Ransomware Attack Associated With Disruptions at Adjacent Emergency Departments in the US.

Importance: Cyberattacks on health care delivery organizations are increasing in frequency and sophistication. Ransomware infections have been associated with significant operational disruption, but data describing regional associations of these cyberattacks with neighboring hospitals have not been previously reported, to our knowledge. Objective: To examine an institution's emergency department (ED) patient volume and stroke care metrics during a month-long ransomware attack on a geographically proximal but separate health care delivery organization. Design, Setting, and Participants: This before and after cohort study compares adult and pediatric patient volume and stroke care metrics of 2 US urban academic EDs in the 4 weeks prior to the ransomware attack on May 1, 2021 (April 3-30, 2021), as well as during the attack and recovery (May 1-28, 2021) and 4 weeks after the attack and recovery (May 29 to June 25, 2021). The 2 EDs had a combined mean annual census of more than 70 000 care encounters and 11% of San Diego County's total acute inpatient discharges. The health care delivery organization targeted by the ransomware constitutes approximately 25% of the regional inpatient discharges. Exposure: A month-long ransomware cyberattack on 4 adjacent hospitals. Main Outcomes and Measures: Emergency department encounter volumes (census), temporal throughput, regional diversion of emergency medical services (EMS), and stroke care metrics. Results: This study evaluated 19 857 ED visits at the unaffected ED: 6114 (mean [SD] age, 49.6 [19.3] years; 2931 [47.9%] female patients; 1663 [27.2%] Hispanic, 677 [11.1%] non-Hispanic Black, and 2678 [43.8%] non-Hispanic White patients) in the preattack phase, 7039 (mean [SD] age, 49.8 [19.5] years; 3377 [48.0%] female patients; 1840 [26.1%] Hispanic, 778 [11.1%] non-Hispanic Black, and 3168 [45.0%] non-Hispanic White patients) in the attack and recovery phase, and 6704 (mean [SD] age, 48.8 [19.6] years; 3326 [49.5%] female patients; 1753 [26.1%] Hispanic, 725 [10.8%] non-Hispanic Black, and 3012 [44.9%] non-Hispanic White patients) in the postattack phase. Compared with the preattack phase, during the attack phase, there were significant associated increases in the daily mean (SD) ED census (218.4 [18.9] vs 251.4 [35.2]; P < .001), EMS arrivals (1741 [28.8] vs 2354 [33.7]; P < .001), admissions (1614 [26.4] vs 1722 [24.5]; P = .01), patients leaving without being seen (158 [2.6] vs 360 [5.1]; P < .001), and patients leaving against medical advice (107 [1.8] vs 161 [2.3]; P = .03). There were also significant associated increases during the attack phase compared with the preattack phase in median waiting room times (21 minutes [IQR, 7-62 minutes] vs 31 minutes [IQR, 9-89 minutes]; P < .001) and total ED length of stay for admitted patients (614 minutes [IQR, 424-1093 minutes] vs 822 minutes [IQR, 497-1524 minutes]; P < .001). There was also a significant increase in stroke code activations during the attack phase compared with the preattack phase (59 vs 102; P = .01) as well as confirmed strokes (22 vs 47; P = .02). Conclusions and Relevance: This study found that hospitals adjacent to health care delivery organizations affected by ransomware attacks may see increases in patient census and may experience resource constraints affecting time-sensitive care for conditions such as acute stroke. These findings suggest that targeted hospital cyberattacks may be associated with disruptions of health care delivery at nontargeted hospitals within a community and should be considered a regional disaster.

Hospital case-volume is associated with case-fatality after aneurysmal subarachnoid hemorrhage.

BACKGROUND: Inverse association between hospital case-volume and case-fatality has been observed for various nonsurgical interventions and surgical procedures. AIMS: To study the impact of hospital case-volume on outcome after aneurysmal subarachnoid hemorrhage (aSAH). METHODS: We included aSAH patients who underwent aneurysm coiling or clipping from tertiary care medical centers across three continents using the Dr Foster Stroke GOAL database 2007-2014. Hospitals were categorized by annual case-volume (low volume: <41/year; intermediate: 41-70/year; high: >70/year). Primary outcome was 14-day in-hospital case-fatality. We calculated proportions, and used multiple logistic regression to adjust for age, sex, differences in comorbidity or disease severity, aneurysm treatment modality, and hospital. RESULTS: We included 8525 patients (2363 treated in low volume hospitals, 3563 treated in intermediate volume hospitals, and 2599 in high-volume hospitals). Crude 14-day case-fatality for hospitals with low case-volume was 10.4% (95% confidence interval (CI) 9.2-11.7%), for intermediate volume 7.0% (95% CI 6.2-7.9%; adjusted odds ratio (OR) 0.63 (95%CI 0.47-0.85)) and for high volume 5.4% (95% CI 4.6-6.3%; adjusted OR 0.50 (95% CI 0.33-0.74)). In patients with clipped aneurysms, adjusted OR for 14-day case-fatality was 0.46 (95% CI 0.30-0.71) for hospitals with intermediate case-volume and 0.42 (95% CI 0.25-0.72) with high case-volume. In patients with coiled aneurysms, adjusted OR was 0.77 (95% CI 0.55-1.07) for hospitals with intermediate case-volume and 0.56 (95% CI 0.36-0.87) with high case-volume. CONCLUSIONS: Even within a subset of large, tertiary care centers, intermediate and high hospital case-volume is associated with lower case-fatality after aSAH regardless of treatment modality, supporting centralization to higher volume centers.

Outcome After Clipping and Coiling for Aneurysmal Subarachnoid Hemorrhage in Clinical Practice in Europe, USA, and Australia.

BACKGROUND: Within randomized clinical trials (RCTs), coiling of the ruptured aneurysm to prevent rebleeding results in better outcomes than clipping in patients with aneurysmal subarachnoid hemorrhage (aSAH). OBJECTIVE: To study the association of coiling and clipping with outcome after aSAH in daily clinical practice. METHODS: In this controlled, nonrandomized study, we compared outcomes after endovascular coiling and neurosurgical clipping of ruptured intracranial aneurysms in an administrative dataset of 7658 aSAH patients (22 tertiary care hospitals from Europe, USA, Australia; 2007-2013). Because the results contradicted those of the randomized trials, findings were further explored in a large clinical dataset from 2 European centers (2006-2016) of 1501 patients. RESULTS: In the administrative dataset, the crude 14-d case-fatality rate was 6.4% (95% confidence interval [CI] 5.6%-7.2%) after clipping and 8.2% (95% CI 7.4%-9.1%) after coiling. After adjustment for age, sex, and comorbidity/severity, the odds ratio (OR) for 14-d case-fatality after coiling compared to clipping was 1.32 (95% CI 1.10-1.58). In the clinical dataset crude 14-d case fatality rate was 5.7% (95% CI 4.2%-7.8%) for clipping and 9.0% (95% CI 7.3%-11.2%) for coiling. In multivariable logistic regression analysis, the OR for 14-d case-fatality after coiling compared to clipping was 1.7 (95% CI 1.1-2.7), for 90-d case-fatality 1.28 (95% CI 0.91-1.82) and for 90-d poor functional outcome 0.78 (95% CI 0.6-1.01). CONCLUSION: In clinical practice, coiling after aSAH is associated with higher 14-d case-fatality than clipping and nonsuperior outcomes at 90 d. Both options need to be considered in aSAH patients. Further studies should address the reasons for the discrepancy between current data and those from the RCTs.

The Sustained DeyeCOM Sign as a Predictor of Large Vessel Occlusions and Stroke Mimics.

INTRODUCTION: Rapid imaging in acute stroke is critical and often occurs before full examination. Early, reliable examination findings clarify diagnosis and improve treatment times. The DeyeCOM sign has been described as a predictor of ischemic stroke. In this study, we evaluate a sustained DeyeCOM sign on serial computed tomography scans in prediction of large vessel occlusion. METHODS: Between April and June 2017, we retrospectively reviewed 46 patients with acute stroke from the University of California, San Diego Stroke Registry, who had both computed tomography and computed tomography angiography as part of their acute work-up. A DeyeCOM(+) sign was defined as a conjugate gaze deviation on imaging of at least 15°. DeyeCOM(++) was defined as sustained gaze deviation on both scans. RESULTS: Three groups of patients were observed: DeyeCOM(++), nonsustained gaze deviation, and no gaze deviation (DeyeCOM(--)). All patients in the DeyeCOM(++) (8 of 8, 100%) had large vessel occlusion. Of those with nonsustained gaze deviation, 2 of 7 (29%) had large vessel occlusion. No patients in the DeyeCOM(--) (0 of 31, 100%) had large vessel occlusion. The specificity and sensitivity of DeyeCOM(++) for large vessel occlusion was 100% (confidence interval [CI] .90-1.0) and 80% (CI .44-.97). The specificity and sensitivity of DeyeCOM(--) for absence of large vessel occlusion was 100% (CI .69-1.0) and 86% (CI .70-.95). CONCLUSIONS: DeyeCOM(++) had 100% specificity for large vessel occlusion, whereas DeyeCOM(--) had a 100% specificity for absence of large vessel occlusion. Sustained DeyeCOM, whether positive or negative, is a strong predictor of ultimate diagnosis that could lead to quicker endovascular treatment times.

Stroke Severity Is a Crucial Predictor of Outcome: An International Prospective Validation Study.

BACKGROUND: Stroke is among the leading causes of morbidity and mortality worldwide. Without reliable prediction models and outcome measurements, comparison of care systems is impossible. We analyzed prospectively collected data from 4 countries to explore the importance of stroke severity in outcome prediction. METHODS AND RESULTS: For 2 months, all acute ischemic stroke patients from the hospitals participating in the Global Comparators Stroke GOAL (Global Outcomes Accelerated Learning) collaboration received a National Institutes of Health Stroke Scale (NIHSS) score on admission and a modified Rankin Scale score at 30 and 90 days. These data were added to the administrative data set, and risk prediction models including age, sex, comorbidity index, and NIHSS were derived for in-hospital death within 7 days, all in-hospital death, and death and good outcome at 30 and 90 days. The relative importance of each variable was assessed using the proportion of explained variation. Of 1034 admissions for acute ischemic stroke, 614 had a full set of NIHSS and both modified Rankin Scale values recorded; of these, 507 patients could be linked to administrative data. The marginal proportion of explained variation was 0.7% to 4.0% for comorbidity index, and 11.3 to 25.0 for NIHSS score. The percentage explained by the model varied by outcome (16.6-29.1%) and was highest for good outcome at 30 and 90 days. There was high agreement between 30- and 90-day modified Rankin Scale scores (weighted κ=0.82). CONCLUSIONS: In this prospective pilot study, the baseline NIHSS score was essential for prediction of acute ischemic stroke outcomes, followed by age; whereas traditional comorbidity index contributed little to the overall model. Future studies of stroke outcomes between different care systems will benefit from including a baseline NIHSS score.

Feasibility and Safety of Using External Counterpulsation to Augment Cerebral Blood Flow in Acute Ischemic Stroke-The Counterpulsation to Upgrade Forward Flow in Stroke (CUFFS) Trial.

BACKGROUND: External counterpulsation (ECP) increases perfusion to a variety of organs and may be helpful for acute stroke. METHODS: We conducted a single-blinded, prospective, randomized controlled feasibility and safety trial of ECP for acute middle cerebral artery (MCA) ischemic stroke. Twenty-three patients presenting within 48 hours of symptom onset were randomized into one of two groups. One group was treated with ECP for 1 hour at a pressure of up to 300 mmHg ("full pressure"). During the procedure, we also determined the highest possible pressure that would augment MCA mean flow velocity (MFV) by 15%. The other group was treated with ECP at 75 mmHg ("sham pressure"). Transcranial Doppler MCA flow velocities and National Institutes of Health Stroke Scale (NIHSS) scores of both groups were checked before, during, and after ECP. Outcomes were assessed at 30 days after randomization. RESULTS: Although the procedures were feasible to implement, there was a frequent inability to augment MFV by 15% despite maximal pressures in full-pressure patients. In sham-pressure patients, however, MFV frequently increased as shown by increases in peak systolic velocity and end diastolic velocity. In both groups, starting ECP was often associated with contemporaneous improvements in NIHSS stroke scores. There were no between-group differences in NIHSS, modified Rankin Scale Scores, and Barthel Indices, and no device or treatment-related serious adverse events, deaths, intracerebral hemorrhages, or episodes of acute neuro-worsening. CONCLUSIONS: ECP was safe and feasible to use in patients with acute ischemic stroke. It was associated with unexpected effects on flow velocity, and contemporaneous improvements in NIHSS score regardless of pressure used, with a possibility that even very low ECP pressures had an effect. Further study is warranted.

Seizures and Meperidine: Overstated and Underutilized.

Meperidine is used for pain control and treatment of shivering. Concerns about neurotoxicity, particularly seizures, have led to efforts limiting meperidine use. We reviewed the body of evidence linking meperidine to seizures. We searched PubMed for the terms meperidine, normeperidine, pethidine, and norpethidine; each was combined with the terms: seizure, epilepsy, epileptogenic, toxicity, overdose, seizure threshold, and convulsion. Articles were assessed for relevance. Semiologies were reviewed to ascertain seizure likelihood. Our search yielded 351 articles, of which 66 were relevant. Of these, 33 had primary clinical data on meperidine-associated seizures, comprising 50 patients. Twenty events were deemed likely to be seizures, 26 indeterminate, and 4 unlikely. Most studies were case reports. Confounding comorbidities were frequent. The evidence base for meperidine-associated seizures in man is scant. Seizure risk associated with meperidine appears to be overstated. The utility of meperidine should continue to be explored, especially for therapeutic hypothermia.

The "DeyeCOM Sign": Predictive Value in Acute Stroke Code Evaluations.

BACKGROUND: Rapid diagnosis in stroke is critical. Computed tomography is often performed initially, even before a neurologic examination. Gaze deviation has been correlated with stroke diagnosis in some cohorts. Conjugate gaze deviation on stroke code imaging, the "DeyeCOM sign," may have emergency stroke care implications. METHODS: We evaluated stroke code imaging from the University of California, San Diego database (2007-2013) for "DeyeCOM sign" diagnostic and predictive utility. Patients were grouped as DeyeCOM+ if conjugate gaze deviation was noted. The differences were assessed using the Fisher exact test for categorical and the Wilcoxon rank-sum test for continuous variables. RESULTS: We evaluated 342 patients; 106 (31%) were DeyeCOM+. Mean age was 63. The most common diagnoses in the DeyeCOM+ group were ischemic stroke (50.94%), transient ischemic attack (8.49%), other (8.49%), somatization (6.6%), and hemorrhage (5.66%). The National Institutes of Health Stroke Scale was greater in stroke patients than that in nonstroke (8.2 versus 3.8; P < .0001), and in DeyeCOM+ compared with DeyeCOM- (6.8 versus 5.6; P = .03). DeyeCOM+ patients were more likely to have a +gaze score (26.4% versus 9.8%; P < .0001), and +gaze patients were more likely to have final stroke diagnosis (26.0% versus 3.6%; P < .0001). There was no overall difference between groups in final stroke diagnosis; however, patients with deviation of 15° or more were more likely to have final diagnosis stroke (63.9% versus 47.9%; P = .03). CONCLUSIONS: DeyeCOM+ patients scored higher and were more likely to have +gaze on the stroke scale, and deviation of 15° or more was correlated with final diagnosis stroke. In current environments, there is pressure to complete stroke evaluations rapidly. Reliable imaging information obtained early (such as gaze deviation on scan correlating with scale score and final stroke diagnosis) could augment decision making even with negative imaging.

Defining mild stroke: outcomes analysis of treated and untreated mild stroke patients.

BACKGROUND: Mild deficit is a relative contraindication to administration of intravenous recombinant tissue plasminogen activator (IV rtPA) for acute ischemic stroke. However, what constitutes "mild" deficit is vague. Prior studies showed patients with mild strokes have substantial disability rates at hospital discharge and at 90 days. We investigated whether the application of a new definition altered the rates of disability overall and assessed the effects of thrombolysis. METHODS: This analysis included all adult acute ischemic stroke patients from a prospective registry of consecutive patients (University of California San Diego Specialized Programs of Translational Research in Acute Stroke (SPOTRIAS) database, 2003-2014) with 90-day modified Rankin Scale (mRS) score available who were defined as "mild" using either: National Institutes of Health Stroke Scale (NIHSS) 0-5 or a "Re-examining Acute Eligibility for Thrombolysis" (TREAT) Task Force definition (NIHSS 0-5 and nondisabling based on prespecified syndromes). Dichotomized 90-day mRS were compared between treated and untreated patients using the 2 definitions. RESULTS: Of 802 ischemic stroke patients with mRS scores available, 184 had baseline mRS (0) and met TREAT criteria; 45 (24.5%) were rtPA treated. Among the treated patients, 35.6% had 90-day mRS (2-6), versus 28.8% in the untreated group, a nonsignificant difference after adjusting for baseline NIHSS (P = .47). None of the 45 treated patients had symptomatic hemorrhage. Outcomes were similar using the simpler NIHSS 0-5 definition. CONCLUSIONS: About one third of mild stroke patients were not functionally independent at 90 days, irrespective of treatment or mild definition applied, calling into question the treatment efficacy of IV rtPA for mild strokes and what constitutes an appropriate definition of "mild." Randomized studies are necessary to determine rtPA treatment efficacy in mild stroke patients.

Association of Hispanic ethnicity with acute ischemic stroke care processes and outcomes.

BACKGROUND: Few studies have examined the actual hospital arrival mode, emergency department (ED) care processes, and early outcomes in Hispanic vs non-Hispanic acute ischemic stroke (AIS) patients. We evaluated processes and prognosis by Hispanic ethnicity among AIS patients encountered in urban setting. METHODS: We retrospectively reviewed prospectively-collected data on 1,117 AIS patients presenting within 12 hours of ictus to five hospitals in a tertiary-level stroke center network in San Diego, California. Variables of interest included pre-hospital factors, ED care processes, and favorable outcome (day-90 modified Rankin Scale [mRS] score of 0-1); all of which were adjusted for pre-specified covariates in a multivariable logistic regression model. RESULTS: There were 192 Hispanic AIS patients (17.2% of cohort) encountered from June 2004 to March 2011. Hispanic patients were significantly more likely to be younger, female, and diabetic. Hispanic patients arrived by ambulance (vs other arrival modes) less frequently (adjusted OR .56; 95% CI: .38-.81), trended toward a longer time of stroke onset to treatment decision (351.6 vs. 320.02 minutes, P=.07), and experienced a favorable day-90 outcome less often (adjusted OR .52, CI: .28-.96). However, for the day-90 outcome, there was no interaction between ambulance arrival and Hispanic ethnicity (P=.5614). DISCUSSION: Hispanic AIS patients in this study were less likely to arrive at the hospital by ambulance, and experienced half the odds of a favorable outcome compared to others. Strategies to boost ambulance utilization among Hispanic AIS patients and identify contributors to this worrisome outcome disparity are needed.

Endovascular therapeutic hypothermia for acute ischemic stroke: ICTuS 2/3 protocol.

Therapeutic hypothermia improves neurological outcome after out-of-hospital cardiac arrest or neonatal hypoxic-ischemic injury. Although supported by preclinical evidence, therapeutic hypothermia for acute stroke remains under study. In the Intravascular Cooling in the Treatment of Stroke (ICTuS) trial, awake stroke patients were successfully cooled using an endovascular cooling catheter and a novel antishivering regimen. In the ICTuS-L study, the combination of endovascular hypothermia and thrombolysis proved feasible; while hypothermia was associated with no increased risk of bleeding complications, there was an increased association with pneumonia. Despite efforts to expedite, cooling began on average six-hours after stroke onset. We designed a novel Phase 2/3 trial to further test the safety of combined thrombolysis and endovascular hypothermia and to determine if the combination shows superiority compared with thrombolysis alone. ICTuS 2 (n = 400) will assess four hypotheses, and if milestones are met, ICTuS 3 (n = 1200) will begin as a seamless continuation for a total sample of 1600 patients. The ICTuS 2 milestones include (1) target temperature reached within six-hours of symptom onset; (2) no increased risk of pneumonia; (3) no increase in signs/symptoms of fluid overload due to chilled saline infusions; and (4) sufficient recruitment to complete the trial on time. The ICTuS 2/3 protocol contains novel features - based on the previous ICTuS and ICTuS-L trials - designed to achieve these milestones. Innovations include scrupulous pneumonia surveillance, intravenous chilled saline immediately after randomization to induce rapid cooling, and a requirement for catheter placement within two-hours of thrombolysis. An Investigational Device Exemption has been obtained and an initial group of sites initiated.

Imaging negative stroke: diagnoses and outcomes in intravenous tissue plasminogen activator-treated patients.

BACKGROUND: Intravenous (IV) Alteplase (tissue plasminogen activator [t-PA]) improves outcome in patients with acute ischemic stroke. Of those with full recovery, some may not have had ischemia. We analyzed the frequency and post-treatment outcomes of stroke code patients with no imaging evidence of stroke to establish the incidence of neuroimaging negative cerebral ischemia (NNCI) and stroke mimics treated with t-PA. In addition, we compared these patients with the group of stroke patients with imaging evidence of acute stroke to determine whether there was a difference in adverse events and functional outcomes. METHODS: We included all adult stroke patients treated with IV t-PA within 3 hours of stroke onset from the University of California, San Diego, Specialized Programs of Translational Research in Acute Stroke database through January 2013. The imaging positive stroke (IPS) code group comprised patients with neuroimaging evidence of acute ischemic stroke, whereas the imaging negative stroke code (INS) group included those patients without neuroimaging evidence of acute cerebral ischemia. All final diagnoses were reviewed by an adjudicating body. We reviewed medical records and neuroimaging; compared discharge diagnosis, 90-day modified Rankin Scale (mRS) score, and incidence of intracranial hemorrhage; and adjusted for age, admission National Institutes of Health Stroke Scale (NIHSS), prestroke mRS, and diabetes in multivariable models. RESULTS: We identified 106 patients, 74 IPS patients and 32 INS patients, who had similar baseline characteristics, except for baseline NIHSS (IPS 12.9 ± 8.2, INS 8.0 ± 5.6, P = .002) and incidence of cardiac arrhythmias (IPS 32.4%, INS 12.5%, P = .034). The diagnoses in the INS group were stroke (23, 72%)-representing NNCI, somatization (6, 19%), tumor (1, 3%), seizure (1, 3%), and migraine (1, 3%). All IPS patients were diagnosed with acute ischemic stroke. Adjusted for age, baseline NIHSS, prestroke mRS, and diabetes, the INS patients had significantly higher rates (odds ratio 3.04, P = .036) of good functional outcome (90-day mRS score 0-1). Intracerebral hemorrhage (ICH) was found in 24% of the IPS patients and was symptomatic in 6.8%. None of the INS patients had ICH. CONCLUSIONS: Because most INS patients were found to have NNCI, which may represent either transient ischemic attack or aborted stroke, and there were no intracerebral hemorrhages in the INS group, our data support the safety of administering IV t-PA to all patients in whom acute ischemic stroke is clinically suspected. We have demonstrated that NNCI patients and stroke mimics are common, and future larger scale prospective studies are required to delineate the true frequencies of each and to evaluate differences in outcomes.

Does symptom onset to primary stroke center time goals affect stroke outcome?

BACKGROUND: Treating acute ischemic stroke (AIS) within 4.5 hours and door-to-needle time of less than 60 minutes may optimize recovery. It is unknown if onset to Primary Stroke Center (PSC) time goals affect outcome. The purpose of this study was to examine effects of symptom onset to PSC time goals on outcome. METHODS: Analysis included prospectively collected data from the University of California San Diego Specialized Program of Treatment Research in Acute Stroke. All AIS patients treated with intravenous recombinant tissue plasminogen activator were included if treated within 270 minutes, and 90-day modified Rankin Scale (mRS) score was known. Primary outcome of the 90-day mRS was analyzed using multivariable logistic regression. Good outcome was defined as a 90-day mRS score of 0-2. Variables assessed were time from onset to arrival, stroke code, neurologic exam, imaging, laboratories, treatment decision, and treatment (by quartiles). RESULTS: Two hundred ninety-one patients were included (49.8% female, mean age 70.6 ± 16.1, median National Institutes of Health Stroke Scale 10, SD = 8.5). Good outcome occurred in 45% of patients. Significant baseline differences included HTN (P ≤ .001), A fib (P ≤ .001), prestroke mRS (P < .001), and Hispanic ethnicity (P = .011). Comparing good with poor outcome groups: mean onset to arrival was 70.6 min versus 62.5 min (P = .129) and mean onset to treatment was 140.1 min versus 134.9 min (P = .118). Controlling for prespecified covariates, no PSC time goals were significant predictors of the 90-day outcome. CONCLUSIONS: In our Comprehensive Stroke Center (CSC), onset to PSC time goals were not significant predictors of the 90-day outcome. Expedited care processes in CSC may compensate for differences in outcome. These results should be validated in a larger cohort and in PSCs versus CSCs.

Pooled assessment of computed tomography interpretation by vascular neurologists in the STRokE DOC telestroke network.

BACKGROUND AND PURPOSE: The objective of this pooled analysis was to determine the level of agreement between central read and each of 2 groups (spoke radiologists and hub vascular neurologists) in interpreting head computed tomography (CT) scans of stroke patients presenting to telestroke network hospitals. METHODS: The Stroke Team Remote Evaluation Using a Digital Observation Camera (STRokE DOC and STRokE DOC-AZ TIME) trials were prospective, randomized, and outcome blinded comparing telemedicine and teleradiology with telephone-only consultations. In each trial, the CT scans of the subjects were interpreted by the hub vascular neurologist in the telemedicine arm and by the spoke radiologist in the telephone arm. We obtained a central read for each CT using adjudicating committees blinded to treatment arm and outcome. The data were pooled and the results reported for the entire population. Kappa statistics and exact agreement rates were used to assess interobserver agreement for radiographic contraindication to recombinant tissue plasminogen activator (rt-PA), presence of hemorrhage, tumor, hyperdense artery, acute stroke, prior stroke, and early ischemic changes. RESULTS: Among 261 analyzed cases, the agreement with central read for the presence of radiological rt-PA contraindication was excellent for hub vascular neurologist (96.2%, κ = .81, 95% CI .64-.97), spoke radiologist report (94.7%, κ = .64, 95% CI .39-.88), and overall (95.4%, κ = .74, 95% CI .59-.88). For rt-PA-treated patients (N = 65), overall agreement was 98.5%, and vascular neurologist agreement with central read was 100%. CONCLUSIONS: Both vascular neurologists and reports from spoke radiologists had excellent reliability in identifying radiologic rt-PA contraindications. These pooled findings demonstrate that telestroke evaluation of head CT scans for acute rt-PA assessments is reliable.

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.

Diffusion-weighted imaging-fluid attenuated inversion recovery mismatch in nocturnal stroke patients with unknown time of onset.

BACKGROUND: More than a quarter of patients with ischemic stroke (IS) are excluded from thrombolysis because of an unknown time of symptom onset. Recent evidence suggests that a mismatch between diffusion-weighted imaging (DWI) and fluid attenuated inversion recovery (FLAIR) imaging could be used as a surrogate for the time of stroke onset. We compared used the DWI-FLAIR mismatch and the FLAIR/DWI ratio to estimate the time of onset in a group of patients with nocturnal strokes and unknown time of onset. METHODS: We used a prospectively collected acute IS patient database with MRI as the initial imaging modality. Nineteen selected nocturnal stroke patients with unknown time of onset were compared with 22 patients who had an MRI scan within 6 hours from stroke onset (control A) and 19 patients who had an MRI scan between 6 and 12 hours (control B). DWI and FLAIR signal was rated as normal or abnormal. FLAIR/DWI ratio was calculated from independent DWI and FLAIR ischemic lesion volumes using semiautomatic software. RESULTS: The DWI-FLAIR mismatch was different among groups (unknown 43.7%; control A 63.6%; control B 10.5%; Fisher-Freeman-Halton test; P = .001). There were significant differences in FLAIR/DWI ratio among the 3 groups (unknown 0.05 ± 0.12; control A 0.17 ± 0.15; control B 0.04 ± 0.06; Kruskal-Wallis test; P < .0001). Post-hoc pairwise comparisons revealed that FLAIR/DWI ratio from the unknown group was significantly different from the control B group (P = .0045) but not different from the control A group. DWI volumes were not different among the 3 groups. CONCLUSIONS: A large proportion of patients with nocturnal IS and an unknown time of stroke initiation have a DWI-FLAIR mismatch, suggesting a recent onset of stroke.

Intravenous tissue plasminogen activator for patients with minor ischemic stroke.

BACKGROUND: Patients with minor ischemic stroke (MIS) are frequently excluded from thrombolytic therapy. Denial of therapy to these patients, however, remains controversial. We compared outcomes in patients with MIS who received intravenous (IV) tissue plasminogen activator (t-PA) with those who were not treated. METHODS: We selected adult patients with stroke onset within 3 hours from a prospectively collected stroke registry. MIS was defined as an admission National Institutes of Health Stroke Scale (NIHSS) score ≤ 5. The primary outcome was a 90-day modified Rankin scale (mRS) score of 0 to 1. Secondary outcomes were a Barthel index (BI) score ≥ 95 at 90 days, symptomatic intracranial hemorrhage (SICH), and death. Multivariable logistic regression was performed to determine the association between outcomes adjusting for age, history of diabetes, and NIHSS score at admission. Reasons for t-PA exclusion were obtained. RESULTS: We identified 133 patients with MIS; 59 patients received IV t-PA. The NIHSS score (mean ± SD) at admission was higher in the t-PA treated group (3.4 ± 1.4 v 1.9 ± 1.3 in the untreated group; P < .0001). Other baseline characteristics were not significantly different between the 2 groups. At 90 days, 57.6% of patients in the t-PA group and 68.9% of patients in the untreated group had a mRS score of 0 to 1 (odds ratio [OR] 0.93, 95% confidence interval [CI] 0.39-2.2; P = .87). A BI score of 95 to 100 was achieved in 75% of patients in the IV t-PA group versus 78.9% in the untreated group (OR 1.18, 95% CI 0.43-3.23; P = .74). There were 3 deaths (5.1%) in the IV t-PA group and 3 deaths (4.1%) in the control group. CONCLUSIONS: In our sample, patients with MIS treated with IV t-PA have similar outcomes as patients not receiving thrombolysis. A randomized trial or larger observational study is needed confirm or reject these findings.