A qualitative study of barriers and facilitators to using tenecteplase to treat acute ischemic stroke.

BACKGROUND: Tenecteplase (TNK) is emerging as an alternative to alteplase (ALT) for thrombolytic treatment of acute ischemic stroke (AIS). Compared to ALT, TNK has a longer half-life, shorter administration time, lower cost, and similarly high efficacy in treating large vessel occlusion. Nevertheless, there are barriers to adopting TNK as a treatment for AIS. This study aimed to identify thematic barriers and facilitators to adopting TNK as an alternative to ALT as a thrombolytic for eligible AIS patients. METHODS: Qualitative research methodology using hermeneutic cycling and purposive sampling was used to interview four stroke clinicians in Texas. Interviews were recorded and transcribed verbatim. Enrollment was complete when saturation was reached. All members of the research team participated in content analysis during each cycle and in thematic analysis after saturation. RESULTS: Interviews were conducted between November 2022 and February 2023 with stroke center representatives from centers that either had successfully adopted TNK, or had not yet adopted TNK. Three themes and eight sub-themes were identified. The theme "Evidence" had three sub-themes: Pro-Con Balance, Fundamental Knowledge, and Pharmacotherapeutics. The theme "Process Flow" had four subthemes: Proactive, Reflective self-doubt, Change Process Barriers, and Parameter Barriers. The theme "Consensus" had one sub-theme: Getting Buy-In. CONCLUSION: Clinicians experience remarkably similar barriers and facilitators to adopting TNK. The results lead to a hypothesis that providing evidence to support a practice change, and identifying key change processes, will help clinicians achieve consensus across teams that need to 'buy in' to adopting TNK for AIS treatment.

Multicenter exploration of tenecteplase transition factors: A quantitative analysis.

BACKGROUND: Tenecteplase (TNK) is gaining recognition as a novel therapy for acute ischemic stroke (AIS). Despite TNK offering a longer half-life, time and cost saving benefits and comparable treatment and safety profiles to Alteplase (ALT), the adoption of TNK as a treatment for AIS presents challenges for hospital systems. OBJECTIVE: Identify barriers and facilitators of TNK implementation at acute care hospitals in Texas. METHODS: This prospective survey used open-ended questions and Likert statements generated from content experts and informed by qualitative research. Stroke clinicians and nurses working at 40 different hospitals in Texas were surveyed using a virtual platform. RESULTS: The 40 hospitals had a median of 34 (IQR 24.5-49) emergency department beds and 42.5 (IQR 23.5-64.5) inpatient stroke beds with 506.5 (IQR 350-797.5) annual stroke admissions. Fifty percent of the hospitals were Comprehensive Stroke Centers, and 18 (45 %) were solely using ALT for treatment of eligible AIS patients. Primary facilitators to TNK transition were team buy-in and a willingness of stroke physicians, nurses, and pharmacists to adopt TNK. Leading barriers were lack of clinical evidence supporting TNK safety profile inadequate evidence supporting TNK use and a lack of American Heart Association guidelines support for TNK administration in all AIS cases. CONCLUSION: Understanding common barriers and facilitators to TNK adoption can assist acute care hospitals deciding to implement TNK as a treatment for AIS. These findings will be used to design a TNK adoption Toolkit, utilizing implementation science techniques, to address identified obstacles and to leverage facilitators.

Door to needle time trends after transition to tenecteplase: A Multicenter Texas stroke registry.

BACKGROUND: Tenecteplase (TNK) is considered a promising option for the treatment of acute ischemic stroke (AIS) with the potential to decrease door-to-needle times (DTN). This study investigates DTN metrics and trends after transition to tenecteplase. METHODS: The Lone Star Stroke (LSS) Research Consortium TNK registry incorporated data from three Texas hospitals that transitioned to TNK. Subject data mapped to Get-With-the-Guidelines stroke variables from October 1, 2019 to March 31, 2023 were limited to patients who received either alteplase (ALT) or TNK within the 90 min DTN times. The dataset was stratified into ALT and TNK cohorts with univariate tables for each measured variable and further analyzed using descriptive statistics. Logistic regression models were constructed for both ALT and TNK to investigate trends in DTN times. RESULTS: In the overall cohort, the TNK cohort (n = 151) and ALT cohort (n = 161) exhibited comparable population demographics, differing only in a higher prevalence of White individuals in the TNK cohort. Both cohorts demonstrated similar clinical parameters, including mean NIHSS, blood glucose levels, and systolic blood pressure at admission. In the univariate analysis, no difference was observed in median DTN time within the 90 min time window compared to the ALT cohort [40 min (30-53) vs 45 min (35-55); P = .057]. In multivariable models, DTN times by thrombolytic did not significantly differ when adjusting for NIHSS, age (P = .133), or race and ethnicity (P = .092). Regression models for the overall cohort indicate no significant DTN temporal trends for TNK (P = .84) after transition; nonetheless, when stratified by hospital, a single subgroup demonstrated a significant DTN upward trend (P = 0.002). CONCLUSION: In the overall cohort, TNK and ALT exhibited comparable temporal trends and at least stable DTN times. This indicates that the shift to TNK did not have an adverse impact on the DTN stroke metrics. This seamless transition is likely attributed to the similarity of inclusion and exclusion criteria, as well as the administration processes for both medications. When stratified by hospital, the three subgroups demonstrated variable DTN time trends which highlight the potential for either fatigue or unpreparedness when switching to TNK. Because our study included a multi-ethnic cohort from multiple large Texas cities, the stable DTN times after transition to TNK is likely applicable to other healthcare systems.

Endovascular Thrombectomy for Acute Ischemic Strokes: Current US Access Paradigms and Optimization Methodology.

Background and Purpose- Timely access to endovascular thrombectomy (EVT) centers is vital for best acute ischemic stroke outcomes. Methods- US stroke-treating centers were mapped utilizing geo-mapping and stratified into non-EVT or EVT if they reported ≥1 acute ischemic stroke thrombectomy code in 2017 to Center for Medicare and Medicaid Services. Direct EVT-access, defined as the population with the closest facility being an EVT-center, was calculated from validated trauma-models adapted for stroke. Current 15- and 30-minute access were described nationwide and at state-level with emphasis on 4 states (TX, NY, CA, IL). Two optimization models were utilized. Model-A used a greedy algorithm to capture the largest population with direct access when flipping 10% and 20% non-EVT to EVT-centers to maximize access. Model-B used bypassing methodology to directly transport patients to the nearest EVT centers if the drive-time difference from the geo-centroid to hospital was within 15 minutes from the geo-centroid to the closest non-EVT center. Results- Of 1941 stroke-centers, 713 (37%) were EVT. Approximately 61 million (19.8%) Americans have direct EVT access within 15 minutes while 95 million (30.9%) within 30 minutes. There were 65 (43%) EVT centers in TX with 22% of the population currently within 15-minute access. Flipping 10% hospitals with top population density improved access to 30.8%, while bypassing resulted in 45.5% having direct access to EVT centers. Similar results were found in NY (current, 20.9%; flipping, 34.7%; bypassing, 50.4%), CA (current, 25.5%; flipping, 37.3%; bypassing, 53.9%), and IL (current, 15.3%; flipping, 21.9%; bypassing, 34.6%). Nationwide, the current direct access within 15 minutes of 19.8% increased by 7.5% by flipping the top 10% non-EVT to EVT-capable in all states. Bypassing non-EVT centers by 15 minutes resulted in a 16.7% gain in coverage. Conclusions- EVT-access within 15 minutes is limited to less than one-fifth of the US population. Optimization methodologies that increase EVT centers or bypass non-EVT to the closest EVT center both showed enhanced access. Results varied by states based on the population size and density. However, bypass showed more potential for maximizing direct EVT-access. National and state efforts should focus on identifying gaps and tailoring solutions to improve EVT-access.

Racial disparities in post-stroke functional outcomes in young patients with ischemic stroke.

BACKGROUND AND PURPOSE: Recent studies show rising incidence of stroke in the young, for which risk factors are not well characterized. There is evidence of increased risk in certain racial and ethnic groups. We assessed racial differences in risk factors, stroke etiology, and outcomes among young stroke patients. METHODS: Using data from our inpatient registry for ischemic stroke, we reviewed patients aged 18-50 who were admitted 01/2013 to 04/2018. Race/ethnicity were characterized as non-Hispanic White (NHW), non-Hispanic Black (NHB), Hispanic (HIS). For univariate comparisons Chi-square and Kruskal-Wallis tests were performed as appropriate. Multivariable logistic regression was used to assess impact of race on day seven modified Rankin score (mRS). RESULTS: Among 810 patients with race and outcome data who were admitted in the study period, median age was 43, 57.1% were male, and 36.5% NHW, 43.2% NHB, 20.2% HIS. History of hypertension (HTN), type II diabetes (DM II), smoking, heart failure (CHF), prior stroke, and end-stage renal disease varied significantly by race. Compared to NHW, NHB had higher odds of HTN (OR 2.28, 1.65-3.15), CHF (OR 2.17, 1.06-4.46), and DM II 1.92 (1.25-2.94) while HIS had higher odds of DM II (OR 2.52, 1.55-4.10) and lower odds of smoking (OR 0.56, 0.35-0.90). Arrival NIHSS was higher in NHB, but etiology and rates of tpA treatment and thrombectomy did not vary by race. Compared to NHW patients, NHB (OR 0.50 CI (0.31-0.78)) and HIS (OR 0.37 CI (0.21-0.67)) were less likely to have good functional outcome (mRS <2) at day 7 in adjusted analyses. CONCLUSIONS: In this study, there was a higher prevalence of several modifiable risk factors in NHB and HIS young stroke patients and early functional outcome was worse in these groups. Our study suggests a need for targeted prevention efforts for younger populations at highest risk for stroke.

Racial and gender differences in stroke severity, outcomes, and treatment in patients with acute ischemic stroke.

BACKGROUND: Previous research has indicated that women and blacks have worse outcomes after acute ischemic stroke (AIS). Little research has been done to investigate the combined influence of race and gender in the presentation, treatment, and outcome of patients with AIS. We sought to determine the association of race and gender on initial stroke severity, thrombolysis, and functional outcome after AIS. METHODS: AIS patients who presented to 2 academic medical centers in the United States (2004-2011) were identified through prospective registries. In-hospital strokes were excluded. Stroke severity, measured by admission National Institutes of Health Stroke Scale (NIHSS) scores, treatment with tissue plasminogen activator (tPA), neurologic deterioration (defined by a ≥2-point increase in NIHSS score), and functional outcome at discharge, measured by the modified Rankin Scale, were investigated. These outcomes were compared across race/gender groups. A subanalysis was conducted to assess race/gender differences in exclusion criteria for tPA. RESULTS: Of the 4925 patients included in this study, 2346 (47.6%) were women and 2310 (46.9%) were black. White women had the highest median NIHSS score on admission (8), whereas white men had the lowest median NIHSS score on admission (6). There were no differences in outcomes between black men and white men. A smaller percentage of black women than white women were treated with tPA (27.6% versus 36.6%, P < .0001), partially because of a greater proportion of white women presenting within 3 hours (51% versus 45.5%, P = .0005). Black women had decreased odds of poor functional outcome relative to white women (odds ratio [OR] = .85, 95% confidence interval [CI] .72-1.00), but after adjustment for baseline differences in age, NIHSS, and tPA use, this association was no longer significant (OR = 1.2, 95% CI .92-1.46, P = .22). Black women with an NIHSS score less than 7 on admission were at lower odds of receiving tPA than the other race/gender groups, even after adjusting for arriving within 3 hours and admission glucose (OR = .66, 95% CI .44-.99, P = .0433). CONCLUSION: Race and gender were not significantly associated with short-term outcome, although black women were significantly less likely to be treated with tPA. Black women had more tPA exclusions than any other group. The primary reason for tPA exclusion in this study was not arriving within 3 hours of stroke symptom onset. Given the growth in incident strokes projected in minority groups in the next 4 decades, identifying factors that contribute to black women not arriving to the emergency department in time are of great importance.

Short-term bleeding events observed with clopidogrel loading in acute ischemic stroke patients.

INTRODUCTION: The Fast Assessment of Stroke and Transient Ischemic Attack to Prevent Early Recurrence trial raised concern that loading doses of clopidogrel may increase hemorrhagic complications. We investigated if similar rates of hemorrhage occur in patients with acute ischemic stroke (AIS) of varying severity. METHODS: Patients meeting inclusion criteria were divided into 2 groups: the LOAD group and non-LOAD group. The LOAD group was defined as patients who were administered a loading dose of 300 mg or more of clopidogrel with or without aspirin within 24 hours of admission. The non-LOAD group was devised using propensity score (PS): 55 patients who received a loading dose of clopidogrel of 300 mg or more were matched on PS to 55 patients who did not receive loading doses. These patients were taken from a pool of 341 consecutive ischemic patients ineligible for intravenous or intra-arterial fibrinolysis, 162 of whom received a clopidogrel loading dose and the remainder of whom did not. The frequency of hemorrhage was compared between the 2 groups using Student t test and chi-square. Logistic regression was used to assess the relationship between loading dose and serious bleeding events (symptomatic intracerebral hemorrhage [sICH] or transfusion for systemic bleeding). RESULTS: AIS patients (N = 596) were screened during the 31-month period of this retrospective study. Of this sample, 170 patients were excluded: 149 patients were excluded because they were treated with intravenous tissue plasminogen activator (IV t-PA) alone, 11 were excluded because they were treated with IV t-PA combined with intra-arterial therapy (IAT), and 10 were excluded for treatment with IAT alone. An additional 85 patients were excluded because they were not admitted to the stroke service or because they had an in-hospital stroke. Baseline characteristics of the groups were well matched. There were no significant differences in the rates of sICH, transfusion, hemorrhagic transformation, or systemic bleeding. Clopidogrel loading was not associated with increased odds of serious bleeding events in the crude model (odds ratio [OR] .92, 95% confidence interval [CI] .27-3.13) or after adjusting for covariates and confounders of interest (OR 1.06, 95% CI .28-4.04). DISCUSSION: Contrary to our original hypothesis, patients with AIS receiving clopidogrel loading doses within 24 hours of symptom onset did not appear to experience a higher rate of new serious bleeding events during acute hospitalization when compared with patients who did not receive loading doses. The Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke trial is expected to provide insight into the safety of clopidogrel loading as an acute intervention after cerebral ischemia.

Sex differences in endovascular thrombectomy outcomes in large vessel occlusion: a propensity-matched analysis from the SELECT study.

BACKGROUND: Sex disparities in acute ischemic stroke outcomes are well reported with IV thrombolysis. Despite several studies, there is still a lack of consensus on whether endovascular thrombectomy (EVT) outcomes differ between men and women. OBJECTIVE: To compare sex differences in EVT outcomes at 90-day follow-up and assess whether progression in functional status from discharge to 90-day follow-up differs between men and women. METHODS: From the Selection for Endovascular Treatment in Acute Ischemic Stroke (SELECT) prospective cohort study (2016-2018), adult men and women (≥18 years) with anterior circulation large vessel occlusion (internal carotid artery, middle cerebral artery M1/M2) treated with EVT up to 24 hours from last known well were matched using propensity scores. Discharge and 90-day modified Rankin Scale (mRS) scores were compared between men and women. Furthermore, we evaluated the improvement in mRS scores from discharge to 90 days in men and women using a repeated-measures, mixed-effects regression model. RESULTS: Of 285 patients, 139 (48.8%) were women. Women were older with median (IQR) age 69 (57-81) years vs 64.5 (56-75), p=0.044, had smaller median perfusion deficits (Tmax >6 s) 109 vs 154 mL (p<0.001), and had better collaterals on CT angiography and CT perfusion but similar ischemic core size (relative cerebral blood flow <30%: 7.6 (0-25.2) vs 11.4 (0-38) mL, p=0.22). In 65 propensity-matched pairs, despite similar discharge functional independence rates (women: 42% vs men: 48%, aOR=0.55, 95% CI 0.18 to 1.69, p=0.30), women exhibited worse 90-day functional independence rates (women: 46% vs men: 60%, aOR=0.41, 95% CI 0.16 to 1.00, p=0.05). The reduction in mRS scores from discharge to 90 days also demonstrated a significantly larger improvement in men (discharge 2.49 and 90 days 1.88, improvement 0.61) than in women (discharge 2.52 and 90 days 2.44, improvement 0.08, p=0.036). CONCLUSION: In a propensity-matched cohort from the SELECT study, women had similar discharge outcomes as men following EVT, but the improvement from discharge to 90 days was significantly worse in women, suggesting the influence of post-discharge factors. Further exploration of this phenomenon to identify target interventions is warranted. TRIAL REGISTRATION NUMBER: NCT02446587.

Emergency department shift change is associated with pneumonia in patients with acute ischemic stroke.

BACKGROUND AND PURPOSE: Emergency department (ED) nurses play a pivotal role in early acute ischemic stroke patient management. We hypothesized that patients exposed to ED nursing shift changes (SC) may develop pneumonia (PNA) more frequently and have worse early outcomes than do patients who have continuity of care until stroke unit admission. METHODS: Consecutive acute ischemic stroke patients presenting to our ED were studied using chart review and prospectively collected registry data. We evaluated the association of patient presence during an ED SC (ie, 07:00-08:00, 19:00-20:00) with length of stay in the ED, PNA rates, and early outcome measures (discharge disposition, modified Rankin Scale score, and death). RESULTS: Three hundred sixty-six consecutive acute ischemic stroke patients met the criteria. Of those, 54.9% were present during an SC. After adjusting for baseline National Institutes of Health Stroke Scale, admission glucose, and intravenous tissue-type plasminogen activator, patients present during SC were half as likely to be discharged home or to inpatient rehab (OR, 0.50; 95% CI, 0.26-0.96; P=0.04) and were 2.5 times more likely to develop PNA (OR, 2.54; 95% CI, 1.02-6.30; P=0.045). After additional adjustment for time in the ED, the difference in favorable discharge disposition was no longer significant, but SC was associated with 5 times the odds of PNA (OR, 5.35; 95% CI, 1.34-21.39; P=0.018) compared with patients with continuity of care. CONCLUSIONS: In our center, acute ischemic stroke patients present during an ED nursing SC experienced higher rates of PNA and had decreased rates of favorable discharge disposition compared with patients with continuity of care. Strategies to prevent PNA and improve hand-off communication during SC may reduce this risk.

Decade-Long Nationwide Trends and Disparities in Use of Comfort Care Interventions for Patients With Ischemic Stroke.

Background Stroke remains one of the leading causes of disability and death in the United States. We characterized 10-year nationwide trends in use of comfort care interventions (CCIs) among patients with ischemic stroke, particularly pertaining to acute thrombolytic therapy with intravenous tissue-type plasminogen activator and endovascular thrombectomy, and describe in-hospital outcomes and costs. Methods and Results We analyzed the National Inpatient Sample from 2006 to 2015 and identified adult patients with ischemic stroke with or without thrombolytic therapy and CCIs using validated International Classification of Diseases, Ninth Revision (ICD-9) codes. We report adjusted odds ratios (ORs) and 95% CI of CCI usage across five 2-year periods. Of 4 249 201 ischemic stroke encounters, 3.8% had CCI use. CCI use increased over time (adjusted OR, 4.80; 95% CI, 4.15-5.55) regardless of acute treatment type. Advanced age, female sex, White race, non-Medicare insurance, higher income, disease severity, comorbidity burden, and discharge from non-northeastern teaching hospitals were independently associated with receiving CCIs. In the fully adjusted model, thrombolytic therapy and endovascular thrombectomy, respectively, conferred a 6% and 10% greater likelihood of receiving CCIs. Among CCI users, there was a significant decline in in-hospital mortality compared with all other dispositions over time (adjusted OR, 0.46; 95% CI, 0.38-0.56). Despite longer length of stay, CCI hospitalizations incurred 16% lower adjusted costs. Conclusions CCI use among patients with ischemic stroke has increased regardless of acute treatment type. Nonetheless, considerable disparities persist. Closing the disparities gap and optimizing access, outcomes, and costs for CCIs among patients with stroke are important avenues for further research.

Prolonged Emergency Department Length of Stay as a Predictor of Adverse Outcomes in Patients with Intracranial Hemorrhage.

OBJECTIVES: Extended time in the emergency department (ED) has been related to adverse outcomes among stroke patients. We examined the associations of ED nursing shift change (SC) and length of stay in the ED with outcomes in patients with intracerebral hemorrhage (ICH). METHODS: Data were collected on all spontaneous ICH patients admitted to our stroke center from 7/1/08-6/30/12. Outcomes (frequency of pneumonia, modified Rankin Scale (mRS) score at discharge, NIHSS score at discharge, and mortality rate) were compared based on shift change experience and length of stay (LOS) dichotomized at 5 hours after arrival. RESULTS: Of the 162 patients included, 60 (37.0%) were present in the ED during a SC. The frequency of pneumonia was similar in the two groups. Exposure to an ED SC was not a significant independent predictor of any outcome. LOS in the ED ≥5 hours was a significant independent predictor of discharge mRS 4-6 (OR 3.638, 95% CI 1.531-8.645, and P = 0.0034) and discharge NIHSS (OR 3.049, 95% CI 1.491-6.236, and P = 0.0023) but not death. CONCLUSIONS: Our study found no association between nursing SC and adverse outcome in patients with ICH but confirms the prior finding of worsened outcome after prolonged length of stay in the ED.