Validation of dried blood spots for capturing hepatitis C virus diversity for genomic surveillance.

Dried blood spots (DBS) have emerged as a promising alternative to traditional venous blood for hepatitis C virus (HCV) testing. However, their capacity to accurately reflect the genetic diversity of HCV remains poorly understood. We employed deep sequencing and advanced phylogenetic analyses on paired plasma and DBS samples from two common subtypes to evaluate the suitability of DBS for genomic surveillance. Results demonstrated that DBS captured equivalent viral diversity compared to plasma with no phylogenetic discordance observed. The ability of DBS to accurately reflect the profile of viral genetic diversity suggests it may be a promising avenue for future surveillance efforts to curb HCV outbreaks.

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.

"Expected to happen": perspectives on post-release overdose from recently incarcerated people with opioid use disorder.

BACKGROUND: Opioid-related overdose is the leading cause of death for people recently released from incarceration, however treatment with medications for opioid use disorder (MOUD) during incarceration can reduce the mortality risk. This study seeks to qualitatively analyze perceptions of post-release overdose risk from the perspectives of people who received MOUD while incarcerated in one of eight Massachusetts jails during 2021-2022 using the Risk Environment Framework to guide analyses. METHODS: N = 38 participants with lived experience of MOUD treatment during incarceration who are now living in the community were interviewed on factors that may contribute to or protect against post-release overdose risk. Themes were identified inductively and deductively using the Risk Environment Framework and its domains, which organizes themes along physical, social, economic, and policy environments on both the micro- and macro- scales. RESULTS: The physical risk environment included loss of opioid tolerance during incarceration, polysubstance use, and the toxicity of the regional drug supply as key producers of increased risk for post-release overdose. Social drivers of risk included peer group risk norms-including peer-driven harm reduction practices and interpersonal relationships between drug sellers and buyers-as well as macro-level social determinants of health such as housing insecurity and availability of mental health services. Economic drivers of post-release overdose risk included lack of income generation during incarceration and employment challenges. Participants discussed several aspects of policy that contribute to post-release overdose risk, including availability of harm reduction supplies, public health services, and broader policy around MOUD. CONCLUSIONS: The perspectives of people with lived experience are vital to understanding the disproportionate risks of overdose for those recently released from incarceration. Our results highlight the intersectional factors that produce and reproduce the post-release overdose risk environment, providing support for interventions across each domain of the Risk Environment Framework. By capturing perspectives from people with lived experience of OUD and incarceration during this critical period of risk, we can better identify interventions that target and mitigate overdose-related harm in this population.

Association of spatial proximity to fixed-site syringe services programs with HCV serostatus and injection equipment sharing practices among people who inject drugs in rural New England, United States.

BACKGROUND: Hepatitis C virus (HCV) disproportionately affects rural communities, where health services are geographically dispersed. It remains unknown whether proximity to a syringe services program (SSP) is associated with HCV infection among rural people who inject drugs (PWID). METHODS: Data are from a cross-sectional sample of adults who reported injecting drugs in the past 30 days recruited from rural counties in New Hampshire, Vermont, and Massachusetts (2018-2019). We calculated the road network distance between each participant's address and the nearest fixed-site SSP, categorized as ≤ 1 mile, 1-3 miles, 3-10 miles, and > 10 miles. Staff performed HCV antibody tests and a survey assessed past 30-day injection equipment sharing practices: borrowing used syringes, borrowing other used injection equipment, and backloading. Mixed effects modified Poisson regression estimated prevalence ratios (aPR) and 95% confidence intervals (95% CI). Analyses were also stratified by means of transportation. RESULTS: Among 330 PWID, 25% lived ≤ 1 mile of the nearest SSP, 17% lived 1-3 miles of an SSP, 12% lived 3-10 miles of an SSP, and 46% lived > 10 miles from an SSP. In multivariable models, compared to PWID who lived within 1 mile of an SSP, those who lived 3 to 10 miles away had a higher prevalence of HCV seropositivity (aPR: 1.25, 95% CI 1.06-1.46), borrowing other used injection equipment (aPR: 1.23, 95% CI 1.04-1.46), and backloading (aPR: 1.48, 95% CI 1.17-1.88). Similar results were observed for PWID living > 10 miles from an SSP: aPR [HCV]: 1.19, 95% CI 1.01-1.40; aPR [borrowing other used equipment]:1.45, 95% CI 1.29-1.63; and aPR [backloading]: 1.59, 95% CI 1.13-2.24. Associations between living 1 to 3 miles of an SSP and each outcome did not reach statistical significance. When stratified by means of transportation, associations between distance to SSP and each outcome (except borrowing other used injection equipment) were only observed among PWID who traveled by other means (versus traveled by automobile). CONCLUSIONS: Among PWID in rural New England, living farther from a fixed-site SSP was associated with a higher prevalence of HCV seropositivity, borrowing other used injection equipment, and backloading, reinforcing the need to increase SSP accessibility in rural areas. Means of transportation may modify this relationship.

The relationship between felt stigma and non-fatal overdose among rural people who use drugs.

BACKGROUND: Drug overdose deaths in the United States exceeded 100,000 in 2021 and 2022. Substance use stigma is a major barrier to treatment and harm reduction utilization and is a priority target in ending the overdose epidemic. However, little is known about the relationship between stigma and overdose, especially in rural areas. We aimed to characterize the association between felt stigma and non-fatal overdose in a multi-state sample of rural-dwelling people who use drugs. METHODS: Between January 2018 and March 2020, 2,608 people reporting past 30-day opioid use were recruited via modified chain-referral sampling in rural areas across 10 states. Participants completed a computer-assisted survey of substance use and substance-related attitudes, behaviors, and experiences. We used multivariable logistic regression with generalized estimating equations to test the association between felt stigma and recent non-fatal overdose. RESULTS: 6.6% of participants (n = 173) reported an overdose in the past 30 days. Recent non-fatal overdose was significantly associated with felt stigma after adjusting for demographic and substance use-related covariates (aOR: 1.47, 95% CI: 1.20-1.81). The association remained significant in sensitivity analyses on component fear of enacted stigma items (aOR: 1.48, 95% CI: 1.20-1.83) and an internalized stigma item (aOR: 1.51, 95% CI: 1.07-2.14). CONCLUSIONS: Felt stigma related to substance use is associated with higher risk of non-fatal overdose in rural-dwelling people who use drugs. Stigma reduction interventions and tailored services for those experiencing high stigma are underutilized approaches that may mitigate overdose risk.

Diffusion of medications for opioid use disorder treatment in jail settings: a convergent mixed methods study of jail staff perspectives.

BACKGROUND: Implementation of medications for opioid use disorder (MOUD) in jails varies by facility and across states. Organizational climate, including staff attitudes toward change and exposure to education, can influence perceptions of innovations like MOUD in jails. Using a mixed methods design, we aimed to understand the association between organizational climate and jail staff perceptions of MOUD. METHODS: Jail staff (n = 111) who operate MOUD programs in 6 Massachusetts jails completed surveys that included the Organizational Readiness for Implementing Change (ORIC) survey. Random effects logistic regression models assessed associations between organizational climate and several outcomes of perceived MOUD efficacy, acceptability, and knowledge, while controlling for covariates. Jail staff (N = 61) participated in qualitative interviews and focus groups focused on organizational climate and knowledge diffusion, which we analyzed using inductive and deductive methods. RESULTS: The results indicate that organizational change readiness on the ORIC was associated with positive perceptions of MOUD, and educational resources facilitated MOUD implementation. Greater ORIC was associated with higher perception of methadone as highly acceptable for jail populations (Odds ratio [OR] 2.3, 95% Confidence Interval [CI] 1.2 to 4.4), and high knowledge of methadone (OR 2.3, 95% CI 1.1 to 4.9), with similar magnitude of effects for buprenorphine. High levels of training for jail staff on methadone and buprenorphine were also associated with higher knowledge of these medications (Methadone: OR 7.2, 95% CI 2.2 to 23.2; Buprenorphine: OR 3.4, 95% CI 1.2 to 9.5). Qualitative results point towards the importance of organizational climate and elucidate educational strategies to improve staff perceptions of MOUD. CONCLUSION: Results underscore the importance of organizational climate for successful implementation of jail MOUD programs and provide support for medication-specific educational resources as a facilitator of successful MOUD implementation in jail settings. Findings highlight implementation strategies that may improve jail staff perceptions of MOUD.

Association of random and observed urine drug screening with long-term retention in opioid treatment programs.

BACKGROUND: In the US, opioid treatment providers (OTPs) have wide latitude to perform urine drug screening (UDS) and discharge clients for positive results. OTP clients have identified randomized and directly observed UDS as potentially stigmatizing, but little research has examined the association between UDS modality and retention in OTPs. METHODS: This cross-sectional study uses the 2016-2017 NDATSS wave among OTPs that administered methadone. The exposure was a 4-level variable based on whether OTPs had a high percentage (≥ 90% of clients) who experienced randomized, observed, both, or neither modality of UDS. The outcome was the proportion of clients retained in treatment 1 year or longer (long-term retention). Analyses were conducted using fractional logit regression with survey weighting and presented as percentages and 95% confidence intervals. We also present how policies for involuntary clinic discharge modify these effects. RESULTS: 150 OTPs were eligible with a median of 310 clients. 40 (27%) OTPs did not highly utilize either randomized or observed UDS, 22 (15%) only highly utilized observed UDS, 42 (28%) only highly utilized randomized UDS and 46 (31%) utilized both practices on ≥ 90% of clients. Adjusted estimates for long-term retention ranged from 57.7% in OTPs that conducted both randomized and observed UDS on ≥ 90% of clients and 70.4% in OTPs that did not highly utilize these practices. Involuntary discharge may moderate this relationship. CONCLUSION: Findings showed an association between high utilization of randomized and observed UDS and decreased long-term retention, suggesting that UDS modality may impact long-term OTP retention.

Prison Buprenorphine Implementation and Postrelease Opioid Use Disorder Outcomes.

Importance: Agonist medications for opioid use disorder (MOUD), buprenorphine and methadone, in carceral settings might reduce the risk of postrelease opioid overdose but are uncommonly offered. In April 2019, the Massachusetts Department of Correction (MADOC), the state prison system, provided buprenorphine for incarcerated individuals in addition to previously offered injectable naltrexone. Objective: To evaluate postrelease outcomes after buprenorphine implementation. Design, Setting, and Participants: This cohort study with interrupted time-series analysis used linked data across multiple statewide data sets in the Massachusetts Public Health Data Warehouse stratified by sex due to differences in carceral systems. Eligible participants were individuals sentenced and released from a MADOC facility to the community. The study period for the male sample was January 2014 to November 2020; for the female sample, January 2015 to October 2019. Data were analyzed between February 2022 and January 2024. Exposure: April 2019 implementation of buprenorphine during incarceration. Main Outcomes and Measures: Receipt of MOUD within 4 weeks after release, opioid overdose, and all-cause mortality within 8 weeks after release, each measured as a percentage of monthly releases who experienced the outcome. Segmented linear regression analyzed changes in outcome rates after implementation. Results: A total of 15 225 individuals were included. In the male sample there were 14 582 releases among 12 688 individuals (mean [SD] age, 35.0 [10.8] years; 133 Asian and Pacific Islander [0.9%], 4079 Black [28.0%], 4208 Hispanic [28.9%], 6117 White [41.9%]), a rate of 175.7 releases per month; the female sample included 3269 releases among 2537 individuals (mean [SD] age, 34.9 [9.8] years; 328 Black [10.0%], 225 Hispanic [6.9%], 2545 White [77.9%]), a rate of 56.4 releases per month. Among male participants at 20 months postimplementation, the monthly rate of postrelease buprenorphine receipt was higher than would have been expected under baseline trends (21.2% vs 10.6% of monthly releases; 18.6 additional releases per month). Naltrexone receipt was lower than expected (1.0% vs 6.0%; 8.8 fewer releases per month). Monthly rates of methadone receipt (1.4%) and opioid overdose (1.8%) were not significantly different than expected. All-cause mortality was lower than expected (1.9% vs 2.8%; 1.5 fewer deaths per month). Among female participants at 7 months postimplementation, buprenorphine receipt was higher than expected (31.6% vs 9.5%; 12.4 additional releases per month). Naltrexone receipt was lower than expected (3.4% vs 7.2%) but not statistically significantly different. Monthly rates of methadone receipt (1.1%), opioid overdose (4.8%), and all-cause mortality (1.6%) were not significantly different than expected. Conclusions and Relevance: In this cohort study of state prison releases, postrelease buprenorphine receipt increased and naltrexone receipt decreased after buprenorphine became available during incarceration.

Receipt of medications for opioid use disorder before and after incarceration in Massachusetts State prisons, 2014-2019.

BACKGROUND: Little is known about how use patterns of medications for opioid use disorder (MOUDs) evolve from pre-incarceration to post-incarceration among incarcerated individuals with opioid use disorder. This article describes pre- and post-incarceration MOUD receipt during a period when naltrexone was the only type of MOUD offered in a state prison system, the Massachusetts Department of Correction (MADOC). METHODS: A retrospective cohort study of individuals with opioid use disorder who had an incarceration episode in MADOC during January 2015 to March 2019. The data source was the Massachusetts Public Health Data Warehouse, a multi-sector data platform that links individual-level data from multiple statewide datasets. We described patterns of MOUD receipt during the four weeks prior to and after an incarceration episode. Multivariable logistic regression models characterized predictors of post-incarceration MOUD receipt. RESULTS: In the male sample (n=691 incarcerations), from the pre- to post-incarceration periods, receipt of buprenorphine increased (14.3 % to 18.3 %), naltrexone increased (5.0 % to 10.5 %), and methadone decreased (4.7 % to 1.7 %). Similarly, in the female sample (n=892 incarcerations), from the pre- to post-incarceration periods, receipt of buprenorphine increased (10.3 % to 12.3 %, naltrexone increased (4.5 % to 9.3 %), and methadone decreased (5.0 % to 2.9 %). Much of the post-release naltrexone receipt occurred among participants in MADOC's pre-release naltrexone program. CONCLUSIONS: MOUD receipt was low but increased slightly in the post-incarceration period. This change was driven by increases in buprenorphine and naltrexone and despite decreases in methadone.

Contextual barriers and enablers to establishing an addiction-focused consultation team for hospitalized adults with opioid use disorder.

BACKGROUND: Hospitalization presents an opportunity to begin people with opioid use disorder (OUD) on medications for opioid use disorder (MOUD) and link them to care after discharge; regrettably, people admitted to the hospital with an underlying OUD typically do not receive MOUD and are not connected with subsequent treatment for their condition. To address this gap, we launched a multi-site randomized controlled trial to test the effectiveness of a hospital-based addiction consultation team (the Substance Use Treatment and Recovery Team (START)) consisting of an addiction medicine specialist and care manager team that provide collaborative care and a specified intervention to people with OUD during the inpatient stay. Successful implementation of new practices can be impacted by organizational context, though no previous studies have examined context prior to implementation of addiction consultation services (ACS). This study assessed pre-implementation context for implementing a specialized ACS and tailoring it accordingly. METHODS: We conducted semi-structured interviews with hospital administrators, physicians, physician assistants, nurses, and social workers at the three study sites between April and August 2021 before the launch of the pragmatic trial. Using an analytical framework based on the Consolidated Framework for Implementation Research, we completed a thematic analysis of interview data to understand potential barriers or enablers and perceptions about acceptability and feasibility. RESULTS: We interviewed 28 participants across three sites. The following themes emerged across sites: (1) START is an urgently needed model for people with OUD; (2) Intervention adaptations are recommended to meet local and cultural needs; (3) Linking people with OUD to community clinicians is a highly needed component of START; (4) It is important to engage stakeholders across departments and roles throughout implementation. Across sites, participants generally saw a need for change from usual care to support people with OUD, and thought the START was acceptable and feasible to implement. Differences among sites included tailoring the START to support the needs of varying patient populations and different perceptions of the prevalence of OUD. CONCLUSIONS: Hospitals planning to implement an ACS in the inpatient setting may wish to engage in a systematic pre-implementation contextual assessment using a similar framework to understand and address potential barriers and contextual factors that may impact implementation. Pre-implementation work can help ensure the ACS and other new practices fit within each unique hospital context.

Buprenorphine treatment and clinical outcomes under the opioid use disorder cascade of care.

BACKGROUND: Challenges to engagement and retention on buprenorphine undermine treatment of individuals with opioid use disorder (OUD). Under the OUD Cascade of Care framework, we sought to identify patient characteristics and treatment response associated with superior clinical outcomes. METHODS: A retrospective cohort study of specialty buprenorphine treatment patients entering treatment (n=19,487) based on EHR records from a large multi-state buprenorphine treatment network (2011-2019). Person-level care episodes were evaluated across treatment intake, engagement (i.e. 2+ visits in the month following intake), and retention at 6, 12, and 24 months. Time to achieving 90 days of continuous opioid abstinence was assessed using Cox proportional hazards regressions models and also assessed as a predictor of long-term retention. RESULTS: Most patients engaged (82.4 %), but retention steadily declined over 6-month (38.7 %), 12-month (26.2 %), and 24-month (17.1 %) timepoints. Opioid-positive baseline tests were associated with lower hazards of achieving continuous abstinence for both buprenorphine-positive (aHR=0.33, p<.001) and buprenorphine-negative (aHR=0.49,p<.001) intakes. Opioid abstinence was associated with buprenorphine-positive baseline testing (aHR=1.59,p<.001), especially for those testing opioid-negative (aHR=1.82,p<.001). Patients who achieved and sustained abstinence at 6 months in care were 4.1 and 5.5 times as likely to achieve 12-month and 24-month retention, respectively, compared to patients with intermittent opioid use. CONCLUSION: Treatment discontinuation was concentrated early in care and buprenorphine and opioid status at intake were prognostic of achieving and sustaining abstinence. Early abstinence was associated with higher likelihood of subsequent stage progression. Implementing interventions to support early clinical stability for high-risk patients is critical to improve clinical outcomes.

Barriers to Healthcare and Social Service Utilization Among Rural Older Adults Who Use Drugs.

The objective of this study was to understand barriers to healthcare and social service utilization among older adults residing in rural areas who use drugs. A cross-sectional survey of persons who use opioids or inject drugs in rural counties with high overdose rates across ten states was conducted. For this analysis, participants were restricted to only the 375 individuals aged 50 and older. They were asked about barriers to utilizing healthcare and social services. Multivariate analyses were conducted. The most common barriers were a lack of transportation and a fear of stigma. The average number of barriers was 2.53. Those who were either uninsured or homeless endorsed 37% more barriers. For every five-year increase in age, the number of barriers reduced by 15%. Efforts to reduce these barriers may include expanding eligibility for transportation and housing services and leveraging trusted community members to broker linkages to providers to overcome stigma.

Behavioral and Health Outcome Differences by Heroin or Methamphetamine Preference Among People in Rural US Communities Who Use Both Substances.

Background: The United States' (US) opioid overdose epidemic has evolved into a combined stimulant/opioid epidemic, a pattern driven in part by mitigating opioid overdose risk, variable substance availability, and personal preferences. This study aimed to investigate the association between self-reported substance preference (heroin or methamphetamine) and behavioral/health outcomes among individuals who used both heroin and methamphetamine in the rural US. Methods: The Rural Opioid Initiative is a consortium of 8 research cohorts from 10 states and 65 rural counties that recruited individuals reporting past 30-day injection of any substance or opioid substance use by any route from 1/2018 to 3/2020. Analyses were restricted to participants ⩾18 years, who self-reported either heroin or methamphetamine as their preferred substance and past 30-day use of both heroin and methamphetamine. We examined cross-sectional associations between preferred substance (heroin versus methamphetamine) and behavioral and health outcomes using random effects meta-analysis with adjusted regression models. Results: Among 1239 participants, 61% (n = 752) reported heroin as their preferred substance. Adjusting for age, sex, and race/ethnicity, methamphetamine preference was associated with lower prevalence ratios for current naloxone possession (adjusted prevalence ratio [aPR] = 0.68; 95% Confidence Interval [95% CI] = 0.59-0.78; P-value ⩽ .001), of ever being told they had the hepatitis C virus (HCV; aPR = 0.72; 95% CI: 0.61-0.85; P-value ⩽ .001) and a personal history of overdose (aPR = 0.81; 95% CI = 0.73-0.90; P-value ⩽ .001). Conclusion: In our study analyzing associations between preferred substance and various behavioral and health outcomes amongst people who use both heroin and methamphetamine, a majority of participants preferred heroin. Methamphetamine preference was associated with lower prevalence of naloxone possession, ever being told they had HCV, and prior history of an overdose. This study underscores the need for targeted harm reduction services for people who prefer methamphetamine in rural areas.