticoid receptor antagonist PT150 on stress-induced fentanyl seeking in male and female rats.

Rationale: Opioid use disorder (OUD) is highly comorbid with stress-related disorders, and stress can serve as a trigger for reinstatement of drug seeking. Glucocorticoid receptor (GR) antagonists such as mifepristone (RU-486) may be effective against stress-induced drug seeking. In the current study, PT150 (formerly ORG-34517), a more selective GR antagonist, was tested using two models of stress-induced drug seeking, namely footshock and yohimbine.

Early Determination of Prognosis in Neonatal Moderate or Severe Hypoxic-Ischemic Encephalopathy.

Background And Objectives: Early determination of prognosis is important in neonates with hypoxic-ischemic encephalopathy (HIE). Our objective was to test scoring systems developed earlier (original scoring system) and develop new prognostic models.

Methods: Secondary analysis of data from the multicenter randomized controlled trial of longer, deeper, or usual care cooling in neonatal HIE (NCT01192776) that enrolled 364 neonates diagnosed with moderate or severe HIE.

Performance, acceptability, and validation of a phone application bowel diary.

Aims: To assess performance, acceptability, external validity, and reliability of a phone application electronic bowel diary (PFDN Bowel eDiary).

Methods: Women reporting refractory accidental bowel leakage (ABL) were enrolled in a randomized, crossover trial evaluating paper versus eDiary documentation of bowel movements (BM) and fecal incontinence episodes (FIE). Events were characterized by the presence or absence of urgency and Bristol stool scale consistency.