Supplementary data are available at Bioinformatics online.

A new QTc formula was developed which eliminates the relationship between QT and HR. At faster HRs, the 2 most commonly used QTcs provide numerical values at the extremes of QTc. Compared to existing formulae, the new formula had the best performance.

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 Knowing the case fatality rates of recurrent venous thromboembolism (VTE) and major bleeding is important for weighing the relative risks and benefits of anticoagulation and deciding on the duration of anticoagulant therapy, but these rates are uncertain in patients with cancer-associated thrombosis. Methods We performed a systematic review and a meta-analysis to determine the incidence of recurrent VTE and major bleeding and their respective case fatality rates in patients with cancer-associated VTE. Results Our analysis included 29 studies (15 prospective cohort studies and 14 randomized controlled trials) from 1980 to January 2019. Data from 8,000 cancer patients with 4,786 patient-years of follow-up were summarized. Rates of recurrent VTE and fatal recurrent VTE were 23.7 (95% confidence interval [CI]: 20.1–27.8) and 1.9 (95% CI: 0.8–4.0) per 100 patient-years of follow-up, respectively, with a case fatality rate of 14.8% (95% CI: 6.6–30.1%). The rates of major bleeding and fatal major bleeding events were 13.1 (95% CI: 10.3–16.7) and 0.8 (95% CI: 0.3–2.1) per 100 patient-years of follow-up, respectively, with a case fatality rate of 8.9% (95% CI: 3.5–21.1%). While the estimates of case fatality vary by anticoagulation regimen and study design, the differences between them were not statistically significant. Conclusion In cancer patients receiving anticoagulation, the case fatality rate of recurrent VTE is higher than the case fatality rate of major bleeding. These findings may help to inform decisions regarding the management of anticoagulation in patients with active cancer and VTE.

Both genetic variants and brain region abnormalities are recognized to play a role in cognitive decline. We explore the association between singlenucleotide polymorphisms (SNPs) in linkage regions for Alzheimer's disease and rates of decline in brain structure using data from the Alzheimers Disease Neuroimaging Initiative (ADNI).