Peer-Assisted Telemedicine for Hepatitis C (PATHS): Process evaluation results from a State Opioid Response-funded program.

INTRODUCTION: The opioid crisis and the hepatitis C virus epidemic perpetuate and potentiate each other in a syndemic with escalating morbidity. Policy-driven funding can help resolve the syndemic through collaborative solutions that rapidly translate evidence-based interventions into real-world applications. METHODS: We report development and programmatic evaluation of Peer-Assisted Telemedicine for Hepatitis C (PATHS), which utilizes State Opioid Response (SOR) funding to scale-up a positive randomized trial of peer-assisted telemedicine HCV treatment. PATHS employs staff within an academic medical center and partners with people with lived experience of drug use, "peers," to recruit rural-dwelling people who use drugs living with HCV. PATHS staff record patient data by abstracting clinical records or directly communicating with patients and peers. Peers are funded by a separate SOR-supported program administered through the state health authority. Peers support patients through HCV screening, treatment initiation via telemedicine, adherence, and cure. RESULTS: Between March 2021 and June 2024, PATHS expanded to 18 of Oregon's 36 counties. In that time, PATHS diagnosed 198 rural PWUD with HCV. One hundred sixty-seven (84.3 %) linked to telemedicine and of these, 145 (86.8 %) initiated treatment. Of those who initiated treatment, 91 (62.8 %) completed treatment, of which 61 (67.0 %) are cured. CONCLUSIONS: By rapidly translating a clinical innovation in HCV treatment to achieve highly effective real-world results, PATHS models how policy-driven funding can facilitate collaboration between community partners, academic medical centers, and state health departments to end the opioid-HCV syndemic.

A longitudinal examination of the psychometric properties of the English perceived stress scale- four (PSS-4) in mental health counsellors using item response theory.

We examined the longitudinal psychometric properties of the Perceived Stress Scale - 4 items version (PSS-4) using item response theory with a sample of 361 mental health counsellors. Participants completed the PSS-4 at three timepoints at six-month intervals in a one-year period. There were 290 participants who (80.3%) identified as female, 51 (14.1%) identified as male, eight (2.2%) identified as gender variant/non-conforming, seven (1.9%) wrote in their own gender identity (e.g., genderqueer, gender expansive), three (0.8%) identified as Transgender male, and two (0.6%) did not respond to the item. The racial and ethnic backgrounds were as follows: White (87.3%), Multiracial (5.5%), Latino or Hispanic or Spanish (2.8%), Black or African American (1.4%), Asian (0.8%), Middle Eastern (0.8%), and five did not respond to the item (1.4%). We found unidimensionality evidence of the PSS-4 across all three timepoints and response categories were monotonically ordered. We also found that across all timepoints, the average person location was lower than the average item location, suggesting that the PSS-4 may not be well-targeted for this sample of mental health counsellors. We observed no significant interactions between timepoints, hours worked per week, and length of employment. Implications of the findings, including a discussion of the utility of the PSS-4 as a global measure of stress and with mental health counsellors.

Buprenorphine discontinuation in telehealth-only treatment for opioid use disorder: A longitudinal cohort analysis.

INTRODUCTION: At the beginning of the COVID-19 pandemic, federal agencies permitted telehealth initiation of buprenorphine treatment for opioid use disorder (OUD) without in-person assessment. It remains unclear how telehealth-only buprenorphine treatment impacts time to discontinuation and patient reported treatment outcomes. METHODS: A longitudinal observational cohort study conducted September 2021 through March, 2023 enrolled participants with OUD initiating buprenorphine (≤ 45 days) with internet and phone access in Oregon and Washington. The intervention was a fully telehealth-only (THO) app versus treatment as usual (TAU) in office-based settings with some telehealth. We assessed self-reported buprenorphine discontinuation at 4-,12-, and 24-weeks. Generalized estimating equations (GEE) calculated unadjusted and adjusted relative risk ratios (RR) for discontinuation averaged over the study period. Secondary outcomes included change in the Brief Addiction Monitor (BAM) and the visual analogue craving scale. Generalized linear models estimated average within-group and between-group differences over time. RESULTS: Participants (n = 103 THO; n = 56 TAU) had a mean age of 37 years (SD = 9.8 years) and included 52 % women, 83 % with Medicaid insurance, 80 % identified as White, 65 % unemployed/student, and 19 % unhoused. There were differences in gender (THO = 54 % women vs. TAU = 44 %, p = .04), unemployed status (60 % vs 75 %, p = .02), and stable housing (84 % vs 73 %, p = .02). Rates of buprenorphine discontinuation were low in the THO (4 %) and TAU (13 %) groups across 24 weeks. In the adjusted analysis, the risk of discontinuation was 61 % lower in the THO group (aRR = 0.39, 95 % CI [0.17, 0.89], p = .026). Decreases occurred over time on the harms subscale of the BAM (within-group difference - 0.85, p = .0004 [THO], and - 0.68, p = .04 [TAU]) and cravings (within-group difference - 13.47, p = .0001 [THO] vs -7.65, p = .01 [TAU]). CONCLUSIONS: A telehealth-only platform reduced the risk of buprenorphine discontinuation compared to office-based TAU. In-person evaluation to receive buprenorphine may not be necessary for treatment-seeking patients. CLINICAL TRIALS IDENTIFIER: NCT03224858.

Four years of real-world sexual function outcomes after Rezum therapy in men with and without baseline erectile dysfunction.

BACKGROUND: Rezum alleviates lower urinary tract symptoms secondary to benign prostatic hyperplasia (BPH) while preserving sexual function, but long-term sexual function outcomes are lacking in patients with baseline erectile dysfunction (ED). AIM: The study sought to analyze 4 years of real-world sexual function outcomes of Rezum using the International Index of Erectile Function (IIEF) questionnaire, stratified by baseline ED status. METHODS: Participants included multiethnic Rezum-treated patients from a single outpatient office. IIEF domains and BPH medication usage were compared at baseline and 6, 12, and 48 months using t tests, Mann-Whitney U tests, chi-square tests, and Wilcoxon signed rank tests. OUTCOMES: Primary outcomes over 4 years included the IIEF functional domains (erectile function [EF], orgasmic function [OF], sexual desire [SD], intercourse satisfaction [IS], overall satisfaction [OS]) and BPH medication usage. RESULTS: A total of 91 patients were included: 40 (44%) in the ED cohort and 51 (56%) in the no ED cohort. History of diabetes was more prevalent in the ED cohort (35% vs 15.7%; P = .048). Baseline scores in the EF, OF, IS, and OS domains were lower in the ED cohort. Compared with baseline, there were no significant changes in any IIEF domains in either cohort at 6 months. At 12 months, the ED cohort had significant percent decreases in OF (-25%; P = .02), SD (-22.2%; P = .04), and OS (-33.3%; P = .004); the no ED cohort had a significant percent increase in EF (5%; P = .04). At 48 months, the no ED cohort had no significant changes in any IIEF domains, while the ED cohort had significant percent increases in EF (30%; P = .01), SD (22.5%; P = .02), IS (20%; P = .01), and OS (58.3%; P = .008). Both cohorts significantly discontinued BPH medications at all follow-ups. At 48 months, there were no cases of de novo ED in the no ED cohort. CLINICAL IMPLICATIONS: As modern BPH therapies continue to demonstrate efficacy in alleviating lower urinary tract symptoms, the preservation or improvement of sexual function emerges as an increasingly important consideration for patients, with our study suggesting Rezum as a compelling option. STRENGTHS AND LIMITATIONS: Our study has the strength of long-term Rezum outcomes in an ethnically diverse patient population, stratified by the presence of baseline ED, but is limited by retrospective design, single-center nature, and small sample sizes at long-term follow-ups. CONCLUSION: Rezum preserved long-term sexual function in patients without baseline ED and improved sexual function in those with baseline ED; however, individuals with ED may experience temporary decreases in sexual function at 12 months.

Driving through stop signs: predicting stop codon reassignment improves functional annotation of bacteriophages.

The majority of bacteriophage diversity remains uncharacterized, and new intriguing mechanisms of their biology are being continually described. Members of some phage lineages, such as the Crassvirales, repurpose stop codons to encode an amino acid by using alternate genetic codes. Here, we investigated the prevalence of stop codon reassignment in phage genomes and its subsequent impacts on functional annotation. We predicted 76 genomes within INPHARED and 712 vOTUs from the Unified Human Gut Virome Catalogue (UHGV) that repurpose a stop codon to encode an amino acid. We re-annotated these sequences with modified versions of Pharokka and Prokka, called Pharokka-gv and Prokka-gv, to automatically predict stop codon reassignment prior to annotation. Both tools significantly improved the quality of annotations, with Pharokka-gv performing best. For sequences predicted to repurpose TAG to glutamine (translation table 15), Pharokka-gv increased the median gene length (median of per genome median) from 287 to 481 bp for UHGV sequences (67.8% increase) and from 318 to 550 bp for INPHARED sequences (72.9% increase). The re-annotation increased median coding capacity from 66.8% to 90.0% and from 69.0% to 89.8% for UHGV and INPHARED sequences predicted to use translation table 15. Furthermore, the proportion of genes that could be assigned functional annotation increased, including an increase in the number of major capsid proteins that could be identified. We propose that automatic prediction of stop codon reassignment before annotation is beneficial to downstream viral genomic and metagenomic analyses.

Developing the Open Psychedelic Evaluation Nexus consensus measures for assessment of supervised psilocybin services: An e-Delphi study.

BACKGROUND: Voter initiatives in Oregon and Colorado authorize legal frameworks for supervised psilocybin services, but no measures monitor safety or outcomes. AIMS: To develop core measures of best practices. METHODS: A three-phase e-Delphi process recruited 36 experts with 5 or more years' experience facilitating psilocybin experiences in various contexts (e.g., ceremonial settings, indigenous practices, clinical trials), or other pertinent psilocybin expertise. Phase I, an on-line survey with qualitative, open-ended text responses, generated potential measures to assess processes, outcomes, and structure reflecting high quality psilocybin services. In Phase II, experts used seven-point Likert scales to rate the importance and feasibility of the Phase I measures. Measures were priority ranked. Qualitative interviews and analysis in Phase III refined top-rated measures. RESULTS: Experts (n = 36; 53% female; 71% white; 56% heterosexual) reported currently providing psilocybin services (64%) for a mean of 15.2 [SD 13.1] years, experience with indigenous psychedelic practices (67%), and/or conducting clinical trials (36%). Thematic analysis of Phase I responses yielded 55 candidate process measures (e.g., preparatory hours with client, total dose of psilocybin administered, documentation of touch/sexual boundaries), outcome measures (e.g., adverse events, well-being, anxiety/depression symptoms), and structure measures (e.g., facilitator training in trauma informed care, referral capacity for medical/psychiatric issues). In Phase II and III, experts prioritized a core set of 11 process, 11 outcome, and 17 structure measures that balanced importance and feasibility. CONCLUSION: Service providers and policy makers should consider standardizing core measures developed in this study to monitor the safety, quality, and outcomes of community-based psilocybin services.

Decoding huge phage diversity: a taxonomic classification of Lak megaphages.

High-throughput sequencing for uncultivated viruses has accelerated the understanding of global viral diversity and uncovered viral genomes substantially larger than any that have so far been cultured. Notably, the Lak phages are an enigmatic group of viruses that present some of the largest known phage genomes identified in human and animal microbiomes, and are dissimilar to any cultivated viruses. Despite the wealth of viral diversity that exists within sequencing datasets, uncultivated viruses have rarely been used for taxonomic classification. We investigated the evolutionary relationships of 23 Lak phages and propose a taxonomy for their classification. Predicted protein analysis revealed the Lak phages formed a deeply branching monophyletic clade within the class Caudoviricetes which contained no other phage genomes. One of the interesting features of this clade is that all current members are characterised by an alternative genetic code. We propose the Lak phages belong to a new order, the 'Grandevirales'. Protein and nucleotide-based analyses support the creation of two families, three sub-families, and four genera within the order 'Grandevirales'. We anticipate that the proposed taxonomy of Lak megaphages will simplify the future classification of related viral genomes as they are uncovered. Continued efforts to classify divergent viruses are crucial to aid common analyses of viral genomes and metagenomes.

Evaluation of respondent-driven sampling in seven studies of people who use drugs from rural populations: findings from the Rural Opioid Initiative.

BACKGROUND: Accurate prevalence estimates of drug use and its harms are important to characterize burden and develop interventions to reduce negative health outcomes and disparities. Lack of a sampling frame for marginalized/stigmatized populations, including persons who use drugs (PWUD) in rural settings, makes this challenging. Respondent-driven sampling (RDS) is frequently used to recruit PWUD. However, the validity of RDS-generated population-level prevalence estimates relies on assumptions that should be evaluated. METHODS: RDS was used to recruit PWUD across seven Rural Opioid Initiative studies between 2018-2020. To evaluate RDS assumptions, we computed recruitment homophily and design effects, generated convergence and bottleneck plots, and tested for recruitment and degree differences. We compared sample proportions with three RDS-adjusted estimators (two variations of RDS-I and RDS-II) for five variables of interest (past 30-day use of heroin, fentanyl, and methamphetamine; past 6-month homelessness; and being positive for hepatitis C virus (HCV) antibody) using linear regression with robust confidence intervals. We compared regression estimates for the associations between HCV positive antibody status and (a) heroin use, (b) fentanyl use, and (c) age using RDS-1 and RDS-II probability weights and no weights using logistic and modified Poisson regression and random-effects meta-analyses. RESULTS: Among 2,842 PWUD, median age was 34 years and 43% were female. Most participants (54%) reported opioids as their drug of choice, however regional differences were present (e.g., methamphetamine range: 4-52%). Many recruitment chains were not long enough to achieve sample equilibrium. Recruitment homophily was present for some variables. Differences with respect to recruitment and degree varied across studies. Prevalence estimates varied only slightly with different RDS weighting approaches, most confidence intervals overlapped. Variations in measures of association varied little based on weighting approach. CONCLUSIONS: RDS was a useful recruitment tool for PWUD in rural settings. However, several violations of key RDS assumptions were observed which slightly impacts estimation of proportion although not associations.

Nanopore and Illumina sequencing reveal different viral populations from human gut samples.

The advent of viral metagenomics, or viromics, has improved our knowledge and understanding of global viral diversity. High-throughput sequencing technologies enable explorations of the ecological roles, contributions to host metabolism, and the influence of viruses in various environments, including the human intestinal microbiome. However, bacterial metagenomic studies frequently have the advantage. The adoption of advanced technologies like long-read sequencing has the potential to be transformative in refining viromics and metagenomics. Here, we examined the effectiveness of long-read and hybrid sequencing by comparing Illumina short-read and Oxford Nanopore Technology (ONT) long-read sequencing technologies and different assembly strategies on recovering viral genomes from human faecal samples. Our findings showed that if a single sequencing technology is to be chosen for virome analysis, Illumina is preferable due to its superior ability to recover fully resolved viral genomes and minimise erroneous genomes. While ONT assemblies were effective in recovering viral diversity, the challenges related to input requirements and the necessity for amplification made it less ideal as a standalone solution. However, using a combined, hybrid approach enabled a more authentic representation of viral diversity to be obtained within samples.

The long and short of it: benchmarking viromics using Illumina, Nanopore and PacBio sequencing technologies.

Viral metagenomics has fuelled a rapid change in our understanding of global viral diversity and ecology. Long-read sequencing and hybrid assembly approaches that combine long- and short-read technologies are now being widely implemented in bacterial genomics and metagenomics. However, the use of long-read sequencing to investigate viral communities is still in its infancy. While Nanopore and PacBio technologies have been applied to viral metagenomics, it is not known to what extent different technologies will impact the reconstruction of the viral community. Thus, we constructed a mock bacteriophage community of previously sequenced phage genomes and sequenced them using Illumina, Nanopore and PacBio sequencing technologies and tested a number of different assembly approaches. When using a single sequencing technology, Illumina assemblies were the best at recovering phage genomes. Nanopore- and PacBio-only assemblies performed poorly in comparison to Illumina in both genome recovery and error rates, which both varied with the assembler used. The best Nanopore assembly had errors that manifested as SNPs and INDELs at frequencies 41 and 157 % higher than found in Illumina only assemblies, respectively. While the best PacBio assemblies had SNPs at frequencies 12 and 78 % higher than found in Illumina-only assemblies, respectively. Despite high-read coverage, long-read-only assemblies recovered a maximum of one complete genome from any assembly, unless reads were down-sampled prior to assembly. Overall the best approach was assembly by a combination of Illumina and Nanopore reads, which reduced error rates to levels comparable with short-read-only assemblies. When using a single technology, Illumina only was the best approach. The differences in genome recovery and error rates between technology and assembler had downstream impacts on gene prediction, viral prediction, and subsequent estimates of diversity within a sample. These findings will provide a starting point for others in the choice of reads and assembly algorithms for the analysis of viromes.

Structure- and machine learning-guided engineering demonstrate that a non-canonical disulfide in an anti-PD-1 rabbit antibody does not impede antibody developability.

Rabbits produce robust antibody responses and have unique features in their antibody repertoire that make them an attractive alternative to rodents for in vivo discovery. However, the frequent occurrence of a non-canonical disulfide bond between complementarity-determining region (CDR) H1 (C35a) and CDRH2 (C50) is often seen as a liability for therapeutic antibody development, despite limited reports of its effect on antibody binding, function, and stability. Here, we describe the discovery and humanization of a human-mouse cross-reactive anti-programmed cell death 1 (PD-1) monoclonal rabbit antibody, termed h1340.CC, which possesses this non-canonical disulfide bond. Initial removal of the non-canonical disulfide resulted in a loss of PD-1 affinity and cross-reactivity, which led us to explore protein engineering approaches to recover these. First, guided by the sequence of a related clone and the crystal structure of h1340.CC in complex with PD-1, we generated variant h1340.SA.LV with a potency and cross-reactivity similar to h1340.CC, but only partially recovered affinity. Side-by-side developability assessment of both h1340.CC and h1340.SA.LV indicate that they possess similar, favorable properties. Next, and prompted by recent developments in machine learning (ML)-guided protein engineering, we used an unbiased ML- and structure-guided approach to rapidly and efficiently generate a different variant with recovered affinity. Our case study thus indicates that, while the non-canonical inter-CDR disulfide bond found in rabbit antibodies does not necessarily constitute an obstacle to therapeutic antibody development, combining structure- and ML-guided approaches can provide a fast and efficient way to improve antibody properties and remove potential liabilities.

Adolescent Residential Addiction Treatment In The US: Uneven Access, Waitlists, And High Costs.

Drug overdose deaths among adolescents are increasing in the United States. Residential treatment facilities are one treatment option for adolescents with substance use disorders, yet little is known about their accessibility or cost. Using the Substance Abuse and Mental Health Services Administration's treatment locator and search engine advertising data, we identified 160 residential addiction treatment facilities that treated adolescents with opioid use disorder as of December 2022. We called facilities while role-playing as the aunt or uncle of a sixteen-year-old child with a recent nonfatal overdose, to inquire about policies and costs. Eighty-seven facilities (54.4 percent) had a bed immediately available. Among sites with a waitlist, the mean wait time for a bed was 28.4 days. Of facilities providing cost information, the mean cost of treatment per day was $878. Daily costs among for-profit facilities were triple those of nonprofit facilities. Half of facilities required up-front payment by self-pay patients. The mean up-front cost was $28,731. We were unable to identify any facilities for adolescents in ten states or Washington, D.C. Access to adolescent residential addiction treatment centers in the United States is limited and costly.

Dissemination and implementation of an evidence-based voluntary medical male circumcision program: The Spear & Shield program.

Despite compelling evidence linking voluntary medical male circumcision (VMMC) with 60-70% HIV risk reduction in sub-Saharan Africa, Zambian men have been especially reluctant to undergo VMMC. The Government of Zambia set targets for VMMC uptake and promoted community-level interventions. Spear & Shield (S&S) is an innovative, evidence-based, service program promoting VMMC uptake while ensuring both VMMC supply and demand. This study assessed the large-scale provincial rollout of the program (S&S2) utilizing the RE-AIM model for translating interventions into the community. The S&S2 study was conducted between November 2015 and December 2020, and sequentially rolled out over four Zambian provinces in 96 clinics; 24 observation clinics received VMMC training only. Local clinic healthcare workers were trained to conduct the VMMC procedure and HIV counselors were trained to lead S&S group sessions. Using the RE-AIM model, primary outcomes were: Reach, the number, proportion, and representativeness of S&S attendees; Effectiveness, the impact of S&S2 on VMMC uptake; Adoption, the number, proportion, and representativeness of clinics implementing S&S2; Implementation, fidelity to the S&S intervention manual; and Maintenance, the extent to which S&S2 became an element of standard care within community clinics. Initially, n = 109 clinics were recruited; 96 were sustained and randomized for activation (Adoption). A total of 45,630 clinic patients (n = 23,236 men and n = 22,394 women) volunteered to attend the S&S sessions (Reach). The S&S2 program ran over 2,866 clinic-months (Implementation). Although the study did not target individual-level VMMCs, ~58,301 additional VMMCs were conducted at the clinic level (Effectiveness). Fidelity to the S&S intervention by group leaders ranged from 42%-95%. Sustainability of the program was operationalized as the number of CHCs initially activated that sustained the program. Intervention delivery ended, however, when study funding ceased (Maintenance). The S&S2 program successfully utilized the RE-AIM model to achieve study goals for implementation and dissemination in four Zambian provinces. Innovative VMMC programs such as S&S2 can improve the uptake of VMMC, one of the most effective strategies in the HIV prevention arsenal.

Associations between stimulant use and return to illicit opioid use following initiation onto medication for opioid use disorder.

AIM: The aim of this study was to estimate how ongoing stimulant use affects return to illicit opioid use after initiation onto medication for opioid use disorder (MOUD). DESIGN: This was a secondary analysis of pooled data from two clinical trials comparing buprenorphine (BUP-NX) and extended-release naltrexone (XR-NTX). SETTING: Thirteen opioid treatment programs and HIV clinics across 10 states in the United States from 2014 to 2019 took part in this study. PARTICIPANTS: A total of 528 participants who initiated MOUD as part of trial participation were included. Nearly half (49%) were between 30 and 49 years of age, 69% were male and 66% were non-Hispanic White. MEASUREMENTS: The primary outcome was first self-reported day of non-prescribed opioid use following MOUD initiation, and the exposure of interest was daily stimulant use (methamphetamine, amphetamines or cocaine). Both were defined using time-line follow-back. Among participants reporting at least 1 day of illicit opioid use, we also examined relapse to ongoing use, defined as (1) 7 days of continuous opioid use or (2) 4 consecutive weeks with self-reported opioid use, one or more positive urine drug screens (UDS) for opioids or one or more missing UDS. FINDINGS: Forty-seven per cent of participants reported stimulant use following MOUD initiation, 58% returned to illicit opioid use and 66% of those relapsed to ongoing use. Stimulant use was strongly associated with increased risk of misusing opioids after MOUD initiation when measured daily [adjusted hazard ratio (aHR) = 9.23, 95% confidence interval (CI) = 6.80-12.50, P < 0.001] and over a 7-day period (aHR = 1.27 for each additional day, CI = 1.18-1.37, P < 0.001). Using stimulants weekly or more often was associated with increased likelihood of relapse to ongoing opioid use compared with less than weekly or no stimulant use (adjusted odds ratio = 2.30, CI = 1.05-5.39, P = 0.044). CONCLUSIONS: People initiated on medication for opioid use disorder who subsequently use stimulants appear to be more likely to return to and continue using non-prescribed opioids compared with those without stimulant use. The association appears to be stronger among patients who initiate buprenorphine compared with those who initiate extended-release naltrexone.

Viral metagenomics reveals diverse virus-host interactions throughout the soil depth profile.

IMPORTANCE: Soil viruses can moderate the roles that their host microbes play in global carbon cycling. However, given that most studies investigate the surface layer (i.e., top 20 cm) of soil, the extent to which this occurs in subsurface soil (i.e., below 20 cm) is unknown. Here, we leveraged public sequencing data to investigate the interactions between viruses and their hosts at soil depth intervals, down to 115 cm. While most viruses were detected throughout the soil depth profile, their adaptation to host microbes varied. Nonetheless, we uncovered evidence for the potential of soil viruses to encourage their hosts to recycle plant-derived carbon in both surface and subsurface soils. This work reasons that our understanding of soil viral functions requires us to continue to dig deeper and compare viruses existing throughout soil ecosystems.

Recent Incarceration, Substance Use, Overdose, and Service Use Among People Who Use Drugs in Rural Communities.

Importance: Drug use and incarceration have a substantial impact on rural communities, but factors associated with the incarceration of rural people who use drugs (PWUD) have not been thoroughly investigated. Objective: To characterize associations between recent incarceration, overdose, and substance use disorder (SUD) treatment access among rural PWUD. Design, Setting, and Participants: For this cross-sectional study, the Rural Opioid Initiative research consortium conducted a survey in geographically diverse rural counties with high rates of overdose across 10 US states (Illinois, Wisconsin, North Carolina, Oregon, Kentucky, West Virginia, Ohio, Massachusetts, New Hampshire, and Vermont) between January 25, 2018, and March 17, 2020, asking PWUD about their substance use, substance use treatment, and interactions with the criminal legal system. Participants were recruited through respondent-driven sampling in 8 rural US regions. Respondents who were willing to recruit additional respondents from their personal networks were enrolled at syringe service programs, community support organizations, and through direct community outreach; these so-called seed respondents then recruited others. Of 3044 respondents, 2935 included participants who resided in rural communities and reported past-30-day injection of any drug or use of opioids nonmedically via any route. Data were analyzed from February 8, 2022, to September 15, 2023. Exposure: Recent incarceration was the exposure of interest, defined as a report of incarceration in jail or prison for at least 1 day in the past 6 months. Main Outcomes and Measures: The associations between PWUD who were recently incarcerated and main outcomes of treatment use and overdose were examined using logistic regression. Results: Of 2935 participants, 1662 (56.6%) were male, 2496 (85.0%) were White; the mean (SD) age was 36 (10) years; and in the past 30 days, 2507 (85.4%) reported opioid use and 1663 (56.7%) reported injecting drugs daily. A total of 1224 participants (41.7%) reported recent incarceration, with a median (IQR) incarceration of 15 (3-60) days in the past 6 months. Recent incarceration was associated with past-6-month overdose (adjusted odds ratio [AOR], 1.38; 95% CI, 1.12-1.70) and recent SUD treatment (AOR, 1.62; 95% CI, 1.36-1.93) but not recent medication for opioid use disorder (MOUD; AOR, 1.03; 95% CI, 0.82-1.28) or currently carrying naloxone (AOR, 1.02; 95% CI, 0.86-1.21). Conclusions and Relevance: In this cross-sectional study of PWUD in rural areas, participants commonly experienced recent incarceration, which was not associated with MOUD, an effective and lifesaving treatment. The criminal legal system should implement effective SUD treatment in rural areas, including MOUD and provision of naloxone, to fully align with evidence-based SUD health care policies.

Treatment Initiation, Substance Use Trajectories, and the Social Determinants of Health in Persons Living With HIV Seeking Medication for Opioid Use Disorder.

BACKGROUND: People living with HIV and opioid use disorder (OUD) are disproportionally affected by adverse socio-structural exposures negatively affecting health, which have shown inconsistent associations with uptake of medications for OUD (MOUD). This study aimed to determine whether social determinants of health (SDOH) were associated with MOUD uptake and trajectories of substance use in a clinical trial of people seeking treatment. METHODS: Data are from a 2018 to 2019 randomized trial comparing the effectiveness of different MOUD to achieve viral suppression among people living with HIV and OUD. SDOH were defined by variables mapping to Healthy People 2030 domains: education (Education Access and Quality), income (Economic Stability), homelessness (Neighborhood and Built Environment), criminal justice involvement (Social and Community Context), and recent SUD care (Health Care Access and Quality). Associations between SDOH and MOUD initiation were assessed with Cox proportional hazards models, and SDOH and substance use over time with generalized estimating equation models. RESULTS: Participants (N = 114) averaged 47 years old, 63% were male, 56% were Black, and 12% Hispanic. Participants reported an average of 2.3 out of 5 positive SDOH indicators (SD = 1.2). Stable housing was the most commonly reported SDOH (61%), followed by no recent criminal justice involvement (59%), having a high-school level education or greater (56%), income stability (45%), and recent SUD care (13%). Each additional favorable SDOH was associated with a 25% increase in the likelihood of MOUD initiation during the study period [adjusted HR = 1.25, 95% CI = (1.01, 1.55), P = .044]. Positive SDOH were also associated with a decrease in the odds of baseline opioid use and a greater reduction in opioid use during subsequent weeks of the study (P < .001 for a joint test of baseline and slope differences). CONCLUSIONS: Positive social determinants of health, in aggregate, may increase the likelihood of MOUD treatment initiation among people living with HIV and OUD.

Increasing early infant male circumcision uptake in Zambia: Like father like son.

Voluntary Medical Male Circumcision (VMMC) is an effective strategy for HIV prevention in areas with high prevalence of, and risk for, HIV. More than 361,000 male neonates are born each year in Zambia, many of whom could be eligible for Early-Infant Medical Circumcision (EIMC). Building on successful implementation strategies utilized in our Spear & Shield program, this pilot study, "Like Father, Like Son" (LFLS), evaluated the feasibility and acceptability of offering combined EIMC and VMMC services and couple-level behavioral interventions. A total of N = 702 pregnant women and their male partners (n = 351 couples) were recruited and enrolled. Couples were assessed twice pre-birth, 2 weeks post birth, and 6 months post birth. Expectant mothers were an average of 15.05 weeks pregnant (SD = 8.83). Thirty-nine pregnancies did not result in a live birth (11%), 14 couples withdrew from the study or were lost to follow-up prior to delivery (4%), and 148 babies were born female (42%), leaving 150 couples with a male infant in the analytic sample (43%). The LFLS study achieved significantly higher EIMC rates (35%) in comparison with previously observed EIMC study rates in Zambia (11%), and significantly higher than hypothetical comparison rates up to 30%. Relative to baseline rates, odds of VMMC among couples' older sons increased by 31% at post-intervention and by 90% at two-weeks following birth. Overall, this pilot study found the LFLS intervention to be feasible, acceptable, and effective in doubling the rate of EIMC in comparison with a previous longitudinal study in Zambia. Future research should consider a family-centric approach to promotion of male circumcision for infants and adolescents. LFLS may be effective in promoting father-son "bonding" by MC status; a bond that may be a bridge to increase both EIMC and VMMC uptake in newborns and couples' older sons and is a novel leverage point for promotion of this HIV prevention strategy.

A randomized controlled trial for a peer-facilitated telemedicine hepatitis c treatment intervention for people who use drugs in rural communities: study protocol for the "peer tele-HCV" study.

BACKGROUND: Hepatitis C virus (HCV) transmission is primarily driven by injection drug use, and acute HCV infection rates are increased in rural communities with substantial barriers to care. Treatment of HCV in persons who use drugs (PWUD) is cost effective, decreases high risk behaviors and HCV transmission, and achieves high rates of treatment completion and sustained viral response. Adapting HCV care delivery to utilize peer support specialists, telemedicine technology, and streamlined testing and treatment strategies can better reach rural populations living with HCV. METHODS: This is an open label, two-arm, non-blinded, randomized controlled trial designed to test the superiority of peer-facilitated and streamlined telemedicine HCV care (peer tele-HCV) compared to enhanced usual care (EUC) among PWUD in rural Oregon. In the intervention arm, peers conduct HCV screening in the community, facilitate pretreatment evaluation and linkage to telemedicine hepatitis C treatment providers, and support participants in HCV medication adherence. For participants assigned to EUC, peers facilitate pretreatment evaluation and referral to community-based treatment providers. The primary outcome is sustained virologic response at 12 weeks post treatment (SVR12). Secondary outcomes include: (1) HCV treatment initiation, (2) HCV treatment completion, (3) engagement with harm reduction resources, (4) rates of substance use, and (5) engagement in addiction treatment resources. The primary and secondary outcomes are analyzed using intention-to-treat (ITT) comparisons between telemedicine and EUC. A qualitative analysis will assess patient, peer, and clinician experiences of peer-facilitated telemedicine hepatitis C treatment. DISCUSSION: This study uses a novel peer-based telemedicine delivery model with streamlined testing protocols to improve access to HCV treatment in rural communities with high rates of injection drug use and ongoing disease transmission. We hypothesize that the peer tele-HCV model will increase treatment initiation, treatment completion, SVR12 rates, and engagement with harm reduction services compared to EUC. Trial registration This trial has been registered with ClinicalTrials.gov (clinicaltrials.gov NCT04798521).

A gender-based secondary analysis of the ADAPT-2 combination naltrexone and bupropion treatment for methamphetamine use disorder trial.

BACKGROUND AND AIMS: Socio-cultural (gender) and biological (sex)-based differences contribute to psychostimulant susceptibility, potentially affecting treatment responsiveness among women with methamphetamine use disorder (MUD). The aims were to measure (i) how women with MUD independently and compared with men respond to treatment versus placebo and (ii) among women, how the hormonal method of contraception (HMC) affects treatment responsiveness. DESIGN: This was a secondary analysis of ADAPT-2, a randomized, double-blind, placebo-controlled, multicenter, two-stage sequential parallel comparison design trial. SETTING: United States. PARTICIPANTS: This study comprised 126 women (403 total participants); average age = 40.1 years (standard deviation = 9.6) with moderate to severe MUD. INTERVENTIONS: Interventions were combination intramuscular naltrexone (380 mg/3 weeks) and oral bupropion (450 mg daily) versus placebo. MEASUREMENTS: Treatment response was measured using a minimum of three of four negative methamphetamine urine drug tests during the last 2 weeks of each stage; treatment effect was the difference between weighted treatment responses of each stage. FINDINGS: At baseline, women used methamphetamine intravenously fewer days than men [15.4 versus 23.1% days, P = 0.050, difference = -7.7, 95% confidence interval (CI) = -15.0 to -0.3] and more women than men had anxiety (59.5 versus 47.6%, P = 0.027, difference = 11.9%, 95% CI = 1.5 to 22.3%). Of 113 (89.7%) women capable of pregnancy, 31 (27.4%) used HMC. In Stage 1 29% and Stage 2 5.6% of women on treatment had a response compared with 3.2% and 0% on placebo, respectively. A treatment effect was found independently for females and males (P < 0.001); with no between-gender treatment effect (0.144 females versus 0.100 males; P = 0.363, difference = 0.044, 95% CI = -0.050 to 0.137). Treatment effect did not differ by HMC use (0.156 HMC versus 0.128 none; P = 0.769, difference = 0.028, 95% CI -0.157 to 0.212). CONCLUSIONS: Women with methamphetamine use disorder receiving combined intramuscular naltrexone and oral bupropion treatment achieve greater treatment response than placebo. Treatment effect does not differ by HMC.