Faculty Bibliography

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: Alcohol and drug use are often under-identified in primary care settings. While prior research indicates that patients are generally supportive of alcohol screening, less is known about attitudes toward drug screening or the collection of this information in electronic health records (EHRs). As a part of an implementation study of EHRintegrated substance use screening in primary care, conducted in the NIDA Clinical Trials Network, patients were surveyed on their attitudes toward screening for substance use during medical visits.
METHOD(S): Surveys were administered to patients in four urban academic primary care clinics on a quarterly basis, for one year following the introduction of a screening program. English-speaking adult patients presenting for a primary care visit were eligible. Participants were recruited from the waiting room and self-administered an 18-item survey exploring attitudes toward screening and discussing substance use with healthcare providers.
RESULT(S): A total of 479 patients completed the survey (mean age 54.1; 58% female; 58% white, 23% black; 19% Hispanic/Latino). Participants overwhelmingly felt that they should be asked about their substance use (91%), and deemed it appropriate for their doctor to recommend reducing use if it could adversely affect their health (92%). Most (87%) were equally comfortable discussing alcohol or drug use. A majority (63%) preferred discussing substance use with their doctor over other medical staff. Responses weremixed regarding screening modality: 55%preferred face-to-face, 22% had no preference, 14% preferred self- administration. Participants reported that they would be honest with their provider (94%), but 32% were concerned about medical record confidentiality.
CONCLUSION(S): Primary care patients strongly supported being screened for drug and alcohol use, and would be comfortable discussing it with their doctor. However, patients' concerns about having their substance use documented in their medical record could pose a barrier to achieving accurate responses. These findings suggest a need to educate patients on the confidentiality of medical records and the value of disclosing substance use for their medical care

BACKGROUND: Under-treatment of drug and alcohol use in primary care settings has been attributed, in part, to medical providers' negative attitudes toward substance use. As a part of an implementation study of electronic health record-integrated substance use screening in primary care clinics, conducted in the NIDA Clinical Trials Network, we assessed baseline attitudes among medical staff.
METHOD(S): Eligible participants were primary care providers and medical assistants in 4 urban academic primary care clinics. Prior to implementation of a substance use screening program, participants completed the Substance Abuse Attitudes Survey (SAAS), a validated 50-item self-administered survey that measures attitudes to substance use in 5 domains: permissiveness, non-moralism, nonstereotyping, treatment intervention, and treatment optimism. Participants were asked to rate their level of agreement with each item on a five-point Likert scale.
RESULT(S): In total, 131/191 (69% response rate) eligible staff completed the survey. Participants had mean age 42; 76% were female; 11% Hispanic/Latino, 6% Black, 25% Asian. The majority of the sample was physicians (78%), while 11% were nurse practitioners, and 11% were medical assistants. Participants had an overall average of 13.2 years in practice. Approximately onethird reported moderate to high satisfaction treating patients with drug problems (35.1%) and alcohol problems (33.6%). The proportion of participants having positive attitudes in each of the following domains were: non-moralism (64.1%); non-stereotyping (55.7%); treatment intervention (47.3%); treatment optimism (48.9%); and permissiveness (44.3%). Negative attitudes toward permissiveness reflect responses to items addressing health effects of substance use, especially among teens.
CONCLUSION(S): While most primary care staff did not endorse moralistic or stereotyping statements about alcohol and drug use, attitudes toward addiction treatment were mixed, with less than half endorsing positive attitudes toward treatment effectiveness. These results suggest a need to improve attitudes, particularly toward addiction treatment. This could be accomplished through education and increased exposure to effective interventions that can be delivered by primary care providers, including officebased treatment for alcohol and opioid use disorder

Few studies examine the effectiveness of treatments for opioid use disorder (OUD) among Black individuals despite recent evidence suggesting opioid overdose death rates are, in some cases, highest and increasing at a faster rate among Black people compared to other racial/ethnic groups. This secondary analysis study investigated treatment preference, retention, and relapse rates amongst a subgroup of 73 Black participants with OUD (81% male, mean age 39.05, SD = 11.80) participating in a 24-week multisite randomized clinical trial ("X:BOT") comparing the effectiveness of extended-release naltrexone (XR-NTX) and sublingual buprenorphine-naloxone (BUP-NX) between 2014 and 2017. Chi-square analyses were used to investigate treatment preference assessed at baseline, and logistic regression analyses were used to investigate differences in the odds of retention and relapse assessed over the 24-week course of treatment between treatment groups. Our findings suggest no differences in preference for XR-NTX versus BUP-NX. However, similar to the parent trial, there was an induction hurdle such that only 59.5% of those randomized to XR-NTX successfully initiated medication compared to 91.6% of those randomized to BUP-NX (OR = 0.13, 95% CI = 0.04, 0.52). No significant differences were found in treatment retention (intention-to-treat: OR = 1.19, 95% CI = 0.43, 3.28; per-protocol [i.e., those who initiated medication]: OR = 0.60, 95% CI = 0.20, 1.82) or relapse rates between treatment groups (intention-to-treat: OR = 1.53, 95% CI = 0.57, 4.13; per-protocol: OR = 0.69, 95% CI = 0.23, 2.06). Although there is a significant initiation hurdle with XR-NTX, once inducted, both medications appear similar in effectiveness, but as in the main study, dropout rates were high. Future research is needed on how to improve adherence.

Purpose: Almost uniformly, patients with frequent Emergency Department (ED) use and severe alcohol use disorders (AUDs) do not receive alcohol pharmacotherapy and are excluded from research as they are difficult to engage and retain and suffer from myriad bio-psychosocial comorbidities. We assessed the feasibility and acceptability of initiating and continuing treatment with extended-release naltrexone (XR-NTX) as well as studying its effects in this challenging population and clinical setting.
Method(s): In this randomized, open-label study, ED patient-participants with > 4 ED visits and moderate- severe AUD were randomized (1:1) to XR-NTX and research assistant-delivered care management or treatment as usual enhanced by a one-time warm referral and motivation enhancement. XR-NTX was first administered during the index ED visit. Thereafter, participants could receive up to 11 additional doses at clinic visits with arrangements to allow unscheduled visits. Non-clinical research visits (both arms) were scheduled at 3, 6, and 12 months with a considerable date variation permitted and expected. Drinking was assessed via 30-day timeline followback with heavy drinking day (HDD) thresholds of 5 for males and 4 for females. Resuts: The 48 participants were aged 55.0 +/- 8.2, 88% male, 51% white, 79% homeless, and reported an average of 23.4 HDDs in the priormonth and 24.4 standard drinks/drinking day. Approximately 70%lacked reliable contact information. Research visit attendance was 70.8%, 77.1%, and 70.8%with a median time to first visit of 126 days [Interquartile Range: 89-242]. In the XR-NTX arm (N = 24), a total of 173 injections were administered with amean of 7.2 per participant; 20 (83%) participants received 2 or more injections, 14 (56%) received 6 or more injections, and 6 (24%) received 12 injections. There was a significantly greater decrease in HDDs per month among those receiving XR-NTX compared to those who did not: 15.3 (95%CI 9.7-21.0) and 9.6 (95%CI 1.5-17.6), respectively. Baseline rates were imputed for two missing participants in each arm.
Conclusion(s): Among this population whose complicated AUDs pose considerable challenges from clinical and research perspectives, initiating and continuing treatment with XR-NTX was feasible, acceptable, and demonstrated promising preliminary drinking outcomes. Additional sensitivity analyses and evaluation of other outcomes of interest are underway. Further study on a larger scale is warranted

OBJECTIVES/OBJECTIVE:The effectiveness of treatment incorporating relapse prevention medications for opioid use disorder (OUD) is typically examined in research using rigidly predefined endpoints of success versus failure, usually over a single episode of care. But this perspective may not adequately portray the nonlinear trajectories typical of real-world treatment courses in this chronic, remitting, and relapsing disorder. METHODS:This descriptive study examined 12-month treatment trajectories of n = 60 patients enrolled at a single site of a larger multisite randomized controlled trial examining the comparative effectiveness of buprenorphine versus extended-release naltrexone. While the parent study provided medication treatment through the research protocol for 6 months, this study documents treatment up to 12 months, including medications, provided through standard community resources (treatment as usual) outside of the protocol. RESULTS:Some patients continued medications past the end of the study intervention, whereas others did not. Some patients initiated medications other than the one assigned by the study. Some patients switched from 1 medication to the other. Many patients returned to treatment after 1 or more periods of dropout and/or relapse. Patients utilized multiple episodes of bed-based care, including short-term acute residential and long-term residential treatment, and also recovery housing supports. Described trajectories are also depicted graphically. At 12 months, while rates of continuous treatment retention were low (8%), rates of cross-sectional treatment engagement including return to treatment after drop out were higher (35%). CONCLUSIONS:This description of nonlinear treatment trajectories highlights the potential benefits of flexibility and optimism in the promotion of re-engagement, despite interim outcomes that might traditionally be considered "failure" endpoints.

Objectives: To study the health-related quality of life (HRQoL) of persons with opioid use disorder (OUD) initiating medication treatment.
Method(s): We conducted a secondary analysis of data collected from a clinical trial funded by the National Drug Abuse Treatment Clinical Trials Network, where participants (N=570) in residential treatment were randomized to initiating extended-release naltrexone (XR-NTX) or buprenorphine-naloxone (BUP-NX) for the prevention of opioid relapse. A generalized structural equation latent-class model was used to identify associations and describe HRQoL trajectories over the 24-week trial and subsequent 28- and 36-week follow-ups for all participants regardless of success initiating treatment.
Result(s): Two latent classes were identified and defined: HRQoL "pharmacotherapy responsive" (82.3%), and HRQoL "baseline sensitive" (17.7%). The pharmacotherapy responsive class was characterized by HRQoL that tended to increase over time and a significant positive association between HRQoL and whether BUP-NX or XR-NTX was received in the past 30 days. The baseline sensitive class was characterized by lower average receipt of pharmacotherapy, initial increase in HRQoL with gradual decrease over time, and no significant HRQoL response to pharmacotherapy. HRQoL changes over time among patients in this class were sensitive to age, race, marital status, and motivation at baseline. Compared to the pharmacotherapy responsive class, the baseline sensitive class included higher proportions of participants who were female, white, married, less educated, and less motivated at baseline. The pharmacotherapy responsive class participants had, on average, less severe medical, drug, legal, and psychiatric problems at baseline.
Conclusion(s): The majority of persons with OUD enrolled in this trial experienced improvements in HRQoL that were associated with pharmacotherapy, while a smaller sub-group with lower average receipt of pharmacotherapy had HRQoL changes that were associated with baseline characteristics but not pharmacotherapy. Our analysis provides insights for improved person-centered care for OUD patients receiving pharmacotherapy who are not adherent to treatment.
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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

Background and Objectives: To rapidly develop, implement, and evaluate emergency department (ED) clinical protocols for initiation of buprenorphine (E

Importance/UNASSIGNED:Opioid addiction is a major public health problem. Despite availability of evidence-based treatments, relapse and dropout are common outcomes. Efforts aimed at identifying reuse risk and gaining more precise understanding of the mechanisms conferring reuse vulnerability are needed. Objective/UNASSIGNED:To use tools from computational psychiatry and decision neuroscience to identify changes in decision-making processes preceding opioid reuse. Design, Setting, and Participants/UNASSIGNED:A cohort of individuals with opioid use disorder were studied longitudinally at a community-based treatment setting for up to 7 months (1-15 sessions per person). At each session, patients completed a risky decision-making task amenable to computational modeling and standard clinical assessments. Time-lagged mixed-effects logistic regression analyses were used to assess the likelihood of opioid use between sessions (t to t + 1; within the subsequent 1-4 weeks) from data acquired at the current session (t). A cohort of control participants completed similar procedures (1-5 sessions per person), serving both as a baseline comparison group and an independent sample in which to assess measurement test-retest reliability. Data were analyzed between January 1, 2018, and September 5, 2019. Main Outcomes and Measures/UNASSIGNED:Two individual model-based behavioral markers were derived from the task completed at each session, capturing a participant's current tolerance of known risks and ambiguity (partially unknown risks). Current anxiety, craving, withdrawal, and nonadherence were assessed via interview and clinic records. Opioid use was ascertained from random urine toxicology tests and self-reports. Results/UNASSIGNED:Seventy patients (mean [SE] age, 44.7 [1.3] years; 12 women and 58 men [82.9% male]) and 55 control participants (mean [SE] age, 42.4 [1.5] years; 13 women and 42 men [76.4% male]) were included. Of the 552 sessions completed with patients (mean [SE], 7.89 [0.59] sessions per person), 252 (45.7%) directly preceded opioid use events (mean [SE], 3.60 [0.44] sessions per person). From the task parameters, only ambiguity tolerance was significantly associated with increased odds of prospective opioid use (adjusted odds ratio, 1.37 [95% CI, 1.07-1.76]), indicating patients were more tolerant specifically of ambiguous risks prior to these use events. The association of ambiguity tolerance with prospective use was independent of established clinical factors (adjusted odds ratio, 1.29 [95% CI, 1.01-1.65]; P = .04), such that a model combining these factors explained more variance in reuse risk. No significant differences in ambiguity tolerance were observed between patients and control participants, who completed 197 sessions (mean [SE], 3.58 [0.21] sessions per person); however, patients were more tolerant of known risks (B = 0.56 [95% CI, 0.05-1.07]). Conclusions and Relevance/UNASSIGNED:Computational approaches can provide mechanistic insights about the cognitive factors underlying opioid reuse vulnerability and may hold promise for clinical use.