Joshua Stillman

Symptomatic Intracerebral Hemorrhage Among Eligible Warfarin-Treated Patients Receiving Intravenous Tissue Plasminogen Activator for Acute Ischemic Stroke

OBJECTIVE To determine whether warfarin-treated patients with an international normalized ratio less than 1.7 who receive intravenous tissue plasminogen activator for acute ischemic stroke are at increased risk for symptomatic intracerebral hemorrhage. DESIGN Retrospective study. SETTING Academic hospital. PATIENTS Consecutive patients with acute ischemic stroke who are treated with intravenous tissue plasminogen activator. MAIN OUTCOME MEASURE Symptomatic intracerebral hemorrhage. RESULTS One hundred seven patients were included (mean age, 69.2 years; 43.9% men; median National Institutes of Health Stroke Scale score, 14; median onset-to-treatment time, 140 minutes; baseline warfarin use, 12.1%). The median international normalized ratio was 1.04 (range, 0.82-1.61). The overall rate of symptomatic intracerebral hemorrhage was 6.5%, but it was nearly 10-fold higher among patients taking warfarin compared with those not taking warfarin at baseline (30.8% vs 3.2%, respectively; P = .004). Baseline warfarin use remained strongly associated with symptomatic intracerebral hemorrhage (P = .004) after adjusting for relevant covariates, including age, atrial fibrillation, National Institutes of Health Stroke Scale score, and international normalized ratio. CONCLUSIONS Despite an international normalized ratio less than 1.7, warfarin-treated patients are more likely than those not taking warfarin to experience symptomatic intracerebral hemorrhage following treatment with intravenous tissue plasminogen activator. Larger studies in this subgroup are warranted.

High-Dose Lovastatin for Acute Ischemic Stroke: Results of the Phase I Dose Escalation Neuroprotection with Statin Therapy for Acute Recovery Trial (NeuSTART)

Background: Hydroxymethylglutaryl coenzyme A reductase inhibitors (‘statins’) reduce the neuronal injury in dose-dependent fashion in rodent stroke models. We sought to determine whether lovastatin at doses above those currently approved can be administered safely within 24 h after an acute ischemic stroke. Methods: We conducted a phase 1B dose-finding study using an adaptive design novel to stroke trials, the continual reassessment method, to find the highest tolerated dose of lovastatin. Planned doses were 1, 3, 6, 8 and 10 mg/kg/day for 3 days. The primary safety outcomes were myotoxicity and hepatotoxicity. The model was calibrated to select a dose causing 7–13% toxicity. Results: We enrolled 33 patients (16 men/17 women, age range 23–82 years). Three patients were treated at 1 mg/kg, 10 at 3 mg/kg, 12 at 6 mg/kg, and 8 at 8 mg/kg. Thirty of the 33 patients (90.9%) completed at least 11 of 12 doses. Two patients at the 6-mg/kg dose level experienced transient mild elevations in transaminases without clinical sequelae. After an initial dose reduction, the dose was re-escalated to 8 mg/kg, and no further patients reached safety outcomes. No clinical liver disease, myopathy, or creatine phosphokinase elevations occurred. The final model-based toxicity at 8 mg/kg was 13%; no patient was treated at 10 mg/kg. Conclusions: Lovastatin at doses above those currently approved by the Food and Drug Administration is feasible for 3 days after an acute ischemic stroke and the maximum tolerated dose is estimated to be 8 mg/kg/day. Further randomized studies are warranted to confirm its safety and to demonstrate its efficacy in improving functional outcomes after stroke.

Too good to treat? Outcomes in patients not receiving thrombolysis due to mild deficits or rapidly improving symptoms

Introduction Among ischemic stroke patients arriving within the treatment window, rapidly improving symptoms or having a mild deficit (i.e. too good to treat) is a common reason for exclusion. Several studies have reported poor outcomes in this group. We addressed the question of early neurological deterioration in too good to treat patients in a larger prospective cohort study. Methods Admission and discharge information were collected prospectively in acute stroke patients who presented to the emergency room within three-hours from onset. The primary outcome measure was change in the National Institutes of Health Stroke Scale from baseline to discharge. Secondary outcomes were discharge National Institutes of Health Stroke Scale #>4, not being discharged home, and discharge modified Rankin scale. Results Of 355 patients who presented within three-hours, 127 (35.8%) had too good to treat listed as the only reason for not receiving thrombolysis, with median admission National Institutes of Health Stroke Scale = 1 (range = 0 to 19). At discharge, seven (5.5%) showed a worsening of National Institutes of Health Stroke Scale ≥1, and nine (7.1%) had a National Institutes of Health Stroke Scale #>4. When excluding prior stroke (remaining n = 97), discharge status was even more benign: only five (5.2%) had a discharge National Institutes of Health Stroke Scale #>4, and two (2.1%) patients were not discharged home. Conclusion We found that a small proportion of patients deemed too good to treat will have early neurological deterioration, in contrast to other studies. Decisions about whether to treat mild stroke patients depend on the outcome measure chosen, particularly when considering discharge disposition among patients who have had prior stroke. The decision to thrombolyze may ultimately rest on the nature of the presentation and deficit.

Safety of thrombolysis in patients over the age of 80.

Background:The safety of intravenous thrombolysis (IVT) in patients with acute ischemic stroke over the age of 80 is unclear. We hypothesized that patients over the age of 80 can be safely treated with IVT. Methods:Admission and discharge data were collected on all patients at a single tertiary care center presenting within 12 hours of onset. Collected data included treatment with IVT, demographics, pretreatment National Institutes of Health Stroke Scale score, length of stay, mortality, and discharge disposition. Analyses were restricted to patients over the age of 80, and the primary outcome was in-hospital mortality. Logistic regression was used to examine whether IVT was associated with mortality. Results:Between January 1, 2005 and May 30, 2010, 112 patients over the age of 80 presented within 3 hours of ischemic stroke onset, and 31 received IVT. There were 15 deaths. In multivariable models adjusted for age, sex, race-ethnicity, and National Institutes of Health Stroke Scale, treatment with IVT, compared with no treatment, was not associated with in-hospital death (adjusted odds ratio, 1.2; 95% confidence interval, 0.3-4.3). Conclusions:Treating ischemic stroke patients over 80 years with IVT was not associated with an increase in mortality in an urban tertiary care center.

Discharge educational strategies for reduction of vascular events (DESERVE): design and methods

Rationale Stroke and vascular risk factors disproportionately affect minority populations, with Blacks and Hispanics experiencing a 2.5- and 2.0-fold greater risk compared with whites, respectively. Patients with transient ischemic attacks and mild, nondisabling strokes tend to have short hospital stays, rapid discharges, and inaccurate perceptions of vascular risk. Aim The primary aim of the Discharge Educational Strategies for Reduction of Vascular Events (DESERVE) trial is to evaluate the efficacy of a novel community health worker-based multilevel discharge intervention vs. standard discharge care on vascular risk reduction among racially/ethnically diverse transient ischemic attack/mild stroke patients at one-year postdischarge. We hypothesize that those randomized to the discharge intervention will have reduced modifiable vascular risk factors as determined by systolic blood pressure compared with those receiving usual care. Sample size estimates Given 300 subjects per group and alpha of 0.05, the power to detect a 6 mmHg reduction in systolic blood pressure is 89%. Design DESERVE trial is a prospective, randomized, multicenter clinical trial of a novel discharge behavioral intervention. Patients with transient ischemic attack/mild stroke are randomized during hospitalization or emergency room visit to intervention or usual care. Intervention begins prior to discharge and continues postdischarge. Study outcomes The primary outcome is difference in systolic blood pressure reduction between groups at 12 months. Secondary outcomes include between-group differences in change in glycated hemoglobin, smoking rates, medication adherence, and recurrent stroke/transient ischemic attack at 12 months. Discussion DESERVE will evaluate whether a novel discharge education strategy leads to improved risk factor control in a racially diverse population.

Door-to-Needle Delays in Minor Stroke: A Causal Inference Approach

Background and Purpose— Thrombolysis rates among minor stroke (MS) patients are increasing because of increased recognition of disability in this group and guideline changes regarding treatment indications. We examined the association of delays in door-to-needle (DTN) time with stroke severity. Methods— We performed a retrospective analysis of all stroke patients who received intravenous tissue-type plasminogen activator in our emergency department between July 1, 2011, and February 29, 2016. Baseline characteristics and DTN were compared between MS (National Institutes of Health Stroke Scale score ⩽5) and nonminor strokes (National Institutes of Health Stroke Scale score >5). We applied causal inference methodology to estimate the magnitude and mechanisms of the causal effect of stroke severity on DTN. Results— Of 315 patients, 133 patients (42.2%) had National Institutes of Health Stroke Scale score ⩽5. Median DTN was longer in MS than nonminor strokes (58 versus 53 minutes; P=0.01); fewer MS patients had DTN ⩽45 minutes (19.5% versus 32.4%; P=0.01). MS patients were less likely to use emergency medical services (EMS; 62.6% versus 89.6%, P<0.01) and to receive EMS prenotification (43.9% versus 72.4%; P<0.01). Causal analyses estimated MS increased average DTN by 6 minutes, partly through mode of arrival. EMS prenotification decreased average DTN by 10 minutes in MS patients. Conclusions— MS had longer DTN times, an effect partly explained by patterns of EMS prenotification. Interventions to improve EMS recognition of MS may accelerate care.

The Influence of Language Discordance Between Patient and Physician on Time-to-Thrombolysis in Acute Ischemic Stroke

Background and purpose: Reducing door-to-imaging (DIT) time is a major focus of acute stroke quality improvement initiatives to promote rapid thrombolysis. However, recent data suggest that the imaging-to-needle (ITN) time is a greater source of treatment delay. We hypothesized that language discordance between physician and patient would contribute to prolonged ITN time, as rapidly taking a history and confirming last known well require facile communication between physician and patient. Methods: This is a retrospective analysis of all patients who received tissue plasminogen activator (tPA) in our emergency department between July 2011 and December 2014. Baseline characteristics and relevant time intervals were compared between encounters where the treating neurologist and patient spoke the same language (concordant cases) and where they did not (discordant cases). Results: A total of 279 patients received tPA during the study period. English was the primary language for 51%, Spanish for 46%, and other languages for 3%; 59% of cases were classified as language concordant and 41% as discordant. We found no differences in median DIT (24 vs 25, P = .5), ITN time (33 vs 30, P = .3), or door-to-needle time (DTN; 58 vs 55, P = .1) between concordant and discordant groups. Similarly, among patients with the fastest and slowest ITN times, there were no differences. Conclusion: In a high-volume stroke center with a large proportion of Spanish speakers, language discordance was not associated with changes in DIT, ITN time, or DTN time.

Language barriers between physicians and patients are not associated with thrombolysis of stroke mimics

Background:Acute stroke is a time-sensitive condition in which rapid diagnosis must be made in order for thrombolytic treatment to be administered. A certain proportion of patients who receive thrombolysis will be found on further evaluation to have a diagnosis other than stroke, so-called “stroke mimics.” Little is known about the role of language discordance in the emergency department diagnosis of acute ischemic stroke. Methods:This is a retrospective analysis of all acute ischemic stroke patients who received IV tissue plasminogen activator (tPA) in our emergency department between July 2011 and December 2015. Baseline characteristics, patient language, and final diagnosis were compared between encounters in which the treating neurologist and patient spoke the same language (concordant cases) and encounters in which they did not (discordant cases). Results:A total of 350 patients received IV tPA during the study period. English was the primary language for 52.6%, Spanish for 44.9%, and other languages for 2.6%; 60.3% of cases were classified as language concordant and 39.7% as discordant. We found no significant difference in the proportion of stroke mimics in the language concordant compared to discordant groups (16.6% vs 9.4%, p = 0.06). Similarly, the proportion of stroke mimics did not differ between English- and Spanish-speaking patients (15.8% vs 11.5%, p = 0.27). Conclusions:Language discordance was not associated with acute stroke misdiagnosis among patients treated with IV tPA. Prospective evaluation of communication during acute stroke encounters is needed to gain clarity on the role of language discordance in acute stroke misdiagnosis.

E-Mail Is an Effective Tool for Rapid Feedback in Acute Stroke

Objective: To determine whether e-mail is a useful mechanism to provide prompt, case-specific data feedback and improve door-to-needle (DTN) time for acute ischemic stroke treated with intravenous tissue plasminogen activator (IV-tPA) in the emergency department (ED) at a high-volume academic stroke center. Methods: We instituted a quality improvement project at Columbia University Medical Center where clinical details are shared via e-mail with the entire treatment team after every case of IV-tPA administration in the ED. Door-to-needle and component times were compared between the prefeedback (January 2013 to March 2015) and postfeedback intervention (April 2015 to June 2016) periods. Results: A total of 273 cases were included in this analysis, 102 (37%) in the postintervention period. Median door-to-stroke code activation (2 vs 0 minutes, P < .01), door-to-CT Scan (21 vs 18 minutes, P < .01), and DTN (54 vs 49 minutes, P = .17) times were shorter in the postintervention period, although the latter did not reach statistical significance. The proportion of cases with the fastest DTN (≤45 minutes) was higher in the postintervention period (29.2% vs 42.2%, P = .03). Conclusion: E-mail is a simple and effective tool to provide rapid feedback and promote interdisciplinary communication to improve acute stroke care in the ED.