Nai-Fang Chi | Taipei Medical University (original) (raw)

Papers by Nai-Fang Chi

Research paper thumbnail of Monogenic Causes in Familial Stroke Across Intracerebral Hemorrhage and Ischemic Stroke Subtypes Identified by Whole-Exome Sequencing

Cellular and Molecular Neurobiology, Dec 29, 2022

Whole exome sequencing (WES) has been used to detect rare causative variants in neurological dise... more Whole exome sequencing (WES) has been used to detect rare causative variants in neurological diseases. However, the efficacy of WES in genetic diagnosis of clinically heterogeneous familial stroke remains inconclusive. We prospectively searched for disease-causing variants in unrelated probands with defined familial stroke by candidate gene/hotspot screening and/or WES, depending on stroke subtypes and neuroimaging features at a referral center. The clinical significance of each variant was determined according to the American College of Medical Genetics guidelines. Among 161 probands (mean age at onset 53.2 ± 13.7 years; male 63.4%), 33 participants (20.5%) had been identified with 19 pathogenic/likely pathogenic variants (PVs; WES applied 152/161 = 94.4%). Across subtypes, the highest hit rate (HR) was intracerebral hemorrhage (ICH, 7/18 = 38.9%), particularly with the etiological subtype of structural vasculopathy (4/4 = 100%, PVs in ENG, KRIT1, PKD1, RNF213); followed by ischemic small vessel disease (SVD, 15/48 = 31.3%; PVs in NOTCH3, HTRA1, HBB). In contrast, large artery atherosclerosis (LAA, 4/44 = 9.1%) and cardioembolism (0/11 = 0%) had the lowest HR. NOTCH3 was the most common causative gene (16/161 = 9.9%), presenting with multiple subtypes of SVD (n = 13), ICH (n = 2), or LAA (n = 1). Importantly, we disclosed two previously unreported PVs, KRIT1 p.E379* in a familial cerebral cavernous malformation, and F2 p.F382L in a familial cerebral venous sinus thrombosis. The contribution of monogenic etiologies was particularly high in familial ICH and SVD subtypes in our Taiwanese cohort. Utilizing subtype-guided hotspot screening and/or subsequent WES, we unraveled monogenic causes in 20.5% familial stroke probands, including 1.2% novel PVs. Genetic diagnosis may enable early diagnosis, management and lifestyle modification. Yo-Tsen Liu and I.-Hui Lee have contributed equally to this work.

Research paper thumbnail of Abstract WP126: Impaired Dynamic Cerebral Autoregulation Predicts Cerebral Hyperperfusion Syndrome After Carotid Angioplasty and Stenting

Stroke, 2016

Introduction: Cerebral hyperperfusion syndrome (CHS) is a devastating complication after carotid ... more Introduction: Cerebral hyperperfusion syndrome (CHS) is a devastating complication after carotid revascularization procedure such as carotid angioplasty and stenting (CAS). Although there is no reliable predictor of CHS after CAS, it is believed CHS is caused by impaired cerebral autoregulation (CA). However, there is no study using CA assessment as a predictor of the occurrence of CHS after CAS. Hypothesis: Impaired preoperative CA index is associated with occurrence of CHS after CAS. Methods: 17 patients with 70-95% stenosis of internal carotid artery who were scheduled to have CAS were enrolled. All patients had dynamic CA assessment 1 day before CAS by analyzing the relationship between the blood pressure of peripheral artery and the flow of stenotic internal carotid artery. Two dynamic CA indexes were measured: time domain analysis (mean pressure-flow correlation coefficient index, Mx) and frequency domain analysis (phase difference at 0.05-0.15Hz measured by a nonlinear analyt...

Research paper thumbnail of Artificial neural network-based analysis of the safetand efficacy of thrombolysis for ischemic stroke in older adults in Taiwan

Research paper thumbnail of Safety and efficacy of extending intravenous thrombolysis treatment for acute ischemic stroke in Taiwan

Neurology Asia, 2019

Recombinant tissue plasminogen activator (rt-PA) is the most effective treatment for acute ischem... more Recombinant tissue plasminogen activator (rt-PA) is the most effective treatment for acute ischemic stroke and the exclusion criteria of rt-PA has been revised to extend its application. However, in Taiwan, National Health Insurance (NHI) did not follow the latest international consensus due to safety concerns. The present study investigated whether extending the application of rt-PA in Taiwan was safe and effective. The medical records from the Shuang Ho hospital stroke registry between August 2009 and December 2016 were retrospectively reviewed. Post rt-PA intracranial hemorrhage (ICH) and modified Rankin Scale (mRS) score at 3-month after stroke were the primary and secondary outcomes, respectively. Differences were analyzed through Fisher’s exact test and Student’s t test. A p-value of <0.05 was considered statistically significant. Overall, there were 243 patients categorized into two groups: NHI exclusion criteria adherence (n = 160) and non-adherence (n = 83). There was no...

Research paper thumbnail of Application of hyperglycemia/diabetes-derived polygenic risk scores on the risk of poor outcomes after an ischemic stroke

Journal of the Chinese Medical Association, 2021

Unfavorable prognoses are often accompanied for hyperglycemic stroke patients. This study aimed t... more Unfavorable prognoses are often accompanied for hyperglycemic stroke patients. This study aimed to construct a hyperglycemia/diabetes-derived polygenic risk score (PRS) to improve the predictive performance for poor outcome risks after a stroke and to evaluate its potential clinical application. A hospital-based cohort study was conducted including 1320 first-ever acute ischemic stroke (AIS) patients and 1210 patients who completed the follow-up at 3 months. PRSs were calculated for hyperglycemia/diabetes mellitus using results from genome-wide association studies in Asians. An unfavorable functional outcome was defined as a modified Rankin Scale score of ≥3 at 3, 6, and 12 months of follow-up. The prediction of a poor prognosis was evaluated using measures of model discrimination, calibration, and net reclassification improvement (NRI). The second to fourth PRS quartiles (≥Q2) were significantly associated with higher risks of unfavorable outcomes at 3 months compared with the first quartile as the reference group after adjusting for age, baseline stroke severity, hypertension, diabetes, dyslipidemia, smoking, heart disease, and ischemic stroke subtype (p for trend <0.0001). The addition of the PRS to traditional risk predictors of poor outcomes after an AIS significantly improved the model fit (likelihood ratio test p < 0.0001) and enhanced measures of reclassification (NRI, 0.245; 95% confidence interval [CI], 0.195-0.596). The corrected C-index for the PRS combining traditional risk factors at 3 months after a stroke was 0.899 (95% CI, 0.878-0.980). Among hyperglycemic AIS patients, those who did not take an antidiabetic drug and whose PRS was ≥Q2 had higher risks of an unfavorable outcome at 3 months compared with patients who took the medicine. The hyperglycemia/diabetes-derived PRS was associated with poor outcomes after an AIS, but further studies are needed to validate its use for clinical applications.

Research paper thumbnail of Etiology and risk factors of intracranial hemorrhage and ischemic stroke in young adults

Journal of the Chinese Medical Association, 2021

Background: Young stroke incidence has increased worldwide with lifestyle changes. Etiology and r... more Background: Young stroke incidence has increased worldwide with lifestyle changes. Etiology and risk factors for both ischemic and hemorrhagic stroke in young Asians remain underexplored. Methods: We retrospectively reviewed consecutive acute stroke patients aged 16–45 years admitted to the Taipei Veterans General Hospital between 2009 and 2019 to analyze etiologic subtypes, risk factors, and serial modified Rankin Scale scores for 1 year and compare the age groups of 16–30 and 31–45 years. Results: Among 670 young Taiwanese patients (mean age at onset 37.5 ± 7.0 years; male 65.1%), there were 366 nontraumatic spontaneous hemorrhagic stroke (including 259 intracerebral hemorrhage [ICH] and 107 subarachnoid hemorrhage, SAH), 292 ischemic stroke and 12 cerebral venous thromboses. Notably, ICH was more prevalent in patients aged 16–30 than in those aged 31–45 (54.8% vs 36.8%). Specifically, structural vasculopathy (e.g., arteriovenous malformation, cavernoma) was the most common etiologic subtype in patients aged 16–30 (p < 0.001), whereas hypertensive ICH was the most common subtype in patients aged 31–45 (p < 0.001). On the other hand, the top ischemic subtype for both age groups was other determined diseases (e.g., arterial dissection, autoimmune diseases, moyamoya disease, etc.) rather than large artery atherosclerosis. Hyperlipidemia, diabetes, and cigarette smoking were more common risk factors for infarction than ICH. Familial stroke patients whose first- or second-degree relatives had a stroke by age 80 (n = 104, 15.5%) had more infarctions than those without a familial stroke history. In multivariate analyses, initial stroke severity, and infarction type were important predictors of favorable outcomes after 3 months. At the 1-year follow-up, patients with ICH and SAH had worse functional outcomes and survival rates than those with infarction. Conclusion: An aggressive approach to elucidate the etiology of stroke is indicated because structural vasculopathy-induced ICH and other determined infarction are distinctively prevalent in young adults, particularly those aged 16–30.

Research paper thumbnail of Development and validation of risk score to estimate 1-year late poststroke epilepsy risk in ischemic stroke patients

Clinical Epidemiology, 2018

Objective: This study aimed to develop and validate a prognostic model for the 1-year risk of lat... more Objective: This study aimed to develop and validate a prognostic model for the 1-year risk of late poststroke epilepsy (PSE). Materials and methods: We included patients initially diagnosed with ischemic stroke between 2003 and 2014 in a National Health Insurance claims-based cohort in Taiwan. Patients were further divided into development and validation cohorts based on their year of stroke diagnosis. Multivariable Cox regression with backward elimination was used to analyze the association between 1-year PSE and risk factors before and on stroke admission. Results: In total, 1,684 (1.93%) and 725 (1.87%) ischemic stroke patients comprising the development and validation cohorts, respectively, experienced late PSE within 1 year after stroke. Seven clinical variables were examined to be independently associated with 1-year risk of PSE. We developed a risk score called "PSEiCARe" ranging from 0 to 16 points, comprising the following factors: prolonged hospital stay (>2 weeks, 1 point), seizure on admission (6 points), elderly patients (age ≥80 years, 1 point), intensive care unit stay on admission (3 points), cognitive impairment (dementia, 2 points), atrial fibrillation (2 points), and respiratory tract infection (pneumonia) on admission (1 point). Patients were further classified into low-, medium-, high-, and very-high-risk groups. The incidence (per 100 person-years) was 0.64 (95% CI: 0.56-0.71) for the low-risk, 2.62 (95% CI: 2.43-2.82) for the medium-risk, 10.3 (95% CI: 9.48-11.3) for the high-risk, and 28.2 (95% CI: 24.0-33.0) for the very-high-risk groups. Discrimination and calibration were satisfactory, with a Harrell's C of 0.762 in the development model and 0.792 in the validation model. Conclusion: PSEiCARe is an easy-to-use prognostic score that integrates patient characteristics and clinical factors on stroke admission to predict 1-year PSE risk; it has the potential to assist individualized patient management and improve clinical practice, thereby preventing the occurrence of late PSE.

Research paper thumbnail of Comparing Different Recording Lengths of Dynamic Cerebral Autoregulation: 5 versus 10 Minutes

BioMed Research International, 2018

We compared the dynamic cerebral autoregulation (dCA) indices between 5- and 10-minute data lengt... more We compared the dynamic cerebral autoregulation (dCA) indices between 5- and 10-minute data lengths by analyzing 37 patients with ischemic stroke and 51 controls in this study. Correlation coefficient (Mx) and transfer function analysis were applied for dCA analysis. Mx and phase shift in all frequency bands were not significantly different between 5- and 10-minute recordings [mean difference: Mx = 0.02; phase shift of very low frequency (0.02–0.07 Hz) = 0.3°, low frequency (0.07–0.20 Hz) = 0.6°, and high frequency (0.20–0.50 Hz) = 0.1°]. However, the gains in all frequency bands of a 5-minute recording were slightly but significantly higher than those of a 10-minute recording (mean difference of gain: very low frequency = 0.05 cm/s/mmHg, low frequency = 0.11 cm/s/mmHg, and high frequency = 0.14 cm/s/mmHg). The intraclass correlation coefficients between all dCA indices of 5- and 10-minute recordings were favorable, especially in Mx (0.93), phase shift in very low frequency (0.87), ...

Research paper thumbnail of The effect of rheumatoid arthritis on the risk of cerebrovascular disease and coronary artery disease in young adults

Journal of the Chinese Medical Association, 2018

Background: Only a few studies have investigated the affect of rheumatoid arthritis (RA) on the r... more Background: Only a few studies have investigated the affect of rheumatoid arthritis (RA) on the risk of cerebrovascular disease (CVD)/coronary artery disease (CAD) in young adults. This study, therefore, examined the association between RA and the risk of CVD/CAD in young adults and the interaction effects between cardiovascular risk factors and RA on the risk of CVD/CAD. Methods: Data regarding 52,840 subjects (10,568 patients with RA and 42,272 age-, sex-, urbanization-, and income-matched non-RA controls) were collected from the National Health Insurance Research Database (NHIRD) in 2006. All subjects were followed until a CVD or CAD diagnosis, or death, or December 31, 2011. The hazard ratios (HRs) of CVD/CAD were estimated using Cox proportional hazard models. The interaction effects between cardiovascular risk factors and RA on the risk of CVD/CAD were assessed using additive and multiplicative models. Results: RA increased the risk of CVD/CAD in young adults, especially those at risk of ischemic stroke (adjusted HR, 3.48; 95% confidence interval (CI), 2.16e5.61). Even without comorbidity at baseline, patients with RA still had a 2.35-fold greater risk of CVD/CAD relative to those without RA. RA and hypertension interacted positively on the risk of CVD/CAD. The highest CVD/CAD risk was found in patients with RA and hypertension (HR, 9.08; 95% CI, 7.22e11.41) relative to subjects without RA and hypertension. Conclusion: RA is an independent risk factor for CVD/CAD in young adults. The government should develop policies for preventing early onset hypertension to reduce the incidence of CVD/CAD among young patients with RA.

Research paper thumbnail of Percutaneous coronary intervention in patients hospitalized for non-ST-elevation myocardial infarction and the risk of postdischarge ischemic stroke at 6-month, 1-year, and 3-year follow-ups

Heart and Vessels, 2019

Percutaneous coronary intervention (PCI) is suggested for treating patients with non-ST-elevation... more Percutaneous coronary intervention (PCI) is suggested for treating patients with non-ST-elevation myocardial infarction (NSTEMI) to reduce adverse cardiovascular events. However, the short- and long-term effects of PCI on the risk of postdischarge ischemic stroke (IS) in patients hospitalized for NSTEMI remain unclear. This study investigated the association of PCI on the risk of postdischarge IS in patients hospitalized for NSTEMI at different period follow-ups. A population-based cohort study was conducted using data from Taiwan’s National Health Insurance Research Database. Propensity score matching (PSM) was used to select 6079 pairs of the patients with NSTEMI treated invasively by PCI (received PCI during hospitalization) and initial conservative strategy (did not receive PCI during hospitalization) with similar baseline characteristics for evaluation. After adjustment for patients’ clinical variables and the duration of dual antiplatelet therapy, PCI was associated with a decreased risk of postdischarge IS at 6-month, 1-year, and 3-year follow-ups [adjusted hazard ratio (aHR) = 0.41, 95% confidence interval (CI) = 0.26–0.67, p < 0.001; aHR = 0.61, 95% CI 0.43–0.86, p = 0.004; and aHR = 0.69, 95% CI 0.54–0.89, p = 0.005respectively]. In the patients who had a CHA2DS2-VASc score of ≥2, PCI was also associated with a decreased risk of postdischarge IS at 6-month, 1-year, and 3-year follow-ups (aHR = 0.54, 95% CI 0.36–0.83, p = 0.005; aHR = 0.72, 95% CI 0.52–1.00, p = 0.048; and aHR =0.73, 95% CI 0.58–0.91, p = 0.005, respectively). These findings suggested that PCI might reduce the risk of postdischarge IS in patients hospitalized for NSTEMI.

Research paper thumbnail of Emotional and Social Dysfunction Questionnaire--Chinese Version

Research paper thumbnail of Effect of early percutaneous coronary intervention on 1-year risk of pneumonia and pneumonia-related adverse outcomes in patients with acute myocardial infarction

EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology, Jan 18, 2017

To investigate the association between early percutaneous coronary intervention (PCI) and pneumon... more To investigate the association between early percutaneous coronary intervention (PCI) and pneumonia risk in patients with acute myocardial infarction (AMI) by using Taiwan's National Health Insurance Research Database. In total, 4,732 patients with non-ST-elevation myocardial infarction (NSTEMI) and 5,465 with ST-elevation myocardial infarction (STEMI) who had received PCI during AMI hospitalisation (early PCI) were evaluated. Patients who did not receive PCI during AMI hospitalisation (deferred PCI) were matched through propensity score matching. The incidence rates (per 100 person-months) of pneumonia hospitalisation, pneumonia-related respiratory failure, and pneumonia-related death associated with early PCI in patients with NSTEMI were 0.36 (95% confidence interval [CI]=0.32-0.42), 0.12 (95% CI=0.10-0.16), and 0.08 (95% CI=0.06-0.11), respectively. In patients with STEMI, the incidence rates (per 100 person-months) of the aforementioned adverse events were 0.16 (95% CI=0.13-...

Research paper thumbnail of Epistasis Analysis for Estrogen Metabolic and Signaling Pathway Genes on Young Ischemic Stroke Patients

PLoS ONE, 2012

Background: Endogenous estrogens play an important role in the overall cardiocirculatory system. ... more Background: Endogenous estrogens play an important role in the overall cardiocirculatory system. However, there are no studies exploring the hormone metabolism and signaling pathway genes together on ischemic stroke, including sulfotransferase family 1E (SULT1E1), catechol-O-methyl-transferase (COMT), and estrogen receptor a (ESR1). Methods: A case-control study was conducted on 305 young ischemic stroke subjects aged 50 years and 309 agematched healthy controls. SULT1E1-64G/A, COMT Val158Met, ESR1 c.4542397 T/C and c.4542351 A/G genes were genotyped and compared between cases and controls to identify single nucleotide polymorphisms associated with ischemic stroke susceptibility. Gene-gene interaction effects were analyzed using entropy-based multifactor dimensionality reduction (MDR), classification and regression tree (CART), and traditional multiple regression models. Results: COMT Val158Met polymorphism showed a significant association with susceptibility of young ischemic stroke among females. There was a two-way interaction between SULT1E1-64G/A and COMT Val158Met in both MDR and CART analysis. The logistic regression model also showed there was a significant interaction effect between SULT1E1-64G/A and COMT Val158Met on ischemic stroke of the young (P for interaction = 0.0171). We further found that lower estradiol level could increase the risk of young ischemic stroke for those who carry either SULT1E1 or COMT risk genotypes, showing a significant interaction effect (P for interaction = 0.0174). Conclusions: Our findings support that a significant epistasis effect exists among estrogen metabolic and signaling pathway genes and gene-environment interactions on young ischemic stroke subjects.

Research paper thumbnail of The 2020 Taiwan Stroke Society guidelines for blood pressure control at the acute stage of ischemic stroke

Journal of the Formosan Medical Association

Research paper thumbnail of Effects of Modafinil and Armodafinil in Patients With Obstructive Sleep Apnea: A Meta-analysis of Randomized Controlled Trials

Clinical Therapeutics, 2016

Obstructive sleep apnea (OSA) is associated with nocturnal hypoxemia, excessive daytime sleepines... more Obstructive sleep apnea (OSA) is associated with nocturnal hypoxemia, excessive daytime sleepiness (EDS), and sympathetic hyperactivation. Continuous positive airway pressure is the first-line treatment for OSA. However, some patients may have residual EDS. Modafinil and its R-enantiomer, armodafinil, are wakefulness-promoting agents known to be effective in alleviating sleepiness. We performed a systematic review and meta-analysis of data from published randomized controlled trials (RCTs) that evaluated the efficacy of modafinil and armodafinil in treating EDS in patients with OSA. Electronic databases, including PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials, were searched for articles on OSA published before October 2015. We identified 11 RCTs of modafinil involving 723 patients and 5 RCTs of armodafinil involving 1009 patients. A pooled estimate of the mean differences in sleepiness parameters versus placebo were calculated using the random-effects model. Epworth Sleepiness Scale scores improved significantly in the modafinil group (weighted mean difference [WMD], -2.96 [95% confidence interval (CI), -3.73 to -2.19]) and in the armodafinil group (WMD, -2.63; 95% CI, -3.4 to -1.85) compared with those in the placebo group. Sleep latency, as measured on the Maintenance of Wakefulness Test, was significantly prolonged in the modafinil group (WMD, 2.51 [95% CI, 1.5-3.52]) and in the armodafinil group (WMD, 2.71 [95% CI, 0.04-5.37]). Patients tolerated the adverse events with both medications well. The findings from our study suggest that both modafinil and armodafinil significantly improved subjective and objective daytime sleepiness. Thus, modafinil and armodafinil may be recommended to patients with OSA, particularly those with EDS.

Research paper thumbnail of Associations Between Cerebral Vasoreactivity and Cognitive Function in the Middle-Aged Non-Demented Population

Journal of Alzheimer's Disease

Background: Increasing evidence shows early vascular dysregulation in the pathophysiology of Alzh... more Background: Increasing evidence shows early vascular dysregulation in the pathophysiology of Alzheimer’s disease (AD) in elderly population. Objective: We wondered about the relationship between vascular health and cognitive performance in middle-aged adults. The present study aims to evaluate whether and which brain vascular hemodynamic parameters are associated with cognitive functions in a middle-aged, non-demented population. Methods: We recruited 490 middle-aged community-based participants (30–60 years). Transcranial color-coded sonography was used to measure cerebral vascular hemodynamics, including mean flow velocity, pulsatility index, and breath-holding index (BHI) in the middle cerebral arteries (MCAs). Cognitive functions were assessed using the Montreal Cognitive Assessment (MoCA). A multivariate linear regression model was used to determine the association between the MoCA scores and each intracranial hemodynamic parameter. Results: In 369 participants (median age 52 y...

Research paper thumbnail of A Mobile Application for Predicting 90-day Outcomes after IV Thrombolysis in Ischemic Stroke (P3.069)

Neurology, 2015

OBJECTIVE: To develop and validate a mobile application to estimate 90-day outcomes in ischemic s... more OBJECTIVE: To develop and validate a mobile application to estimate 90-day outcomes in ischemic stroke patients after IV thrombolysis (rt-PA) BACKGROUND: The clinical utility of scores for predicting symptomatic intracranial hemorrhage (sICH) or adverse 90-day outcome has been reported. We derived a computationally-simple score for predicting sICH to evaluate its ability to predict 90-day outcomes in an external dataset, and to develop an iOS-based mobile application to use this score at the bedside. DESIGN/METHODS: We retrospectively analyzed data from 312 patients who received IV rt-PA during the NINDS rt-PA trial. Clinical outcomes were assessed at 90 days using modified Rankin Scale (mRS) scores. Adverse and favorable outcomes were defined as mRS 蠅 5, and mRS ≤ 1. Agreement between our clinical score and clinical outcomes were assessed using univariate logistic regression reporting odds ratios, Hosmer-Lemeshow statistics and areas under the ROC curve. P-values < 0.05 (two-tai...

Research paper thumbnail of Comparison of On-hour vs Off-hour Patient Cohorts at a Primary Stroke Center: Onset-To-Treatment Duration and Clinical Outcomes after IV Thrombolysis (S21.005)

Neurology, 2015

OBJECTIVE: To compare OTT durations and clinical outcomes in ischemic stroke patients whose sympt... more OBJECTIVE: To compare OTT durations and clinical outcomes in ischemic stroke patients whose symptoms originated during on- vs off-hours at a Primary Stroke Center. BACKGROUND: Symptom onset-to-treatment (OTT) duration is an independent predictor of symptomatic intracerebral hemorrhage (sICH) and adverse outcomes after stroke. Recent studies have raised concerns for OTT duration and clinical outcomes disparities between stroke patients whose symptoms originate during on-hours vs off-hours. DESIGN/METHODS: We conducted a retrospective cohort study using clinical data from 210 consecutive patients receiving IV rtPA between 1/2009 and 12/2013 at Yale New Haven Hospital. On-hours were 8am to 5pm; off-hours were 5pm to 8 am. Stroke severity was assessed by baseline NIHSS scores, clinical outcomes were assessed by presence of sICH and stroke-related fatalities. OTT durations and clinical outcomes were compared using Mann-Whitney tests, two-sample tests of proportions and two-sample t-tests...

Research paper thumbnail of Abstract W P265: Improved Symptomatic ICH Rates for Ischemic Stroke Patients Receiving IV rtPA

Introduction: Symptomatic intracranial hemorrhage (sICH) is a concerning complication after the a... more Introduction: Symptomatic intracranial hemorrhage (sICH) is a concerning complication after the administration of IV r-tPA for treatment of acute ischemic stroke. Results from the NINDS trial demonstrated a 6.2% sICH rate. As such, acute stroke teams have used this data as a benchmark to compare their program’s complication rate related to IV r-tPA treatment in acute ischemic stroke. Hypothesis: We examined the percent of acute ischemic stroke patients treated with IV r-tPA each year who developed sICH, and compared our sICH rate with the NINDS benchmark data for this adverse outcome. We anticipated that the sICH rate would decline with additional experience and expanded use of evaluation and treatment protocols at our institution. Methods: Clinical data was analyzed from consecutive patients (n = 187) receiving IV rt-PA therapy from January 2009 until December 2012 at the Yale-New Haven Hospital. Adverse outcome was assessed by presence of symptomatic intracerebral hemorrhage (sICH...

Research paper thumbnail of Abstract W P64: DRAGON Score Outperforms 7 Other Hemorrhagic Transformation Scores in Ischemic Stroke Patients Treated With IV r-tPA

Introduction: Hemorrhagic transformation (HT) is a major complication of IV r-tPA therapy followi... more Introduction: Hemorrhagic transformation (HT) is a major complication of IV r-tPA therapy following ischemic stroke. At least 8 scores have been proposed to predict HT in patients undergoing IV thrombolytic therapy; however, studies comparing these 8 scores in an independent dataset are missing. Hypothesis: We tested the hypothesis that stroke metrics can predict adverse outcome after r-tPA therapy. Methods: Clinical data was analyzed from consecutive patients (n = 187) receiving IV r-tPA therapy from January 2009 until May 2013 at the Yale New Haven Stroke Center. 8 stroke metrics were calculated for each patient: DRAGON, ASTRAL, Stroke-TPI, HAT score, MSS, SITS-ICH, SEDAN and SPAN-100. Adverse outcome was assessed by presence of symptomatic intracerebral hemorrhage (sICH). The NINDS trial defined a hemorrhage as symptomatic if it was not seen on a previous CT scan and there had subsequently been either a suspicion of hemorrhage or any decline in neurologic status. Univariate logis...

Research paper thumbnail of Monogenic Causes in Familial Stroke Across Intracerebral Hemorrhage and Ischemic Stroke Subtypes Identified by Whole-Exome Sequencing

Cellular and Molecular Neurobiology, Dec 29, 2022

Whole exome sequencing (WES) has been used to detect rare causative variants in neurological dise... more Whole exome sequencing (WES) has been used to detect rare causative variants in neurological diseases. However, the efficacy of WES in genetic diagnosis of clinically heterogeneous familial stroke remains inconclusive. We prospectively searched for disease-causing variants in unrelated probands with defined familial stroke by candidate gene/hotspot screening and/or WES, depending on stroke subtypes and neuroimaging features at a referral center. The clinical significance of each variant was determined according to the American College of Medical Genetics guidelines. Among 161 probands (mean age at onset 53.2 ± 13.7 years; male 63.4%), 33 participants (20.5%) had been identified with 19 pathogenic/likely pathogenic variants (PVs; WES applied 152/161 = 94.4%). Across subtypes, the highest hit rate (HR) was intracerebral hemorrhage (ICH, 7/18 = 38.9%), particularly with the etiological subtype of structural vasculopathy (4/4 = 100%, PVs in ENG, KRIT1, PKD1, RNF213); followed by ischemic small vessel disease (SVD, 15/48 = 31.3%; PVs in NOTCH3, HTRA1, HBB). In contrast, large artery atherosclerosis (LAA, 4/44 = 9.1%) and cardioembolism (0/11 = 0%) had the lowest HR. NOTCH3 was the most common causative gene (16/161 = 9.9%), presenting with multiple subtypes of SVD (n = 13), ICH (n = 2), or LAA (n = 1). Importantly, we disclosed two previously unreported PVs, KRIT1 p.E379* in a familial cerebral cavernous malformation, and F2 p.F382L in a familial cerebral venous sinus thrombosis. The contribution of monogenic etiologies was particularly high in familial ICH and SVD subtypes in our Taiwanese cohort. Utilizing subtype-guided hotspot screening and/or subsequent WES, we unraveled monogenic causes in 20.5% familial stroke probands, including 1.2% novel PVs. Genetic diagnosis may enable early diagnosis, management and lifestyle modification. Yo-Tsen Liu and I.-Hui Lee have contributed equally to this work.

Research paper thumbnail of Abstract WP126: Impaired Dynamic Cerebral Autoregulation Predicts Cerebral Hyperperfusion Syndrome After Carotid Angioplasty and Stenting

Stroke, 2016

Introduction: Cerebral hyperperfusion syndrome (CHS) is a devastating complication after carotid ... more Introduction: Cerebral hyperperfusion syndrome (CHS) is a devastating complication after carotid revascularization procedure such as carotid angioplasty and stenting (CAS). Although there is no reliable predictor of CHS after CAS, it is believed CHS is caused by impaired cerebral autoregulation (CA). However, there is no study using CA assessment as a predictor of the occurrence of CHS after CAS. Hypothesis: Impaired preoperative CA index is associated with occurrence of CHS after CAS. Methods: 17 patients with 70-95% stenosis of internal carotid artery who were scheduled to have CAS were enrolled. All patients had dynamic CA assessment 1 day before CAS by analyzing the relationship between the blood pressure of peripheral artery and the flow of stenotic internal carotid artery. Two dynamic CA indexes were measured: time domain analysis (mean pressure-flow correlation coefficient index, Mx) and frequency domain analysis (phase difference at 0.05-0.15Hz measured by a nonlinear analyt...

Research paper thumbnail of Artificial neural network-based analysis of the safetand efficacy of thrombolysis for ischemic stroke in older adults in Taiwan

Research paper thumbnail of Safety and efficacy of extending intravenous thrombolysis treatment for acute ischemic stroke in Taiwan

Neurology Asia, 2019

Recombinant tissue plasminogen activator (rt-PA) is the most effective treatment for acute ischem... more Recombinant tissue plasminogen activator (rt-PA) is the most effective treatment for acute ischemic stroke and the exclusion criteria of rt-PA has been revised to extend its application. However, in Taiwan, National Health Insurance (NHI) did not follow the latest international consensus due to safety concerns. The present study investigated whether extending the application of rt-PA in Taiwan was safe and effective. The medical records from the Shuang Ho hospital stroke registry between August 2009 and December 2016 were retrospectively reviewed. Post rt-PA intracranial hemorrhage (ICH) and modified Rankin Scale (mRS) score at 3-month after stroke were the primary and secondary outcomes, respectively. Differences were analyzed through Fisher’s exact test and Student’s t test. A p-value of <0.05 was considered statistically significant. Overall, there were 243 patients categorized into two groups: NHI exclusion criteria adherence (n = 160) and non-adherence (n = 83). There was no...

Research paper thumbnail of Application of hyperglycemia/diabetes-derived polygenic risk scores on the risk of poor outcomes after an ischemic stroke

Journal of the Chinese Medical Association, 2021

Unfavorable prognoses are often accompanied for hyperglycemic stroke patients. This study aimed t... more Unfavorable prognoses are often accompanied for hyperglycemic stroke patients. This study aimed to construct a hyperglycemia/diabetes-derived polygenic risk score (PRS) to improve the predictive performance for poor outcome risks after a stroke and to evaluate its potential clinical application. A hospital-based cohort study was conducted including 1320 first-ever acute ischemic stroke (AIS) patients and 1210 patients who completed the follow-up at 3 months. PRSs were calculated for hyperglycemia/diabetes mellitus using results from genome-wide association studies in Asians. An unfavorable functional outcome was defined as a modified Rankin Scale score of ≥3 at 3, 6, and 12 months of follow-up. The prediction of a poor prognosis was evaluated using measures of model discrimination, calibration, and net reclassification improvement (NRI). The second to fourth PRS quartiles (≥Q2) were significantly associated with higher risks of unfavorable outcomes at 3 months compared with the first quartile as the reference group after adjusting for age, baseline stroke severity, hypertension, diabetes, dyslipidemia, smoking, heart disease, and ischemic stroke subtype (p for trend <0.0001). The addition of the PRS to traditional risk predictors of poor outcomes after an AIS significantly improved the model fit (likelihood ratio test p < 0.0001) and enhanced measures of reclassification (NRI, 0.245; 95% confidence interval [CI], 0.195-0.596). The corrected C-index for the PRS combining traditional risk factors at 3 months after a stroke was 0.899 (95% CI, 0.878-0.980). Among hyperglycemic AIS patients, those who did not take an antidiabetic drug and whose PRS was ≥Q2 had higher risks of an unfavorable outcome at 3 months compared with patients who took the medicine. The hyperglycemia/diabetes-derived PRS was associated with poor outcomes after an AIS, but further studies are needed to validate its use for clinical applications.

Research paper thumbnail of Etiology and risk factors of intracranial hemorrhage and ischemic stroke in young adults

Journal of the Chinese Medical Association, 2021

Background: Young stroke incidence has increased worldwide with lifestyle changes. Etiology and r... more Background: Young stroke incidence has increased worldwide with lifestyle changes. Etiology and risk factors for both ischemic and hemorrhagic stroke in young Asians remain underexplored. Methods: We retrospectively reviewed consecutive acute stroke patients aged 16–45 years admitted to the Taipei Veterans General Hospital between 2009 and 2019 to analyze etiologic subtypes, risk factors, and serial modified Rankin Scale scores for 1 year and compare the age groups of 16–30 and 31–45 years. Results: Among 670 young Taiwanese patients (mean age at onset 37.5 ± 7.0 years; male 65.1%), there were 366 nontraumatic spontaneous hemorrhagic stroke (including 259 intracerebral hemorrhage [ICH] and 107 subarachnoid hemorrhage, SAH), 292 ischemic stroke and 12 cerebral venous thromboses. Notably, ICH was more prevalent in patients aged 16–30 than in those aged 31–45 (54.8% vs 36.8%). Specifically, structural vasculopathy (e.g., arteriovenous malformation, cavernoma) was the most common etiologic subtype in patients aged 16–30 (p < 0.001), whereas hypertensive ICH was the most common subtype in patients aged 31–45 (p < 0.001). On the other hand, the top ischemic subtype for both age groups was other determined diseases (e.g., arterial dissection, autoimmune diseases, moyamoya disease, etc.) rather than large artery atherosclerosis. Hyperlipidemia, diabetes, and cigarette smoking were more common risk factors for infarction than ICH. Familial stroke patients whose first- or second-degree relatives had a stroke by age 80 (n = 104, 15.5%) had more infarctions than those without a familial stroke history. In multivariate analyses, initial stroke severity, and infarction type were important predictors of favorable outcomes after 3 months. At the 1-year follow-up, patients with ICH and SAH had worse functional outcomes and survival rates than those with infarction. Conclusion: An aggressive approach to elucidate the etiology of stroke is indicated because structural vasculopathy-induced ICH and other determined infarction are distinctively prevalent in young adults, particularly those aged 16–30.

Research paper thumbnail of Development and validation of risk score to estimate 1-year late poststroke epilepsy risk in ischemic stroke patients

Clinical Epidemiology, 2018

Objective: This study aimed to develop and validate a prognostic model for the 1-year risk of lat... more Objective: This study aimed to develop and validate a prognostic model for the 1-year risk of late poststroke epilepsy (PSE). Materials and methods: We included patients initially diagnosed with ischemic stroke between 2003 and 2014 in a National Health Insurance claims-based cohort in Taiwan. Patients were further divided into development and validation cohorts based on their year of stroke diagnosis. Multivariable Cox regression with backward elimination was used to analyze the association between 1-year PSE and risk factors before and on stroke admission. Results: In total, 1,684 (1.93%) and 725 (1.87%) ischemic stroke patients comprising the development and validation cohorts, respectively, experienced late PSE within 1 year after stroke. Seven clinical variables were examined to be independently associated with 1-year risk of PSE. We developed a risk score called "PSEiCARe" ranging from 0 to 16 points, comprising the following factors: prolonged hospital stay (>2 weeks, 1 point), seizure on admission (6 points), elderly patients (age ≥80 years, 1 point), intensive care unit stay on admission (3 points), cognitive impairment (dementia, 2 points), atrial fibrillation (2 points), and respiratory tract infection (pneumonia) on admission (1 point). Patients were further classified into low-, medium-, high-, and very-high-risk groups. The incidence (per 100 person-years) was 0.64 (95% CI: 0.56-0.71) for the low-risk, 2.62 (95% CI: 2.43-2.82) for the medium-risk, 10.3 (95% CI: 9.48-11.3) for the high-risk, and 28.2 (95% CI: 24.0-33.0) for the very-high-risk groups. Discrimination and calibration were satisfactory, with a Harrell's C of 0.762 in the development model and 0.792 in the validation model. Conclusion: PSEiCARe is an easy-to-use prognostic score that integrates patient characteristics and clinical factors on stroke admission to predict 1-year PSE risk; it has the potential to assist individualized patient management and improve clinical practice, thereby preventing the occurrence of late PSE.

Research paper thumbnail of Comparing Different Recording Lengths of Dynamic Cerebral Autoregulation: 5 versus 10 Minutes

BioMed Research International, 2018

We compared the dynamic cerebral autoregulation (dCA) indices between 5- and 10-minute data lengt... more We compared the dynamic cerebral autoregulation (dCA) indices between 5- and 10-minute data lengths by analyzing 37 patients with ischemic stroke and 51 controls in this study. Correlation coefficient (Mx) and transfer function analysis were applied for dCA analysis. Mx and phase shift in all frequency bands were not significantly different between 5- and 10-minute recordings [mean difference: Mx = 0.02; phase shift of very low frequency (0.02–0.07 Hz) = 0.3°, low frequency (0.07–0.20 Hz) = 0.6°, and high frequency (0.20–0.50 Hz) = 0.1°]. However, the gains in all frequency bands of a 5-minute recording were slightly but significantly higher than those of a 10-minute recording (mean difference of gain: very low frequency = 0.05 cm/s/mmHg, low frequency = 0.11 cm/s/mmHg, and high frequency = 0.14 cm/s/mmHg). The intraclass correlation coefficients between all dCA indices of 5- and 10-minute recordings were favorable, especially in Mx (0.93), phase shift in very low frequency (0.87), ...

Research paper thumbnail of The effect of rheumatoid arthritis on the risk of cerebrovascular disease and coronary artery disease in young adults

Journal of the Chinese Medical Association, 2018

Background: Only a few studies have investigated the affect of rheumatoid arthritis (RA) on the r... more Background: Only a few studies have investigated the affect of rheumatoid arthritis (RA) on the risk of cerebrovascular disease (CVD)/coronary artery disease (CAD) in young adults. This study, therefore, examined the association between RA and the risk of CVD/CAD in young adults and the interaction effects between cardiovascular risk factors and RA on the risk of CVD/CAD. Methods: Data regarding 52,840 subjects (10,568 patients with RA and 42,272 age-, sex-, urbanization-, and income-matched non-RA controls) were collected from the National Health Insurance Research Database (NHIRD) in 2006. All subjects were followed until a CVD or CAD diagnosis, or death, or December 31, 2011. The hazard ratios (HRs) of CVD/CAD were estimated using Cox proportional hazard models. The interaction effects between cardiovascular risk factors and RA on the risk of CVD/CAD were assessed using additive and multiplicative models. Results: RA increased the risk of CVD/CAD in young adults, especially those at risk of ischemic stroke (adjusted HR, 3.48; 95% confidence interval (CI), 2.16e5.61). Even without comorbidity at baseline, patients with RA still had a 2.35-fold greater risk of CVD/CAD relative to those without RA. RA and hypertension interacted positively on the risk of CVD/CAD. The highest CVD/CAD risk was found in patients with RA and hypertension (HR, 9.08; 95% CI, 7.22e11.41) relative to subjects without RA and hypertension. Conclusion: RA is an independent risk factor for CVD/CAD in young adults. The government should develop policies for preventing early onset hypertension to reduce the incidence of CVD/CAD among young patients with RA.

Research paper thumbnail of Percutaneous coronary intervention in patients hospitalized for non-ST-elevation myocardial infarction and the risk of postdischarge ischemic stroke at 6-month, 1-year, and 3-year follow-ups

Heart and Vessels, 2019

Percutaneous coronary intervention (PCI) is suggested for treating patients with non-ST-elevation... more Percutaneous coronary intervention (PCI) is suggested for treating patients with non-ST-elevation myocardial infarction (NSTEMI) to reduce adverse cardiovascular events. However, the short- and long-term effects of PCI on the risk of postdischarge ischemic stroke (IS) in patients hospitalized for NSTEMI remain unclear. This study investigated the association of PCI on the risk of postdischarge IS in patients hospitalized for NSTEMI at different period follow-ups. A population-based cohort study was conducted using data from Taiwan’s National Health Insurance Research Database. Propensity score matching (PSM) was used to select 6079 pairs of the patients with NSTEMI treated invasively by PCI (received PCI during hospitalization) and initial conservative strategy (did not receive PCI during hospitalization) with similar baseline characteristics for evaluation. After adjustment for patients’ clinical variables and the duration of dual antiplatelet therapy, PCI was associated with a decreased risk of postdischarge IS at 6-month, 1-year, and 3-year follow-ups [adjusted hazard ratio (aHR) = 0.41, 95% confidence interval (CI) = 0.26–0.67, p < 0.001; aHR = 0.61, 95% CI 0.43–0.86, p = 0.004; and aHR = 0.69, 95% CI 0.54–0.89, p = 0.005respectively]. In the patients who had a CHA2DS2-VASc score of ≥2, PCI was also associated with a decreased risk of postdischarge IS at 6-month, 1-year, and 3-year follow-ups (aHR = 0.54, 95% CI 0.36–0.83, p = 0.005; aHR = 0.72, 95% CI 0.52–1.00, p = 0.048; and aHR =0.73, 95% CI 0.58–0.91, p = 0.005, respectively). These findings suggested that PCI might reduce the risk of postdischarge IS in patients hospitalized for NSTEMI.

Research paper thumbnail of Emotional and Social Dysfunction Questionnaire--Chinese Version

Research paper thumbnail of Effect of early percutaneous coronary intervention on 1-year risk of pneumonia and pneumonia-related adverse outcomes in patients with acute myocardial infarction

EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology, Jan 18, 2017

To investigate the association between early percutaneous coronary intervention (PCI) and pneumon... more To investigate the association between early percutaneous coronary intervention (PCI) and pneumonia risk in patients with acute myocardial infarction (AMI) by using Taiwan's National Health Insurance Research Database. In total, 4,732 patients with non-ST-elevation myocardial infarction (NSTEMI) and 5,465 with ST-elevation myocardial infarction (STEMI) who had received PCI during AMI hospitalisation (early PCI) were evaluated. Patients who did not receive PCI during AMI hospitalisation (deferred PCI) were matched through propensity score matching. The incidence rates (per 100 person-months) of pneumonia hospitalisation, pneumonia-related respiratory failure, and pneumonia-related death associated with early PCI in patients with NSTEMI were 0.36 (95% confidence interval [CI]=0.32-0.42), 0.12 (95% CI=0.10-0.16), and 0.08 (95% CI=0.06-0.11), respectively. In patients with STEMI, the incidence rates (per 100 person-months) of the aforementioned adverse events were 0.16 (95% CI=0.13-...

Research paper thumbnail of Epistasis Analysis for Estrogen Metabolic and Signaling Pathway Genes on Young Ischemic Stroke Patients

PLoS ONE, 2012

Background: Endogenous estrogens play an important role in the overall cardiocirculatory system. ... more Background: Endogenous estrogens play an important role in the overall cardiocirculatory system. However, there are no studies exploring the hormone metabolism and signaling pathway genes together on ischemic stroke, including sulfotransferase family 1E (SULT1E1), catechol-O-methyl-transferase (COMT), and estrogen receptor a (ESR1). Methods: A case-control study was conducted on 305 young ischemic stroke subjects aged 50 years and 309 agematched healthy controls. SULT1E1-64G/A, COMT Val158Met, ESR1 c.4542397 T/C and c.4542351 A/G genes were genotyped and compared between cases and controls to identify single nucleotide polymorphisms associated with ischemic stroke susceptibility. Gene-gene interaction effects were analyzed using entropy-based multifactor dimensionality reduction (MDR), classification and regression tree (CART), and traditional multiple regression models. Results: COMT Val158Met polymorphism showed a significant association with susceptibility of young ischemic stroke among females. There was a two-way interaction between SULT1E1-64G/A and COMT Val158Met in both MDR and CART analysis. The logistic regression model also showed there was a significant interaction effect between SULT1E1-64G/A and COMT Val158Met on ischemic stroke of the young (P for interaction = 0.0171). We further found that lower estradiol level could increase the risk of young ischemic stroke for those who carry either SULT1E1 or COMT risk genotypes, showing a significant interaction effect (P for interaction = 0.0174). Conclusions: Our findings support that a significant epistasis effect exists among estrogen metabolic and signaling pathway genes and gene-environment interactions on young ischemic stroke subjects.

Research paper thumbnail of The 2020 Taiwan Stroke Society guidelines for blood pressure control at the acute stage of ischemic stroke

Journal of the Formosan Medical Association

Research paper thumbnail of Effects of Modafinil and Armodafinil in Patients With Obstructive Sleep Apnea: A Meta-analysis of Randomized Controlled Trials

Clinical Therapeutics, 2016

Obstructive sleep apnea (OSA) is associated with nocturnal hypoxemia, excessive daytime sleepines... more Obstructive sleep apnea (OSA) is associated with nocturnal hypoxemia, excessive daytime sleepiness (EDS), and sympathetic hyperactivation. Continuous positive airway pressure is the first-line treatment for OSA. However, some patients may have residual EDS. Modafinil and its R-enantiomer, armodafinil, are wakefulness-promoting agents known to be effective in alleviating sleepiness. We performed a systematic review and meta-analysis of data from published randomized controlled trials (RCTs) that evaluated the efficacy of modafinil and armodafinil in treating EDS in patients with OSA. Electronic databases, including PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials, were searched for articles on OSA published before October 2015. We identified 11 RCTs of modafinil involving 723 patients and 5 RCTs of armodafinil involving 1009 patients. A pooled estimate of the mean differences in sleepiness parameters versus placebo were calculated using the random-effects model. Epworth Sleepiness Scale scores improved significantly in the modafinil group (weighted mean difference [WMD], -2.96 [95% confidence interval (CI), -3.73 to -2.19]) and in the armodafinil group (WMD, -2.63; 95% CI, -3.4 to -1.85) compared with those in the placebo group. Sleep latency, as measured on the Maintenance of Wakefulness Test, was significantly prolonged in the modafinil group (WMD, 2.51 [95% CI, 1.5-3.52]) and in the armodafinil group (WMD, 2.71 [95% CI, 0.04-5.37]). Patients tolerated the adverse events with both medications well. The findings from our study suggest that both modafinil and armodafinil significantly improved subjective and objective daytime sleepiness. Thus, modafinil and armodafinil may be recommended to patients with OSA, particularly those with EDS.

Research paper thumbnail of Associations Between Cerebral Vasoreactivity and Cognitive Function in the Middle-Aged Non-Demented Population

Journal of Alzheimer's Disease

Background: Increasing evidence shows early vascular dysregulation in the pathophysiology of Alzh... more Background: Increasing evidence shows early vascular dysregulation in the pathophysiology of Alzheimer’s disease (AD) in elderly population. Objective: We wondered about the relationship between vascular health and cognitive performance in middle-aged adults. The present study aims to evaluate whether and which brain vascular hemodynamic parameters are associated with cognitive functions in a middle-aged, non-demented population. Methods: We recruited 490 middle-aged community-based participants (30–60 years). Transcranial color-coded sonography was used to measure cerebral vascular hemodynamics, including mean flow velocity, pulsatility index, and breath-holding index (BHI) in the middle cerebral arteries (MCAs). Cognitive functions were assessed using the Montreal Cognitive Assessment (MoCA). A multivariate linear regression model was used to determine the association between the MoCA scores and each intracranial hemodynamic parameter. Results: In 369 participants (median age 52 y...

Research paper thumbnail of A Mobile Application for Predicting 90-day Outcomes after IV Thrombolysis in Ischemic Stroke (P3.069)

Neurology, 2015

OBJECTIVE: To develop and validate a mobile application to estimate 90-day outcomes in ischemic s... more OBJECTIVE: To develop and validate a mobile application to estimate 90-day outcomes in ischemic stroke patients after IV thrombolysis (rt-PA) BACKGROUND: The clinical utility of scores for predicting symptomatic intracranial hemorrhage (sICH) or adverse 90-day outcome has been reported. We derived a computationally-simple score for predicting sICH to evaluate its ability to predict 90-day outcomes in an external dataset, and to develop an iOS-based mobile application to use this score at the bedside. DESIGN/METHODS: We retrospectively analyzed data from 312 patients who received IV rt-PA during the NINDS rt-PA trial. Clinical outcomes were assessed at 90 days using modified Rankin Scale (mRS) scores. Adverse and favorable outcomes were defined as mRS 蠅 5, and mRS ≤ 1. Agreement between our clinical score and clinical outcomes were assessed using univariate logistic regression reporting odds ratios, Hosmer-Lemeshow statistics and areas under the ROC curve. P-values < 0.05 (two-tai...

Research paper thumbnail of Comparison of On-hour vs Off-hour Patient Cohorts at a Primary Stroke Center: Onset-To-Treatment Duration and Clinical Outcomes after IV Thrombolysis (S21.005)

Neurology, 2015

OBJECTIVE: To compare OTT durations and clinical outcomes in ischemic stroke patients whose sympt... more OBJECTIVE: To compare OTT durations and clinical outcomes in ischemic stroke patients whose symptoms originated during on- vs off-hours at a Primary Stroke Center. BACKGROUND: Symptom onset-to-treatment (OTT) duration is an independent predictor of symptomatic intracerebral hemorrhage (sICH) and adverse outcomes after stroke. Recent studies have raised concerns for OTT duration and clinical outcomes disparities between stroke patients whose symptoms originate during on-hours vs off-hours. DESIGN/METHODS: We conducted a retrospective cohort study using clinical data from 210 consecutive patients receiving IV rtPA between 1/2009 and 12/2013 at Yale New Haven Hospital. On-hours were 8am to 5pm; off-hours were 5pm to 8 am. Stroke severity was assessed by baseline NIHSS scores, clinical outcomes were assessed by presence of sICH and stroke-related fatalities. OTT durations and clinical outcomes were compared using Mann-Whitney tests, two-sample tests of proportions and two-sample t-tests...

Research paper thumbnail of Abstract W P265: Improved Symptomatic ICH Rates for Ischemic Stroke Patients Receiving IV rtPA

Introduction: Symptomatic intracranial hemorrhage (sICH) is a concerning complication after the a... more Introduction: Symptomatic intracranial hemorrhage (sICH) is a concerning complication after the administration of IV r-tPA for treatment of acute ischemic stroke. Results from the NINDS trial demonstrated a 6.2% sICH rate. As such, acute stroke teams have used this data as a benchmark to compare their program’s complication rate related to IV r-tPA treatment in acute ischemic stroke. Hypothesis: We examined the percent of acute ischemic stroke patients treated with IV r-tPA each year who developed sICH, and compared our sICH rate with the NINDS benchmark data for this adverse outcome. We anticipated that the sICH rate would decline with additional experience and expanded use of evaluation and treatment protocols at our institution. Methods: Clinical data was analyzed from consecutive patients (n = 187) receiving IV rt-PA therapy from January 2009 until December 2012 at the Yale-New Haven Hospital. Adverse outcome was assessed by presence of symptomatic intracerebral hemorrhage (sICH...

Research paper thumbnail of Abstract W P64: DRAGON Score Outperforms 7 Other Hemorrhagic Transformation Scores in Ischemic Stroke Patients Treated With IV r-tPA

Introduction: Hemorrhagic transformation (HT) is a major complication of IV r-tPA therapy followi... more Introduction: Hemorrhagic transformation (HT) is a major complication of IV r-tPA therapy following ischemic stroke. At least 8 scores have been proposed to predict HT in patients undergoing IV thrombolytic therapy; however, studies comparing these 8 scores in an independent dataset are missing. Hypothesis: We tested the hypothesis that stroke metrics can predict adverse outcome after r-tPA therapy. Methods: Clinical data was analyzed from consecutive patients (n = 187) receiving IV r-tPA therapy from January 2009 until May 2013 at the Yale New Haven Stroke Center. 8 stroke metrics were calculated for each patient: DRAGON, ASTRAL, Stroke-TPI, HAT score, MSS, SITS-ICH, SEDAN and SPAN-100. Adverse outcome was assessed by presence of symptomatic intracerebral hemorrhage (sICH). The NINDS trial defined a hemorrhage as symptomatic if it was not seen on a previous CT scan and there had subsequently been either a suspicion of hemorrhage or any decline in neurologic status. Univariate logis...