Redesigning a Stopped Clinical Trial as an Emulated Trial Using Real-World Data to Explore the Effectiveness of Slow-Release Oral Morphine as a Treatment for Opioid Use Disorder.

Canada is currently experiencing a problematic opioid crisis with increasing mortality rates. Traditional randomized controlled trials (RCTs) that examine the effectiveness of pharmacological treatment options for people with opioid use disorder (OUD) are challenging to conduct. An increasingly popular methodology is through the implementation of emulated clinical trials, a methodology in which key elements of a "target" RCT are replicated using previously collected healthcare-based data. They can possibly address some of the common challenges found in the conduct of RCTs, such as prolonged timelines, high cost, and poor participant recruitment. In effect, emulated trials accelerate knowledge generation by producing real-world evidence that can be akin to phase 3 effectiveness trials, without any need to recruit live participants or administer investigational products. During the COVID-19 pandemic, several trials were stopped due to increased pandemic-related research restrictions, leaving important questions about OUD treatment unanswered. In this commentary, we describe the transition of a traditional RCT to an emulated trial spurred by challenges posed by the COVID-19 pandemic. We describe our transition using a notable published framework with regards to the population sample, interventions, outcomes, and proposed analyses. This commentary aims to help other researchers and trialists apply emulated trials in substance use research and beyond, emphasizing the role of this methodology in clinical research and advancing scientific knowledge that could be otherwise lost or unattainable.

Characterizing the Use of Healthcare Access Supports Among People Who Use Drugs in Vancouver, Canada, 2017 to 2020: A Cohort Study.

BACKGROUND: For structurally marginalized populations, including people who use drugs (PWUD), equitable access to healthcare can be achieved through healthcare access supports. However, few studies characterized utilization of formal (eg, outreach workers, healthcare professionals) and informal (eg, friends/family) supports. Therefore, we sought to estimate the prevalence of and factors associated with receiving each type of support among PWUD. METHODS: We used data from 2 prospective cohort studies of PWUD in Vancouver, Canada, in 2017 to 2020. We constructed separate multivariable generalized linear mixed-effects models to identify factors associated with receiving each of the 3 types of supports (ie, healthcare professionals, outreach workers/peer navigators, and informal supports) compared to no supports. RESULTS: Of 996 participants, 350 (35.1%) reported receiving supports in the past 6 months at baseline, through informal supports (6.2%), outreach workers (14.1%), and healthcare professionals (20.9%). In multivariable analyses, HIV positivity, chronic pain, and avoiding healthcare due to the past mistreatment were positively associated with receiving supports from each of healthcare professionals and outreach workers. Men were less likely to receive any types of the supports (all P < .05). CONCLUSIONS: Utilization of healthcare access supports was relatively low in this sample. However, formal supports appeared to have reached PWUD exhibiting more comorbidities and experiencing discrimination in healthcare. Further efforts to make formal supports more available would benefit PWUD with unmet healthcare needs, particularly men.

Receipt of COVID-19 emergency funds and engagement in sex work during COVID-19 among people who use drugs: evidence from Vancouver, Canada.

BACKGROUND: During the early period of the COVID-19 pandemic, public health orders disrupted income generation in numerous sectors and many governments provided emergency financial support. Access to government support and changes in engagement in sex work during the early period of the pandemic among people who use drugs (PWUD) are not well described. In the present study, we investigate the prevalence and correlates of engaging in sex work during the COVID-19 pandemic, among PWUD in Vancouver, Canada. METHODS: Data derived from three harmonized cohorts of PWUD. Using multivariable logistic regression, we characterized factors associated with engaging in sex work in the last month between July 17 and November 30, 2020. Reports of changes in frequency of engagement in sex work since the pandemic were also collected. RESULTS: Of the 864 individuals included in this analysis, 55 (6.4%) reported sex work engagement in the last month. Among these participants, 40.7% reported receiving COVID-19 income support in the past month vs. 52.7% of the rest of the sample, though receipt of income support in the past six months was similar between the two groups (72.2% vs. 75.7%, p = 0.624). In multivariable analysis, receipt of financial support in the last month was negatively associated with engagement in sex work in the last month (adjusted odds ratio [AOR] = 0.44 [95% confidence interval [CI]: 0.24-0.81]). Among 69 participants who responded to a question regarding changes in engagement in sex work, 38 (55.1%) reported a decrease, 11 (15.9%) reported an increase, 19 (27.5%) reported no change, and 1 (1.4%) reported cessation. CONCLUSIONS: Findings document that engagement in sex work appears to have declined early in the pandemic. Participants who received income support in the past month were less likely to report recent engagement in sex work. Findings suggest that recent receipt of income support may have contributed to reductions in engagement in sex work. Additional investigation is warranted.

Does This Patient Have Alcohol Use Disorder?: The Rational Clinical Examination Systematic Review.

Importance: The accuracy of screening tests for alcohol use disorder (defined as a problematic pattern of alcohol use leading to clinically significant impairment or distress) requires reassessment to align with the latest definition in the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (DSM-5). Objective: To assess the diagnostic accuracy of screening tools in identifying individuals with alcohol use disorder as defined in the DSM-5. Data Sources and Study Selection: The databases of MEDLINE and Embase were searched (January 2013-February 2023) for original studies on the diagnostic accuracy of brief screening tools to identify alcohol use disorder according to the DSM-5 definition. Because diagnosis of alcohol use disorder does not include excessive alcohol use as a criterion, studies of screening tools that identify excessive or high-risk drinking among younger (aged 9-18 years), older (aged ≥65 years), and pregnant persons also were retained. Data Extraction and Synthesis: Sensitivity, specificity, and likelihood ratios (LRs) were calculated. When appropriate, a meta-analysis was performed to calculate a summary LR. Results: Of 4303 identified studies, 35 were retained (N = 79 633). There were 11 691 individuals with alcohol use disorder or a history of excessive drinking. Across all age categories, a score of 8 or greater on the Alcohol Use Disorders Identification Test (AUDIT) increased the likelihood of alcohol use disorder (LR, 6.5 [95% CI, 3.9-11]). A positive screening result using AUDIT identified alcohol use disorder better among females (LR, 6.9 [95% CI, 3.9-12]) than among males (LR, 3.8 [95% CI, 2.6-5.5]) (P = .003). An AUDIT score of less than 8 reduced the likelihood of alcohol use disorder similarly for both males and females (LR, 0.33 [95% CI, 0.20-0.52]). The abbreviated AUDIT-Consumption (AUDIT-C) has sex-specific cutoff scores of 4 or greater for males and 3 or greater for females, but was less useful for identifying alcohol use disorder (males: LR, 1.8 [95% CI, 1.5-2.2]; females: LR, 2.0 [95% CI, 1.8-2.3]). The AUDIT-C appeared useful for identifying measures of excessive alcohol use in younger people (aged 9-18 years) and in those older than 60 years of age. For those younger than 18 years of age, the National Institute on Alcohol Abuse and Alcoholism age-specific drinking thresholds were helpful for assessing the likelihood of alcohol use disorder at the lowest risk threshold (LR, 0.15 [95% CI, 0.11-0.21]), at the moderate risk threshold (LR, 3.4 [95% CI, 2.8-4.1]), and at the highest risk threshold (LR, 15 [95% CI, 12-19]). Among persons who were pregnant and screened within 48 hours after delivery, an AUDIT score of 4 or greater identified those more likely to have alcohol use disorder (LR, 6.4 [95% CI, 5.1-8.0]), whereas scores of less than 2 for the Tolerance, Worried, Eye-Opener, Amnesia and Cut-Down screening tool and the Tolerance, Annoyed, Cut-Down and Eye-Opener screening tool identified alcohol use disorder similarly (LR, 0.05 [95% CI, 0.01-0.20]). Conclusions and Relevance: The AUDIT screening tool is useful to identify alcohol use disorder in adults and in individuals within 48 hours postpartum. The National Institute on Alcohol Abuse and Alcoholism youth screening tool is helpful to identify children and adolescents with alcohol use disorder. The AUDIT-C appears useful for identifying various measures of excessive alcohol use in young people and in older adults.

Sexually transmitted and blood-borne infection risk reduction with methadone and buprenorphine/naloxone among people with prescription-type opioid use disorder: Findings from a Canadian pragmatic randomized trial.

INTRODUCTION: People who use drugs are disproportionally affected by sexually transmitted and blood-borne infections (STBBIs). While the benefits of methadone in reducing injecting-risk behaviours are well documented, less is known on its impacts on sexual-related risks, as well as its comparative effectiveness to buprenorphine/naloxone, particularly in the context of highly potent opioids. The aim of this study was to estimate the relative effects of buprenorphine/naloxone and methadone on injecting and STBBI risks among people with prescription-type opioid use disorder (POUD). METHODS: Secondary analysis of a pan-Canadian pragmatic 24-week randomized clinical trial comparing methadone and buprenorphine/naloxone models of care among 272 people with POUD (including licit or illicit opioid analgesics, fentanyl). The Risk Behaviour Survey was used to collect injecting and sexual risks at baseline, and weeks 12 and 24. RESULTS: In total, 210 participants initiated treatment (103 buprenorphine/naloxone and 107 methadone). At baseline, 113/205 (55.1%) participants reported recently injecting drugs, 37/209 (17.7%) unsafe injection practices and 67/162 (41.4%) high-risk sex. Both methadone and buprenorphine/naloxone were associated with reductions in the prevalence of injection drug use and high-risk sex at weeks 12 and 24 with no interactions between treatment arm and time. CONCLUSION: Methadone and buprenorphine/naloxone were similarly effective in reducing injecting and sexual risk behaviours among people with POUD. CLINICAL TRIALS REGISTRATION: clinicaltrials.gov NCT03033732.

Patterns of Socioeconomic Marginalization among People Who Use Drugs: A Gender-Stratified Repeated Measures Latent Class Analysis.

Socioeconomic factors are important correlates of drug use behaviors and health-related outcomes in people who use drugs (PWUD) residing in urban areas. However, less is known about the complex overlapping nature of socioeconomic conditions and their association with a range of individual, drug use, and health-related factors in men and women who use drugs. Data were obtained from two community-recruited prospective cohorts of PWUD. Using a gender-stratified approach, we conducted repeated measures latent class analyses (RMLCA) to identify discrete latent socioeconomic subgroups. Multivariable generalized estimating equations were then used to identify correlates of class membership. Between June 2014 and December 2018, RMLCA of 9844 observations from 1654 participants revealed five distinct patterns of socioeconomic status for both men and women. These patterns were primarily distinguished by variations in income, material and housing security, income generation activity, exposure to violence, criminal justice involvement, and police contact. Across gender, progressive increases in exposure to multiple dimensions of socioeconomic disadvantage were found to be associated with frequent use of opioids and stimulants, accessing social services, and being hepatitis C virus antibody-positive. Similar but less congruent trends across gender were observed for age, binge drug use, engagement with opioid agonist therapy, and living with HIV. Gendered patterns of multiple and overlapping dimensions of socioeconomic adversity aligned with patterns of frequent drug use and health-related concerns, highlighting priority areas for gender-inclusive, multilevel responses to mitigate health disparities and meet the diverse socioeconomic needs of urban-dwelling men and women who use drugs.

Longitudinal polysubstance use patterns and non-fatal overdose: A repeated measures latent class analysis.

BACKGROUND: Polysubstance use (PSU) is common among people who use opioids (PWUO) and has been associated with drug-related harms. We aimed to identify latent longitudinal PSU classes among a cohort of PWUO and characterize non-fatal overdose risks among different sub-classes over time. METHODS: We used longitudinal data (2005-2018) from three ongoing prospective cohorts of people who use drugs in Vancouver, Canada. The primary outcome of interest was self-reported non-fatal overdose during the past six months. The primary exposure of interest was longitudinal PSU patterns among PWUO, obtained from repeated measures latent class analysis (RMLCA) of weekly substance use-related outcome indicators. Multivariable generalized estimating equations models were built to assess the association between latent PSU class membership and non-fatal overdose, adjusting for potential sociodemographic, behavioural, and structural confounders. RESULTS: 2627 PWUO were included in the analysis, and 1094 (41.6 %) had experienced at least one non-fatal overdose during the study period. RMLCA revealed five distinct latent longitudinal PSU classes, including low/infrequent use (Class 1; 30 %), primarily opioid and methamphetamine use (Class 2; 22 %), primarily cannabis use (Class 3; 15 %), primarily opioid and crack use (Class 4; 29 %), and frequent PSU (Class 5; 4 %). In comparison with Class 1 (low), membership in all latent PSU classes except Class 3 (cannabis) was associated with increased odds of non-fatal overdose: Class 2 (opioids + meth) vs. Class 1 (Adjusted odds ratios [aOR] = 2.20, 95 % confidence intervals [CI]: 1.51-3.22), Class 4 (opioids + crack) vs. Class 1 (aOR = 1.06, 95 % CI: 0.85-1.33), and Class 5 (frequent) vs. Class 1 (aOR = 2.39, 95 % CI: 1.92-2.97). CONCLUSION: Our findings highlighted the heterogeneous characteristics of PWUO in terms of patterns of PSU and non-fatal overdose risk. The diverse nature of PWUO and the potential additive or multiplicative impact of using several substances on overdoses should be reflected across the substance use treatment continuum and care provision.

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.

Evaluation of audit and feedback to family physicians on prescribing of opioid analgesics to opioid-naïve patients: A pragmatic randomized delay trial.

BACKGROUND: Exposure to opioid analgesics have historically raised concern for a risk of developing opioid use disorder. Prescriber audit-and-feedback interventions may reduce opioid prescribing, but some studies have shown detrimental effects for current users. We examined the effectiveness of an audit and feedback intervention, named Portrait, to reduce initiation of opioid analgesics among opioid-naïve patients experiencing pain. METHODS: REDONNA was a single-blinded, two-arm (Early vs Delayed mailing) randomized trial of a portrait for eligible family physicians (FPs) in British Columbia (BC), Canada. The primary outcome was the change in the number of initiations of opioid analgesic prescriptions written by FPs for acute/chronic pain management. We compared outcomes for a 6-month window before vs. after each mailed intervention, using differences in percent differences (DPD) with 95% confidence intervals (CI) and odds ratios (OR) from logistic regressions adjusted for clustering of patients by FP. RESULTS: In the Early (n = 2260) and Delayed (n = 2156) groups, opioid initiations per month were the same in the Before (2.10 Early; 2.06 Delayed) and After (1.94 Early; 1.95 Delayed) windows. The DPD was -2.1% (CI: -4.4% to 0.3%), and ORs were: 0.98 (CI: 0.96 to 1.01) for any opioid, 0.97 (CI: 0.94 to 1.01) for codeine (62% of initiations), and 1.0 (CI: 0.97 to 1.07) for tramadol (25% of initiations). There were no differences in mean quantity of tablets, mean milligrams of morphine equivalents (MME), or mean number of days. CONCLUSION: Portrait had no impact on FPs' rates of prescribing opioid analgesics to opioid-naïve patients experiencing pain. TRIAL REGISTRATION: The study was registered prospectively on 30 March 2020 at the ISRCTN Register (https://www.isrctn.com/ISRCTN34246811).

Police seizure of drugs without arrest among people who use drugs in Vancouver, Canada, before provincial 'decriminalization' of simple possession: a cohort study.

BACKGROUND: Several jurisdictions in Canada have recently considered decriminalizing possession of illicit drugs for personal use (henceforth, simple possession) as part of their responses to the ongoing drug toxicity/overdose crisis. In this context, we sought to examine an early implementation case of a de facto depenalization policy of simple possession offences in Vancouver, Canada, that was enacted in 2006. Specifically, we characterized experiences of people who use drugs (PWUD) whose drugs were discretionally seized by police without arrest. METHODS: Data were derived from three prospective cohorts of community-recruited PWUD in Vancouver over 16 months in 2019-2021. We conducted multivariable generalized estimating equations analyses to determine the prevalence of and factors associated with drug seizure. Sub-analyses used data collected in 2009-2012 and examined the trends over time. RESULTS: Among 995 participants who were interviewed in 2019-2021, 63 (6.3%) had their drugs seized by police at least once in the past 6 months. In multivariable analyses, factors significantly associated with drug seizure included: homelessness (adjusted odds ratio [AOR]: 1.98; 95% confidence interval [CI] 1.09-3.61), working in the unregulated drug market (AOR: 4.93; 95% CI 2.87-8.49), and naloxone administration (AOR: 2.15; 95% CI 1.23-3.76). In 2009-2012, 67.8% reported having obtained new drugs immediately after having their drugs seized by police. Odds of drug seizure were not significantly different between the two time periods (2019-2021 vs. 2009-2012) (AOR: 0.93; 95% CI: 0.64-1.35). CONCLUSIONS: Despite the depenalization policy, the Vancouver Police Department has continued to seize illicit drugs from PWUD, even in cases where no arrest occurred. This policing practice may create health and safety risks for PWUD as it forces PWUD to increase the engagement with the unregulated illicit drug market. Our findings support calls for abolishing this often-undocumented discretionary policing practice that may exacerbate ongoing health inequities and interfere with peer-based overdose prevention efforts.

Longitudinal latent polysubstance use patterns among a cohort of people who use opioids in Vancouver, Canada.

INTRODUCTION: Polysubstance use (PSU) practices are increasing among people who use opioids (PWUO). However, several aspects of longitudinal PSU patterns among PWUO remain understudied. This study aims to identify person-centred longitudinal patterns of PSU among a cohort of PWUO. METHODS: Using longitudinal data (2005-2018) from three prospective cohort studies including people who use drugs in Vancouver, Canada, we used repeated measures latent class analysis to identify different PSU classes among PWUO. Multivariable generalised estimating equations models weighted by the respective posterior membership probabilities were applied to identify covariates of membership in different PSU classes over time. RESULTS: Overall, 2627 PWUO (median age at baseline: 36 [quartile 1-3: 25-45]) were included between 2005 and 2018. We found five distinct PSU patterns, including low/infrequent probability of regular substance use (Class 1; 30%), primarily opioid and methamphetamine use (Class 2; 22%), primarily cannabis use (Class 3; 15%), primarily opioid and crack use (Class 4; 29%) and frequent PSU (Class 5; 4%). Membership in Class 2, 4 and 5 was positively associated with several behavioural and socio-structural adversities. DISCUSSION AND CONCLUSIONS: Findings of this longitudinal study suggest PSU is the norm among PWUO and highlights the heterogeneous characteristics of PWUO. The diversities within the population of PWUO need to be recognised in addiction care and treatment as well as optimising resource allocation in the response to the overdose crisis.

Experiences of violence during the COVID-19 pandemic among people who use drugs in a Canadian setting: a gender-based cross-sectional study.

OBJECTIVES: People who use drugs (PWUD) experience disproportionately high rates of violent victimization. Emerging research has demonstrated that the COVID-19 pandemic has exacerbated violence against some priority populations (e.g., women), however there is limited research examining the impact of the pandemic on the experiences of violence of PWUD. METHODS: Using data collected between July and November 2020 from three prospective cohort studies of PWUD in Vancouver, Canada, we employed multivariable logistic regression stratified by gender to identify factors associated with recent experiences of violence, including the receipt of COVID-19 emergency income support. RESULTS: In total, 77 (17.3%) of 446 men, and 54 (18.8%) of 288 women experienced violence in the previous six months. Further, 33% of men and 48% of women who experienced violence reported that their experience of violence was intensified since the COVID-19 pandemic began. In the multivariable analyses, sex work (Adjusted Odds Ratio [AOR] = 2.15, 95% confidence interval [CI]: 1.06-4.35) and moderate to severe anxiety or depression (AOR = 3.00, 95% CI: 1.37-6.57) were associated with experiencing violence among women. Among men, drug dealing (AOR = 1.93, 95%CI: 1.10-3.38), street-based income sources (AOR = 1.93, 95%CI: 1.10-3.38), homelessness (AOR = 2.54, 95%CI: 1.40-4.62), and regular employment (AOR = 2.97, 95% CI: 1.75-5.04) were associated with experiencing violence. CONCLUSION: Our study results suggest economic conditions and gender were major factors associated with experiencing violence among our sample of PWUD during COVID-19. These findings highlight criminalization of drug use and widespread socioeconomic challenges as barriers to addressing violence among PWUD during periods of crisis.

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.

The impact of the COVID-19 pandemic on access to supervised consumption programs.

BACKGROUND: Supervised consumption sites (SCS) and overdose prevention sites (OPS) have been increasingly implemented in response to the ongoing overdose epidemic in Canada. Although there has been a dramatic increase in overdose deaths since the start of the SARS-CoV 2 (COVID-19) pandemic, little is known about how SCS access may have been affected by this pandemic. Therefore, we sought to characterize potential changes in access to SCS during the COVID-19 pandemic among people who use drugs (PWUD) in Vancouver, Canada. METHODS: Between June and December 2020, data were collected through the Vancouver Injection Drug Users Study (VIDUS) and the AIDS Care Cohort to Evaluate Exposure to Survival Services (ACCESS), two cohort studies involving people who use drugs. Multivariable logistic regression was used to examine individual, social and structural factors associated with self-reported reduced frequency of SCS/OPS use since COVID-19. RESULTS: Among 428 participants, 223 (54.7%) self-identified as male. Among all individuals surveyed, 63 (14.8%) reported a decreased frequency of use of SCS/OPS since COVID-19. However, 281 (66%) reported that they "did not want to" access SCS in the last 6 months. In multivariable analyses, younger age, self-reported fentanyl contamination of drugs used and reduced ease of access to SCS/OPS since COVID-19 were positively associated with a decreased frequency of use of SCS/OPS since COVID-19 (all p < 0.05). CONCLUSIONS: Approximately 15% of PWUD who accessed SCS/OPS reported reduced use of these programs during the COVID-19 pandemic, including those at heightened risk of overdose due to fentanyl exposure. Given the ongoing overdose epidemic, efforts must be made to remove barriers to SCS access throughout public health crises.

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.

Factors associated with improvements in symptoms of anxiety and depression among gay, bisexual and other men who have sex with men (gbMSM) in Vancouver, Canada: A prospective cohort study.

BACKGROUND: Depression and anxiety are commonly experienced among gay, bisexual and other men-who-have-sex-with-men (gbMSM). We explored factors associated with improvements in mental health symptoms among gbMSM with abnormal depression and anxiety scores over a period of four years, in Vancouver, Canada. METHODS: Sexually active gbMSM ≥16 years of age were recruited using respondent-driven sampling from February 2012 to February 2015. Participants completed a computer-assisted questionnaire which included the Hospital Anxiety and Depression Scale (HADS), and psychometric scales to measure loneliness, self-esteem and social connectedness, every 6 months until July 2019. Generalized linear mixed models were used to assess factors associated with normal/borderline HADS scores (<11) following a previous abnormal score (≥11) for each of anxiety and depression subscales. RESULTS: We recruited 694 participants, of whom 580 had at least one follow-up visit. Across all visits, 43.6 % of participants ever had abnormal anxiety scores and 16.2 % ever had abnormal depression scores. Among those with abnormal anxiety scores, 34.9 % of follow-up visits demonstrated reductions in anxiety scores. Among those with abnormal depression scores 51.0 % of follow-up visits demonstrated reductions in depression scores. Reductions in anxiety scores were associated with increased self-esteem, decreased loneliness and the number of gbMSM seen/spoken to in the previous month. Reductions in depression scores were associated with increased self-esteem, decreased loneliness and having a regular partner. CONCLUSION: Improvements in mental health symptoms were frequently observed. Social connectedness was related with improved anxiety and depression symptoms. Interventions to improve social connectedness may help to improve mental health for gbMSM.

Crystal methamphetamine use and methadone maintenance treatment dissatisfaction: A prospective cohort study in Vancouver, Canada.

BACKGROUND: Patient satisfaction is key to the success of methadone maintenance treatment (MMT), and yet how MMT satisfaction is affected by the increasingly common use of crystal methamphetamine among people receiving opioid treatment remains poorly understood. We aimed to assess the association between crystal methamphetamine use and MMT dissatisfaction. METHODS: We employed generalized estimating equations to examine the relationship between crystal methamphetamine use and MMT dissatisfaction among patients receiving MMT within two prospective cohorts in Vancouver, Canada, between December 2016 and March 2020. RESULTS: Of the 836 participants receiving MMT, the median age was 47 years, and 55.3 % self-identified as male at baseline. In a multivariable model, those reporting more than weekly crystal methamphetamine use were more likely to report MMT dissatisfaction (Odds ratio: 1.40, 95 % confidence interval: 1.05-1.86) compared to those reporting less than monthly crystal methamphetamine use. CONCLUSIONS: Among our sample of people receiving MMT, we noted a positive association of frequent crystal methamphetamine use with MMT dissatisfaction. Our study suggests a need for novel strategies to better understand and address frequent methamphetamine use among those receiving MMT, particularly given recent shifts in substance use patterns involving the rising co-use of methamphetamines and opioids.

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.

Comprehensive needle and syringe program and opioid agonist therapy reduce HIV and hepatitis c virus acquisition among people who inject drugs in different settings: A pooled analysis of emulated trials.

BACKGROUND AND AIMS: Although the Netherlands, Canada and Australia were early adopters of harm reduction for people who inject drugs (PWID), their respective HIV and hepatitis C (HCV) epidemics differ. We measured the pooled effect of needle and syringe program (NSP) and opioid agonist therapy (OAT) participation on HIV and HCV incidence in these settings. DESIGN: For each cohort, we emulated the design and statistical analysis of a target trial using observational data. SETTING AND PARTICIPANTS: We included PWID at risk of HIV or HCV infection from the Amsterdam Cohort Studies (1985-2013), Vancouver Injection Drug Users Study (1997-2009) and Melbourne Injecting Drug User Cohort Study (SuperMIX) (2010-2021). MEASUREMENTS: Separately for each infection and cohort (only HCV in SuperMIX), marginal structural models were used to compare the effect of comprehensive (on OAT and 100% NSP coverage or on OAT only if no recent injection drug use) versus no/partial NSP/OAT (no OAT and/or <100% NSP coverage) participation. Pooled hazard ratios (HR) and 95% CI were calculated using random-effects meta-analysis. FINDINGS: We observed 94 HIV seroconversions and 81 HCV seroconversions among 2023 and 430 participants, respectively. Comprehensive NSP/OAT led to a 41% lower risk of HIV acquisition (pooled HR = 0.59, 95% CI = 0.36-0.96) and a 76% lower risk of HCV acquisition (pooled HR = 0.24, 95% CI = 0.11-0.51), compared with no/partial NSP/OAT, with little heterogeneity between studies for both infections (I2  = 0%). CONCLUSIONS: In the Netherlands, Canada and Australia, comprehensive needle and syringe program and opioid agonist therapy participation appears to substantially reduce HIV and hepatitis C acquisition compared with no or partial needle and syringe program/opioid agonist therapy participation. These findings from an emulated trial design reinforce the critical role of comprehensive access to harm reduction in optimizing infection prevention for people who inject drugs.

Treatment interruptions and community connectedness among gbMSM living with HIV in Metro Vancouver, Canada.

HIV treatment interruptions are a major public health concern that demonstrate a lack of engagement in care and is detrimental to the health of people living with HIV. Community connectedness have demonstrated a protective effect for psychosocial health but are not well understood for HIV treatment outcomes. We explored associations between community connectedness and treatment interruptions among gay, bisexual and other men who have sex with men (gbMSM) living with HIV in Vancouver, British Columbia. We analyzed survey data from the Momentum Health Study and identified treatment interruptions through data linkages with the provincial HIV Drug Treatment Program as episodes lasting more than 60 days beyond an expected antiretroviral therapy refill date from February 2012 to July 2019. We built a mixed-effects logistic regression model, adjusting for confounders. Of 213 gbMSM living with HIV, 54 experienced treatment interruption (25.4%) over a median five-year follow-up. Multivariable results found the number gbMSM who spoken to in the past month (aOR = 0.995; 95% CI = 0.991, 1.000 (per 100-unit increase)) and attending a gay community meeting more than once per month (aOR = 0.32; 95% CI = 0.11, 0.89) were associated with lower odds of treatment interruptions. These results highlight the importance of social connections in facilitating effective HIV care.