IL17RB genetic variants are associated with acamprosate treatment response in patients with alcohol use disorder: A proteomics-informed genomics study.

Acamprosate is a Food and Drug Administration (FDA) approved medication for the treatment of alcohol use disorder (AUD). However, only a subset of patients achieves optimal treatment outcomes. Currently, no biological measures are utilized to predict response to acamprosate treatment. We applied our established pharmaco-omics informed genomics strategy to identify potential biomarkers associated with acamprosate treatment response. Specifically, our previous open-label acamprosate clinical trial recruited 442 patients with AUD who were treated with acamprosate for three months. We first performed proteomics using baseline plasma samples to identify potential biomarkers associated with acamprosate treatment outcomes. Next, we applied our established "proteomics-informed genome-wide association study (GWAS)" research strategy, and identified 12 proteins, including interleukin-17 receptor B (IL17RB), associated with acamprosate treatment response.​ A GWAS for IL17RB concentrations identified several genome-wide significant signals. Specifically, the top hit single nucleotide polymorphism (SNP) rs6801605 with a minor allele frequency of 38% in the European American population mapped 4 kilobase (Kb) upstream of IL17RB, and intron 1 of the choline dehydrogenase (CHDH) gene on chromosome 3 (p: 4.8E-20). The variant genotype (AA) for the SNP rs6801605 was associated with lower IL17RB protein expression. In addition, we identified a series of genetic variants in IL17RB that were associated with acamprosate treatment outcomes. Furthermore, the variantgenotypes for all of those IL17RB SNPs were protective for alcohol relapse. Finally, we demonstrated that the basal level of mRNA expression of IL17RB was inversely correlated with those of nuclear factor-κB (NF-κB) subunits, and a significantly higher expression of NF-κB subunits was observed in AUD patients who relapsed to alcohol use. In summary, this study illustrates that IL17RB genetic variants might contribute to acamprosate treatment outcomes. This series of studies represents an important step toward generating functional hypotheses that could be tested to gain insight into mechanisms underlying acamprosate treatment response phenotypes. (The ClinicalTrials.gov Identifier: NCT00662571).

Prevalence of stress and related factors among healthcare students: a cross - sectional study in Can Tho City, Vietnam.

Background: Stress is a major public health issue that can impact both physical and mental well-being. It is prevalent in many areas of modern life, including education. Healthcare students are at a high risk of experiencing stress due to the unique demands of their fields of study. Study design and methods: An online survey was conducted on 2,515 undergraduate students pursuing degrees in medicine, preventive medicine, pharmacy, and nursing at Can Tho University of Medicine and Pharmacy in Can Tho City, Vietnam. Results: Using the Perceived Stress Scale-10 (PSS-10), it was found that 35.2% of students reported mild stress, 62.7% had moderate stress, and only 2.1% experienced severe stress. Multivariable logistic regression analysis revealed nine significant factors associated with students' stress levels (p ≤ 0.05). Particularly, medicine students exhibited a significantly higher level of moderate and severe stress (95% CI = 1.22-2.01), 1.57 times higher than preventive medicine students. Sixth-year students had a stress level 1.58 times higher (95% CI = 1.11-2.26) than first-year students. Students achieving excellent and very good academic performances in the last semester had a stress level 1.60 times higher (95% CI = 1.16-2.22) than students with average and lower academic performance. Students living at home had a stress level 1.73 times higher (95% CI = 1.05-2.84) than students living in their relatives' houses. Students who rarely or never had a part-time job during academic years had a stress level 1.70 times higher (95% CI = 1.31-2.20) than those who often or sometimes had a part-time job. Students with a family history of smoking addiction had a stress level 1.69 times higher (95% CI = 1.28-2.22) than students without such a family history. Students who rarely or never received concern and sharing from family had a stress level 7.41 times higher (95% CI = 5.07-10.84) than students who often or sometimes received concern and sharing from family. Students who were often or sometimes cursed by family had a stress level 2.04 times higher (95% CI = 1.09-3.81) than students who were rarely or never cursed by family. Students without close friends had a stress level 1.46 times higher (95% CI = 1.11-1.91) than students with close friends. Conclusions: The rates of mild and moderate stress levels were significantly higher than severe stress level among healthcare students. Research has provided scientific findings as the basis for determining risk factors and imposing solutions that aim to reduce the rate of stress in students. Therefore, it helps students overcome difficulties and enhance their physical and mental health.

Association Between Clinician-Level Factors and Patient Outcomes in Virtual and In-Person Outpatient Treatment for Substance Use Disorders: Multilevel Analysis.

BACKGROUND: The use of virtual treatment services increased dramatically during the COVID-19 pandemic. Unfortunately, large-scale research on virtual treatment for substance use disorder (SUD), including factors that may influence outcomes, has not advanced with the rapidly changing landscape. OBJECTIVE: This study aims to evaluate the link between clinician-level factors and patient outcomes in populations receiving virtual and in-person intensive outpatient services. METHODS: Data came from patients (n=1410) treated in a virtual intensive outpatient program (VIOP) and an in-person intensive outpatient program (IOP), who were discharged between January 2020 and March 2021 from a national treatment organization. Patient data were nested by treatment providers (n=58) examining associations with no-shows and discharge with staff approval. Empathy, comfort with technology, perceived stress, resistance to change, and demographic covariates were examined at the clinician level. RESULTS: The VIOP (ß=-5.71; P=.03) and the personal distress subscale measure (ß=-6.31; P=.003) were negatively associated with the percentage of no-shows. The VIOP was positively associated with discharges with staff approval (odds ratio [OR] 2.38, 95% CI 1.50-3.76). Clinician scores on perspective taking (ß=-9.22; P=.02), personal distress (ß=-9.44; P=.02), and male clinician gender (ß=-6.43; P=.04) were negatively associated with in-person no-shows. Patient load was positively associated with discharge with staff approval (OR 1.04, 95% CI 1.02-1.06). CONCLUSIONS: Overall, patients in the VIOP had fewer no-shows and a higher rate of successful discharge. Few clinician-level characteristics were significantly associated with patient outcomes. Further research is necessary to understand the relationships among factors such as clinician gender, patient load, personal distress, and patient retention.

Epigenetic regulation of GABA catabolism in iPSC-derived neurons: The molecular links between FGF21 and histone methylation.

OBJECTIVE: Fibroblast growth factor 21 (FGF21) analogs have been tested as potential therapeutics for substance use disorders. Prior research suggests that FGF21 administration might affect alcohol consumption and reward behaviors. Our recent report showed that plasma FGF21 levels were positively correlated with alcohol use in patients with alcohol use disorder (AUD). FGF21 has a short half-life (0.5-2 h) and crosses the blood-brain barrier. Therefore, we set out to identify molecular mechanisms for both the naïve form of FGF21 and a long-acting FGF21 molecule (PF-05231023) in induced pluripotent stem cell (iPSC)-derived forebrain neurons. METHODS: We performed RNA-seq in iPSC-derived forebrain neurons treated with naïve FGF21 or PF-05231023 at physiologically relevant concentrations. We obtained plasma levels of FGF21 and GABA from our previous AUD clinical trial (n = 442). We performed ELISA for FGF21 in both iPSC-derived forebrain neurons and forebrain organoids. We determined protein interactions using co-immunoprecipitation. Finally, we applied ChIP assays to confirm the occupancy of REST, EZH2 and H3K27me3 by FGF21 using iPSC-derived forebrain neurons with and without drug exposure. RESULTS: We identified 4701 and 1956 differentially expressed genes in response to naïve FGF21 or PF-05231023, respectively (FDR < 0.05). Notably, 974 differentially expressed genes overlapped between treatment with naïve FGF21 and PF-05231023. REST was the most important upstream regulator of differentially expressed genes. The GABAergic synapse pathway was the most significant pathway identified using the overlapping genes. We also observed a significant positive correlation between plasma FGF21 and GABA concentrations in AUD patients. In parallel, FGF21 and PF-05231023 significantly induced GABA levels in iPSC-derived neurons. Finally, functional genomics studies showed a drug-dependent occupancy of REST, EZH2, and H3K27me3 in the promoter regions of genes involved in GABA catabolism which resulted in transcriptional repression. CONCLUSIONS: Our results highlight a significant role in the epigenetic regulation of genes involved in GABA catabolism related to FGF21 action. (The ClinicalTrials.gov Identifier: NCT00662571).

Deep Brain Stimulation for Substance Use Disorders? An Exploratory Qualitative Study of Perspectives of People Currently in Treatment.

OBJECTIVE: Although previous studies have discussed the promise of deep brain stimulation (DBS) as a possible treatment for substance use disorders (SUDs) and collected researcher perspectives on possible ethical issues surrounding it, none have consulted people with SUDs themselves. We addressed this gap by interviewing people with SUDs. METHODS: Participants viewed a short video introducing DBS, followed by a 1.5-hour semistructured interview on their experiences with SUDs and their perspective on DBS as a possible treatment option. Interviews were analyzed by multiple coders who iteratively identified salient themes. RESULTS: We interviewed 20 people in 12-step-based, inpatient treatment programs (10 [50%] White/Caucasian, 7 Black/African American [35%], 2 Asian [10%], 1 Hispanic/Latino [5%], and 1 [5%] Alaska Native/American Indian; 9 women [45%], 11 men [55%]). Interviewees described a variety of barriers they currently faced through the course of their disease that mirrored barriers often associated with DBS (stigma, invasiveness, maintenance burdens, privacy risks) and thus made them more open to the possibility of DBS as a future treatment option. CONCLUSIONS: Individuals with SUDs gave relatively less weight to surgical risks and clinical burdens associated with DBS than previous surveys of provider attitudes anticipated. These differences derived largely from their experiences living with an often-fatal disease and encountering limitations of current treatment options. These findings support the study of DBS as a treatment option for SUDs, with extensive input from people with SUDs and advocates.

Nonpartner Violence Perpetration Among Emerging Adults: Associations With Polysubstance Use and Trait Mindfulness.

Objective: Violence is a leading cause of death among individuals ages 18-25, with alcohol misuse consistently linked with violence perpetration. However, the association between polysubstance use and violence perpetration is less clear, despite the frequency of use of alcohol with other drugs. Additionally, protective factors such as mindfulness that may reduce violence perpetration among emerging adults have been understudied. This cross-sectional study examined the association between substance use, trait mindfulness, and violence perpetration outside of romantic relationships, utilizing a compensatory model of resilience. Methods: Data were drawn from a sample of 665 emerging adults ages 18-25, recruited from an urban Emergency Department (68% men). Participants self-administered a computer survey that assessed non-partner violence perpetration (NPV), alcohol use, marijuana use, prescription drug misuse, and trait mindfulness. Fifteen percent reported non-partner violence perpetration over the past six months. Results: Multivariate logistic regression tested associations between violence perpetration, substance use, trait mindfulness, and demographic characteristics. Results showed that alcohol use alone (OR= 3.04), prescription opioid use alone (OR = 3.58), alcohol and marijuana use (OR = 3.75), and use of all three substances (OR= 7.78) were positively associated with violence perpetration. Post-hoc contrasts demonstrated the polysubstance use significantly increased risk over single substance use. Trait mindfulness (OR= 0.97) was negatively associated with violence perpetration after controlling for substance use. Conclusions: Findings suggest that polysubstance use may increase risk for violence. Interventions that address polysubstance use, potentially including mindfulness, could reduce non-partner violence perpetration among emerging adults and requires further study.

Adaptive interventions for alcohol misuse and violent behaviors among adolescents and emerging adults in the emergency department: A sequential multiple assignment randomized controlled trial protocol.

Alcohol use and violent behaviors among youth are associated with morbidity and mortality. An emergency department (ED) visit provides an opportunity to initiate prevention efforts. Despite promising findings from our single session SafERteens brief intervention (BI), impact is limited by modest effect sizes, with data lacking on optimal boosters to enhance effects. This paper describes the protocol for a sequential, multiple assignment, randomized trial (SMART). Adolescents and emerging adults (ages 14-20) in the ED screening positive for alcohol use and violent behaviors (physical aggression) were randomly assigned to: 1) SafERteens BI + Text Messaging (TM), or 2) SafERteens BI + remote Health Coach (HC). Participants completed weekly surveys over 8 weeks after the ED visit to tailor intervention content and measure mechanisms of change. At one-month, intervention response/non-response is determined (e.g., binge drinking or violent behaviors). Responders are re-randomized to continued intervention condition (e.g., maintenance) or minimized condition (e.g., stepped down). Non-responders are re-randomized to continued condition (e.g., maintenance), or intensified condition (e.g., stepped up). Outcomes were measured at 4 and 8 months, including primary outcomes of alcohol consumption and violence, with secondary outcomes of alcohol consequences and violence consequences. Although the original goal was to enroll 700 participants, COVID-19 impacts on research diminished recruitment in this trial (enrolled n = 400). Nonetheless, the proposed SMART is highly innovative by blending real-time assessment methodologies with adaptive intervention delivery among teens with comorbid alcohol misuse and violent behaviors. Findings will inform the content and timing booster interventions to alter risk behavior trajectories. Trial Registration:ClinicalTrials.govNCT03344666. University of Michigan # HUM00109156.

Genetic predisposition to major depressive disorder differentially impacts alcohol consumption and high-risk drinking situations in men and women with alcohol use disorder.

Lifetime history of major depressive disorder (MDD) has a sex-specific association with pretreatment alcohol consumption in patients with alcohol dependence. Here, we investigated the association of genetic load for MDD estimated using a polygenic risk score (PRS) with pretreatment alcohol consumption assessed with Timeline Follow Back in a sample of 287 men and 156 women meeting DSM-IV-TR criteria for alcohol dependence. Preferred drinking situations were assessed using the Inventory of Drug Taking Situations (IDTS). Linear models were used to test for association of normalized alcohol consumption measures with the MDD-PRS, adjusting for ancestry, age, sex, and number of days sober at baseline. We fit models both with and without adjustment for MDD history and alcohol-use-related PRSs as covariates. Higher MDD-PRS was associated with lower 90-day total alcohol consumption in men (ß = -0.16, p = 0.0012) but not in women (ß = 0.11, p = 0.18). The association of MDD-PRS with IDTS measures was also sex-specific: higher MDD-PRS was associated with higher propensity to drink in temptation-related situations in women, while the opposite (negative association)was found in men. MDD-PRS was not associated with lifetime MDD history in our sample, and adjustment for lifetime MDD and alcohol-related PRSs did not impact the results. Our results suggest that genetic load for MDD impacts pretreatment alcohol consumption in a sex-specific manner, which is similar to, but independent from, the effect of history of MDD. The clinical implications of these findings and contributing biological and psychological factors should be investigated in future studies.

Single cell transcriptomics reveals distinct transcriptional responses to oxycodone and buprenorphine by iPSC-derived brain organoids from patients with opioid use disorder.

The opioid epidemic represents a national crisis. Oxycodone is one of the most prescribed opioid medications in the United States, whereas buprenorphine is currently the most prescribed medication for opioid use disorder (OUD) pharmacotherapy. Given the extensive use of prescription opioids and the global opioid epidemic, it is essential to understand how opioids modulate brain cell type function at the single-cell level. We performed single nucleus RNA-seq (snRNA-seq) using iPSC-derived forebrain organoids from three male OUD subjects in response to oxycodone, buprenorphine, or vehicle for seven days. We utilized the snRNA-seq data to identify differentially expressed genes following drug treatment using the Seurat integrative analysis pipeline. We utilized iPSC-derived forebrain organoids and single-cell sequencing technology as an unbiased tool to study cell-type-specific and drug-specific transcriptional responses. After quality control filtering, we analyzed 25787 cells and identified sixteen clusters using unsupervised clustering analysis. Our results reveal distinct transcriptional responses to oxycodone and buprenorphine by iPSC-derived brain organoids from patients with OUD. Specifically, buprenorphine displayed a significant influence on transcription regulation in glial cells. However, oxycodone induced type I interferon signaling in many cell types, including neural cells in brain organoids. Finally, we demonstrate that oxycodone, but not buprenorphine activated STAT1 and induced the type I interferon signaling in patients with OUD. These data suggest that elevation of STAT1 expression associated with OUD might play a role in transcriptional regulation in response to oxycodone. In summary, our results provide novel mechanistic insight into drug action at single-cell resolution.

Plasma TNFSF10 levels associated with acamprosate treatment response in patients with alcohol use disorder.

Acamprosate is an anti-craving drug used in alcohol use disorder (AUD) pharmacotherapy. However, only a subset of patients achieves optimal treatment outcomes. The identification of predictive biomarkers of acamprosate treatment response in patients with AUD would be a substantial advance in addiction medicine. We designed this study to use proteomics data as a quantitative biological trait as a step toward identifying inflammatory modulators that might be associated with acamprosate treatment outcomes. The NIAAA-funded Mayo Clinic Center for the Individualized Treatment of Alcoholism study had previously recruited 442 AUD patients who received 3 months of acamprosate treatment. However, only 267 subjects returned for the 3-month follow-up visit and, as a result, had treatment outcome information available. Baseline alcohol craving intensity was the most significant predictor of acamprosate treatment outcomes. We performed plasma proteomics using the Olink target 96 inflammation panel and identified that baseline plasma TNF superfamily member 10 (TNFSF10) concentration was associated with alcohol craving intensity and variation in acamprosate treatment outcomes among AUD patients. We also performed RNA sequencing using baseline peripheral blood mononuclear cells from AUD patients with known acamprosate treatment outcomes which revealed that inflammation-related pathways were highly associated with relapse to alcohol use during the 3 months of acamprosate treatment. These observations represent an important step toward advancing our understanding of the pathophysiology of AUD and molecular mechanisms associated with acamprosate treatment response. In conclusion, applying omics-based approaches may be a practical approach for identifying biologic markers that could potentially predict alcohol craving intensity and acamprosate treatment response.

Genome-wide association study for circulating FGF21 in patients with alcohol use disorder: Molecular links between the SNHG16 locus and catecholamine metabolism.

OBJECTIVE: Alcohol consumption can increase circulating levels of fibroblast growth factor 21 (FGF21). The effects of FGF21 in the central nervous system are associated with the regulation of catecholamines, neurotransmitters that play a crucial role in reward pathways. This study aims to identify genetic variants associated with FGF21 levels and evaluate their functional role in alcohol use disorder (AUD). METHODS: We performed a genome-wide association study (GWAS) using DNA samples from 442 AUD subjects recruited from the Mayo Clinic Center for the Individualized Treatment of Alcoholism Study. Plasma FGF21 levels were measured using Olink proximity extension immunoassays. Alcohol consumption at time of entry into the study was measured using the self-reported timeline followback method. Functional genomic studies were performed using HepG2 cells and induced pluripotent stem cell (iPSC)-derived brain organoids. RESULTS: Plasma FGF21 levels were positively correlated with recent alcohol consumption and gamma-glutamyl transferase levels, a commonly used marker for heavy alcohol use. One variant, rs9914222, located 5' of SNHG16 on chromosome 17 was associated with plasma FGF21 levels (p = 4.60E-09). This variant was also associated with AUD risk (ß: -3.23; p:0.0004). The rs9914222 SNP is an eQTL for SNHG16 in several brain regions, i.e., the variant genotype was associated with decreased expression of SNHG16. The variant genotype for the rs9914222 SNP was also associated with higher plasma FGF21 levels. Knockdown of SNHG16 in HepG2 cells resulted in increased FGF21 concentrations and decreased expression and enzyme activity for COMT, an enzyme that plays a key role in catecholamine metabolism. Finally, we demonstrated that ethanol significantly induced FGF21, dopamine, norepinephrine, and epinephrine concentrations in iPSC-derived brain organoids. CONCLUSIONS: GWAS for FGF21 revealed a SNHG16 genetic variant associated with FGF21 levels which are associated with recent alcohol consumption. Our data suggest that SNHG16 can regulate FGF21 concentrations and decrease COMT expression and enzyme activity which, in turn, have implications for the regulation of catecholamines. (The ClinicalTrials.gov Identifier: NCT00662571).

In-Person Versus Telehealth Setting for the Delivery of Substance Use Disorder Treatment: Ecologically Valid Comparison Study.

BACKGROUND: The COVID-19 pandemic has profoundly transformed substance use disorder (SUD) treatment in the United States, with many web-based treatment services being used for this purpose. However, little is known about the long-term treatment effectiveness of SUD interventions delivered through digital technologies compared with in-person treatment, and even less is known about how patients, clinicians, and clinical characteristics may predict treatment outcomes. OBJECTIVE: This study aims to analyze baseline differences in patient demographics and clinical characteristics across traditional and telehealth settings in a sample of participants (N=3642) who received intensive outpatient program (IOP) substance use treatment from January 2020 to March 2021. METHODS: The virtual IOP (VIOP) study is a prospective longitudinal cohort design that follows adult (aged ≥18 years) patients who were discharged from IOP care for alcohol and substance use-related treatment at a large national SUD treatment provider between January 2020 and March 2021. Data were collected at baseline and up to 1 year after discharge from both in-person and VIOP services through phone- and web-based surveys to assess recent substance use and general functioning across several domains. RESULTS: Initial baseline descriptive data were collected on patient demographics and clinical inventories. No differences in IOP setting were detected by race (χ22=0.1; P=.96), ethnicity (χ22=0.8; P=.66), employment status (χ22=2.5; P=.29), education level (χ24=7.9; P=.10), or whether participants presented with multiple SUDs (χ28=11.4; P=.18). Significant differences emerged for biological sex (χ22=8.5; P=.05), age (χ26=26.8; P<.001), marital status (χ24=20.5; P<.001), length of stay (F2,3639=148.67; P<.001), and discharge against staff advice (χ22=10.6; P<.01). More differences emerged by developmental stage, with emerging adults more likely to be women (χ23=40.5; P<.001), non-White (χ23=15.8; P<.001), have multiple SUDs (χ23=453.6; P<.001), have longer lengths of stay (F3,3638=13.51; P<.001), and more likely to be discharged against staff advice (χ23=13.3; P<.01). CONCLUSIONS: The findings aim to deepen our understanding of SUD treatment efficacy across traditional and telehealth settings and its associated correlates and predictors of patient-centered outcomes. The results of this study will inform the effective development of data-driven benchmarks and protocols for routine outcome data practices in treatment settings.

Telehealth Services for Substance Use Disorders During the COVID-19 Pandemic: Longitudinal Assessment of Intensive Outpatient Programming and Data Collection Practices.

BACKGROUND: The onset of the COVID-19 pandemic necessitated the rapid transition of many types of substance use disorder (SUD) treatments to telehealth formats, despite limited information about what makes treatment effective in this novel format. OBJECTIVE: This study aims to examine the feasibility and effectiveness of virtual intensive outpatient programming (IOP) treatment for SUD in the context of a global pandemic, while considering the unique challenges posed to data collection during an unprecedented public health crisis. METHODS: The study is based on a longitudinal study with a baseline sample of 3642 patients who enrolled in intensive outpatient addiction treatment (in-person, hybrid, or virtual care) from January 2020 to March 2021 at a large substance use treatment center in the United States. The analytical sample consisted of patients who completed the 3-month postdischarge outcome survey as part of routine outcome monitoring (n=1060, 29.1% response rate). RESULTS: No significant differences were detected by delivery format in continuous abstinence (χ22=0.4, P=.81), overall quality of life (F2,826=2.06, P=.13), financial well-being (F2,767=2.30, P=.10), psychological well-being (F2,918=0.72, P=.49), and confidence in one's ability to stay sober (F2,941=0.21, P=.81). Individuals in hybrid programming were more likely to report a higher level of general health than those in virtual IOP (F2,917=4.19, P=.01). CONCLUSIONS: Virtual outpatient care for the treatment of SUD is a feasible alternative to in-person-only programming, leading to similar self-reported outcomes at 3 months postdischarge. Given the many obstacles presented throughout data collection during a pandemic, further research is needed to better understand under what conditions telehealth is an acceptable alternative to in-person care.

Technology-Facilitated Abuse Prevalence and Associations Among a Nationally Representative Sample of Young Men.

PURPOSE: We undertook a study to determine the prevalence and associations of technology-facilitated abuse (TFA)-insults, harassment, coercion, or threats carried out using digital tools such as smartphones and computers-among a US nationally representative sample of young men. METHODS: Analyses were based on 1,079 men aged 18 to 35 years who completed questionnaires during August and September of 2014 and reported ever having been in a romantic relationship. We used validated measures to assess demographics, health service use, mental health and substance use, and TFA delivered to and received from partners in the past year. We calculated survey-weighted descriptive statistics and conducted multinomial logistic regression analysis. RESULTS: Overall, 4.1% of men reported delivering TFA only, 8.0% receiving TFA only, and 25.6% both delivering and receiving TFA. Men were more likely to report only delivering TFA if they identified as Hispanic (adjusted odds ratio [AOR] = 2.72; 95% CI, 1.13 to 6.57), used marijuana (AOR = 1.31; 95% CI, 1.02 to 1.68), and used prescription opioids for nonmedical reasons (AOR 2.86; 95% CI, 1.48 to 5.54). Men were more likely to report only receiving TFA if they identified as Hispanic (AOR = 2.55; 95% CI, 1.01 to 6.43) and used prescription opioids for nonmedical reasons (AOR = 2.43; 95% CI, 1.34 to 4.39), whereas a primary care connection appeared protective (AOR = 0.43; 95% CI, 0.22 to 0.86). Men were more likely to report both delivering and receiving TFA if they identified as non-Hispanic Black (AOR = 2.83; 95% CI, 1.44 to 5.58), owned a smartphone (AOR = 1.80; 95% CI, 1.05 to 3.09), had ever had mental health care visits (AOR = 1.86; 95% CI, 1.16 to 2.98), misused alcohol (AOR = 1.10; 95% CI, 1.04 to 1.17), and used prescription opioids for nonmedical reasons (AOR = 1.79; 95% CI, 1.04 to 3.08). CONCLUSIONS: We found that TFA was prevalent among young men, with 1 in 25 reporting delivery only, 1 in 12 reporting receipt only, and 1 in 4 reporting both. Primary care physicians can consider assessing TFA among male patients and developing interventions to mitigate this behavior.VISUAL ABSTRACT.

Prevention of sexual violence among college students: Current challenges and future directions.

Objective Preventing sexual violence among college students is a public health priority. This paper was catalyzed by a summit convened in 2018 to review the state of the science on campus sexual violence prevention. We summarize key risk and vulnerability factors and campus-based interventions, and provide directions for future research pertaining to campus sexual violence. Results and Conclusions: Although studies have identified risk factors for campus sexual violence, longitudinal research is needed to examine time-varying risk factors across social ecological levels (individual, relationship, campus context/broader community and culture) and data are particularly needed to identify protective factors. In terms of prevention, promising individual and relational level interventions exist, including active bystander, resistance, and gender transformative approaches; however, further evidence-based interventions are needed, particularly at the community-level, with attention to vulnerability factors and inclusion for marginalized students.

The role of recovery housing during outpatient substance use treatment.

BACKGROUND: Recovery housing generally refers to alcohol- and drug-free living environments that provide peer support for those wanting to initiate and sustain recovery from alcohol and other drug (AOD) disorders. Despite a growing evidence base for recovery housing, relatively little research has focused on how recovery housing may benefit individuals accessing outpatient substance use treatment. METHODS: Using administrative and qualitative data from individuals attending an outpatient substance use treatment program in the Midwestern United States that provides recovery housing in a structured sober living environment, this mixed methods study sought to: (1) determine whether individuals who opted to live in structured sober living during outpatient treatment (N = 138) differed from those who did not (N = 842) on demographic, clinical, or service use characteristics; (2) examine whether living in structured sober living was associated with greater likelihood of satisfactory discharge and longer lengths of stay in outpatient treatment; and (3) explore what individuals (N = 7) who used the structured sober living during outpatient treatment were hoping to gain from the experience. RESULTS: Factors associated with the use of recovery housing during outpatient treatment in multivariate models included gender, age, and receiving more services across episodes of care. Living in structured sober housing was associated with greater likelihood of satisfactory discharge and longer length of stays in outpatient treatment. Focus group participants reported needing additional structure and recovery support, with many noting that structure and accountability, learning and practicing life, coping, and other recovery skills, as well as receiving social and emotional support from others were particularly beneficial aspects of the sober living environment. CONCLUSIONS: Findings underscore the importance of safe and supportive housing during outpatient substance use treatment as well as the need for future research on how housing environments may affect engagement, retention, and outcomes among individuals accessing outpatient substance use treatment.

The Dynamics of Interpersonal Relationships: Understanding Power and Control Tactics Among College Students.

Intimate partner violence (IPV) is a significant public health problem among college students and many students have difficulty identifying unhealthy and abusive behaviors. The aims of this mixed methods study are to: (a) create an inclusive tool that illustrates the power and control experiences of a diverse group of young adult college students, (b) ensure a broad scope of tactics are illustrated (related to technology and different types of relationships), and (c) measure the experience of these tactics, including how IPV knowledge, attitudes, and self-efficacy are influenced by a more inclusive tool. In Phase I, semi-structured interviews were conducted with students (n = 33) and staff (n = 10) at campus sexual assault centers at the three University of Michigan (UM) campuses to explore power and control tactics utilized by perpetrators on college campuses. Content analysis revealed 13 categories of tactics in college relationships. A draft tool was created and assessed for accuracy using cognitive interviews with students (n = 20) from all three campuses in Phase II. Cognitive interviews resulted in the following changes to the final tool: (a) new presentation of the Socioecological Model, (b) identification of substance use as a facilitator for multiple forms of violence, and (c) edits to tactic descriptions. In Phase III, 250 students at UM-Ann Arbor participated in a quasi-experimental evaluation in which 133 interacted with the tool and 117 received access to usual care (campus sexual misconduct policy). Both groups answered survey questions about IPV knowledge, attitudes, self-efficacy, and experiences at baseline, and after one month and five months. Among all college participants in Phase III, 33.5% had experienced lifetime IPV and 25.2% had experienced IPV in the past year. There were no significant differences among IPV knowledge, attitudes, or self-efficacy by group. The Dynamics of Interpersonal Coercion Among College Students tool was created by incorporating current tactics utilized among a diverse college population.

Adapting to the Pandemic: Protocol of a Web-Based Perinatal Health Study to Improve Maternal and Infant Outcomes.

BACKGROUND: The identification of interconnected health risks during the perinatal period offers an opportunity to prevent negative maternal and infant health outcomes. Marijuana, opioid, and other substance use during pregnancy is a rapidly growing public health concern with significant and costly health consequences for the woman and the developing fetus. Pregnant persons who misuse substances are disproportionately more likely to engage in risky sexual behaviors resulting in sexually transmitted infections (STIs), which are on the rise in this population and can lead to adverse effects on maternal health and on fetal development. OBJECTIVE: Our goal is to continue testing an innovative and low-cost technology-delivered intervention, the Health Check-Up for Expectant Moms (HCEM), which simultaneously targets alcohol and drug use and STI risk during pregnancy, both of which are on the rise during the COVID-19 pandemic. METHODS: We describe the ways in which we have adapted the web-based HCEM intervention to continue recruitment and study enrollment during the pandemic. RESULTS: Study recruitment, visits, and participant safety assessments were all successfully modified during the initial year of the COVID-19 pandemic. Compared to in-person recruitment that occurred prepandemic, remote recruitment yielded a greater proportion of women enrolled in the study (83/136, 61.0% vs 43/52, 83%) in a shorter period (12 months vs 7 months). CONCLUSIONS: Despite study challenges related to the pandemic, including time and effort adapting to a remote protocol, remote recruitment and visits for this study were found to constitute a successful approach. TRIAL REGISTRATION: ClinicalTrials.gov NCT03826342; https://clinicaltrials.gov/ct2/show/NCT03826342. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/30367.

Stealthing Perpetration and Victimization: Prevalence and Correlates Among Emerging Adults.

"Stealthing" is a form of sexual violence wherein a sexual partner purposefully removes a condom during penetration without the receptive partner's knowledge. Given the role of substance use in sexual violence broadly, we examined demographic and substance use correlates of stealthing perpetration (SP) and victimization (SV) among emerging adults. Participants comprised 2,550 18- to 25-year-olds (M age = 20.8, SD = 2.3), recruited via social media (48% female; 53.9% non-Hispanic White; 46.0% had another racial/ethnic identity; 67.4% heterosexual; 85.3% had some college education). Unadjusted analyses (t tests, χ2 analysis) and adjusted logistic regression analyses examined associations between demographics (age, education, race/ethnicity, sexual orientation) and substance use (binge drinking, marijuana use, other illegal drug use, and prescription drug misuse) with male SP and male and female SV. Five percent of males and 18.9% of females reported SV; 6.1% of males reported SP. In adjusted analyses, significant correlates of SP were: non-Hispanic White race/ethnicity (odds ratio [OR] = 0.39), binge drinking (OR = 1.39), cannabis use (OR = 1.37), and other drug use (OR = 1.43). Significant correlates of male SV were: non-Hispanic White race/ethnicity (OR = 0.28), non-heterosexual orientation (OR = 0.24), binge drinking (OR = 1.49), and other illegal drug use (OR = 1.79). Significant correlates of female SV were: older age (OR = 1.13), non-Hispanic White race/ethnicity (OR = 0.57), binge drinking (OR = 1.28), cannabis use (OR = 1.29), and other drug use (OR = 1.22). Consistent with literature linking alcohol to sexual violence, binge drinking correlated with both SV and SP, with other substance use also playing a role. Data are needed to explore these relationships using longitudinal, event-level assessments to investigate the influence of acute intoxication. Interventions to reduce sexually transmitted infections, unintended pregnancy, and sexual assault should include content on stealthing and substance use.