Patient and public involvement in systematic reviews: frequency, determinants, stages, barriers, and dissemination.

OBJECTIVES: To investigate the frequency, determinants, stages, and barriers of patient and public involvement (PPI) in systematic reviews and to explore its association with the dissemination of reviews. STUDY DESIGN AND SETTING: We examined systematic reviews that required the inclusion of a PPI declaration, published in The BMJ between January 1, 2015, and December 31, 2022. Multivariable analysis was used to assess the association between PPI and key variables. We investigated the association between PPI and the dissemination of reviews using Altmetric scores, citations, and full-text views. RESULTS: A total of 217 systematic reviews were included, of which 56 (25.8%, 95% CI 20.0%-31.6%) included PPI, with a steady increase from 5.9% (1/17) in 2015 to 44.4% (4/35) in 2022. Of the 217 systematic reviews, 160 (73.7%) involved methodologists as co-authors. Factors significantly associated with a higher proportion of PPI included the publication year after 2019 (adjusted odds ratio [aOR] 2.46, 95% CI 1.26-4.83), the involvement of methodologist (aOR 3.08; 95% CI 1.27-7.47), and being led by researchers from high-income countries (aOR 5.47; 95% CI 1.23-24.30). Reviews that included PPI had higher Altmetric scores per month (6.6 vs 3.4, P = .002) and more monthly full-text (1048.6 vs 636.5, P < .001) and PDF (217.7 vs 129.0, P < .001) views than reviews without PPI. However, there was no difference in the monthly citations (2.2 vs 2.0, P = .365) between reviews with and without PPI. CONCLUSION: The proportion of systematic reviews reporting PPI in The BMJ has increased over time, possibly due to journal policies, but it still remains at a low level. Reviews led by researchers from high-income countries or involving methodologists are associated with a higher frequency of PPI within The BMJ. Furthermore, reviews incorporating PPI within The BMJ have a higher potential for broad dissemination.

Exploring the diverse definitions of 'evidence': a scoping review.

OBJECTIVES: To systematically collect and analyse diverse definitions of 'evidence' in both health and social sciences, and help users to correctly use the term 'evidence' and rethink what is the definition of 'evidence' in scientific research. DESIGN: Scoping review. METHODS: Definitions of evidence in the health sciences and social sciences were included. We have excluded the definition of evidence applied in the legal field, abstracts without full text, documents not published in either Chinese or English and so on. We established a multidisciplinary working group and systematically searched five electronic databases including Medline, Web of Science, EBSCO, the Chinese Social Sciences Citation Index and the Chinese Science Citation Database from their inception to 26 February 2022. We also searched websites and reviewed the reference lists of the identified studies. Six reviewers working in pairs, independently, selected studies according to the inclusion and exclusion criteria, and extracted information. Any differences were discussed in pairs, and if there was disagreement, it was resolved via discussion or with the help of a third reviewer. Reviewers extracted document characteristics, the original content for the definitions of 'evidence', assessed definitions as either intensional or extensional, and any citations for the given definition. RESULTS: Forty-nine documents were finally included after screening, and 68 definitions were obtained. After excluding duplicates, a total of 54 different definitions of 'evidence' were identified. There were 42 intensional definitions and 12 extensional definitions. The top three definiens were 'information', 'fact' and 'research/study'. The definition of 'evidence' differed between health and social sciences. The term 'research' appeared most frequently in the definitions. CONCLUSIONS: The definition of 'evidence' has gradually attracted the attention of many scholars and decision-makers in health and social sciences. Nevertheless, there is no widely recognised and accepted definition in scientific research. Given the wide use of the term, we need to think about whether, or under what circumstances, a standardised, clear, meaningful and widely applicable definition of 'evidence' might be helpful.

Various application roles for Campbell systematic reviews: a citation analysis.

OBJECTIVES: Systematic reviews (SRs) are becoming essential evidence in the decision-making process within the field of social sciences. This study aimed to investigate how Campbell SRs were cited and explore their specific application roles. STUDY DESIGN AND SETTING: We included Campbell SRs published between 2016 and 2020 by searching the Wiley online library, and retrieved the articles and documents citing Campbell SRs from the Web of Science and Google Scholar by December 31, 2021. We described the characteristics of the SRs and citations, and formulated a set of application roles by analyzing the sentences or paragraphs where the SRs were cited. RESULTS: Sixty nine Campbell SRs were published between 2016 and 2020; they were cited in 641 articles or documents a total of 1,289 times. The primary types of articles that cited Campbell SRs were cross-sectional studies (n = 226, 35.3%), SRs (n = 112, 17.5%), randomized controlled trials (n = 77, 12.0%), and policy reports (n = 57, 8.8%). Articles utilizing Campbell SRs were predominantly led by authors from the United States (n = 184, 28.7%), the United Kingdom (n = 98, 15.3%), and Australia (n = 51, 8.0%). We formulated a set of 10 application roles for the Campbell SRs, of which the most frequent were: describing the current status in the field of interest (n = 691, 53.6%), corroboration of the results (n = 140, 10.9%), identifying research gaps (n = 130, 10.1%), and providing methodological references (n = 126, 9.8%); the role of supporting policy recommendations or decisions accounted for 6.0% (n = 77) of the citations. Approximately 12% of Campbell SRs were used to support policy recommendations or decisions. CONCLUSION: Campbell SRs are widely applied, particularly in scientific research, to describe the current status in the field of interest. Although the current application of Campbell SRs in supporting policy recommendations and decisions may not be predominant, there is a growing recognition of their value in using Campbell SRs to inform decision-making.

Risk factors for metachronous esophageal squamous cell carcinoma after endoscopic or surgical resection of esophageal carcinoma: a systematic review and meta-analysis.

Background: early-stage esophageal carcinoma (EC) patients lack typical clinical signs and symptoms and are often diagnosed and treated at a late stage, leading to a poor prognosis and a high incidence of metachronous esophageal squamous cell carcinoma (MESCC) and second primary carcinoma (SPC). The aims of the review were to identify and quantify risk factors for MESCC and analysis location of SPC in postoperative patients with EC; to predict incidence of MESCC over follow-up time. Methods: an electronic search of studies reporting potential risk factors, the incidence of MESCC, and the location of SPC were performed on PubMed, Web of Science, Cochrane Library, Embase, and Scopus from inception to 10 November 2022. The Newcastle-Ottawa scale was used to assess the study quality, and the qualitative strength of evidence rating of all items was provided. The meta-regression model was used to predict the incidence of MESCC over follow-up time, the location distribution of SPC was presented using clustered column chart, while the publication bias was assessed using funnel plots and Egger's test. Results: smoking, age, history of multiple other cancer, and Lugol-voiding lesions (LVLs) were determined to be the risk factors of MESCC. LVLs were qualitatively determined as "definite" and the history of multiple other cancer as "likely." The overall pooled MESCC incidence was 20.3% (95% CI: 13.8% to 26.8%), with an increase of 0.20% for each additional year of follow-up. The head and neck were the most common locations for SPC, followed by the esophagus. Conclusion: timely investigating the age of patients, previous history of cancer and monitoring the number of LVLs in the first 5 years after operation are of great significance to identify high-risk populations of MESCC for timely medical care. Education and behavior correction about smoking are advocated. Tumor markers should be regularly detected in the head and neck, esophagus, and stomach. Endoscopic resection was associated with a higher incidence of MESCC, which provided a reference for doctors to choose the removal method. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022377030.

How about the evidence assessment tools used in education and management systematic reviews?

Objectives: To systematically analyze the use of evidence assessment tools in systematic reviews of management and education. Study design and setting: We systematically searched selected literature databases and websites to identify systematic reviews on management and education. We extracted general information of the included studies and information about the evidence assessment tool they applied, including whether it was used for methodological quality assessment, reporting quality assessment or evidence grading, as well as the name, reference, publication year, version and original intended use of the tool, the role of the tool in the systematic review, and whether the quality determination criteria were given. Results: A total of 299 systematic reviews were included, of which only 34.8% used evidence assessment tools. A total of 66 different evidence assessment tools were used, of which Risk of Bias (ROB) and its updated version (n = 16, 15.4%) were the most frequent. The specific roles of the evidence assessment tools were reported clearly in 57 reviews, and 27 reviews used two tools. Conclusion: Evidence assessment tools were seldom used in systematic reviews in social sciences. The understanding and reporting of evidence assessment tools among the researchers and users still needs improvement.

Is short-term and long-term exposure to black carbon associated with cardiovascular and respiratory diseases? A systematic review and meta-analysis based on evidence reliability.

OBJECTIVE: Adverse health effects of fine particles (particulate matter2.5) have been well documented by a series of studies. However, evidences on the impacts of black carbon (BC) or elemental carbon (EC) on health are limited. The objectives were (1) to explored the effects of BC and EC on cardiovascular and respiratory morbidity and mortality, and (2) to verified the reliability of the meta-analysis by drawing p value plots. DESIGN: The systematic review and meta-analysis using adapted Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach and p value plots approach. DATA SOURCES: PubMed, Embase and Web of Science were searched from inception to 19 July 2021. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Time series, case cross-over and cohort studies that evaluated the associations between BC/EC on cardiovascular or respiratory morbidity or mortality were included. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently selected studies, extracted data and assessed risk of bias. Outcomes were analysed via a random effects model and reported as relative risk (RR) with 95% CI. The certainty of evidences was assessed by adapted GRADE. The reliabilities of meta-analyses were analysed by p value plots. RESULTS: Seventy studies met our inclusion criteria. (1) Short-term exposure to BC/EC was associated with 1.6% (95% CI 0.4% to 2.8%) increase in cardiovascular diseases per 1 µg/m3 in the elderly; (2) Long-term exposure to BC/EC was associated with 6.8% (95% CI 0.4% to 13.5%) increase in cardiovascular diseases and (3) The p value plot indicated that the association between BC/EC and respiratory diseases was consistent with randomness. CONCLUSIONS: Both short-term and long-term exposures to BC/EC were related with cardiovascular diseases. However, the impact of BC/EC on respiratory diseases did not present consistent evidence and further investigations are required. PROSPERO REGISTRATION NUMBER: CRD42020186244.

COVID-19 vaccine guidelines was numerous in quantity but many lack transparent reporting of methodological practices.

OBJECTIVE: To describe the current status of COVID-19 vaccine guidelines. STUDY DESIGN AND SETTING: We searched databases, Google and guideline platforms to retrieve COVID-19 vaccine guidelines published between January 1, 2020 and July 8, 2021. We worked in pairs to identify the eligible guidelines and extract data of whether the methodology, funding, and conflict of interests were assessed/reported, and so on. Results were presented descriptively. RESULTS: A total of 106 COVID-19 vaccine guidelines were included. In the first half of 2021, on average 15 guidelines were published every month. Fifty (47.2%) guidelines addressed the vaccination of people with specific medical conditions, and 18 (17.0%) guidelines focused on adverse effects after vaccination. Only 28 (26.4%) guidelines reported the methodology they used. Four (3.8%) of guidelines assessed both the quality of evidence and strength of recommendations; 42 (39.6%) and 65 (61.3%) guidelines reported their funding sources and conflict of interest, respectively. Most guidelines were published in English (n = 92, 86.8%). CONCLUSION: A high number of guidelines on COVID-19 vaccines have been published in the recent months, but most of them lack clear and transparent reporting of methodology, funding, and conflicts of interest. Rigorous methodological and reporting quality evaluation of these guidelines is needed.

A quality evaluation of guidelines on five different viruses causing public health emergencies of international concern.

This project aims to evaluate the methods and reporting quality of practice guidelines of five different viruses that have caused Public Health Emergencies of International Concern (PHEIC) over 20 past years: the severe acute respiratory syndrome coronavirus (SARS-CoV), Ebola virus, Middle East respiratory syndrome coronavirus (MERS-CoV), Zika virus and the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We systematically searched databases, guideline websites and government health agency websites from their inception to February 02, 2020 to extract practice guidelines for SARS-CoV, Ebola virus, MERS-CoV, Zika virus, SARS-CoV-2 and the diseases they caused. The literature was screened independently by four researchers. Then, fifteen researchers evaluated the quality of included guidelines using the AGREE-II (Appraisal of Guidelines for Research and Evaluation II, for methodological quality) instrument and RIGHT (Reporting Items for practice Guidelines in Healthcare, for reporting quality) statement. Finally, a total of 81 guidelines were included, including 21 SARS-CoV guidelines, 11 Ebola virus (EBOV) guidelines, 9 MERS-CoV guidelines, 10 Zika Virus guidelines and 30 SARS-CoV-2 guidelines. The evaluation of the methodological quality indicated that the mean scores of each domain for guidelines of each virus were all below 60%, the scores for guidelines in the domains of "clarity of presentation" being the highest and in the "editorial independence" lowest. The mean reporting rate of each domain for guidelines of each virus was also less than 60%: the reporting rates for the domain "background" were highest, and for the domain "funding and interests" lowest. The methodological and reporting quality of the practice guidelines for SARS-CoV, Ebola virus, MERS-CoV, Zika virus and SARS-CoV-2 guidelines tend to be low. We recommend to follow evidence-based methodology and the RIGHT statement on reporting when developing guidelines.

Ilexgenin A exerts anti-inflammation and anti-angiogenesis effects through inhibition of STAT3 and PI3K pathways and exhibits synergistic effects with Sorafenib on hepatoma growth.

Recently, we reported that Ilexgenin A exhibits anti-cancer activities and induces cell arrest. Here, we investigated the effect of Ilexgenin A on the inflammation, angiogenesis and tumor growth of hepatocellular carcinoma (HCC). Our current study revealed that Ilexgenin A significantly inhibited the inflammatory cytokines TNF-α and IL-6 levels and downregulated pro-angiogenic factor VEGF production and transcription in HepG2 cells. The underlying mechanism for Ilexgenin A effects appears to be through inhibiting STAT3 and PI3K pathways. Furthermore, we found that not only Ilexgenin A inhibited STAT3 and PI3K pathways in HepG2 cells but also blocked these signaling pathways in HUVECs. Most importantly, by employing two HCC xenografts models - HepG2 and H22, we showed that Ilexgenin A reduced tumor growth and exhibited synergy effect with Sorafenib. ELISA assay, histological analysis and immunohistochemistry examination revealed that the expression of VEGF and MVD was significantly decreased after the treatment with Ilexgenin A and the combination. Moreover, Ilexgenin A could enhance caspase-3/7 activity in vitro and transmission electron microscope indicated that the combination induced evident apoptosis of tumor cells and caused the structural changes of mitochondria in vivo. Although no apparent adverse effects occurred during the treatment period, Sorafenib monotherapy elicited hepatotoxicity for specific expression in the increased level of AST and the ratio of AST/ALT. However, the combination could remedy this adverse effect. In conclusion, the results described in the present study identifies Ilexgenin A as a promising therapeutic candidate that modulates inflammation, angiogenesis, and HCC growth.

A novel pentacyclic triterpenoid, Ilexgenin A, shows reduction of atherosclerosis in apolipoprotein E deficient mice.

Ilexgenin A (IA), a novel pentacyclic triterpenoid, is a compound extracted from leaves of Ilex hainanensis Merr. In this study, we explored the efficacy of IA on atherosclerosis and its underlying mechanism. We determined that treatment with IA attenuated atherosclerosis in high-fat diet-induced apolipoprotein E deficient mice via a series of effects involving regulation of lipid parameters, decrease of atherosclerosis-related indexes, inhibition of inflammatory cytokines secretion and pathological changes of main organs. Furthermore, the underlying mechanism of IA was investigated on oxidized low-density lipoprotein (Ox-LDL)-induced THP-1 cells. We showed that pre-treatment with IA decreased active inflammation cytokines involving interleukin-6 (IL-6), IL-1 and tumor necrosis factor-α (TNF-α) expression in a concentration-dependent manner. In addition, we confirmed that IA inhibited the phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), IKKα phosphorylation and NF-κB activity induced by Ox-LDL. Overall, these findings define IA as a novel drug candidate for anti-atherosclerotic therapy.

Effects of Xuezhikang in patients with dyslipidemia: a multicenter, randomized, placebo-controlled study.

BACKGROUND: Xuezhikang (XZK) is an extract of fermented red yeast rice that has lipid-lowering properties. OBJECTIVE: To evaluate the effects of XZK on lipids in subjects with dyslipidemia but no coronary heart disease. METHODS: A total of 116 adults with baseline non-high-density lipoprotein cholesterol (non-HDL-C) levels of approximately 208 mg/dL and low-density lipoprotein cholesterol (LDL-C) levels of approximately 175 mg/dL were randomized to either placebo or XZK 1200 or 2400 mg daily and treated for 12 weeks. RESULTS: A majority of the patients were white (53.4%) or Asian (37.1%). Daily XZK 1200 mg and 2400 mg for 4 to 12 weeks resulted in statistically significant (P < .001) and clinically meaningful decreases in non-HDL-C (∼24% reduction) and LDL-C (∼27% reduction) compared with placebo. XZK treatment at either dose enabled approximately 50% of subjects to reduce their LDL-C levels by ≥ 30%. Doubling the XZK daily dose from 1200 to 2400 mg at treatment week 8 caused an additional 4.6% reduction in LDL-C. Significant benefits were also observed across secondary efficacy variables, including total cholesterol (TC), apolipoprotein B (Apo B), triglycerides, HDL-C, the TC/HDL-C ratio, and the Apo B/Apo A-I ratio, at treatment week 8 or 12. XZK was safe and well tolerated. Safety and tolerability profiles were similar across treatment groups. Most adverse events were gastrointestinal. No subject experienced myopathy or markedly elevated liver transaminases or creatine kinase. CONCLUSION: Xuezhikang significantly reduced non-HDL-C and LDL-C, and was well tolerated. Further, longer-term studies in more diverse patient populations are needed to corroborate these findings.

A water-soluble inclusion complex of pedunculoside with the polymer ß-cyclodextrin: a novel anti-inflammation agent with low toxicity.

More than 50% of new drug candidates in drug discovery are lipophilic and exhibit poor aqueous solubility, which results in poor bioavailability and a lack of dose proportionality. Here, we improved the solubility of pedunculoside (PE) by generating a water-soluble inclusion complex composed of PE and the polymer ß-cyclodextrin (CDP). We characterized this novel complex by 1H NMR, FT-IR, UV-vis spectroscopy, powder X-ray diffractometry and thermogravimetric analysis. The ratio of ß-cyclodextrin (ß-CD) units in CDP to PE was determined to be 2∶1. The KD value of the inclusion complex was determined to be 4.29×10(-3) mol•L(-1). In contrast to the low solubility of PE, the water-solubility of the PE-CDP complex was greatly enhanced. A preclinical toxicological study indicated that PE-CDP was well tolerated for a single administration. Importantly, the anti-inflammation potency of the PE-CDP complex was higher than that of PE. As a result, the formation of inclusion complexes by water-soluble CDP opens up possible aqueous applications of insoluble drug candidates in drug delivery.

[Latent structure model evaluation of syndrome elements and features in 826 hypertriglyceridemia patients].

OBJECTIVE: To evaluate main Chinese medical syndrome elements and features of hypertriglyceridemia patients. METHODS: Using latent structure model (LSM) method, the latent structure diagram of 826 hypertriglyceridemia patients were established. Hypertriglyceridemia syndrome elements and features were interpreted by using latent probability, conditional probability, mutual information, and cumulative information coverage to quantify symptoms/syndromes data,as well as using manual interpretation methods. RESULTS: The accumulative information coverage rate reaching 95% was taken as the judgment standard for major syndrome elements. In the 826 hypertriglyceridemia patients, moderate and severe symptoms/syndromes (with the latent probability being 35% and 60% respectively) were dominant. The syndrome elements mainly included qi deficiency, qi stagnation,fire heat, stasis blood, yin deficiency, and yang deficiency. The main targets were dominated in Xin, Gan, and Shen. CONCLUSION: LSM based syndrome element evaluation method could quantify the association degree of each variable (syndrome element; Chinese medical symptoms) and the occurrence probability.