Office-based buprenorphine treatment of opioid use disorder (OUD) does not typically include in-person directly observed therapy (DOT), potentially leading to non-adherence. Video DOT technologies ...may safeguard against this issue and thus enhance likelihood of treatment success. We describe the rationale and protocol for the Trial of Adherence Application for Buprenorphine treatment (TAAB) study, a pilot randomized controlled trial (RCT) to evaluate the effects of video DOT delivered via a smartphone app on office-based buprenorphine treatment outcomes, namely illicit opioid use and retention.
Participants will be recruited from office-based opioid addiction treatment programs in outpatient clinics at two urban medical centers and randomized to either video DOT (intervention) delivered via a HIPAA-compliant, asynchronous, mobile health (mHealth) technology platform, or treatment-as-usual (control). Eligibility criteria are: 18 years or older, prescribed sublingual buprenorphine for a cumulative total of 28 days or less from the office-based opioid treatment program, and able to read and understand English. Patients will be considered ineligible if they are unable or unwilling to use the intervention, provide consent, or complete weekly study visits. All participants will complete 13 in-person weekly visits and be followed via electronic health record data capture at 12- and 24-weeks post-randomization. Data gathered include the following: demographics; current and previous treatment for OUD; self-reported diversion of prescribed buprenorphine; status of their mental and physical health; and self-reported lifetime and past 30-day illicit substance use. Participants provide urine samples at each weekly visit to test for illicit drugs and buprenorphine. The primary outcome is percentage of weekly urines that are negative for opioids over the 12-weeks. The secondary outcome is engagement in treatment at week 12.
Video DOT delivered through mHealth technology platform offers possibility of improving patients' buprenorphine adherence by providing additional structure and accountability. The TAAB study will provide important preliminary estimates of the impact of this mHealth technology for patients initiating buprenorphine, as well as the feasibility of study procedures, thus paving the way for further research to assess feasibility and generate preliminary data for design of a future Phase III trial. Trial Registration ClinicalTrails.gov, NCT03779997, Registered on December 19, 2018.
Little is known about prevalence and treatment of OUD among youth engaged in primary care (PC). Medications are the recommended treatment of opioid use disorder (OUD) for adolescents and young adults ...(youth). This study describes the prevalence of OUD, the prevalence of medication treatment for OUD, and patient characteristics associated with OUD treatment among youth engaged in PC.
This cross-sectional study includes youth aged 16-25 years engaged in PC. Eligible patients had ≥ 1 PC visit during fiscal years (FY) 2014-2016 in one of 6 health systems across 6 states. Data from electronic health records and insurance claims were used to identify OUD diagnoses, office-based OUD medication treatment, and patient demographic and clinical characteristics in the FY of the first PC visit during the study period. Descriptive analyses were conducted in all youth, and stratified by age (16-17, 18-21, 22-25 years).
Among 303,262 eligible youth, 2131 (0.7%) had a documented OUD diagnosis. The prevalence of OUD increased by ascending age groups. About half of youth with OUD had documented depression or anxiety and one third had co-occurring substance use disorders. Receipt of medication for OUD was lowest among youth 16-17 years old (14%) and highest among those aged 22-25 (39%).
In this study of youth engaged in 6 health systems across 6 states, there was low receipt of medication treatment, and high prevalence of other substance use disorders and mental health disorders. These findings indicate an urgent need to increase medication treatment for OUD and to integrate treatment for other substance use and mental health disorders.
Aims
To examine patient and medication characteristics associated with retention and continued illicit opioid use in methadone (MET) versus buprenorphine/naloxone (BUP) treatment for opioid ...dependence.
Design, settings and participants
This secondary analysis included 1267 opioid‐dependent individuals participating in nine opioid treatment programs between 2006 and 2009 and randomized to receive open‐label BUP or MET for 24 weeks.
Measurements
The analyses included measures of patient characteristics at baseline (demographics; use of alcohol, cigarettes and illicit drugs; self‐rated mental and physical health), medication dose and urine drug screens during treatment, and treatment completion and days in treatment during the 24‐week trial.
Findings
The treatment completion rate was 74% for MET versus 46% for BUP (P < 0.01); the rate among MET participants increased to 80% when the maximum MET dose reached or exceeded 60 mg/day. With BUP, the completion rate increased linearly with higher doses, reaching 60% with doses of 30–32 mg/day. Of those remaining in treatment, positive opioid urine results were significantly lower odds ratio (OR) = 0.63, 95% confidence interval (CI) = 0.52–0.76, P < 0.01 among BUP relative to MET participants during the first 9 weeks of treatment. Higher medication dose was related to lower opiate use, more so among BUP patients. A Cox proportional hazards model revealed factors associated with dropout: (i) BUP versus MET, hazard ratio (HR) = 1.61, CI = 1.20–2.15, (ii) lower medication dose (<16 mg for BUP, <60 mg for MET; HR = 3.09, CI = 2.19–4.37), (iii) the interaction of dose and treatment condition (those with higher BUP dose were 1.04 times more likely to drop out than those with lower MET dose, and (iv) being younger, Hispanic and using heroin or other substances during treatment.
Conclusions
Provision of methadone appears to be associated with better retention in treatment for opioid dependence than buprenorphine, as does use of provision of higher doses of both medications. Provision of buprenorphine is associated with lower continued use of illicit opioids.
Two commonly prescribed treatments for opioid addiction are methadone and buprenorphine. Although these drugs show some efficacy in treating opioid dependence, treatment response varies among ...individuals. It is likely that genetic factors have a role in determining treatment outcome. This study analyses the pharmacogenetic association of six polymorphisms in OPRD1, the gene encoding the delta-opioid receptor, on treatment outcome in 582 opioid addicted European Americans randomized to either methadone or buprenorphine/naloxone (Suboxone) over the course of a 24-week open-label clinical trial. Treatment outcome was assessed as the number of missed or opioid-positive urine drug screens over the 24 weeks. In the total sample, no single-nucleotide polymorphisms (SNPs) in OPRD1 were significantly associated with treatment outcome in either treatment arm. However, sex-specific analyses revealed two intronic SNPs (rs581111 and rs529520) that predicted treatment outcome in females treated with buprenorphine. Females with the AA or AG genotypes at rs581111 had significantly worse outcomes than those with the GG genotype when treated with buprenorphine (P=0.03, relative risk (RR)=1.67, 95% confidence interval (CI) 1.06-2.1). For rs529520, females with the AA genotype had a significantly worse outcome than those with the CC genotype when (P=0.006, RR=2.15, 95% CI 1.3-2.29). No significant associations were detected in males. These findings suggest that rs581111 and rs52920 may be useful when considering treatment options for female opioid addicts, however, confirmation in an independent sample is warranted.
Abstract Buprenorphine is an effective long-term opioid agonist treatment. As the only pharmacological treatment for opioid dependence readily available in office-based settings, buprenorphine may ...facilitate a historic shift in addiction treatment from treatment facilities to general medical practices. Although many patients have benefited from the availability of buprenorphine in the United States, almost half of current prescribers are addiction specialists suggesting that buprenorphine treatment has not yet fully penetrated general practice settings. We examined factors affecting willingness to offer buprenorphine treatment among physicians with different levels of prescribing experience. Based on their prescribing practices, physicians were classified as experienced, novice, or as a nonprescriber and asked to assess the extent to which a list of factors impacted their prescription of buprenorphine. Several factors affected willingness to prescribe buprenorphine for all physicians: staff training; access to counseling and alternate treatment; visit time; buprenorphine availability; and pain medications concerns. Compared with other physicians, experienced prescribers were less concerned about induction logistics and access to expert consultation, clinical guidelines, and mental health services. They were more concerned with reimbursement. These data provide important insight into physician concerns about buprenorphine and have implications for practice, education, and policy change that may effectively support widespread adoption of buprenorphine.
To address the US opioid epidemic, there is an urgent clinical need to provide persons with opioid use disorder (OUD) with effective medication treatments for OUD (MOUD). Formulations of sublingual ...buprenorphine/naloxone (SL-BUP/NLX) are considered the standard of care for OUD including within the Veterans Healthcare Administration (VHA). However, poor retention on MOUD undermines its effectiveness. Long-acting injectable monthly buprenorphine (INJ-BUP) (e.g., Sublocade®) has the potential to improve retention and therefore reduce opioid use and overdose. Designing and conducting studies for OUD pose unique challenges. The strategies and solutions to some of these considerations in designing Cooperative Studies Program (CSP) 2014, Buprenorphine for Treating Opioid Use Disorder in Veterans (VA-BRAVE), a randomized, 20-site, clinical effectiveness trial comparing INJ-BUP to SL-BUP/NLX conducted within the VHA may provide valuable guidance for others confronted with similar investigation challenges.
This 52-week, parallel group, open-label, randomized controlled trial (RCT) evaluates the comparative effectiveness of two current FDA-approved formulations of buprenorphine: (1) daily SL-BUP/NLX vs. (2) monthly (28-day) INJ-BUP for Veterans with moderate to severe OUD (n = 952). The primary outcomes are (1) retention in MOUD and (2) opioid abstinence. Secondary outcomes include measures of other drug use, psychiatric symptoms, medical outcomes including prevalence rates of HIV, hepatitis B and C as well as social outcomes (housing instability, criminal justice involvement), service utilization and cost-effectiveness. Special considerations in conducting a comparative effectiveness trial with this population and during COVID-19 pandemic were also included.
The evaluation of the extended-release formulation of buprenorphine compared to the standard sublingual formulation in real-world VHA settings is of paramount importance in addressing the opioid epidemic. The extent to which this new treatment facilitates retention, decreases opioid use, and prevents severe sequelae of OUD has not been studied in any long-term trial to date. Positive findings in this trial could lead to widespread adoption of MOUD, and, if proven superior INJ-BUP, by clinicians throughout the VHA and beyond. This treatment has the potential to reduce opioid use among Veterans, improve medical, psychological, and social outcomes, and save lives at justifiable cost. Trial registration Registered at Clinicaltrials.gov NCT04375033.
•Polysubstance use patterns over the 28-days pre OUD treatment were identified.•Polysubstance use patterns were differentially related to relapse during treatment.•Individuals using cocaine, heroin, ...opioids, and THC had a higher risk of relapse.•High levels of opioid use pre-treatment predicted high risk of relapse.•High levels of heroin use pre-treatment predicted high risk of relapse.
While polysubstance use has consistently been associated with higher rates of relapse, few studies have examined subgroups with specific combinations and time course of polysubstance use (i.e., polysubstance use patterns). This study aimed to classify and compare polysubstance use patterns, and their associations with relapse to regular opioid use in 2637 participants in three large opioid use disorder (OUD) treatment trials.
We explored the daily patterns of self-reported substance use in the 28 days prior to treatment entry. Market basket analysis (MBA) and repeated measure latent class analysis (RMLCA) were used to examine the subgroups of polysubstance use patterns, and multiple logistic regression was used to examine associations between identified classes and relapse.
MBA and RMLCA identified 34 “associations rules” and 6 classes, respectively. Specific combinations of polysubstance use and time course (high baseline use and rapid decrease of use prior to initiation) predicts a worse relapse outcome. MBA showed individuals who co-used cocaine, heroin, prescription opioids, and cannabis had a higher risk for relapse (OR = 2.82, 95%CI = 1.13, 7.03). In RMLCA, higher risk of relapse was observed in individuals who presented with high baseline prescription opioid (OR = 1.9, 95% CI = 1.3, 2.76) or heroin use (OR = 3.54, 95%CI = 1.86, 6.72), although use decreased in both cases prior to treatment initiation.
Our analyses identified subgroups with distinct patterns of polysubstance use. Different patterns of polysubstance use differentially predict relapse outcomes. Interventions tailored to these individuals with specific polysubstance use patterns prior to treatment initiation may increase the effectiveness of relapse prevention.
Isosorbide is a rigid, sugar-derived building block that has shown promise in high-performance materials, albeit with a lack of available controlled polymerization methods. To this end, we provide ...mechanistic insights into the cationic and quasi-zwitterionic ring-opening polymerization (ROP) of an annulated isosorbide derivative (1,4:2,5:3,6-trianhydro-d-mannitol, 5). Ring-opening selectivity of this tricyclic ether was achieved, and the polymerization is selectively directed toward different macromolecular architectures, allowing for formation of either linear or cyclic polymers. Notably, straightforward recycling of unreacted monomer can be accomplished via sublimation. This work provides the first platform for tailored polymer architectures from isosorbide via ROP.
We evaluated the association of mental illnesses with clinical outcomes among US veterans and evaluated the effects of Primary Care-Mental Health Integration (PCMHI).
A total of 4 461 208 veterans ...were seen in the Veterans Health Administration's patient-centered medical homes called Patient Aligned Care Teams (PACT) in 2010 and 2011, of whom 1 147 022 had at least 1 diagnosis of depression, posttraumatic stress disorder (PTSD), substance use disorder (SUD), anxiety disorder, or serious mental illness (SMI; i.e., schizophrenia or bipolar disorder). We estimated 1-year risk of emergency department (ED) visits, hospitalizations, and mortality by mental illness category and by PCMHI involvement.
A quarter of all PACT patients reported 1 or more mental illnesses. Depression, SMI, and SUD were associated with increased risk of hospitalization or death. PTSD was associated with lower odds of ED visits and mortality. Having 1 or more contact with PCMHI was associated with better outcomes.
Mental illnesses are associated with poor outcomes, but integrating mental health treatment in primary care may be associated with lower risk of those outcomes.
PDF
