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Background: Hematoma enlargement (HE) after intracerebral hemorrhage (ICH) is a therapeutic target for improving outcomes. Hemostatic therapies to prevent HE may be more effective the earlier they are attempted. An understanding of HE in first 1 to 2 hours specifically in the prehospital setting would help guide future treatment interventions in this time frame and setting. Methods: Patients with spontaneous ICH within 4 hours of symptom onset were prospectively evaluated between May 2014 and April 2020 as a prespecified substudy within a multicenter trial of prehospital mobile stroke unit versus standard management. Baseline computed tomography scans obtained 6 mL if baseline ICH volume was < 20 mL and 33% increase if baseline volume >20 mL. The association between time from symptom onset to baseline computed tomography (hours) and HE was investigated using Wilcoxon rank-sum test when time was treated as a continuous variable and using Fisher exact test when time was categorized. Kruskal-Wallis and Wilcoxon rank-sum tests evaluated differences in baseline volumes and HE. Univariable and multivariable logistic regression analyses were conducted to identify factors associated with HE and variable selection was performed using cross-validated L1-regularized (Lasso regression). This study adhered to STROBE guidelines (Strengthening the Reporting of Observational Studies in Epidemiology) for cohort studies. Results: One hundred thirty-nine patients were included. There was no difference between baseline ICH volumes obtained 2 hours (n=45) from symptom onset (median [interquartile range], 13 mL [6–24] versus 14 mL [6–30] versus 12 mL [4–19]; P =0.65). However, within the same 3 time epochs, initial hematoma growth (volume/time from onset) was greater with earlier baseline scanning (median [interquartile range], 17 mL/hour [9–35] versus 9 mL/hour [5–23]) versus 4 mL/hour [2–7]; P 2 hours; P =0.02). HE did not occur between the scans repeated at 1 hour and 24 hours. No association between baseline variables and HE was detected in multivariable analyses. Conclusions: HE in the next hour occurs in 28% of ICH patients with baseline imaging within the first hour after symptom onset, and in 17% of those with baseline imaging between 1 and 2 hours. These patients would be a target for ultraearly hemostatic intervention.

Background: Few data exists on acute stroke treatment in patients with pre-existing disability (PD) since they are usually excluded from clinical trials. Methods: A pre-specified subgroup analysis of tPA-eligible patients with PD enrolled in a prospective multicenter trial of Mobile Stroke Units (MSUs) vs standard management by emergency medical services (EMS). All patients had baseline mRS scores. Co-primary outcomes were mean utility-weighted modified Rankin Scale score (uw-mRS) and return to baseline mRS at 90 days. Linear and logistic regression models compared outcomes in patients with vs without PD, and patients with PD treated by MSU vs EMS. Time metrics, safety, quality of life, and health-care utilization were also compared. Results: Of 1047 patients, 254 had baseline mRS >= 2 (159 MSU, 95 EMS; 31% mRS 2, 52% mRS 3, 17% mRS 4). Compared to patients without disability, patients with PD were older, had higher NIHSS, more comorbidities, less often lived at home, were treated slower, and had less thrombectomy. Patients with PD had worse 90-day uw-mRS (0.39 vs 0.80), higher mortality, more health-care utilization and worse quality of life than patients without PD. However, rates of symptomatic intracranial hemorrhage and final diagnoses of stroke mimics were similar between groups, and 52% of patients with PD returned to their baseline mRS. Patients with PD treated within the first hour had better 90-day uw-mRS than those treated later (0.48 vs 0.36, p=0.01). Comparing patients with PD treated by MSU vs EMS, time from last-known-well to tPA bolus was shorter (82 vs 111 min), and 24% vs 0% were treated in the first hour. Among patients with PD, MSU patients had non-significantly better 90-day uw-mRS (0.41 vs 0.35, p=0.09) and higher rate of returning to baseline mRS (56% vs 44%, p=0.09) than EMS patients. There was no interaction between either time to treatment (p=0.24) or MSU vs EMS group assignment (p= 0.42), 90-day uw-mRS, and PD vs no disability status. Conclusion: Although outcomes after stroke are less favorable in patients with vs without PD, in a large, controlled trial, we found no interaction between baseline disability and the benefit of MSU treatment. Our data support the earliest treatment of acute stroke patients regardless of premorbid functional status.

Background Mobile stroke units (MSUs) are ambulances with staff and a computed tomographic scanner that may enable faster treatment with tissue plasminogen activator (t-PA) than standard m...

COVID-19 has been associated with a hypercoagulable state causing cardiovascular and neurovascular complications. To further characterize cerebrovascular disease (CVD) in COVID-19, we review the current literature of published cases and additionally report the clinical presentation, laboratory and diagnostic testing results of 12 cases with COVID-19 infection and concurrent CVD from two academic medical centers in Houston, TX, USA, between March 1 and May 10, 2020. To date, there are 12 case studies reporting 47 cases of CVD in COVID-19. However, only 4 small case series have described the clinical and laboratory findings in patients with COVID-19 and concurrent stroke. Viral neurotropism, endothelial dysfunction, coagulopathy and inflammation are plausible proposed mechanisms of CVD in COVID-19 patients. In our case series of 12 patients, 10 patients had an ischemic stroke, of which 1 suffered hemorrhagic transformation and two had intracerebral hemorrhage. Etiology was determined to be embolic without a clear cause identified in 6 ischemic stroke patients, while the remaining had an identifiable source of stroke. The majority of the patients had elevated inflammatory markers such as D-dimer and interleukin-6. In patients with embolic stroke of unclear etiology, COVID-19 may have played a direct or indirect role in the processes that eventually led to the strokes while in the remaining cases, it is unclear if infection contributed partially or was an incidental finding.

Introduction: Mobile Stroke Units (MSUs) improve clinical outcome in patients treated with tPA compared to standard management by Emergency Medical Services (EMS), but the impact of MSUs on outcomes in patients with large vessel occlusions (LVOs) having endovascular thrombectomy (EVT) has yet to be determined. Methods: A pre-specified substudy of tPA-eligible stroke patients with LVOs on CT and/or CTA who were enrolled in the Benefits of Stroke Treatment Using a Mobile Stroke Unit (BEST-MSU), a prospective multicenter controlled trial comparing MSU with standard EMS management, was conducted. The primary outcome was the score on the 90-day utility-weighted modified Rankin Scale (uw-mRS). Secondary outcomes were rate of early neurologic recovery (30% improvement in NIHSS score) at 24 hours and functional independence (mRS 0-1) at 90 days. Results: A total of 295 patients were included, 169 in the MSU group and 126 in the EMS group. Baseline characteristics were comparable between the groups, with the exception of baseline NIHSS (MSU median 19.0 [IQR 13.0, 23.0] vs EMS 16.0 [11.0, 20.0], p=0.003). 92% MSU vs 87% EMS LVO patients received tPA, and 78% vs 85% went on to have EVT. MSU LVO patients had faster tPA bolus from symptom onset (65.0 min [50.5, 92.0] vs 96.0 [79.3, 130.0], p Conclusions: In tPA-eligible LVO stroke patients, MSU management was associated with better clinical outcomes compared with standard EMS management.

Introduction: Blood pressure fluctuations in the acute phase of large vessel occlusion (LVO) ischemic stroke are associated with infarct progression and poor outcomes. We evaluated the association of prehospital blood pressure variations on a Mobile Stroke Unit (MSU) with early neurological change. Methods: Prospectively-derived data were analyzed from tPA-eligible LVO patients treated and transported on the MSU, identified by hyperdense artery on CT or arterial occlusion on CTA. Patients were categorized by change in mean arterial pressure (ΔMAP) of > 10 mm Hg vs Δ MAP < 10 mmHg from arrival of MSU on-scene to arrival to the emergency department (ED). A sub-analysis of patients with ΔMAP > 10 mm Hg compared those whose MAP decreased by > 10 mm Hg vs those whose MAP increased by > 10 mm Hg. The primary outcome was 24-hour change in NIHSS. Groups were compared using Chi-square/Fisher’s exact test for categorical variables and Wilcoxon rank sum test for continuous variables. Results: A total of 39 tPA-eligible LVO patients were identified, 19 with ΔMAP < 10mm Hg and 20 with ΔMAP > 10mm Hg. Baseline characteristics were comparable between groups including NIHSS (18.0 [11.0, 21.0] vs 20.0 [16.8, 25.8]) (Table 1). A similar percentage from each group received tPA and thrombectomy. Upon presentation to ED, 7/19 (37%) patients with ΔMAP < 10mm Hg had a 30% improvement in NIHSS, compared to 4/20 (20%) patients with ΔMAP >10mm Hg (p=0.417). The 24-hour change in NIHSS was also similar (ΔMAP < 10mm Hg = 7.0 [3.5, 12.0] vs ΔMAP > 10 mm Hg 10.0 [4.0, 16.0], p=0.517). Among patients with ΔMAP of 10mm Hg group, those with MAP decrease by > 10 mm Hg had a 10 point [7.0, 16.0] improvement in NIHSS vs 6.0 [2.5, 15.0] point improvement in those whose MAP increased by > 10 mm Hg (p=0.169). Conclusion: Though limited by a small sample size, prehospital blood pressure fluctuations in LVO stroke patients on a MSU were not associated with early clinical changes.

Tissue plasminogen activator (tPA) requires a one-hour infusion after the bolus. The frequency of delay or interruption of the tPA infusion may be useful in weighing the advantages of Tenecteplase (TNKase, TNK) which does not require an infusion.Utilizing the Benefits of Stroke Treatment Delivered Using a Mobile Stroke Unit Compared to Standard Management by Emergency Medical Services study database, we calculated the frequency and magnitude of tPA infusion delay or interruption.Of 497 patients treated with tPA on the Houston Mobile Stroke Unit (MSU), 41 (8.3%) had delay or interruption of the infusion for reasons that did not reflect a side effect of, or contraindication to, tPA. Nine received less than 90% of their calculated dose (median 62%, range 28-88%), and eleven had more than a 10% prolongation of their infusion (median 19 min, range 7-210 min). Six patients (1.2%) had infusion stopped for a valid concern for tPA side effect or contraindication.Interruption or discontinuation of the tPA infusion occurs in 8% of patients treated on a MSU providing an opportunity for more complete and faster treatment with TNK.

Background: Prehospital automated large vessel occlusion (LVO) detection in Mobile Stroke Units (MSUs) could accelerate identification and treatment of patients with LVO acute ischemic stroke. Here, we evaluate the performance of a machine learning (ML) model on CT angiograms (CTAs) obtained from 2 MSUs to detect LVO. Methods: Patients evaluated on MSUs in Houston and Los Angeles with out-of-hospital CTAs were identified. Anterior circulation LVO was defined as an occlusion of the intracranial internal carotid artery, middle cerebral artery (M1 or M2), or anterior cerebral artery vessels and determined by an expert human reader. A ML model to detect LVO was trained and tested on independent data sets consisting of in-hospital CTAs and then tested on MSU CTA images. Model performance was determined using area under the receiver-operator curve statistics. Results: Among 68 patients with out-of-hospital MSU CTAs, 40% had an LVO. The most common occlusion location was the middle cerebral artery M1 segment (59%), followed by the internal carotid artery (30%), and middle cerebral artery M2 (11%). Median time from last known well to CTA imaging was 88.0 (interquartile range, 59.5–196.0) minutes. After training on 870 in-hospital CTAs, the ML model performed well in identifying LVO in a separate in-hospital data set of 441 images with area under receiver-operator curve of 0.84 (95% CI, 0.80–0.87). ML algorithm analysis time was under 1 minute. The performance of the ML model on the MSU CTA images was comparable with area under receiver-operator curve 0.80 (95% CI, 0.71–0.89). There was no significant difference in performance between the Houston and Los Angeles MSU CTA cohorts. Conclusions: In this study of patients evaluated on MSUs in 2 cities, a ML algorithm was able to accurately and rapidly detect LVO using prehospital CTA acquisitions.

Objective To quantify in-hospital systolic blood pressure variability among patients with intracerebral hemorrhage, determine the association between high systolic blood pressure variability (HSBPV) and 90-day severe disability or death, and examine the association between pre-hospital factors and HSBPV. Methods Adult, radiologically confirmed, intracerebral hemorrhage patients enrolled in a multi-site cohort were included. Using a semi-automated algorithm, systolic blood pressure values recorded from routine non-invasive systolic blood pressure monitoring in critical and acute care settings were extracted for the duration of hospitalization. Inter and intra-patient systolic blood pressure variability was quantified using generalized estimating equation methods. Modified Poisson and logistic regression models were fit to determine the association between HSBPV and 90-day severe disability or death and between pre-hospital characteristics and HSBPV, respectively. Results A total of 566 patients managed at four certified stroke centers were included. Over 120,000 systolic blood pressure readings were analyzed, and a standard deviation (SD) of 13.0 was parameterized as a cut-off point to categorize HSBPV. Patients with HSBPV had a greater risk of 90-day severe disability or death (relative risk: 1.20, 95% confidence interval: 1.04–1.39), after controlling for age, pre-morbid functional status, and other disease severity measures. Greater likelihood of in-hospital HSBPV was independently observed in elderly, female patients, and in patients with high admission systolic blood pressure. Conclusion Quantification of HSBPV is feasible utilizing routinely collected systolic blood pressure readings, and a singular cut-off parameter for systolic blood pressure variability demonstrated association with 90-day severe disability or death. Elderly, female, and patients with high admission systolic blood pressure may be more likely to demonstrate HSBPV during hospitalization.

Objective: Hematoma enlargement (HE) occurs after spontaneous intracerebral hemorrhage (ICH) but no studies have evaluated the frequency of HE in first 1-2 h after symptom onset. We evaluated HE in the first 2h after onset using a mobile stroke unit (MSU). Methods: Patients with spontaneous ICH within 4.5h were evaluated on the Houston MSU between 5/2014 and 4/2020. Baseline CT scans from the MSU were compared with scans repeated within 1h [median 67min (IQR 57-82 min]. Significant HE was defined as >6 ml if baseline volume was 20 ml. Kruskal-Wallis and Wilcoxon rank sum tests evaluated differences in baseline volumes and HE. Intraclass correlation coefficient (ICC) evaluated agreement between two ICH measurement techniques (ABC/2 vs semi-automated). Results: 163 patients had baseline CTs, of whom 60 had repeat 1h CTs (table 1). There was no difference between baseline volume and time of CT from symptom onset {2h median (IQR) = 14 ml (6-28) vs. 16 ml (7-32) vs. 12 ml (4-24), P=0.42)}. There was also no correlation between time from onset and difference in volume between baseline and 1 h repeat imaging. However, 9/60 patients had significant HE from baseline to 1 h repeat imaging; all of these occurred in patients initially imaged within 2 h of onset (6/24 within 1h, 3/20 within 1-2h) (P=0.03) (figure 1). High reliability was seen between the two methods measuring volumes (ICC = 0.84). Conclusion: Significant HE in the next hour occurs in 25% of ICH patients imaged within the first hour after symptom onset, and 17% imaged between 1-2 hours of onset. These patients would be a target for ultra-early hemostatic intervention.

Introduction: The benefit of intravenous tPA in acute ischemic stroke patients with large vessel occlusions (LVOs) is limited but time dependent. We evaluated pre-hospital treatment with tPA on the Mobile Stroke Unit (MSU) to explore the recanalization rate in patients with LVOs and its effect on clinical improvement upon ED arrival. Methods: Prospectively derived data were analyzed from patients on the Houston MSU who were treated with tPA and had LVOs identified by hyperdense artery on MSU CT or arterial occlusion on MSU CTA. The primary outcome was early recanalization, categorized as resolution of LVO on repeat vascular imaging in the ED or on emergent angiography versus no recanalization. Secondary outcome was change in baseline NIHSS at 24 hours. Differences in NIHSS were evaluated using Wilcoxon rank sum test with continuity correction. Results: Seventy-one patients received tPA and had proximal LVOs both in the anterior and posterior circulation. Eleven had recanalization on CTA upon ED arrival (15.5%), while 7 had recanalization on emergent angiography (9.9%). The total early recanalization rate with tPA was 25.4%. Forty-seven patients with persistent LVOs on ED arrival (66.2%) underwent endovascular thrombectomy (EVT). Time from symptom onset (last known normal) to tPA bolus did not differ significantly between the early recanalization vs non-early recanalization groups (64.5 minutes [IQR 43.0-78.5] vs 64.0 minutes [52.5-92.0]; p = 0.41). Early recanalization resulted in greater improvement in baseline to ED arrival NIHSS (median NIHSS change 4.0 [0-11.8] vs 0 [0-3.5]; p = 0.01). There were no differences in ED arrival to 24 hour NIHSS between the early recanalization versus non-early recanalization groups irrespective of EVT. Conclusions: Recanalization by ED arrival occurs in 25% of LVO patients with tPA treatment on a MSU and was associated with early clinical improvement. Subsequent EVT did not “make up” for the clinical benefit of early recanalization.

Introduction: Most clinical research stopped during COVID due to possible impact on data quality and personnel safety. We aimed to assess the impact of COVID on study conduct at sites that continued to enroll patients during the pandemic. Methods: BEST-MSU is an ongoing study of Mobile Stroke Units (MSU) vs standard management of tPA eligible acute stroke patients in the pre-hospital setting. MSU personnel include a vascular neurologist via telemedicine, and a nurse, CT tech, and medics on board using appropriate PPE. During COVID, consent, 90 d mRS and EQ5D could be obtained by phone instead of in person, otherwise management was the same. We compared patient demographics, study metrics, and infection of study personnel during intra- vs pre-COVID eras. Results: Four of 6 BEST-MSU sites continued to enroll during COVID. There was no difference in intra- (n= 41) vs pre- (n= 763) COVID enrolled tPA eligible patients’ age, sex, race (45% vs 41% Black), ethnicity (23% vs 19% Hispanic), or NIHSS (12 vs 12). MSU alert frequency did not change, but percent of screened patients enrolled and treated with tPA declined to 12% from 23% (p Conclusion: Clinical research in the pre-hospital setting can be carried out accurately and safely during a pandemic. Study enrollment and tPA treatment rates declined, but otherwise there was no difference in patient demographics, deterioration of study processes, or serious infection of study staff.

Most clinical research stopped during COVID due to possible impact on data quality and personnel safety. We aimed to assess the impact of COVID on acute stroke clinical trial conduct at sites that continued to enroll patients during the pandemic. BEST-MSU is an ongoing study of Mobile Stroke Units (MSU) vs standard management of tPA-eligible acute stroke patients in the pre-hospital setting. MSU personnel include a vascular neurologist via telemedicine, and a nurse, CT technologist, paramedics and emergency medicine technicians on-board. During COVID, consent, 90-day modified Rankin Scale (mRS) and EQ5D were obtained by phone instead of in-person, but other aspects of management were similar to the pre-COVID period. We compared patient demographics, study metrics, and infection of study personnel during intra- vs pre-COVID eras. Five of 6 BEST-MSU sites continued to enroll during COVID. There were no differences in intra- (n = 57) vs pre- (n = 869) COVID enrolled tPA eligible patients’ age, sex, race (38.6% vs 38.0% Black), ethnicity (15.8% vs 18.6% Hispanic), or NIHSS (median 11 vs 9). The percent of screened patients enrolled and adjudicated tPA eligible declined from 13.6% to 6.6% (p < .001); study enrollment correlated with local stay-at-home and reopening orders. There were no differences in alert to MSU arrival or arrival to tPA times, but MSU on-scene time was 5 min longer (p = .01). There were no differences in ED door to CT, tPA treatment or thrombectomy puncture times, hospital length of stay, discharge disposition, or remote vs in-person 90-day mRS or EQ5D. One MSU nurse tested positive but did not require hospitalization. Clinical research in the pre-hospital setting can be carried out accurately and safely during a pandemic. tPA eligibility rates declined, but otherwise there were no differences in patient demographics, deterioration of study processes, or serious infection of study staff. Trial registration: NCT02190500

Objectives Studies face challenges with missing 5-level EQ-5D (EQ-5D-5L) data, often because of the need for longitudinal EQ-5D-5L data collection. There is a dearth of validated methodologies for dealing with missing EQ-5D-5L data in the literature. This study, for the first time, examined the possibility of using retrospectively collected EQ-5D-5L data as proxies for the missing data. Methods Participants who had prospectively completed a 3rd month postdischarge EQ-5D-5L instrument (in-the-moment collection) were randomly interviewed to respond to a 2nd “retrospective collection” of their 3rd month EQ-5D-5L at 6th, 9th, or 12th month after hospital discharge. A longitudinal single imputation was also used to assess the relative performance of retrospective collection compared with the longitudinal single imputation. Concordances between the in-the-moment, retrospective, and imputed measures were assessed using intraclass correlation coefficients and weighted kappa statistics. Results Considerable agreement was observed on the basis of weighted kappa (range 0.72-0.95) between the mobility, self-care, and usual activities dimensions of EQ-5D-5L collected in-the-moment and retrospectively. Concordance based on intraclass correlation coefficients was good to excellent (range 0.79-0.81) for utility indices computed, and excellent (range 0.93-0.96) for quality-adjusted life-years computed using in-the-moment compared with retrospective EQ-5D-5L. The longitudinal single imputation did not perform as well as the retrospective collection method. Conclusions This study demonstrates that retrospective collection of EQ-5D-5L has high concordance with “in-the-moment” EQ-5D-5L and could be a valid and attractive alternative for data imputation when longitudinally collected EQ-5D-5L data are missing. Future studies examining this method for other disease areas and populations are required to provide more generalizable evidence.

Background: The 90-day modified Rankin Scale is a widely used outcome after stroke but is sometimes hard to ascertain due to loss to follow-up. Missing outcomes can result in biased and/or inefficient estimates in clinical trials. The aim of this study is to assess the validity of acquiring the 90-day modified Rankin Scale at a later point of time when the patient has been lost at 90 days to impute the missing value. Methods: Participants who had prospectively completed a 90-day modified Rankin Scale questionnaire on their own in the Benefits of Stroke Treatment Using a Mobile Stroke Unit study were randomly interviewed to recall the 90-day modified Rankin Scale at 6, 9, or 12 months after hospital discharge over the phone. Concordance between the two scores was assessed using kappa and weighted kappa statistics. Logistic regression was used to identify factors associated with inconsistent reporting of the 90-day modified Rankin Scale. Results: Substantial agreement was observed between in-the-moment and retrospective 90-day modified Rankin Scale recalled at 6, 9, or 12 months (weighted kappa = 0.93, 95% confidence interval: 0.89–0.98; weighted kappa = 0.93, 95% confidence interval: 0.85–1.00 and weighted kappa = 0.89, 95% confidence interval: 0.82–0.95, respectively). Conclusion: Retrospective recall of 90-day modified Rankin Scale at a later time point is a valid means to impute missing data in stroke clinical trials.

Background and Purpose— Endovascular thrombectomy (ET) door-to-puncture time (DTPT) is a modifiable metric. One of the most important, yet time-consuming steps, is documentation of large vessel occlusion by computed tomography angiography (CTA). We hypothesized that obtaining CTA on board a Mobile Stroke Unit and direct alert of the ET team shortens DTPT by over 30 minutes. Methods— We compared DTPT between patients having CTA onboard the Mobile Stroke Unit then subsequent ET from September 2018 to November 2019 and patients in Mobile Stroke Unit from August 2014 to August 2018, when onboard CTA was not yet being used. We also correlated DTPT with change in National Institutes of Health Stroke Scale between baseline and 24 hours. Results— Median DTPT was 53.5 (95% CI, 35–67) minutes shorter with onboard CTA and direct ET team notification: 41 minutes (interquartile range, 30.0–63.5) versus 94.5 minutes (interquartile range, 69.8–117.3; P P P =0.07). Conclusions— Prehospital Mobile Stroke Unit management including on-board CTA and ET team alert substantially shortens DTPT. Registration— URL: https://clinicaltrials.gov ; Unique identifier: NCT02190500.

Introduction: Endovascular thrombectomy (ET) is an effective but time sensitive treatment of acute ischemic stroke. Time from Emergency Department (ED) arrival to start of ET (door-to-puncture time, DTPT) is a modifiable metric. One of the most time consuming steps in prolonging DTPT is identification of large vessel occlusion (LVO) by CT angiography (CTA). BEST-MSU is a prospective multicenter comparative effectiveness study of tPA-eligible patients managed on a mobile stroke unit (MSU) vs Emergency Medical Services (Standard Management, SM). After discovering that DTPT was greater than 60 minutes in both groups at three BEST-MSU centers in 2018, we began to routinely obtain CTA on the MSU and directly alert the ET team at receiving hospitals if a LVO was identified. We hypothesized this would shorten DTPT by over 30 minutes. Methods: In this single center experience, we compared the median (interquartile range, IQR) DTPT and MSU on-scene time for MSU patients having on-board CTA and then ET from 9/2018 to 7/2019 to corresponding MSU ET patients (excluding any that had on-board CTA) from 8/2014 to 8/2018. All CTAs were completed after tPA bolus and during tPA infusion on a Ceretom 8 slice scanner with OptiStat hand injector. All imaging occurred on-scene with the MSU stationary. Consent was obtained for all patients and strict radiation safety guidelines followed. Results: 13 consecutive patients having CTA on-board the MSU and then ET were compared to 84 patients in the pre-on-board CTA group. Baseline characteristics including median NIHSS score (20 in both groups) and frequency of tPA (85% on-board CTA vs 89% pre-on-board CTA) were comparable. Median DTPT was 60 minutes shorter with on-board CTA and direct notification of the interventional team from the MSU; 34 minutes (IQR 30-57) vs 94.5 minutes (IQR 69.75-117.25) (p < 0.001). Despite the additional time to obtain the CTA on the MSU, on-scene time was only slightly prolonged and did not offset the reduction in DTPT (on-board CTA 30 minutes (IQR 28-33) vs pre-on-board CTA 27 minutes (IQR 23-31) (p = 0.01). Conclusion: Pre-hospital identification and notification of LVO by a MSU allows a one hour reduction of DTPT, and can be utilized to establish a direct to angiosuite protocol.

Mobile Stroke Units (MSUs) deliver acute stroke treatment on-scene in coordination with Emergency Medical Services (EMS). One criticism of the MSU approach is the limited range of a single MSU. The Houston MSU is evaluating MSU implementation, and we developed a rendezvous approach as an innovative solution to expand the range and number of patients treated.In addition to direct 911 dispatch of our MSU to the scene within our 7-mile catchment area, we empowered more distant EMS units to activate the MSU. We also monitored EMS radio communications to identify possible patients. For these distant patients, the MSU met the EMS unit en route to the stroke center and treated the patient at that intermediate location. The distribution of the distance from MSU base station to site of stroke and time from 911 alert to tissue plasminogen activator (tPA) bolus were compared between patients treated on-scene and by rendezvous using Wilcoxon rank sum test.Over 4 years, 338 acute ischemic stroke patients were treated with tPA on our MSU. Of these, 169 (50%) were treated on-scene after MSU dispatch at a median of 6.4 miles (IQR 6.4 miles) from MSU base station. 169 (50%) were treated by 'rendezvous' pathway with assessment and treatment of stroke a median of 12.4 miles from base (IQR 5.5 miles) (p0.0001). Time (min) from MSU alert to tPA bolus did not differ: 36.0 ± 10.0 for on-scene vs 37.0 ± 10.0 with rendezvous (p=0.65). 13% of patients alerted via direct 911 dispatch were treated vs 44% of rendezvous patients.Adding a rendezvous approach to an MSU dispatch pathway doubles the range of operations and the number of patients treated by an MSU in an urban area, without incurring delay.

Supplemental material, Online_Supplement for Retrospective collection of 90-day modified Rankin Scale is accurate by Mengxi Wang, Suja S Rajan, Asha P Jacob, Noopur Singh, Stephanie A Parker, Ritvij Bowry, James C Grotta and Jose-Miguel Yamal in Clinical Trials

IMPORTANCE: So far, uncertainty remains as to whether there is sufficient cumulative evidence that mobile stroke unit (MSU; specialized ambulance equipped with computed tomography scanner, point-of-care laboratory, and neurological expertise) use leads to better functional outcomes compared with usual care. OBJECTIVE: To determine with a systematic review and meta-analysis of the literature whether MSU use is associated with better functional outcomes in patients with acute ischemic stroke (AIS). DATA SOURCES: MEDLINE, Cochrane Library, and Embase from 1960 to 2021. STUDY SELECTION: Studies comparing MSU deployment and usual care for patients with suspected stroke were eligible for analysis, excluding case series and case-control studies. DATA EXTRACTION AND SYNTHESIS: Independent data extraction by 2 observers, following the PRISMA and MOOSE reporting guidelines. The risk of bias in each study was determined using the ROBINS-I and RoB2 tools. In the case of articles with partially overlapping study populations, unpublished disentangled results were obtained. Data were pooled in random-effects meta-analyses. MAIN OUTCOMES AND MEASURES: The primary outcome was excellent outcome as measured with the modified Rankin Scale (mRS; score of 0 to 1 at 90 days). RESULTS: Compared with usual care, MSU use was associated with excellent outcome (adjusted odds ratio [OR], 1.64; 95% CI, 1.27-2.13; P

Background Intracerebral hemorrhage is a devastating disease with no specific treatment modalities. A significant proportion of patients with intracerebral hemorrhage are transferred to large stroke treatment centers, such as Comprehensive Stroke Centers, because of perceived need for higher level of care. However, evidence of improvement in patient-centered outcomes for these patients treated at larger stroke treatment centers as compared to community hospitals is lacking. Methods / design “Efficient Resource Utilization for Patients with Intracerebral Hemorrhage (EnRICH)” is a prospective, multisite, state-wide, cohort study designed to assess the impact of level of care on long-term patient-centered outcomes for patients with primary / non-traumatic intracerebral hemorrhage. The study is funded by the Texas state legislature via the Lone Star Stroke Research Consortium. It is being implemented via major hub hospitals in large metropolitan cities across the state of Texas. Each hub has an extensive network of “spoke” hospitals, which are connected to the hub via traditional clinical and administrative arrangements, or by telemedicine technologies. This infrastructure provides a unique opportunity to track outcomes for intracerebral hemorrhage patients managed across a health system at various levels of care. Eligible patients are enrolled during hospitalization and are followed for functional, quality of life, cognitive, resource utilization, and dependency outcomes at 30 and 90 days post discharge. As a secondary aim, an economic analysis of the incremental cost-effectiveness of treating intracerebral hemorrhage patients at higher levels of care will be conducted. Discussion Findings from EnRICH will provide much needed evidence of the effectiveness and efficiency of regionalized care for intracerebral hemorrhage patients. Such evidence is required to inform policy and streamline clinical decision-making.

Rationale Mobile stroke units speed treatment for acute ischemic stroke, thereby possibly improving outcomes. Aim To compare mobile stroke unit and standard management clinical outcomes, healthcare utilization, and cost-effectiveness in tissue plasminogen activator-eligible acute ischemic stroke patients calling 911. Sample size 693. Eighty percent power with 0.05 type I error rate to detect a difference of 0.09 in mean utility-weighted modified Rankin scale between groups. Design Phase III, multicenter, prospective cluster-randomized (mobile stroke unit versus standard management weeks) comparative effectiveness study in tissue plasminogen activator-eligible patients. Outcomes Primary: Ninety-day mean utility-weighted modified Rankin scale. Coprimary: cost-effectiveness based on EQ5D quality of life and one year poststroke costs. Analysis Two-sample t-test and linear regression adjusting for covariates; incremental cost-effectiveness ratio and net benefit regression. Results As of March 2017, 288 tissue plasminogen activator-eligible patients have been enrolled (173 in the mobile stroke unit arm and 115 in the standard management arm). Two new centers start in early 2017 with target end of recruitment September 2019. Conclusion This is the first randomized study to test for disability, healthcare utilization, and cost-effectiveness of a mobile stroke unit. The progress of the study suggests that it is feasible. Management of tissue plasminogen activator eligible acute ischemic stroke patients by a mobile stroke unit could potentially result in less disability and healthcare utilization, and be cost effective. Mobile stroke units are very costly. This trial may determine if the fixed cost can be justified by a reduction in disability and healthcare utilization. Clinical Trial Registration NCT02190500.

Background and Purpose— The BEST-MSU study (Benefits of Stroke Treatment Delivered Using a Mobile Stroke Unit) is a comparative effectiveness trial in patients randomized to mobile stroke unit or standard management. A substudy tested interrater agreement for tissue-type plasminogen activator eligibility between a telemedicine vascular neurologist and onboard vascular neurologist. Methods— On scene, both the telemedicine vascular neurologist and onboard vascular neurologist independently evaluated the patient, documenting their tissue-type plasminogen activator treatment decision, National Institutes of Health Stroke Scale score, and computed tomographic interpretation. Agreement was determined using Cohen κ statistic. Telemedicine-related technical failures that impeded remote assessment were recorded. Results— Simultaneous and independent telemedicine vascular neurologist and onboard vascular neurologist assessment was attempted in 174 patients. In 4 patients (2%), the telemedicine vascular neurologist could not make a decision because of technical problems. The telemedicine vascular neurologist agreed with the onboard vascular neurologist on 88% of evaluations (κ=0.73). Conclusions— Remote telemedicine vascular neurologist assessment is reliable and accurate, supporting either telemedicine vascular neurologist or onboard vascular neurologist assessment on our mobile stroke unit. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT02190500.

Background and Purpose— Mobile stroke units (MSUs) can speed treatment with intravenous tPA (tissue-type plasminogen activator). We previously showed substantial agreement between a telemedicine-based vascular neurologist (TM-VN) and an onboard vascular neurologist (OB-VN) for the evaluation of patients with stroke for tPA eligibility on an MSU. However, the time efficiency of the telemedicine-based evaluation remained uncertain. In this study, we examined the speed of decision and treatment from MSU arrival for the TM-VN compared with an OB-VN. Methods— In 50 consecutive situations, the TM-VN served as the primary decision maker. Times from MSU arrival to tPA decision and tPA bolus were compared with the same metrics for when the OB-VN served as the primary decision maker. Results— Time to tPA decision for the TM-VN was 21 minutes (interquartile range, 16.25–26) versus 18 minutes (interquartile range, 14–22) for the OB-VN ( P =0.01). Initiation of tPA bolus was 24 minutes (interquartile range, 19.75–30) for the TM-VN versus 24 minutes (interquartile range, 19–27.75) for the OB-VN ( P =0.5). Conclusions— Assessment by a TM-VN is comparable with an OB-VN in making decisions about tPA administration on an MSU and does not lead to treatment delays. Clinical Trial Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT02190500.

Background: Standard gamble (SG) directly measures patients’ valuation of their health state. We compare in-hospital and day-90 SG utilities (SGU) among intracerebral hemorrhage patients and report a 3-way association between SGU, EuroQoL-5 dimension, and modified Rankin Scale at day 90. Methods and Results: Patients with intracerebral hemorrhage underwent in-hospital and day-90 assessments for the modified Rankin Scale, EuroQoL-5 dimension, and SG. SG provides patients a choice between their current health state and a hypothetical treatment with varying chances of either perfect health or a painless death. Higher SGU (scale, 0–1) indicates lower risk tolerance and thus higher valuation of the current health state. Logistic regression was used to estimate the likelihood of low SGU (≤0.6), and Wilcoxon paired signed-rank test compared in-hospital and day-90 SGU. In-hospital and day-90 SG was obtained from 381 and 280 patients, respectively, including 236 paired observations. Median (interquartile range) in-hospital and day-90 SGUs were 0.85 (0.40–0.98) and 0.98 (0.75–1.00; P P =0.007), higher National Institutes of Health Stroke Scale, and intracerebral hemorrhage scores ( P Conclusions: Divergence between directly (SGU) and indirectly (EuroQoL-5 dimension) assessed utilities at high levels of functional disability warrant careful prognostication of intracerebral hemorrhage outcomes and should be considered in designing early end-of-life care discussions with families and patients.

Background and Purpose- The impact of a mobile stroke unit (MSU) on access to intraarterial thrombectomy (IAT) is a prespecified BEST-MSU substudy (Benefits of Stroke Treatment Delivered Using a Mobile Stroke Unit Compared to Standard Management by Emergency Medical Services). On the MSU, IAT decision-making steps, such as computed tomography, neurological exam, and tPA (tissue-type plasminogen activator) treatment are completed before emergency department arrival. We hypothesized that such pre-ED assessment of potential IAT patients on an MSU improves the time from ED arrival to skin puncture time (door-to-puncture-time, DTPT). Methods- BEST-MSU is a prospective comparative effectiveness study of MSU versus standard management by emergency medical services (EMS). We compared ED DTPT among the following groups of MSU and EMS patients: all IAT patients, IAT patients post-tPA, and IAT patients post-tPA meeting thrombolytic adjudication criteria over the first 4 years of the study. Results- From August 2014 to July 2018, a total of 161 patients underwent IAT. Ninety-four patients presented to the ED via the MSU and 67 by EMS. One hundred forty patients received tPA before IAT, 85 in the MSU arm, and 55 in the EMS arm. One hundred twenty-six patients received tPA within thrombolytic adjudication criteria: 76 MSU and 50 EMS. DTPT in minutes was shorter for MSU patients (all IAT MSU versus EMS 89 versus 99, P=0.01; IAT post-tPA MSU versus EMS 93 versus 100, P=0.03; and IAT post-tPA within adjudicated criteria MSU versus EMS 93 versus 99.5, P=0.03). From 2014 to 2018, DTPT decreased at a faster rate for EMS compared with MSU-managed patients, improving by about an hour. Conclusions- Pre-ED IAT evaluation on an MSU results in faster DTPT compared with arrival by EMS. Since 2014, dramatic improvement in ED IAT metrics has attenuated this difference. However, DTPT in all groups indicates substantial room for improvement.

Purpose: Mobile Stroke Units (MSU) deliver acute stroke treatment on-scene in coordination with Emergency Medical Services (EMS) prior to transport to a stroke center. One criticism is the limited range of a single MSU. The Houston MSU is the only one in the U.S. using a rendezvous system with EMS to expand its range. Methods: In addition to direct 911 dispatch of our MSU directly to the scene for tPA eligible patients within our “catchment” area (8 miles), we asked more distant EMS units to notify the MSU and also monitored EMS radio communication to identify eligible patients. For these “distant” patients, the MSU meets the EMS unit enroute to the stroke center and treats the patient at that intermediate location (usually a parking lot). The distribution of the distance from MSU base station to site of stroke and time from alert to tPA bolus were compared between patients treated on scene and by rendezvous using Wilcoxon rank sum test. Results: From August 18, 2014 to July 20, 2018, 290 acute ischemic stroke patients were treated with tPA on our MSU. Of these, 140 (48.3%) were treated on scene by direct 911 dispatch, with a median of 7 miles (IQR 5 miles) from MSU base station. 150 (51.7%) patients were treated by rendezvous. They had their strokes a median of 13 miles from base (IQR 6 miles) (p Conclusion: A “rendezvous system” significantly expands the range of operations for a MSU in an urban area, doubling the number of patients treated, without incurring delay. This approach might be even more useful in rural areas.

Background: Mobile stroke units (MSUs) permit advanced cerebrovascular diagnosis, triage, and treatment to be delivered in the field. While the range of acute cerebral ischemia and intraparenchymal hemorrhage patients encountered by MSUs has been described, the frequency, determinants, and outcomes of patients presenting with extraparenchymal intracranial hemorrhages (subdurals/subarachnoid/epidural) has not been well delineated. Methods: We analyzed consecutive transports among MSU programs in 3 cites, Los Angeles, Houston and Cleveland from program inception through August 2018 in the two former and through 2015 in the latter. Frequency and demographic, presenting, and treatment features of patients with subdural hematoma (SDH) and subarachnoid hemorrhage (SAH) were quantified. Results: Among 850 overall transports, extraparenchymal intracranial hemorrhages accounted for 18 (2.1%), and included 11 (1.3%) SDH and 7 (0.8%) SAH. Among the SDH patients, age was mean 70/median 77 (range 28 to 85). Special features of SDH cases included: acute on chronic blood on CT in 36%, seizures in 9%, and isolated head trauma in 9%. Among SAH patients, mean age was 57 (range 41-75). Special features of SDH/SAH cases included accompanying intraparenchymal hemorrhage in 17%. Of the 18 combined SDH/SAH patients (67% women), 4 (22%) required field intubation, 1 (5%) was actively treated in the field with KCentra to reverse anticoagulation, and 5 (28%) were treated in the field with antihypertensives. (See Figure for exemplar cases.) Conclusions: Extraparenchymal intracranial hemorrhages account for about 1 in 50 cases managed in Mobile Stroke Units. MSU response permits immediate definitive diagnosis by CT imaging, earlier start of indicated medical therapies, and direct routing to neurosurgically-capable stroke centers.

Introduction: Early ischemic changes (EIC) on non-contrast computed tomography (NCCT) can appear within 6 hours of last known normal (LKN), and can be quantified using the Alberta Stroke Program Early CT Score (ASPECTS). However, there is lack of data describing when EIC first appear. We leveraged our Mobile Stroke Unit (MSU) to determine the incidence of EIC on NCCT within 1 hour of LKN. Methods: Prospectively derived data were analyzed from patients on our MSU who were independently adjudicated as tissue plasminogen activator (tPA) eligible, had NCCT within 1 hour of LKN, and had definite strokes based on subsequent testing. EIC, defined as ASPECTS ≤ 7, was measured and correlated to time from LKN, stroke severity (National Institutes of Health Stroke Scale, NIHSS), and presence of large vessel occlusion (LVO) on neuroimaging. All scans were obtained on an 8 slice Ceretom (Neurologica Corp) and graded by a Vascular Neurology fellow, with random scans compared with a Vascular Neurology attending (κ=0.69). Results: 80 tPA eligible patients with NCCT within 1 hour of LKN were identified. 57 had definite strokes and/or strokes reversed by tPA. Of these, 54 (95%) had NCCT with sufficient diagnostic quality. Mean ASPECTS was 9.2 (median 10, interquartile range (IQR) 9-10) with a mean of 45.3 minutes (median 46, IQR 39-52) from LKN. Average NIHSS was 14.9. EIC (e.g. ASPECTS 6, 6, 7, 7) was identified in 4 patients (7%). There was no association between ASPECTS and time from LKN to CT (p=0.63), stroke severity (p=0.12) or presence of LVO (p= 0.09); the LVO analysis was limited by the small number of EIC patients (n=4). Conclusions: Based on our experience, EIC may be present but ASPECTS is not < 6 within the first hour after LKN. Close scrutiny of NCCT for EIC within this timeframe may not be necessary for determining eligibility for tPA or endovascular thrombectomy.

Introduction: The impact of a Mobile stroke unit (MSU) on access to Endovascular Thrombectomy (ET) is a pre-specified BEST-MSU sub-study. On the MSU, ET decision-making steps such as CT, neurologic exam, and tPA treatment are completed prior to Emergency Room (ER) arrival. We hypothesized that such pre-ER assessment of potential ET patients on a MSU improves metrics. Methods: BEST-MSU is a prospective comparative effectiveness study of MSU vs Standard Management by Emergency Medical Services (SM). We compared ER door-to-puncture-time (mins, DTPT) among the following groups of MSU and SM patients: all ET patients (ETP), ET patients post-tPA (ETT), and ET patients post-tPA meeting thrombolytic adjudication criteria (ETTA) over the first four years of the study. Results: There were 161 ETP (67 SM, 94 MSU), 140 ETT (55 SM, 85 MSU), and 126 ETTA (50 SM, 76 MSU) patients. DTPT was shorter for MSU patients (ETP 89 vs 99, p=0.01; ETT 93 vs 100, p=0.03; ETTA 93 vs 99.5, p=0.03). From 2015 to 2018, DTPT decreased at a faster rate for SM compared with MSU-managed patients, improving by about an hour (Figure). Conclusion: Pre-ER ET evaluation on a MSU results in faster DTPT. Since 2015, dramatic improvement in ER ET metrics has attenuated this difference. However, DTPT of 90-100 mins in all groups indicates substantial room for improvement.

Objective: Mobile stroke units offer improved time to administration of thrombolytics for ischemic stroke patients. Acquisition of intravenous (IV) access, however, can be challenging in the prehospital environment leading to treatment delays. Intraosseous (IO) access is commonly used in the prehospital setting for a variety of conditions and may serve as a viable means for tPA (tissue plasminogen activator) administration. Methods/Results: We describe 3 cases in which tPA was administered via IO access on a mobile stroke unit as part of the Benefits of Stroke Treatment Delivered Using a Mobile Stroke Unit Compared to Standard Management by Emergency Medical Services (BEST-MSU) trial. Conclusion: No adverse events were observed in the process of obtaining IO access or administering tPA.

Introduction: High in-hospital SBP variability (HSBPV) is an emerging marker for poor outcomes among Intracerebral Hemorrhage (ICH) patients. We aimed to determine the risk of severe disability or death (SDD) at day-90 among ICH patients with HSPBV and explore pre-hospital factors associated with HSPBV. Methods: Adult, radiologically confirmed primary ICH patients were prospectively enrolled and followed-up until day-90. All routinely collected SBP values were recorded for the inpatient stay. Inter and intra-patient SBPV was quantified using generalized estimating equations. Modified Rankin Scale (mRS) Score of 4 - 6 was defined as SDD. Poisson and logistic regression models were fit to determine the risk of day-90 SDD, and the association of pre-hospital characteristics with HSBPV. Results: A total of 566 patients [mean age: 63.5, females 36.6% (207 of 566)] were included. Total in-hospital follow-up period was 4,908 days [median (IQR) per patient = 8.7 (3-11)]. Over 120,500 SBP readings were analyzed. Inter and intra-patient mean SBP standard deviation (SD) was 11.1 and 13.2, respectively. A SD of 13.0 was parameterized as a cut-off for HSBPV. HSBPV patients had a 17% higher adjusted risk of day-90 SDD (Relative Risk, 95% CI: 1.17, 1.02-1.35) (Table). Older age and female sex were independently associated with HSBPV after controlling for hemorrhage volume, pre-morbid mRS, and Glasgow Coma Scale (Figure). Conclusion: Quantification of HSBPV is feasible utilizing routinely collected SBP readings. HSBPV is associated with poor outcomes. Elderly and female patients may be more likely to demonstrate HSBPV during hospitalization.

Introduction: Systolic blood pressure (SBP) regulation is the cornerstone of intracerebral hemorrhage (ICH) management, and SBP variability (SBPV) is associated with poor outcomes. We aimed to determine SBPV patterns and associated factors in a prospective cohort of ICH patients. Methods: Primary ICH patients are consented, assessed in-hospital and followed up at 30 and 90 days. All SBP values and BP management details for the hospital stay were collected from electronic medical records. Day and night intervals were defined as 0601 - 2159hrs and 2200 - 0600hrs, respectively. Mean and standard deviation (SD) were calculated for all intervals in each patient. Overall, between and within patient SBPV for day and night was characterized by generalized estimating equation (GEE)-based methods. We identified patients with a high SBPV (HSBPV) and built logistic regression models to determine associated factors. Results: Thus far, 158 patients have been enrolled, with detailed SBP data was available for 126. Total in-hospital follow-up period is 1,446 days [Median (IQR): 8 (4.25 - 15)]. We analyzed 34,740 SBP readings, yielding 3,010 day/night intervals. The in-hospital mean (SD) SBP was 138.2 (15.6) mmHg. GEE-based estimates for mean night SBP were significantly lower compared to day (137.2 v 139.1 mmHg, p < 0.01). Mean SBP SD was 9.1 mmHg between patients while 13.4 mmHg within patients’ individual readings. HSBPV was defined as SD > 13 mmHg. Age and high admission SBP were independently associated with HSBPV after controlling for sex, race, admission NIHSS, ICH score, hemorrhage volume and Nicardipine infusion use (Figure). Enrollments are continuing and updated data with outcomes will be presented. Conclusion: Characterization of patients with HSBPV can help in triage and management decisions based on risk-stratification. Elderly patients may be at a higher risk of SBPV, warranting exploration of possible SBPV contribution to poor outcomes in the elderly.

Introduction: Readmission (RA) after stroke is an established quality of care metric and is tied to reimbursements. Administrative databases lack stroke-specific severity indicators and information on post-discharge mortality. We report the cumulative incidence of 30-day RA for patients with primary intracerebral hemorrhage (ICH) from a statewide prospective cohort. Methods: Eligible ICH patients are consented to participate in the cohort to assess the impact of level of care on patient-centered outcomes across Texas. Patients undergo inpatient evaluation, followed by 30- and 90-day assessments for functional, cognitive, quality of life, dependency, and resource utilization outcomes. We defined 30-day RA as any RA that was assessed 30 days post-acute care hospitalization for the index ICH event. We used survival analyses to provide hazard ratios (HR) and 95% confidence interval (CI), while modeling post-discharge mortality as a competing risk. Results: Thus far, 158 patients have been enrolled with RA information available for 104. The overall RA rate is 5.1 / 1000 person-days (CI: 3.1-8.3). Among the various factors evaluated (Table 1), 30-day RA is significantly higher for patients with a higher ICH score (HR: 5.67, CI: 1.45-22.19), whereas post-discharge rehabilitation (as compared to discharge to home) appears to reduce the risk of RA, even after accounting for institution-free period of observation (HR: 0.11, CI: 0.01-0.86). Among patients with a high ICH score, those discharged home had significantly higher risk of RA as compared to those who received rehabilitation (Figure 1). Enrollment is continuing; updated analyses will be presented. Conclusion: Stroke-specific disease severity factors are important to identify to develop effective preventive strategies against RA, and need to be controlled for when comparing RA metrics across patient populations. Influence of post-stroke rehab on curtailing RA for ICH patients needs to be explored further.

Background: Mobile stroke units (MSU) can speed treatment with intravenous tissue plasminogen activator (tPA) for stroke patients. MSUs may use either an on-board (OB) or telemedicine (TM) based vascular neurologist (VN) for deciding tPA treatment. In the first phase of this study, we showed that agreement on giving tPA between a TM and OB-VN on a MSU is the same as between two VNs evaluating the same patient on site in the emergency department. In that phase, the actual treatment was determined by the OB-VN so that the TM-VN decision was delayed. In this phase, we determined the time from MSU arrival to tPA treatment decision and treatment when the TM-VN was the primary decision-maker and compared these to the same metrics for the OB-VN in the first phase. Methods: After MSU arrival on-scene, with the assistance of the OB nurse and paramedic, the TM-VN directed the evaluation of the patient, the CT scan was directly pushed to the TM-VN via a cloud-based picture archiving and communication system, and the TM-VN made the decision whether or not to treat. Times from MSU arrival to tPA decision and tPA bolus were compared to the same metrics for the OB-VN during the first phase of the study using a 2-sample t-test with log-transformation to satisfy t-test assumptions. Median times and interquartile range (IQR) were calculated for each group (Table 1). Results: The TM-VN was, on average, 3 minutes slower in making the tPA decision compared with the OB-VN (OB: 18 minutes [IQR 14-23] versus TM: 21 minutes [IQR 16-26], p=0.05). There was no difference however, in the time to tPA bolus between the two groups [OB: 23 minutes (IQR 19-30) versus TM: 24 minutes (IQR 19-28), p=0.70, with 95% confidence interval [-2.18-3.24]. Conclusion: A telemedicine based VN can treat a patient with tPA on a MSU as quickly as an on-board VN.

Introduction: Value-based care and patient-perceived outcomes are increasingly important. Standard Gamble (SG) derived utilities directly measure patients’ preferences for health states and form the basis of health economic analyses. We describe distribution of and factors associated with SG utilities (SGU) in a cohort of intracerebral hemorrhage (ICH) patients, and explore changes in SGU over 90 days post-discharge. Methods: Our study is a multisite cohort aiming to evaluate the comparative effectiveness of ICH patient management at various levels of care across Texas. Consented patients undergo assessments including SG in-hospital, and 30 and 90 days post-discharge. The SG assesses patients’ risk-taking behavior toward achieving a perfect health status, and outputs utility on a scale of 0 - 1 (Figure 1). Median and interquartile range (IQR) are reported for inpatient and day-90 SGU. Quantile regression was used to evaluate factors associated with SGU. Difference in median (DIM) and 95% confidence interval (CI) for the difference are reported. Results: 158 patients have been enrolled. Inpatient and day-90 SG was obtained from 132 and 54 patients respectively. Median inpatient SGU are significantly lower for older patients, white patients (compared to black patients), and those with higher ICH scores (Table 1). Median day-90 SGU was higher than inpatient SGU (DIM: 0.27; 95% CI: 0.08-0.46). Age >65 and higher ICH score were independently associated with lower SGU (Age: DIM -0.30; 95% CI -0.49, -0.11) (ICH Score: DIM -0.59; 95% CI -0.97, -0.21). Patients with mRS scores 0-3 at day 90 had higher SGU values compared to those with mRS scores 4-5 (DIM: 0.25, 95% CI: 0.09 - 0.41). Enrollment continues; updated analyses to be presented. Conclusion: Direct assessment of preferences for a morbid condition like ICH provides unique insight into patient values. Assessment of SGU may be routinely conducted in ICH patient studies to generate evidence for comparative effectiveness.

Background: Peroxisome proliferator activated receptor-gamma (PPAR-γ) agonists enhanced hematoma resolution and improved functional recovery in our animal model of intracerebral haemorrhage (ICH). We conducted a translational Phase 2 randomized, controlled clinical trial to determine the maximum tolerated dose (MTD) of the PPAR-γ agonist, pioglitazone (PIO), in patients with spontaneous ICH. Methods: Patients with spontaneous ICH within 24 hours of symptom onset were randomly allocated to PIO or placebo. Patients received escalating doses of PIO daily for three days, followed by a 30 mg maintenance dose for the duration of treatment. The primary safety outcome was mortality at Day 14. Secondary measures of safety included mortality at 3 and 6 months, symptomatic cerebral oedema, hypoglycaemia, respiratory, cardiovascular, hematologic, and hepatotoxicity. Secondary measures of clinical outcomes included modified Rankin Scale (mRS) score, National Institute of Health Stroke Scale (NIHSS) score, Barthel index (BI) Stroke Impact Scale (SIS) and EuroQol (EQ) at 3 and 6 months. The MTD was determined using the Continual Reassessment Method (CRM). Findings: From March 2009 to April 2013, 84 patients (42 PIO, 42 control) were enrolled with a dose range from 7·5-135 mg/day. The primary safety outcome of death within 14 days occurred in two (2%) patients. The MTD of PIO based on CRM was 75 mg/day. Secondary measures of safety and clinical outcomes were similar between treatment groups. Interpretation: Short-term, escalating doses of PIO were tolerated in ICH patients without an increase in adverse events compared to placebo. These results provide the foundation for an efficacy trial evaluating PIO as a potential treatment for patients with spontaneous ICH. Clinical Trial Number: SHRINC was registered with ClinicalTrials.gov (NCT00827892). Funding Statement: The SHRINC Trial was funded by the National Institute of Neurological Disorders and Stroke, the American Heart Association Clinical Research Program and the National Institutes of Health/National Center for Research Resources. Declaration of Interests: The authors state: "I/We declare no competing interests." Ethics Approval Statement: IRB NUMBER: HSC-MS-08-0410, Approval to conduct this trial was sought from the Institutional Review Board (IRB) for the University of Texas Health Science Center at Houston (UTHSC-H). IRB APPROVAL DATE: 12/16/2011

Background and Purpose— Faster treatment with intravenous tissue-type plasminogen activator (tPA) is likely to improve outcomes. Optimizing prehospital triage by mobile stroke units (MSUs) may speed treatment times. The Benefits of Stroke Treatment Delivered Using a Mobile Stroke Unit (BEST-MSU) study was launched in May 2014 using the first MSU in the United States to compare stroke management using an MSU versus standard management (SM). Herein, we describe the results of the prespecified, nonrandomized run-in phase designed to obtain preliminary data on study logistics. Methods— The run-in phase consisted of 8 MSU weeks when all-patient care occurred on the MSU and 2 SM weeks when the MSU nurse met personnel on scene or at the emergency department to ensure comparability with MSU patients. Telemedicine was independently performed in 9 MSU cases. Results— Of 130 alerts, 24 MSU and 2 SM patients were enrolled. Twelve of 24 MSU patients received tPA on board; 4 were treated within 60 minutes of last seen normal, and 4 went on to endovascular treatment. There were no hemorrhagic complications. Four had primary intracerebral hemorrhage. Agreement on tPA eligibility between the onsite and telemedicine physician was 90%. Conclusions— The run-in phase provided a tPA treatment rate of 1.5 patients per week, assured us that treatment within 60 minutes of onset is possible, and enabled enrollment of patients on SM weeks. We also recognized the opportunity to assess the effect of the MSU on endovascular treatment and intracerebral hemorrhage. Challenges include the need to control biased patient selection on MSU versus SM weeks and establish inter-rater agreement for tPA treatment using telemedicine.

Thrombelastography (TEG) measures coagulation in venous blood. We hypothesized that TEG, by reflecting clot subtype and ex vivo fibrinolysis, might predict fibrinolytic response to tPA as reflected by rapid clinical improvement or hemorrhagic transformation of the infarct. 171 acute ischemic stroke patients treated with tPA were prospectively enrolled. Venous blood for TEG was drawn before and 10 min after tPA bolus. We measured rapid clinical improvement (RCI = 8 point improvement on NIHSS or total NIHSS of 0, 1 at 36 h), Hemorrhagic transformation (HT = any blood on imaging within 36 h), and hyperdense middle cerebral artery sign (HDMCA = biomarker for erythrocyte-rich clot). Multivariable regression models compared TEG parameters after adjusting for potential confounders. No differences in pre- or post-tPA TEG were found between patients with or without RCI. Also, there was no correlation between TEG and HDMCA. Clotting was slightly prolonged in patients with HT (p = 0.046). We failed to find a robust association between TEG and clinical response to tPA. It is likely that arterial clot lysis is determined by factors unrelated to coagulation status as measured by TEG in the venous circulation. It is unlikely that TEG will be useful to predict clinical response to tPA, but may help predict bleeding.

Ischemic stroke results from blocked arteries in the brain, with earlier thrombolysis with intravenous tissue plasminogen activator (tPA) and/or mechanical thrombectomy resulting in improved clinical outcomes. Mobile Stroke Unit (MSU) can speed up the treatment with tPA and facilitate faster triage for patients to hospitals for mechanical thrombectomy. The first registry-based MSU study in Germany demonstrated faster treatment times with tPA using a MSU, a higher proportion of patients being treated within the first “golden hour,” and a suggestion of improved 3-month clinical outcomes. The first multicenter, prospective, randomized clinical trial comparing MSU versus standard care was started in 2014 after the launch of the MSU in Houston, TX, demonstrating the feasibility and safety of MSU operation in the United States, and reliability of telemedicine to evaluate stroke patients for tPA eligibility. Although conclusive evidence from clinical trials to support MSUs as being cost effective and improving clinical outcomes is still needed, there are a myriad of other clinical and research applications of MSUs that could have profound implications for managing patients with neurological emergencies.