Post-Overdose Extended-Release Buprenorphine Initiation Facilitated by a Partnership Between Emergency Medical Services and an Outpatient Substance Use Disorder Observation Unit.

BACKGROUND: People who experience a nonfatal opioid overdose and receive naloxone are at high risk of subsequent overdose death but experience gaps in access to medications for opioid use disorder. The immediate post-naloxone period offers an opportunity for buprenorphine initiation. Limited data indicate that buprenorphine administration by emergency medical services (EMS) after naloxone overdose reversal is safe and feasible. We describe a case in which a partnership between a low-barrier substance use disorder (SUD) observation unit and EMS allowed for buprenorphine initiation with extended-release injectable buprenorphine after naloxone overdose reversal. CASE: A man in his 40's with severe opioid use disorder and numerous prior opioid overdoses experienced overdose in the community. EMS was activated and he was successfully resuscitated with intranasal naloxone, administered by bystanders and EMS. He declined emergency department (ED) transport and consented to transport to a 24/7 SUD observation unit. The patient elected to start buprenorphine due to barriers attending opioid treatment programs daily. His largest barrier was unsheltered homelessness. His severe opioid withdrawal symptoms were successfully treated with 16/4 mg sublingual buprenorphine/naloxone and 300 mg extended-release injectable buprenorphine (XR-buprenorphine), without precipitated withdrawal. Two weeks later, he reported no interval fentanyl use. DISCUSSION: We describe the case of a patient successfully initiated onto XR-buprenorphine in the immediate post-naloxone period via a partnership between an outpatient low-barrier addiction programs and EMS. Such partnerships offer promise in expanding buprenorphine access and medication choice, particularly for the high-risk population of patients who decline ED transport.

How Would You Manage HIV Pre-exposure Prophylaxis in This Patient With Medical Comorbidities? : Grand Rounds Discussion From Beth Israel Deaconess Medical Center.

Despite advances in treatment, HIV infection remains an important cause of morbidity and mortality, with more than 30 000 new cases diagnosed in the United States each year. There are several interventions traditionally used to prevent HIV transmission, but these vary in effectiveness and there are challenges to their implementation. In 2014, the Centers for Disease Control and Prevention published initial guidance on the use of antiretroviral pre-exposure prophylaxis (PrEP) to prevent transmission of HIV infection in persons at risk based on multiple studies that showed it to be highly efficacious in various populations. It was updated in 2021 to reflect new drug options. The U.S. Preventive Services Task Force also recently updated its recommendations for PrEP, which strongly support its use in persons at risk. Despite its well-established effectiveness, the implementation of PrEP in clinical practice has been variable, especially among populations underserved by the medical system and marginalized by society. Fewer than one third of persons in the United States who are eligible for PrEP currently receive it. Here, 2 physicians experienced in HIV PrEP debate how best to identify patients who might benefit from PrEP, how to decide what regimen to use, and how to monitor therapy.

Addressing Unmet PrEP Needs in Women: Impact of a Laboratory-Driven Protocol at an Urban, Essential Hospital.

Background: HIV pre-exposure prophylaxis (PrEP) uptake in women remains low. We developed a laboratory result-driven protocol to link women with a positive bacterial sexually transmitted infection (STI) to HIV PrEP at an urban safety-net hospital. Methods: Electronic health records of women with positive chlamydia, gonorrhea, and/or syphilis tests were reviewed, and those eligible for PrEP were referred for direct or primary care provider-driven outreach. We assessed the proportion of women with STIs who received PrEP offers, acceptance, and prescriptions before (July 1, 2018-December 31, 2018) and after (January 1, 2019-June 30, 2020) implementation to evaluate changes in the delivery of key elements of the PrEP care cascade (ie, PrEP offers, acceptance, and prescribing) for women with STIs after protocol implementation. Results: The proportion of women who received PrEP offers increased from 7.6% to 17.6% (P < .001). After multivariable adjustment, only the postintervention period was associated with PrEP offers (odds ratio [OR], 2.49; 95% CI, 1.68-3.68). In subgroup analyses, PrEP offers increased significantly among non-Hispanic Black (OR, 2.75; 95% CI, 1.65-4.58) and Hispanic (OR, 5.34; 95% CI, 1.77-16.11) women but not among non-Hispanic White women (OR, 1.49; 95% CI, 0.54-4.05). Significant changes in PrEP acceptance and prescriptions were not observed in the sample overall. Conclusions: A laboratory result-driven protocol was associated with a significant increase in PrEP offers to Black and Hispanic women with STI. These results provide concrete suggestions for health systems seeking to increase PrEP access and equity among women.

Feasibility of paying people who use drugs cash to distribute naloxone within their networks.

INTRODUCTION: Immediate access to naloxone is needed to prevent fatal opioid-related overdoses in the presence of fentanyl analogs saturating the opioid supply. Peer models engage impacted populations who are not accessing naloxone through standard venues, yet compensating peers who utilize syringe service programs with cash stipends to distribute naloxone within networks of people who use drugs is not well described. METHODS: As part of the HEALing Communities Study, syringe service program-based interventions were developed in Holyoke and Gloucester, MA, which paid people who use drugs ("peers") cash to distribute naloxone. Early program outcomes were evaluated for the time each program was funded within the HCS study period. RESULTS: During 22 study-months of observation, peers in two communities distributed 1104 naloxone kits. The total cost of peer compensation for program delivery was $10,510. The rate of peer-distributed naloxone per 100 K population reached 109 kits/mo and 222 kits/mo in the two communities. Participating peers addressed gaps in harm reduction outreach and distributed naloxone and other harm reduction equipment to individuals who were not syringe service program participants, expanding organizational reach. Being compensated with unrestricted cash stipends supported dignity and acknowledged peers' work in overdose prevention. CONCLUSION: The underutilization of compensated peer models is often attributed to funding and organizational barriers. These programs demonstrate that providing cash stipends to peers is feasible and expanded naloxone distribution at two existing syringe service programs. Providing cash stipends for peers who engage in secondary naloxone distribution offers promise in delivering naloxone to people not accessing syringe services.

Novel Uses of Methadone Under the "72-Hour Rule" to Facilitate Transitions of Care and Low-Dose Buprenorphine Induction in an Outpatient Bridge Clinic.

BACKGROUND: Federal regulations restrict methadone for opioid use disorder (OUD) treatment to licensed opioid treatment programs (OTPs). However, providers in other settings can administer methadone for opioid withdrawal under the "72-hour rule" while linking to further care. Prior work has demonstrated that methadone initiation in a low-barrier bridge clinic is associated with high OTP linkage and 1-month retention rates. We describe 2 other novel applications of the 72-hour rule in which methadone withdrawal management facilitated linkage to inpatient hospitalization and outpatient buprenorphine induction. CASE PRESENTATIONS: Patient 1 was a 46-year-old woman with OUD complicated by serious injection-related infections. Severe opioid withdrawal limited her ability to tolerate emergency department wait times and receive inpatient care. We administered methadone for opioid withdrawal in an outpatient bridge clinic immediately before emergency department referral; this enabled hospital admission for intravenous antibiotics and anticoagulation. Patient 2 was a 36-year-old man with OUD desiring buprenorphine treatment. He had been unable to complete traditional buprenorphine induction without experiencing precipitated withdrawal. Thus, we recommended a low-dose buprenorphine induction overlapping with a full opioid agonist. Given the patient's preference to stop using fentanyl immediately, he received 72 hours of methadone for withdrawal treatment during the induction phase and successfully transitioned to buprenorphine without significant concomitant fentanyl use. CONCLUSION: In addition to facilitating OTP linkage, on-demand 72-hour methadone administration for opioid withdrawal can reduce barriers to acute medical care and buprenorphine treatment.

Mobile treatment for opioid use disorder: Implementation of community-based, same-day medication access interventions.

BACKGROUND: Medications for Opioid Use Disorder (MOUD) are lifesaving, but <20 % of individuals in the US who could benefit receive them. As part of the NIH-supported HEALing Communities Study (HCS), coalitions in several communities in Massachusetts and Ohio implemented mobile MOUD programs to overcome barriers to MOUD receipt. We defined mobile MOUD programs as units that provide same-day access to MOUD at remote sites. We aimed to (1) document the design and organizational structure of mobile programs providing same-day or next-day MOUD, and (2) explore the barriers and facilitators to implementation as well as the successes and challenges of ongoing operation. METHODS: Program staff from five programs in two states (n = 11) participated in semi-structured interviews. Two authors conducted thematic analysis of the transcripts based on the domains of the social-ecological model and the semi-structured interview guide. RESULTS: Mobile MOUD units sought to improve immediate access to MOUD ("Our answer is pretty much always, 'Yes, we'll get you started right here, right now,'"), advance equity ("making sure that we have staff who speak other languages, who are on the unit and have some resources that are in different languages,"), and decrease opioid overdose deaths. Salient program characteristics included diverse staff, including staff with lived experience of substance use ("She just had that personal knowledge of where we should be going"). Mobile units offered harm reduction services, broad medical services (in particular, wound care), and connection to transportation programs and incorporated consistency in service provision and telemedicine access. Implementation facilitators included trusting relationships with partner organizations (particularly pharmacies and correctional facilities), nuanced understanding of local politics, advertising, protocol flexibility, and on-unit prescriber hours. Barriers included unclear licensing requirements, staffing shortages and competing priorities for staff, funding challenges due to inconsistency in grant funding and low reimbursement ("It's not really possible that billing in and of itself is going to be able to sustain it"), and community stigma toward addiction services generally. CONCLUSIONS: Despite organizational, community, and policy barriers, participants described mobile MOUD units as an innovative way to expand access to life-saving medications, promote equity in MOUD treatment, and overcome stigma.

Intranasal Naloxone for Opioid Overdose.

This JAMA Insights describes indications for naloxone use in preventing opioid overdoses and benefits vs barriers to its availability following FDA approval of its availability without a prescription.

Facilitating exit from encampments: combining low-barrier transitional housing with stabilizing treatment for substance related problems.

BACKGROUND: Tent encampments in the neighborhood surrounding Boston Medical Center (BMC) grew to include 336 individuals at points between 2019 and 21, prompting public health concerns. BMC, the City of Boston, and Commonwealth of Massachusetts partnered in 2/2022 to offer low-barrier transitional housing to encampment residents and provide co-located clinical stabilization services for community members with substance use disorders (SUDs) experiencing homelessness. METHODS: To meet the needs of some of the people who had been living in encampments, BMC established in a former hotel: 60 beds of transitional housing, not contingent upon sobriety; and a low-barrier SUD-focused clinic for both housing residents and community members, offering walk-in urgent care, SUD medications, and infection screening/prevention; and a 24/7 short-stay stabilization unit to manage over-intoxication, withdrawal, and complications of substance use (e.g., abscesses, HIV risk, psychosis). A secure medication-dispensing cabinet allows methadone administration for withdrawal management. Housing program key metrics include retention in housing, transition to permanent housing, and engagement in SUD treatment and case management. Clinical program key metrics include patient volume, and rates of initiation of medication for opioid use disorder. RESULTS: Housing: Between 2/1/22-1/31/2023, 100 people entered the low-barrier transitional housing (new residents admitted as people transitioned out); 50 former encampment residents and 50 unhoused people referred by Boston Public Health Commission. Twenty-five residents transferred to permanent housing, eight administratively discharged, four incarcerated, and four died (two overdoses, two other substance-related). The remaining 59 residents remain housed; none voluntarily returned to homelessness. One hundred residents (100%) engaged with case management, and 49 engaged with SUD treatment. CLINICAL: In the first 12 months, 1722 patients (drawn from both the housing program and community) had 7468 clinical visits. The most common SUDs were opioid (84%), cocaine (54%) and alcohol (47%) and 61% of patients had a co-occurring mental health diagnosis in the preceding 24-months. 566 (33%) patients were started on methadone and accepted at an Opioid Treatment Program (OTP). CONCLUSIONS: During the 1st year of operation, low-barrier transitional housing plus clinical stabilization care was a feasible and acceptable model for former encampment residents, 49% of whom engaged with SUD treatment, and 25% of whom transitioned to permanent housing.

Survey assessment of HIV pre-exposure prophylaxis availability in student health services in New England colleges and universities.

Objective: To determine HIV pre-exposure prophylaxis (PrEP) availability at student health services (SHS) in New England. Methods: We conducted an electronic survey of medical directors of SHS at New England colleges and universities. We measured the availability and volume of PrEP prescribing, barriers and facilitators to prescribing and provider knowledge. Results: Of 143 institutions surveyed, 39% completed questionnaires; 75% were private and 93% were 4 years. Thirty-six percent of institutions did not offer PrEP. Those offering PrEP started a mean of 2.0 per 1000 students/year. PrEP was available at more schools with higher vs. lower endowments (100 vs. 38%, p = 0.002), 4- vs. 2-year programs (68 vs. 0%, p = 0.042), and private vs. public schools (73 vs. 38%, p = 0.043). Conclusions: PrEP was not available at one in three New England SHS and prescribing rates at institutions that offered PrEP were low. Interventions are needed to improve PrEP access.

Peer recovery coaching for comprehensive HIV, hepatitis C, and opioid use disorder management: The CHORUS pilot study.

Introduction: Amidst a surge in HIV and hepatitis C virus (HCV) infections in persons who use drugs, medications that effectively prevent HIV and treat opioid use disorder and HCV remain underutilized. Methods: We developed a 6-month peer recovery coaching intervention (brief motivational interviewing followed by weekly virtual or in-person coaching) and collected data on uptake of medications for opioid use disorder (MOUD), HIV pre-exposure prophylaxis (PrEP), and HCV treatment. The primary outcomes were intervention acceptability and feasibility. Results: At a Boston substance use disorder bridge clinic, we enrolled 31 HIV-negative patients who used opioids. Participants reported high intervention satisfaction at 6 months (95% "satisfied" or "very satisfied"). At study completion, 48% of the participants were on MOUD, 43% who met CDC guidelines were on PrEP, and 22% with HCV were engaged with treatment. Conclusions: A peer recovery coaching intervention is feasible and acceptable, with positive preliminary findings regarding MOUD, PrEP and HCV treatment uptake.

Substance use disorder bridge clinics: models, evidence, and future directions.

BACKGROUND: The opioid overdose and polysubstance use crises have led to the development of low-barrier, transitional substance use disorder (SUD) treatment models, including bridge clinics. Bridge clinics offer immediate access to medications for opioid use disorder (MOUD) and other SUD treatment and are increasingly numerous. However, given relatively recent implementation, the clinical impact of bridge clinics is not well described. METHODS: In this narrative review, we describe existing bridge clinic models, services provided, and unique characteristics, highlighting how bridge clinics fill critical gaps in the SUD care continuum. We discuss available evidence for bridge clinic effectiveness in care delivery, including retention in SUD care. We also highlight gaps in available data. RESULTS: The first era of bridge clinic implementation has yielded diverse models united in the mission to lower barriers to SUD treatment entry, and preliminary data indicate success in patient-centered program design, MOUD initiation, MOUD retention, and SUD care innovation. However, data on effectiveness in linking to long-term care are limited. CONCLUSIONS: Bridge clinics represent a critical innovation, offering on-demand access to MOUD and other services. Evaluating the effectiveness of bridge clinics in linking patients to long-term care settings remains an important research priority; however, available data show promising rates of treatment initiation and retention, potentially the most important metric amidst an increasingly dangerous drug supply.

Impact of COVID-19 on Sexually Transmitted Infection and HIV Screening at an Urban Safety-Net Hospital.

HIV and other sexually transmitted infections (STIs) are on the rise nationally and internationally. The coronavirus 2019 (COVID-19) pandemic drove a shift toward telemedicine and prioritization of symptomatic treatment over asymptomatic screening. The impact in safety-net settings, which faced disproportionate baseline STI/HIV rates rooted in structural inequities, and where many patients lack telemedicine resources, is not yet known. This study describes the impact of COVID-19 on STI/HIV testing at an urban safety-net hospital. We used descriptive statistics to compare hospital-wide chlamydia, gonorrhea, syphilis, and HIV testing volume and positivity rates in the following periods: prepandemic (July 1, 2019-February 29, 2020), peak-pandemic (March 1, 2020-May 31, 2020), and postpeak (June 1, 2020-August 31, 2021). STI and HIV test volume dropped sharply in March 2020. STI testing during the peak-pandemic period was 42% of prepandemic baseline (mean 1145 vs. 2738 tests/month) and nadired in April 2020 (766 tests/month). Similarly, peak-pandemic HIV testing was 43% of prepandemic baseline (mean 711 vs. 1635 tests/month) and nadired in April 2020 with 438 tests/month, concentrated in emergency department and inpatient settings. STI and HIV testing rates did not return to baseline for a full year. STI and HIV test positivity rates were higher in the peak-pandemic period compared with the prepandemic baseline. Given the precipitous decline in STI and HIV testing during the pandemic, safety-net settings should develop low-barrier alternatives to traditional office-based testing to mitigate testing gaps, high positivity rates, and associated morbidity.

Pre-Paid Phone Distribution: A Tool for Improving Healthcare Engagement for People with Substance Use Disorder.

BACKGROUND: The COVID-19 pandemic drove significant disruptions in access to substance use disorder (SUD) treatment and harm reduction services. Healthcare delivery via telemedicine has increasingly become the norm, rendering access to a phone essential for engagement in care. METHODS: Adult patients with SUD who lacked phones (n = 181) received a free, pre-paid phone during encounters with inpatient and outpatient SUD programs. We evaluated changes in healthcare engagement including completed in-person and telemedicine outpatient visits and telephone encounters 30 days before and after phone receipt. We used descriptive statistics, where appropriate, and paired t-tests to assess the change in healthcare engagement measures. RESULTS: Patients were predominantly male (64%) and white (62%) with high rates of homelessness (81%) and opioid use disorder (89%). When comparing 30 days before to 30 days after phone receipt, there was a significant increased change in number of telemedicine visits by 0.3 (95% CL [0.1,0.4], p < 0.001) and telephone encounters by 0.2 (95% CL [0.1,0.3], p = 0.004). There was no statistically significant change in in-person outpatient visits observed. CONCLUSIONS: Pre-paid phone distribution to patients with SUD was associated with an increased healthcare engagement including telemedicine visits and encounters.

HIV Exposure Prophylaxis Delivery in a Low-barrier Substance Use Disorder Bridge Clinic during a Local HIV Outbreak at the Onset of the COVID-19 Pandemic.

OBJECTIVES: People who inject drugs (PWID) may experience high human immunodeficiency virus (HIV) risk and inadequate access to biomedical HIV prevention. Emerging data support integrating HIV post-exposure and pre-exposure prophylaxis (PEP, PrEP) into services already accessed by PWID. We describe PEP/PrEP eligibility and receipt in a low-barrier substance use disorder bridge clinic located in an area experiencing an HIV outbreak among PWID at the onset of the COVID-19 pandemic. METHODS: Retrospective chart review of new patients at a substance use disorder bridge clinic in Boston, MA (January 15, 2020-May 15, 2020) to determine rates of PEP/PrEP eligibility and prescribing. RESULTS: Among 204 unique HIV-negative patients, 85.7% were assessed for injection-related and 23.0% for sexual HIV risk behaviors. Overall, 55/204 (27.0%) met CDC criteria for HIV exposure prophylaxis, including 7/204 (3.4%) for PEP and 48/204 (23.5%) for PrEP. Four of 7 PEP-eligible patients were offered PEP and all 4 were prescribed PEP. Thirty-two of 48 PrEP eligible patients were offered PrEP, and 7/48 (14.6%) were prescribed PrEP. Additionally, 6 PWID were offered PrEP who lacked formal CDC criteria. CONCLUSIONS: Bridge clinics patients have high rates of PEP/PrEP eligibility. The majority of patients with identified eligibility were offered PEP/PrEP, suggesting that upstream interventions that increase HIV risk assessment may support programs in initiating PEP/PrEP care. Additional work is needed to understand why patients declined PEP/PrEP. PrEP offers to PWID who did not meet CDC criteria also suggested provider concern regarding the sensitivity of CDC criteria among PWID. Overall, bridge clinics offer a potential opportunity to increase biomedical HIV prevention service delivery.

Effect of police action on low-barrier substance use disorder service utilization.

BACKGROUND: Police action can increase risky substance use patterns by people who use drugs (PWUD), but it is not known how increased police presence affects utilization of low-barrier substance use disorder bridge clinics. Increased police presence may increase or decrease treatment-seeking behavior. We examined the association between Operation Clean Sweep (OCS), a 2-week police action in Boston, MA, and visit volume in BMC's low-barrier buprenorphine bridge clinic. METHODS: In this retrospective cohort, we used segmented regression to investigate whether the increased police presence during OCS was associated with changes in bridge clinic visits. We used General Internal Medicine (GIM) clinic visit volume as a negative control. We examined visits during the 6 weeks prior, 2 weeks during, and 4 weeks after OCS (June 18-September 11, 2019). RESULTS: Bridge clinic visits were 2.8 per provider session before, 2.0 during, and 3.0 after OCS. The mean number of GIM clinic visits per provider session before OCS was 7.0, 6.8 during, and 7.0 after OCS. In adjusted segmented regression models for bridge clinic visits per provider session, there was a nonsignificant level increase (0.643 P = 0.171) and significant decrease in slope (0.100, P = 0.045) during OCS. After OCS completed, there was a significant level increase (1.442, P = 0.003) and slope increase in visits per provider session (0.141, P = 0.007). There was no significant change in GIM clinic volume during the study period. CONCLUSIONS: The increased policing during OCS was associated with a significant decrease in bridge clinic visits. Following the completion of OCS, there was a significant increase in clinic visits, suggesting pent-up demand for medications for opioid use disorder, a life-saving treatment.

Prevalence of HIV Preexposure Prophylaxis Prescribing Among Persons With Commercial Insurance and Likely Injection Drug Use.

Importance: Although HIV preexposure prophylaxis (PrEP) implementation among persons who inject drugs has been inadequate, national HIV monitoring programs do not include data on PrEP, and specific trends in PrEP use are not well understood. Objective: To estimate HIV PrEP uptake among commercially insured persons with opioid or stimulant use disorder by injection drug use (IDU) status. Design, Setting, and Participants: This cross-sectional study used deidentified data from the MarketScan Commercial Claims and Encounters Database to identify a sample of 547 709 commercially insured persons without HIV but with opioid and/or stimulant use disorder, including 110 592 with evidence of IDU between January 1, 2010, and December 31, 2019. Data were analyzed from November 1, 2020, to July 1, 2021. Exposures: Persons with opioid and/or stimulant use disorder and evidence of IDU were identified through claims data. Main Outcomes and Measures: The outcome was receipt of tenofovir disoproxil fumarate and emtricitabine for PrEP as identified from filled pharmacy claims. Multivariable logistic regression was used to assess the association of demographic and clinical characteristics with receipt of PrEP. Results: The study cohort included 211 609 (28.6%) females and 336 100 (61.4%) males with a combined mean (SD) age of 34.8 (13.1) years, including 110 592 individuals with evidence of IDU. During the study period, 508 (0.09%) persons with opioid and/or stimulant use disorder, including 170 (0.15%) with evidence of IDU, received PrEP. Receipt of PrEP increased from 0.001 to 0.243 per 100 person-years from 2010 through 2019 among the entire cohort and from 0.000 to 0.295 per 100 person-years among those with IDU. In multivariable analysis, PrEP use was more likely among males (adjusted odds ratio [aOR] 8.72; 95% CI, 6.39-11.89), persons with evidence of IDU (aOR, 1.47; 95% CI, 1.21-1.79), and persons with evidence of sexual risk indications for PrEP (aOR, 23.68; 95% CI, 19.57-28.66). Conclusions and Relevance: In this cross-sectional study of commercially insured persons with opioid and/or stimulant use disorder, HIV PrEP delivery remained low, including among those with evidence of IDU. PrEP should be consistently offered alongside substance use disorder treatment and other harm reduction and HIV prevention services.

Bridge clinic implementation of "72-hour rule" methadone for opioid withdrawal management: Impact on opioid treatment program linkage and retention in care.

BACKGROUND: Methadone for opioid use disorder (OUD) treatment is restricted to licensed opioid treatment programs (OTPs) with substantial barriers to entry. Underutilized regulations allow non-OTP providers to administer methadone for opioid withdrawal for up to 72 h while arranging ongoing care. Our low-barrier bridge clinic implemented a new pathway to treat opioid withdrawal and facilitate OTP linkage utilizing the "72-hour rule." METHODS: Patients presenting to a hospital-based bridge clinic were evaluated for OUD, opioid withdrawal, and treatment goals. Eligible patients were offered methadone opioid withdrawal management with rapid OTP referral. OTPs accepted patients as direct admissions. We described bridge clinic patients who received at least one dose of methadone between March-August 2021 and key clinical outcomes including OTP referral completion within 72 h. For the subset of patients referred to our two primary OTP partners, we described OTP linkage (i.e., attended at least one OTP visit within one month) and OTP retention at one month. RESULTS: Methadone was administered during 150 episodes of care for 142 unique patients, the majority of whom were male (73%), white (67%), and used fentanyl (85%). In 92% of episodes (138/150), a plan for ongoing care was in place within 72 h. Among 121 referrals to two primary OTP partners, 87% (105/121) linked and 58% (70/121) were retained at one month. CONCLUSIONS: Methadone administration for opioid withdrawal with direct OTP admission under the "72-hour rule" is feasible in an outpatient bridge clinic and resulted in high OTP linkage and 1-month retention rates. This model has the potential to improve methadone access.

Expression of the preadipocyte marker ZFP423 is dysregulated between well-differentiated and dedifferentiated liposarcoma.

BACKGROUND: Well-differentiated and dedifferentiated liposarcomas are rare soft tissue tumors originating in adipose tissue that share genetic abnormalities but have significantly different metastatic potential. Dedifferentiated liposarcoma (DDLPS) is highly aggressive and has an overall 5-year survival rate of 30% as compared to 90% for well-differentiated liposarcoma (WDLPS). This discrepancy may be connected to their potential to form adipocytes, where WDLPS is adipogenic but DDLPS is adipogenic-impaired. Normal adipogenesis requires Zinc Finger Protein 423 (ZFP423), a transcriptional coregulator of Perixosome Proliferator Activated Receptor gamma (PPARG2) mRNA expression that defines committed preadipocytes. Expression of ZFP423 in preadipocytes is promoted by Seven-In-Absentia Homolog 2 (SIAH2)-mediated degradation of Zinc Finger Protein 521 (ZFP521). This study investigated the potential role of ZFP423, SIAH2 and ZFP521 in the adipogenic potential of WDLPS and DDLPS. METHODS: Human WDLPS and DDLPS fresh and paraffin-embedded tissues were used to assess the gene and protein expression of proadipogenic regulators. In parallel, normal adipose tissue stromal cells along with WDLPS and DDLPS cell lines were cultured, genetically modified, and induced to undergo adipogenesis in vitro. RESULTS: Impaired adipogenic potential in DDLPS was associated with reduced ZFP423 protein levels in parallel with reduced PPARG2 expression, potentially involving regulation of ZFP521. SIAH2 protein levels did not define a clear distinction related to adipogenesis in these liposarcomas. However, in primary tumor specimens, SIAH2 mRNA was consistently upregulated in DDLPS compared to WDLPS when assayed by fluorescence in situ hybridization or real-time PCR. CONCLUSIONS: These data provide novel insights into ZFP423 expression in adipogenic regulation between WDLPS and DDLPS adipocytic tumor development. The data also introduces SIAH2 mRNA levels as a possible molecular marker to distinguish between WDLPS and DDLPS.