The impact of the COVID-19 pandemic on people who use drugs in three Canadian cities: a cross-sectional analysis.

BACKGROUND: The COVID-19 pandemic had a disproportionate impact on the health and wellbeing of people who use drugs (PWUD) in Canada. However less is known about jurisdictional commonalities and differences in COVID-19 exposure and impacts of pandemic-related restrictions on competing health and social risks among PWUD living in large urban centres. METHODS: Between May 2020 and March 2021, leveraging infrastructure from ongoing cohorts of PWUD, we surveyed 1,025 participants from Vancouver (n = 640), Toronto (n = 158), and Montreal (n = 227), Canada to describe the impacts of pandemic-related restrictions on basic, health, and harm reduction needs. RESULTS: Among participants, awareness of COVID-19 protective measures was high; however, between 10 and 24% of participants in each city-specific sample reported being unable to self-isolate. Overall, 3-19% of participants reported experiencing homelessness after the onset of the pandemic, while 20-41% reported that they went hungry more often than usual. Furthermore, 8-33% of participants reported experiencing an overdose during the pandemic, though most indicated no change in overdose frequency compared the pre-pandemic period. Most participants receiving opioid agonist therapy in the past six months reported treatment continuity during the pandemic (87-93%), however, 32% and 22% of participants in Toronto and Montreal reported missing doses due to service disruptions. There were some reports of difficulty accessing supervised consumption sites in all three sites, and drug checking services in Vancouver. CONCLUSION: Findings suggest PWUD in Canada experienced difficulties meeting essential needs and accessing some harm reduction services during the COVID-19 pandemic. These findings can inform preparedness planning for future public health emergencies.

Integrated supervised consumption services and hepatitis C testing and treatment among people who inject drugs in Toronto, Canada: A cross-sectional analysis.

Despite the availability of publicly funded hepatitis C (HCV) treatment in Canada, treatment gaps persist, particularly among people who inject drugs. We estimate correlates of HCV care cascade engagement (testing, diagnosis, and treatment) among people who inject drugs in Toronto, Canada and examine the effect of accessing differing supervised consumption service (SCS) models on self-reported HCV testing and treatment. This is a cross-sectional baseline analysis of 701 people who inject drugs surveyed in the Toronto, Ontario integrated Supervised Injection Services (OiSIS-Toronto) study between November 2018 and March 2020. We examine correlates of self-reported HCV care cascade outcomes including SCS model, demographic, socio-structural, drug use, and harm reduction characteristics. Overall, 647 participants (92%) reported ever receiving HCV testing, of whom 336 (52%) had been diagnosed with HCV. Among participants who reported ever being diagnosed with HCV, 281 (84%) reported chronic HCV, of whom 130 (46%) reported HCV treatment uptake and 151 (54%) remained untreated. Compared to those with no SCS use, participants who had ever injected at an integrated SCS model with co-located HCV care had greater prevalence of both ever receiving HCV testing (adjusted prevalence ratio [aPR]: 1.12, 95% confidence interval [CI]: 1.02-1.24) and ever receiving HCV treatment (aPR: 1.67, 95% CI: 1.04-2.69). Over half of participants diagnosed with chronic HCV reported remaining untreated. Our findings suggest that integrated SCS models with co-located HCV care represent key strategies for linkage to HCV care, but that more is needed to support scale-up.

Controlled-release hydromorphone and risk of infection in adults: a systematic review.

BACKGROUND: Preliminary evidence suggests that people who inject drugs (PWID) may be at an increased risk of developing infective endocarditis (IE), hepatitis C virus (HCV) infection, and/or human immunodeficiency virus (HIV) infection from hydromorphone controlled-release formulation. The hypothesized mechanism is related to insolubility of the drug, which promotes reuse, leading to contamination of injecting equipment. However, this relationship has not been confirmed. We aimed to conduct a systematic review including adult PWID exposed to controlled-release hydromorphone and the risk of acquiring IE, HCV, and HIV. METHODS: We searched MEDLINE, EMBASE, and Evidence Based Medicine reviews from inception until September 2021. Following pilot testing, two reviewers conducted all screening of citations and full-text articles, as well as abstracted data, and appraised risk of bias using the Newcastle-Ottawa scale and Effective Practice and Organization of Care tool. Equity issues were examined using the PROGRESS-PLUS framework. Discrepancies were resolved consistently by a third reviewer. Meta-analysis was not feasible due to heterogeneity across the studies. RESULTS: After screening 3,231 citations from electronic databases, 722 citations from unpublished sources/reference scanning, and 626 full-text articles, five studies were included. Five were cohort studies, and one was a case-control study. The risk of bias varied across the studies. Two studies reported on gender, as well as other PROGRESS-PLUS criteria (race, housing, and employment). Three studies focused specifically on the controlled-release formulation of hydromorphone, whereas two studies focused on all formulations of hydromorphone. One retrospective cohort study found an association between controlled-release hydromorphone and IE, whereas a case-control study found no evidence of an association. One retrospective cohort study found an association between the number of hydromorphone controlled-release prescriptions and prevalence of HCV. None of the studies specifically reported on associations with HIV. DISCUSSION: Very few studies have examined the risk of IE, HCV, and HIV infection after exposure to controlled-release hydromorphone. Very low-quality and scant evidence suggests uncertainty around the risks of blood-borne infections, such as HCV and IE to PWID using this medication.

Length of initial prescription at hospital discharge and long-term medication adherence for elderly, post-myocardial infarction patients: a population-based interrupted time series study.

BACKGROUND: Preliminary evidence suggests that providing longer duration prescriptions at discharge may improve long-term adherence to secondary preventative cardiac medications among post-myocardial infarction (MI) patients. We implemented and assessed the effects of two hospital-based interventions-(1) standardized prolonged discharge prescription forms (90-day supply with 3 repeats for recommended cardiac medications) plus education and (2) education only-on long-term cardiac medication adherence among elderly patients post-MI. METHODS: We conducted an interrupted time series study of all post-MI patients aged 65-104 years in Ontario, Canada, discharged from hospital between September 2015 and August 2018 with ≥ 1 dispensation(s) for a statin, beta blocker, angiotensin system inhibitor, and/or secondary antiplatelet within 7 days post-discharge. The standardized prolonged discharge prescription forms plus education and education-only interventions were implemented at 2 (1,414 patients) and 4 (926 patients) non-randomly selected hospitals in September 2017 for 12 months, with all other Ontario hospitals (n = 143; 18,556 patients) comprising an external control group. The primary outcome, long-term cardiac medication adherence, was defined at the patient-level as an average proportion of days covered (over 1-year post-discharge) ≥ 80% across cardiac medication classes dispensed at their index fill. Primary outcome data were aggregated within hospital groups (intervention 1, 2, or control) to monthly proportions and independently analyzed using segmented regression to evaluate intervention effects. A process evaluation was conducted to assess intervention fidelity. RESULTS: At 12 months post-implementation, there was no statistically significant effect on long-term cardiac medication adherence for either intervention-standardized prolonged discharge prescription forms plus education (5.4%; 95% CI - 6.4%, 17.2%) or education only (1.0%; 95% CI - 28.6%, 30.6%)-over and above the counterfactual trend; similarly, no change was observed in the control group (- 0.3%; 95% CI - 3.6%, 3.1%). During the intervention period, only 10.8% of patients in the intervention groups received ≥ 90 days, on average, for cardiac medications at their index fill. CONCLUSIONS: Recognizing intervention fidelity was low at the pharmacy level, and no statistically significant post-implementation differences in adherence were found, the trends in this study-coupled with other published retrospective analyses of administrative data-support further evaluation of this simple intervention to improve long-term adherence to cardiac medications. TRIAL REGISTRATION: ClinicalTrials.gov : NCT03257579 , registered June 16, 2017 Protocol available at: https://pubmed.ncbi.nlm.nih.gov/33146624/ .

Validation of Self-reported Opioid Agonist Treatment Among People Who Inject Drugs Using Prescription Dispensation Records.

BACKGROUND: Studies of people who inject drugs (PWID) commonly use questionnaires to determine whether participants are currently, or have recently been, on opioid agonist treatment for opioid use disorder. However, these previously unvalidated self-reported treatment measures may be susceptible to inaccurate reporting. METHODS: We linked baseline questionnaire data from 521 PWID in the Ontario integrated Supervised Injection Services cohort in Toronto (November 2018-March 2020) with record-level health administrative data. We assessed the validity (sensitivity, specificity, positive and negative predictive value [PPV and NPV]) of self-reported recent (in the past 6 months) and current (as of interview) opioid agonist treatment with methadone or buprenorphine-naloxone relative to prescription dispensation records from a provincial narcotics monitoring system, considered the reference standard. RESULTS: For self-reported recent opioid agonist treatment, sensitivity was 78% (95% CI = 72, 83), specificity was 90% (95% CI = 86, 94), PPV was 90% (95% CI = 85, 93), and NPV was 79% (95% CI = 74, 84). For self-reported current opioid agonist treatment, sensitivity was 84% (95% CI = 78, 90), specificity was 87% (95% CI = 83, 91), PPV was 74% (95% CI = 67, 81), and NPV was 93% (95% CI = 89, 95). CONCLUSIONS: Self-reported opioid agonist treatment measures were fairly accurate among PWID, with some exceptions. Inaccurate recall due to a lengthy lookback window may explain underreporting of recent treatment, whereas social desirability bias may have led to overreporting of current treatment. These validation data could be used in future studies of PWID to adjust for misclassification in similar self-reported treatment measures.

Association Between Depressive Symptoms or Depression and Health Outcomes for Low Back Pain: a Systematic Review and Meta-analysis.

BACKGROUND: Study results vary on whether depressive symptoms are associated with worse prognosis for low back pain (LBP). We assessed the association between depressive symptoms or depression and health outcomes in persons with LBP. METHODS: We searched MEDLINE, Embase, CINAHL, and PsycINFO from inception to June 2020. Eligible studies were cohort and case-control studies assessing the association between depressive symptoms (questionnaires) or depression (diagnoses) and health outcomes in persons aged ≥16 years with LBP in the absence of major pathology. Reviewers independently screened articles, extracted data, and assessed risk of bias using the Quality in Prognosis Studies tool. We classified exploratory versus confirmatory studies based on phases of prognostic factor investigation. We conducted random-effects meta-analyses and descriptive synthesis where appropriate. RESULTS: Of 13,221 citations screened, we included 62 studies (63,326 participants; 61 exploratory studies, 1 confirmatory study). For acute LBP, depressive symptoms were associated with self-reported disability (descriptive synthesis: 6 studies), worse recovery (descriptive synthesis: 5 studies), and slower traffic injury-related claim closure (1 study), but not pain or work-related outcomes. Depressive symptoms were associated with greater primary healthcare utilization for acute LBP (1 confirmatory study). For chronic LBP, depressive symptoms were associated with higher pain intensity (descriptive synthesis: 9 studies; meta-analysis: 3 studies, 2902 participants, ß=0.11, 95% confidence interval (CI) 0.05-0.17), disability (descriptive synthesis: 6 studies; meta-analysis: 5 studies, 3549 participants, ß=0.16, 95% CI 0.04-0.29), and worse recovery (descriptive synthesis: 2 studies; meta-analysis: 2 studies, 13,263 participants, relative risk (RR)=0.91, 95% CI 0.88-0.95), but not incident chronic widespread pain (1 study). DISCUSSION: Depressive symptoms may be associated with self-reported disability and worse recovery in persons with acute and chronic LBP, and greater primary healthcare utilization for acute LBP. Our review provides high-quality prognostic factor information for LBP. Healthcare delivery that addresses depressive symptoms may improve disability and recovery in persons with LBP. Confirmatory studies are needed to assess the association between depressive symptoms and health outcomes in persons with LBP. PROTOCOL REGISTRATION: PROSPERO database (CRD42019130047).

Impacts of two behavior change interventions on determinants of medication adherence: process evaluation applying the health action process approach and habit theory alongside a randomized controlled trial.

Investigating the mechanisms of behavior change interventions provides a more fulsome understanding of how and why interventions work (or don't work). We assessed mechanisms of two interventions (mailouts alone, and mailouts plus telephone support, informed by the Health Action Process Approach (HAPA) and Habit Theory), designed to increase medication adherence after myocardial infarction. We conducted a process evaluation alongside a pragmatic trial. Medication adherence was assessed via self-report at 12-months in the trial, and participants in all trial groups were invited to contemporaneously complete an additional questionnaire assessing targeted mechanisms (HAPA constructs and automaticity). We used multiple regression-based mediation models to investigate indirect effects. Of 589 respondents, 497 were analyzed (92 excluded due to missing data). Mailouts plus telephone support had statistically significant but small effects on intention, social support, action planning, coping planning, and automaticity. There were no indirect effects of interventions on medication adherence via these constructs. Therefore, while this intervention led to changes in proposed mechanisms, these changes were not great enough to lead to behavior change. Refinements (and subsequent evaluation) of the interventions are warranted, and our findings indicate that this could involve offering more intensive support to form plans and identify cues for taking medications, in addition to providing physical supports to encourage self-monitoring, feedback, and habit formation. Trial registration: ClinicalTrials.gov: NCT02382731.

Comparative Efficacy and Safety of Ultra-Long-Acting, Long-Acting, Intermediate-Acting, and Biosimilar Insulins for Type 1 Diabetes Mellitus: a Systematic Review and Network Meta-Analysis.

BACKGROUND: Increasing availability of competing biosimilar alternatives makes it challenging to make treatment decisions. The purpose of this review is to evaluate the comparative efficacy and safety of ultra-long-/long-/intermediate-acting insulin products and biosimilar insulin compared to human/animal insulin in adults with type 1 diabetes mellitus (T1DM). METHODS: MEDLINE, EMBASE, CENTRAL, and grey literature were searched from inception to March 27, 2019. Randomized controlled trials (RCTs), quasi-experimental studies, and cohort studies of adults with T1DM receiving ultra-long-/long-/intermediate-acting insulin, compared to each other, as well as biosimilar insulin compared to human/animal insulin were eligible for inclusion. Two reviewers independently screened studies, abstracted data, and appraised risk-of-bias. Pairwise meta-analyses and network meta-analyses (NMA) were conducted. Summary effect measures were mean differences (MD) and odds ratios (OR). RESULTS: We included 65 unique studies examining 14,200 patients with T1DM. Both ultra-long-acting and long-acting insulin were superior to intermediate-acting insulin in reducing A1c, FPG, weight gain, and the incidence of major, serious, or nocturnal hypoglycemia. For fasting blood glucose, long-acting once a day (od) was superior to long-acting twice a day (bid) (MD - 0.44, 95% CI: - 0.81 to - 0.06) and ultra-long-acting od was superior to long-acting bid (MD - 0.73, 95% CI - 1.36 to - 0.11). For weight change, long-acting od was inferior to long-acting bid (MD 0.58, 95% CI: 0.05 to 1.10) and long-acting bid was superior to long-action biosimilar od (MD - 0.90, 95% CI: - 1.67 to - 0.12). CONCLUSIONS: Our results can be used to tailor insulin treatment according to the desired results of patients and clinicians and inform strategies to establish a competitive clinical market, address systemic barriers, expand the pool of potential suppliers, and favor insulin price reduction. PROSPERO REGISTRATION: CRD42017077051.

The Ontario Integrated Supervised Injection Services Cohort Study of People Who Inject Drugs in Toronto, Canada (OiSIS-Toronto): Cohort Profile.

The Ontario Integrated Supervised Injection Services cohort in Toronto, Canada (OiSIS-Toronto) is an open prospective cohort of people who inject drugs (PWID). OiSIS-Toronto was established to evaluate the impacts of supervised consumption services (SCS) integrated within three community health agencies on health status and service use. The cohort includes PWID who do and do not use SCS, recruited via self-referral, snowball sampling, and community/street outreach. From 5 November 2018 to 19 March 2020, we enrolled 701 eligible PWID aged 18+ who lived in Toronto. Participants complete interviewer-administered questionnaires at baseline and semi-annually thereafter and are asked to consent to linkages with provincial healthcare administrative databases (90.2% consented; of whom 82.4% were successfully linked) and SCS client databases. At baseline, 86.5% of participants (64.0% cisgender men, median ([IQR] age= 39 [33-49]) had used SCS in the previous 6 months, of whom most (69.7%) used SCS for <75% of their injections. A majority (56.8%) injected daily, and approximately half (48.0%) reported fentanyl as their most frequently injected drug. As of 23 April 2021, 291 (41.5%) participants had returned for follow-up. Administrative and self-report data are being used to (1) evaluate the impact of integrated SCS on healthcare use, uptake of community health agency services, and health outcomes; (2) identify barriers and facilitators to SCS use; and (3) identify potential enhancements to SCS delivery. Nested sub-studies include evaluation of "safer opioid supply" programs and impacts of COVID-19.

Developing an explanatory theoretical model for engagement with a web-based mental health platform: results of a mixed methods study.

BACKGROUND: With the growing need for accessible, high-quality mental health services, especially during the COVID-19 pandemic, there has been increasing development and uptake of web-based interventions in the form of self-directed mental health platforms. The Big White Wall (BWW) is a web-based platform for people experiencing mental illness and addiction that offers a range of evidence-based self-directed treatment strategies. Drawing on existing data from a large-scale evaluation of the implementation of BWW in Ontario, Canada (which involved a pragmatic randomized controlled trail with an embedded qualitative process evaluation), we sought to investigate the influences on the extent to which people engage with BWW. METHODS: In this paper we drew on BWW trial participants' usage data (number of logins) and the qualitative data from the process evaluation that explored participants' experiences, engagement with and reactions to BWW. RESULTS: Our results showed that there were highly complex relationships between the influences that contributed to the level of engagement with BWW intervention. We found that a) how people expected to benefit from using a platform like BWW was an important indicator of their future usage, b) moderate perceived symptoms were linked with higher engagement; whereas fewer actual depressive symptoms predicted use and anxiety had a positive linear relationship with usage, and that c) usage depended on positive early experiences with the platform. CONCLUSIONS: Our findings suggest that the nature of engagement with platforms such as BWW is not easily predicted. We propose a theoretical framework for explaining the level of user engagement with BWW that might also be generalizable to other similar platforms.

Feasibility of an Electronic Health Tool to Promote Physical Activity in Primary Care: Pilot Cluster Randomized Controlled Trial.

BACKGROUND: Physical inactivity is associated with increased health risks. Primary care providers (PCPs) are well positioned to support increased physical activity (PA) levels through screening and provision of PA prescriptions. However, PCP counseling on PA is not common. OBJECTIVE: This study aimed to assess the feasibility of implementing an electronic health (eHealth) tool to support PA counseling by PCPs and estimate intervention effectiveness on patients' PA levels. METHODS: A pragmatic pilot study was conducted using a stepped wedge cluster randomized trial design. The study was conducted at a single primary care clinic, with 4 pre-existing PCP teams. Adult patients who had a periodic health review (PHR) scheduled during the study period were invited to participate. The eHealth tool involved an electronic survey sent to participants before their PHR via an email or a tablet; data were used to automatically produce tailored resources and a PA prescription in the electronic medical record of participants in the intervention arm. Participants assigned to the control arm received usual care from their PCP. Feasibility was assessed by the proportion of completed surveys and patient-reported acceptability and fidelity measures. The primary effectiveness outcome was patient-reported PA at 4 months post-PHR, measured as metabolic equivalent of task (MET) minutes per week. Secondary outcomes assessed determinants of PA, including self-efficacy and intention to change based on the Health Action Process Approach behavior change theory. RESULTS: A total of 1028 patients receiving care from 34 PCPs were invited to participate and 530 (51.55%) consented (intervention [n=296] and control [n=234]). Of the participants who completed a process evaluation, almost half (88/178, 49.4%) stated they received a PA prescription, with only 42 receiving the full intervention including tailored resources from their PCP. A cluster-level linear regression analysis yielded a non-statistically significant positive difference in MET-minutes reported per week at follow-up between intervention and control conditions (mean difference 1027; 95% CI -155 to 2209; P=.09). No statistically significant differences were observed for secondary outcomes. CONCLUSIONS: Our results suggest that it is feasible to build an eHealth tool that screens and provides tailored resources for PA in a primary care setting but suboptimal intervention fidelity suggests greater work must be done to address PCP barriers to resource distribution. Participant responses to the primary effectiveness outcome (MET-minutes) were highly variable, reflecting a need for more robust measures of PA in future trials to address limitations in patient-reported data. TRIAL REGISTRATION: ClinicalTrials.gov NCT03181295; https://clinicaltrials.gov/ct2/show/NCT03181295.

Extending access to a web-based mental health intervention: who wants more, what happens to use over time, and is it helpful? Results of a concealed, randomized controlled extension study.

BACKGROUND: Web-based mental health applications may be beneficial, but adoption is often low leaving optimal implementation and payment models unclear. This study examined which users were interested in extended access to a web-based application beyond an initial 3-month trial period and evaluated if an additional 3 months of access was beneficial. METHODS: This study was a concealed extension of a multi-center, pragmatic randomized controlled trial that assessed the benefit of 3 months of access to the Big White Wall (BWW), an anonymous web-based moderated, multi-component mental health application offering self-directed activities and peer support. Trial participants were 16 years of age or older, recruited from hospital-affiliated mental health programs. Participants who received access to the intervention in the main trial and completed 3-month outcome assessments were offered participation. We compared those who were and were not interested in an extension of the intervention, and re-randomized consenting participants 1:1 to receive extended access or not over the subsequent 3 months. Use of the intervention was monitored in the extension group and outcomes were measured at 3 months after re-randomization in both groups. The primary outcome was mental health recovery as assessed by total score on the Recovery Assessment Scale (RAS-r), as in the main trial. Linear mixed models were used to examine the time by group interaction to assess for differences in responses over the 3-month extension study. RESULTS: Of 233 main trial participants who responded, 119 (51.1%) indicated an interest in receiving extended BWW access. Those who were interested had significantly higher baseline anxiety symptoms compared to those who were not interested. Of the 119, 112 were re-randomized (55 to extended access, 57 to discontinuation). Only 21 of the 55 extended access participants (38.2%) used the intervention during the extension period. Change in RAS-r scores over time was not significantly different between groups (time by group, F(1,77) = 1.02; P = .31). CONCLUSIONS: Only half of eligible participants were interested in extended access to the intervention with decreasing use over time, and no evidence of added benefit. These findings have implications for implementation and payment models for this type of web-based mental health intervention. TRIAL REGISTRATION: Clinicaltrials.gov NCT02896894 . Registered retrospectively on September 12, 2016.

Measuring the frequency and variation of unnecessary care across Canada.

BACKGROUND: Through the Choosing Wisely Canada (CWC) campaign, national medical specialty societies have released hundreds of recommendations against health care services that are unnecessary, i.e. present little to no benefit or cause avoidable harm. Despite growing interest in unnecessary care both within Canada and internationally, prior research has typically avoided taking a national or even multi-jurisdictional approach in measuring the extent of the issue. This study estimates use of three unnecessary services identified by CWC recommendations across multiple Canadian jurisdictions. METHODS: Two retrospective cohort studies were conducted using administrative health care data collected between fiscal years 2011/12 and 2012/13 to respectively quantify use of 1) diagnostic imaging (spinal X-ray, CT or MRI) among Albertan patients following a visit for lower back pain and 2) cardiac tests (electrocardiogram, chest X-ray, stress test, or transthoracic echocardiogram) prior to low-risk surgical procedures in Alberta, Saskatchewan, and Ontario. A cross-sectional study of the 2012 Canadian Community Health Survey was also conducted to estimate 3) the proportion of females aged 40-49 that reported having a routine mammogram in the past two years. RESULTS: Use of unnecessary care was relatively frequent across all three services and jurisdiction measured: 30.7% of Albertan patients had diagnostic imaging within six months of their initial visit for lower back pain; a cardiac test preceded 17.9 to 35.5% of low-risk surgical procedures across Alberta, Saskatchewan, and Ontario; and 22.2% of Canadian women aged 40-49 at average-risk for breast cancer reported having a routine screening mammogram in the past two years. CONCLUSIONS: The use of potentially unnecessary care appears to be common in Canada. This investigation provides methodology to facilitate future measurement efforts that may incorporate additional jurisdictions and/or unnecessary services.

A Web-Based Mental Health Platform for Individuals Seeking Specialized Mental Health Care Services: Multicenter Pragmatic Randomized Controlled Trial.

BACKGROUND: Web-based self-directed mental health applications are rapidly emerging to address health service gaps and unmet needs for information and support. OBJECTIVE: The aim of this study was to determine if a multicomponent, moderated Web-based mental health application could benefit individuals with mental health symptoms severe enough to warrant specialized mental health care. METHODS: A multicenter, pragmatic randomized controlled trial was conducted across several outpatient mental health programs affiliated with 3 hospital programs in Ontario, Canada. Individuals referred to or receiving treatment, aged 16 years or older, with access to the internet and an email address, and having the ability to navigate a Web-based mental health application were eligible. A total of 812 participants were randomized 2:1 to receive immediate (immediate treatment group, ITG) or delayed (delayed treatment group, DTG) access for 3 months to the Big White Wall (BWW), a multicomponent Web-based mental health intervention based in the United Kingdom and New Zealand. The primary outcome was the total score on the Recovery Assessment Scale, revised (RAS-r) which measures mental health recovery. Secondary outcomes were total scores on the Patient Health Questionnaire-9 item (PHQ-9), the Generalized Anxiety Disorder Questionnaire-7 item (GAD-7), the EuroQOL 5-dimension quality of life questionnaire (EQ-5D-5L), and the Community Integration Questionnaire. An exploratory analysis examined the association between actual BWW use (categorized into quartiles) and outcomes among study completers. RESULTS: Intervention participants achieved small, statistically significant increases in adjusted RAS-r score (4.97 points, 95% CI 2.90 to 7.05), and decreases in PHQ-9 score (-1.83 points, 95% CI -2.85 to -0.82) and GAD-7 score (-1.55 points, 95% CI -2.42 to -0.70). Follow-up was achieved for 55% (446/812) at 3 months, 48% (260/542) of ITG participants and 69% (186/270) of DTG participants. Only 58% (312/542) of ITG participants logged on more than once. Some higher BWW user groups had significantly greater improvements in PHQ-9 and GAD-7 relative to the lowest use group. CONCLUSIONS: The Web-based application may be beneficial; however, many participants did not engage in an ongoing way. This has implications for patient selection and engagement as well as delivery and funding structures for similar Web-based interventions. TRIAL REGISTRATION: ClinicalTrials.gov NCT02896894; https://clinicaltrials.gov/ct2/show/NCT02896894 (Archived by WebCite at http://www.webcitation.org/78LIpnuRO).

Mediation analysis with a time-to-event outcome: a review of use and reporting in healthcare research.

BACKGROUND: Mediation analysis tests whether the relationship between two variables is explained by a third intermediate variable. We sought to describe the usage and reporting of mediation analysis with time-to-event outcomes in published healthcare research. METHODS: A systematic search of Medline, Embase, and Web of Science was executed in December 2016 to identify applications of mediation analysis to healthcare research involving a clinically relevant time-to-event outcome. We summarized usage over time and reporting of important methodological characteristics. RESULTS: We included 149 primary studies, published from 1997 to 2016. Most studies were published after 2011 (n = 110, 74%), and the annual number of studies nearly doubled in the last year (from n = 21 to n = 40). A traditional approach (causal steps or change in coefficient) was most commonly taken (n = 87, 58%), and the majority of studies (n = 114, 77%) used a Cox Proportional Hazards regression for the outcome. Few studies (n = 52, 35%) mentioned any of the assumptions or limitations fundamental to a causal interpretation of mediation analysis. CONCLUSION: There is increasing use of mediation analysis with time-to-event outcomes. Current usage is limited by reliance on traditional methods and the Cox Proportional Hazards model, as well as low rates of reporting of underlying assumptions. There is a need for formal criteria to aid authors, reviewers, and readers reporting or appraising such studies.

Prescribed safer opioid supply: A scoping review of the evidence.

BACKGROUND: Safer opioid supply programs provide prescription pharmaceutical opioids, often with supportive services, to people at high risk of experiencing harms related to substance use. However, questions regarding the effectiveness and safety of this practice remain. We conducted a scoping review of literature describing client outcomes from formal opioid supply programs providing prescriptions for pharmaceutical opioids, and the perceptions of involved clients/providers. METHODS: We performed a scoping review of peer-reviewed studies and grey literature published between January 1, 2012, to September 12, 2023. We included articles reporting either safer opioid supply client outcomes or clients/providers perspectives. Extracted data included study objectives, substance use patterns, client outcomes, client/provider perspectives, and estimates of effectiveness and/or harm. RESULTS: Our search yielded 1,597 articles. Following removal of duplicates and application of exclusion criteria, 24 publications comprising 17 peer-reviewed and seven grey literature publications were included in our study. We generated eight themes summarizing topics in the available literature: opioid-related toxicities, infectious complications, other clinical outcomes, client-reported outcomes, program access barriers, diversion, program retention, and costs to the healthcare system. Specific findings included low rates of opioid toxicities, improved physical and mental health, and improved quality of life among clients. A lack of access to adequate opioid doses and the limited range of opioid options offered within safer opioid supply programs was described by clients and providers as a potential reason for diversion and a barrier to program access. CONCLUSIONS: Generally, evidence suggests that safer opioid supply programs are beneficial to clients through measurable outcomes. However, the available literature has important limitations, including limited inferences about the effectiveness, safety, and potential for diversion within safer opioid supply programs. Further research is needed to support the ongoing evaluation of safer opioid supply programs as one component of a multifactorial response to escalating rates of substance-related harms.

A cross-sectional assessment of injection of "salts" and HIV transmission-related behaviours among a cohort of people who inject drugs in Kyrgyzstan.

INTRODUCTION: Despite the increasing availability of new psychoactive substances (hereafter referred to as "salts") in Eastern Europe and Central Asia, there is a dearth of epidemiological data on the relationship between injecting "salts" and HIV risk behaviours. This is particularly relevant in settings where injection drug use accounts for a substantial proportion of the HIV burden, such as in Kyrgyzstan, a former Soviet Republic. This study assessed whether injecting "salts" is associated with sexual and injection-related HIV risk behaviours among people who inject drugs in Kyrgyzstan. METHODS: The Kyrgyzstan InterSectional Stigma Study is a cohort of people who inject drugs in Kyrgyzstan's capital of Bishkek and the surrounding rural administrative division of Chuy Oblast. We conducted a cross-sectional analysis using survey data collected from cohort participants between July and November 2021, which included information on injection drug use (including "salts") and HIV risk behaviours. To minimize confounding by measured covariates, we used inverse-probability-weighted logistic and Poisson regression models to estimate associations between recent "salt" injection and HIV risk behaviours. RESULTS: Of 181 participants included in the analysis (80.7% men, 19.3% women), the mean age was 40.1 years (standard deviation [SD] = 8.8), and 22% (n = 39) reported that they had injected "salts" in the past 6 months. Among people who injected "salts," 72% (n = 28) were men, and most were ethnically Russian 59% (n = 23), with a mean age of 34.6 (SD = 9.6). Injecting "salts" was significantly associated with a greater number of injections per day (adjusted relative risk [aRR] = 1.59, 95% confidence interval [CI] = 1.30-1.95) but lower odds of using syringe service programmes in the past 6 months (adjusted odds ratio [aOR] = 0.20, 95% CI = 0.12-0.32). Injecting "salts" was also significantly associated with lower odds of condomless sex in the past 6 months (aOR = 0.42, 95% CI = 0.24-0.76) and greater odds of having ever heard of pre-exposure prophylaxis (aOR = 4.80, 95% CI = 2.61-8.83). CONCLUSIONS: (PWID) people who inject drugs who inject "salts" are a potentially emergent group with increased HIV acquisition risk in Kyrgyzstan. Targeted outreach bundled with comprehensive harm reduction and pre-exposure prophylaxis services are needed to prevent transmission of HIV and other blood-borne viruses.

Validation of case-ascertainment algorithms using health administrative data to identify people who inject drugs in Ontario, Canada.

OBJECTIVES: Health administrative data can be used to improve the health of people who inject drugs by informing public health surveillance and program planning, monitoring, and evaluation. However, methodological gaps in the use of these data persist due to challenges in accurately identifying injection drug use (IDU) at the population level. In this study, we validated case-ascertainment algorithms for identifying people who inject drugs using health administrative data in Ontario, Canada. STUDY DESIGN AND SETTING: Data from cohorts of people with recent (past 12 months) IDU, including those participating in community-based research studies or seeking drug treatment, were linked to health administrative data in Ontario from 1992 to 2020. We assessed the validity of algorithms to identify IDU over varying look-back periods (ie, all years of data [1992 onwards] or within the past 1-5 years), including inpatient and outpatient physician billing claims for drug use, emergency department (ED) visits or hospitalizations for drug use or injection-related infections, and opioid agonist treatment (OAT). RESULTS: Algorithms were validated using data from 15,241 people with recent IDU (918 in community cohorts and 14,323 seeking drug treatment). An algorithm consisting of ≥1 physician visit, ED visit, or hospitalization for drug use, or OAT record could effectively identify IDU history (91.6% sensitivity and 94.2% specificity) and recent IDU (using 3-year look back: 80.4% sensitivity, 99% specificity) among community cohorts. Algorithms were generally more sensitive among people who inject drugs seeking drug treatment. CONCLUSION: Validated algorithms using health administrative data performed well in identifying people who inject drugs. Despite their high sensitivity and specificity, the positive predictive value of these algorithms will vary depending on the underlying prevalence of IDU in the population in which they are applied.

Centralized Triage of Suspected Coronary Artery Disease Using Coronary Computed Tomographic Angiography to Optimize the Diagnostic Yield of Invasive Angiography.

Background: Coronary computed tomographic angiography (CCTA) is preferable to invasive coronary angiography (ICA) for coronary artery disease (CAD) diagnosis in elective patients without known CAD. Methods: We conducted a nonrandomized interventional study involving 2 tertiary care centres in Ontario. From July 2018 to February 2020, outpatients referred for elective ICA were identified through a centralized triage process and were recommended to undergo CCTA first instead of ICA. Patients with borderline or obstructive CAD on CCTA were recommended to undergo subsequent ICA. Intervention acceptability, fidelity, and effectiveness were assessed. Results: A total of 226 patients were screened, with 186 confirmed to be eligible, of whom 166 had patient and physician approval to proceed with CCTA (89% acceptability). Among consenting patients, 156 (94%) underwent CCTA first; 43 (28%) had borderline/obstructive CAD on CCTA, and only 1 with normal/nonobstructive CAD on CCTA was referred for subsequent ICA against protocol (99% fidelity). Overall, 119 of 156 CCTA-first patients did not have ICA within the following 90 days (i.e., 76% potentially avoided ICA, due to the intervention). Among the 36 who underwent ICA post-CCTA per protocol, 24 had obstructive CAD (66.7% diagnostic yield). If all patients who were referred for and underwent ICA at either centre between July 2016 and February 2020 (n = 694 pre-implementation; n = 333 post-implementation) had had CCTA first, an additional 42 patients per 100 would have had an obstructive CAD finding on their ICA (95% confidence interval = 26-59). Conclusion: A centralized triage process, in which elective outpatients referred for ICA are instead referred for CCTA first, appears to be acceptable and effective in diagnosing obstructive CAD and improving efficiencies in our healthcare system.

Contexte: La coronarographie par tomodensitométrie (coro-TDM) est préférable à la coronarographie invasive chez les patients sans coronaropathie connue chez qui le diagnostic d'une coronaropathie n'est pas urgent. Méthodologie: Nous avons réalisé une étude interventionnelle non randomisée dans deux centres de soins tertiaires en Ontario. Les patients ambulatoires pour qui une coronarographie invasive non urgente a été demandée entre juillet 2018 et février 2020 ont été recensés par un processus centralisé de triage et se sont fait recommander de subir d'abord une coro-TDM. Les patients qui présentaient une co-ronaropathie obstructive ou dont les résultats se trouvaient tout juste à la limite de ce diagnostic lors de la coro-TDM se faisaient recommander une coronarographie invasive subséquente. L'acceptabilité de l'intervention, sa fidélité et son efficacité ont été évaluées. Résultats: Au total, 226 patients ont été sélectionnés et 186 ont été jugés admissibles. Parmi ces derniers, 166 ont accepté de subir la coro-TDM recommandée par le médecin (acceptabilité de 89 %). Parmi les patients ayant donné leur consentement, 156 (94 %) se sont d'abord soumis à une coro-TDM, et 43 (28 %) présentaient une coronaropathie obstructive ou des résultats limites selon cet examen. Seulement un patient ne présentant pas de coronaropathie ou présentant une coronaropathie non obstructive à la coro-TDM a été orienté vers une coronarographie invasive subséquente, contrairement au protocole (fidélité de 99 %). En tout, 119 des 156 patients s'étant d'abord soumis à une coro-TDM n'ont pas eu à subir une coronarographie invasive dans les 90 jours suivants (76 % d'entre eux ont potentiellement évité une coronarographie invasive grâce à cette première intervention). Parmi les 36 patients qui ont subi une coronarographie invasive après la coro-TDM, comme le recommandait le protocole, 24 présentaient une coronaropathie obstructive (rendement diagnostique de 66,7 %). Si tous les patients qui ont été orientés vers une coronarographie invasive et qui se sont soumis à cet examen dans l'un ou l'autre des centres entre juillet 2016 et février 2020 (n = 694 avant l'instauration; n = 333 après l'instauration) avaient d'abord passé une coro-TDM, une coronaropathie obstructive aurait été décelée lors de la coronarographie invasive chez 42 patients de plus par tranche de 100 patients (intervalle de confiance à 95 % : 26 à 59). Conclusion: Le recours à un processus de triage centralisé permettant de faire d'abord passer une coro-TDM aux patients ambulatoires dans une situation non urgente qui doivent subir une coronarographie invasive semble être un moyen acceptable et efficace de diagnostiquer la coronaropathie obstructive et d'améliorer l'efficacité dans notre système de santé.

First-line opioid agonist treatment as prevention against assisting others in initiating injection drug use: A longitudinal cohort study of people who inject drugs in Vancouver, Canada.

Background: Among people who inject drugs, frequent injecting and experiencing withdrawal are associated with facilitating others' first injections. As these factors may reflect an underlying substance use disorder, we investigated whether first-line oral opioid agonist treatment (OAT; methadone or buprenorphine/naloxone) reduces the likelihood that people who inject drugs help others initiate injecting. Methods: We used questionnaire data from semi-annual visits between December 2014-May 2018 on 334 people who inject drugs with frequent non-medical opioid use in Vancouver, Canada. We estimated the effect of current first-line OAT on subsequent injection initiation assistance provision (i.e., helped someone initiate injecting in the following six months) using inverse-probability-weighted estimation of repeated measures marginal structural models to reduce confounding and informative censoring by time-fixed and time-varying covariates. Results: By follow-up visit, 54-64% of participants reported current first-line OAT whereas 3.4-6.9% provided subsequent injection initiation assistance. Per the primary weighted estimate (n = 1114 person-visits), participants currently on first-line OAT (versus no OAT) were 50% less likely, on average, to subsequently help someone initiate injecting (relative risk [RR]=0.50, 95% CI=0.23-1.11). First-line OAT was associated with reduced risk of subsequent injection initiation assistance provision in participants who, at baseline, injected opioids less than daily (RR=0.15, 95% CI=0.05-0.44) but not in those who injected opioids daily (RR=0.86, 95% CI=0.35-2.11). Conclusions: First-line OAT seemingly reduces the short-term likelihood that people who inject drugs facilitate first injections. However, the extent of this potential effect remains uncertain due to imprecise estimation and observed heterogeneity by baseline opioid injecting frequency.