Christopher Streib

BACKGROUND: The mGlide RCT (randomized controlled trial) evaluated whether a pharmacist-led, mobile health technology facilitated care model improves hypertension control in diverse populations. METHODS: We recruited adult English, Spanish, or Hmong-speaking patients with uncontrolled hypertension from a large health care system and smaller community clinics serving low-income patients. Participants were randomized 1:1 to mGlide or usual care. The 6-month intervention included daily blood pressure (BP) self-monitoring using a smartphone and wireless monitor, automated app-based data sharing, and responsive medication adjustment by a pharmacist-led provider-team. Comparison participants received a digital monitor. Outcomes included mean 6-month systolic BP (SBP), 12-month sustained BP control, 24-hour ambulatory BP and patient activation. RESULTS: A total of 395 participants (mean age, 66.9 years; 46.6% women; mean [SD] SBP, 143.4 [16.5] mm Hg) were randomized to mGlide (n=198) or usual care (n=197). Mean (SD) 6-month SBP (mm Hg) was lower in the mGlide arm (128.1 [13.9] versus 134.0 [16.0]). The adjusted mean difference between groups for the primary outcome of 6-month SBP favored mGlide: −5.8 mm Hg (95% CI, −8.6 to −3.0), sustained at 12 months (−5.7 mm Hg [−8.7 to −2.6]). The mGlide arm also had a 4.8 mm Hg ( P =0.014) lower 24-hour average ambulatory SBP. The 6-month intervention effect varied significantly by activation level, with a difference of −12.6 mm Hg (−20.5 to −4.8) SBP among the lowest versus −2.5 mm Hg (−6.5 to 1.6) among the highest activation level participants. CONCLUSIONS: A mobile health-facilitated care model with pharmacist-led medication adjustment was effective in lowering BP in diverse populations. Patients with low activation benefited more from the intervention; activation levels may inform efficient intervention selection. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03612271.

Background: Intravenous thrombolysis for acute ischemic stroke (AIS) is a proven effective treatment. Whether thrombolysis in patients with AIS with recent direct oral anticoagulant (DOAC) use is safe and efficacious is not well established. We aimed to compare outcomes of patients with AIS and recent DOAC use who received thrombolysis to those otherwise eligible but excluded due to recent DOAC use. Methods: This study included patients for the GWTG (Get With The Guidelines) registry with a diagnosis of AIS within 4.5 hours from last known normal, on a DOAC, and either (1) received intravenous thrombolysis, or (2) were excluded from thrombolysis with coagulopathy being the only reason for exclusion. We used univariate and adjusted binary logistic regression models with clustering by site to compare the 2 groups’ functional status (ambulation on discharge and discharge disposition) and reported rates of safety outcomes in the thrombolysis group. Results: The study sample included 48 907 patients with AIS using a DOAC; 4702 received thrombolysis and 44 205 did not. In adjusted logistic regression models, patients with recent DOAC use receiving thrombolysis had increased odds of independent ambulation at discharge (odds ratio [OR], 1.35[ 95% CI, 1.21–1.50]) and home discharge (OR, 1.33 [95% CI, 1.22–1.46]). The rate of symptomatic intracranial hemorrhage with intravenous thrombolysis in patients with recent DOAC use was 3.5% (95% CI, 3.0%–4.1%). Conclusions: In this study, intravenous thrombolysis was associated with improved functional outcomes in patients with recent DOAC use and appeared safe. Given the study limitations, findings require validation by prospective trials.

IV thrombolysis only (IVT-O) is the primary reperfusion therapy for most stroke patients. At least 50% of IVT-O patients remain disabled. We assessed 2 therapies added to IVT-O aimed at increasing clot lysis or preventing arterial reocclusion. This 3-arm, adaptive, single-blinded, randomized controlled phase III clinical trial was conducted at 57 US sites. Patients with acute ischemic stroke (AIS) within 3 hours of onset receiving IV tissue plasminogen activator or tenecteplase were randomized to argatroban (100 μg/kg bolus and 12-hour infusion at 3 μg/kg/min), eptifibatide (135 μg/kg bolus and 2-hour infusion at 0.75 μg/kg/min), or placebo (bolus and 12-hour infusion). The primary end point was utility-weighted 90-day modified Rankin Scale score (uwmRS score; worst = 0, best = 10). This prespecified secondary analysis was conducted on the intent-to-treat population in the IVT-O cohort using a Bayesian normal dynamic linear model. Of 514 patients enrolled into Multi-arm Optimization of Stroke Thrombolysis (MOST) before the study was stopped for futility, 260 were in the IVT-O cohort (118 treated with placebo, 114 with eptifibatide, and 28 with argatroban; mean age 66 years, 46.9% female). Baseline variables were similar across groups (median NIH Stroke Scale score 8, mean time from symptom onset to IVT 105 minutes, mean time from IVT bolus to study drug start 62 minutes). A clot was visible in 30.8% of patients. There was only a 1% or 2.5% chance that argatroban or eptifibatide, respectively, was superior to placebo for the primary outcome (mean uwmRS scores [SD] of 5.5 [3.6], 6.6 [3.2], and 7.4 [2.6] for argatroban, eptifibatide, and placebo, respectively). No secondary outcomes favored either treatment group. The risk difference for symptomatic hemorrhage between the argatroban and eptifibatide arms vs placebo was -0.8% (p = 0.82) and 1.8% (p = 0.36). Mortality was 3.4% with placebo, 14.3% for argatroban (p = 0.03), and 11.4% for eptifibatide (p = 0.02). There was no benefit in any subgroup. Outcomes in patients treated with IVT-O were not improved by adding either argatroban or eptifibatide. Increased bleeding was not observed, but mortality was higher in both investigational arms. Limitations included small sample size in the argatroban subgroup. This study was registered on ClinicalTrials.gov (registration number: NCT03735979) on November 8, 2018. The first patient was enrolled on October 15, 2019. This study provides Class II evidence that in patients with AIS treated with IVT within 3 hours of onset, argatroban or eptifibatide does not improve outcomes vs thrombolysis alone but does increase mortality.

BACKGROUND: Obtaining timely informed consent is a key barrier in acute ischemic stroke clinical trial recruitment. Electronic consent (eConsent) allows electronic delivery and documentation of the informed consent process, which may optimize recruitment. eConsent in acute ischemic stroke clinical trials, however, is limited and understudied. We conducted a post hoc analysis of eConsent adoption in MOST (Multi-Arm Optimization of Stroke Thrombolysis Trial), a phase III acute ischemic stroke clinical trial, and studied the impact on recruitment. METHODS: From October 10, 2019, to July 5, 2023, MOST enrolled 514 participants at 57 sites in the United States. Study databases were reviewed to determine informed consent modality for each participant: paper—in person, paper—remote, eConsent—in person, and eConsent—remote. Study sites could use paper consent or eConsent for each enrollment. eConsent adoption trends and participant demographic diversity were reported using descriptive statistics. We utilized χ ² and Kruskal-Wallis tests to compare individual site enrollment, remote consent utilization, baseline neuroimaging-to-randomization times, data clarification requests, and reportable consent-related unanticipated events. RESULTS: eConsent was utilized for 173 (33.7%) of 514 participants. Of 57 sites, 32 (56.1%) utilized eConsent at least once: those sites had higher median enrollment over the course of the entire trial than non-eConsent sites (7.5 [interquartile range, 5–17] versus 3 [interquartile range, 2–4]; P P <0.001). Participant demographic diversity and baseline neuroimaging-to-randomization times were similar between eConsent—in person and paper—in person (median, 58.5 [interquartile range, 46.5–72.5] versus 55 [interquartile range, 39–70] minutes). Consent documentation adherence was superior with eConsent—in person compared with paper—in person including decreased data clarification requests (44 versus 81 per 100 participants) and reportable unanticipated events (6 versus 25 per 100 participants). CONCLUSIONS: eConsent in MOST was associated with higher individual site enrollment, higher remote consent rates, and improved consent documentation adherence over paper consent. Our study outlines the potential advantages of eConsent adoption in future acute ischemic stroke clinical trials and stroke research networks.

Introduction: The modified Rankin scale (mRS) is an important metric in stroke research, often used as a primary outcome in clinical trials and observational studies. The mRS can be assessed retrospectively from electronic health records (EHR), though this process is labor-intensive and prone to inter-rater variability. Large language models (LLMs) have demonstrated potential in automating clinical text classification. We hypothesize that a fine-tuned LLM can analyze EHR text and classify mRS scores for clinical and research applications. Methods: We performed a retrospective cohort study of patients admitted to a specialist stroke neurology service at a large academic hospital system between August 2020 and June 2023. Each patient’s medical record was reviewed at two time points: (1) hospital discharge and (2) approximately 90 days post-discharge. Two independent researchers assigned an mRS score at each time point. Two separate models were trained on EHR passages with corresponding mRS scores as labeled outcomes: (1) a multiclass model to classify all seven mRS scores and (2) a binary model to classify functional independence (mRS 0–2) versus non-independence (mRS 3–6). Four-fold cross-validation was conducted, using accuracy and Cohen’s kappa as model performance metrics. Results: A total of 2,290 EHR passages with corresponding mRS scores were included in model training. The multiclass model—considering all seven scores of the mRS—attained an accuracy of 77% and a weighted Cohen’s Kappa of 0.92. Class-specific accuracy was highest for mRS 4 (90%) and lowest for mRS 2 (28%). The binary model—considering only functional independence vs non-independence —attained an accuracy of 92% and Cohen’s Kappa of 0.84. Conclusion: Our findings demonstrate that LLMs can be successfully trained to determine mRS scores through EHR text analysis. With further advancements, fully automated LLMs could scale across large clinical datasets, enabling data-driven public health strategies and optimized resource allocation.

The objective of this study was to estimate the incidence, timing, and type of new cancer diagnosis among patients with cryptogenic stroke. We used data from the ARCADIA trial, which enrolled patients with cryptogenic stroke and atrial cardiopathy. Participants were prospectively followed, and serious adverse events were assessed every 3 months or sooner if investigators were alerted between visits to an event. Kaplan-Meier statistics were used to estimate the cumulative incidence of a cancer diagnosis within the first year after randomization. Among 878 participants without baseline history of cancer, 13 (1.5%) were diagnosed with incident cancer in the year after randomization, comprising 12 solid cancers (3 prostate, 2 breast, 2 gastrointestinal, and 5 other primary sites) and 1 hematologic cancer (non-Hodgkin lymphoma). The cumulative incidences of a cancer diagnosis were 0% at 3 months, 0.6% (95% CI 0.2%-1.5%) at 6 months, and 2.0% (95 CI 1.1%-3.4%) at 1 year. The median time from index stroke to cancer diagnosis was 261 days (interquartile range 183-358). In a multicenter cryptogenic stroke cohort with prospective follow-up, the 1-year cumulative incidence of a cancer diagnosis was 2%. This rate may be an underestimation because of the clinical trial population and exclusion of cancers diagnosed immediately after stroke. ClinicalTrials.gov Identifier: NCT03192215. Registered June 20, 2017. First patient enrolled February 1, 2018.

SUMMARY: Cerebral amyloid angiopathy (CAA) is a progressive neurodegenerative small vessel disease that is associated with intracranial hemorrhage and cognitive impairment in the elderly. The clinical and radiographic presentations have many overlapping features with vascular cognitive impairment, hemorrhagic stroke, and Alzheimer disease (AD). Amyloid-β-related angiitis (ABRA) is a form of primary CNS vasculitis linked to CAA, with the development of spontaneous autoimmune inflammation against amyloid in the vessel wall with resultant vasculitis. The diagnosis of ABRA and CAA is important. ABRA is often fatal if untreated and requires prompt immunosuppression. Important medical therapies such as anticoagulation and antiamyloid agents for AD are contraindicated in CAA. Here, we present a biopsy-proved case of ABRA with underlying occult CAA. Initial 1.5T and 3T MR imaging did not suggest CAA per the Boston Criteria 2.0. ABRA was not included in the differential diagnosis due to the lack of any CAA-related findings on conventional MR imaging. However, a follow-up 7T MR imaging revealed extensive cortical/subcortical cerebral microbleeds, cortical superficial siderosis, and intragyral hemorrhage in extensive detail throughout the supratentorial brain regions, which radiologically supported the diagnosis of ABRA in the setting of CAA. This case suggests an increased utility of high-field MR imaging to detect occult hemorrhagic neuroimaging findings with the potential to both diagnose more patients with CAA and diagnose them earlier.

BACKGROUND: Inpatient telestroke programs have emerged as a solution to provide timely stroke care in underserved areas, but their successful implementation and factors influencing their effectiveness remain underexplored. This study aimed to qualitatively evaluate the perspectives of inpatient clinicians located at spoke hospitals participating in a newly established inpatient telestroke program to identify implementation barriers and facilitators. METHODS: This was a formative evaluation relying on semistructured qualitative interviews with 16 inpatient providers (physicians and nurse practitioners) at 5 spoke sites of a hub-and-spoke inpatient telestroke program. The Integrated-Promoting Action on Research Implementation in Health Services framework guided data analysis, focusing on the innovation, recipients, context, and facilitation aspects of implementation. Interviews were transcribed and coded using thematic analysis. RESULTS: Fifteen themes were identified in the data and mapped to the Integrated-Promoting Action on Research Implementation in Health Services framework. Themes related to the innovation (the telestroke program) included easy access to stroke specialists, the benefits of limiting patient transfers, concerns about duplicating tests, and challenges of timing inpatient telestroke visits and notes to align with discharge workflow. Themes pertaining to recipients (care team members and patients) were communication gaps between teams, concern about the supervision of inpatient telestroke advanced practice providers and challenges with nurse empowerment. With regard to the context (hospital and system factors), providers highlighted familiarity with telehealth technologies as a facilitator to implementing inpatient telestroke, yet highlighted resource limitations in smaller facilities. Facilitation (program implementation) was recognized as crucial for education, standardization, and buy-in. CONCLUSIONS: Understanding barriers and facilitators to implementation is crucial to determining where programmatic changes may need to be made to ensure the success and sustainment of inpatient telestroke services.

BACKGROUND The mGlide randomized clinical trial (RCT) is an NIH-funded study, evaluating whether a mobile health (mHealth)-based intervention that facilitates an active partnership between interprofessional health-care teams and patients results better hypertension (HTN) control than a state-of-clinical-care comparison in patients with uncontrolled HTN. The intervention uses readily available smartphone technology. OBJECTIVE The mGlide RCT was implemented in diverse health systems and was ongoing during the pandemic. The protocol was previously published. We describe the differential impact of the pandemic and consequent protocol updates and study timeline changes. METHODS We enrolled participants with uncontrolled HTN who were stroke survivors or primary care patients with elevated cardiovascular disease (CVD) risk from diverse health systems. Planned recruitment sites included primary care clinics and specialty stroke service in an integrated academic health system as well as university-affiliated community clinics and federally qualified health centers (FQHC). The FQHC and community clinics predominantly serve low-income patients and diverse racial/ethnic minorities - including African American, Hmong, and Latino patients. The primary aim tests the clinical effectiveness of reducing SBP of the 6-month mHealth intervention versus standard of care. Secondary aims evaluate sustained HTN control at 12 months, provider experiences of system usability, patient experiences, (including medication adherence, medication use self-efficacy, self-rated health, and quality of life), and adverse event rates. RESULTS Trial recruitment commenced in 2019 and enrollment of 395 participants was completed in August 2023. The last follow-up will be completed in August 2024. The pandemic severely disrupted trial operations. On 3/16/2020, a moratorium on active clinical research was enacted within our health system in order to minimize in-person contact. All mGlide recruitment, enrollment, and follow-up activities ceased. Subsequently, the research team developed remote enrollment and follow-up processes that were utilized until COVID-19 vaccines became available in early 2021. A differential pandemic impact on health system research capacity was noted. The standalone FQHC had the highest rates of study drop-outs and was not able to recover its research capacity post-pandemic. Many clinics, however, including community clinics were impacted in the short-term but recovered their research capacity. Enrollments at the integrated health system were least impacted. Some rural clinics that were added for recruitment later in the study, (September 2022), showed robust participation. The Data Safety Monitoring Board reviewed two interim analyses (December 2021 and October 2022) and recommended that the primary analysis use a continuous endpoint of mean systolic blood pressure difference between the two arms in addition to a dichotomous endpoint of <140 mm Hg. Consequently, the needed sample size was lowered. CONCLUSIONS We describe the dynamics of implementing a technology-based intervention with real-world challenges when participants and healthcare systems are significantly impacted by a disruptive pandemic. CLINICALTRIAL Clinicaltrials.gov: NCT03612271 https://clinicaltrials.gov/study/NCT03612271

Occlusion of the artery of Percheron (AOP) produces bilateral thalamic infarction classically leading to deficits of arousal. This nonspecific presentation complicates the diagnosis of acute ischemic stroke. We sought to describe the spectrum of clinical presentation, diagnostic neuroimaging findings, and outcomes in AOP infarction (AOPi). We conducted a keyword search of our health system's neuroimaging database from 2014 to 2022 to identify patients with AOPi. We abstracted patient demographics, clinical presentation, neuroimaging findings, acute treatment, and modified Rankin Scale (mRS) scores (at baseline, 3 months, and 12 months). We used descriptive statistics to report our findings. Our initial keyword search identified 192 potential AOPi cases. Fifteen cases of AOPi were confirmed and included in our study (8 female [53%], median age 65 years [interquartile range (IQR): 59.5-79.5], median presenting NIHSS 6 [IQR: 2-22]). Common clinical findings on presentation were systolic blood pressure (SBP) > 140: 12 patients (80%); decreased level of consciousness (LOC): 11 patients (73%); diplopia: 8 patients (57%); disorientation: 6 patients (42%); dysarthria: 4 patients (28%); and acute memory/cognitive disturbance: 3 patients (21%). Twelve cases (80%) presented to the emergency department (ED). Median time from symptom onset to ED arrival was 774.5 minutes (IQR: 202.25-3789.0), 4 cases (27%) arrived within 4.5 hours, and one patient (7%) received intravenous thrombolysis. The median time from ED arrival to stroke diagnosis was 519.0 minutes (IQR: 227.5-1307). Head CT was only diagnostic when obtained >570 minutes from time last known well; MRI was diagnostic at all time points. Rates of functional independence (mRS ≤2) at baseline, 3 months, and 12 months were 64%, 21%, and 18%, respectively. The diagnosis of stroke was considerably delayed in patients with AOPi, and only one patient received IV thrombolysis. SBP >140, impaired consciousness, and diplopia were the most common findings at presentation. CT was often nondiagnostic, but MRI demonstrated bilateral thalamic infarct in all cases. AOPi caused considerable long-term morbidity. Clinicians should maintain a high degree of suspicion for AOP stroke and consider thrombolysis in appropriately selected patients.