Sexually transmitted and blood-borne infection risk reduction with methadone and buprenorphine/naloxone among people with prescription-type opioid use disorder: Findings from a Canadian pragmatic randomized trial.

INTRODUCTION: People who use drugs are disproportionally affected by sexually transmitted and blood-borne infections (STBBIs). While the benefits of methadone in reducing injecting-risk behaviours are well documented, less is known on its impacts on sexual-related risks, as well as its comparative effectiveness to buprenorphine/naloxone, particularly in the context of highly potent opioids. The aim of this study was to estimate the relative effects of buprenorphine/naloxone and methadone on injecting and STBBI risks among people with prescription-type opioid use disorder (POUD). METHODS: Secondary analysis of a pan-Canadian pragmatic 24-week randomized clinical trial comparing methadone and buprenorphine/naloxone models of care among 272 people with POUD (including licit or illicit opioid analgesics, fentanyl). The Risk Behaviour Survey was used to collect injecting and sexual risks at baseline, and weeks 12 and 24. RESULTS: In total, 210 participants initiated treatment (103 buprenorphine/naloxone and 107 methadone). At baseline, 113/205 (55.1%) participants reported recently injecting drugs, 37/209 (17.7%) unsafe injection practices and 67/162 (41.4%) high-risk sex. Both methadone and buprenorphine/naloxone were associated with reductions in the prevalence of injection drug use and high-risk sex at weeks 12 and 24 with no interactions between treatment arm and time. CONCLUSION: Methadone and buprenorphine/naloxone were similarly effective in reducing injecting and sexual risk behaviours among people with POUD. CLINICAL TRIALS REGISTRATION: clinicaltrials.gov NCT03033732.

Impact of baseline methamphetamine/amphetamine use on discontinuation of methadone and buprenorphine/naloxone among people with prescription-type opioid use disorder in Canada.

BACKGROUND AND OBJECTIVES: Although concurrent stimulant use is common among people with opioid use disorder (OUD), there is little evidence on its impacts on opioid agonist therapy (OAT) outcomes. This study sought to determine the impact of baseline methamphetamine/amphetamine use on discontinuation of OAT among individuals with prescription-type OUD (POUD) initiating methadone or buprenorphine/naloxone as part of a pragmatic randomized trial in Canada. METHODS: Secondary analysis of a pan-Canadian pragmatic trial conducted between 2017 and 2020 comparing supervised methadone versus flexible take-home dosing buprenorphine/naloxone models of care. Cox proportional hazard models were used to evaluate the effect of baseline methamphetamine/amphetamine use (measured by urine drug test [UDT]) on two discontinuation outcomes (i.e., assigned OAT discontinuation, any OAT discontinuation). RESULTS: Two hundred nine (n = 209) participants initiated OAT, of which 96 (45.9%) had positive baseline methamphetamine/amphetamine UDT. Baseline methamphetamine/amphetamine use was associated with shorter median times in assigned OAT (21 vs. 168 days, hazard ratio [aHR] = 2.45, 95% confidence interval [CI] = 1.60-3.76) and any OAT (25 days vs. 168 days, aHR = 2.06, CI = 1.32-3.24). No interaction between methamphetamine/amphetamine and assigned OAT was observed for either outcome (p > .05). CONCLUSION AND SCIENTIFIC SIGNIFICANCE: This study offers novel insights on the impact of methamphetamine/amphetamine use on OAT outcomes among people with POUD. Methamphetamine/amphetamine use was common and was associated with increased risk of OAT discontinuation. Supplementary interventions, including treatment for stimulant use, are needed to improve retention in OAT and optimize treatment outcomes in this population.

Does This Patient Have Alcohol Use Disorder?: The Rational Clinical Examination Systematic Review.

Importance: The accuracy of screening tests for alcohol use disorder (defined as a problematic pattern of alcohol use leading to clinically significant impairment or distress) requires reassessment to align with the latest definition in the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (DSM-5). Objective: To assess the diagnostic accuracy of screening tools in identifying individuals with alcohol use disorder as defined in the DSM-5. Data Sources and Study Selection: The databases of MEDLINE and Embase were searched (January 2013-February 2023) for original studies on the diagnostic accuracy of brief screening tools to identify alcohol use disorder according to the DSM-5 definition. Because diagnosis of alcohol use disorder does not include excessive alcohol use as a criterion, studies of screening tools that identify excessive or high-risk drinking among younger (aged 9-18 years), older (aged ≥65 years), and pregnant persons also were retained. Data Extraction and Synthesis: Sensitivity, specificity, and likelihood ratios (LRs) were calculated. When appropriate, a meta-analysis was performed to calculate a summary LR. Results: Of 4303 identified studies, 35 were retained (N = 79 633). There were 11 691 individuals with alcohol use disorder or a history of excessive drinking. Across all age categories, a score of 8 or greater on the Alcohol Use Disorders Identification Test (AUDIT) increased the likelihood of alcohol use disorder (LR, 6.5 [95% CI, 3.9-11]). A positive screening result using AUDIT identified alcohol use disorder better among females (LR, 6.9 [95% CI, 3.9-12]) than among males (LR, 3.8 [95% CI, 2.6-5.5]) (P = .003). An AUDIT score of less than 8 reduced the likelihood of alcohol use disorder similarly for both males and females (LR, 0.33 [95% CI, 0.20-0.52]). The abbreviated AUDIT-Consumption (AUDIT-C) has sex-specific cutoff scores of 4 or greater for males and 3 or greater for females, but was less useful for identifying alcohol use disorder (males: LR, 1.8 [95% CI, 1.5-2.2]; females: LR, 2.0 [95% CI, 1.8-2.3]). The AUDIT-C appeared useful for identifying measures of excessive alcohol use in younger people (aged 9-18 years) and in those older than 60 years of age. For those younger than 18 years of age, the National Institute on Alcohol Abuse and Alcoholism age-specific drinking thresholds were helpful for assessing the likelihood of alcohol use disorder at the lowest risk threshold (LR, 0.15 [95% CI, 0.11-0.21]), at the moderate risk threshold (LR, 3.4 [95% CI, 2.8-4.1]), and at the highest risk threshold (LR, 15 [95% CI, 12-19]). Among persons who were pregnant and screened within 48 hours after delivery, an AUDIT score of 4 or greater identified those more likely to have alcohol use disorder (LR, 6.4 [95% CI, 5.1-8.0]), whereas scores of less than 2 for the Tolerance, Worried, Eye-Opener, Amnesia and Cut-Down screening tool and the Tolerance, Annoyed, Cut-Down and Eye-Opener screening tool identified alcohol use disorder similarly (LR, 0.05 [95% CI, 0.01-0.20]). Conclusions and Relevance: The AUDIT screening tool is useful to identify alcohol use disorder in adults and in individuals within 48 hours postpartum. The National Institute on Alcohol Abuse and Alcoholism youth screening tool is helpful to identify children and adolescents with alcohol use disorder. The AUDIT-C appears useful for identifying various measures of excessive alcohol use in young people and in older adults.

Impact of Depressive Symptom Severity on Buprenorphine/Naloxone and Methadone Outcomes in People With Prescription-Type Opioid Use Disorder: Results From a Pragmatic Randomized Controlled Trial.

OBJECTIVE: To evaluate the impact of depressive symptom severity on opioid use and treatment retention in individuals with prescription-type opioid use disorder (POUD). METHOD: We analyzed data from a multi-centric, pragmatic, open-label, randomized controlled trial comparing buprenorphine/naloxone to methadone models of care in 272 individuals with POUD. Opioid use was self-reported every two weeks for 24 weeks using the Timeline Followback. Depressive symptom severity was self-reported with the Beck Depression Inventory at baseline, week 12 and week 24. RESULTS: Baseline depressive symptom severity was not associated with opioid use nor treatment retention. At week 12, moderate depressive symptoms were associated with greater opioid use while mild to severe depressive symptoms were associated with lowered treatment retention. At week 24, moderate depressive symptoms were associated with greater opioid use. CONCLUSIONS: Ongoing depressive symptoms lead to poorer outcomes in POUD. Clinicians are encouraged to use integrative approaches to optimize treatment outcomes. This study was registered in ClinicalTrials.gov (NCT03033732) on January 27th, 2017, prior to participants enrollment.

The FASTER-BUP Study, Extended-Release Injectable Buprenorphine for the Treatment of Opioid Use Disorder Among Individuals at High Risk of Overdose: Protocol for an Observational Prospective Study.

North America is facing an unprecedented public health emergency of opioid-related morbidity and mortality. The mortality benefits of oral medication treatment for opioid use disorder (MOUD), such as methadone or buprenorphine, are well documented. However, barriers to access and long-term engagement have prevented maximizing their benefits. Long-acting injectable buprenorphine formulations were developed to address some of the challenges associated with oral MOUD. The "Pilot study to assess the feasibility, efficacy, and safety of extended-release injectable buprenorphine for the treatment of opioid use disorder among individuals at high risk of overdose" (FASTER-BUP) was developed to explore this treatment option in populations at high risk of overdose in a real-world Canadian setting. FASTER-BUP is a 24-week observational prospective study evaluating the feasibility and clinical utility of extended-release injectable buprenorphine (XR-BUP) for the treatment of opioid use disorder (OUD) among 40 adults at high risk of overdose (ie, lifetime history of overdose or a positive urine drug test (UDT) for fentanyl within 30 days prior to screening) in Vancouver, BC. The primary outcome is retention in treatment and secondary outcomes include: use of unregulated opioids, safety, overdose events, treatment satisfaction, changes in drug-related problems, changes in quality of life, opioid cravings, health service utilization, and criminal activity. FASTER-BUP is the first study to explore XR-BUP among individuals at high risk of overdose in a real-world Canadian setting. This commentary provides a brief narrative about the study thus far and presents insights on key adaptations to the study protocol, including those adopted to mitigate recruitment challenges.

Associations of Methadone and BUP/NX Dose Titration Patterns With Retention in Treatment and Opioid Use in Individuals With Prescription-Type Opioid Use Disorder: Secondary Analysis of the OPTIMA Study.

INTRODUCTION: Methadone and buprenorphine/naloxone (BUP/NX) titration parameters (eg, range, duration, and rate) can vary during opioid use disorder (OUD) treatment. We describe methadone and BUP/NX titration patterns and their associations with treatment outcomes among individuals with a prescription-type OUD. METHODS: We used data from a 24-week open-label, multicenter randomized controlled trial, including N = 167 participants aged 18-64 years old with prescription-type OUD who received at least a first dose of treatment. Descriptive analyses of methadone and BUP/NX titration patterns were conducted, that is, range and duration from first to maximum dose, and rate (range/duration ratio). Outcomes included percentage of opioid-positive urine drug screens (UDS) and treatment retention. Adjusted linear and logistic regressions were used to study associations between titration patterns and percentage of opioid-positive UDS and treatment retention. RESULTS: Methadone doses were increased by a mean dose range of 42.4 mg over a mean duration of 42.2 days. BUP/NX doses were increased by a mean dose range of 8.4 mg over a mean duration of 28.7 days. Only methadone dose titration range (odds ratio: 1.03; 95% CI, 1.01 to 1.05) and duration (odds ratio: 1.03; 95% CI, 1.01 to 1.05) were associated with higher retention. Only methadone dose titration rate was associated with lower percentage of opioid-positive UDS at weeks 12-24 ( B : -2.77; 95% CI, -4.72 to -0.81). CONCLUSIONS: Specific parameters of methadone titration were associated with treatment outcomes and may help in personalizing treatment schedules. Sustained methadone dose titration, when indicated, may help increase retention, whereas faster dose titration for methadone may help decrease opioid use.

Characterising methamphetamine/amphetamine use among opioid agonist therapy-seeking adults with prescription-type opioid use disorder in Canada.

INTRODUCTION: There has been a significant increase in methamphetamine/amphetamine use in North America, particularly among people who use opioids. Despite its association with several negative health consequences, the population of people who use methamphetamine/amphetamine with opioids is not well characterised. The aim of this study was to investigate correlates of methamphetamine/amphetamine use among adults with prescription-type opioid use disorder (POUD) starting methadone or buprenorphine/naloxone as part of a pragmatic randomised treatment trial in Canada. METHODS: Multivariable logistic regression analyses were used to determine factors associated with baseline methamphetamine/amphetamine use (measured by urine drug test [UDT]) among participants of a pan-Canadian pragmatic trial conducted between 2017 and 2020 comparing supervised methadone versus flexible take-home dosing buprenorphine/naloxone models of care in people with POUD (e.g., licit or illicit, including fentanyl, prescribed or not). RESULTS: The sample included 269 participants, of which 142 (52.8%) had positive baseline methamphetamine/amphetamine UDT. In the multivariable model, positive fentanyl UDT (adjusted odds ratio [AOR] 13.21, 95% confidence interval [CI] 6.45, 28.30), non-fatal overdose in the last 6 months (AOR 2.26, CI 1.01, 5.17) and a lifetime history of opioid agonist therapy exposure prior to study entry (AOR 2.30, CI 1.09, 4.87) remained positively associated with baseline methamphetamine/amphetamine use. DISCUSSION AND CONCLUSIONS: In this sample of people with POUD, methamphetamine/amphetamine use was associated with markers of complex and severe OUD, including overdose risk. This suggests the need for targeted interventions to optimise treatment outcomes and prevent future overdoses in this population. CLINICAL TRIAL REGISTRATION: Available at: ClinicalTrials.gov NCT03033732.

What is the ideal time to begin tapering opioid agonist treatment? A protocol for a retrospective population-based comparative effectiveness study in British Columbia, Canada.

INTRODUCTION: Opioid agonist treatment (OAT) tapering involves a gradual reduction in daily medication dose to ultimately reach a state of opioid abstinence. Due to the high risk of relapse and overdose after tapering, this practice is not recommended by clinical guidelines, however, clients may still request to taper off medication. The ideal time to initiate an OAT taper is not known. However, ethically, taper plans should acknowledge clients' preferences and autonomy but apply principles of shared informed decision-making regarding safety and efficacy. Linked population-level data capturing real-world tapering practices provide a valuable opportunity to improve existing evidence on when to contemplate starting an OAT taper. Our objective is to determine the comparative effectiveness of alternative times from OAT initiation at which a taper can be initiated, with a primary outcome of taper completion, as observed in clinical practice in British Columbia (BC), Canada. METHODS AND ANALYSIS: We propose a population-level retrospective observational study with a linkage of eight provincial health administrative databases in BC, Canada (01 January 2010 to 17 March 2020). Our primary outcomes include taper completion and all-cause mortality during treatment. We propose a 'per-protocol' target trial to compare different durations to taper initiation on the likelihood of taper completion. A range of sensitivity analyses will be used to assess the heterogeneity and robustness of the results including assessment of effectiveness and safety. ETHICS AND DISSEMINATION: The protocol, cohort creation and analysis plan have been classified and approved as a quality improvement initiative by Providence Health Care Research Ethics Board and the Simon Fraser University Office of Research Ethics. Results will be disseminated to local advocacy groups and decision-makers, national and international clinical guideline developers, presented at international conferences and published in peer-reviewed journals electronically and in print.

Geohelmintiasis en la Argentina: Una revisión sistemática / Soil transmitted helminthiasis in Argentina: A systematic review

Con el objetivo de analizar la prevalencia y distribución de las geohelmintiasis en la Argentina e identificar las áreas de mayor riesgo, realizamos una revisión sistemática de los estudios poblacionales publicados entre 1980 y 2011, indexados en las bases MEDLINE/ PUBMED y/o LILACS. También se incluyeron los datos de prevalencia basal del Programa Nacional de Desparasitación Masiva (PNDM, 2005). Se identificaron 310 publicaciones, de las que solo 24 artículos con información sobre 26 relevamientos, realizados en 8 provincias y un total de 5495 individuos evaluados, cumplían los criterios de inclusión. La prevalencia de geohelmintiasis varió ampliamente: Ascaris lumbricoides 0-67%, uncinarias 0-90%, Trichuris trichiura 0-24.5%, Strongyloides stercoralis 0-83%. La prevalencia acumulada estimada de los 4 geohelmintos principales varió entre 0.8 y 88.6%. Los datos basales del PNDM con información de 1943 niños de 12 provincias confirman esta heterogeneidad con rangos de prevalencia acumulada entre 0 y 42.7%. Los estudios incluidos en esta revisión muestran que la distribución de geohelmintiasis en la Argentina es heterogénea, con focos de alta prevalencia (> 20%) en el noreste y noroeste del país, los que podrían beneficiarse de una estrategia de desparasitación masiva. En muchos casos esta alta prevalencia es debida a uncinarias y estrongiloidiosis, lo que debe tenerse en cuenta para definir las estrategias diagnósticas y terapéuticas para su control. Asimismo, se resalta la escasez o ausencia de datos, con información de menos de la mitad de las provincias y menos de 8000 individuos evaluados.

A systematic review of surveys performed between 1980 and 2011 (published in MEDLINE/Pubmed and/or LILACS indexed journals, available in the baseline data from a Mass Deworming National Program (MDNP, 2005) was used to identify the prevalence, distribution and detection of risk areas for soil transmitted helminth infections (STH) in Argentina. We found 310 publications in the database using the pre-defined key-words (medical subject headings) for research purposes. Only 24 articles with 26 surveillance sites in 8 provinces and a total of 5495 surveyed individuals fulfilled the inclusion criteria. Frequency rates for STH had a wide range: Ascaris lumbricoides: 0-67%, hookworms: 0-90%, Trichuris trichiura: 0-24.6 and Strongyloides stercoralis: 0-83%. The estimated combined incidence varied from 0.8% to 88.6%. Baseline surveys from the MDNP reporting on 1943 children from 12 provinces confirmed the heterogeneity, with combined STH frequency rates ranging from 0 to 42.7%. Surveys included in this review showed that the distribution of STH in Argentina is not homogeneous, with areas of high incidence (> 20%) in the northeastern and northwestern provinces where mass deworming activities would be highly beneficial. In several surveys, the high overall incidence was mostly due to hookworms and S. stercoralis, a situation to be considered when selecting diagnostic and therapeutic control strategies. The scarcity or absence of data from various provinces and the availability of less than 8000 surveyed individuals should be considered.