Blood Astrocyte Biomarkers in Alzheimer Disease: A Systematic Review and Meta-Analysis.

Background And Objectives: Neuroinflammation, particularly early astrocyte reactivity, is a significant driver of Alzheimer disease (AD) pathogenesis. It is unclear how the levels of astrocyte biomarkers change in patients across the AD continuum and which best reflect AD-related change. We performed a systematic review and meta-analysis of 3 blood astrocyte biomarkers (glial fibrillary acidic protein [GFAP], chitinase-3-like protein 1 [YKL-40], and S100B) in patients clinically diagnosed with AD.

Adaptive Randomization Method to Prevent Extreme Instances of Group Size and Covariate Imbalance in Stroke Trials.

Background: A recent review of randomization methods used in large multicenter clinical trials within the National Institutes of Health Stroke Trials Network identified preservation of treatment allocation randomness, achievement of the desired group size balance between treatment groups, achievement of baseline covariate balance, and ease of implementation in practice as critical properties required for optimal randomization designs. Common-scale minimal sufficient balance (CS-MSB) adaptive randomization effectively controls for covariate imbalance between treatment groups while preserving allocation randomness but does not balance group sizes. This study extends the CS-MSB adaptive randomization method to achieve both group size and covariate balance while preserving allocation randomness in hyperacute stroke trials.

Large vessel occlusive stroke with milder baseline severity shows better collaterals and reduced harm from thrombectomy transfer delays.

Background: Patients with large vessel occlusion (LVO) stroke presenting with milder baseline clinical severity are common and require endovascular thrombectomy. However, such patients are difficult to recognize using pre-hospital severity-based triage tools and therefore are likely to require a secondary inter-hospital transfer if transported to a non-thrombectomy center. Given the potential for milder severity to represent better underlying cerebrovascular collateral circulation, it is unknown whether transfer delays are still associated with poorer post-stroke outcomes in this patient group.

Reporting and analysis of process-of-care time measures in clinical trials for hyperacute stroke interventions: a scoping review protocol.

Objective: The objective of this scoping review is to investigate the reporting and comparison of process-of-care time measures in hyperacute stroke trials and systematic reviews of trials (subsequently referred to as "studies").

Introduction: Stroke is a leading cause of death and disability worldwide. A crucial factor in determining the effectiveness of stroke care in improving patient outcomes is time; therefore, time measures are frequently reported in studies of hyperacute stroke interventions.

Comparison of tenecteplase with alteplase for the early treatment of ischaemic stroke in the Melbourne Mobile Stroke Unit (TASTE-A): a phase 2, randomised, open-label trial.

Background: Mobile stroke units (MSUs) equipped with a CT scanner reduce time to thrombolytic treatment and improve patient outcomes. We tested the hypothesis that tenecteplase administered in an MSU would result in superior reperfusion at hospital arrival, when compared with alteplase.

Methods: The TASTE-A trial is a phase 2, randomised, open-label trial at the Melbourne MSU and five tertiary hospitals in Melbourne, VIC, Australia.

Common scale minimal sufficient balance: An improved method for covariate-adaptive randomization based on the Wilcoxon-Mann-Whitney odds ratio statistic.

Minimal sufficient balance (MSB) is a recently suggested method for adaptively controlling covariate imbalance in randomized controlled trials in a manner which reduces the impact on randomness of allocation over other approaches by only intervening when the imbalance is sufficiently significant. Despite its improvements, the approach is unable to consider the relative clinical importance or magnitude of imbalance in each covariate weight, and ignores any imbalance which is not statistically significant, even when these imbalances may collectively justify intervention. We propose the common scale MSB (CS-MSB) method which addresses these limitations, and present simulation studies comparing our proposed method to MSB.