Efficacy of Omaveloxolone in Friedreich's Ataxia: Delayed-Start Analysis of the MOXIe Extension.

BACKGROUND: MOXIe was a two-part study evaluating the safety and efficacy of omaveloxolone in patients with Friedreich's ataxia, a rare, progressive neurological disease with no proven therapy. MOXIe part 2, a randomized double-blind placebo-controlled trial, showed omaveloxolone significantly improved modified Friedreich's Ataxia Rating Scale (mFARS) scores relative to placebo. Patients who completed part 1 or 2 were eligible to receive omaveloxolone in an open-label extension study. OBJECTIVE: The delayed-start study compared mFARS scores at the end of MOXIe part 2 with those at 72 weeks in the open-label extension period (up to 144 weeks) for patients initially randomized to omaveloxolone versus those initially randomized to placebo. METHODS: We performed a noninferiority test to compare the difference between treatment groups (placebo to omaveloxolone versus omaveloxolone to omaveloxolone) using a single mixed model repeated measures (MMRM) model. In addition, slopes of the change in mFARS scores were compared between both groups in the open-label extension. RESULTS: The noninferiority testing demonstrated that the difference in mFARS between omaveloxolone and placebo observed at the end of placebo-controlled MOXIe part 2 (-2.17 ± 1.09 points) was preserved after 72 weeks in the extension (-2.91 ± 1.44 points). In addition, patients previously randomized to omaveloxolone in MOXIe part 2 continued to show no worsening in mFARS relative to their extension baseline through 144 weeks. CONCLUSIONS: These results support the positive results of MOXIe part 2 and indicate a persistent benefit of omaveloxolone treatment on disease course in Friedreich's ataxia. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Safety and Efficacy of Omaveloxolone in Friedreich Ataxia (MOXIe Study).

OBJECTIVE: Friedreich ataxia (FA) is a progressive genetic neurodegenerative disorder with no approved treatment. Omaveloxolone, an Nrf2 activator, improves mitochondrial function, restores redox balance, and reduces inflammation in models of FA. We investigated the safety and efficacy of omaveloxolone in patients with FA. METHODS: We conducted an international, double-blind, randomized, placebo-controlled, parallel-group, registrational phase 2 trial at 11 institutions in the United States, Europe, and Australia (NCT02255435, EudraCT2015-002762-23). Eligible patients, 16 to 40 years of age with genetically confirmed FA and baseline modified Friedreich's Ataxia Rating Scale (mFARS) scores between 20 and 80, were randomized 1:1 to placebo or 150mg per day of omaveloxolone. The primary outcome was change from baseline in the mFARS score in those treated with omaveloxolone compared with those on placebo at 48 weeks. RESULTS: One hundred fifty-five patients were screened, and 103 were randomly assigned to receive omaveloxolone (n = 51) or placebo (n = 52), with 40 omaveloxolone patients and 42 placebo patients analyzed in the full analysis set. Changes from baseline in mFARS scores in omaveloxolone (-1.55 ± 0.69) and placebo (0.85 ± 0.64) patients showed a difference between treatment groups of -2.40 ± 0.96 (p = 0.014). Transient reversible increases in aminotransferase levels were observed with omaveloxolone without increases in total bilirubin or other signs of liver injury. Headache, nausea, and fatigue were also more common among patients receiving omaveloxolone. INTERPRETATION: In the MOXIe trial, omaveloxolone significantly improved neurological function compared to placebo and was generally safe and well tolerated. It represents a potential therapeutic agent in FA. ANN NEUROL 2021;89:212-225.

Is legalization of recreational cannabis associated with levels of use and cannabis use disorder among youth in the United States? A rapid systematic review.

Cannabis legalization policies are rapidly changing in the United States. While there are concerns that recreational legalization will negatively affect young people, previous reviews have not provided clear indication of such effects. The purpose of this rapid systematic review was to examine whether recreational legalization was associated with increases in prevalence of cannabis use and use disorder among adolescents and young adults. PubMed/MEDLINE, Embase, Scopus, PsycInfo, Web of Science, Dissertations & Theses Global, the Trip Database, and OpenGrey were searched from date of inception through Marcy 17, 2022 to retrieve all relevant records. English language and human subject filters were applied. Two reviewers screened abstracts and titles, assessed full text articles, and coded the final included articles. Studies including primarily 10- to 19-year-olds were classified as adolescent, and those between 18 and 26 years as young adult. Our search identified 33 research reports (22 with adolescent samples; 14 young adult). For adolescents, ten studies reported no change in use prevalence associated with legalization, six reported a decrease, and seven reported an increase. Among young adults, most studies (8) showed an increase in at least one prevalence measure, four showed no change, and one showed a decrease. Only two adolescent and one young adult study examined cannabis use disorder, both adolescent studies showed an increase, and the young adult showed no change. The majority of studies had risk of bias. Recreational legalization may be associated with increases in prevalence of cannabis use in young adults while results for adolescents are mixed. Policymakers and practitioners should consider appropriate prevention and treatment options for young people.Trial Registration: PROSPERO #CRD42021276984.

Gaps in Screening Recommendations Must Be Addressed to Protect Youth and Adults from Substance Use-Related Harm.

Background: In June 2020, the U.S. Preventive Services Task Force (USPSTF) issued a final recommendation on screening for unhealthy drug use in adults and adolescents. It assigned a "B" rating on a recommendation for screening in primary care for adults when services for accurate diagnosis, effective treatment, and appropriate care can be provided or referred, but declined to recommend the same for adolescents, concluding that current evidence is insufficient to assess the balance of benefits and harms. Objectives: To examine and provide recommendations to address gaps in the USP ST recommendation on screening for unhealthy drug use. Results: The lack of recommendation to screen adolescents represents a critical gap and highlights the need for research on adolescent substance use screening. While research is limited, available evidence shows short-term benefits from youth screening and early intervention and no evidence of harm. The lack of recommendation for youth leaves practitioners without guidance and incentive to intervene with youth who use substances, discourages expansion/support of youth screening, and reinforces treatment barriers. The statement also lacks guidance to address barriers to implementing screening in adults. Despite promotion of the practice, implementation in primary care is sporadic. Providers should be made aware of implementation barriers and the clinical guides and training available to facilitate implementation. Conclusions/Importance: Screening and intervention are vital for addressing the addiction crisis, and USPSTF recommendations are critical for making preventive health care services accessible and affordable. These gaps must be addressed for the recommendation statement to reach its full life-saving potential.

Identifying the Physical and Mental Healthcare Needs of Opioid Treatment Program Clients.

Background: Individuals with opioid use disorder (OUD) often have significant medical and behavioral health needs that are unaddressed. Opioid treatment programs (OTP) are uniquely positioned to provide integrated services for OUD, physical and mental health but are underutilized for this purpose. This study aims to describe the physical and mental healthcare needs of OTP clients in order to inform integrated care implementation in OTPs. Method: OTP clients (n = 1261) in an integrated care program in the Bronx borough of New York City were assessed for mental health symptoms (e.g., anxiety, depression), chronic disease indicators (e.g., blood pressure, cholesterol), and general functioning (e.g., capability of managing healthcare needs). Results: Symptoms of anxiety, post-traumatic stress, and depression were common. Self-reported health status and level of functioning were generally poor. Heavy smoking and obesity were the most frequent physical health risks. Other chronic disease indicators (e.g., blood pressure) showed 25-46% may be at risk. Sixty percent had multiple mental health risks and 85% had multiple physical health risks. Older clients had a higher rate of hypertension and diabetes risk than younger clients. Conclusions: Integrated care programs in OTPs must be prepared to address and coordinate care for chronic mental and physical health conditions in addition to OUD.

Study Design and Baseline Characteristics of the CARDINAL Trial: A Phase 3 Study of Bardoxolone Methyl in Patients with Alport Syndrome.

INTRODUCTION: Alport syndrome is a rare genetic disorder that affects as many as 60,000 persons in the USA and a total of 103,000 persons (<5 per 10,000) in the European Union [1, 2]. It is the second most common inherited cause of kidney failure and is characterized by progressive loss of kidney function that often leads to end-stage kidney disease. Currently, there are no approved disease-specific agents for therapeutic use. We designed a phase 3 study (CARDINAL; NCT03019185) to evaluate the safety, tolerability, and efficacy of bardoxolone methyl in patients with Alport syndrome. METHODS: The CARDINAL phase 3 study is an international, multicenter, double-blind, placebo-controlled, randomized registrational trial. Eligible patients were of ages 12-70 years with confirmed genetic or histologic diagnosis of Alport syndrome, eGFR 30-90 mL/min/1.73 m2, and urinary albumin to creatinine ratio (UACR) ≤3,500 mg/g. Patients with B-type natriuretic peptide values >200 pg/mL at baseline or with significant cardiovascular histories were excluded. Patients were randomized 1:1 to bardoxolone methyl or placebo, with stratification by baseline UACR. RESULTS: A total of 371 patients were screened, and 157 patients were randomly assigned to receive bardoxolone methyl (n = 77) or placebo (n = 80). The average age at screening was 39.2 years, and 23 (15%) were <18 years of age. Of the randomized population, 146 (93%) had confirmed genetic diagnosis of Alport syndrome, and 62% of patients had X-linked mode of inheritance. Mean baseline eGFR was 62.7 mL/min/1.73 m2, and the geometric mean UACR was 141.0 mg/g. The average annual rate of eGFR decline prior to enrollment in the study was -4.9 mL/min/1.73 m2 despite 78% of the patient population receiving ACE inhibitor (ACEi) or ARB therapy. DISCUSSION/CONCLUSION: CARDINAL is one of the largest interventional, randomized controlled trials in Alport syndrome conducted to date. Despite the use of ACEi or ARB, patients were experiencing significant loss of kidney function prior to study entry.

Bardoxolone Methyl Improves Kidney Function in Patients with Chronic Kidney Disease Stage 4 and Type 2 Diabetes: Post-Hoc Analyses from Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes Study.

BACKGROUND: Increases in measured inulin clearance, measured creatinine clearance, and estimated glomerular filtration rate (eGFR) have been observed with bardoxolone methyl in 7 studies enrolling approximately 2,600 patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). The largest of these studies was Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes (BEACON), a multinational, randomized, double-blind, placebo-controlled phase 3 trial which enrolled patients with T2D and CKD stage 4. The BEACON trial was terminated after preliminary analyses showed that patients randomized to bardoxolone methyl experienced significantly higher rates of heart failure events. We performed post-hoc analyses to characterize changes in kidney function induced by bardoxolone methyl. METHODS: Patients in -BEACON (n = 2,185) were randomized 1: 1 to receive once-daily bardoxolone methyl (20 mg) or placebo. We compared the effects of bardoxolone methyl and placebo on a post-hoc composite renal endpoint consisting of ≥30% decline from baseline in eGFR, eGFR <15 mL/min/1.73 m2, and end-stage renal disease (ESRD) events (provision of dialysis or kidney transplantation). RESULTS: Consistent with prior studies, patients randomized to bardoxolone methyl experienced mean increases in eGFR that were sustained through study week 48. Moreover, increases in eGFR from baseline were sustained 4 weeks after cessation of treatment. Patients randomized to bardoxolone methyl were significantly less likely to experience the composite renal endpoint (hazards ratio 0.48 [95% CI 0.36-0.64]; p < 0.0001). CONCLUSIONS: Bardoxolone methyl preserves kidney function and may delay the onset of ESRD in patients with T2D and stage 4 CKD.

Topical application of RTA 408 lotion activates Nrf2 in human skin and is well-tolerated by healthy human volunteers.

BACKGROUND: Topical application of the synthetic triterpenoid RTA 408 to rodents elicits a potent dermal cytoprotective phenotype through activation of the transcription factor Nrf2. Therefore, studies were conducted to investigate if such cytoprotective properties translate to human dermal cells, and a topical lotion formulation was developed and evaluated clinically. METHODS: In vitro, RTA 408 (3-1000 nM) was incubated with primary human keratinocytes for 16 h. Ex vivo, RTA 408 (0.03, 0.3, or 3 %) was applied to healthy human skin explants twice daily for 3 days. A Phase 1 healthy volunteer clinical study with RTA 408 Lotion (NCT02029716) consisted of 3 sequential parts. In Part A, RTA 408 Lotion (0.5 %, 1 %, and 3 %) and lotion vehicle were applied to individual 4-cm(2) sites twice daily for 14 days. In Parts B and C, separate groups of subjects had 3 % RTA 408 Lotion applied twice daily to a 100-cm(2) site for 14 days or a 500-cm(2) site for 28 days. RESULTS: RTA 408 was well-tolerated in both in vitro and ex vivo settings up to the highest concentrations tested. Further, RTA 408 significantly and dose-dependently induced a variety of Nrf2 target genes. Clinically, RTA 408 Lotion was also well-tolerated up to the highest concentration, largest surface area, and longest duration tested. Moreover, significant increases in expression of the prototypical Nrf2 target gene NQO1 were observed in skin biopsies, suggesting robust activation of the pharmacological target. CONCLUSIONS: Overall, these data suggest RTA 408 Lotion is well-tolerated, activates Nrf2 in human skin, and appears suitable for continued clinical development.

Mechanisms contributing to adverse cardiovascular events in patients with type 2 diabetes mellitus and stage 4 chronic kidney disease treated with bardoxolone methyl.

BACKGROUND: Bardoxolone methyl, an Nrf2-activating and nuclear factor-κB-inhibiting semisynthetic oleanane triterpenoid compound, was evaluated in a phase 3 trial (BEACON) in patients with type 2 diabetes mellitus (T2DM) and stage 4 chronic kidney disease (CKD). The trial was terminated because of an increase in heart failure events in the bardoxolone methyl group, many of which appeared related to fluid retention. Thus, additional analyses were conducted to explain these serious adverse events. METHODS: Patients (n = 2,185) were randomized to receive once-daily bardoxolone methyl (20 mg) or placebo. Twenty-four-hour urine collections were analyzed in a subset of the BEACON population and from a separate, open-label pharmacology study in patients with stage 3b/4 CKD and T2DM administered 20 mg bardoxolone methyl once daily for 56 consecutive days. RESULTS: Bardoxolone-methyl-treated patients in the BEACON substudy had a clinically meaningful reduction in urine volume and sodium excretion at week 4 relative to baseline (p < 0.05), and a separate study revealed that decreased sodium excretion and urine output occurred in some patients with stage 4 CKD but not those with stage 3b CKD. The clinical phenotype of fluid overload and heart failure in BEACON was similar to that observed with endothelin receptor antagonists in advanced CKD patients, and preclinical data demonstrate that bardoxolone methyl modifies endothelin signaling. CONCLUSIONS: The totality of the evidence suggests that through modulation of the endothelin pathway, bardoxolone methyl may pharmacologically promote acute sodium and volume retention and increase blood pressure in patients with more advanced CKD.

The Role of Intermediaries in Connecting Community-Dwelling Adults to Local Physical Activity and Exercise: A Scoping Review.

Introduction: Connecting inactive individuals to local physical activity (PA) and exercise, via intermediaries (professionals who can facilitate and support connections to non-medical services) may be an effective method to tackle physical inactivity. Evidence regarding the processes of intermediaries, the profile of people referred, how connections to local PA and exercise are made and outcomes of these connections is lacking. Methods: This scoping review followed guidelines from the Joanna Briggs Institute. Searches of four electronic databases (Embase, Medline, Web of Science, CINAHL) and an extensive grey literature search were conducted from inception to June 2022. Full-text studies which reported on community-dwelling adults (population), and the processes of intermediaries (concept) when connecting to local PA and exercise (context) were considered for inclusion. A logic model was created to map processes to outcomes. Evidence advances and gaps were identified. Results: N = 28 studies were identified. Participants referred to an intermediary were older, female, and with poorer health. Where possible, the processes of referral, assessment, follow-up and discharge by intermediaries were described, as well as the local PA and exercise services used. Short-term PA outcomes appeared positive after working with intermediaries, but many studies were poorly described, and the review was not designed to examine effectiveness of this intervention. Discussion/Conclusion: Many aspects of the processes were poorly described. More robust studies evaluating the processes of intermediaries are needed, as well as further exploration of the optimum processes in improving PA outcomes.

Exploration of Evaluation Practices in Social Prescribing Services in Ireland: A Cross-Sectional Observational Study.

National health services in Ireland and the UK fund the majority of social prescribing services and have issued recommendations for evaluation. However, it is not known what outcomes are prioritised for evaluation within individual services and what evaluation methods are used to capture recommended outcomes. A survey was carried out to examine evaluation practices of social prescribing services on the island of Ireland. This study used a cross-sectional observational design. The sample was all the staff involved in delivering and/or managing SP services on the island of Ireland. Questionnaires were distributed at a national SP conference and online. Closed-response questions were analysed using descriptive statistics. Content analysis was used for open-ended questions. Eighty-four usable surveys were returned (50% from the Republic of Ireland and 50% from Northern Ireland). All respondents (100%) agreed on the importance of measuring SP outcomes. The most frequently measured outcomes were health and well-being (89.2%) and loneliness (84%). The least frequently measured outcome was the satisfaction of healthcare professionals referring to SP: 78.4% of respondents never measured this outcome. The most frequently used measurement tool was the Short Warwick Edinburgh Mental Well-Being Scale, with 38/76 (50%) respondents using this measure. There was a lack of standardised measures identified for some outcomes. For example, 70% of respondents reported always measuring physical activity (PA), but only four respondents identified a specific PA measure. In open-ended questions, respondents recommended flexibility in evaluation methods to reflect the complexity and individualised focus of SP. They also identified the need for protected time to complete evaluations and recommended a national strategy to inform priorities in evaluations. This study demonstrates a wide variation on the island of Ireland on how SP services are measuring outcomes, with many outcomes rarely or never measured using standardised measures. Agreement is needed on a core outcome set for social prescribing in order to guide service delivery and evaluations.

Technology Access and Perceptions of Telehealth Services Among Young Adults Involved in the Court System.

PURPOSE: This study examined access to technology and telehealth among young adults (ages 18-24) who were court-involved and were recruited from an alternative sentencing program in New York City. METHODS: Using sequential mixed methods design, we examined demographic factors linked with access to technology and perceived usefulness of the Internet among n = 321 young adults who were court-involved (75% male, 65% African American, 35% Latinx). We then conducted in-depth interviews with 27 young adults to elicit first-person account of their access to, interest in, and experience with technology and telehealth. RESULTS: Although most participants had access to a phone with a data plan, a substantial proportion reported inconsistent access to the technology critical to telehealth. Certain young adults were more likely to lack consistent access to the technology needed for telehealth, including Black young adults, males, those with less than a high school diploma, those with a history of homelessness, and those who had difficulties paying for basic necessities. Qualitative interviews revealed that most had a strong self-efficacy using technology, while distrust of technology, inexperience with and skepticism of telehealth, low perceived need for care, and medical mistrust were common significant barriers in this underserved population. DISCUSSION: Findings underscored the critical need to address medical mistrust and increase access to and utilization of care among young adults who are court-involved. Results can inform the development and implementation of interventions designed to improve accessibility and acceptability of telehealth.

Referral to and engagement in substance use disorder treatment within opioid intervention courts in New York: a qualitative study of implementation barriers and facilitators.

BACKGROUND: People with opioid use disorder (OUD) are frequently in contact with the court system and have markedly higher rates of fatal opioid overdose. Opioid intervention courts (OIC) were developed to address increasing rates of opioid overdose among court defendants by engaging court staff in identification of treatment need and referral for opioid-related services and building collaborations between the court and OUD treatment systems. The study goal was to understand implementation barriers and facilitators in referring and engaging OIC clients in OUD treatment. METHODS: Semi-structured interviews were conducted with OIC stakeholders (n = 46) in 10 New York counties in the United States, including court coordinators, court case managers, and substance use disorder treatment clinic counselors, administrators, and peers. Interviews were recorded and transcribed and thematic analysis was conducted, guided by the Exploration, Preparation, Implementation, Sustainment (EPIS) framework, employing both inductive and deductive coding. RESULTS: Results were conceptualized using EPIS inner (i.e., courts) and outer (i.e., OUD treatment providers) implementation contexts and bridging factors that impacted referral and engagement to OUD treatment from the OIC. Inner factors that facilitated OIC implementation included OIC philosophy (e.g., non-punitive, access-oriented), court organizational structure (e.g., strong court staff connectedness), and OIC court staff and client characteristics (e.g., positive medications for OUD [MOUD] attitudes). The latter two also served as barriers (e.g., lack of formalized procedures; stigma toward MOUD). Two outer context entities impacted OIC implementation as both barriers and facilitators: substance use disorder treatment programs (e.g., attitudes toward the OIC and MOUD; operational characteristics) and community environments (e.g., attitudes toward the opioid epidemic). The COVID-19 pandemic and bail reform were macro-outer context factors that negatively impacted OIC implementation. Facilitating bridging factors included staffing practices that bridged court and treatment systems (e.g., peers); barriers included communication and cultural differences between systems (e.g., differing expectations about OIC client success). CONCLUSIONS: This study identified key barriers and facilitators that OICs may consider as this model expands in the United States. Referral to and engagement in OUD treatment within the OIC context requires ongoing efforts to bridge the treatment and court systems, and reduce stigma around MOUD.

Standard Versus Family-Based Screening, Brief Intervention, and Referral to Treatment for Adolescent Substance Use in Primary Care: Protocol for a Multisite Randomized Effectiveness Trial.

BACKGROUND: Screening, brief intervention, and referral to treatment for adolescents (SBIRT-A) is widely recommended to promote detection and early intervention for alcohol and other drug (AOD) use in pediatric primary care. Existing SBIRT-A procedures rely almost exclusively on adolescents alone, despite the recognition of caregivers as critical protective factors in adolescent development and AOD use. Moreover, controlled SBIRT-A studies conducted in primary care have yielded inconsistent findings about implementation feasibility and effects on AOD outcomes and overall developmental functioning. There is urgent need to investigate the value of systematically incorporating caregivers in SBIRT-A procedures. OBJECTIVE: This randomized effectiveness trial will advance research and scope on SBIRT-A in primary care by conducting a head-to-head test of 2 conceptually grounded, evidence-informed approaches: a standard adolescent-only approach (SBIRT-A-Standard) versus a more expansive family-based approach (SBIRT-A-Family). The SBIRT-A-Family approach enhances the procedures of the SBIRT-A-Standard approach by screening for AOD risk with both adolescents and caregivers; leveraging multidomain, multireporter AOD risk and protection data to inform case identification and risk categorization; and directly involving caregivers in brief intervention and referral to treatment activities. METHODS: The study will include 2300 adolescents (aged 12-17 y) and their caregivers attending 1 of 3 hospital-affiliated pediatric settings serving diverse patient populations in major urban areas. Study recruitment, screening, randomization, and all SBIRT-A activities will occur during a single pediatric visit. SBIRT-A procedures will be delivered digitally on handheld tablets using patient-facing and provider-facing programming. Primary outcomes (AOD use, co-occurring behavior problems, and parent-adolescent communication about AOD use) and secondary outcomes (adolescent quality of life, adolescent risk factors, and therapy attendance) will be assessed at screening and initial assessment and 3-, 6-, 9-, and 12-month follow-ups. The study is well powered to conduct all planned main and moderator (age, sex, race, ethnicity, and youth AOD risk status) analyses. RESULTS: This study will be conducted over a 5-year period. Provider training was initiated in year 1 (December 2023). Participant recruitment and follow-up data collection began in year 2 (March 2024). We expect the results from this study to be published in early 2027. CONCLUSIONS: SBIRT-A is widely endorsed but currently underused in pediatric primary care settings, and questions remain about optimal approaches and overall effectiveness. In particular, referral to treatment procedures in primary care remains virtually untested among youth. In addition, whereas research strongly supports involving families in interventions for adolescent AOD, SBIRT-A effectiveness trial testing approaches that actively engage family members in primary care are absent. This trial is designed to help fill these research gaps to inform the critical health decision of whether and how to include caregivers in SBIRT-A activities conducted in pediatric primary care. TRIAL REGISTRATION: ClinicalTrials.gov NCT05964010; https://www.clinicaltrials.gov/study/NCT05964010. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/54486.

Ignoring Norms with a Little Help from My Friends: Social Support Reduces Normative Influence on Drinking Behavior.

Alcohol norms are strong predictors of drinking. However, the extent to which norms influence behavior depends on how closely people attend to them; people are more likely to attend to norms when their affiliation needs are unfulfilled by members of their social networks (Cullum, O'Grady, & Tennen, 2011). Therefore, we predicted that Perceived Social Support (PSS) would moderate the relationship between norms and drinking such that people with low levels of PSS would be more motivated to attend to norms. College students (N = 498) completed measures of PSS and peer alcohol norms and then reported on their drinking behavior daily for 30 days. As predicted, we found when PSS was low, student drinking was strongly influenced by peer norms, but there was no relationship between norms and drinking when PSS was high. Findings suggest that when affiliation needs are high, norms are more influential on drinking behavior.

Educators' views of eating disorder prevention programs.

Further understanding of educators' views of eating disorder prevention can further engage them in this effort. No previous studies of educators have used acceptability methodology or compared eating disorder prevention to other prevention efforts. Educators (n = 135) rated the acceptability of five sample programs and provided their opinions about eating disorder and other prevention programs. The results indicated primarily psychoeducational and general well-being programs were most acceptable. Educators-specified trained professionals should implement programs during school hours to male and female junior high students. Although eating disorder prevention was perceived as important, it was not rated as vital as other programs, such as substance abuse prevention.

A cross-sectional study of the relationship between depression status, health care coverage, and sexual orientation.

Health care coverage is an important factor in receipt of behavioral healthcare. This study uses data from the New York City Community Health Survey to examine how sexual minority status impacts the relationship between depression status and having health care coverage. Approximately 10% of the sample (n = 9571; 47% 45+ years old; 35% White Non-Hispanic; 7% sexual minority) reported probable depression and low health care coverage. Compared to heterosexual participants, a greater proportion of sexual minority participants had low health care coverage (17% vs. 9%) and probable depression (19% vs. 9%). Logistic regression examining the association between probable depression status and health care coverage showed that those with probable depression have odds of low health care coverage that are were 3.08 times those who did not have probable depression; this relationship was not modified by sexual orientation. Continued research to understand the interplay of health care coverage, mental health, and sexual orientation is needed.

The POP (Permanent Supportive Housing Overdose Prevention) Study: protocol for a hybrid type 3 stepped-wedge cluster randomized controlled trial.

BACKGROUND: Permanent supportive housing (PSH)-subsidized housing paired with support services such as case management-is a key part of national strategic plans to end homelessness. PSH tenants face high overdose risk due to a confluence of individual and environmental risk factors, yet little research has examined overdose prevention in PSH. METHODS: We describe the protocol for a hybrid type 3 stepped-wedge cluster randomized controlled trial (RCT) of overdose prevention practice implementation in PSH. We adapted evidence-based overdose prevention practices and implementation strategies for PSH using input from stakeholder focus groups. The trial will include 20 PSH buildings (with building size ranging from 20 to over 150 tenants) across New York City and New York's Capital Region. Buildings will be randomized to one of four 6-month intervention waves during which they will receive a package of implementation support including training in using a PSH Overdose Prevention (POP) Toolkit, time-limited practice facilitation, and learning collaboratives delivered to staff and tenant implementation champions appointed by each building. The primary outcome is building-level fidelity to a defined list of overdose prevention practices. Secondary and exploratory implementation and effectiveness outcomes will be examined using PSH staff and tenant survey questionnaires, and analysis of tenant Medicaid data. We will explore factors related to implementation success, including barriers and facilitators, using qualitative interviews with key stakeholders. The project is being conducted through an academic-community partnership, and an Advisory Board including PSH tenants and other key stakeholders will be engaged in all stages of the project. DISCUSSION: We describe the protocol for a hybrid type 3 stepped-wedge cluster RCT of overdose prevention practice implementation in PSH. This study will be the first controlled trial of overdose prevention implementation in PSH settings. The research will make a significant impact by testing and informing future implementation strategies to prevent overdose for a population at particularly high risk for overdose mortality. Findings from this PSH-focused research are expected to be broadly applicable to other housing settings and settings serving people experiencing homelessness. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05786222 , registered 27 March 2023.

Clinics Optimizing MEthadone Take-homes for opioid use disorder (COMET): Protocol for a stepped-wedge randomized trial to facilitate clinic level changes.

INTRODUCTION: Regulatory changes made during the COVID-19 public health emergency (PHE) that relaxed criteria for take-home dosing (THD) of methadone offer an opportunity to improve quality of care with a lifesaving treatment. There is a pressing need for research to study the long-term effects of the new PHE THD rules and to test data-driven interventions to promote more effective adoption by opioid treatment programs (OTPs). We propose a two-phase project to develop and test a multidimensional intervention for OTPs that leverages information from large State administrative data. METHODS AND ANALYSIS: We propose a two-phased project to develop then test a multidimensional OTP intervention to address clinical decision making, regulatory confusion, legal liability concerns, capacity for clinical practice change, and financial barriers to THD. The intervention will include OTP THD specific dashboards drawn from multiple State databases. The approach will be informed by the Health Equity Implementation Framework (HEIF). In phase 1, we will employ an explanatory sequential mixed methods design to combine analysis of large state administrative databases-Medicaid, treatment registry, THD reporting-with qualitative interviews to develop and refine the intervention. In phase 2, we will conduct a stepped-wedge trial over three years with 36 OTPs randomized to 6 cohorts of a six-month clinic-level intervention. The trial will test intervention effects on OTP-level implementation outcomes and patient outcomes (1) THD use; 2) retention in care; and 3) adverse healthcare events). We will specifically examine intervention effects for Black and Latinx clients. A concurrent triangulation mixed methods design will be used: quantitative and qualitative data collection will occur concurrently and results will be integrated after analysis of each. We will employ generalized linear mixed models (GLMMs) in the analysis of stepped-wedge trials. The primary outcome will be weekly or greater THD. The semi-structured interviews will be transcribed and analyzed with Dedoose to identify key facilitators, barriers, and experiences according to HEIF constructs using directed content analysis. DISCUSSION: This multi-phase, embedded mixed methods project addresses a critical need to support long-term practice changes in methadone treatment for opioid use disorder following systemic changes emerging from the PHE-particularly for Black and Latinx individuals with opioid use disorder. By combining findings from analyses of large administrative data with lessons gleaned from qualitative interviews of OTPs that were flexible with THD and those that were not, we will build and test the intervention to coach clinics to increase flexibility with THD. The findings will inform policy at the local and national level.

Change and Stability in Active and Passive Social Influence Dynamics during Natural Drinking Events: A Longitudinal Measurement-Burst Study.

We examined the link between social norms and active social influences occurring during natural social drinking contexts. Across 4 yearly measurement-bursts, college students (N = 523) reported daily for 30-day periods on drinking norms, drinking offers, how many drinks they accepted, and personal drinking levels during social drinking events. In contexts where drinking norms were higher, students were more likely to both receive and comply with drinking offers. These acute social influences were highly stable throughout college, but affected men and women differently across time: Women received more drinking offers than men, especially at the beginning of college and when norms were higher, but men complied with more drinking offers per occasion. These effects were not attributable to between-person differences in social drinking motives or drinking levels, nor to within-person patterns of situation-selection. The present work suggests that context-specific drinking norms catalyze active social influence attempts, and further promote compliance drinking.