Faculty Bibliography

BACKGROUND/UNASSIGNED:Histotripsy is a novel, non-invasive, non-ionising, non-thermal method of mechanical tumour disruption that received US FDA approval in October 2023 for the treatment of liver tumours. This study aims to summarise and evaluate the safety and outcomes data following histotripsy of primary and secondary liver tumours. METHODS/UNASSIGNED:statistic and Cochran's Q test. Publication bias was assessed using funnel plot visual inspection and Egger's regression test. Finally, the histotripsy technology was assessed using the IDEAL framework to inform the design of future trials. This work was registered with PROSPERO (CRD420261299804). FINDINGS/UNASSIGNED:= 6.6%). No significant publication bias was detected for mortality and safety outcomes; however, formal assessment of publication bias was limited by the small number of studies for these and all outcomes. All radiological control outcomes showed substantial heterogeneity across studies. INTERPRETATION/UNASSIGNED:Although there is notable heterogeneity across studies, pooled results indicate that histotripsy has high rates of technical feasibility and local control with a favourable side effect profile. Interpretation of these findings is limited by the small number of available studies, variability in outcome definitions and imaging assessment methods, and short follow-up durations. These results underscore the need for larger, prospectively designed studies with standardised reporting frameworks and longer follow-up to more precisely characterise the clinical, radiologic, and quantitative imaging outcomes following histotripsy. FUNDING/UNASSIGNED:None.

BACKGROUND:Individuals with opioid use disorder (OUD) may experience fewer barriers to treatment following incarceration if offered in-jail medications for OUD (MOUD). We aimed to identify care trajectories of community OUD treatment after incarceration and examine the association between receiving in-jail MOUD and experiencing specific community treatment trajectories. METHODS:This retrospective cohort study using matched New York City (NYC) health care administrative data included adults with OUD incarcerated on or after May 2011 and discharged during 2014-2017. We defined states of community OUD treatment at the weekly level over one year following index jail discharge and performed state sequence analysis (SSA) to identify trajectories of treatment after jail and assessed the influence of receiving in-jail MOUD on treatment trajectories. RESULTS:Of 14,923 eligible individuals, 26.2% received in-jail MOUD. SSA identified eight clusters of community care trajectories: continuous methadone treatment (9.7%), methadone treatment discontinuation (3.7%), methadone treatment and reincarceration (6.7%), methadone treatment initiation (4.8%), continuous reincarceration (3.5%), short reincarceration with little community treatment (20.3%), long reincarceration with little community treatment (7.0%), and no community OUD treatment or reincarceration (44.5%). Receiving in-jail MOUD was associated with belonging to the continuous methadone treatment cluster compared to the no community OUD treatment or reincarceration cluster (adjusted OR: 12.5, 95% CI: 9.9-15.7). CONCLUSION/CONCLUSIONS:We identified eight unique patterns of community OUD treatment after jail release. Receipt of in-jail MOUD was associated with belonging to the continuous methadone treatment cluster. These findings suggest that provision of in-jail MOUD could improve methadone uptake in the community.

BACKGROUND AND AIM/UNASSIGNED:Extended-release injectable naltrexone (XR-Naltrexone) is an effective treatment for opioid use disorder (OUD); however, initiation can be challenging as it requires an opioid-free period. This exploratory analysis examines patient characteristics associated with successful initiation of XR-Naltrexone in the National Drug Abuse Treatment Clinical Trials Network (CTN-0051) Extended-Release Naltrexone versus Buprenorphine for Opioid Treatment (X:BOT) trial. METHODS/UNASSIGNED:Patient demographics and clinical variables associated with successful XR-Naltrexone initiation were examined among 283 participants with OUD randomized to XR-Naltrexone in the X:BOT trial. Variables included severity of opioid use, characteristics of opioid and other substance use, treatment history, psychiatric history, baseline depression, and pain. Logistic regression models were used to estimate the effect of variables on the odds of induction success. RESULTS/UNASSIGNED:204 (72%) of 283 participants randomized to receive XR-Naltrexone completed successful induction. Housing status and pain were significantly associated with XR-Naltrexone induction status. Reported homelessness was significantly associated with higher odds of successful XR-Naltrexone induction (OR: 2.31; 95% CI: 1.12, 4.76). Individuals that reported moderate or extreme pain on the EuroQoL had half the odds of successful induction compared to those without pain (OR: 0.49; 95% CI: 0.27, 0.89). CONCLUSIONS/UNASSIGNED:Among patients with OUD initiating treatment on inpatient units, homelessness was associated with greater likelihood of successfully initiating XR-Naltrexone, while chronic pain was associated with lower likelihood of XR-Naltrexone initiation. Future research on XR-Naltrexone initiation should consider tailoring treatment based on housing status and other social determinants, and evaluation and management of pain.

BACKGROUND AND AIMS/OBJECTIVE:There are currently no brief quantitative assessments that capture the drug patterns of people who engage in use of more than one drug on the same day or simultaneously. The current study examined the retest reliability, acceptability and feasibility of a new quantitative assessment to measure polysubstance use. DESIGN/METHODS:A tool for assessing simultaneous and same-day polysubstance behaviors, the polysubstance assessment tool (PAT) was developed in interviewer-administered and electronic self-administered formats. Participants were allocated 1:1 to receive either version of the PAT and returned one to three days later to repeat the assessment. SETTING/METHODS:New York City, New York, USA. PARTICIPANTS/METHODS:Adults (18 + years, n = 115) who reported use of more than one drug per day in the last 30 days. MEASUREMENTS/METHODS:Test-retest reliability estimates for dichotomous items were assessed using Cohen's kappa, Gwet's Agreement Coefficient 1 (AC1) and percent agreement. Continuous items were assessed with two-way mixed effects intraclass correlations. Bivariate analyses examined acceptability using nine Likert-type survey questions. Feasibility was examined via time to completion. FINDINGS/RESULTS:Overall reliability was moderate to excellent [Gwet's AC1 range 0.70-0.96; intraclass correlation (ICC) range 0.62-0.88]. Reliability was higher for simultaneous polysubstance use (Gwet's AC1 = 0.90) as compared with same-day (Gwet's AC1 = 0.70). Acceptability was high, with no statistically significant difference between the self- and interviewer-administered versions of the tool. Median time to completion was 7 minutes, and was statistically significantly lower for the self-administered tool (median = 5 minutes) compared with the interviewer-administered version (median = 8 minutes) (P < 0.001). CONCLUSIONS:A new polysubstance assessment tool appears to have good reliability and can be considered by researchers seeking a quantitative measure of polysubstance use behaviors given its simplicity, high acceptability and quick completion time.

RATIONALE AND OBJECTIVES/OBJECTIVE:Prostate multiparametric magnetic resonance imaging (MRI) is recommended for prostate cancer detection, staging, and surveillance. Incidental bladder lesions are encountered on these studies but remain under-characterized in the literature. The patient characteristics associated with malignancy for these lesions are not well defined. We evaluated the prevalence, histopathologic outcomes, clinical characteristics, and associations with malignancy for incidental bladder lesions on prostate MRI. MATERIALS AND METHODS/METHODS:A retrospective review included 31,241 patients undergoing prostate MRI examinations from January 2013 to January 2023. Imaging reports and medical records were analyzed for incidental bladder lesions, demographic data, clinical symptoms, urinalysis findings, and histopathologic outcomes. Lesions were categorized based on biopsy results or negative clinical follow-up for bladder tumors in chart review. Logistic regression analysis and receiver operating characteristic analyses were performed. RESULTS:Incidental bladder lesions occurred in 0.74% (230/31,241) of examinations, with biopsy-confirmed bladder cancer in 0.11% of patients (34/31,241) or 14.8% (34/230) of cases with lesions. In multivariable analysis, gross hematuria had the strongest association with biopsy-proven bladder cancer (OR 9.26, 95% CI 4.12-20.79, p<0.001). A logistic regression model incorporating age, smoking status, and gross hematuria yielded area under the curve of 0.762 for bladder cancer. CONCLUSION/CONCLUSIONS:Incidental bladder lesions on prostate MRI may represent opportunities for early detection of bladder cancer, but also have potential for harms related to unnecessary procedures. Considering the presence of gross hematuria, possibly stated as part of the MRI referral or patient questionnaire, could improve risk stratification of encountered bladder lesions and early cancer detection.

OBJECTIVES/OBJECTIVE:People receiving medications for opioid use disorder often continue to experience opioid withdrawal, creating barriers to improved outcomes. Emerging evidence suggests the existence of distinct opioid withdrawal subtypes characterized by high and low levels of withdrawal severity, highlighting the need for personalized treatment approaches. To inform clinical practice, we identified subgroups of adults based on levels of opioid withdrawal over time during opioid use disorder (OUD) treatment. METHODS:We conducted a secondary analysis of the Clinical Trials Network (CTN-0051) Extended-Release Naltrexone versus Buprenorphine for Opioid Treatment trial using latent class growth analysis to identify subgroups of withdrawal. Four hundred and seventy-four participants in an OUD trial were randomized to receive extended-release naltrexone (XR-NTX) or sublingual buprenorphine-naloxone (BUP-NX). Withdrawal symptoms were measured using the Subjective Opiate Withdrawal Scale (SOWS) at 10 timepoints. We identified classes and compared their predictors of withdrawal and time to return to opioid use. RESULTS:Two distinct trajectories - low and high sustained opioid withdrawal - were identified in each treatment arm. Most participants were in the low withdrawal class (n = 176; 86 % XR-NTX and n = 241; 89 % BUP-NX) with fewer in the high sustained withdrawal class (n = 28; 14 % XR-NTX and n = 29; 11 % BUP-NX). Differences in lifetime history of anxiety and depression and in quality of life domains (mobility, usual activities, and pain/discomfort) were primarily observed among XR-NTX participants, with only one baseline mobility difference emerging between BUP-NX classes. In the XR-NTX arm, time to return to use was significantly shorter in the high sustained withdrawal class compared to the low withdrawal class, whereas BUP-NX classes did not differ on time to return to use. DISCUSSION AND CONCLUSIONS/CONCLUSIONS:Our findings demonstrate the existence of distinct high and low opioid withdrawal subtypes among individuals receiving XR-NTX and BUP-NX. These results underscore the importance of personalized withdrawal management strategies and highlight the need to consider individual withdrawal trajectories when optimizing treatments. Future research should focus on identifying predictors of withdrawal severity to improve clinical outcomes.

BACKGROUND:Individuals involved in the criminal legal system represent one of the most disproportionately affected populations in the opioid overdose crisis. Despite evidence of medications for opioid use disorder (MOUD) reducing overdose mortality, illicit opioid use, and recidivism, most correctional facilities do not offer these treatments. Sublocade and Brixadi, two distinct, branded, formulations of extended-release buprenorphine (XR-B), offer a promising approach to improving MOUD treatment adherence and reducing post-release overdose deaths. METHODS:This hybrid pilot study will utilize a partially randomized preference trial (PRPT) design to compare the preliminary effectiveness, feasibility, acceptability and other outcomes between Sublocade and Brixadi initiation. We aim to enroll 60 incarcerated individuals with opioid use disorder who are interested in XR-B and have a scheduled release within 120 days. Participants will choose their preferred injectable treatment or, if ambivalent, be randomly assigned. All participants will receive monthly XR-B injections pre-release and continue for three months post-release, with additional administrative follow-up for another three months. The primary outcome is post-release treatment retention; other outcomes will be assessed using the Proctor taxonomy. Data will be collected using clinical assessments, surveys, and administrative databases. DISCUSSION/CONCLUSIONS:This study explores differences in XR-B formulations during the high-risk time of transition out of prison. It combines a hybrid implementation science and preference trial design-two methodologies that can help address the specific challenges of research in carceral environments. By understanding implementation of XR-B in a prison setting, findings can provide valuable insights to guide other facilities in adopting this life-saving treatment.

INTRODUCTION/BACKGROUND:Expanding access to medication for opioid use disorder (MOUD) to people involved in the carceral system is a priority for the New Hampshire Department of Corrections (NHDOC), where more than 40% of residents have an opioid use disorder (OUD). NHDOC participated in the multi-site Justice Community Opioid Innovation Network (JCOIN) clinical trial, "Long-acting buprenorphine vs. naltrexone opioid treatments in criminal justice system-involved adults (EXIT-CJS)". We examine the contributing factors to the expansion of the NHDOC MOUD program from 2021 to 2023, including participation in EXIT-CJS, which occurred from 2019 to 2024. METHODS:Data on quarterly MOUD prescribing and EXIT-CJS enrollments were abstracted from the NHDOC medical records from July 1, 2021- December 31, 2023 as part of a quality improvement initiative. To examine factors influencing expansion of the program, conversations were conducted with NHDOC leadership team and clinical staff. RESULTS:From 2021 to 2023, the quarterly number of patients treated with MOUD at the NHDOC increased by more than 400% from a total of 165 patients in July-September 2021, to 685 patients in October-December 2023. At the policy level, elimination of the federal DATA-Waiver (X-Waiver) Program allowed additional providers to prescribe MOUD. At the organizational level, support from NHDOC leadership, including Medical and Forensics and the Commissioner's Office, encouraged broader engagement in MOUD from providers, multidisciplinary staff, and security. This work was augmented through receipt of State Opioid Response (SOR) dollars with a requirement to continue to advance education for NHDOC staff on the efficacy of MOUD. Resulting discussions between medical providers, experts on addiction treatment, staff and residents supported a culture change in attitudes about MOUD. During this same time window, the NHDOC made significant adjustments in the distribution of MOUD by adjusting the nursing administration process thus reducing the stigma associated with being a patient on MOUD and treating MOUD medication administration like all other medical conditions. DISCUSSION/CONCLUSIONS:Policy-related, organizational, and individual factors contributed to the expansion of the MOUD program at the NHDOC. EXIT-CJS recruitment occurred synergistically with the expansion of the MOUD program. As NHDOC was engaged as a site in EXIT-CJS, study recruitment increased awareness of extended-release treatment options among residents and staff.

BACKGROUND AND AIMS/OBJECTIVE:It is unclear if findings from randomized controlled trials (RCT) of medications for opioid use disorder apply to real-world settings. We estimated the effectiveness of buprenorphine-naloxone (BUP-NX) versus extended-release naltrexone (XR-NTX) on treatment interruption in a RCT and an observational study based on real-world data. DESIGN/METHODS:Target trial emulation to harmonize the protocol and statistical analyses of X:BOT (target trial) and the observational study (observational emulation). Baseline was randomization in the target trial and medically managed opioid withdrawal (MMOW) discharge in the observational emulation. SETTINGS/METHODS:X:BOT trial and Massachusetts Public Health Data Warehouse observational data (United States). PARTICIPANTS/METHODS:The target trial included all X:BOT participants. The observational emulation trial included MMOW discharges from January 2014 to May 2016. MEASUREMENTS/METHODS:Treatment strategies were BUP-NX versus XR-NTX initiation within 28 days of baseline. The outcome was treatment interruption (earliest of treatment discontinuation, incarceration, MMOW readmission, death). We estimated the 24-week risk and risk difference. FINDINGS/RESULTS:In the target trial, 94% (269/287) and 66% (187/283) of participants randomized to BUP-NX or XR-NTX initiated their assigned treatment within 28 days, respectively. In the observational emulation, BUP-NX and XR-NTX were initiated within 28 days in 9% (5209/59 076) and 3% (1813/59 076) of MMOW discharges, respectively. The adjusted 24-week treatment interruption risks (95% confidence interval) for BUP-NX and XR-NTX were 68% (60%,77%) and 72% (60%,83%) in the target trial [risk difference, -4 percentage points (pp; -17 pp,11 pp)] and 82% (81%,83%) and 93% (92%,95%) in the observational emulation [risk difference,-11 pp (-13 pp,-10 pp)]. CONCLUSIONS:Buprenorphine-naloxone might be superior to extended-release naltrexone in real-world settings where the majority of people struggle to remain on medications for opioid use disorder. Buprenorphine-naloxone initiators had a lower risk of treatment interruption than extended-release naltrexone initiators in an observational emulation, but similar risks in a randomized controlled trial, although confidence intervals were wide. Trial participation, study size and residual confounding may explain these differences.

The current study aimed to understand motivations of high-risk polysubstance use. Semistructured interviews were conducted in New York City with 20 individuals with frequent recent polysubstance use. Two analysts coded the interviews (κ = 93.97). Five themes related to motivation for polysubstance use were found: (1) balance, prolong, or enhance effects, (2) self-medicate physical ailments, (3) cope with emotional distress, (4) drug-induced cravings, and (5) responding to social contexts. Individuals reported simultaneous or sequential co-use to balance, prolong or enhance a 'high' (theme 1). Participants engaged in polysubstance use to alleviate withdrawal symptoms, to induce sleep and self-medicate physical pain (theme 2) and to provide relief from emotional distress (theme 3). Other themes included drug-induced cravings (theme 4) and responding to social contexts (theme 5) including both social situations and economic availability. Motivations for polysubstance use may provide important insight into harm reduction and treatment settings solutions.