Principles for Primary Care Screening in the Context of Population Health.

A key component of primary care pediatrics is health promotion through screening: applying a test or procedure to detect a previously unrecognized disease or disease risk. How do we decide whether to screen? In 1965, Wilson and Jungner published an influential set of screening principles focused on the health problem's importance, the screening tool's performance, and the evidence for treatment efficacy. However, if we want realistic estimates of the population effects of routine screening, we must also account for the health care system's real-world functioning and disparities in care. We offer revised principles to guide discussions about routine screening in the primary care setting. We add to Wilson and Jungner's principles: 1. A focus on life course epidemiology and its consequences for population health, 2. A need to screen for the early stages of chronic health problems, 3. A concern for screening's acceptability to providers and the community, 4. A recommendation for estimating the uncertainty in benefits and harms in evaluating screening, 5. Inclusion of systematic plans for population data collection and monitoring, and 6. Recognition that achieving population health improvement requires a high-performing system with sufficient throughput and monitoring to deliver accessible, affordable, and effective care, especially for the groups experiencing the greatest inequities in access. Above all, instead of assuming best practices in treatment delivery and monitoring after screening, we argue for realism about the health care system functioning in routine practice.

Mortality in adolescents and young adults following a first presentation to the emergency department for alcohol.

BACKGROUND AND METHODS: We conducted a population-based, retrospective cohort study of first-time emergency department (ED) visits in adolescents and young adults (AYA) due to alcohol and compared mortality to AYA with nonalcohol ED visits between 2009 and 2015 using standardized all-cause mortality ratios (age, sex, income, and rurality). We described the cause of death for AYA and examined the association between clinical factors and mortality rates in the alcohol cohort using proportional hazard models. RESULTS: A total of 71,776 AYA had a first-time ED visit due to alcohol (56.1% male, mean age 20.7 years) between 2009 and 2015, representing 3.3% of the 2,166,838 AYA with an ED visit in this time period. At 1 year, there were 2396 deaths, 248 (10.3%) following an ED visit related to alcohol. First-time alcohol ED visits were associated with a threefold higher risk in mortality at 1 year (0.35% vs. 0.10%, adjusted hazard ratio [aHR] 3.07, 95% confidence interval [CI] 2.69-3.51). Mortality was associated with age 25-29 years (aHR 3.88, 95% CI 2.56-5.86), being male (aHR 1.98, 95% CI 1.49-2.62), having a history of mental health or substance use (aHR 3.22, 95% CI 1.64-6.32), cause of visit being withdrawal/dependence (aHR 2.81, 95% CI 1.96-4.02), and having recurrent ED visits (aHR 1.97, 95% CI 1.27-3.05). Trauma (42.7%), followed by poisonings from drugs other than opioids (38.3%), and alcohol (28.6%) were the most common contributing causes of death. CONCLUSION: Incident ED visits due to alcohol in AYA are associated with a high risk of 1-year mortality, especially in young adults, those with concurrent mental health or substance use disorders, and those with a more severe initial presentation. These findings may help inform the need and urgency for follow-up care in this population.

Components of Outpatient Child and Youth Concurrent Disorders Programs: A Critical Interpretive Synthesis: Composantes des programmes de troubles concomitants des enfants et des jeunes ambulatoires : une synthèse interprétative critique.

OBJECTIVE: Co-occurring mental health and substance use disorders (concurrent disorders) lead to significant morbidity in children and youth. Programs for integrated treatment of concurrent disorders have been developed; however, there exists little guidance outlining their structure and activities. Our objective was to synthesize available information on outpatient child and youth concurrent disorders programs and produce a comprehensive framework detailing the components of such programs. METHODS: We used a four-stage critical interpretive synthesis design: (1) systematic review of published and grey literature, (2) data abstraction to identify program components and purposive sampling to fill identified gaps, (3) organization of components into a structured framework, (4) feedback from programs. We employed an iterative process by which programs reviewed data abstraction and framework development and provided feedback. RESULTS: Through systematic review (yielding 1,408 records total and 7 records eligible for inclusion) and outreach strategies (yielding an additional 7 eligible records), we identified 11 programs (4 American, 7 Canadian) and 2 theoretical models from which data could be abstracted. Program activities were categorized into 12 overarching constructs that make up the components of the framework: accessibility, engagement, family involvement, integrated assessment, psychotherapy for patients, psychotherapy for families, medication management, health promotion, case management, vocational support, recreation and social support, and transition services. Program components are informed by the philosophical orientation of the program and models of care. This framework considers health system factors, clinical service factors, program development, and community partnership that impact program structure and activities. Multidisciplinary teams provide care and include addiction medicine, psychiatry, psychology, nursing, social work, occupational therapy, recreation therapy, peer support, and program evaluation. CONCLUSION: We developed a comprehensive framework describing components of child and youth outpatient concurrent disorders programs. This framework may assist programs currently operating, and those in development, to reflect on their structure and activities.

Trends in Rates of Opioid Agonist Treatment and Opioid-Related Deaths for Youths in Ontario, Canada, 2013-2021.

Importance: Data suggest that the opioid crisis in North America has recently been reflected in opioid-related mortality among youths. Despite recommendation for its use, youths encounter barriers to accessing OAT, including stigma, burden of witnessed dosing, and lack of availability of youth-oriented services and prescribers comfortable treating this population. Objective: To compare rates of opioid agonist treatment (OAT) and opioid-related mortality between youths aged 15 to 24 years and adults aged 25 to 44 years in Ontario, Canada, over time. Design, Setting, and Participants: This cross-sectional analysis of rates of OAT and opioid-related deaths between 2013 and 2021 used data obtained from the Ontario Drug Policy Research Network, Public Health Ontario, and Statistics Canada. Individuals included in the analysis were aged 15 to 44 years and residing in Ontario, the most populous province in Canada. Exposures: Youths aged 15 to 24 years compared with adults aged 25 to 44 years. Main Outcomes and Measures: OAT (methadone, buprenorphine, and slow-release oral morphine) per 1000 population and opioid-related deaths per 100 000 population. Results: Between 2013 and 2021, 1021 youths aged 15 to 24 years died from opioid toxicity; 710 were male (69.5%). In the final year of the study period, 225 youths (146 male [64.9%]) died from opioid toxicity, and 2717 (1494 male [55.0%]) were dispensed OAT. Over the study period, the rate of opioid-related deaths among youths in Ontario increased 369.2% from 2.6 to 12.2 per 100 000 population (48 to 225 total deaths) and the rate of OAT use decreased 55.9% from 3.4 to 1.5 per 1000 (6236 to 2717 individuals). For adults aged 25 to 44 years, the rate of opioid-related deaths increased 371.8% from 7.8 to 36.8 per 100 000 (283 to 1502 deaths), and the rate of OAT increased 27.8% from 7.9 to 10.1 per 1000 population (28 667 to 41 200 individuals). Trends for youths and adults persisted across both sexes. Conclusions and Relevance: The findings of this study suggest that opioid-related deaths are increasing among youths while OAT use is paradoxically declining. The reasons for these observed trends require further investigation, including a consideration of changing trends in opioid use and opioid use disorder among youths, barriers to OAT, and opportunities to optimize care and reduce harms for youths who use substances.

Trends in Office-Based Anxiety Treatment Among US Children, Youth, and Young Adults: 2006-2018.

BACKGROUND AND OBJECTIVES: Anxiety disorder diagnoses in office-based settings increased for children through the mid-2010s, but recent changes in diagnosis and treatment are not well understood. The objectives of the current study were to evaluate recent trends in anxiety disorder diagnosis and treatment among children, adolescents, and young adults. METHODS: This study used serial cross-sectional data from the National Ambulatory Medical Care Survey (2006-2018), a nationally representative annual survey of US office-based visits. Changes in anxiety disorder diagnosis and 4 treatment categories (therapy alone, therapy and medications, medications alone, or neither) are described across 3 periods (2006-2009, 2010-2013, 2014-2018). Multinomial logistic regression compared differences in treatment categories, adjusting for age group, sex, and race/ethnicity, contrasting the last and middle periods with the first. RESULTS: The overall proportion of office visits with an anxiety disorder diagnosis significantly increased from 1.4% (95% confidence interval [CI] 1.2-1.7; n = 9 246 921 visits) in 2006 to 2009 to 4.2% (95% CI 3.4-5.2; n = 23 120 958 visits) in 2014 to 2018. The proportion of visits with any therapy decreased from 48.8% (95% CI 40.1-57.6) to 32.6% (95% CI 24.5-41.8), but there was no significant change in the overall use of medications. The likelihood of receiving medication alone during office visits was significantly higher in the last, relative to the first period (relative risk ratio = 2.42, 95% CI 1.24-4.72). CONCLUSIONS: The proportion of outpatient visits that included a diagnosis of anxiety increased over time, accompanied by a decrease in the proportion of visits with therapy.

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.

Mirtazapine for the treatment of amphetamine and methamphetamine use disorder: A systematic review and meta-analysis.

BACKGROUND: Amphetamine-type stimulants continue to dominate the global drug markets. Despite this, no pharmacotherapy has been approved for treatment of amphetamine and methamphetamine use disorder (AMD). We evaluate the efficacy of mirtazapine in the treatment of AMD, given emerging evidence that it may alleviate methamphetamine and amphetamine (MA/A) cravings and withdrawals. METHODS: We searched five databases from inception until January 28, 2021 for studies with a comparator group evaluating mirtazapine for treatment of AMD. We collected data on reduction in MA/A use, treatment retention, sexual behaviors, depression symptoms, cravings and adverse events. We assessed certainty of evidence using GRADE. Where appropriate, we conducted fixed-effect meta-analyses weighted by inverse variance and calculated the absolute risk reduction. RESULTS: Among the 206 studies screened, we included two parallel-arm placebo-controlled RCTs conducted among cis-gender men and transgender women (n = 180). We found that mirtazapine use likely results in a small reduction of methamphetamine use compared to placebo after 12-weeks (relative risk [RR]=0.81, 95% confidence interval [CI]: 0.63, 1.03; n = 133; moderate certainty evidence due to imprecision). We also found that the use of mirtazapine probably does not improve retention in treatment (RR=1.01, 95% CI: 0.91, 1.12; n = 180; moderate certainty evidence) or depression symptom severity (mean difference [MD]=0.45, 95% CI: -2.88, 3.78; n = 53; moderate certainty evidence). There were no serious adverse events. CONCLUSIONS AND RELEVANCE: Mirtazapine probably results in a small reduction in continued methamphetamine use among cisgender men and transgender women with AMD, but probably does not improve patients' retention in treatment or depression symptom severity. STUDY REGISTRATION: PROSPERO ID: CRD42021236806.

Virtual psychiatric care fast-tracked: reflections inspired by the COVID-19 pandemic.

For many patients and healthcare providers, the move to virtual psychiatric care has been fast-tracked by the COVID-19 pandemic. In this article, we consider a patient perspective and a provider perspective on the transition to virtual psychiatric care and its strengths and limitations, as well as a call for much-needed future research.

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.

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).

Sensitivity and specificity of self-reported psychiatric diagnoses amongst patients treated for opioid use disorder.

BACKGROUND: Patients with opioid use disorder (OUD) frequently present with comorbid psychiatric illnesses which have significant implications for their treatment outcomes. Notably, these are often identified by self-report. Our study examined the sensitivity and specificity of self-reported psychiatric diagnoses against a structured diagnostic interview in a cohort of patients receiving outpatient pharmacological treatment for OUD. METHODS: Using cross-sectional data from adults receiving outpatient opioid agonist treatment for OUD in clinics across Ontario, Canada, we compared participants' self-reported psychiatric diagnoses with those identified by the Mini Neuropsychiatric Interview (MINI) Version 6.0 administered at the time of study entry. Sensitivity and specificity were calculated for self-report of psychiatric diagnoses. RESULTS: Amongst a sample of 683 participants, 24% (n = 162) reported having a comorbid psychiatric disorder. Only 104 of these 162 individuals (64%) reporting a comorbidity met criteria for a psychiatric disorder as per the MINI; meanwhile, 304 (75%) participants who self-reported no psychiatric comorbidity were in fact identified to meet MINI criteria for a psychiatric disorder. The sensitivity and specificity for any self-reported psychiatric diagnoses were 25.5% (95% CI 21.3, 30.0) and 78.9% (95% CI 73.6, 83.6), respectively. CONCLUSIONS: Our findings raise questions about the utility of self-reported psychiatric comorbidity in patients with OUD, particularly in the context of low sensitivity of self-reported diagnoses. Several factors may contribute to this including remittance and relapse of some psychiatric illnesses, underdiagnosis, and the challenge of differentiating psychiatric and substance-induced disorders. These findings highlight that other methods should be considered in order to identify comorbid psychiatric disorders in patients with OUD.

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.

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.

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

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

Exploring the Impact of Modifiable Factors on Serum BDNF in Psychiatric Patients and Community Controls.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) has been a focus of psychiatric research for the past two decades. BDNF has been shown to impact neural function and development. Studies have investigated serum BDNF as a biomarker for psychiatric disorders such as depression and schizophrenia. In some studies, investigators attempt to control for variables such as smoking status, exercise, or diet. However, the relationship between these factors and BDNF is not clearly established. Furthermore, some studies have questioned whether a difference in the impact of BDNF exists between psychiatric and healthy populations. PURPOSE: We aim to examine the association between serum BDNF levels and modifiable risk factors such as body mass index (BMI), smoking, exercise levels, and diet. Subsequently, we aim to examine whether the relationship between these risk factors and serum BDNF is different between psychiatric and control populations. PATIENTS AND METHODS: We use cross-sectional data from an age- and sex-matched case-control study of participants with psychiatric inpatients and community controls without psychiatric diagnoses. Participants completed comprehensive assessments at study enrolment including sociodemographic information, smoking status, exercise, diet, and BMI. Serum BDNF levels were collected from participants. Linear regression analysis was performed to determine the association between modifiable factors and serum BDNF level. RESULTS: A significant association was found between sedentary activity level and lower serum BDNF levels (Beta coefficient = -2.49, 95% confidence interval [CI] -4.70, -0.28, p = 0.028). Subgroup analysis demonstrated that this association held for psychiatric inpatients but not for community controls; it also held in females (Beta coefficient = -3.18, 95% CI -6.29, -0.07, p = 0.045) but not in males (Beta coefficient = -1.42, 95% CI -4.61, 1.78, p = 0.383). Antidepressant use had a significantly different association between male (Beta coefficient = 3.20, 95% CI 0.51, 5.88, p = 0.020) and female subgroups (Beta coefficient = -3.10, 95% CI -5.75, -0.46, p = 0.022). No significant association was found between other factors and serum BDNF. CONCLUSION: Sedentary activity level may lead to lower serum BDNF levels in individuals with psychiatric diagnoses. Our findings support the notion that physical activity can provide a positive impact as part of treatment for psychiatric illness.

Are patients' goals in treatment associated with expected treatment outcomes? Findings from a mixed-methods study on outpatient pharmacological treatment for opioid use disorder.

OBJECTIVES: Existing methods of measuring effectiveness of pharmacological treatment for opioid use disorder (OUD) are highly variable. Therefore, understanding patients' treatment goals is an integral part of patient-centred care. Our objective is to explore whether patients' treatment goals align with a frequently used clinical outcome, opioid abstinence. DESIGN: Triangulation mixed-methods design. SETTING AND PARTICIPANTS: We collected prospective data from 2030 participants who were receiving methadone or buprenorphine-naloxone treatment for a diagnosis of OUD in order to meet study inclusion criteria. Participants were recruited from 45 centrally-managed outpatient opioid agonist therapy clinics in Ontario, Canada. At study entry, we asked, 'What are your goals in treatment?' and used NVivo software to identify common themes. PRIMARY OUTCOME MEASURE: Urine drug screens (UDS) were collected for 3 months post-study enrolment in order to identify abstinence versus ongoing opioid use (mean number of UDS over 3 months=12.6, SD=5.3). We used logistic regression to examine the association between treatment goals and opioid abstinence. RESULTS: Participants had a mean age of 39.2 years (SD=10.7), 44% were women and median duration in treatment was 2.6 years (IQR 5.2). Six overarching goals were identified from patient responses, including 'stop or taper off of treatment' (68%), 'stay or get clean' (37%) and 'live a normal life' (14%). Participants reporting the goal 'stay or get clean' had lower odds of abstinence at 3 months than those who did not report this goal (OR=0.73, 95% CI 0.59 to 0.91, p=0.005). Although the majority of patients wanted to taper off or stop medication, this goal was not associated with opioid abstinence, nor were any of their other goals. CONCLUSIONS: Patient goals in OUD treatment do not appear to be associated with programme measures of outcome (ie, abstinence from opioids). Future studies are needed to examine outcomes related to patient-reported treatment goals found in our study; pain management, employment, and stopping/tapering treatment should all be explored.