Physician's Attitudes Toward Patients With Opioid Use Disorder and Use of Medications for Opioid Use Disorder Vary by Training.

OBJECTIVES: This study compared whether different addiction treatment educational experiences were associated with physicians' attitudes toward patients with opioid use disorder (OUD) and perceived efficacy of medications for opioid use disorder (MOUD). METHODS: Ohio physicians (n = 2757) with and without a waiver to prescribe buprenorphine (Drug Addiction Treatment Act 2000 [DATA 2000] waiver) were surveyed regarding their attitudes toward treating patients with OUD and on the effectiveness of MOUD. We divided physicians into 3 groups: physicians with DATA 2000 waivers, non-waivered physicians with experiential training, and non-waivered physicians without experiential training. We defined experiential training as educational experience directly working with individuals with OUD including those in recovery. Analysis of variance was used to detect statistically significant group differences. RESULTS: We found significant main effect differences in attitudes toward patients with OUD and perceived efficacy of MOUD between groups (P ≤ .01) for all but one attitude. Post hoc comparisons revealed waivered physicians had the most favorable attitudes. Among physicians without a waiver, those with experiential training had significantly more favorable attitudes toward treating OUD and perceived MOUD to be more effective, including items such as "OUD are treatable illnesses" and "medication assisted treatment is a crucial part of treatment for OUD." CONCLUSION: The results suggest that physicians with DATA 2000 waiver and experiential training, as compared to physicians without either a waiver or experiential training in OUD, are associated with less stigmatizing views of treating patients with OUD and prescribing MOUD. While legislation in December 2022 eliminated DATA 2000 waiver training requirement, these findings suggest an ongoing need for training opportunities.

Reconsidering the usefulness of long-term high-dose buprenorphine.

Buprenorphine has been successfully used for decades in the treatment of opioid use disorder, yet there are complexities to its use that warrant attention to maximize its utility. While the package insert of the combination product buprenorphine\naloxone continues to recommend a maximum dose of 16 mg daily for maintenance, the emergence of fentanyl and synthetic analogs in the current drug supply may be limiting the effectiveness of this standard dose. Many practitioners have embraced and appropriately implemented novel practices to mitigate the sequelae of our current crisis. It has become common clinical practice to stabilize patients with 24 - 32 mg of buprenorphine daily at treatment initiation. Many of these patients, however, are maintained on these high doses (>16 mg/d) indefinitely, even after prolonged stability. Although this may be a necessary strategy in the short term, there is little evidence to support its safety and efficacy, and these high doses may be exposing patients to more complications and side effects than standard doses. Commonly known side effects of buprenorphine that are likely dose-related include hyperhidrosis, sedation, decreased libido, constipation, and hypogonadism. There are also complications related to the active metabolite of buprenorphine (norbuprenorphine) which is a full agonist at the mu opioid receptor and does not have a ceiling on respiratory suppression. Such side effects can lead to medical morbidity as well as decreased medication adherence, and we, therefore, recommend that after a period of stabilization, practitioners consider a trial of decreasing the dose of buprenorphine toward standard dose recommendations. Some patients' path of recovery may never reach this stabilization phase (i.e., several months of adherence to medications, opioid abstinence, and other clinical indicators of stability). Side effects of buprenorphine may not have much salience when patients are struggling for survival and safety, but for those who are fortunate enough to advance in their recovery, the side effects become more problematic and can limit quality of life and adherence.

Influence of Age, Gender and Body Mass Index on Intravenous Pharmacokinetics of Buprenorphine in Children Undergoing Orthopedic Surgery.

Background: Buprenorphine (BPN) is a widely used analgesic in the pediatric population, although there are few studies on the pharmacokinetics and pharmacodynamics of this drug. Objective: The objective was to characterize the pharmacokinetics of BPN after intravenous administration and analyze the effect of age, gender, weight, height, body mass index (BMI), and drug-drug interactions as covariates. Methods: Ninety-nine children (2-10 years), who underwent orthopedic surgery under regional, general, or combined anesthesia were included. Patients evaluated according to the American Society of Anesthesiologists Physical Status Classification, who received intravenous BPN 2 µg/kg were enrolled. Blood was collected from 1-240 min. Drug plasma concentrations were determined by LC-MS/MS. Population pharmacokinetic parameters were obtained with Monolix 2021R1 software. Pearson's correlation and/or ANOVA were used for statistical analysis. Results: Age was associated with changes in clearance and central compartment volume and the female gender was associated with lower intercompartmental clearance, while BMI modified clearance, central and peripheral compartment volume. Concomitant administration of BPN with fentanyl and dexamethasone produced decreases in clearance. Conclusions: The covariates of sex, age, and BMI are directly related to the increase or decrease in BPN pharmacokinetic parameters.

Comparative effectiveness of extended-release naltrexone and sublingual buprenorphine for treatment of opioid use disorder among Medicaid patients.

BACKGROUND AND AIMS: Extended-release naltrexone (XR-NTX) and sublingual buprenorphine (SL-BUP) are both approved for opioid use disorder (OUD) treatment in any medical setting. We aimed to compare the real-world effectiveness of XR-NTX and SL-BUP. DESIGN AND SETTING: This was an observational active comparator, new user cohort study of Medicaid claims records for patients in New Jersey and California, USA, 2016-19. PARTICIPANTS/CASES: The participants were adult Medicaid patients aged 18-64 years who initiated XR-NTX or SL-BUP for maintenance treatment of OUD and did not use medications for OUD in the 90 days before initiation. Our cohort included 1755 XR-NTX and 9886 SL-BUP patients. MEASUREMENTS: We examined two outcomes up to 180 days after medication initiation: (1) composite of medication discontinuation and death and (2) composite of overdose and death. FINDINGS: In adjusted analyses, treatment with XR-NTX was more likely to result in discontinuation or death by the end of follow-up than treatment with SL-BUP: cumulative risk 75.9% [95% confidence interval (CI) = 73.9%, 77.9%] versus 62.2% (95% CI = 61.2%, 63.2%), respectively (risk difference = 13.7 percentage points, 95% CI = 11.4, 16.0). There was minimal difference in the cumulative risk of overdose or death by the end of follow-up: XR-NTX 3.9% (95% CI = 3.0%, 4.8%) versus SL-BUP 3.3% (95% CI = 2.9%, 3.7%); risk difference = 0.5 percentage points, 95% CI = -0.4, 1.5. Results were consistent across sensitivity analyses. CONCLUSIONS: Medicaid patients in California and New Jersey, USA, receiving treatment for opioid use disorder stayed in treatment longer on sublingual buprenorphine than on extended-release naltrexone, but the risk of overdose was similar. Most patients in this study discontinued medication within 6 months, regardless of which medication was initiated.

Impact of childhood adversity on acute subjective effects of stimulant and opioid drugs: Evidence from placebo-controlled studies in healthy volunteers.

BACKGROUND AND AIMS: Early-life adversities are known to alter drug reward processing in rodents. Despite the well-known link between early adversity and the risk of substance use disorder, few studies have measured how childhood adversity affects human drug reward. Here, we assessed the relationship between historical childhood adversities and responses to single doses of methamphetamine, d-amphetamine or buprenorphine in healthy participants. METHODS: Using a secondary analysis approach, we assessed the impact of childhood adversity on drug effects from three randomised, placebo-controlled studies in which healthy volunteers received methamphetamine (20 mg oral; n = 35), d-amphetamine (20 mg oral; n = 54) or buprenorphine (0.2 mg sublingual; n = 35). Ratings of feeling effect, liking, disliking, feeling high and wanting more of the drug were collected 15-210 min post-administration, and heart rate changes were analysed using random-intercept mixed-effect models. The area under the curve from these and previous studies was calculated to visualise the relationship between childhood adversity severity and drug effects. RESULTS: Greater childhood adversity was associated with reduced feel effects (significant three-way interactions b = -0.07, 95% CI [-0.12, -0.02], p = 0.009), like effects (b = -0.07, 95% CI [-0.13, -0.00], p = 0.038) and feel high (b = -0.06, 95% CI [-0.10, -0.01], p = 0.020) towards the stimulant drugs 90-180 min post-administration. CONCLUSIONS: Childhood adversity was not significantly associated with other subjective or heart rate responses to the drugs. Overall, participants with more childhood adversities reported dampened subjective responses to stimulant drugs, but not to buprenorphine. Future studies should examine the generalisability of these relationships, to identify the mechanisms underlying the link between childhood adversity and drug responsiveness.

Association Between Length of Buprenorphine or Methadone Use and Nonprescribed Opioid Use Among Individuals with Opioid Use Disorder: A Cohort Study.

BACKGROUND: Opioid use disorder (OUD) affects millions of individuals each year in the United States. Patient retention in medications for opioid use disorder (MOUD) treatment is suboptimal. This study examines and quantifies the associations between each additional month of buprenorphine or methadone use and nonprescribed opioid use. METHODS: Data were obtained from an 18-month longitudinal, observational cohort study of patients (age ≥ 18 years) treated for OUD. Patients completed a baseline self-reported questionnaire between March 2018 and December 2019 and were asked to complete follow-up questionnaires at approximately 3-, 6-, 12-, and 18-months post-baseline until May 2021. Patients treated with buprenorphine or methadone, without taking other MOUD at least 12 months prior to baseline, were included. Outcomes included past 30-day use of prescription opioids nonmedically, heroin, or illegally made fentanyl. A multivariable, multilevel regression model with a binomial distribution and a logit link was used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). RESULTS: This study included 353 patients taking buprenorphine (mean [standard deviation, SD] age 39 [11] years; 226 [64%] female), and 785 patients taking methadone (mean [SD] age 42 [12] years; 392 [50%] female). Each additional month of MOUD treatment was associated with a 25% decrease in the odds of past 30-day nonprescribed opioid use for patients taking buprenorphine (aOR [95% CI] = 0.75 [0.68-0.83]), and a 17% decrease for patients taking methadone (aOR = 0.83 [0.79-0.87]). The COVID-19 pandemic (aOR = 9.29 [2.96-29.17]; aOR = 3.19 [1.74-5.86]) and MOUD adverse reaction experiences (aOR = 3.07 [1.11-8.48]; aOR = 2.51 [1.01-6.22]) were significantly associated with higher odds of nonprescribed opioid use among buprenorphine and methadone groups. CONCLUSION: Among patients treated with buprenorphine or methadone, with each additional treatment month since baseline, those who continued with treatment appeared to be more likely to report 17% to 25% decreased odds of past 30-day nonprescribed opioid use. Our findings can be used by clinicians in the shared decision-making process with patients, emphasizing the value of sustained retention in MOUD.

Successful administration of extended-release buprenorphine in the emergency department.

INTRODUCTION: The ongoing opioid epidemic in the United States has resulted in a substantial increase in overdose deaths and related morbidity and mortality. Given that emergency departments (ED) frequently serve as the initial point of contact for individuals experiencing opioid overdose or seeking treatment for opioid use disorder (OUD), ED clinicians have a pivotal role to play in providing prompt and effective treatment for OUD. While ED clinicians routinely administer sublingual and other transmucosal formulations of buprenorphine, extended-release buprenorphine (BUP-XR) remains underutilized in the ED. CASE REPORT: We present a case involving the successful administration of BUP-XR in the ED to a patient experiencing spontaneous opioid withdrawal. The patient tolerated test dosing of sublingual buprenorphine (BUP-SL) and subsequently received BUP-XR in the ED. Following this intervention, the patient was referred to the hospital-affiliated substance use disorder outpatient clinic, where he has since demonstrated successful follow-up and retention in treatment. CONCLUSION: Our report adds to the existing limited literature on the administration of BUP-XR in the ED and highlights the need for more comprehensive clinician teaching and guidance, as well as the establishment of in-hospital protocols for BUP-XR. Despite these challenges, our case indicates that initiating BUP-XR could be a viable and effective option for ED patients with OUD.

Perioperative Management of Buprenorphine at an Urban Academic Medical Center.

INTRODUCTION: Buprenorphine is a partial mu opioid receptor agonist with high affinity to its receptor, which raises concerns of blocking or displacing full opioid agonists when used during the perioperative period of surgical patients. However, buprenorphine itself has high analgesic potency and discontinuing buprenorphine may lead to suboptimal pain control and risk for opioid use disorder relapse. There is limited data for the continuation of buprenorphine perioperatively. METHODS: This study is a retrospective cohort study of adult surgical patients taking buprenorphine for opioid use disorder at an urban, teaching, level 1 trauma center. Patients were split into two groups based on whether buprenorphine was continued (n = 46) or held (n = 28) within the first 48 h after surgery. RESULTS: Those who had buprenorphine continued in the first 48 h postoperatively required half the dose of nonbuprenorphine opioids compared to those who had buprenorphine held (113.25 versus 255.75 oral morphine equivalents, P = 0.0040). Both groups had a similar level of analgesia and incidence of adverse events. Nearly all patients who continued buprenorphine in the first 48 h postoperatively were discharged on this agent, while only half of patients who had buprenorphine held were restarted on it at discharge (92.68% versus 56.52%, P = 0.0013). CONCLUSIONS: This present study found lower nonbuprenorphine opioid requirements in patients with continued versus held perioperative buprenorphine use with no difference in degree of analgesia.

Comparison of the efficacy and safety of transdermal buprenorphine patch to conventional analgesics after operative fixation of extra capsular fracture of proximal femur.

INTRODUCTION: Proximal femur fractures are common among older individuals and pose challenges in achieving effective post-operative analgesia. Age-related co-morbidities limit the selection of analgesics in this population. This study aimed to compare the safety and effectiveness of transdermal buprenorphine (TDB) patch with traditional analgesics after fixation of an extracapsular fracture of the proximal femur. METHODOLOGY: A prospective randomized controlled study was conducted over a 2-year period, involving 60 patients who underwent surgery for extra capsular intertrochanteric fracture fixation. The patients were randomly assigned to two groups by random envelope method. Group A received an intravenous formulation of paracetamol and tramadol for the initial 48 h, followed by an oral formulation. Group B received a transdermal buprenorphine (TDB) patch delivering 5 mcg/hour immediately after surgery, which continued for 2 weeks postoperatively. During the 14-day monitoring period, patients' pain scores were assessed using the Visual Analog Scale (VAS) at rest and during movement. The primary objective was to maintain a VAS score of 4 or lower. Rescue analgesics were administered if the VAS score reached 6. The secondary objectives included evaluating the quantity of rescue analgesics required and monitoring for any adverse effects or complications. RESULTS: Pain scores at rest and during movement were significantly lower in Group B at all-time points (p-value 0.0006 - ≤ 0.0001), and the requirement for rescue analgesia was also significantly lower in this group. The administration of the TDB patch did not result in any significant adverse effects. CONCLUSION: TDB patch is secure and offers better compliance and analgesia than other analgesics in the postoperative period whilst treating proximal femur extra capsular fracture.

Policies, adaptations, and ongoing challenges to naloxone, buprenorphine and nonprescription syringe access across four-states: Findings from an environmental scan and key informant interviews.

Background: As the US opioid-involved morbidity and mortality increase, uptake and implementation of evidence-based interventions remain key policy responses. Respond to Prevent was a multi-component, randomized trial implemented in four states and two large pharmacy chains with the aim of improving the pharmacy's capacity to provide naloxone, dispense buprenorphine, and sell nonprescription syringes (NPS). We sought to provide context and assess how policies and organizational practices affect communities and pharmacies across the study states. Methods: Using a multi-method approach we: 1) conducted an environmental scan of published literature and online materials spanning January 2015 to June 2021, 2) created timelines of key events pertaining to those policies and practices and 3) conducted semi-structured interviews with stakeholders (key informants) at the state and local levels (N=36) to provide further context for the policies and practices we discovered. Results: Key informants discussed state policies, pharmacy policies and local practices that facilitated access to naloxone, buprenorphine and NPSs. Interviewees from all states spoke about the impact of naloxone standing orders, active partnerships with community-based harm reduction organizations, and some federal and state policies like Medicaid coverage for naloxone and buprenorphine, and buprenorphine telehealth permissions as key facilitators. They also discussed patient stigma, access in rural settings, and high cost of medications as barriers. Conclusion: Findings underscore the important role harm reduction-related policies play in boosting and institutionalizing interventions in communities and pharmacies while also identifying structural barriers where more focused state and local attention is needed.

The methods and baseline characteristics of a multi-site randomized controlled trial evaluating mindfulness-based relapse prevention in conjunction with peer support to improve adherence to medications for opioid use disorders.

Introduction: Medications for opioid use disorders (MOUD) remain the gold standard for treating OUD, but treatment initiation and adherence remain challenging. Exclusive utilization of pharmacotherapy as a treatment modality for OUD is sub-optimal, and a combination of psychotherapies and pharmacotherapies is recommended. General trends indicate the benefits of peer mentoring and MBRP separately. Therefore, we hypothesize that the combined effect of MBRP and Peer mentoring will produce synergistic improvements in MOUD adherence compared to an enhanced twelve-step facilitation (TSF). Methods: This paper describes the methods and baseline characteristics of a multi-site randomized controlled trial evaluating the effectiveness of a combination of MBRP and peer support (MiMP) compared to an enhanced TSF in improving adherence to MOUD. Both MiMP and TSF are 12-week manualized protocols that utilize licensed therapists. The interventions are delivered in weekly group sessions that last about 75-90 minutes per session. The primary outcome is MOUD adherence. Secondary and exploratory outcomes include relapse, cravings, depression, anxiety, stress, quality of life, and pain catastrophizing. Results: The participants' ages ranged from 21 years to 77 years, with a mean age of 44.5 (SD ± 11.5 years). There was an almost equal distribution of gender and place of residence. Overall, 51.9% (n=54) of participants identified as female and 48.1% (n=50) were male. Similarly, 51.9% (n=54) of participants resided in urban areas, while 48.1% (n=50) resided in rural areas. Participants identified as either black or white, with over three-quarters identifying as white (77.9%, n= 81) and 22.1% (n= 23) as black. Most participants randomized to the 12-step facilitation group were white (93.1%). Relationships and employment status were well distributed between categories. Over half of the participants reported some college or higher education. Over 90% of the participants made less than $75,000 per year. Some participants indicated that they had both public and private health insurance. Discussion and conclusion: This study is innovative in several ways including combining MBRP and peer support, addressing comorbid mental health issues among individuals with OUD, utilizing manualized protocols, and evaluating of both physiological and self-reported measures in assessing cortisol reactivity as a predictor of relapse and treatment outcomes.

Self-help groups and opioid use disorder treatment: An investigation using a machine learning-assisted robust causal inference framework.

OBJECTIVES: This study investigates the impact of participation in self-help groups on treatment completion among individuals undergoing medication for opioid use disorder (MOUD) treatment. Given the suboptimal adherence and retention rates for MOUD, this research seeks to examine the association between treatment completion and patient-level factors. Specifically, we evaluated the causal relationship between self-help group participation and treatment completion for patients undergoing MOUD. METHODS: We used the Substance Abuse and Mental Health Services Administration's (SAMHSA) Treatment Episode Data Set: Discharges (TEDS-D) from 2015 to 2019. The data are filtered by the patient's opioid use history, demographics, treatment modality, and other relevant information. In this observational study, machine learning models (Lasso Regression, Decision Trees, Random Forest, and XGBoost) were developed to predict treatment completion. Outcome Adaptive Elastic Net (OAENet) was used to select confounders and outcome predictors, and the robust McNemars test was used to evaluate the causal relationship between self-help group participation and MOUD treatment completion. RESULTS: The machine-learning models showed a strong association between participation in self-help groups and treatment completion. Our causal analysis demonstrated an average treatment effect on treated (ATT) of 0.260 and a p-value < 0.0001 for the robust McNemars test. CONCLUSIONS: Our study demonstrates the importance of participation in self-help groups for MOUD treatment recipients. We found that participation in MOUD along with self-help groups caused higher chances of treatment completion than MOUD alone. This suggests that policymakers should consider further integrating self-help groups into the treatment for OUD to improve the adherence and completion rate.

Dose-specific clinical outcomes in patients with opioid use disorder treated with 24-32 mg/day of buprenorphine.

BACKGROUND/AIMS: In people with opioid use disorder (OUD), buprenorphine is a vital treatment to decrease opioid use and overdose. The US Food and Drug Administration's prescribing information for buprenorphine advises dosing up to 24 mg/day; however, doses of buprenorphine up to 32 mg have been shown to be safe and effective. We compared outcomes associated increased dosing from 24 to 32 mg/day. DESIGN: Prospective cohort investigation. SETTING: Low-barrier buprenorphine clinic in Washington, District of Columbia, USA. PARTICIPANTS: Participants in the ANCHOR study (people with hepatitis C virus (HCV), OUD, and active opioid misuse who were treated for HCV and offered buprenorphine) who received buprenorphine at doses of 24 and/or 32 mg/day. 72 participants were included in the analysis: 24 (33%) patients stabilized on 24 mg, and 48 (67%) patients stabilized on 32 mg. Patients were predominantly male (78%), Black (96%), unstably housed (57%), and used opioids by injection (93%). MEASUREMENTS: Patient-reported drug use, use frequency, triggers for use, and urine drug screens were collected at each visit. For analysis, the cohort was divided into individuals stabilized on 24 mg (24 mg cohort) or 32 mg (32 mg cohort). Drug use outcomes were assessed between cohorts at 24 mg dosing and at respective maximum dosing. Within the 32 mg cohort, outcomes were compared at 24 mg versus 32 mg dosing. FINDINGS: Within the 32 mg cohort, increased dosing from 24 to 32 mg was associated with a decline in opioid use (68.5% [5.2%] at 24 mg vs 59.5% [5.6%] at 32 mg; P = 0.02), frequency of use per week (1.58 [0.19] at 24 mg vs. 1.15 [0.16] at 32 mg; P = 0.0002) and physiologic triggers for use (38.2% [6.0%] at 24 mg vs 7.0% [1.9%] at 32 mg; P < 0.0001). At the end of the study period, there were significantly more patients retained in the 32 mg cohort (78.7%) compared with the 24 mg cohort (50.0%, P = 0.02). CONCLUSION: Higher buprenorphine dosing (32 mg/day) appears to improve outcomes in people with opioid use disorder, even in the absence of abstinence.

Patient experiences with telehealth treatment for opioid use disorder in Alabama.

INTRODUCTION: Telehealth-only provision of buprenorphine for the treatment of opioid use disorder (OUD) was first made possible during the COVID-19 pandemic. However, Alabama instituted a law in July 2022 that mandated an annual in-person visit in order to receive this treatment. In July 2023, our usually telehealth-only group established a temporary clinic in Birmingham to meet this requirement. METHODS: The study administered a survey instrument to patients at the time of clinic check-in. RESULTS: 158 of 160 (98.8 %) patients completed the survey. Mean distance traveled was 86.4 (standard deviation (SD) 53.7) miles; time required for travel was mean 1.6 (SD 1.0) hours. Twenty-five patients (15.8 %) reported needing to find childcare to attend the visit and 40 patients (25.3 %) reported missing work to attend. Patients disagreed (median 2 on 1-5 Likert scale, interquartile range (IQR) <1-3>) that it is important to see their provider in-person, that seeing their provider in-person improves care or improves their ability to succeed in treatment, and that they have other OUD treatment resources in their community. Patients strongly agreed (median 5, IQR <5-5>) that OUD can be treated by telehealth without the need for an in-person visit. CONCLUSIONS: An annual in-person visits requirement to receive telehealth OUD services imposed a significant burden on patients, was not desired by patients, and may be associated with harm.

Fentanyl and xylazine crisis: Crafting coherent strategies for opioid overdose prevention.

The United States is in the throes of a severe opioid overdose epidemic, primarily fueled by the pervasive use of fentanyl and the emerging threat of xylazine, a veterinary sedative often mixed with fentanyl. The high potency and long duration of fentanyl is compounded by the added risks from xylazine, heightening the lethal danger faced by opioid users. Measures such as enhanced surveillance, public awareness campaigns, and the distribution of fentanyl-xylazine test kits, and naloxone have been undertaken to mitigate this crisis. Fentanyl-related overdose deaths persist despite these efforts, partly due to inconsistent policies across states and resistance towards adopting harm reduction strategies. A multifaceted approach is imperative in effectively combating the opioid overdose epidemic. This approach should include expansion of treatment access, broadening the availability of medications for opioid use disorder, implementation of harm reduction strategies, and enaction of legislative reforms and diminishing stigma associated with opioid use disorder.

Association of primary care engagement with initiation and continuation of medication treatment for opioid use disorder among persons with a history of injection drug use.

BACKGROUND: For patients with opioid use disorder (OUD), primary care can serve as a pathway to medication for OUD (MOUD). No community-based studies have examined whether people with OUD engaged in primary care are more likely to a) initiate or b) continue MOUD. METHODS: Data were collected 2014-2020 from two subsamples of the AIDS Linked to the Intravenous Experience (ALIVE) cohort, a community-recruited cohort of people from Baltimore who have injected drugs: 1) people who reported past-six-month illicit opioid use and no MOUD (360 participants, 789 study visits), and 2) people who reported MOUD and no illicit opioid use in the past six months (561 participants, 2027 visits). Logistic regression was used to estimate associations of past six-month self-reported primary care engagement, respectively, with a) initiating MOUD, b) continuing MOUD, and c) cessation from illicit opioid use without initiating MOUD. RESULTS: Among 360 persons not on MOUD treatment (28 % female, 26 % under 50, 59 % actively injecting drugs), primary care engagement was not associated with either cessation from illicit opioid use or initiating MOUD. Similarly, among persons on MOUD (40 % female, 22 % under 50, 6 % actively injecting drugs) primary care engagement was not associated with continued treatment. CONCLUSIONS: Our findings implicate missed opportunities to initiate and maintain buprenorphine treatment in primary care settings.

Comparative evaluation of craving, sleep quality, sexual function and quality of life in opioid use disorder patients in remission with buprenorphine/naloxone maintenance treatment.

AIM: To compare opioid use disorder (OUD) patients who continue to use opioids and are in remission with buprenorphine-naloxone (B/N) in terms of some parameters and to evaluate the relationship between B/N dose and these parameters. METHOD: We included 141 OUD patients in remission with B/N maintenance treatment for at least 6 months, 141 who still used opioids, and 141 healthy volunteers. Substance Craving Scale (SCS), Pittsburgh Sleep Quality Index (PSQI), Arizona Sexual Experiences Scale (ASEX), and Short Form 36 (SF-36) were administered. RESULTS: PSQI scores and ASEX scores were higher in those who continued to use opiates than in OUD in remission, and in OUD in remission compared to controls. OUD patients with current opioid use also had lower SF-36 scores compared to both patients in remission and healthy controls. SCS, PSQI, ASEX, and SF-36 scores were similar when the three groups were examined based on the dosage of B/N (below 8, 8-15, and 16 mg/day and above) use in OUD in remission. CONCLUSIONS: Quality of life, craving, sleep and sexual functions improved significantly with B/N; however, these effects are not dependent on B/N dosage.

Effects of prenatal exposure to methadone or buprenorphine and maternal separation on anxiety-like behavior in rats.

BACKGROUND: The use of medications for opioid use disorder such as methadone or buprenorphine is increasing among pregnant women. However, long-term effects of this treatment on the children's health are not well understood. A key challenge is distinguishing the effects of opioid exposure from other confounding factors associated with human opioid use, such as reduced maternal care. In this study, we therefore used a multi-risk factor design to examine anxiety-like behavior in rats prenatally exposed to methadone or buprenorphine, with or without maternal separation the first two weeks after birth. METHODS: Female Sprague Dawley rats were exposed to methadone (10mg/kg/day), buprenorphine (1mg/kg/day) or sterile water throughout gestation. Half of the offspring in each litter experienced maternal separation for 3h per day from postnatal day 2 to 12. Male and female offspring (6-9 weeks) were tested in the open field, light-dark transition and elevated plus maze tests to assess anxiety-like behavior. RESULTS: Offspring exposed to buprenorphine and not subjected to maternal separation displayed increased anxiety-like behavior in 3 out of 6 outcomes in the light-dark transition and elevated plus maze tests. Maternal separation did not exacerbate, but rather diminished this behavior. Males and females responded differently to methadone, with a trend towards reduced anxiety for males and increased anxiety for females. CONCLUSIONS: Prenatal exposure to methadone or buprenorphine may increase the risk of developing anxiety-like behavior later in life, but the effect depends on specific subgroup characteristics. Further research is required to draw definitive conclusions.

Buprenorphine for acute pain in older adults: a systematic review with meta-analysis.

BACKGROUND: Buprenorphine, a partial opioid agonist, has emerging evidence as an alternative to full agonist opioids for treatment of acute pain. This systematic review aimed to evaluate the safety and efficacy of buprenorphine for acute pain in older adults. METHODS: PubMed Medline, Embase, Cochrane Central Register of Controlled Trials, CINHAL, Web of Science database, and Google Scholar were searched. We included articles that reported buprenorphine as an intervention to treat acute pain among patients 60 years or older. Primary outcome was difference in pain scores for patients treated with buprenorphine compared to other analgesia. Secondary outcomes included adverse events, opioid consumption, and patient satisfaction. Meta-analysis was conducted on difference in pain scores and differences in nausea and vomiting. RESULTS: Twenty-two studies were included (n = 2610). Buprenorphine was administered as nerve blocks in six studies, transdermal in eight, intravenous or intramuscular in five, sublingual in two studies, and both intravenous and sublingual in one study. 10 out of 20 (50%) studies found improved pain control in buprenorphine groups. Meta-analysis found no significant difference in pain scores between buprenorphine and control analgesia at 24 hours (Cohen's d = -0.29 [95% CI -0.85 to 0.27]) and 7 days (Cohen's d = -0.89 [95% CI -2.66-0.88]). Six studies (54.5%) found reduced opioid consumption in patients receiving buprenorphine. There was no difference in adverse effects in most studies. CONCLUSIONS: This review did not find buprenorphine to be superior to alternative analgesia; however the mixed results provide scientific rationale for future studies testing buprenorphine in older populations.

Assessing predictors of adequate individual buprenorphine maintenance dosage for the treatment of opioid use disorder: Listening to the patient.

OBJECTIVE: Dose optimization plays a key role in determining clinical outcomes in patients on opioid agonist treatment (OAT). The objective of this study was to identify the variables independently associated with buprenorphine/naloxone (B/N) dose adequacy in patients with opiate use disorder (OUD). METHOD: Cross-sectional study of a convenience sample of patients with OUD treated with B/N (n = 315) in four regions in Spain. The Opiate Dosage Adequacy Scale (ODAS) was used to determine B/N dose adequacy. The ODAS evaluate the six components of the "dose adequacy" construct, as follows: continued use of heroin; narcotic blockade or crossed tolerance; objective opioid withdrawal symptoms (OWS); subjective OWS; craving for heroin; and overmedication. A binomial logistic regression analysis was performed to identify the variables associated with the condition "ODAS Adequate B/N dose". Participants completed a battery of instruments to assess sociodemographic, substance use, clinical, and treatment variables. RESULTS: The B/N dose was considered adequate in 231 of the 315 participants (73.3 %). Two variables, satisfaction with B/N as a medication (OR=5.764, 95 % CI=2.211-15.030) and patient-perceived participation in B/N dose decisions (OR=1.790, 95 % CI=1221-2623), were independently, significantly, and positively associated with the "ODAS Adequate B/N dose" condition. While the severity of heroin dependence was significantly associated with buprenorphine dose adequacy in the bivariate analyses, significance was lost in the full regression model. CONCLUSION: Satisfaction with B/N as a medication and patient-perceived involvement in the dose decision are associated with clinician-assessed dose adequacy. In the context of good clinical practice, it is important to take into account both of these variables to individualize the prescribed dose through a shared decision-making process.