bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 2275: Frailty Independently Predicts Poor Outcomes But Not Quality Of Care: An Analysis Of VA Ischemic Stroke Patients
Authors: Haque Sulsal , Reeves Mathew J , Ofner Susan , Ordin Diana , Williams Linda S , Bravata Dawn
Published: March 2022

Background:
Frailty is a geriatric syndrome characterized by progressive multi-system physiologic decline that is difficult to operationalize clinically. Frailty indices which represent an accumulation of age-related deficits are one method of quantifying frailty, but have not been applied to stroke patients. Our objectives were to create a frailty index (FI) and determine its independent contribution to mortality, discharge disposition and quality of care in ischemic stroke patients.

Methods:
Chart abstraction data were obtained on a sample of 3965 patients admitted with ischemic stroke to 131 VA hospitals in 2007. Data on 38 deficits were used to create a FI that included: co-morbidities (e.g. previous stroke, MI, diabetes), pre-stroke function (e.g. ambulatory status, functional independence measure), social history (e.g. alcohol, smoking, living alone) and first admission lab values (e.g. creatinine, glucose). The FI (expressed as a %) was calculated for each subject as the number of deficits divided by the maximum number (n=38). Multiple logistic regression models were used to determine the independent effect of FI on in-hospital mortality and discharge home, while adjusting for age, sex, and NIHSS. Quality of care was defined by a composite compliance score expressed as a percent of 14 pre-determined quality indicators; a multivariable linear regression model was used to determine the independent effect of FI on the composite score, after adjusting for age, sex, and NIHSS.

Results:
The mean FI was 15%. In-hospital mortality was 5% and 70% of patients were discharged home. Multivariable logistic regression results (
Table 1
) showed that for every 1% increase in the FI, the odds of dying in hospital increased by 4% (p=0.0003) independent of age, sex and NIHSS. Similarly for every 1% increase in the FI, the odds of being discharged home was 3% lower (p <0.0001). Results of the multivariable model of quality of care showed that there was no significant relationship between frailty and the composite compliance score. (p=0.34)

Conclusions:
Higher FI scores were associated with increased in-hospital mortality and decreased likelihood of going home, independent of age, sex and NIHSS. However quality of care was not affected by frailty. Further work is required to define the relationships between frailty and stroke outcomes and quality of care. A FI based measure of frailty could provide added information to stroke prognostic models and assessments of quality of care processes.
Abstract 2278: Factors Associated with the Levels of Circulating Endothelial Progenitor Cells in Patients with Acute, Subacute and Chronic stroke.
Authors: Martí-Fàbregas Joan , Delgado-Mederos Raquel , Crespo Javier , Dinia Lavinia , Peña Esther , Fernández Ana , Pérez Jesús , Martínez-Ramírez Sergi , Jiménez-Xarrié Elena , Marín Rebeca , Badimon Lina , RENEVAS
Published: March 2022

Introduction
In patients with ischemic stroke, the levels of circulating Endothelial Progenitor Cells (EPCs) have been infrequently studied. Our study was focused on investigating the EPC counts in patients with acute, subacute and chronic ischemic stroke and analyzing the associated variables.

Methods
We prospectively studied consecutive patients with ischemic stroke within the first 48 hours from symptoms onset. We evaluated demographic data (age, sex); classical vascular risk factors (high blood pressure, diabetes mellitus, hypercholesterolemia, coronary artery disease, peripheral vascular disease, previous ischemic stroke, smoking, alcohol abuse, obesity, number or risk factors); thrombolysis; treatment with statins before and after stroke; etiology (sss-TOAST criteria); severity of the neurological deficit (NIHSS score). Blood samples were collected at baseline (n=146), day 7 (n=121) and day 90 (n=92) after stroke onset. EPCs were measured by flow cytometry within 30 minutes after blood collection. We considered that a cell was an EPC when it was labeled for the following 3 markers: CD34, AC133 and KDR. EPC counts were adjusted for the lymphomonocytic population in each sample and expressed as %. Statistics: Non-parametric bivariate analyses, logistic regression analysis.

Results
We included 146 patients (mean age 70.8±12.2 y, 63% men). In the baseline sample, the following variables were associated with the EPCs count: alcohol abuse (p=0.08), hipercolesterolemia (p=0.029), pre-treatment with statins (p=0.015) and etiology (p=0.037). There were no variables associated with the EPCs count at 7 days. Variables associated with the EPCs count at 3 months were: treatment with statins after stroke (p=0.017), old cerebral infarction (p=0.059) and obesity (p=0.029). The multivariate analysis showed that pre-treatment with statins (OD 3.11, 95%CI 1.34-7.19, p=0.008) and stroke of unknown etiology (p=0.032) independently predicted higher EPC counts at baseline. No variables were independently associated with EPCs counts at 7 days. Finally, at day 90, treatment with statins after stroke was the only variable independently associated with higher EPC counts (OR 11.7, 95%CI 1.5-86, p=0.016).

Conclusion
In conclusion, prior treatment with statins and stroke etiology are predictors of EPC counts in patients with acute ischemic stroke, while treatment with statins after stroke is independently associated with EPC count at 3 months. The increase in EPCs may be one of the pleiotropic effects of statins that improve the outcome of patients with ischemic stroke.
Abstract 2279: Ethnic Comparisons in Pre-Stroke Awareness and Treatment of Hypertension in Stroke Subjects: Modification by SES and Acculturation
Authors: Levine Deborah A , Morgenstern Lewis B , Langa Kenneth M , Skolarus Lesli E , Smith Melinda A , Lisabeth Lynda D
Published: March 2022

Background and Objectives:
Mexican Americans (MAs) have higher stroke incidence rates than non-Hispanic whites (NHWs). Ethnic differences in the pre-stroke treatment of risk factors could potentially explain this disparity and may be exacerbated by low socio-economic status or less acculturation. We assessed pre-stroke awareness and treatment of hypertension by ethnicity, education and English proficiency in a population-based stroke surveillance project.

Methods:
Among 1,111 stroke subjects aged ≥45 years in the Brain Attack Surveillance in Corpus Christi (BASIC) project from 01/2000-06/2006, we examined pre-stroke hypertension prevalence (medical record documentation of hypertension diagnosis) at the time of the index stroke by ethnicity (MA vs. NHW). Among those with prevalent hypertension, we measured awareness (self-report of hypertension) and treatment (self-report of anti-hypertensive medication use). We first compared awareness and treatment of hypertension by ethnicity overall. We then compared ethnic differences in awareness and treatment of hypertension using 2 approaches: 1) after stratification by education (<high school vs. ≥high school); and 2) after dichotomizing MAs by self-reported language fluency. Limited English proficiency (EP) was defined as Spanish only (less accultured) and EP was defined as English only/bilingual (more accultured).We adjusted associations for age, gender, education, diabetes, coronary artery disease, and previous stroke using logistic regression.

Results:
MAs (mean age 68.3 ± 12.1 years; n=566) were more likely than NHWs (mean age 74.4 ± 11.7 years; n=545) to report <high school education (71% vs. 23%; P<0.001). Thirty-two percent of MAs reported limited EP. Hypertension prevalence was 74% in both MAs and NHWs. There was a trend toward MAs having greater awareness than NHWs (89% vs. 85%; P=0.15) but similar treatment (89-90%) of hypertension. Among high school graduates, we found non-significant trends toward greater awareness but less treatment of hypertension in MAs compared with NHWs (
Figure 1
). Compared with MAs with EP, NHWs and MAs with limited EP had less awareness of hypertension but similar treatment (
Figure 2
). After adjustment for socio-demographics and co-morbidities, differences in hypertension awareness were no longer significant (NHWs: aOR, 0.96; 95%CI, 0.52-1.79; MAs with limited EP: aOR, 0.57; 95%CI, 0.27-1.19; MAs with EP: referent).

Conclusion:
We found little evidence that differences in pre-stroke awareness and treatment of hypertension may explain ethnic disparities in stroke.
Abstract 2304: The Use of Teleneurology Consult for Stroke Care in a Rural Community Hospital
Authors: Kueider Sandra , Eastwood Julie S
Published: March 2022

Background and Issues
Management of acute strokes in our rural facility involved the attending physician telephoning for consultation with a neurologist to determine treatment and/or transfer options since we did not have 24/7 neurology coverage. Based on chart review over a period of 6 months, the turn-around time from ED physician call to neurologist returning the call was approximately 22 minutes. However, the neurologist must make a recommendation based on the relation of the ED physician information without visualization of the patient. Prior to the implementation of the teleneurology program our data collection spanned from April 1, 2009-September 30, 2009. There were 60 patients who had a diagnosis of stroke presenting to our ED. Of those 60 patients: 2 hemorrhagic, 38 ischemic and 30 TIA. Of those 60 patients, 20 had neurology consult, 40 did not, and 3 of the 60 received tPA. 6 had a NIH scale documented and 10 had a Glasgow Coma Scale documented (5 of 10 also had the NIH scale).

Purpose
The telemedicine program at our facility was initiated to offer all patients presenting to the ED with stroke symptoms to timely and effective treatment. The technology would allow the neurologist to view the patient information, CT reports, speak to and visualize the patient, formalizing the consult and treatment responsibility for the patient in a very short amount of time.

Methods
Our facility uses the telemedicine program Specialist on Call (SOC). Patients presenting with stroke-like symptoms are all candidates for use of teleneurology consultation. The ED physician consults the SOC neurologist with a guaranteed call back time of 15 minutes. After consult, the neurologist makes recommendation to the ED physician. The patient is either admitted to our facility or transferred to our sister hospital where the Stroke Center is located. The SOC neurologist would also determine tPA administration.

Results
Since implementation of the teleneurology program May 16, 2011 there have been 25 patients diagnosed with stroke, 14 were SOC cases, none recommended to receive tPA. ED physician call to specialist consult time has decreased to 15 minutes or less. We have also seen a decrease in transfers.

Conclusions
Implementation of the teleneurology program at our rural hospital as provided our community access to 24/7 neurological consultation. Patients/families that have been involved with the SOC program expressed great satisfaction the program.
Abstract 2308: Timing Of Intra-arterial Cell Transplantation Drastically Affects The Behavior Of The Transplanted Cells And Functional Recovery After Stroke
Authors: Ishizaka Shunsuke , Horie Nobutaka , Satoh Katsuya , Nagata Izumi , Nishida Noriyuki
Published: March 2022

Background and Purpose-
Intra-arterial delivery of human bone marrow stromal cells(hBMSCs)results in a migration of the greater number of cells compared to intra-venous delivery in an acute stage after stroke. However, it remains unclear how the timing of intra-arterial administration affects the cell migration, repair process and functional recovery. In this study, we test the hypothesis that the timing of intra-arterial cell transplantation changes the behavior of the transplanted cells and host environment, which is very important to achieve the optimal effect of transplantation.

Methods-
Sprague-Dawley rats (8week, 270∼300g) received 1X10
6
hBMSCs injected intra-arterially via polyethylene catheter at 1, 4 and 7 days (Day1,4 and 7 group) after 75 min middle cerebral artery occlusion following reperfusion. At the time point of transplantation, regional cerebral blood flow (rCBF) of ischemic core and periinfarct area was examined with transcranial laser Doppler flowmetry (LDF). Animals were sacrificed at 3 and 21 days after transplantation to assess the distribution of the cells, vascular density and final infarct volume with immunohistochemistry. Behavior assessment was also performed until 21 days after stroke.

Results-
In the periinfarct area of cerebral cortex, the number of hBMSCs was significantly greater in Day4 group than that in Day 1 group (
p
=0.0001). On the other hand, there was no significant difference between Day1 and 4 groups in the periinfarct area of striatum. Fewer cells were found in both areas in Day 7 group. In Day1 group, the majority of hBMSCs migrated at ischemic core of cerebral cortex and striatum. rCBF of the ischemic core in cortex was the greatest in Day1 group. Otherwise, rCBF of the periinfarct area in cortex was the greatest in Day4 group. The number of hBMSCs was correlated with rCBF of each area. In Day1 and 4 groups, animals showed a significant increase in vascular density in the periinfarct area of cerebral cortex. However, a reduction of infarct volume and neurological recovery were seen in only Day1 group, but not in Day4 and Day7 group.

Conclusions-
Our results suggest that the change of host cerebral hemodynamics after stroke drastically affect the distribution of hBMSCs, which delivered intra-arterially. It is important to establish the optimal timing of intra-arterial delivery of stem cells after stroke.
Abstract 2314: Selecting Endovascular Treatment Strategy According to the Location of Intracranial Occlusion in Acute Stroke
Authors: PAGOLA JORGE , RUBIERA MARTA , FLORES ALAN , RODRIGUEZ-LUNA DAVID , PIñEIRO SOCORRO , QUINTANA MANOLO , ALVAREZ-SABIN JOSE , MOLINA CARLOS A , RIBO MARC
Published: March 2022

Background Intra-arterial thrombolysis (IAT), with or without mechanical clot disruption, used to be the first line endovascular treatment strategy in acute stroke. However, the use of costly retrievers (RET) is progressively taking over despite the lack of comparative studies. Methods Acute stroke patients with confirmed ICA or MCA occlusion who underwent endovascular therapy were prospectively included in our database. Before retrievers were available patients were treated with IA-tPA up to 20mg plus guidewire mechanical clot disruption: IAT group. After retrievers were available in our Center patients were primarily treated with a Merci®, Solitaire® or Trevo® according to availability and physician preferences. Recanalization (REC) was considered when TIMI score was ≥2a on final angiogram. The primary outcome, dramatic clinical improvement (DCI), was defined as a ≥10 points decrease in NIHSS score from baseline to discharge or 7 days. Symptomatic intracranial hemorrhage (SICH), long-term outcome (mRS≤2) and mortality were also analyzed. Results Of the 136 included patients (76 MCA, 57 ICA), 92 (67%) received IAT and 45 (33%) RET (8 Merci, 20 Solitaire, 13 Trevo, 4 Multiple). There were no differences in baseline clinical characteristics including stroke severity, groin-to-REC and onset-to-REC times (table).There were no significant differences in REC rate (IAT 74.4% Vs RET 78%; p=0.082), rate of DCI (35.4% Vs 48.5%; p=0.21), SICH (7% vs 8%, p=0.84), clinical long-term outcome (27% vs 35%, p=0.45) or mortality (32% vs 28%, p=0.72). Among patients with TICA occlusions (28 IAT, 15 RET), DCI rate was significantly higher in the RET group compared to the IAT group (IAT 33% Vs RET 67%; p=0.031). The number needed to treat (NNT) to achieve one additional DCI patient with RET compared to IAT was 20 for MCA occlusions, and only 3 for TICA occlusions. Conclusion In major anterior circulation stroke patients, IAT and RET showed similar results in terms of safety and efficacy. The IAT approach should not be prematurely discarded. However, in patients with TICA occlusions, Retrievers may be considered as the first therapeutic option.
Abstract 2316: Benefits Of Clinical Trial Participation For Risk Factor Control: Experience From The SPS3 Study
Authors: Lau Helena , White Carole , Coffey Christopher , Romero Jose , Pikula Aleksandra , Babikian Viken , Kase Carlos , Benavente Oscar
Published: March 2022

Objective:
To assess for unplanned effects of trial participation as measured by changes in smoking, alcohol use, and exercise.

Background:
Trial effect is a non-specific element of trial participation that has been difficult to quantify. Recent trials are beginning to measure this with promising results. The SPS3 study tests the effects of antiplatelet therapy and intensive blood pressure control on stroke recurrence and cognitive decline. The protocol does not mandate interventions for modifying lifestyle behaviors but local study investigators provide guidance for these changes at their discretion. This provides an opportunity to evaluate a “trial effect”, beyond the study interventions.

Design/Methods:
SPS3 subjects who completed at least one 3-month visit were included (n=2935). Definitions used by CDC for risk factors were applied to SPS3. Hypothesis tests were performed to determine differences between SPS3 group at baseline and general population (CDC, n=210000). Kaplan-Meier plots were used to determine time from baseline to behavior changes. Log-rank tests were performed to determine influence of age, gender, education, and ethnicity in risk factor outcomes.

Results:
At baseline, smoking status was comparable between SPS3 and CDC groups (19.9%, 20.6% respectively); alcohol use was significantly lower (27.9%, 52% respectively); and exercise was comparable (50.8%, 48.8% respectively). Of the 583 smokers at baseline; 323 (55%) stopped while 152 (47%) restarted over the mean follow-up of 36 months. Of the 820 regular alcohol users at baseline, 536 (65%) stopped while 278 (52%) restarted again. Of the 1444 who did not exercise at least 3 times per week at baseline, 1209 (84%) started while 855 (71%) stopped again. There were no significant differences in these three health behaviors by age, gender, education, or race. A marginally significant effect by age was observed related to alcohol. Subjects ≤64 yr old at baseline were more likely to stop regular alcohol use than those >64 (p=0.054).

Conclusion:
Independent of the study intervention, SPS3 participants significantly modified their health behaviors. Our findings suggest that it is important to address trial effect and its impact on the outcomes.
Abstract 2329: A Randomized Double Blind, Placebo controlled Phase 1a Clinical Trial of THR-18, a PAI-1 Derived peptide, in Normal Volunteers
Authors: Leker Ronen R , Aharon Arnon , Nimrod Rami , Lamensdorf Itschak
Published: March 2022

Background:
THR-18 is an 18-mer peptide derived from the sequence of human plasminogen activator inhibitor 1 (PAI-1) that has the ability to bind at the docking site of tissue plasminogen activator (tPA) and not to its catalytic site, thereby uncoupling the beneficial clot-dissolving properties of tPA from its deleterious non-fibrinolytic effects. THR-18 is being developed as an adjunct to tPA in the treatment of acute ischemic stroke and aims to address some of the limiting properties of tPA such as limited response rate, relatively high re-occlusion rate, limited safety profile and short therapeutic window.

Methods:
this was a phase 1a randomized double blind, placebo controlled study aiming to asses the safety of THR-18 in healthy volunteers. Subjects were treated in five different dose and dose regimen tiers of THR-18 or placebo and were carefully monitored for the occurrence of any side effects. The pharmacokinetics profile of THR-18 in serum was also studied.

Results:
Pharmcokinetic studies for bolus administration of THR-18 showed a linear Cmax with a half-life of 3-7 minutes. Administration of THR-18 as a 10% bolus followed by continuous drip of the remaining 90% over 60 minutes resulted in stable plasma concentrations over 60 minutes. THR-18 was well tolerated with no severe or serious adverse events at doses of 0.25-1 mg/kg. At the dose of 0.5mg/kg and 1mg/kg, a slight and transient drop in blood pressure with orthostatic hypotension was noted.

Discussion:
THR-18 appears to be safe and well tolerated in healthy volunteers at doses up to 1 mg/kg. Following the encouraging safety results of THR-18 a phase 1b/2a study assessing the safety of THR-18 in stroke patients is currently ongoing.
Abstract 2332: Prestroke Physical Activity And Functional Recovery In Patients With Ischemic Stroke And Arterial Occlusion (africa Study)
Authors: Ricciardi Ciocchini Ana Clara , Pérez de la Ossa Herrero Natalia , Sobrino Moreiras Tomás , Millán Torné Mónica , Prat Sánchez Luís , Almendrote Muñóz Miriam , Gomis Cortina Meritxell , Reverté Villarroya Silvia , Dorado Bouix Laura , López-Cancio Martínez Elena , Arenillas Lara Juan Francisco , Dávalos Errando Antonio
Published: March 2022

Objective:
AFRICA study aims 1) to investigate the association between prestroke physical activity (PhA) and short-term functional outcome in patients with an acute anterior territory arterial occlusion and 2) to study its relationship with long-term functional recovery and biological signatures of neurorepair. This analysis focuses on the first objective.

Methods:
Prestroke PhA was measured with the international physical activity (IPQ), METS and PASE questionnaires in patients with an acute middle cerebral artery (MCA) or terminal intracranial carotid artery (TICA) occlusion of less than 8 hours duration detected by transcranial Duplex. Primary variable was good functional outcome at 3 months (Rankin scale ≤ 2). Secondary variables were hemorrhagic transformation (HT) at 24-36h, infarct volume at day 30 and early recanalization in patients treated with i.v. tPA (TIBI 4 o 5 within 2h after bolus).

Results:
We studied 159 consecutive patients. Mean age was 68 and median NIHSS 17); 96 patients were treated with i.v. tPA and 55 with mechanical thrombectomy, in 28 cases after failed i.v. tPA and in 27 cases as a first choice, whereas 36 patients did not receive reperfusion therapies. The 3 PhA scales were highly correlated (coeff. >0.97), so we selected IPQ for our purpose. Compared to patients with low level (group A, n=69) and medium level (group B, n=45) of PhA, patients with high level of PhA (group C, n=45) were younger, (median age 76/72/65 for A/B/C), showed lower systolic BP, stroke severity (median NIHSS, 20/14/11), and frequency of TICA occlusion (35%/2%/4%) (all p<0.001). Intravenous tPA was given in 29%/53.3%/53.3% (p 0.032), whereas mechanical thrombectomy alone (17%/16%/18%) or in combination with i.v. tPA (19%/16%/18%) was comparable. The higher the level of PhA the higher the rate of good functional outcome (4%/69%/89%) and early recanalization after i.v. tPA (0%/35%/62%), and the smaller the volume of infarction (107/9/5 cc) (all p<0,001). No differences were found in the rate of HT. Adjusted OR of good outcome was 170 [18-1591] for group C and 62 [8-455] for group B compared to the reference group (A) after adjusting for age, NIHSS score, serum glucose, systolic BP and postprocedural (i.v or i.a) recanalization.

Conclusion:
Prestroke PhA is associated with better short-term functional outcome and higher rate of recanalization after i.v. tPA in patients with acute ischemic stroke. These effects are robust, but a confounding bias cannot be ruled out due to imbalances in some prognostic baseline variables.
Abstract 2333: The Role Of Extrasynaptic NMDA Receptor In Mediating Neuronal Survival- And Death-related Signaling
Authors: Zhou Xianju , Soellner Deborah , Nunez Jopseph , Wang Hongbing
Published: March 2022

The N-methyl-D-aspartate receptors (NMDARs) play an important role in synaptic plasticity and excitotoxicity. Physiological activation of NMDARs is associated with synaptic plasticity and neuronal survival, whereas excessive activation of NMDARs contributes to neuronal death. Previous studies suggest that activation of synaptic NMDARs promotes neuronal survival. In contrast, activation of extrasynaptic NMDARs results in neuronal cell death. However, the precise roles of NMDARs at different subcellular locations are not completely understood. Here we present new evidence that activation of extrasynaptic NMDARs alone does not cause neuronal death; whereas co-activation of extrasynaptic and synaptic NMDARS does. Specifically, after blocking synaptic NMDARs with MK801 and bicuculline, higher concentration of NMDA or glutamate activated extrasynaptic NMDARs, but did not lead any significant neuronal death in DIV14 or much older cultures. Consistently, 75 min oxygen glucose deprivation, a cellular ischemic stroke model, did no cause any obvious neuronal death after blockade of synaptic NMDARs. In contrast, without pretreatment of bicuculline and MK801, oxygen glucose deprivation induced 73.6 % cell death. Additionally, we obtained the same conclusion with another protocol, a combination of low dose of NMDA (15 μM, supposed to activate only synaptic NMDARs) and MK801, to block synaptic NMDARs. Further, we show that activation of either synaptic or extrasynaptic NMDARs promoted neuronal survival signaling and did not disturb intracellular calcium homeostasis. However, co-activation of synaptic and extrasynaptic NMDARs led to shut-off of neuronal survival signaling, triggered neuronal death signaling, and disturbed intracellular calcium homeostasis. More importantly, by examining NMDAR-related survival signaling and calcium signaling, we found that activation of extrasynaptic NMDARs requires a higher concentration of ligand, suggesting that extrasynaptic NMDARs have a relative lower ligand affinity compared to synaptic NMDARs. These findings will provide new evidence on the role of extrasynaptic NMDARs, and suggest a new direction for designing neuroprotective drugs to selectively block extrasynaptic NMDARs while leaving synaptic NMDAR functions intact.
Abstract 2339: Predictors of Warfarin Use in Atrial Fibrillation in the United States
Authors: Coleman Craig I , Baczek Victoria L , Chen Wendy T , Kluger Jeffrey
Published: March 2022

Introduction:
Warfarin has been shown to be highly efficacious in preventing stroke in patients with atrial fibrillation (AF), yet it is still vastly underused for this purpose in the United States (US).

Objective:
To perform a meta-analysis to evaluate the association between prescriber and/or patient characteristics and subsequent prescription of warfarin for stroke prevention in patients with AF.

Methods:
Observational studies conducted only in the US using multivariate analysis to determine the relationship between prescriber and/or patient characteristics and the odds of receiving warfarin for stroke prevention in AF were identified from searches in the MEDLINE and EMBASE (1996-October 2010), as well as a manual review of references. Estimates of effect of prescriber and/or patient characteristics from individual studies were pooled to calculate summary odds ratios (ORs) with 95% confidence intervals (CIs) using a random-effects model.

Results:
Twenty-eight studies reporting the results of 33 unique multivariate analyses were identified. Warfarin use across included studies ranged from 9.1%-79.8%, with a median of 49.1%. There was a moderately strong correlation between increased warfarin use and time (r=0.60, p=0.002). Upon meta-analysis, characteristics associated with a statistically significant increase in the odds of warfarin use included history of cerebrovascular accident (OR=1.59, 95%CI 1.15-2.18), congestive heart failure (OR=1.36, 95%CI 1.18-1.57), and male gender (OR=1.12, 95%CI 1.04-1.21). Those associated with a statistically significant reduction in the odds of warfarin use included alcohol or drug abuse (OR=0.62, 95%CI 0.40-0.96), perceived barriers to compliance (OR=0.87, 95%CI 0.76-0.99), contraindication(s) to warfarin (OR=0.81, 95%CI 0.69-0.96), dementia (OR=0.32, 95%CI 0.14-0.75), falls (OR=0.60, 95%CI 0.43-0.85), gastrointestinal hemorrhage (OR=0.47, 95%CI 0.40-0.55), intracranial hemorrhage (OR=0.39, 95%CI 0.28-0.55), hepatic impairment (OR=0.59, 95%CI 0.50-0.70), renal impairment (OR=0.69, 95%CI 0.60-0.80), older compared to younger age (OR=0.57, 95%CI 0.39-0.82) and age per 10-year increase (OR=0.78, 95%CI 0.68-0.90).

Conclusion:
Warfarin use appears suboptimal, but has improved somewhat over time. Evidence suggests that the decision to prescribe warfarin for stroke prevention in patients with AF is based upon multiple prescriber and patient characteristics.
Abstract 2349: Atrial Fibrillation or Flutter is Found in 45.4% of Elderly Patients with Nonhemorrhagic Stroke
Authors: Haft Jacob I , Teichholz Louis E
Published: March 2022

The incidence of stroke in patients(pts) with diagnosed atrial fibrillation or flutter (AF) is well known but, because AF that is associated with stroke may be intermittent and not diagnosed, the role of AF in pts with nonhemorrhagic stroke remains unclear. To obtain data on the importance of AF in ischemic stroke pts we reviewed the clinical records and all the ECGs in a 14 year institutional data base of all pts admitted with nonhemorrhagic stroke to HUMC from 1/1/2005 to 12/31/2007. To determine if AF is more frequently the cause of stroke in the elderly we studied the nonhemorrhagic stroke pts ≥ 75 Y.O. and determined the incidence of CHADS2≥2 and of echo abnormalities in these elderly pts. Of 987 pts with ischemic stroke 310 pts (31.4%, 95% confidence limits 28.6, 34.4) had AF. Of these 987, 529 pts were ≥75 years of age; 240 of these elderly stroke pts had AF (45.4%, CL 41.2, 49.6). This was significantly more than the 15.2% incidence of documented AF in pts < 75 (p<.0001). In the pts ≥75 who had AF, CHADS2 was ≥2 in 220 pts, 91.67% (CL 87.5,94.5); 17 of the remaining 20 pts had echocardiograms and 12 had left atria or left ventrcular enlargement or ejection fraction <50%. Hence 97.89 % of these elderly stroke pts with AF had CHADS 2 or echo abnormalities. These findings that AF is found in over 31% of ischemic stroke pts suggests that AF is more commonly the cause of, or mechanism for ischemic stroke than previously thought, especially in the elderly with over 45% of stroke pts over 74 having AF. AF and associated emboli may be the mechanism whereby the stroke risk factors (hypertension, heart failure, diabetes and advanced age) cause stroke. Because the diagnosis of AF made from the ECG database was serendipitous and not prospective, it is likely that the incidence of AF is even higher. In pts with intermittent AF the frequency of episodes and time in AF increase as they age; the serendipitous diagnosis of intermittent AF from an ECG data base is less likely in younger pts. The finding that 91% of these elderly stroke pts with AF had CHADS2 abnormalities supports the value of this index in determining which pts should be anticoagulated. By adding the presence of echo abnormalities we have defined the population of AF pts that includes 97.9% of the pts who may go onto stroke and who will benefit from anticoagulation. Nonhemorrhagic stroke pts with these risk factors who do not have diagnosed AF should be meticulously studied to rule out AF, since anticoagualtion in pts found to have AF will markedly lessen the incidence of a recurrent stroke.

Conclusions:
AF is very commonly found in pts with nonhemmorrhagic stroke, especially in the elderly, and is probably the mechanism whereby many of the stroke risk factors cause stroke. Stroke pts with CHADS2≥2 or echo abnormalities who have not had AF diagnosed should be meticulously studied for occult intermittent AF so they can receive anicoagulation to prevent a further stroke.
Abstract 2351: Poor Quality of Life and Low Social Support are Predictive of Depressive Symptoms in Chronic Stroke
Authors: Taylor-Piliae Ruth E , Coull Bruce M
Published: March 2022

Background:
Depression is a common yet often unrecognized consequence of stroke, affecting between 20-50% of all survivors. Reported underlying factors affecting depression in acute and chronic stroke include: functional disability, lesion location, time since stroke, female gender, age, cognitive impairment, history of major depression, low social support, poor quality of life, and inferior sleep quality.

Purpose:
To examine potential independent predictors of depressive symptoms in chronic stroke.

Methods:
Cross-sectional design using baseline data from the first 100 community-dwelling stroke survivors enrolled in an exercise intervention study. Eligible subjects included men and women aged ≥ 50 years and at ≥ 3 months post-stroke. Prior to their baseline study visit; subjects completed a comprehensive, self-administered health survey including medical history and valid/reliable questionnaires: Center for Epidemiological Studies Depression (CES-D) scale, Multidimensional Scale of Perceived Social Support, Medical Outcomes Study SF-36, and Pittsburgh Sleep Quality Index. At the baseline visit, functional disability (Modified Rankin Scale), and cognitive impairment (Mini-Mental Status Exam) were assessed using standardized procedures. Multiple linear regression was conducted to explore potential independent predictors of depressive symptoms.

Results:
Subjects (n=100) were on average 70±10 years old, and 39±49 months post-stroke. The majority reported an ischemic stroke (68%), were married (59%), White/European-American (78%), men (54%), college-educated (79%), and annual income ≥$50,000 (32%). Hemiparesis was common (right-side=39%, left-side=42%). A total of 35% of subjects had a CES-D scores ≥16, with 21% reporting a history of major depression. Approximately 64% of the variance in depressive symptoms, could be explained by the optimal combination of the independent variables in the model: functional disability, lesion location, time since stroke, gender, age, cognitive impairment, history of major depression, social support, quality of life, and sleep quality (R
2
=0.64, F
12,87
=12.97, p<0.01). Only poor quality of life (t
1,87
=-6.99, p<0.01) and low social support (t
1,87
=-2.14, p=0.04) contributed uniquely and significantly to the severity of depressive symptoms among these stroke survivors.

Conclusion:
Depressive symptoms are prevalent in chronic stroke survivors, even among an educated and economically advantaged population. Our findings are similar to reports by others that poor quality of life and low social support are major contributors to depressive symptoms in chronic stroke; and should be routinely assessed and monitored to improve long-term rehabilitation efforts, promote wellness and community reintegration.
Abstract 2361: Comparison of Ageing-related White Matter Lesion Quantification by Volume and Visual Rating Scores
Authors: Valdes-Hernandez Maria D , Morris Zoe , Royle Natalie A , Munoz Maniega Susana , Dickie David A , Aribisala Benjamin S , Bastin Mark E , Deary Ian J , Wardlaw Joanna M
Published: March 2022

Background:
White matter lesions (WMLs) increase with age and are associated with stroke, cognitive decline and dementia. WMLs can be quantified by visual rating scores, or by computational measurement of WML volume, but the concurrence between these two methods has not been widely studied. We compared WML visual ratings and computed volumes to determine agreement and sources of disagreement.

Methods:
We used subjects from the Lothian Birth Cohort 1936 who had brain MRI. We rated WMLs visually on FLAIR using the Fazekas scale and measured WML volume using a validated multispectral image fusion technique: MCMxxxVI (
sourceforge.net/projects/bric1936
). We summed the deep and periventricular Fazekas scores and calculated the correlation between the total Fazekas score (0-6) and WML volume (Spearman's ρ). We sought explanations for outliers, such as stroke lesions.

Results:
Amongst 672 subjects with full brain imaging data, the median Fazekas score was 2 and the median WML volume was 7.7 ml (IQR 13.6ml). The Fazekas score and WML volume were highly correlated (Spearman ρ=0.73, p<0.001). Including stroke lesions, most of which were small but which can inflate WML volume values, gave a similar correlation (Spearman ρ=0.75, p<0.001). In 114 subjects (17% of the total) the z-scores of WML volume and Fazekas rating differed by >1, most of whom had a total Fazekas score of 1 (n=26, WML volume:0-14.8ml) or 2 (n=63, WML volume:0-34.37ml). The main reasons for disagreements were: 1) subtle WMLs visually identified which were omitted from the WML volume; 2) prominent periventricular caps with thin ventricular body lining obtaining a Fazekas periventricular score of 1 or 2 but a large WML volume; and 3) small deep white matter focal lesions which increase disproportionally the score obtained in the rating scale if they are beginning to coalesce but add little to the WML volume which may range from <0.5 to >12ml.

Conclusions:
WML visual rating and volumes show high correlation, but subtle WMLs and two features that are not well differentiated in the WML score weakened the agreement. Methods to improve computational WML quantification (e.g. adaptive filtering) would improve measurement of subtle WML areas. Consideration should be given to modifying WML scores to differentiate ventricular caps from other periventricular lesions and small but early coalescent from larger deep WMLs.
Abstract 2363: Are White Matter Lesions Associated with Deep or Superficial Brain Atrophy or both?
Authors: Aribisala Benjamin S , Valdes Hernandez Maria C , Royle Natalie A , Maniega Susana M , Bastin Mark E , Deary Ian J , Wardlaw Joanna M
Published: March 2022

Introduction
White matter lesions (WMLs) are associated with cognitive decline, dementia and increased risk of stroke. Cerebral atrophy is also associated with future cognitive impairment and dementia. Both WMLs and atrophy are commonly found on MRI scans of elderly people, but whether they are related, and the strength of any relationship remains unclear.

Hypotheses
We hypothesised that 1) WMLs are associated with brain atrophy, 2) are more associated with deep (white matter) than superficial (cortical) atrophy, and 3) the association is similar for volumetric and visually rated WMLs.

Methods
We performed structural brain MRI on subjects from the Lothian Birth Cohort 1936 (
www.lothianbirthcohort.ed.ac.uk
) and measured intracranial (ICV), brain tissue (BTV), CSF ventricular, superficial subarachnoid space (SSS), grey matter (GM), normal appearing white matter (NAWM) and WML volumes using validated software (MCMxxxVI,
http://sourceforge.net/projects/bric1936/
). We also measured CSF + venous sinuses (V) + dural (D) volume (CSF+V+D) combined to further assess ICV changes due to brain atrophy and rated WMLs using the Fazekas scale. We used Spearman partial correlation to test associations between WMLs and brain atrophy, controlled for gender and ICV and performed general linear modelling (GLM).

Results
Amongst 672 subjects, mean age 73±1year, greater WML volume correlated: with reduced BTV (r=-0.10, P=0.01) and NAWM (r= -0.15, P<0.01), increased ventricular volume (r= 0.11, P<0.01) and CSF+V+D (r=0.11, P=0.01) but not with SSS (r=0.03, P=0.39), GM (r=-0.07, P=0.09) or CSF (r=0.06, P=0.13). A 1mm
3
increase in WML volume was associated with 0.43mm
3
decrease in BTV. We found similar associations for Fazekas WML scores. Gender and original brain size (i.e. ICV) explained 77.6% and 23.8% of the variance in BTV and ventricular volume, respectively, but WMLs explained <1% of either (GLM).

Conclusions
WMLs, assessed using both measured volumes and visual rating scales, are associated with brain atrophy mostly through deep white matter loss. Studies of brain atrophy in ageing or dementia should assess venous sinuses, dura and CSF, not just CSF, as sinuses and dura expand to occupy space left by brain atrophy. Further work to determine causes of age-related brain atrophy is required as WMLs only explain a small proportion of it.
Abstract 2388: Is Fatigue Associated With Symptoms Of Post Traumatic Stress Disorder In Subjects Following Stroke?
Authors: Mulroy Martin , Cooney John , Walsh Suzanne M , Harbison Joseph
Published: March 2022

Introduction:
Significant fatigue affecting quality of life is reported by up to 60% of stroke patients in the 6 months post event. We have previously reported an association between post fatigue and anxiety measured by Hospital Anxiety and Depression Score in stroke survivors. Stroke presents frequently as an unexpected potentially life threatening event with features similar to traumatic episodes such as accidents etc. Traumatic events may in turn be associated with development of the anxiety disorder Post Traumatic Stress Disorder (PTSD). We hypothesised that post-stroke fatigue may be related to a PTSD like phenomenon.

Method:
Independent patients (modified Rankin score <3) who were cognitively intact (AMTS >6) with a history of stroke attending a secondary prevention clinic were approached to participate in the study. All underwent a detailed 1-2 hour interview including assessment of fatigue using 2 tools, the Fatigue Assessment Scale (FAS) and the Fatigue Severity Score (FSS). PTSD severity was assessed using the Clinician Administered PTSD Scale (CAPS). The CAPS is a 30-item structured interview that corresponds to the DSM-IV criteria for PTSD. The CAPS is a standard criterion for the assessment and diagnosis of PTSD.

Results:
The study was terminated early after 18 patients completed assessments (15 male, median 70 years) due to unexpected distress experienced by some patients in completing the CAPS requiring referral to psychological support services. CAPS correlated strongly with FAS (r=0.72 (95%CI 0.39-0.89) p=0.0007). Seven subjects had a FAS score>20, of these 3 had symptoms of moderate to severe PTSD. No subjects with a FAS <21 had such symptoms (p=0.04, Fishers Exact test). The FSS also correlated with the CAPS but less strongly (r=0.50, p=0.03)

Conclusion:
Symptoms of PTSD are found in a proportion of patients following stroke. Although subject numbers are small there appears to be a strong correlation between fatigue severity and symptoms of PTSD in patients with stroke.
Abstract 24: Normalization of Blood Pressure and the Inhibition of Local Angiotensin II Prevent Aneurysm Rupture in Mice
Authors: Tada Yoshiteru ,   The Univ of Tokushima Graduate Sch, Tokushima, Japan, Wada Kosuke , Makino Hiroshi , Liang Elena I , Kudo Mari , Murakami Shoko , Nagahiro Shinji , Hashimoto Tomoki
Published: March 2022

Background and Purpose
Hypertension is generally considered as a major risk factor for aneurysmal subarachnoid hemorrhage. The renin-angiotensin system plays a crucial role in the regulation of blood pressure. Angiotensin II type 2 receptor (AT2R) counters most effects of angiotensin II type 1 receptor (AT1R). In our recently established mouse model of intracranial aneurysms, aneurysmal rupture occurs at a high incidence and results in neurological symptoms. We hypothesized that either normalization of blood pressure or inhibition of local renin angiotensin system alone can prevent aneurysmal subarachnoid hemorrhage. Furthermore, we tested relative contributions of AT1R and AT2R.

Methods
Intracranial aneurysms were induced in male mice using a combination of a single injection of elastase into the cerebrospinal fluid and deoxycorticosterone acetate (DOCA) salt hypertension. Six days after aneurysm induction, we started treatments with vehicle control (VC; n=87), hydralazine (direct vasodilator, 250mg/L in drinking water; n=15), angiotensin-converting enzyme inhibitor (captopril; 6mg/kg/day; n=17), an AT1R antagonist (losartan 30mg/kg/day; n=37), the same AT1R antagonist and an AT2R antagonist (PD123319; 10mg/kg/day; n=16), and an AT2R agonist (
CGP42112
; 1ug/kg/min; n=16), and continued for 15 days. Mice were sacrificed when the mice developed neurological symptoms, or at day 21 if mice did not develop any symptoms. Symptom-free survival curves were analyzed using Kaplan-Meier analysis.

Results
Normalization of blood pressure by hydralazine significantly reduced the rate of symptomatic ruptured aneurysms (mice with symptomatic ruptured aneurysms / mice with any aneurysms), and improved symptom free survival curve compared to the vehicle control group (P < 0.05). As expected, losartan or captopril did not affect DOCA salt induced hypertension. However, these treatments reduced the rate of symptomatic ruptured aneurysms (P < 0.05). Whereas the AT2R antagonist abolished the protective effect of losartan (
Figure
), the AT2R agonist alone reduced the rate of aneurysmal rupture (P < 0.05).

Conclusions
Either normalization of blood pressure or inhibition of local renin-angiotensin system was protective against aneurysmal rupture. Moreover, our data suggested potentially protective effects of AT2R activation against aneurysmal rupture. These data may be useful in choosing anti-hypertensive agents for patients with unruptured aneurysms.
Abstract 2414: Genome-wide Association Analyses From The Vitamin Intervention For Stroke Prevention (visp) Trial Identify Genetic Loci That Influence Post-stroke Measures Of Inflammation And Thrombosis
Authors: Sale Michele M , Chen Wei-Min , Chen Fang , Hsu Fang-Chi , Keene Keith L , Mychaleckyj Josyf C , Doheny Kimberly F , Boehm Corinne D , Laurie Cathy C , Gogarten Stephanie , Bookman Ebony B , Coull Bruce M , Furie Karen L , Worrall Bradford B , GARNET
Published: March 2022

The Vitamin Intervention for Stroke Prevention (VISP) trial was a multi-center, controlled, double blinded clinical trial, designed to determine whether the daily intake of high dose folic acid, vitamins B
6
and B
12
reduced recurrent cerebral infarction. As part of GARNET (the Genomics and Randomized Trials Network), we have performed a Genome-Wide Association Study (GWAS), using the Illumina Omni 1M SNP platform in 2,100 ischemic stroke patients from VISP. Extensive quality control (QC) measures were performed, resulting in a total of 737,081 SNPs for analysis. We have performed GWA analyses for baseline quantitative measures of creatinine, total cholesterol (TC), high density lipoprotein (HDL), triglycerides (TG), C-reactive protein (CRP), Factor
1+2
thrombin-antithrombin (TAT), tissue plasminogen activator (tPA), thrombomodulin (TM) and von Willebrand factor (vWF), using linear regression approaches implemented in PLINK. Principal component analysis (PCA), implemented in KING, was utilized to address confounders due to population substructure. Inverse normal transformation was performed for each of the quantitative traits, prior to analysis. Genome wide association analyses were performed using age, sex and the top 10 principal components as covariates. There is no inflation in our GWAS scan results (GC lambda ≤ 1.012 in all scans). We observed three associated loci that exceed genome wide significance (≤6.8×10
-8
): in or near the CETP gene for HDL (6.5×10
-10
), the CRP gene for CRP (7.4×10
-10
), and at the ABO locus for vWF (8.7×10
-31
). The most strongly associated SNPs for other traits were closest to the following genes: GABRA3 for creatinine (
rs994424
, 5.7×10
-6
), SPATA13 for TC (rs9553189, 3.2×10
-7
), between ARMCX2 and NXF5 genes on the X chromosome for TG (rs2213369, 1.7×10
-6
); the ZIC4 gene for TAT (rs17565826, 4.1×10-6); LOC283089 for tPA (rs3011337, 3.6×10
-6
); and JAZF1 for TM (rs10258132, 1.1×10
-6
). Putative novel associations with these traits will require confirmation in larger independent samples. Our GWAS scan has successfully replicated associations for SNPs in the CETP, CRP and ABO genes for HDL, CRP and vWF respectively in an ischemic stroke population.