Efficacy and Safety of Minocycline-Containing Bismuth Quadruple Therapies Versus Standard First-Line Bismuth Quadruple Therapies for Helicobacter pylori Eradication: A Systematic Review and Meta-Analysis

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The manucript presents the effect of minocycline containing quadruple therapy compared rto traditional regimen. I have the following concerns:

1,.For understanding by the common readers, it is not sufficient to give the ORs and CI: the rates of eradication must be given in percentages and the difference between the groups also must be calculated

2. The results are hindered by low number of cases and high heterogeneity in some subgroups

3.Trivial data from the interoduiction section could be deleted

4.It seems that parts of discussion section are included into result section

5. Graham, coined a simple grading scale for assessment of erasdication results. If usded, it seems clear, that minocycline does not add many to the rates, most of results does nopc achieve results over,90.-95%, grqaeed good or excellent.

6. H. pylori must be written wirth aldine in all places  

7. Availability and price of minocycline as compared to standard regimens should be mentioned, because unfortunately, some, if not most of efficient therapies have only very limited availability (capsule treatment, bismuth preparation, tetracycline, potassium channel inhibitors as vonoprazan or even amoxicillin! etc)

8. If accepted as superior to BQTs, to whom recommend the authors minocycline-based quadruple therapies? (First-line? rescue? cultured-oriented or  personalized treatment? diagnosis-oriented treatment, i.e. peptic ulcer only?) 

Comments on the Quality of English Language

The reviewer is not a native English speaker 

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

Manuscript ID	:	idr-4045296
Manuscript Title	:	Efficacy and Safety of Minocycline-containing Bismuth Quadruple Therapies Versus Standard First-Line Bismuth Quadruple Therapies for Helicobacter pylori Eradication: A Systematic Review and Meta-Analysis
Reviewer	:

 

Comments

This manuscript addresses an important and clinically relevant question regarding the role of minocycline-containing bismuth quadruple therapy (MBQT) as an alternative to conventional bismuth quadruple therapy (BQT) for H. pylori eradication. However, several critical issues need to be addressed to improve the clarity, methodological transparency, and interpretability of the findings. Overall, revisions are needed to ensure that conclusions are appropriately aligned with the presented evidence and that limitations are clearly acknowledged. Detailed comments are provided below.

 

Introduction

1. In line 85-103, the authors elaborated on the comparison of conventional BQT to MBQT. However, the explanation was not balanced because the concern of conventional BQT is the availability of tetracycline and its adverse effects. However, the prominent explanation of MBQT was its efficacy, with minimal explanation of adverse events and no explanation of the availibility of minocycline in comparison to tetracycline. Please add more explanation about the availibility of minocycline.
2. In the result section, there are variation of antibiotics that were used in the comparator group that was not yet elaborated in the introduction, the explanation of limitation of the current antibiotics in the BQT protocol may increase the clarity of the importance of this study (not only focusing on tetracycline and minocycline)
3. In line 104-107, the authors explained the non-inferiority of MBQT to tetracycline-based regimens from a meta-analysis that cited reference number 14. However, the reference was referred to the protocol of systematic review and meta-analysis with no result. Please ensure this explanation and reference.
4. In addition to antibiotics, it is also important to elaborate on anti-acid therapy in the introduction.

 

Methods

5. In line 129-138, please add the exclusion criteria and the language limitation (i.e. only included the studies that published in English)
6. In line 201, the safety is equal to the incidence of adverse events, therefore, it should be “… efficacy and safety (incidence of adverse events).”
7. In line 201-203, the definition of intention-to-treat (ITT), modified ITT, and per-protocol (PP) analysis should be elaborated to prevent the misinterpretation and improve the clarity of the objectives of this study
8. To increase the elaboration of the results, it is recommended that the pooled size effect of the compliance rate be included in this study.
9. In line 203-206, the definition of “total adverse events” should be mentioned clearly, because the meta-analysis only evaluated the total adverse events (minimal one of the adverse events that was listed).
10. Please elaborate on the plan to evaluate the high heterogeneity, study with high risk of bias, and high publication bias (including why Egger’s regression test for publication bias was not conducted in this study) that may have altered the interpretation of the result of the pooled effect size.

 

Results

11. In line 228-234, please add the summary protocol (country, intervention group, comparator group, duration of the therapy) used in the included studies to elaborate the variation of the protocol, particularly in the comparator group.
12. The pooled size effect of the mITT result is not interpretable because it only consists of two studies with very wide confidence intervals and high heterogeneity, which may alter the interpretation. It is recommended to focus on ITT analysis and mIT analysis. The difference in the definition and objective of ITT and mITT should be elaborated first in the methods.
13. The efficacy of the intervention protocol was significantly higher in PP analysis but without a significant difference in ITT analysis and adverse events rate. This result should be extended by evaluating the compliance rate of the intervention and comparator groups.
14. In line 309-311, please change the sentence to directly interpret the result as not significantly different even if the OR is 0.81, because the confidence interval was crossing over the value of 1.
15. The interpretation of the result at line 313-315 should be revised because the safety outcome is not significantly different, and the significant result was only from the PP analysis.
16. Please add another analysis to evaluate the effect of the high-risk bias studies.

 

Discussion

17. The statement in line 330-334 should be revised because the ITT analysis is not significantly different and the significant result was only from the PP analysis.
18. Line 364-365 are not coherent with the prior explanation of the high risk of dizziness and vestibular and neurologic adverse events. In addition, the pooled size effect of adverse event analysis in this study was based on the total adverse events.
19. In line 372-374 and 399-402, the authors explained the result of another analysis that was not included in the results section. Please provide and interpret the data in the Results section.
20. In line 372-380, the authors argue that the possible mechanism of diarrhea reduction was caused by the alteration of gut microbiota composition, however, this statement should be based on recent study, please add the reference of this statement.
21. Please add a discussion about the compliance comparison between MBQT and conventional BQT.
22. Line 415-416 should be explained with reference.
23. Line 417-421 should be revised carefully. The background of tailoring treatment for pylori eradication regimens in the Maastricht VI/Florence consensus was to use antibiotics based on antimicrobial susceptibility tests. The statement from Maastricht VI/Florence is not coherent with the next suggestion to consider minocycline as a substitute for tetracycline.

 

Conclusion

24. In line 423-425, please specify the “effective” based on PP analysis.
25. Please explain the limitations in interpreting the results of this study in the Conclusion.

 

 

 

Comments for author File: Comments.pdf

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

None

Author Response

There are no reviewer comments to address