PROTOCOL: Assessment of publication time in Campbell systematic reviews: A cross-sectional survey.

This is the protocol for a Campbell systematic review. The objectives are as follows. This study has three main objectives: (1) To examine the time duration from title registration to publication of the protocol for a Campbell systematic review and publication of the completed Campbell systematic review; (2) To describe publication times in accordance with the characteristics of the reviews, which include year of publication, type of review, number of authors, number of collaborative institutions, the time gap between the date the search was conducted and review publication, and the length and complexity of the included review (including the number of pages, the number of tables and figures, the number of studies included in the review, the number and type of analyses undertaken, and the number of references); (3) To describe the differences in publication times between Campbell Review Groups.

Quality Assessment of Cancer Pain Clinical Practice Guidelines.

Introduction: Several clinical practice guidelines (CPGs) for cancer pain have been published; however, the quality of these guidelines has not been evaluated so far. The purpose of this study was to evaluate the quality of CPGs for cancer pain and identify gaps limiting knowledge. Methods: We systematically searched seven databases and 12 websites from their inception to July 20, 2021, to include CPGs related to cancer pain. We used the validated Appraisal of Guidelines for Research and Evaluation Instrument II (AGREE II) and Reporting Items for Practice Guidelines in Healthcare (RIGHT) checklist to assess the methodology and reporting quality of eligible CPGs. The overall agreement among reviewers with the intraclass correlation coefficient (ICC) was calculated. The development methods of CPGs, strength of recommendations, and levels of evidence were determined. Results: Eighteen CPGs published from 1996 to 2021 were included. The overall consistency of the reviewers in each domain was acceptable (ICC from 0.76 to 0.95). According to the AGREE II assessment, only four CPGs were determined to be recommended without modifications. For reporting quality, the average reporting rates for all seven domains of CPGs was 57.46%, with the highest domain in domain 3 (evidence, 68.89%) and the lowest domain in domain 5 (review and quality assurance, 33.3%). Conclusion: The methodological quality of cancer pain CPGs fluctuated widely, and the complete reporting rate in some areas is very low. Researchers need to make greater efforts to provide high-quality guidelines in this field to clinical decision-making.

[QUADAS-C-A tool for assessing risk of bias regarding Quality Assessment of Diagnostic Accuracy Studies-Comparative].

This paper introduced the Quality Assessment of Diagnostic Accuracy Studies-Comparative (QUADAS-C), illustrated the comparison with the QUADAS-2, and using QUADAS-C together with QUADAS-2 to present QUADAS-C results through systematic reviews. Like the domain for QUADAS-2, QUADAS-C retained four domains, including patient selection, index test, reference standard, flow, and timing, and comprised additional questions for each QUADAS-2 part. Unlike the QUADAS-2 tool, the starting question of each domain for QUADAS-C was designed to summarize the risk of biased information captured by QUADAS-2. QUADAS-C only dealt with the risk of bias but did not include the part of concerns regarding applicability. The answers to signaling questions for each domain of QUADAS-C would lead to a 'low''high' or 'unclear' risk of biased judgment for the original study.

Progress and challenges of network meta-analysis.

In the past years, network meta-analysis (NMA) has been widely used among clinicians, guideline makers, and health technology assessment agencies and has played an important role in clinical decision-making and guideline development. To inform further development of NMAs, we conducted a bibliometric analysis to assess the current status of published NMA methodological studies, summarized the methodological progress of seven types of NMAs, and discussed the current challenges of NMAs.

Clinical trials in COVID-19 management & prevention: A meta-epidemiological study examining methodological quality.

OBJECTIVE: To describe the characteristics of Covid-19 randomized clinical trials (RCTs) and examine the association between trial characteristics and the likelihood of finding a significant effect. STUDY DESIGN: We conducted a systematic review to identify RCTs (up to October 21, 2020) evaluating drugs or blood products to treat or prevent Covid-19. We extracted trial characteristics (number of centers, funding sources, and sample size) and assessed risk of bias (RoB) using the Cochrane RoB 2.0 tool. We performed logistic regressions to evaluate the association between RoB due to randomization, single vs. multicentre, funding source, and sample size, and finding a statistically significant effect. RESULTS: We included 91 RCTs (n = 46,802); 40 (44%) were single-center, 23 (25.3%) enrolled <50 patients, 28 (30.8%) received industry funding, and 75 (82.4%) had high or probably high RoB. Thirty-eight trials (41.8%) reported a statistically significant effect. RoB due to randomization and being a single-center trial were associated with increased odds of finding a statistically significant effect. CONCLUSIONS: There is high variability in RoB among Covid-19 trials. Researchers, funders, and knowledge-users should be cognizant of the impact of RoB due to randomization and single-center trial status in designing, evaluating, and interpreting the results of RCTs. REGISTRATION: CRD42020192095.

Is interleukin-2 an optimal marker for diagnosing tuberculosis infection? A systematic review and meta-analysis.

BACKGROUND: Latent tuberculosis infection (LTBI) is a huge reservoir for the deadlier TB disease. Accurate identification of LTBI is a key strategy to eliminate TB. Therefore, a systematic review and meta-analysis approach was used to assess diagnostic potential of IL-2 for LTBI. METHODS: PubMed, Web of Science, the Cochrane Library and Embase were searched. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), area under the summary receiver operating characteristic curve (AUROC) and hierarchical summary receiver operating characteristic curve (HSROC) were estimated by bivariate and HSROC models. RESULTS: Twenty-seven studies including 1404 participants and 1986 samples met the inclusion criteria. The pooled sensitivity, specificity, PLR, NLR, DOR and AUROC of IL-2 were separately as 87%, 98%, 34.78, 0.14, 256.41 and 0.98, indicating a very powerful differentiating ability of IL-2 for LTBI from non-TB controls. For differentiating ATB from LTBI, the pooled sensitivity, specificity, PLR, NLR, DOR and AUROC of IL-2 were 83%, 76%, 3.41, 0.22, 15.47 and 0.87, respectively, suggesting a good differentiating ability of IL-2. CONCLUSIONS: These findings showed that IL-2 is a powerful marker for differentiating LTBI from non-TB controls and a good marker for differentiating ATB from LTBI individuals.

Use of AMSTAR-2 in the methodological assessment of systematic reviews: protocol for a methodological study.

BACKGROUND: Systematic reviews (SRs) with or without meta-analyses (MAs) are widely used in resolving questions in various healthcare areas (such as, traditional Chinese medicine, public health and surgery), and they are the cornerstone of evidence-based healthcare. However, the reliability of SRs is typically influenced by their methodological quality. AMSTAR (A Measurement Tool to Assess Systematic Reviews) and AMSTAR-2 tools can assess the methodological quality of SRs, and the use of AMSTAR has been investigated. However, AMSTAR-2 is now widely used to evaluate the methodological quality of SRs, but the use of AMSTAR-2 for determining the methodological quality of SRs has not yet been investigated and assessed thoroughly. Thus, we designed the present study to investigate the use of AMSTAR-2 in studies that assessed the methodological quality of a sample of SRs with the AMSTAR-2 and provide references to potential users of AMSTAR-2 tool. METHODS: Four commonly used electronic databases including PubMed, EmBase, the Cochrane Library, and Web of Science will be searched following a comprehensive search strategy to identify and retrieve studies that have used AMSTAR-2 tool for evaluating the methodological quality of SRs. Two independent authors will retrieve bibliometric information and methodological data, including all author names, time of publication, and journal names, whether a specific score value was given for each item, and whether overall quality assessment was performed. Descriptive statistical analyses will be used to present the study results, e.g., frequencies and percentages, mean and standard deviation (SD) or median and interquartile range (IQR). In addition, subgroup analyses will be performed to identify the methodological differences (e.g., the reporting of study designs included in SRs) between overviews and methodological studies. The risk ratio (RR) with 95% confidence interval (95% CI) will be calculated to measure the methodological differences. Cytoscape 3.7.1 software tool will be used to construct collaboration network maps. Further, Microsoft Office Excel 2016 and Stata 12.0 will be used to manage and analyze data. DISCUSSION: The results of this study will identify any gaps in the use of AMSTAR-2 and important bibliometric features, such as active researchers and journals, provide guidance to researchers in various healthcare areas (such as, traditional Chinese medicine and public health) for using AMSTAR-2 tool and help them in developing cooperation and submitting their manuscripts.

Diagnostic significance assessment of the circulating cell-free DNA in ovarian cancer: An updated meta-analysis.

BACKGROUND: Recently, disagreements remain in increasing evidence about the potential value of circulating cell-free DNA (cfDNA) as a noninvasive diagnostic biomarker for ovarian cancer (OC). Here, this update meta-analysis was performed to further assess the diagnostic performance of circulating cfDNA in discriminating OC from non-cancerous individuals. METHODS: We performed a systemic literature search of PubMed, Embase, Web of Science, Cochrane Library, OVID, Chinese National Knowledge Infrastructure (CNKI) and Wanfang databases to obtain 22 eligible articles including a total of 1125 patients and 1244 controls. The pooled sensitivity, specificity, diagnostic odds ratio (DOR) and area under receiver operating characteristics curves (AUROC) of the included studies for cfDNA in diagnosing OC patients were used to estimate the diagnostic value. The clinical utility of cfDNA was evaluated by Fagan nomogram. Heterogeneity was explored utilizing subgroup analysis and meta-regression. RESULTS: The pooled sensitivity and specificity were 73% and 90%, the DOR and AUROC were 25.29 and 0.90, respectively. Subgroup analyses and meta-regression, according to patients' region, study design, clinical stage, specimen types, detection indicators, simple size, publication year revealed there were no significant sources of heterogeneity. Additionally, subgroup analyses showed qualitative detection (methylation detection); TNM stage I-IV, publication year 2011-2018, serum-based cfDNA assays exhibited better diagnostic performance as compared to quantitative detection, TNM stage III-IV, publication year 2002-2010; plasma-based cfDNA assays, and more participants and prospective studies manifested superior diagnostic accuracy. The result of sensitivity analysis indicated no study exclusively contributed to the heterogeneity and Deeks' funnel plot suggested no evidence of significant publication bias. CONCLUSIONS: Our meta-analysis found the qualitative detection (methylation); TNM stage I-IV, publication year 2011-2018 were related to more effective diagnostic accuracy for OC. However, serum-based cell-free DNA detection should be cautiously interpreted due to unclear factors. Hence, further large-scale longitudinal studies are required to validate the diagnostic potential of cell-free DNA. The present study provides to accrue knowledge of cell-free DNA levels for future researches.

Comprehensive assessment gene signatures for clear cell renal cell carcinoma prognosis.

There are many prognostic gene signature models in clear cell renal cell carcinoma (ccRCC). However, different results from various methods and samples are hard to contribute to clinical practice. It is necessary to develop a robust gene signature for improving clinical practice in ccRCC.A method was proposed to integrate least absolute shrinkage and selection operator and multiple Cox regression to obtain mRNA and microRNA signature from the cancer genomic atlas database for predicting prognosis of ccRCC. The gene signature model consisted by 5 mRNAs and 1 microRNA was identified. Prognosis index (PI) model was constructed from RNA expression and median value of PI is used to classified patients into high- and low-risk groups.The results showed that high-risk patients showed significantly decrease survival comparison with low-risk groups [hazard ratio (HR) =7.13, 95% confidence interval = 3.71-13.70, P < .001]. As the gene signature was mainly consisted by mRNA, the validation data can use transcriptomic data to verify. For comparison of the performance with previous works, other gene signature models and 4 datasets of ccRCC were retrieved from publications and public database. For estimating PI in each model, 3 indicators including HR, concordance index , and the area under the curve of receiver operating characteristic for 3 years were calculated across 4 independent datasets.The comparison results showed that the integrative model from our study was more robust than other models via comprehensive analysis. These findings provide some genes for further study their functions and mechanisms in ccRCC tumorigenesis and malignance, and may be useful for effective clinical decision making of ccRCC patients.

Assessing the methodological and reporting quality of network meta-analyses in Chinese medicine.

BACKGROUND: An increasing number of network meta-analyses (NMAs) in traditional Chinese medicine (TCM) have been published recently, but the quality of them was lack of assessment. This study aims to evaluate the methodological and reporting quality of NMAs in TCM. METHODS: Six electronic databases, including PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), Embase, China National Knowledge Infrastructure (CNKI), Wanfang and Chinese Biomedical Literature Database (CBM) from inception to January 2018, were searched. NMAs of TCM were included. A measurement tool to assess the methodological quality of systematic reviews (AMSTAR) and the PRISMA Extension Statement for Reporting of Systematic Reviews Incorporating Network Meta-analyses of Health Care Interventions (PRISMA-NMA) were used to assess the methodological and reporting quality of the included NMAs. RESULTS: A total of 40 NMAs, including 2535 randomized controlled trials (RCTs), were included. They were published between December 2012 and November 2017. The median score and interquartile range of methodological and reporting quality was 7 (6-8) and 22 (19.1-27.1). Serious methodological flaws existed in the following aspects: the status of publication (22.5%), a list of studies provided (0%), assessment of publication bias (37.5%), and conflicts of interest (12.5%). Several items need to be improved in reporting, especially for Protocol and registration (2.5%), Data items (22.5%), Risk of bias across studies (Methods section) (37.5%), Results of individual studies (27.5%), Risk of bias across studies (Results section) (40%), Results of additional analyses (35%), and Funding (15%). CONCLUSIONS: The methodological and reporting quality of NMAs in TCM is moderate. Identified shortcomings of published NMAs should be taken into consideration in further trainings of authors and editors of NMAs in TCM. Future researchers should be encouraged to apply PRISMA-NMA, and a recognized tool for the assessment of NMA methodology was wanted.

Standard-Dose Proton Pump Inhibitors in the Initial Non-eradication Treatment of Duodenal Ulcer: Systematic Review, Network Meta-Analysis, and Cost-Effectiveness Analysis.

Background: Short-term use of standard-dose proton pump inhibitors (PPIs) is the first-line initial non-eradication treatment for duodenal ulcer (DU), but the choice on individual PPI drug is still controversial. The purpose of this study is to compare the efficacy, safety, and cost-effectiveness of standard-dose PPI medications in the initial non-eradication treatment of DU. Methods: We searched PubMed, Embase, Cochrane Library, Clinicaltrials.gov, China National Knowledge Infrastructure, VIP database, and the Wanfang database from their earliest records to September 2017. Randomized controlled trials (RCTs) evaluating omeprazole (20 mg/day), pantoprazole (40 mg/day), lansoprazole (30 mg/day), rabeprazole (20 mg/day), ilaprazole (10 mg/day), ranitidine (300 mg/day), famotidine (40 mg/day), or placebo for DU were included. The outcomes were 4-week ulcer healing rate (4-UHR) and the incidence of adverse events (AEs). A network meta-analysis (NMA) using a Bayesian random effects model was conducted, and a cost-effectiveness analysis using a decision tree was performed from the payer's perspective over 1 year. Results: A total of 62 RCTs involving 10,339 participants (eight interventions) were included. The NMA showed that all the PPIs significantly increased the 4-UHR compared to H2 receptor antagonists (H2RA) and placebo, while there was no significant difference for 4-UHR among PPIs. As to the incidence of AEs, no significant difference was observed among PPIs, H2RA, and placebo during 4-week follow-up. Based on the costs of both PPIs and management of AEs in China, the incremental cost-effectiveness ratio per quality-adjusted life year (in US dollars) for pantoprazole, lansoprazole, rabeprazole, and ilaprazole compared to omeprazole corresponded to $5134.67, $17801.67, $25488.31, and $44572.22, respectively. Conclusion: Although the efficacy and tolerance of different PPIs are similar in the initial non-eradication treatment of DU, pantoprazole (40 mg/day) seems to be the most cost-effective option in China.

Epidemiology Characteristics, Methodological Assessment and Reporting of Statistical Analysis of Network Meta-Analyses in the Field of Cancer.

Because of the methodological complexity of network meta-analyses (NMAs), NMAs may be more vulnerable to methodological risks than conventional pair-wise meta-analysis. Our study aims to investigate epidemiology characteristics, conduction of literature search, methodological quality and reporting of statistical analysis process in the field of cancer based on PRISMA extension statement and modified AMSTAR checklist. We identified and included 102 NMAs in the field of cancer. 61 NMAs were conducted using a Bayesian framework. Of them, more than half of NMAs did not report assessment of convergence (60.66%). Inconsistency was assessed in 27.87% of NMAs. Assessment of heterogeneity in traditional meta-analyses was more common (42.62%) than in NMAs (6.56%). Most of NMAs did not report assessment of similarity (86.89%) and did not used GRADE tool to assess quality of evidence (95.08%). 43 NMAs were adjusted indirect comparisons, the methods used were described in 53.49% NMAs. Only 4.65% NMAs described the details of handling of multi group trials and 6.98% described the methods of similarity assessment. The median total AMSTAR-score was 8.00 (IQR: 6.00-8.25). Methodological quality and reporting of statistical analysis did not substantially differ by selected general characteristics. Overall, the quality of NMAs in the field of cancer was generally acceptable.

The assessment of the quality of reporting of systematic reviews/meta-analyses in diagnostic tests published by authors in China.

BACKGROUND: The quality of reporting in systematic reviews (SRs)/meta-analyses (MAs) of diagnostic tests published by authors in China has not been evaluated. The aims of present study are to evaluate the quality of reporting in diagnostic SRs/MAs using the PRISMA statement and determine the changes in the quality of reporting over time. METHODS: According to the inclusion and exclusion criteria, we searched five databases including Chinese Biomedical Literature Database, PubMed, EMBASE, the Cochrane Library, and Web of knowledge, to identify SRs/MAs on diagnostic tests. The searches were conducted on July 14, 2012 and the cut off for inclusion of the SRs/MAs was December 31(st) 2011. The PRISMA statement was used to assess the quality of reporting. Analysis was performed using Excel 2003, RevMan 5. RESULTS: A total of 312 studies were included. Fifteen diseases systems were covered. According to the PRISMA checklist, there had been serious reporting flaws in following items: structured summary (item 2, 22.4%), objectives (item 4, 18.9%), protocol and registration (item 5, 2.6%), risk of bias across studies (item 15, 26.3%), funding (item 27, 28.8%). The subgroup analysis showed that there had been some statistically significant improvement in total compliance for 9 PRISMA items after the PRISMA was released, 6 items were statistically improved regarding funded articles, 3 items were statistically improved for CSCD articles, and there was a statistically significant increase in the proportion of reviews reporting on 22 items for SCI articles (P<0.050). CONCLUSION: The numbers of diagnostic SRs/MAs is increasing annually. The quality of reporting has measurably been improved over the previous years. Unfortunately, there are still many deficiencies in the reporting including protocol and registration, search, risk of bias across studies, and funding. Future Chinese reviewers should address issues on these aspects.