Risk, Clinical Course, and Outcome of Ischemic Stroke in Patients Hospitalized With COVID-19: A Multicenter Cohort Study

BACKGROUND AND PURPOSE: The frequency of ischemic stroke in patients with coronavirus disease 2019 (COVID-19) varies in the current literature, and risk factors are unknown. We assessed the incidence, risk factors, and outcomes of acute ischemic stroke in hospitalized patients with COVID-19. METHODS: We included patients with a laboratory-confirmed SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) infection admitted in 16 Dutch hospitals participating in the international CAPACITY-COVID registry between March 1 and August 1, 2020. Patients were screened for the occurrence of acute ischemic stroke. We calculated the cumulative incidence of ischemic stroke and compared risk factors, cardiovascular complications, and in-hospital mortality in patients with and without ischemic stroke. RESULTS: We included 2147 patients with COVID-19, of whom 586 (27.3%) needed treatment at an intensive care unit. Thirty-eight patients (1.8%) had an ischemic stroke. Patients with stroke were older but did not differ in sex or cardiovascular risk factors. Median time between the onset of COVID-19 symptoms and diagnosis of stroke was 2 weeks. The incidence of ischemic stroke was higher among patients who were treated at an intensive care unit (16/586; 2.7% versus nonintensive care unit, 22/1561; 1.4%; P=0.039). Pulmonary embolism was more common in patients with (8/38; 21.1%) than in those without stroke (160/2109; 7.6%; adjusted risk ratio, 2.08 [95% CI, 1.52–2.84]). Twenty-seven patients with ischemic stroke (71.1%) died during admission or were functionally dependent at discharge. Patients with ischemic stroke were at a higher risk of in-hospital mortality (adjusted risk ratio, 1.56 [95% CI, 1.13–2.15]) than patients without stroke. CONCLUSIONS: In this multicenter cohort study, the cumulative incidence of acute ischemic stroke in hospitalized patients with COVID-19 was ≈2%, with a higher risk in patients treated at an intensive care unit. The majority of stroke patients had a poor outcome. The association between ischemic stroke and pulmonary embolism warrants further investigation

Influence of genotyping error in linkage mapping for complex traits – an analytic study

<p>Abstract</p> <p>Background</p> <p>Despite the current trend towards large epidemiological studies of unrelated individuals, linkage studies in families are still thoroughly being utilized as tools for disease gene mapping. The use of the single-nucleotide-polymorphisms (SNP) array technology in genotyping of family data has the potential to provide more informative linkage data. Nevertheless, SNP array data are not immune to genotyping error which, as has been suggested in the past, could dramatically affect the evidence for linkage especially in selective designs such as affected sib pair (ASP) designs. The influence of genotyping error on selective designs for continuous traits has not been assessed yet.</p> <p>Results</p> <p>We use the identity-by-descent (IBD) regression-based paradigm for linkage testing to analytically quantify the effect of simple genotyping error models under specific selection schemes for sibling pairs. We show, for example, that in extremely concordant (EC) designs, genotyping error leads to decreased power whereas it leads to increased type I error in extremely discordant (ED) designs. Perhaps surprisingly, the effect of genotyping error on inference is most severe in designs where selection is least extreme. We suggest a genomic control for genotyping errors via a simple modification of the intercept in the regression for linkage.</p> <p>Conclusion</p> <p>This study extends earlier findings: genotyping error can substantially affect type I error and power in selective designs for continuous traits. Designs involving both EC and ED sib pairs are fairly immune to genotyping error. When those designs are not feasible the simple genomic control strategy that we suggest offers the potential to deliver more robust inference, especially if genotyping is carried out by SNP array technology.</p

Diagnostic accuracy of contrast-enhanced MR angiography in severe carotid stenosis: meta-analysis with metaregression of different techniques

Contrast-enhanced magnetic resonance angiography (CE-MRA) has become a well-established noninvasive imaging method for the assessment of severe carotid stenosis (70–99% by NASCET criteria). However, CE-MRA is not a standardised technique, but encompasses different concurrent techniques. This review analyses possible differences. A bivariate random effects meta-analysis of 17 primary diagnostic accuracy studies confirmed a high pooled sensitivity of 94.3% and specificity of 93.0% for carotid CE-MRA in severe carotid stenosis. Sensitivity was fairly uniform among the studies, while specificity showed significant variation (I2 = 73%). Metaregressions found significant differences for specificity with two covariates: specificity was higher when using not only maximum intensity projection (MIP) images, but also three-dimensional (3D) images (P = 0.01). Specificity was also higher with electronic images than with hardcopies (P = 0.02). The timing technique (bolus-timed, fluoroscopically triggered or time-resolved) did not result in any significant differences in diagnostic accuracy. Some nonsignificant trends were found for the percentages of severe carotid disease, acquisition time and voxel size. In conclusion, in CE-MRA of severe carotid stenosis the three major timing techniques yield comparably high diagnostic accuracy, electronic images are more specific than hardcopies, and 3D images should be used in addition to MIP images to increase the specificity

A Reliability-Generalization Study of Journal Peer Reviews: A Multilevel Meta-Analysis of Inter-Rater Reliability and Its Determinants

Background: This paper presents the first meta-analysis for the inter-rater reliability (IRR) of journal peer reviews. IRR is defined as the extent to which two or more independent reviews of the same scientific document agree. Methodology/Principal Findings: Altogether, 70 reliability coefficients (Cohen’s Kappa, intra-class correlation [ICC], and Pearson product-moment correlation [r]) from 48 studies were taken into account in the meta-analysis. The studies were based on a total of 19,443 manuscripts; on average, each study had a sample size of 311 manuscripts (minimum: 28, maximum: 1983). The results of the meta-analysis confirmed the findings of the narrative literature reviews published to date: The level of IRR (mean ICC/r 2 =.34, mean Cohen’s Kappa =.17) was low. To explain the study-to-study variation of the IRR coefficients, meta-regression analyses were calculated using seven covariates. Two covariates that emerged in the metaregression analyses as statistically significant to gain an approximate homogeneity of the intra-class correlations indicated that, firstly, the more manuscripts that a study is based on, the smaller the reported IRR coefficients are. Secondly, if the information of the rating system for reviewers was reported in a study, then this was associated with a smaller IRR coefficient than if the information was not conveyed. Conclusions/Significance: Studies that report a high level of IRR are to be considered less credible than those with a low level o