The objective of this study is to evaluate the effectiveness and safety of ozone therapy (OT) in the treatment of knee osteoarthritis (KOA), which is the most common form of the disease. We analysed systematic reviews (SRs) of randomised controlled trials (RCTs) using the \"A MeaSurement Tool to Assess systematic Reviews\" (AMSTAR2) instrument to evaluate their quality. We developed a narrative synthesis report with eight SRs (15 RCTs/3,685 patients) to summarise the findings. The AMSTAR2 analysis indicated that all reviews had critically low confidence ratings. Statistically significant effects in pain reduction using OT compared to placebo groups were reported in three SRs. OT was shown to be comparable to other therapies in one SR and not superior in the other five. Six SRs highlighted the need for additional RCTs with improved methodological quality to confirm the efficacy of OT for KOA. SRs found fewer consistent effects for improving joint function. Regarding safety, seven SRs reported a low prevalence of minor adverse events linked with OT. Finally, this umbrella review highlights the beneficial effects and safety of OT in the treatment of KOA, particularly in pain control. The low methodological quality of RCTs and SRs limits the possibility of drawing conclusions on the effectiveness of the procedure in comparison to other therapies. Ensure adequate compliance with guidelines such as Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and AMSTAR2 has the ability to improve the quality of SRs in this area.

BACKGROUND: Electronic nicotine delivery systems (ENDS), commonly called e-cigarettes, have been examined in clinical studies for their effects on tobacco smoking cessation. In the past 2 years, a dozen or more systematic reviews on ENDS and cigarette smoking cessation have been published that present differing conclusions and recommendations on the use of ENDS.
OBJECTIVE: Our umbrella review aims to synthesize the findings from current systematic reviews to investigate the quit rates and the percentage of participants abstinent from cigarette smoking using ENDS. Additionally, we will examine the quit rates with ENDS in comparison to other established cessation treatments.
METHODS: The search will retrieve systematic reviews that include both clinical trials and experimental studies on the use of ENDS for smoking cessation. We will also include nonrandomized cohort studies that track ENDS use and the subsequent abstinence from smoking. Databases searches will be conducted in Embase, Scopus, PubMed, and 7 additional registries. Secondary searches will include reference checking, citation chasing, and consultations with topic experts. Two reviewers will perform a title and abstract exclusion followed by a full-paper inclusion process. Data extraction will be conducted by 1 reviewer and completely checked by a second reviewer. Each systematic review will be assessed by 2 reviewers for methodological quality using AMSTAR2 (A Measurement Tool to Assess Systematic Reviews, version 2) and for reporting bias using categories from the Centre for Evidence-Based Medicine\'s Catalogue of Bias. Unreported discrepancies between the protocol and the published review will be identified.
RESULTS: The umbrella review started on March 1, 2023. At the time of publication, the study selection was being conducted and the pilot testing of the data extraction and bias assessment forms were in progress. The review is expected to be completed by December 31, 2023, followed by the submission of the review for journal publication. A second-order meta-analysis will calculate the range and average of quit rates for ENDS. A vote counting of the direction of effect, based on quit rates, will be used to present the relative effectiveness of ENDS for smoking cessation compared to other cessation treatments (including no treatment). A citation matrix will list primary studies with their bias ratings from all the systematic reviews. The effect of overlapping studies between the systematic reviews will be calculated using the corrected coverage area analysis. A sensitivity analysis will examine the impact of the intensity of cessation treatment on quit rates. Depending on the availability of data, subgroup analyses will be conducted based on participants\' gender, age, prior quit attempts, and nicotine dependence. The strength or weakness of the evidence synthesis will be assessed using a stratification of evidence technique. Reporting bias will be presented with a tabulation of bias indicators. Publication bias will be assessed.
CONCLUSIONS: The use of ENDS for smoking cessation is a highly controversial subject. Through an exhaustive synthesis of the available data, we will present the quit rates of cigarette smoking cessation obtained with ENDS and how they compare to quit rates obtained from other established cessation treatments. The critical quality and bias assessment of the systematic reviews will indicate the most reliable sources to inform treatment considerations and policy development.
BACKGROUND: PROSPERO CRD42023406165; https://tinyurl.com/4ekzpbrj.
UNASSIGNED: PRR1-10.2196/47711.

Systematic reviews and meta-analyses pool data from individual studies to generate a higher level of evidence to be evaluated by guidelines. These reviews ultimately guide clinicians and stakeholders in health-related decisions. However, the informativeness and quality of evidence synthesis inherently depend on the quality of what has been pooled into meta-research projects. Moreover, beyond the quality of included individual studies, only a methodologically correct process, in relation to systematic reviews and meta-analyses themselves, can produce a reliable and valid evidence synthesis. Hence, quality of meta-research projects also affects evidence synthesis reliability. In this overview, the authors provide a synthesis of advantages and disadvantages and main characteristics of some of the most frequently used tools to assess quality of individual studies, systematic reviews, and meta-analyses. Specifically, the tools considered in this work are the Newcastle-Ottawa scale (NOS) and the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) for observational studies, the Consolidated Standards of Reporting Trials (CONSORT), the Jadad scale, the Cochrane risk of bias tool 2 (RoB2) for randomized controlled trials, the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) and the Assessment of Multiple Systematic Reviews 2 (AMSTAR2), and AMSTAR-PLUS for meta-analyses. WHAT IS ALREADY KNOWN?: The informativeness and quality of evidence synthesis inherently depend on the quality of what has been pooled into meta-research projects. Beyond the quality of included individual studies, only a methodologically correct process, in relation to systematic reviews and meta-analyses themselves, can produce a reliable and valid evidence synthesis. WHAT IS NEW?: In this overview, the authors provide a synthesis of advantages and disadvantages and main characteristics of some of the most frequently used tools to assess quality of individual studies, systematic reviews, and meta-analyses. POTENTIAL IMPACT: This overview serves as a starting point and a brief guide to identify and understand the main and most frequently used tools for assessing the quality of studies included in meta-research. The authors here share their experience in publishing several meta-research-related articles covering different areas of medical sciences.