Extended-Release 7-Day Injectable Buprenorphine for Patients With Minimal to Mild Opioid Withdrawal.

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.

Scaling Emergency Department Opioid Use Disorder Treatment Across California to Reduce Overdose Deaths, 2019-2023.

Since April 2019, CA Bridge has worked with emergency departments (EDs) in diverse geographic and emergency care settings across California to scale up low-threshold buprenorphine access, patient navigation programs, harm reduction services, and take-home naloxone. Between April 2019 and June 2023, 268 (81.0%) of 331 acute care hospitals in California received funding and technical assistance from CA Bridge and completed data reporting. These hospitals provided navigation services during 279 025 patient encounters and gave patients buprenorphine in 89 549 ED visits. (Am J Public Health. Published online ahead of print June 27, 2024:e1-e5. https://doi.org/10.2105/AJPH.2024.307710).

Emergency Department Access to Buprenorphine for Opioid Use Disorder.

Importance: Although substantial evidence supports buprenorphine for treatment of opioid use disorder (OUD) in controlled trials, prospective study of patient outcomes in clinical implementation of emergency department (ED) buprenorphine treatment is lacking. Objective: To examine the association between buprenorphine treatment in the ED and follow-up engagement in OUD treatment 1 month later. Design, Setting, and Participants: This multisite cohort study was conducted in 7 California EDs participating in a statewide implementation project to improve access to buprenorphine treatment. The study population included ED patients aged at least 18 years identified with OUD between April 1, 2021, and June 30, 2022. Data analysis was performed in October 2023. Exposure: All participants were offered buprenorphine treatment for OUD (either in ED administration, prescription, or both), the uptake of which was examined as the exposure of interest. Main Outcomes and Measures: The primary outcome was engagement in OUD treatment 30 days after the ED visit, determined by patient report or clinical documentation. The association of ED buprenorphine treatment with subsequent OUD treatment engagement was estimated using hierarchical generalized linear models. Results: This analysis included 464 ED patients with OUD. Their median age was 36.0 (IQR, 29.0-38.7) years, and most were men (343 [73.9%]). With regard to race and ethnicity, 64 patients (13.8%) self-identified as non-Hispanic Black, 183 (39.4%) as Hispanic, and 185 as non-Hispanic White (39.9%). Most patients (396 [85.3%]) had Medicaid insurance, and more than half (262 [57.8%]) had unstable housing. Self-reported fentanyl use (242 [52.2%]) and a comorbid mental health condition (328 [71.5%]) were common. Interest in buprenorphine treatment was high: 398 patients (85.8%) received buprenorphine treatment; 269 (58.0%) were administered buprenorphine in the ED and 339 (73.1%) were prescribed buprenorphine. With regard to OUD treatment engagement at 30 days after the ED visit, 198 participants (49.7%) who received ED buprenorphine treatment remained engaged compared with 15 participants (22.7%) who did not receive ED buprenorphine treatment. An association of ED buprenorphine treatment with subsequent OUD treatment engagement at 30 days was observed (adjusted risk ratio, 1.97 [95% CI, 1.27-3.07]). Conclusions and Relevance: The findings of this cohort study suggest that among patients with OUD presenting to EDs implementing low-threshold access to medications for OUD, buprenorphine treatment was associated with a substantially higher likelihood of follow-up treatment engagement 1 month later. Future research should investigate techniques to optimize both the uptake and effectiveness of buprenorphine initiation in low-threshold settings such as the ED.

ASAM Clinical Considerations: Buprenorphine Treatment of Opioid Use Disorder for Individuals Using High-potency Synthetic Opioids.

ABSTRACT: Treatment of opioid use disorder (OUD) with buprenorphine has evolved considerably in the last decade as the scale of the OUD epidemic has increased along with the emergence of high-potency synthetic opioids (HPSOs) and stimulants in the drug supply. These changes have outpaced the development of prospective research, so a clinical consideration document based on expert consensus is needed to address pressing clinical questions. This clinical considerations document is based on a narrative literature review and expert consensus and will specifically address considerations for changes to the clinical practice of treatment of OUD with buprenorphine for individuals using HPSO. An expert panel developed 6 key questions addressing buprenorphine initiation, stabilization, and long-term treatment for individuals with OUD exposed to HPSO in various treatment settings. Broadly, the clinical considerations suggest that individualized strategies for buprenorphine initiation may be needed. The experience of opioid withdrawal negatively impacts the success of buprenorphine treatment, and attention to its management before and during buprenorphine initiation should be proactively addressed. Buprenorphine dose and dosing frequency should be individualized based on patients' treatment needs, the possibility of novel components in the drug supply should be considered during OUD treatment, and all forms of opioid agonist treatment should be offered and considered for patients. Together, these clinical considerations attempt to be responsive to the challenges and opportunities experienced by frontline clinicians using buprenorphine for the treatment of OUD in patients using HPSOs and highlight areas where prospective research is urgently needed.

High-Dose Buprenorphine Initiation in the Emergency Department Among Patients Using Fentanyl and Other Opioids.

This cohort study examines buprenorphine treatment initiation, response, and follow-up among patients presenting to California emergency departments (EDs) who reported fentanyl or other opioid use.

Prehospital Buprenorphine Treatment for Opioid Use Disorder by Paramedics: First Year Results of the EMS Buprenorphine Use Pilot.

BACKGROUND: Prehospital initiation of buprenorphine treatment for Opioid Use Disorder (OUD) by paramedics is an emerging potential intervention to reach patients at greatest risk for opioid-related death. Emergency medical services (EMS) patients who are at high risk for overdose deaths may never engage in treatment as they frequently refuse transport to the hospital after naloxone reversal. The potentially important role of EMS as the initiator for medication for opioid use disorder (MOUD) in the most high-risk patients has not been well described. SETTING: This project relies on four interventions: a public access naloxone distribution program, an electronic trigger and data sharing program, an "Overdose Receiving Center," and a paramedic-initiated buprenorphine treatment. For the final intervention, paramedics followed a protocol-based pilot that had an EMS physician consultation prior to administration. RESULTS: There were 36 patients enrolled in the trial study in the first year who received buprenorphine. Of those patients receiving buprenorphine, only one patient signed out against medical advice on scene. All other patients were transported to an emergency department and their clinical outcome and 7 and 30 day follow ups were determined by the substance use navigator (SUN). Thirty-six of 36 patients had follow up data obtained in the short term and none experienced any precipitated withdrawal or other adverse outcomes. Patients had a 50% (18/36) rate of treatment retention at 7 days and 36% (14/36) were in treatment at 30 days. CONCLUSION: In this small pilot project, paramedic-initiated buprenorphine in the setting of data sharing and linkage with treatment appears to be a safe intervention with a high rate of ongoing outpatient treatment for risk of fatal opioid overdoses.

48-hour Induction of Transdermal Buprenorphine to Sublingual Buprenorphine/Naloxone: The IPPAS Method.

Buprenorphine is an effective medication for the treatment of opioid use disorder. However, the traditional method of buprenorphine induction requires a period of abstinence and the development of at least moderate withdrawal, which can be barriers in starting treatment. We present the case of a hospitalized patient with opioid use disorder using unregulated fentanyl, who underwent a transdermal buprenorphine induction over 48 hours to initiate sublingual buprenorphine/naloxone on the third day. The patient experienced minimal levels of withdrawal and did not experience precipitated withdrawal. The ease of use of this novel induction method over previously published induction protocols can greatly improve the accessibility of buprenorphine for patients and healthcare staff.

Effectiveness of Substance Use Navigation for Emergency Department Patients With Substance Use Disorders: An Implementation Study.

STUDY OBJECTIVE: We implemented a whole person care-informed intervention delivered by substance use navigators (SUN) for emergency department (ED) patients with substance use disorders. METHODS: This was an implementation study of adult patients discharged from 3 public hospital EDs between September 1, 2021 through January 31, 2022 with cocaine, methamphetamine, alcohol, and opioid use-related diagnoses. The primary effectiveness outcome was treatment engagement within 30 days of ED discharge among patients with and without the SUN intervention. We used logistic regression and nearest neighbor propensity score matching without replacement to control for confounding effects. RESULTS: There were 1,328 patients in the cohort, and 119 (9.0%) received the SUN intervention; 50.4% of patients in the SUN intervention group and 15.9% of patients without the SUN intervention were engaged in outpatient treatment within 30 days of ED discharge (difference in proportions: 34.5%, 95% confidence interval [CI] 25.3% to 43.8%). In the unadjusted analysis, the SUN intervention was associated with higher rates of treatment engagement after ED discharge for patients with alcohol, opioid, and cocaine-related diagnoses; patients with methamphetamine-related diagnoses had low engagement rates with or without the SUN intervention. In addition, the SUN intervention was associated with higher odds of treatment engagement in the multivariable model (aOR 3.7, 95% CI 2.4 to 5.8) and in the propensity score-matched analysis (OR 2.1, 95% CI 1.2 to 3.5). CONCLUSION: A whole person care-informed intervention delivered by SUNs for ED patients with substance use disorders was strongly associated with higher engagement rates in addiction treatment after discharge.

A Neuropharmacological Model to Explain Buprenorphine Induction Challenges.

Buprenorphine induction for treating opioid use disorder is being implemented in emergency care. During this era of high-potency synthetic opioid use, novel and divergent algorithms for buprenorphine induction are emerging to optimize induction experience, facilitating continued treatment. Specifically, in patients with chronic fentanyl or other drug exposures, some clinicians are using alternative buprenorphine induction strategies, such as quickly maximizing buprenorphine agonist effects (eg, macrodosing) or, conversely, giving smaller initial doses and slowing the rate of buprenorphine dosing to avoid antagonist/withdrawal effects (eg, microdosing). However, there is a lack of foundational theory and empirical data to guide clinicians in evaluating such novel induction strategies. We present data from clinical studies of buprenorphine induction and propose a neuropharmacologic working model, which posits that acute clinical success of buprenorphine induction (achieving a positive agonist-to-withdrawal balance) is a nonlinear outcome of the opioid balance at the time of initial buprenorphine dose and mu-opioid-receptor affinity, lipophilicity, and mu-opioid-receptor intrinsic efficacy (the "ALE value") of the prior opioid. We discuss the rationale for administering smaller or larger doses of buprenorphine to optimize the patient induction experience during common clinical situations.

Buprenorphine for High-dose Tramadol Dependence: A Case Report of Successful Outpatient Treatment.

INTRODUCTION: During the coronavirus disease 2019 pandemic caused by the severe acute respiratory syndrome coronavirus 2, deaths from opiate drug overdoses reached their highest recorded annual levels in 2020. Medication-assisted treatment for opiate use disorder has demonstrated efficacy in reducing opiate overdoses and all-cause mortality and improving multiple other patient-centered outcomes. Treatment of tramadol dependence in particular poses unique challenges due to its combined action as opioid agonist and serotonin-norepinephrine reuptake inhibitor. Tramadol puts patients with dependence at risk for atypical withdrawal syndromes when attempting to reduce use. Little evidence is available to guide treatment of tramadol dependence. CASE REPORT: We present a case of high-dose tramadol addiction that began with misuse of medically prescribed tramadol for treatment of musculoskeletal back pain. The patient's use reached oral consumption of 5000-6000 milligrams of illicit tramadol daily. She complained of common complications of tramadol use disorder including memory impairment, excessive sedation, and tramadol-induced seizures. The patient was referred to the emergency department in a withdrawal crisis seeking treatment where she was successfully managed with buprenorphine and phenobarbital and then linked to ongoing outpatient treatment. CONCLUSION: Our report adds to the limited guidance currently available on the acute management of tramadol withdrawal and treatment of tramadol use disorder. Our case suggests the initiation of high-dose buprenorphine may be an effective and feasible option for emergency clinicians.

The Social Context of Unhealthy Alcohol Use Among Emergency Department Patients: A Cross Sectional Study.

BACKGROUND: Housing status and additional social determinants of health are important data for clinicians and policy makers to design and implement effective interventions for emergency department (ED) patients with unhealthy alcohol use (UAU). METHODS: We surveyed patients in an urban, safety-net ED from June to August 2018. UAU was assessed by a validated single-item screening question endorsed by the National Institute on Alcohol Abuse and Alcoholism. Housing status was assessed using items validated for housing stability. RESULTS: Seven hundred fifty-eight patients completed the survey (60% response rate), and 296 (39%; 95% confidence interval: 36%-43%) reported UAU. Patients with and without UAU had the same rates of ED visits (median 2, interquartile range: 1-4; P = 0.69) and hospitalizations (median 0, interquartile range: 0-0; P = 0.31) in the 12 months before index visit. Patients with UAU were more likely to lack stable housing compared to patients without UAU (69% vs 59%; P = 0.006). Illicit drug use and prescription drug misuse was more common in patients with UAU compared to those without UAU (29% vs 14%, P < 0.001; and 18% vs 10%; P < 0.001, respectively). Only 60 (20.3%) of the 296 patients with UAU had a documented diagnosis of UAU in the medical record. CONCLUSIONS: UAU is common in the general ED patient population and usually not clinically recognized. Patients with UAU have high rates of homelessness and co-occurring substance use. Future studies should consider strategies to incorporate social determinants of health and harm reduction treatments into ED-based interventions for UAU.

Prehospital Initiation of Buprenorphine Treatment for Opioid Use Disorder by Paramedics.

Prehospital initiation of buprenorphine treatment for Opioid Use Disorder (OUD) by paramedics is an emerging potential intervention. Many patients who may be at high risk for overdose deaths may never engage in treatment because they frequently refuse transport. Recent data have demonstrated a significant increase in both short and long term mortality following an opioid overdose. We describe 3 preliminary cases with a novel intervention of initiating Buprenorphine in the prehospital setting for symptoms of opioid withdrawal, regardless of etiology. In addition, we describe tracking of long term engagement in additional services as part of an integrated approach to combatting the opioid epidemic through EMS focused interventions.

Synergistic Effect of Ketamine and Buprenorphine Observed in the Treatment of Buprenorphine Precipitated Opioid Withdrawal in a Patient With Fentanyl Use.

BACKGROUND: Optimal treatment of buprenorphine precipitated opioid withdrawal (BPOW) is unclear. Full agonist treatment of BPOW is limited by buprenorphine's high-affinity blockade at mu-opioid receptors (µORs). Buprenorphine's partial agonism (low intrinsic efficacy) at µORs can limit the effectiveness of even massive doses once BPOW has begun. Adjunct medications, such as clonidine, are rarely effective in severe BPOW. Ketamine is an N -methyl-D-aspartate receptor antagonist with a potentially ideal pharmacologic profile for treatment of BPOW. Ketamine reduces opioid withdrawal symptoms independently of direct µOR binding, synergistically potentiates the effectiveness of buprenorphine µOR signaling, reverses (resensitizes) fentanyl induced µOR receptor desensitization, and inhibits descending pathways of hyperalgesia and central sensitization. Ketamine's rapid antidepressant effects potentially address depressive symptoms and subjective distress that often accompanies BPOW. Ketamine is inexpensive, safe, and available in emergency departments. To date, neither ketamine as treatment for BPOW nor to support uncomplicated buprenorphine induction has been described. CASE DESCRIPTION: We report a case of an illicit fentanyl-using OUD patient who experienced severe BPOW during an outpatient low-dose cross taper buprenorphine induction (ie, "microdose"). The BPOW was successfully treated in the emergency department with a combination of ketamine (0.6 mg/kg intravenous over 1 hour) combined with high-dose buprenorphine (16 mg sublingual single dose); 3 days later he was administered a month-long dose of extended-release subcutaneous buprenorphine which was repeated monthly (300 mg). At 90 days the patient remained in treatment and reported continuous abstinence from fentanyl use. CONCLUSIONS: This single case observation raises important questions about the potential therapeutic role of ketamine as a treatment for BPOW. BPOW is an important clinical problem for which there is currently only limited guidance and no universally accepted approach. Prospective study comparing the effectiveness of differing pharmacologic approaches to treat BPOW is urgently needed.

Implementation of Oral and Extended-Release Naltrexone for the Treatment of Emergency Department Patients With Moderate to Severe Alcohol Use Disorder: Feasibility and Initial Outcomes.

STUDY OBJECTIVE: Despite evidence supporting naltrexone as an effective treatment for alcohol use disorder, its use in emergency department (ED) patients has not been described. We implemented a protocol that combined substance use navigation with either oral naltrexone or extended-release intramuscular naltrexone for patients with alcohol use disorder as a strategy to improve follow-up in addiction treatment after ED discharge. METHODS: In this descriptive study, we analyzed the results from adult patients discharged from the ED with moderate to severe alcohol use disorder who received either oral naltrexone or extended-release intramuscular naltrexone between May 1, 2020, and October 31, 2020, and assessed their engagement in formal addiction treatment within 30 days after discharge from the ED. RESULTS: Among 59 patients with moderate to severe alcohol use disorder who accepted naltrexone treatment, 41 received oral naltrexone and 18 received extended-release intramuscular naltrexone. The mean (SD) age of the patients was 45.2 (13.4) years; 22 patients (37.3%) were Latinx, 18 (30.5%) were Black, and 16 (27.1%) were White. Among all patients, 9 (15.3%) attended follow-up formal addiction treatment within 30 days after discharge; 5 patients (27.8%) who received extended-release intramuscular naltrexone and 4 patients (9.8%) who received oral naltrexone attended follow-up treatment within 30 days. CONCLUSION: We implemented a clinical protocol for ED patients with moderate to severe alcohol use disorder using oral naltrexone and extended-release intramuscular naltrexone together with substance use navigation. Identification of alcohol use disorder, a brief intervention, and initiation of naltrexone resulted in a 15% follow-up rate in formal addiction treatment. Future work should prospectively examine the effectiveness of naltrexone as well as the effect of substance use navigation for ED patients with alcohol use disorder.

Rapid Adoption of Low-Threshold Buprenorphine Treatment at California Emergency Departments Participating in the CA Bridge Program.

STUDY OBJECTIVE: We retrospectively evaluated the implementation of low-threshold emergency department (ED) buprenorphine treatment at 52 hospitals participating in the CA Bridge Program using the RE-AIM (reach, effectiveness, adoption, implementation, maintenance) framework. METHODS: The CA Bridge model included low-threshold buprenorphine, connection to outpatient care, and harm reduction. Implementation began in March 2019. Participating hospitals reported aggregated clinical data monthly after program initiation. Outcomes included identification of opioid use disorder, buprenorphine administration, and linkage to outpatient addiction treatment. Multivariable models assessed associations between hospital location (rural versus urban) and teaching status (clinical teaching hospital versus community hospital) and outcomes in adopting the CA Bridge Program. RESULTS: Reach: A diverse and geographically distributed group of 52 California hospitals were enrolled in 2 phases (March and August 2019); 12 (23%) were rural and 13 (25%) were teaching hospitals. Effectiveness: Over a 14-month implementation period, 12,009 opioid use disorder patient encounters were identified, including 7,179 (59.7%) where buprenorphine was administered and 4,818 (40.1%) where follow-up visits were attended. Adoption: In multivariable analysis, adoption did not differ significantly between rural and urban or teaching and nonteaching hospitals. IMPLEMENTATION: By program completion, all 52 (100%) hospitals treated opioid use disorder with buprenorphine; 45 (86.5%) administered buprenorphine after naloxone reversal; 41 (84.6%) offered buprenorphine for inpatients; 48 (92.3%) initiated buprenorphine in pregnant women; and 29 (55.8%) offered take-home naloxone. Maintenance: At 8-month follow-up, all 52 sites reported continued buprenorphine treatment. CONCLUSION: Low-threshold ED buprenorphine treatment implemented with a harm reduction approach and active navigation to outpatient addiction treatment was successful in achieving buprenorphine treatment for opioid use disorder in diverse California communities.

High-Dose Buprenorphine Induction in the Emergency Department for Treatment of Opioid Use Disorder.

Importance: Emergency departments (EDs) sporadically use a high-dose buprenorphine induction strategy for the treatment of opioid use disorder (OUD) in response to the increasing potency of the illicit opioid drug supply and commonly encountered delays in access to follow-up care. Objective: To examine the safety and tolerability of high-dose (>12 mg) buprenorphine induction for patients with OUD presenting to an ED. Design, Setting, and Participants: In this case series of ED encounters, data were manually abstracted from electronic health records for all ED patients with OUD treated with buprenorphine at a single, urban, safety-net hospital in Oakland, California, for the calendar year 2018. Data analysis was performed from April 2020 to March 2021. Interventions: ED physicians and advanced practice practitioners were trained on a high-dose sublingual buprenorphine induction protocol, which was then clinically implemented. Main Outcomes and Measures: Vital signs; use of supplemental oxygen; the presence of precipitated withdrawal, sedation, and respiratory depression; adverse events; length of stay; and hospitalization during and 24 hours after the ED visit were reported according to total sublingual buprenorphine dose (range, 2 to >28 mg). Results: Among a total of 391 unique patients (median [interquartile range] age, 36 [29-48] years), representing 579 encounters, 267 (68.3%) were male and 170 were (43.5%) Black. Homelessness (88 patients [22.5%]) and psychiatric disorders (161 patients [41.2%]) were common. A high dose of sublingual buprenorphine (>12 mg) was administered by 54 unique clinicians during 366 (63.2%) encounters, including 138 doses (23.8%) greater than or equal to 28 mg. No cases of respiratory depression or sedation were reported. All 5 (0.8%) cases of precipitated withdrawal had no association with dose; 4 cases occurred after doses of 8 mg of buprenorphine. Three serious adverse events unrelated to buprenorphine were identified. Nausea or vomiting was rare (2%-6% of cases). The median (interquartile range) length of stay was 2.4 (1.6-3.75) hours. Conclusions and Relevance: These findings suggest that high-dose buprenorphine induction, adopted by multiple clinicians in a single-site urban ED, was safe and well tolerated in patients with untreated OUD. Further prospective investigations conducted in multiple sites would enhance these findings.

Voting with their feet: Social factors linked with treatment for opioid use disorder using same-day buprenorphine delivered in California hospitals.

BACKGROUND: Medication for opioid use disorder (MOUD) using buprenorphine in primary or specialty care settings is accessed primarily by persons with private health insurance, stable housing, and no polysubstance use. This paper applies Social Cognitive Theory to frame links between social factors and treatment outcomes among patients with social and economic disadvantages who are seeking MOUD at California Bridge Program (CA Bridge) hospitals. METHODS: Electronic medical records for patients identified with OUD between January-April, 2020 receiving care at CA Bridge hospitals defined outcomes: hospital-administered buprenorphine; provision of buprenorphine prescription at discharge. Multi-level models assessed whether social factors-housing status, insurance type, and co-methamphetamine use-predicted outcomes while accounting for group-level effects of treating hospital and controlling for age, race/ethnicity, and gender. RESULTS: 15 CA Bridge hospitals yielded 845 patient records. Most patients received hospital-administered buprenorphine (58 %) and/or a buprenorphine prescription (55 %); 26 % received neither treatment. Patients with unstable housing had greater odds of hospital-administered buprenorphine compared to patients with stable housing. Patients with Medicaid had greater odds of receiving a buprenorphine prescription compared to patients with other insurance. Co-methamphetamine use was not associated with outcomes. CONCLUSIONS: Patients with OUD are successful in accessing same-day MOUD in CA Bridge hospital settings over a significant period. Importantly, access to MOUD in these settings was facilitated for patients traditionally not treated using buprenorphine, i.e., those with housing instability, Medicaid insurance, and co-methamphetamine use. Findings suggest barriers to MOUD for patients with social and economic disadvantages can be lowered by changing treatment delivery.

The design and conduct of a randomized clinical trial comparing emergency department initiation of sublingual versus a 7-day extended-release injection formulation of buprenorphine for opioid use disorder: Project ED Innovation.

ED-INNOVATION (Emergency Department-INitiated bupreNOrphine VAlidaTION) is a Hybrid Type-1 Implementation-Effectiveness multisite emergency department (ED) study funded through The Helping to End Addiction Long-termSM Initiative, or NIH HEAL InitiativeSM efforts to increase access to medications for opioid use disorder (OUD). We use components of Implementation Facilitation to enhance adoption of ED-initiated buprenorphine (BUP) at approximately 30 sites. Subsequently we compare the effectiveness of two BUP formulations, sublingual (SL-BUP) and 7-day extended-release injectable (CAM2038, XR-BUP) in a randomized clinical trial (RCT) of approximately 2000 patients with OUD on the primary outcome of engagement in formal addiction treatment at 7 days. Secondary outcomes assessed at 7 and 30 days include self-reported opioid use, craving and satisfaction, health service utilization, overdose events, and engagement in formal addiction treatment (30 days) and receipt of medications for OUD (at 7 and 30 days). A sample size of 1000 per group provides 90% power at the 2-sided significance level to detect a difference in the primary outcome of 8% and accommodates a 15% dropout rate. We will compare the cost effectiveness of the two treatments on the primary outcome using the incremental cost-effectiveness ratio. We will also conduct an ancillary study in approximately 75 patients experiencing minimal to no opioid withdrawal who will undergo XR-BUP initiation. If the ancillary study demonstrates safety, we will expand the eligibility criteria for the RCT to include individuals with minimal to no opioid withdrawal. The results of these studies will inform implementation of ED-initiated BUP in diverse EDs which has the potential to improve treatment access.

Sharp decline in hospital and emergency department initiated buprenorphine for opioid use disorder during COVID-19 state of emergency in California.

The California Bridge Program supports expansion of medications for opioid use disorder (MOUD) in emergency departments (EDs) and hospital inpatient units across the state. Here, we describe the change in activity before and after the coronavirus disease 2019 (COVID-19) California statewide shutdown. Of the 70 participating hospitals regionally distributed across California, 52 report MOUD-related activity monthly. We analyzed data on outcomes of OUD care and treatment: identification of OUD, acceptance of referral, receipt of buprenorphine prescription, administration of buprenorphine, and follow-up linkage to outpatient OUD treatment, from May 2019 to April 2020. In estimating the expected number of patients who met each outcome in April 2020, we found decreases in the expected to observed number of patients across all outcomes (all p-values<0.002): 37% (from 1053 to 667) decrease in the number of patients identified with OUD, 34% (from 632 to 420) decrease in the number of patients who accepted a referral, 48% (from 521 to 272) decrease in the number of patients who were prescribed buprenorphine, 53% (from 501 to 234) decrease in the number of patients who were administered buprenorphine, and 33% (from 416 to 277) decrease in the number of patients who attended at least one follow-up visit for addiction treatment. The COVID-19 California statewide shutdown was associated with an abrupt and large decrease in the progress toward expanded access to OUD treatment.