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.

Comparative effectiveness of urine drug screening strategies alongside opioid agonist treatment in British Columbia, Canada: a population-based observational study protocol.

INTRODUCTION: Urine drug tests (UDTs) are commonly used for monitoring opioid agonist treatment (OAT) responses, supporting the clinical decision for take-home doses and monitoring potential diversion. However, there is limited evidence supporting the utility of mandatory UDTs-particularly the impact of UDT frequency on OAT retention. Real-world evidence can inform patient-centred approaches to OAT and improve current strategies to address the ongoing opioid public health emergency. Our objective is to determine the safety and comparative effectiveness of alternative UDT monitoring strategies as observed in clinical practice among OAT clients in British Columbia, Canada from 2010 to 2020. METHODS AND ANALYSIS: We propose a population-level retrospective cohort study of all individuals 18 years of age or older who initiated OAT from 1 January 2010 to 17 March 2020. The study will draw on eight linked health administrative databases from British Columbia. Our primary outcomes include OAT discontinuation and all-cause mortality. To determine the effectiveness of the intervention, we will emulate a 'per-protocol' target trial using a clone censoring approach to compare fixed and dynamic UDT monitoring strategies. A range of sensitivity analyses will be executed to determine the robustness of our results. 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.

Use of serum biomarkers to predict the development and severity of osteochondrosis lesions in the distal portion of the femur in pigs.

OBJECTIVE: To evaluate the use of serum biomarkers of cartilage and bone metabolism to predict the occurrence and severity of osteochondrosis (OC) lesions in the distal portion of the femur in growing swine. ANIMALS: 71 gilts. PROCEDURES: At an abattoir, serum samples for analysis of 10 biomarkers indicative of cartilage and bone metabolism were obtained prior to processing of the pigs. The distal portion of each pig's left femur was directly examined and cut into longitudinal sections to evaluate the number and severity of abnormalities on the external surface, articular cartilage, and growth plate. Each specimen was categorized as with (n = 56) or without (15) OC, and an overall OC severity score was assigned to affected pigs. Logistic and linear regression analyses were performed to predict odds of OC on the basis of biomarker concentrations and predict the severity of OC values in affected pigs, respectively. RESULTS: Compared with values in unaffected pigs, serum concentrations of C-propeptide of type II collagen (CPII) and cartilage oligomeric matrix protein were significantly increased and concentrations of carboxy-terminal telopeptide of type II collagen 3/4-length fragment (C2C) and pyridinoline cross-links were significantly decreased in affected pigs. A 2-fold increase in CPII concentration increased the odds of pigs having OC by a factor of 97 (95% confidence interval, 6 to infinity). Changes in serum C2C concentration accounted for 49% of the variation in overall OC severity score. CONCLUSIONS AND CLINICAL RELEVANCE: Assessment of serum biomarker concentrations may be useful in the diagnosis of OC and aid in reduction of lameness in swine herds.

Mechanism for lactate-color stabilization in injection-enhanced beef.

In two experiments, the relationship between metmyoglobin (MMb) reduction and lactate to pyruvate conversion with concomitant production of reduced nicotinamide adenine dinucleotide (NADH) via lactic dehydrogenase (LDH) was investigated. In experiment 1, nonenzymatic reduction of horse MMb occurred in a lactate-LDH-NAD system. Exclusion of NAD+, L-lactic acid, or LDH resulted in minimal MMb reduction. Increasing NAD+ and L-lactic acid concentrations increased reduction. In experiment 2, beef strip loins (longissimus lumborum muscle) were injected with combinations of potassium lactate, sodium tripolyphosphate, sodium chloride, and/or sodium acetate. Steaks were packaged in high-oxygen (80% oxygen/20% carbon dioxide) modified-atmosphere packaging and stored for 2-9 days and then placed in a fluorescent-lighted, open-top display case for 5 days at 1 degrees C. Enhancing loins with 2.5% potassium lactate significantly increased LDH activity, NADH concentration, MMb-reducing activity, and subsequent color stability during display. These research results support the hypothesis that enhancing beef with lactate replenishes NADH via increased LDH activity, ultimately resulting in greater meat color stability.