PONE-D-24-45820Clinical Efficacy and Safety of Manipulation on Chronic Ankle Sprains: A Systematic Review and Meta-AnalysisPLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Partly

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: No

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The manuscript provides a systematic review and meta-analysis evaluating the efficacy and safety of manipulation techniques for chronic ankle sprains (CAS). The authors identified 13 studies with a total of 984 cases and performed robust statistical analyses using established tools such as RevMan 5.4 and GRADE. The study addresses a relevant topic with potential clinical impact. However, several areas require clarification and improvement before the manuscript can be considered for publication as following:

- While the authors mention the low methodological quality of the included studies, a more detailed discussion on how this impacts the findings would strengthen the conclusions. Suggestions for mitigating these limitations in future research should also be included. For example, advocating for double-blinded, sham-controlled RCTs with larger sample sizes.

- The substantial heterogeneity in outcomes like the Visual Analogue Scale (VAS) and Baird-Jackson Ankle Score is acknowledged. However, further exploration into the sources of this variability (e.g., differences in manipulation techniques or adjunctive therapies) is needed. This could improve the robustness of the conclusions.

- The manuscript states that the certainty of evidence was low or very low for most outcomes. Including a table summarizing the GRADE results for each outcome would improve the presentation and allow readers to understand the evidence hierarchy better.

- Although no significant adverse events were reported, it would be valuable to discuss whether the sample size is sufficient to detect rare but serious side effects. This could strengthen the statement regarding safety.

- The search strategy and inclusion/exclusion criteria are well described. However, the authors should provide the full search string in a supplementary table to ensure reproducibility.

- The manuscript notes that publication bias could not be evaluated due to the small number of studies. A funnel plot or sensitivity analysis (even with limitations) might provide additional insights.

- The manuscript contains minor grammatical errors and awkward phrasing. For example, "timely and appropriate intervention can effectively reduce the long-term consequences" could be rephrased for clarity. also, in introduction 5th line (long term) was duplicated.

- The figures (e.g., forest plots) are informative but require clearer labeling to enhance readability. The PRISMA flowchart is helpful but should specify reasons for exclusion more succinctly. Tables 1,2 &3 were missed in the pdf file, so I can not review tables.

- The meta-analytic outcomes for the primary and secondary measures are well presented but could be enhanced by briefly summarizing them in the discussion section.

Reviewer #2: Introduction

o The study does not provide a clear definition of chronic ankle sprain. Does this refer to chronic ankle instability? Is it ethical to perform manipulation on ankle sprains, which are typically in the inflammatory stage? What is the intended purpose of manipulation in these cases? If the goal is to improve range of motion, why is this technique being applied to ankle sprains in the inflammatory stage?

o In the sentence of “if left untreated, mistreated, or excercise improperly, the ankle joint may develop continuous localized swelling and scar tissue formation, leading to long term long-term pain, limited mobility, and eventually, chronic ankle sprain (CAS)”, correct the typo 'excercise' to 'exercise' and revise the sentence to eliminate the repeated phrase 'long term long-term.'

o You might elaborate briefly on the benefits or limitations of each conservative treatment mentioned to provide a more balanced overview.

o Clarify what specific benefits manipulation offers compared to other treatments and whether it is supported by modern medical guidelines.

o In the sentence of “Although several clinical studies have evaluated the effectiveness of manipulation in improving CAS, there is still a lack of high-quality evidence to convince the broader medical community of its efficacy, suggest specifying what 'high-quality evidence' entails, such as randomized controlled trials, systematic reviews, or meta-analyses.

Method

o Are there limited keywords used in search strategies?

o Provide the syntax used.

Result - Study Characteristics

o Clarify what "manipulation" entails. Is it a specific manual therapy technique? Defining this term will enhance understanding.

o Provide more context or examples of the "external application of traditional Chinese medicine" for readers unfamiliar with these methods.

o "Among the outcome indicators, 10 studies...reported VAS", expand on what VAS, Baird-Jackson Ankle Score, AOFAS Ankle Hindfoot Scale, and CER measure. Brief descriptions will help readers interpret the findings.

o Provide explanations about control groups such as herbal fumigation, herbal compress.

o What is the difference between functional exercise and physical therapy?

o Correct the typo "hherapy" to "therapy."

o Consider restructuring the sentence for smoother readability, such as: "In three studies [17,19,22], the treatment group received manipulation combined with functional exercises."

Bias Risk Assessment

o In the sentence of "Four studies...reported lost visit data, but all offered clear explanations for the losses and their treatment.", clarify whether the treatment of lost visit data (e.g., imputation methods) was appropriate and how it might impact the results.

o In the sentence of "thereby elevating the potential for performance bias.", consider rephrasing for smoother flow, e.g., "which may have increased the risk of performance bias."

Discussion

o Consider restructuring the opening sentence for better clarity and impact. For example, directly state the key findings instead of introducing the analysis.

o In the sentence of "Moderate-quality evidence revealed that manipulation, both as a standalone treatment and when combined with other conservative therapies...", clarify the meaning of "moderate-quality evidence" by referencing the criteria used (e.g., GRADE).

o In the sentence of "This finding aligns well with previous systematic reviews, particularly the study conducted by Yang [23]..., provide a brief summary of Yang's study to contextualize its relevance.

o In the sentence of "Manipulation could correctly readjust misaligned ankle joints and restore displaced tendons and tissues...", ensure that this claim is adequately supported by referenced studies or data. If speculative, indicate as such.

o In the sentence of "Although rated as poor quality evidence, our systematic reviews suggested that manipulation...", clarify why this evidence is rated as "poor quality" and how this impacts the strength of the conclusions.

o In the sentence of "The specifics of manipulation techniques, including movement type, force, angle, and duration...", suggest that future studies document these parameters in detail to improve reproducibility and understanding of the intervention's effects.

o In the sentence of "The primary limitation of this review lies in the suboptimal methodological quality of the included studies.", suggest adding a specific example of how this limitation affected the conclusions, such as the impact of missing data or lack of blinding.

o In this sentence of "This corrective action not only alleviates pain and discomfort but also promotes healing and recovery.", consider breaking up longer sentences for improved readability.

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Reviewer #1: No

Reviewer #2: No

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Efficacy and safety of Tuina (Chinese Therapeutic Massage) for Chronic Ankle Instability: A Systematic Review and Meta-Analysis of randomized controlled trials

PONE-D-24-45820R1

Dear Dr. Huang,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

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Nan Jiang

Academic Editor

PLOS ONE

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #2: Yes

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: Yes

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4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #2: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #2: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: Thank you for addressing my comments effectively. I appreciate the thoughtful revisions, which have significantly improved the clarity and quality of the manuscript. The changes have been well implemented, and I have no further concerns.

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean? ). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy .

Reviewer #2: No

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