How to report E-values for meta-analyses: Recommended improvements and additions to the new GRADE approach

Objective. This paper assessed the effectiveness of pre-, pro-, and synbiotics on reducing two protein-bound uremic toxins, p-cresyl sulphate (PCS) and indoxyl sulphate (IS).Methods. English language studies reporting serum, urinary, or fecal PCS and/or IS (or their precursors) following pre-, pro-, or synbiotic interventions (>1 day) in human adults were included. Population estimates of differences in the outcomes between the pre- and the postintervention were estimated for subgroups of studies using four meta-analyses. Quality was determined using the GRADE approach.Results. 19 studies met the inclusion criteria, 14 in healthy adults and five in haemodialysis patients. Eight studies investigated prebiotics, six probiotics, one synbiotics, one both pre- and probiotics, and three studies trialled all three interventions. The quality of the studies ranged frommoderatetovery low. 12 studies were included in the meta-analyses with all four meta-analyses reporting statistically significant reductions in IS and PCS with pre- and probiotic therapy.Conclusion. There is a limited but supportive evidence for the effectiveness of pre- and probiotics on reducing PCS and IS in the chronic kidney disease population. Further studies are needed to provide more definitive findings before routine clinical use can be recommended.

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How to report E-values for meta-analyses: Recommended improvements and additions to the new GRADE approach

10.31219/osf.io/xb25k ◽

2021 ◽

Author(s):

Maya B Mathur ◽

Tyler VanderWeele

Keyword(s):

Working Group ◽

Assessment Development ◽

Confounding Bias ◽

Evidence Strength ◽

Specific Proposal ◽

Meta Analyses ◽

Assessing Sensitivity ◽

Grade Approach

In a recent concept paper (Verbeek et al., 2021), the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group provides a preliminary proposal to improve its existing guidelines for assessing sensitivity to uncontrolled confounding in meta-analyses of nonrandomized studies. The new proposal centers on reporting the E-value for the meta-analytic mean and on comparing this E-value to a measured “reference confounder” to determine whether residual uncontrolled confounding in the meta-analyzed studies could or could not plausibly explain away the meta-analytic mean. Although we agree that E-value analogs for meta-analyses could be an informative addition to future GRADE guidelines, we suggest improvements to the Verbeek et al. (2021)’s specific proposal regarding: (1) their interpretation of comparisons between the E-value and the strengths of associations of a reference confounder; (2) their characterization of evidence strength in meta-analyses in terms of only the meta-analytic mean; and (3) the possibility of confounding bias that is heterogeneous across studies.

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Effects of Ashwagandha (Withania somnifera) on VO2max: A Systematic Review and Meta-Analysis

Nutrients ◽

10.3390/nu12041119 ◽

2020 ◽

Vol 12 (4) ◽

pp. 1119 ◽

Cited By ~ 1

Author(s):

Jorge Pérez-Gómez ◽

Santos Villafaina ◽

José Carmelo Adsuar ◽

Eugenio Merellano-Navarro ◽

Daniel Collado-Mateo

Keyword(s):

Systematic Review ◽

Withania Somnifera ◽

Controlled Trial ◽

Meta Analysis ◽

Assessment Development ◽

Before And After ◽

The Mean ◽

Meta Analyses ◽

Grade Approach

The purpose of this study was to systematically review the scientific literature about the effects of supplementation with Ashwagandha (Withania somnifera) on maximum oxygen consumption (VO2max), as well as to provide directions for clinical practice. A systematic search was conducted in three electronic databases following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Guidelines (PRISMA). The inclusion criteria were: (a) VO2max data, with means ± standard deviation before and after the supplement intervention, (b) the study was randomized controlled trial (RCT), (c) the article was written in English. The quality of evidence was evaluated according to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. A meta-analysis was performed to determine effect sizes. Five studies were selected in the systematic review (162 participants) and four were included in the meta-analysis (142 participants). Results showed a significant enhancement in VO2max in healthy adults and athletes (p = 0.04). The mean difference was 3.00 (95% CI from 0.18 to 5.82) with high heterogeneity. In conclusion, Ashwagandha supplementation might improve the VO2max in athlete and non-athlete people. However, further research is need to confirm this hypothesis since the number of studies is limited and the heterogeneity was high.

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Systematic reviews of observational studies of Risk of Thrombosis and Bleeding in General and Gynecologic Surgery (ROTBIGGS): introduction and methodology

Systematic Reviews ◽

10.1186/s13643-021-01814-2 ◽

2021 ◽

Vol 10 (1) ◽

Author(s):

Lauri I. Lavikainen ◽

Gordon H. Guyatt ◽

Yung Lee ◽

Rachel J. Couban ◽

Anna L. Luomaranta ◽

...

Keyword(s):

Systematic Reviews ◽

Observational Studies ◽

Risk Of Bias ◽

Gynecologic Surgery ◽

Patient Risk ◽

Trade Off ◽

Risk Estimates ◽

Modeling Studies ◽

Meta Analyses ◽

Grade Approach

Abstract Background Venous thromboembolism (VTE) and bleeding are serious and potentially fatal complications of surgical procedures. Pharmacological thromboprophylaxis decreases the risk of VTE but increases the risk of major post-operative bleeding. The decision to use pharmacologic prophylaxis therefore represents a trade-off that critically depends on the incidence of VTE and bleeding in the absence of prophylaxis. These baseline risks vary widely between procedures, but their magnitude is uncertain. Systematic reviews addressing baseline risks are scarce, needed, and require innovations in methodology. Indeed, systematic summaries of these baseline risk estimates exist neither in general nor gynecologic surgery. We will fill this knowledge gap by performing a series of systematic reviews and meta-analyses of the procedure-specific and patient risk factor stratified risk estimates in general and gynecologic surgeries. Methods We will perform comprehensive literature searches for observational studies in general and gynecologic surgery reporting symptomatic VTE or bleeding estimates. Pairs of methodologically trained reviewers will independently assess the studies for eligibility, evaluate the risk of bias by using an instrument developed for this review, and extract data. We will perform meta-analyses and modeling studies to adjust the reported risk estimates for the use of thromboprophylaxis and length of follow up. We will derive the estimates of risk from the median estimates of studies rated at the lowest risk of bias. The primary outcomes are the risk estimates of symptomatic VTE and major bleeding at 4 weeks post-operatively for each procedure stratified by patient risk factors. We will apply the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to rate evidence certainty. Discussion This series of systematic reviews, modeling studies, and meta-analyses will inform clinicians and patients regarding the trade-off between VTE prevention and bleeding in general and gynecologic surgeries. Our work advances the standards in systematic reviews of surgical complications, including assessment of risk of bias, criteria for arriving at the best estimates of risk (including modeling of the timing of events and dealing with suboptimal data reporting), dealing with subgroups at higher and lower risk of bias, and use of the GRADE approach. Systematic review registration PROSPERO CRD42021234119

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Methodological Approaches for Assessing Certainty of the Evidence in Umbrella Reviews: a Systematic Review

10.21203/rs.3.rs-543971/v1 ◽

2021 ◽

Author(s):

Saranrat Sadoyu ◽

Kaniz Afroz Tanni ◽

Nontaporn Punrum ◽

Sobhon Paengtrai ◽

Nai Ming Lai ◽

...

Keyword(s):

Journal Impact Factor ◽

Observational Studies ◽

Experimental Designs ◽

Cochrane Library ◽

Methodological Rigor ◽

Methodological Approaches ◽

Meta Analyses ◽

The Cochrane Library ◽

Journal Impact ◽

Grade Approach

Abstract Objective: To identify and describe the methodological approaches for assessing the certainty of the evidence in umbrella reviews (URs) of meta-analyses (MAs).Study Design and Setting: We included URs that included SR-MAs of interventions and non-interventions. We searched from 3 databases including PubMed, Embase, and The Cochrane Library from 2010 to 2020.Results: 138 URs have been included consisting of 96 and 42 URs of interventions and non-interventions, respectively. Only 31 (32.3%) of URs of interventions assessed certainty of evidence, in which the GRADE approach was the most frequently used method (N=20, 64.5%) followed by creditability assessments (N=6, 12.9%). Conversely, thirty (71.4%) of URs of non-interventions assessed certainty of evidence, in which the criteria for credibility assessment were mainly used (N=28; 93%). URs published in journals with high journal impact factor (JIF) are more likely to assess certainty of evidence than URs published in low JIFs. Conclusions: Only one-third of URs that included MAs of experimental designs have assessed the certainty of the evidence in contrast to the majority of the URs of observational studies. Therefore, guidance and standards are required to ensure the methodological rigor and consistency of certainty of evidence assessment for URs.

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Ivermectin for Prevention and Treatment of COVID-19 Infection: a Systematic Review and Meta-analysis

10.21203/rs.3.rs-317485/v1 ◽

2021 ◽

Author(s):

Andrew Bryant ◽

Theresa A Lawrie ◽

Therese Dowswell ◽

Edmund Fordham ◽

Scott Mitchell ◽

...

Keyword(s):

Low Cost ◽

Meta Analysis ◽

Severe Disease ◽

Risk Of Bias ◽

Bibliographic Databases ◽

Average Risk ◽

Risk Of Death ◽

Secondary Outcomes ◽

Meta Analyses ◽

Grade Approach

Abstract Background Re-purposed medicines may have role in combating the SARS-CoV-2 virus. The antiparasitic medicine ivermectin, which has anti-viral and anti-inflammatory properties, has been tested in numerous clinical trials with promising results.Methods We assessed the efficacy of ivermectin treatment and/or prophylaxis among people with, or at high risk of covid-19 infection. We searched bibliographic databases up to February 2021 and two review authors sifted for studies, extracted data and assessed risk of bias. Meta-analyses were conducted and certainty of the evidence was assessed using GRADE approach.Findings Twenty-one RCTs involving 2741 participants met review inclusion. Meta-analysis of 13 trials found ivermectin reduced risk of death compared with no ivermectin (average Risk Ratio 0.32, 95% confidence interval (CI) 0.14 to 0.72; n=1892; I2=57%; low to moderate-certainty evidence. Low-certainty evidence found ivermectin prophylaxis reduced covid-19 infection by an average 86% (95% CI 79% to 91%). Secondary outcomes provided very-low or low certainty evidence. Low certainty evidence suggests that that there may be no benefit with ivermectin for ‘need for mechanical ventilation’, whereas effect estimates for ‘improvement’ and ‘deterioration’ favoured ivermectin use. Severe adverse events were rare and evidence of no difference was assessed as low to very low-certainty. Evidence on other secondary outcomes was very low certainty.Interpretation Low to moderate-certainty evidence suggests reductions in covid-19 deaths and infections may be possible by using ivermectin. Employing ivermectin early on may reduce the number of people progressing to severe disease. The apparent safety and low cost suggest that ivermectin could have an impact on the SARS-CoV-2 pandemic globally.

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Systematic Review of Nutrition Supplements in Chronic Kidney Diseases: A GRADE Approach

Nutrients ◽

10.3390/nu13020469 ◽

2021 ◽

Vol 13 (2) ◽

pp. 469

Author(s):

Pei-Chin Lin ◽

Chu-Lin Chou ◽

Shih-Hsiang Ou ◽

Te-Chao Fang ◽

Jin-Shuen Chen

Keyword(s):

Systematic Review ◽

Kidney Diseases ◽

Meta Analysis ◽

Cochrane Library ◽

Public Health Issue ◽

Omega 3 ◽

Renal Protection ◽

Beneficial Effects ◽

Meta Analyses ◽

Grade Approach

Chronic kidney disease (CKD) is cumulative worldwide and an increasing public health issue. Aside from the widely known protein restriction and medical therapy, less evident is the renal protection of nutrition supplements in CKD patients. This systematic review (SR), using a Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach, aims to summarize and quantify evidence about the prevention effects of vitamin D and analogues, omega-3 polyunsaturated fatty acid (omega-3 PUFA), dietary fiber, coenzyme Q10 (CoQ10), and biotics on CKD progression. This study was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement to examine SRs and/or meta-analysis of clinical controlled trials identified from PubMed, Embase, and the Cochrane Library. Finally, seventeen SRs were included in the qualitative analysis. The beneficial effects of these nutrition supplements in CKD patients mostly seem to be at low to very low evidence on proteinuria, kidney function, and inflammations and did not appear to improve CKD prognosis. The recommendation of nutrition supplements in CKD patients needs to discuss with physicians and consider the benefits over the adverse effects. Longer follow-up of larger randomized trials is necessary to clarify the benefits of nutrition supplements in CKD patients.

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Tocilizumab and sarilumab alone or in combination with corticosteroids for COVID-19: A systematic review and network meta-analysis

10.1101/2021.07.05.21259867 ◽

2021 ◽

Author(s):

Dena Zeraatkar ◽

Ellen Cusano ◽

Juan Pablo Diaz Martinez ◽

Anila Qasim ◽

Sophia O Mangala ◽

...

Keyword(s):

Systematic Review ◽

Standard Care ◽

Meta Analysis ◽

Analysis Data ◽

Risk Of Bias ◽

Risk Of Death ◽

Study Selection ◽

Receptor Blockers ◽

Meta Analyses ◽

Grade Approach

Objective: To compare the effects of interleukin-6 (IL-6) receptor blockers, with or without corticosteroids, on mortality in patients with COVID-19. Design: Systematic review and network meta-analysis Data sources: WHO COVID-19 database, a comprehensive multilingual source of global covid-19 literature, and two prospective meta-analyses Study selection: Trials in which people with suspected, probable, or confirmed COVID-19 were randomized to IL-6 receptor blockers (with or without corticosteroids), corticosteroids, placebo, or standard care. Results: We assessed the risk of bias of included trials using a modification of the Cochrane risk of bias 2.0 tool. We performed a Bayesian fixed effect network meta-analysis and assessed the certainty of evidence using the GRADE approach. We identified 45 eligible trials (20,650 patients), 36 (19,350 patients) of which could be included in the network meta-analysis. 27 of 36 trials were rated at high risk of bias, primarily due to lack of blinding. Tocilizumab (20 more per 1000, 15 fewer to 59 more; low certainty) and sarilumab (11 more per 1000, 38 fewer to 55 more; low certainty) alone may not reduce the risk of death. Tocilizumab, in combination with corticosteroids, probably reduces the risk of death compared to corticosteroids alone (35 fewer per 1000, 52 fewer to 18 more; moderate certainty) and sarilumab, in combination with corticosteroids, may reduce the risk of death compared to corticosteroids alone (43 fewer, 73 fewer to 12 more; low certainty). Tocilizumab and sarilumab, both in combination with corticosteroids, may have similar effects (8 more per 1000, 20 fewer to 35 more; low certainty). Conclusion: IL-6 receptor blockers, when added to standard care that includes corticosteroids, in patients with severe or critical COVID-19, probably reduce mortality. Tocilizumab and sarilumab may have similar effectiveness.

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Many Meta-Analyses Lack Original Disclosures

Clinical Endocrinology News ◽

10.1016/s1558-0164(11)70214-0 ◽

2011 ◽

Vol 6 (4) ◽

pp. 58

Author(s):

JANE ANDERSON

Keyword(s):

Meta Analyses

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Associations of coronary and peripheral artery disease with presence, expansion, and rupture of abdominal aortic aneurysm – a grin without a cat!

VASA ◽

10.1024/0301-1526/a000606 ◽

2017 ◽

Vol 46 (3) ◽

pp. 151-158 ◽

Cited By ~ 4

Author(s):

Hisato Takagi ◽

Takuya Umemoto

Keyword(s):

Abdominal Aortic Aneurysm ◽

Aortic Aneurysm ◽

Peripheral Artery Disease ◽

Literature Search ◽

Systematic Literature Search ◽

Peripheral Artery ◽

Epidemiological Evidence ◽

Abdominal Aortic ◽

Artery Disease ◽

Meta Analyses

Abstract. Both coronary and peripheral artery disease are representative atherosclerotic diseases, which are also known to be positively associated with presence of abdominal aortic aneurysm. It is still controversial, however, whether coronary and peripheral artery disease are positively associated with expansion and rupture as well as presence of abdominal aortic aneurysm. In the present article, we overviewed epidemiological evidence, i. e. meta-analyses, regarding the associations of coronary and peripheral artery disease with presence, expansion, and rupture of abdominal aortic aneurysm through a systematic literature search. Our exhaustive search identified seven meta-analyses, which suggest that both coronary and peripheral artery disease are positively associated with presence of abdominal aortic aneurysm, may be negatively associated with expansion of abdominal aortic aneurysm, and might be unassociated with rupture of abdominal aortic aneurysm.

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