Profiling cerebrovascular function in migraine: A systematic review and meta-analysis

Previous studies have investigated whether migraine is a circulatory disorder, as migraineurs are at heightened risk of cerebrovascular disease. However, in most cases, systemic vascular function was evaluated, which may not reflect abnormalities in the cerebral circulation. Therefore, we aimed to determine whether cerebrovascular function differs between migraineurs and controls. A systematic literature search was conducted across three electronic databases to search for studies that compared cerebrovascular function in migraineurs to controls. Where applicable, meta-analyses were used to determine standardised mean differences (SMD) between migraineurs and controls. Seventy articles were identified, 40 of which contained quantitative data. Meta-analyses showed pulsatility index (PI) was higher (SMD = 0.23; 95%CI = 0.05 to 0.42, P = 0.01) and cerebrovascular responsiveness (CVR) to hypercapnia was lower (SMD=−0.34; 95%CI=−0.67 to −0.01, P = 0.04) in the posterior circulation of migraineurs, particularly those without aura. The meta-analyses also indicated that migraineurs have higher resting mean blood flow velocity in both anterior (SMD = 0.14; 95%CI = 0.05 to 0.23, P = 0.003) and posterior circulations (SMD = 0.20; 95%CI = 0.05 to 0.34, P = 0.007). Compared to healthy controls, migraineurs have altered cerebrovascular function, evidenced by elevated PI (representing arterial stiffness) and impaired CVR to hypercapnia (representing cerebral vasodilator function). Future studies should investigate whether improvement of cerebrovascular function is able to alleviate migraine.

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Leishmanicidal effects of resveratrol and its derivatives: a systematic review and meta-Analysis

10.21203/rs.3.rs-25274/v1 ◽

2020 ◽

Author(s):

Nasrin Amiri Dashatan ◽

Marzieh Ashrafmansouri ◽

Mehdi Koushki ◽

Nayebali Ahmadi

Keyword(s):

Systematic Review ◽

Publication Bias ◽

Data Extraction ◽

Meta Analysis ◽

Sensitivity Analyses ◽

Protective Effects ◽

Random Effects Models ◽

Important Health ◽

Mean Differences ◽

Meta Analyses

Abstract Background Leishmaniasis is one of the most important health problems worldwide. The evidence has suggested that resveratrol and its derivatives have anti-leishmanial effects; however, the results are inconsistent and inconclusive. The aim of this study was to assess the effect of resveratrol and its derivatives on the Leishmania viability through a systematic review and meta-analysis of available relevant studies. Methods The electronic databases PubMed, ScienceDirect, Embase, Web of Science and Scopus were queried between October 2000 and April 2020 using a comprehensive search strategy. The eligible articles selected and data extraction conducted by two reviewers. Mean differences of IC50 (concentration leading to reduction of 50% of Leishmania) for each outcome was calculated using random-effects models. Sensitivity analyses and prespecified subgroup were conducted to evaluate potential heterogeneity and the stability of the pooled results. Publication bias was evaluated using the Egger’s and Begg’s tests. We also followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines for this review. Results Ten studies were included in the meta-analysis. We observed that RSV and its derivatives had significant reducing effects on Leishmania viability in promastigote [24.02 µg/ml; (95% CI 17.1, 30.8); P < 0.05; I2 = 99.8%; P heterogeneity = 0.00] and amastigote [18.3 µg/ml; (95% CI 13.5, 23.2); P < 0.05; I2 = 99.6%; P heterogeneity = 0.00] stages of Leishmania. A significant publication bias was observed in the meta-analysis. Sensitivity analyses showed a similar effect size while reducing the heterogeneity. Subgroup analysis indicated that the pooled effects of leishmanicidal of resveratrol and its derivatives were affected by type of stilbenes and Leishmania species. Conclusions Our findings clearly suggest that the strategies for the treatment of leishmaniasis should be focused on natural products such as RSV and its derivatives. Further study is needed to identify the mechanisms mediating this protective effects of RSV and its derivatives in leishmaniasis.

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Effects of the endocrine disruptor vinclozolin in male reproduction: a systematic review and meta-analysis†

Biology of Reproduction ◽

10.1093/biolre/ioab018 ◽

2021 ◽

Author(s):

Mariana Feijó ◽

Roberta V L Martins ◽

Sílvia Socorro ◽

Luísa Pereira ◽

Sara Correia

Keyword(s):

Systematic Review ◽

Publication Bias ◽

Meta Analysis ◽

Endocrine Disrupting Chemicals ◽

Reproductive Organs ◽

Male Reproduction ◽

Mean Differences ◽

Trim And Fill ◽

Meta Analyses ◽

Q Statistic

Abstract Endocrine-disrupting chemicals have become an issue of scientific and public discussion. Vinclozolin (VNZ) is a fungicide that competitively antagonizes the binding of natural androgens to their receptor, disturbing the function of tissues that are sensitive to these hormones, as is the case of the male reproductive organs. A systematic review with meta-analyses of rodent studies was conducted to answer the following question: Does exposure to VNZ affect sperm parameters and testicular/epididymal weight? The methodology was prespecified according to the Cochrane Handbook for Systematic Reviews and PRISMA recommendations. Sixteen articles met the inclusion criteria, comprising a total of 1189 animals. The risk of publication bias was assessed using the Trim and Fill adjustment, funnel plot, and Egger regression test. Heterogeneity and inconsistency across the findings were tested using the Q-statistic and I2 of Higgins, respectively. Sensitivity was also analyzed. Statistical analysis was performed on Comprehensive Meta-Analysis software (Version 2.0), using random models and weighted mean differences along with a 95% confidence interval. Sperm motility, counts, daily sperm production (evidence of publication bias), and epididymis weight were decreased in VNZ-treated animals. Exposure length and dose, as well as the time point of exposure, influenced the obtained results. Despite the moderate/high heterogeneity observed, the sensitivity analysis overall demonstrated the robustness of the findings. The quality scores of the included studies were superior to 4 in a total of 9, then classified as good. The obtained data corroborate the capability of VNZ exposure to disrupt spermatogenic output and compromise male fertility.

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Comparing the Effects of Docosahexaenoic and Eicosapentaenoic Acids on Inflammation Markers Using Pairwise and Network Meta-Analyses of Randomized Controlled Trials

Advances in Nutrition ◽

10.1093/advances/nmaa086 ◽

2020 ◽

Author(s):

Cécile Vors ◽

Janie Allaire ◽

Sonia Blanco Mejia ◽

Tauseef A Khan ◽

John L Sievenpiper ◽

...

Keyword(s):

Randomized Clinical Trials ◽

Meta Analysis ◽

Cochrane Library ◽

Eligibility Criteria ◽

Necrosis Factor Alpha ◽

Assessment Development ◽

Evaluation Approach ◽

Tnf Α ◽

Mean Differences ◽

Meta Analyses

ABSTRACT Recent data from randomized clinical trials (RCTs) suggest that DHA may have stronger anti-inflammatory effects than EPA. This body of evidence has not yet been quantitatively reviewed. The aim of this study was to compare the effect of DHA and EPA on several markers of systemic inflammation by pairwise and network meta-analyses of RCTs. MEDLINE, EMBASE, and The Cochrane Library were searched through to September 2019. We included RCTs of ≥7 d on adults regardless of health status that directly compared the effects of DHA with EPA and RCTs of indirect comparisons, in which the effects of DHA or EPA were compared individually to a control fatty acid. Differences in circulating concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and adiponectin were the primary outcome measures. Data were pooled by pairwise and network meta-analysis and expressed as mean differences (MDs) with 95% CIs. Heterogeneity was assessed (Cochran Q statistic) and quantified (I2 statistic) in the pairwise meta-analysis. Inconsistency and transitivity were evaluated in the network meta-analysis. The certainty of evidence was assessed using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. Eligibility criteria were met by 5 RCTs (N = 411) for the pairwise meta-analysis and 20 RCTs (N = 1231) for the network meta-analysis. In the pairwise meta-analysis, DHA and EPA had similar effects on plasma CRP [MDDHA versus EPA = 0.14 mg/L (95% CI: –0.57, 0.85); I2 = 61%], IL-6 [MDDHA versus EPA = 0.10 pg/mL (–0.15, 0.34); I2 = 40%], and TNF-α [MDDHA versus EPA = –0.10 pg/mL (–0.37, 0.18); I2 = 40%]. In the network meta-analysis, the effects of DHA and EPA on plasma CRP [MDDHA versus EPA = –0.33 mg/L (–0.75, 0.10)], IL-6 [MDDHA versus EPA = 0.09 pg/mL (–0.12, 0.30)], and TNF-α [MDDHA versus EPA = –0.02 pg/mL (–0.25, 0.20)] were also similar. DHA and EPA had similar effects on plasma adiponectin in the network meta-analysis. Results from pairwise and network meta-analyses suggest that supplementation with either DHA or EPA does not differentially modify systemic markers of subclinical inflammation.

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Dry Eye Disease and Tear Cytokine Levels—A Meta-Analysis

International Journal of Molecular Sciences ◽

10.3390/ijms21093111 ◽

2020 ◽

Vol 21 (9) ◽

pp. 3111 ◽

Cited By ~ 3

Author(s):

Matilde Roda ◽

Ivan Corazza ◽

Maria Letizia Bacchi Reggiani ◽

Marco Pellegrini ◽

Leonardo Taroni ◽

...

Keyword(s):

Dry Eye ◽

Meta Analysis ◽

Interferon Γ ◽

Dry Eye Disease ◽

Eye Disease ◽

Model Study ◽

Newcastle Ottawa Scale ◽

Mean Differences ◽

Meta Analyses ◽

Factor Α

Background—It is recognized that inflammation is an underlying cause of dry eye disease (DED), with cytokine release involved. We systematically reviewed literature with meta-analyses to quantitatively summarize the levels of tear cytokines in DED. Methods—The PubMed, Embase, Web of Science, Ovid, Cochrane, and Scopus databases were reviewed until September 2019, and original articles investigating tear cytokines in DED patients were included. Differences of cytokines levels of DED patients and controls were summarized by standardized mean differences (SMD) using a random effects model. Study quality was assessed by applying Newcastle-Ottawa-Scale and the GRADE quality score. Methods of analytical procedures were included as covariate. Results—Thirteen articles investigating 342 DED patients and 205 healthy controls were included in the meta-analysis. The overall methodological quality of these studies was moderate. Systematic review of the selected articles revealed that DED patients had higher tear levels of interleukin (IL)-1β, IL-6, chemokine IL-8, IL-10, interferon-γ, IFN-γ, and tumor necrosis factor-α, TNF-α as compared to controls. Evidence was less strong for IL-2 and IL-17A. Conclusions—Data show that levels of tear cytokines in DED and control display a great variability, and further studies of higher quality enrolling a higher number of subjects are needed, to define a cut-off value.

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Suggestibility in functional neurological disorder: a meta-analysis

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2020-323706 ◽

2020 ◽

pp. jnnp-2020-323706

Author(s):

Lillian Wieder ◽

Richard Brown ◽

Trevor Thompson ◽

Devin B. Terhune

Keyword(s):

Neurological Disorder ◽

Data Extraction ◽

Meta Analysis ◽

Random Effect ◽

Data Sets ◽

Predisposing Factor ◽

Somatisation Disorder ◽

Mean Differences ◽

Meta Analyses ◽

Functional Neurological Disorder

ObjectiveResponsiveness to direct verbal suggestions (suggestibility) has long been hypothesised to represent a predisposing factor for functional neurological disorder (FND) but previous research has yielded conflicting results. The aim of this study was to quantitatively evaluate whether patients with FND display elevated suggestibility relative to controls via meta-analysis.MethodsFour electronic databases were searched in November 2019, with the search updated in April 2020, for original studies assessing suggestibility using standardised behavioural scales or suggestive symptom induction protocols in patients with FND (including somatisation disorder) and controls. The meta-analysis followed Cochrane, Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-analyses Of Observational Studies in Epidemiology (MOOSE) guidelines. Data extraction and study quality coding were performed by two independent reviewers. Standardised suggestibility scores and responsiveness to symptom induction protocols were used to calculate standardised mean differences (SMDs) between groups.ResultsOf 26 643 search results, 19 articles presenting 11 standardised suggestibility data sets (FND: n=316; control: n=360) and 11 symptom suggestibility data sets (FND: n=1285; control: n=1409) were included in random-effect meta-analyses. Meta-analyses revealed that patients with FND displayed greater suggestibility than controls on standardised behavioural scales (SMD, 0.48 (95% C, 0.15 to 0.81)) and greater responsiveness to suggestive symptom induction (SMD, 1.39 (95% CI 0.92 to 1.86)). Moderation analyses presented mixed evidence regarding the extent to which effect sizes covaried with methodological differences across studies. No evidence of publication bias was found.ConclusionsThese results corroborate the hypothesis that FND is characterised by heightened responsiveness to verbal suggestion. Atypical suggestibility may confer risk for FND and be a cognitive marker that can inform diagnosis and treatment of this condition.

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Altered central and blood glutathione in Alzheimer Disease and Mild Cognitive Impairment: a meta-analysis

10.21203/rs.3.rs-430047/v1 ◽

2021 ◽

Author(s):

Jinghan J Chen ◽

Mathura Thiyagarajah ◽

Jianmeng Song ◽

Clara Chen ◽

Nathan Herrmann ◽

...

Keyword(s):

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Alzheimer Disease ◽

Publication Bias ◽

Subgroup Analysis ◽

Meta Analysis ◽

Random Effects Models ◽

Mean Differences ◽

Meta Analyses

Abstract Background: Increasing evidence implicates oxidative stress (OS) in Alzheimer Disease (AD) and Mild Cognitive Impairment (MCI). Depletion of the brain antioxidant glutathione (GSH) may be important in OS-mediated neurodegeneration, though studies of post-mortem brain GSH changes in AD have been inconclusive. Recent in vivo measurements of brain and blood GSH may shed light on GSH changes earlier in the disease.Aim: To quantitatively review in vivo GSH in AD and MCI compared to healthy controls (HC) using meta-analyses. Method: Studies with in vivo brain or blood GSH levels in MCI or AD with a HC group were identified using Medline, PsychInfo, and Embase (1947-June 2020). Standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated for outcomes using random effects models. Outcome measures included brain GSH (Meshcher-Garwood Point Resolved Spectroscopy (MEGA-PRESS) versus non-MEGA-PRESS), and blood GSH (intracellular versus extracellular) in AD and MCI. The Q statistic and Egger’s test were used to assess heterogeneity and risk of publication bias, respectively. Results: For brain GSH, 4 AD (AD=135, HC=223) and 4 MCI (MCI=213, HC=211) studies were included. For blood GSH, 26 AD (AD=1203, HC=1135) and 7 MCI (MCI=434, HC=408) studies were included. Brain GSH overall did not differ in AD or MCI compared to HC; however, the subgroup of studies using MEGA-PRESS reported lower brain GSH in AD (SMD [95%CI] -1.45 [-1.83, -1.06], p<0.001) and MCI (-1.15 [-1.71, -0.59], z=4.0, p<0.001). AD had lower intracellular and extracellular blood GSH overall (-1.10 [-1.58, -0.62], z=4.46, p<0.001). In a subgroup analysis, intracellular GSH was lower in MCI (-0.66 [-1.11, -0.21], p=0.025). Heterogeneity was observed throughout (I2 >85%) and not fully accounted by subgroup analysis. Egger’s test indicated risk of publication bias.Conclusion: Blood intracellular GSH decrease is seen in MCI, while both intra- and extracellular decreases were seen in AD. Brain GSH is decreased in AD and MCI in subgroup analysis. Potential bias and heterogeneity suggest the need for measurement standardization and additional studies to explore sources of heterogeneity.

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Reliability of Mouse Behavioural Tests of Anxiety: a Systematic Review and Meta-Analysis on the Effects of Anxiolytics.

10.1101/2021.07.28.454267 ◽

2021 ◽

Author(s):

Marianna Rosso ◽

Robin Wirz ◽

Ariane Vera Loretan ◽

Nicole Alessandra Sutter ◽

Charlène Tatiana Pereira da Cunha ◽

...

Keyword(s):

Systematic Review ◽

Meta Analysis ◽

Risk Of Bias ◽

Control Treatment ◽

Test Results ◽

Animal Models Of Anxiety ◽

Mean Differences ◽

Behavioural Tests ◽

Meta Analyses ◽

Quality Checklist

Animal research on anxiety and anxiety disorders relies on valid animal models of anxiety. However, the validity of widely used rodent behavioural tests of anxiety has repeatedly been questioned, as they often fail to produce consistent results across independent replicate studies using different study populations or different anxiolytic compounds. In this study, we assessed the sensitivity of behavioural tests of anxiety in mice to detect anxiolytic effects of drugs prescribed to treat anxiety in humans. To this end, we conducted a pre-registered systematic review of studies reporting tests of anxiolytic compounds against a control treatment using common behavioural tests of anxiety in mice. PubMed and EMBASE were searched on August 21 st 2019 for studies published in English and 814 papers were identified for inclusion. Risk of bias was assessed based on Syrcle’s risk of bias tool and the Camarades study quality checklist on a randomly selected subsample of 180 papers. Meta-analyses on effect sizes of treatments using standardized mean differences (Hedges’ g) showed that only two of 17 test measures reliably detected effects of anxiolytic compounds other than diazepam. Further, we report considerable variation in both direction and size of effects of most anxiolytics on most outcome variables, indicating poor replicability of test results. This was corroborated by high heterogeneity in most test measures. Finally, we found an overall high risk of bias. Our findings indicate a general lack of sensitivity of common behavioural tests of anxiety in mice to anxiolytic compounds and cast serious doubt on both construct and predictive validity of most of those tests. The use of animals to model human conditions can be justified only if the expected results are informative, reproducible, and translatable. In view of scientifically valid and ethically responsible research, we call for a revision of behavioural tests of anxiety in mice and the development of more predictive tests .

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DERIVING TREATMENT RECOMMENDATIONS FROM EVIDENCE WITHIN RANDOMIZED TRIALS The Role and Limitation of Meta-Analysis

International Journal of Technology Assessment in Health Care ◽

10.1017/s0266462399015238 ◽

1999 ◽

Vol 15 (2) ◽

pp. 304-315 ◽

Cited By ~ 18

Author(s):

Nick Freemantle ◽

James Mason ◽

Martin Eccles

Keyword(s):

Meta Analysis ◽

Development Project ◽

Weighted Mean ◽

The North ◽

Guidelines Development ◽

Substantial Investment ◽

Mean Differences ◽

Meta Analyses ◽

Robust Measures ◽

Choice Of Therapy

Meta-analysis is commonly used in reviews of the effectiveness of medical technologies, but this approach has not been used in direct support of guidelines development groups. This paper describes the approach of the North of England Guidelines Development Project in describing the evidence using meta-analyses that were conducted explicitly to address questions on the choice of therapy raised by the guidelines development groups. Particular emphasis is placed on the context within which the contributing trials were conducted and the extent to which systematic differences between trials (heterogeneity) was observed, described, and explained. There is a trade-off between internal and external validity for different metrics when presenting the results of trials. More interpretable metrics, such as risk differences or weighted mean differences, are confounded by study design issues and strong assumptions. More robust measures such as odds ratios or standardized weighted mean differences are difficult to interpret physically. Individual patient data may prove particularly helpful in addressing pivotal questions on the magnitude of effects of interventions, though accessing and reanalyzing these data requires a substantial investment in time and other resources.

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The Effects of Sesame Consumption on Glycemic Control in Adults: A Systematic Review and Meta-Analysis of Randomized Clinical Trial

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/2873534 ◽

2021 ◽

Vol 2021 ◽

pp. 1-11

Author(s):

Alireza Yargholi ◽

Mohammad Hasan Najafi ◽

Mohammad Ali Zareian ◽

Jessie Hawkins ◽

Laila Shirbeigi ◽

...

Keyword(s):

Systematic Review ◽

Meta Analysis ◽

Cochrane Library ◽

Control Group ◽

Diabetic Patients ◽

Online Searching ◽

Glycemic Indices ◽

Mean Differences ◽

Meta Analyses ◽

Natural Herb

Objectives. In recent years, diabetes has become a global health problem that creates a tremendous economic burden for many countries. Clinical trials evaluating the hypoglycemic effects of sesame consumption have produced conflicting results. This systematic review and meta-analysis was conducted to evaluate the effectiveness of sesame as a popular natural herb on glycemic indices in adults. Methods. The search for related articles in PubMed, Scopus, Google Scholar, and Cochrane library was conducted through May 2021. Results were reported as weighted mean differences (WMD) with 95% confidence intervals (CI) using a random-effects model. Results. A total of 605 studies were identified through online searching, and a total of eight RCTs representing 382 participants were included in this study. The meta-analyses revealed that sesame consumption significantly decreases serum fasting blood sugar (FBS): (WMD: −28.23 mg/dl; 95% CI (−39.16, −17.13), I2 = 97.6%; 95% CI (96, 98)), and hemoglobin A1c (HbA1c): (WMD: −1.00%; 95% CI (−1.11, −0.88), I2 = 0%; 95% CI (0, 79)) as compared to the control group. Conclusion. This study provides evidence of the hypoglycemic effects of sesame consumption, particularly in diabetic patients. Additional RCTs on sesame and its preparations should be conducted in different populations to increase generalizability.

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Internet- and Mobile-Based Interventions for Mental and Somatic Conditions in Children and Adolescents

Zeitschrift für Kinder- und Jugendpsychiatrie und Psychotherapie ◽

10.1024/1422-4917/a000625 ◽

2020 ◽

Vol 48 (1) ◽

pp. 33-46 ◽

Cited By ~ 12

Author(s):

Matthias Domhardt ◽

Lena Steubl ◽

Harald Baumeister

Keyword(s):

Mental Disorders ◽

Children And Adolescents ◽

Effect Size ◽

Treatment Effects ◽

Meta Analysis ◽

Mental Healthcare ◽

Quality Ratings ◽

Meta Review ◽

Mean Differences ◽

Meta Analyses

Abstract. This meta-review integrates the current meta-analysis literature on the efficacy of internet- and mobile-based interventions (IMIs) for mental disorders and somatic diseases in children and adolescents. Further, it summarizes the moderators of treatment effects in this age group. Using a systematic literature search of PsycINFO and MEDLINE/PubMed, we identified eight meta-analyses (N = 8,417) that met all inclusion criteria. Current meta-analytical evidence of IMIs exists for depression (range of standardized mean differences, SMDs = .16 to .76; 95 % CI: –.12 to 1.12; k = 3 meta-analyses), anxiety (SMDs = .30 to 1.4; 95 % CI: –.53 to 2.44; k = 5) and chronic pain (SMD = .41; 95 % CI: .07 to .74; k = 1) with predominantly nonactive control conditions (waiting-list; placebo). The effect size for IMIs across mental disorders reported in one meta-analysis is SMD = 1.27 (95 % CI: .96 to 1.59; k = 1), the effect size of IMIs for different somatic conditions is SMD = .49 (95 % CI: .33 to .64; k = 1). Moderators of treatment effects are age (k = 3), symptom severity (k = 1), and source of outcome assessment (k = 1). Quality ratings with the AMSTAR-2-checklist indicate acceptable methodological rigor of meta-analyses included. Taken together, this meta-review suggests that IMIs are efficacious in some health conditions in youths, with evidence existing primarily for depression and anxiety so far. The findings point to the potential of IMIs to augment evidence based mental healthcare for children and adolescents.

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