The Potential Role of Previous Physical Exercise Program to Reduce Seizure Susceptibility: A Systematic Review and Meta-Analysis of Animal Studies

Background: Clinical and pre-clinical studies indicate a reduction in seizure frequency as well as a decrease in susceptibility to subsequently evoked seizures after physical exercise programs. In contrast to the influence of exercise after epilepsy previously established, various studies have been conducted attempting to investigate whether physical activity reduces brain susceptibility to seizures or prevents epilepsy. We report a systematic review and meta-analysis of different animal models that addressed the impact of previous physical exercise programs to reduce seizure susceptibility.Methods: We included animal model (rats and mice) studies before brain insult that reported physical exercise programs compared with other interventions (sham, control, or naïve). We excluded studies that investigated animal models after brain insult, associated with supplement nutrition or drugs, that did not address epilepsy or seizure susceptibility, ex vivo studies, in vitro studies, studies in humans, or in silico studies. Electronic searches were performed in the MEDLINE (PubMed), Web of Science (WOS), Scopus, PsycINFO, Scientific Electronic Library Online (SciELO) databases, and gray literature, without restrictions to the year or language of publication. We used SYRCLE's risk of bias tool and CAMARADES checklist for study quality. We performed a synthesis of results for different types of exercise and susceptibility to seizures by random-effects meta-analysis.Results: Fifteen studies were included in the final analysis (543 animals), 13 of them used male animals, and Wistar rats were the most commonly studied species used in the studies (355 animals). The chemoconvulsants used in the selected studies were pentylenetetrazol, penicillin, kainic acid, pilocarpine, and homocysteine. We assessed the impact of study design characteristics and the reporting of mitigations to reduce the risk of bias. We calculated a standardized mean difference effect size for each comparison and performed a random-effects meta-analysis. The meta-analysis included behavioral analysis (latency to seizure onset, n = 6 and intensity of motor signals, n = 3) and electrophysiological analysis (spikes/min, n = 4, and amplitude, n = 6). The overall effect size observed in physical exercise compared to controls for latency to seizure onset was −130.98 [95% CI: −203.47, −58.49] (seconds) and the intensity of motor signals was −0.40 [95% CI: −1.19, 0.40] (on a scale from 0 to 5). The largest effects were observed in electrophysiological analysis for spikes/min with −26.96 [95% CI: −39.56, −14.36], and for spike amplitude (μV) with −282.64 [95% CI: −466.81, −98.47].Discussion:Limitations of evidence. A higher number of animal models should be employed for analyzing the influence of exerciseon seizure susceptibility. The high heterogeneity in our meta-analysis is attributable to various factors, including the number of animals used in each study and the limited number of similar studies. Interpretation. Studies selected in this systematic review and meta-analysis suggest that previous physical exercise programs can reduce some of the main features related to seizure susceptibility [latency seizure onset, spikes/min, and spike amplitude (μV)] induced by the administration of different chemoconvulsants.Systematic Review Registration: PROSPERO, identifier CRD42021251949; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=251949.

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Animal models of chemotherapy-induced peripheral neuropathy: a machine-assisted systematic review and meta-analysis

10.1101/293480 ◽

2018 ◽

Cited By ~ 2

Author(s):

Gillian L. Currie ◽

Helena N. Angel-Scott ◽

Lesley Colvin ◽

Fala Cramond ◽

Kaitlyn Hair ◽

...

Keyword(s):

Systematic Review ◽

Peripheral Neuropathy ◽

Experimental Design ◽

Animal Models ◽

Study Design ◽

Outcome Measure ◽

Meta Analysis ◽

Risk Of Bias ◽

Behavioural Tests ◽

The Impact

AbstractBackground and aimsChemotherapy-induced peripheral neuropathy (CIPN) can be a severely disabling side-effect of commonly used cancer chemotherapeutics, requiring cessation or dose reduction, impacting on survival and quality of life. Our aim was to conduct a systematic review and meta-analysis of research using animal models of CIPN to inform robust experimental design.MethodsWe systematically searched 5 online databases (PubMed, Web of Science, Citation Index, Biosis Previews and Embase (September 2012) to identify publications reporting in vivo CIPN modelling. Due to the number of publications and high accrual rate of new studies, we ran an updated search November 2015, using machine-learning and text mining to identify relevant studies.All data were abstracted by two independent reviewers. For each comparison we calculated a standardised mean difference effect size then combined effects in a random effects meta- analysis. The impact of study design factors and reporting of measures to reduce the risk of bias was assessed. We ran power analysis for the most commonly reported behavioural tests.Results341 publications were included. The majority (84%) of studies reported using male animals to model CIPN; the most commonly reported strain was Sprague Dawley rat. In modelling experiments, Vincristine was associated with the greatest increase in pain-related behaviour (−3.22 SD [−3.88; −2.56], n=152, p=0). The most commonly reported outcome measure was evoked limb withdrawal to mechanical monofilaments. Pain-related complex behaviours were rarely reported. The number of animals required to obtain 80% power with a significance level of 0.05 varied substantially across behavioural tests. Overall, studies were at moderate risk of bias, with modest reporting of measures to reduce the risk of bias.ConclusionsHere we provide a comprehensive summary of the field of animal models of CIPN and inform robust experimental design by highlighting measures to increase the internal and external validity of studies using animal models of CIPN. Power calculations and other factors, such as clinical relevance, should inform the choice of outcome measure in study design.

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The impact of physical exercise on the fatigue symptoms in patients with multiple sclerosis: a systematic review and meta-analysis

BMC Neurology ◽

10.1186/s12883-020-01654-y ◽

2020 ◽

Vol 20 (1) ◽

Cited By ~ 3

Author(s):

Nazanin Razazian ◽

Mohsen Kazeminia ◽

Hossein Moayedi ◽

Alireza Daneshkhah ◽

Shamarina Shohaimi ◽

...

Keyword(s):

Multiple Sclerosis ◽

Systematic Review ◽

Physical Exercise ◽

Meta Analysis ◽

The Impact

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Effect of dose administration aids on adherence to self-administered medications: a systematic review protocol

BMJ Open ◽

10.1136/bmjopen-2019-030536 ◽

2019 ◽

Vol 9 (10) ◽

pp. e030536

Author(s):

Kanika Chaudhri ◽

Madeleine Kearney ◽

Richard O Day ◽

Anthony Rodgers ◽

Emily Atkins

Keyword(s):

Systematic Review ◽

Health Outcomes ◽

Meta Analysis ◽

Study Participant ◽

Risk Of Bias ◽

Cochrane Library ◽

Secondary Outcome ◽

Dose Administration ◽

Common Solution ◽

The Impact

IntroductionForgetting to take a medication is the most common reason for non-adherence to self-administered medication. Dose administration aids (DAAs) are a simple and common solution to improve unintentional non-adherence for oral tablets. DAAs can be in the form of compartmentalised pill boxes, automated medication dispensing devices, blister packs and sachets packets. This protocol aims to outline the methods that will be used in a systematic review of the current literature to assess the impact of DAAs on adherence to medications and health outcomes.Methods and analysisRandomised controlled trials will be identified through electronic searches in databases including EMBASE, MEDLINE, CINAHL and the Cochrane Library, from the beginning of each database until January 2020. Two reviewers will independently screen studies and extract data using the standardised forms. Data extracted will include general study information, characteristics of the study, participant characteristics, intervention characteristics and outcomes. Primary outcome is to assess the effects of DAAs on medication adherence. Secondary outcome is to evaluate the changes in health outcomes. The risk of bias will be ascertained by two reviewers in parallel using The Cochrane Risk of Bias Tool. A meta-analysis will be performed if data are homogenous.Ethics and disseminationEthics approval will not be required for this study. The results of the review described within this protocol will be disseminated through publication in a peer-reviewed journal and relevant conference presentations.PROSPERO registration numberCRD42018096087

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Considering the methodological limitations in the evidence base of antidepressants for depression: a reanalysis of a network meta-analysis

BMJ Open ◽

10.1136/bmjopen-2018-024886 ◽

2019 ◽

Vol 9 (6) ◽

pp. e024886 ◽

Cited By ~ 24

Author(s):

Klaus Munkholm ◽

Asger Sand Paludan-Müller ◽

Kim Boesen

Keyword(s):

Systematic Review ◽

Clinical Study ◽

Effect Size ◽

Meta Analysis ◽

Evidence Base ◽

Risk Of Bias ◽

Depression Symptom ◽

Meta Analyses ◽

The Impact ◽

Clinical Study Reports

ObjectivesTo investigate whether the conclusion of a recent systematic review and network meta-analysis (Ciprianiet al) that antidepressants are more efficacious than placebo for adult depression was supported by the evidence.DesignReanalysis of a systematic review, with meta-analyses.Data sources522 trials (116 477 participants) as reported in the systematic review by Ciprianiet aland clinical study reports for 19 of these trials.AnalysisWe used the Cochrane Handbook’s risk of bias tool and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to evaluate the risk of bias and the certainty of evidence, respectively. The impact of several study characteristics and publication status was estimated using pairwise subgroup meta-analyses.ResultsSeveral methodological limitations in the evidence base of antidepressants were either unrecognised or underestimated in the systematic review by Ciprianiet al. The effect size for antidepressants versus placebo on investigator-rated depression symptom scales was higher in trials with a ‘placebo run-in’ study design compared with trials without a placebo run-in design (p=0.05). The effect size of antidepressants was higher in published trials compared with unpublished trials (p<0.0001). The outcome data reported by Ciprianiet aldiffered from the clinical study reports in 12 (63%) of 19 trials. The certainty of the evidence for the placebo-controlled comparisons should be very low according to GRADE due to a high risk of bias, indirectness of the evidence and publication bias. The mean difference between antidepressants and placebo on the 17-item Hamilton depression rating scale (range 0–52 points) was 1.97 points (95% CI 1.74 to 2.21).ConclusionsThe evidence does not support definitive conclusions regarding the benefits of antidepressants for depression in adults. It is unclear whether antidepressants are more efficacious than placebo.

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Drug treatments for covid-19: living systematic review and network meta-analysis

BMJ ◽

10.1136/bmj.m2980 ◽

2020 ◽

pp. m2980 ◽

Cited By ~ 49

Author(s):

Reed AC Siemieniuk ◽

Jessica J Bartoszko ◽

Long Ge ◽

Dena Zeraatkar ◽

Ariel Izcovich ◽

...

Keyword(s):

Systematic Review ◽

Mechanical Ventilation ◽

Standard Care ◽

Interferon Beta ◽

Meta Analysis ◽

Risk Of Bias ◽

Drug Discontinuation ◽

Duration Of Symptoms ◽

Risk Of Death ◽

The Impact

Abstract Objective To compare the effects of treatments for coronavirus disease 2019 (covid-19). Design Living systematic review and network meta-analysis. Data sources WHO covid-19 database, a comprehensive multilingual source of global covid-19 literature, up to 3 December 2020 and six additional Chinese databases up to 12 November 2020. Study selection Randomised clinical trials in which people with suspected, probable, or confirmed covid-19 were randomised to drug treatment or to standard care or placebo. Pairs of reviewers independently screened potentially eligible articles. Methods After duplicate data abstraction, a bayesian network meta-analysis was conducted. Risk of bias of the included studies was assessed using a modification of the Cochrane risk of bias 2.0 tool, and the certainty of the evidence using the grading of recommendations assessment, development and evaluation (GRADE) approach. For each outcome, interventions were classified in groups from the most to the least beneficial or harmful following GRADE guidance. Results 85 trials enrolling 41 669 patients met inclusion criteria as of 21 October 2020; 50 (58.8%) trials and 25 081 (60.2%) patients are new from the previous iteration; 43 (50.6%) trials evaluating treatments with at least 100 patients or 20 events met the threshold for inclusion in the analyses. Compared with standard care, corticosteroids probably reduce death (risk difference 17 fewer per 1000 patients, 95% credible interval 34 fewer to 1 more, moderate certainty), mechanical ventilation (29 fewer per 1000 patients, 54 fewer to 1 more, moderate certainty), and days free from mechanical ventilation (2.6 fewer, 0.2 fewer to 5.0 fewer, moderate certainty). The impact of remdesivir on mortality, mechanical ventilation, length of hospital stay, and duration of symptoms is uncertain, but it probably does not substantially increase adverse effects leading to drug discontinuation (0 more per 1000, 9 fewer to 40 more, moderate certainty). Azithromycin, hydroxychloroquine, lopinavir/ritonavir, interferon-beta, and tocilizumab may not reduce risk of death or have an effect on any other patient-important outcome. The certainty in effects for all other interventions was low or very low. Conclusion Corticosteroids probably reduce mortality and mechanical ventilation in patients with covid-19 compared with standard care, whereas azithromycin, hydroxychloroquine, interferon-beta, and tocilizumab may not reduce either. Whether or not remdesivir confers any patient-important benefit remains uncertain. Systematic review registration This review was not registered. The protocol is included as a supplement. Readers’ note This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication. This version is the second update of the original article published on 30 July 2020 ( BMJ 2020;370:m2980), and previous versions can be found as data supplements. When citing this paper please consider adding the version number and date of access for clarity.

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Effect of Acupuncture on Polycystic Ovary Syndrome in Animal Models: Study Protocol for a Systematic Review and Meta-Analysis

10.21203/rs.3.rs-144670/v1 ◽

2021 ◽

Author(s):

Jinjin Gao ◽

Wei Li ◽

Yangyang Li ◽

Yan Li

Keyword(s):

Systematic Review ◽

Animal Models ◽

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Meta Analysis ◽

Risk Of Bias ◽

Reproductive Age ◽

Model Assessment ◽

Ovary Syndrome ◽

Complementary And Alternative Therapy

Abstract Background: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders among women of reproductive age. As a widely used complementary and alternative therapy, acupuncture is increasingly used to treat PCOS. However, the effect of acupuncture in treating PCOS is uncertain and the mechanisms are unclear. This systematic review aims to determine the efficacy of acupuncture on PCOS in animal preclinical models.Methods: We will search the following databases: PubMed, Web of Science, China National Knowledge Infrastructure and Chinese Science and Technology Periodical Database. We will only include animal experiments of acupuncture in treating PCOS. The primary outcome will be homeostatic model assessment- insulin resistance. The risk of bias will be assessed using the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) risk of bias tool. Confidence in the cumulative evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. All meta-analyses will be conducted using Review Manager 5.4. Discussion: To the best of our knowledge, the use of acupuncture in treating PCOS has not yet been systematically reviewed in animal models. The evidence generated from this systematic review and meta-analysis could benefit future researches. Systematic review registration: OSF (Registration DOI: 10.17605/OSF.IO/FNM37)

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The Impact of Histopathological Features on the Prognosis of Oral Squamous Cell Carcinoma: A Comprehensive Review and Meta-Analysis

Frontiers in Oncology ◽

10.3389/fonc.2021.784924 ◽

2021 ◽

Vol 11 ◽

Author(s):

Eder da Silva Dolens ◽

Mauricio Rocha Dourado ◽

Alhadi Almangush ◽

Tuula A. Salo ◽

Clarissa Araujo Gurgel Rocha ◽

...

Keyword(s):

Systematic Review ◽

Squamous Cell Carcinoma ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Meta Analysis ◽

Risk Of Bias ◽

Histopathological Features ◽

Increased Risk ◽

The Impact

ObjectiveOver many decades, studies on histopathological features have not only presented high-level evidence of contribution for treatment directions and prognosis of oral squamous cell carcinoma (OSCC) but also provided inconsistencies, making clinical application difficult. The 8th TNM staging system of OSCC has acknowledged the importance of some histopathological features, by incorporating depth of invasion (DOI) to T category and extranodal extension (ENE) to N category. The aim of this systematic review with meta-analysis is to determine the most clinically relevant histopathological features for risk assessment and treatment planning of OSCC and to elucidate gaps in the literature.MethodsA systematic review was conducted using PRISMA guidelines, and the eligibility criteria were based on population, exposure, comparison, outcome, and study type (PECOS). PubMed, Cochrane, Scopus, and Web of Science were searched for articles exploring the impact of histopathological features on OSCC outcomes with Cox multivariate analysis. Pooled data were subjected to an inverse variance method with random effects or fixed effect model, and the risk of bias was evaluated using quality in prognosis studies (QUIPS). Quality of evidence was assessed with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria.ResultsThe study included 172 articles published from 1999 to 2021. Meta-analyses confirmed the prognostic potential of DOI, ENE, perineural invasion, lymphovascular invasion, and involvement of the surgical margins and brought promising results for the association of bone invasion, tumor thickness, and pattern of invasion with increased risk for poor survival. Although with a small number of studies, the results also revealed a clinical significance of tumor budding and tumor-stroma ratio on predicted survival of patients with OSCC. Most of the studies were considered with low or moderate risk of bias, and the certainty in evidence varied from very low to high.ConclusionOur results confirm the potential prognostic usefulness of many histopathological features and highlight the promising results of others; however, further studies are advised to apply consistent designs, filling in the literature gaps to the pertinence of histopathological markers for OSCC prognosis.Systematic Review RegistrationInternational Prospective Register of Systematic Reviews (PROSPERO), identifier CRD42020219630.

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Prevalence of multimorbid degenerative lumbar spinal stenosis with knee and/or hip osteoarthritis: protocol for a systematic review and meta-analysis

10.21203/rs.3.rs-20819/v2 ◽

2020 ◽

Author(s):

James J. Young ◽

Jan Hartvigsen ◽

Rikke K. Jensen ◽

Ewa M. Roos ◽

Carlo Ammendolia ◽

...

Keyword(s):

Systematic Review ◽

Data Extraction ◽

Meta Analysis ◽

Hip Osteoarthritis ◽

Healthcare Setting ◽

Risk Of Bias ◽

Sample Population ◽

Case Definitions ◽

Prevalence Estimates ◽

The Impact

Abstract Background: Lumbar spinal stenosis (LSS) and knee and hip osteoarthritis (OA) are prevalent conditions in the aging population and published literature suggests they share many symptoms and often are present at the same time in patients. However, no prevalence estimates of multimorbid LSS and knee and/or hip OA are currently available. The primary objective of this systematic review is therefore to estimate the prevalence of multimorbid LSS with knee and/or hip OA using radiological, clinical, and combined case definitions. Methods: This systematic review protocol has been designed according to the guidelines from the Cochrane Collaboration and are reported according the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols. A comprehensive search will be performed in the following databases: MEDLINE, EMBASE, CENTRAL, and CINAHL. Forward citation tracking will be performed in Web of Science. No restriction for publication data and language will be applied in the literature search, but only articles in English will be included. The search strategy will include the following domains: LSS, knee OA, and hip OA. Retrieved citations will be screened by two authors independently. Disagreements will be discussed until consensus, and a third reviewer will be consulted if consensus cannot be reached. Data extraction and assessment of methodological quality will be done by two authors independently, using a standardized data extraction form and a modified Risk of Bias Tool for Prevalence studies. Meta-analysis estimating prevalence with 95% CI will be performed using a random effects model. Meta-regression analyses will be performed to investigate the impact of the following covariates: LSS clinical presentations, sample population, healthcare setting, risk of bias, and other patient characteristics on prevalence estimates for multimorbid LSS and knee and/or hip OA.Discussion: The results of this review will provide the first estimates of the prevalence of multimorbid LSS and hip and knee OA based on various case definitions. The impact of covariates such as LSS clinical presentations, sample population, healthcare setting, risk of bias, and patient characteristics on prevalence estimates will also be presented. Systematic review registration: Submitted to PROSPERO, awaiting registration

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The efficacy and safety of Momordica charantia L. in animal models of type 2 diabetes mellitus; A systematic review and meta-analysis

10.1101/681494 ◽

2019 ◽

Cited By ~ 1

Author(s):

Emanuel L. Peter ◽

Prakash B. Nagendrappa ◽

Anita Kaligirwa ◽

Patrick Engeu Ogwang ◽

Crispin Duncan Sesaazi

Keyword(s):

Diabetes Mellitus ◽

Systematic Review ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Animal Models ◽

Publication Bias ◽

Methodological Quality ◽

Meta Analysis ◽

Risk Of Bias

AbstractBackgroundMomordica charantia L. (Cucurbitaceae) has been used to control hyperglycemia in people with type 2 diabetes mellitus in Asia, South America, and Africa for decades. However, a meta-analysis of clinical trials confirmed very low-quality evidence of its efficacy. To potentially increase the certainty of evidence, we evaluated the effect of M. charantia L. in comparison with vehicle on glycemic control in animal models of type 2 diabetes mellitus.MethodsReview authors searched in MEDLINE, Web of Science, Scopus, and CINAHL databases without language restriction through April 2019. Two authors independently evaluated full texts, assessed the risk of bias, and extracted data. We analyzed the influence of study design and evidence of publication bias.ResultsThe review included 66 studies involving 1861 animals. They had a follow up between 7 and 90 days. Majority 29 (43.9%) used Wistar albino rats, and 37 (56.1%) used male animals. Thirty-two (48%) used an aqueous extract of fresh fruits. M. charantia L. reduced fasting plasma glucose (FPG) and glycosylated hemoglobin A1c in comparison to vehicle control (42 studies, 815 animals; SMD, −6.86 [95% CI; −7.95, −5.77], 3 studies, 59 animals; SMD; −7.76 [95%CI; −12.50, −3.01]) respectively. Magnitude of FPG was large in Wistar albino rat subgroup; SMD; −10.29, [95%CI; −12.55, −8.03]. Publication bias changed FPG to non-significant −2.46 SMD, [95%CI; - 5.10, 0.17]. We downgraded the evidence to moderate quality due to poor methodological quality, high risk of bias, unexplained heterogeneity, suspected publication bias, and lack of standardized dose.ConclusionM. charantia L. lowers elevated plasma glucose level in type 2 diabetes mellitus animal models. Publication bias and poor methodological quality call for future researches to focus on standardizing dose with chemical markers and provide measures to improve preclinical type 2 diabetes mellitus studies.Systematic review registration CRD42019119181

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The impact of eHealth group interventions on the mental, behavioural, and physical health of adults: A systematic review protocol

10.21203/rs.3.rs-37015/v2 ◽

2020 ◽

Cited By ~ 1

Author(s):

Cheryl L Currie ◽

Richard Larouche ◽

M. L. Voss ◽

Erin K. Higa ◽

Rae Spiwak ◽

...

Keyword(s):

Mental Health ◽

Systematic Review ◽

Physical Health ◽

Meta Analysis ◽

Primary Objective ◽

Risk Of Bias ◽

Community Dwelling ◽

Controlled Trials ◽

Sex And Gender ◽

The Impact

Abstract Background: COVID-19 has resulted in an increased demand for mental health services globally. There is emerging evidence for the efficacy for group eHealth interventions that support population-based mental health and wellbeing, but a systematic review is lacking. The primary objective of this systematic review is to summarize the evidence for eHealth group counselling and coaching programs for adults. A second objective is to assess, within studies selected for our primary objective, the impact of programs that encourage PA on outcomes compared to those that do not.Methods and Design: Randomized controlled trials that assess the impact of eHealth group counselling or coaching programs on mental health, health behaviour, or physical health conditions or concerns among community dwelling adults will be searched in MEDLINE, PsycInfo, CINHAL, and the Central Register of Controlled Trials. The review will be structured using PRISMA guidelines. Studies will be synthesized using the Cochrane Handbook and Synthesis Without Meta-Analysis (SWiM) reporting guideline. Quality will be evaluated using GRADE. Risk of bias will be assessed using the Cochrane Risk of Bias tool with higher quality studies prioritized when drawing conclusions. The role of sex and gender will be considered as well as possible gender biases at all stages of the review.Discussion: This review will examine the effectiveness of eHealth counselling and coaching programs delivered to adults in a group format. Findings will inform the decisions of governments, communities, and health care organizations responding to the COVID-19 pandemic in Canada. Systematic review registration: The protocol has been registered at the International Prospective Register of Systematic Reviews (PROSPERO: CRD42020187551).

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