PONE-D-22-20609Evaluation of Triclosan Coated Suture in Obstetrical Surgery: A Prospective Randomized Controlled StudyPLOS ONE

Dear Dr. BETTAIEB,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

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We look forward to receiving your revised manuscript.

Kind regards,

Antonio Simone Laganà, M.D., Ph.D.

Academic Editor

PLOS ONE

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Additional Editor Comments:

The topic of the manuscript is interesting. Nevertheless, the reviewers raised several concerns: considering this point, I invite authors to perform the required major revisions.

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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: No

Reviewer #3: Yes

Reviewer #4: Yes

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

Reviewer #1: Yes

Reviewer #2: No

Reviewer #3: Yes

Reviewer #4: No

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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: No

Reviewer #2: No

Reviewer #3: Yes

Reviewer #4: 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: No

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

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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: Dear Authors,

This manuscript tried to assess the effectiveness of Triclosan coated sutures in reducing SSI, the rate of wound healing complications, and the cost impact of triclosan-coated suture use from a hospital perspective. I have reviewed the manuscript and would like to suggest following changes in a section-wise manner.

Overall, there are many grammatical and typographical mistakes.

1. Abstract

Abstract seems well written.

2. Introduction

This section needs to be well written and arranged into relevant paragraphs. The authors should first talk in brief about the SSI, risk factors, basics of the suture in the discussion, and how sutures are related to the development of SSI. Following this, the authors should mention recent studies pertaining to the topic and highlight the literature gap. Then, the authors should state how the current study aims to fill the gap.

3. Methodology

The authors have mentioned inclusion, non-inclusion and exclusion criteria. However, there should be only inclusion and exclusion criteria.

There are grammatical and typographical mistakes. Such as chi2 should be replaced with chi-square, Caesar section with caesarean section, and many more.

Also, format the section in proper paragraphs based on the journal’s guidelines. Please make sure to double-check and address all the mistakes.

4. Results

Please format the tables based on the journal’s guidelines. The statistical values mentioned in brackets are confusing.

5. Discussion

The first paragraph should mention the noteworthy findings of the study. The authors should compare and contrast these findings with other studies in subsequent paragraphs. The discussion is too brief. Also, author should add a paragraph regarding limitations and future implications of this study.

6. Conclusion

The conclusion is well written.

7. References

Please format the references based on the journal’s guidelines.

Reviewer #2: A mono-centric prospective controlled randomized trial in pregnant women with elective or emergency caesarian delivery. Patients, surgeons and outcome’s assessor triple blinded to treatment. Three hundred eighty patients were randomly assigned to closure with polyglactin non coated suture VICRYL, or with polyglactin coated suture VICRYL Plus after caesarian section. The primary outcome was the rate of SSIs within 30 days after surgery. SSI rate was 2.5% in Triclosan group compared to 8.1% with non-coated

suture. Use of Triclosan coated suture was associated with 69% reduction in SSI rate (p = 0.037; OR:0.294; CI95%:0.094 – 0.921). The authors claim a total of 5312 USD (33 USD per procedure) was saved with TCS coated suturing; 590 USD per prevented SSI.

Major comments:

No trial registration given.

It seems to be this trial: https://ichgcp.net/clinical-trials-registry/NCT02847936

However, the sample size in that registered trial is 400 and not 296 patients.

Sample size calculations: expected wound infection rates were 2% with coated suture use versus 9% for the control group. On the basis of a two-sided chi2 test for equality of proportions, 80% power to detect a relative risk reduction of 5%, 296 patients were needed, 148 patients per arm. The sample size is powered to test a null hypothesis of this difference: 9% vs 2% is an ARR of 7% and a RRR of 78%. The actual results showed an ARR of 5.6% (8.1-2.5%) and a RRR of 69%. This means that the null hypothesis may be false as the study is underpowered to correctly test a smaller difference than 7%. In other words, the conclusion of the effectiveness of triclosan coated sutures needs to be toned down considerably, coming from an underpowered study.

What was used as standard skin prep? Specifiy at 'surgical procedure'.

"..a scrub nurse verified the randomization list..." (p. 12) Explain this. How could there be a list that the scrub nurse was allowed to look into. Proper computer randomisation allocates treatment group per patient separately. A pre-randomised list of treatment allocations does not count as proper randomisation.

p.13 who did the wound surveillance and decides whether or not a patient was seen by a senior surgeon for suspicion of wound infection?

Cost estimation section needs to be deleted completely, as well as the related conclusion. This is not a proper nor adequate economic analysis. 'Cesarian cost = Bundle cost + Suture material cost + Hospital stay cost' and 'SSI cost = SSI bundle cost + Drugs cost + Investigation tests cost + Reintervention cost + Hospital stay cost' is not accurate, oversimplified, no details supplied, and only a very rough 'quick & dirty' estimate which must be left out because of imprecision and not following the rules of cost analyses.

Statistical analyses paragraph is too concise, lacks detail.

Table 1 baseline characteristics. Since this is a RCT, no statistics must be performed on baseline characteristics as randomisation should take care of random distribution. Delete p value column and related text in results.

Table 2 risk factor for SSI does not contribute to trial results presentation

p.19 'In multivariate regression, only use of non-coated suture was associated with a higher risk of

SSI.' But none of the multivariate data are shown. Do we simply need to believe the authors without any possibility of peer review of the multivariate data? It's also not made available in supplementary materials.

Reviewer #3: This randomized controlled trial assessed the effectiveness of Triclosan coated suture in reducing SSIs rate after caesarian delivery, and to evaluate the cost impact of antimicrobial suture use. They had interesting finding. And the study is well written.

All information about the procedure was described in detail in Method section.

Only one minor concern.

Abstract: 'CI95%' should be '95%CI'.

Reviewer #4: A randomized controlled study was conducted which aimed to assess the effectiveness of Triclosan coated suture in reducing surgical site infections (SSIs) after cesarean delivery. The secondary aim was to compare rates of wound healing complications. A statistically significant reduction in the SSI rate was observed with the Triclosan coated suture compared to the control. Furthermore, Triclosan was associated with statistically lower risks of wound oedema, dehiscence and hematoma compared to the control.

Major revision

Provide a comprehensive “Statistical analysis” section. List and describe all the statistical methods used for the analysis.

Minor revisions:

1- Abstract: Define the abbreviation SSI.

2- Page 4, last line: Write out chi-square.

3- Page 5, Randomization: Provide further details of the randomization process. If block randomization was used, state the block size.

4- Page 8, Statistical analysis: The statements “p degrees of significance” and “the results were presented with their p” are confusing. Please clarify or restate.

5- Page 8, Statistical analysis: Indicate the type of nonparametric tests used and the specific data that was analyzed with these tests.

6- Page 8: Provide corresponding percentages for the counts in these sentences.

A. “One hundred seventy women were allocated in group 1 and 170 in group 2.”

B. “Ultimately, 160 patients remained in the Triclosan arm and 158 in the control arm . . .”

7-Page 8: Define groups 1 and 2 at first mention.

8- Table I: In addition to means, provide standard deviations. In addition to counts, provide percentages. If the data is not normally distributed, provide median, first and third quartiles.

9- Page 11, Second paragraph: Provide 95% confidence intervals for the 2.5% and 8.1%.

10- In the “Statistical analysis” section indicate that both univariate and multivariate analysis were performed. The univariate results are shown in Table II. Clarify.

11- Page 13, lines 1-3: Clarify which factors remained in the multivariate regression model.

12- In the “Statistical analysis” section list and thoroughly describe the use of all statistical methods. Indicate if univariate or multivariate logistic regression was used for the wound healing disturbances (results shown on page 13 and Table III). For further clarity, in the title of Table III, indicate if the results are univariate or multivariate.

13- Page 13: Provide the discharge rates and summarize the healing times in the two groups.

14- Page 14: Provide measures of dispersion for each hospital cost. Indicate if the summary statistics are means, medians, etc.

15- To assist in the review process, add line numbering to the document.

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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 #1: Yes: Ayush Anand

Reviewer #2: Yes: Prof MA Boermeester

Reviewer #3: Yes: Jian-Hong Zhong

Reviewer #4: No

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PONE-D-22-20609R1Evaluation of Triclosan Coated Suture in Obstetrical Surgery: A Prospective Randomized Controlled StudyPLOS ONE

Dear Dr. BETTAIEB,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Dec 10 2022 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Antonio Simone Laganà, M.D., Ph.D.

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Additional Editor Comments:

The reviewers have still some concerns that need to be addressed by the authors.

Please check carefully the English grammar and style.

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Reviewers' comments:

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 #1: (No Response)

Reviewer #3: All comments have been addressed

Reviewer #4: (No Response)

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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 #1: Partly

Reviewer #3: Yes

Reviewer #4: Yes

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

Reviewer #1: Yes

Reviewer #3: Yes

Reviewer #4: 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 #1: Yes

Reviewer #3: Yes

Reviewer #4: (No Response)

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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 #1: No

Reviewer #3: Yes

Reviewer #4: 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 #1: Dear Author, I have reviewed the manuscript and unfortunately, I will not be able to recommend it for publication. This manuscript needs to be extensively edited for english language. Discussion section is not written well.

Reviewer #3: All my comments have been addressed. I think the paper is suitable for publication in PLOS ONE. Thanks again.

Reviewer #4: Minor Revisions:

1- Lines 159 & 165: State the statistical method(s) used for the bivariate and univariate analyses.

2- Table I: To improve clarity, place "n=160" in the Group 1 header and "n=158" in the Group 2 header. Remove these numbers from the cell entries.

3- Lines 190 and 195: Provide 95% confidence intervals for the proportions: 5.3%, 2.5%, and 8.1%. In the Statistical Analysis section, include the statistical method used to estimate the CIs.

4- Table II:

a- In the title state the statistical method used for the bivariate analysis.

b- Provide a measure of dispersion for all means.

c- In similar fashion to comment #2 above, include the sample sizes in the header row and remove them from the individual cells.

5- Table IV: In similar fashion to comment #2 above, include the sample sizes in the header row and remove them from the individual cells.

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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 #1: Yes: Ayush Anand

Reviewer #3: Yes: Jian-Hong Zhong

Reviewer #4: No

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[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Evaluation of Triclosan Coated Suture in Obstetrical Surgery: A Prospective Randomized Controlled Study

PONE-D-22-20609R2

Dear Dr. BETTAIEB,

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.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Antonio Simone Laganà, M.D., Ph.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

I carefully evaluated the revised version of this manuscript.

Authors have performed the required changes, improving significantly the quality of the paper.

Reviewers' comments: