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.

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.

Genetic basis of cannabis use: a systematic review.

BACKGROUND: With the increase in cannabis use rates, cannabis use disorder is being reported as one of the most common drug use disorders globally. Cannabis use has several known physical, psychological, and social adverse events, such as altered judgement, poor educational outcomes, and respiratory symptoms. The propensity for taking cannabis and the development of a cannabis use disorder may be genetically influenced for some individuals. Heritability estimates suggest a genetic basis for cannabis use, and several genome-wide association studies (GWASs) have identified possible regions of association, albeit with inconsistent findings. This systematic review aims to summarize the findings from GWASs investigating cannabis use and cannabis use disorder. METHODS: This systematic review incorporates articles that have performed a GWAS investigating cannabis use or cannabis use disorder. MEDLINE, Web of Science, EMBASE, CINAHL, GWAS Catalog, GWAS Central, and NIH Database of Genotype and Phenotype were searched using a comprehensive search strategy. All studies were screened in duplicate, and the quality of evidence was assessed using the quality of genetic association studies (Q-Genie) tool. All studies underwent qualitative synthesis; however, quantitative analysis was not feasible. RESULTS: Our search identified 5984 articles. Six studies met our eligibility criteria and were included in this review. All six studies reported results that met our significance threshold of p ≤ 1.0 × 10-7. In total 96 genetic variants were identified. While meta-analysis was not possible, this review identified the following genes, ANKFN1, INTS7, PI4K2B, CSMD1, CST7, ACSS1, and SCN9A, to be associated with cannabis use. These regions were previously reported in different mental health conditions, however not in relation to cannabis use. CONCLUSION: This systematic review summarized GWAS findings within the field of cannabis research. While a meta-analysis was not possible, the summary of findings serves to inform future candidate gene studies and replication efforts. Systematic Review Registration PROSPERO CRD42020176016.

Association between vaping and health outcomes in patients with opioid use disorder: a systematic review protocol.

INTRODUCTION: Vaping behaviour has increased in popularity and is particularly important to examine how it effects health outcomes in vulnerable populations, including those with opioid use disorder (OUD). With polysubstance use including cigarette and cannabis use being highly prevalent in the OUD population and cannabis/nicotine increasingly being consumed by vaping, vaping may have an important contribution to health outcomes in these individuals. The primary objective of this review is to systematically assess the literature related to patients with OUD and the effects vaping has shown on their physical and mental health. METHOD AND ANALYSIS: A systematic search of databases including MEDLINE, Embase, PsycINFO, Web of Science, Cumulative Index to Nursing and Allied Health Literature, Cochrane Library, Cochrane Clinical Trials Registry, the National Institutes for Health Clinical Trials Registry and the WHO International Clinical Trials Registry Platform from inception to 31 December 2020 will be conducted. Identified citations will be screened by two reviewers to determine eligibility at the title and abstract level, and then at the full text and data extraction phases. Any disagreements in inclusion will be resolved through unblinded discussion by these reviewers, with any remaining disagreements being resolved by a third reviewer. Data collection from eligible studies will be conducted according to the data extraction form tested prior to abstraction. Included studies will be examined for quality and bias and will be meta-analysed where applicable. This protocol is reported in keeping with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines. ETHICS AND DISSEMINATION: The results for this review will be disseminated through publications in peer-reviewed journals, posters and presentations at scientific conferences. Additionally, we are collaborating with the Canadian Addiction Treatment Centre clinics to help disseminate the findings for this review. As this is a systematic review, no ethics approval is needed. REVIEW REGISTRATION NUMBER: CRD42020178441.

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).

Genetic determinants of cannabis use: a systematic review protocol.

BACKGROUND: With the legalization of cannabis in Canada, there is an increase trend in use. Cannabis has been known to have several health implications, one of which is the development of cannabis use disorder (CUD). CUD is more common in males than females, as well as in certain ethnic groups such as Native Americans. Additionally, both environmental and genetic risk factors have been found for cannabis use. The objective of this systematic review will be to summarize the genetic variants associated with cannabis use which have reached borderline genome-wide significance. METHODS: This systematic review will incorporate articles that have performed a genome-wide association study (GWAS) investigating cannabis use. MEDLINE, Web of Science, EMBASE, GWAS Catalog, GWAS Central, and NIH Database of Genotype and Phenotype will be searched using a comprehensive search strategy. The quality of genetic association studies (Q-Genie) tool will be utilized to assess the quality of the included studies. All screening and data extraction will occur independently by two authors. If feasible, a random-effects meta-analysis will be conducted on pooled odds ratios of single nucleotide polymorphisms reaching borderline genome-wide significance. DISCUSSION: This systematic review will synthesize available GWAS on cannabis use. Results from this review will inform and direct further investigation of genetic variants associated with cannabis use. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020176016.

Feasibility of behavioral activation group therapy in reducing depressive symptoms and improving quality of life in patients with depression: the BRAVE pilot trial.

BACKGROUND: Depression impacts the lives of millions of people worldwide. Behavioral activation (BA), derived from cognitive behavioral therapy, has the potential for improving depressive symptoms in patients with depression. Studies evaluating the effectiveness of BA specifically in the context of group therapy programs in a hospital setting for patients with depression are limited. In this study, we report findings from a pilot trial evaluating group BA for major depressive disorder. OBJECTIVE: The objectives of this pilot trial are to assess the potential of a full trial of BA group therapy in a large-scale tertiary care setting and to provide preliminary information about possible results regarding mood symptoms and quality of life in adults with depression. METHODS: Using a parallel single-cohort pragmatic pilot randomized controlled trial design, we evaluated the potential of conducting a large trial of BA effectiveness among adults with depression. Participants were randomized to the intervention (BA in addition to usual care) or control (support group in addition to usual care) groups and were assessed weekly for 18 consecutive weeks. Participants randomized to intervention underwent 28 2-h group BA therapy visits administered by trained therapists and completed assessments to examine treatment outcomes. Feasibility was measured in terms of enrollment rates (min. 20%), completion rates of study (min. 80%), and completion rates of weekly measurement scales (min. 80%). The reporting of this pilot trial is in accordance with the CONSORT extension for randomized pilot and feasibility trials. RESULTS: We randomized 20 individuals of mean age of 48.8 years (standard deviation = 9.7) with a DSM-5 diagnosis of major depressive disorder to intervention (n = 10) or control (n = 10) groups. Based on our feasibility criteria, our recruitment rate was excellent (20/27; 74%), study completion was found to be a moderate (80% of the total participants in both arms completed the study; BA = 100%, control = 60%), and completeness of measurements on a weekly basis was adequate overall (82%; BA = 86%, control = 79%). CONCLUSIONS: The study has demonstrated the potential feasibility to perform a larger scale trial upon modifications to the control group to avoid the low rate of study completion (60%) in this group. TRIAL REGISTRATION: ClinicalTrials NCT02045771, Registered January 22, 2014.

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.

The association between health conditions and cannabis use in patients with opioid use disorder receiving methadone maintenance treatment.

BACKGROUND: Cannabis is the most commonly used substance among patients in methadone maintenance treatment (MMT) for opioid use disorder. Current treatment programmes neither screen nor manage cannabis use. The recent legalisation of cannabis in Canada incites consideration into how this may affect the current opioid crisis. AIMS: Investigate the health status of cannabis users in MMT. METHOD: Patients were recruited from addiction clinics in Ontario, Canada. Regression analyses were used to assess the association between adverse health conditions and cannabis use. Further analyses were used to assess sex differences and heaviness of cannabis use. RESULTS: We included 672 patients (49.9% cannabis users). Cannabis users were more likely to consume alcohol (odds ratio 1.46, 95% CI 1.04-2.06, P = 0.029) and have anxiety disorders (odds ratio 1.75, 95% CI 1.02-3.02, P = 0.043), but were less likely to use heroin (odds ratio 0.45, 95% CI 0.24-0.86, P = 0.016). There was no association between cannabis use and pain (odds ratio 0.98, 95% CI 0.94-1.03, P = 0.463). A significant association was seen between alcohol and cannabis use in women (odds ratio 1.79, 95% CI 1.06-3.02, P = 0.028), and anxiety disorders and cannabis use in men (odds ratio 2.59, 95% CI 1.21-5.53, P = 0.014). Heaviness of cannabis use was not associated with health outcomes. CONCLUSIONS: Our results suggest that cannabis use is common and associated with psychiatric comorbidities and substance use among patients in MMT, advocating for screening of cannabis use in this population. DECLARATION OF INTEREST: None.

Adverse Outcomes Associated with Prescription Opioids for Acute Low Back Pain: A Systematic Review and Meta-Analysis.

BACKGROUND: Acute low back pain (ALBP) is a common clinical complaint that can last anywhere from 24 hours to 12 weeks. In recent years, there has been an opioid epidemic which is linked to the increased availability of prescription opioids. Though guidelines recommend that in the treatment of ALBP, opioids should be used when other treatments fail, we have seen an increase in opioid prescriptions for ALBP. With this crisis, it is important to examine if there are any adverse outcomes associated with prescribing opioids for ALBP. OBJECTIVE: We aim to review the published literature to examine the adverse outcomes associated with opioid use for ALBP. STUDY DESIGN: We performed a systematic review with meta-analysis in accordance with our published protocol and PRISMA guidelines. SETTING: The review was conducted at McMaster University. METHODS: Various electronic databases for articles published from inception to September 30, 2017, inclusive. Both randomized clinical trials and observational studies on the impact of opioid use in ALBP in the adult population were included. Eight pairs of independent reviewers performed screening, data extraction, and assessment of methodological quality. The identified articles were assessed for risk of bias using sensitivity analysis. Trials with comparative outcomes were reported in a meta-analysis using a fixed effects model. RESULTS: A total of 13,889 studies were initially screened for the review and a total of 4 studies were included in the full review, of which 2 studies were meta-analyzed. Our results showed that prescribing opioids for ALBP was significantly associated with long-term continued opioid use (1.57, 95% CI, 1.06-2.33). There was no significant association found between unemployment duration and prescribing opioids for ALBP (3.54, 95% CI, -7.57 to 14.66). LIMITATIONS: Due to the limited number of studies that considered unemployment, only an unpooled analysis was conducted. Among the included studies there was both statistical and clinical heterogeneity due to differences in methodology, study design, risk of selection or performance bias. Most of the studies had an unclear or high risk of bias and poorly defined side effects. CONCLUSIONS: Due to the lack of literature examining long-term adverse outcomes associated with prescribing opioids for ALBP, no definitive conclusions can be made. However, with the literature available, there does seem to be risk associated with prescribing opioids for ALBP so there is a great need to conduct further investigations examining these adverse outcomes for ALBP patients. KEY WORDS: Acute low back pain, opioids, prescriptions, low back pain, long-term use, opioid use disorder.