PONE-D-24-35124Regular gargling with a Cetylpyridinium Chloride plus Zinc containing mouthwash can reduce upper respiratory symptomsPLOS ONE

Dear Dr. Muniz,

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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PLOS 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: 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: 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: No

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: During the detailed review of this work, we will be able to identify some questions that are not clear and, on the other hand, allow some questions to be asked.

Therefore, I begin my contribution:

1. I thank you once again for trusting me to review this work. Starting with the title, it was not clear what type of analysis was done. If it was a comparison, an efficacy, an effect, an efficiency, I suggest that the title present one of these words that will allow the reader to understand the work much better on a first reading.

2. TITLE: Here in the abstract it is a little clearer. But I suggest that the title be clearer for reading, probably by incorporating the word Effect.

3. INTRODUCTION: In the second paragraph, they begin by talking about the prevalence rates of people who have respiratory infections in the United States of America, since the study originated in Brazil. It would be interesting to present the prevalence and/or incidence rates, so that the reader has a clear idea of the situation in which Brazil finds itself in comparison to the data from the United States.

4. At the end of the introduction. Where the objective of the study is stated, I suggest that it be rewritten to include the word Effect. This will make it clearer and more understandable for the reader.

5. PARTICIPANTS: Within the eligibility criteria. The authors mention that the participants should have good systemic health. What is not clear is whether the patients had any symptoms of respiratory infection. If they did, I suggest that this be written. If not, justify why these patients were not included.

6. Within the exclusion criteria. The authors mention that patients with arthritis and carpal tunnel syndrome could not participate in the study. Why? Justify your answer.

7. EXPERIMENTAL GROUPS: The authors mention the composition of the experimental groups:

a. The negative control group: The authors mention that this group received a toothbrush and a fluoride toothpaste. What is not clear is why this group did not receive a placebo as a product.

8. SAMPLE CALCULATION: It is not clear how the calculation was performed, what it was based on to arrive at the sample number, I suggest that it be explained and rewritten for the readers' understanding. Since this is a phase 3 of a clinical trial

9. RENDERING AND ALLOCATION OF PARTICIPANTS: Upon reading, it is not clear how the participants were allocated to their respective experimental groups, which experimental unit was taken into consideration to allocate these patients. I suggest you specify

10. RESULTS: The authors reported in their results that 01 participant in the control group had adverse effects. One of these patients needed antibiotics for intestinal surgery. What was the justification for remaining in the study? Justify

11. The authors mentioned that 02 participants in the test group used antibiotics. One of them for pain associated with gastritis caused by Helicobacter pillori and the other for presenting a clinical picture of tonsillitis. Why were they not removed from the study? Within the eligibility criteria, it was written by the authors that they should not have used antibiotics. Justify

12. In the results, the authors demonstrated that there was a decrease in hoarseness and chest pressure in the participants in the control group. What is this due to?

13. DISCUSSION: The authors state that due to a subjective test applied to the participants, they demonstrated better results in the absence of upper respiratory symptoms. The questionnaire (WURSSR-21) used serves as a specific tool to assess quality of life in patients with respiratory infection.

Reviewer #2: Major Revision

This appears to be a well conducted clinical trial. However, I am very puzzled by the reporting (see below).

Lines 28 and elsewhere

I suggest replace: ‘Negative Control’ by ‘Control’

Lines 130-132 & 160-161& Tables 1 & 2

Although I am not familiar with the WURSS-21 Daily Symptom Report which, as the authors state, uses the Likert Scale from 0 to 7 but the mean scores given in Tables 1 and 2 are all close to zero with the corresponding SD suggesting negative values are possible. I presume this is a consequence of rescaling to obtain a binary response for analysis. Why not use the Likert Scale itself? This seems very strange so the rational and process used by the authors need to be clearly explained in the paper.

Line 161 95% confidence intervals are mentioned here but are not included in the tables.

Line 163 Since there are only two groups better to use the t-test (however ANOVA is not incorrect)

Lines 164-165

The Tukey multiple comparison test does not appear appropriate when comparing 2 groups.

Tables 1 & 2

Assuming the measures summarised are OK, the difference between the groups needs to be included. For example, Runny nose 0.153 – 0.178 = −0.025 and the 95%CI added.

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Reviewer #1: No

Reviewer #2: No

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Efficacy of regular gargling with a Cetylpyridinium Chloride plus Zinc containing mouthwash can reduce upper respiratory symptoms

PONE-D-24-35124R1

Dear Dr. Muniz,

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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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,

Maria Giulia Nosotti, Master's Degree

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 #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

**********

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: The authors have responded appropriately to suggestions made in my earlier review I have no further comments.

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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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