Systematic Review and Meta-analysis of Methodological Quality in In Vivo Animal Studies of Subarachnoid Hemorrhage

2020 ◽  
Vol 11 (6) ◽  
pp. 1175-1184 ◽  
Author(s):  
Basil E. Grüter ◽  
Davide Croci ◽  
Salome Schöpf ◽  
Edin Nevzati ◽  
Donato d’Allonzo ◽  
...  
Keyword(s):  
Systematic Review ◽  
Subarachnoid Hemorrhage ◽  
Methodological Quality ◽  
Animal Studies ◽  
Meta Analysis

scholarly journals Efficacy of Melatonin in Animal Models of Subarachnoid Hemorrhage: A Systematic Review and Stratified Meta-Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiangyu Hu ◽  
Yuwei Zhu ◽  
Fangfang Zhou ◽  
Cuiying Peng ◽  
Zhiping Hu ◽  
...  
Keyword(s):  
Systematic Review ◽  
Subarachnoid Hemorrhage ◽  
Animal Models ◽  
Animal Studies ◽  
Meta Analysis ◽  
Severe Disease ◽  
Clinical Trial Design ◽  
Neurological Deficits ◽  
Protective Effects ◽  
China National Knowledge Infrastructure

Background and Purpose: Subarachnoid hemorrhage (SAH) is a severe disease characterized by sudden headache, loss of consciousness, or focal neurological deficits. Melatonin has been reported as a potential neuroprotective agent of SAH. It provides protective effects through the anti-inflammatory effects or the autophagy pathway. Our systematic review aims to evaluate the efficacy of melatonin administration on experimental SAH animals and offer support for the future clinical trial design of the melatonin treatment following SAH.Methods: The following online databases were searched for experimentally controlled studies of the effect of melatonin on SAH models: PubMed, Web of Knowledge, Embase, and China National Knowledge Infrastructure (all until March 2021). The melatonin effect on the brain water content (BWC) and neurological score (NS) were compared between the treatment and control groups using the standardized mean difference (SMD).Results: Our literature identified 160 possible articles, and most of them were excluded due to duplication (n = 69) and failure to meet the inclusion criteria (n = 56). After screening the remaining 35 articles in detail, we excluded half of them because of no relevant outcome measures (n = 16), no relevant interventions (n = 3), review articles (n = 1), duplicated publications (n = 1), and studies on humans or cells (n = 2). Finally, this systematic review contained 12 studies between 2008 and 2018. All studies were written in English except for one study in Chinese, and all of them showed the effect of melatonin on BWC and NS in SAH models.Conclusion: Our research shows that melatonin can significantly improve the behavior and pathological results of SAH animal models. However, due to the small number of studies included in this meta-analysis, the experimental design and experimental method limitations should be considered when interpreting the results. Significant clinical and animal studies are still required to evaluate whether melatonin can be used in the adjuvant treatment of clinical SAH patients.

scholarly journals Bioinorganic supplementation of calcium phosphate-based bone substitutes to improve in vivo performance: a systematic review and meta-analysis of animal studies

2020 ◽  
Vol 8 (17) ◽  
pp. 4792-4809
Author(s):  
Irene Lodoso-Torrecilla ◽  
Raquel Klein Gunnewiek ◽  
Eline-Claire Grosfeld ◽  
Rob B. M. de Vries ◽  
Pamela Habibović ◽  
...  
Keyword(s):  
Systematic Review ◽  
Calcium Phosphate ◽  
Animal Studies ◽  
Meta Analysis ◽  
Bone Substitutes ◽  
Biological Performance

Supplementation of CaP-based bone substitutes with bioinorganics affects biological performance.

scholarly journals Pharmacologic Reduction of Angiographic Vasospasm in Experimental Subarachnoid Hemorrhage: Systematic Review and Meta-Analysis

2012 ◽  
Vol 32 (9) ◽  
pp. 1645-1658 ◽  
Author(s):  
Tommaso Zoerle ◽  
Don C Ilodigwe ◽  
Hoyee Wan ◽  
Katarina Lakovic ◽  
Mohammed Sabri ◽  
...  
Keyword(s):  
Systematic Review ◽  
Subarachnoid Hemorrhage ◽  
Animal Models ◽  
Animal Studies ◽  
Meta Analysis ◽  
Angiographic Vasospasm ◽  
Standard Mean Difference ◽  
Methodologic Quality ◽  
Experimental Subarachnoid Hemorrhage ◽  
Pharmacologic Treatments

Animal models have been developed to simulate angiographic vasospasm secondary to subarachnoid hemorrhage (SAH) and to test pharmacologic treatments. Our aim was to evaluate the effect of pharmacologic treatments that have been tested in humans and in preclinical studies to determine if animal models inform results reported in humans. A systematic review and meta-analysis of SAH studies was performed. We investigated predictors of translation from animals to humans with multivariate logistic regression. Pharmacologic reduction of vasospasm was effective in mice, rats, rabbits, dogs, nonhuman primates (standard mean difference of −1.74; 95% confidence interval −2.04 to −1.44) and humans. Animal studies were generally of poor methodologic quality and there was evidence of publication bias. Subgroup analysis by drug and species showed that statins, tissue plasminogen activator, erythropoietin, endothelin receptor antagonists, calcium channel antagonists, fasudil, and tirilazad were effective whereas magnesium was not. Only evaluation of vasospasm >3 days after SAH was independently associated with successful translation. We conclude that reduction of vasospasm is effective in animals and humans and that evaluation of vasospasm >3 days after SAH may be preferable for preclinical models.

scholarly journals Effect of Endothelin Receptor Antagonists on Clinically Relevant Outcomes after Experimental Subarachnoid Hemorrhage: A Systematic Review and Meta-Analysis

2015 ◽  
Vol 35 (7) ◽  
pp. 1085-1089 ◽  
Author(s):  
Kamil G Laban ◽  
Mervyn DI Vergouwen ◽  
Rick M Dijkhuizen ◽  
Emily S Sena ◽  
Malcolm R Macleod ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Subarachnoid Hemorrhage ◽  
Animal Studies ◽  
Meta Analysis ◽  
Case Fatality ◽  
Endothelin Receptor Antagonists ◽  
Endothelin Receptor

In clinical trials, endothelin receptor antagonists (ETRAs) reduced vasospasm but did not improve functional outcome after subarachnoid hemorrhage (SAH). We assessed the effects of treatment with ETRAs on clinically relevant outcomes in animal studies modelling SAH by performing a systematic review of the literature for controlled animal studies of ETRAs for the treatment of SAH. Primary outcomes were neurobehavioral outcomes and case fatality. Secondary outcomes were cerebral vasospasm and cerebral blood flow. Summary estimates were calculated using normalized mean difference random effects meta-analysis. We included 27 studies (55 experiments, 639 animals). Neurobehavioral scores were reported in none of the experiments, and case fatality in 8 (15%). Treatment with ETRAs was associated with a pooled odds ratio for case fatality of 0.61 (95% confidence interval (CI), 0.27 to 1.39); a 54% increase (95% CI, 39 to 69) in cerebral arterial diameter; and a 93% increase (95% CI, 58 to 129) in cerebral blood flow. We conclude that there is no evidence from animal studies that treatment with an ETRA improves clinically relevant outcomes after SAH. The reduction in cerebral vasospasm observed in animal studies is consistent with that observed in clinical trials, an effect that is not associated with better functional outcome in patients.

scholarly journals Systematic review and stratified meta-analysis of the efficacy of carnosine in animal models of ischemic stroke

2016 ◽  
Vol 36 (10) ◽  
pp. 1686-1694 ◽  
Author(s):  
Charles K Davis ◽  
Peter J Laud ◽  
Zsanett Bahor ◽  
GK Rajanikant ◽  
Arshad Majid
Keyword(s):  
Systematic Review ◽  
Ischemic Stroke ◽  
Methodological Quality ◽  
Infarct Volume ◽  
Weighted Mean Difference ◽  
Meta Analysis ◽  
Young Male ◽  
In Vivo Models

Carnosine is a naturally occurring pleotropic dipeptide which influences multiple deleterious mechanisms that are activated during stroke. Numerous published studies have reported that carnosine has robust efficacy in ischemic stroke models. To further evaluate these data, we have conducted a systematic review and meta-analysis of published studies. We included publications describing in vivo models of ischemic stroke where the neuroprotective efficacy of carnosine was being evaluated through the reporting of infarct volume and/or neurological score as outcomes. Overall efficacy was evaluated using weighted mean difference random effects meta-analysis. We also evaluated for study quality and publication bias. We identified eight publications that met our inclusion criteria describing a total of 29 comparisons and 454 animals. Overall methodological quality of studies was moderate (median = 4/9). Carnosine reduced infarct volume by 29.4% (95% confidence interval (CI), 24.0% to 34.9%; 29 comparisons). A clear dose-response effect was observed, and efficacy was reduced when carnosine was administered more than 6 h after ischemia. Our findings suggest that carnosine administered before or after the onset of ischemia exhibits robust efficacy in experimental ischemic stroke. However, the methodological quality of some of the studies was low and testing occurred only in healthy young male animals.

scholarly journals Can Lycopene Impact the Androgen Axis in Prostate Cancer?: A Systematic Review of Cell Culture and Animal Studies

Nutrients ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 633 ◽  
Author(s):  
Catherine Applegate ◽  
Joe Rowles ◽  
John Erdman
Keyword(s):  
Prostate Cancer ◽  
Systematic Review ◽  
Animal Studies ◽  
Tumor Regression ◽  
Meta Analysis ◽  
Normal Prostate ◽  
First Line Therapy ◽  
Normal Prostate Tissue

First-line therapy for advanced or metastatic prostate cancer (PCa) involves the removal of tumor-promoting androgens by androgen deprivation therapy (ADT), resulting in transient tumor regression. Recurrent disease is attributed to tumor adaptation to survive, despite lower circulating androgen concentrations, making the blockage of downstream androgen signaling a chemotherapeutic goal for PCa. Dietary intake of tomato and its predominant carotenoid, lycopene, reduce the risk for PCa, and preclinical studies have shown promising results that tomato and lycopene can inhibit androgen signaling in normal prostate tissue. The goal of this systematic review was to evaluate whether mechanistic evidence exists to support the hypothesis that tomato or lycopene interact with the androgen axis in PCa. Eighteen studies (n = 5 in vivo; n = 13 in vitro) were included in the final review. A formal meta-analysis was not feasible due to variability of the data; however, the overall estimated directions of effect for the compared studies were visually represented by albatross plots. All studies demonstrated either null or, more commonly, inhibitory effects of tomato or lycopene treatment on androgen-related outcomes. Strong mechanistic evidence was unable to be ascertained, but tomato and lycopene treatment appears to down-regulate androgen metabolism and signaling in PCa.

scholarly journals Evaluation of the efficacy of casein phosphopeptide-amorphous calcium phosphate on remineralization of white spot lesions in vivo and in vitro: A systematic review and meta-analysis

2019 ◽  
Author(s):  
Xuandong Lin ◽  
Xueling Ma ◽  
Tengfei Zhong ◽  
Fangfang Xie
Keyword(s):  
Systematic Review ◽  
Methodological Quality ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
White Spot Lesions ◽  
Average Surface Roughness ◽  
Average Surface ◽  
Casein Phosphopeptide

Abstract Abstract Background: This systematic review with meta-analyses sought to answer whether casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) provided a remineralizing benefit superior to that of nonintervention or placebo. Methods: The Cochrane databases, PubMed, EmBase, and Ovid up to May, 2019, were scanned, with no restrictions. Study information extraction and methodological quality assessments were accomplished independently by two reviewers. The “Criteria for judging risk of bias in the ‘Risk of bias’ assessment tool” was used for methodological quality assessment. The continuous data was analyzed by mean difference (MD) or standardized mean difference (SMD) with a 95% confidence interval (CI). Review Manager 5.3 was used for statistical analysis. Outcome variables include quantitative light-induced fluorescence in vivo, average surface roughness and surface microhardness in vitro. Results: There were significant differences in the quantitative light-induced fluorescence (SMD = −0.43, 95% CI: [−0.79, −0.07], P = 0.02), average surface roughness (SMD = −8.21, 95% CI: [−10.37, −6.04], P < 0.01), Vickers microhardness (SMD = 1.19, 95% CI: [0.72, 1.66], P < 0.01), and Knoop microhardness (SMD = 3.52, 95% CI: [2.68, 4.36], P < 0.01) between the CPP-ACP and control groups or baseline. Conclusion: Within the limitations of this meta-analysis, CPP-ACP exhibited excellent remineralization effects evaluated in vivo and in vitro, indicating outstanding restoration of form, aesthetics, and function in treating white spot lesions.

scholarly journals Conjugates for use in peptide therapeutics: a systematic review and meta-analysis

2021 ◽  
Author(s):  
Ashan Wijesinghe ◽  
Sarika Kumari ◽  
Valerie Booth
Keyword(s):  
Systematic Review ◽  
Half Life ◽  
Animal Studies ◽  
Meta Analysis ◽  
Unbiased Manner ◽  
Recombinant Peptides ◽  
Therapeutic Peptides ◽  
Major Bottleneck ◽  
Significant Extension

While peptides can be excellent therapeutics for several conditions, their limited in vivo half-lives have been a major bottleneck in the development of therapeutic peptides. Conjugating the peptide to an inert chemical moiety is a strategy that has repeatedly proven to be successful in extending the half-life of some therapeutics. This systematic review and meta-analysis was conducted to examine the available literature and assess it in an unbiased manner to determine which conjugates, both biological and synthetic, provide the greatest increase in therapeutic peptide half-life. Systematic searches run on PubMed, Scopus and SciFinder databases resulted in 845 studies pertaining to the topic, 16 of these were included in this review after assessment against pre-specified inclusion criteria registered on PROSPERO (# CRD42020222579 ). The most common reasons for exclusion were non-IV administration and large peptide size. Of the 16 studies that were included, a diverse suite of conjugates that increased half-life from 0.1 h to 33.57 h was identified. Amongst these peptides, the largest increase in half-life was seen when conjugated with glycosaminoglycans. A meta-analysis of studies that contained fatty acid conjugates indicated that acylation contributed to a statistically significant extension of half-life. Additionally, another meta-analysis followed by a sensitivity analysis suggested that conjugation with specifically engineered recombinant peptides might contribute to a more efficient extension of peptide half-life as compared to PEGylation. Moreover, we confirmed that while polyethylene glycol is a good synthetic conjugate, its chain length likely has an impact on its effectiveness in extending half-life. Furthermore, we found that most animal studies do not include as much detail when reporting findings as compared to human studies. Inclusion of additional experimental detail on aspects such as independent assessment and randomization may be an easily accomplished strategy to drive more conjugated peptides towards clinical studies.

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