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Introduction: Perioperative opioid analgesia has been extensively reexamined during the opioid epidemic. Multiple studies have demonstrated over prescription of opioids, demonstrating the need for change in prescribing practices. A standard opioid prescribing protocol was implemented to evaluate opioid prescribing trends and practices. Objectives: To evaluate opioid use after primary ventral, inguinal, and incisional hernia repair and to assess clinical factors that may impact opioid prescribing and consumption. Secondary outcomes include the number of refills, patients without opioid requirement, difference in opioid use based on patient characteristics and adherence to prescribing protocol. Methods: This is a prospective observational study examining patients undergoing inguinal, primary ventral and incisional hernias between February and November 2019. A standardized prescribing protocol was implemented and utilized for postoperative prescribing. All data was captured in the abdominal core health quality collaborative (ACHQC) and opioid use was standardized via morphine milligram equivalents (MME). Results: 389 patients underwent primary ventral, incisional, and inguinal hernia repair, with a total of 285 included in the final analysis. 170 (59.6%) of patients reported zero opioid use postoperatively. Total opioid MME prescribed and high MME consumption were significantly higher after incisional hernia repair with a greater number of refills were required. Compliance with prescribing protocol resulted in lower MME prescription, but not actual lower MME consumption. Conclusions: Implementation of a standardized protocol for opioid prescribing after surgery decreases the total MME prescribed. Compliance with our protocol significantly reduced this disparity, which has the potential for decreasing abuse, misuse, and diversion of opioids by better estimating actual postoperative analgesic requirements. [ABSTRACT FROM AUTHOR]

Reducing treatment burden is a priority for people with cystic fibrosis, whose health has benefited from using new modulators that substantially increase CFTR protein function. The SIMPLIFY study aimed to assess the effects of discontinuing nebulised hypertonic saline or dornase alfa in individuals using the CFTR modulator elexacaftor plus tezacaftor plus ivacaftor (ETI). The SIMPLIFY study included two parallel, multicentre, open-label, randomised, controlled, non-inferiority trials at 80 participating clinics across the USA in the Cystic Fibrosis Therapeutics Development Network. We included individuals with cystic fibrosis aged 12–17 years with percent predicted FEV 1 (ppFEV 1) of 70% or more, or those aged 18 years or older with ppFEV 1 of 60% or more, if they had been taking ETI and either (or both) mucoactive therapies (≥3% hypertonic saline or dornase alfa) for at least 90 days before screening. Participants on both hypertonic saline and dornase alfa were randomly assigned to one of the two trials, and those on a single therapy were assigned to the applicable trial. All participants were then randomly assigned 1:1 to continue or discontinue therapy for 6 weeks using permuted blocks of varying size, stratified by baseline ppFEV 1 (week 0; ≥90% or <90%), single or concurrent use of hypertonic saline and dornase alfa, previous SIMPLIFY study participation (yes or no), and age (≥18 or <18 years). For participants randomly assigned to continue their therapy during a given trial, this therapy was instructed to be taken at least once daily according to each participant's pre-existing, clinically prescribed regimen. Hypertonic saline concentration was required to be at least 3%. The primary objective for each trial was to determine whether discontinuing was non-inferior to continuing, measured by the 6-week change in ppFEV 1 in the per-protocol population. We established a non-inferiority margin of –3% for the difference between groups in the 6-week change in ppFEV 1. Safety outcomes were analysed in the intention-to-treat population. This study is registered with ClinicalTrials.gov , NCT04378153. From Aug 25, 2020, to May 25, 2022, a total of 672 unique participants were screened for eligibility for one or both trials, resulting in 847 total random assignments across both trials with 594 unique participants. 370 participants were randomly assigned in the hypertonic saline trial and 477 in the dornase alfa trial. Participants across both trials had an average ppFEV 1 of 96·9%. Discontinuing treatment was non-inferior to continuing treatment with respect to the absolute 6-week change in ppFEV 1 in both the hypertonic saline trial (–0·19% [95% CI –0·85 to 0·48] in the discontinuation group [n=133] vs 0·14% [–0·51 to 0·78] in the continuation group [n=140]; between-group difference –0·32% [–1·25 to 0·60]) and dornase alfa trial (0·18% [–0·38 to 0·74] in the discontinuation group [n=199] vs –0·16% [–0·73 to 0·41] in the continuation group [n=193]; between-group difference 0·35% [–0·45 to 1·14]), with consistent results in the intention-to-treat populations. In the hypertonic saline trial, 64 (35%) of 184 in the discontinuation group versus 44 (24%) of 186 participants in the continuation group and, in the dornase alfa trial, 89 (37%) of 240 in the discontinuation group versus 55 (23%) of 237 in the continuation group had at least one adverse event. In individuals with cystic fibrosis on ETI with relatively well preserved pulmonary function, discontinuing daily hypertonic saline or dornase alfa for 6 weeks did not result in clinically meaningful differences in pulmonary function when compared with continuing treatment. [ABSTRACT FROM AUTHOR]

Discusses importance of family therapy as part of armamentarium of school-based social work. Provides rationale for school-based intervention. Argues that family therapy should be emphasized in school because school social workers are in strategic position to assess family dysfunction. Notes that adolescents' problems must be understood in context of improperly functioning families before help can be effective. (Author/NB)

CX‑072 is an anti‑PD‑L1 (programmed death ligand 1) Probody therapeutic (Pb‐Tx) designed to be preferentially activated by proteases in the tumor microenvironment and not in healthy tissue. Here, we report the model‐informed drug development of CX‐072. A quantitative systems pharmacology (QSP) model that captured known mechanisms of Pb‐Tx activation, biodistribution, elimination, and target engagement was used to inform clinical translation. The QSP model predicted that a trough level of masked CX‐072 (intact CX‐072) of 13–99 nM would correspond to a targeted, 95% receptor occupancy in the tumor. The QSP model predictions appeared consistent with preliminary human single‑dose pharmacokinetic (PK) data following CX‐072 0.03–30.0 mg/kg as monotherapy: CX‑072 circulated predominantly as intact CX‐072 with minimal evidence of target‐mediated drug disposition. A preliminary population PK (POPPK) analysis based upon 130 subjects receiving 0.03–30.0 mg/kg as monotherapy included a provision for a putative time‐dependent and dose‐dependent antidrug antibody (ADA) effect on clearance (CL) with a mixture model. Preliminary POPPK estimates for intact CX‐072 time‐invariant CL and volume of distribution were 0.306 L/day and 4.84 L, respectively. Exposure–response analyses did not identify statistically significant relationships with best change from baseline sum of measurements and either adverse events of grade ≥ 3 or of special interest. Simulations suggested that > 95% of patients receiving CX‐072 10 mg/kg every two weeks would exceed the targeted trough level regardless of ADA, and that dose adjustment by body weight was not necessary, supporting a fixed 800 mg dose for evaluation in phase II. [ABSTRACT FROM AUTHOR]

Background: Recent data on opioid consumption indicate that patients typically require far less than is prescribed. Prisma Health Upstate Hernia Center adopted standardized postoperative prescribing after hernia repair and began tracking patient-reported opioid utilization. The aim of this study is to evaluate patient opioid use after hernia repair in order to guide future prescribing.Methods: All patients who underwent primary ventral (umbilical and epigastric), incisional, and inguinal hernia repair between February and May 2019 were reviewed. Patients reported the number of opioid pills taken at their first postoperative visit and documented either in the progress note or in the Americas Hernia Society Quality Collaborative (AHSQC) patient-reported outcomes (PRO) questionnaire. All demographic, operative, and outcomes data were captured prospectively in the AHSQC. Opioid use reported as milligram morphine equivalents (MME).Results: A total of 162 surgeries were performed during the study period, and 107 had patient-reported opioid use for analysis. Inguinal hernia repair was performed in 36 patients, 10 primary ventral hernia repairs, and 61 incisional hernia repairs. No opioid use was reported in 63.9% of inguinal hernias, 60% of primary ventral hernias, and 20% of incisional hernias. Inguinal hernia patients consumed a mean of 10.5 MME, primary ventral patients 11 MME, and incisional hernia patients 78.5 MME.Conclusion: Patients require little to no opioid after primary ventral or inguinal hernia repair and opioid-free surgery is feasible. Incisional hernia is more heterogenous, but the majority of patients still required less opioid than previously thought. [ABSTRACT FROM AUTHOR]

New voluntary agencies have grown out of the social changes of the 1960s. These grass-roots organizations, such as coffee houses, legal aid societies, and community counseling centers, differ in program style and attitude from traditional social agencies and may be more effective with alienated and cynical young people. (SJL)