A Systematic Review and Meta-Analysis of the Efficacy of Piracetam and Piracetam-Like Compounds in Experimental Stroke

Wheble, Philippa; Sena, Emily S.; Macleod, Malcolm

doi:10.1159/000111493

Cited by 32 publications

(18 citation statements)

References 46 publications

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“…26 Two studies unpublished at the time of the search were provided by 1 of the authors (27 and Sena and Macleod, unpublished data, 2007); this gave a total of 13 meta-analyses that described outcome in 15 635 animals (the Table).…”

Section: Resultsmentioning

confidence: 99%

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Empirical Evidence of Bias in the Design of Experimental Stroke Studies

Crossley

Sena

Goehler

et al. 2008

Stroke

216

185

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Background and Purpose-At least part of the failure in the transition from experimental to clinical studies in stroke has been attributed to the imprecision introduced by problems in the design of experimental stroke studies. Using a metaepidemiologic approach, we addressed the effect of randomization, blinding, and use of comorbid animals on the estimate of how effectively therapeutic interventions reduce infarct size. Methods-Electronic and manual searches were performed to identify meta-analyses that described interventions in experimental stroke. For each meta-analysis thus identified, a reanalysis was conducted to estimate the impact of various quality items on the estimate of efficacy, and these estimates were combined in a meta-meta-analysis to obtain a summary measure of the impact of the various design characteristics. Results-Thirteen meta-analyses that described outcomes in 15 635 animals were included. Studies that included unblinded induction of ischemia reported effect sizes 13.1% (95% CI, 26.4% to 0.2%) greater than studies that included blinding, and studies that included healthy animals instead of animals with comorbidities overstated the effect size by 11.5% (95% CI, 21.2% to 1.8%). No significant effect was found for randomization, blinded outcome assessment, or high aggregate CAMARADES quality score. Conclusions-We provide empirical evidence of bias in the design of studies, with studies that included unblinded induction of ischemia or healthy animals overestimating the effectiveness of the intervention. This bias could account for the failure in the transition from bench to bedside of stroke therapies.

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Section: Resultsmentioning

confidence: 99%

“…12,18,20,22,25,26 Studies not reporting blinded induction of ischemia had a significant overestimation of the effect of the therapy being studied, overestimating the effect size by 13.3% (95% CI, 0.2% to 26.4%; Figure 2). …”

Section: Blinded Induction Of Ischemiamentioning

confidence: 99%

Empirical Evidence of Bias in the Design of Experimental Stroke Studies

Crossley

Sena

Goehler

et al. 2008

Stroke

216

185

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“…Other researchers have used ratios of the results for similar continuous data that required logarithmic processing [19]. Other groups have normalized data to outcomes in the control group [20]. The results of both groups were expressed as percentages, but these results cannot be directly compared.…”

Section: Discussionmentioning

confidence: 99%

“…Particularly because animal data often comes from many small studies, there is even more demand for pooling results by meta-analytic methods than for large clinical trials. neuroprotection [19][20][21][22][23][24][25][26]. Meta-analytic methodology has also been employed to study the genetics of stem cells [27].…”

Section: Introductionmentioning

confidence: 99%

Intravenous Route of Cell Delivery for Treatment of Neurological Disorders: A Meta-Analysis of Preclinical Results

Janowski

Walczak

Date

2010

Stem Cells and Development

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The last decade has been marked by a growing interest in an employment of intravenous cell delivery for treatment of neurological disorders. Numerous preclinical experimental studies have reported functional benefits, and have recently been followed by clinical trials. Some early clinical studies have indicated only modest positive effects, suggesting that the optimal conditions have not been defined yet. Thus, the evaluation of factors that influence outcomes, on the level of the whole population of preclinical studies by advanced statistical analysis, is warranted. PubMed search was conducted from the inception through 2006, and 60 preclinical studies were found and subjected to analysis. Categorical and continuous independent variables (IVs) were extracted. Three distinct outcomes of interest were selected as dependent variables (DVs) and named treatment effects: morphological, behavioral, and molecular, respectively. Mean outcomes, standard deviations (SDs), and animal numbers were retrieved and calculated by individual comparisons of experimental and control groups, based on the Hedges g formula, and were expressed as effect sizes (ESs) and variances. Publication bias and homogeneity were evaluated. The mainspring analyses were performed under a random effect model using Proc Mixed (SAS, version 9.2). A significant heterogeneity and publication bias were found. The ES pooling revealed large treatment effects. Univariate and multivariate meta-regression revealed that cell-related variables explained most of the heterogeneity. Cells retrieved from established lines and genetic modification of cells warrants the highest efficiency, in a dose-dependent manner. The stratified analysis of molecular effect measures revealed that apoptosis inhibition is the strongest brain tissue-positive change induced by cell therapy.

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“…В частности, в клинических рекоменда-циях European Stroke Organization (ESO) 2008 го-да приводится утверждение с высоким уровнем доказательности (класс I, уровень А), что в на-стоящее время отсутствуют рекомендации по лечению острого ишемического инсульта при по-мощи нейропротективных препаратов [1]. Мно-гие нейропротективные средства оказывают по-ложительный эффект в лечении эксперимен-тального ишемического инсульта у животных, что реализуется за счет различных противоише-мических механизмов, приводящих в итоге к уменьшению гибели нейронов в зоне пенумбры [7,8]. К сожалению, аналогичных достоверных положительных результатов в лечении инсуль-та с помощью церебропротективных препаратов у людей пока не получено [9].…”

Section: ошибка 5: применение ноотропов и вазоак-тивных препаратов наunclassified

Mistakes in Outpatient Neurological Practice. Part Ii

Кандыба

2015

Rossiĭskiĭ semeĭnyĭ vrach

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Во второй части статьи продолжается анализ некоторых ошибок в отечественной амбулаторной прак-тике при диагностике и лечении неврологических заболеваний. Приводятся современные данные о резуль-татах научных и клинических исследований по изучению эффективности использования церебропротек-тивных, ноотропных и вазоактивных препаратов в лечении инсульта, дисциркуляторной энцефалопатии и сосудистой деменции. Основу лечения хронической ишемии мозга составляет раннее выявление и кор-рекция факторов риска сердечно-сосудистых заболеваний. Гипердиагностика сосудисто-мозговых забо-леваний и переоценка их роли в развитии когнитивных расстройств, приводит к ошибочному использова-нию лекарственных препаратов с недоказанной эффективностью.Ключевые слова: неврологические ошибки, инсульт, хроническая ишемия мозга, сосудистая деменция.In the second part of this article continues the analysis of some errors in the national outpatient practice in the diagnosis and treatment of neurological diseases. Given the current data about the results of scientific and clinical studies on the efficiency cerebroprotective, nootropic and vasoactive drugs in the treatment of stroke, discirculatory encephalopathy and vascular dementia. The mainstay of treatment of chronic ischemia of the brain is early detection and correction of risk factors for cardiovascular diseases. Overdiagnosis of cerebrovascular diseases and their role in the development of cognitive disorders lead to erroneous use of drugs with unproven efficacy.

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A Systematic Review and Meta-Analysis of the Efficacy of Piracetam and Piracetam-Like Compounds in Experimental Stroke

Cited by 32 publications

References 46 publications

Empirical Evidence of Bias in the Design of Experimental Stroke Studies

Empirical Evidence of Bias in the Design of Experimental Stroke Studies

Intravenous Route of Cell Delivery for Treatment of Neurological Disorders: A Meta-Analysis of Preclinical Results

Mistakes in Outpatient Neurological Practice. Part Ii

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