bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract WP328: Veterans Administration National Telestroke Program: A Distributed Hub System of Acute Stroke Care
Authors: Martini Sharyl R , Anderson Jane , Murphy Katherine , Plue Laurie , Martin Holly , Williams Linda , Graham Glenn
Published: January 2019

Purpose:
Access to acute stroke expertise is a challenge for rural communities. The Department of Veterans Affairs (VA) emphasizes access to care throughout its network of 170 medical centers, many of which serve rural communities.

Methods:
To increase access to acute stroke expertise for rural veterans, we designed and implemented a nationwide system of emergency stroke care within the VA. Unique aspects of the program include (1) its “distributed hub”—a network of stroke neurologists that remain in their current job and location while dedicating a portion of their time to VA NTSP; (2) the nationwide distribution of “spoke” sites; (3) use of “off the shelf” mobile technologies; (4) interprofessional training curriculum utilizing whole-hospital simulations to inform iterative rapid-cycle process improvement; (5) consultant curriculum emphasizing the “tele” aspects of telestroke care; (6) monthly SCAN-ECHO educational conferences; and (7) a dedicated research team that evaluates process measures and outcomes through chart review of all ischemic strokes and all telestroke consults at participating facilities, as well as surveys/interviews with veterans, site staff, and NTSP neurologists.

Results:
VA NTSP is currently live at 12 sites. Our team has performed over 250 telestroke consults, 58% for rural veterans. We have trained 20 consultants and 18 sites. Although most of our initial 8 sites had never treated acute stroke, veterans with acute ischemic stroke who received telestroke consults during the first 2 quarters had mean a “door to CT” time of 16 minutes, 63.5% received CT within 25 minutes; and 92.3% of eligible patients were treated with alteplase. Median door to needle (DTN) time was 62 minutes, and 41.7% had DTN times < 60 minutes. Satisfaction is high for veterans (6.5/7) as well as site staff (8.8/10). Additional data from 3
rd
and 4
th
quarters will be provided.

Conclusions:
Our “distributed hub” model of nationwide stroke care has been effective in bringing acute stroke expertise to rural as well as urban VAs. Partnering with sites to develop and test local processes that address unique barriers while maintaining high standards of acute stroke care is a key factor in this success.
Abstract WP33: DEFUSE 3 Trial Outcomes not Affected by the Enrollment Rates of the Participating Centers
Authors: Mlynash Michael , Lansberg Maarten G , Kemp Stephanie , Christensen Soren , Heit Jeremy J , Marks Michael P , Albers Gregory W
Published: January 2019

Introduction:
Heterogeneity of outcomes between enrolling sites can affect the results of multicenter trials. We investigated if key DEFUSE 3 trial outcomes differed between low and high enrolling sites.

Methods:
DEFUSE 3, a randomized trial assessing the efficacy of mechanical thrombectomy in patients who could be treated 6 to 16 hours from last known to be well, was conducted at 38 US centers from the NIH StrokeNet network. We grouped centers by the number of the enrolled patients and compared rates of independent functional outcome (mRS 0-2 at 90-days) and successful recanalization (TICI score of 2b-3) between groups using Fisher’s exact test.

Results:
The 38 DEFUSE 3 centers enrolled a median of 4 (IQR 3-5) patients (range 1 to 15; Table). Rates of functional independence did not differ between centers when they were dichotomized by total enrollments. The rates of functional independence in the EVT arm were 38% in sites with 1-5 enrollments vs 52% in sites with 6-15 enrollments (p=0.21). Rates of functional independence in the medical arm were 19% in sites with 1-5 enrollments and 15% in sites with 6-15 enrollments (p=0.78). Similarly, there was no difference in rates of functional independence between the EVT and medical groups when centers were grouped by tertiles of total enrollments (1-4, 5-8, 9-15), p=0.40 for EVT and 0.78 for medical arm; or quartiles (1-3, 4-5, 6-12, 13-15) p=0.17 for EVT and 0.89 for medical arm. Similarly, there was no difference in the rates of recanalization between groups when dichotomized: 75% (1-5 patients) vs 77% (6-15 patients), p=0.50; trichotomized (71%, 79%, 78%, p=0.75); or assessed by quartiles (74%, 76%, 73%, 82%, p=0.91).

Conclusions:
Enrollment rate heterogeneity among the StrokeNet centers participating in the DEFUSE 3 trial did not affect the rates of functional independence or successful recanalization.
Abstract WP339: Modulation of Gut Microbiota Improves Outcomes After Ischemic Stroke by Reducing Lipopolysaccharide-Induced Inflammation in the Ischemic Brain of Diabetic Mice
Authors: Kurita Naohide , Yamashiro Kazuo , Kuroki Takuma , Tanaka Ryota , Ueno Yuji , Urabe Takao , Yamashiro Yuichiro , Hattori Nobutaka
Published: January 2019

Background and Aims:
Gut dysbiosis, an imbalance of gut microbiota, is associated with host inflammation due to the translocation of Gram-negative bacteria-derived lipopolysaccharide (LPS), resulting from increased gut permeability. Inflammation plays a key role in the pathophysiology of ischemic stroke. Here, we investigated the effect of gut dysbiosis on acute ischemic brain injury.

Methods:
Fecal bacteria were analyzed via 16S and 23S rRNA-targeted quantitative reverse transcription-polymerase chain reaction and the outcome of focal cerebral ischemia was examined in lean littermates (db/+), type 2 diabetic mice (db/db), and db/db mice with oral administration of the non-absorbable antibiotic polymyxin B (db/db+PL-B) (n=5-9/group).

Results:
Mice from the db/db+PL-B group had selectively attenuated fecal bacterial count of the Gram-negative bacteria
Enterobacteriaceae
(p<0.01), and reduced plasma LPS levels (p<0.05) and gut permeability (p<0.05) without a change in plasma glucose levels compared to those in
db/db
mice. Polymyxin B was not detected in the blood of db/db+PL-B mice. In addition, antibiotic pre-treatment significantly reduced infarct size (p<0.05), blood-brain barrier leakage (p<0.05), inflammatory reactions in the brain, such as IL-6 (p<0.01), IL-1β (p<0.01), and TNF-α (p<0.05), improved neurological function (p<0.05), and survival rates (p<0.05) following cerebral ischemia. Furthermore, db/db + PL-B mice had significantly reduced LPS (p<0.05) and expression of TLR4 (p<0.01), the LPS receptor, and inflammatory cytokine levels, such as IL-6 (p<0.01), IL-1β(p<0.01), and TNF-α (p<0.05), in the ischemic hemisphere.

Conclusions:
These findings suggest that LPS-induced inflammation may be a mechanism that links gut dysbiosis to ischemic cerebral injury, and that modulation of gut microbiota may be a potential therapeutic strategy to improve the stroke outcome.
Abstract WP342: Activate the Pentose Phosphate Pathway to Reduce the Cerebral Ischemia/Reperfusion Injury: The Impact of Heat Shock Protein 27 Phosphorylation
Authors: Matsuo Kazuya , Hosoda Kohkichi , Tanaka Jun , Yamamoto Yusuke , Imahori Taichiro , Nakai Tomoaki , Irino Yasuhiro , Shinohara Masakazu , Sasayama Takashi , Kohmura Eiji
Published: January 2019

Introduction:
Based on metabolomics with gas chromatography-mass spectrometry, we showed that pentose phosphate pathway (PPP) is activated during cerebral ischemia and reperfusion in rat cerebral cortex. Especially, heat shock protein 27 (HSP27) phosphorylation seems to play an important role in activating glucose 6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme in PPP. To confirm the hypothesis that HSP27 phosphorylation can be a potential target for the treatment of ischemic stroke, we used KU55933 and geranylgeranylacetone (GGA). KU55933 is the inhibitor of ataxia telangiectasia mutated kinase (ATMK), inhibiting the phosphorylation of HSP27. GGA can induce the expression of HSP families in various organs.

Methods:
First, 10 μl of KU55933 or DMSO was injected into the lateral ventricle of male Wistar rats (n=5 each). One hour after the injection, 1.5-h middle cerebral artery occlusion (MCAO) and following 24-h reperfusion were performed to evaluate the effect. Next, intracerebroventricular (ICV) injection of 10 μl of GGA or DMSO was performed 3-h prior to 1-h MCAO/24-h reperfusion. Infarct size, immunoblotting, G6PD activity, and protein carbonyl indicating protein oxidation, were examined.

Results:
ICV injection of KU-55933 significantly reduced the phosphorylated HSP27 (pHSP27) and G6PD activity (Fig. 1A and B). In addition, it increased the infarct size and the protein carbonyl (Fig. 1 C and D). In contrast, ICV injection of GGA increased both HSP27 and pHSP27, which resulted in significant reduction of the infarct size (19.9% vs 31.3%, p<0.01) (Fig. 1 E and F).

Conclusions:
ATMK contribute the antioxidative effect with phosphorylation of HSP27 during cerebral ischemia/reperfusion. GGA may be a potential therapeutic drug for ischemic stroke. Further studies are required prior to clinical application, including investigation that use more convenient route of administration; and that evaluate the effect of GGA administration after MCAO.
Abstract WP343: DHA Adjusts Macrophage Phenotypic Responses After Stroke
Authors: Liu Sanxin , Cai Wei , Hu Mengyan , Lu Zhengqi
Published: January 2019

Background:
Immune responses after stroke, including both
in situ
glial cell activation and peripheral immune cell infiltration, play critical roles in ischemic brain injury. Systemic docosahexaenoic acid (DHA) has been explored as a clinically feasible protectant in stroke models. However, the mechanism for DHA-afforded neuroprotection remains elusive. This study evaluated the effect of systemic DHA treatment after transient cerebral ischemia and elucidated a mechanism involving immune regulation of macrophages.

Methods:
Transient middle cerebral artery occlusion (tMCAO) was induced for 1 hour. DHA (i.p., 10mg/kg) was administered immediately after reperfusion and repeated daily for 3 days. Stroke outcomes, systemic inflammatory status and microglia/macrophage phenotypic alterations were assessed 3 days after stroke. Macrophage depletions were induced by clodronate liposomes injection. Primary macrophage cultures were used to evaluate the direct effect of DHA on macrophages.

Results:
Post-stroke DHA injection efficiently reduced brain infarct and ameliorated neurological deficits 3 days after tMCAO. Systemic DHA treatment significantly inhibited immune cell infiltration (macrophages, neutrophils, T lymphocytes and B lymphocytes) and promoted macrophage polarization towards an anti-inflammatory M2 phenotype in the ischemic brain. Meanwhile, systemic DHA administration inhibited the otherwise elevated pro-inflammatory factors in blood and shifted circulating macrophage polarity toward M2 phenotype after ischemic stroke. The numbers of circulating immune cells in blood and spleen, however, were equivalent between DHA and vehicle treated groups. The protective effects of DHA were macrophage-dependent, as macrophage depletion abolished DHA-afforded neuroprotection.
In vitro
studies confirmed that DHA suppressed production of chemokines and pro-inflammatory cytokines from macrophages under inflammatory stimulation.

Conclusion:
Post-stroke DHA treatment ameliorated acute ischemic brain injury in a macrophage-dependent manner. DHA enhanced macrophage phenotypic shift toward an anti-inflammatory phenotype and therefore reduced central and peripheral inflammation after stroke.
Abstract WP349: L-Glutamine Induces Heat Shock Protein 70 Expression & Attenuates Brain Ischemic Injury in Mice
Authors: Luo Longlong , Li Yongfang , Yuan Fang , Wang Liping , Li Wanlu , Ma Yuanyuan , He Tingting , Qu Meijie , Liang Huaibin , Wang Yuyang , Tang Yaohui , Zhang Zhijun , Yang Guo-Yuan , Wang Yongting
Published: January 2019

Introduction:
Oxidative stress plays an important role in ischemic stroke pathogenesis. L-glutamine (L-GLN) was shown to have antioxidant activity and was approved by the FDA in July 2017 for the treatment of sickle cell disease. In this study, we aim to investigate the effect of L-GLN in attenuating ischemic brain injury using a mouse middle cerebral artery occlusion (tMCAO) model.

Methods:
Ninety-minute tMCAO was used to induce a focal cerebral ischemic injury. Animals (n=135) were divided into four groups: (1) Sham, (2) Saline, (3) L-GLN, and (4) L-GLN plus HSP70 ATPase activity inhibitor Apoptozole (Az). Treatments were delivered intraperitoneally once daily for the first three days after ischemic surgery. Neurobehavioral tests were performed before tMCAO and at 1, 3, 7, and 14 days after tMCAO using the modified neurological severity score (mNSS), elevated body swing test (EBST), and rotarod test. Infarction volume was assessed by cresyl violet staining of brain sections. The expression levels of heat shock proteins and its signaling pathway related proteins were evaluated by Western Blot and real time-PCR. The level of oxidative stress was evaluated by malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-PX) assays. Astrocyte and neuron cell cultures and oxygen glucose deprivation (OGD) model was used to further examine the molecular pathways involved in the protective effects by L-GLN.

Results:
L-GLN reduced brain infarct volume and promoted neurobehavioral recovery in mice suffering from ischemic injury. Such beneficial effect was abolished by the coadministration of AZ. L-GLN induced the up-regulation of HSP70, reduced oxidative stress level, and reduced the expression of IL-1beta and IL-6 in ischemic mice brain. In L-GLN group, SOD and GSH-PX activities are significantly increased compared to the Saline group. Nrf2 was upregulated in the L-GLN group while co-treatment with AZ abolished this upregulation. Cell culture experiments revealed that the conditioned media from astrocytes cultured with the presents of L-GLN attenuated the apoptosis of neurons after OGD.

Conclusion:
L-GLN attenuates ischemic brain injury in part through HSP70 related pathways and holds potential in post-stroke treatment.
Abstract WP354: Racial and Ethnic Disparities in Risk for Pregnancy-Related Stroke: The National Inpatient Sample
Authors: Zambrano Maria D , Friedman Alexander M , Boehme Amelia K , Huang Yongmei , Miller Eliza
Published: January 2019

Background:
Significant racial disparities exist in obstetrics. Stroke is a major cause of maternal morbidity and mortality in the US. We sought to determine if the risk for stroke differed by race during delivery and postpartum admissions.

Methods:
Using the Nationwide Inpatient Sample from 1998 to 2014, we analyzed two separate cohorts: (i) women hospitalized for a delivery, and (ii) women readmitted postpartum. Women age 15-54 were included. Race and ethnicity were characterized as white, black, Hispanic, Asian/Pacific Islander, Native American, other, and unknown. Overall risk for stroke by race was determined. Risk for stroke was further characterized by (i) hemorrhagic stroke, (ii) ischemic stroke, and (iii) stroke associated with preeclampsia or gestational hypertension (PEC/GHTN). Log-linear regression models including demographics, hospital factors, and comorbid risk were used to analyze overall stroke risk.

Results:
Of 67.7 million delivery and 1.1 million postpartum hospitalizations, 8,241 and 11,073 women were diagnosed with stroke respectively. Black women were at 64% higher risk than white women for stroke during delivery and 66% higher risk for stroke during postpartum admissions (Table). Black women were at 139%, 96%, and 103% higher risk for hemorrhagic, ischemic, and PEC/GHTN-associated stroke during delivery hospitalizations. Risk for black women was also increased postpartum. Relative to white women, Hispanic women were at significantly increased risk for hemorrhagic and PEC/HTN-associated stroke. In adjusted models, black women were at 33% and 37% increased risk for stroke during delivery and postpartum hospitalizations while risk for Hispanic women did not differ.

Conclusion:
Black women, in particular, are at increased risk for pregnancy-related stroke, both during delivery hospitalizations and postpartum, across clinical scenarios. Broad systemic efforts will be required to reduce disparities in maternal stroke risk.
Abstract WP362: Association Between t-PA Treatment and Mortality After Stroke: Results from the Ontario Stroke Registry
Authors: Fang Jiming , Yu Amy Y , Kapral Moira K
Published: January 2019

Introduction:
Thrombolysis with tissue plasminogen activator (tPA) is associated with better functional outcomes after acute ischemic stroke, but its effect on survival is uncertain. We studied the association between tPA and long-term mortality in a large population-based cohort, and compared the causes of death in those who did and did not receive tPA.

Methods:
We used the Ontario Stroke Registry to identify patients with incident acute ischemic stroke presenting to 11 regional stroke centers in Ontario, Canada (Jul 2003 - Mar 2013), and linked to the Office of the Registrar General Deaths database to determine mortality and cause of death until Dec 2015. We categorized the cause of death as stroke, non-stroke cardiovascular (CV), and non-CV. Using propensity score matching (1:1) to adjust for differences in baseline characteristics, we compared the 2-year all-cause mortality rate between patients treated with tPA and those who were not, and calculated the sub-distribution hazard ratio (sdHR) to study the association between tPA and cause of death, accounting for the competing risks of each cause of death.

Results:
Of 26,943 patients with ischemic stroke, 4,448 (16.5%) were treated with tPA. After matching for sex, age, ethnicity, time to hospital arrival, stroke severity, comorbidities, medications, and care in a stroke unit, we had 3,371 pairs treated and not treated with tPA. Treatment with tPA was associated with a trend toward reduced all-cause mortality at 2 years (HR 0.93, 95%CI 0.85-1.00). In the analyses of cause of death, tPA treatment was associated with lower non-CV mortality (sdHR: 0.80, 95%CI 0.68-0.93) but not stroke mortality (sdHR 1.02, 95%CI 0.91-1.16) or CV mortality (sdHR 0.95, 95%CI 0.81-1.11).

Conclusions:
We found that thrombolysis administration was associated with lower non-stroke mortality at two years, with no increase in mortality due to stroke or other cardiovascular disease. These findings are consistent with results from the Third International Stroke Trial, and support the long-term benefit of thrombolysis in selected patients.
Abstract WP368: CT Perfusion and Radiation Exposure in Acute Ischemic Stroke: A Quality Improvement Study
Authors: Modak Janhavi M , Lee Jun W , Reeves Christopher , Staff Ilene , Ollenschleger Martin D
Published: January 2019

Introduction:
Treatment of acute ischemic stroke has undergone a paradigm shift after recently published trials DAWN & DEFUSE-3. Imaging techniques like CT perfusion (CTP) can identify eligible candidates who may benefit from intervention, however, this entails screening patients with CTP, resulting in higher radiation & contrast exposure.

Methods:
Acute ischemic stroke patients admitted between Sept 2017 & Feb 2018, who underwent CTP screening at Hartford Hospital were considered for this study. Patients admitted between April & Sept 2017 who underwent CT Angiogram (CTA) Head alone for screening were considered for controls. A standard CTP algorithm was utilized, with image acquisition time initially set at 60 secs and later reduced to 45 secs. Imaging (CTP RAPID, CTA) related variables were analyzed. SPSS was used for statistical analysis.

Results:
We assessed 50 patients who underwent CTP screening (CTP group) in the extended stroke window (6-24 hours) and 45 patients who served as controls. In the CTP group, 90% scans were of optimal quality, whereas 10% were deemed suboptimal. For CTP associated radiation exposure, the median dose length product (DLP) was 1420.3 mGy-cm (IQR 1420 to 1775.31 mGy-cm). The median DLP was 2401.89 mGy-cm in patients with 60 sec CTP acquisition time, significantly higher compared to 1420.3 mGy-cm in patients with 45 sec acquisition time (p<0.001). The median total radiation exposure (excluding endovascular intervention) during entire hospitalization for the CTP group was 5260 mGy-cm as compared to 3222.27 mGy-cm for controls, which was statistically significant (p<0.001). No radiation related adverse events were observed in the CTP group. In terms of contrast exposure, there was no significant difference in Sr creatinine obtained at day one or at discharge when compared to baseline (p=0.46). Amongst 50 patients screened with CT perfusion, 16 patients (32%) were deemed eligible for endovascular therapy.

Conclusions:
Although CT perfusion screening may result in higher radiation exposure, the perfusion protocols may be optimized to reduce the amount of radiation imparted to patients without compromising on the scan quality. Despite additional contrast exposure, no significant effects were observed on the renal function.
Abstract WP374: 30 Days Unplanned Readmission (30-DR) in Cerebral Vein Thrombosis: US National Retrospective Analysis
Authors: Patel Smit D , Topiwala Karan , Tarasaria Karan , Lima Jussie , Mehta Tapan , Mui Gracia
Published: January 2019

Introduction:
Thrombosis of the cerebral veins and/or dural sinuses (CVST) results in 0.5% to 1% of all strokes. CVST has a lower mortality rate compared to arterial stroke; however it predisposes to certain complications, which lead to frequent hospital readmissions.

Objective:
To study the readmission rate, reasons for readmissions and predictors of intracranial hemorrhage (ICH).

Method:
Using the Nationwide Readmission Database (NRD) from 2013 -2014 patients with a primary discharge diagnosis of CVST (ICD 9 CM code: 437.6, 325, and 671.5) were identified. Their post-hospitalization course was tracked using the variable “NRD_visitlink,” and the time between re-admissions was calculated by subtracting the variable “NRD_DaysToEvent”. SAS 9.4 was used for data analysis with categorical and continuous variables tested using the Rao Scott Chi-square test and Student’s t-test, respectively. Multivariate logistic regression models were used for categorical dependent variable.

Result:
A total of 3,611 (weighted) Index discharges of CVST were identified. After excluding elective readmissions, 11.32%, 17.04% and 21.81% were the observed readmission rates at 30, 90 and 180 day-follow-up periods respectively. The common causes of 30-day readmission (30-DR) were complications of the puerperium (8.76%), ICH (6.13%), migraine (4.23%), ischemic stroke (2.86%), sepsis (2.30%) and hypertensive complications (1.83%). Epilepsy related readmissions were observed only in the 90-day (1.95%) and 180-day (2.51%) follow up periods. The mean 30-DR cost was lower vs. Index admission (Mean ± SE $ 12,439±1139 vs. $ 16314±652; P value <0.0001) while the length of stay (LOS) during readmission was also lower compared to Index LOS (Mean ± SE 5.0±0.4 vs. 6.4±0.2 ;< 0.0001). After adjusting age and gender, multivariate predictors of increase risk of ICH readmission were hypertension (OR 4.79 CL 1.38-16.59; P=0.0068), primary hypercoagulable state (OR 3.34, CL 1.12-9.99; P=0.0306), meningitis (OR 17.77 CL 2.51-125.96, P=0.0041) and chronic kidney disease (OR 3.80CL 1.04-13.85, P=0.0434).

Conclusion:
Puerperal complications, ICH, epilepsy and sepsis are the most common complications prompting re-hospitalization in patients diagnosed with CVST.
Abstract WP380: Hospital-Level Variability in Diagnostic Testing and Ischemic Stroke Subtype Documentation
Authors: Prabhakaran Shyam , Messe Steven R , Kleindorfer Dawn , Smith Eric E , Fonarow Gregg C , Zhao Xin , Lytle Barbara , Cigarroa Joaquin , Schwamm Lee H
Published: January 2019

Objective:
Documentation of ischemic stroke subtype has clinical and research implications. We aimed to assess hospital-level variability in subtype documentation and diagnostic testing patterns in the Get With The Guidelines (GWTG)-Stroke registry.

Methods:
We identified patients admitted with ischemic stroke to GWTG-Stroke participating hospitals between January 1, 2016 and September 30, 2017. Sites were instructed on use of the TOAST criteria for subtype documentation. We assessed hospital-level variability in TOAST subtype documentation and, among those with subtype documented, the performance of echocardiography, cerebrovascular imaging, and cardiac rhythm monitoring.

Results:
Among 607,563 patients with ischemic stroke from 1,906 sites, 348,715 (57.4%) had documented ischemic stroke subtype. Considerable hospital-level variability was observed in subtype documentation (Figure A). Patients with subtype documentation were more likely to be inter-facility transfers and treated at higher volume and academic centers, have complete medical history data, and have higher rates on achievement and quality measures. Carotid and intracranial vascular imaging (69.1% and 58.7%, respectively), echocardiography (74.3%), and cardiac rhythm monitoring (76.2%) were performed most frequently in cryptogenic stroke (CS) patients compared to other subtypes (Figure B; p<0.001 for each comparison). Among CS patients, short-term cardiac rhythm monitoring (65.7%) was most common with only 6.1% undergoing extended surface cardiac rhythm monitoring and 4.4% receiving extended implantable cardiac rhythm monitoring.

Conclusions:
In a large contemporary nationwide dataset of acute ischemic stroke hospitalizations, we observed that stroke subtype is documented in 57.4% of records, raising an important opportunity for quality improvement. Furthermore, diagnostic testing patterns suggest incomplete evaluation is common, even among patients with CS.
Abstract WP383: Disseminating Acute Stroke Feedback to Emergency Care Providers
Authors: Ebersole Joseph M , Scheving William , Froehler Michael T , Espaillat Kiersten , Closser James B , Self Wesley H , Ward Michael J
Published: January 2019

Introduction:
Emergency department (ED) clinicians find that feedback on acute stroke patients is rewarding, valuable to professional development, and critical to practice improvement. However, feedback is rarely provided despite the effectiveness of this practice in changing behavior. We sought to evaluate the feasibility and usability of an electronic stroke outcome reporting tool to provide feedback to ED personnel.

Methods:
We conducted an IRB-approved pilot study in May 2018 at 3 Nashville hospitals. ED staff signed up to receive de-identified reports of clinical (e.g., survival) and operational (e.g., time-to-tPA) outcomes of patients with acute ischemic stroke. Reports were electronically transmitted 72 hours after ED arrival. Providers were surveyed on usefulness of these reports and likelihood to change, and could claim continuing medical education (CME). Descriptive statistics were used to describe survey results.

Results:
We enrolled 232 ED personnel; 107 (46%) nurses, 57 (25%) attending physicians, 26 (11%) resident physicians, 15 (7%) EMS providers, and 27 (12%) other staff. CME was initiated or claimed by 22 staff. During the study, outcome reports (
Figure
) were transmitted for 56 patients with acute ischemic stroke. There was a mean of 6.0 (SD 2.0) staff/case and 4.1 (SD 1.5) were registered. Reports were viewed by a mean of 2.6 (SD 1.5) registered staff. 97.1% found the reports useful and 36.2% reported likeliness to change practice. On a scale of 1-to-100, nurses rated the reports as most useful (81.9, SD 15), followed by ED residents (77.7, SD 14.7), then ED attendings (73.0, SD 16.8).

Conclusions:
Electronic reporting of stroke outcomes was feasible, efficient, and useful. Limitations to widespread use include the time required to produce reports which may be addressed through electronic data pulls. Future research should address the effectiveness of this reporting tool as a source of useful provider education.
Abstract WP412: Use of Interactive Cluster Heatmaps and Text Analytics in the Escape-na1 Phase 3 Clinical Trial for Pharmacovigilance of Adverse Events and Site Performance
Authors: Rizwan Arsalan P , Adams Corey , Tymianski Michael
Published: January 2019

Introduction:
Stroke trial subjects sustain numerous adverse events (AE’s) which may be related to the disease under study or to the therapeutic intervention. In studies involving pharmacovigilance of multiple AE’s, ongoing oversight of AEs by investigators and trial sponsors is critical to ensure the safety and well being of trial subjects. Static cluster heatmaps are used extensively in the field of gene expression studies and text analytics are used widely to monitor text on social media sites such as Twitter. Here we present novel dynamic tools using static cluster heatmaps and text analytics to aid with the visualization of AEs and of clinical site performance in AE reporting in the ESCAPE-NA-1 trial (Clinicaltrials.gov NCT 02930018).

Methodology:
In an interactive cluster heatmap display, the frequency of AEs is color coded in cells, with the rows corresponding to either sites or patients and columns correspond to unique AEs. Clustering is visualized on a heatmap by addition of row and column dendrograms. Quantification of AEs in the clinical trial is performed through text analytics and the results are visualized using a word cloud. Difference of AE across sites is visualized using a comparison cloud, a cloud that compares frequencies across sites. A cluster heatmap and word cloud are made interactive by formatting into HTML.

Results:
The main results obtained from interactive AE cluster heatmaps are patient ,site and AE clusters (Figure 1). The results obtained from text analytics are word clouds that convey overall AEs frequency and AEs frequency across sites (Figure 1). Due to active status of the trial, we will share the methodology of constructing interactive AE cluster heatmaps and word clouds and broad visual results without providing specifics of sites or AEs.

Conclusion:
Interactive cluster heatmaps and word clouds constructed via text analytics are a novel way of visualizing complex multidimensional AE data from clinical trials.
Abstract WP415: Electronic Stroke Care Pathway Significantly Increases Quality Improvement Metric Documentation and Patient Education
Authors: Dunn Aaron N , Pasadyn Selena R , May Francis J , Wisco Dolora R
Published: January 2019

Introduction:
Stroke accounts for 1 in 20 deaths in the US, and increasing stroke healthcare costs are projected to rise to $185 billion yearly by 2030. Care Pathways use standardized electronic medical record (EMR) documentation, order sets, and clinical decision support to streamline institution-wide care delivery and have been shown to improve outcomes. We hypothesize that the Acute Ischemic Stroke (AIS) Care Pathway increases EMR documentation of quality improvement metrics.

Methods:
The AIS Care Pathway was implemented starting in 11/2015. It streamlines workflow by providing users with EMR documentation tools, order sets, and clinical aids. We compared the documentation of quality improvement metrics in patients on and off the Care Path, including stroke education and documentation of last known well (LKW), NIH stroke scale (NIHSS), and modified Rankin Scale (mRS).

Results:
In 2017, 2,728 patients were diagnosed with AIS; 77% of patients were placed On Care Path, and 23% were Not On Care Path. Documentation of LKW (81% vs 29%, p<0.01), admission NIHSS (100% vs 62%, p<0.01), admission mRS (99% vs 60%, p<0.01), discharge NIHSS (75% vs 46%, p<0.01), and discharge mRS (78% vs 49%, p<0.01) were significantly higher for patients On Care Path compared to those Not On Care Path (Table 1). Likewise, a higher proportion of patients On Care Path received nursing stroke education (74% vs 48%, p<0.01).

Conclusions:
AIS Care Pathway significantly increases documentation of quality improvement metrics and education related to stroke care. These are electronically abstracted data that can eliminate the need for manual abstraction.
Abstract WP416: Preceding Therapeutic Anticoagulation in Patients With Atrial Fibrillation Reduces Both the Severity of Stroke and the Risk of In-Hospital Complications--Data From the Chinese Stroke Center Alliance (CSCA)
Authors: Wang Chunjuan , Li Zixiao , Gu Hongqiu , Yang Xin , Wang Caiyun , Zhang Fuying , Zong Lixia , Wang Yilong , Wang Yongjun
Published: January 2019

Objectives:
To determine the association of preceding therapeutic anticoagulation with stroke severity and in-hospital complications.

Method:
All acute ischemic stroke patients with known history of AF, who were included into CSCA, were divided into five groups: not receiving any antithrombotic therapy, only antiplatelet therapy, receiving subtherapeutic warfarin (international normalized ratio [INR] <2), receiving therapeutic warfarin (INR≥2) and receiving non-vitamin K antagonist oral anticoagulants (NOACs). Stroke severity was measured by the National Institutes of Health Stroke Scale (NIHSS, a score ≥16 indicating moderate or severe stroke), and in-hospital complications included pneumonia, deep vein thrombosis, pulmonary embolism, seizures, hydrocephalus, urinary tract infections, hemorrhoids, depression, myocardial infarction and gastrointestinal bleeding.

Results:
Of 25 475 patients (mean [SD] age, 73.7 [10.6] years; 51.1% male), none were receiving NOACs, 438 (1.7%) were receiving therapeutic warfarin, 2 520 (9.9%) were receiving subtherapeutic warfarin, 5 847 (23.0%) were receiving antiplatelet therapy only, and 16 670 (65.4%) were not receiving any antithrombotic treatment before onset of stroke. Among 22 113 high-risk patients (prestroke CHA2DS2-VASc score ≥2), 19 546 (88.4%) were neither receiving warfarin nor NOACs before stroke. After adjusting for potential confounders, compared with no antithrombotic treatment, preceding use of therapeutic warfarin, untheraputic warfarin, or antiplatelet therapy only was associated with lower odds of moderate or severe stroke (adjusted odds ratio [95% CI], 0.71 [0.53-0.93], 0.88 [0.78-0.99], and 0.87 [0.80-0.96], respectively) and in-hospital complications (adjusted odds ratio [95% CI], 0.79 [0.62-1.00], 0.88 [0.79-0.98], and 0.99 [0.91-1.07], respectively).

Conclusions:
Among Chinese patients with acute ischemic stroke and known history of atrial fibrillation, therapeutic anticoagulation was associated not only with lower odds of moderate or severe stroke but also with lower odds of in-hospital complications.
Abstract WP417: A Score for Hemorrhagic Transformation Prediction in Acute Ischemic Stroke Not Treated With Recanalization Therapies
Authors: Andrade Joao B , Carvalho Joao J , Lima Fabricio O , Silva Gisele S
Published: January 2019

Introduction:
Hemorrhagic Transformation (HT) in patients not treated with recanalization therapies remains a poorly understood phenomenon.

Hypothesis:
HT in patients not treated with reperfusion therapies can be predicted based on simple data. We also proposed an easy-to-use clinical scale for predicting HT in this population.

Methods:
A total of 492 patients admitted to a Stroke Unit were randomly selected between January 2015 and December 2017. All patients were followed for seven days. A multivariable model was built, and independent predictive factors were used to produce a predictive grading score for HT. Receiver operating characteristic (ROC) analysis was conducted to assess prognostic performance. The optimal cut point score to distinguish between HT-positive and negative groups was defined with the Youden index.

Results:
HT occurred in 19.3% (N = 95) of the patients. Factors independently associated with HT included: age ≤60 years (OR:2.2 95% CI:1.2-4, p=0.01 ), male gender (OR:3.4 95% CI:1.8-6.3 , p<0.001), lacunar syndrome (OR:0.12 95% CI:0.27-0.56, p=0.007), blood glucose at admission ≥180mg/dL (OR:2.7 95% CI:1.3-5.7, p=0.009), ASPECTS ≤7 (OR:5.3 95% CI:2.9-9.7, p<0.001), hyperdense middle cerebral artery (MCA) (OR:2.7 95% CI:1.3-5.9, p=0.007), leukoaraiosis (OR:1.9 95% CI:1.1-3.5, p=0.02), Diabetes Mellitus (OR:2.2 95% CI:1.1-4.5, p=0.02) and cardioembolism (OR:3.2 95% CI:1.8-5.9, p<0.001). The score derived from the logistic regression analysis was: log(p/1-p) = -4.34 +0.79(age) +1.24(male) -2.08(lacunar) +0.99(glucose) +1.67(ASPECTS) +0.99(MCA) +0.67(leukoaraiosis) +0.79(Diabetes) +1.18(cardioembolism). Scores ranged from -8 to 23. The scale had an area under the curve (AUC) of 0.84 (0.81-0.88) for general HT and 0.85 (0.80-0.91) for symptomatic HT. Each point on the scale had an odds ratio of 1.39 (1.26-1.53) for predicting HT. The cut point was 8 with a sensitivity of 82.1% for general HT and 88.6% for symptomatic HT.

Conclusions:
Our risk score suggests that the individual risk for HT in patients with acute ischemic stroke not treated with reperfusion therapies can be assessed using simple data, including epidemiological characteristics, laboratory data, neuroimaging findings and etiologic classification.
Abstract WP435: Blood Pressure Reduction on Two-Year Mortality and Major Disability in Acute Ischemic Stroke With Various Severities
Authors: He Jiang , Chen Jing , Xu Tan , Wang Dali , Chen Chung-Shiuan , Sun Yingxian , Zhang Yonghong ,   the CATIS investigators
Published: January 2019

Introduction:
We conducted a prespecified subgroup analysis to assess whether disease severity modifies the effect of early antihypertensive treatment on two-year mortality and major disability in acute ischemic stroke patients.

Methods:
The China Antihypertensive Trial in Acute Ischemic Stroke, a randomized, single-blind, blinded end-points trial, was conducted in 4,071 patients with ischemic stroke within 48 hours of onset and elevated systolic BP (SBP). Patients were randomly assigned to receive antihypertensive treatment (n=2,038) or to discontinue all antihypertensive medications (n=2,033) during hospitalization. Post-treatment follow-ups were conducted at 3, 12, and 24 months after hospital discharge. The primary outcome was a composite of death and major disability at the two-year follow-up visit.

Results:
At 24 hours after randomization, mean SBP differences (95% CIs) were -8.5 (-10.0 to -7.1), -9.8 (-11.4 to -8.3), and -9.1 (-14.4 to -3.8) mmHg between the treatment and control groups (all P <0.001) for patients with a baseline NIHSS score of 0-4, 5-15, and ≥16, respectively. At day 7 after randomization, the corresponding mean SBP differences were -9.3 (-10.5 to -8.2), -9.1 (-10.3 to -7.8), and -10.1 (-15.1 to -5.1) mm Hg between the treatment and control groups (all P <0.001). The event rates of primary outcome were not statistically significantly different between the antihypertensive treatment group and the control group according to baseline NIH stroke score or Rankin score (Table).

Conclusions:
Among patients with acute ischemic stroke, BP reduction with antihypertensive medications during hospitalization did not reduce or increase the composite outcome of death and major disability over two years according to disease severity at baseline.
Abstract WP455: Intracranial Pressure Monitoring in Patients With Spontaneous Intracerebral Hemorrhage
Authors: Chen Ching-Jen , Ding Dale , Ironside Natasha , Buell Thomas J , Southerland Andrew M , Testai Fernando D , Flaherty Matthew , Walsh Kyle B , Coleman Elisheva R , Woo Daniel , Worrall Bradford B ,   ERICH Investigators
Published: January 2019

Objective:
The role of ICP monitoring in patients with spontaneous ICH is unknown, andthe associated complications may offset its benefits. The aim of the study was to compare the outcomes of ICH patients who underwent ICP monitoring to those who were managed by care-guided imaging and/or clinical exam alone.

Methods:
This was aretrospective, matched cohort analysis from a multicenter, prospective study with recruitment of 3,000 multi-ethnic cases of spontaneous ICH between September 2010 and October 2015. ICH patients with ICP monitoring were propensity-score matched, in a 1:1 ratio, to those without ICP monitoring. The primary outcome was mortality at 90 days. Secondary outcomes were in-hospital mortality, use of hyperosmolar (mannitol or hypertonic saline) therapy, surgical ICH evacuation, length of hospital stay, and the following 90-day outcomes: modified Rankin Scale (mRS) excellent (0-1) and good (0-2), Barthel Index, and health-related quality of life (HRQoL) (EuroQol Group 5-Dimension [EQ-5D] and EQ-5D Visual Analog Scale [VAS] scores).

Results:
The ICP and no ICP monitoring cohorts comprised 566 and 2,434 patients, respectively. The matched cohorts each included 420 patients. The 90-day and in-hospital mortality rates were similar between the matched cohorts. Infection rate was higher in the ICP monitoring cohort (5.7% vs. 1.2%, aOR=5.066, p=0.001).Shift analysis 90-day mRS favored no ICP monitoring (aOR=1.628, p<0.001). The following outcomes were lower in the ICP monitoring cohort: excellent (6% vs. 15%; aOR=0.375, p<0.001) and good (16% vs. 30%; aOR=0.465, p<0.001) outcome, Barthel Index (median 15 vs. 45; aβ=-12.050, p<0.001), EQ-5D score (median 0.178 vs. 0.437; aβ=-0.064, p=0.026), and ED-5Q VAS score (median 40 vs. 50; aβ=-6.662, p=0.004) at 90 days. In a subgroup analysis of patients with admission GCS score ≤8, despite lower EQ-5D scores at 90 days in the ICP monitoring cohort, no difference in 90-day mortality, in-hospital mortality, excellent or good outcome, 90-day of mRS scores, ED-5Q VAS scores, and Barthel Index were observed between the ICP and no ICP monitoring cohorts.

Conclusion:
The findings of this study do not support the routine utilization of ICP monitoring in patients with ICH.
Abstract WP457: Long-Term Outcome of Resuming Anticoagulation Treatment After Anticoagulation-Associated Intracerebral Hemorrhage
Authors: Beckett Lisa , DiCristina Heather , Wagner Thomas , Wright Kathryn , Capone Kellie , Monczewski Maureen , Kester Margaret , Bourdages George , Zand Ramin
Published: January 2019

Background and Purpose:
The risk and benefit of restarting oral anticoagulation (OAC) therapy among patients with atrial fibrillation (AF) and an episode of anticoagulation-associated intracerebral hemorrhage (ICH) remain unclear. Many clinicians and patients prefer not to resume OAC after an OAC-associated ICH. Here, we analyzed the long-term outcome of patients with AF who did or did not resume OAC after an OAC-associated ICH.

Methods:
We studied consecutive patients with AF who were discharged from our institution after an OAC-associated ICH event between 2010 and 2017. Baseline characteristics of patients, past medical history, and history of OAC use were recorded. Outcome measures in our study included recurrent ICH, ischemic stroke or systemic emboli, and death.

Results:
Out of 115 patients with AF and OAC-associated ICH, 93 patients (mean age 76.2 ± 10.3 years [44-91 years old], 54.3% men) were included in this study. Thirty-eight (40.9%) patients resumed OAC after the episode of OAC-associated ICH. There was no significant difference among the group who resumed OAC and the patients who did not, in terms of mean follow-up duration (1.9 vs. 2.4 years), the type of initial ICH, as well as history of hypertension, diabetes, previous ischemic stroke, congestive heart failure, coronary artery disease, and tobacco use. Although the incidence rate of recurrent ICH was higher among patients who resumed OAC compared with those who did not (55 vs. 15 cases per 1000 patient-years), the difference was not significant (relative risk 2.9; 95% CI, 0.3-30.8). The incidence rate of ischemic stroke or systemic emboli was slightly lower among patients who had resumed OAC (69 vs. 76 cases per 1000 patient-years). However, the difference was not significant (relative risk 0.9; 95% CI, 0.3-2.7). The mortality rate among patient who did and did not resume OAC was 96 and 121 per 1000 patient-years, respectively (relative risk 0.8; 95% CI, 0.3-1.9).

Conclusions:
We did not observe any significant difference between the group of patients who resumed OAC and the patients who did not in terms of recurrent ICH, ischemic stroke or systemic emboli, and death. However, there was a tendency towards a higher long-term risk of recurrent ICH among patients who resumed OAC.
Abstract WP460: Use of Red Cell Microparticles to Limit Hematoma Growth Following Intracerebral Hemorrhage
Authors: Rehni Ashish K , Navarro Quero Hever , Bidot Carlos , Shukla Vibha , Koch Sebastian , Perez-Pinzon Miguel , Ahn Yeon , Jy Wenche , Dave Kunjan R
Published: January 2019

Currently there is no effective treatment for spontaneous intracerebral hemorrhage (sICH). Limiting hematoma extension in sICH is an attractive therapeutic target. Earlier studies demonstrated that red blood cell-derived microparticles (RMP) enhance platelet function and accelerate coagulation, augmenting both primary and secondary hemostasis. In the present study, we determined the efficacy of RMP in reducing hematoma expansion in a rat model of collagenase-induced sICH. RMPs were prepared from human RBCs using a high-pressure extrusion method. At ~24 hours post-collagenase injection, neurological scores were evaluated, rats were sacrificed, and the hematoma areas on images of brain sections were measured. In an earlier study (presented in an abstract form) we determined optimal RMP dose required to lower hematoma growth following sICH. The hematoma volume was lower by 17, 40 (p<0.001 vs placebo group), and 6% in low dose (7.19 x 10
9
particles / kg b.w.), medium dose (2.55 x 10
10
particles / kg b.w.), and high dose (9.48 x 10
10
particles / kg b.w.) treated groups when compared to placebo group, respectively. For those experiments, total RMP dose was delivered over 2 hours using continuous infusion starting 1 h post-collagenase injection. In the present study we evaluated optimal treatment paradigm using optimal protective (medium) dose as identified above. We evaluated the efficacy of RMP when delivered starting at 1 h post-collagenase injection either via four bolus injections (6.375 x 10
9
particles / kg b.w. per injection) 30 min apart (paradigm B) and when delivered using continuous infusion (2.55 x 10
10
particles / kg b.w.) over 1 hour (paradigm C), and compared with when RMP dose was delivered (2.55 x 10
10
particles / kg b.w.) over 2 hours using continuous infusion (paradigm A). We observed that hematoma volume (mm
3
) for vehicle, and paradigm A, B and C was 71 ± 3 (n = 35), 43 ± 2 (n = 10, p<0.001 vs vehicle), 60 ± 4 (n = 15, p = 0.057 vs vehicle), and 61 ± 4 (n = 15, p = 0.073 vs vehicle), respectively. We observed that neurological score was lower (all p<0.001) in paradigm A (9.3 ± 0.4, n = 10), B (8.7 ± 0.3, n = 15), and C (9.5 ± 0.4, n = 15) groups as compared to placebo group (10.9 ± 0.1, n = 35). Our results indicate that RMPs have potential to lower hematoma growth in sICH patients.
Abstract WP472: Post Alteplase Patient Care ICU vs. a Stroke Unit
Authors: Stilwell Kathy H , Chelf Keri
Published: January 2019

Not all patients who receive Alteplase need to go to the ICU. They can be safely cared for on a Stroke unit with nurses who have been trained to take care of them and have knowledge of stroke. Due to our lack of ICU beds, many times they would end up holding in emergency room. Our Stroke unit nurses were trained in caring for an Alteplase patient in the first twenty four hours. Education was done on Alteplase, Nicardipine, bedside monitors, blood pressure protocols, angioedema treatment, hemorrhagic transformation, how often to take vital signs. By placing the patient directly on the Stroke unit, physical therapy and therapies were initiated on day one. Improved communication and stroke education was demonstrated with patient and family. Data showed that by placing patient on the stroke unit, length of stay was decreased by one day with a cost savings of $2100/day, no missed vital signs or stroke scales and there were no safety concerns.