HIV-1 Tat and morphine interactions dynamically shift striatal monoamine levels and exploratory behaviors over time.

Despite the advent of combination anti-retroviral therapy (cART), nearly half of people infected with HIV treated with cART still exhibit HIV-associated neurocognitive disorders (HAND). HAND can be worsened by co-morbid opioid use disorder. The basal ganglia are particularly vulnerable to HIV-1 and exhibit higher viral loads and more severe pathology, which can be exacerbated by co-exposure to opioids. Evidence suggests that dopaminergic neurotransmission is disrupted by HIV exposure, however, little is known about whether co-exposure to opioids may alter neurotransmitter levels in the striatum and if this in turn influences behavior. Therefore, we assayed motor, anxiety-like, novelty-seeking, exploratory, and social behaviors, and levels of monoamines and their metabolites following 2 weeks and 2 months of Tat and/or morphine exposure in transgenic mice. Morphine decreased dopamine levels, but significantly elevated norepinephrine, the dopamine metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), and the serotonin metabolite 5-hydroxyindoleacetic acid, which typically correlated with increased locomotor behavior. The combination of Tat and morphine altered dopamine, DOPAC, and HVA concentrations differently depending on the neurotransmitter/metabolite and duration of exposure but did not affect the numbers of tyrosine hydroxylase-positive neurons in the mesencephalon. Tat exposure increased the latency to interact with novel conspecifics, but not other novel objects, suggesting the viral protein inhibits exploratory behavior initiation in a context-dependent manner. By contrast, and consistent with prior findings that opioid misuse can increase novelty-seeking behavior, morphine exposure increased the time spent exploring a novel environment. Finally, Tat and morphine interacted to affect locomotor activity in a time-dependent manner, while grip strength and rotarod performance were unaffected. Together, our results provide novel insight into the unique effects of HIV-1 Tat and morphine on monoamine neurochemistry that may underlie their divergent effects on motor and exploratory behavior.

Focus on fentanyl in females: Sex and gender differences in the physiological and behavioral effects of fentanyl.

The prevalence of opioid use disorder and overdose continues to harm the U.S. population and is further exacerbated by the use of the synthetic opioid, fentanyl, and its analogs. Gender differences in the effects of fentanyl are not well understood. The present article reviews evidence for gender and sex differences in the physiological and behavioral effects of fentanyl in humans and animals. Biological sex seems to be a foundational driver in addiction vulnerability and affects mechanisms related to opioid use including fentanyl. Fentanyl has distinct pharmacodynamics and enhanced efficacy relative to other opioids that highlights the need to investigate how females may be uniquely altered by its use. Behavioral and physiological responses to fentanyl are found to differ by sex and gender in many cases, including outputs like affective symptoms, analgesia, tolerance, and withdrawal emphasizing the need for further research about the role of biological sex on fentanyl use.

Association between trajectories of prescription opioid use and risk of opioid use disorder and overdose among US nonmetastatic breast cancer survivors.

PURPOSE: To examine the association between prescription opioid use trajectories and risk of opioid use disorder (OUD) or overdose among nonmetastatic breast cancer survivors by treatment type. METHODS: This retrospective cohort study included female nonmetastatic breast cancer survivors with at least 1 opioid prescription fill in 2010-2019 Surveillance, Epidemiology and End Results linked Medicare data. Opioid mean daily morphine milligram equivalents (MME) calculated within 1.5 years after initiating active breast cancer therapy. Group-based trajectory models identified distinct opioid use trajectory patterns. Risk of time to first OUD/overdose event within 1 year after the trajectory period was calculated for distinct trajectory groups using Cox proportional hazards models. Analyses were stratified by treatment type. RESULTS: Four opioid use trajectories were identified for each treatment group. For 38,030 survivors with systemic endocrine therapy, 3 trajectories were associated with increased OUD/overdose risk compared with early discontinuation: minimal dose (< 5 MME; adjusted hazard ratio [aHR] = 1.73 [95% CI 1.43-2.09]), very low dose (5-25 MME; 2.67 [2.05-3.48]), and moderate dose (51-90 MME; 6.20 [4.69-8.19]). For 9477 survivors with adjuvant chemotherapy, low-dose opioid use was associated with higher OUD/overdose risk (aHR = 7.33 [95% CI 2.52-21.31]) compared with early discontinuation. For 3513 survivors with neoadjuvant chemotherapy, the differences in OUD/OD risks across the 4 trajectories were not significant. CONCLUSIONS: Among Medicare nonmetastatic breast cancer survivors receiving systemic endocrine therapy or adjuvant chemotherapy, compared with early discontinuation, low-dose or moderate-dose opioid use were associated with six- to sevenfold higher OUD/overdose risk. Breast cancer survivors at high-risk of OUD/overdose may benefit from targeted interventions (e.g., pain clinic referral).

Sexually transmitted and blood-borne infection risk reduction with methadone and buprenorphine/naloxone among people with prescription-type opioid use disorder: Findings from a Canadian pragmatic randomized trial.

INTRODUCTION: People who use drugs are disproportionally affected by sexually transmitted and blood-borne infections (STBBIs). While the benefits of methadone in reducing injecting-risk behaviours are well documented, less is known on its impacts on sexual-related risks, as well as its comparative effectiveness to buprenorphine/naloxone, particularly in the context of highly potent opioids. The aim of this study was to estimate the relative effects of buprenorphine/naloxone and methadone on injecting and STBBI risks among people with prescription-type opioid use disorder (POUD). METHODS: Secondary analysis of a pan-Canadian pragmatic 24-week randomized clinical trial comparing methadone and buprenorphine/naloxone models of care among 272 people with POUD (including licit or illicit opioid analgesics, fentanyl). The Risk Behaviour Survey was used to collect injecting and sexual risks at baseline, and weeks 12 and 24. RESULTS: In total, 210 participants initiated treatment (103 buprenorphine/naloxone and 107 methadone). At baseline, 113/205 (55.1%) participants reported recently injecting drugs, 37/209 (17.7%) unsafe injection practices and 67/162 (41.4%) high-risk sex. Both methadone and buprenorphine/naloxone were associated with reductions in the prevalence of injection drug use and high-risk sex at weeks 12 and 24 with no interactions between treatment arm and time. CONCLUSION: Methadone and buprenorphine/naloxone were similarly effective in reducing injecting and sexual risk behaviours among people with POUD. CLINICAL TRIALS REGISTRATION: clinicaltrials.gov NCT03033732.

A Dyadic Framework of Care for Opioid-exposed Birthing Persons and Their Infants and Children.

OBJECTIVE: To develop a dyadic-centered framework focused on clinical care, surveillance, and research for birthing persons with opioid use disorder (OUD) and their infants and children. STUDY DESIGN: Between February and March 2023, an analysis was conducted within the US Department of Health and Human Services (HHS) of activities directed at opioid-exposed birthing persons and their infants and children (the dyad) to identify: 1) number of activities, stratified by type and 2) characteristics across health and supportive activities that serve the dyad vs birthing persons or infants and children individually. Descriptive and thematic analyses were used to assess quantity and characteristics of fiscal year 2023-2024 activities aggregated across eleven HHS agencies. RESULTS: Of 181 activities examined, 75 met inclusion criteria specific to serving birthing persons with OUD and opioid-exposed infants and children. Sixty-two percent of activities were dyad focused. Five categories of dyadic activities were identified: research (45%), education and training (28%), health and supportive services (21%), surveillance (4%), and quality improvement (2%). Eight specific characteristics were key to dyadic activities: a life course and generational approach, emphasis on relationship, dyadic outcomes, service wraparound, payment structures supporting dyadic care, data linkage, and social determinants of health. CONCLUSIONS: This analysis of HHS activities directed at birthing persons with OUD and opioid-exposed infants and children showed that most programs had a dyadic focus. Synthesizing elements identified from activities serving the dyad facilitated the development of a dyadic framework integrating clinical care, public health surveillance, and research.

Experiences of Aging with Opioid Use Disorder and Comorbidity in Opioid Treatment Programs: A Qualitative Analysis.

BACKGROUND: The number of older adults entering opioid treatment programs (OTPs) to treat opioid use disorder (OUD) is increasing. However, the lived experiences of aging in OTPs have not been examined. OBJECTIVE: To explore the aging experience with OUD and barriers to medical care for older adults who receive care in OTPs. DESIGN: From November 2021 to July 2022, we conducted 1-to-1, semi-structured qualitative interviews in English and Spanish, audio-recorded, transcribed, systematically coded, and analyzed to identify key themes regarding the challenges of aging with OUD and managing chronic diseases. PARTICIPANTS: Thirty-six adults aged ≥ 55 enrolled in OTPs in San Diego, California. APPROACH: A descriptive qualitative approach was used. Major themes and subthemes were identified through thematic analysis until thematic saturation was reached. KEY RESULTS: All participants were on methadone and had a mean age of 63.4 (SD 5.1) years; 11 (30.6%) identified as female, 14 (39%) as Hispanic/Latino, and 11 (36%) as Black, with a mean duration of methadone treatment of 5.6 years. Chronic diseases were common, with 21 (58.3%) reporting hypertension, 9 (25%) reporting untreated hepatitis C, and 32 (88.9%) having ≥ 2 chronic diseases. Three major themes emerged: (1) avoidance of medical care due to multiple intersectional stigmas, including those related to drug use, substance use disorder (SUD) treatment, ageism, and housing insecurity; (2) increasing isolation with aging and loss of family and peer groups; (3) the urgent need for integrating medical and aging-focused care with OUD treatment in the setting of increasing health and functional challenges. CONCLUSIONS: Older adults with OUD reported increasing social isolation and declining health while experiencing multilevel stigma and discrimination. The US healthcare system must transform to deliver age-friendly care that integrates evidence-based geriatric models of care incorporated with substance use disorder treatment and addresses the intersectional stigma this population has experienced in healthcare settings.

Prescribing and Acceptance of Medications for Opioid Use Disorder in VA Primary Care: Veteran and Provider Perspectives.

BACKGROUND: Medications to treat opioid use disorder (MOUD) such as buprenorphine/naloxone can effectively treat OUD and reduce opioid-related mortality, but they remain underutilized, especially in non-substance use disorder settings such as primary care (PC). OBJECTIVE: To uncover the factors that can facilitate successful prescribing of MOUD and uptake/acceptance of MOUD by patients in PC settings in the Veterans Health Administration. DESIGN: Semi-structured qualitative telephone interviews with 77 providers (e.g., primary care providers, hospitalists, nurses, addiction psychiatrists) and 22 Veteran patients with experience taking MOUD. Interviews were recorded, transcribed, and analyzed thematically using a combination a priori/inductive approach. KEY RESULTS: Providers and patients shared their general perceptions and experiences with MOUD, including high satisfaction with buprenorphine/naloxone with few side effects and caveats, although some patients reported drawbacks to methadone. Both providers and patients supported the idea of prescribing MOUD in PC settings to prioritize patient comfort and convenience. Providers described individual-level barriers (e.g., time, stigma, perceptions of difficulty level), structural-level barriers (e.g., pharmacy not having medications ready, space for inductions), and organizational-level barriers (e.g., inadequate staff support, lack of nursing protocols) to PC providers prescribing MOUD. Facilitators centered on education and knowledge enhancement, workflow and practice support, patient engagement and patient-provider communication, and leadership and organizational support. The most common barrier faced by patients to starting MOUD was apprehensions about pain, while facilitators focused on personal motivation, encouragement from others, education about MOUD, and optimally timed provider communication strategies. CONCLUSIONS: These findings can help improve provider-, clinic-, and system-level supports for MOUD prescribing across multiple settings, as well as foster communication strategies that can increase patient acceptance of MOUD. They also point to how interprofessional collaboration across service lines and leadership support can facilitate MOUD prescribing among non-addiction providers.

Assessing Substance Use Disorder Symptoms with a Checklist among Primary Care Patients with Opioid Use Disorder and/or Long-Term Opioid Treatment: An Observational Study.

BACKGROUND: Primary care (PC) offers an opportunity to treat opioid use disorders (OUD). The Substance Use Symptom Checklist ("Checklist") can assess DSM-5 substance use disorder (SUD) symptoms in PC. OBJECTIVE: To test the psychometric properties of the Checklist among PC patients with OUD or long-term opioid therapy (LTOT) in Kaiser Permanente Washington (KPWA). DESIGN: Observational study using item response theory (IRT) and differential item functioning (DIF) analyses of measurement consistency across age, sex, race and ethnicity, and receipt of treatment. PATIENTS: Electronic health records (EHR) data were extracted for all adult PC patients visiting KPWA 3/1/15-8/30/2020 who had ≥ 1 Checklist documented and indication of either (a) clinically-recognized OUD (i.e., documented OUD diagnosis and/or OUD medication treatment) or (b) LTOT in the year prior to the checklist. MAIN MEASURE: The Checklist includes 11 items reflecting DSM-5 criteria for SUD. We described the prevalence of 2 SUD symptoms reported on the Checklist (consistent with mild-severe DSM-5 SUD). Analyses were conducted in the overall sample and in two subsamples (clinically-recognized OUD and LTOT only). KEY RESULTS: Among 2007 eligible patients, 39.9% endorsed ≥ 2 SUD symptoms (74.3% in the clinically-recognized OUD subsample and 13.1% in LTOT subsample). IRT indicated that a unidimensional model for the 11 checklist items had excellent fit (comparative fit index = 0.998) with high item-level discrimination parameters for the overall sample and both subsamples. DIF across age, race and ethnicity, and treatment was observed for one item each, but had minimal impact on expected number of criteria (0-11) patients endorse. CONCLUSIONS: The Substance Use Symptom Checklist measured SUD symptoms consistent with DSM-5 conceptualization (scaled, unidimensional) in patients with clinically-recognized OUD and LTOT and had similar measurement properties across demographic subgroups. The Checklist may support symptom assessment in patients with OUD and diagnosis in patients with LTOT.

Integrating Buprenorphine for Opioid Use Disorder into Rural, Primary Care Settings.

BACKGROUND: Medications for opioid use disorder (MOUD) including buprenorphine are effective, but underutilized. Rural patients experience pronounced disparities in access. To reach rural patients, the US Department of Veterans Affairs (VA) has sought to expand buprenorphine prescribing beyond specialty settings and into primary care. OBJECTIVE: Although challenges remain, some rural VA health care systems have begun offering opioid use disorder (OUD) treatment with buprenorphine in primary care. We conducted interviews with clinicians, leaders, and staff within these systems to understand how this outcome had been achieved. DESIGN: Using administrative data from the VA Corporate Data Warehouse (CDW), we identified rural VA health care systems that had improved their rate of primary care-based buprenorphine prescribing over the period 2015-2020. We conducted qualitative interviews (n = 30) with staff involved in implementing or prescribing buprenorphine in these systems to understand the processes that had facilitated implementation. PARTICIPANTS: Clinicians, staff, and leaders embedded within rural VA health care systems located in the Northwest, West, Midwest (2), South, and Northeast. APPROACH: Qualitative interviews were analyzed using a mixed inductive/deductive approach. KEY RESULTS: Interviews revealed the processes through which buprenorphine was integrated into primary care, as well as processes insufficient to enact change. Implementation was often initially catalyzed through a targeted hire. Champions then engaged clinicians and leaders one-on-one to "pitch" the case, describe concordance between buprenorphine prescribing and existing goals, and delineate the supportive role that they could provide. Sites were prepared for implementation by developing new clinical teams and redesigning clinical processes. Each of these processes was made possible with the active, instrumental support of leadership. CONCLUSIONS: Results suggest that rural systems seeking to improve buprenorphine accessibility in primary care may need to alter primary care structures to accommodate buprenorphine prescribing, whether through new hires, team development, or clinical redesign.

Outpatient-Based Opioid Treatment Engagement and Attendance: A Prospective Cohort Study of Homeless-Experienced Adults.

BACKGROUND: The opioid overdose epidemic disproportionately impacts people experiencing homelessness. Outpatient-based opioid treatment (OBOT) programs have been established in homeless health care settings across the USA, but little is known about the success of these programs in engaging and retaining this highly marginalized patient population in addiction care. OBJECTIVE: To evaluate predictors of initial engagement and subsequent attendance in a homeless-tailored OBOT program. DESIGN: Prospective cohort study with 4 months of follow-up. PARTICIPANTS: A total of 148 homeless-experienced adults (≥18 years) who newly enrolled in the Boston Healthcare for the Homeless Program (BHCHP) OBOT program over a 1-year period (1/6/2022-1/5/2023). MAIN MEASURES: The primary outcomes were (1) initial OBOT program engagement, defined as having ≥2 additional OBOT visits within 1 month of OBOT enrollment, and (2) subsequent OBOT program attendance, measured monthly from months 2 to 4 of follow-up. KEY RESULTS: The average age was 41.7 years (SD 10.2); 23.6% were female, 35.8% were Hispanic, 12.8% were non-Hispanic Black, and 43.9% were non-Hispanic White. Over one-half (57.4%) were initially engaged. OBOT program attendances during months 2, 3, and 4 were 60.8%, 50.0%, and 41.2%, respectively. One-quarter (24.3%) were initially engaged and then attended the OBOT program every month during the follow-up period. Participants in housing or residential treatment programs (vs. unhoused; adjusted odds ratios (aORs) = 2.52; 95% CI = 1.17-5.44) and those who were already on or initiated a medication for opioid use disorder (OUD) (aOR = 6.53; 95% CI = 1.62-26.25) at the time of OBOT enrollment had higher odds of engagement. Older age (aOR = 1.74 per 10-year increment; 95% CI = 1.28-2.38) and initial engagement (aOR = 3.50; 95% CI = 1.86-6.59) conferred higher odds of attendance. CONCLUSIONS: In this study, over half initially engaged with the OBOT program, with initial engagement emerging as a strong predictor of subsequent OBOT program attendance. Interventions aimed at enhancing initial OBOT program engagement, including those focused on housing and buprenorphine initiation, may improve longer-term outcomes in this marginalized population.

Pregnancy Rates Among Women Treated with Medication for Opioid Use Disorder.

BACKGROUND: Treatment-seeking people with opioid use disorder (OUD) who are capable of pregnancy need accurate information about the potential impact of medication to treat OUD (MOUD) on fertility to make informed choices about treatment that are consistent with their reproductive wishes. There is a dearth of research on fertility associated with MOUD receipt in birthing people with OUD. OBJECTIVE: To estimate the association between treatment with MOUD and odds of conception among birthing people using national administrative claims. DESIGN: Retrospective case-crossover study using multi-state US administrative data (2006-2016). Dates of conception were estimated from delivery dates and served as "case" days for which MOUD exposures were compared to those on all other ("control") days of insurance enrollment. PARTICIPANTS: Treatment-seeking people with OUD with a delivery during the observation period. MAIN MEASURES: Odds ratios for conception from within-person fixed effects models were modeled as a function of exposure to MOUD (buprenorphine, methadone, extended-release depot naltrexone, or oral naltrexone) using conditional logistic regression. KEY RESULTS: A total of 21,928 births among 19,133 people with OUD were identified. In the sample, 5873 people received buprenorphine, 1825 methadone, 486 extended-release naltrexone, and 714 oral naltrexone. Participants could receive more than one type of MOUD. Mean age was 28.2 years (SD = 2.2; range = 16-45), with 76.2% having Medicaid. vs. commercial insurance. Compared to no MOUD, periods of methadone (aOR = 0.55 [95% CI = 0.48-0.63]) or buprenorphine receipt (aOR = 0.84 [0.77-0.91]) were associated with fewer conceptions. Treatment periods with extended-release depot naltrexone compared to no medication were associated with higher odds of conception (aOR = 1.75 [1.22-2.50]) and there was no significant difference in conception with oral naltrexone (aOR = 1.02 [0.67-1.54]). CONCLUSIONS: The association between MOUD and odds of conception among birthing people varied by type of MOUD, with extended-release naltrexone associated with higher odds of conceiving compared to no treatment. Clinical studies are urgently needed to investigate these findings further.

Patients' and Clinicians' Experiences with In-person, Video, and Phone Modalities for Opioid Use Disorder Treatment: A Qualitative Study.

BACKGROUND: Opioid use disorder (OUD) is a chronic condition that requires regular visits and care continuity. Telehealth implementation has created multiple visit modalities for OUD care. There is limited knowledge of patients' and clinicians' perceptions and experiences related to multi-modality care and when different modalities might be best employed. OBJECTIVE: To identify patients' and clinicians' experiences with multiple visit modalities for OUD treatment in primary care. DESIGN: Comparative case study, using video- and telephone-based semi-structured interviews. PARTICIPANTS: Patients being treated for OUD (n = 19) and clinicians who provided OUD care (n = 15) from two primary care clinics within the same healthcare system. APPROACH: Using an inductive approach, interviews were analyzed to identify patients' and clinicians' experiences with receiving/delivering OUD care via different visit modalities. Clinicians' and patients' experiences were compared using a group analytical process. KEY RESULTS: Patients and clinicians valued having multiple modalities available for care, with flexibility identified as a key benefit. Patients highlighted the decreased burden of travel and less social anxiety with telehealth visits. Similarly, clinicians reported that telehealth decreased medical intrusion into the lives of patients stable in recovery. Patients and clinicians saw the value of in-person visits when establishing care and for patients needing additional support. In-person visits allowed the ability to conduct urine drug testing, and to foster relationships and trust building, which were more difficult, but not impossible via a telehealth visit. Patients preferred telephone over video visits, as these were more private and more convenient. Clinicians identified benefits of video, including being able to both hear and see the patient, but often deferred to patient preference. CONCLUSIONS: Considerations for utilization of visit modalities for OUD care were identified based on patients' needs and preferences, which often changed over the course of treatment. Continued research is needed determine how visit modalities impact patient outcomes.

Hospital Addiction Medicine Consultation Service Orders and Outcomes by Patient Race and Ethnicity in an Urban, Safety-Net Hospital.

BACKGROUND: Hospital admissions involving substance use disorders are increasing and represent an opportunity to engage patients in substance use treatment. Addiction medicine consultation services improve access to medications for opioid use disorder (MOUD) and patient outcomes. However, as hospitals continue to adopt addiction medicine consultation services it is important to identify where disparities may emerge in the process of care. OBJECTIVE: To describe addiction medicine consultation service use by race and ethnicity as well as substance to identify opportunities to reduce substance use treatment disparities. DESIGN: Retrospective cohort study using 2016-2021 Electronic Health Record data from a large Midwest safety-net hospital. PARTICIPANTS: Hospitalized adults aged 18 or older, with one or more substance use disorders. MAIN MEASURES: Consultation orders placed, patient seen by consult provider, and receipt of MOUD by self-reported race. KEY RESULTS: Between 2016 and 2021, we identified 16,895 hospitalized patients with a substance use disorder. Consultation orders were placed for 6344 patients and 2789 were seen by the consult provider. Black patients were less likely (aOR = 0.58; 95% CI: 0.53-0.63) to have an addiction medicine consultation order placed and, among patients with a consultation order, were less likely (aOR = 0.74; 95% CI: 0.65-0.85) to be seen by the consult provider than White patients. Overall, Black patients with OUD were also less likely to receive MOUD in the hospital (aOR = 0.63; 95% CI: 0.50-0.79) compared to White patients. However, there were no differences in MOUD receipt among Black and White patients seen by the consult provider. CONCLUSIONS: Using Electronic Health Record data, we identified racial and ethnic disparities at multiple points in the inpatient addiction medicine consultation process. Addressing these disparities may support more equitable access to MOUD and other substance use treatment in the hospital setting.

In-Hospital Methadone Enrollment: a Novel Program to Facilitate Linkage from the Hospital to the Opioid Treatment Program for Vulnerable Patients with Opioid Use Disorder.

INTRODUCTION: Methadone ameliorates opioid withdrawal among hospitalized patients with opioid use disorder (OUD). To continue methadone after hospital discharge, patients must enroll in an opioid treatment program (OTP) per federal regulations. Uncontrolled opioid withdrawal is a barrier to linkage from hospital to OTP. AIM: Describe a federally compliant In-Hospital Methadone Enrollment Team (IN-MEET) that enrolls hospitalized patients with OUD into an OTP with facilitated hospital to OTP linkage. SETTING: Seven hundred-bed university hospital in Aurora, CO. PROGRAM DESCRIPTION: A physician dually affiliated with a hospital's addiction consultation service and a community OTP completes an in-hospital, face-to-face medical assessment required by federal law and titrates methadone to comfort. An OTP-affiliated nurse with hospital privileges completes a psychosocial evaluation and provides case management by arranging transportation and providing weekly telephone check-ins. PROGRAM EVALUATION METRICS: IN-MEET enrollments completed, hospital to OTP linkage, and descriptive characteristics of patients who completed IN-MEET enrollments compared to patients who completed community OTP enrollments. RESULTS: Between April 2019 and April 2023, our team completed 165 IN-MEET enrollments. Among a subset of 73 IN-MEET patients, 56 (76.7%) presented to the OTP following hospital discharge. Compared to community OTP enrolled patients (n = 1687), a higher percentage of IN-MEET patients were older (39.7 years, standard deviation [SD] 11.2 years vs. 36.1 years, SD 10.6 years) and were unhoused (n = 43, 58.9% vs. n = 199, 11.8%). Compared to community OTP enrolled patients, a higher percentage of IN-MEET patients reported heroin or fentanyl as their primary substance (n = 53, 72.6% vs. n = 677, 40.1%), reported methamphetamine as their secondary substance (n = 27, 37.0% vs. n = 380, 22.5%), and reported they injected their primary substance (n = 46, 63.0% vs. n = 478, 28.3%). CONCLUSION: IN-MEET facilitates hospital to OTP linkage among a vulnerable population. This model has the potential to improve methadone access for hospitalized patients who may not otherwise seek out treatment.

Association Between Cost-Sharing and Buprenorphine Prescription Abandonment.

BACKGROUND: Prior studies suggest cost-sharing decreases buprenorphine dispensing. However, these studies used databases that only report prescriptions filled by patients, not those that were "abandoned." Consequently, the studies could not calculate the probability of buprenorphine prescription abandonment or evaluate whether cost-sharing is associated with abandonment. OBJECTIVE: To evaluate the association between cost-sharing and buprenorphine prescription abandonment. DESIGN: Cross-sectional analysis of the IQVIA Formulary Impact Analyzer, a pharmacy transaction database representing 63% of U.S. retail pharmacies. The database includes transaction records ("claims") for prescriptions even if they are not filled. PARTICIPANTS: Buprenorphine claims in 2022 among commercially insured and Medicare patients. MAIN MEASURES: We evaluated the association between cost-sharing per 30-day supply and abandonment using logistic regression, controlling for patient characteristics, product type, and buprenorphine use in the prior 180 days. We assessed for effect modification by prior buprenorphine use. KEY RESULTS: Analyses included 2,346,994 and 1,242,596 buprenorphine prescription claims for commercially insured and Medicare patients, respectively. Among these claims, mean (SD) cost-sharing per 30-day supply was $28.1 (46.4) and $8.4 (20.2), and 1.5% and 1.2% were abandoned. Each $10 increase in cost-sharing per 30-day supply was associated with a 0.09 (95% CI: 0.09, 0.10) and 0.09 (95% CI: 0.08, 0.10) percentage-point increase in abandonment among commercially insured and Medicare patients. Among commercially insured and Medicare patients without prior buprenorphine use, respectively, a $10 increase in cost-sharing per 30-day supply was associated with a 0.12 (95% CI: 0.11, 0.14) and 0.13 (95% CI: 0.07, 0.18) percentage-point higher increase in the probability of abandonment compared with patients with > 90 days of prior buprenorphine use. CONCLUSIONS: Among commercially insured and Medicare patients, buprenorphine prescription abandonment is rare and only minimally associated with cost-sharing. Findings suggest elimination of buprenorphine cost-sharing should only be one component of a larger, multi-faceted campaign to increase buprenorphine dispensing.

Multilevel Factors Impacting Substance Use Treatment Access, Engagement, and Racial Equity Among Opioid Overdose Survivors in Boston, MA.

BACKGROUND: There are well-documented racial/ethnic inequities in drug-related overdoses and access to evidence-based opioid use services nationally and in Boston, MA. OBJECTIVE: To qualitatively explore the drivers of racial/ethnic inequities in access to opioid use disorder treatment and services in Boston. DESIGN: Semi-structured qualitative interviews. PARTICIPANTS: Using purposive sampling, researchers recruited 59 opioid overdose survivors in Boston who self-identified as Black, Hispanic or Latino/a/x, and/or White. APPROACH: Interviewers administered a socio-demographic and drug use survey, and used a semi-structured interview guide to explore experiences with and perspectives on substance use treatment and services. KEY RESULTS: Participants' racial/ethnic identities were distributed across three subgroups: non-Hispanic Black (n = 18; 31%), non-Hispanic White (n = 18; 31%), and Latino/a/x (n = 23; 39%). Qualitative analysis identified multiple themes that were organized into four social-ecological levels after analysis. At the individual level, some participants emphasized the importance of personal responsibility and individual motivation in determining access to services. Participants expressed a range of perspectives about using medication for opioid use disorder treatment; Black and Latino/a/x participants were more likely than White participants to have critical perspectives. At the interpersonal level, experiences of bias, stigma, and racism from staff in healthcare and treatment settings were common. At the program/process level, participants described challenges connecting to services following overdose and barriers within specific programs, with Black and Latino/a/x participants experiencing particular gaps. At the systems level, the limited availability of housing, employment, and mental health care negatively impacted treatment access and engagement. CONCLUSION: A racism lens was used during data interpretation to apply the themes at a broader population level. Through this lens, the identified barriers can be understood to have a disproportionate impact on people of color. Findings call for programmatic and policy solutions that address racism, break down stigma, and ensure equitable access to evidence-based services and social supports.

Barriers and Facilitators to Establishing Partnerships for Substance Use Disorder Care Transitions Between Safety-Net Hospitals and Community-Based Organizations.

BACKGROUND: The effectiveness of hospital-based transitional opioid programs (TOPs), which aim to connect patients with substance use disorders (SUD) to ongoing treatment in the community following initiation of medication for opioid use disorder (MOUD) treatment in the hospital, hinges on successful patient transitions. These transitions are enabled by strong partnerships between hospitals and community-based organizations (CBOs). However, no prior study has specifically examined barriers and facilitators to establishing SUD care transition partnerships between hospitals and CBOs. OBJECTIVE: To identify barriers and facilitators to developing partnerships between hospitals and CBOs to facilitate care transitions for patients with SUDs. DESIGN: Qualitative study using semi structured interviews conducted between November 2022-August 2023. PARTICIPANTS: Staff and providers from hospitals affiliated with four safety-net health systems (n=21), and leaders and staff from the CBOs with which they had established partnerships (n=5). APPROACH: Interview questions focused on barriers and facilitators to implementing TOPs, developing partnerships with CBOs, and successfully transitioning SUD patients from hospital settings to CBOs. KEY RESULTS: We identified four key barriers to establishing transition partnerships: policy and philosophical differences between organizations, ineffective communication, limited trust, and a lack of connectivity between data systems. We also identified three facilitators to partnership development: strategies focused on building partnership quality, strategic staffing, and organizing partnership processes. CONCLUSIONS: Our findings demonstrate that while multiple barriers to developing hospital-CBO partnerships exist, stakeholders can adopt implementation strategies that mitigate these challenges such as using mediators, cross-hiring, and focusing on mutually beneficial services, even within resource-limited safety-net settings. Policymakers and health system leaders who wish to optimize TOPs in their facilities should focus on adopting implementation strategies to support transition partnerships such as inadequate data collection and sharing systems.

Independent and joint contributions of physical disability and chronic pain to incident opioid use disorder and opioid overdose among Medicaid patients.

BACKGROUND: Chronic pain has been extensively explored as a risk factor for opioid misuse, resulting in increased focus on opioid prescribing practices for individuals with such conditions. Physical disability sometimes co-occurs with chronic pain but may also represent an independent risk factor for opioid misuse. However, previous research has not disentangled whether disability contributes to risk independent of chronic pain. METHODS: Here, we estimate the independent and joint adjusted associations between having a physical disability and co-occurring chronic pain condition at time of Medicaid enrollment on subsequent 18-month risk of incident opioid use disorder (OUD) and non-fatal, unintentional opioid overdose among non-elderly, adult Medicaid beneficiaries (2016-2019). RESULTS: We find robust evidence that having a physical disability approximately doubles the risk of incident OUD or opioid overdose, and physical disability co-occurring with chronic pain increases the risks approximately sixfold as compared to having neither chronic pain nor disability. In absolute numbers, those with neither a physical disability nor chronic pain condition have a 1.8% adjusted risk of incident OUD over 18 months of follow-up, those with physical disability alone have an 2.9% incident risk, those with chronic pain alone have a 3.6% incident risk, and those with co-occurring physical disability and chronic pain have a 11.1% incident risk. CONCLUSIONS: These findings suggest that those with a physical disability should receive increased attention from the medical and healthcare communities to reduce their risk of opioid misuse and attendant negative outcomes.

Genetic and non-genetic predictors of risk for opioid dependence.

BACKGROUND: Elucidation of the interaction of biological and psychosocial/environmental factors on opioid dependence (OD) risk can inform our understanding of the etiology of OD. We examined the role of psychosocial/environmental factors in moderating polygenic risk for opioid use disorder (OUD). METHODS: Data from 1958 European ancestry adults who participated in the Yale-Penn 3 study were analyzed. Polygenic risk scores (PRS) were based on a large-scale multi-trait analysis of genome-wide association studies (MTAG) of OUD. RESULTS: A total of 420 (21.1%) individuals had a lifetime diagnosis of OD. OUD PRS were positively associated with OD (odds ratio [OR] 1.42, 95% confidence interval [CI] 1.21-1.66). Household income and education were the strongest correlates of OD. Among individuals with higher OUD PRS, those with higher education level had lower odds of OD (OR 0.92, 95% CI 0.85-0.98); and those with posttraumatic stress disorder (PTSD) were more likely to have OD relative to those without PTSD (OR 1.56, 95% CI 1.04-2.35). CONCLUSIONS: Results suggest an interplay between genetics and psychosocial environment in contributing to OD risk. While PRS alone do not yet have useful clinical predictive utility, psychosocial factors may help enhance prediction. These findings could inform more targeted clinical and policy interventions to help address this public health crisis.

Implementation of perinatal quality collaborative statewide initiative improves obstetrical opioid use disorder care and outcomes.

BACKGROUND: Maternal deaths resulting from opioid use disorder have been increasing across the United States. Opioid use disorder among pregnant persons is associated with adverse pregnancy outcomes, including preterm birth, along with racial disparities in optimal opioid use disorder care. OBJECTIVE: This study aimed to evaluate whether the Illinois Perinatal Quality Collaborative implementation of the Mothers and Newborns affected by Opioids - Obstetric quality improvement initiative was associated with improvement in opioid use disorder identification, provision of optimal opioid use disorder care for birthing patients, and reduction in racial gaps in optimal opioid use disorder care. STUDY DESIGN: Using a prospective cohort design, hospitals reported monthly key measures for all patients with opioid use disorder at delivery between July 2018 and December 2020. The Illinois Perinatal Quality Collaborative facilitates collaborative learning opportunities, rapid response data, and quality improvement support. Generalized linear mixed-effects regression models were used to evaluate improvement in optimal opioid use disorder care, including increases in linkages to medication-assisted treatment, recovery treatment services, and naloxone counseling across time, and to determine whether optimal opioid use disorder care was associated with positive outcomes, such as lower odds of preterm birth. RESULTS: A total of 91 hospitals submitted data on 2095 pregnant persons with opioid use disorder. For the primary outcomes, the rates of patients receiving medication-assisted treatment and recovery treatment services improved across the initiative from 41% to 78% and 48% to 67%, respectively. For the secondary outcomes, the receipt of recovery treatment services and both recovery treatment services and medication-assisted treatment provided prenatally before delivery admission was associated with lower odds of preterm birth (adjusted odds ratio: 0.67 [95% confidence interval, 0.50-0.91] and 0.49 [95% confidence interval, 0.31-0.75], respectively). During the first quarter of the initiative, Black patients with opioid use disorder were less likely to be linked to medication-assisted treatment than White patients (23% vs 48%, respectively); however, an increase in medication-assisted treatment rates across the initiative occurred for all patients, with the greatest improvement for Black patients with an associated reduction in this disparity gap with >70% of both Black and White patients linked to medication-assisted treatment. CONCLUSION: The Mothers and Newborns affected by Opioids - Obstetric initiative was associated with improvement in optimal opioid use disorder care for pregnant patients across Illinois hospitals, additionally racial disparities in opioid use disorder care was reduced across the initiative. Our findings implicate how optimal opioid use disorder care can improve pregnancy outcomes and close persistent racial gaps for pregnant individuals with opioid use disorder.