Smoking Does Not Alter Treatment Effect of Intravenous Thrombolysis in Mild to Moderate Acute Ischemic Stroke—A Dutch String-of-Pearls Institute (PSI) Stroke Study

Background:The smoking-thrombolysis paradox refers to a better outcome in smokers who suffer from acute ischemic stroke (AIS) following treatment with thrombolysis. However, studies on this subject have yielded contradictory results and an interaction analysis of exposure to smoking and thrombolysis in a large, multicenter database is lacking. Methods:Consecutive AIS patients admitted within 12 h of symptom onset between 2009 and 2014 from the prospective, multicenter stroke registry (Dutch String-of-Pearls Stroke Study) were included for this analysis. We performed a generalized linear model for functional outcome 3 months post-stroke depending on risk of the exposure variables (smoking yes/no, thrombolysis yes/no). The following confounders were adjusted for: age, smoking, hypertension, atrial fibrillation, diabetes mellitus, stroke severity, and stroke etiology. Results:Out of 468 patients, 30.6% (N= 143) were smokers and median baseline NIHSS was 3 (interquartile range 1-6). Smoking alone had a crude and adjusted relative risk (RR) of 0.99 (95% CI 0.89-1.10) and 0.96 (95% CI 0.86-1.01) for good outcome (modified Rankin Score <= 2), respectively. A combination of exposure variables (smoking and thrombolysis) did not change the results significantly [crude RR 0.87 (95% CI 0.74-1.03], adjusted RR 1.1 (95%CI 0.90-1.30)]. Smoking alone had an adjusted RR of 1.2 (95% CI 0.6-2.7) for recanalization following thrombolysis (N= 88). Conclusions:In patients with mild to moderate AIS admitted within 12 h of symptom onset, smoking did not modify treatment effect of thrombolysis

Optimising acute stroke care organisation: a simulation study to assess the potential to increase intravenous thrombolysis rates and patient gains

Objectives: To assess potential increases in intravenous thrombolysis (IVT) rates given particular interventions in the stroke care pathway. Design: Simulation modelling was used to compare the performance of the current pathway, best practices based on literature review and an optimised model. Setting: Four hospitals located in the North of the Netherlands, as part of a centralised organisational model. Participants: Ischaemic stroke patients prospectively ascertained from February to August 2010. Intervention: The interventions investigated included efforts aimed at patient response and mode of referral, prehospital triage and intrahospital delays. Primary and secondary outcome measures: The primary outcome measure was thrombolysis utilisation. Secondary measures were onset-treatment time (OTT) and the proportion of patients with excellent functional outcome (modified Rankin scale (mRS) 0–1) at 90 days. Results: Of 280 patients with ischaemic stroke, 125 (44.6%) arrived at the hospital within 4.5 hours, and 61 (21.8%) received IVT. The largest improvements in IVT treatment rates, OTT and the proportion of patients with mRS scores of 0–1 can be expected when patient response is limited to 15 min (IVT rate +5.8%; OTT −6 min; excellent mRS scores +0.2%), door-to- needle time to 20 min (IVT rate +4.8%; OTT −28 min; excellent mRS scores+3.2%) and 911 calls are increased to 60% (IVT rate +2.9%; OTT −2 min; excellent mRS scores+0.2%). The combined implementation of all potential best practices could increase IVT rates by 19.7% and reduce OTT by 56 min. Conclusions: Improving IVT rates to well above 30% appears possible if all known best practices are implemented

Entering new fields of simulation application - challenges faced in simulation modelling of stroke systems

Stroke is a major cause of death and long-term disability world-wide. To improve functional outcome treatment with intravenous tissue plasminogen activator (tPA) is the most effective medical treatment for acute brain infarction within 4.5 hours after the onset of stroke symptoms. Unfortunately, tPA remains substantially underutilized. Acute stroke care organization is among the dominant factors determining undertreatment. Recently, simulation has been suggested and successfully implemented as a tool for optimizing stroke care pathway logistics. Starting from a number of pioneering simulation studies challenges in simulation application and simulation methodology are identified. The definition of a domain specific modelling framework for acute stroke care is advocated to master system complexities, facilitate joint team work in solution finding, organize model data collection and make a further entrance to the field

Optimizing cutoff scores for the Barthel Index and the modified Rankin Scale for defining outcome in acute stroke trials

Background and Purpose - There is little agreement on how to assess outcome in acute stroke trials. Cutoff scores for the Barthel Index (BI) and modified Rankin Scale (mRS) are frequently arbitrarily chosen to dichotomize favorable and unfavorable outcome. We investigated sensitivity and specificity of BI cutoff scores in relation to the mRS to obtain the optimal corresponding BI and mRS scores. Methods - BI and mRS scores were collected from 1034 ischemic stroke patients. Sensitivity and specificity were calculated for BI cutoff scores from 45 to 100 in mRS score 1, 2, and 3 and were plotted in receiver operator characteristic (ROC) curves. Results - The cutoff scores for the BI with the highest sum of sensitivity and specificity were 95 (sensitivity 85.6%; specificity 91.7%), 90 (sensitivity 90.7%; specificity 88.1%), and 75 ( sensitivity 95.7%; specificity, 88.5%) for, respectively, mRS 1, 2, and 3. The area under the ROC curve was 0.933 in mRS 1, 0.960 in mRS 2, and 0.979 in mRS 3. Conclusions - The optimal cutoff scores for the BI were 95 for mRS 1, 90 for mRS 2, and 75 for mRS 3. For future acute stroke trials that assess stroke outcome with the BI and mRS, we recommend the use of these BI cutoff score(s) with the corresponding mRS cutoff score(s), to ensure the use of consistent and uniform end points

Admission hyperglycemia and outcome after intravenous thrombolysis:is there a difference among the stroke-subtypes?

Background: The prognostic influence of hyperglycemia in acute stroke has been well established. While in cortical stroke there is a strong association between hyperglycemia and poor outcome, this relation is less clear in lacunar stroke. It has been suggested that this discrepancy is present among patients treated with intravenous tissue plasminogen activator (tPA), but confirmation is needed. Methods: In two prospectively collected cohorts of patient treated with intravenous tPA for acute ischemic stroke, we investigated the effect of hyperglycemia (serum glucose level > 8 mmol/L) on functional outcome in lacunar and non-lacunar stroke. Poor functional outcome was defined as modified Rankin Scale score >= 3 at 3 months. Results: A total of 1012 patients was included of which 162 patients (16 %) had lacunar stroke. The prevalence of hyperglycemia did not differ between stroke subtypes (22 % vs 21 %, p = 0.85). In multivariate analysis hyperglycemia was associated with poor functional outcome in non-lacunar stroke (OR 2.1, 95 % CI 1.39-3.28, p = 0.001). In patients with lacunar stroke, we did not find an association (OR 1.8, 95 % CI 0.62-4.08, p = 0.43). Conclusion: This study confirms a difference in prognostic influence of hyperglycemia between non-lacunar and lacunar ischemic stroke

Centralising acute stroke care within clinical practice in the Netherlands:lower bounds of the causal impact

Background: Authors in previous studies demonstrated that centralising acute stroke care is associated with an increased chance of timely Intra-Venous Thrombolysis (IVT) and lower costs compared to care at community hospitals. In this study we estimated the lower bound of the causal impact of centralising IVT on health and cost outcomes within clinical practice in the Northern Netherlands. Methods: We used observational data from 267 and 780 patients in a centralised and decentralised system, respectively. The original dataset was linked to the hospital information systems. Literature on healthcare costs and Quality of Life (QoL) values up to 3 months post-stroke was searched to complete the input. We used Synthetic Control Methods (SCM) to counter selection bias. Differences in SCM outcomes included 95% Confidence Intervals (CI). To deal with unobserved heterogeneity we focused on recently developed methods to obtain the lower bounds of the causal impact. Results: Using SCM to assess centralising acute stroke 3 months post-stroke revealed healthcare savings of $US 1735 (CI, 505 to 2966) while gaining 0.03 (CI, − 0.01 to 0.73) QoL per patient. The corresponding lower bounds of the causal impact are$US 1581 and 0.01. The dominant effect remained stable in the deterministic sensitivity analyses with $US 1360 (CI, 476 to 2244) as the most conservative estimate. Conclusions: In this study we showed that a centralised system for acute stroke care appeared both cost-saving and yielded better health outcomes. The results are highly relevant for policy makers, as this is the first study to address the issues of selection and unobserved heterogeneity in the evaluation of centralising acute stroke care, hence presenting causal estimates for budget decisions