Imaging Utilization and Cost of Substance Use in an Urban Academic Medical Center During the Contemporary Opioid Epidemic.

RATIONALE AND OBJECTIVES: To determine the recent impact of illicit substance use on imaging utilization and associated costs. METHODS: Retrospective study from an inner city urban multi-site academic medical center. Institutional Review Board (IRB) approval was obtained with a waiver of informed consent. A substance use cohort comprised patients 12 years old presenting to the Emergency Department (ED) January 2017 to June 2019 with a positive urine toxicology and an ICD code associated with substance use. The comparison cohort was randomly selected from a group of ED patients who presented with no or negative urine toxicology and no documented substance use ICD code. Data extracted from the EMR included demographics, number and type of imaging studies, Charlson comorbidity index, and in-hospital mortality during the study period. RESULTS: The substance use and comparison cohorts comprised 3191 and 3200 patients, respectively. The substance use cohort was older on average (mean age 45.67 ± 14.88 vs 43.91 ± 20.57 years), more often male (63% [2026/3191] vs. 39% [1255/3200]) and had a mean Charlson score 88% higher than the comparison cohort (3.33 vs 1.78). The majority of both cohorts were ethnic minorities (<10% white). The substance use cohort had significantly more imaging vs the comparison cohort, total 36,413 (mean 11.41 exams/patient) vs total 12,399 (mean 3.87 exams/patient), p < 0.0001, and was higher for all modalities except mammography. Average imaging costs per patient were nearly 300% higher for the substance use vs comparison cohort, ($1287.18 vs. $434.70). CONCLUSION: Imaging utilization and associated costs were substantially higher for patients with a positive urine toxicology and substance use related ICD codes compared to the broader ED population in an underserved urban population.

Assessing fragility of statistically significant findings from randomized controlled trials assessing pharmacological therapies for opioid use disorders: a systematic review.

BACKGROUND: The fragility index is a statistical measure of the robustness or "stability" of a statistically significant result. It has been adapted to assess the robustness of statistically significant outcomes from randomized controlled trials. By hypothetically switching some non-responders to responders, for instance, this metric measures how many individuals would need to have responded for a statistically significant finding to become non-statistically significant. The purpose of this study is to assess the fragility index of randomized controlled trials evaluating opioid substitution and antagonist therapies for opioid use disorder. This will provide an indication as to the robustness of trials in the field and the confidence that should be placed in the trials' outcomes, potentially identifying ways to improve clinical research in the field. This is especially important as opioid use disorder has become a global epidemic, and the incidence of opioid related fatalities have climbed 500% in the past two decades. METHODS: Six databases were searched from inception to September 25, 2021, for randomized controlled trials evaluating opioid substitution and antagonist therapies for opioid use disorder, and meeting the necessary requirements for fragility index calculation. Specifically, we included all parallel arm or two-by-two factorial design RCTs that assessed the effectiveness of any opioid substitution and antagonist therapies using a binary primary outcome and reported a statistically significant result. The fragility index of each study was calculated using methods described by Walsh and colleagues. The risk of bias of included studies was assessed using the Revised Cochrane Risk of Bias tool for randomized trials. RESULTS: Ten studies with a median sample size of 82.5 (interquartile range (IQR) 58, 179, range 52-226) were eligible for inclusion. Overall risk of bias was deemed to be low in seven studies, have some concerns in two studies, and be high in one study. The median fragility index was 7.5 (IQR 4, 12, range 1-26). CONCLUSIONS: Our results suggest that approximately eight participants are needed to overturn the conclusions of the majority of trials in opioid use disorder. Future work should focus on maximizing transparency in reporting of study results, by reporting confidence intervals, fragility indexes, and emphasizing the clinical relevance of findings. TRIAL REGISTRATION: PROSPERO CRD42013006507. Registered on November 25, 2013.

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.