Assessment and prognostic value of serum uric acid and neuron-specific enolase on the efficacy of intravenous thrombolytic therapy in cerebral infarction.

Assessment and prognostic value of serum uric acid (SUA) and neuron-specific enolase (NSE) on the efficacy of intravenous thrombolytic therapy in cerebral infarction. A retrospective analysis was performed on clinical data of 159 patients with acute cerebral infarction who received rt-PA intravenous thrombolytic therapy from 2015 to 2020 and patients with an mRS>2 points were assigned to the poor prognosis group and with mRS≤2 to the good prognosis group. The receiver operating characteristic curve (ROC) was used to examine the prognostic value of SUA and NSE in intravenous thrombolytic therapy for acute cerebral infarction, and logistic regression analysis was utilized to elucidate the predictive features. SUA levels were adversely correlated with prognosis, whereas NSE was positively correlated with prognosis (r=0.465 and -0.501, P=0.000 and 0.000). The ROC curve showed that the predictive accuracy of SUA was 77.4% and of NSE was 71%. SUA≤337.5 mmol/l and NSE≥24.50 ng/ml are considered viable criteria to predict the curative effect and prognostic value of intravenous thrombolytic therapy for acute cerebral infarction. SUA and NSE demonstrate great potential to accurately predict the therapeutic effect and prognosis of intravenous thrombolytic therapy for acute cerebral infarction.

Cerebral hemodynamic changes assessment by transcranial doppler ultrasound in patients with acute cerebral infarction before and after treatment with butylphthalide.

To assess cerebral hemodynamic changes by transcranial doppler ultrasound in patients with acute cerebral infarction before and after treatment with butylphthalide, A total of 90 patients with acute cerebral infarction admitted to our hospital from January 2019 to January 2020 were selected and equally divided into the control group and the experimental group according to the order of admission. The control group was treated with conventional treatment, while the experimental group was additionally given butylphthalide drug treatment. The experimental group obtained better hemodynamic indexes as compared with the control group (P<0.05). The experimental group yielded a notably higher total clinical effective rate after treatment in contrast with the control group (P<0.05). After treatment, the serum indexes of the experimental group were evidently lower than those of the control group (P<0.05). After treatment, a remarkably lower NIHSS score of the experimental group than the control group was observed (P<0.05). The BI index score of the experimental group after treatment was considerably higher than that of the control group (P<0.05). After treatment, the MMSE score in the experimental group was significantly higher than it was in the control group (P<0.05). The treatment of butylphthalide in patients with acute cerebral infarction can effectively improve the clinical symptoms of the patients and the cerebral hemodynamics of the patients tested by TCD found that this treatment yields an excellent therapeutic effect and is worthy of promotion and application.

[Clinical comprehensive evaluation of Ginkgolide Injection in treatment of cerebral infarction].

This clinical value-oriented comprehensive evaluation of drugs was carried out in accordance with Guidelines for Management of Comprehensive Clinical Evaluation of Drugs(trial version 2021), with the qualitative and quantitative evaluation methods adopted. Based on the evidence-based medicine, epidemiology, clinical medicine, pharmacoeconomics, mathematical statistics, and health technology evaluation(HTA), the clinical value of Ginkgolide Injection was evaluated from the "6+1" dimension by giving weight to the criterion level and index level and calculating with multi-criteria decision analysis(MCDA) model and CSC v2.0. After entering the market, Ginkgolide Injection has been subjected to phase Ⅳ clinical trial, spontaneous reporting system(SRS)-based data monitoring, systematic review and Meta-analysis, acute toxicity and long-term toxicity assays, active monitoring, and RCTs, and the evidence of safety was sufficient. The results of active monitoring showed that the incidence of adverse reactions was 0.09%(rare), mainly manifested as flushing, dizziness, rash, nausea, and vomiting. According to the nested case-control study, the adverse reactions of this drug had nothing to do with the product batch, implying that the drug quality was controllable. The adverse reactions mainly resulted from the pharmacodynamic reactions. Because the drug was effective in resisting platelet aggregation, the resulting adverse reactions such as flushing, dizziness, headache, and phlebitis were caused by vasodilation. Skin rash and gastrointestinal symptoms were mainly attributed to the patients' sensitivity to drugs and their own allergic constitution. According to the sufficiency of evidence and the incidence of adverse reactions in the safety research, the safety of Ginkgolide Injection was grade A. The results of Meta-analysis showed that Ginkgolide Injection combined with conventional western medicine was superior to conventional western medicine in improving the clinical effective rate, neurological function score, and activity of daily living score of patients with cerebral infarction. The validity evidence was evaluated according to the PICO principle to be high. According to the GREAD evaluation principle, the quality of such evidence as clinical effective rate, National Institute of Health stroke scale(NIHSS), and Barthel Index(BI) was evaluated, and the results demonstrated that the evidence quality of clinical effective rate and activity of daily living score was medium. The effectiveness of Ginkgolide Injection was grade A. According to the economic report of Ginkgolide Injection, it had short-term and long-term pharmacoeconomic advantages in the treatment of ischemic stroke, and the economic evidence value was good. According to the CASP economic evaluation checklist, the overall quality evaluation results of the economic report are basically clear. To be specific, the economic evidence quality was high. Based on the comprehensive economic evidence quality and economic value, the economy of this drug was grade A. The innovation of this product was evaluated from three aspects: clinical innovation, enterprise service system innovation, and industrial innovation. Ginkgolide Injection could be used 24 h after intravenous thrombolysis for improving patients' neurological function without increasing bleeding, indicating its important clinical innovation. There were many innovations in ensuring drug supply, especially at the grass roots, drug safety, effectiveness, and reasonable price, which has provided reference for establishing enterprise philosophy, managing drug resources, developing process and technology, and determining enterprise management and marketing. Therefore, its innovation was grade A. The drug had no special medication plan in use, exhibiting good suitability for doctors, nurses, and patients. The suitability was grade B. Compared with similar drugs, its price was at a medium level, meaning good affordability, sufficient production capacity, and easy accessibility. Its accessibility was therefore grade B. This drug belonged to Chinese medicinal injection. The large-sample real-world research revealed rich human use experience, so it was grade C for the traditional Chinese medicine characteristic. According to the comprehensive evaluation, the clinical value of Ginkgolide Injection in the treatment of cerebral infarction fell into class A. It is suggested that it can be transformed into the relevant policy results of basic clinical medication management according to the procedure.

[Clinical comprehensive evaluation of Diemailing~® Kudiezi Injection in treatment of cerebral infarction].

Clinical comprehensive evaluation was conducted in "6+1" dimensions(safety, effectiveness, economy, innovation, suitability, accessibility, and characteristics of traditional Chinese medicine) to reflect the advantages and characteristics of Diemai-ling~® Kudiezi Injection in the treatment of cerebral infarction. This study adopted a combination of qualitative and quantitative evaluation methods. Based on the methodologies of evidence-based medicine, epidemiology, clinical medicine, evidence-based pharmacy, pharmacoeconomics, mathematical statistics, and health technology assessment(HTA), experts gave weight to the criterion layer and index layer, and multi-criteria decision analysis(MCDA) model and CSC v2.0 were used for calculations to evaluate the clinical value of Diemailing~® Kudiezi Injection. The existing evidence showed that active monitoring and a number of randomized controlled trials(RCTs) have been carried out after the listing of Diemailing~® Kudiezi Injection. Since the total incidence of adverse reactions is 0.099% and the incidence of adverse drug reactions(ADR) is rare, the safety evaluation is grade A. The evidence value of effectiveness demonstrated that Diemailing~® Kudiezi Injection combined with conventional western medicine improves the total effective rate of neurological deficit score and quality of daily life in the acute stage of cerebral infarction, which is superior to that in the conventional western medicine treatment group, and the level of evidence is high. Therefore, its efficacy is assessed as grade A. According to the results of economic research, when Diemailing~® Kudiezi Injection combined with conventional western medicine treatment is compared with conventional western medicine treatment, the Diemailing~® Kudiezi Injection group has a greater incremental effect, but the cost is affordable. Given the overall quality evaluation results of economic report is clear, it is evaluated as grade B. The innovation is grade A. The drug is favorable for clinical operation by medical staff and can be accepted by patients due to easy usage without special technical and management requirements. Since the drug exhibits good suitability for clinicians, nurses, pharmacists, and patients, it is evaluated as grade B. Considering its moderate price among similar drugs and good affordability and availability, it is evaluated as grade B. Diemailing~® Kudiezi Injection can evidently improve the clinical symptoms and neurological deficits of fire toxin syndrome of acute cerebral infarction, and this medicine belongs to ethnic medicine. Large-sample active monitoring research has been conducted with rich experience in human use. Therefore, the characteristics of traditional Chinese medicine are evaluated as grade A. The comprehensive clinical evaluation of Diemailing~® Kudiezi Injection is class A. We suggest that it can be directly transformed into relevant policy results of basic clinical medication management by procedure.

[Analysis on disease burden and direct medical cost of Xueshuan Xinmaining Tablets in patients with cerebral infarction and coronary heart disease].

The increasing burden of cardiovascular disease in China has become a major public health problem, and the prevention and treatment of cardiovascular disease is in urgent need. For the reality of integrated Chinese and Western medicine in the Chinese health care system, we can consider the service ability of traditional Chinese medicine. Xueshuan Xinmaining Tablet is a kind of Chinese patent medicine commonly used in the treatment of recovery stage of ischemic stroke and angina pectoris of coronary heart disease. Based on the data of hospitalized patients covered by national urban basic medical insurance of China Medical Insurance Research Association in 2013, this study evaluated the treatment cost and detailed composition of the cost for the patients with cerebral infarction and coronary heart disease treated by Xueshuan Xinmaining Tablets. At the same time, the differences in disease burden and direct medical expenses among Xueshuan Xinmaining Tablets group, Western medicine group and another commonly used Chinese patent medicine group were analyzed. Among the three groups of patients with cerebral infarction and coronary heart disease, the hospitalization rates caused by various causes(44.4% and 29.6%) and diseases(20.8% and 5.2%) in Xueshuan Xinmaining Tablets group were the lowest(all P<0.01), and the number of hospitalization times in half a year was highest in the common Chinese patent medicine group(all P<0.01). In patients with cerebral infarction, the median annual total outpatient expenses were 7 476.8, 7 601.8, 15 650.1 yuan respectively in Western medicine group, Xueshuan Xinmaining Tablets group and the common Chinese patent medicine group(P<0.01), and the median hospitalization expenses were 11 620.2, 14 988.9, 13 325.6 yuan respectively(P=0.058). In patients with coronary heart disease, the total outpatient expenses of the three groups were 6 831.4, 10 228.6, 13 132.4 yuan respectively(P<0.01), and the total hospitalization expenses were 13 354.7, 14 911.5, 15 725.3 yuan respectively(P=0.134). The results showed that in patients with cerebral infarction and coronary heart disease, the hospitalization rate was lowest in Xueshuan Xinmaining Tablets group, beneficial to the turnover of hospital beds and full use of hospital medical resources. The total annual outpatient cost of Xueshuan Xinmaining Tablets group was lower than that of common Chinese patent medicine group, beneficial to reduce the burden of disease.

Clinical evidence and GRADE assessment for breviscapine injection (DengZhanHuaSu) in patients with acute cerebral infarction.

ETHNOPHARMACOLOGICAL RELEVANCE: Breviscapine injections (DengZhanHuaSu, DZHS) is a famous Chinese patent medicine authorized by China Food and Drug Administration, which is widely used to treat acute cerebral infarction (ACI) in China. AIM OF THE STUDY: In the present study, meta-analysis has been performed in determining the efficacy and safety of DZHS combined with conventional treatment (CT) for ACI and GRADE assessment. MATERIALS AND METHODS: Randomized controlled trials (RCTs) testing the use of DZHS for treating ACI were screened by searching the databases of the Cochrane Library, PubMed, Embase, and Web of Science as well as four Chinese databases. Meta-analysis was carried out with RevMan 5.3 and Stata 16.0 software. The quality of research evidence was assessed by the GRADEprofiler (GRADEpro version: 3.6). RESULTS: Forty-three studies (n = 4618) were included. When compared to the control groups, the total effective rate of the national institutes of health stroke scale (NIHSS) was higher in the experimental group with DZHS (RR = 1.23, 95% CI = 1.19 to 1.28, P < 0.001; RR = 1.29, 95% CI = 1.21 to 1.38, P < 0.001); clinical symptoms and signs were improved in the experimental group with DZHS (RR = 1.17, 95% CI = 1.10 to 1.24, P < 0.001; RR = 1.25, 95% CI = 1.11 to 1.42, P < 0.001); the incidence of adverse reactions was reduced in the experimental group with DZHS (RR = 0.50, 95% CI = 0.26 to 0.98, P = 0.044); and the NIHSS score was decreased in the experimental group with DZHS (WMD = -3.30, 95% CI = -3.86 to -2.73, P < 0.001). CONCLUSIONS: DZHS combined with CT is conditionally recommended to improve the total effective rate of the NIHSS, clinical symptoms, and neurological deficits and reduce the incidence of adverse reactions, and no serious adverse reactions were noted. The GRADE assessment indicates that the overall certainty quality of evidence is low. Further large-scale, well-designed and high-quality RCTs are needed to confirm the positive results. PROSPERO registration No. CRD42019128856.

Assessment of post discharge medication prescription among Lebanese patients with cerebral infarction: Results of a cross-sectional study.

OBJECTIVES: The study objective was to investigate the degree of physician adherence with the international guidelines for post-stroke discharge medications among Lebanese hospitals. PATIENT AND METHODS: This retrospective observational study was conducted in three Lebanese hospitals between January 2016 and December 2017. RESULTS: Out of 200 patients with stroke, 64.7 % were males. The difference of systolic blood pressure from baseline, 2 h, and after 24 h showed significant decrease by mean value 25.18 ± 33.45 (P < 0.001), and 6.44 ± 22.11 (P = 0.019) respectively. Also diastolic blood pressure showed significant decrease between baseline and after 24 h by a mean value 12.17 ± 13.63 (P value <0.001). Concerning post discharge medications adherence, antithrombotic drugs showed the highest percentage (73 %) followed by antihypertensive and lipid lowering agents by comparable results (47.5 % and 40.7 % respectively). The physician adherence for the three medications together showed (30.4 %). CONCLUSION: Secondary prevention for critical diseases such as stroke appears to be inadequate in the study area.

Neuroprotective effect of Convolvulus pluricaulis Choisy in oxidative stress model of cerebral ischemia reperfusion injury and assessment of MAP2 in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Convolvulus pluricaulis Choisy commonly known as Shankhapushpi, is traditionally prescribed for nerve debility, loss of memory, epilepsy and as nervine tonic. Plant also proved to have diverse pharmacological activity but the neuroprotection in ischemic stroke were not found. AIM OF THE STUDY: To investigate the effect of Convolvulus pluricaulis against bilateral common carotid artery (BCCA) occlusion induced cerebral ischemic reperfusion injury. MATERIALS AND METHODS: The neuroprotective activity of Convolvulus pluricaulis against bilateral common carotid artery (BCCA) occlusion induced cerebral ischemic reperfusion (I/S) injury. Sprague-Dawley rats of either sex (200-250 g) were divided into nine groups of 8 rats each. Sham and control group, saline treated 10 ml/kg orally. Third group treated with Quercetin 25 mg/kg orally and fourth to ninth groups treated with chloroform and ethanol extract of Convolvulus pluricaulis 100, 200, and 400 mg/kg (p.o.) respectively. Control, Quercetin and extract treated groups underwent 30 min BCCA occlusion and 24 h reperfusion on 10th day but sham underwent same surgery without BCCA occlusion and 24 h reperfusion on 10th day. The antioxidant enzymatic and non-enzymatic levels were estimated by UV spectroscopic method and cerebral infarction area, Blood brain barrier disruption, microtubule-associated protein 2 immunohistochemical and histopathological studies were carried out. RESULTS: The results of the study indicate that the chloroform and ethanol extract of Convolvulus pluricaulis showed neuroprotective activity by a significant decrease in lipid peroxidation (p < 0.001) and an increase in superoxide dismutase (p < 0.01, p < 0.001), catalase (p < 0.01, p < 0.001), glutathione (p < 0.001), and total thiol (p < 0.001) levels in extract-treated groups as compared to control group. Measurement of cerebral infarction area, blood brain barrier disruption, microtubule-associated protein 2 immunohistochemical and histopathological studies further supported the protective effect of the extract. CONCLUSIONS: Present study revile that Convolvulus pluricaulis has potent neuroprotection against bilateral common carotid artery (BCCA) occlusion induced cerebral ischemic reperfusion injury.

Study on essential drug use status and its influencing factors among cerebral infarction inpatients in county level hospitals of Anhui Province, China.

BACKGROUND AND PURPOSE: Drug costs is one of the main components of hospitalization expenditure for cerebral infarction inpatients. In China, the National Essential Medicine System (NEMS) was created to relieve the heavy drug-cost burden for patients. The objective of this study was to investigate essential drug-use status and its influencing factors among cerebral infarction inpatients in county-level hospitals of Anhui province, China. METHODS: Three county-level hospitals were selected through a multi-stage cluster random sampling method. The hospitalization cost data of cerebral infarction inpatients in the three hospitals were extracted from the Anhui provincial information platform of the New Rural Cooperative Insurance System (NCMS), and whether the proportion of essential drug cost in the total drug cost reached the median value of 33.05% which was set as the evaluation index for essential drug-use status. Questionnaires for hospitals and physicians were designed and given to them to assess influencing factors. RESULTS: We retrieved the cost data of 2,189 inpatients from the NCMS platform and investigated 51 corresponding physicians in total. The drug costs accounted for 52.6% of the total hospitalization cost, and essential drug costs alone accounted for 37.0% of the total drug costs. The essential drug-cost proportion was high among physicians with a higher recognition degree on NEMS, older age, lower final academic degree, longer work experience and lower professional title. Married physicians and those with tight organizational affiliation also prescribed more essential drugs. CONCLUSIONS: Increasing the proportion of essential drugs was an effective way to reduce the disease burden for cerebral infarction patients. Perfecting the NEMS, increasing government investment, reinforcing education and propaganda, and formulating relevant incentive and restrictive mechanisms were all effective ways to promote and increase the number of essential drug prescriptions written by physicians.

Efficacy and Safety of Vinpocetine as Part of Treatment for Acute Cerebral Infarction: A Randomized, Open-Label, Controlled, Multicenter CAVIN (Chinese Assessment for Vinpocetine in Neurology) Trial.

OBJECTIVE: The objective of this study was to evaluate the efficacy and safety of intravenous vinpocetine administration as part of a comprehensive treatment for acute cerebral infarction in a Chinese population. METHODS: 610 acute cerebral infarction patients were randomized into two groups: the vinpocetine group (469 patients) received cytidine disphosphate choline 0.4-0.5 g in combination with aspirin 75-100 mg or clopidogrel 75 mg once daily, plus vinpocetine 30 mg intravenously once daily for 7 days, while the control group (141 patients) received cytidine disphosphate choline 0.4-0.5 g in combination with aspirin 75-100 mg or clopidogrel 75 mg once daily for 7 days. Additionally, patients received medications for symptoms such as hypertension, hyperglycemia, hyperlipidemia, and intracranial hypertension when necessary. Mini-Mental State Examination (MMSE), National Institutes of Health Stroke Scale (NIHSS), modified Rankin Scale, and Barthel Index (BI) scores and transcranial doppler (TCD) were assessed at baseline, 7, 14, and 90 days after treatment. Adverse events (AEs) and abnormalities in blood, urine, liver, and kidney function were monitored. RESULTS: MMSE, NIHSS, and BI scores were significantly higher in the vinpocetine group than in the control group 90 days after treatment, indicating significantly improved cognitive skill, neurological function, and quality of life (QOL) in the vinpocetine group versus the control group. Importantly, such effects of vinpocetine were maintained over time. In addition, TCD monitoring showed significantly increased cerebral blood flow associated with vinpocetine versus control. No significant difference in safety was noted between the two groups. CONCLUSIONS: When used as part of treatment for acute cerebral infarction, vinpocetine improves patients' cerebral blood flow, cognitive quality, neurological functions, and QOL. Vinpocetine could be an effective and safe component of treatment regimen for acute cerebral infarction.

National data on stroke outcomes in Thailand.

Stroke is a major public health problem worldwide. There are limited data on national stroke prevalence and outcomes after the beginning of the thrombolytic therapy era in Thailand. This study aimed to investigate the prevalence and factors associated with mortality in stroke patients in Thailand using the national reimbursement databases. Clinical data retrieved included individuals under the universal coverage, social security, and civil servant benefit systems between 1 October 2009 and 30 September 2010. The stroke diagnosis code was based on the International Classification of Diseases 10th revision system including G45 (transient cerebral ischemic attacks and related syndromes), I61 (intracerebral hemorrhage), and I63 (cerebral infarction). The prevalence and stroke outcomes were calculated from these coded data. Factors associated with death were evaluated by multivariable logistic regression analysis. We found that the most frequent stroke subtype was cerebral infarction with a prevalence of 122 patients per 100,000 of population, an average length of hospital stay of 6.8 days, an average hospital charge of 20,740 baht (∼$USD 691), a mortality rate of 7%, and thrombolytic prescriptions of 1%. The significant factors associated with stroke mortality were septicemia, pulmonary embolism, pneumonia, myocardial infarction, status epilepticus, and heart failure. In conclusion, the prevalence and outcomes of stroke in Thailand were comparable with other countries. The era of thrombolytic therapy has just begun in Thailand.

Visual assessment of magnetic resonance imaging perfusion lesions in a large patient group.

PURPOSE: Few magnetic resonance imaging (MRI) studies of stroke have evaluated the value of visual assessment of perfusion/diffusion mismatch, which is crucial for routine application. In this study an attempt was made to visually assess perfusion lesions resembling the acute clinical situation and identify parameters with the highest interobserver reliability when used to define a perfusion/diffusion mismatch and the highest accuracy for prediction of infarct growth. METHODS: Magnetic resonance imaging was performed within 6 h of symptom onset and again 1-11 days thereafter in 86 consecutive stroke patients who received intravenous thrombolytic therapy. The MRI protocol included diffusion-weighted imaging apparent diffusion coefficient (DWI/ADC), fluid-attenuated inversion recovery (FLAIR) and perfusion imaging (PI). Maps for different perfusion parameters, e.g. cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT) and time to peak (TTP) were calculated. Areas of perfusion deficits of all perfusion parameters were visually compared to corresponding ADCs and final infarct size by two independent observers. RESULTS: The final infarct size was overestimated by TTP (in 81/83 patients by raters 1 and 2, respectively), MTT (82/83) and CBF (65/74) lesions. The ADC lesions were rated smaller than the final infarct size in 43/38 cases by raters 1 and 2 and the CBV decrease was rated to underestimate final infarct size in 40/31 cases. The only significantly increased OR of 3.883 (95 % CI 1.466-10.819, p = 0.004, rater 1)/5.142 (95 % CI 1.828-15.142, p = 0.001, rater 2) for predicting infarct growth was observed for the presence of a CBV > ADC mismatch, which also showed the highest kappa value of 0.407. CONCLUSIONS: All mismatch patterns were prone to high interrater variability when assessed under conditions resembling the clinical setting. Of all tested mismatch patterns the CBV > ADC mismatch was the strongest predictor of lesion growth while visual assessment of TTP and CBF generally resulted in an overestimation of infarct sizes and the presence of a TTP > ADC or CBF > ADC mismatch was not significantly predictive for lesion growth. Visual inspection of these most commonly used mismatch patterns has a low value for the prediction of infarct growth and thus the estimation of the penumbra in ischemic stroke patients.

Systematic assessment and meta-analysis of the efficacy and safety of fasudil in the treatment of cerebral vasospasm in patients with subarachnoid hemorrhage.

PURPOSE: Cerebral vasospasm (CVS) is a frequent and unpredictable complication in patients with subarachnoid hemorrhage (SAH) and often leads to poor outcomes. This study was aimed at evaluating the efficacy and safety of fasudil in the treatment of CVS in patients with SAH. METHODS: A search was conducted using the full-text database of Chinese scientific journals, the Wanfang Database (January 1999 to November 2010), the Chinese Medical Association Digital Journal Database, PubMed, the Cochrane library, OVID, and EMBase (searching through November 2010). RESULTS: A total of 8 studies met the inclusion criteria. The incidence rates of symptomatic CVS and CVS confirmed by angiography among the patients in the fasudil group were only 48% (odds ratio [OR] = 0.48, 95% confidence interval [CI]: 0.32-0.72, P = 0.0005) and 40% (OR = 0.40, 95% CI: 0.24-0-67, P = 0.0004) respectively of that of the control group. The odds ratios of cerebral infarction for all cases and cerebral infarction for CVS cases in the fasudil group were only 50% (OR = 0.50, 95% CI: 0.34-0.76, P = 0.0009) and 43% (OR = 0.43, 95% CI: 0.26-0.70, P = 0.0008) respectively of that of the control group. CONCLUSIONS: Fasudil greatly reduces the occurrence of CVS and cerebral infarction in SAH patients, significantly improves the clinical outcomes of the patients (as assessed by the Glasgow Outcome Scale). Because of the limited number of trials and samples available for analysis, the conclusions from the present study still need to be validated with results from large randomized, controlled clinical trials.

Regional differences in acute stroke admission and thrombolysis rates in the German federal state of Hesse.

BACKGROUND: Using data from the mandatory quality assurance program for stroke care in Hesse, we analyze regional differences in thrombolysis rates and infer some ways in which care can be improved. METHODS: We identified 7707 patients with acute ischemic stroke who were admitted to hospital within 3 hours of symptom onset in 2007 and 2008, and we determined the local thrombolysis rate district by district. In order to exclude the possibility that the observed local differences in thrombolysis rates might be accounted for, in large part, by off-label thrombolysis procedures, we further narrowed down the subgroup of patients who underwent thrombolysis to the 1108 patients admitted within 2 hours of symptom onset. We also analyzed the local thrombolysis rates for patients who were primarily referred to stroke units. RESULTS: The overall thrombolysis rate among patients admitted within 3 hours of symptom onset was 19%, varying locally from 6% to 35%. Among patients admitted within 2 hours of symptom onset, the local thrombolysis rate ranged from 13% to 85%. Even in patients primarily referred to stroke units, the local thrombolysis rate ranged from 8% to 44% in the 3-hour group and from 16% to 62% in the 2-hour group. CONCLUSION: Local thrombolysis rates vary unexpectedly widely across the state of Hesse. The care of patients with acute stroke after they reach the hospital urgently needs critical reappraisal and improvement.

Asymptomatic hemorrhagic transformation of infarction and its relationship with functional outcome and stroke subtype: assessment from the Tinzaparin in Acute Ischaemic Stroke Trial.

BACKGROUND AND PURPOSE: Asymptomatic hemorrhagic transformation of infarction (AHTI) is common, but its risk factors and relationship with functional outcome are poorly defined. METHODS: The analyses used data from the Tinzapararin in Acute Ischaemic Stroke Trial, a randomized controlled trial assessing tinzaparin (low molecular weight heparin) versus aspirin in 1484 patients with acute ischemic stroke. CT head scans (baseline, day 10) were adjudicated for the presence of hemorrhagic transformation. Stroke subtype was classified according to modified Trial of Org 10172 in Acute Stroke Treatment (small vessel, large vessel, cardioembolic) and the Oxfordshire Community Stroke Project (total anterior, partial anterior, lacunar, and posterior circulatory syndromes). Modified Rankin scale and Barthel Index were measured at 3 and 6 months. Analyses were adjusted for age, sex, severity, blood pressure, infarct volume, and treatment. Symptomatic hemorrhage was excluded. RESULTS: At day 10, AHTI did not differ between aspirin (300 mg; 32.8%) and medium-dose (100 IU/kg; 36.0%) and high-dose (175 IU/kg; 31.4%) tinzaparin groups (P = 0.44). Relative to lacunar stroke, AHTI on follow-up CT was significantly increased in total anterior circulation syndrome (odds ratio, 11.5; 95% CI, 7.1 to 18.7) and partial anterior circulation syndrome (odds ratio, 7.2; 95% CI, 4.5 to 11.4) stroke. Similarly, relative to small vessel disease, AHTI was increased in large vessel (odds ratio, 15.1; 95% CI, 9.4 to 24.3) and cardioembolic (odds ratio, 14.1; 95% CI, 8.5 to 23.5) stroke. After adjustment for infarct volume, the presence of AHTI was not associated with outcome at 3 or 6 months as measured by the modified Rankin Scale and Barthel Index. CONCLUSIONS: AHTI is increased in ischemic stroke with cortical syndromes and of large vessel or cardioembolic etiology. Heparin does not increase AHTI. AHTI is not associated with functional outcome.

[Recurrent idiopathic cerebral infarction in a 5-year-old boy, with emphasis on the importance of platelet aggregation analysis for appropriate selection of anti-platelet drugs].

We present a 5-year-old boy with recurrent idiopathic cerebral infarction in which analysis of platelet hyperaggregability was useful in choosing appropriate anti-platelet drugs. The patient presented with gait disturbance at the age of 5 years and 1 month. Brain MRI demonstrated multiple infarctions in the right thalamus and left cerebellum. There were no apparent underlying diseases including hematological, cardiac and vascular abnormalities. He was diagnosed as idiopathic cerebral infarction. First, we administered ticlopidine and he remained stable with persistent mild intention tremor in the left upper extremity for 4 months. Then he developed the second stroke at the age of 5 years and 5 months, and multiple infarctions in the right celebellum and cerebellar vermis were demonstrated. On platelet aggregation analysis, adenosine diphosphate (ADP)-induced aggregation was inhibited, probably due to ticlopidine administration. Collagen- and epinephrine-induced platelet aggregation showed hyperaggregation, so we started to administer cilostazol, which inhibits only epinephrine-induced hyperaggregation. We also added aspirin, which inhibits collagen-induced hyperaggregation. The combination of anti-platelet drugs inhibited epinephrine-, collagen- and ADP-induced hyperaggregation in this patient. He has been stable on the triple combination of anti-platelet drugs without further episodes of cerebral infarction or transient ischemic attack for 4 years to date. Appropriate selection of anti-platelet therapy was achieved by the simple and repeatable platelet aggregation analyses, which must be considered even in pediatric patients with cerebral infarction.

[Incremental cost-effectiveness of dipyridamole + acetylsalicylic acid in secondary prevention of ischemic noncardioembolic stroke]. / Inkrementelle Kosteneffektivität von Dipyridamol + Acetylsalicylsäure in der Sekundärprävention bei ischämischem nichtkardioembolischem Schlaganfall.

BACKGROUND AND PURPOSE: The aim of secondary prevention in stroke is to avoid restrokes. The current standard treatment in Germany is a lifelong therapy with low-dose acetylsalicylic acid (ASA). As the incidence of restrokes remains relatively high from a health-care payer's perspective, the question arises, whether the combination of dipyridamole + acetylsalicylic acid (Dip + ASA) is cost-effective in comparison with a therapy based on ASA only. METHODS: A decision-analytic cross-sectional epidemiologic steady-state model of the German population compares the effects of two strategies of secondary prevention with Dip + ASA (12 months vs. open end) and with ASA monotherapy. RESULTS: The model predicts the following estimates: the annual incidence of initial ischemic strokes in Germany is estimated at 130,000 plus an extra 34,000 restrokes (base year 2005). Additionally, there are 580,000 people that experienced a stroke > 12 months earlier, of whom 135,000 had a restroke. Every year, nearly 89,000 Germans die of the consequences of an ischemic stroke. If Dip + ASA would have been the standard therapy in secondary prevention of ischemic stroke, an additional 7,500 persons could have been saved in 2005. Statutory health insurance would have to spend 33,000 Euro for every additional life year gained with Dip + ASA as secondary prevention strategy. If secondary prevention with Dip + ASA would be limited to the first 12 months after an initial stroke, which is the time of the highest risk for a restroke, the incremental cost-effectiveness ratio is about 7,000 Euro per life year gained. The results proved to be robust in sensitivity analyses. CONCLUSION: Secondary prevention with Dip + ASA is cost-effective in comparison to treatment with ASA in monotherapy, because its incremental cost-effectiveness ratio is within common ranges of social willingness to pay. From the standpoint of the patient as well as the health-care payer, focusing on the first 12 months after the initial incident for intensified preventive drug treatment with Dip + ASA should be valuable from a medical as well as a health-economic perspective.

Pharmacoeconomic analysis of cilostazol for the secondary prevention of cerebral infarction.

BACKGROUND: The antiplatelet agent, cilostazol, is known to reduce the risk of subsequent cerebral infarction. However, the cost effectiveness of such treatment in comparison to aspirin has not been studied. METHODS AND RESULTS: A Markov model was developed to calculate the health outcomes and associated costs for 65-year-old patients with cerebral infarction who were treated with 200 mg/day cilostazol or 81 mg/day aspirin. Cilostazol was more effective, but also more expensive than aspirin. Cilostazol would extend quality-adjusted life years (QALY) by 0.64, while increasing life-time costs by approximately Yen 1.1 million. The incremental cost-effectiveness ratio of cilostazol in comparison with aspirin was estimated to be Yen 1.8 million per QALY. CONCLUSIONS: The use of cilostazol to prevent recurrence of cerebral infarction appears to be cost effective.

Significant variation in mortality and functional outcome after acute ischaemic stroke between Western countries: data from the tinzaparin in acute ischaemic stroke trial (TAIST).

BACKGROUND: The medical care of patients with acute stroke varies considerably between countries. This could lead to measurable differences in mortality and functional outcome. OBJECTIVE: To compare case mix, clinical management, and functional outcome in stroke between 11 countries. METHODS: All 1484 patients from 11 countries who were enrolled into the tinzaparin in acute ischaemic stroke trial (TAIST) were included in this substudy. Information collected prospectively on demographics, risk factors, clinical features, measures of service quality (for example, admission to a stroke unit), and outcome were assessed. Outcomes were adjusted for treatment assignment, case mix, and service relative to the British Isles. RESULTS: Differences in case mix (mostly minor) and clinical service (many of prognostic relevance) were present between the countries. Significant differences in outcome were present between the countries. When assessed by geographical region, death or dependency were lower in North America (odds ratio (OR) adjusted for treatment group only = 0.52 (95% confidence interval, 0.39 to 0.71) and north west Europe (OR = 0.54 (0.37 to 0.78)) relative to the British Isles; similar reductions were found when adjustments were made for 11 case mix variables and five service quality measures. Similarly, case fatality rates were lower in North America (OR = 0.44 (0.30 to 0.66)) and Scandinavia (OR = 0.50 (0.33 to 0.74)) relative to the British Isles, whether crude or adjusted for case mix and service quality. CONCLUSIONS: Both functional outcome and case fatality vary considerably between countries, even when adjusted for prognostic case mix variables and measures of good stroke care. Differing health care systems and the management of patients with acute stroke may contribute to these findings.