Faculty Bibliography

BACKGROUND:The distinct pharmacological properties and clinical uses of extended-release naltrexone (XR-NTX) and sublingual buprenorphine-naloxone (BUP-NX) present challenges in analyzing patient outcomes. METHODS:We conducted a secondary analysis of a multi-site randomized trial comparing XR-NTX with sublingual BUP-NX treatment for opioid use disorder initiated during inpatient detoxification and continued in outpatient treatment. Urine testing data for non-study opioids from the last 22 weeks of the 24-week trial were analyzed in both a per-protocol sample (n = 474 participants who received at least one dose of medication) and a completers sample (n = 211 participants who received all XR-NTX doses or all BUP-NX prescriptions). The present analyses sought to identify differences in the weekly percentages of opioid-positive urine tests between participants treated with the two medications. RESULTS:The proportion of opioid-positive tests in both conditions was less than 20 % for 21 of the 22 weeks in the per-protocol sample and all 22 weeks in the completers sample. Generalized linear mixed model analyses revealed a significant treatment (XR-NTX vs. BUP-NX) X week (weeks 3-24) interaction in the per-protocol sample but not the completers sample. In the per-protocol analysis, the BUP-NX, compared to XR-NTX, had significantly greater proportions of opioid-positive tests in 14 out of the 22 weeks. CONCLUSIONS:Longitudinal modeling approaches that utilize flexible procedures for handling missing data can offer a different perspective on study findings. Results from the present analyses suggest that XR-NTX appeared to be somewhat more effective than BUP-NX in reducing illicit opioid use in the per-protocol sample.

BACKGROUND:The National Drug Abuse Treatment Clinical Trials Network (CTN) multisite comparative-effectiveness study ("X:BOT") by Lee et al. (2018) found that, once initiated, extended-release naltrexone (XR-NTX) is as similarly safe and effective as sublingual buprenorphine-naloxone (BUP-NX) for the treatment of opioid use disorder (OUD). However, the detoxification hurdle makes XR-NTX much more difficult to initiate than BUP-NX. This hurdle highlights the need to better understand how patients transition from active opioid use to XR-NTX treatment. OBJECTIVE:To explore patient-identified barriers and facilitators to initiating antagonist treatment (XR-NTX) within the context of an inpatient hospital setting and to reflect postdischarge experiences of those who did and did not initiate XR-NTX treatment. METHOD/METHODS:We used a convenience sampling strategy to identify study candidates, with the intention of recruiting approximately an equal number of medication-initiated and noninitiated patients. Study participants (N = 14) included 13 males and 1 female with OUD randomized to the XR-NTX arm of the X:BOT study at 1 of the 8 study sites. Seven participants in this sample initiated XR-NTX treatment, and seven did not. Each participant completed one semistructured qualitative interview. We analyzed transcripts using deductive and inductive approaches to conventional content analysis. RESULTS:Although the majority of participants viewed opioid blockade, once-monthly dosing, and no dependence or withdrawal as favorable attributes of XR-NTX, participant ambivalence and lack of familiarity with antagonist treatment were barriers to treatment initiation. The long duration of action and the perceived "commitment" to the medication (e.g., "At the time, a month sounded like a year") compounded the patients' concerns and ambivalence. The majority of those who initiated XR-NTX described it as an effective treatment for OUD, with treatment satisfaction and sustained abstinence emerging as central themes among this population. Some participants who did not successfully initiate XR-NTX expressed regret and a willingness to try XR-NTX in the future. CONCLUSION/CONCLUSIONS:Achieving full opioid detoxification is one, but not the only, barrier to initiating treatment with XR-NTX. Additional participant-identified barriers to XR-NTX initiation include fears and ambivalence regarding antagonist treatment. Once initiated, participants perceive XR-NTX to be an effective treatment for maintaining abstinence from opioids. XR-NTX appealed to participants due to the autonomy it affords with once-monthly dosing and no physical dependence.

Background: Primary care clinics often struggle to choose the approach to alcohol and drug screening that is best suited to their resources, workflows, and patient populations. We are conducting a multi-site study to inform the implementation and feasibility of electronic health record (EHR)-integrated screening.
Method(s): In two urban academic health systems, researchers worked with stakeholders from 6 clinics to define and implement their optimal screening approach. All clinics used single-item screening questions for alcohol/drugs followed by AUDIT-C/DAST-10. Clinics chose between: (a) screening at routine vs. annual visits; and (b) staff-administered vs computer self-administered screening. Results were recorded in the EHR, and data was extracted quarterly to describe implementation outcomes including screening rate and detected prevalence of unhealthy (moderate-high risk) use among those screened. Findings are from the first 3 to 12 months post-implementation at each clinic.
Result(s): Across sites, of 84 311 patients with primary care visits, 58 492 (69%) were screened. In the four clinics with mature (9-12 months) implementation, screening rates ranged from 42% to 95%. Rates were lower (10%-22%) in the two clinics that recently launched. Screening at routine encounters, in comparison to annual visits, achieved higher screening rates for alcohol (90%-95% vs 42%-62%) and drugs (90%-94% vs 38%-60%). Staff-administered screening, in comparison to patient self-administered screening, had lower rates of detection of unhealthy alcohol use (2% vs 15-37%). Detection of unhealthy drug use was low, ranging from 0.3% to 1.5%.
Conclusion(s): EHR-integrated screening was feasible to implement in at least four of the six clinics; 1-year results (available Fall 2019) will determine feasibility at all sites. Self-administered screening at routine primary care visits achieved the highest rates of screening and detection of unhealthy alcohol use. Although limited by differences among clinics and their patient populations, this study provides insight into outcomes that may be expected with commonly used screening strategies in primary care.
Summary: This multi-site study conducted in the NIDA Clinical Trials Network seeks to inform the implementation and feasibility of EHR-integrated screening for substance use in primary care. This study will provide insight into outcomes that may be expected with commonly used screening strategies in primary care and may assist in fine-tuning the most appropriate approach to alcohol and drug screening best suited for primary care clinics, based on their individual resources, workflows, and patient populations

PURPOSE/OBJECTIVE:Young adults are disproportionately affected by the current opioid crisis. Although medications for opioid use disorder are broadly effective, with reductions in morbidity and mortality, the particular effectiveness of medications for opioid use disorder among young adults is less well understood. METHODS:This secondary analysis compared young adults (aged 18-25 years) with older adults (aged ≥26 years) in a large comparative effectiveness trial ("XBOT") that randomized subjects to extended-release naltrexone or sublingual buprenorphine-naloxone for 6 months. Opioid relapse was defined by opioid use over four consecutive weeks or seven consecutive days, using urine testing and self-report. RESULTS:Among subjects in the intention-to-treat sample (n = 570, all randomized participants), a main effect of age group was found, with higher relapse rates among young adults (70.3%) compared with older adults (58.2%), with an odds ratio of 1.72 (95% confidence interval = 1.08-2.70), p = .02. In the per-protocol sample (n = 474, only participants who started medication), relapse rates were higher among young adults (66.3%) compared with older adults (50.8%), with an odds ratio of 1.91 (95% confidence interval = 1.19-3.06). Among the intention-to-treat sample, survival analysis revealed a significant time-by-age group interaction (p = .01) with more relapse over time in young adults. No significant interactions between age and medication group were detected. CONCLUSIONS:Young adults have increased rates of relapse compared with older adults, perhaps because of vulnerabilities that increase their risk for treatment dropout and medication nonadherence, regardless of medication assignment. These results suggest that specialized, developmentally informed interventions may be needed to improve retention and successful treatment of opioid use disorder among young adults.

OBJECTIVE:To examine the health-related quality-of-life (HRQoL) of persons with opioid use disorder (OUD) seeking treatment in an inpatient detoxification or short-term residential setting; continuing treatment as outpatients. METHODS:We conducted a secondary analysis of data from a clinical trial (N = 508) where participants were randomized to extended-release naltrexone or buprenorphine-naloxone for the prevention of opioid relapse. We used a generalized structural equation regression mixture model to identify associations of HRQoL (EQ-5D) trajectories, including latent characteristics, over the 24-week trial and 36-week follow-up period, among participants who reported HRQoL beyond baseline. This novel framework accounted for baseline and time-varying characteristics, while simultaneously identifying latent classes. RESULTS:We identified two subpopulations: HRQoL "pharmacotherapy responsive" (82.3 %) and HRQoL "characteristic sensitive" (17.7 %). The pharmacotherapy responsive subpopulation was characterized by a shortterm HRQoL improvement and then stable HRQoL over time, and by a positive association between HRQoL and receiving pharmacotherapy in the past 30 days. The characteristic sensitive subpopulation was characterized by an initial improvement in HRQoL with a gradual decline over time, and no significant HRQoL response to pharmacotherapy. HRQoL changes over time in this subpopulation were more influenced by baseline demographic, socioeconomic, and psychosocial characteristics. CONCLUSION/CONCLUSIONS:Our findings suggest that while HRQoL may be improved and sustained through targeted efforts to promote use of pharmacotherapy for many persons with OUD, an identifiable subpopulation may require additional services that address socioeconomic and psychosocial issues to achieve HRQoL benefits. Our analysis provides insight for improving individualized care for persons with opioid use disorder seeking treatment.

BACKGROUND:Sublingual buprenorphine-naloxone (BUP-NX), an FDA-approved treatment for opioid use disorder (OUD), combines buprenorphine (a partial mu/kappa agonist) with naloxone (a mu/ kappa antagonist). Extended-release injection naltrexone (XR-NTX; a mu receptor antagonist and kappa receptor partial agonist) is also an FDA-approved treatment for OUD. However, while some patients respond well to these medications, many others leave treatment and relapse. OBJECTIVES/OBJECTIVE:Determine whether gene variants in the opioid gene system are associated with better or worse treatment response. METHODS:= 334), two outcomes measures were assessed: received first dose (yes/no) and received last dose (yes/no). Separate logistic regressions were used to each model outcome measure as a function of treatment (XR-NTX vs BUP-NX), each gene variant, and their interaction. RESULTS:There were no significant main effects of gene variant on receiving first dose or last dose. There were also no significant gene variant by treatment interactions. CONCLUSIONS:The outcome of treatment of OUD with medications is likely a complex function of multiple factors, including environmental, psychosocial, and possibly genetic, such that major effects of genetic variants may be unlikely.