PONE-D-23-10920Effect of oclacitinib (Apoquel) administration on development of surgical site infection following clean orthopedic stifle surgeryPLOS ONE

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Reviewers' comments:

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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: Yes

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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: No

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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: 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: Excellent work. Just a few additions to be considered:

1. Please mention the CDC guidelines for SSI. Including clinical and lab signs

2. Please highlight adjustment of the logistic regression for comorbidities

Reviewer #2: The manuscript titled: “Effect of oclacitinib (Apoquel) administration on development of surgical site infection following clean orthopedic stifle surgery” explores risk factors associated with specific types of surgeries in dogs. The main focus is on the effect of oclacitinib even though the effects of other variables are statistically more significant. As the authors point out the main drawback of this study is the retrospective design. I have some concerns about some results being presented with very little detail and a few other issues I think the authors need to address prior to publication.

Title: I would urge the authors to rethink the title. While very clear and concise, it does give the image of a clinical trial where one group has received oclacitinib and the other has not. The retrospective nature of the study should be mentioned.

Abstract: Since there was a very significant statistical correlation between anesthesia time and wound infection there would be much more sense in mentioning that first in the abstract.

Line 53-54: The fact that this minimizes the need for antibiotics could also be mentioned. Further, I am not sure about the “overall hospital cleanliness”, perhaps this could be rephrased to have something to do with hospital hygiene?

Line 103-104: Could an owner have taken their dog to another veterinary clinic due to SSI signs and thus have been left out? Is there a possibility of bias, e.g. an owner with a dog that develops SSI not trusting the veterinary hospital where the procedure was first performed and thus seeking help elsewhere? This could be discussed.

Line 111-112: How well was this prophylactic time adhered to? In my experience there is huge variation in when the antibiotic is administered (anywhere from a couple of hours before incision to a few minutes after).

Line 114-115: Why is a triple-antibiotic ointment used? If all goes to plan it shouldn’t be, correct?

Line 130-131: These are the factors selected that may have affected SSI, there are plenty more, such as body temperature during the procedure, other medications (e.g. corticosteroids), time of prophylactic antibiotics administration etc. Please rephrase.

Results: The results could be presented more clearly. E.g. the white blood cell count is not presented, only the p-values. This makes it impossible for the reader to interpret the results. I would ask the authors add these values (similar to the surgery time) for all variables investigated. Also, it could be preferrable to have the results presented in a table.

Line 177-179: Why are no p-values displayed?

Line 183-184: Why is the p-value not displayed here? Please add for consistency.

Discussion: While I agree with what the authors are saying here, I would still urge them to also look at this from a purely proportional perspective; an overall SSI rate in clean orthopedic procedures of 8/100 patients may still be manageable, but 19/100 is catastrophic and cause for serious concern. The authors correctly point out that the results may have been statistically significant if more cases with the treatment were discovered, but I think some discussion could be added from a more practical point-of-view rather than a statistical one.

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Reviewer #1: Yes: Mahmoud Elfiky

Reviewer #2: Yes: Thomas Sven Christer Grönthal

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A retrospective evaluation of the effect of oclacitinib (Apoquel) administration on development of surgical site infection following clean orthopedic stifle surgery

PONE-D-23-10920R1

Dear Dr. Motz,

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.

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Kind regards,

Robert Jeenchen Chen, MD, MPH

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

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: All comments have been addressed

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 #1: Yes

Reviewer #2: Yes

**********

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

Reviewer #1: Yes

Reviewer #2: Yes

**********

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 #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 #1: Yes

Reviewer #2: Yes

**********

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: I have seen the Author replying to all reviewers' comments.

I have one comment, coming from a Medical background; the CDC SSI guidelines are based on Human pathology. Applying them to Veterinary diseases requires a reference.

Reviewer #2: The authors have addressed all my comments, but I detected one very small detail; cell counts in the results should be presented as per mm^3. E.g. "3.74-11.9 mm3" should be "3.74-11.9 /mm3".

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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: Mahmoud Elfiky

Reviewer #2: Yes: Thomas Grönthal

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