Jeanmarie Perrone’s research while affiliated with University of Pennsylvania and other places

Importance The alpha-2 agonist xylazine is increasingly detected as an adulterant in illicitly manufactured fentanyl. There is concern that xylazine may be responsible for an emerging pattern of necrotizing wounds among people who use drugs, but the clinical features of wounds associated with xylazine remain poorly characterized. Objective To systematically characterize the location, wound bed surface, and chronicity of wounds among persons with confirmed xylazine exposure. Design, Setting, and Participants This case series at 3 academic medical hospitals in Philadelphia, Pennsylvania, included patients with emergency department or inpatient encounters from April 2022 to February 2023 who had a wound-related chief complaint and xylazine detected with urine gas chromatography–mass spectroscopy. Exposure Xylazine. Main Outcomes and Measures The location, size, wound bed, and chronicity of wounds associated with xylazine using electronic medical record abstraction and Fisher exact tests. Results Of 59 wounds from 29 unique patients with confirmed xylazine exposure (mean [SD] age, 39.4 [8.8] years; 15 [52%] male; all using fentanyl, and 23 [79%] routinely injecting opioids), 53 wounds (90%) were located on extremities, and 41 (69%) involved extensor surfaces. Five wounds (9%) involved exposed deep structures such as bone or tendon. Of 57 wounds with photographs, 34 (60%) had wound beds of predominantly devitalized tissue (eschar or slough). Based on patient report, 28 wounds (48%) were acute (<1 month old), 12 (20%) were subacute (present for 1-3 months), and 17 (29%) were chronic (developed ≥3 months prior). Subacute and chronic wounds were more often medium or large in size (odds ratio, 48.5; 95% CI, 8.2-1274.8; P < .001) and more frequently had devitalized wound beds (odds ratio, 9.5; 95% CI, 2.9-37.0; P < .001). Conclusions and Relevance In this case series of hospitalized patients with confirmed xylazine exposure, wounds were commonly located on extensor surfaces of the extremities, frequently had devitalized tissue or exposed deep structures, and were more likely to have larger and necrotic wound beds the longer they had persisted. This systematic characterization of xylazine-associated wounds may inform identification, management, and research to address this emerging public health threat.

Background Emergency department (ED)–initiated buprenorphine provides a low barrier access point and safety net to mitigate opioid overdose risk and increase treatment engagement. We sought to describe trends and patterns of buprenorphine utilization from the ED using national data. Methods This is a retrospective review of the National Hospital Ambulatory Medical Care Survey between 2014 and 2021. Our primary outcomes were trends in ED buprenorphine utilization. We described patient demographics, visit characteristics, and conducted trend analyses. We utilized logistic regression to determine predictors of buprenorphine prescribing. Results Between 2014 and 2021, there were 341,875 ED visits in which buprenorphine was administered, with no change over time ( P = 0.08). There were 392,031 visits where buprenorphine was prescribed at ED discharge, with an increase over time ( P = 0.01). The largest rise in rate for discharge prescriptions occurred between 2019 and 2020 (37,737 [0.03%] visits vs 126,041 [0.10%]) (233% increase in rate, P < 0.0001). Conclusions Although there was an increase in buprenorphine prescribing at ED discharge, there was no increase in administration. The acceleration in prescribing between 2019 and 2020 suggests that the ED may have been a safety net for patients who lost access to addiction care during COVID-19. Future studies should explore reasons for disparities and barriers to buprenorphine utilization.

Importance Buprenorphine treatment of opioid use disorder (OUD) is safe and effective, but opioid withdrawal during treatment initiation is associated with poor retention in care. As fentanyl has replaced heroin in the drug supply, case reports and surveys have indicated increased concern for buprenorphine-precipitated withdrawal (PW); however, some observational studies have found a low incidence of PW. Objective To estimate buprenorphine PW incidence and assess factors associated with PW among emergency department (ED) or hospitalized patients. Design, Setting, and Participants This retrospective cohort study at 3 academic hospitals in Philadelphia, Pennsylvania, included adults with OUD who underwent traditional or high-dose buprenorphine initiation between January 1, 2020, and December 31, 2021. Exclusion criteria included low-dose buprenorphine initiation and missing documentation of opioid withdrawal severity within 4 hours of receiving buprenorphine. Exposure Buprenorphine initiation with an initial dose of at least 2 mg of sublingual buprenorphine after a Clinical Opiate Withdrawal Scale (COWS) score of 8 or higher. Additional exposures included 4 predefined factors potentially associated with PW: severity of opioid withdrawal before buprenorphine (COWS score of 8-12 vs ≥13), initial buprenorphine dose (2 vs 4 or ≥8 mg), body mass index (BMI) (<25 vs 25 to <30 or ≥30; calculated as weight in kilograms divided by height in meters squared), and urine fentanyl concentration (0 to <20 vs 20 to <200 or ≥200 ng/mL). Main Outcome and Measures The main outcome was PW incidence, defined as a 5-point or greater increase in COWS score from immediately before to within 4 hours after buprenorphine initiation. Logistic regression was used to estimate the odds of PW associated with the 4 aforementioned predefined factors. Results The cohort included 226 patients (150 [66.4%] male; mean [SD] age, 38.6 [10.8] years). Overall, 26 patients (11.5%) met criteria for PW. Among patients with PW, median change in COWS score was 9 points (IQR, 6-13 points). Of 123 patients with confirmed fentanyl use, 20 (16.3%) had PW. In unadjusted and adjusted models, BMI of 30 or greater compared with less than 25 (adjusted odds ratio [AOR], 5.12; 95% CI, 1.31-19.92) and urine fentanyl concentration of 200 ng/mL or greater compared with less than 20 ng/mL (AOR, 8.37; 95% CI, 1.60-43.89) were associated with PW. Conclusions and Relevance In this retrospective cohort study, 11.5% of patients developed PW after buprenorphine initiation in ED or hospital settings. Future studies should confirm the rate of PW and assess whether bioaccumulated fentanyl is a risk factor for PW.

Importance Buprenorphine is an effective yet underused treatment for opioid use disorder (OUD). Objective To evaluate the feasibility (acceptability, tolerability, and safety) of 7-day injectable extended-release buprenorphine in patients with minimal to mild opioid withdrawal. Design, Setting, and Participants This nonrandomized trial comprising 4 emergency departments in the Northeast, mid-Atlantic, and Pacific geographic areas of the US included adults aged 18 years or older with moderate to severe OUD and Clinical Opiate Withdrawal Scale (COWS) scores less than 8 (minimal to mild), in which scores range from 0 to 7, with higher scores indicating increasing withdrawal. Exclusion criteria included methadone-positive urine, pregnancy, overdose, or required admission. Outcomes were assessed at baseline, daily for 7 days by telephone surveys, and in person at 7 days. Patient recruitment occurred between July 13, 2020, and May 25, 2023. Intervention Injection of a 24-mg dose of a weekly extended-release formulation of buprenorphine (CAM2038) and referral for ongoing OUD care. Main Outcomes and Measures Primary feasibility outcomes included the number of patients who (1) experienced a 5-point or greater increase in the COWS score or (2) transitioned to moderate or greater withdrawal (COWS score ≥13) within 4 hours of extended-release buprenorphine or (3) experienced precipitated withdrawal within 1 hour of extended-release buprenorphine. Secondary outcomes included injection pain, satisfaction, craving, use of nonprescribed opioids, adverse events, and engagement in OUD treatment. Results A total of 100 adult patients were enrolled (mean [SD] age, 36.5 [8.7] years; 72% male). Among the patients, 10 (10.0% [95% CI, 4.9%-17.6%]) experienced a 5-point or greater increase in COWS and 7 (7.0% [95% CI, 2.9%-13.9%]) transitioned to moderate or greater withdrawal within 4 hours, and 2 (2.0% [95% CI, 0.2%-7.0%]) experienced precipitated withdrawal within 1 hour of extended-release buprenorphine. A total of 7 patients (7.0% [95% CI, 2.9%-13.9%]) experienced precipitated withdrawal within 4 hours of extended-release buprenorphine, which included 2 of 63 (3.2%) with a COWS score of 4 to 7 and 5 of 37 (13.5%) with a COWS score of 0 to 3. Site pain scores (based on a total pain score of 10, in which 0 indicated no pain and 10 was the worst possible pain) after injection were low immediately (median, 2.0; range, 0-10.0) and after 4 hours (median, 0; range, 0-10.0). On any given day among those who responded, between 29 (33%) and 31 (43%) patients reported no cravings and between 59 (78%) and 75 (85%) reported no use of opioids; 57 patients (60%) reported no days of opioid use. Improving privacy (62%) and not requiring daily medication (67%) were deemed extremely important. Seventy-three patients (73%) were engaged in OUD treatment on day 7. Five serious adverse events occurred that required hospitalization, of which 2 were associated with medication. Conclusions and Relevance This nonrandomized trial of the feasibility of a 7-day buprenorphine injectable in patients with minimal to mild opioid withdrawal (COWS scores, 0-7) found the formulation to be acceptable, well tolerated, and safe in those with COWS scores of 4 to 7. This new medication formulation could substantially increase the number of patients with OUD receiving buprenorphine. Trial Registration ClinicalTrials.gov Identifier: NCT04225598

BACKGROUND The increasing use of social media to share lived and living experiences of substance use presents a unique opportunity to obtain information on side-effects, usage patterns, and opinions on novel psychoactive substances (NPS). However, due to the large volume of data, obtaining useful insights through natural language processing (NLP) technologies such as large language models (LLMs) is challenging. OBJECTIVE To develop a retrieval-augmented generation (RAG) architecture for medical question answering pertaining to clinicians’ queries on emerging issues associated with health-related topics using user-generated medical information on social media. METHODS We proposed a two-layer RAG framework for query-focused answer generation and evaluated a proof-of-concept for the framework in the context of query-focused summary generation from social media forums, focusing on emerging drug-related information. We compared the performance of a quantized large language model (LLM), deployable in low-resource settings, with GPT-4. RESULTS Our framework achieves comparable median scores in terms of relevance, length, hallucination, coverage, and coherence when evaluated using GPT-4 and Nous-Hermes-2-7B-DPO, evaluated over 20 queries with 52 samples. CONCLUSIONS Retrieval augmented generation using LLMs is useful for medical question answering in resource-constrained settings.

Background Stigma among medical trainees toward people with opioid use disorder (OUD) compounds the problems associated with opioid addiction. People with OUD who experience overt and implicit stigma from healthcare providers are less likely to seek and receive treatment, further restricting their access to already limited resources. The objective of our study was to assess an educational strategy to mitigate stigma toward people with OUD among first-year medical students. Methods This study assessed perceptions of stigma toward people with OUD among first-year medical students using an adaptation of a brief, validated opioid stigma scale before and after an educational intervention. The intervention consisted primarily of a recorded panel in which people with a history of OUD shared their experiences with stigma followed by small group discussions. Results After the educational intervention, students were more likely to respond that (1) they believed most people held negative beliefs about people with OUD and (2) they personally disagreed with negative statements about people with OUD. Conclusions Educational interventions addressing stigma toward people with OUD are potentially effective and should be integrated into medical curricula. Such interventions are a crucial part of the effort to improve the medical care of people with OUD.