bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract TMP114: Interrogation of Brain Endothelial Cell Gene Expression Reveals Cyclooxygenase-2 as a Therapeutic Target After Subarachnoid Hemorrhage
Authors: Tso Michael K , Turgeon Paul J , Bosche Bert , Lee Charles K , Nie Tian , D’Abbondanza Josephine A , Ai Jinglu , Marsden Philip A , Macdonald Robert L
Published: June 2021

Introduction:
The pathophysiology of subarachnoid hemorrhage (SAH) is complex and includes disruption of the blood-brain barrier (BBB). We have previously optimized methods to freshly isolate BBB endothelial cells (BECs) and performed genome-wide expression profiling to uncover new therapeutic targets in an unbiased manner. In this study we validated 2 of the most highly upregulated targets, cyclooxygenase-2 (Cox2) and angiopoietin-2 (Angpt2).

Methods:
The prechiasmatic blood injection mouse model of SAH was used with experimental end-points at 24h. BBB disruption was assessed using intraperitoneal-injected cadaverine-based fluorescent dye. Global neurobehavioral assessments utilized the modified Garcia score. BECs were purified either by magnetic-based sorting for CD45-CD31+ cells or by fluorescence-activated cell sorting for Tie2+Pdgfrb- cells. Microarray results from RNA extracted from BECs were validated with real-time PCR. Immunofluorescence of coronal brain sections and enzyme-linked immunosorbent assays of brain homogenates were performed to determine protein expression. Intraperitoneal injections of the Cox2 inhibitor celecoxib (10mg/kg) were administered 30min and 12h after SAH induction.

Results:
CD45-CD31+ BECs derived from SAH mice demonstrated 6.6-fold and 5.4-fold increase in Cox2 and Angpt2 gene expression, respectively (n=4 per group, p<0.05, p<0.01). Tie2+Pdgfrb- BECs similarly showed 5.8-fold and 5.3-fold increase in Cox2 and Angpt2 gene expression after SAH, respectively (n=4 per group, p<0.05, p<0.05), which demonstrates the robustness of these results. We observed increased Cox2 protein expression in intraparenchymal vessels and increased Angpt2 protein expression in brain homogenates after SAH. Celecoxib treatment resulted in modest reduction in BBB disruption and improved neurobehavioral outcomes. Celecoxib treatment abrogated SAH-induced upregulation of Cox2 expression, but not Angpt2, in BECs.

Conclusions:
In summary, we identified Cox2 as a potential therapeutic target in SAH. The observed beneficial effects of celecoxib treatment suggest that Cox2 may be critical to BBB disruption after SAH and its mechanism appears to be independent of Angpt2.
Abstract TMP116: White Matter Hyperintensity Lesion Patterns in Patients With Cardioembolic Strokes
Authors: Mayasi Yunis M , Helenius Johana , Henninger Nils
Published: June 2021

Background:
Among patients with a cardioembolic stroke, atrial fibrillation (AF) is a common comorbidity that is associated with a worse outcome. Mounting data indicates that AF may relate to stroke pathogenesis through mechanisms other than cerebral thromboembolic complications. We sought to identify different WMH patterns between patients with AF vs. non-AF related embolic ischemic strokes.

Methods:
We retrospectively analyzed consecutive patients with acute anterior circulation embolic ischemic stroke included in an academic medical center’s stroke registry. The stroke etiology was determined using the Causative Classification System of ischemic stroke. WMH lesion burden was assessed according to the Fazekas scale. An independent blinded examiner classified the different WMH-patterns, which included 5 categories: periventricular, subcortical spots, posterior subcortical patches, anterior subcortical patches, and severe confluent subcortical patches. Their association with AF was investigated using multivariable logistic regression (with backward elimination).

Results:
Overall, 174 patients (94 with and 80 without AF) were included. In unadjusted analyses, patients with AF had a significantly higher rate of anterior subcortical patches (p=0.018) and a lower rate of a periventricular pattern (p=0.022). After adjusting for WMH lesion burden, presence of multiple infarcts, infarct volume, the CHA2DS2-VASc score as well as pertinent two-way and three-way interactions the presence of anterior subcortical patches (OR 2.41, 95%-CI 1.02-5.72, p=0.045) and a higher CHA2DS2-VASc score (per point, OR 1.28, 95%-CI 1.08-1.52, p=0.005) were independently associated with AF.

Conclusions:
We found that AF is associated with specific WMH lesion patterns on MRI. The clinical significance of this observation remains to be clarified; yet it suggests that the well-established link between stroke and AF extends beyond thromboembolism and may reflect an underlying cardiovasculopathy that can be characterized by WMH. If confirmed in future studies further investigation into the underlying pathophysiological mechanisms may provide novel avenues to AF detection and treatment.
Abstract TMP119: Early Cerebral Ischemic Events in Symptomatic Carotid Stenosis are Related to Plaque Inflammation
Authors: Paliwal Prakash R , Sinha Arvind K , Teoh Hock L , Hallinan James , Du Zhengdao , Du Zhengdao , Chen Jin T , Ting Eric Y , Wong Lily Y , Chan Bernard P , Sharma Vijay K
Published: June 2021

Background and aims:
Symptomatic carotid stenosis is associated with an increased risk of early stroke recurrence. Severity of the stenosis, current basis of revascularization, explains only the cerebral ischemic mechanism of regional hypoperfusion. Plaque inflammation, the initiating event for plaque rupture and thromboembolism (artery-to-artery embolism), is not evaluated routinely. Using 18F-fluorodeoxyglucose positron-emission tomography (FDG-PET)/computed tomography (CT) and high resolution magnetic resonance imaging (HR-MRI), we investigated the role of plaque imaging and stroke recurrence in our cohort of stroke patients with recently symptomatic carotid stenosis.

Methods:
This ongoing prospective study included consecutive patients within 30-days of recent stroke and ipsilateral carotid stenosis (≥50%). FDG uptake was quantified as mean standardized uptake values (SUV, g/ml). The ratio of T1 hyperintensity of carotid plaque to the ipsilateral sternocleidomastoid muscle (SCM) was recorded on T1-weighted fat suppressed images. Patients were followed prospectively for stroke recurrence within 90-days. Embolic potential of carotid plaque is estimated by presence of spontaneous microembolic signals (MES) on extended transcranial Doppler monitoring of ipsilateral middle cerebral artery.

Results:
Of the 33 patients included in the study, 6 (18%) suffered from recurrent cerebral ischemic event in the same vascular territory within 90-days. Compared to patients without subsequent cerebral ischemic events, patients with recurrent cerebral ischemia showed higher mean T1 carotid-SCM ratio (2.49 versus 1.53; p<0.0001) and higher mean SUV value in the carotid plaque (3.52g/ml versus 1.51g/ml; p<0.0001). Higher T1 carotid-SCM ratio on HR-MRI (OR 4.249, 95%CI 1.818-5.18; p<0.0001), higher mean SUV on FDG-PET (OR 3.050, 95%CI 5.586-28.571; p=0.005) and MES on TCD (OR 2.186, 95%CI 1.652-47.619;p=0.037) were independent predictors of recurrent cerebral ischemia.

Conclusions:
FDG-PET/CT and HR-MRI imaging of carotid stenosis helps in identification of patients at higher risk of subsequent cerebral ischemic events and may aid in better therapeutic decision-making.
Abstract TMP14: Should 45-Minute Door to Needle Time be the New Standard of Care? Analysis of Categorized Treatment Time in a Large, Multi-hospital Registry
Authors: Kansara Amit , Lucas Lindsay , Corless Leslie , Bhatt Archit , Baraban Elizabeth
Published: June 2021

Introduction:
With the introduction of American Stroke Association’s Target Stroke and Target Stroke2, hospitals have emphasized faster door to needle time (DTN) for acute ischemic stroke based on criteria of less than 60 minutes and less than 45 minutes, but little is known about its impact on outcomes. In this study, we evaluated outcomes based on similarly categorized treatment times across a large multi-hospital system in the Pacific Northwest.

Methods:
Data obtained from a multi-hospital health system’s Get With The Guidelines registry included patients discharged between January 2011 and June 2016 and treated with IV alteplase. Primary outcomes were discharge disposition, modified Rankin score (mRS) at discharge and 90-days, disability categorized as none/slight (mRS≤2) and moderate or greater (mRS ≥3) and treatment-related hemorrhagic complications. DTN was categorized into three groups: <45 minutes, 45-60 minutes, or >60 minutes. Generalized linear mixed regression models were used to analyze the effect of DTN group on outcomes after adjusting for the following covariates: admit NIHSS score, gender, age, last known well to arrival time, intra-arterial intervention, and history of co-morbid conditions. Adjusted odds ratios (AOR) and p-values were reported.

Results:
A total of 2,434 patients met inclusion criteria. DTN times were broken down as follows: 25% percent (n=610) of patients were < 45 minutes, 28.1% (n=684) were 45-60 minutes and 46.8% (n=1140) were > 60 minutes. Patients with DTN > 60 minutes were more likely than patients with DTN < 45 minutes to have moderate or greater disability at 90 days (AOR=2.43; p=.042), have a treatment-related hemorrhage (AOR=2.00; p=.045), be discharged to a skilled nursing facility or inpatient rehab versus home (AOR=2.29; p=.022), or be discharged to hospice or expired versus home (AOR=2.47; p=.014). Patients with DTN between 45 and 60 minutes were also more likely than patients with DTN < 45 minutes to be discharged to hospice or expired versus home (AOR=3.21;p=.022). There was no significant effect of DTN on discharge mRS (p=.691).

Conclusion:
DTN time less than 45 minutes is associated with reduced mortality, less severe disability, fewer hemorrhagic complications and higher rates of home discharge.
Abstract TMP22: Thrombus Volume as Predictor of Successful Recanalization in the Acute Stroke Patients With Thrombolytic Treatment
Authors: Yoo Joonsang , Baek Jang-Hyun , Song Dongbeom , Kim Kyoungsub , Kim Young Dae , Nam Hyo Suk , Heo Ji Hoe
Published: June 2021

Introduction:
The prediction of non-recanalization after IV thrombolysis (IVT) may be helpful to avoid unnecessary treatment and determine the strategy of recanalization treatment. Thrombus volume and density can be measured using software, which may provide accurate and reliable information on thrombus characteristics.

Hypothesis:
We hypothesized that the thrombus volume and/or density could predict non-recanalization after IVT.

Methods:
This was a post-hoc analysis of prospective cohort who underwent thin-section noncontrast CT (1 or 1.25 mm) and recanalization therapy. Among them, this study considered patients who received IVT due to anterior circulation stroke from Nov. 2006 to Dec. 2015. The volume and density of thrombus were measured semi-automatically using 3-dimensional software. Recanalization was assessed on CT angiography at the end of IVT or conventional angiography in cases further treated with intra-arterial treatment. Successful recanalization was defined as arterial occlusive lesion grade 2 or 3.

Results:
Among 345 patients considered, 218 with visible thrombus in the intracranial arteries were included for this study. Successful recanalization was achieved in 79 patients (36.2%). Thrombus volume was significantly larger in patients with non-recanalization than those with successful recanalization (median [interquartile range]: 117.8mm
3
[60.0 - 216.8 mm
3
] vs. 56.9 mm
3
[31.1 - 105.0 mm
3
]. p<0.001). In the multivariate analysis, thrombus volume was independently associated with non-recanalization (p<0.001). Recanalization failed in all cases with thrombus > 300 mm
3
, and in 41 of 44 cases (93.2%) with thrombus > 200 mm
3
. Thrombus density did not differ between the groups (non-recanalization vs. successful recanalization: 54.0 ± 9.1 vs. 52.6 ± 8.5, p=0.263).

Conclusions:
Thrombus volume was predictive of non-recanalization after IVT. Measurements of thrombus volume may be helpful to determine the strategy of recanalization treatment.
Abstract TMP25: Effects of Age and Ethnicity on the Benefits and Risks of Low- versus Standard-dose Alteplase in Acute Ischemic Stroke Patients: The Enchanted Trial
Authors: Wang Xia , Robinson Thompson , Arima Hisatomi. , Broderick Joseph , Demchuk Andrew , Donnan Geoffrey , Kim Jong , Lavados pablo , Lee Tsong Hai , Lindley Richard , Martins Sheila , Pandian Jeyaraj , Chalmers John , Anderson Craig
Published: June 2021

Background and Purpose:
As lower doses of alteplase reduce the risk of symptomatic intracerebral hemorrhage (sICH), older and Asian people may benefit more from low-dose alteplase than other patients with acute ischemic stroke (AIS).

Methods:
Data from the ENhanced Control of Hypertension ANd Thrombolysis strokE study (ENCHANTED), an international, multi-center, prospective, randomized, open-label, blinded-endpoint trial, were analyzed to assess effects of low- (0.6mg/kg body weight) vs. standard-dose (0.9mg/kg) alteplase in AIS patients, by age and ethnicity (Asian vs. non-Asian), pre-specified subgroup analyses, on key efficacy and safety outcomes.

Results:
3297 patients (1248 female), mean age 67 years were included. After adjusting for baseline characteristics and management variables over the first seven days, increasing age was associated with poor outcome, defined by ordinal analysis of the modified Rankin score (mRS) (shift to a less favorable outcome, P trend <0.0001). In the comparison between low- and standard-dose alteplase, no significant differences were observed for 90-day poor outcome by age deciles and ethnicity. Less sICH was observed with low-dose alteplase, and this was consistent for age and ethnicity. There was no ethnic difference in the treatment effects by age, severity, and time to treatment.

Conclusions:
Increasing age predicts poor outcome in thrombolysis-treated AIS patients. There was no heterogeneity in the treatment effects of low- vs. standard-dose alteplase. Decisions about intravenous thrombolysis should be based on variables other than age and ethnicity.
Abstract TMP29: Non-invasive Identification of Culprit Carotid Atheroma Using Sodium Fluoride-positron Emission Tomography
Authors: Evans Nicholas R , Tarkin Jason M , Chowdhury Mohammed M , Malani Sangam , Rudd James H , Warburton Elizabeth A
Published: June 2021

Introduction:
Microcalcification is a histopathological feature of atheroma at risk of rupture; so-called “vulnerable plaques.” Positron emission tomography (PET) using
18
F-sodium fluoride (NaF) has been used to detect microcalcification in
ex vivo
histology, though its use
in vivo
has been limited. We investigated the utility of NaF-PET to identify culprit carotid artery atheroma non-invasively
in vivo
in the setting of acute ischemic stroke.

Methods:
Symptomatic carotid artery stenosis of ≥50% was imaged using NaF-PET within 14 days of ipsilateral ischemic stroke. Symptomatic arteries were compared to contralateral asymptomatic carotid arteries. NaF dose was 125 MBq with 60 minute uptake on a GE Discovery 690 with 64 slice computed tomography. NaF uptake was measured using standardized uptake values for each artery’s single region of maximum uptake (SUVmax) and the mean of the three slices representing the most diseased segment (MDS-SUVmax). Arteries were compared using Wilcoxon signed-rank testing.

Results:
Fifty-two carotid arteries were analyzed: 26 symptomatic, 26 asymptomatic. Median SUVmax was higher in symptomatic than asymptomatic arteries: 2.16 (IQR 0.76) and 1.88 (IQR 0.94) respectively (p<0.001). MDS-SUVmax was 2.04 (IQR 0.66) in symptomatic and 1.76 (IQR 0.83) in asymptomatic carotids (p<0.001). Calcium scores did not differ between symptomatic and asymptomatic arteries (p=0.34).

Conclusions:
The ability to identify culprit carotid atheroma using NaF-PET
in vivo
represents an important advance in vascular imaging. This has important implications for understanding atherosclerosis pathophysiology, as well as potential clinical applications to identify and risk-stratify vulnerable carotid atheroma.
Abstract TMP33: High Intensity Signal in the Plaque on 3DTOF MRA is Associated With Ischemic Stroke in the Patients With Low Grade Carotid Artery Stenosis
Authors: Yamada Kiyofumi , Kawasaki Masanori , Nakahara Shigehiro , Sato Yoshikazu , Uchida Kazutaka , Shirakawa Manabu , Yoshimura Shinichi
Published: June 2021

Background:
Carotid artery stenosis is one of the major causes of ischemic strokes. However, degree of stenosis is not always correlated with frequency of ischemic strokes. Recently, it was reported that carotid intraplaque hemorrhage (IPH) was associated with accelerated plaque growth, luminal narrowing and development of symptomatic events. Maximum intensity projection (MIP) images are easily reformatted within from 5 minute, routine time-of-flight (TOF) sequences. The aim of this study was to evaluate the relationships between high intensity signal (HIS) in the carotid plaques on MIP images detected by routine three-dimensional TOF magnetic resonance angiography (3D-TOF MRA) and ischemic strokes.

Materials and Methods:
One hundred fifty two patients with low-grade carotid artery stenosis (North American Symptomatic Carotid Endarterectomy Trial criteria: 30% - 49%) were included. IPH was defined as the presence of HIS in the carotid plaques on MIP images of 3D-TOF MRA using the previously reported criteria. We analyzed the relationship between the presence of HIS in the plaques and prior ischemic strokes defined as ischemic lesions on diffusion weighed images of the brain.

Results:
HIS in the carotid plaque was present in 56 (37%) of 152 carotid arteries. Prior ipsilateral ischemic strokes were observed more frequently in HIS-positive group (12 of 56, 21.4%) than HIS-negative group (1 of 34: 2.9%) [p<0.001]. In multivariate logistic regression analysis, HIS (Odds ratio: 77.7, 95%CI: 6.4 - 944.0, p<0.001) and diabetes mellitus type 2 (odds ratio: 10.45, 95%CI: 1.6 - 67.9, p=0.014) were independent determinants of prior ischemic strokes after adjustment for age.

Conclusions:
HIS in the carotid plaques on MIP images of 3D-TOF MRA was an independent determinant of prior ischemic stroke in patients with low-grade carotid artery stenosis, and this finding may provide a reliable risk stratification of future stroke in patients with low-grade carotid artery stenosis.
Abstract TMP40: Sociodemographic Predictors of Return to Home after Inpatient Stroke Rehabilitation
Authors: Ifejika Nneka L , Cai Chunyan C , Noser Elizabeth A , Grotta James C , Savitz Sean I
Published: June 2021

Background:
Interpersonal relationships are understudied components of the stroke treatment paradigm, which become important when patients require long-term care. In this study, we analyzed sociodemographic factors that impact return to home after inpatient rehabilitation (IR).

Methods:
Stroke patients were identified by ICD9/10 code from a prospective multicenter rehabilitation registry between Jan 2005 & July 2016 (n=6447). Patients were analyzed based upon "Home" vs "Not Home" or "Married" vs "Not Married" groups. Descriptive statistics were provided for all patients. Marital status was used as a proxy for caregiver support. We hypothesized that increased discharge functional independence measure (FIM), ambulation and no insurance predicted return to home. A “return home model” was developed using multivariable regression with a stepwise approach. Odds ratio & 95% CI were calculated.

Results:
5378 patients returned Home, 1069 did not return Home. Home patients tended to be younger, married, ambulatory and minorities, with a discharge FIM>75 (p<0.0001). Aphasia, dysphagia and UTI were significantly higher in the “Not Home” group (p<0.0001). Married patients had more stroke risk factors and impairments, indicating increased caregiver needs (Figure). In the model, being a minority and being a woman increased the odds of returning home. Advancing age, being widowed, divorced, separated or never married decreased the odds of returning home. We confirmed that ambulation, increasing discharge FIM and no insurance predicted return to home (Figure).

Conclusions:
Being married, a woman or a minority increases the odds of returning home after inpatient rehabilitation. Caregiver training and social support for unmarried and male patients are important areas of improvement. Strategies to ensure the successful transition of stroke rehabilitation patients to home are needed, including prospective studies of non-spousal caregiver support.
Abstract TMP43: Therapy Time, Settings and Transitions Across All Post-Acute Care (PAC) Settings in the First Year After Stroke in Medicare Patients
Authors: Burke James F , Feng Crystal , Skolarus Lesli E
Published: June 2021

Introduction:
Post-acute care (PAC) may be an important factor in recovery, yet little is known about stroke patients’ receipt of PAC across settings. To optimize future PAC, we described all settings in which stroke survivors receive therapy, the total time receiving therapy in each setting and transitions between settings.

Methods:
All Medicare fee-for-service patients admitted in 2011 and discharged alive with a primary diagnosis of acute ischemic stroke or intracerebral hemorrhage (ICD-9-CM 431, 433.x1, 434.x1, 436) were identified from the Medicare Inpatient file. Medicare Standard Analytic Files were used to identify therapy in all PAC settings — hospital, Inpatient Rehabilitation Facilities (IRF), Skilled Nursing Facilities (SNF), Home Health (HH) and Outpatient for 12 months after the index stroke admission. Physical (PT), occupational (OT) and speech therapy (SLP) were identified using CPT and revenue codes. For each therapy modality, minutes of therapy was estimated by cross-walking Medicare billing codes to the American Medical Association’s average intra-service time for each code. We then estimated time in each therapy modality, total therapy time in each PAC setting and the number of transitions between settings.

Results:
Our cohort included 186,168 patients, 59% female with a mean age of 80.1 (SD 8.2). 86%, 78% and 74% received any PT, OT or SLP. For patients who received a specific therapy modality, the median therapy minutes was: 762 PT, 661 OT, and 684 SLP. Of all patients, 22% received PT in an IRF, 38% in a SNF, 23% in HH and 36%. For patients who received PT in a given setting, the median number of minutes per setting was: 86 hospital, 747 IRF, 718, 446 HH, and 553 outpatient. Slightly smaller proportions received OT and SLP for slightly shorter times across settings.

Multiple care transitions were common. Of all patients, 75% had more than 1 transition, 45% have 3+, 25% have 5+, 14% have 7+ and 6% have 9+ in the 12 months following stroke.

Conclusions:
During the first year following their stroke, the median stroke survivor who receive therapy spends 35 hours in therapy and has 3 transitions between settings. Most therapy is delivered outside of the hospital and settings transitions are common raising concerns for care fragmentation.
Abstract TMP45: Predicting Long-term Body Function, Activity & Participation After Stroke: The Prevailing Role of Cognition in Determining Functional Outcome
Authors: Kapoor Arunima , Lanctot Krista , Bayley Mark , Kiss Alex , Swartz Richard
Published: June 2021

Background:
Stroke can impact multiple levels of function and result in complex disability. Few studies have examined limitations across the range of functions from body function to social participation, or explored the impact of post-stroke comorbidities, such as depression, obstructive sleep apnea (OSA) and cognition, on function, especially in the long-term. We aimed to determine post-stroke predictors of multiple levels of functioning approximately 2 years after a stroke, and to specifically evaluate the impact of depressive symptoms, OSA and cognitive impairment on outcome.

Hypothesis:
We hypothesized that in addition to traditional predictors of outcome–age and stroke severity–depression, OSA and cognitive impairment will predict functional outcome in multiple domains.

Methods:
Baseline assessment of depression, apnea and cognitive impairment with 2-year follow-up assessment of functional outcome to evaluate each of the three levels of functioning as stated in the WHO International Classification of Functioning: Body Function (Montreal Cognitive Assessment), Activity (modified Rankin) and Participation (Reintegration to Normal Living Index).

Results:
A total of 162 patients were enrolled at approximately 2 years and 5 months post-stroke. Forty one percent had activity limitations, 58% were cognitively impaired and 68% had restrictions in participation. Long-term activity limitation was predicted by greater age (OR = 0.95), stroke severity (OR = 1.69) and cognitive impairment (OR = 1.28) at baseline. Body function impairment was predicted by greater age (OR = 0.96), and cognitive impairment (OR = 1.49). Participation restriction was predicted by cognitive impairment (OR = 1.26).

Conclusion:
Baseline cognition predicts long-term function in multiple domains and is a better predictor of long-term participation than age or baseline stroke severity. In view of the widespread impact of post-stroke cognitive impairment on every level of functioning, routine post-stroke cognitive screening and target interventions are warranted. Greater attention to functional domains beyond activity could further optimize recovery and enhance outcome after stroke.
Abstract TMP46: Is There an Effect of Statins on Ischemic Stroke Functional Outcomes in the Oldest Old?
Authors: Alcusky Matthew , Hume Anne L , Lapane Kate L
Published: June 2021

Background:
The net health benefit of statin use in the oldest patients remains controversial. Preclinical models and previous clinical studies have suggested statins may exhibit neuroprotective effects in stroke, however evidence in the very old remains limited. Our objective was to compare changes in functional status before and after acute ischemic stroke (AIS) between statin users and non-users in a national cohort.

Methods:
A patient’s first hospitalization for AIS from 04/01/11 to 12/31/2012 was selected from Medicare Part A claims. Patients with a pre-hospitalization nursing home Minimum Data Set assessment and a post-hospitalization assessment in a skilled nursing facility were included. Pre-stroke statin exposure was defined using Part D claims. Functional status was measured continuously and categorically (dependent:<20, partially dependent(PD):20-59, assisted independent(AI):60-100) using Shah’s modified Barthel Index (mBI). Multivariable logistic regression examined the association of statins with a minimum clinically important mBI decrease of 10 points among non-dependent patients.

Results:
Among 10,203 patients with an assessment before hospitalization, 7.2% died, and 48.7% were included (mean age: 83.6±9.6; 74.5% women). Statin use was common (36.5%), while acute treatment was infrequent (thrombolysis: 4.9%; thrombectomy: 0.1%). The distribution of functional dependence, PD, and AI shifted from 17.3%, 56.1%, and 26.7% at baseline to 49.7%, 44.4%, and 5.9% post-stroke, respectively.

A consistent association with 10-point mBI decline was observed for statin exposure among all non-dependent (OR: 0.8; 95%CI: 0.7-1.0) and within strata of PD (OR:0.8; 95%CI: 0.7-1.0) and AI patients (OR: 0.8; 95%CI: 0.5-1.3). In contrast, acute treatment was more strongly associated with function in AI (OR: 0.5; 95%CI: 0.2-1.0) versus PD patients (OR: 1.0; 95%CI: 0.7-1.5).

Conclusion:
In this high-burden population, our results are suggestive of a possible protective association for pre-stroke statin exposure. Further research is needed to examine temporal and dose-response relationships between statin exposure and functional outcomes across diverse patient populations.
Abstract TMP48: Longitudinal Course of Depressive Symptoms Following Stroke: Preliminary Results From the Discharge Educational Strategies for Reduction of Vascular Events (DESERVE) Study
Authors: Goldmann Emily , Boden-Albala Bernadette
Published: June 2021

It is well-established that depression is common after stroke. Much less is known about the longitudinal course of depressive symptoms in stroke survivors. Data for this study came from the DESERVE trial of a skills-based intervention to reduce vascular risk in mild/moderate stroke/TIA patients. Depressive symptoms were assessed at baseline (pre-discharge), 6 months and 1 year post-discharge using the Center for Epidemiologic Studies - Depression (CES-D) scale. Discrete mixture models identified distinct trajectories of depressive symptom severity over time and assigned patients to trajectory groups. We ran Poisson models using linear and quadratic parameters and chose the best-fitting model based on Bayesian information criterion and interpretability. Associations between baseline characteristics and trajectory group membership were examined using ANOVA and bivariable multinomial logistic regression. So far, 285 patients completed all three study waves and ≥ 1 depression assessment. A four-group model was selected: 1)
resistance
- low depressive symptom level at all waves (50% of patients); 2)
delayed
- low baseline symptom level, increasing to clinically significant levels (CES-D > 16) by 6 months, remaining high at 1 year (18%); 3)
recovery
- clinically significant baseline symptom levels, dropping to low levels by 6 months, remaining low at 1 year (22%); 4)
chronic
- severe symptoms at all waves (10%). Hispanic patients had greater odds of delayed symptoms vs. resistance compared to non-Hispanics. Moderate stroke patients had greater odds of delayed and chronic symptoms vs. resistance compared to mild stroke patients. Patients with stroke history had greater odds of delayed symptoms and recovery vs. resistance compared to those without; those with psychiatric history had greater odds of recovery and chronic symptoms vs. resistance compared to those without. Those with chronic symptoms had significantly greater baseline disability compared to other groups. The course of post-stroke depressive symptoms is heterogeneous and associated with race/ethnicity and several clinical factors. Targeted interventions may be required to prevent the development of depression and address chronic symptoms that may interfere with stroke recovery.
Abstract TMP49: Depressive Symptoms After Stroke are Linked Longitudinally between Stroke Survivors and Their Family Caregivers
Authors: Roth David L , Sheehan Orla C , Huang Jin , Rhodes J. D , Judd Suzanne E , Haley William E
Published: June 2021

Background:
Multiple previous investigations have documented persistent elevations in depressive symptoms after stroke for stroke survivors and for family caregivers. However, relatively few studies have examined both groups simultaneously, and none have tested for possible predictive linkages in longitudinal analyses.

Methods:
We collected interview data from 248 stroke survivors and their primary family caregivers who were enrolled in the Caring for Adults Recovering from the Effects of Stroke (CARES) project. CARES is an ancillary study to the national REasons for Geographic and Racial Differences in Stroke (REGARDS) study. Stroke survivors and caregivers were interviewed at 9-, 18-, 27- and 36-months after an adjudicated stroke event. Measures administered to both groups included the 20-item Center for Epidemiological Studies Depression Scale (CESD) and the 12-item Short Form Health Survey (SF-12) of health-related quality of life. Cross-lagged panel analyses were used to investigate linkages between stroke survivors and caregivers over time on these measures.

Results:
Clinically significant levels of depressive symptoms, as defined by a score of 16 or more on the CESD, were found for 17.0% of the stroke survivors and 13.7% of the caregivers at 9-months after stroke. Longitudinal models revealed that high stroke survivor depressive symptoms at 9-months post-stroke predicted increases in caregiver depressive symptoms at 18-months post-stroke (standardized adjusted regression coefficient = 0.18, p = 0.003). No longitudinal predictive effects were found for caregiver depressive symptoms on stroke survivor outcomes or for the SF-12 measures.

Conclusions:
Clinically significant levels of depressive symptoms were relatively rare 9-months after stroke in this population-based sample of stroke survivors and family caregivers. Stroke survivor depressive symptoms longitudinally predict caregiver depressive symptoms, but caregiver well-being was not found to longitudinally predict stroke survivor depression or quality of life. Treating elevated depressive symptoms in stroke survivors may also improve caregiver well-being.
Abstract TMP5: The Smoking-Thrombolysis Paradox in Large Vessel Occlusion Acute Ischemic Stroke Undergoing Endovascular Therapy
Authors: Bouslama Mehdi , Rebello Leticia C , Haussen Diogo C , Grossberg Jonathan A , Doppelheuer Shannon , Anderson Aaron , Belagaje Samir R , Frankel Michael R , Nogueira Raul G
Published: June 2021

Background and Purpose:
The smoking-thrombolysis paradox has been well described in myocardial infarction. However, its existence in the stroke population remains elusive. In the past decade, several studies have investigated the phenomenon with mixed results. We sought to determine whether clinical outcomes differ between smokers and non-smokers with acute ischemic stroke undergoing endovascular therapy.

Methods:
We reviewed our prospectively collected endovascular database at a tertiary care academic institution. All patients who underwent endovascular therapy for acute large vessel occlusion acute ischemic stroke were categorized into current smokers and non-smokers. Baseline characteristics, procedural radiological as well as outcome parameters where compared.

Results:
A total of 968 patients qualified for the study of which 189 (19.5%) were current smokers. Smokers were younger (60.78±11.95 vs. 66.41±15.05 years, p<0.001), had higher rates of dyslipidemia (49.7% vs 31.7%, p<0.001) and posterior circulation strokes (13.2% vs 7.8%, p=0.02,) and lower rates of atrial fibrillation (21.1% vs 37.9%, p<0.001). There were no statistically significant differences between groups in terms of stroke severity (as assessed by NIHSS), baseline CT perfusion core and hypoperfusion volumes, CT angiogram collateral scores as well as procedural variables. On univariate analysis, smokers had higher rates of good outcomes at 90 days (modified Rankin scale, mRS 0-2: 53.8% vs 42.8%, p=0.01) and similar rates of successful reperfusion (mTICI 2b-3) (92.1% vs 87.7%, p=0.09), parenchymal hematomas (4.2% vs 4%, p=0.84) and mortality at 90 days (20.2% vs 25.7%, p=0.14). Multivariate analysis showed that smoking was not independently associated with good outcomes. Stratifying for (1) stroke etiology and (2) anterior vs. posterior circulation topology yielded similar results.

Conclusion:
In stroke patients treated with mechanical thrombectomy, smoking does not seem to be associated with outcomes regardless of stroke subtype or location.
Abstract TMP54: Seasonal Patterns of Ischemic Stroke in the United States
Authors: Chu Stacy Y , Cox Margueritte , Fonarow Gregg C , Smith Eric , Schwamm Lee H , Bhatt Deepak L , Xian Ying , Matsouaka Roland , Sheth Kevin N
Published: June 2021

Background:
Seasonal variation in stroke occurrence and outcomes has been reported in small populational studies but the significance of a seasonal effect is uncertain. The important patient and climate variables underlying this phenomenon have not yet been identified.

Methods:
Using Get With The Guidelines-Stroke data from 2011 to 2015, we studied 457,638 consecutive ischemic stroke patients at 896 sites. We calculated the relative prevalence of acute stroke admissions in each season. Baseline characteristics and discharge outcomes were compared across seasons and the effects of season, climate region (as defined by the National Climatic Data Center), and climate variables on outcomes were analyzed using logistic regression. In secondary analyses, odds ratios were calculated for various outcomes.

Results:
Among all cases of ischemic stroke, there was significant difference in the frequency distributions of cases across seasons (p<.0001), with the highest percentage of strokes occurring in winter (25.5%). Across seasons, winter patients had the highest percentage of atrial fibrillation (17.7%), longest median time to arrival (202 minutes), highest in-hospital mortality (4.4%), and most discharge mRS scores > 3 (43.7%). P<.0001 for all the above. Higher precipitation and temperature were associated with reduced mortality independent of climate region or season (OR .93, CI .89-.97, p=.0005 and OR .97, CI .97-.98, p<.0001, respectively). Odds ratios for in-hospital mortality are summarized in the accompanying table.

Conclusions:
More patients presented with acute ischemic stroke in winter relative to other seasons, accompanied by trends toward poorer outcomes. Although an association with mortality was seen for winter in our unadjusted analysis, confounding variables likely exist. Precipitation and temperature were independently associated with stroke mortality.
Abstract TMP55: Polysomnographic and Sleep-related Variables Associated to Leukoaraiosis in Patients with Obstructive Sleep Apnea
Authors: Duque Kevin R , Villafuerte Brian , Adrianzen Fiorella , Zamudio Rodrigo , Mendiola Andrea , Navarro Tito , Vizcarra Darwin
Published: June 2021

Introduction:
Obstructive sleep apnea (OSA) is a biological plausible risk factor for leukoaraiosis (LA). We tested the hypothesis that polysomnographic (PSG) and sleep-related variables are associated to LA in OSA patients.

Methods:
Cross-sectional study in which PSG records, medical histories and brain 1.5T MRI were collected from all consecutive patients who had attended a Sleep Medicine Center between 2009-2014. LA was graded from 0 to 9 with the ’Atherosclerosis Risk In Communities’ study scale. OSA was defined by The International Classification of Sleep Disorders, 2014, and its severity categorizing according to apnea-hypopnea index (AHI, <15 mild, 15 to <30 moderate, 30 to <45 severe and ≥45 very severe). A multinomial logistic regression was performed to describe the association between OSA severity and LA (divided into 2 groups: mild-to-moderate LA and non-to-minimal LA). The covariates for all regression models were age, gender, BMI, hypertension, ischemic stroke, myocardial infarction, diabetes and pack-year of smoking.

Results:
From 82 OSA patients (77% male; mean age 58±9 years, range 19-91), 54 (66%) had LA. Mild-to-moderate LA was found in 13 patients (8 mild and 5 moderate LA) and non-to-minimal LA in 69 (41 minimal and 28 non LA). Spearman’s correlation coefficient between AHI and LA grade was 0.41 (p<0.001). Furthermore, the higher OSA severity, the higher LA severity (p<0.001, for Jonckheere-Terpstra test for ordered alternatives). In the multinomial logistic regression model adjusted for cofounders, severe OSA patients had higher risk for mild or moderate LA (HR 12.8, 95% IC 1.2-141) compared to mild-to-moderate OSA patients. Additionally, self-reported habitual sleep duration from 7 to 9 hours (HR 0.36, 90% IC 0.14-0.90) and proportion of time in apnea/hypopnea over total sleep time (HR 1.04 for one unit increase, 90% IC 1.01-1.08) could be associated with the presence of LA (adjusted only for age and gender). In a multiple regression analysis with all the aforementioned variables, age (p=0.002), diabetes (p=0.003), and OSA severity (p=0.04) were predictors of the presence of LA.

Conclusion:
Patients with severe OSA had higher risk for mild to moderate LA when compared to patients with mild or moderate OSA.
Abstract TMP59: Interplay of Racial and Geographical Differences in Stroke Type and Risk Factors Among Indigenous West Africans; African Americans and European Americans
Authors: Owolabi Mayowa , Howard George , Gebregziabher Mulugeta , Sarfo Fred , Irvin Ryan , Armstrong Kevin , Akinyemi Rufus , Tiwari Hemant , Lackland Dan , Bennett Aleena , Arnett Donna , Howard Virginia , Ovbiagele Bruce
Published: June 2021

Introduction:
The relative contributions of racial and environmental factors to the higher risk of stroke in people of African ancestry are not clear due to limited opportunities to evaluate stroke type and risk among indigenous Africans, in comparison with Africans in diaspora and their host populations. This knowledge could provide insights into avenues for similar vs. unique approaches to managing stroke risk in Africans.

Objective:
To compare the pattern of stroke and contribution of vascular risk factors to stroke among indigenous Africans, African Americans and European Americans.

Methods:
SIREN is a large multicenter case-control study involving several sites in West Africa, the ancestral home of 71% African Americans, whilst REGARDS is a cohort study including African and European Americans in the United States. Stroke diagnosis and type were confirmed using CT or MRI scan. Traditional vascular risk factors were assessed using history, physical examination and laboratory investigations. We compared data from acute stroke cases age≥55 years in SIREN and REGARDS in the distribution of key socio-demographic and clinical risk factors based on harmonized standard definitions.

Results:
There were 811 stroke subjects in the SIREN population (A) and 452 African Americans (B) and 665 European Americans (C) from the REGARDS study with a progressive increment in mean age of 68.0 ± 9.3, 73.0 ± 8.3 and 76.0 ± 8.3 years respectively, p<0.0001. Hemorrhagic stroke occurred in 291/811 (27.0%), 36/452 (8.0%) and 36/665 (5.4%), in A, B, and C (p < 0.001) respectively. There were significant differences in prevalence of vascular risk factors among the three groups namely hypertension: 92.8%, 82.5% & 64.2%, p<0.01; mean LDL cholesterol (mg/dl): 121±52, 116±32, 110±33 (p< 0.03); cardiac diseases: 12.5%, 25.0% & 31.7% (p< 0.01); sedentary lifestyle:8%, 37.7% and 34.0% (p<0.001); and 2.0%, 18.3% & 14.4% were current smokers in A, B and C respectively (p<0.001).

Conclusion:
Environmental risk factors such as cigarette smoking may contribute to the higher proportion of ischemic stroke in African-Americans compared to indigenous Africans, while racial factors may contribute to the higher proportion of hypertension among stroke subjects of African ancestry.
Abstract TMP61: Preliminary Results of a Population Based Outcomes Pilot Study: the Greater Cincinnati/Northern Kentucky Stroke Study
Authors: Kissela Brett M , Alwell Kathleen A , Khoury Jane , Moomaw Charles J , Haverbusch Mary , Woo Daniel , Flaherty Mattheh L , Star Michael , Demel Stacie L , Ferioli Simona , Mackey Jason , Kleindorfer Dawn
Published: June 2021

Background:
We previously followed a cohort of survivors longitudinally with direct interview for outcomes. We then proved that we could obtain similar outcomes by tracking people in a health information exchange followed by first phone call contact at 3 months, thus minimizing contact. This study sought to determine the feasibility of estimating population-based post-stroke outcomes using information available in the electronic medical record (EMR) without any patient contact.

Methods:
Our study is a retrospective population-based epidemiology project that ascertains hospitalized strokes via ICD-discharge codes (ICD-9 430-436, ICD-10 I60-I67, G45-G46). Our study region encompasses 5 greater Cincinnati counties; study period 1/1/15-12/31/15. For this pilot outcomes study, we identified all ischemic strokes that presented to a system of 4 hospitals and performed phone calls at 3 and 6 months to determine current place of residence and functional outcomes including the modified Rankin Score (mRS) and the Euroqol (EQ-5D). Simultaneously, our lead Study Coordinator reviewed all available EMR records and used this information to estimate outcome status blinded to phone call results. We compared the “gold-standard” of interview-determined place of residence, mRS and EQ-5D to those estimated from EMR using the either the Kappa statistic or interclass correlation (ICC), as appropriate.

Results:
See Table for details. Using standard definitions of Kappa/ICC, estimation of 3- and 6-mo place of residence was “almost perfect” and estimation of mRS grade and EQ-5D was “substantial”. Censoring observations where no EMR information was available did not reduce Kappa/ICC.

Conclusion:
This work shows promise in using EMR information to accurately estimate post-stroke outcomes without patient contact, to allow a population-based estimation of outcome. Future work will involve machine-learning to improve our accuracy in outcomes estimation from EMR information.
Abstract TMP65: Depth of Hospital Participation in Telestroke is Associated with Faster Door-to-Needle Time for Stroke Patients
Authors: Moreno Arianna , Saddiqui Khawja A , Viswanathan Anand , Whitney Cynthia , Rost Natalia , Schwamm Lee H , Sauser Zachrison Kori
Published: June 2021

Background:
Telestroke increases tPA use at spoke hospitals, yet its effect on door-to-needle (DTN) times is unknown. More frequent use of telestroke may introduce delays in DTN time or may improve it as practice leads to streamlined processes.

Hypothesis:
We hypothesize that spoke hospitals with more frequent contact to a hub hospital will have shorter DTN times than those with less frequent contact.

Methods:
We identified 367 patients treated with tPA by conventional or telestroke methods in the MGH Telestroke network for whom date and time data were available. Strength of the spoke-MGH connection was the primary predictor variable, defined as the number of all telestroke consults (tPA and non-tPA) done at each spoke hospital during the year of the patient’s presentation. Patient-level regression analyses examined the relationship between DTN time and spoke-MGH connection. We controlled for hospitals’ tPA volume, temporal trends, and clustering within hospitals.

Results:
Sixteen spoke hospitals contributed data on 367 tPA-treated patients from 2006-2016. Hospitals treated a median of 12.5 patients with tPA (IQR 7-33.5). Median hospital-level DTN was 78.8 minutes (IQR 71.3-85). Median number of telestroke consults per year was 37 (IQR 15-60). Among all 367 patients, median DTN was 76 minutes (IQR 61-98), and 24.8% of patients were treated within 60 minutes (n=91). Strength of connection between the spoke and hub hospital was significantly associated with faster DTN time for patients (1.8 minute gain per 10 additional consults, p<0.001) and increased likelihood of tPA delivery within 60 minutes (OR 1.01, p<0.001).

Conclusion:
More frequent contact between a telestroke spoke and its hub was associated with faster tPA delivery for patients, even after accounting for hospitals’ tPA volume and secular trends in DTN improvements. This highlights added benefits of increased utilization of telestroke.