Meta-Analysis of Proptosis Response in Thyroid Eye Disease: Efficacy of EUGOGO Recommended Treatment Regimen With IV Methylprednisolone

Abstract Background: The European Group on Graves’ Orbitopathy (EUGOGO) recommends intravenous methylprednisolone (IVMP) as the first line treatment for moderate-to-severe active thyroid eye disease (TED). While many studies with varying doses of IVMP have reported improvements in inflammation, via clinical activity score (CAS) reduction, the reported improvements in the major progressive outcome of TED, proptosis, vary widely. A reduction in proptosis of ≥2 millimeter (mm) is considered by clinicians and EUGOGO as clinically meaningful. A meta-analysis of existing literature on use of IVMP in TED management, specifically proptosis response, was conducted. Methods: PubMed and Embase were searched for relevant randomized controlled trials (RCTs) and observational studies that included patients with moderate-to-severe active TED receiving treatment with the EUGOGO recommended dose of IVMP (4.5-5g over 12 weeks) from the inception of the databases to date of search (October 2020); regular alerts were established to capture any recent studies. The outcome of interest was change from baseline to week 12 in proptosis in mms. Single-arm meta-analyses were conducted for IVMP using the DerSimonian-Laird random-effects models and forest plots were generated. Pooled means and corresponding 95% confidence intervals (CIs) were calculated. The primary analysis included all identified studies. Sensitivity analyses were conducted based on study design, study characteristics (smoking status), and methodologies (weighted Bayesian meta-analyses based on study design). Results: The search retrieved 12 studies (10 single-center, 8 RCTs, 4 observational studies: 7 from China, 4 from EU, 1 from Turkey), reporting proptosis for 498 patients that were used for the meta-analysis. No placebo-controlled study with the EUGOGO recommended dose of IVMP was found. All studies included patients who were 18 years or older with moderate-to-severe TED and most (n=11) studies included patients with CAS of ≥3. For studies that reported this data, the mean or median (if mean not reported) age ranged from 35 to 52 years and duration of TED symptoms ranged from 4 to 13.6 months. Treatment with IVMP resulted in a reduction of 0.94 mm (95% CI: -1.57 to -0.32) in proptosis from baseline to week 12. The results from the sensitivity analyses were aligned with those from the primary analysis. Conclusions: Among patients with moderate-to-severe TED, this meta-analysis found the EUGOGO-recommended dose of IVMP may result in modest, but not clinically meaningful, improvements in proptosis. However, these results should be interpreted with caution given the paucity of published data and the lack of risk/benefit analyses with glucocorticoid use as compared to the recently FDA-approved therapy, teprotumumab, for the treatment of TED.

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Association between hearing loss and frailty: a systematic review and meta-analysis

BMC Geriatrics ◽

10.1186/s12877-021-02274-y ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Rong Tian ◽

Osvaldo P. Almeida ◽

Dona M. P. Jayakody ◽

Andrew H. Ford

Keyword(s):

Systematic Review ◽

Hearing Loss ◽

Observational Studies ◽

Meta Analysis ◽

Later Life ◽

Sensitivity Analyses ◽

Cross Sectional ◽

Quality Rating ◽

Meta Analyses ◽

Study Quality Assessment

Abstract Background Frailty is associated with poor health outcomes in later life. Recent studies suggested that hearing loss may be a potentially modifiable risk factor associated with frailty. Methods This systematic review and meta-analysis aimed to investigate the association between hearing loss and frailty in observational studies of adults aged 50 years or over. We included observational studies with participants ≥ 50 years old that have clear descriptions of hearing and frailty measurement methods. Meta-analyses were conducted using measurement of risk and 95 % confidence interval of each individual study. Quality assessment, risk of bias, heterogeneity and sensitivity analyses were also conducted. Our study followed PRISMA guidelines. Results Our search identified 4508 manuscripts published in English between 1 and 2000 and 9 February 2021. Sixteen articles reported acceptable measurements of both hearing loss and frailty. Two papers were not suitable for meta-analysis. Twelve sets of cross-sectional data involving 12,313 participants, and three sets of longitudinal data involving 3042 participants were used in the meta-analysis. Hearing loss was associated with an 87 % increase in the risk of frailty among cross-sectional studies (risk ratio [RR] 1.87; 95 %CI 1.63–2.13) and 56 % among longitudinal studies (RR 1.56; 95 %CI 1.29–1.88). There was considerable heterogeneity among studies, but their quality rating, sample size or approach used to assess hearing loss did not change the results substantially. Conclusions The findings of this systematic review and meta-analysis of observational studies suggest that hearing loss increases the risk of frailty in later life. Whether this relationship is causal remains to be determined.

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Meta-analysis

Oxford Handbook of Medical Statistics ◽

10.1093/med/9780198743583.003.0013 ◽

2020 ◽

pp. 529-568

Author(s):

Janet L. Peacock ◽

Philip J. Peacock

Keyword(s):

Publication Bias ◽

Study Design ◽

Observational Studies ◽

Meta Analysis ◽

Clinical Heterogeneity ◽

Statistical Issues ◽

Meta Analyses

This chapter describes the statistical issues involved in performing meta-analyses. It discusses the sources and effects of publication bias and considers ways of correcting for it. It also discusses statistical and clinical heterogeneity and considers how these can be addressed in meta-analyses. Finally, it describes individual patient meta-analysis. Throughout, the chapter includes both trials and observational studies, discussing the challenges that each study design brings and giving examples.

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How to critically read ecological meta-analyses.

10.7287/peerj.preprints.38 ◽

2013 ◽

Author(s):

Christopher J. Lortie ◽

Gavin Stewart ◽

Hannah Rothstein ◽

Joseph Lau

Keyword(s):

Empirical Research ◽

Observational Studies ◽

Meta Analysis ◽

Knowledge Synthesis ◽

Sensitivity Analyses ◽

Careful Examination ◽

Manipulative Experiments ◽

Study Sites ◽

Meta Analyses ◽

Clear Statement

Meta-analysis offers ecologists a powerful tool for knowledge synthesis. Albeit a form of review, it also shares many similarities with primary empirical research. Consequently, critical reading of meta-analyses incorporates criteria from both sets of approaches particularly because ecology is a discipline that embraces heterogeneity and broad methodologies. The most important issues in critically assessing a meta-analysis initially include transparency, replicability, and clear statement of purpose by the authors. Specific to ecology more so than other disciplines, tests of the same hypothesis are generally conducted at different study sites, have variable ecological contexts (i.e., seasonality), and use very different methods. Clear reporting and careful examination of heterogeneity in ecological meta-analyses is thus crucial. Ecologists often also test similar hypotheses with different species, and in these meta-analyses, the reader should expect exploration of phylogenetic dependencies. Finally, observational studies not only provide the substrate for potential current manipulative experiments in this discipline but also form an important body of literature historically for synthesis. Sensitivity analyses of observational versus manipulative experiments when aggregated in the same ecological meta-analysis are also frequent and appropriate. This brief conceptual review is not intended as an instrument to rate meta-analyses for ecologists but does provide the appropriate framing for those purposes and directs the reader to ongoing developments in this direction in other disciplines.

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How to critically read ecological meta-analyses.

10.7287/peerj.preprints.38v2 ◽

2013 ◽

Cited By ~ 1

Author(s):

Christopher J. Lortie ◽

Gavin Stewart ◽

Hannah Rothstein ◽

Joseph Lau

Keyword(s):

Empirical Research ◽

Observational Studies ◽

Meta Analysis ◽

Knowledge Synthesis ◽

Sensitivity Analyses ◽

Careful Examination ◽

Manipulative Experiments ◽

Study Sites ◽

Meta Analyses ◽

Clear Statement

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A Network Meta-Analysis to Compare Effectiveness of Baricitinib and Other Treatments in Rheumatoid Arthritis Patients with Inadequate Response to Methotrexate

Journal of Health Economics and Outcomes Research ◽

10.36469/jheor.2020.12273 ◽

2020 ◽

Vol 7 (1) ◽

pp. 10-23

Keyword(s):

Rheumatoid Arthritis ◽

Meta Analysis ◽

Patient Characteristics ◽

Janus Kinase ◽

Sensitivity Analyses ◽

Baseline Risk ◽

Inadequate Response ◽

Primary Analysis ◽

American College Of Rheumatology ◽

Meta Analyses

Background/Objectives: This article compares the effectiveness of baricitinib (BARI) 4 mg (oral, Janus kinase [JAK] 1/2 inhibitor) versus other targeted synthetic/biologic disease-modifying antirheumatic drugs, in combination with methotrexate (MTX), in moderate-to-severe rheumatoid arthritis patients with inadequate response (IR) to MTX. Methods: A systematic literature review was conducted to identify randomized controlled trials (RCTs) of the interventions of interest. Bayesian network meta-analyses (NMA) were used to compare American College of Rheumatology (ACR) responses at 24 weeks. A series of prespecified sensitivity analyses addressed the potential impact of, among others, baseline risk, treatment effect modifiers, and trial design on treatment response. Results: Nineteen RCTs were included in the NMA (primary analysis). For ACR20, BARI 4 mg + MTX was found to be more effective than adalimumab (ADA) 40 mg + MTX (Odds Ratio [OR] 1.33), abatacept (ABA) 10 mg + MTX (IV/4 weeks) (OR 1.45), infliximab (IFX) 3 mg + MTX (IV/8 wks) (OR 1.63), and rituximab (RTX) 1000 mg + MTX (OR 1.63). No differences were found on ACR50. For ACR70, BARI 4 mg + MTX was more effective than ADA 40 mg + MTX (OR 1.37), ABA 10 mg + MTX (OR 1.86), and RTX 1000 mg + MTX (OR 2.26). Sensitivity analysis including 10 additional RCTs with up to 20% of patients with prior biologic use showed BARI 4 mg + MTX to be more effective than tocilizumab (TCZ) 8 mg + MTX on ACR20 (OR 1.44). Results for all sensitivity analyses were consistent with the direction and magnitude of the primary results. Key limitations include the time span in which trials were conducted (1999–2017), during which patient characteristics and treatment approaches might have changed. Conclusion: This NMA suggests that BARI 4 mg + MTX is an efficacious treatment option in the MTX-IR population as evidenced by the robustness of results.

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Arthrodesis of First Metatarsophalangeal Joint by Plate and Screws for Treatment of Hallux Rigidus (Systematic Review and Meta-Analysis)

QJM ◽

10.1093/qjmed/hcab104.016 ◽

2021 ◽

Vol 114 (Supplement_1) ◽

Author(s):

Ossama Abdelraoof El Shazly ◽

Mohamed Mokhtar Abdellah ◽

Mostafa Abdelnabee Abouzaid

Keyword(s):

Systematic Review ◽

Observational Studies ◽

Plate Fixation ◽

Meta Analysis ◽

Metatarsophalangeal Joint ◽

Hallux Rigidus ◽

Superficial Infection ◽

First Metatarsophalangeal Joint ◽

Non Union ◽

Meta Analyses

Abstract Background With continued loss of dorsiflexion of the 1st MTP, degenerative changes occur within the joint with severe restriction of movement and increase in pain, which leads to the condition known as hallux rigidus. The amount of dorsiflexion may be reduced to 0-10 degrees with pain on both active and passive motion. Objectives Systematically reviewing available evidence from published articles to assess the effectiveness of arthrodesis of first metatarsophalangeal joint by plate and screws in hallux rigidus. The assessment also would encompass safety, side effects, and complications of this mode of treatment. Materials and Methods We performed this systematic review and meta-analysis in accordance to the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and Meta-analysis Of Observational Studies in Epidemiology (MOOSE) statement. PRISMA and MOOSE are reporting checklists for Authors, Editors, and Reviewers of Meta-analyses of interventional and observational studies. According to International committee of medical journal association (ICJME), reviewers must report their findings according to each of the items listed in those checklists. Results Previous results for arthrodesis have been favourable with a union rate of almost 96%. In the present systematic review and meta-analysis, the overall effect estimates showed that the union rates after plate and screw arthrodesis for 1st MTPJ was 96.2% (95% CI 94 – 98.4%). In addition, the overall effect estimates showed that the non-union rates after plate and screw arthrodesis for 1st MTPJ was 4.2% (95% CI 2.4 – 6.1%). Moreover, the overall effect estimates showed that the satisfaction rates after plate and screw arthrodesis for 1st MTPJ was 94.5% (95% CI 90 – 99%). In the present study, the overall effect estimates showed that the overall complications rate after plate and screw arthrodesis for 1st MTPJ was 7.2% (95% CI 2.5 – 12%). The overall effect estimates showed that the malunion rates after plate and screw arthrodesis for 1st MTPJ was 2.7% (95% CI 0 – 6.4%). Additionally, the overall effect estimates showed that the hardware removal and superficial infection rates after plate and screw arthrodesis for 1st MTPJ were 2% and 2.9%, respectively. Conclusion Our analysis showed that plate and screws fixation is effective techniques that can be used for first MTPJ arthrodesis in patients with hallux rigidus. We found that the screw and plate fixation has a significantly lower rate of nonunion compared with the screw alone, as reported by the literature. However, owing to the small group sizes and methodologic shortcomings, we were unable to identify the clinically superior fixation technique for first MTPJ arthrodesis arthrodesis.

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Use of Statins and Breast Cancer: A Meta-Analysis of Seven Randomized Clinical Trials and Nine Observational Studies

Journal of Clinical Oncology ◽

10.1200/jco.2005.02.7045 ◽

2005 ◽

Vol 23 (34) ◽

pp. 8606-8612 ◽

Cited By ~ 139

Author(s):

Stefanos Bonovas ◽

Kalitsa Filioussi ◽

Nikolaos Tsavaris ◽

Nikolaos M. Sitaras

Keyword(s):

Breast Cancer ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Publication Bias ◽

Observational Studies ◽

Fixed Effects ◽

Randomized Clinical Trials ◽

Meta Analysis ◽

Sensitivity Analyses ◽

Fixed Effects Model

Purpose A growing body of evidence suggests that statins may have chemopreventive potential against breast cancer. Laboratory studies demonstrate that statins induce apoptosis and reduce cell invasiveness in various cell lines, including breast carcinoma cells. However, the clinical relevance of these data remains unclear. The nonconclusive nature of the epidemiologic data prompted us to conduct a detailed meta-analysis of the studies published on the subject in peer-reviewed literature. Patients and Methods A comprehensive search for articles published up until 2005 was performed; reviews of each study were conducted; and data were abstracted. Before meta-analysis, the studies were evaluated for publication bias and heterogeneity. Pooled relative risk (RR) estimates and 95% CIs were calculated using the random and the fixed-effects models. Subgroup and sensitivity analyses were also performed. Results Seven large randomized trials and nine observational studies (five case-control and four cohort studies) contributed to the analysis. We found no evidence of publication bias or heterogeneity among the studies. Statin use did not significantly affect breast cancer risk (fixed effects model: RR = 1.03; 95% CI, 0.93 to 1.14; random effects model: RR = 1.02; 95% CI, 0.89 to 1.18). When the analyses were stratified into subgroups, there was no evidence that study design substantially influenced the estimate of effects. Furthermore, the sensitivity analysis confirmed the stability of our results. Conclusion Our meta-analysis findings do not support a protective effect of statins against breast cancer. However, this conclusion is limited by the relatively short follow-up times of the studies analyzed. Further studies are required to investigate the potential decrease in breast cancer risk among long-term statin users.

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Comparative efficacy and safety of oral or transdermal opioids in the treatment of knee or hip osteoarthritis: a systematic review and Bayesian network meta-analysis protocol

BMJ Open ◽

10.1136/bmjopen-2018-022142 ◽

2018 ◽

Vol 8 (10) ◽

pp. e022142

Author(s):

Jun Wang ◽

Yin Wang ◽

Hui Zhang ◽

Ming Lu ◽

Weilu Gao ◽

...

Keyword(s):

Bayesian Network ◽

Meta Analysis ◽

Hip Osteoarthritis ◽

Sensitivity Analyses ◽

Cochrane Library ◽

Efficacy And Safety ◽

Meta Analyses ◽

Transdermal Opioids ◽

And Function

IntroductionOsteoarthritis is a common degenerative joint disease that eventually leads to disability and poor quality of life. The main symptoms are joint pain and mobility disorders. If the patient has severe pain or other analgesics are contraindicated, opioids may be a viable treatment option. To evaluate and compare the efficacy and safety of opioids in the treatment of knee or hip osteoarthritis, we will integrate direct and indirect evidence using a Bayesian network meta-analysis to establish hierarchies of these drugs.Methods and analysisWe will search the Medical Literature Analysis and Retrieval System Online, Excerpta Medica database, Cumulative Index to Nursing and Allied Health Literature, Cochrane Library, Web of Science and PsycINFO databases as well as published and unpublished research in international registries and regulatory agency websites for osteoarthritis reports published prior to 5 January 2018. There will be no restrictions on the language. Randomised clinical trials that compare oral or transdermal opioids with other various opioids, placebo or no treatment for patients with knee or hip osteoarthritis will be included. The primary outcomes of efficacy will be pain and function. We will use pain and function scales to evaluate the main outcomes. The secondary outcomes of safety will be defined as the proportion of patients who have stopped treatment due to side effects. Pairwise meta-analyses and Bayesian network meta-analyses will be performed for all related outcome measures. We will conduct subgroup analyses and sensitivity analyses to assess the robustness of our findings. The Grading of Recommendations, Assessment, Development and Evaluations framework will be used to assess the quality of the evidence contributing to each network assessment.Ethics and disseminationThis study does not require formal ethical approval because individual patient data will not be included. The findings will be disseminated through peer-reviewed publications or conference presentations.PROSPERO registration numberCRD42018085503.

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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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