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1.
Front Neurol ; 15: 1351150, 2024.
Article En | MEDLINE | ID: mdl-38813247

Background: Hyperglycemia affects the outcomes of endovascular therapy (EVT) for acute ischemic stroke (AIS). This study compares the predictive ability of diabetes status and glucose measures on EVT outcomes using nationwide registry data. Methods: The study included 1,097 AIS patients who underwent EVT from the Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke. The variables analyzed included diabetes status, admission glucose, glycated hemoglobin (HbA1c), admission glucose-to-HbA1c ratio (GAR), and outcomes such as 90-day poor functional outcome (modified Rankin Scale score ≥ 2) and symptomatic intracranial hemorrhage (SICH). Multivariable analyses investigated the independent effects of diabetes status and glucose measures on outcomes. A receiver operating characteristic (ROC) analysis was performed to compare their predictive abilities. Results: The multivariable analysis showed that individuals with known diabetes had a higher likelihood of poor functional outcomes (odds ratios [ORs] 2.10 to 2.58) and SICH (ORs 3.28 to 4.30) compared to those without diabetes. Higher quartiles of admission glucose and GAR were associated with poor functional outcomes and SICH. Higher quartiles of HbA1c were significantly associated with poor functional outcomes. However, patients in the second HbA1c quartile (5.6-5.8%) showed a non-significant tendency toward good functional outcomes compared to those in the lowest quartile (<5.6%). The ROC analysis indicated that diabetes status and admission glucose had higher predictive abilities for poor functional outcomes, while admission glucose and GAR were better predictors for SICH. Conclusion: In AIS patients undergoing EVT, diabetes status, admission glucose, and GAR were associated with 90-day poor functional outcomes and SICH. Admission glucose was likely the most suitable glucose measure for predicting outcomes after EVT.

2.
Stroke ; 55(3): 532-540, 2024 Mar.
Article En | MEDLINE | ID: mdl-38314590

BACKGROUND: Timely intravenous thrombolysis and endovascular thrombectomy are the standard reperfusion treatments for large vessel occlusion stroke. Currently, it is unknown whether a low-dose thrombolytic agent (0.6 mg/kg alteplase) can offer similar efficacy to the standard dose (0.9 mg/kg alteplase). METHODS: We enrolled consecutive patients in the multicenter Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke who had received combined thrombolysis (within 4.5 hours of onset) and thrombectomy treatment from January 2019 to April 2023. The choice of low- or standard-dose alteplase was based on the physician's discretion. The outcomes included successful reperfusion (modified Thrombolysis in Cerebral Infarction score, 2b-3), symptomatic intracerebral hemorrhage, 90-day modified Rankin Scale score, and 90-day mortality. The outcomes between the 2 groups were compared using multivariable logistic regression and inverse probability of treatment weighting-adjusted analysis. RESULTS: Among the 2242 patients in the Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke, 734 (33%) received intravenous alteplase. Patients in the low-dose group (n=360) were older, had more women, more atrial fibrillation, and longer onset-to-needle time compared with the standard-dose group (n=374). In comparison to low-dose alteplase, standard-dose alteplase was associated with a lower rate of successful reperfusion (81% versus 87%; adjusted odds ratio, 0.63 [95% CI, 0.40-0.98]), a numerically higher incidence of symptomatic intracerebral hemorrhage (6.7% versus 3.9%; adjusted odds ratio, 1.81 [95% CI, 0.88-3.69]), but better 90-day modified Rankin Scale score (functional independence [modified Rankin Scale score, 0-2], 47% versus 31%; adjusted odds ratio, 1.91 [95% CI, 1.28-2.86]), and a numerically lower mortality rate (9% versus 15%; adjusted odds ratio, 0.73 [95% CI, 0.43-1.25]) after adjusting for covariates. Similar results were observed in the inverse probability of treatment weighting-adjusted models. The results were consistent across predefined subgroups and age strata. CONCLUSIONS: Despite the lower rate of successful reperfusion and higher risk of symptomatic intracerebral hemorrhage with standard-dose alteplase, standard-dose alteplase was associated with a better functional outcome in patients receiving combined thrombolysis and thrombectomy.


Ischemic Stroke , Thrombectomy , Tissue Plasminogen Activator , Female , Humans , Cerebral Hemorrhage/epidemiology , Endovascular Procedures , Fibrinolytic Agents/administration & dosage , Fibrinolytic Agents/adverse effects , Ischemic Stroke/drug therapy , Ischemic Stroke/surgery , Registries , Thrombectomy/methods , Tissue Plasminogen Activator/administration & dosage , Tissue Plasminogen Activator/adverse effects , Treatment Outcome
3.
Ann Med ; 55(1): 2225144, 2023 12.
Article En | MEDLINE | ID: mdl-37345693

BACKGROUND: Motor recovery following a stroke is related to the initial stroke severity and corticospinal tract integrity. One of the outcomes representing corticospinal tract integrity is the motor evoked potential (MEP). This study aimed to investigate the predictive value of MEP for motor recovery in patients with acute ischemic stroke. PATIENTS AND METHODS: Patients with hemiparesis secondary to initial acute ischemic stroke were enrolled. MEPs of the upper limb were assessed as preserved (MEP+) or absent (MEP-) response ≤10 days post-stroke. Fugl-Meyer assessment (FMA) was performed at baseline and post-stroke at 30 and 90 days. A modified Rankin scale (mRS) was conducted at 90 days post-stroke. Patients were divided into two groups according to the highest FMA score of MEP- patients. Generalized estimating equations and logistic regression were used for our study analysis. RESULTS: Sixty-one participants were included in this study. The highest FMA score of MEP- patients ≤10 days after stroke was 38. Among patients with an initial FMA score ≤38, FMA scores at 30 and 90 days post-stroke were significantly higher in MEP + patients than in MEP- patients. Proportional recovery at 30 and 90 days post-stroke was significantly higher in MEP + patients than in MEP- patients. MEP + patients had a higher percentage of good functional outcomes than MEP- patients, without statistical difference. Among patients with initial FMA score >38, FMA scores were 60.4 ± 4.8 and 63.9 ± 2.9 and proportional recovery was 65.2 ± 27.0% and 83.7 ± 24.6% at 30 and 90 days post-stroke, respectively. CONCLUSIONS: Among patients with moderate-to-severe ischemic stroke, MEP + patients had better motor recoveries (approximately 70%) than MEP- patients at 90 days post-stroke. MEP + patients had better functional outcomes than MEP- patients.


Key MessagesAmong patients with moderate-to-severe ischemic stroke, those with positive motor-evoked potentials (MEPs) had better motor recovery than those with negative MEPs at 90 days post-stroke.Assessment of motor-evoked potentials is a reliable method for predicting motor recovery in patients with moderate-to-severe ischemic stroke.Corticospinal tract function of patients with acute ischemic stroke was tested with transcranial magnetic stimulation.


Ischemic Stroke , Stroke , Humans , Evoked Potentials, Motor , Stroke/complications , Paresis/diagnosis , Paresis/etiology
4.
Eval Health Prof ; 46(2): 127-134, 2023 06.
Article En | MEDLINE | ID: mdl-35722661

The study aimed to analyze the psychometric properties of a newly developed Chinese screening tool, the Chinese Version of the Speech Disorders in Parkinson's Disease Questionnaire (SDPD-C). The SDPD-C contains a 24-item questionnaire with four assessment domains. Overall, 93 patients with idiopathic Parkinson's disease (PD) (age 70.1 ± 8.9 years) and 76 healthy older adults (age 67.2 ± 8.1 years) participated in the psychometric analysis study. The internal consistency of the SDPD-C was .91 (four dimensions: .69-.85), and test-retest reliability was .91 (four dimensions: .85-.88). The SDPD-C was highly correlated with the Voice Handicap Index-10 and Movement Disorder Society-Unified Parkinson's Disease Rating Scale II 2.1 (r = .83 and .78, respectively). The SDPD-C scores also differed significantly between stages 1 and 4 of the Hoehn and Yahr Scale (p < .05). The area under the receiver operating characteristic curve was .955 (95% confidence interval, .927-.983; asymptotic significance p < .001), and the optimal cut-off score of this study was 36, with a sensitivity of .849 and specificity of .947. The results indicate that SDPD-C showed good reliability, validity, accuracy, and discrimination. It can be used as a screening tool for speech disorders in patients with PD.


Parkinson Disease , Humans , Aged , Middle Aged , Parkinson Disease/complications , Parkinson Disease/diagnosis , Psychometrics , Reproducibility of Results , Language , Speech Disorders/diagnosis , Speech Disorders/etiology , Surveys and Questionnaires
5.
Front Neurol ; 13: 875491, 2022.
Article En | MEDLINE | ID: mdl-35860493

Background: Machine learning algorithms for predicting 30-day stroke readmission are rarely discussed. The aims of this study were to identify significant predictors of 30-day readmission after stroke and to compare prediction accuracy and area under the receiver operating characteristic (AUROC) curve in five models: artificial neural network (ANN), K nearest neighbor (KNN), random forest (RF), support vector machine (SVM), naive Bayes classifier (NBC), and Cox regression (COX) models. Methods: The subjects of this prospective cohort study were 1,476 patients with a history of admission for stroke to one of six hospitals between March, 2014, and September, 2019. A training dataset (n = 1,033) was used for model development, and a testing dataset (n = 443) was used for internal validation. Another 167 patients with stroke recruited from October, to December, 2019, were enrolled in the dataset for external validation. A feature importance analysis was also performed to identify the significance of the selected input variables. Results: For predicting 30-day readmission after stroke, the ANN model had significantly (P < 0.001) higher performance indices compared to the other models. According to the ANN model results, the best predictor of 30-day readmission was PAC followed by nasogastric tube insertion and stroke type (P < 0.05). Using a machine learning ANN model to obtain an accurate estimate of 30-day readmission for stroke and to identify risk factors may improve the precision and efficacy of management for these patients. Conclusion: Using a machine-learning ANN model to obtain an accurate estimate of 30-day readmission for stroke and to identify risk factors may improve the precision and efficacy of management for these patients. For stroke patients who are candidates for PAC rehabilitation, these predictors have practical applications in educating patients in the expected course of recovery and health outcomes.

6.
Front Cardiovasc Med ; 9: 826898, 2022.
Article En | MEDLINE | ID: mdl-35433849

Background: Few studies have compared the optimal duration and intensity of organized multidisciplinary neurological/rehabilitative care delivered in a regional/district hospital with the standard rehabilitative care delivered in the general neurology/rehabilitation ward of a medical center. This study measured functional outcomes and conducted cost-utility analysis of an organized multidisciplinary postacute care (PAC) project in secondary care compared with standard rehabilitative care delivered in tertiary care. Methods: This prospective cohort study enrolled 1,476 patients who had a stroke between March 2014 and March 2018 and had a modified Rankin scale score of 2-4. After exact matching for age ± 1 year, sex, year of stroke diagnosis, nasogastric tube, and Foley catheter and propensity score matching for the other covariates, we obtained 120 patients receiving PAC (the PAC group) from four regional/district hospitals and 120 patients not receiving PAC (the non-PAC group) from two medical centers. Results: At baseline, the non-PAC group showed significantly better functional outcomes than the PAC group, including EuroQol-5 dimensions (EQ-5D), Mini-Mental State Examination (MMSE) and Barthel index (BI). During weeks 7-12 of rehabilitation, improvements in all functional outcomes were significantly larger in the PAC group (P < 0.001) except for Functional Oral Intake Scale (FOIS). Cost-utility analysis revealed that the PAC group had a significantly lower mean (± standard deviation) of direct medical costs (US$3,480 ± $1,758 vs. US$3,785 ± $3,840, P < 0.001) and a significantly higher average gain of quality-adjusted life years (0.1993 vs. 0.1233, P < 0.001). The PAC project was an economically "dominant" strategy. Conclusions: The PAC project saved costs and significantly improved the functional outcomes of patients with stroke with slight to moderately severe disabilities. Randomized control trials are required to corroborate these results.

7.
Medicine (Baltimore) ; 101(9): e28973, 2022 Mar 04.
Article En | MEDLINE | ID: mdl-35244065

ABSTRACT: Cerebrovascular disease is the second commonest cause of mortality globally and among the commonest causes of disability. However, research executed to probe the heavy metal exposure-stroke incidence relationship is scarce. Accordingly, we executed our study to probe the relationship of heavy metal concentrations (ie, concentrations of lead [Pb], mercury [Hg], cadmium [Cd], and arsenic) in the serum and urine of acute ischemic stroke (AIS) patients with several patient variables.For enrollment, we chose patients who had a first AIS within 7 days after the onset of a stroke. Thus, 33 newly diagnosed patients with AIS were recruited. We determined the aforementioned metals' concentrations by executing inductively coupled plasma mass spectrometry. We also gauged the association between such metal concentrations and patient variables by employing Spearman correlation coefficient. To examine the differences in metal concentrations between the different variables, we implemented an independent Mann-Whitney U test.In our cohort analysis, we noted serum Pb and Cd concentrations to be positively correlated with serum creatinine and hemoglobin. Serum and urine Cd concentrations had a negative correlation with impaired HbA1c in AIS patients. Urine Hg had a positive correlation with C-reactive protein in the participants. Participants who smoked or consumed alcohol had significantly higher Pb and Cd levels in serum than did those who neither smoked nor drank. Patients with AIS who smoked or consumed alcohol had high levels of serum Pb and serum Cd than did those who did not. Patients with AIS who consumed alcohol had significantly higher Pb and Hg urine concentrations than did those who did not.Our study indicated that serum Cd and Pb elevation increased the AIS risk in southern Taiwan patients.


Environmental Exposure , Ischemic Stroke/epidemiology , Metals, Heavy/blood , Metals, Heavy/urine , Adult , Aged , Arsenic/adverse effects , Arsenic/blood , Arsenic/urine , Cadmium/adverse effects , Cadmium/blood , Cadmium/urine , Cross-Sectional Studies , Female , Humans , Ischemic Stroke/blood , Lead/adverse effects , Lead/blood , Lead/urine , Male , Mercury/blood , Mercury/urine , Metals, Heavy/adverse effects , Middle Aged , Smoking , Taiwan/epidemiology
8.
Sci Rep ; 12(1): 3176, 2022 02 24.
Article En | MEDLINE | ID: mdl-35210496

We examined the effects of using mobile devices with immersive virtual reality for a short period on the physiological parameters of both eyes. The average age of the 50 participants (23 men and 27 women) was 17.72 ± 1.48 years, and refractive error ranged from 0 D to - 5.00 D. All the participants wore + 3.00 D glasses and underwent a 5-min relaxation adjustment through the atomization method. The participants wore immersive virtual reality (VR) glasses to watch a movie on a roller coaster for 10 min. Their relevant physiological parameters of the eyes were measured both before and after using VR glasses. Compared with before VR use, no significant difference (P > 0.05) was observed in the near-horizontal vergence and refractive error but a significant difference (P < 0.05) was observed in the amplitude of accommodation, intraocular pressure, divergence/convergence, and stereopsis after VR use. The corneal elastic coefficient was > 0.2 MPa, and we used Friedenwald's eye rigidity relationship to obtain the K value (0.065-0.09). Approximately 10% of the participants experienced cybersickness symptoms such as nausea and dizziness. The use of VR to watch three-dimensional movies reduced intraocular pressure, which may help prevent or treat glaucoma. Moreover, the binocular convergence was higher when viewing near-field objects in VR than in the real world. Therefore, individuals with convergence excess may experience symptoms. Binocular parallax is the most likely cause of cybersickness symptoms. Thus, mobile VR devices with higher quality and comfort are necessary.


Computers, Handheld , Depth Perception , Eyeglasses/adverse effects , Intraocular Pressure , Ocular Physiological Phenomena , Virtual Reality , Adolescent , Female , Humans , Male , Young Adult
9.
Clin Ophthalmol ; 15: 3431-3439, 2021.
Article En | MEDLINE | ID: mdl-34408398

PURPOSE: This study used low-level laser irradiation on auricular points for the eyes of junior college teenagers with myopia to observe the changes in refractive errors and eye accommodation. According to the Sterner's study, we used the relationship between the amplitude and subjective symptoms to assess the degree of improvement in visual fatigue caused by changes in accommodation. METHODS: Participants were 49 healthy junior college teenagers, with an average age of 16.04±0.80 years old, and the refractive errors of both eyes were between -1.50 D and -5.00 D. All participants underwent refractive error tests before and after class and after a 30-min break. In a 30-min break, all participants underwent two tests of with (experimental group) and without (control group) low-level laser irradiation on the auricular points. Then, refractive error tests were conducted to evaluate the participants' eye accommodation. RESULTS: The results revealed that with treatment of the auricular points with and without low-level laser irradiation, the refractive error of the participants' binocular left and right eyes decreased by -0.12 D (-0.18 D) in the experimental grou and by -0.05 D (-0.02D) in the control group. For the amplitudes of accommodation (AA) examination, the AA of the participants' binocular in the experimental group became 7.98 ± 1.35 D (7.65 ± 1.37 D). The AA of participants' binocular can recover to the level before the class. CONCLUSION: The results indicated that low-level laser irradiation at auricular points restored the eye accommodation faster than did natural closing of the eyes.

10.
Article En | MEDLINE | ID: mdl-34300144

In this large-scale prospective cohort study, a propensity score matching method was applied in a natural experimental design to investigate how post-acute care (PAC) after stroke affects functional status and to identify predictors of functional status. The main objective of this study was to examine longitudinal changes in various measures of functional status in stroke patients and predictors of scores for these measures before and after PAC. A group of patients who had received PAC for stroke at one of two medical centers (PAC group, n = 273) was compared with a group who had received standard care for stroke at one of four hospitals (three regional hospital and one district hospital; non-PAC group, n = 273) in Taiwan from March, 2014, to October, 2018. The patients completed the functional status measures before rehabilitation, the 12th week and the 1st year after rehabilitation. Generalized estimating equations were used to estimate differences-in-differences models for examining the effects of PAC. The average age was 68.0 (SD = 8.1) years, and males accounted for 57.9%. During the follow-up period, significant risk factors for poor functional outcomes were advanced age, hemorrhagic stroke, and poor function scores before rehabilitation (p < 0.05). Between-group comparisons at subsequent time points revealed significantly higher functional status scores in the PAC group versus the non-PAC group (p < 0.001). Notably, for all functional status measures, between-group differences in total scores significantly increased over time from baseline to 1 year post-rehabilitation (p < 0.001). The contribution of this study is its further elucidation of the clinical implications and health policy implications of rehabilitative care after stroke. Specifically, it improves understanding of the effects of PAC in stroke patients at different follow-up times. Therefore, a policy implication of this study is that standard care for stroke should include intensive rehabilitative PAC to maximize recovery of overall function.


Stroke Rehabilitation , Stroke , Aged , Humans , Male , Propensity Score , Prospective Studies , Recovery of Function , Stroke/therapy , Subacute Care , Taiwan/epidemiology
11.
Heliyon ; 7(4): e06877, 2021 Apr.
Article En | MEDLINE | ID: mdl-33981906

A prism device is utilized in this study for modifying the eye convergence to reduce eye accommodation and enhance the comfort in viewing 3D video. Without changing the contents of 3D films, it aims to apply the myosis, convergence, and accommodation visual triad of eyeballs viewing near distance to not change the eyeball pupillary distance when viewing 3D films. Without convergence, the discomfort caused by intraocular muscle contraction when viewing near distance is reduced. Such an effect of a small prism lens is also proven in this study. When viewing 3D films with 1.0△ lenses, the physiological accommodation reaction of eyes would reduce (the right eye decreases 65% and the left eye decreases 70%), revealing the decreasing tension of intraocular muscle. The subjective psychological evaluation result also shows that viewing 3D images with small prism lenses could enhance the comfort. The evaluation of optical simulation, physiological reaction, and mental fatigue proves that the small prism lens proposed in this study could actually improve the comfort in viewing 3D films.

12.
J Atheroscler Thromb ; 28(2): 146-156, 2021 Feb 01.
Article En | MEDLINE | ID: mdl-32418948

AIM: Chronic kidney disease (CKD) is associated with unfavorable outcomes in patients with ischemic stroke. One major metabolic derangement of CKD is dyslipidemia, which can be managed by statins. This study aimed to investigate whether the association of statins with post-stroke outcomes would be affected by renal function. METHODS: We evaluated the association of statin therapy at discharge with 3-month outcomes according to the estimated glomerular filtration rate (eGFR) of 50,092 patients with acute ischemic stroke from the Taiwan Stroke Registry from August 2006 to May 2016. The outcomes were mortality, functional outcome as modified Rankin Scale (mRS), and recurrent ischemic stroke at 3 months after index stroke. RESULTS: Statin therapy at discharge was associated with lower risks of mortality (adjusted hazard ratio [aHR], 0.41; 95% confidence interval [CI], 0.34 to 0.50) and unfavorable functional outcomes (mRS 3-5; aHR, 0.80; 95% CI, 0.76 to 0.84) in ischemic stroke patients. After stratification by eGFR, the lower risk of mortality associated with statins was limited to patients with an eGFR above 15 mL/min/1.73 m2. Using statins at discharge was correlated with a lower risk of unfavorable functional outcomes in patients with an eGFR of 60-89 mL/min/1.73 m2. Statin therapy in patients with an eGFR of 60-89 mL/min/1.73 m2 may be associated with a higher risk of recurrent ischemic stroke compared with nonusers (aHR, 1.29; 95% CI, 1.07 to 1.57). CONCLUSIONS: In patients with acute ischemic stroke, the associations of statins with mortality and functional outcomes was dependent on eGFR.


Dyslipidemias , Glomerular Filtration Rate , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Ischemic Stroke , Renal Insufficiency, Chronic , Aged , Comorbidity , Dyslipidemias/blood , Dyslipidemias/drug therapy , Dyslipidemias/etiology , Female , Functional Status , Humans , Ischemic Stroke/blood , Ischemic Stroke/diagnosis , Ischemic Stroke/mortality , Ischemic Stroke/physiopathology , Kidney Function Tests/methods , Kidney Function Tests/statistics & numerical data , Male , Middle Aged , Outcome Assessment, Health Care/methods , Registries , Renal Insufficiency, Chronic/diagnosis , Renal Insufficiency, Chronic/epidemiology , Renal Insufficiency, Chronic/physiopathology , Risk Assessment , Risk Factors , Secondary Prevention/methods , Taiwan/epidemiology
13.
Stroke ; 51(4): 1248-1256, 2020 04.
Article En | MEDLINE | ID: mdl-32151234

Background and Purpose- The observation that smokers with stroke could have better outcome than nonsmokers led to the term "smoking paradox." The controversy of such a complex claim has not been fully settled, even though different case mix was noted. Analyses were conducted on 2 independent data sets to evaluate and determine whether such a paradox truly exists. Methods- Taiwan Stroke Registry with 88 925 stroke cases, and MJ cohort with 541 047 adults participating in a medical screening program with 1630 stroke deaths developed during 15 years of follow-up (1994-2008). Primary outcome for stroke registry was functional independence at 3 months by modified Rankin Scale score ≤2, for individuals classified by National Institutes of Health Stroke Scale score at admission. For MJ cohort, mortality risk by smoking status or by stroke history was assessed by hazard ratio. Results- A >11-year age difference in stroke incidence was found between smokers and nonsmokers, with a median age of 60.2 years for current smokers and 71.6 years for nonsmokers. For smokers, favorable outcome in mortality and in functional assessment in 3 months with modified Rankin Scale score ≤2 stratified by the National Institutes of Health Stroke Scale score was present but disappeared when age and sex were matched. Smokers without stroke history had a ≈2-fold increase in stroke deaths (2.05 for ischemic stroke and 1.53 for hemorrhagic stroke) but smokers with stroke history, 7.83-fold increase, overshadowing smoking risk. Quitting smoking at earlier age reversed or improved outcome. Conclusions- "The more you smoke, the earlier you stroke, and the longer sufferings you have to cope." Smokers had 2-fold mortality from stroke but endured stroke disability 11 years longer. Quitting early reduced or reversed the harms.


Databases, Factual/trends , Smoking/epidemiology , Smoking/trends , Stroke/diagnosis , Stroke/epidemiology , Survivors , Adult , Aged , Cohort Studies , Female , Follow-Up Studies , Humans , Male , Middle Aged , Registries , Self Report , Smoking/adverse effects , Taiwan/epidemiology , Young Adult
15.
N Engl J Med ; 380(19): 1795-1803, 2019 05 09.
Article En | MEDLINE | ID: mdl-31067369

BACKGROUND: The time to initiate intravenous thrombolysis for acute ischemic stroke is generally limited to within 4.5 hours after the onset of symptoms. Some trials have suggested that the treatment window may be extended in patients who are shown to have ischemic but not yet infarcted brain tissue on imaging. METHODS: We conducted a multicenter, randomized, placebo-controlled trial involving patients with ischemic stroke who had hypoperfused but salvageable regions of brain detected on automated perfusion imaging. The patients were randomly assigned to receive intravenous alteplase or placebo between 4.5 and 9.0 hours after the onset of stroke or on awakening with stroke (if within 9 hours from the midpoint of sleep). The primary outcome was a score of 0 or 1 on the modified Rankin scale, on which scores range from 0 (no symptoms) to 6 (death), at 90 days. The risk ratio for the primary outcome was adjusted for age and clinical severity at baseline. RESULTS: After 225 of the planned 310 patients had been enrolled, the trial was terminated because of a loss of equipoise after the publication of positive results from a previous trial. A total of 113 patients were randomly assigned to the alteplase group and 112 to the placebo group. The primary outcome occurred in 40 patients (35.4%) in the alteplase group and in 33 patients (29.5%) in the placebo group (adjusted risk ratio, 1.44; 95% confidence interval [CI], 1.01 to 2.06; P = 0.04). Symptomatic intracerebral hemorrhage occurred in 7 patients (6.2%) in the alteplase group and in 1 patient (0.9%) in the placebo group (adjusted risk ratio, 7.22; 95% CI, 0.97 to 53.5; P = 0.05). A secondary ordinal analysis of the distribution of scores on the modified Rankin scale did not show a significant between-group difference in functional improvement at 90 days. CONCLUSIONS: Among the patients in this trial who had ischemic stroke and salvageable brain tissue, the use of alteplase between 4.5 and 9.0 hours after stroke onset or at the time the patient awoke with stroke symptoms resulted in a higher percentage of patients with no or minor neurologic deficits than the use of placebo. There were more cases of symptomatic cerebral hemorrhage in the alteplase group than in the placebo group. (Funded by the Australian National Health and Medical Research Council and others; EXTEND ClinicalTrials.gov numbers, NCT00887328 and NCT01580839.).


Brain Ischemia/diagnostic imaging , Fibrinolytic Agents/therapeutic use , Perfusion Imaging , Stroke/drug therapy , Time-to-Treatment , Tissue Plasminogen Activator/therapeutic use , Aged , Aged, 80 and over , Brain/diagnostic imaging , Brain Ischemia/drug therapy , Cerebral Hemorrhage/chemically induced , Computed Tomography Angiography , Female , Fibrinolytic Agents/adverse effects , Humans , Infusions, Intravenous , Magnetic Resonance Angiography , Male , Middle Aged , Nervous System Diseases/epidemiology , Nervous System Diseases/prevention & control , Stroke/diagnostic imaging , Stroke/mortality , Therapeutic Equipoise , Tissue Plasminogen Activator/adverse effects
16.
J Clin Med ; 8(3)2019 Mar 03.
Article En | MEDLINE | ID: mdl-30832391

Autonomic dysfunctions including impaired baroreflex sensitivity (BRS) can develop after acute ischemic stroke (AIS) and may predispose patients to subsequent cardiovascular adverse events and serve as potential indicators of long-term mortality. This study aimed to determine the potential short-term prognostic significance of BRS after AIS. All patients admitted to Kaohsiung Veterans General Hospital within 72 h after onset of first-ever AIS between April 2008 and December 2012 were enrolled. Autonomic evaluation with continuous 10-minute monitoring of beat-to-beat hemodynamic and intracranial parameters was performed within 1 week after stroke by using the Task Force Monitor and transcranial Doppler. The 176 enrolled AIS patients were divided into high-BRS and low-BRS groups. All but two enrolled patients (who died within 3 months after stroke) attended scheduled follow-ups. The high-BRS group had significantly lower National Institutes of Health Stroke Scale (NIHSS) scores at 1 and 2 weeks after stroke and at discharge; lower modified Rankin scale (mRS) scores 1, 3, 6, and 12 months after stroke; and lower rates of complications and stroke recurrence compared to the low-BRS group. This study provides novel evidence of the utility of BRS to independently predict outcomes after AIS. Furthermore, modifying BRS may hold potential in future applications as a novel therapeutic strategy for acute stroke.

17.
J Clin Med ; 7(10)2018 Oct 05.
Article En | MEDLINE | ID: mdl-30301188

Recent studies have indicated that several anti-hypertensive drugs may delay the development and progression of Alzheimer's disease (AD). However, the relationships among AD, hypertension, and oxidative stress remain to be elucidated. Here, we aimed to determine whether reactive oxygen species (ROS) reduction by resveratrol in the brain leads to cognitive impairment reduction in rats with angiotensin II (Ang-II)-induced early AD. Male Wistar Kyoto (WKY) rats with Ang-II-induced AD were treated with losartan or resveratrol for two weeks. Our results show decreased blood pressure, increased hippocampal brain-derived neurotrophic factor (BDNF) level, and decreased nucleus tractus solitarius (NTS) ROS production in the Ang-II groups with losartan (10 mg/kg), or resveratrol (10 mg/kg/day) treatment. Furthermore, losartan inhibition of hippocampal TauT231 phosphorylation activated AktS473 phosphorylation, and significantly abolished Ang-II-induced Aß precursors, active caspase 3, and glycogen synthase kinase 3ß (GSK-3ß)Y216 expressions. Consistently, resveratrol showed similar effects compared to losartan. Both losartan and resveratrol restored hippocampal-dependent contextual memory by NADPH oxidase 2 (NOX2) deletion and superoxide dismutase 2 (SOD2) elevation. Our results suggest that both losartan and resveratrol exert neuroprotective effects against memory impairment and hippocampal damage by oxidative stress reduction in early stage AD rat model. These novel findings indicate that resveratrol may represent a pharmacological option similar to losartan for patients with hypertension at risk of AD during old age.

18.
J Am Heart Assoc ; 7(19): e009856, 2018 10 02.
Article En | MEDLINE | ID: mdl-30371321

Background Clopidogrel was thought to be superior to aspirin for secondary prevention of vascular diseases in clinical trials. In this study we assessed the safety and efficacy of clopidogrel versus aspirin in real-world practice by using the Taiwan Stroke Registry. Methods and Results Patients with ischemic stroke (2006-2016) on aspirin or clopidogrel for secondary stroke prevention were identified in the Taiwan Stroke Registry. Stroke recurrence and mortality rates in patients receiving aspirin (N=34 679) were compared with those receiving clopidogrel (N=7611) during a 12-month follow-up period. Propensity score matching and conditional Cox proportional hazards regression model were applied to control confounding factors with 6443 patients in each group. After propensity score matching, stroke recurrence rates were comparable between groups, with 223 patients in the aspirin (3.46%) and 244 in the clopidogrel group (3.79%) (hazard ratio=1.13, 95% confidence interval=0.89-1.43, P=0.311). However, the mortality rate was significantly higher in the clopidogrel group (362 patients, 5.62%) than in the aspirin group (302 patients, 4.69%) (hazard ratio=1.30, 95% confidence interval=1.07-1.58, P=0.008). Results were consistent before and after propensity score matching. Conclusions Clopidogrel was as effective as aspirin for prevention of recurrent stroke in real-world practice. However, the mortality rate was significantly higher in the clopidogrel than in the aspirin group.


Aspirin/therapeutic use , Clopidogrel/therapeutic use , Propensity Score , Registries , Secondary Prevention/methods , Stroke/prevention & control , Aged , Female , Follow-Up Studies , Humans , Incidence , Male , Platelet Aggregation Inhibitors/therapeutic use , Recurrence , Retrospective Studies , Stroke/epidemiology , Survival Rate/trends , Taiwan/epidemiology , Treatment Outcome
19.
Atherosclerosis ; 277: 15-20, 2018 10.
Article En | MEDLINE | ID: mdl-30170219

BACKGROUND AND AIMS: This study investigated risks of short-term (1 and 3 months) and long-term (1-year) recurrent stroke associated with glomerular filtration rate (eGFR) in patients with acute ischemic stroke. METHODS: From the Taiwan Stroke Registry data, we identified 45,876 acute ischemic stroke patients from April 2006 to April 2014 and classified them into 4 groups based on the eGFR at admission: ≥ 90, 60-89, 30-59, and <30 mL/min/1.73 m2 or on dialysis. The risks of 1-month, 3-month and 1-year recurrent stroke related to the eGFR levels were investigated. RESULTS: Both the risks of short-term and long-term recurrent stroke increased as the eGFR levels declined. The 1-month recurrent incidence rates increased steadily from 0.54 to 0.59, 0.84 and 0.89 per 1000 person-days, as the eGFR declined from ≥90 to 60-89, 30-59, and <30 mL/min/1.73 m2 or on dialysis, respectively. Compared to patients with eGFR ≥90 mL/min/1.73 m2, the adjusted subhazard ratio of 1-month recurrent stroke decreased from 1.69 (95% confidence interval (CI) = 1.24-2.31) for patients with eGFR < 30 mL/min/1.73 m2 or on dialysis to 1.14 (95% CI = 0.91-1.43) for patients with eGFRs of 60-89 mL/min/1.73 m2, considering the competing risk of deaths. Similar patterns were also observed for the adjusted HRs of 3-month and 1-year recurrent stroke, but with reduced hazard values, by the corresponding eGFR levels. CONCLUSIONS: There is an independent graded association between an increased risk of recurrent stroke and declining eGFR levels in patients with acute ischemic stroke.


Brain Ischemia/epidemiology , Glomerular Filtration Rate , Kidney Diseases/epidemiology , Kidney/physiopathology , Stroke/epidemiology , Aged , Aged, 80 and over , Brain Ischemia/diagnosis , Brain Ischemia/physiopathology , Databases, Factual , Female , Humans , Incidence , Kidney Diseases/diagnosis , Kidney Diseases/physiopathology , Kidney Diseases/therapy , Male , Middle Aged , Prognosis , Recurrence , Renal Dialysis , Risk Assessment , Risk Factors , Stroke/diagnosis , Stroke/physiopathology , Taiwan/epidemiology , Time Factors
20.
J Biomed Sci ; 25(1): 49, 2018 May 25.
Article En | MEDLINE | ID: mdl-29801491

BACKGROUND: Few studies have examined the relationship between the amounts of heavy metal and stroke incidence. The aim of this study was to explore the relationship between levels of heavy metals, including Pb, Hg, As, and Cd, in patients with acute ischemic stroke (AIS). METHODS: We selected patients with first-ever AIS onset within 1 week as our study group. Healthy controls were participants without a history of stroke or chronic disease, except hypertension. The serum levels of Pb, Hg, As, and Cd in participants in the experimental and control groups were determined. All participants received a 1-g infusion of edetate calcium disodium (EDTA). Urine specimens were collected for 24 h after EDTA infusion and measured for heavy metal levels. RESULTS: In total, 33 patients with AIS and 39 healthy controls were enrolled in this study. The major findings were as follows: (1) The stroke group had a significantly lower level of serum Hg (6.4 ± 4.3 µg/L vs. 9.8 ± 7.0 µg/L, P = 0.032, OR = 0.90, 95% CI = 0.81-0.99) and a lower level of urine Hg (0.7 ± 0.7 µg/L vs. 1.2 ± 0.6 µg/L, P = 0.006, OR = 0.27, 95% CI = 0.11-0.68) than the control group. (2) No significant difference in serum Pb (S-Pb), As (S-As), and Cd (S-Cd) levels and urine Pb (U-Pb), As (U-As) and Cd (U-Cd) levels was observed in either group. CONCLUSIONS: Our study found low levels of serum and urine Hg in first-ever patients with AIS, providing new evidence of dysregulated heavy metals in patients with AIS.


Brain Ischemia/epidemiology , Environmental Pollutants/adverse effects , Metals, Heavy/adverse effects , Stroke/epidemiology , Aged , Brain Ischemia/chemically induced , Female , Humans , Incidence , Male , Middle Aged , Stroke/chemically induced , Taiwan/epidemiology
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