This paper briefly introduces the definition, classification and significance of effect modification in epidemiological studies, summarizes the difference between effect modifier and confounders, and analyze the influence as well as the role of effect modification in epidemiological studies and Meta-analysis. In this paper, the possible scenarios of effect modification and related analysis strategy in Meta-analysis are indicated by graphics, aiming to arouse researchers' attention to effect modification. This paper also demonstrates how to identify and deal with effect modification in Meta-analysis through a study case of "Efficacy of sodium-glucose cotransporter 2 inhibitors in patients with type 2 diabetes", and shows the analysis process and interpretation of results of subgroup analysis and Meta-regression methods respectively. The advantages and disadvantages of these two methods are summarized to provide reference for the method selection of future research.

This paper briefly introduces the characteristics, research significance, and global reporting status of effect modification in network Meta-analysis, demonstrates the heterogeneity caused by effect modification in network Meta-analysis, and emphasizes the importance of exploring effect modification in network Meta-analysis. This paper also summarizes the normalized description and analysis strategies of effect modification in network Meta-analysis. Finally, by the case of "comparison of efficacy of three new hypoglycemic drugs in reducing body weight in type 2 diabetes patients", this paper demonstrates the realization of subgroup analysis and network Meta-regression in exploring effect modification, summarizes the advantages and disadvantages of the two methods, to provide references for future researchers.

Objective:Differences between randomized controlled trial (RCT) results and real world study (RWS) results may not represent a true efficacy-effectiveness gap because efficacy-effectiveness gap estimates may be biased when RWS and RCT differ significantly in study design or when there is bias in RWS result estimation. Secondly, when there is an efficacy- effectiveness gap, it should not treat every patient the same way but assess the real-world factors influencing the intervention's effectiveness and identify the subgroup likely to achieve the desired effect.Methods:Six databases (PubMed, Embase, Web of Science, CNKI, Wanfang Data, and VIP) were searched up to 31 st December 2022 with detailed search strategies. A scoping review method was used to integrate and qualitatively describe the included literature inductively. Results:Ten articles were included to discuss how to use the RCT research protocol as a template to develop the corresponding RWS research protocol. Moreover, based on correctly estimating the efficacy-effectiveness gap, evaluate the intervention effect in the patient subgroup to confirm the subgroup that can achieve the expected benefit-risk ratio to bridge the efficacy-effectiveness gap.Conclusion:Using real-world data to simulate key features of randomized controlled clinical trial study design can improve the authenticity and effectiveness of study results and bridge the efficacy-effectiveness gap.

This paper briefly introduces the unique advantages, overall analysis ideas and existing analysis methods of individual patient data Meta-analysis in terms of effect modification. In addition to Meta-regression and subgroup analysis, this paper also introduces the analysis methods based on part of individual patient data integrated with aggregated data and summarizes the current reporting of the above mentioned methods. In addition, the application and results interpretation of the above mentioned methods in individual patient data Meta-analysis are presented in this paper by taking "Effects of sodium-glucose cotransporter 2 inhibitors on SBP in patients with type 2 diabetes" as an example and by introducing their advantages and limitations.

Objective:Randomized controlled trials (RCT) usually have strict implementation criteria. The included subjects' characteristics of the conditions for the intervention implementation are quite different from the actual clinical environment, resulting in discrepancies between the risk-benefit of interventions in actual clinical use and the risk-benefit shown in RCT. Therefore, some methods are needed to enhance the extrapolation of RCT results to evaluate the real effects of drugs in real people and clinical practice settings.Methods:Six databases (PubMed, Embase, Web of Science, CNKI, Wanfang Data, and VIP) were searched up to 31 st December 2022 with detailed search strategies. A scoping review method was used to integrate and qualitatively describe the included literature inductively. Results:A total of 12 articles were included. Three methods in the included literature focused on: ①improving the design of traditional RCT to increase population representation; ②combining RCT Data with real-world data (RWD) for analysis;③calibrating RCT results according to real-world patient characteristics.Conclusions:Improving the design of RCT to enhance the population representation can improve the extrapolation of the results of RCT. Combining RCT data with RWD can give full play to the advantages of data from different sources; the results of the RCT were calibrated against real-world population characteristics so that the effects of interventions in real-world patient populations can be predicted.

This paper introduces the conducting systematic reviews and Meta-analyses of observational studies of etiology (COSMOS-E) and illustrates the critical issues of COSMOS-E with a published systematic review. This document provides researchers with guidance on all steps in systematic reviews of observational studies of etiology, from shaping the research question, defining exposure and outcomes, to assessing the risk of bias and statistical analysis.

Comprehensive interventions have been widely used in health system, public health, education and communities and have become increasingly focus of systematic reviews. There have been many reporting guidelines about systematic reviews, but they do not take the features of comprehensive interventions in medical area into consideration. As a result, PRISMA-CI has been developed as an extension of PRISMA, which adds or modifies the essential items of PRISMA. This paper introduces the items of PRISMA-CI and explains the items with an example to help authors, publishers, and readers understand PRISMA-CI and use it in systematic reviews on comprehensive interventions. As it become more and more popular with comprehensive interventions, PRISMA-CI will provide important structure and guidance for its systematic review and Meta-analysis.

Objective To compare the clinical outcomes of mini-invasive plate osteosynthesis ( MIPO ) and conventional open plating for complex fractures of midshaft clavicle. Methods The authors retrospec-tively reviewed the data of complex fractures of midshaft clavicle ( AO/OTA types 15-B2 and 15-B3 ) which had been treated with MIPO or conventional open plating between January 2010 to February 2016. Forty-one patients were treated with MIPO and 43 with conventional open plating. The 2 groups were compared in terms of incision length, hospital stay, bone union time, postoperative Constant score and Disabilities of the Arm, Shoulder and Hand ( DASH ) score, patients'satisfaction and complications. Results The average follow-up was 21. 2 ± 9. 2 months for MIPO group and 23. 1 ± 11. 8 months for conventional open plating group. The incision length ( 4. 3 ± 0. 5 cm ) , hospital stay ( 7. 7 ± 1. 9 d ) and union time ( 10. 6 ± 3. 2 w ) in the MIPO group were signifi-cantly shorter than those in the conventional open plating group ( 8. 4 ± 1. 3 cm, 9. 6 ± 3. 1 d and 12. 3 ± 3. 9 w, respectively ) ( P <0. 05 ) . The MIPO group had significantly lower incidences of hypertrophic scarring and dysesthesia in the area of incision but significantly higher patients'satisfaction than the conventional open plating group ( P <0. 05 ) . There were no significant differences in the Constant score or DASH score at 3 months, 6 months and the final follow-up ( P > 0. 05 ) . Conclusion In the treatment of complex fractures of midshaft clavicle, although both MIPO and conventional open plating can lead to similar functional outcomes, MIPO may be advantageous over conventional open plating in smaller surgical incision, more rapid fracture union, shorter hospital stay and higher patients'satisfaction.

Objective To evaluate the clinical outcomes of split fractures of humeral greater tuberosity treated by our self-designed new type of anatomical locking plate.Methods From September 2012 to February 2017,23 patients were treated for acute split fracture of the humeral greater tuberosity using our self-designed new type of anatomical locking plate.They were 13 males and 10 females with a mean age of 52.8 years (range,from 25 to 81 years).Of them,6 were beyond 60 years old, 12 had comminuted fracture,10 were complicated with glenohumeral dislocation,and 12 with rotator cuff tear.The patients were evaluated clinically with Constant-Murley score,visual analog scale (VAS),range of motion and complications at the last follow-ups.Results This series were followed up for 12 to 30 months (mean,23.2 months).All the fractures healed after an average time of 10.6 weeks (range,from 8 to 12 weeks).Their mean Constant-Murley Score was 92.1 points (range,from 70 to 100 points),giving an excellent and good rate of 95.7％ (22/23);their VAS scores averaged 0.8 points (range,from 0 to 4 points).Their forward flexion averaged 160.6°,abduction 157.8°,external rotation 46.4°,and internal rotation up to the T11 level,respectively.Their complications rate was 17.4％ (4/23).One case of axillary nerve injury,one case of relapse of glenohumeral dislocation at sports,and 2 cases of stiff shoulder were observed.Conclusion Split fractures of the humeral greater tuberosity can be successfully treated with our new type of anatomical locking plate which serves as a new alternative treatment.

This paper reviews the concept of risk of bias,followed by demonstrating why assessment of risk of bias in systematic reviews should be different from that of quality of evidence,methodological quality,reporting quality,precision,and external validity.We also discuss the recent development of tools for risk of bias assessment,the problems with the tools themselves,and the challenges in using these tools.This review may help systematic reviewers understand risk of bias assessment and the use of assessment tools.