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Efficacy and safety of cinepazide maleate injection in patients with acute ischemic stroke: a multicenter, randomized, double-blind, placebo-controlled trial.
Ni, J, Chen, H, Chen, G, Ji, Y, Yi, F, Zhang, Z, Yang, Y, Wu, J, Cai, X, Shao, B, et al
BMC neurology. 2020;(1):282
Abstract
BACKGROUND Ischemic stroke is a leading cause of morbidity and mortality. Thrombolytic therapy improves disability and survival rates; however, to be effective, it must be given within 4.5 h of onset. Moreover, thrombolytic therapy is frequently contraindicated. Therefore, alternative therapeutic options are required. In China, cinepazide maleate injection has been shown to improve the cerebral collateral circulation and further reduce disability in stroke patients; however, very few studies investigating this therapy have been conducted to date. Therefore, this study aimed to further confirm the efficacy and safety of cinepazide maleate injection in patients with acute ischemic stroke. METHODS Patients with acute ischemic stroke were administered an intravenous infusion of 320 mg cinepazide maleate or placebo once daily for 14 days. All patients were also administered basic therapy (citicoline sodium). The primary efficacy endpoint was the proportion of patients with a modified Rankin scale (mRS) ≤2 on day 90. Secondary efficacy endpoints included Barthel Index ≥95. Safety was evaluated by recording all adverse events (AEs), monitoring laboratory parameters and vital signs, and electrocardiogram. RESULTS In total, 937 patients with an acute ischemic stroke were included, with a mean (standard deviation, SD) National Institutes of Health Stroke Scale score of 8.8 (2.4) and a mean (SD) stroke onset of 30.9 (11.4) hours prior. Following treatment for 90 days, the proportion of patients with an mRS score ≤ 2 was significantly higher in the cinepazide maleate group than in the control group (60.9% vs. 50.1%; p = 0.0004). Moreover, the proportion of patients with a Barthel Index of ≥95 on day 90 was also significantly higher in the cinepazide maleate group than in the control group (53.4% vs. 46.7%; p = 0.0230). There were no statistically significant differences in safety parameters between the cinepazide maleate and control groups. CONCLUSIONS The results of this study show that cinepazide maleate injection is superior to placebo in improving neurological function and activities of daily living, reducing disability, and promoting functional recovery in patients with acute ischemic stroke. Cinepazide maleate injection was safe and well tolerated with no unexpected AEs reported. TRIAL REGISTRATION Chinese Clinical Trial Registry CTR20160292 and ChiCTR1900023827 . Retrospectively registered June 13, 2019.
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Ginkgol Biloba extract as an adjunctive treatment for ischemic stroke: A systematic review and meta-analysis of randomized clinical trials.
Ji, H, Zhou, X, Wei, W, Wu, W, Yao, S
Medicine. 2020;(2):e18568
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OBJECTIVE Ginkgo biloba extract (GBE) is widely used as an adjunctive treatment for ischemic stroke. This meta-analysis aimed to evaluate the effectiveness and safety of GBE specifically for long-term users at the convalescence stage of ischemic stroke. METHODS MEDLINE, Cochrane Central Register of Controlled Trials, Embase Database, WHO Clinical Trials Registration Platform, Chinese National Knowledge Infrastructure, Wanfang Database, and Chinese Scientific Journal Database were searched from inception to 20 September 2018. Risk ratio (RR) and mean difference (MD) with a 95% confidence interval (CI) were used as effect estimates using RevMan software (5.3; Review Manager [RevMan], Nordic Cochrane Centre, Copenhagen, Denmark). A meta-analysis was performed where data were available. A trial sequential analysis was used to control random errors for recurrence rate and the GRADE (grading of recommendations, assessment, development, and evaluations) approach was used to assess the quality of the body of evidence. The meta-analysis design was registered on PROSPERO (CRD42018110211, http://www.crd.york.ac.uk/PROSPERO). RESULTS We identified 15 randomized clinical trials involving 1829 participants. The majority of the included trials were of high risk of bias in methodological quality. For acute ischemic stroke, adding GBE to conventional therapy led to higher Barthel index scores (MD: 5.72; 95% CI: 3.11-8.33) and lower neurological function deficit scores (MD: -1.39; 95% CI: -2.15 to -0.62). For patients in their convalescence (or sequelae) stage of ischemic stroke, GBE was superior in improving dependence (MD: 7.17; 95% CI: 5.96-8.38) and neurological function deficit scores (MD: -1.15; 95% CI: -1.76 to -0.53) compared with placebo or conventional therapy, but there was no difference in vascular events (RR: 0.70; 95% CI: 0.44-1.14), recurrence rate (RR: 0.57; 95% CI: 0.26-1.25; trial sequential analysis: conclusive) and mortality (RR: 1.07; 95% CI: 0.41-2.81). CONCLUSIONS GBE appears to improve neurological function and dependence compared with conventional therapy for ischemic stroke at different stages and appears generally safe for clinical application. The lack of improvement in recurrence rate was confirmed by trial sequential analysis. Due to the generally weak evidence, further large, rigorous trials are warranted.
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[Oropharyngeal dysphagia in stroke: diagnostic and therapeutic aspects].
Terré, R
Revista de neurologia. 2020;(12):444-452
Abstract
INTRODUCTION The prevalence of oropharyngeal dysphagia is high after a stroke. Clinically, it manifests as alterations affecting swallowing efficiency and safety, with the consequent morbidity and mortality associated with nutritional and respiratory alterations. AIM: To carry out an updated review of the diagnostic and therapeutic aspects of oropharyngeal dysphagia after a stroke that can be applied in daily clinical practice, and of the non-invasive neurostimulation techniques. DEVELOPMENT The process of diagnosis and treatment of oropharyngeal dysphagia aims to screen, identify and diagnose patients at risk of dysphagia, and establish the dietary and therapeutic measures that ensure proper nutrition and hydration of patients under safe conditions. The diagnosis is based on the clinical examination of swallowing and on instrumental examinations such as videofluoroscopy and fibro-endoscopy. Therapeutic measures include compensatory and rehabilitative strategies (active manoeuvres, motor control exercises, neuromuscular electrostimulation and botulinum toxin treatment). Neurostimulation techniques include non-invasive central stimulation and intrapharyngeal electrical stimulation. CONCLUSION The prevalence of oropharyngeal dysphagia is high after a stroke. Diagnosis should include a clinical evaluation and an instrumental examination, and thus objectively indicate the treatment, which will include compensatory and restorative measures with which to reduce the associated morbidity and mortality.
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Vertigo and dizziness in the emergency room.
Zwergal, A, Dieterich, M
Current opinion in neurology. 2020;(1):117-125
Abstract
PURPOSE OF REVIEW To provide an update on diagnostic algorithms for differential diagnosis of acute vertigo and dizziness and swift identification of potentially harmful causes. RECENT FINDINGS About 25% of patients with acute vertigo and dizziness have a potentially life-threatening diagnosis, including stroke in 4-15%. Diagnostic work-up relies on the combination of symptom features (triggers, duration, history of vertigo/dizziness, accompanying symptoms) and a comprehensive vestibular, ocular motor, and balance exam. The latter includes head impulse, head-shaking nystagmus, positional nystagmus, gaze-holding, smooth pursuit, skew deviation, and Romberg's test. Recent standardized diagnostic algorithms (e.g., HINTS, TriAGe+) suggest the combination of several elements to achieve a good diagnostic accuracy in differentiation of central and peripheral vestibular causes. Neuroimaging with MRI must be applied and interpreted with caution, as small strokes are frequently overlooked, especially in the acute setting (false-negative rate of up to 50%). SUMMARY Diagnostic differentiation of acute vertigo and dizziness remains a complex task, which can be tackled by a structured clinical assessment focusing on symptom characteristics and constellations of ocular motor and vestibular findings. Specific challenges arise in cases of transient or atypical vestibular syndromes.
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Interim effects of salt substitution on urinary electrolytes and blood pressure in the China Salt Substitute and Stroke Study (SSaSS).
Huang, L, Tian, M, Yu, J, Li, Q, Liu, Y, Yin, X, Wu, JH, Marklund, M, Wu, Y, Li, N, et al
American heart journal. 2020;:136-145
Abstract
The Salt Substitute and Stroke Study is an ongoing 5-year large-scale cluster randomized trial investigating the effects of potassium-enriched salt substitute compared to usual salt on the risk of stroke. The study involves 600 villages and 20,996 individuals in rural China. Intermediate risk markers were measured in a random subsample of villages every 12 months over 3 years to track progress against key assumptions underlying study design. Measures of 24-hour urinary sodium, 24-hour urinary potassium, blood pressure and participants' use of salt substitute were recorded, with differences between intervention and control groups estimated using generalized linear mixed models. The primary outcome of annual event rate in the two groups combined was determined by dividing confirmed fatal and non-fatal strokes by total follow-up time in the first 2 years. The mean differences (95% CI) were -0.32 g (-0.68 to 0.05) for 24-hour urinary sodium, +0.77 g (+0.60 to +0.93) for 24-hour urinary potassium, -2.65 mmHg (-4.32 to -0.97) for systolic blood pressure and +0.30 mmHg (-0.72 to +1.32) for diastolic blood pressure. Use of salt substitute was reported by 97.5% in the intervention group versus 4.2% in the control group (P<.0001). The overall estimated annual event rate for fatal and non-fatal stroke was 3.2%. The systolic blood pressure difference and the annual stroke rate were both in line with the statistical assumptions underlying study design. The trial should be well placed to address the primary hypothesis at completion of follow-up.
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Carotid Intima-Media Thickness Progression as Surrogate Marker for Cardiovascular Risk: Meta-Analysis of 119 Clinical Trials Involving 100 667 Patients.
Willeit, P, Tschiderer, L, Allara, E, Reuber, K, Seekircher, L, Gao, L, Liao, X, Lonn, E, Gerstein, HC, Yusuf, S, et al
Circulation. 2020;(7):621-642
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BACKGROUND To quantify the association between effects of interventions on carotid intima-media thickness (cIMT) progression and their effects on cardiovascular disease (CVD) risk. METHODS We systematically collated data from randomized, controlled trials. cIMT was assessed as the mean value at the common-carotid-artery; if unavailable, the maximum value at the common-carotid-artery or other cIMT measures were used. The primary outcome was a combined CVD end point defined as myocardial infarction, stroke, revascularization procedures, or fatal CVD. We estimated intervention effects on cIMT progression and incident CVD for each trial, before relating the 2 using a Bayesian meta-regression approach. RESULTS We analyzed data of 119 randomized, controlled trials involving 100 667 patients (mean age 62 years, 42% female). Over an average follow-up of 3.7 years, 12 038 patients developed the combined CVD end point. Across all interventions, each 10 μm/y reduction of cIMT progression resulted in a relative risk for CVD of 0.91 (95% Credible Interval, 0.87-0.94), with an additional relative risk for CVD of 0.92 (0.87-0.97) being achieved independent of cIMT progression. Taken together, we estimated that interventions reducing cIMT progression by 10, 20, 30, or 40 μm/y would yield relative risks of 0.84 (0.75-0.93), 0.76 (0.67-0.85), 0.69 (0.59-0.79), or 0.63 (0.52-0.74), respectively. Results were similar when grouping trials by type of intervention, time of conduct, time to ultrasound follow-up, availability of individual-participant data, primary versus secondary prevention trials, type of cIMT measurement, and proportion of female patients. CONCLUSIONS The extent of intervention effects on cIMT progression predicted the degree of CVD risk reduction. This provides a missing link supporting the usefulness of cIMT progression as a surrogate marker for CVD risk in clinical trials.
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Cilostazol Versus Aspirin in Ischemic Stroke Patients With High-Risk Cerebral Hemorrhage: Subgroup Analysis of the PICASSO Trial.
Kim, BJ, Kwon, SU, Park, JH, Kim, YJ, Hong, KS, Wong, LKS, Yu, S, Hwang, YH, Lee, JS, Lee, J, et al
Stroke. 2020;(3):931-937
Abstract
Background and Purpose- Although cilostazol has shown less hemorrhagic events than aspirin, only marginal difference was observed in hemorrhagic stroke events among patients at high risk for cerebral hemorrhage. To identify patients who would most benefit from cilostazol, this study analyzed interactions between treatment and subgroups of the PICASSO trial (Prevention of Cardiovascular Events in Asian Ischemic Stroke Patients With High Risk of Cerebral Hemorrhage). Methods- Ischemic stroke patients with a previous intracerebral hemorrhage or multiple microbleeds were randomized to treatment with cilostazol or aspirin and followed up for a mean 1.8 years. Efficacy, defined as the composite of any stroke, myocardial infarction, and vascular death, and safety, defined as the incidence of hemorrhagic stroke, were analyzed in the 2 groups. Interactions between treatment and age, sex, presence of hypertension and diabetes mellitus, index of high-risk cerebral hemorrhage, and white matter lesion burden were analyzed for primary and key secondary outcomes. Changes in vital signs and laboratory results were compared in the 2 groups. Results- Among all 1534 patients enrolled, a significant interaction between treatment group and index of high risk for cerebral hemorrhage on hemorrhagic stroke (P for interaction, 0.03) was observed. Hemorrhagic stroke was less frequent in the cilostazol than in the aspirin group in patients with multiple microbleeds (1 versus 13 events; hazard ratio, 0.08 [95% CI, 0.01-0.61]; P=0.01). A marginal interaction between treatment group and white matter change on any stroke (P for interaction, 0.08) was observed. Cilostazol reduced any stroke significantly in patients with mild (5 versus 16 events; hazard ratio, 0.36 [95% CI, 0.13-0.97]; P=0.04)-to-moderate (16 versus 32 events; hazard ratio, 0.50 [95% CI, 0.29-0.92]; P=0.03) white matter changes. Heart rate and HDL (high-density lipoprotein) cholesterol level were significantly higher in the cilostazol group than in the aspirin group at follow-up. Conclusions- Cilostazol may be more beneficial for ischemic stroke patients with multiple cerebral microbleeds and before white matter changes are extensive. Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT01013532.
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Quick and effective improvement of leucine enriched dietary supplement on malnutrition in acute stroke patients receiving enteral tube feeding.
Mori, T, Yoshioka, K
BMC emergency medicine. 2020;(1):56
Abstract
BACKGROUND Malnutrition often occurs in acute stroke patients receiving enteral tube feeding (ETF). Unless malnutrition is improved, their clinical outcome is poor. However, strategies to improve malnutrition in these patients have not been established. Branched-chain amino acids (BCAA) may enhance protein synthesis and attenuate inflammation. Our study aimed to investigate whether a leucine enriched BCAA dietary supplement (LEBDs) could quickly increase serum levels of albumin (Alb) or transthyretin (TTR) and decrease high-sensitivity C-reactive protein (CRP) in the development of severe malnutrition within a few days after stroke onset compared to standard BCAA dietary supplement (SBDs). METHODS We retrospectively included acute stroke patients who: 1) were admitted between August 2016 and July 2017; 2) underwent ETF for 7 days or longer after admission, and 3) underwent blood examination of Alb, TTR, and CRP on admission, the fifth day and the seventh day. We defined severe malnutrition as severe hypoproteinemia: decrease of TTR to less than 15 mg/dl on the 5th day. In LEBDs and SBDs groups, patients started to receive a dietary supplement containing leucine of 1.44 and 0. 72 g twice a day on the fifth day, respectively. We evaluated Alb (g/dl), TTR (mg/dl), and CRP (mg/dl) on admission, the fifth day, and the seventh day. RESULTS Twenty-nine patients met our inclusion criteria:15 in LEBDs and 14 in SBDs. In LEBDs and SBDs groups, the median Alb was 3.5 and 3.3 g/dl, TTR was 12.7 and 10.7 mg/dl, and CRP was 1.02 and 0.673 mg/dl on admission, respectively. In LEBDs, the median Alb and TTR decreased to 2.6 g/dl and 11.9 mg/dl, and CRP increased to 5.337 mg/dl on the fifth day. On the 7th day, TTR increased, and CRP decreased, although Alb did not improve. In SBDs, the median Alb and TTR decreased to 2.6 g/dl and 9.7 mg/dl, and CRP increased to 4.077 mg/dl on the fifth day. On the 7th day, Alb, TTR, and CRP did not improve. CONCLUSION In acute stroke patients receiving leucine enriched BCAA dietary supplement, quick improvements in transthyretin and CRP were observed.
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Association between caveolin-1 and stroke: a systematic review and meta-analysis.
Geng, T, Feng, L, Fang, YT, Wang, ZQ, Liu, GF
European review for medical and pharmacological sciences. 2020;(19):10054-10060
Abstract
OBJECTIVE Caveolin-1 plays critical roles in regulating signal transduction and cholesterol trafficking in cells. However, the relationship between caveolin-1 and stroke remains less reported. MATERIALS AND METHODS In this study, we reviewed information from seventeen studies to get the qualitative evidence of the influence of the caveolin-1 on stroke and collected data from three of the seventeen studies to conduct meta-analysis. The original studies classified participants into two groups with stroke group and control group, respectively. The random-effect model was used in the meta-analysis with the standardized mean difference (SMD) as the measure indicator. RESULTS Our data showed that the SMD (95% confidence intervals, CIs) between the control group and the stroke group was -0.5449 [-2.3344, 1.0000]. For the subgroup analysis, The SMD (95% confidence intervals, CIs) between the control group and the ischemic stroke group was -1.4589 [-5.0129, 2.0951], and between the control group and the hemorrhagic stroke group was 0.3438 [-0.4140, 1.1017]. CONCLUSIONS Although the differences are not statistically significant between the two groups, the high level of caveolin-1 are associated with the stroke, which may remedy the stroke. Besides, an opposite result was observed for the association of the caveolin-1 on the ischemic stroke and hemorrhagic stroke. To confirm this association, further studies are necessary.
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[Anticoagulation in vulnerable elderly patients with atrial fibrillation : risks and benefits].
Coutaz, M
Revue medicale suisse. 2020;(706):1718-1720
Abstract
Atrial fibrillation is a common cardiac disease of aging. The risk of stroke and bad prognosis increase with age and atrial fibrillation. Compared with younger people, elderly people have higher risks for both thrombosis and bleeding. Stroke prevention with oral anticoagulants is the cornerstone of the management of atrial fibrillation but is often questioned because of the risk of bleeding, furthermore comorbidities, comedications, fall risks, poor compliance. These factors frequently found in frail elderly patients complicate the management of antithrombotic therapy. This article reviews the evidence for the risks and benefits of anticoagulation in the elderly with atrial fibrillation, by comparing the new oral anticoagulants to vitamin K antagonists.