Collaborating to heal addiction and mental health in primary care (CHAMP): A protocol for a hybrid type 2a trial.

BACKGROUND: The gold-standard treatment for opioid use disorder (OUD) is medication for OUD (MOUD). However, less than a quarter of people with OUD initiate MOUD. Expanding the Collaborative Care Model (CoCM) to include primary care patients with OUD could improve access to and initiation of MOUD. This paper presents the methods and baseline sample characteristics of a Hybrid Type 2a trial comparing the effectiveness of CoCM for OUD and co-occurring mental health symptoms (MHS) to CoCM for MHS only. METHOD: 42 primary care clinics were cluster randomized and 254 primary care patients with OUD and elevated MHS were enrolled. Recruitment was terminated early by the Data and Safety Monitoring Board for futility. Participants completed research assessments at baseline, 3 months, and 6 months. The multiple primary outcomes were past-month number of days of nonmedical opioid use and SF12 Mental Health Component Summary (MCS) scores. RESULTS: MCS scores were over a standard deviation below the national mean (M = 34.5). Nearly half (47.6 %) of participants had previously overdosed in their lifetimes. Three quarters (76.0 %) were already being prescribed MOUD at baseline, only 30.4 % reported non-medical use of opioids, and only 33.9 % reported being bothered by opioid cravings. CONCLUSION: The unexpectedly high proportion of enrollees already prescribed MOUD at baseline indicates that most patients were in the maintenance rather than acute phase of treatment. Challenges identifying and enrolling patients in the acute phase of OUD treatment implies that intervention effectiveness will depend on its success preventing the discontinuation of MOUD rather than initiating MOUD.

Immediate Effects of Mindful Awareness in Body-oriented Therapy as an Adjunct to Medication for Opioid Use Disorder.

Objective: While effective, medication for opioid use disorder (MOUD) treatment outcomes can be limited by co-occurring polysubstance use, mental health and chronic pain conditions. Interoceptive training may facilitate well-being and support medication treatment for MOUD. This study examined the pre-post effects of the mindfulness-based intervention Mindful Awareness in Body-oriented Therapy (MABT) as an adjunct to MOUD. MABT teaches interoceptive awareness skills to promote self-care and emotion regulation. Methods: People stabilized on medication for OUD (N = 303) from 6 community clinics in Northwestern United States were recruited and randomly assigned to MABT plus MOUD or MOUD only. In a mixed-methods study, we used an intent-to-treat approach to examine the proportion of days abstinent from non-prescribed opioids, and other substance use (primary outcomes) at baseline and 3 months post-intervention. Secondary outcomes included symptoms of mental health distress; emotional regulation difficulties; pain and physical symptom indicators; interoceptive awareness and mindfulness skills. Participant experience of MABT was collected through post-intervention surveys. Changes in outcomes were assessed using linear mixed models; content analysis was used to analyze the qualitative data. Results: Levels of overall substance use were low and did not differ between groups. Significant improvements in PTSD symptoms, interoceptive awareness, pain severity, pain activity interference, and physical symptom frequency were found for those who received MABT compared to MOUD only. Conclusion: In this stable MOUD population, substance use outcomes were not improved, however MABT demonstrated significant positive changes across multiple health outcomes critical for improving MOUD treatment. Clinical Trials Registration: NCT04082637 on 9/3/2019.

Trauma exposure across the lifespan among individuals engaged in treatment with medication for opioid use disorder: differences by gender, PTSD status, and chronic pain.

BACKGROUND: There is little study of lifetime trauma exposure among individuals engaged in medication treatment for opioid use disorder (MOUD). A multisite study provided the opportunity to examine the prevalence of lifetime trauma and differences by gender, PTSD status, and chronic pain. METHODS: A cross-sectional study examined baseline data from participants (N = 303) enrolled in a randomized controlled trial of a mind-body intervention as an adjunct to MOUD. All participants were stabilized on MOUD. Measures included the Trauma Life Events Questionnaire (TLEQ), the Brief Pain Inventory (BPI), and the Posttraumatic Stress Disorder Checklist (PCL-5). Analyses involved descriptive statistics, independent sample t-tests, and linear and logistic regression. RESULTS: Participants were self-identified as women (n = 157), men (n = 144), and non-binary (n = 2). Fifty-seven percent (n = 172) self-reported chronic pain, and 41% (n = 124) scored above the screening cut-off for PTSD. Women reported significantly more intimate partner violence (85%) vs 73%) and adult sexual assault (57% vs 13%), while men reported more physical assault (81% vs 61%) and witnessing trauma (66% vs 48%). Men and women experienced substantial childhood physical abuse, witnessed intimate partner violence as children, and reported an equivalent exposure to accidents as adults. The number of traumatic events predicted PTSD symptom severity and PTSD diagnostic status. Participants with chronic pain, compared to those without chronic pain, had significantly more traumatic events in childhood (85% vs 75%). CONCLUSION: The study found a high prevalence of lifetime trauma among people in MOUD. Results highlight the need for comprehensive assessment and mental health services to address trauma among those in MOUD treatment. TRIAL REGISTRATION: NCT04082637.

Mental Health Distress Is Associated With Higher Pain Interference in Patients With Opioid Use Disorder Stabilized on Buprenorphine or Methadone.

BACKGROUND: The relationships between opioid use disorder (OUD), chronic pain, and mental health distress are complex and multidirectional. The objective of this exploratory study was to examine the relationship between mental health conditions and Chronic pain severity and interference among patients stabilized on either buprenorphine or methadone. METHODS: We report baseline data from a randomized trial of a mind-body intervention conducted at 5 outpatient clinics that provided either buprenorphine or methadone treatment. Validated scales were used to measure substance use, mental health distress, and pain severity and interference. Statistical analyses examined the relationship between mental health conditions and pain severity and interference. RESULTS: Of 303 participants, 57% (n = 172) reported Chronic pain. A total of 88% (n = 268) were prescribed buprenorphine. Mental health conditions were common, with one-quarter of the sample screening positive for all 3 mental health conditions (anxiety, depression, and posttraumatic stress disorder [PTSD]). Compared to participants without Chronic pain, participants with Chronic pain were more likely to screen positive for moderate-severe anxiety (47% vs 31%); moderate-severe depression (54% vs 41%); and the combination of anxiety, depression, and PTSD (31% vs 18%). Among participants with Chronic pain, mental health conditions were associated with higher pain interference. Pain severity was higher among participants with mental health conditions, but only reached statistical significance for depression. Pain interference scores increased with a higher number of co-occurring mental health conditions. CONCLUSIONS: Among individuals stabilized on either buprenorphine or methadone, highly symptomatic and comorbid mental health distress is common and is associated with increased pain interference. Adequate screening for, and treatment of, mental health conditions in patients with OUD and Chronic pain is needed.

Nurse Care Management for Opioid Use Disorder Treatment: The PROUD Cluster Randomized Clinical Trial.

Importance: Few primary care (PC) practices treat patients with medications for opioid use disorder (OUD) despite availability of effective treatments. Objective: To assess whether implementation of the Massachusetts model of nurse care management for OUD in PC increases OUD treatment with buprenorphine or extended-release injectable naltrexone and secondarily decreases acute care utilization. Design, Setting, and Participants: The Primary Care Opioid Use Disorders Treatment (PROUD) trial was a mixed-methods, implementation-effectiveness cluster randomized clinical trial conducted in 6 diverse health systems across 5 US states (New York, Florida, Michigan, Texas, and Washington). Two PC clinics in each system were randomized to intervention or usual care (UC) stratified by system (5 systems were notified on February 28, 2018, and 1 system with delayed data use agreement on August 31, 2018). Data were obtained from electronic health records and insurance claims. An implementation monitoring team collected qualitative data. Primary care patients were included if they were 16 to 90 years old and visited a participating clinic from up to 3 years before a system's randomization date through 2 years after. Intervention: The PROUD intervention included 3 components: (1) salary for a full-time OUD nurse care manager; (2) training and technical assistance for nurse care managers; and (3) 3 or more PC clinicians agreeing to prescribe buprenorphine. Main Outcomes and Measures: The primary outcome was a clinic-level measure of patient-years of OUD treatment (buprenorphine or extended-release injectable naltrexone) per 10 000 PC patients during the 2 years postrandomization (follow-up). The secondary outcome, among patients with OUD prerandomization, was a patient-level measure of the number of days of acute care utilization during follow-up. Results: During the baseline period, a total of 130 623 patients were seen in intervention clinics (mean [SD] age, 48.6 [17.7] years; 59.7% female), and 159 459 patients were seen in UC clinics (mean [SD] age, 47.2 [17.5] years; 63.0% female). Intervention clinics provided 8.2 (95% CI, 5.4-∞) more patient-years of OUD treatment per 10 000 PC patients compared with UC clinics (P = .002). Most of the benefit accrued in 2 health systems and in patients new to clinics (5.8 [95% CI, 1.3-∞] more patient-years) or newly treated for OUD postrandomization (8.3 [95% CI, 4.3-∞] more patient-years). Qualitative data indicated that keys to successful implementation included broad commitment to treat OUD in PC from system leaders and PC teams, full financial coverage for OUD treatment, and straightforward pathways for patients to access nurse care managers. Acute care utilization did not differ between intervention and UC clinics (relative rate, 1.16; 95% CI, 0.47-2.92; P = .70). Conclusions and Relevance: The PROUD cluster randomized clinical trial intervention meaningfully increased PC OUD treatment, albeit unevenly across health systems; however, it did not decrease acute care utilization among patients with OUD. Trial Registration: ClinicalTrials.gov Identifier: NCT03407638.

Integrating Opioid Use Disorder Treatment Into Primary Care Settings.

Importance: Medication for opioid use disorder (MOUD) (eg, buprenorphine and naltrexone) can be offered in primary care, but barriers to implementation exist. Objective: To evaluate an implementation intervention over 2 years to explore experiences and perspectives of multidisciplinary primary care (PC) teams initiating or expanding MOUD. Design, Setting, and Participants: This survey-based and ethnographic qualitative study was conducted at 12 geographically and structurally diverse primary care clinics that enrolled in a hybrid effectiveness-implementation study from July 2020 to July 2022 and included PC teams (prescribing clinicians, nonprescribing behavioral health care managers, and consulting psychiatrists). Survey data analysis was conducted from February to April 2022. Exposure: Implementation intervention (external practice facilitation) to integrate OUD treatment alongside existing collaborative care for mental health services. Measures: Data included (1) quantitative surveys of primary care teams that were analyzed descriptively and triangulated with qualitative results and (2) qualitative field notes from ethnographic observation of clinic implementation meetings analyzed using rapid assessment methods. Results: Sixty-two primary care team members completed the survey (41 female individuals [66%]; 1 [2%] American Indian or Alaskan Native, 4 [7%] Asian, 5 [8%] Black or African American, 5 [8%] Hispanic or Latino, 1 [2%] Native Hawaiian or Other Pacific Islander, and 46 [4%] White individuals), of whom 37 (60%) were between age 25 and 44 years. An analysis of implementation meetings (n = 362) and survey data identified 4 themes describing multilevel factors associated with PC team provision of MOUD during implementation, with variation in their experience across clinics. Themes characterized challenges with clinical administrative logistics that limited the capacity to provide rapid access to care and patient engagement as well as clinician confidence to discuss aspects of MOUD care with patients. These challenges were associated with conflicting attitudes among PC teams toward expanding MOUD care. Conclusions and Relevance: The results of this survey and qualitative study of PC team perspectives suggest that PC teams need flexibility in appointment scheduling and the capacity to effectively engage patients with OUD as well as ongoing training to maintain clinician confidence in the face of evolving opioid-related clinical issues. Future work should address structural challenges associated with workload burden and limited schedule flexibility that hinder MOUD expansion in PC settings.

Extended-release Naltrexone Is Not Linked to Hepatotoxicity in Adults Experiencing Homelessness and Alcohol Use Disorder.

OBJECTIVES: The use of extended-release naltrexone (XR-NTX) as treatment for alcohol use disorder (AUD) has been limited by a prior black box warning for hepatotoxicity. We performed a secondary analysis of data from a randomized clinical trial to compare serum liver enzyme levels for those randomized to XR-NTX versus placebo. METHODS: The parent study aimed to test the efficacy of combined pharmacobehavioral harm-reduction treatment in improving alcohol and quality-of-life outcomes for adults experiencing homelessness and AUD. We compared the 2 arms that received intramuscular injections of either 380 mg XR-NTX (n = 74) or placebo (n = 77). Outcomes included ( a ) liver enzyme levels and ( b ) liver enzyme values categorized as normal (<1× upper limit of normal [ULN]), elevated (1-3× ULN), or high (>3× ULN). We performed multinomial logistic regression and negative binomial generalized estimating equations modeling to assess the effects of treatment group and the time × treatment group interaction on liver enzyme outcomes. RESULTS: The mean age was 47.9 ± 9.9 years, and the mean baseline alcohol consumption was 23.2 ± 14.0 drinks per day. There were no significant differences in the development of liver enzyme elevations 1 to 3× ULN or more than 3× ULN (all P s > 0.25) or in the change in liver enzyme values (all P s > 0.41) between the placebo and the XR-NTX groups over the treatment course. CONCLUSIONS: In our study of adults experiencing homelessness and AUD, receipt of XR-NTX was not associated with hepatotoxicity. These findings support the use of XR-NTX to treat AUD even in patients who are drinking heavily and physiologically dependent on alcohol.

Trauma Exposure Across the Lifespan among Individuals Engaged in Treatment with Medication for Opioid Use Disorder: Differences by Gender, PTSD Status, and Chronic Pain.

Background: There is little study of lifetime trauma exposure among individuals engaged in medication treatment for opioid use disorder (MOUD). A multisite study provided the opportunity to examine the prevalence of lifetime trauma and differences by gender, PTSD status, and chronic pain. Methods: A cross-sectional study examined baseline data from participants (N = 303) enrolled in a randomized controlled trial of a mind-body intervention as an adjunct to MOUD. All participants were stabilized on MOUD. Measures included the Trauma Life Events Questionnaire (TLEQ), the Brief Pain Inventory (BPI), and the Posttraumatic Stress Disorder Checklist (PCL-5). Analyses involved descriptive statistics, independent sample t-tests, and linear and logistic regression. Results: Participants were self-identified as women (n = 157), men (n = 144), and non-binary (n = 2). Fifty-seven percent (n = 172) self-reported chronic pain, and 41% (n = 124) scored above the screening cut-off for PTSD. Women reported significantly more intimate partner violence (85%) vs 73%) and adult sexual assault (57% vs 13%), while men reported more physical assault (81% vs 61%) and witnessing trauma (66% vs 48%). Men and women experienced substantial childhood physical abuse, witnessed intimate partner violence as children, and reported an equivalent exposure to accidents as adults. The number of traumatic events predicted PTSD symptom severity and PTSD diagnostic status. Participants with chronic pain, compared to those without chronic pain, had significantly more traumatic events in childhood (85% vs 75%). Conclusions: The study found a high prevalence of lifetime trauma among people in MOUD. Results highlight the need for comprehensive assessment and mental health services to address trauma among those in MOUD treatment. Trial Registration: NCT04082637.

Peer providers and linkage with buprenorphine care after hospitalization: A retrospective cohort study.

Background: People with opioid use disorder (OUD) are increasingly started on buprenorphine in the hospital, yet many patients do not attend outpatient buprenorphine care after discharge. Peer providers, people in recovery themselves, are a growing part of addiction care. We examine whether patients who received a low-intensity, peer-delivered intervention during hospitalization had a greater rate of linking with outpatient buprenorphine care relative to those not seen by a peer. Methods: This was a retrospective cohort study of adults with OUD who were started on buprenorphine during hospitalization. The primary outcome was receipt of a buprenorphine prescription within 30 days of discharge. Secondary outcomes included attendance at a follow-up visit with a buprenorphine provider within 30 days and hospital readmission within 90 days. Modified Poisson regression analyses tested for differences in the rate ratios (RR) of each binary outcome for patients who were versus were not seen by a peer provider. Peer notes in the electronic health record were reviewed to characterize peer activities. Results: 111 patients met the study inclusion criteria, 31.5% of whom saw a peer provider. 55.0% received a buprenorphine prescription within 30 days of hospital discharge. Patients with versus without peer provider encounters did not significantly differ in the rates of receiving a buprenorphine prescription (RR = 1.06, 95% CI: 0.74-1.51), hospital readmission (RR = 1.45, 95% CI: 0.80-2.64), or attendance at a buprenorphine follow-up visit (RR = 1.03, 95% CI: 0.68-1.57). Peers most often listened to or shared experiences with patients (68.6% of encounters) and helped facilitate medical care (60.0% of encounters). Conclusions: There were no differences in multiple measures of buprenorphine follow-up between patients who received this low-intensity peer intervention and those who did not. There is need to investigate what elements of peer provider programs contribute to patient outcomes and what outcomes should be assessed when evaluating peer programs.

Low Dose Buprenorphine Induction With Full Agonist Overlap in Hospitalized Patients With Opioid Use Disorder: A Retrospective Cohort Study.

OBJECTIVE: To describe the outcomes of buprenorphine/naloxone low dose induction with overlap of full opioid agonists among hospitalized patients with opioid use disorder (OUD) as an alternative to standard induction strategies. METHODS: Retrospective cohort study of patients with OUD who were admitted to the hospital over a 1-year period and initiated ono buprenorphine using initial doses of 0.5 mg and gradually increased while the patient remained on full agonists. Descriptive variables included basic demographics, reason for switching to buprenorphine, baseline opioid and morphine equivalent dose. The primary outcome was a successful transition defined by the patient leaving the hospital with a buprenorphine prescription. Bivariate analysis identified factors associated with unsuccessful medication transitions. Secondary outcomes included reported withdrawal symptoms and 30 day follow up to an outpatient buprenorphine program. RESULTS: Sixty two patients underwent low dose with overlap induction during the study period. Fourteen patients were on methadone for OUD before hospital admission. Fifty one patients (82%) successfully left the hospital with a prescription for buprenorphine. Factors associated with lower likelihood of success included older age, transitioning due to discharge placement needs and presence of withdrawal symptoms during the transition. Overall, 66% (N = 23) of patients referred within the same health care system followed up within 30 days. CONCLUSIONS: Low dose inductions with overlap of full opioid agonists were largely successful in transitioning hospitalized patients from full agonist opioids to buprenorphine. However, there were several factors associated with lower likelihood of success. Future work could focus on treatment of withdrawal symptoms and system-level changes ensuring patient-centered medication decisions.

Video directly observed therapy for patients receiving office-based buprenorphine - A pilot randomized controlled trial.

BACKGROUND: We conducted a pilot study to assess feasibility of using video directly-observed therapy (DOT) for patients initiating buprenorphine to evaluate whether it is associated with better opioid use disorder (OUD) outcomes when compared to treatment-as-usual (TAU). METHODS: Pilot randomized controlled trial of adult patients with OUD initiating buprenorphine treatment (n = 78) at two sites (Seattle, WA and Boston, MA) from January 2019 to May 2020. Intervention was video DOT using a HIPAA-compliant smartphone application to record taking daily buprenorphine. Study smartphones, text reminders to upload a video, and calendar summaries of video DOT adherence were provided. Main outcomes were 1) percentage of 12 weekly urine drug tests (UDT) negative for illicit opioids and 2) engagement in treatment at week 12 (i.e., having an active prescription for buprenorphine within the last 7 days). RESULTS: Of 78 enrolled, 20 (26 %) were female; 29 (37 %) non-white; and 31 (40 %) homeless. The mean (standard deviation) percentage of doses confirmed by video was 31 % (34 %). In intention-to-treat analysis, the average percentage of weekly opioid negative UDT was 50 % (95 % CI: 40-63 %) in the intervention arm versus 64 % (95 % CI: 55-74 %) among controls; RR = 0.78 (95 % CI: 0.60-1.02, p = 0.07). Engagement at week 12 was 69 % (95 % CI: 56-86 %) v. 82 % (95 % CI: 71-95 %) in the intervention vs. TAU arms, respectively; RR = 0.84 (95 % CI: 0.65-1.10, p = 0.20). CONCLUSIONS: The video DOT intervention did not result in improvements in illicit opioid use and treatment engagement compared to TAU. The study was limited by low rates of intervention use. TRIAL REGISTRATION: ClinicalTrails.gov, NCT03779997, Registered on December 19, 2018.

Staff Attitudes toward Buprenorphine before and after Implementation of an Office-Based Opioid Treatment Program in an Urban Teaching Clinic.

PURPOSE: Improving access to buprenorphine treatment is necessary to address the national opioid use disorder (OUD) crisis. This study investigates attitudes about buprenorphine prescribing among staff at a primary care clinic and compares attitudes before and after implementation of an office-based opioid treatment (OBOT) program. METHODS: Providers and staff in an academic primary care clinic were surveyed prior to and one year following implementation of an OBOT program. Descriptive statistics, Pearson's Chi-2 tests and logistic regression models were used to compare staff and provider attitudes about use of buprenorphine for OUD and to compare attitudes before and after OBOT implementation. RESULTS: At baseline, 20% of staff indicated strong belief that buprenorphine is an effective treatment for OUD and 16% indicated strong belief that primary care providers should prescribe it. Staff appeared less likely than providers to believe strongly that buprenorphine is effective (OR 0.24, 95% CI= 0.08-.78, p = 0.02; aOR 0.28, 95% CI=.08-1.0, p = 0.05 adjusted for age, race and gender). Following implementation of an OBOT program, the percentage of staff who believed strongly in the effectiveness of buprenorphine for OUD increased from 20% to 40% (p = 0.31), and the percentage who believed that primary care providers (PCPs) should prescribe it increased from 16% to 30% (p = 0.52). CONCLUSIONS: Staff in a primary care clinic were less likely than providers to believe in the effectiveness of buprenorphine treatment or that PCPs should prescribe it for OUD. That their beliefs substantially changed after implementation of an OBOT program suggests that direct experience impacts attitudes.

Perspectives on electronic portal use among patients treated with medications for opioid use disorder in primary care.

OBJECTIVES: Office-based opioid treatment (OBOT) with buprenorphine is increasingly integrated in primary care to treat opioid use disorder (OUD). Online portals seek to engage patients in care of their chronic medical conditions, yet we know little about how patients with OUD experience these portals. Our study explores how patients with OUD perceive the impact of portal use on addiction treatment and clinical care. MATERIALS AND METHODS: We purposively sampled patients with an active portal account enrolled in an OBOT program embedded within primary care, stratifying by recent or distant portal use. The study conducted individual semistructured interviews to understand how patients perceived and interfaced with the portal until the study reached saturation of themes. The research team analyzed the data via thematic analysis and three investigators independently coded the data to identify themes, which all authors then refined. RESULTS: Among 17 participants, 9 were recent users and 8 were distant. Though we stratified analyses by level of portal use, the study observed no differences in resultant themes, thus the study combined themes, which we present here. Portal use was felt to (1) facilitate and reinforce OUD and other substance use treatment goals, (2) improve health care participation, (3) enable monitoring and addressing broader health concerns beyond SUD treatment, and (4) have mixed impacts on patient-provider trust. DISCUSSION: Our findings suggest that patients with OUD identify aspects of the patient portal contributing to their engagement and retention in substance use treatment. Lingering concerns remain about the potential of portal use to negatively impact the patient-provider relationship.

Buprenorphine utilization among all Washington State residents' based upon prescription monitoring program data - Characteristics associated with two measures of retention and patterns of care over time.

BACKGROUND: Opioid use disorder is a serious health condition for which buprenorphine is proven effective, yet providers substantially underutilize buprenorphine. We present two approaches to measuring treatment duration, factors associated with retention, and patterns of care. METHODS: The study determined incident buprenorphine prescribing for all Washingtonians utilizing prescription monitoring program data from 2012 to 2019. The study calculated episode of care and cumulative time in care. Generalized linear models estimated associations among the length of the first episode of care and cumulative time in care with sex, age, and rurality. Cox proportional hazards models estimated the time to discontinuing buprenorphine for the first four episodes of care and time to discontinuing the last episode of care. RESULTS: Mean and median duration of the first episode were 320 and 84 days, respectively, and for cumulative time in care 308 and 195 days. A minority of peoples' first episodes exceeded 180 days (37%). Being female and older were significantly associated with longer first episodes and cumulative time in care. Survival analyses indicated that the proportion of those still in care at 6, 12, and 24 months into their first episode of care declined for those with more than one episode of care; conversely the study found much smaller differences in retention for the last episode of care, indicating that many people were eventually able to be retained in care for longer periods of time. CONCLUSION: Episodes of care and cumulative time on buprenorphine were both short compared to minimum quality recommendations of 180 days. Median cumulative time in care was double that of the first episode, highlighting that many people engage in subsequent episodes of substantial length. Episode of care and cumulative care analyses should inform states, payers, health care systems and providers in measuring and setting treatment duration goals.

Combining behavioral harm-reduction treatment and extended-release naltrexone for people experiencing homelessness and alcohol use disorder in the USA: a randomised clinical trial.

BACKGROUND: The rate of alcohol-related mortality in people experiencing homelessness and alcohol use disorder is high and necessitates accessible and effective treatment for alcohol use disorder. However, typical abstinence-based treatments do not optimally engage this population. Recent studies have shown that harm-reduction treatment, which does not require abstinence, but instead aims to incrementally reduce alcohol-related harm and improve health-related quality of life, is acceptable to and effective for this population. The aim of this study was to test the efficacy of combined pharmacological and behavioural harm-reduction treatment for alcohol use disorder (HaRT-A) in people experiencing homelessness and alcohol use disorder. METHODS: This randomised clinical trial was done at three community-based service sites (low-barrier shelters and housing programmes) in Seattle (WA, USA). Eligible participants were adults (aged 21-65 years) who met the DSM-IV-TR criteria for alcohol use disorder and who experienced homelessness in the past year. Participants were randomly assigned (1:1:1:1) by permuted block randomisation, stratified by site, to receive either HaRT-A plus intramuscular injections of 380 mg extended-release naltrexone (XR-NTX; HaRT-A plus XR-NTX group); HaRT-A plus placebo injection (HaRT-A plus placebo group); HaRT-A alone (HaRT-A alone group); or community-based supportive services as usual (services-as-usual control group). Patients assigned to receive HaRT-A attended sessions at baseline (week 0) and in weeks 1, 4, 8, and 12. XR-NTX and placebo injections were administered in weeks 0, 4, and 8. During the study, participants, interventionists, and investigators were masked to group assignment in the two injection arms. All participants were invited to follow-up assessments at weeks 4, 8, 12, 24, and 36. The primary outcomes were self-reported alcohol use quantity (ie, alcohol quantity consumed on peak drinking occasion, as measured with the Alcohol Quantity Use Assessment questionnaire) and frequency (measured with the Addiction Severity Index), alcohol-related harm (measured with the Short Inventory of Problems-2R questionnaire), and physical and mental health-related quality of life (measured with the Short Form-12 survey). Using piecewise growth modelling and an intention-to-treat model, we compared the effects of the three active treatment groups with the services-as-usual control group, and the HaRT-A plus XR-NTX group with the HaRT-A plus placebo group, over the 12-week treatment course and during the 24 weeks following treatment withdrawal. Safety analyses were done on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, NCT01932801. FINDINGS: Between Oct 14, 2013, and Nov 30, 2017, 417 individuals experiencing homelessness and alcohol use disorder were screened, of whom 308 were eligible and randomly assigned to the HaRT-A plus XR-NTX group (n=74), the HaRT-A plus placebo group (n=78), the HaRT-A alone group (n=79), or the services-as-usual control group (n=77). Compared with the services-as-usual control group, the HaRT-A plus XR-NTX group showed significant improvements from baseline to 12 weeks post-treatment across four of the five primary outcomes: peak alcohol quantity (linear B -0·48 [95% CI -0·79 to -0·18] p=0·010; full model Cohen's d=-0·68), alcohol frequency (linear B -4·42 [-8·09 to -0·76], p=0·047; full model Cohen's d=-0·16), alcohol-related harm (linear B -2·22 [-3·39 to -1·06], p=0·002; full model Cohen's d=-0·56), and physical health-related quality of life (linear B 0·66 [0·23 to 1·10], p=0·012; full model Cohen's d=0·43). Compared with the services-as-usual control group, the HaRT-A plus placebo group showed significant improvements in three of the five primary outcomes: peak alcohol quantity (linear B -0·41 [95% CI -0·67 to -0·15] p=0·010; full model Cohen's d=-0·23), alcohol frequency (linear B -5·95 [-9·72 to -2·19], p=0·009; full model Cohen's d=-0·13), and physical health-related quality of life (linear B 0·53 [0·09 to 0·98], p=0·050; full model Cohen's d=0·35). Compared with the services-as-usual control group, the HaRT-A alone group showed significant improvements in two of the five primary outcomes: alcohol-related harm (linear B -1·58 [95% CI -2·73 to -0·42] p=0·025; full model Cohen's d=-0·40) and physical health-related quality of life (linear B 0·63 [0·18 to 1·07], p=0·020; full model Cohen's d=0·41). After treatment discontinuation at 12 weeks, the active treatment groups plateaued, whereas the services-as-usual group showed improvements. Thus, during the post-treatment period (weeks 12 to 36), the services-as-usual control group showed greater reductions in alcohol-related harm compared with both the HaRT-A plus XR-NTX group (linear B 0·96 [0·24 to 1·67], p=0·028; full model Cohen's d=0·24) and the HaRT-A alone group (linear B 1·02 [0·35 to 1·70], p=0·013; full model Cohen's d=0·26). During the post-treatment period, the services-as-usual control group significantly improved on mental health-related quality of life compared with the HaRT-A alone group (linear B -0·46 [-0·79 to -0·12], p=0·024; full model Cohen's d=-0·28), and on physical health-related quality of life compared with the HaRT-A plus XR-NTX group (linear B -0·42 [-0·67 to -0·17], p=0·006; full model Cohen's d=-0·27), the HaRT-A plus placebo group (linear B -0·42 [-0·69 to -0·15], p=0·009; full model Cohen's d=-0·27), and the HaRT-A alone group (linear B -0·47 [-0·72 to -0·22], p=0·002; full model Cohen's d=-0·31). For all other primary outcomes, there were no significant linear differences between the services-as-usual and active treatment groups. When comparing the HaRT-A plus placebo group with the HaRT-A plus XR-NTX group, there were no significant differences for any of the primary outcomes. Missing data analysis indicated that participants were more likely to drop out in the services-as-usual control group than in the active treatment groups; however, primary outcome findings were found to be robust to attrition. Participants in the HaRT-A plus XR-NTX, HaRT-A plus placebo, and HaRT-A alone groups were not more likely to experience adverse events than those in the services-as-usual control group. INTERPRETATION: Compared with existing services, combined pharmacological and behavioural harm-reduction treatment resulted in decreased alcohol use and alcohol-related harm and improved physical health-related quality of life during the 12-week treatment period for people experiencing homelessness and alcohol use disorder. Although not as consistent, there were also positive findings for behavioural harm-reduction treatment alone. Considering the non-significant differences between participants receiving HaRT-A plus placebo and HaRT-A plus XR-NTX, the combined pharmacological and behavioural treatment effect cannot be attributed to XR-NTX alone. Future studies are needed to further investigate the relative contributions of the pharmacological and behavioural components of harm-reduction treatment for alcohol use disorder, and to ascertain whether a maintenance treatment approach could extend these positive outcome trajectories. FUNDING: National Institute on Alcohol Abuse and Alcoholism.

Prevalence and Medication Treatment of Opioid Use Disorder Among Primary Care Patients with Hepatitis C and HIV.

BACKGROUND: Hepatitis C and HIV are associated with opioid use disorders (OUD) and injection drug use. Medications for OUD can prevent the spread of HCV and HIV. OBJECTIVE: To describe the prevalence of documented OUD, as well as receipt of office-based medication treatment, among primary care patients with HCV or HIV. DESIGN: Retrospective observational cohort study using electronic health record and insurance data. PARTICIPANTS: Adults ≥ 18 years with ≥ 2 visits to primary care during the study (2014-2016) at 6 healthcare systems across five states (CO, CA, OR, WA, and MN). MAIN MEASURES: The primary outcome was the diagnosis of OUD; the secondary outcome was OUD treatment with buprenorphine or oral/injectable naltrexone. Prevalence of OUD and OUD treatment was calculated across four groups: HCV only; HIV only; HCV and HIV; and neither HCV nor HIV. In addition, adjusted odds ratios (AOR) of OUD treatment associated with HCV and HIV (separately) were estimated, adjusting for age, gender, race/ethnicity, and site. KEY RESULTS: The sample included 1,368,604 persons, of whom 10,042 had HCV, 5821 HIV, and 422 both. The prevalence of diagnosed OUD varied across groups: 11.9% (95% CI: 11.3%, 12.5%) for those with HCV; 1.6% (1.3%, 2.0%) for those with HIV; 8.8% (6.2%, 11.9%) for those with both; and 0.92% (0.91%, 0.94%) among those with neither. Among those with diagnosed OUD, the prevalence of OUD medication treatment was 20.9%, 16.0%, 10.8%, and 22.3%, for those with HCV, HIV, both, and neither, respectively. HCV was not associated with OUD treatment (AOR = 1.03; 0.88, 1.21), whereas patients with HIV had a lower probability of OUD treatment (AOR = 0.43; 0.26, 0.72). CONCLUSIONS: Among patients receiving primary care, those diagnosed with HCV and HIV were more likely to have documented OUD than those without. Patients with HIV were less likely to have documented medication treatment for OUD.

PRimary Care Opioid Use Disorders treatment (PROUD) trial protocol: a pragmatic, cluster-randomized implementation trial in primary care for opioid use disorder treatment.

BACKGROUND: Most people with opioid use disorder (OUD) never receive treatment. Medication treatment of OUD in primary care is recommended as an approach to increase access to care. The PRimary Care Opioid Use Disorders treatment (PROUD) trial tests whether implementation of a collaborative care model (Massachusetts Model) using a nurse care manager (NCM) to support medication treatment of OUD in primary care increases OUD treatment and improves outcomes. Specifically, it tests whether implementation of collaborative care, compared to usual primary care, increases the number of days of medication for OUD (implementation objective) and reduces acute health care utilization (effectiveness objective). The protocol for the PROUD trial is presented here. METHODS: PROUD is a hybrid type III cluster-randomized implementation trial in six health care systems. The intervention consists of three implementation strategies: salary for a full-time NCM, training and technical assistance for the NCM, and requiring that three primary care providers have DEA waivers to prescribe buprenorphine. Within each health system, two primary care clinics are randomized: one to the intervention and one to Usual Primary Care. The sample includes all patients age 16-90 who visited the randomized primary care clinics from 3 years before to 2 years after randomization (anticipated to be > 170,000). Quantitative data are derived from existing health system administrative data, electronic medical records, and/or health insurance claims ("electronic health records," [EHRs]). Anonymous staff surveys, stakeholder debriefs, and observations from site visits, trainings and technical assistance provide qualitative data to assess barriers and facilitators to implementation. The outcome for the implementation objective (primary outcome) is a clinic-level measure of the number of patient days of medication treatment of OUD over the 2 years post-randomization. The patient-level outcome for the effectiveness objective (secondary outcome) is days of acute care utilization [e.g. urgent care, emergency department (ED) and/or hospitalizations] over 2 years post-randomization among patients with documented OUD prior to randomization. DISCUSSION: The PROUD trial provides information for clinical leaders and policy makers regarding potential benefits for patients and health systems of a collaborative care model for management of OUD in primary care, tested in real-world diverse primary care settings. Trial registration # NCT03407638 (February 28, 2018); CTN-0074 https://clinicaltrials.gov/ct2/show/NCT03407638?term=CTN-0074&draw=2&rank=1.