Redesigning a Stopped Clinical Trial as an Emulated Trial Using Real-World Data to Explore the Effectiveness of Slow-Release Oral Morphine as a Treatment for Opioid Use Disorder.

Canada is currently experiencing a problematic opioid crisis with increasing mortality rates. Traditional randomized controlled trials (RCTs) that examine the effectiveness of pharmacological treatment options for people with opioid use disorder (OUD) are challenging to conduct. An increasingly popular methodology is through the implementation of emulated clinical trials, a methodology in which key elements of a "target" RCT are replicated using previously collected healthcare-based data. They can possibly address some of the common challenges found in the conduct of RCTs, such as prolonged timelines, high cost, and poor participant recruitment. In effect, emulated trials accelerate knowledge generation by producing real-world evidence that can be akin to phase 3 effectiveness trials, without any need to recruit live participants or administer investigational products. During the COVID-19 pandemic, several trials were stopped due to increased pandemic-related research restrictions, leaving important questions about OUD treatment unanswered. In this commentary, we describe the transition of a traditional RCT to an emulated trial spurred by challenges posed by the COVID-19 pandemic. We describe our transition using a notable published framework with regards to the population sample, interventions, outcomes, and proposed analyses. This commentary aims to help other researchers and trialists apply emulated trials in substance use research and beyond, emphasizing the role of this methodology in clinical research and advancing scientific knowledge that could be otherwise lost or unattainable.

Management of illicit substances in hospital: An evaluation of policy and procedure implementation.

Previous research has identified illicit substance use on hospital property as an ongoing concern, particularly in inpatient mental health units. This research, combined with concerns raised by healthcare providers, patients, and patients' families, resulted in one hospital in a medium-sized city in Canada enacting two internal strategies for the management of illicit substances on hospital property. The unit-based Green-Yellow-Red procedure employs environmental scanning and regular risk assessment to report the incidence rate of illicit substances suspected and/or found in the unit, to inform staff of the extent of necessary interventions which should ensue. The hospital-wide Management of Illicit Substances protocol includes ten steps which can be followed by any staff member who suspects they have found an illicit substance or related paraphernalia on hospital grounds. This paper discusses the creation and implementation of these two strategies, as well as associated challenges and outcomes of each. Overall, these strategies have effectively functioned to mitigate the potential dangers of exposure to illicit substances for staff and patients alike. These results stand to encourage other institutions to implement similar strategies in order to better manage situations in which illicit substances are suspected or discovered on hospital property.

Increased gray matter following mindfulness-based stress reduction in breast cancer survivors with chronic neuropathic pain: preliminary evidence using voxel-based morphometry.

PURPOSE: To investigate the impact of Mindfulness-Based Stress Reduction (MBSR) on gray matter volume (GMV) in female breast cancer survivors who suffer from chronic neuropathic pain (CNP). METHODS: Voxel-based morphometry (VBM) was used to explore differences in GMV in 13 MBSR trainees and 10 waitlisted controls, with MRI scans and self-report measures completed pre- and post-8 weeks of training. RESULTS: Compared to controls, the MBSR group had greater GMV in the angular gyrus and middle frontal gyrus post-training. The MBSR group's right parahippocampal gyrus GMV increased from pre- to post-training, whereas the control group's left parahippocampal gyrus, precuneus, middle temporal gyrus, and right cuneus GMV decreased over the same time period. Pain interference was significantly reduced and mindfulness was significantly increased following MBSR for the intervention group only. CONCLUSIONS: MBSR was associated with increased GMV in regions where GMV is known to (1) increase with mindfulness and reorientation of attention and (2) decrease with the experience of chronic neuropathic pain. By contrast, the control group's decreases in GMV may be due to the negative effects of CNP which potentially may be reduced with MBSR, though further research is needed. IMPLICATIONS FOR CANCER SURVIVORS: Given the poor efficiency of pharmacotherapies in a high percentage of women with neuropathic pain following breast cancer treatment, adjunct methods are required. MBSR may affect the brain to help alter attention and perception of pain, thus playing a potentially important role in the path to wellness for breast cancer survivors.

Posttraumatic Stress Disorder Symptomatology and Substance Use in an Outpatient Concurrent Disorders Sample.

OBJECTIVE: Posttraumatic stress disorder (PTSD) and substance use disorders (SUDs) present a complex and often severe clinical presentation within a concurrent disorders context. The objective of this study was to examine associations between PTSD symptoms and SUD outcomes to better understand the clinical phenomenon of comorbid PTSD and SUD. Multivariate statistical methods were used to test the hypothesis that elevated PTSD symptoms, both at the level of global severity and specific PTSD symptom clusters, are associated with greater substance use and related problems. METHODS: Data were collected from an intake assessment battery within a specialized concurrent disorders outpatient service in Hamilton, ON. The sample comprised 326 participants (mean age = 37.19, 45.4% female). Structural equation models examined associations between PTSD and alcohol, cannabis, and substance use frequency and problems, controlling for age and sex. Alcohol was ultimately dropped from the model due to non-significant bivariate associations. RESULTS: Higher global PTSD symptomatology was significantly associated with higher cannabis and other substance use frequency and related problems. Analyses using PTSD cluster scores showed higher scores for alterations in arousal were positively associated with cannabis-related problems, drug-related problems, and cannabis and other substance use frequency. Avoidance was significantly associated with cannabis frequency and cannabis-related problems. In general, effect sizes were small in magnitude, accounting for between 9% and 25% of variance. CONCLUSION: Significant cluster-level associations indicate the importance of specific PTSD symptoms (hyperarousal, avoidance) in relation to substance use when identifying therapeutic targets among individuals presenting with comorbid PTSD-SUD. This multivariate approach provides a higher resolution and potentially more clinically informative representation of the complex clinical presentation of PTSD and SUD in a concurrent disorder population and could guide the development of more effective treatment paths.