IMPORTANCE The utility-weighted modified Rankin Scale (UW-mRS) has been proposed as a patient-centered alternative primary outcome for stroke clinical trials. However, to date, there is no clear consensus on an approach to weighting the mRS. OBJECTIVE To characterize the between-study variability in utility weighting of the mRS in a population of patients who experienced stroke and its implications when applied to the results of a clinical trial. DATA SOURCES In this systematic review and meta-analysis, MEDLINE, Embase, and PsycINFO were searched from January 1987 through May 2019 using major search terms for stroke, health utility, and mRS. STUDY SELECTION Original research articles published in English were reviewed. Included were studies with participants 18 years or older with ischemic or hemorrhagic stroke, transient ischemic attack, or subarachnoid hemorrhage, with mRS scores and utility weights evaluated concurrently. A total of 5725 unique articles were identified. Of these, 283 met criteria for full-text review, and 24 were included in the meta-analysis. DATA EXTRACTION AND SYNTHESIS PRISMA guidelines for systematic review were followed. Data extraction was performed independently by multiple researchers. Data were pooled using mixed models. MAIN OUTCOMES AND MEASURES The mean utility weights and 95% CIs were calculated for each mRS score and health utility scale. Geographic differences in weighting for the EuroQoL 5-dimension (EQ-5D) and Stroke Impact Scale-based UW-mRS were explored using inverse variance-weighted linear models. The results of 18 major acute stroke trials cited in current guidelines were then reanalyzed using the UW-mRS weighting scales identified in the systematic review. RESULTS The meta-analysis included 22 389 individuals; the mean (SD) age of participants was 65.9 (4.0) years, and the mean (SD) proportion of male participants was 58.2% (7.5%). For all health utility scales evaluated, statistically significant differences were observed between the mean utility weights by mRS score. For studies using an EQ-5D-weighted mRS, between-study variance was higher for worse (mRS 2-5) compared with better (mRS 0-1) scores. Of the 18 major acute stroke trials with reanalyzed results, 3 had an unstable outcome when using different UW-mRSs. CONCLUSIONS AND RELEVANCE Multiple factors, including cohort-specific characteristics and health utility scale selection, can influence mRS utility weighting. If the UW-mRS is selected as a primary outcome, the approach to weighting may alter the results of a clinical trial. Researchers using (continued) Key Points Question Is a preexisting health utilityweighted outcome scale suitable for use in a clinical trial, or is a study-specific approach more appropriate? Findings Among 24 studies including 22 389 individuals, this systematic review and meta-analysis found statistically significant between-study differences for studies reporting utility weighting of the modified Rankin Scale. When applied to the results of major acute stroke trials, different studysp...

Aim To capture pandemic experiences of people with opioid use disorder (OUD) to better inform the programs that serve them. Design We designed, conducted, and analyzed semi-structured qualitative interviews using grounded theory. We conducted interviews until theme saturation was reached and we iteratively developed a codebook of emerging themes. Individuals with lived experience of substance use provided feedback at all steps of the study. Setting We conducted phone or in-person interviews in compliance with physical distancing and public health regulations in outdoor Vancouver parks or well-ventilated indoor spaces between June to September 2020. Participants Using purposive sampling, we recruited participants (n = 19) who were individuals with OUD enrolled in an intensive community outreach program, had visited one of two emergency departments, were over 18, lived within catchment, and were not already receiving opioid agonist therapy. Measurements We audio-recorded interviews, which were later transcribed verbatim and checked for accuracy while removing all identifiers. Interviews explored participants’ knowledge of COVID-19 and related safety measures, changes to drug use and healthcare services, and community impacts of COVID-19. Results One third of participants were women, approximately two thirds had stable housing, and ages ranged between 23 and 59 years old. Participants were knowledgeable on COVID-19 public health measures. Some participants noted that fear decreased social connection and reluctance to help reverse overdoses; others expressed pride in community cohesion during crisis. Several participants mentioned decreased access to housing, harm reduction, and medical care services. Several participants reported using drugs alone more frequently, consuming different or fewer drugs because of supply shortages, or using more drugs to replace lost activities. Conclusion COVID-19 had profound effects on the social lives, access to services, and risk-taking behaviour of people with opioid use disorder. Pandemic public health measures must include risk mitigation strategies to maintain access to critical opioid-related services.

Background: Emerging data suggest that direct oral anticoagulants may be a suitable choice for anticoagulation for cerebral venous thrombosis (CVT). However, conducting high-quality trials in CVT is challenging as it is a rare disease with low rates of adverse outcomes such as major bleeding and functional dependence. To facilitate the design of future CVT trials, SECRET (Study of Rivaroxaban for Cerebral Venous Thrombosis) assessed (1) the feasibility of recruitment, (2) the safety of rivaroxaban compared with standard-of-care anticoagulation, and (3) patient-centered functional outcomes. Methods: This was a phase II, prospective, open-label blinded-end point 1:1 randomized trial conducted at 12 Canadian centers. Participants were aged ≥18 years, within 14 days of a new diagnosis of symptomatic CVT, and suitable for oral anticoagulation; they were randomized to receive rivaroxaban 20 mg daily, or standard-of-care anticoagulation (warfarin, target international normalized ratio, 2.0–3.0, or low-molecular-weight heparin) for 180 days, with optional extension up to 365 days. Primary outcomes were annual rate of recruitment (feasibility); and a composite of symptomatic intracranial hemorrhage, major extracranial hemorrhage, or mortality at 180 days (safety). Secondary outcomes included recurrent venous thromboembolism, recanalization, clinically relevant nonmajor bleeding, and functional and patient-reported outcomes (modified Rankin Scale, quality of life, headache, mood, fatigue, and cognition) at days 180 and 365. Results: Fifty-five participants were randomized. The rate of recruitment was 21.3 participants/year; 57% of eligible candidates consented. Median age was 48.0 years (interquartile range, 38.5–73.2); 66% were female. There was 1 primary event (symptomatic intracranial hemorrhage), 2 clinically relevant nonmajor bleeding events, and 1 recurrent CVT by day 180, all in the rivaroxaban group. All participants in both arms had at least partial recanalization by day 180. At enrollment, both groups on average reported reduced quality of life, low mood, fatigue, and headache with impaired cognitive performance. All metrics improved markedly by day 180. Conclusions: Recruitment targets were reached, but many eligible participants declined randomization. There were numerically more bleeding events in patients taking rivaroxaban compared with control, but rates of bleeding and recurrent venous thromboembolism were low overall and in keeping with previous studies. Participants had symptoms affecting their well-being at enrollment but improved over time. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03178864.

Background Successful stroke trials require adequate recruitment. In this observational study, we assessed reasons for refusal to provide informed consent in eligible patients approached for clinical trial participation at the Vancouver Stroke Program. Methods We assessed screening logs from four trials that were actively recruiting at our center: three randomized trials, two of which investigated different antithrombotic strategies for secondary prevention (NAVIGATE-ESUS, NCT02313909 12/2014; DATAS-II, NCT02295826 11/2014) and one that investigated surgery plus medical management versus medical management alone for primary prevention (CREST-2, NCT02089217 03/2014). The fourth study was observational and non-randomized; all participants received an external monitoring device (PROPHECY, NCT03712865 10/2018). Screening logs from June 2015 to April 2017 were reviewed retrospectively. Subsequently, we used a prospective structured case report form for screening (May 2017–March 2018). We assessed and compared refusal rates between trials, demographics of those refusing consent, and their reasons for doing so. We used descriptive statistics, chi-square and Fisher’s exact tests as appropriate for non-parametric data, and t-tests for parametric data. We examined likelihood of refusal by sex using multivariable logistic regression models including age and trial intervention as co-variables. Results A total of 235 patients (43% women) were approached for consent. More patients refused the surgical (59%) and antithrombotic trials (53%) compared with the non-randomized external monitoring device study (13%) ( p < 0.001). Surgical trial refusals were primarily due to a desire for certainty in receiving a particular intervention (39%), with the majority of those patients wanting surgery. Refusals for the antithrombotic trials were mainly due to concerns with the potential side effects of the study drug (41%); refusals in the device trial were mainly due to disinterest (46%). Women refused participation more often than men (48% vs 33%). Women remained less likely to consent than men, even after adjustment for age and trial intervention (OR 0.46, 95% CI 0.26–0.82, p = 0.009). Conclusions Concern surrounding drug safety, randomization, and disinterest were the chief deterrents to enrolment; there were also differences in rates of consent by gender. A better understanding of why patients refuse participation in stroke trials may help to develop future patient-directed communication strategies to improve enrolment. Further research is required to better understand the reasons underlying gender disparities in consent rates. Electronic supplementary material The online version of this article (10.1186/s13063-019-3434-0) contains supplementary material, which is available to authorized users.

Our novel videoconference protocol for the NIHTB-CB is equivalent to the standard protocol in healthy participants, and may provide a solution for researchers seeking to engage study participants at remote sites. If the NIHTB-CB is used longitudinally to monitor patients, corrections for repeated measures may be required.