Browsing by Author "Woo, Daniel"

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    Acute Ischemic Stroke, Depressed Left Ventricular Ejection Fraction, and Sinus Rhythm: Prevalence and Practice Patterns
    (American Heart Association, 2022) Baker, Anna D.; Schwamm, Lee H.; Sanborn, Danita Y.; Furie, Karen; Stretz, Christoph; Grory, Brian Mac; Yaghi, Shadi; Kleindorfer, Dawn; Sucharew, Heidi; Mackey, Jason; Walsh, Kyle; Flaherty, Matt; Kissela, Brett; Alwell, Kathleen; Khoury, Jane; Khatri, Pooja; Adeoye, Opeolu; Ferioli, Simona; Woo, Daniel; Martini, Sharyl; De Los Rios La Rosa, Felipe; Demel, Stacie L.; Madsen, Tracy; Star, Michael; Coleman, Elisheva; Slavin, Sabreena; Jasne, Adam; Mistry, Eva A.; Haverbusch, Mary; Merkler, Alexander E.; Kamel, Hooman; Schindler, Joseph; Sansing, Lauren H.; Faridi, Kamil F.; Sugeng, Lissa; Sheth, Kevin N.; Sharma, Richa; Neurology, School of Medicine
    Background: There are limited data about the epidemiology and secondary stroke prevention strategies used for patients with depressed left ventricular ejection fraction (LVEF) and sinus rhythm following an acute ischemic stroke (AIS). We sought to describe the prevalence of LVEF ≤40% and sinus rhythm among patients with AIS and antithrombotic treatment practice in a multi-center cohort from 2002 to 2018. Methods: This was a multi-center, retrospective cohort study comprised of patients with AIS hospitalized in the Greater Cincinnati Northern Kentucky Stroke Study and 4 academic, hospital-based cohorts in the United States. A 1-stage meta-analysis of proportions was undertaken to calculate a pooled prevalence. Univariate analyses and an adjusted multivariable logistic regression model were performed to identify demographic, clinical, and echocardiographic characteristics associated with being prescribed an anticoagulant upon AIS hospitalization discharge. Results: Among 14 338 patients with AIS with documented LVEF during the stroke hospitalization, the weighted pooled prevalence of LVEF ≤40% and sinus rhythm was 5.0% (95% CI, 4.1-6.0%; I2, 84.4%). Of 524 patients with no cardiac thrombus and no prior indication for anticoagulant who survived postdischarge, 200 (38%) were discharged on anticoagulant, 289 (55%) were discharged on antiplatelet therapy only, and 35 (7%) on neither. There was heterogeneity by site in the proportion discharged with an anticoagulant (22% to 45%, P<0.0001). Cohort site and National Institutes of Health Stroke Severity scale >8 (odds ratio, 2.0 [95% CI, 1.1-3.8]) were significant, independent predictors of being discharged with an anticoagulant in an adjusted analysis. Conclusions: Nearly 5% of patients with AIS have a depressed LVEF and are in sinus rhythm. There is significant variation in the clinical practice of antithrombotic therapy prescription by site and stroke severity. Given this clinical equipoise, further study is needed to define optimal antithrombotic treatment regimens for secondary stroke prevention in this patient population.
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    Deriving Place of Residence, Modified Rankin Scale, and EuroQol-5D Scores from the Medical Record for Stroke Survivors
    (Karger, 2021) Sucharew, Heidi; Kleindorfer, Dawn; Khoury, Jane C.; Alwell, Kathleen; Haverbusch, Mary; Stanton, Robert; Demel, Stacie; De Los Rios La Rosa, Felipe; Ferioli, Simona; Jasne, Adam; Mistry, Eva; Moomaw, Charles J.; Mackey, Jason; Slavin, Sabreena; Star, Michael; Walsh, Kyle; Woo, Daniel; Kissela, Brett M.; Neurology, School of Medicine
    Introduction: We sought to determine the feasibility and validity of estimating post-stroke outcomes using information available in the electronic medical record (EMR) through comparison with outcomes obtained from telephone interviews. Methods: The Greater Cincinnati Northern Kentucky Stroke Study is a retrospective population-based epidemiology study that ascertains hospitalized strokes in the study region. As a sub-study, we identified all ischemic stroke patients who presented to a system of 4 hospitals during the study period 1/1/2015–12/31/2015 and were discharged alive. Enrolled subjects (or proxies for cognitively-disabled patients) were contacted by telephone at 3 and 6 months post-stroke to determine current place of residence and two functional outcomes—the modified Rankin Score (mRS) and the EuroQol (EQ-5D). Concurrently, the lead study coordinator, blinded to the telephone assessment outcomes, reviewed all available EMRs to estimate outcome status. Agreement between outcomes estimated from the EMR with “gold-standard” data obtained from telephone interviews was analyzed using the kappa statistic or interclass correlation (ICC), as appropriate. For each outcome, EMR-determined results were evaluated for added value beyond the information readily available from the stroke hospital stay. Results: Of 381 ischemic strokes identified, 294 (median [IQR] age 70 [60–79] years, 4% black, 52% female) were interviewed post-stroke. Agreement between EMR and telephone for 3-month residence was very good (kappa=0.84, 95% CI 0.74–0.94), good for mRS (weighted kappa=0.75, 95% CI 0.70–0.80), and good for EQ-5D (ICC=0.74, 95% CI 0.68–0.79). Similar results were observed at 6 months post stroke. At both 3 and 6 months post stroke, EMR-determined outcomes added value in predicting the gold standard telephone results beyond the information available from the stroke hospitalization; the added fraction of new information ranged from 0.25 to 0.59. Conclusions: Determining place of residence, mRS, and EQ-5D outcomes derived from information recorded in the EMR post-stroke, without patient contact, is feasible and has good agreement with data obtained from direct contact. However, we note that the level of agreement for mRS and EQ-5D was higher for proxy interviews and that the EMR often reflects health care providers’ judgments that tend to overestimate disability and underestimate quality of life.
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    Exome-chip association analysis of intracranial aneurysms
    (American Academy of Neurology, 2020-02-04) van 't Hof, Femke N.G.; Lai, Dongbing; van Setten, Jessica; Bots, Michiel L.; Vaartjes, Ilonca; Broderick, Joseph; Woo, Daniel; Foroud, Tatiana; Rinkel, Gabriel J.E.; de Bakker, Paul I.W.; Ruigrok, Ynte M.; Medical and Molecular Genetics, School of Medicine
    Objective: To investigate to what extent low-frequency genetic variants (with minor allele frequencies <5%) affect the risk of intracranial aneurysms (IAs). Methods: One thousand fifty-six patients with IA and 2,097 population-based controls from the Netherlands were genotyped with the Illumina HumanExome BeadChip. After quality control (QC) of samples and single nucleotide variants (SNVs), we conducted a single variant analysis using the Fisher exact test. We also performed the variable threshold (VT) test and the sequence kernel association test (SKAT) at different minor allele count (MAC) thresholds of >5 and >0 to test the hypothesis that multiple variants within the same gene are associated with IA risk. Significant results were tested in a replication cohort of 425 patients with IA and 311 controls, and results of the 2 cohorts were combined in a meta-analysis. Results: After QC, 995 patients with IA and 2,080 controls remained for further analysis. The single variant analysis comprising 46,534 SNVs did not identify significant loci at the genome-wide level. The gene-based tests showed a statistically significant association for fibulin 2 (FBLN2) (best p = 1 × 10-6 for the VT test, MAC >5). Associations were not statistically significant in the independent but smaller replication cohort (p > 0.57) but became slightly stronger in a meta-analysis of the 2 cohorts (best p = 4.8 × 10-7 for the SKAT, MAC ≥1). Conclusion: Gene-based tests indicated an association for FBLN2, a gene encoding an extracellular matrix protein implicated in vascular wall remodeling, but independent validation in larger cohorts is warranted. We did not identify any significant associations for single low-frequency genetic variants.
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    Gender and Time to Arrival among Ischemic Stroke Patients in the Greater Cincinnati/Northern Kentucky Stroke Study
    (Elsevier, 2016-03) Madsen, Tracy E.; Sucharew, Heidi; Katz, Brian; Alwell, Kathleen A.; Moomaw, Charles J.; Kissela, Brett M.; Flaherty, Matthew L.; Woo, Daniel; Khatri, Pooja; Ferioli, Simona; Mackey, Jason; Martini, Sharyl; De Los Rios La Rosa, Felipe; Kleindorfer, Dawn O.; Department of Neurology, IU School of Medicine
    Background Some studies of stroke patients report longer pre-hospital delays in women, but others conflict; studies vary in their inclusion of factors including age and stroke severity. We aimed to investigate the relationship between gender and time to emergency department (ED) arrival and the influence of age and stroke severity on this relationship. Methods Ischemic stroke patients ≥ 20 years old who presented to 15 hospitals within a 5-county region of Greater Cincinnati/Northern Kentucky during 2010 were included. Time from symptom onset to ED arrival and covariates were abstracted by study nurses and reviewed by study physicians. Data were analyzed using logistic regression with time to arrival dichotomized at ≤ 3 hours, in the overall sample and then stratified by NIHSS and age. Results 1991 strokes (55% women) were included. Time to arrival was slightly longer in women (geometric mean 337 minutes [95%CI 307–369] vs. 297 [95%CI 268–329], p =0.05), and 24% of women vs. 27% of men arrived within 3 hours (p=0.15). After adjusting for age, race, NIHSS, living situation, and other covariates, gender was not associated with delayed time to arrival (OR=1.00, 95%CI 0.78–1.28). This did not change across age or NIHSS categories. Conclusions After adjusting for factors including age, NIHSS, and living alone, women and men with ischemic stroke had similar times to arrival. Arrival time is not likely a major contributor to differences in outcome between men and women.
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    Genome-wide association study of intracranial aneurysm identifies a new association on chromosome 7
    (Ovid Technologies Wolters Kluwer – American Heart Association, 2014-11) Foroud, Tatiana; Lai, Dongbing; Koller, Daniel; van’t Hof, Femke; Kurki, Mitja I.; Anderson, Craig S.; Brown, Robert D.; Connolly, E. Sander; Eriksson, Johan G.; Flaherty, Matthew; Fornage, Myriam; von und zuFraunberg, Mikael; Gaál, Emília I.; Laakso, Aki; Hernesniemi, Juha; Huston, John; Jääskeläinen, Juha E.; Kiemeney, Lambertus A.; Kivisaari, Riku; Kleindorfer, Dawn; Ko, Nerissa; Lehto, Hanna; Mackey, Jason; Meissner, Irene; Moomaw, Charles J.; Mosley, Thomas H.; Moskala, Marek; Niemelä, Mika; Palotie, Aarno; Pera, Joanna; Rinkel, Gabriel; Ripke, Stephan; Rouleau, Guy; Ruigrok, Ynte; Sauerbeck, Laura; Słowik, Agnieszka; Vermeulen, Sita H.; Woo, Daniel; Worrall, Bradford B.; Broderick, Joseph; Department of Medical & Molecular Genetics, IU School of Medicine
    BACKGROUND AND PURPOSE: Common variants have been identified using genome-wide association studies which contribute to intracranial aneurysms (IA) susceptibility. However, it is clear that the variants identified to date do not account for the estimated genetic contribution to disease risk. METHODS: Initial analysis was performed in a discovery sample of 2617 IA cases and 2548 controls of white ancestry. Novel chromosomal regions meeting genome-wide significance were further tested for association in 2 independent replication samples: Dutch (717 cases; 3004 controls) and Finnish (799 cases; 2317 controls). A meta-analysis was performed to combine the results from the 3 studies for key chromosomal regions of interest. RESULTS: Genome-wide evidence of association was detected in the discovery sample on chromosome 9 (CDKN2BAS; rs10733376: P<1.0×10(-11)), in a gene previously associated with IA. A novel region on chromosome 7, near HDAC9, was associated with IA (rs10230207; P=4.14×10(-8)). This association replicated in the Dutch sample (P=0.01) but failed to show association in the Finnish sample (P=0.25). Meta-analysis results of the 3 cohorts reached statistical significant (P=9.91×10(-10)). CONCLUSIONS: We detected a novel region associated with IA susceptibility that was replicated in an independent Dutch sample. This region on chromosome 7 has been previously associated with ischemic stroke and the large vessel stroke occlusive subtype (including HDAC9), suggesting a possible genetic link between this stroke subtype and IA.
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    Geographic Disparities in Case Fatality and Discharge Disposition Among Patients With Primary Intracerebral Hemorrhage
    (American Heart Association, 2023) Bako, Abdulaziz T.; Potter, Thomas; Pan, Alan; Tannous, Jonika; Rahman, Omar; Langefeld, Carl; Woo, Daniel; Britz, Gavin; Vahidy, Farhaan S.; Medicine, School of Medicine
    Background: We evaluate nationwide trends and urban–rural disparities in case fatality (in‐hospital mortality) and discharge dispositions among patients with primary intracerebral hemorrhage (ICH). Methods and Results: In this repeated cross‐sectional study, we identified adult patients (≥18 years of age) with primary ICH from the National Inpatient Sample (2004–2018). Using a series of survey design Poisson regression models, with hospital location–time interaction, we report the adjusted risk ratio (aRR), 95% CI, and average marginal effect (AME) for factors associated with ICH case fatality and discharge dispositions. We performed a stratified analysis of each model among patients with extreme loss of function and minor to major loss of function. We identified 908 557 primary ICH hospitalizations (overall mean age [SD], 69.0 [15.0] years; 445 301 [49.0%] women; 49 884 [5.5%] rural ICH hospitalizations). The crude ICH case fatality rate was 25.3% (urban hospitals: 24.9%, rural hospitals:32.5%). Urban (versus rural) hospital patients had a lower likelihood of ICH case fatality (aRR, 0.86 [95% CI, 0.83–0.89]). ICH case fatality is declining over time; however, it is declining faster in urban hospitals (AME, −0.049 [95% CI, −0.051 to −0.047]) compared with rural hospitals (AME, −0.034 [95% CI, −0.040 to −0.027]). Conversely, home discharge is increasing significantly among urban hospitals (AME, 0.011 [95% CI, 0.008–0.014]) but not significantly changing in rural hospitals (AME, −0.001 [95% CI, −0.010 to 0.007]). Among patients with extreme loss of function, hospital location was not significantly associated with ICH case fatality or home discharge. Conclusions: Improving access to neurocritical care resources, particularly in resource‐limited communities, may reduce the ICH outcomes disparity gap.
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    Health Factors Associated With Development and Severity of Poststroke Dysphagia: An Epidemiological Investigation
    (American Heart Association, 2024) Krekeler, Brittany N.; Schieve, Heidi J. P.; Khoury, Jane; Ding, Lili; Haverbusch, Mary; Alwell, Kathleen; Adeoye, Opeolu; Ferioloi, Simona; Mackey, Jason; Woo, Daniel; Flaherty, Matthew; De Los Rios La Rosa, Felipe; Demel, Stacie; Star, Michael; Coleman, Elisheva; Walsh, Kyle; Slavin, Sabreena; Jasne, Adam; Mistry, Eva; Kleindorfer, Dawn; Kissela, Brett; Neurology, School of Medicine
    Background: Dysphagia after stroke is common and can impact morbidity and death. The purpose of this population-based study was to determine specific epidemiological and health risk factors that impact development of dysphagia after acute stroke. Methods and results: Ischemic and hemorrhagic stroke cases from 2010 and 2015 were identified via chart review from the GCNKSS (Greater Cincinnati Northern Kentucky Stroke Study), a representative sample of ≈1.3 million adults from southwestern Ohio and northern Kentucky. Dysphagia status was determined on the basis of clinical assessments and necessity for alternative access to nutrition via nasogastric or percutaneous endoscopic gastrostomy tube placement. Comparisons between patients with and without dysphagia were made to determine differences in baseline characteristics and premorbid conditions. Multivariable logistic regression determined factors associated with increased risk of dysphagia. Dysphagia status was ascertained from 4139 cases (1709 with dysphagia). Logistic regression showed that increased age, Black race, higher National Institutes of Health Stroke Scale score at admission, having a hemorrhagic stroke (versus infarct), and right hemispheric stroke increased the risk of developing dysphagia after stroke. Factors associated with reduced risk included history of high cholesterol, lower prestroke modified Rankin Scale score, and white matter disease. Conclusions: This study replicated previous findings of variables associated with dysphagia (older age, worse stroke, right-sided hemorrhagic lesions), whereas other variables identified were without clear biological rationale (eg, Black race, history of high cholesterol, and presence of white matter disease) and should be investigated in future studies to determine biological relevance and potential influence in stroke recovery.
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    Heritability of circle of Willis variations in families with intracranial aneurysms
    (Public Library of Science, 2018-01-29) Sánchez van Kammen, Mayte; Moomaw, Charles J.; Schaaf, Irene C. van der; Brown, Robert D., Jr.; Woo, Daniel; Broderick, Joseph P.; Mackey, Jason S.; Rinkel, Gabriël J. E.; Huston, John, III; Ruigrok, Ynte M.; Neurology, School of Medicine
    BACKGROUND: Intracranial aneurysms more often occur in the same arterial territory within families. Several aneurysm locations are associated with specific circle of Willis variations. We investigated whether the same circle of Willis variations are more likely to occur in first-degree relatives than in unrelated individuals. METHODS: We assessed four circle of Willis variations (classical, A1-asymmetry, incomplete posterior communicating artery and fetal circulation) in two independent groups of families with familial aneurysms and ≥2 first-degree relatives with circle of Willis imaging on MRA/CTA. In each (index) family we determined the proportion of first-degree relatives with the same circle of Willis variation as the proband and compared it to the proportion of first-degree relatives of a randomly selected unrelated (comparison) family who had the same circle of Willis variation as the index family's proband. Concordance in index families and comparison families was compared with a conditional logistic events/trials model. The analysis was simulated 1001 times; we report the median concordances, odds ratios (ORs), and 95% confidence intervals (95%CI). The groups were analysed separately and together by meta-analysis. RESULTS: We found a higher overall concordance in circle of Willis configuration in index families than in comparison families (meta-analysis, 244 families: OR 2.2, 95%CI 1.6-3.0) mostly attributable to a higher concordance in incomplete posterior communicating artery (meta-analysis: OR 2.8, 95%CI 1.8-4.3). No association was found for the other three circle of Willis variations. CONCLUSIONS: In two independent groups of families with familial aneurysms, the incomplete PcomA variation occurred more often within than between families suggesting heritability of this circle of Willis variation. Further studies should investigate genetic variants associated with circle of Willis formation.
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    Intracranial Aneurysm Classifier Using Phenotypic Factors: An International Pooled Analysis
    (MDPI, 2022-08-30) Morel, Sandrine; Hostettler, Isabel C.; Spinner, Georg R.; Bourcier, Romain; Pera, Joanna; Meling, Torstein R.; Alg, Varinder S.; Houlden, Henry; Bakker, Mark K.; van’t Hof, Femke; Rinkel, Gabriel J.E.; Foroud, Tatiana; Lai, Dongbing; Moomaw, Charles J.; Worrall, Bradford B.; Caroff, Jildaz; Constant-dits-Beaufils, Pacôme; Karakachoff, Matilde; Rimbert, Antoine; Rouchaud, Aymeric; Gaal-Paavola, Emilia I.; Kaukovalta, Hanna; Kivisaari, Riku; Laakso, Aki; Jahromi, Behnam Rezai; Tulamo, Riikka; Friedrich, Christoph M.; Dauvillier, Jerome; Hirsch, Sven; Isidor, Nathalie; Kulcsàr, Zolt; Lövblad, Karl O.; Martin, Olivier; Machi, Paolo; Pereira, Vitor Mendes; Rüfenacht, Daniel; Schaller, Karl; Schilling, Sabine; Slowik, Agnieszka; Jaaskelainen, Juha E.; von und zu Fraunberg, Mikael; Jiménez-Conde, Jordi; Cuadrado-Godia, Elisa; Soriano-Tárraga, Carolina; Millwood, Iona Y.; Walters, Robin G.; The @neurIST project; The ICAN Study Group; Genetics and Observational Subarachnoid Haemorrhage (GOSH) Study Investigators; International Stroke Genetics Consortium (ISGC); Kim, Helen; Redon, Richard; Ko, Nerissa U.; Rouleau, Guy A.; Lindgren, Antti; Niemelä, Mika; Desal, Hubert; Woo, Daniel; Broderick, Joseph P.; Werring, David J.; Ruigrok, Ynte M.; Bijlenga, Philippe; Medical and Molecular Genetics, School of Medicine
    Intracranial aneurysms (IAs) are usually asymptomatic with a low risk of rupture, but consequences of aneurysmal subarachnoid hemorrhage (aSAH) are severe. Identifying IAs at risk of rupture has important clinical and socio-economic consequences. The goal of this study was to assess the effect of patient and IA characteristics on the likelihood of IA being diagnosed incidentally versus ruptured. Patients were recruited at 21 international centers. Seven phenotypic patient characteristics and three IA characteristics were recorded. The analyzed cohort included 7992 patients. Multivariate analysis demonstrated that: (1) IA location is the strongest factor associated with IA rupture status at diagnosis; (2) Risk factor awareness (hypertension, smoking) increases the likelihood of being diagnosed with unruptured IA; (3) Patients with ruptured IAs in high-risk locations tend to be older, and their IAs are smaller; (4) Smokers with ruptured IAs tend to be younger, and their IAs are larger; (5) Female patients with ruptured IAs tend to be older, and their IAs are smaller; (6) IA size and age at rupture correlate. The assessment of associations regarding patient and IA characteristics with IA rupture allows us to refine IA disease models and provide data to develop risk instruments for clinicians to support personalized decision-making.
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    A PheWAS study of a large observational epidemiological cohort of African Americans from the REGARDS study
    (Biomed Central, 2019-01-31) Zhao, Xueyan; Geng, Xin; Srinivasasainagendra, Vinodh; Chaudhary, Ninad; Judd, Suzanne; Wadley, Virginia; Gutiérrez, Orlando M.; Wang, Henry; Lange, Ethan M.; Lange, Leslie A.; Woo, Daniel; Unverzagt, Frederick W.; Safford, Monika; Cushman, Mary; Limdi, Nita; Quarells, Rakale; Arnett, Donna K.; Irvin, Marguerite R.; Zhi, Degui; Psychiatry, School of Medicine
    BACKGROUND: Cardiovascular disease, diabetes, and kidney disease are among the leading causes of death and disability worldwide. However, knowledge of genetic determinants of those diseases in African Americans remains limited. RESULTS: In our study, associations between 4956 GWAS catalog reported SNPs and 67 traits were examined among 7726 African Americans from the REasons for Geographic and Racial Differences in Stroke (REGARDS) study, which is focused on identifying factors that increase stroke risk. The prevalent and incident phenotypes studied included inflammation, kidney traits, cardiovascular traits and cognition. Our results validated 29 known associations, of which eight associations were reported for the first time in African Americans. CONCLUSION: Our cross-racial validation of GWAS findings provide additional evidence for the important roles of these loci in the disease process and may help identify genes especially important for future functional validation.