Prescribe to Save Lives: An Intervention to Increase Naloxone Prescribing Among HIV Clinicians.

OBJECTIVES: Overdose is a major cause of preventable death among persons living with HIV. This study aimed to increase HIV clinicians' naloxone prescribing, which can reduce overdose mortality. METHODS: We enrolled 22 Ryan White-funded HIV practices and implemented onsite, peer-to-peer training, posttraining academic detailing, and pharmacy peer-to-peer contact around naloxone prescribing in a nonrandomized stepped wedge design. Human immunodeficiency virus clinicians completed surveys to assess attitudes toward prescribing naloxone at preintervention and 6 and 12 months postintervention. Aggregated electronic health record data measured the number of patients with HIV prescribed and the number of HIV clinicians prescribing naloxone by site over the study period. Models controlled for calendar time and clustering of repeated measures among individuals and sites. RESULTS: Of 122 clinicians, 119 (98%) completed a baseline survey, 111 (91%) a 6-month survey, and 93 (76%) a 12-month survey. The intervention was associated with increases in self-reported "high likelihood" to prescribe naloxone (odds ratio [OR], 4.1 [1.7-9.4]; P = 0.001). Of 22 sites, 18 (82%) provided usable electronic health record data that demonstrated a postintervention increase in the total number of clinicians who prescribed naloxone (incidence rate ratio, 2.9 [1.1-7.6]; P = 0.03) and no significant effects on sites having at least one clinician who prescribed naloxone (OR, 4.1 [0.7-23.8]; P = 0.11). The overall proportion of all HIV patients prescribed naloxone modestly increased from 0.97% to 1.6% (OR, 2.2 [0.7-6.8]; P = 0.16). CONCLUSION: On-site, practice-based, peer-to-peer training with posttraining academic detailing was a modestly effective strategy to increase HIV clinicians' prescribing of naloxone.

COVID-19 impact on opioid overdose after jail release in Massachusetts.

Introduction: Release from incarceration is a high-risk period for opioid overdose. Concern about COVID-19 spread in jails led to early releases; it is unknown whether pandemic era releases of persons with opioid use disorder (OUD) contributed to increases in community overdose rates. Methods: Observational data compared overdose rates three months after release among jailed persons with OUD released before (9/1/2019-3/9/2020) and during the pandemic (3/10/2020-8/10/2020) from seven jails in Massachusetts. Data on overdoses come from the Massachusetts Ambulance Trip Record Information System and Registry of Vital Records Death Certificate file. Other information came from jail administrative data. Logistic models regressed overdose on release period, controlling for MOUD received, county of release, race/ethnicity, sex, age, and prior overdose. Results: Pandemic releases with OUD had a higher risk of fatal overdose (adjusted odds ratio [aOR] 3.06; 95% CI, 1.49 to 6.26); 20 persons released with OUD (1.3%) experienced a fatal overdose within three months of release, versus 14 (0.5%) pre-pandemic. MOUD had no detectable relationship with overdose mortality. Pandemic release did not impact non-fatal overdose rates (aOR 0.84; 95% CI 0.60 to 1.18), though in-jail methadone treatment was protective (aOR 0.34; 95% CI 0.18 to 0.67). Conclusions: Persons with OUD released from jail during the pandemic experienced higher overdose mortality compared to pre-pandemic, but the number of deaths was small. They did not experience significantly different rates of non-fatal overdose. Early jail releases during the pandemic were unlikely to explain much, if any, of the observed increase in community overdoses in Massachusetts.

Prescribe to Save Lives: Improving Buprenorphine Prescribing Among HIV Clinicians.

BACKGROUND: HIV clinicians are uniquely positioned to treat their patients with opioid use disorder using buprenorphine to prevent overdose death. The Prescribe to Save Lives (PtSL) study aimed to increase HIV clinicians' buprenorphine prescribing via an overdose prevention intervention. METHODS: The quasi-experimental stepped-wedge study enrolled 22 Ryan White-funded HIV clinics and delivered a peer-to-peer training to clinicians with follow-up academic detailing that included overdose prevention education and introduced buprenorphine prescribing. Site-aggregated electronic medical record (EMR) data measured with the change in X-waivered clinicians and patients prescribed buprenorphine. Clinicians completed surveys preintervention and at 6- and 12-month postintervention that assessed buprenorphine training, prescribing, and attitudes. Analyses applied generalized estimating equation models, adjusting for time and clustering of repeated measures among individuals and sites. RESULTS: Nineteen sites provided EMR prescribing data, and 122 clinicians returned surveys. Of the total patients with HIV across all sites, EMR data showed 0.38% were prescribed buprenorphine pre-intervention and 0.52% were prescribed buprenorphine postintervention. The intervention increased completion of a buprenorphine training course (adjusted odds ratio 2.54, 95% confidence interval: 1.38 to 4.68, P = 0.003) and obtaining an X-waiver (adjusted odds ratio 2.11, 95% confidence interval: 1.12 to 3.95, P = 0.02). There were nonsignificant increases at the clinic level, as well. CONCLUSIONS: Although the PtSL intervention resulted in increases in buprenorphine training and prescriber certification, there was no meaningful increase in buprenorphine prescribing. Engaging and teaching HIV clinicians about overdose and naloxone rescue may facilitate training in buprenorphine prescribing but will not result in more treatment with buprenorphine without additional interventions.

Massachusetts Justice Community Opioid Innovation Network (MassJCOIN).

A major driver of the U.S. opioid crisis is limited access to effective medications for opioid use disorder (MOUD) that reduce overdose risks. Traditionally, jails and prisons in the U.S. have not initiated or maintained MOUD for incarcerated individuals with OUD prior to their return to the community, which places them at high risk for fatal overdose. A 2018 law (Chapter 208) made Massachusetts (MA) the first state to mandate that five county jails deliver all FDA-approved MOUDs (naltrexone [NTX], buprenorphine [BUP], and methadone). Chapter 208 established a 4-year pilot program to expand access to all FDA-approved forms of MOUD at five jails, with two more MA jails voluntarily joining this initiative. The law stipulates that MOUD be continued for individuals receiving it prior to detention and be initiated prior to release among sentenced individuals where appropriate. The jails must also facilitate continuation of MOUD in the community on release. The Massachusetts Justice Community Opioid Innovation Network (MassJCOIN) partnered with these seven diverse jails, the MA Department of Public Health, and community treatment providers to conduct a Type 1 hybrid effectiveness-implementation study of Chapter 208. We will: (1) Perform a longitudinal treatment outcome study among incarcerated individuals with OUD who receive NTX, BUP, methadone, or no MOUD in jail to examine postrelease MOUD initiation, engagement, and retention, as well as fatal and nonfatal opioid overdose and recidivism; (2) Conduct an implementation study to understand systemic and contextual factors that facilitate and impede delivery of MOUDs in jail and community care coordination, and strategies that optimize MOUD delivery in jail and for coordinating care with community partners; (3) Calculate the cost to the correctional system of implementing MOUD in jail, and conduct an economic evaluation from state policy-maker and societal perspectives to compare the value of MOUD prior to release from jail to no MOUD among matched controls. MassJCOIN made significant progress during its first six months until the COVID-19 pandemic began in March 2020. Participating jail sites restricted access for nonessential personnel, established other COVID-19 mitigation policies, and modified MOUD programming. MassJCOIN adapted research activities to this new reality in an effort to document and account for the impacts of COVID-19 in relation to each aim. The goal remains to produce findings with direct implications for policy and practice for OUD in criminal justice settings.

The opioid epidemic in rural northern New England: An approach to epidemiologic, policy, and legal surveillance.

The opioid crisis presents substantial challenges to public health in New England's rural states, where access to pharmacotherapy for opioid use disorder (OUD), harm reduction, HIV and hepatitis C virus (HCV) services vary widely. We present an approach to characterizing the epidemiology, policy and resource environment for OUD and its consequences, with a focus on eleven rural counties in Massachusetts, New Hampshire and Vermont between 2014 and 2018. We developed health policy summaries and logic models to facilitate comparison of opioid epidemic-related polices across the three states that could influence the risk environment and access to services. We assessed sociodemographic factors, rates of overdose and infectious complications tied to OUD, and drive-time access to prevention and treatment resources. We developed GIS maps and conducted spatial analyses to assess the opioid crisis landscape. Through collaborative research, we assessed the potential impact of available resources to address the opioid crisis in rural New England. Vermont's comprehensive set of policies and practices for drug treatment and harm reduction appeared to be associated with the lowest fatal overdose rates. Franklin County, Massachusetts had good access to naloxone, drug treatment and SSPs, but relatively high overdose and HIV rates. New Hampshire had high proportions of uninsured community members, the highest overdose rates, no HCV surveillance data, and no local access to SSPs. This combination of factors appeared to place PWID in rural New Hampshire at elevated risk. Study results facilitated the development of vulnerability indicators, identification of locales for subsequent data collection, and public health interventions.

Initiation of extended release naltrexone (XR-NTX) for opioid use disorder prior to release from prison.

BACKGROUND: Opioid use disorder is common in prison populations, and prison release is a high-risk time for relapse and overdose. Initiation of extended release injectable naltrexone (XR-NTX)) prior to prison release might decrease relapse among opioid-dependent persons. OBJECTIVE: This pilot study examined the feasibility and acceptability of XR-NTX injection prior to prison release among adult inmates with opioid use disorder, followed by six months of community XR-NTX treatment. It sought to determine effects on treatment retention and abstinence compared to post-release XR-NTX initiation. METHODS: Recruitment for the study took place at the RIDOC's Adult Correctional Institute (ACI). Volunteers with a history of opioid dependence and a release date scheduled within 1-2months were self-referred in response to recruitment fliers. Consented volunteers were randomized to XR-NTX treatment prior to release followed by 5 monthly treatments in the community (pre-release) or six XR-NTX treatments in the community (post-release). RESULTS: Of 26 volunteers consented, 15 were randomized (9 pre-release, 6 post-release). The pre-release group generally had better treatment retention: 100% received the first NTX injection (vs. 67% post-release), 78% received more than one injection (vs. 17%) and 22% received all 6 injections (vs. 0%). The pre-release group also had greater abstinence, with a higher proportion of self-reported opioid free days in the first month after release (83% vs. 46%, fewer positive urine drug tests in the 6months after release (22% vs. 33%), and more days of opioid receptor blockade during the first two weeks after release, a high risk time for overdose death. CONCLUSIONS: Initiation of XR-NTX injection prior to release from prison might be an effective approach to reduce relapse to opioids, but these findings require confirmation in a larger trial.

Do patient characteristics moderate the effect of extended-release naltrexone (XR-NTX) for opioid use disorder?

BACKGROUND: Extended release naltrexone (XR-NTX) injected intramuscularly monthly has been shown to reduce relapse in persons with opioid use disorder. Baseline factors, including patients' demographics, comorbidities and lifestyle, may help identify patients who will benefit most or least from XR-NTX treatment. METHODS: Potential moderators of XR-NTX's effect were examined in the largest North American randomized open-label effectiveness trial of XR-NTX. Relapse status (Yes/No) at 6-month follow-up was regressed on treatment group (XR-NTX, N=153; or Treatment-as-Usual [TAU], N=155), baseline covariates, and their two-way interaction to identify moderator effects. Baseline covariates included age, gender, summary scores for depression, suicidal thoughts, drug abuse risk, substance use, medical, psychiatric and employment status, socialization, legal and family/social issues, history of abuse and quality of life measures. RESULTS: Alcohol use to intoxication in the 30days before randomization was a significant moderator: during the treatment phase, those who reported being recently intoxicated before randomization to XR-NTX relapsed to opioids at a rate (56%) similar to TAU (58%), while those without alcohol intoxication in the prior 30days had a lower rate of opioid relapse (41% vs. 65%, respectively, P<0.04). CONCLUSIONS: XR-NTX appeared to work equally well across subgroups with diverse demographic, addiction, mental health and environmental characteristics, with the possible exception of working better among those without recent alcohol intoxication. These findings should be reassuring to practitioners increasingly using XR-NTX as medical addiction therapy in diverse and often vulnerable populations.

The Need for Psychosocial Interventions to Facilitate the Transition to Extended-Release Naltrexone (XR-NTX) Treatment for Opioid Dependence: A Concise Review of the Literature.

Given the increase of opioid dependence and opioid-related morbidity and mortality, improving treatment options for individuals with opioid dependence warrants increased attention. This article provides a concise review of work in this area. Remission from opioid dependence can be very difficult to sustain, particularly in the absence of opioid replacement or opioid antagonist therapy. For those who wish to transition from opioid use or opioid replacement therapy to opioid antagonist therapy, a significant challenge can be the period of withdrawal symptoms that must be endured prior to the initiation of opioid antagonist therapy. Studies that have incorporated psychosocial interventions into detoxification protocols have found that they can result in improved treatment outcomes. Interventions based on Acceptance and Commitment Therapy have shown promise in the treatment of clinical disorders that present with symptoms similar to those of opioid withdrawal and have been found to positively impact outcomes among those tapering from methadone. However, the use of an Acceptance and Commitment Therapy-based intervention has yet to be studied among opioid-dependent patients transitioning to XR-NTX, and its value to those transitioning to XR-NTX is currently unknown.

Extended-Release Naltrexone to Prevent Opioid Relapse in Criminal Justice Offenders.

BACKGROUND: Extended-release naltrexone, a sustained-release monthly injectable formulation of the full mu-opioid receptor antagonist, is effective for the prevention of relapse to opioid dependence. Data supporting its effectiveness in U.S. criminal justice populations are limited. METHODS: In this five-site, open-label, randomized trial, we compared a 24-week course of extended-release naltrexone (Vivitrol) with usual treatment, consisting of brief counseling and referrals for community treatment programs, for the prevention of opioid relapse among adult criminal justice offenders (i.e., persons involved in the U.S. criminal justice system) who had a history of opioid dependence and a preference for opioid-free rather than opioid maintenance treatments and who were abstinent from opioids at the time of randomization. The primary outcome was the time to an opioid-relapse event, which was defined as 10 or more days of opioid use in a 28-day period as assessed by self-report or by testing of urine samples obtained every 2 weeks; a positive or missing sample was computed as 5 days of opioid use. Post-treatment follow-up occurred at weeks 27, 52, and 78. RESULTS: A total of 153 participants were assigned to extended-release naltrexone and 155 to usual treatment. During the 24-week treatment phase, participants assigned to extended-release naltrexone had a longer median time to relapse than did those assigned to usual treatment (10.5 vs. 5.0 weeks, P<0.001; hazard ratio, 0.49; 95% confidence interval [CI], 0.36 to 0.68), a lower rate of relapse (43% vs. 64% of participants, P<0.001; odds ratio, 0.43; 95% CI, 0.28 to 0.65), and a higher rate of opioid-negative urine samples (74% vs. 56%, P<0.001; odds ratio, 2.30; 95% CI, 1.48 to 3.54). At week 78 (approximately 1 year after the end of the treatment phase), rates of opioid-negative urine samples were equal (46% in each group, P=0.91). The rates of other prespecified secondary outcome measures--self-reported cocaine, alcohol, and intravenous drug use, unsafe sex, and reincarceration--were not significantly lower with extended-release naltrexone than with usual treatment. Over the total 78 weeks observed, there were no overdose events in the extended-release naltrexone group and seven in the usual-treatment group (P=0.02). CONCLUSIONS: In this trial involving criminal justice offenders, extended-release naltrexone was associated with a rate of opioid relapse that was lower than that with usual treatment. Opioid-use prevention effects waned after treatment discontinuation. (Funded by the National Institute on Drug Abuse; ClinicalTrials.gov number, NCT00781898.).

Extended-release naltrexone to prevent relapse among opioid dependent, criminal justice system involved adults: rationale and design of a randomized controlled effectiveness trial.

BACKGROUND: Extended-release naltrexone (XR-NTX, Vivitrol; Alkermes Inc.) is an injectable monthly sustained-release mu opioid receptor antagonist. XR-NTX is a potentially effective intervention for opioid use disorders and as relapse prevention among criminal justice system (CJS) populations. METHODS: This 5-site open-label randomized controlled effectiveness trial examines whether XR-NTX reduces opioid relapse compared with treatment as usual (TAU) among community dwelling, non-incarcerated volunteers with current or recent CJS involvement. The XR-NTX arm receives 6 monthly XR-NTX injections at Medical Management visits; the TAU group receives referrals to available community treatment options. Assessments occur every 2 weeks during a 24-week treatment phase and at 12- and 18-month follow-ups. The primary outcome is a relapse event, defined as either self-report or urine toxicology evidence of ≥10 days of opioid use in a 28-day (4 week) period, with a positive or missing urine test counted as 5 days of opioid use. RESULTS: We describe the rationale, specific aims, and design of the study. Alternative design considerations and extensive secondary aims and outcomes are discussed. CONCLUSIONS: XR-NTX is a potentially important treatment and relapse prevention option among persons with opioid dependence and CJS involvement. ClinicalTrials.gov: NCT00781898.

Medication-assisted treatment in criminal justice agencies affiliated with the criminal justice-drug abuse treatment studies (CJ-DATS): availability, barriers, and intentions.

Medication-assisted treatment (MAT) is underutilized in the treatment of drug-dependent, criminal justice populations. This study surveyed criminal justice agencies affiliated with the Criminal Justice Drug Abuse Treatment Studies (CJ-DATS) to assess use of MAT and factors influencing use of MAT. A convenience sample (N = 50) of criminal justice agency respondents (e.g., jails, prisons, parole/probation, and drug courts) completed a survey on MAT practices and attitudes. Pregnant women and individuals experiencing withdrawal were most likely to receive MAT for opiate dependence in jail or prison, whereas those reentering the community from jail or prison were the least likely to receive MAT. Factors influencing use of MAT included criminal justice preferences for drug-free treatment, limited knowledge of the benefits of MAT, security concerns, regulations prohibiting use of MAT for certain agencies, and lack of qualified medical staff. Differences across agency type in the factors influencing use and perceptions of MAT were also examined. MAT use is largely limited to detoxification and maintenance of pregnant women in criminal justice settings. Use of MAT during the community reentry period is minimal. Addressing inadequate knowledge and negative attitudes about MAT may increase its adoption, but better linkages to community pharmacotherapy during the reentry period might overcome other issues, including security, liability, staffing, and regulatory concerns. The CJ-DATS collaborative MAT implementation study to address inadequate knowledge, attitudes, and linkage will be described.

Front-loaded versus weekly counseling for treatment of tobacco addiction.

INTRODUCTION: Approximately 60%-70% of cigarette smokers who try to quit relapse by 2 weeks postcessation. We tested the efficacy of a front-loaded (FL) counseling intervention whose goal was to increase the likelihood of successful early abstinence and subsequent long-term abstinence. METHODS: We randomized 278 adult smokers to an FL or weekly behavioral smoking cessation counseling schedule. The total number of sessions across treatment was the same for both groups. However, those assigned to the FL schedule received 6 counseling sessions in the first 2 weeks postcessation, while those in the weekly condition received 2 sessions. Participants in both groups also received standard nicotine patch treatment. RESULTS: At 1 year postcessation, FL participants were significantly less likely to have relapsed when continuous abstinence was used as the definition of abstinence/relapse (11.7% abstinent vs. 6.3%, hazard ratio [HR] = 0.69, p = .007); and there were nonsignificant trends for FL subjects to have better outcomes when abstinence was defined as never smoking for 7 or more consecutive days nor for 7 or more consecutive episodes (18.4% abstinent vs. 14.8%, HR = 0.83, p = .20) and as point prevalence abstinence (15.6% abstinent vs. 12.9%, p = .11). The relationship between FL counseling treatment and continuous abstinence was partially mediated by higher postcessation levels of social support perceived from counseling and greater use of cessation-related coping strategies. CONCLUSIONS: We conclude that FL counseling is a promising treatment model that should be evaluated further, perhaps using modifications of the FL schedule used in this study.

A prospective study of persistence in the prediction of smoking cessation outcome: results from a randomized clinical trial.

Research has had mixed success in identifying pretreatment variables which can be used to guide treatment and enhance outcome. A critical first step in the process is to identify variables that reliably predict outcome. Some recent studies, largely retrospective, have found mixed evidence on the relationship between task persistence and smoking outcome measures. In the present study, we use data from a randomized clinical trial (N=241) to prospectively investigate the ability of persistence to predict outcome. Findings from multivariate analyses did not support our hypotheses: persistence did not predict outcome. We discuss these findings in relation to previous studies by focusing on theoretical and measurement issues related to the study of persistence in smoking cessation research. We conclude by recommending directions for future research, including conceptual clarification of the relationship between persistence and theoretically related constructs and investigations of variables that may moderate relationships between these constructs and cessation outcome.

The influence of gender, race, and menthol content on tobacco exposure measures.

Research has suggested that race, gender, and menthol cigarette use influence tobacco-smoke exposure measures and smoking-related disease risk. For example, a high proportion of Black smokers prefer menthol cigarettes and, despite smoking fewer cigarettes per day (CPD) than do Whites, tend to have higher cotinine levels. Additionally, Black males are more at risk for smoking-related lung cancer. High cotinine levels and smoking menthol cigarettes may lead to higher toxin intake, which contributes to increased disease risk. We explored the relationship between tobacco exposure variables (i.e., cotinine, CPD, carbon monoxide [CO], nicotine content, and nicotine dependence) with respect to race, gender, and menthol content in a sample of 307 smokers recruited from the greater Boston area to participate in a smoking cessation treatment trial. The pattern of correlations between tobacco exposure measures and cotinine showed a consistently positive correlation between cotinine and CO in all smokers and a correlation between cotinine and CPD in those who smoked nonmenthol cigarettes. Cotinine and CPD correlations varied by gender and race among menthol cigarette smokers. Consistently, we found a significant gender x race x menthol interaction on salivary cotinine level as well as cotinine/CPD ratio. These findings suggest that the relationship between number of cigarettes consumed and salivary cotinine is more complex than previously believed. It is not sufficient to look at race alone; researchers and clinicians need to look at race and gender concurrently, as well as type of cigarette consumed.