Andria L. Ford

Reducing Door-to-Needle Times Using Toyota’s Lean Manufacturing Principles and Value Stream Analysis

Background and Purpose— Earlier tissue-type plasminogen activator (tPA) treatment for acute ischemic stroke increases efficacy, prompting national efforts to reduce door-to-needle times. We used lean process improvement methodology to develop a streamlined intravenous tPA protocol. Methods— In early 2011, a multidisciplinary team analyzed the steps required to treat patients with acute ischemic stroke with intravenous tPA using value stream analysis (VSA). We directly compared the tPA-treated patients in the “pre-VSA” epoch with the “post-VSA” epoch with regard to baseline characteristics, protocol metrics, and clinical outcomes. Results— The VSA revealed several tPA protocol inefficiencies: routing of patients to room, then to CT, then back to the room; serial processing of workflow; and delays in waiting for laboratory results. On March 1, 2011, a new protocol incorporated changes to minimize delays: routing patients directly to head CT before the patient room, using parallel process workflow, and implementing point-of-care laboratories. In the pre and post-VSA epochs, 132 and 87 patients were treated with intravenous tPA, respectively. Compared with pre-VSA, door-to-needle times and percent of patients treated ⩽60 minutes from hospital arrival were improved in the post-VSA epoch: 60 minutes versus 39 minutes (P<0.0001) and 52% versus 78% (P<0.0001), respectively, with no change in symptomatic hemorrhage rate. Conclusions— Lean process improvement methodology can expedite time-dependent stroke care without compromising safety.

Comprehensive stroke centers and the 'weekend effect': the SPOTRIAS experience.

Background and Purpose: Previous studies have found mortality among ischemic stroke patients to be higher on weekends. We sought to evaluate whether weekend admission was associated with worse outcomes in a large comprehensive stroke center (CSC) cohort. Methods: Consecutive ischemic stroke patients presenting within 6 h of symptom onset were identified using the 8 CSC SPOTRIAS (Specialized Programs of Translational Research in Acute Stroke) database. Patients who received intra-arterial therapy or who were enrolled in a nonobservational clinical trial were excluded. All patients meeting the inclusion criteria were then divided into two groups: weekday admissions or weekend admissions. Weekend admission was defined as Friday 17:01 to Monday 08:59. The remainder were classified as weekday admissions. Multivariate logistic regression was used, adjusting for age, stroke severity on admission [according to the National Institutes of Health Stroke Scale (NIHSS)] and admission glucose, in order to compare the outcomes of the weekend versus the weekday groups. Results: Eight thousand five hundred and eighty-one subjects from the combined SPOTRIAS database were screened from 2002 to 2009; 2,090 (24.4%) of these met the inclusion criteria. There was no significant difference in tissue plasminogen activator treatment rates between the weekday and weekend groups (58.5 vs. 60.4%, p = 0.397). Weekend admission was not a significant independent predictor of inhospital mortality (8.4 vs. 9.9%, p = 0.056), length of stay (4 vs. 5 days, p = 0.442), favorable discharge disposition (38.0 vs. 42.2%, p = 0.122), favorable functional outcome at discharge (41.6 vs. 43.4%, p = 0.805), favorable 90-day functional outcome (54.2 vs. 46.9%, p = 0.301), or 90-day mortality (18.2 vs. 19.8%, p = 0.680) when adjusting for age, NIHSS and admission glucose. Conclusions: In this large cohort of ischemic stroke patients treated at CSCs, we did not observe the ‘weekend effect.’ This may be due to access to stroke specialists 24 h a day on 365 days a year, nurses with stroke experience and the organized system for delivering care that is available at CSCs. These results suggest that EMS protocol should be reexamined regarding the preferential delivery of weekend stroke victims to hospitals that provide all levels of reperfusion therapy. This further highlights the importance of organized stroke care.

Cerebral amyloid angiopathy: progressive disruption of the neurovascular unit.

Cellular elements of the neurovascular unit are essential for the physiological functioning of brain vessels. If any of these vascular elements are disturbed the consequences can be dire. Cerebral amyloid angiopathy (CAA), a disorder caused by the accumulation of amyloid in cerebral vessels, provides a case study of progressive neurovascular unit dysfunction leading to failure of vascular reactivity, smooth muscle cell loss, and eventual frank breakdown of vessel integrity resulting in recurrent and sometimes fatal intracerebral hemorrhage.

A simple bedside stroke dysphagia screen, validated against videofluoroscopy, detects dysphagia and aspiration with high sensitivity.

BACKGROUND Early identification of dysphagia is associated with lower rates of pneumonia after acute stroke. The Barnes-Jewish Hospital Stroke Dysphagia Screen (BJH-SDS) was previously developed as a simple bedside screen performed by nurses for sensitive detection of dysphagia and was previously validated against the speech pathologists clinical assessment for dysphagia. In this study, acute stroke patients were prospectively enrolled to assess the accuracy of the BJH-SDS when tested against the gold standard test for dysphagia, the videofluoroscopic swallow study (VFSS). METHODS Acute stroke patients were prospectively enrolled at a large tertiary care inpatient stroke unit. The nurse performed the BJH-SDS at the bedside. After providing consent, patients then underwent VFSS for determination of dysphagia and aspiration. The VFSS was performed by a speech pathologist who was blinded to the results of the BJH-SDS. Sensitivity and specificity were calculated. Pneumonia rates were assessed across the 5-year period over which the BJH-SDS was introduced into the stroke unit. RESULTS A total of 225 acute stroke patients were enrolled. Sensitivity and specificity of the screen to detect dysphagia were 94% and 66%, respectively. Sensitivity and specificity of the screen to detect aspiration were 95% and 50%, respectively. No increase in pneumonia was identified during implementation of the screen (P = .33). CONCLUSION The BJH-SDS, validated against videofluoroscopy, is a simple bedside screen for sensitive identification of dysphagia and aspiration in the stroke population.

Defining the Ischemic Penumbra Using Magnetic Resonance Oxygen Metabolic Index

Background and Purpose— Penumbral biomarkers promise to individualize treatment windows in acute ischemic stroke. We used a novel magnetic resonance imaging approach that measures oxygen metabolic index (OMI), a parameter closely related to positron emission tomography–derived cerebral metabolic rate of oxygen utilization (CMRO2), to derive a pair of ischemic thresholds: (1) an irreversible-injury threshold that differentiates ischemic core from penumbra and (2) a reversible-injury threshold that differentiates penumbra from tissue not-at-risk for infarction. Methods— Forty patients with acute ischemic stroke underwent magnetic resonance imaging at 3 time points after stroke onset: <4.5 hours (for OMI threshold derivation), 6 hours (to determine reperfusion status), and 1 month (for infarct probability determination). A dynamic susceptibility contrast method measured cerebral blood flow, and an asymmetrical spin echo sequence measured oxygen extraction fraction, to derive OMI (OMI=cerebral blood flow×oxygen extraction fraction). Putative ischemic threshold pairs were iteratively tested using a computation-intensive method to derive infarct probabilities in 3 tissue groups defined by the thresholds (core, penumbra, and not-at-risk tissue). An optimal threshold pair was chosen based on its ability to predict infarction in the core, reperfusion-dependent survival in the penumbra, and survival in not-at-risk tissue. The predictive abilities of the thresholds were then tested within the same cohort using a 10-fold cross-validation method. Results— The optimal OMI ischemic thresholds were found to be 0.28 and 0.42 of normal values in the contralateral hemisphere. Using the 10-fold cross-validation method, median infarct probabilities were 90.6% for core, 89.7% for nonreperfused penumbra, 9.95% for reperfused penumbra, and 6.28% for not-at-risk tissue. Conclusions— OMI thresholds, derived using voxel-based, reperfusion-dependent infarct probabilities, delineated the ischemic penumbra with high predictive ability. These thresholds will require confirmation in an independent patient sample.

Impact of Acute Ischemic Stroke Treatment in Patients >80 Years of Age The Specialized Program of Translational Research in Acute Stroke (SPOTRIAS) Consortium Experience

Background and Purpose Few studies have addressed outcomes among patients ≥80 years treated with acute stroke therapy. In this study, we outline in-hospital outcomes in (1) patients ≥80 years compared to their younger counterparts, and (2) those over age 80 receiving intra-arterial therapy (IAT) compared to those treated with intravenous recombinant tissue plasminogen activator (IVrtPA).Background and Purpose— Few studies have addressed outcomes among patients ≥80 years treated with acute stroke therapy. In this study, we outline in-hospital outcomes in (1) patients ≥80 years compared with their younger counterparts; and (2) those over >80 years receiving intra-arterial therapy (IAT) compared with those treated with intravenous recombinant tissue-type plasminogen activator (IV rtPA). Methods— Stroke centers within the Specialized Program of Translational Research in Acute Stroke (SPOTRIAS) prospectively collected data on all patients treated with IV rtPA or IAT from January 1, 2005, to December 31, 2010. IAT was defined as receiving any endovascular therapy; IAT was further divided into bridging therapy when the patient received both IAT and IV rtPA and endovascular therapy alone. In-hospital mortality was compared in (1) all patients aged ≥80 years versus younger counterparts; and (2) IAT, bridging therapy, and endovascular therapy alone versus IV rtPA only among those age ≥80 years using multivariable logistic regression. An age-stratified analysis was also performed. Results— A total of 3768 patients were included in the study; 3378 were treated with IV rtPA alone and 808 with IAT (383 with endovascular therapy alone and 425 with bridging therapy). Patients ≥80 years (n=1182) had a higher risk of in-hospital mortality compared with younger counterparts regardless of treatment modality (OR, 2.13; 95% CI, 1.60–2.84). When limited to those aged ≥80 years, IAT (OR, 0.95; 95% CI, 0.60–1.49), bridging therapy (OR, 0.82; 95% CI, 0.47–1.45), or endovascular therapy alone (OR, 1.15; 95% CI, 0.64–2.08) versus IV rtPA were not associated with increased in-hospital mortality. Conclusions— IAT does not appear to increase the risk of in-hospital mortality among those aged >80 years compared with IV thrombolysis alone.

Signal Evolution and Infarction Risk for Apparent Diffusion Coefficient Lesions in Acute Ischemic Stroke Are Both Time- and Perfusion-Dependent

Background and Purpose— This study aimed to examine the temporal relationship between tissue perfusion and apparent diffusion coefficient (ADC) changes within 6 hours of ischemic stroke onset and how different reperfusion patterns may affect tissue outcome in ADC lesions. Methods— Thirty-one participants were sequentially imaged at 3 hours, 6 hours, and 1 month post-stroke. Three regions of interest (ROIs) were defined within initial ADC lesions: ROI (1)reperf_3hour hyperacute reperfusion (within 3 hours), ROI (2)reperf_6hour acute reperfusion (3 to 6 hours), and ROI (3)nonreperf no reperfusion (by 6 hours). For each ROI, changes in ADC (&Dgr;ADC) from 3 to 6 hours and risks of infarction were examined. Results— The magnitude of initial ADC reduction was similar in all 3 ROIs (P=0.51). &Dgr;ADC was strongly associated with reperfusion (P<0.0001) but not with initial ADC reduction (P=0.83). &Dgr;ADC in ROI (1)reperf_3hour and ROI (2)reperf_6hour was significantly larger than that of ROI (3)nonreperf (P<0.05). Positive &Dgr;ADC was obtained from 3 to 6 hours in ROI (1)reperf_3hour that had restored perfusion before 3 hours, demonstrating a temporal delay between reperfusion and ADC changes. Risks of infarction were significantly higher in ROI (3)nonreperf than those in ROI (1)reperf_3hour and ROI (2)reperf_6hour. Conclusions— Improvement in ADC did not occur coincidently with reperfusion but showed a temporal delay. Regions with similar initial ADC reductions at 3 hours had different evolution of ADC and infarction risks depending on when or if tissue reperfused. These findings provide a physiological basis for the observation that a single ADC measurement at a fixed time after stroke onset may not accurately predict tissue outcome.

Preexisting Statin Use Is Associated With Greater Reperfusion in Hyperacute Ischemic Stroke

Background and Purpose— Statin pretreatment has been associated with improved outcomes in patients with ischemic stroke. Although several mechanisms have been examined in animal models, few have been examined in patients. We hypothesized that patients using statins before stroke onset may have greater reperfusion than patients not using statins. Methods— Acute ischemic stroke patients underwent 2 MR scans: within 4.5 (tp1) and at 6 hours (tp2) after stroke onset. Regions of reperfusion were defined by prolonged mean transit time (MTT) at tp1, which normalized at tp2. Four MTT thresholds were assessed to ensure that results were not spuriously based on an arbitrary threshold. Baseline characteristics, relative reperfusion, and change in NIHSS between tp1 and 1-month follow-up (&Dgr;NIHSS) were compared between patients who were using statins at stroke onset and those who were not. Results— Thirty-one stroke patients were prospectively enrolled; 12 were using statins and 19 were not. Baseline characteristics did not differ between the 2 groups except the statin group had greater coronary artery disease (P=0.03). Patients using statins showed significantly greater reperfusion compared to untreated patients across all MTT thresholds. For MTT of 4 seconds, median relative reperfusion was 50% (interquartile range, 30%–56%) in the preexisting statin group versus 13% (interquartile range, 5%–36%) in the untreated group (P=0.014). The statin group had greater &Dgr;NIHSS (8.8±4.0 points) compared to the untreated group (4.4±5.7 points; P=0.028). Conclusions— Statin use before ischemic stroke onset was associated with greater early reperfusion and NIHSS improvement. Further studies in larger populations are required to confirm our preliminary findings.

Variability in the use of intravenous thrombolysis for mild stroke: experience across the SPOTRIAS network.

BACKGROUND Current guidelines do not define the lower severity threshold for thrombolysis. In this study, we describe the variability of treatment of mild stroke patients across a network of academic stroke centers. METHODS Stroke centers within the Specialized Program of Translational Research in Acute Stroke (SPOTRIAS) prospectively collect data on patients treated with intravenous recombinant tissue plasminogen activator (IV rt-PA), including demographics, pretreatment National Institutes of Health Stroke Scale (NIHSS) scores, and in-hospital mortality. We examined the variability in proportion of total tissue plasminogen activator-treated patients in the NIHSS categories (0-3, 4-5, or ≥ 6) and associated outcomes. RESULTS A total of 2514 patients with reported NIHSS scores were treated with IV rt-PA between January 1, 2005 and December 31, 2009. The proportion of patients with mild stroke (NIHSS scores of 0-3) who were treated with IV rt-PA varied substantially across the centers (2.7-18.0%; P < .001). There were 5 deaths in the 256 treated with an NIHSS score of 0-3 (2.0%). The proportion of treated patients across the network with an NIHSS score of 0 to 3 increased from 4.8% in 2005 to 10.7% in 2009 (P = .001). CONCLUSIONS There is substantial variability in the proportion of treated patients who have mild stroke across the SPOTRIAS centers, reflecting a paucity of data on how to best treat patients with mild stroke. Randomized trial data for this group of patients are needed to clarify the use of rt-PA in patients with the mildest strokes.

Imaging and Treatment of Patients with Acute Stroke: An Evidence-Based Review

SUMMARY: Evidence-based medicine has emerged as a valuable tool to guide clinical decision-making, by summarizing the best possible evidence for both diagnostic and treatment strategies. Imaging plays a critical role in the evaluation and treatment of patients with acute ischemic stroke, especially those who are being considered for thrombolytic or endovascular therapy. Time from stroke-symptom onset to treatment is a strong predictor of long-term functional outcome after stroke. Therefore, imaging and treatment decisions must occur rapidly in this setting, while minimizing unnecessary delays in treatment. The aim of this review was to summarize the best available evidence for the diagnostic and therapeutic management of patients with acute ischemic stroke.