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Background: Nitrous oxide has shown potentially as an efficacious intervention for treatment-resistant depression, yet there remains insufficient evidence pertaining to repeated administration of nitrous oxide over time and active placebo-controlled studies with optimal blinding. Thus, we aim to examine the feasibility and preliminary efficacy of a six-week follow up study examining the effects of a 4 week course of weekly administered nitrous oxide as compared to the active placebo, midazolam. Methods: In this randomized, active placebo-controlled, pilot trial, 40 participants with treatment-resistant depression will receive either inhaled nitrous oxide (1 hour at 50% concentration) plus intravenous saline (100mL) or inhaled oxygen (1 hour at 50% concentration) plus intravenous midazolam (0.02 mg/kg in 100mL, up to 2mg) once per week, for 4 consecutive weeks. Participants will be followed up for 6 weeks starting from the first treatment visit. Primary feasibility outcomes include recruitment rate, withdrawal rate, adherence, missing data, and adverse events. The primary exploratory clinical outcome is change in Montgomery-Åsberg Depression Rating Scale (MADRS) score at day 42 of the study. Other exploratory clinical outcomes include remission (defined as MADRS score <10), response (defined as ≥ 50% reduction in MADRS score), and adverse side effects. Discussion: This pilot study will provide valuable information regarding the feasibility and preliminary efficacy of repeated nitrous oxide administration over time for treatment-resistant depression. If feasible, this study will inform the design of a future definitive trial of nitrous oxide as an efficacious and fast-acting treatment for treatment-resistant depression. Trial registration: ClinicalTrials.gov NCT04957368. Registered on July 12, 2021. [ABSTRACT FROM AUTHOR]

Background and Aims: Sudden discontinuation of buprenorphine in the treatment of opioid use disorder can increase the risk of subsequent relapse and overdose. Little is known about buprenorphine use in the perioperative period. The aim of this study was to determine the rate of buprenorphine continuation after hospital discharge following surgery and factors associated with continuation. Design: A population‐based retrospective cohort study was conducted using administrative data from Ontario, Canada, between 2012 and 2018. The cohort included individuals on continuous buprenorphine prior to surgery. Logistic regression modeling was used to estimate the association of buprenorphine continuation with demographic, opioid agonist treatment, surgical and health service use factors. Setting: Administrative databases from Institute for Clinical Evaluative Sciences (ICES) were used, which capture the Ontario, Canada, population. The data sets describe physician billing, monitoring of controlled substances and hospital discharges. Participants: Adults (≥ 18 years, n = 2176) had received a buprenorphine/naloxone product continuously for at least 60 days for the treatment of opioid use disorder and subsequently underwent a surgical procedure. Measurements Continuation (versus discontinuation) of buprenorphine prescriptions in the 14 days after surgical discharge was recommended. Exposures included demographic, comorbidity, opioid agonist treatment, surgical and health service use characteristics. Findings About 176 (8.1%) of the 2176 patients discontinued buprenorphine after surgery. Inpatient surgery (versus ambulatory) was associated with reduced odds of continuation, with an unadjusted odds ratio (OR) of 0.17 [95% confidence interval (CI) = 0.12–0.25] and an adjusted OR of 0.16 (95% CI = 0.11–0.23) after accounting for age, sex, rural residence, neighborhood income quintile, Charlson comorbidity index, psychiatric hospitalizations in the past 5 years and recent dispensed supply of buprenorphine (number needed to harm of 6.6). Conclusions: In Ontario, Canada, from 2012 to 2018, most patients receiving continuous preoperative buprenorphine therapy continued buprenorphine use after surgery. Inpatient surgery was a strong predictor of discontinuation compared with ambulatory procedures. [ABSTRACT FROM AUTHOR]

Objective: Recent Canadian data show that the prescribing of opioids has declined while the number of opioid deaths continues to rise. This study aimed to assess the relationship between neighborhood-level opioid prescription rates and opioid-related mortality among individuals without an opioid prescription. Method: This was a nested case-control study using data in Ontario from 2013 to 2019. Neighborhood-level data were analyzed by using dissemination areas that consist of 400-700 people. Cases were defined as individuals who had an opioid-related death without an opioid prescription filled in the year prior. Cases and controls were matched using a disease risk score. After matching, there were 2,401 cases and 8,813 controls. The primary exposure was the total volume of opioids dispensed within the individual's dissemination area in the 90 days before the index date. Conditional logistic regression was used to examine the association between opioid prescriptions and the risk of overdose. Results: There was no significant association between the total volume of opioid prescriptions dispensed in a dissemination area and opioid-related mortality. In subgroup analyses stratifying the cohort into prescription and nonprescription opioid-related mortality, the number of prescriptions dispensed was positively associated with prescription opioid-related mortality. There was also a significant inverse association between the increased total volume of opioids dispensed and nonprescription opioid mortality. Conclusions: Our results suggest that prescription opioids dispensed within a neighborhood can have both potential benefits and harms. The opioid epidemic requires a nuanced approach that ensures appropriate pain care for patients while also creating a safer environment for opioid use through harm-reduction strategies. [ABSTRACT FROM AUTHOR]

Introduction Cannabis and cannabinoids continue to gain popularity as adjuncts or alternatives to opioids in pain management, with evolving evidence of effectiveness. The relationship between cannabis and opioid use has previously been investigated in smaller cohorts or ecological samples, but not yet in a nationally representative sample. Methods A cross-sectional analysis of adults in the USA was undertaken using National Health and Nutrition Examination Survey (NHANES) data from 2009 to 2018. The primary exposure was self-reported use of at least one opioid-containing prescription medication in the 30 days prior to survey administration. The outcome of interest was self-reported cannabis use in the same period. Multivariable logistic regression was used to adjust for sociodemographic and health-related covariates, and NHANES survey sample weights were included in modeling. Prescription opioid users were then subclassified as short-term users (<90 days) or chronic users (=90 days) in secondary analysis. Results A total 10,928 survey respondents were included in analyses, representing 110 million adults in the USA aged 18-59. In this weighted cohort, 5.6%±0.4% reported a recent opioid prescription. Among prescription opioid users, 18.4%±3.1% reported recent cannabis use, not significantly different from 17.7%±0.7% among non-users (OR 1.05, 95% CI 0.81 to 1.36, p=0.714). After adjustment for covariates, opioid users were significantly less likely to have recently used cannabis (adjusted OR, aOR 0.70, 95% CI 0.51 to 0.97, p=0.032). When opioid users were subclassified by duration of prescription, there was no detectable difference in recent cannabis use between chronic opioid users and short-term opioid users (aOR 1.11, 95% CI 0.70 to 1.78, p=0.649). Conclusion Recent prescription opioid use was associated with decreased odds of cannabis use in this cross-sectional analysis of a nationally representative cohort. These findings suggest that use of cannabis or prescription opioids may not independently promote use of the other. [ABSTRACT FROM AUTHOR]