Association of initial opioid prescription duration and an opioid refill by pain diagnosis: Evidence from outpatient settings in ten US health systems.

OBJECTIVE: The Centers for Disease Control and Prevention's 2022 Clinical Practice Guideline for Prescribing Opioids for Pain cautioned that inflexible opioid prescription duration limits may harm patients. Information about the relationship between initial opioid prescription duration and a subsequent refill could inform prescribing policies and practices to optimize patient outcomes. We assessed the association between initial opioid duration and an opioid refill prescription. METHODS: We conducted a retrospective cohort study of adults ≥19 years of age in 10 US health systems between 2013 and 2018 from outpatient care with a diagnosis for back pain without radiculopathy, back pain with radiculopathy, neck pain, joint pain, tendonitis/bursitis, mild musculoskeletal pain, severe musculoskeletal pain, urinary calculus, or headache. Generalized additive models were used to estimate the association between opioid days' supply and a refill prescription. RESULTS: Overall, 220,797 patients were prescribed opioid analgesics upon an outpatient visit for pain. Nearly a quarter (23.5%) of the cohort received an opioid refill prescription during follow-up. The likelihood of a refill generally increased with initial duration for most pain diagnoses. About 1 to 3 fewer patients would receive a refill within 3 months for every 100 patients initially prescribed 3 vs. 7 days of opioids for most pain diagnoses. The lowest likelihood of refill was for a 1-day supply for all pain diagnoses, except for severe musculoskeletal pain (9 days' supply) and headache (3-4 days' supply). CONCLUSIONS: Long-term prescription opioid use increased modestly with initial opioid prescription duration for most but not all pain diagnoses examined.

Family-Based Telehealth Initiative to Improve Nutrition and Physical Activity for Children With Obesity and Its Utility During COVID-19: A Mixed Methods Evaluation.

Guidelines recommend primary care providers refer children with obesity to behavioral interventions, but given limited program availability, access, and parental engagement, referrals remain rare. We developed telehealth coaching interventions for families whose children received care at a health system in Pennsylvania, United States in 2019-2020. Intervention referrals were facilitated by the pediatrician and/or project team for 6-12-year-old children with obesity following well-child visits. Participants chose one of three 26-week interventions focused on healthy eating, physical activity, or a hybrid clinical/nutrition intervention. Interventions engaged parents as change agents, enhancing self-efficacy to model and reinforce behavior and providing resources to help create a healthy home environment. We enrolled 77 of 183 eligible parent/child dyads. We used mixed methods to evaluate the interventions. Repeated measures models among participants showed significant reductions in obesogenic nutrition behaviors post-intervention and at 1-year follow-up, including a reduction in sugar-sweetened beverage intake of 2.14 servings/week (95% confidence interval: -3.45, -0.82). There were also improvements in obesoprotective nutrition behaviors (e.g., frequency of family meals, parental self-efficacy related to meal management). One year post-baseline, we observed no significant differences in changes in body mass index (BMI) z-scores comparing child participants with matched controls. Given potential impacts of COVID-19 community restrictions on study outcomes, we conducted qualitative interviews with 13 participants during restrictions, which exemplified how disrupted routines constrained children's healthy behaviors but that intervention participation prepared parents by providing cooking and physical activities at home. Findings support the potential of a telehealth-delivered nutrition intervention to support adoption of healthy weight behaviors.

Haploinsufficiency at the protein kinase A RI alpha gene locus leads to fertility defects in male mice and men.

Carney complex (CNC) is a familial multiple neoplasia syndrome characterized by spotty skin pigmentation, cardiac and cutaneous myxomas, and endocrine tumors. CNC is inherited as an autosomal dominant trait and is transmitted with greater frequency by women vs. men. Nearly two thirds of CNC patients are heterozygous for inactivating mutations in the gene encoding the protein kinase A (PKA) type I alpha regulatory subunit (RI alpha), PRKAR1. We report here that male mice heterozygous for the Prkar1a gene have severely reduced fertility. Sperm from Prkar1a heterozygous mice are morphologically abnormal and reduced in number. Genetic rescue experiments reveal that this phenotype results from elevated PKA catalytic activity in germ cells as early as the pachytene stage of spermatogenesis. Consistent with this defect in the male mutant mice, sperm from CNC patients heterozygous for PRKAR1A mutations were also found to be morphologically aberrant and decreased in number. We conclude that unregulated PKA activity in male meiotic or postmeiotic germ cells leads to structural defects in mature sperm and results in reduced fertility in mice and humans, contributing to the strikingly reduced transmission of PRKAR1A inactivating mutations by male patients with CNC.