Impact of baseline methamphetamine/amphetamine use on discontinuation of methadone and buprenorphine/naloxone among people with prescription-type opioid use disorder in Canada.

BACKGROUND AND OBJECTIVES: Although concurrent stimulant use is common among people with opioid use disorder (OUD), there is little evidence on its impacts on opioid agonist therapy (OAT) outcomes. This study sought to determine the impact of baseline methamphetamine/amphetamine use on discontinuation of OAT among individuals with prescription-type OUD (POUD) initiating methadone or buprenorphine/naloxone as part of a pragmatic randomized trial in Canada. METHODS: Secondary analysis of a pan-Canadian pragmatic trial conducted between 2017 and 2020 comparing supervised methadone versus flexible take-home dosing buprenorphine/naloxone models of care. Cox proportional hazard models were used to evaluate the effect of baseline methamphetamine/amphetamine use (measured by urine drug test [UDT]) on two discontinuation outcomes (i.e., assigned OAT discontinuation, any OAT discontinuation). RESULTS: Two hundred nine (n = 209) participants initiated OAT, of which 96 (45.9%) had positive baseline methamphetamine/amphetamine UDT. Baseline methamphetamine/amphetamine use was associated with shorter median times in assigned OAT (21 vs. 168 days, hazard ratio [aHR] = 2.45, 95% confidence interval [CI] = 1.60-3.76) and any OAT (25 days vs. 168 days, aHR = 2.06, CI = 1.32-3.24). No interaction between methamphetamine/amphetamine and assigned OAT was observed for either outcome (p > .05). CONCLUSION AND SCIENTIFIC SIGNIFICANCE: This study offers novel insights on the impact of methamphetamine/amphetamine use on OAT outcomes among people with POUD. Methamphetamine/amphetamine use was common and was associated with increased risk of OAT discontinuation. Supplementary interventions, including treatment for stimulant use, are needed to improve retention in OAT and optimize treatment outcomes in this population.

Characterising methamphetamine/amphetamine use among opioid agonist therapy-seeking adults with prescription-type opioid use disorder in Canada.

INTRODUCTION: There has been a significant increase in methamphetamine/amphetamine use in North America, particularly among people who use opioids. Despite its association with several negative health consequences, the population of people who use methamphetamine/amphetamine with opioids is not well characterised. The aim of this study was to investigate correlates of methamphetamine/amphetamine use among adults with prescription-type opioid use disorder (POUD) starting methadone or buprenorphine/naloxone as part of a pragmatic randomised treatment trial in Canada. METHODS: Multivariable logistic regression analyses were used to determine factors associated with baseline methamphetamine/amphetamine use (measured by urine drug test [UDT]) among participants of a pan-Canadian pragmatic trial conducted between 2017 and 2020 comparing supervised methadone versus flexible take-home dosing buprenorphine/naloxone models of care in people with POUD (e.g., licit or illicit, including fentanyl, prescribed or not). RESULTS: The sample included 269 participants, of which 142 (52.8%) had positive baseline methamphetamine/amphetamine UDT. In the multivariable model, positive fentanyl UDT (adjusted odds ratio [AOR] 13.21, 95% confidence interval [CI] 6.45, 28.30), non-fatal overdose in the last 6 months (AOR 2.26, CI 1.01, 5.17) and a lifetime history of opioid agonist therapy exposure prior to study entry (AOR 2.30, CI 1.09, 4.87) remained positively associated with baseline methamphetamine/amphetamine use. DISCUSSION AND CONCLUSIONS: In this sample of people with POUD, methamphetamine/amphetamine use was associated with markers of complex and severe OUD, including overdose risk. This suggests the need for targeted interventions to optimise treatment outcomes and prevent future overdoses in this population. CLINICAL TRIAL REGISTRATION: Available at: ClinicalTrials.gov NCT03033732.

Prevalence and Correlates of Heavy Alcohol use among People Living with HIV who use Unregulated Drugs in Vancouver, Canada.

Among people living with HIV (PLWH), heavy alcohol use is associated with many negative health consequences. However, the impacts of heavy alcohol use are not well described for PLWH who use drugs. Thus, we investigated the prevalence and correlates of heavy alcohol use among a cohort of people who use drugs (PWUD) living with HIV in Vancouver, Canada. We accessed data from an ongoing community-recruited prospective cohort of PLWH who use drugs with linked comprehensive HIV clinical monitoring data. We used generalized linear mixed-effects modeling to identify factors longitudinally associated with periods of heavy alcohol use between December 2005 and December 2019. Of the 896 participants included, 291 (32.5%) reported at least one period with heavy alcohol use. Periods of recent incarceration (Adjusted Odds Ratio [AOR] = 1.48, 95% Confidence Interval [CI]: 1.01-2.17), encounters with police (AOR = 1.87, 95% CI: 1.37-2.56), and older age (AOR = 1.05, 95% CI: 1.02-1.07) were positively associated with heavy alcohol use. Engagement in drug or alcohol treatment (AOR = 0.54, 95% CI: 0.42-0.70) and male gender (AOR = 0.46; 95% CI: 0.27-0.78) were negatively associated with heavy alcohol use. We observed that heavy alcohol use was clearly linked to involvement with the criminal justice system. These findings, together with the protective effects of substance use treatment, suggest the need to expand access for drug and alcohol treatment programs overall, and in particular through the criminal justice system to reduce alcohol-related harms among PLWH who use drugs.

"I'm just searching to get better": Constructions of treatment citizenship on injectable opioid agonist treatment.

BACKGROUND: As part of the response to Canada's worsening overdose crisis driven by a toxic, adulterated drug supply, there has been increased attention to and expansion of drug treatment, options, including injectable opioid agonist treatment (iOAT). iOAT typically involves the, witnessed daily injection of opioids under healthcare provider supervision. There is a robust, evidence base on iOAT; however, there has been less focus on how people engage with this; treatment outside of clinical trials. This paper examines how people engage with iOAT programs, in expanded treatment settings in Canada, focusing on how the broader socio-structural context, shapes patient subjectivities in treatment. METHODS: This study draws on critical ethnographic and community-based research approaches, conducted with people accessing four iOAT programs in Vancouver's Downtown Eastside; neighbourhood from May 2018 to November 2019. Data included in-depth baseline and followup, interviews and approximately 50 h of observation fieldwork conducted in one iOAT, program and with a subsample of participants in the surrounding neighbourhood. Analysis, leveraged the concepts of biological citizenship and structural vulnerability. RESULTS: This analysis characterized three narrative frames-regular long-term engagers, pain, patients, and sporadic and short-term engagers-through in-depth case presentations of participants with distinct types of engagement with iOAT programs. Participants within these, narrative frames described a dominant form of iOAT citizenship, an autonomous patient who, regularly engages in treatment and avoids pleasure. However, structural vulnerabilities, including, homelessness and housing instability, entrenched poverty, criminal-legal system engagement, and unmanaged pain, shaped the ability of participants to make claims to this normative model of citizenship. CONCLUSION: This study examined how structural vulnerabilities impact people's construction and ability to make iOAT citizenship claims. Findings point to the need for changes within and outside of iOAT programs, such as lower threshold treatment models, improved social services (e.g., secure housing), and pain management support.

The FASTER-BUP Study, Extended-Release Injectable Buprenorphine for the Treatment of Opioid Use Disorder Among Individuals at High Risk of Overdose: Protocol for an Observational Prospective Study.

North America is facing an unprecedented public health emergency of opioid-related morbidity and mortality. The mortality benefits of oral medication treatment for opioid use disorder (MOUD), such as methadone or buprenorphine, are well documented. However, barriers to access and long-term engagement have prevented maximizing their benefits. Long-acting injectable buprenorphine formulations were developed to address some of the challenges associated with oral MOUD. The "Pilot study to assess the feasibility, efficacy, and safety of extended-release injectable buprenorphine for the treatment of opioid use disorder among individuals at high risk of overdose" (FASTER-BUP) was developed to explore this treatment option in populations at high risk of overdose in a real-world Canadian setting. FASTER-BUP is a 24-week observational prospective study evaluating the feasibility and clinical utility of extended-release injectable buprenorphine (XR-BUP) for the treatment of opioid use disorder (OUD) among 40 adults at high risk of overdose (ie, lifetime history of overdose or a positive urine drug test (UDT) for fentanyl within 30 days prior to screening) in Vancouver, BC. The primary outcome is retention in treatment and secondary outcomes include: use of unregulated opioids, safety, overdose events, treatment satisfaction, changes in drug-related problems, changes in quality of life, opioid cravings, health service utilization, and criminal activity. FASTER-BUP is the first study to explore XR-BUP among individuals at high risk of overdose in a real-world Canadian setting. This commentary provides a brief narrative about the study thus far and presents insights on key adaptations to the study protocol, including those adopted to mitigate recruitment challenges.

Safety and Efficacy of Rapid Methadone Titration for Opioid Use Disorder in an Inpatient Setting: A Retrospective Cohort Study.

OBJECTIVES: Inpatient guidelines for methadone titration do not exist, whereas outpatient guidelines lack flexibility and do not consider individual opioid tolerance. The evaluation of rapid, adaptable titration protocols may allow more patient-centered and effective treatment for opioid use disorder in the fentanyl era. METHODS: This study performed a retrospective chart review of patients 18 years or older with opioid use disorder who were initiated on methadone at a single academic urban hospital using a rapid divided dose protocol between November 2019 and November 2020. The primary outcome was adverse events associated with methadone, specifically opioid toxicity or sedation requiring increased medical observation or intervention. The secondary outcome was total daily dose of methadone received on day 7 of titration. RESULTS: Ninety-eight patients were included for a total of 168 visits. Sixty-five (66%) were male, with a median age of 38 years (interquartile range, 31-42 years). Sedation occurred in 2 patients (1%), who required either naloxone administration or transfer to an intensive care unit for monitoring. Of the 135 visits where patients received at least 7 days of methadone, the mean dose on day 1 was 41 mg (SD, 9.6 mg) and on day 7 was 65 mg (SD, 20.9 mg). CONCLUSIONS: In this inpatient cohort, rapid methadone titration was well tolerated and resulted in patients reaching higher doses of methadone than would be possible with a standard schedule, with few adverse events. Given the known effective dose range, this approach may result in shorter time to clinical stabilization and suggests that alternative methadone titration schedules may be safe and effective in appropriately selected patients.

Cytisine for smoking cessation: A systematic review and meta-analysis.

BACKGROUND: Cytisine is a smoking cessation medication. This systematic review incorporates recently published randomized controlled trials (RCTs) to provide an updated evidence-based assessment of cytisine's efficacy and safety. METHODS: We searched Cochrane Library, MEDLINE, and EMBASE, for RCTs comparing cytisine to other smoking cessation treatments in adults who smoke. PRIMARY OUTCOME: 6-month biochemically verified continuous abstinence. Other outcomes: abstinence at longest follow-up, adverse events, mortality, and health-related quality of life (HRQOL). We used Grading of Recommendations Assessment, Development and Evaluation (GRADE) to assess evidence certainty. RESULTS: We included 14 RCTs involving 9953 adults. Cytisine was superior to placebo (risk ratio [RR] 2.25, 95% confidence interval [CI] 1.13-4.47; 5 RCTs, 4325 participants), but not varenicline (RR 1.13, 95% CI 0.65-1.95; 2 RCTs, 2131 participants) for the primary outcome. Cytisine was superior to placebo (RR 2.78, 95% CI 1.64-4.70; 8 RCTs, 5762 participants) and nicotine replacement therapy [NRT] (RR 1.39, 95% CI 1.12-1.73; 2 RCTs, 1511 participants), but not varenicline (RR 1.02, 95% CI 0.72-1.44; 4 RCTs, 2708 participants) for abstinence at longest follow-up. Cytisine increased mostly gastrointestinal adverse events compared to placebo (RR 1.15; 95% CI 1.06-1.25; 8 RCTs, 5520 participants) and NRT (RR 1.52, 95% CI 1.26-1.84; 1 RCT, 1310 participants) but less adverse events compared to varenicline (RR 0.67; 95% CI 0.48-0.95; 3 RCTs, 2484 participants). CONCLUSION: Cytisine shows greater efficacy than placebo and NRT, but more adverse events. It is comparable to varenicline, with fewer adverse events. This can inform clinicians and guidelines on cytisine for smoking cessation.

Using a cascade of care framework to identify gaps in access to medications for alcohol use disorder in British Columbia, Canada.

BACKGROUND AND AIMS: Despite the significant burden of alcohol use disorder (AUD) and availability of safe and effective medications for AUD (MAUD), population-level estimates of access and engagement in AUD-related care are limited. The aims of this study were to generate a cascade of care for AUD in British Columbia (BC), Canada, and to estimate the impacts of MAUD on health outcomes. DESIGN: This was a retrospective population-based cohort study using linked administrative health data. SETTING: British Columbia, Canada, 2015-2019. PARTICIPANTS: Using a 20% random sample of BC residents, we identified 7231 people with moderate-to-severe alcohol use disorder (PWAUD; overall prevalence = 0.7%). MEASUREMENTS: We developed a six-stage AUD cascade (from diagnosis to ≥6 months retention in MAUD) among PWAUD. We evaluated trends over time and estimated the impacts of access to MAUD on AUD-related hospitalizations, emergency department visits and death. FINDINGS: Between 2015 and 2019, linkage to AUD-related care decreased (from 80.4% to 46.5%). However, rates of MAUD initiation (11.4% to 24.1%) and retention for ≥1 (7.0% to 18.2%), ≥3 (1.2% to 4.3%) or ≥6 months (0.2% to 1.6%) increased significantly. In adjusted analyses, access to MAUD was associated with reduced odds of experiencing any AUD-related adverse outcomes, with longer retention in MAUD showing a trend to greater odds reduction: adjusted odds ratio (95% CI) ranging from 0.59 (0.48-0.71) for MAUD retention <1 month to 0.37 (0.21-0.67) for ≥6 months retention. CONCLUSIONS: Access to medications for alcohol use disorder among people with moderate-to-severe alcohol use disorder in British Colombia, Canada increased between 2015 and 2019; however, initiation and retention remained low. There was a trend between longer retention in medications for alcohol use disorder and greater reductions in the odds of experiencing alcohol use disorder-related adverse outcomes.

Impacts of the COVID-19 pandemic on enrollment in medications for opioid use disorder (MOUD) in Vancouver, Canada: An interrupted time series analysis.

BACKGROUND: In anticipation of COVID-19 related disruptions to opioid use disorder (OUD) care, new provincial and federal guidance for the management of OUD and risk mitigation guidance (RMG) for prescription of pharmaceutical opioids were introduced in British Columbia, Canada, in March 2020. This study evaluated the combined impacts of the COVID-19 pandemic and counteracting OUD policies on enrollment in medications for OUD (MOUD). METHODS: Using data from three cohorts of people with presumed OUD in Vancouver, we conducted an interrupted time series analysis to estimate the combined effects impact of the COVID-19 pandemic and counteracting OUD policies on the prevalence of enrollment in MOUD overall, as well as in individual MOUDs (methadone, buprenorphine/naloxone, slow-release oral morphine) between November 2018 and November 2021, controlling for pre-existing trends. In sub-analysis we considered RMG opioids together with MOUD. RESULTS: We included 760 participants with presumed OUD. In the post-COVID-19 period, MOUD and slow-release oral morphine prevalence rates showed an estimated immediate increase in level (+7.6%, 95% CI: 0.6%, 14.6% and 1.8%, 95% CI: 0.3%, 3.3%, respectively), followed by a decline in the monthly trend (-0.8% per month, 95% CI: -1.4%, -0.2% and -0.2% per month, 95% CI: -0.4, -0.1, respectively). There were no significant changes in the prevalence trends of enrollment in methadone, buprenorphine/naloxone, or when RMG opioids were considered together with MOUD. CONCLUSIONS: Despite immediate improvements in MOUD enrollment in the post-COVID-19 period, this beneficial trend reversed over time. RMG opioids appeared to have provided additional benefits to sustain retention in OUD care.

Women's experiences in injectable opioid agonist treatment programs in Vancouver, Canada.

BACKGROUND: Injectable opioid agonist treatment (iOAT) has recently been expanded in some geographical contexts in Canada as part of a response to the escalating overdose crisis. Complex gendered dynamics, including power differentials, violence, and social norms, shape the overdose crisis and drug treatment programs which can adversely impact women's experiences. This qualitative study examines how social (e.g., gender, income, housing) and structural factors (e.g., program policies) impact women's experiences of iOAT. METHODS: Qualitative interviews were completed with 16 women enrolled in four iOAT programs in Vancouver, Canada. Approximately 50 hours of ethnographic observations were conducted. Interview transcripts and ethnographic fieldnotes were analyzed using a critical feminist lens by applying the concepts of embodiment, relationality, and social control to understand women's engagement and self-reported treatment outcomes. RESULTS: Initial iOAT engagement was a relational process, including initiating treatment with a partner and engaging with iOAT to (re)build personal relationships. Relationships with iOAT providers, including flexibility and support with medication administration, were important to women, providing an affirming embodied experience and a greater sense of agency. However, program operations (e.g., mandated daily attendance, program crowding) incompatible with women's needs (e.g., employment) could undermine these positive experiences. Women's reported outcomes highlight a tension between achieving more agency and the constraints of intensive and stigmatized treatment. CONCLUSION: This study highlights how iOAT is both a source of care and control for women from a relational and embodied perspective. Findings underscore the need for gender-attentive and flexible drug treatment services to meet the varied needs of women and the importance of providing relational care for women accessing iOAT.

Experiencing homelessness and progression through the HIV cascade of care among people who use drugs.

OBJECTIVE: To investigate the longitudinal association between periods of homelessness and progression through the HIV cascade of care among people who use drugs (PWUD) with universal access to no-cost HIV treatment and care. DESIGN: Prospective cohort study. METHODS: Data were analysed from the ACCESS study, including systematic HIV clinical monitoring and a confidential linkage to comprehensive antiretroviral therapy (ART) dispensation records. We used cumulative link mixed-effects models to estimate the longitudinal relationship between periods of homelessness and progression though the HIV cascade of care. RESULTS: Between 2005 and 2019, 947 people living with HIV were enrolled in the ACCESS study and 304 (32.1%) reported being homeless at baseline. Homelessness was negatively associated with overall progression through the HIV cascade of care [adjusted partial proportional odds ratio (APPO) = 0.56, 95% confidence interval (CI): 0.49-0.63]. Homelessness was significantly associated with lower odds of progressing to each subsequent stage of the HIV care cascade, with the exception of initial linkage to care. CONCLUSIONS: Homelessness was associated with a 44% decrease in the odds of overall progression through the HIV cascade of care, and a 41-54% decrease in the odds of receiving ART, being adherent to ART and achieving viral load suppression. These findings support calls for the integration of services to address intersecting challenges of HIV, substance use and homelessness among marginalized populations such as PWUD.

Re-incarceration and associated social, structural and behavioural factors among people who use drugs in an urban Canadian setting.

BACKGROUND: People who use drugs (PWUD) are disproportionately incarcerated, however little is known about specific substance use, social and structural factors associated with re-incarceration among PWUD. We aimed to identify the socio-structural and substance use factors associated with re-incarceration among structurally-marginalized PWUD. METHODS: We used longitudinal data from two prospective cohorts of PWUD in Vancouver, Canada. We included adults reporting at least one incarceration event in the last six months and who completed at least one additional follow-up study visit. We performed multivariable extended Cox regression to explore factors associated with re-incarceration. RESULTS: Among 468 eligible participants, the median age was 40 years (Q1-Q3 = 34-46 years), 346 (73.9%) were men, 177 (37.8%) identified as Indigenous, and 227 (48.5%) experienced at least one re-incarceration event. Incidence rate of re-incarceration was 157 incarceration events per 1000 person years. In multivariable analyses, homelessness (adjusted hazard ratio [AHR] = 2.17; 95% confidence interval [95% CI]: 1.79-2.61), community judicial supervision (AHR = 3.89; 95% CI: 3.21-4.71) and re-incarceration during the study period (once: AHR = 1.95, 95% CI: 1.55-2.44; two or more events: AHR = 1.53, 95% CI: 1.23-1.90) were positively associated with re-incarceration. Among substance use variables that included illicit drugs, only heavy alcohol use remained significantly associated with re-incarceration across analyses after adjustment (AHR = 1.32; 95% CI: 1.06-1.65). Engagement in addiction treatment (AHR = 0.63; 95% CI: 0.53-0.75), mental illness (AHR = 0.70; 95% CI: 0.59-0.84) and age (AHR = 0.96; 95% CI: 0.95-0.97) were negatively associated with re-incarceration. CONCLUSION: Access to housing and substance use services, including treatment for alcohol use disorder, following incarceration may reduce re-incarceration among PWUD. The high rates of re-incarceration of PWUD in our sample underscores how structural factors-such as homelessness and criminalization of substance use-drive re-incarceration among PWUD.

Trends in cocaine and crystal methamphetamine injection over time in a Canadian setting between 2008 and 2018.

OBJECTIVE: Unregulated stimulant use is rising globally, though trends in use of cocaine and crystal methamphetamine (CM), the two most commonly used unregulated stimulants in North America, are poorly characterized in many settings. In this study we examined patterns and associations between the injection of cocaine and CM over time in an urban Canadian setting. METHODS: The study collected data from two prospective cohorts of people who inject drugs in Vancouver, Canada, between 2008 and 2018. We applied a time series analysis, using multivariable linear regression to detect relationships between reported CM and cocaine injection and year, controlling for covariates. The study used cross-correlation to evaluate the relative trajectories of each substance over time. RESULTS: Among 2056 participants, per annum rates of reported injection cocaine use declined significantly over the duration of this study from 45 % to 18 % (p < 0.001), while rates of CM injection increased from 17 % to 32 % (p < 0.001). Multivariable linear regression showed that recent CM injection was negatively associated with recent cocaine injection (ß = -0.609, 95 % CI = -0.750, -0.467). Cross-correlation demonstrated that injection CM use was associated with a decrease in the likelihood of cocaine injection 12 months later (p = 0.002). CONCLUSIONS: These findings demonstrate an epidemiological shift in patterns of injection stimulant use, with rising CM injection associated with a corresponding decrease in cocaine injection over time. Strategies are urgently needed that help to treat and reduce harm among the growing population of people who inject CM.

Increasing trends and incidence of nonfatal overdose among women sex workers who use drugs in British Columbia: The role of criminalization-related barriers to harm reduction.

BACKGROUND: Structurally marginalized women who use drugs experience disproportionately elevated health and social inequities that require specialized responses to mitigate risk of overdose. This study aimed to longitudinally investigate incidence and predictors of first nonfatal overdose among women sex workers who use drugs. METHODS: Data (2010-2019) were drawn from AESHA (An Evaluation of Sex Workers Health Access), a community-based, prospective, open cohort of > 900 women sex workers in Metro Vancouver, Canada. Incidence was examined and Cox regression modelled time-updated predictors of first nonfatal overdose. Time series analysis examined annual trends. RESULTS: Among 273 eligible participants, 23% (n = 63) reported a first nonfatal overdose over follow-up with an incidence density of 5.87/100 person-years. In multivariable analysis, independent predictors of time to nonfatal overdose were police-related barriers to harm reduction (Adjusted Hazard Ratio [AHR]=2.62; 95% confidence interval [CI] 1.51-4.54), binge alcohol use (AHR=2.28; 95%CI 1.16-4.45), opioid use (AHR=2.23; 95%CI 1.15-4.33), and crystal methamphetamine use (AHR=2.07; 95%CI 1.27-3.39). Time series analysis demonstrated a significantly increasing trend in first nonfatal overdose, with annual proportions increasing 0.59% (95%CI 0.39-0.78%) every year, on average. CONCLUSIONS: This study provides strong longitudinal evidence from the longest-standing cohort of sex workers in North America. Nonfatal overdose in this setting is a critical public health concern. Criminalization-related barriers to harm reduction strongly predicted nonfatal overdose. Structural changes to legal and policing practices alongside gender-sensitive addiction services are urgently needed.

Association of sex work and social-structural factors with non-fatal overdose among women who use drugs in Vancouver, Canada.

BACKGROUND: Women who use drugs (WWUD) and engage in sex work experience disproportionate sex- and drug-related harms, such as HIV, however comparatively little is known about their overdose risk. Therefore, we examined the association between sex work and overdose and secondarily explored the association of social-structural factors, such as policing and gendered violence, with overdose. METHODS: Data were derived from two community cohort studies based in Vancouver, Canada between 2005 to 2018. We used logistic regression with GEE to examine the associations between a) sex work and nonfatal overdose and b) social-structural and individual variables with overdose among WWUD who engaged in sex work during the study. Sex work, overdose, and other variables were time-updated, captured every six months. RESULTS: Among 857 WWUD included, 56% engaged in sex work during the study. Forty-three percent of WWUD engaged in sex work had at least one overdose compared to 26% of WWUD who did not. Sex work was not significantly associated with an increased odds of overdose (AOR = 1.14, 95% CI: 0.93-1.40). In the exploratory analysis amongst 476 WWUD engaged in sex work, social-structural variables associated with overdose in the multivariable model included exposure to: punitive policing (OR = 1.97, 95% CI: 1.30-2.96) and physical or sexual violence (OR = 2.55, 95% CI: 1.88-3.46). CONCLUSIONS: WWUD engaged in sex work had an increased overdose burden that may be driven by social-structural factors rather than sex work itself. Interventions that address policing and gendered violence represent potential targets for effective overdose prevention.

The Cannabis-Dependent Relationship Between Methadone Treatment Dose and Illicit Opioid Use in a Community-Based Cohort of People Who Use Drugs.

Background: Methadone maintenance treatment (MMT) is an effective treatment for opioid use disorder. However, subtherapeutic dosing may lead to continued opioid use by failing to suppress opioid withdrawal and craving. Preclinical and pilot experimental research suggests that cannabinoids may reduce opioid withdrawal and craving. We sought to test whether the association between low methadone dose and illicit opioid use differs according to concurrent cannabis use patterns. Methods: Data for this study were derived from two community-recruited cohorts of people (≥18 years old) who use illicit drugs in Vancouver, Canada. We used generalized estimating equations to estimate the adjusted association between lower daily MMT dose (<90 mg/day) and daily illicit opioid use, testing for interaction between dose and daily cannabis use. Results: Between December 2005 and December 2018, 1389 participants reported MMT enrolment and were included in the study. We observed a significant interaction (p<0.01) between daily cannabis and lower MMT dose on concurrent daily illicit opioid use: lower MMT doses increased the odds of daily illicit opioid use by 86% (adjusted odds ratio [AOR]=1.86, 95% confidence interval [CI]=1.61-2.16) during periods of no or low-frequency cannabis use and by 30% during periods of daily cannabis use (AOR=1.30, 95% CI=1.01-1.67). Discussion: This study provides preliminary observational evidence that cannabis may mitigate some of the negative effects of subtherapeutic MMT dosing, guiding future clinical investigations into the safety and efficacy of cannabis and cannabinoids as adjunct treatment for MMT.

Methadone Dose, Cannabis Use, and Treatment Retention: Findings From a Community-based Sample of People Who Use Unregulated Drugs.

OBJECTIVES: Lower daily methadone dose is negatively associated with retention in methadone maintenance treatment (MMT). Cannabis use during MMT is common, with many patients reporting its use for opioid withdrawal mitigation. We sought to test whether the association between lower MMT dose and treatment retention differs by concurrent high-frequency cannabis use in a community sample of people on MMT. METHODS: We obtained data from participants initiating MMT in 2 community-recruited prospective cohorts of people who use drugs in Vancouver, Canada. We built multivariable Cox frailty models to estimate the relationships between MMT dose (<90 mg/d vs ≥90 mg/d) and time to treatment discontinuation. We included an interaction term to test whether high-frequency (≥daily) cannabis use modified the measured effect of lower treatment dose on treatment retention. RESULTS: Between December 2005 and December 2018, 829 participants (54.1%) initiated at least 1 MMT episode and were included in the analysis. Lower MMT dose was strongly positively associated with treatment discontinuation regardless of concurrent high-frequency cannabis use (interaction P > 0.05). Structural factors including homelessness and incarceration were significantly and positively associated with treatment discontinuation. CONCLUSIONS: Although we previously found the magnitude and strength of the relationship between lower MMT dose and high-frequency unregulated opioid use to be tempered during high-frequency cannabis use periods, this effect measure modification does not appear to translate to time retained in treatment. Cannabis-based interventions to promote retention in MMT are unlikely to produce long-term benefit without addressing external factors that place MMT patients at increased risk of treatment discontinuation.

Perceived Mistreatment in Health Care Settings and its Relationship with HIV Clinical Outcomes in HIV-positive People who Use Drugs in Vancouver, Canada.

People living with HIV (PLWH) often experience stigma and discrimination by health care professionals. We investigated the prevalence of perceived mistreatment in health care settings and its associations with HIV clinical outcomes and health care-seeking behaviour using data from a long-running prospective cohort of PLWH who use drugs. Of the 857 participants included, 19% reported at least one instance of perceived mistreatment during the study period. In adjusted longitudinal analyses, perceived mistreatment was positively associated with not being on ART in the same follow-up period, and participants who reported perceived mistreatment were less likely to report seeing a physician in the subsequent follow-up period. Daily use of injection drugs was positively associated with reporting perceived mistreatment. These findings demonstrate the implications of negative health care interactions in a population that must consistently engage with the health care system, and the need for stigma-reducing educational interventions for health care professionals.