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...

Background: The Montreal Cognitive Assessment (MoCA) is a commonly used cognitive outcome in stroke trials. However, it may be insufficiently sensitive to detect impairment in high-functioning stroke survivors. The National Institutes of Health (NIH) Toolbox Cognition Battery (NIHTB-CB), a 30-min comprehensive tablet-based cognitive assessment, may be a better choice to characterize cognitive issues in this cohort. Methods: We compared MoCA and NIHTB-CB performance in young stroke survivors (18–55 years) with excellent functional outcomes (modified Rankin Scale 0–1) reporting subjective cognitive complaints to that of age-matched healthy controls. We recruited 53 stroke survivors and 53 controls. We performed a sensitivity analysis in those participants with normal MoCA scores (≥26). Results: Median MoCA scores were not significantly different between stroke survivors (27.0 vs. 28.0) and healthy controls. Mean T scores for NIHTB-CB fluid (44.9 vs. 54.2), crystallized (53.8 vs. 60.0), and total cognition (49.1 vs. 58.4) components were significantly lower in stroke survivors compared to healthy controls (p < 0.001 for all). In participants scoring within normal range (≥26) on the MoCA, NIHTB-CB scores for all components remained significantly lower in stroke survivors. Conclusions: In young stroke survivors with excellent functional outcomes and subjective cognitive complaints, the NIHTB-CB, but not the MoCA, was able to detect differences in cognitive performance between stroke survivors and healthy controls. The NIHTB-CB may be a suitable outcome measure for cognition in clinical trials examining higher-functioning young stroke survivors.

Background and Purpose: Endovascular thrombectomy (EVT) reduces 90-day disability in patients following acute ischemic stroke due to large vessel occlusion. Patient-reported outcome measures after EVT, such as health-related quality of life and specific functional domains, are less well described. Methods: We report outcomes on the EuroQol-5D (EQ-5D) from the ESCAPE (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times) randomized controlled trial at 90 days after stroke. Death was assigned an index value of 0 for EQ-5D. We used quantile regression to evaluate the association between EVT and EQ-5D index scores and logistic regression for the association between EVT and symptom-free status among 90-day survivors for each EQ-5D dimension (self-care, usual activities, mobility, pain/discomfort, and anxiety/depression), assessing for modification by age or sex and adjusting for baseline factors including stroke severity, affected hemisphere, and receipt of alteplase. Lastly, the association between severe disability at 90 days and EQ-5D was evaluated with assessment for modification by EVT, age, and sex. Results: There were 165 patients randomized to EVT and 150 patients randomized to control. Median EQ-5D was significantly higher for those who received EVT compared with best medical management (0.80 versus 0.60; P <0.001). After accounting for the greater number of deaths in the elderly, there was evidence of modification of treatment effect by age, with older age associated with a larger effect size difference in EQ-5D with EVT. Those receiving EVT had higher odds of symptom-free status in self-care, usual activities, mobility for those aged 60 to 79 years, and pain/discomfort for women, but there was no association with anxiety/depression. Severe disability at 90 days was associated with lower EQ-5D in older compared with younger individuals, and the association was not modified by EVT. Conclusions: Patients treated with EVT report substantially improved health-related quality of life, with relatively greater impact in older individuals and observed benefit across multiple dimensions.

Background Health state utility values are commonly used to provide summary measures of health‐related quality of life in studies of stroke. Contemporaneous summaries are needed as a benchmark to contextualize future observational studies and inform the effectiveness of interventions aimed at improving post‐stroke quality of life. Methods and Results We conducted a systematic search of the literature using Medline, EMBASE, and Web of Science from January 1995 until October 2020 using search terms for stroke, health‐related quality of life, and indirect health utility metrics. We calculated pooled estimates of health utility values for EQ‐5D‐3L, EQ‐5D‐5L, AQoL, HUI2, HUI3, 15D, and SF‐6D using random effects models. For the EQ‐5D‐3L we conducted stratified meta‐analyses and meta‐regression by key subgroups. We screened 14 251 abstracts and 111 studies met our inclusion criteria (sample size range 11 to 12 447). EQ‐5D‐3L was reported in 78% of studies (study n=87; patient n=56 976). The pooled estimate for EQ‐5D‐3L at ≥3 months following stroke was 0.65 (95% CI, 0.63–0.67), which was ≈20% below population norms. There was high heterogeneity (I 2 >90%) between studies, and estimates differed by study size, case definition of stroke, and country of study. Women, older individuals, those with hemorrhagic stroke, and patients prior to discharge had lower pooled EQ‐5D‐3L estimates. Conclusions Pooled estimates of health utility for stroke survivors were substantially below population averages. We provide reference values for health utility in stroke to support future clinical and economic studies and identify subgroups with lower healthy utility. Registration URL: https://www.crd.york.ac.uk/prospero/ . Unique Identifier: CRD42020215942.

In response to the coronavirus disease 2019 (COVID-19) pandemic, rapid development, clinical testing, and regulatory approval of vaccines occurred. The tozinameran COVID-19 vaccine is the first mRNA vaccine approved for use in humans. Transverse myelitis is a rare inflammatory disorder of the spinal cord that is associated with traditional vaccinations. There are rare case reports describing an association between mRNA vaccines and transverse myelitis. Herein, we describe a case of transverse myelitis following mRNA vaccination. A healthy 26-year-old woman developed saddle anesthesia, numbness, and allodynia in the S1-S4 distribution within three days of receiving the first dose of tozinameran COVID-19 vaccine. She had decreased sensation to pinprick, temperature, and light touch in S1-S4 distribution and a positive Rhomberg test. An MRI brain and spine demonstrated a short segment T2 hyperintense and diffusely enhancing lesion at T5. Cerebrospinal fluid studies demonstrated pleocytosis and elevated IgG index. A five-day course of IV methylprednisolone resulted in minimal improvements in her symptoms. Stage III clinical trials may be underpowered to detect more rare adverse effects such as transverse myelitis. Therefore, it is imperative to have ongoing surveillance and reporting of adverse events associated with COVID-19 vaccines to ensure transparency with regard to potential risks to patients obtaining the vaccine and algorithms in place for detection and urgent treatment if required. Nonetheless, the safety and efficacy of vaccination against COVID-19 are well established and greatly outweigh any potential risks associated with the vaccine. Given the individual, societal, and global health benefits of vaccination we strongly advocate for ongoing vaccinations against COVID-19.