Primary outcome reporting in clinical trials for older adults with depression.

BACKGROUND: Findings from randomised controlled trials (RCTs) are synthesised through meta-analyses, which inform evidence-based decision-making. When key details regarding trial outcomes are not fully reported, knowledge synthesis and uptake of findings into clinical practice are impeded. AIMS: Our study assessed reporting of primary outcomes in RCTs for older adults with major depressive disorder (MDD). METHOD: Trials published between 2011 and 2021, which assessed any intervention for adults aged ≥65 years with a MDD diagnosis, and that specified a single primary outcome were considered for inclusion in our study. Outcome reporting assessment was conducted independently and in duplicate with a 58-item checklist, used in developing the CONSORT-Outcomes statement, and information in each RCT was scored as 'fully reported', 'partially reported' or 'not reported', as applicable. RESULTS: Thirty-one of 49 RCTs reported one primary outcome and were included in our study. Most trials (71%) did not fully report over half of the 58 checklist items. Items pertaining to outcome analyses and interpretation were fully reported by 65% or more of trials. Items reported less frequently included: outcome measurement instrument properties (varied from 3 to 30%) and justification of the criteria used to define clinically meaningful change (23%). CONCLUSIONS: There is variability in how geriatric depression RCTs report primary outcomes, with omission of details regarding measurement, selection, justification and definition of clinically meaningful change. Outcome reporting deficiencies may hinder replicability and synthesis efforts that inform clinical guidelines and decision-making. The CONSORT-Outcomes guideline should be used when reporting geriatric depression RCTs.

A drink equals how many cigarettes? Equating mortality risks from alcohol and tobacco use in Canada.

Objective: To quantify and communicate risk equivalencies for alcohol-and tobacco-attributable mortality by comparing per standard drinks consumed to per number of cigarettes smoked in Canada. Methods: Alcohol-and tobacco-attributable premature deaths (≤75 years of age) and years of life lost (YLL) were estimated using a lifetime risk modeling approach. Alcohol-attributable death statistics were obtained from the 2023 Canadian Guidance on Alcohol and Health data source. Tobacco-attributable death statistics were derived from the Mortality Population Risk Tool (MPoRT) model. Results: The risk of alcohol use on premature death and YLL increased non-linearly with the number of drinks consumed, while the risk for tobacco use on these two measures increased linearly with the number of cigarettes smoked. Males who consumed 5 drinks/day-a standard drink contains 13.45 grams of alcohol in Canada-had an equivalent risk as smoking 4.9 cigarettes/day (when modeling for premature death) and 5.1 cigarettes/day (when modeling for YLL). Females who consumed 5 drinks/day experienced an equivalent risk as smoking 4.2 cigarettes/day for premature deaths and YLL. At all levels of alcohol consumption females and males who consumed <5 drinks/day have less risks from consuming a standard drink than from smoking a cigarette. For males who consumed 5 drinks/day, the increased risks of death from per drink consumed and per cigarette smoked were equal. Conclusion: Risk equivalencies comparing alcohol use to tobacco use could help people who drink improve their knowledge and understanding of the mortality risks associated with increased number of drinks consumed per day.

Why do only some cohort studies find health benefits from low volume alcohol use? A systematic review and meta-analysis of study characteristics that may bias mortality risk estimates.

OBJECTIVE: Assumptions about alcohol's health benefits profoundly influence global disease burden estimates and drinking guidelines. Utilising theory and evidence, we identify and test study characteristics that may bias estimates of all-cause mortality risk associated with low volume drinking. METHOD: We identified 107 longitudinal studies by systematic review with 724 estimates of association between alcohol consumption and all-cause mortality for 4,838,825 participants with 425,564 recorded deaths. "Higher quality" studies had a mean cohort age of ≤55 years, followed-up beyond 55 years, and excluded former and occasional drinkers from abstainer reference groups. "Low volume" alcohol use was defined as between one drink per week (>1.30g ethanol/day) and two drinks per day (<25g ethanol/day). Mixed linear regression was used to model relative risks (RRs) of mortality for subgroups of higher versus lower quality studies. RESULTS: As predicted, studies with younger cohorts and separating former and occasional drinkers from abstainers estimated similar mortality risk for low volume drinkers (RR=0.98, 0.87-1.11) as abstainers. Studies not meeting these quality criteria estimated significantly lower risk for low volume drinkers (RR=0.84, 0.79-0.89). In exploratory analyses, studies controlling for smoking and/or socio-economic status had significantly reduced mortality risks for low volume drinkers. However, mean RR estimates for low volume drinkers in non-smoking cohorts were above 1.0 (RR=1.16, 0.91-1.41). CONCLUSIONS: Studies with lifetime selection biases may create misleading positive health associations. These biases pervade the field of alcohol epidemiology and can confuse communications about health risks. Future research should investigate whether smoking status mediates, moderates or confounds alcohol-mortality risk relationships.

A systematic review of relative risks for the relationship between chronic alcohol use and the occurrence of disease.

Alcohol use is causally linked to the development of and mortality from numerous diseases. The aim of this study is to provide an update to a previous systematic review of meta-analyses that quantify the sex-specific dose-response risk relationships between chronic alcohol use and disease occurrence and/or mortality. An updated systematic search of multiple databases was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria to identify meta-analyses published from January 1, 2017, to March 8, 2021, which quantified the risk relationships between chronic alcohol use and the risk of disease occurrence and/or mortality. This systematic review was not preregistered. The comparator was people who have never consumed at least one standard drink of alcohol. Measurements included relative risks, odds ratios, and hazard ratios of disease occurrence and/or mortality based on long-term alcohol intake measured in grams per day. The systematic search yielded 5953 articles, of which 14 were included in the narrative review. All diseases showed an increased risk of occurrence as alcohol use increased. At all doses examined, alcohol had a significant detrimental effect on tuberculosis, lower respiratory infections, oral cavity and pharyngeal cancers, esophageal cancer, colorectal cancer, liver cancer, laryngeal cancer, epilepsy, hypertension, liver cirrhosis, and pancreatitis (among men). For ischemic heart disease, ischemic stroke, and intracerebral hemorrhage, protective effects from low-dose chronic alcohol use among both men and women were observed. Low-dose alcohol consumption also had a protective effect for diabetes mellitus and pancreatitis among women (approximately to 50 g/day and 30 g/day, respectively). Alcohol use increases the risk of numerous infectious and noncommunicable diseases in a dose-response manner. Higher levels of alcohol use have a clear detrimental impact on health; however, at lower levels of use, alcohol can have both disease-specific protective and detrimental effects.

Heterogeneity across outcomes reported in clinical trials for older adults with depression: a systematic survey.

OBJECTIVES: The objective of our study was to identify outcomes reported in trials for older adults with depression and describe outcome heterogeneity. STUDY DESIGN AND SETTING: We searched four databases to identify trials assessing any intervention for major depressive disorder among older adults published between 2011 and 2021. We grouped reported outcomes thematically and mapped them onto core outcome areas (physiological/clinical, life impact, resource use, adverse events, and death) and used descriptive analysis to summarize outcome heterogeneity. RESULTS: There were 434 total outcomes reported by 49 included trials, which were measured using 135 different outcome measurement instruments and grouped into 100 unique outcome terms. Most outcome terms mapped to the physiological/clinical core area (47%), followed by life impact (42%). More than half of all terms (53%) were reported by only a single study. Most trials (n = 31/49) reported a single, discernible primary outcome. The most commonly reported outcome "depressive symptom severity" was assessed by 36 studies using 19 different outcome measurement instruments. CONCLUSION: There is substantial heterogeneity in the outcomes and outcome measurement instruments used in geriatric depression trials. A standard set of outcomes and accompanying measurement tools is necessary to facilitate comparison and synthesis of trial findings.

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

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

The Inclusion of Patients' Reported Outcomes to Inform Treatment Effectiveness Measures in Opioid Use Disorder. A Systematic Review.

Introduction: Patient centred care is needed now more than ever in the treatment of opioid use disorder. Trials, policy makers, and service providers have most often used treatment retention and opioid urine screens as measures of treatment effectiveness. However, patients receiving medication for opioid use disorder treatment (MOUD) may prioritise the use of different ways to assess treatment success. Objective: The aim of this review is to synthesize literature examining the self-reported goals patients would like to achieve in MOUD for opioid use disorder. Methods: We searched MEDLINE, EMBASE, PsycINFO, Cumulative Index to Nursing and Allied Health Literature, Web of Science, Cochrane Library, Cochrane Clinical Trials Registry, the National Institutes for Health Clinical Trials Registry, and the WHO International Clinical Trials Registry Platform from inception until April 30th, 2021. No restrictions were placed on language, age, or type of MOUD. A qualitative synthesis is presented given that a meta-analysis was not possible. Results: The search yielded a total of 21,082 records from which 8 met criteria for inclusion in the qualitative synthesis. We identified a total of 43 patient-reported treatment goals from the 8 studies. Twelve domains were created from the 43 goals reported. These domains cover a range of important areas for patients' goals related to living a normal life, physical health, mental health, treatment, and substance use specific areas. Conclusion: This review highlights several patient goals that they would like to achieve during treatment for opioid use disorder that are not commonly considered as markers of treatment effectiveness. Goals related to health, living a normal life, and overall substance use concerns by patients should be taken into consideration by clinical trialists, researchers, policy makers, service providers, patients, and communities engaged in developing and tailoring treatment plans for opioid use disorder. Systematic Review Registration: PROSPERO CRD42018095553.

National suicide management guidelines recommending family-based prevention, intervention and postvention and their association with suicide mortality rates: systematic review.

BACKGROUND: Suicidal behaviour remains a major public health concern and countries have responded by authoring guidelines to help mitigate death by suicide. Guidelines can include family-based recommendations, but evidence for the level and category of family-based involvement that is needed to effectively prevent suicide is unclear. AIMS: To explore the association between family-based recommendations in guidelines and countries' crude suicide rates. PROSPERO registration: CRD42019130195. METHOD: MEDLINE, Embase, PsycInfo, Web of Science and WHO MiNDbank databases and grey literature were searched within the past 20 years (1 January 2000 to 22 June 2020) for national guidelines giving family-based recommendations in any of three categories (prevention, intervention and postvention). RESULTS: We included 63 guidelines from 46 countries. All identified guidelines included at least one family-based recommendation. There were no statistically significant differences seen between mean World Health Organization crude suicide rates for countries that included only one, two or all three categories of family-based recommendations. However, a lower spread of crude suicide rates was seen when guideline recommendations included all three categories (mean crude suicide rates for one category: 11.09 (s.d. = 5.71); for two categories: 13.42 (s.d. = 7.76); for three categories: 10.68 (s.d. = 5.20); P = 0.478). CONCLUSIONS: Countries should work towards a comprehensive national suicide guideline that includes all categories of family-based recommendations. Countries with previously established guidelines should work towards the inclusion of evidence-based recommendations that have clear implementation plans to potentially help lower suicide rates.

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

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

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

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

Delirium and other neuropsychiatric manifestations of COVID-19 infection in people with preexisting psychiatric disorders: a systematic review.

BACKGROUND: Psychiatric disorders increase risk of neuropsychiatric disease and poor outcomes, yet little is known about the neuropsychiatric manifestations of COVID-19 in the psychiatric population. The primary objective is to synthesize neuropsychiatric outcomes of COVID-19 in people with preexisting psychiatric disorders. METHODS: Data were collected during an ongoing review of the impact of pandemics on people with existing psychiatric disorders. All study designs and gray literature were included. Medline, PsychInfo, CINAHL, EMBASE, and MedRx were searched from inception to September 1 2020. Risk of bias was assessed using a published tool that can accommodate all study types. Two independent authors screened the studies and extracted data. Data were narratively synthesized, as there were insufficient data to meta-analyze. Evidence was appraised according to GRADE. RESULTS: Four case reports were included, comprising 13 participants from three countries. Many large-sample, relevant papers were omitted for not reporting psychiatric history, despite reporting other comorbidities. Included participants (n = 13) were hospitalized with COVID-19 and appeared to meet criteria for delirium. Myoclonus, rigidity, and alogia were also reported. The most commonly reported preexisting psychiatric diagnoses were mood disorders, schizophrenia, and alcohol use disorder. CONCLUSIONS: People with preexisting psychiatric disorders may experience delirium, rigidity, myoclonus, and alogia during COVID-19 infection; although higher quality and longitudinal data are needed to better understand these phenomena. Relevant COVID-19 literature does not always report psychiatric history, despite heightened neuropsychiatric vulnerability within this population. TRIAL REGISTRATION:  PROSPERO (CRD42020179611).

Outcomes reported in randomised controlled trials of major depressive disorder in older adults: protocol for a methodological review.

INTRODUCTION: Major depressive disorder (MDD or depression) is prevalent among adults aged 65 years and older. The effectiveness and safety of interventions used to treat depression is often assessed through randomised controlled trials (RCTs). However, heterogeneity in the selection, measurement and reporting of outcomes in RCTs renders comparisons between trial results, interpretability and generalisability of findings challenging. There is presently no core outcome set (COS) for use in RCTs that assess interventions for older adults with MDD. We will conduct a methodological review of the literature for outcomes reported in trials for adults 65 years and older with depression to assess the heterogeneity of outcome measures. METHODS AND ANALYSIS: RCTs evaluating pharmacotherapy, psychotherapy, or any other treatment intervention for older adults with MDD published in the last 10 years will be located using electronic database searches (MEDLINE, Embase, PsycINFO and the Cochrane Central Register of Controlled Trials). Reviewers will conduct title and abstract screening, full-text screening and data extraction of trials eligible for inclusion independently and in duplicate. Outcomes will be synthesised and mapped to core outcome-domain frameworks. We will summarise characteristics associated with trials and outcomes. ETHICS AND DISSEMINATION: We hope that findings from our methodological review will reduce variability in outcome selection, measurement and reporting and facilitate the development of a COS for older adults with MDD. Our review will also inform evidence synthesis efforts in identifying the best treatment practices for this clinical population. Ethics approval is not required, as this study is a literature review. PROSPERO REGISTRATION NUMBER: CRD42021244753.

Corrigendum to 'A comparison of electronically-delivered and face to face cognitive behavioural therapies in depressive disorders: A systematic review and meta-analysis' [EClinicalMedicine 24 (2020) 100442].

[This corrects the article DOI: 10.1016/j.eclinm.2020.100442.].

The Role of Perceived Social Support in the Association Between Stressful Life Events and Suicidal Behavior.

Background: Suicide is a serious public health concern for which there have been well-established protective and risk factors reported in literature. There is a lack of evidence on the indirect effects of other variables on these factors. Specifically, the association between stressful life events and suicidal behavior may be affected by perceived social support, but its role in this association is largely uninvestigated. Objectives: Thus, this paper aims to explore the role of perceived social support in the association between stressful life events and suicidal behavior. Perceived social support will be explored as a mediator and as a moderator in this association. Methods: Data were obtained from the Determinants of Suicidal Behavior Conventional and Emergent Risk (DISCOVER), a study conducted to identify risk factors of suicidal behavior. The study participants are individuals with suicide attempts admitted to hospital. Participants (n = 343) were recruited from hospital setting. Suicidal behavior was measured using two outcomes (1) the occurrence of a suicide attempt (2) level of suicide intent as measured by the Pierce Suicide Intent Scale. Perceived social support was measured using the Sarason Social Support Questionnaire. Results: Stressful life events were significantly associated with suicide attempts (OR 1.440, 95% CI 1.440, 1.682, p < 0.001) and perceived social support (B -0.785, 95% CI -1.501, -0.068, p = 0.032). There was no significant mediation effect by perceived social support in the association between stressful life events and suicide attempts (Sobel's test statistic 1.64, p = 0.100). Perceived social support did not moderate the relationship between stressful life events and suicide attempts [(OR 1.007, 95% CI 0.987, 1.027, p = 0.514] or the relationship between stressful life events and level of suicidal intent (B -0.043, 95% CI -0.132, 0.046, p = 0.343). Conclusion: Stressful life events are associated with increased risk of suicide attempts. The study also identified an inverse relationship between stressful life events and perceived social support. These associations were independent of perceived social support. This study highlights the effects of stressful life events on suicide risk is not affected by perceived social support, requiring further investigation into measures to reduce the impact of social stressors on people with risk of suicide.

Factors affecting participant recruitment and retention in borderline personality disorder research: a feasibility study.

BACKGROUND: Previous studies have shown that stigma is a major barrier to participation in psychiatric research and that individuals who participate in psychiatric research may differ clinically and demographically from non-participants. However, few studies have explored research recruitment and retention challenges in the context of personality disorders. AIM: To provide an analysis of the factors affecting participant recruitment and retention in a study of borderline personality disorder among general psychiatric inpatients. METHODS: Adult inpatients in a tertiary psychiatric hospital were approached about participating in a cross-sectional study of borderline personality disorder. Recruitment rates, retention rates, and reasons for declining participation or withdrawing from the study were collected. Demographic characteristics were compared between participants and non-participants and between patients who remained in the study and those who withdrew. RESULTS: A total of 71 participants were recruited into the study between January 2018 and March 2020. Recruitment and retention rates were 45% and 70%, respectively. Lack of interest was the most commonly cited reason for non-participation, followed by scheduling conflicts and concerns regarding mental/physical well-being. Age and sex were not predictors of study participation or retention. CONCLUSIONS: More research is needed to explore patients' perspectives and attitudes towards borderline personality disorder diagnosis and research, determine effects of different recruitment strategies, and identify clinical predictors of recruitment and retention in personality disorder research.

Investigating and addressing the immediate and long-term consequences of the COVID-19 pandemic on patients with substance use disorders: a scoping review and evidence map protocol.

INTRODUCTION: The COVID-19 pandemic has driven unprecedented social and economic reform in efforts to curb the impact of disease. Governments worldwide have legislated non-essential service shutdowns and adapted essential service provision in order to minimise face-to-face contact. We anticipate major consequences resulting from such policies, with marginalised populations expected to bear the greatest burden of such measures, especially those with substance use disorders (SUDs). METHODS AND ANALYSIS: We aim to conduct (1) a scoping review to summarise the available evidence evaluating the impact of the COVID-19 pandemic on patients with SUDs, and (2) an evidence map to visually plot and categorise the current available evidence evaluating the impact of COVID-19 on patients with SUDs to identify gaps in addressing high-risk populations. ETHICS AND DISSEMINATION: Ethics approval is not required for this scoping review as we plan to review publicly available data. This is part of a multistep project, whereby we intend to use the findings generated from this review in combination with data from an ongoing prospective cohort study our team is leading, encompassing over 2000 patients with SUDs receiving medication-assisted therapy in Ontario prior to and during the COVID-19 pandemic.

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

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

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

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

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

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

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

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