Examining inequities in access to opioid agonist treatment (OAT) take-home doses (THD): A Canadian OAT guideline synthesis and systematic review.

BACKGROUND: Daily supervised Opioid Agonist Treatment (OAT) medication has been identified as a barrier to treatment retention. Canadian OAT guidelines outline take-home dose (THD) criteria, yet, OAT prescribers use their clinical judgement to decide whether an individual is 'clinically stable' to receive THD. There is limited information regarding whether these decisions may result in inequitable access to THD, including in the context of updated COVID-19 guidance. The current Canadian OAT THD guideline synthesis and systematic review aimed to address this knowledge gap. METHODS: This systematic review included a two-pronged approach. First, we searched available academic literature in Embase, Medline, and PsychINFO up until October 12th, 2022, to identify studies that compared characteristics of individuals on OAT who had and had not been granted access to THD to explore potential inequities in access. Next, we identified all Canadian national and provincial OAT guidelines through a semi-structured grey literature search (conducted between September-October 2022) and extracted all THD 'stability' and allowances/timeline criteria to compare against characteristics identified in the literature search. Data from both review arms were synthesized and narratively presented. RESULTS: A total of n = 56 guidelines and n = 7 academic studies were included. The systematic review identified a number of patient characteristics such as age, sex, race/ethnicity, marital status, housing, employment, neighborhood income, drug use, mental health, health service utilization, as well as treatment duration that were associated with differential access to THD. The Canadian OAT THD guideline synthesis identified many of these same characteristics as 'stability' criteria, underscoring the potential for Canadian OAT guidelines to result in inequitable access to THD. CONCLUSIONS: This two-pronged literature review demonstrated that current guidelines likely contribute to inequitable OAT THD access due primarily to inconsistent 'stability' criteria across guidelines. More research is needed to understand differential OAT THD access with a focus on prescriber decision-making and evaluating associated treatment and safety outcomes. The development of a client-centered, equity-focused, and evidence-informed decision making framework that incorporates more clear definitions of 'stability' criteria and indications for prescriber discretion is warranted.

Association of hospital-based substance use supports on emergency department revisits: a retrospective cohort study in Sudbury, Canada from 2018 to 2022.

BACKGROUND: This study compares emergency department (ED) revisits for patients receiving hospital-based substance-use support compared to those who did not receive specialized addiction services at Health Sciences North in Sudbury, Ontario, Canada. METHODS: The study is a retrospective observational study using administrative data from all patients presenting with substance use disorder (SUD) at Health Sciences North from January 1, 2018, and August 31, 2022 with ICD-10 codes from the Discharge Abstract Database (DAD) and the National Ambulatory Care Database (NACRS). There were two interventions under study: addiction medicine consult services (AMCS group), and specialized addiction medicine unit (AMU group). The AMCS is a consult service offered for patients in the ED and those who are admitted to the hospital. The AMU is a specialized inpatient medical unit designed to offer addiction support to stabilize patients that operates under a harm-reduction philosophy. The primary outcome was all cause ED revisit within 30 days of the index ED or hospital visit. The secondary outcome was all observed ED revisits in the study period. Kaplan-Meier curves were used to measure the proportion of 30-day revisits by exposure group. Odds ratios and Hazard Ratios were calculated using logistic regression models with random effects and Cox-proportional hazard model respectively. RESULTS: A total of 5,367 patients with 10,871 ED index visits, and 2,127 revisits between 2018 and 2022 are included in the study. 45% (2,340/5,367) of patient were not admitted to hospital. 30-day revisits were less likely among the intervention group: Addiction Medicine Consult Services (AMCS) in the ED significantly reduced the odds of revisits (OR 0.53, 95% CI 0.39-0.71, p < 0.01) and first revisits (OR 0.42, 95% CI 0.33-0.53, p < 0.01). The AMU group was associated with lower revisits odds (OR 0.80, 95% CI 0.66-0.98, p = 0.03). For every additional year of age, the odds of revisits slightly decreased (OR 0.99, 95% CI 0.98-1.00, p = 0.01) and males were found to have an increased risk compared to females (OR 1.50, 95% CI 1.35-1.67, p < 0.01). INTERPRETATION: We observe statistically significant differences in ED revisits for patients receiving hospital-based substance-use support at Health Sciences North. Hospital-based substance-use supports could be applied to other hospitals to reduce 30-day revisits.

A genome-wide association, polygenic risk score and sex study on opioid use disorder treatment outcomes.

Opioid use disorder continues to be a health concern with a high rate of opioid related deaths occurring worldwide. Medication Assisted Treatments (MAT) have been shown to reduce opioid withdrawal, cravings and opioid use, however variability exists in individual's treatment outcomes. Sex-specific differences have been reported in opioid use patterns, polysubstance use and health and social functioning. Candidate gene studies investigating methadone dose as an outcome have identified several candidate genes and only five genome-wide associations studies have been conducted for MAT outcomes. This study aimed to identify genetic variants associated with MAT outcomes through genome-wide association study (GWAS) and test the association between genetic variants previously associated with methadone dose through a polygenic risk score (PRS). Study outcomes include: continued opioid use, relapse, methadone dose and opioid overdose. No genome-wide significance SNPs or sex-specific results were identified. The PRS identified statistically significant results (p < 0.05) for the outcome of methadone dose (R2 = 3.45 × 10-3). No other PRS was statistically significant. This study provides evidence for association between a PRS and methadone dose. More research on the PRS to increase the variance explained is needed before it can be used as a tool to help identify a suitable methadone dose within this population.

Genetics of cannabis use in opioid use disorder: A genome-wide association and polygenic risk score study.

BACKGROUND: Individuals with an Opioid Use Disorder (OUD) have increased rates of cannabis use in comparison to the general population. Research on the short- and long-term impacts of cannabis use in OUD patients has been inconclusive. A genetic component may contribute to cannabis cravings. AIMS: Identify genetic variants associated with cannabis use through Genome-wide Association Study (GWAS) methods and investigate a Polygenic Risk Score (PRS). In addition, we aim to identify any sex differences in effect size for genetic variants reaching or nearing genome-wide significance in the GWAS. METHODS: The study outcomes of interest were: regular cannabis use (yes/no) (n = 2616), heaviness of cannabis use (n = 1293) and cannabis cravings (n = 836). Logistic and linear regressions were preformed, respectively, to test the association between genetic variants and each outcome, regular cannabis use and heaviness of cannabis use. GWAS summary statistics from a recent large meta-GWAS investigating cannabis use disorder were used to conduct PRS's. Findings are limited to a European ancestry sample. RESULTS: No genome-wide significant associations were found. Rs1813412 (chromosome 17) for regular cannabis use and rs62378502 (chromosome 5) for heaviness of cannabis use were approaching genome-wide significance. Both these SNPs were nominally significant (p<0.05) within males and females, however sex did not modify the association. The PRS identified statistically significant association with cannabis cravings. The variance explained by all PRSs were less than 1.02x10-2. CONCLUSION: This study provides promising results in understanding the genetic contribution to cannabis use in individuals living with OUD.

Building an inpatient addiction medicine consult service in Sudbury, Canada: preliminary data and lessons learned in the era of COVID-19.

OBJECTIVE: The goal of this study was to (1) Describe the patient population of a newly implemented addiction medicine consult service (AMCS); (2) Evaluate referrals to community-based addiction support services and acute health service use, over time; (3) Provide lessons learned. METHODS: A retrospective observational analysis was conducted at Health Sciences North in Sudbury, Ontario, Canada, with a newly implemented AMCS from November 2018 and July 2021. Data were collected using the hospital's electronic medical records. The outcomes measured included the number of emergency department visits, inpatient admissions, and re-visits over time. An interrupted time-series analysis was performed to measure the effect of AMCS implementation on acute health service use at Health Sciences North. RESULTS: A total of 833 unique patients were assessed through the AMCS. A total of 1,294 referrals were made to community-based addiction support services, with the highest proportion of referrals between August and October 2020. The post-intervention trend for ED visits, ED re-visits, ED length of stay, inpatient visits, re-visits, and inpatient length of stay did not significantly differ from the pre-intervention period. CONCLUSION: Implementation of an AMCS provides a focused service for patients using with substance use disorders. The service resulted in a high referral rate to community-based addiction support services and limited changes in health service usage.

Cannabis use and opioid relapse: An exploratory survival analysis of prospectively collected data.

Importance: It is known that only minority of patients with opioid use disorder (OUD) receive treatment, of which only a fraction successfully complete treatment as intended. Factors associated with poor treatment outcomes remain unclear, and there is emerging but conflicting evidence that cannabis use may mitigate opioid use. Objective: To analyze predictors of relapse amongst patients receiving buprenorphine-naloxone for OUD and identify the association between cannabis use and time to relapse. Design: Data were prospectively collected between May 2018 and October 2020, and patients were followed for 12 months. Setting: Thirty-one outpatient opioid agonist treatment clinics across Ontario, Canada. Participants: All patients 16 years of age or older receiving buprenorphine-naloxone for OUD who had a urine toxicology screen negative for opioids at baseline were eligible for inclusion. Of the 488 patients consecutively sampled, 466 were included. Exposure: Cannabis use. Main outcome and measure: Relapse to opioid use assessed using urine toxicology screens. We employed a multivariable Cox-proportional hazard model for our analyses. Results: We found that cannabis use was not protective against relapse [hazard ratio (HR) = 1.03, 95% confidence interval (CI): 0.78, 1.36, p = 0.84]. We found that participants who have been in treatment for at least two years had a 44% decrease in the hazard of relapse compared to those in treatment for less than a year (HR = 0.56, 95% CI: 0.34, 0.92, p = 0.021). We also found that the hazard of relapse was 2.6 times higher for participants who were intravenous drug users (HR = 2.61, 95% CI: 1.74, 3.91, p < 0.001), and that for every 1mg increase in the participants' buprenorphine-naloxone dose, the hazard of relapse is 2% greater (HR = 1.02, 95% CI: 1.01, 1.03, p < 0.001). Conclusion: Our analysis failed to show cannabis to be protective against relapse to opioid use in patients receiving buprenorphine-naloxone for OUD. We identified that individuals who inject drugs, are on higher doses of buprenorphine-naloxone, or have been in treatment for less than two years have a higher hazard for relapse. The presence of such factors may thus warrant closer patient follow-up and more stringent treatment protocols to mitigate risk of relapse and potential overdose.

Association of prescribed oral stimulants on cocaine use among patients enrolled in opioid agonist treatment: A retrospective longitudinal cohort study.

Objectives: The objective of this study was to measure the association of prescribed oral stimulants with the consumption of cocaine among a population of patients receiving Opioid Agonist Therapy (OAT). Methods: The study was a retrospective clinical cohort study using the medical records of all patients receiving OAT who attended treatment clinics within the Canadian Addiction Treatment Centers (CATC) in Ontario from April 2014 to February 2021. Linear mixed-effects models were fit for the exposure of prescribed oral stimulants, and the outcome of a positive urinalysis drug screen for cocaine. Covariates for age, sex, and a random effect for patients were fitted to account for differences between and within patient observations over time. Results: Among patients receiving OAT therapy n = 314 patients were prescribed oral stimulants and n = 11,879 patients were not prescribed oral stimulants among Ontario CATC clinics (n = 92, n = 145 physicians), the mean age at enrollment for patients receiving oral stimulants was 37.0, SD = 8.8, with 43.6% female patients and for patients not receiving oral stimulants mean age was 36.6, SD = 10.7, with 39.6% female patients. Linear mixed effects models showed no difference in cocaine-positive urine tests over time for fixed effects B = 0.001, however, when considering the Interclass correlation coefficient (ICC) between the fixed effects, we found that time since the prescription of an oral stimulant was associated with a decrease of ICC = -0.14 in cocaine positive urine tests. Increasing age at prescription ICC = -0.92, and being male ICC = -0.23 were associated with decreasing cocaine-positive urine. Conclusion: The use of oral stimulant prescriptions to treat cocaine use had no clinically significant benefit in a real-world setting. Patients who receive prescriptions for oral stimulants consume more cocaine before and after treatment compared to patients without an oral stimulant prescription. We also observed that cocaine use was reduced with increased time since treatment initiation.

Measuring treatment attrition at various stages of engagement in Opioid Agonist Treatment in Ontario Canada using a cascade of care framework.

BACKGROUND: The cascade of care framework is an effective way to measure attrition at various stages of engagement in Opioid Agonist Treatment (OAT). The primary objective of the study was to describe the cascade of care for patients who have accessed OAT from a network of specialized addiction clinics in Ontario, Canada. The secondary objectives were to evaluate correlates associated with retention in OAT at various stages and the impact of patients' location of the residence on retention in OAT. DESIGN: A multi-clinic retrospective cohort study was conducted using electronic medical record (EMR) data from the largest network of OAT clinics in Canada (70 clinics) from 2014 to 2020. Study participants included all patients who received OAT from the network of clinics during the study period. MEASUREMENTS: In this study, four stages of the cascade of care framework were operationalized to identify treatment engagement patterns, including patients retained within 90 days, 90 to 365 days, one to 2 years, and more than 2 years. Correlates associated with OAT retention for 90 days, 90 to 365 days, 1 to 2 years, and more than 2 years were also evaluated and compared across rural and urban areas in northern and southern Ontario. RESULTS: A total of 32,487 patients were included in the study. Compared to patients who were retained in OAT for 90 days, patients who were retained for 90 to 365 days, 1 to 2 years, or more than 2 years were more likely to have a higher number of treatment attempts, a higher number of average monthly urine drug screening and a lower proportion of positive urine drug screening results for other drug use. CONCLUSION: Distinct sociodemographic and clinical factors are likely to influence treatment retention at various stages of engagement along the OAT continuum. Research is required to determine if tailored strategies specific to people at different stages of retention have the potential to improve outcomes of OAT.

A multi-methods and longitudinal study of patients' perceptions in injectable opioid agonist treatment: Implications for advancing patient-centered methodologies in substance use research.

BACKGROUND: Patients' perceptions are vital to the delivery and evaluation of substance use treatment. They are most frequently collected at one time-point and measured using patient satisfaction questionnaires or qualitative methodologies. Interestingly, the findings of these studies often diverge, as satisfaction scores tend to be highly positive, while qualitative findings suggest dissatisfaction and areas for improvement. This divergence limits current understandings of patients' perceptions and their potential change over time in treatment. OBJECTIVE: This study explores the relationship between open-ended positive and negative perceptions of treatment and patient satisfaction scores over time. METHODS: The RUTH (Research on the Utilization of Therapeutic Hydromorphone) prospective cohort study included 131 participants receiving injectable diacetylmorphine or hydromorphone in Canada's first injectable opioid agonist treatment (iOAT) program. The study collected the Client Satisfaction Questionnaire (CSQ-8) at eight time-points over an 18-month period. Following a multi-methods approach, the study complemented the CSQ-8 with open-ended positive and negative comments of iOAT. The research team analyzed these comments thematically at each time-point to develop positive and negative perception themes. We then used growth curve modeling to explore the relationship between positive and negative perception themes and patient satisfaction over time. FINDINGS: Over the eight time-points, six positive and eight negative perception themes emerged, broadly reflecting structural (e.g., expansion of iOAT), process (e.g., schedules), relational (e.g., interactions with providers), and outcome-related (e.g., met/unmet needs) perceptions of iOAT. On average, participants reported high satisfaction (grand mean = 29.2 out of 32), and scores did not significantly change over time. However, we did find significant unexplained variation within participants in their satisfaction trajectories and between participants in their initial satisfaction scores. In conditional growth curve models, the theme "unfavorable interactions with providers" had the strongest independent effect on overall satisfaction trajectories. CONCLUSIONS: This study provides an example of how open-ended comments can be integrated with patient satisfaction questionnaire data to gather a comprehensive and patient-centered evaluation of substance use treatment. Considering the iOAT context specifically, relational dynamics and daily treatment access were significant predictors of patient satisfaction over time and may be attributes of iOAT that require further investigation.

Factors Associated With Increased Opioid Use During the COVID-19 Pandemic: A Prospective Study of Patients Enrolled in Opioid Agonist Treatment.

OBJECTIVES: The opioid use disorder (OUD) crisis in North America has become "an epidemic within a pandemic" in the context of the COVID-19 virus. We aimed to explore the association between the COVID-19 pandemic and changes in opioid use patterns among patients receiving treatment for OUD. METHODS: We used prospectively collected data from 456 patients attending 31 opioid agonist clinics across Ontario, Canada. All included participants underwent routine urine drug screens (UDSs) both before and after the onset of the COVID-19 pandemic. A paired sample t -test was used to compare the proportion of opioid-positive UDSs collected pre- and post-pandemic, and linear regression analysis was used to explore factors associated with this change. RESULTS: Participants had a mean age of 39.9 years (standard deviation = 10.9), 52%were male, and 81%were receivingmethadone treatment. The percentage of opioid-positive UDSs increased significantly during the pandemic, on average by 10.6% (95% confidence interval [CI] 8.17, 12.95, P < 0.001). Continued opioid use before the pandemic was associated with 9.43% increase, on average, in the percentage of opioid-positive UDSs during the pandemic (95% CI 3.79, 15.07). Self-reported past-month cocaine (adjusted betacoefficient 6.83, 95% CI 0.92, 12.73) and amphetamine (adjusted beta-coefficient 13.13, 95% CI 5.15, 21.1) use at study entry were also associated with increases in opioid-positive UDSs. CONCLUSIONS: Increased opioid use is one measure of the negative impact the COVID-19 pandemic has had on individuals with OUD, an already marginalized population. Understanding factors associated with worse outcomes is essential to ensuring that treatment programs appropriately adapt to better serve this population during the pandemic.

Sex-Specific Risk Factors and Health Disparity Among Hepatitis C Positive Patients Receiving Pharmacotherapy for Opioid Use Disorder: Findings From a Propensity Matched Analysis.

BACKGROUND: The incidence of opioid-related fatality has reached unparalleled levels across North America. Patients with comorbid hepatitis C virus (HCV) remain the most vulnerable and difficult to treat. Considering the unique challenges associated with this population, we aimed to re-examine the impact of HCV on response to medication assistant treatment for opioid use disorder and establish sex-specific risk factors affecting care. METHODS: This study employs a multi-center prospective cohort design, with 1-year follow-up. Patients aged ≥18, receiving methadone for opioid use disorder were recruited from a network of outpatient opioid addiction treatment centers across Southern Ontario, Canada. Patients with ≥50% positive opioid urine screens over 1 year of follow-up were classified as poor responders. The prognostic impact of HCV on response was established using a propensity score matched analysis. Sex-specific regression models were constructed to evaluate risk factors for treatment response. RESULTS: Among participants eligible for inclusion (n = 1234), HCV was prevalent in 25% (n = 307). HCV patients exhibited significantly higher rates of high-risk opioid consumption patterns 35.29% (standard deviation 0.478). Sex-specific examination revealed females with HCV incur a 2 times increased risk for high-risk opioid consumption behaviors (female odds ratio: 1.95, 95% confidence interval 1.23, 3.10; P = 0.01). CONCLUSIONS: Findings from this study establish the link between HCV and poor treatment response, with differentially higher risk among female patients. In light of the high potential for overdose among this population, concerted efforts are required for distinguishing the source for sex-based disparities, in addition to establishing trauma and gender informed treatment protocols.

Evidence of Increased Age and Sex Standardized Death Rates Among Individuals Who Accessed Opioid Agonist Treatment Before the Era of Synthetic Opioids in Ontario, Canada.

Objective The objective of this study was to evaluate age-sex standardized death rates (ASDR) from all causes from 2011 to 2015 among people who have accessed opioid agonist treatment (OAT) and compare rates living in the Northern and Southern areas of Ontario. Methods Routinely collected administrative health data was used to calculate crude death rates and age-sex standardized death rates (ASDRs) per 1,000,000 population of individuals who accessed OAT and compared the rates geographically from 2011 to 2015. The weighted ASDRs for each year were calculated by using the mid-year population of these regions. The rate ratios were calculated considering the base year as 2011.  Results A total of 55,924 adults who accessed OAT were included between January 1, 2011, and December 31, 2015. The majority of patients in the cohort - 52.3% - were between 15 and 34 years old, 32.5% were female, 11.3% were in the lowest income group, 71.1% lived in Southern areas. Overall, the ASDR steadily increased during the study period and spiked in 2015. We found that among individuals who had accessed OAT, living in Southern Ontario was associated with a lower risk of all-cause mortality than those living in Northern Ontario. ASDR for Northern Ontario was 20.0 (95% confidence interval (CI)= 10.2-34.2) in 2011, and 103.5(95%CI=78.5-133.5) in 2015, which was a five-fold increase from 2011. Whereas in Southern Ontario, ASDR in 2011 was 13.8 (95% CI= 11.5-16.5), and in 2015 ASDR was 60.8 (95%CI=55.8-66.1), which was only a 4-fold increase from 2011 Conclusion Our findings demonstrate evidence of a steadily increasing ASDR among individuals who accessed OAT with higher rates in Northern areas of the province before the era of synthetic opioids in Ontario, Canada.

Exploring the effectiveness of dextroamphetamine for the treatment of stimulant use disorder: a qualitative study with patients receiving injectable opioid agonist treatment.

BACKGROUND: A high proportion of people receiving both oral and injectable opioid agonist treatment report concurrent use of stimulants (i.e. cocaine and or amphetamines), which has been associated with higher rates of continued illicit opioid use and treatment dropout. A recent randomized controlled trial demonstrated the effectiveness of dextroamphetamine (a prescribed stimulant) at reducing craving for and use of cocaine among patients receiving injectable opioid agonist treatment. Following this evidence, dextroamphetamine has been prescribed to patients with stimulant use disorder at a clinic in Vancouver. This study investigates perceptions of the effectiveness of dextroamphetamine from the perspective of these patients. METHODS: Data were collected using small focus groups and one-on-one interviews with patients who were currently or formerly receiving dextroamphetamine (n = 20). Thematic analysis was conducted using an iterative approach, moving between data collection and analysis to search for patterns in the data across transcripts. This process led to the defining and naming of three central themes responding to the research question. RESULTS: Participants reported a range of stimulant use types, including cocaine (n = 8), methamphetamine (n = 8), or both (n = 4). Three central themes were identified as relating to participants' perceptions of the effectiveness of the medication: 1) achieving a substitution effect (i.e. extent to which dextroamphetamine provided a substitution for the effect they received from use of illicit stimulants); 2) Reaching a preferred dose (i.e. speed of titration and effect of the dose received); and 3) Ease of medication access (i.e. preference for take home doses (i.e. carries) vs. medication integrated into care at the clinic). CONCLUSION: In the context of continued investigation of pharmacological treatments for stimulant use disorder, the present study has highlighted how the study of clinical outcomes could be extended to account for factors that contribute to perceptions of effectiveness from the perspective of patients. In practice, elements of treatment delivery (e.g. dosing and dispensation protocols) can be adjusted to allow for various scenarios (e.g. on site vs. take home dosing) by which dextroamphetamine and other pharmacological stimulants could be implemented to provide "effective" treatment for people with a wide range of treatment goals and needs.

Patient-Reported Goals of Youths in Canada Receiving Medication-Assisted Treatment for Opioid Use Disorder.

Importance: In the literature on opioid use disorder (OUD), opioid abstinence is used as an outcome measure for individuals receiving medication-assisted treatment (MAT), without consideration of patient-reported goals (PRGs). Objectives: To identify common PRGs for youths receiving MAT for OUD and assess whether these patients achieve their stated goals. Design, Setting, and Participants: This prospective cohort study examined data from 152 individuals aged 16 to 25 years (noninclusive) recruited between May 22, 2018, and March 11, 2020, from 45 outpatient MAT clinics in the Pharmacogenetics of Opioid Substitution Treatment Response study. Youths receiving MAT for OUD were included and were followed up for 3 months. Exposures: Medication-assisted treatment for OUD. Main Outcomes and Measures: The frequency of each PRG; the success of goal attainment, compared between those who reported specific PRGs and those who did not; and associations between reporting certain goals and achieving them. Results: Among the 152 youths in the study, 82 were male (53.9%), and the mean (SD) age was 22.8 (1.8) years. Ten overarching goals were identified, with the most common being to taper the dose of or stop MAT (96 [63.2%]), avoid use of recreational substances (71 [46.7%]), manage OUD symptoms (25 [16.4%]), live a normal life (14 [9.2%]), improve mental health (11 [7.2%]), and gain employment (8 [5.3%]). Overall, individuals who reported PRGs had similar odds of achieving them as those who did not for the goals of taper dose of or stop MAT (OR, 1.98; 95% CI, 0.88-4.46; P = .10), avoid recreational substances (OR, 1.34; 95% CI, 0.65-2.74; P = .43), manage OUD symptoms (ß coefficient, -0.93; 95% CI, -4.24 to 2.38; P = .58), and improve mental health (ß coefficient, -0.76; 95% CI, -6.31 to 4.78; P = .79). Furthermore, multivariable logistic regression showed that goals to taper the dose of or stop MAT (odds ratio, 1.90; 95% CI, 0.78-4.63; P = .16) or avoid recreational substances (odds ratio, 1.27; 95% CI, 0.60-2.67; P = .53) were not associated with achieving these respective outcomes. Conclusions and Relevance: This study suggests that youths have highly variable PRGs regarding MAT for OUD and that reporting a goal may not mean one is at higher odds of achieving it. There is a need to develop treatment plans that effectively incorporate PRGs. In addition, the finding that most youths aim to minimize or stop their MAT dose warrants the creation of a tapering protocol to guide clinicians. Because a diagnosis of OUD has substantial psychosocial implications in this population, clinicians must ensure that these dimensions of care are part of routine clinical practice.

Factors associated with opioid overdose during medication-assisted treatment: How can we identify individuals at risk?

BACKGROUND: Due to the loss of tolerance to opioids during medication-assisted treatment (MAT), this period may represent a time of heightened risk for overdose. Identifying factors associated with increased risk of overdose during treatment is therefore paramount to improving outcomes. We aimed to determine the prevalence of opioid overdoses in patients receiving MAT. Additionally, we explored factors associated with opioid overdose during MAT and the association between length of time enrolled in MAT and overdose. METHODS: Data were collected prospectively from 2360 participants receiving outpatient MAT in Ontario, Canada. Participants were divided into three groups by overdose status: no history of overdose, any lifetime history of overdose, and emergency department visit for opioid overdose in the last year. We used a multivariate multinomial regression model to assess demographic and clinical factors associated with overdose status. RESULTS: Twenty-four percent of participants reported a lifetime history of overdose (n = 562), and 8% reported an emergency department (ED) visit for opioid overdose in the last year (n = 179). Individuals with a recent ED visit for opioid overdose were in treatment for shorter duration (odds ratio [OR] 0.92, 95% confidence interval [CI] 0.87, 0.97, p = 0.001). Individuals with a lifetime or recent history of overdose were more likely to be younger in age (OR 0.93, 95% CI 0.89, 0.98, p = 0.007 and OR 0.84, 95% CI 0.77, 0.92, p < 0.001, respectively), report more physical symptoms (OR 1.02, 95% CI 1.01, 1.03, p = 0.005 and OR 1.03, 95% CI 1.01, 1.05, p = 0.005, respectively), and had higher rates of non-prescription benzodiazepine use (OR 1.87, 95% CI 1.32, 2.66, p < 0.001 and OR 2.34, 95% CI 1.43, 3.81, p = 0.001, respectively) compared to individuals with no history of overdose. CONCLUSIONS: A considerable number of patients enrolled in MAT have experienced overdose. Our study highlights that there are identifiable factors associated with a patient's overdose status that may represent areas for intervention. In particular, longer duration in MAT is associated with a decreased risk of overdose.

Cannabis use in patients treated for opioid use disorder pre- and post-recreational cannabis legalization in Canada.

BACKGROUND: As the legalization of recreational cannabis becomes more widespread, its impact on individuals with substance use disorders must be studied. Amidst an ongoing opioid crisis, Canada's legalization of recreational cannabis in October 2018 provides an important setting for investigation. We examined changes to cannabis use patterns in patients receiving medication-assisted treatment (MAT) for opioid use disorder (OUD) following legalization. METHODS: This study includes cross-sectional data from 602 participants recruited 6 months pre-legalization and 788 participants recruited 6 months post-legalization, providing information on cannabis use. Regression analysis was used to estimate the association between legalization and cannabis use patterns. We collected longitudinal urine drug screens (UDSs) detecting cannabis-metabolites for 199 participants recruited pre-legalization and followed prospectively post-legalization. Conditional logistic regression was used to assess the association between legalization and UDS results. RESULTS: Past-month cannabis use was self-reported by 54.8 and 52.3% of participants recruited pre- and post-legalization, respectively. Legalization was not associated with changes in any measured cannabis characteristics: cannabis use (OR 0.91, 95% CI 0.73-1.13), days of use/month (B -0.42, 95% CI - 2.05-1.21), money spent, or cannabis source. There was no association between legalization and prevalence of cannabis use on UDS (OR 1.67, 95% CI 0.93-2.99) or percentage of cannabis-positive UDSs (OR 1.00, 95% CI 0.99-1.01). Participants overwhelmingly reported that legalization would have no impact on their cannabis use (85.7%). CONCLUSIONS: Amongst patients treated for OUD, no significant change in cannabis use was observed following legalization; however, high rates of cannabis use are noted.

The future of precision medicine in opioid use disorder: inclusion of patient-important outcomes in clinical trials

Opioid use has reached an epidemic proportion in Canada and the United States that is mostly attributed to excess availability of prescribed opioids for pain. This excess in opioid use led to an increase in the prevalence of opioid use disorder (OUD) requiring treatment. The most common treatment recommendations include medication-assisted treatment (MAT) combined with psychosocial interventions. Clinical trials investigating the effectiveness of MAT, however, have a limited focus on effectiveness measures that overlook patient-important outcomes. Despite MAT, patients with OUD continue to suffer negative consequences of opioid use. Patient goals and personalized medicine are overlooked in clinical trials and guidelines, thus missing an opportunity to improve prognosis of OUD by considering precision medicine in addiction trials. In this mixed-methods study, patients with OUD receiving MAT (n=2,031, mean age 39.1 years [SD 10.7], 44% female) were interviewed to identify patient goals for MAT. The most frequently reported patient-important outcomes were to stop treatment (39%) and to avoid all drugs (25%). These results are inconsistent with treatment recommendations and trial outcome measures. We discuss theses inconsistencies and make recommendations to incorporate these outcomes to achieve patient-centered and personalized treatment strategies.

A Retrospective Cohort Study Comparing In-Person and Telemedicine-Based Opioid Agonist Treatment in Ontario, Canada, Using Administrative Health Data.

BACKGROUND: This study evaluated how telemedicine as a modality for opioid agonist treatment compares to in-person care. METHODS: We conducted a retrospective cohort study of patients enrolled in opioid agonist treatment between January 1, 2011, and December 31, 2015, in Ontario, Canada. We compared patients who received opioid agonist treatment predominantly in person, mixed, and predominantly by telemedicine. We used a logistic regression model to evaluate mortality, a Cox proportional hazard model to assess retention, and a negative binomial regression model to evaluate emergency department visits and hospitalizations. The study was performed using administrative health data with physician billing data from the Ontario Health Insurance Plan and prescription data from the Ontario Drug Benefit databases. RESULTS: A total of 55,924 individuals were included in the study. Receiving opioid agonist treatment by predominantly telemedicine was not associated with all-cause mortality (OR = 0.9, 95% CI: 0.8-1.0), 1-year treatment retention (OR = 1.0, 95% CI: 0.9-1.1), or opioid-related emergency department visits and hospitalizations when compared to in-person care. The rate of emergency department visits (IRR = 1.4), the rate of mental health-related emergency department visits (IRR = 1.5), and the rate of mental health-related hospitalizations per year (IRR = 1.2) was higher for patients who received opioid agonist treatment predominantly by telemedicine compared to in person. CONCLUSION: Our findings support the conclusion that telemedicine is equal to in-person care regarding mortality opioid-related emergency department visits and retention, and is a viable option for those seeking opioid agonist treatment.

The association between cannabis use and outcome in pharmacological treatment for opioid use disorder.

BACKGROUND: With the ongoing opioid crisis and policy changes regarding legalization of cannabis occurring around the world, it is necessary to consider cannabis use in the context of opioid use disorder (OUD) and its treatment. We aimed to examine (1) past-month cannabis use in patients with OUD, (2) self-reported cannabis-related side effects and craving, and (3) the association between specific characteristics of cannabis use and opioid use during treatment in cannabis users. METHODS: Participants receiving pharmacological treatment for OUD (n = 2315) were recruited from community-based addiction treatment clinics in Ontario, Canada, and provided information on past-month cannabis use (self-report). Participants were followed for 3 months with routine urine drug screens in order to assess opioid use during treatment. We used logistic regression analysis to explore (1) the association between any cannabis use and opioid use during treatment, and (2) amongst cannabis-users, specific cannabis use characteristics associated with opioid use. Qualitative methods were used to examine responses to the question: "What effect does marijuana have on your treatment?". RESULTS: Past-month cannabis use was reported by 51% of participants (n = 1178). Any cannabis use compared to non-use was not associated with opioid use (OR = 1.03, 95% CI 0.87-1.23, p = 0.703). Amongst cannabis users, nearly 70% reported daily use, and half reported experiencing cannabis-related side effects, with the most common side effects being slower thought process (26.2%) and lack of motivation (17.3%). For cannabis users, daily cannabis use was associated with lower odds of opioid use, when compared  with occasional use (OR = 0.61, 95% CI 0.47-0.79, p < 0.001) as was older age of onset of cannabis use (OR = 0.97, 95% CI 0.94, 0.99, p = 0.032), and reporting cannabis-related side effects (OR = 0.67, 95% CI 0.51, 0.85, p = 0.001). Altogether, 75% of cannabis users perceived no impact of cannabis on their OUD treatment. CONCLUSION: Past-month cannabis use was not associated with more or less opioid use during treatment. For patients who use cannabis, we identified specific characteristics of cannabis use associated with differential outcomes. Further examination of characteristics and patterns of cannabis use is warranted and may inform more tailored assessments and treatment recommendations.