Faculty Bibliography

OBJECTIVE/UNASSIGNED:The authors examined the prevalence and correlates of co-occurring opioid use disorder and opioid overdose among individuals receiving psychiatric services. METHODS/UNASSIGNED:This was a cross-sectional study of adults with continuous enrollment in New York State Medicaid who received at least one psychiatric service in 2020 (N=523,885). Logistic regression models were used to examine the correlates of both opioid use disorder and overdose. RESULTS/UNASSIGNED:In the study sample, the prevalence rate of opioid use disorder was 8.1%; within this group, 7.7% experienced an opioid overdose in the study year. Opioid use disorder rates were lower among younger (18-24 years; 2.0%) and older (≥65 years; 3.1%) adults and higher among men (11.1%) and among those residing in rural areas (9.9%). Compared with Whites (9.4%), opioid use disorder rates were lower for Asian Americans (2.0%, adjusted odds ratio [AOR]=0.22) and Blacks (6.8%, AOR=0.76) and higher for American Indians (13.2%, AOR=1.43) and Hispanics (9.6%, AOR=1.29). Individuals with any substance use (24.9%, AOR=5.20), posttraumatic stress (15.7%, AOR=2.34), bipolar (14.9%, AOR=2.29), or anxiety (11.3%, AOR=2.18) disorders were more likely to have co-occurring opioid use disorder; those with conduct (4.5%, AOR=0.51), adjustment (7.4%, AOR=0.88), or schizophrenia spectrum (7.4%, AOR=0.87) disorders were less likely to have opioid use disorder. Those with suicidality (23.9%, AOR=3.83) or economic instability (23.7%, AOR=3.35) had higher odds of having opioid use disorder. Overdose odds were higher among individuals with suicidality (34.0%, AOR=6.82) and economic instability (16.0%, AOR=2.57). CONCLUSIONS/UNASSIGNED:These findings underscore the importance of providing opioid use disorder screening and treatment for patients receiving psychiatric services.

PURPOSE/OBJECTIVE:The use of magnetic resonance imaging (MRI) in radiotherapy planning is becoming more widespread, particularly with the emergence of MRI-guided radiotherapy systems. Existing guidelines for defining the prostate bed clinical target volume (CTV) show considerable heterogeneity. This study aimed to establish baseline interobserver variability (IOV) for prostate bed CTV contouring on MRI, develop international consensus guidelines, and evaluate its effect on IOV. METHODS AND MATERIALS/METHODS:Participants delineated the CTV on 3 MRI scans, obtained from the Elekta Unity MR-Linac, as per their normal practice. Radiation oncologist contours were visually examined for discrepancies, and interobserver comparisons were evaluated against simultaneous truth and performance level estimation (STAPLE) contours using overlap metrics (Dice similarity coefficient and Cohen's kappa), distance metrics (mean distance to agreement and Hausdorff distance), and volume measurements. A literature review of postradical prostatectomy local recurrence patterns was performed and presented alongside IOV results to the participants. Consensus guidelines were collectively constructed, and IOV assessment was repeated using these guidelines. RESULTS:Sixteen radiation oncologists' contours were included in the final analysis. Visual evaluation demonstrated significant differences in the superior, inferior, and anterior borders. Baseline IOV assessment indicated moderate agreement for the overlap metrics while volume and distance metrics demonstrated greater variability. Consensus for optimal prostate bed CTV boundaries was established during a virtual meeting. After guideline development, a decrease in IOV was observed. The maximum volume ratio decreased from 4.7 to 3.1 and volume coefficient of variation reduced from 40% to 34%. The mean Dice similarity coefficient rose from 0.72 to 0.75 and the mean distance to agreement decreased from 3.63 to 2.95 mm. CONCLUSIONS:Interobserver variability in prostate bed contouring exists among international genitourinary experts, although this is lower than previously reported. Consensus guidelines for MRI-based prostate bed contouring have been developed, and this has resulted in an improvement in contouring concordance. However, IOV persists and strategies such as an education program, development of a contouring atlas, and further refinement of the guidelines may lead to additional improvements.

IMPORTANCE/UNASSIGNED:The HEALing Communities Study (HCS) evaluated the effectiveness of the Communities That HEAL (CTH) intervention in preventing fatal overdoses amidst the US opioid epidemic. OBJECTIVE/UNASSIGNED:To evaluate the impact of the CTH intervention on total drug overdose deaths and overdose deaths involving combinations of opioids with psychostimulants or benzodiazepines. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This randomized clinical trial was a parallel-arm, multisite, community-randomized, open, and waitlisted controlled comparison trial of communities in 4 US states between 2020 and 2023. Eligible communities were those reporting high opioid overdose fatality rates in Kentucky, Massachusetts, New York, and Ohio. Covariate constrained randomization stratified by state allocated communities to the intervention or control group. Trial groups were balanced by urban or rural classification, 2016-2017 fatal opioid overdose rate, and community population. Data analysis was completed by December 2023. INTERVENTION/UNASSIGNED:Increased overdose education and naloxone distribution, treatment with medications for opioid use disorder, safer opioid prescribing practices, and communication campaigns to mitigate stigma and drive demand for evidence-based interventions. MAIN OUTCOMES AND MEASURES/UNASSIGNED:The primary outcome was the number of drug overdose deaths among adults (aged 18 years or older), with secondary outcomes of overdose deaths involving specific opioid-involved drug combinations from death certificates. Rates of overdose deaths per 100 000 adult community residents in intervention and control communities from July 2021 to June 2022 were compared with analyses performed in 2023. RESULTS/UNASSIGNED:In 67 participating communities (34 in the intervention group, 33 in the control group) and including 8 211 506 participants (4 251 903 female [51.8%]; 1 273 394 Black [15.5%], 603 983 Hispanic [7.4%], 5 979 602 White [72.8%], 354 527 other [4.3%]), the average rate of overdose deaths involving all substances was 57.6 per 100 000 population in the intervention group and 61.2 per 100 000 population in the control group. This was not a statistically significant difference (adjusted rate ratio [aRR], 0.92; 95% CI, 0.78-1.07; P = .26). There was a statistically significant 37% reduction (aRR, 0.63; 95% CI, 0.44-0.91; P = .02) in death rates involving an opioid and psychostimulants (other than cocaine), and nonsignificant reductions in overdose deaths for an opioid with cocaine (6%) and an opioid with benzodiazepine (1%). CONCLUSION AND RELEVANCE/UNASSIGNED:In this clinical trial of the CTH intervention, death rates involving an opioid and noncocaine psychostimulant were reduced; total deaths did not differ statistically. Community-focused data-driven interventions that scale up evidence-based practices with communications campaigns may effectively reduce some opioid-involved polysubstance overdose deaths. TRIAL REGISTRATION/UNASSIGNED:ClinicalTrials.gov Identifier: NCT04111939.

IMPORTANCE/UNASSIGNED:Racial and ethnic disparities in access to treatment and quality of treatment for opioid use disorder (OUD) have been identified in usual care settings. In contrast, disparities in treatment quality within clinical trials are relatively unexamined. OBJECTIVE/UNASSIGNED:To estimate racial and ethnic differences in the dose of opioid agonist treatment for OUD in the first 4 weeks of treatment in clinical trials. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This cohort study performed analysis of the methadone and buprenorphine treatment arms of 3 trials conducted by the National Institute on Drug Abuse Clinical Trials Network between May 2006, and January 31, 2017, at multiple Clinical Trials Network sites across the US. Trial participants who were randomized to and initiated buprenorphine or methadone treatment and who identified as Hispanic, non-Hispanic Black, or non-Hispanic White were included in the present study. Data were analyzed from November 1, 2023, to August 5, 2024. EXPOSURE/UNASSIGNED:Combined race and ethnicity as self-classified by the patient at trial enrollment. MAIN OUTCOMES AND MEASURES/UNASSIGNED:The maximum daily dose of buprenorphine or methadone received in each week for the first 4 weeks of treatment. The mean dose and the percentage of patients receiving a higher dose (buprenorphine ≥16 mg and methadone ≥60 mg) were compared across race and ethnicity groups. RESULTS/UNASSIGNED:A total of 1748 patients (1263 who initiated buprenorphine and 485 who initiated methadone treatment) were included in the analysis (1168 [66.8%] male; median age, 33 [IQR, 26-45] years). Of these, 138 patients (7.9%) identified as Black, 273 (15.6%) as Hispanic, and 1337 (76.5%) as White. In week 4, Black patients received buprenorphine doses 2.5 (95% CI -4.6 to -0.5) mg lower and methadone doses 16.7 (95% CI, -30.7 to -2.7) mg lower compared with White patients, after standardizing by age and sex. In week 4, the percentage of patients receiving a higher dose of medication (buprenorphine ≥16 mg; methadone ≥60 mg) was 16.9 (95% CI, -31.9 to -1.9) points lower for Black patients compared with White patients. Hispanic and White patients received similar buprenorphine doses; Hispanic patients received lower methadone doses than White patients. CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this cohort study of data from 3 clinical trials, White patients generally received higher doses of medication than Black patients. Future research is needed to understand the mechanisms of and interventions to reduce disparities in OUD treatment quality and how such disparities impact generalizability of trial results.

OBJECTIVE:The opioid intervention court (OIC) is an innovative, pre-plea treatment court to facilitate rapid linkage to medications for opioid use disorder (MOUD) for people at risk of overdose. This study compares participants in OIC and participants with opioid use problems in a traditional drug treatment court model on (i) initiation for any substance use (SU) treatment, (ii) initiation of MOUD, (iii) number of days to MOUD initiation, and (iv) retention in the OIC program/retention on MOUD. METHODS:We used administrative court records from n = 389 OIC and n = 229 drug court participants in 2 counties in New York State. Differences in outcomes by court were assessed using logistic, multinomial, or linear regressions. RESULTS:After adjusting for current charge severity, gender, race/ethnicity, age, and county, OIC participants were no more likely to initiate any SU treatment but were significantly more likely to initiate MOUD (81.2% OIC vs 45.9% drug court, P < 0.001) and were more quickly linked to any SU treatment (hazard ratio = 1.68, 95% confidence interval = 1.35-2.08) and MOUD (hazard ratio = 4.25, 95% confidence interval = 3.23-5.58) after starting the court. Retention in court/MOUD was higher among drug court participants and may speak to the immediate sanctions (eg, jail) for noncompliance with drug court directives as compared with opioid court, which does not carry such immediate sanctions for noncompliance. CONCLUSIONS:These analyses suggest that the new OIC model can more rapidly link participants to treatment, including MOUD, as compared with traditional drug court model, and may demonstrate improved ability to immediately stabilize and reduce overdose risk in court participants.

IMPORTANCE:Fentanyl has exacerbated the opioid use disorder (OUD) and opioid overdose epidemic. Data on the effectiveness of medications for OUD among patients using fentanyl are limited. OBJECTIVE:To assess the effectiveness of sublingual or extended-release injection formulations of buprenorphine for the treatment of OUD among patients with and without fentanyl use. DESIGN, SETTING, AND PARTICIPANTS:Post hoc analysis of a 24-week, randomized, double-blind clinical trial conducted at 35 outpatient sites in the US from December 2015 to November 2016 of sublingual buprenorphine-naloxone vs extended-release subcutaneous injection buprenorphine (CAM2038) for patients with OUD subgrouped by presence vs absence of fentanyl or norfentanyl in urine at baseline. Study visits with urine testing occurred weekly for 12 weeks, then 6 times between weeks 13 and 24. Data were analyzed on an intention-to-treat basis from March 2022 to August 2023. INTERVENTION:Weekly and monthly subcutaneous buprenorphine vs daily sublingual buprenorphine-naloxone. MAIN OUTCOMES AND MEASURES:Retention in treatment, percentage of urine samples negative for any opioids (missing values imputed as positive), percentage of urine samples negative for fentanyl or norfentanyl (missing values not imputed), and scores on opiate withdrawal scales and visual analog craving scales. RESULTS:Of 428 participants, 123 (subcutaneous buprenorphine, n = 64; sublingual buprenorphine-naloxone, n = 59; mean [SD] age, 39.1 [10.8] years; 75 men [61.0%]) had evidence of baseline fentanyl use and 305 (subcutaneous buprenorphine, n = 149; buprenorphine-naloxone, n = 156; mean [SD] age, 38.1 [11.1] years; 188 men [61.6%]) did not have evidence of baseline fentanyl use. Study completion was similar between the fentanyl-positive (60.2% [74 of 123]) and fentanyl-negative (56.7% [173 of 305]) subgroups. The mean percentage of urine samples negative for any opioid were 28.5% among those receiving subcutaneous buprenorphine and 18.8% among those receiving buprenorphine-naloxone in the fentanyl-positive subgroup (difference, 9.6%; 95% CI, -3.0% to 22.3%) and 36.7% among those receiving subcutaneous buprenorphine and 30.6% among those receiving buprenorphine-naloxone in the fentanyl-negative subgroup (difference, 6.1%; 95% CI, -1.9% to 14.1%), with significant main associations of baseline fentanyl status and treatment group. In the fentanyl-positive subgroup, the mean percentage of urine samples negative for fentanyl during the study was 74.6% among those receiving subcutaneous buprenorphine vs 61.9% among those receiving sublingual buprenorphine-naloxone (difference, 12.7%; 95% CI, 9.6%-15.9%). Opioid withdrawal and craving scores decreased rapidly after treatment initiation across all groups. CONCLUSIONS AND RELEVANCE:In this post hoc analysis of a randomized clinical trial of sublingual vs extended-release injection buprenorphine for OUD, buprenorphine appeared to be effective among patients with baseline fentanyl use. Patients with fentanyl use had fewer opioid-negative urine samples during the trial compared with the fentanyl-negative subgroup. These findings suggest that the subcutaneous buprenorphine formulation may be more effective at reducing fentanyl use. TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT02651584.

BACKGROUND:Evidence-based practices for reducing opioid-related overdose deaths include overdose education and naloxone distribution, the use of medications for the treatment of opioid use disorder, and prescription opioid safety. Data are needed on the effectiveness of a community-engaged intervention to reduce opioid-related overdose deaths through enhanced uptake of these practices. METHODS:In this community-level, cluster-randomized trial, we randomly assigned 67 communities in Kentucky, Massachusetts, New York, and Ohio to receive the intervention (34 communities) or a wait-list control (33 communities), stratified according to state. The trial was conducted within the context of both the coronavirus disease 2019 (Covid-19) pandemic and a national surge in the number of fentanyl-related overdose deaths. The trial groups were balanced within states according to urban or rural classification, previous overdose rate, and community population. The primary outcome was the number of opioid-related overdose deaths among community adults. RESULTS:During the comparison period from July 2021 through June 2022, the population-averaged rates of opioid-related overdose deaths were similar in the intervention group and the control group (47.2 deaths per 100,000 population vs. 51.7 per 100,000 population), for an adjusted rate ratio of 0.91 (95% confidence interval, 0.76 to 1.09; P = 0.30). The effect of the intervention on the rate of opioid-related overdose deaths did not differ appreciably according to state, urban or rural category, age, sex, or race or ethnic group. Intervention communities implemented 615 evidence-based practice strategies from the 806 strategies selected by communities (254 involving overdose education and naloxone distribution, 256 involving the use of medications for opioid use disorder, and 105 involving prescription opioid safety). Of these evidence-based practice strategies, only 235 (38%) had been initiated by the start of the comparison year. CONCLUSIONS:In this 12-month multimodal intervention trial involving community coalitions in the deployment of evidence-based practices to reduce opioid overdose deaths, death rates were similar in the intervention group and the control group in the context of the Covid-19 pandemic and the fentanyl-related overdose epidemic. (Funded by the National Institutes of Health; HCS ClinicalTrials.gov number, NCT04111939.).

Contingency Management (CM) is a psychological treatment that aims to change behavior with financial incentives. In substance use disorders (SUDs), deployment of CM has been enriched by longstanding discussions around the cost-effectiveness of prized-based and voucher-based approaches. In prize-based CM, participants earn draws to win prizes, including small incentives to reduce costs, and the number of draws escalates depending on the duration of maintenance of abstinence. In voucher-based CM, participants receive a predetermined voucher amount based on specific substance test results. While both types have enhanced treatment outcomes, there is room for improvement in their cost-effectiveness: the voucher-based system requires enduring financial investment; the prize-based system might sacrifice efficacy. Previous work in computational psychiatry of SUDs typically employs frameworks wherein participants make decisions to maximize their expected compensation. In contrast, we developed new frameworks that clinical decision-makers choose actions, CM structures, to reinforce the substance abstinence behavior of participants. We consider the choice of the voucher or prize to be a sequential decision, where there are two pivotal parameters: the prize probability for each draw and the escalation rule determining the number of draws. Recent advancements in Reinforcement Learning, more specifically, in off-policy evaluation, afforded techniques to estimate outcomes for different CM decision scenarios from observed clinical trial data. We searched CM schemas that maximized treatment outcomes with budget constraints. Using this framework, we analyzed data from the Clinical Trials Network to construct unbiased estimators on the effects of new CM schemas. Our results indicated that the optimal CM schema would be to strengthen reinforcement rapidly in the middle of the treatment course. Our estimated optimal CM policy improved treatment outcomes by 32% while maintaining costs. Our methods and results have broad applications in future clinical trial planning and translational investigations on the neurobiological basis of SUDs.

BACKGROUND:High levels of missing outcome data for biologically confirmed substance use (BCSU) threaten the validity of substance use disorder (SUD) clinical trials. Underlying attributes of clinical trials could explain BCSU missingness and identify targets for improved trial design. METHODS:We reviewed 21 clinical trials funded by the NIDA National Drug Abuse Treatment Clinical Trials Network (CTN) and published from 2005 to 2018 that examined pharmacologic and psychosocial interventions for SUD. We used configurational analysis-a Boolean algebra approach that identifies an attribute or combination of attributes predictive of an outcome-to identify trial design features and participant characteristics associated with high levels of BCSU missingness. Associations were identified by configuration complexity, consistency, coverage, and robustness. We limited results using a consistency threshold of 0.75 and summarized model fit using the product of consistency and coverage. RESULTS:For trial design features, the final solution consisted of two pathways: psychosocial treatment as a trial intervention OR larger trial arm size (complexity=2, consistency=0.79, coverage=0.93, robustness score=0.71). For participant characteristics, the final solution consisted of two pathways: interventions targeting individuals with poly- or nonspecific substance use OR younger age (complexity=2, consistency=0.75, coverage=0.86, robustness score=1.00). CONCLUSIONS:Psychosocial treatments, larger trial arm size, interventions targeting individuals with poly- or nonspecific substance use, and younger age among trial participants were predictive of missing BCSU data in SUD clinical trials. Interventions to mitigate missing data that focus on these attributes may reduce threats to validity and improve utility of SUD clinical trials.

BACKGROUND AND AIMS/OBJECTIVE:Extended-release naltrexone (XR-NTX) and sublingual buprenorphine (SL-BUP) are both approved for opioid use disorder (OUD) treatment in any medical setting. We aimed to compare the real-world effectiveness of XR-NTX and SL-BUP. DESIGN AND SETTING/METHODS:This was an observational active comparator, new user cohort study of Medicaid claims records for patients in New Jersey and California, USA, 2016-19. PARTICIPANTS/CASES/METHODS:The participants were adult Medicaid patients aged 18-64 years who initiated XR-NTX or SL-BUP for maintenance treatment of OUD and did not use medications for OUD in the 90 days before initiation. Our cohort included 1755 XR-NTX and 9886 SL-BUP patients. MEASUREMENTS/METHODS:We examined two outcomes up to 180 days after medication initiation: (1) composite of medication discontinuation and death and (2) composite of overdose and death. FINDINGS/RESULTS:In adjusted analyses, treatment with XR-NTX was more likely to result in discontinuation or death by the end of follow-up than treatment with SL-BUP: cumulative risk 75.9% [95% confidence interval (CI) = 73.9%, 77.9%] versus 62.2% (95% CI = 61.2%, 63.2%), respectively (risk difference = 13.7 percentage points, 95% CI = 11.4, 16.0). There was minimal difference in the cumulative risk of overdose or death by the end of follow-up: XR-NTX 3.9% (95% CI = 3.0%, 4.8%) versus SL-BUP 3.3% (95% CI = 2.9%, 3.7%); risk difference = 0.5 percentage points, 95% CI = -0.4, 1.5. Results were consistent across sensitivity analyses. CONCLUSIONS:Medicaid patients in California and New Jersey, USA, receiving treatment for opioid use disorder stayed in treatment longer on sublingual buprenorphine than on extended-release naltrexone, but the risk of overdose was similar. Most patients in this study discontinued medication within 6 months, regardless of which medication was initiated.