Clinical trials often struggle to recruit enough participants, with only 10% of eligible patients enrolling. This is concerning for conditions like stroke, where timely decision-making is crucial. Frontline clinicians typically screen patients manually, but this approach can be overwhelming and lead to many eligible patients being overlooked.

To address the problem of efficient and inclusive screening for trials, we developed a matching algorithm using imaging and clinical variables gathered as part of the AcT trial (NCT03889249) to automatically screen patients by matching these variables with the trials’ inclusion and exclusion criteria using rule-based logic. We then used the algorithm to identify patients who could have been enrolled in six trials: EASI-TOC (NCT04261478), CATIS-ICAD (NCT04142125), CONVINCE (NCT02898610), TEMPO-2 (NCT02398656), ESCAPE-MEVO (NCT05151172), and ENDOLOW (NCT04167527). To evaluate our algorithm, we compared our findings to the number of enrollments achieved without using a matching algorithm. The algorithm’s performance was validated by comparing results with ground truth from a manual review of two clinicians. The algorithm’s ability to reduce screening time was assessed by comparing it with the average time used by study clinicians.

The algorithm identified more potentially eligible study candidates than the number of participants enrolled. It also showed over 90% sensitivity and specificity for all trials, and reducing screening time by over 100-fold.

Automated matching algorithms can help clinicians quickly identify eligible patients and reduce resources needed for enrolment. Additionally, the algorithm can be modified for use in other trials and diseases.

Growing evidence suggests that direct oral anticoagulants (DOACs) may be suitable for cerebral venous thrombosis (CVT). The optimal strategy regarding lead-in parenteral anticoagulation (PA) prior to DOAC is unknown.

In this post hoc analysis of the retrospective ACTION-CVT study, we compared patients treated with DOACs as part of routine care: those given “very early” DOAC (no PA), “early” (<5 days PA) and “delayed” (5–21 days PA). We compared baseline characteristics and outcomes between the very early/early and delayed groups. The primary outcome was a composite of day-30 CVT recurrence/extension, new peripheral venous thromboembolism, cerebral edema and intracranial hemorrhage.

Of 231 patients, 11.7% had very early DOAC, 64.5% early (median [IQR] 2 [1–2] days) and 23.8% delayed (5 [5–6] days). More patients had severe clinical/radiological presentations in the delayed group; more patients had isolated headaches in the very early/early group. Outcomes were better in the very early/early groups (90-day modified Rankin Scale of 0–2; 94.3% vs. 83.9%). Primary outcome events were rare and did not differ significantly between groups (2.4% vs. 2.1% delayed; adjusted HR 1.49 [95%CI 0.17–13.11]).

In this cohort of patients receiving DOAC for CVT as part of routine care, >75% had <5 days of PA. Those with very early/early initiation of DOAC had less severe clinical presentations. Low event rates and baseline differences between groups preclude conclusions about safety or effectiveness. Further prospective data will inform care.

Diagnosis of acute ischemia typically relies on evidence of ischemic lesions on magnetic resonance imaging (MRI), a limited diagnostic resource. We aimed to determine associations of clinical variables and acute infarcts on MRI in patients with suspected low-risk transient ischemic attack (TIA) and minor stroke and to assess their predictive ability.

We conducted a post-hoc analysis of the Diagnosis of Uncertain-Origin Benign Transient Neurological Symptoms (DOUBT) study, a prospective, multicenter cohort study investigating the frequency of acute infarcts in patients with low-risk neurological symptoms. Primary outcome parameter was defined as diffusion-weighted imaging (DWI)-positive lesions on MRI. Logistic regression analysis was performed to evaluate associations of clinical characteristics with MRI-DWI-positivity. Model performance was evaluated by Harrel’s c-statistic.

In 1028 patients, age (Odds Ratio (OR) 1.03, 95% Confidence Interval (CI) 1.01–1.05), motor (OR 2.18, 95%CI 1.27–3.65) or speech symptoms (OR 2.53, 95%CI 1.28–4.80), and no previous identical event (OR 1.75, 95%CI 1.07–2.99) were positively associated with MRI-DWI-positivity. Female sex (OR 0.47, 95%CI 0.32–0.68), dizziness and gait instability (OR 0.34, 95%CI 0.14–0.69), normal exam (OR 0.55, 95%CI 0.35–0.85) and resolved symptoms (OR 0.49, 95%CI 0.30–0.78) were negatively associated. Symptom duration and any additional symptoms/symptom combinations were not associated. Predictive ability of the model was moderate (c-statistic 0.72, 95%CI 0.69–0.77).

Detailed clinical information is helpful in assessing the risk of ischemia in patients with low-risk neurological events, but a predictive model had only moderate discriminative ability. Patients with clinically suspected low-risk TIA or minor stroke require MRI to confirm the diagnosis of cerebral ischemia.

Unlike other causes of stroke, symptoms in cerebral venous thrombosis (CVT) can be nonspecific at onset with gradual worsening over time. To explore potential opportunities for earlier diagnosis, we analyzed healthcare interactions in the week prior to hospitalization for patients admitted with incident CVT in British Columbia (BC).

We constructed a population-based cohort (2000–2017) using linked patient-level administrative data to identify patients aged ≥18 diagnosed with CVT in BC. We used descriptive analysis to describe the frequency and types of healthcare encounters within the 7 and 3 days prior to hospitalization. Multivariable logistic regression modeling was performed to examine risk factors associated with prior encounters.

The cohort included 554 patients (mean age 50.9 years, 55.4% female). Within the 7 days prior to CVT hospitalization, 57.9% of patients had ≥1 outpatient encounter and 5.6% had ≥1 inpatient encounter. In the 3 days prior to hospitalization, 46.8% of patients had ≥1 outpatient encounter and 2.0% had ≥1 inpatient encounter. Women more frequently had outpatient interactions within 7 days (64.8% women vs. 35.2% men, p < 0.001) and 3 days (51.8% vs. 48.2%, p = 0.01) before admission. Common provider specialties for outpatient encounters were general practice (58.0%), emergency (8.3%) and neurology (5.7%). Females had higher odds (OR = 1.79) of having ≥1 outpatient encounter after adjusting for confounding.

Within our Canadian cohort, over half of patients had a healthcare encounter within 7 days before their hospitalization with incident CVT. Women more commonly had an outpatient encounter preceding hospital admission.

Stroke outcomes research requires risk-adjustment for stroke severity, but this measure is often unavailable. The Passive Surveillance Stroke SeVerity (PaSSV) score is an administrative data-based stroke severity measure that was developed in Ontario, Canada. We assessed the geographical and temporal external validity of PaSSV in British Columbia (BC), Nova Scotia (NS) and Ontario, Canada.

We used linked administrative data in each province to identify adult patients with ischemic stroke or intracerebral hemorrhage between 2014-2019 and calculated their PaSSV score. We used Cox proportional hazards models to evaluate the association between the PaSSV score and the hazard of death over 30 days and the cause-specific hazard of admission to long-term care over 365 days. We assessed the models’ discriminative values using Uno’s c-statistic, comparing models with versus without PaSSV.

We included 86,142 patients (n = 18,387 in BC, n = 65,082 in Ontario, n = 2,673 in NS). The mean and median PaSSV were similar across provinces. A higher PaSSV score, representing lower stroke severity, was associated with a lower hazard of death (hazard ratio and 95% confidence intervals 0.70 [0.68, 0.71] in BC, 0.69 [0.68, 0.69] in Ontario, 0.72 [0.68, 0.75] in NS) and admission to long-term care (0.77 [0.76, 0.79] in BC, 0.84 [0.83, 0.85] in Ontario, 0.86 [0.79, 0.93] in NS). Including PaSSV in the multivariable models increased the c-statistics compared to models without this variable.

PaSSV has geographical and temporal validity, making it useful for risk-adjustment in stroke outcomes research, including in multi-jurisdiction analyses.

Collateral status is an indicator of a favorable outcome in stroke. Leptomeningeal collaterals provide alternative routes for brain perfusion following an arterial occlusion or flow-limiting stenosis. Using a large cohort of ischemic stroke patients, we examined the relative contribution of various demographic, laboratory, and clinical variables in explaining variability in collateral status.

Patients with acute ischemic stroke in the anterior circulation were enrolled in a multi-center hospital-based observational study. Intracranial occlusions and collateral status were identified and graded using multiphase computed tomography angiography. Based on the percentage of affected territory filled by collateral supply, collaterals were graded as either poor (0–49%), good (50–99%), or optimal (100%). Between-group differences in demographic, laboratory, and clinical factors were explored using ordinal regression models. Further, we explored the contribution of measured variables in explaining variance in collateral status.

386 patients with collateral status classified as poor (n = 64), good (n = 125), and optimal (n = 197) were included. Median time from symptom onset to CT was 120 (IQR: 78–246) minutes. In final multivariable model, male sex (OR 1.9, 95% CIs [1.2, 2.9], p = 0.005) and leukocytosis (OR 1.1, 95% CIs [1.1, 1.2], p = 0.001) were associated with poor collaterals. Measured variables only explained 44.8–53.0% of the observed between-patient variance in collaterals.

Male sex and leukocytosis are associated with poorer collaterals. Nearly half of the variance in collateral flow remains unexplained and could be in part due to genetic differences.

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.

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).

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.

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.

To evaluate an abbreviated NIH Toolbox Cognition Battery (NIHTB-CB) protocol that can be administered remotely without any in-person assessments, and explore the agreement between prorated scores from the abbreviated protocol and standard scores from the full protocol.

Participant-level age-corrected NIHTB-CB data were extracted from six studies in individuals with a history of stroke, mild traumatic brain injury (mTBI), treatment-resistant psychosis, and healthy controls, with testing administered under standard conditions. Prorated fluid and total cognition scores were estimated using regression equations that excluded the three fluid cognition NIHTB-CB instruments which cannot be administered remotely. Paired t tests and intraclass correlations (ICCs) were used to compare the standard and prorated scores.

Data were available for 245 participants. For fluid cognition, overall prorated scores were higher than standard scores (mean difference = +4.5, SD = 14.3; p < 0.001; ICC = 0.86). For total cognition, overall prorated scores were higher than standard scores (mean difference = +2.7, SD = 8.3; p < 0.001; ICC = 0.88). These differences were significant in the stroke and mTBI groups, but not in the healthy control or psychosis groups.

Prorated scores from an abbreviated NIHTB-CB protocol are not a valid replacement for the scores from the standard protocol. Alternative approaches to administering the full protocol, or corrections to scoring of the abbreviated protocol, require further study and validation.

A Canadian Stroke Best Practices consensus statement on Acute Stroke Management during pregnancy was published in 2018. The state of individual practice, however, is unknown.

A survey on treatment of acute stroke in pregnant and post-partum women was distributed via the Canadian Stroke Consortium email list. Descriptive statistics (frequencies and proportions) were calculated for demographic and response variables and free-text responses were coded for thematic content.

Thirty-five participants completed the survey; 12 had experience with intravenous tissue plasminogen activator (IV-tPA), endovascular therapy (EVT), or both in pregnant patients. None had treatment-related complications. The majority (92%) of those who had not yet encountered the issue in practice expressed some reservation about giving IV-tPA to an otherwise eligible pregnant woman. In a theoretical scenario where an otherwise eligible pregnant woman was a candidate for both IV-tPA and EVT, 58% of respondents would have opted for EVT alone. Amongst this cohort comprised mainly of stroke sub-specialists, more than a third had treated pregnant patients with reperfusion therapy.

The reported safety experience with both IV-tPA and EVT was reassuring. Overall, there was a hesitancy towards use of IV-tPA in pregnancy that is discordant with the recent consensus statement. Possible barriers to uptake identified through thematic analysis were concerns regarding risks of bleeding in the pregnant patient, presence of EVT as a perceived alternative, and the need for express consent from the patient and family.