Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association.

Background and Purpose- The purpose of these guidelines is to provide an up-to-date comprehensive set of recommendations in a single document for clinicians caring for adult patients with acute arterial ischemic stroke. The intended audiences are prehospital care providers, physicians, allied health professionals, and hospital administrators. These guidelines supersede the 2013 Acute Ischemic Stroke (AIS) Guidelines and are an update of the 2018 AIS Guidelines. Methods- Members of the writing group were appointed by the American Heart Association (AHA) Stroke Council's Scientific Statements Oversight Committee, representing various areas of medical expertise. Members were not allowed to participate in discussions or to vote on topics relevant to their relations with industry. An update of the 2013 AIS Guidelines was originally published in January 2018. This guideline was approved by the AHA Science Advisory and Coordinating Committee and the AHA Executive Committee. In April 2018, a revision to these guidelines, deleting some recommendations, was published online by the AHA. The writing group was asked review the original document and revise if appropriate. In June 2018, the writing group submitted a document with minor changes and with inclusion of important newly published randomized controlled trials with >100 participants and clinical outcomes at least 90 days after AIS. The document was sent to 14 peer reviewers. The writing group evaluated the peer reviewers' comments and revised when appropriate. The current final document was approved by all members of the writing group except when relationships with industry precluded members from voting and by the governing bodies of the AHA. These guidelines use the American College of Cardiology/AHA 2015 Class of Recommendations and Level of Evidence and the new AHA guidelines format. Results- These guidelines detail prehospital care, urgent and emergency evaluation and treatment with intravenous and intra-arterial therapies, and in-hospital management, including secondary prevention measures that are appropriately instituted within the first 2 weeks. The guidelines support the overarching concept of stroke systems of care in both the prehospital and hospital settings. Conclusions- These guidelines provide general recommendations based on the currently available evidence to guide clinicians caring for adult patients with acute arterial ischemic stroke. In many instances, however, only limited data exist demonstrating the urgent need for continued research on treatment of acute ischemic stroke.

To Treat or Not to Treat?

Background and Purpose- The 2015 updated US Food and Drug Administration alteplase package insert altered several contraindications. We thus explored clinical factors influencing alteplase treatment decisions for patients with minor stroke. Methods- An expert panel selected 7 factors to build a series of survey vignettes: National Institutes of Health Stroke Scale (NIHSS), NIHSS area of primary deficit, baseline functional status, previous ischemic stroke, previous intracerebral hemorrhage, recent anticoagulation, and temporal pattern of symptoms in first hour of care. We used a fractional factorial design (150 vignettes) to provide unconfounded estimates of the effect of all 7 main factors, plus first-order interactions for NIHSS. Surveys were emailed to national organizations of neurologists, emergency physicians, and colleagues. Physicians were randomized to 1 of 10 sets of 15 vignettes, presented randomly. Physicians reported the subjective likelihood of giving alteplase on a 0 to 5 scale; scale categories were anchored to 6 probabilities from 0% to 100%. A conjoint statistical analysis was applied. Results- Responses from 194 US physicians yielded 156 with complete vignette data: 74% male, mean age 46, 80% neurologists. Treatment mean probabilities for individual vignettes ranged from 6% to 95%. Treatment probability increased from 24% for NIHSS score =1 to 41% for NIHSS score =5. The conjoint model accounted for 25% of total observed response variance. In contrast, a model accounting for all possible interactions accounted for 30% variance. Four of the 7 factors accounted jointly for 58% of total relative importance within the conjoint model: previous intracerebral hemorrhage (18%), recent anticoagulation (17%), NIHSS (13%), and previous ischemic stroke (10%). Conclusions- Four main variables jointly account for only a small fraction (<15%) of the total variance related to deciding to treat with intravenous alteplase, reflecting high variability and complexity. Future studies should consider other variables, including physician characteristics.

2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association.

BACKGROUND AND PURPOSE: The purpose of these guidelines is to provide an up-to-date comprehensive set of recommendations for clinicians caring for adult patients with acute arterial ischemic stroke in a single document. The intended audiences are prehospital care providers, physicians, allied health professionals, and hospital administrators. These guidelines supersede the 2013 guidelines and subsequent updates. METHODS: Members of the writing group were appointed by the American Heart Association Stroke Council's Scientific Statements Oversight Committee, representing various areas of medical expertise. Strict adherence to the American Heart Association conflict of interest policy was maintained. Members were not allowed to participate in discussions or to vote on topics relevant to their relations with industry. The members of the writing group unanimously approved all recommendations except when relations with industry precluded members voting. Prerelease review of the draft guideline was performed by 4 expert peer reviewers and by the members of the Stroke Council's Scientific Statements Oversight Committee and Stroke Council Leadership Committee. These guidelines use the American College of Cardiology/American Heart Association 2015 Class of Recommendations and Levels of Evidence and the new American Heart Association guidelines format. RESULTS: These guidelines detail prehospital care, urgent and emergency evaluation and treatment with intravenous and intra-arterial therapies, and in-hospital management, including secondary prevention measures that are appropriately instituted within the first 2 weeks. The guidelines support the overarching concept of stroke systems of care in both the prehospital and hospital settings. CONCLUSIONS: These guidelines are based on the best evidence currently available. In many instances, however, only limited data exist demonstrating the urgent need for continued research on treatment of acute ischemic stroke.

Protocol Deviations before and after Treatment with Intravenous Tissue Plasminogen Activator in Community Hospitals.

BACKGROUND: Protocol deviations before and after tissue plasminogen activator (tPA) treatment for ischemic stroke are common. It is unclear if patient or hospital factors predict protocol deviations. We examined predictors of protocol deviations and the effects of protocol violations on symptomatic intracerebral hemorrhage (sICH). METHODS: We used data from the Increasing Stroke Treatment through Interventional Behavior Change Tactics trial, a cluster-randomized, controlled trial evaluating the efficacy of a barrier assessment and educational intervention to increase appropriate tPA use in 24 Michigan community hospitals, to review tPA treatments between 2007 and 2010. Protocol violations were defined as deviations from the standard tPA protocol, both before and after treatment. Multilevel logistic regression models were fitted to determine if patient and hospital variables were associated with pretreatment or post-treatment protocol deviations. RESULTS: During the study, 557 patients (mean age 70, 52% male, median National Institutes of Health Stroke Scale score 12) were treated with tPA. Protocol deviations occurred in 233 (42%) patients: 16% had pretreatment deviations, 35% had post-treatment deviations, and 9% had both. The most common protocol deviations included elevated post-treatment blood pressure, antithrombotic agent use within 24 hours of treatment, and elevated pretreatment blood pressure. Protocol deviations were not associated with sICH, stroke severity, or hospital factors. Older age was associated with pretreatment protocol deviations (adjusted odds ratio [OR], .52; 95% confidence interval [CI], .30-.92). Pretreatment deviations were associated with post-treatment deviations (adjusted OR, 3.20; 95% CI, 1.91-5.35). CONCLUSIONS: Protocol deviations were not associated with sICH. Aside from age, patient and hospital factors were not associated with protocol deviations.

Marked Regional Variation in Acute Stroke Treatment Among Medicare Beneficiaries.

BACKGROUND AND PURPOSE: Little is known about how regions vary in their use of thrombolysis (intravenous tissue-type plasminogen activator and intra-arterial treatment) for acute stroke. We sought to determine regional variation in thrombolysis treatment and investigate the extent to which regional variation is accounted for by patient demographics, regional factors, and elements of stroke systems of care. METHODS: Retrospective cross-sectional study of all fee-for-service Medicare patients with ischemic stroke admitted via the Emergency Department from 2007 to 2010 who were assigned to 1 of 3436 hospital service areas. Multilevel logistic regression was used to estimate regional thrombolysis rates, determine the variation in thrombolysis treatment attributable to the region and estimate thrombolysis treatment rates and disability prevented under varied improvement scenarios. RESULTS: There were 844 241 ischemic stroke admissions of which 3.7% received intravenous tissue-type plasminogen activator and 0.5% received intra-arterial stroke treatment without or without intravenous tissue-type plasminogen activator over the 4-year period. The unadjusted proportion of patients with ischemic stroke who received thrombolysis varied from 9.3% in the highest treatment quintile compared with 0% in the lowest treatment quintile. Measured demographic and stroke system factors were weakly associated with treatment rates. Region accounted for 7% to 8% of the variation in receipt of thrombolysis treatment. If all regions performed at the level of 75th percentile region, ≈7000 additional patients with ischemic stroke would be treated with thrombolysis. CONCLUSIONS: There is substantial regional variation in thrombolysis treatment. Future studies to determine features of high-performing thrombolysis treatment regions may identify opportunities to improve thrombolysis rates.

Guidelines for the Management of Spontaneous Intracerebral Hemorrhage: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association.

PURPOSE: The aim of this guideline is to present current and comprehensive recommendations for the diagnosis and treatment of spontaneous intracerebral hemorrhage. METHODS: A formal literature search of PubMed was performed through the end of August 2013. The writing committee met by teleconference to discuss narrative text and recommendations. Recommendations follow the American Heart Association/American Stroke Association methods of classifying the level of certainty of the treatment effect and the class of evidence. Prerelease review of the draft guideline was performed by 6 expert peer reviewers and by the members of the Stroke Council Scientific Oversight Committee and Stroke Council Leadership Committee. RESULTS: Evidence-based guidelines are presented for the care of patients with acute intracerebral hemorrhage. Topics focused on diagnosis, management of coagulopathy and blood pressure, prevention and control of secondary brain injury and intracranial pressure, the role of surgery, outcome prediction, rehabilitation, secondary prevention, and future considerations. Results of new phase 3 trials were incorporated. CONCLUSIONS: Intracerebral hemorrhage remains a serious condition for which early aggressive care is warranted. These guidelines provide a framework for goal-directed treatment of the patient with intracerebral hemorrhage.

Prevention of emergency physician migratory contamination in a cluster randomized trial to increase tissue plasminogen activator use in stroke (the INSTINCT trial).

OBJECTIVES: Cluster randomized trials (CRTs) are increasingly used to evaluate quality improvement interventions aimed at health care providers. In trials testing emergency department (ED) interventions, migration of emergency physicians (EPs) between hospitals is an important concern, as contamination may affect both internal and external validity. We hypothesized that geographically isolating EDs would prevent migratory contamination in a CRT designed to increase ED delivery of tissue plasminogen activator (tPA) in stroke (the INSTINCT trial). METHODS: INSTINCT was a prospective, cluster randomized, controlled trial. Twenty-four Michigan community hospitals were randomly selected in matched pairs for study. Contamination was defined at the cluster level, with substantial contamination defined a priori as greater than 10% of EPs affected. Nonadherence, total crossover (contamination+nonadherence), migration distance, and characteristics were determined. RESULTS: Three hundred seven EPs were identified at all sites. Overall, 7 (2.3%) changed study sites. One moved between control sites, leaving 6 (2.0%) total crossovers. Of these, 2 (0.7%) moved from intervention to control (contamination); and 4 (1.3%) moved from control to intervention (nonadherence). Contamination was observed in 2 of 12 control sites, with 17% and 9% contamination of the total site EP workforce at follow-up, respectively. Average migration distance was 42 miles for all EPs moving in the study and 35 miles for EPs moving from intervention to control sites. CONCLUSION: The mobile nature of EPs should be considered in the design of quality improvement CRTs. Increased reporting of contamination in CRTs is encouraged to clarify thresholds and facilitate CRT design.

An emergency department intervention to increase warfarin use for atrial fibrillation.

BACKGROUND: Emergency department (ED) encounters represent lost opportunities to facilitate anticoagulation for stroke prevention in atrial fibrillation (AF). However, screening of warfarin eligibility in the ED may not be feasible. We evaluated whether a practical quality improvement initiative increased postdischarge warfarin use in ED patients with AF. METHODS: This quasiexperimental study was conducted in a single academic health system. Eligible subjects were consecutive patients with AF identified by electrocardiogram during an ED evaluation who were discharged from the ED or the subsequent hospitalization off warfarin. The study consisted of data collection during 2 time periods: (1) preintervention (October 2009 to April 2010), serving as a baseline, and (2) intervention (June 2010 to December 2010). The intervention consisted of a mailing to the subjects and their primary care physicians. The primary outcome was the proportion of subjects taking warfarin 1 month after ED presentation. Differences between the proportion of preintervention and intervention subjects taking warfarin and warfarin or aspirin were compared with Chi-square tests. RESULTS: At 1 month, 111 of 204 (55%) of the eligible preintervention and 90 of 160 (56%) of the eligible intervention group patients participated. There was no difference between the preintervention and intervention groups in the proportion of subjects taking warfarin at 1 month (12% v 9%; P = .54) or the proportion of subjects taking either aspirin or warfarin at 1 month (72% v 75%; P = .59). CONCLUSIONS: This practical stroke prevention quality improvement initiative was not associated with an increase in warfarin use among ED patients with AF.

Time to brain imaging in acute stroke is improving: secondary analysis of the INSTINCT trial.

BACKGROUND AND PURPOSE: Patients with acute ischemic stroke benefit from rapid evaluation and treatment, and timely brain imaging is a necessary component. We determined the effect of a targeted behavioral intervention on door-to-imaging time (DIT) among patients with ischemic stroke treated with tissue-type plasminogen activator. Second, we examined the variation in DIT accounted for by patient-level and hospital-level factors. METHODS: The Increasing Stroke Treatment through Interventional behavioral Change Tactics (INSTINCT) trial was a cluster-randomized, controlled trial involving 24 Michigan hospitals. The intervention aimed to increase tissue-type plasminogen activator utilization. Detailed chart abstractions collected data for 557 patients with ischemic stroke. We used a series of hierarchical linear mixed-effects models to evaluate the effect of the intervention on DIT (difference-in-differences analysis) and used patient-level and hospital-level explanatory variables to decompose variation in DIT. RESULTS: DIT improved over time, without a difference between intervention and control hospitals (intervention: 23.7-19.3 minutes, control: 28.9-19.2 minutes; P=0.56). Adjusted DIT was faster in patients who arrived by ambulance (7.2 minutes; 95% confidence interval, 4.1-10.2), had severe strokes (1.0 minute per +5-point National Institutes of Health Stroke Scale; 95% confidence interval, 0.1-2.0), and presented in the postintervention period (4.9 minutes; 95% confidence interval, 2.3-7.4). After accounting for these factors, 13.8% of variation in DIT was attributable to hospital. Neither hospital stroke volume nor stroke center status was associated with DIT. CONCLUSIONS: Performance on DIT improved similarly in intervention and control hospitals, suggesting that nonintervention factors explain the improvement. Hospital-level factors explain a modest proportion of variation in DIT, but further research is needed to identify the hospital-level factors responsible.

Combined approach to lysis utilizing eptifibatide and recombinant tissue plasminogen activator in acute ischemic stroke-enhanced regimen stroke trial.

BACKGROUND AND PURPOSE: In a previous study, 0.3 and 0.45 mg/kg of intravenous recombinant tissue plasminogen activator (rt-PA) were safe when combined with eptifibatide 75 mcg/kg bolus and a 2-hour infusion (0.75 mcg/kg per minute). The Combined Approach to Lysis Utilizing Eptifibatide and rt-PA in Acute Ischemic Stroke-Enhanced Regimen (CLEAR-ER) trial sought to determine the safety of a higher-dose regimen and to establish evidence for a phase III trial. METHODS: CLEAR-ER was a multicenter, double-blind, randomized safety study. Ischemic stroke patients were randomized to 0.6 mg/kg rt-PA plus eptifibatide (135 mcg/kg bolus and a 2-hour infusion at 0.75 mcg/kg per minute) versus standard rt-PA (0.9 mg/kg). The primary safety end point was the incidence of symptomatic intracranial hemorrhage within 36 hours. The primary efficacy outcome measure was the modified Rankin Scale (mRS) score ≤1 or return to baseline mRS at 90 days. Analysis of the safety and efficacy outcomes was done with multiple logistic regression. RESULTS: Of 126 subjects, 101 received combination therapy, and 25 received standard rt-PA. Two (2%) patients in the combination group and 3 (12%) in the standard group had symptomatic intracranial hemorrhage (odds ratio, 0.15; 95% confidence interval, 0.01-1.40; P=0.053). At 90 days, 49.5% of the combination group had mRS ≤1 or return to baseline mRS versus 36.0% in the standard group (odds ratio, 1.74; 95% confidence interval, 0.70-4.31; P=0.23). After adjusting for age, baseline National Institutes of Health Stroke Scale, time to intravenous rt-PA, and baseline mRS, the odds ratio was 1.38 (95% confidence interval, 0.51-3.76; P=0.52). CONCLUSIONS: The combined regimen of intravenous rt-PA and eptifibatide studied in this trial was safe and provides evidence that a phase III trial is warranted to determine efficacy of the regimen. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00894803.

The impact of emergency physician turnover on planning for prospective clinical trials.

INTRODUCTION: Emergency physician (EP) turnover is a significant issue that can have strong economic impact on hospital systems, as well as implications on research efforts to test and improve clinical practice. This work is particularly important to researchers planning randomized trials directed toward EPs because a large degree of turnover within a physician group would attenuate the effectiveness of the desired intervention. We sought to determine the incidence and factors associated with EP workforce changes. METHODS: In an attempt to determine EP turnover and workforce change, data from the INSTINCT (INcreasing Stroke Treatment through INterventional behavior Change Tactics) trial were used. The INSTINCT trial is a prospective, cluster-randomized, controlled trial evaluating a targeted behavioral intervention to increase appropriate use of tissue plasminogen activator in acute ischemic stroke. Individual EPs staffing each of the study hospitals were identified at baseline and 18 months. Surveys were sent to EPs at both intervals. Models were constructed to investigate relationships between physician/hospital characteristics and workforce change. RESULTS: A total of 278 EPs were identified at baseline. Surveys were sent to all EPs at baseline and 18 months with a response rate of 72% and 74%, respectively. At 18 months, 37 (15.8%) had left their baseline hospital and 66 (26.3%) new EPs were working. Seven EPs switched hospitals within the sample. The total number of EPs at 18 months was 307, a 10.8% overall increase. Among the 24 hospitals, 6 had no EP departures and 5 had no new arrivals. The median proportion of EP workforce departing by hospital was 16% (interquartile range [IQR] = 4%-25%; range = 0%-73%), and the median proportion added was 21% (IQR = 7%-41%; range = 0%-120%). None of the evaluated covariates investigating relationships between physician/hospital characteristics and workforce change were significant. CONCLUSION: EP workforce changes over an 18-month period were common. This has implications for emergency department directors, researchers, and individual EPs. Those planning research involving interventions upon EPs should account for turnover as it may have an impact when designing clinical trials to improve performance on healthcare delivery metrics for time-sensitive medical conditions such as stroke, acute myocardial infarction, or trauma.

Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association.

BACKGROUND AND PURPOSE: The authors present an overview of the current evidence and management recommendations for evaluation and treatment of adults with acute ischemic stroke. The intended audiences are prehospital care providers, physicians, allied health professionals, and hospital administrators responsible for the care of acute ischemic stroke patients within the first 48 hours from stroke onset. These guidelines supersede the prior 2007 guidelines and 2009 updates. METHODS: Members of the writing committee were appointed by the American Stroke Association Stroke Council's Scientific Statement Oversight Committee, representing various areas of medical expertise. Strict adherence to the American Heart Association conflict of interest policy was maintained throughout the consensus process. Panel members were assigned topics relevant to their areas of expertise, reviewed the stroke literature with emphasis on publications since the prior guidelines, and drafted recommendations in accordance with the American Heart Association Stroke Council's Level of Evidence grading algorithm. RESULTS: The goal of these guidelines is to limit the morbidity and mortality associated with stroke. The guidelines support the overarching concept of stroke systems of care and detail aspects of stroke care from patient recognition; emergency medical services activation, transport, and triage; through the initial hours in the emergency department and stroke unit. The guideline discusses early stroke evaluation and general medical care, as well as ischemic stroke, specific interventions such as reperfusion strategies, and general physiological optimization for cerebral resuscitation. CONCLUSIONS: Because many of the recommendations are based on limited data, additional research on treatment of acute ischemic stroke remains urgently needed.

Does preexisting antiplatelet treatment influence postthrombolysis intracranial hemorrhage in community-treated ischemic stroke patients? An observational study.

OBJECTIVES: Intracranial hemorrhage (ICH) after acute stroke thrombolysis is associated with poor outcomes. Previous investigations of the relationship between preexisting antiplatelet use and the safety of intravenous (IV) thrombolysis have been limited by low event rates. The objective of this study was to determine whether preexisting antiplatelet therapy increased the risk of ICH following acute stroke thrombolysis. The primary hypothesis was that antiplatelet use would not be associated with radiographic evidence of ICH after controlling for relevant confounders. METHODS: Consecutive cases of thrombolysis patients treated in the emergency department (ED) were identified using multiple methods. Retrospective data were collected from four hospitals from 1996 to 2004 and 24 other hospitals from 2007 to 2010 as part of a cluster-randomized trial. The same chart abstraction tool was used during both time periods, and data were subjected to numerous quality control checks. Hemorrhages were classified using a prespecified methodology: ICH was defined as presence of hemorrhage in radiographic interpretations of follow-up imaging (primary outcome). Symptomatic ICH (sICH) was defined as radiographic ICH with associated clinical worsening. A multivariable logistic regression model was constructed to adjust for clinical factors previously identified to be related to postthrombolysis ICH. Sensitivity analyses were conducted where the unadjusted and adjusted results from this study were combined with those of previously published external studies on this topic via meta-analytic techniques. RESULTS: There were 830 patients included, with 47% having documented preexisting antiplatelet treatment. The mean (± standard deviation [SD]) age was 69 (± 15) years, and the cohort was 53% male. The unadjusted proportion of patients with any ICH was 15.1% without antiplatelet use and 19.3% with antiplatelet use (absolute risk difference = 4.2%, 95% confidence interval [CI] = -1.2% to 9.6%); for sICH this was 6.1% without antiplatelet use and 9% with antiplatelet use (absolute risk difference = 3.1%, 95% CI = -1% to 6.7%). After adjusting for confounders, antiplatelet use was not significantly associated with radiographic ICH (odds ratio [OR] = 1.1, 95% CI = 0.8 to 1.7) or sICH (OR = 1.3, 95% CI = 0.7 to 2.2). In patients 81 years and older, there was a higher risk of radiographic ICH (absolute risk difference = 11.9%, 95% CI = 0.1% to 23.6%). The meta-analyses combined the findings of this investigation with previous similar work and found increased unadjusted risks of radiographic ICH (absolute risk difference = 4.9%, 95% CI = 0.7% to 9%) and sICH (absolute risk difference = 4%, 95% CI = 2.3% to 5.6%). The meta-analytic adjusted OR of sICH for antiplatelet use was 1.6 (95% CI = 1.1 to 2.4). CONCLUSIONS: The authors did not find that preexisting antiplatelet use was associated with postthrombolysis ICH or sICH in this cohort of community treated patients. Preexisting tobacco use, younger age, and lower severity were associated with lower odds of sICH. The meta-analyses demonstrated small, but statistically significant increases in the absolute risk of radiographic ICH and sICH, along with increased odds of sICH in patients with preexisting antiplatelet use.

A multilevel intervention to increase community hospital use of alteplase for acute stroke (INSTINCT): a cluster-randomised controlled trial.

BACKGROUND: Use of alteplase improves outcome in some patients with stroke. Several types of barrier frequently prevent its use. We assessed whether a standardised, barrier-assessment, multicomponent intervention could increase alteplase use in community hospitals in Michigan, USA. METHODS: In a cluster-randomised controlled trial, we selected adult, non-specialty, acute-care community hospitals in the Lower Peninsula of Michigan, USA. Eligible hospitals discharged at least 100 patients who had had a stroke per year, had less than 100 000 visits to the emergency department per year, and were not academic comprehensive stroke centres. Using a computer-generated randomisation sequence, we selected 12 matched pairs of eligible hospitals. Within pairs, the hospitals were allocated to intervention or control groups with restricted randomisation in January, 2007. Between January, 2007, and December, 2007, intervention hospitals implemented a multicomponent intervention that included qualitative and quantitative assessment of barriers to alteplase use and ways to address the findings, and provided additional support. The primary outcome was change in alteplase use in patients with stroke in emergency departments between the pre-intervention period (January, 2005, to December, 2006) and the post-intervention period (January, 2008, to January, 2010). Physicians in participating hospitals and the coordinating centre could not be masked to group assignment, but were masked to progress made in paired control hospitals. External medical reviewers who were masked to group assignment assessed outcomes. We did intention-to-treat (ITT) and target-population (without one pair that was excluded after randomisation) analyses. This trial is registered at ClinicalTrials.gov, number NCT00349479. FINDINGS: All 24 hospitals completed the study. Overall, 745 of 40 823 patients with stroke received intravenous alteplase treatment. In the ITT analysis, the proportion of patients with stroke who were admitted and treated with alteplase increased between the pre-intervention and post-intervention periods in intervention hospitals (89 [1·25%] of 7119 patients to 235 [2·79%] of 8419) to a greater extent than in control hospitals (99 [1·25%] of 7946 to 194 [2·10%] of 9222), but the difference between groups was not significant (relative risk [RR] 1·37, 95% CI 0·96-1·93; p=0·08). In the target-population analysis, the increase in alteplase use in intervention hospitals (59 [1·00%] of 5882 to 191 [2·62%] of 7288) was significantly greater than in control hospitals (65 [1·09%] of 5957 to 120 [1·72%] of 6989; RR 1·68, 95% CI 1·09-2·57; p=0·02), but was still clinically modest. INTERPRETATION: The intervention did not significantly increase alteplase use in patients with ischaemic stroke. The increase in use of alteplase in the target population was significant, but smaller than the effect to which the study was powered. Additional strategies to increase acute stroke treatment are needed. FUNDING: National Institutes of Health National Institute of Neurological Disorders and Stroke.

Antihypertensive treatment prolongs tissue plasminogen activator door-to-treatment time: secondary analysis of the INSTINCT trial.

BACKGROUND AND PURPOSE: Identifying modifiable tissue plasminogen activator treatment delays may improve stroke outcomes. We hypothesized that prethrombolytic antihypertensive treatment (AHT) may prolong door-to-treatment time (DTT). METHODS: We performed an analysis of consecutive tissue plasminogen activator-treated patients at 24 randomly selected community hospitals in the Increasing Stroke Treatment through Interventional Behavior Change Tactics (INSTINCT) trial between 2007 and 2010. DTT among stroke patients who received prethrombolytic AHT were compared with those who did not receive prethrombolytic AHT. We then calculated a propensity score for the probability of receiving prethrombolytic AHT using logistic regression with demographics, stroke risk factors, home medications, stroke severity (National Institutes of Health Stroke Scale), onset-to-door time, admission glucose, pretreatment blood pressure, emergency medical service transport, and location at time of stroke as independent variables. A paired t test was performed to compare the DTT between the propensity-matched groups. RESULTS: Of 534 tissue plasminogen activator-treated stroke patients analyzed, 95 received prethrombolytic AHT. In the unmatched cohort, patients who received prethrombolytic AHT had a longer DTT (mean increase, 9 minutes; 95% confidence interval, 2-16 minutes) than patients who did not. After propensity matching, patients who received prethrombolytic AHT had a longer DTT (mean increase, 10.4 minutes; 95% confidence interval, 1.9-18.8) than patients who did not receive prethrombolytic AHT. CONCLUSIONS: Prethrombolytic AHT is associated with modest delays in DTT. This represents a potential target for quality-improvement initiatives. Further research evaluating optimum prethrombolytic hypertension management is warranted.

Observational study of telephone consults by stroke experts supporting community tissue plasminogen activator delivery.

OBJECTIVES: Barriers to intravenous (IV) tissue plasminogen activator (tPA) use in ischemic stroke include limited treatment experience of community physicians. Models of acute stroke care have been designed to address these limitations by providing community support. These include support by telephone or televideo, with or without subsequent transport to tertiary care centers. The authors describe the frequency, characteristics, and effect of community phone consultations to a 24/7 stroke "hotline" staffed by stroke physicians at an academic stroke center using such a model. METHODS: Twelve intervention hospitals participating in the INcreasing Stroke Treatment through Interventional behavior Change Tactics (INSTINCT) trial were provided a single-access number ("hotline") for expert consultation on tPA use. Experts consisted of stroke-trained physicians at an academic medical center. Hotline use was not mandated by the study protocol, nor was patient transfer required. Consultants were required to record all treatment questions in a Web-based log. All patients discussed over the hotline and/or treated with tPA in an INSTINCT hospital underwent multilevel chart review by trained nurse coordinators. Cases were linked to logged hotline calls, based on the time of treatment and the initial treating hospital. Physician adjudicators assessed appropriateness of tPA treatment, presence of deviation from standard guidelines, and treatment complications (intracranial hemorrhage [ICH], systemic hemorrhage, or death). RESULTS: Over 27 months, there were a total of 204 hotline calls regarding 116 patients. Ninety-one percent of calls were between 8 a.m. and midnight, and 77% of questions explored issues of eligibility for IV tPA, particularly for minor stroke or improving stroke (26%). A total of 243 patients were treated with IV tPA at the 12 intervention hospitals, 54 of which were following hotline consult. Seventy-six percent of hotline patients in whom tPA was recommended actually received tPA, while 2% of those in whom tPA was not recommended received the medication. There were no differences in protocol deviations (27.8% hotline group vs. 23.8% nonhotline group), incidence of symptomatic ICH (5.6% vs. 7.3%), or in-hospital mortality (5.6% vs. 13.2%). No medico-legal issues have been reported for any case in the study. CONCLUSIONS: Providing tPA decision-making support via telephone consult to community physicians is feasible and safe. Consultants may play a more prominent role in determining tPA ineligibility than acceptance. Future work should include a real-time survey of physician providers to ascertain such potential qualitative benefits of a stroke hotline.

National trends in use of computed tomography in the emergency department.

STUDY OBJECTIVE: The role of computed tomography (CT) in acute illnesses has increased substantially in recent years; however, little is known about how CT use in the emergency department (ED) has changed over time. METHODS: A retrospective study was performed with the 1996 to 2007 National Hospital Ambulatory Medical Care Survey, a large nationwide survey of ED services. We assessed changes during this period in CT use during an ED visit, CT use for specific ED presenting complaints, and disposition after CT use. Main outcomes were presented as adjusted risk ratios (RRs). RESULTS: Data from 368,680 patient visits during the 12-year period yielded results for an estimated 1.29 billion weighted ED encounters, among which an estimated 97.1 million (7.5%) patients received at least one CT. Overall, CT use during ED visits increased 330%, from 3.2% of encounters (95% confidence interval [CI] 2.9% to 3.6%) in 1996 to 13.9% (95% CI 12.8% to 14.9%) in 2007. Among the 20 most common complaints presenting to the ED, there was universal increase in CT use. Rates of growth were highest for abdominal pain (adjusted RR comparing 2007 to 1996=9.97; 95% CI 7.47 to 12.02), flank pain (adjusted RR 9.24; 95% CI 6.22 to 11.51), chest pain (adjusted RR 5.54; 95% CI 3.75 to 7.53), and shortness of breath (adjusted RR 5.28; 95% CI 2.76 to 8.34). In multivariable modeling, the likelihood of admission or transfer after a CT scan decreased over the years but has leveled off more recently (adjusted RR comparing admission or transfer after CT in 2007 to 1996=0.42; 95% CI 0.32 to 0.55). CONCLUSION: CT use in the ED has increased significantly in recent years across a broad range of presenting complaints. The increase has been associated with a decline in admissions or transfers after CT use, although this effect has stabilized more recently.

Provider perceptions of barriers to the emergency use of tPA for acute ischemic stroke: a qualitative study.

BACKGROUND: Only 1-3% of ischemic stroke patients receive thrombolytic therapy. Provider barriers to adhering with guidelines recommending tPA delivery in acute stroke are not well known. The main objective of this study was to describe barriers to thrombolytic use in acute stroke care. METHODS: Twenty-four hospitals were randomly selected and matched into 12 pairs. Barrier assessment occurred at intervention sites only, and utilized focus groups and structured interviews. A pre-specified taxonomy was employed to characterize barriers. Two investigators independently assigned themes to transcribed responses. Seven facilitators (three emergency physicians, two nurses, and two study coordinators) conducted focus groups and interviews of emergency physicians (65), nurses (62), neurologists (15), radiologists (12), hospital administrators (12), and three others (hospitalists and pharmacist). RESULTS: The following themes represented the most important external barriers: environmental and patient factors. Important barriers internal to the clinician included familiarity with and motivation to adhere to the guidelines, lack of self-efficacy and outcome expectancy. The following themes were not substantial barriers: lack of awareness of the existence of acute stroke guidelines, presence of conflicting guidelines, and lack of agreement with the guidelines. CONCLUSIONS: Healthcare providers perceive environmental and patient-related factors as the primary barriers to adherence with acute stroke treatment guidelines. Interventions focused on increasing physician familiarity with and motivation to follow guidelines may be of highest yield in improving adherence. Improving self-efficacy in performing guideline concordant care may also be useful.

Safety of intravenous thrombolytic use in four emergency departments without acute stroke teams.

OBJECTIVES: The objective was to evaluate safety of intravenous (IV) tissue plasminogen activator (tPA) delivered without dedicated thrombolytic stroke teams. METHODS: This was a retrospective, observational study of patients treated between 1996 and 2005 at four southeastern Michigan hospital emergency departments (EDs) with a prospectively defined comparison to the National Institute of Neurological Disorders and Stroke (NINDS) tPA stroke study cohort. Main outcome measures were mortality, intracerebral hemorrhage (ICH), systemic hemorrhage, neurologic recovery, and guideline violations. RESULTS: A total of 273 consecutive stroke patients were treated by 95 emergency physicians (EPs) using guidelines and local neurology resources. One-year mortality was 27.8%. Unadjusted Cox model relative risk (RR) of mortality compared to the NINDS tPA treatment and placebo groups was 1.20 (95% confidence interval [CI] = 0.87 to 1.64) and 1.04 (95% CI = 0.76 to 1.41), respectively. The rate of significant ICH by computed tomography (CT) criteria was 6.6% (odds ratio [OR] = 1.03, 95% CI = 0.56 to 1.90 compared to the NINDS tPA treatment group). The proportions of symptomatic ICH by two other prespecified sets of clinical criteria were 4.8 and 7.0%. The rate of any ICH within 36 hours of treatment was 9.9% (RR = 0.94, 95% CI = 0.58 to 1.51 compared to the NINDS tPA group). The occurrence of major systemic hemorrhage (requiring transfusion) was 1.1%. Functional recovery by the modified Rankin Scale score (mRS = 0 to 2) at discharge occurred in 38% of patients with a premorbid disability mRS < 2. Guideline deviations occurred in the ED in 26% of patients and in 25% of patients following admission. CONCLUSIONS: In these EDs there was no evidence of increased risk with respect to mortality, ICH, systemic hemorrhage, or worsened functional outcome when tPA was administered without dedicated thrombolytic stroke teams. Additional effort is needed to improve guideline compliance.

Attitudes and beliefs of Michigan emergency physicians toward tissue plasminogen activator use in stroke: baseline survey results from the INcreasing Stroke Treatment through INteractive behavioral Change Tactic (INSTINCT) trial hospitals.

BACKGROUND AND PURPOSE: The objective of this study was to determine the baseline proportion of emergency physicians with favorable attitudes and beliefs toward intravenous tissue plasminogen activator (tPA) use in a cohort of randomly selected Michigan hospitals. METHODS: Two hundred seventy-eight emergency physicians from 24 hospitals were surveyed. A confidential, self-administered, pilot-tested survey assessing demographics, practice environment, attitudes, and beliefs regarding tPA use in stroke was used. Main outcome measures assessed belief in a legal standard of care, likelihood of use in an ideal setting, comfort in use without a specialist consultation, and belief that science on tPA use is convincing. ORs with robust 95% CIs (adjusted for clustering) were calculated to quantify the association between responses and physician- and hospital-level characteristics. RESULTS: One hundred ninety-nine surveys completed (gross response rate 71.6%). Ninety-nine percent (95% CI: 97.8 to 100) indicated use of tPA in eligible patients represented either acceptable or ideal patient care. Twenty-seven percent (95% CI: 21.7 to 32.3) indicated use of tPA represented a legal standard of care. Eighty-three percent (95% CI: 78.5 to 87.5) indicated they were "likely" or "very likely" to use tPA given an ideal setting. When asked about using tPA without a consultation, 65% (95% CI: 59.3 to 70.7) indicated they were uncomfortable. Forty-nine percent (95% CI: 43.0 to 55.0) indicated the science regarding use of tPA in stroke is convincing with 30% remaining neutral. Characteristics associated with favorable attitudes included non-emergency medicine board certification; older age, and a smaller hospital practice environment. CONCLUSIONS: In this cohort, emergency physician attitudes and beliefs toward intravenous tPA use in stroke are considerably more favorable than previously reported.