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.

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.

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.

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.

A systematic review of GWAS identified SNPs associated with outcomes of medications for opioid use disorder.

BACKGROUND: Patients with opioid use disorder (OUD) display an interindividual variability in their response to medications for opioid use disorder (MOUD). A genetic basis may explain the variability in this response. However, no consensus has been reached regarding which genetic variants significantly contribute to MOUD outcomes. OBJECTIVES: This systematic review aims to summarize genome-wide significant findings on MOUD outcomes and critically appraise the quality of the studies involved. METHODS: Databases searched from inception until August 21st, 2020 include: MEDLINE, Web of Science, EMBASE, CINAHL and Pre-CINAHL, GWAS Catalog and GWAS Central. The included studies had to be GWASs that assessed MOUD in an OUD population. All studies were screened in duplicate. The quality of the included studies was scored and assessed using the Q-Genie tool. Quantitative analysis, as planned in the protocol, was not feasible, so the studies were analyzed qualitatively. RESULTS: Our search identified 7292 studies. Five studies meeting the eligibility criteria were included. However, only three studies reported results that met our significance threshold of p ≤ 1.0 × 10-7. In total, 43 genetic variants were identified. Variants corresponding to CNIH3 were reported to be associated with daily heroin injection in Europeans, OPRM1, TRIB2, and ZNF146 with methadone dose in African Americans, EYS with methadone dose in Europeans, and SPON1 and intergenic regions in chromosomes 9 and 3 with plasma concentrations of S-methadone, R-methadone, and R-EDDP, respectively, in Han Chinese. LIMITATIONS: The limitations of this study include not being able to synthesize the data in a quantitative way and a conservative eligibility and data collection model. CONCLUSION: The results from this systematic review will aid in highlighting significant genetic variants that can be replicated in future OUD pharmacogenetics research to ascertain their role in patient-specific MOUD outcomes. Systematic review registration number CRD42020169121.

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.

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.

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.

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.

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.

Treatment Outcomes in Patients With Opioid Use Disorder Who Were First Introduced to Opioids by Prescription: A Systematic Review and Meta-Analysis.

OBJECTIVE: Prescription opioid misuse has led to a new cohort of opioid use disorder (OUD) patients who were introduced to opioids through a legitimate prescription. This change has caused a shift in the demographic profile of OUD patients from predominantly young men to middle age and older people. The management of OUD includes medication-assisted treatment (MAT), which produces varying rates of treatment response. In this study, we will examine whether the source of first opioid use has an effect on treatment outcomes in OUD. Using a systematic review of the literature, we will investigate the association between source of first opioid introduction and treatment outcomes defined as continuing illicit opioid use and poly-substance use while in MAT. METHODS: Medline, EMBASE, CINHAL, and PsycInfo were searched from inception to December 31st, 2019 inclusive using a comprehensive search strategy. Five pairs of reviewers conducted screening and data extraction independently in duplicate. The review is conducted and reported according to the PRISMA guidelines. A random-effects model was used for meta analyses assuming heterogeneity among the included studies. RESULTS: The initial search results in 27,345 articles that were screened, and five observational studies were included in the qualitative and quantitative analyses. Our results found that those who were introduced to opioids through a legitimate prescription were significantly less likely to have illicit opioid use (0.70, 95% CI 0.50, 0.99) while on MAT. They were also less likely to use cannabis (0.54, 95% CI 0.32, 0.89), alcohol (0.75, 95% CI 0.59, 0.95), cocaine (0.50, 95% CI 0.29, 0.85), and injection drug use (0.25, 95% CI 0.14, 0.43) than those introduced to opioids through recreational means. CONCLUSION: This study shows that the first exposure to opioids, whether through a prescription or recreationally, influences prognosis and treatment outcomes of opioid use disorder. Although the increased pattern of prescribing opioids may have led to increased OUD in a new cohort of patients, these patients are less likely to continue to use illicit drugs and have a different prognostic and clinical profile that requires a tailored approach to treatment. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42017058143.

GWAS-identified genetic variants associated with medication-assisted treatment outcomes in patients with opioid use disorder: a systematic review and meta-analysis protocol.

BACKGROUND: The burden of opioid use disorder (OUD) has been increasing in North America. Administration of medication-assisted treatments (MATs) for OUD on an individual-dose basis has been shown to affect patient responses to treatment, proving to be, on occasion, dangerous. A genetic basis has been identified for some MAT responses in a candidate gene context, but consensus has not been reached for any genome-wide significant associations. This systematic review aims to identify and assess any genetic variants associated with MAT patient outcomes at genome-wide significance. METHODS: The databases searched by the authors will be: MEDLINE, Web of Science, EMBASE, CINAHL and Pre-CINAHL, GWAS Catalog, GWAS Central, and NIH Database of Genotypes and Phenotypes. A title and abstract screening, full-text screening, data extraction, and quality assessment will be completed in duplicate for each study via Covidence. Treatment outcomes of interest include continued opioid use or abstinence during treatment or at follow-up, time to relapse, treatment retention rates, opioid overdose, other substance use, comorbid psychiatric disorders, risk taking behaviors, MAT plasma concentrations, and mortality rates. Analysis methods applied, if appropriate, will include random effects meta-analysis with pooled odds ratios for all outcomes. Subgroup analyses will also be implemented, when possible. DISCUSSION: This systematic review can hopefully inform the direction of future research, aiding in the development of a safer and more patient-centered treatment. It will be able to highlight genome-wide significant variants that are replicable and associated with MAT patient outcomes. SYSTEMATIC REVIEW REGISTRATION: This systematic review protocol has been registered with the International Prospective Register of Systematic Reviews (PROSPERO) (registration ID CRD42020169121).

National suicide management guidelines with family as an interv'ention and suicide mortality rates: a systematic review protocol.

INTRODUCTION: Suicidal behaviour remains a major public health challenge worldwide. Several countries have developed national suicide guidelines aimed at raising awareness of and preventing deaths by suicide. One of the interventions often mentioned in these national guidelines is the involvement of family members as a protective factor in suicide prevention. However, the level or type of family involvement required to reduce suicidal behaviour is not well understood. Thus, in this systematic review, we seek to determine the effectiveness of family-based interventions as a suicide prevention tool, by comparing suicide mortality rates between countries whose national suicide prevention guidelines include family-based interventions and those whose do not. METHODS AND ANALYSIS: MEDLINE, EMBASE, PsycINFO, Web of Science and WHO MiNDbank databases as well as grey literature such as National Guideline Clearinghouse will be searched. National guidelines for suicide prevention published within the last 20 years (between 1999 and 2019) will be included. Results will be analysed using thematic and qualitative analyses. ETHICS AND DISSEMINATION: The findings of the study will help improve the efficacy of national suicide prevention strategies. Findings will be disseminated using easily accessible summary reports and resources to primary end users. PROSPERO REGISTRATION NUMBER: This protocol has been registered on PROSPERO (CRD42019130195).

The impact of chronic liver disease in patients receiving active pharmacological therapy for opioid use disorder: One-year findings from a prospective cohort study.

INTRODUCTION: Despite the demonstrated benefit of methadone, the incidence opioid-related overdose, and its associated mortality continues to rise at an alarming rate. The impact of high prevalence comorbid features such as chronic liver disease (CLD) on methadone treatment response remain unclear. AIM: To determine whether CLD is associated with poor response to methadone treatment. METHODS: Using a well-established multi-center cohort from the Genetics of Opioid Addiction Study (GENOA), we evaluated if presence of CLD among 1234 eligible patients with opioid use disorder receiving methadone treatment impacted health and behavioural responses to treatment. CLD was classified as any liver disorder/dysfunction present for a minimum period of six months. Serial urine toxicology assessments were used to determine treatment response. The effect of CLD was determined using a multi-variable logistic regression model. RESULTS: CLD was present in 25 % (n = 314) of the population. On average, patients with CLD were found to be older (mean age 44 vs 36 years, p < 0.0001), unemployed (81.8 % vs 61 %, p < 0.0001), and receiving government disability benefits at significantly higher rates (21.9 % vs 11 %, p < 0.0001). Increased levels of physical craving, emotional stress, as well as health risk behaviors were noted in CLD patients. Findings from the multi-variable model demonstrate a 68 % increased risk for dangerous opioid consumption behaviors (Odds Ration [OR]: 1.68, 95 % Confidence Interval [CI] 1.22, 2.31, p = 0.001) among patients with CLD. Methadone dose (OR: 0.76, 95 % CI 0.70, 0.81, p < 0.0001) was shown to be protective with a significant risk reduction of 24 % per 20 mg increase in methadone. Duration in treatment was also found to be protective (OR: 0.99, 95 % CI 0.97, 0.99, p < 0.0001). CONCLUSION: CLD poses a distinct risk for patients with opioid addiction. Closer drug monitoring, and substance use contingency management should be considered to reduce mortality risk in these patients.