Seong Hwan Ahn

Improved Time Intervals by Implementation of Computerized Physician Order Entry-Based Stroke Team Approach

Background: The need for rapid evaluation and treatment of acute stroke patients has been well documented. A computerized physician order entry (CPOE) system can improve communication and provide immediate access to information, which may be useful for an effective team approach program targeted to reduce in-hospital time delays. Methods: To reduce the time from a patient’s arrival at the emergency department to thrombolysis, a team approach program using CPOE was developed, and its efficacy was investigated by comparing time intervals from arrival to evaluation and intravenous tissue-type plasminogen activator (tPA) treatment before and after the implementation of the program. Results: Among 379 consecutive patients who were screened as potential candidates for thrombolysis, 25 patients (6.6%) received tPA during a 1-year period after initiation of the program. Fourteen patients were treated with tPA in the previous year. After program implementation, time from arrival to computed tomography scan was reduced from 34 to 19 min (p = 0.01). Time to report of complete blood count was also shortened from 52 to 33 min (p < 0.01). Finally, time from arrival to tPA treatment was reduced by 23 min (from 79 to 56 min; p < 0.01). Onset-to-door time tended to be longer after the program implementation (from 41 to 60 min; p = 0.14). Conclusions: Implementation of the CPOE-based team approach program significantly reduced time from emergency department arrival to evaluations and treatment.

A Computerized In-Hospital Alert System for Thrombolysis in Acute Stroke

Background and Purpose— An effective stroke code system that can expedite rapid thrombolytic treatment requires effective notification/communication and an organized team approach. We developed a stroke code program based on the computerized physician order entry (CPOE) system and investigated whether implementation of this CPOE-based program is useful for reducing the time from arrival at emergency departments (ED) to evaluation steps and the initiation of thrombolytic treatment in various hospital settings. Methods— The CPOE-based program was implemented by 10 hospitals. Time intervals from arrival at the ED to blood tests, computed tomography scanning, and thrombolytic treatment during the 1-year period before and the 1-year period after the program implementation were compared. Results— Time intervals from ED arrival to evaluation steps were significantly reduced after implementation of the CPOE-based program. Times from ED arrival to CT scan, complete blood counts, and prothrombin time testing were reduced by 7.7 minutes, 5.6 minutes, and 26.8 minutes, respectively (P<0.001). The time from ED arrival to intravenous thrombolysis was reduced from 71.7±33.6 minutes to 56.6±26.9 minutes (P<0.001). The number of patients who were treated with thrombolysis increased from 3.4% (199/5798 patients) before the CPOE-based program to 5.8% (312/5405 patients) afterward (P<0.001). The CPOE implementation also improved the inverse relationship between onset-to-door time and door-to-needle time. Conclusions— The CPOE-based stroke code could be successfully implemented to reduce in-hospital time delay in thrombolytic therapy in various hospital settings. CPOE may be used as an efficient tool to facilitate in-hospital notification/communication and an organized team approach.

Prediction of long-term outcome by percent improvement after the first day of thrombolytic treatment in stroke patients

BACKGROUND We investigated a method for assessing early improvement and predictive factors of early and late outcomes in patients receiving thrombolytic therapy. METHODS A total of 160 consecutive patients who received thrombolytic therapy were included in the study. Using National Institutes of Health Stroke Scale (NIHSS) scores, percent improvement [(baseline NIHSS score-24-hour NIHSS score)/baseline NIHSS score x 100] was calculated and compared with delta (baseline NIHSS score-24-hour NIHSS score) and with major neurological improvement (MNI, NIHSS score of 0-1 or >or=8 point improvement at 24 h) by receiver operating characteristic (ROC) curve analysis. Finally, we investigated the independent predictors of improvement at 24 h after the thrombolytic therapy and of favorable 3-month outcome (modified Rankin scale score 0-2). RESULTS By pairwise comparison of ROC curves, percent improvement was stronger than delta (p=0.004) and MNI (p<0.001) in predicting long-term outcome. First day improvement (FDI), defined as greater than 20% improvement, was a strong predictor of favorable 3-month outcome (OR 12.55, 95% CI 5.41-29.10). Recanalization (OR 3.30, 95% CI 1.28-8.45), absence of carotid T occlusion (OR 0.09, 95% CI 0.02-0.42) and hemorrhagic transformation (OR 0.25, 95% CI 0.09-0.73) were independent predictors of FDI. Independent predictors of favorable 3-month outcome were FDI, current smoking, absence of carotid T occlusion and hemorrhagic transformation. CONCLUSIONS Percent improvement at 24 h after thrombolytic therapy is a useful surrogate marker for predicting the long-term outcome. Our findings highlight the importance of early stroke management.

Interaction between Sleep-Disordered Breathing and Acute Ischemic Stroke

Background and Purpose Sleep-disordered breathing (SDB) is suggested to be strongly associated with ischemic strokes. Risk factors, stroke subtypes, stroke lesion distribution, and the outcome of SDB in stroke patients remain unclear in Korea. Methods We prospectively studied 293 patients (159 men, 134 women; age 68.4±10.5) with acute ischemic stroke. Cardiovascular risk factors, stroke severity, sleep-related stroke onset, distribution of stroke lesions, and 3-month score on the modified Rankin Scale (mRS) were assessed. Stroke severity was assessed by the US National Institutes of Health Stroke Scale (NIHSS) and the mRS. The apnea-hypopnea index (AHI) was determined 6.3±2.2 days after stroke onset with the Apnea Link portable sleep apnea monitoring device. Results The prevalence of SDB (defined as an AHI of ≥10) was 63.1% (111 men, 74 women). Those in the SDB group were older, had higher NIHSS and mRS scores, greater bulbar weakness, and a higher incidence of sleep-associated stroke onset. Among risk-factor profiles, alcohol consumption and atrial fibrillation were significantly related to SDB. The stroke outcome was worse in patients with SDB than in those without SDB. The lesion location and specific stroke syndrome were not correlated with SDB. Conclusions SDB is very common in acute cerebral infarction. Different risk-factor profiles and sleep-related stroke onsets suggest SDB as a cause of ischemic stroke. The higher NIHSS score and greater bulbar involvement in the SDB group seem to show the influence of ischemic stroke on the increased SDB prevalence.

Time-Dependent Computed Tomographic Perfusion Thresholds for Patients With Acute Ischemic Stroke

Background and Purpose— Among patients with acute ischemic stroke, we determine computed tomographic perfusion (CTP) thresholds associated with follow-up infarction at different stroke onset-to-CTP and CTP-to-reperfusion times. Methods— Acute ischemic stroke patients with occlusion on computed tomographic angiography were acutely imaged with CTP. Noncontrast computed tomography and magnectic resonance diffusion–weighted imaging between 24 and 48 hours were used to delineate follow-up infarction. Reperfusion was assessed on conventional angiogram or 4-hour repeat computed tomographic angiography. Tmax, cerebral blood flow, and cerebral blood volume derived from delay-insensitive CTP postprocessing were analyzed using receiver–operator characteristic curves to derive optimal thresholds for combined patient data (pooled analysis) and individual patients (patient-level analysis) based on time from stroke onset-to-CTP and CTP-to-reperfusion. One-way ANOVA and locally weighted scatterplot smoothing regression was used to test whether the derived optimal CTP thresholds were different by time. Results— One hundred and thirty-two patients were included. Tmax thresholds of >16.2 and >15.8 s and absolute cerebral blood flow thresholds of <8.9 and <7.4 mL·min−1·100 g−1 were associated with infarct if reperfused <90 min from CTP with onset <180 min. The discriminative ability of cerebral blood volume was modest. No statistically significant relationship was noted between stroke onset-to-CTP time and the optimal CTP thresholds for all parameters based on discrete or continuous time analysis (P>0.05). A statistically significant relationship existed between CTP-to-reperfusion time and the optimal thresholds for cerebral blood flow (P<0.001; r=0.59 and 0.77 for gray and white matter, respectively) and Tmax (P<0.001; r=−0.68 and −0.60 for gray and white matter, respectively) parameters. Conclusions— Optimal CTP thresholds associated with follow-up infarction depend on time from imaging to reperfusion.

Occult Anterograde Flow Is an Under-Recognized but Crucial Predictor of Early Recanalization With Intravenous Tissue-Type Plasminogen Activator

Background and Purpose— Thrombolysis depends on the ability of blood and thrombolytic agents to permeate thrombus. We devised a novel technique to quantify blood permeating through thrombi and determine whether this parameter predicts early recanalization with intravenous tissue-type plasminogen activator. Methods— Intravenous tissue-type plasminogen activator–treated patients with stroke and complete occlusion on computed tomographic angiography were analyzed using perfusion computed tomography and a delay insensitive algorithm. We generated maps that measure delay in arrival time of contrast within the intracranial arterial tree (T0 maps). A positive sloped regression line of T0 values measured along artery silhouette distal to thrombus was defined as marker of permeable thrombus (occult anterograde flow). Median T0 values at proximal and distal thrombus interface were measured. Early recanalization was assessed on first angiography of subsequent intra-arterial procedure or on a 4-hour computed tomographic angiography. Results— Of 66 patients, occult anterograde flow was detected in 17 (25.8%). Early recanalization was more in patients with occult anterograde flow versus not (66.7 versus 29.7%; P=0.031). Median T0 value (in s) at distal thrombus interface (1.5 versus 3.8; P=0.006) and difference in median T0 value between proximal and distal thrombus interface (1.3 versus 3.7; P=0.014) were less in early recanalizers versus in nonrecanalizers. In multivariable analysis, patients with occult anterograde flow and T0 value difference between proximal and distal thrombus interface ⩽2 s recanalized most (71.4%; odds ratio, 12.15; 95% confidence interval, 2.05–71.91), whereas patients with retrograde flow and T0 value difference >2 s recanalized least (25.9%; odds ratio, 1). Conclusions— Occult anterograde flow through thrombus can be assessed by perfusion computed tomography T0 maps and predicts early recanalization with intravenous tissue-type plasminogen activator robustly.

Efficacy of early administration of escitalopram on depressive and emotional symptoms and neurological dysfunction after stroke: a multicentre, double-blind, randomised, placebo-controlled study.

BACKGROUND Mood and emotional disturbances are common in patients with stroke, and adversely affect the clinical outcome. We aimed to evaluate the efficacy of early administration of escitalopram to reduce moderate or severe depressive symptoms and improve emotional and neurological dysfunction in patients with stroke. METHODS This was a placebo controlled, double-blind trial done at 17 centres in South Korea. Patients who had had an acute stroke within the past 21 days were randomly assigned in a 1:1 ratio to receive oral escitalopram (10 mg/day) or placebo for 3 months. Randomisation was done with permuted blocks stratified by centre, via a web-based system. The primary endpoint was the frequency of moderate or severe depressive symptoms (Montgomery-Åsberg Depression Rating Scale [MADRS] ≥16). Endpoints were assessed at 3 months after randomisation in the full analysis set (patients who took study medication and underwent assessment of primary endpoint after randomisation), in all patients who were enrolled and randomly assigned (intention to treat), and in all patients who completed the trial (per-protocol analysis). This trial is registered with ClinicalTrials.gov, number NCT01278498. FINDINGS Between Jan 27, 2011, and June 30, 2014, 478 patients were assigned to placebo (n=237) or escitalopram (n=241); 405 were included in the full analysis set (195 in the placebo group, 210 in the escitalopram group). The primary outcome did not differ by study group in the full analysis set (25 [13%] patients in the placebo group vs 27 [13%] in the escitalopram group; odds ratio [OR] 1·00, 95% CI 0·56-1·80; p>0·99) or in the intention-to-treat analysis (34 [14%] vs 35 [15%]; OR 1·01, 95% CI 0·61-1·69, p=0·96). The study medication was generally well tolerated; the most common adverse events were constipation (14 [6%] patients who received placebo vs 14 [6%] who received escitalopram), muscle pain (16 [7%] vs ten [4%]), and insomnia (12 [5%] vs 12 [5%]). Diarrhoea was more common in the escitalopram group (nine [4%] patients) than in the placebo group (two [1%] patients). INTERPRETATION Escitalopram did not significantly reduce moderate or severe depressive symptoms in patients with acute stroke. FUNDING Dong-A Pharmaceutical and Ministry for Health, Welfare, and Family Affairs, South Korea.

Histologic features of acute thrombi retrieved from stroke patients during mechanical reperfusion therapy

Background The histologic features of thrombus may differ according to the stroke subtypes. However, in acute reperfusion therapy, fibrin-specific thrombolytics are used based on the assumption that all thrombi are alike. Aims The histologic characteristics of thrombi were compared between patients with different stroke etiologies. Methods Between April 2010 and March 2012, we analyzed thrombi retrieved from acute stroke patients during mechanical thrombectomy. All thrombi were analyzed using component-specific stains such as Martius scarlet blue for fibrins and immunostaining with CD42b antibody for platelets. The stroke subtypes were determined based on the Trial of ORG 10172 in Acute Stroke Treatment classification. Results Among 36 patients, 22 were diagnosed with cardioembolism, 8 with atherothrombosis, and 6 with undetermined etiology. In arteriogenic thrombi, red blood cells were most abundant (56.9 ± 12.2%), and the platelets covered the fibrin layers or were localized at the edge or periphery of the thrombus. In cardiogenic thrombi, fibrin was most abundant (39.5 ± 13.5%), and platelets were clustered within the rich fibrin. Red blood cells proportion was greater in arteriogenic thrombi than in cardiogenic thrombi (p < 0.001), whereas fibrin proportion was greater in cardiogenic thrombi than in arteriogenic thrombi (p = 0.003). Of six patients with undetermined etiology, the thrombi in five showed histologic features and composition similar to that of cardiogenic thrombi. Conclusions Acute thrombi showed different histologic features according to the stroke etiology. The distribution of platelets and proportion of red blood cells and fibrin were major distinguishing factors between stroke subtypes.

Regional Comparison of Multiphase Computed Tomographic Angiography and Computed Tomographic Perfusion for Prediction of Tissue Fate in Ischemic Stroke

Background and Purpose— Within different brain regions, we determine the comparative value of multiphase computed tomographic angiography (mCTA) and computed tomographic perfusion (CTP) in predicting follow-up infarction. Methods— Patients with M1-middle cerebral artery occlusions were prospectively included in this multicenter study. Regional analysis was performed for each patient within Alberta Stroke Program Early CT Score regions M2 to M6. Regional pial vessel filling was assessed on mCTA in 3 ways: (1) Washout of contrast within pial vessels; (2) Extent of maximal pial vessel enhancement compared with contralateral hemisphere; (3) Delay in maximal pial vessel enhancement compared with contralateral hemisphere. Cerebral blood flow, cerebral blood volume, and Tmax data were extracted within these Alberta Stroke Program Early CT Score regions. Twenty-four- to 36-hour magnetic resonance imaging/CT was assessed for infarct in each Alberta Stroke Program Early CT Score region (defined as >20% infarction within that region). Mixed effects logistic regression models were used to compare mCTA and CTP parameters when predicting brain infarction. Area under the receiver operating characteristics was used to assess discriminative value of statistical models. Results— Seventy-seven patients were included. mCTA parameter washout and CTP parameter Tmax were significantly associated with follow-up infarction in all models (P<0.05). The area under the receiver operating characteristic for mCTA models ranged from 92% to 94% and was not different compared with all CTP models (P>0.05). Mean Tmax and cerebral blood volume values were significantly different between each washout score (P<0.01) and each delay score category (P<0.01). Mean Tmax, cerebral blood flow, and cerebral blood volume values were significantly different between each extent score category (P<0.05). Conclusions— Similar to CTP, multiphase CTA can be used to predict tissue fate regionally in acute ischemic stroke patients.

Factors Associated with Ischemic Stroke on Therapeutic Anticoagulation in Patients with Nonvalvular Atrial Fibrillation

Purpose In this study, we investigated the stroke mechanism and the factors associated with ischemic stroke in patients with nonvalvular atrial fibrillation (NVAF) who were on optimal oral anticoagulation with warfarin. Materials and Methods This was a multicenter case-control study. The cases were consecutive patients with NVAF who developed cerebral infarction or transient ischemic attack (TIA) while on warfarin therapy with an international normalized ratio (INR) ≥2 between January 2007 and December 2011. The controls were patients with NVAF without ischemic stroke who were on warfarin therapy for more than 1 year with a mean INR ≥2 during the same time period. We also determined etiologic mechanisms of stroke in cases. Results Among 3569 consecutive patients with cerebral infarction or TIA who had NVAF, 55 (1.5%) patients had INR ≥2 at admission. The most common stroke mechanism was cardioembolism (76.0%). Multivariate analysis demonstrated that smoking and history of previous ischemic stroke were independently associated with cases. High CHADS2 score (≥3) or CHA2DS2-VASc score (≥5), in particular, with previous ischemic stroke along with ≥1 point of other components of CHADS2 score or ≥3 points of other components of CHA2DS2-VASc score was a significant predictor for development of ischemic stroke. Conclusion NVAF patients with high CHADS2/CHA2DS2-VASc scores and a previous ischemic stroke or smoking history are at high risk of stroke despite optimal warfarin treatment. Some other measures to reduce the risk of stroke would be necessary in those specific groups of patients.