PONE-D-23-00704Predicting invasive mechanical ventilation in COVID 19 patients: A validation studyPLOS ONE

Dear Dr. Statlender,

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.

==============================

ACADEMIC EDITOR:I read the paper and the reviewers' review with keen interest. Unfortunately, given the numerous problems encountered by Reviewer #1, I think a major revision of the paper is necessary. It is necessary to be able to address all the points raised by the reviewers before the paper can be properly evaluated.

Please submit your revised manuscript by Aug 25 2023 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,

Samuele Ceruti

Academic Editor

PLOS ONE

Journal Requirements:

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

2. Please note that PLOS ONE has specific guidelines on code sharing for submissions in which author-generated code underpins the findings in the manuscript. In these cases, all author-generated code must be made available without restrictions upon publication of the work. Please review our guidelines at https://journals.plos.org/plosone/s/materials-and-software-sharing#loc-sharing-code and ensure that your code is shared in a way that follows best practice and facilitates reproducibility and reuse.

3. In your Data Availability statement, you have not specified where the minimal data set underlying the results described in your manuscript can be found. PLOS defines a study's minimal data set as the underlying data used to reach the conclusions drawn in the manuscript and any additional data required to replicate the reported study findings in their entirety. All PLOS journals require that the minimal data set be made fully available. For more information about our data policy, please see http://journals.plos.org/plosone/s/data-availability.

Upon re-submitting your revised manuscript, please upload your study’s minimal underlying data set as either Supporting Information files or to a stable, public repository and include the relevant URLs, DOIs, or accession numbers within your revised cover letter. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories. Any potentially identifying patient information must be fully anonymized.

Important: If there are ethical or legal restrictions to sharing your data publicly, please explain these restrictions in detail. Please see our guidelines for more information on what we consider unacceptable restrictions to publicly sharing data: http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions. Note that it is not acceptable for the authors to be the sole named individuals responsible for ensuring data access.

We will update your Data Availability statement to reflect the information you provide in your cover letter

4. Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information.

[Note: HTML markup is below. Please do not edit.]

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

**********

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

Reviewer #1: Yes

Reviewer #2: No

**********

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

**********

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

**********

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: Very interesting paper about a machine learning algorithm to predict invasive mechanical ventilation in COVID-19 patients. The methodology is sound and the article is well written. I would just really encourage the research team to make their deidentified data publicly available in order to further strengthen their methodological claims and allow for the generation of further studies and algorithms by the scientific community.

Reviewer #2: I initially thank the editor for allowing me to review this manuscript. The Israeli group, with this study, set out to internally validate a created algorithm involving respiratory failure and mechanical ventilation. The evaluation of this algorithm was by performing data from COVID-19 patients. The authors conclude their work by stating that during validation a deterioration in the accuracy of the algorithm was observed, while remaining high. The authors also state that the negative predictive value is very high.

Primarily I recommend that the authors change the bibliography entry style to the style required by the journal, to be retrieved in the instructions for authors.

https://journals.plos.org/plosone/s/submission-guidelines or perhaps use an automatic bibliography creator for proper bibliography style selection.

The work is interesting but there are many structural gaps in the manuscript. There is no clear introduction to the topic. Comparison with the present literature is not present in the discussion. Virtually no comparison is made. Most importantly, I recommend the authors to structure the methods part much better, which, as described, completely lacks structure and consistency. The methods are practically the most important part of the work, as they also allow you to understand and evaluate and possibly reproduce the work or think about reproducing it. In your work there is not stated to be a clear methodological structure. I am not claiming that you have not worked with a proper methodological structure, but I remind you that it is necessary to describe it properly during the manuscript.

I also advise authors to correct typos and grammatical errors that are present and repeated in the text, perhaps even having the work seen by a native speaker who can adjust and make the manuscript fluid.

Below you will find my comments structured by sections and lines.

Keyword.

1. First, I advise authors to include keywords in the main manuscript as well, so that when downloading the work, they are found and evaluated, thus slightly facilitating the work of reviewers as well.

2. As for the keywords present it can be said that they are all appropriate for the work done but unfortunately none, except for one, present in the MESH database. (https://www.ncbi.nlm.nih.gov/mesh/)

I recommend a thorough review and correlation with the MESH database.

Below are some suggestions:

- Machine learning tool � machine learning, Algorithms, Artificial Intelligence

- Invasive mechanical ventilation prediction � mechanical ventilations, Probability Learning,

- COIVD- 19 � spelling to be corrected, perhaps include additional keywords, perhaps more generic, e.g., ARDS, Respiratory Distress Syndrome, SARS-CoV-2

Introduction

3. Line 29 The authors state the treatment of respiratory failure, but then cite 2 articles referring to noninvasive ventilation, one of which is recent, instead one quite dated. In this context, it would be ideal to perhaps cite some guidelines, even recent ones, given the updates created for COVID, so that we have something "fresh" and up to date.

4. Line 46 - 66 The authors in this point describe their work done previously. I did not find the need for this full digression on already published work, describing how the calculation is performed and how the prediction is developed. Ideally it would suffice to put the description much more shortened and succinct and then place the appropriate reference. Such a descriptive part should be included in the methods, in a dedicated section with respect to the predictive decision algorithm.

5. Rather, it would also be appropriate to describe and expand a little on the first part with respect to COVID respiratory failure or not, briefly, and describing any additional decision-making models, in addition to those described, or expanding a little on those already correctly cited.

Methods

6. In this section I find much confusion and lack of clarity in the development of the section. This section should perhaps be the most important section of the paper because it should describe the work done step by step, classifying it and clarifying all the variables. Instead, I find much difficulty in expression and a lack of clarity in the exposition and statement of the steps taken.

7. First, the inclusion criteria for which patient data were taken should be clarified.

8. It is important to divide this section into subsections, so precisely to make the work clearer and more structured.

The authors state that they included all patients with COVID-19 infection. Were there no exclusions whatsoever in the patients? Precisely all patients were included. Were DNR patients not admitted? Or were they included in the data as well? The authors state that they included all hypoxemic patients by COVID-19 defining them as patients with an SpO2<88% or PaO2<60mmHg admitted for more than 48 hours. But did these patients have oxygen support? Where were they hospitalized? How were they being cared for from the respiratory point of view?

9. A subsection should be the prediction model, with the part included in the Introduction and with the related calculations that were performed.

10. Another sub-section should also be all the subcategories created during the analysis.

11. The chapter of the statistical analysis done with the results is missing. To be included within the work.

12. Line 116-119 I don't think it is very correct and appropriate to put unventilated and deceased patients in the ventilated category. They are patients with another category and other patients. They should not be included there. Or the authors should amply justify, perhaps with evidence or other references that they also made this inclusion and justify it properly.

Results

13. Figure 2

In the figure it would be important and more precise to also include the significance p-value as well as AUC.

14. Table 2

Completely missing units of measurement.

Abbreviations used (ex. MIMIC, etc.) should be included in all tables.

Discussion

15. The discussion the authors undertake is correct. However, a structural problem is present. The discussion should be a comparison with the present literature. How come the authors, except at the beginning, do not compare with the literature? Even at moments, after the description and inferences made about their results, they should compare them with the present literature and assess whether they are overlapping, similar, probably similar, or completely different. This work is hardly developed in this section of the paper.

**********

6. 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: Antonio Camiro-Zúñiga

Reviewer #2: No

**********

[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.

Predicting invasive mechanical ventilation in COVID 19 patients: A validation study

PONE-D-23-00704R1

Dear Dr. Statlender,

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,

Samuele Ceruti

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

**********

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

**********

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: No

**********

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

**********

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: (No Response)

**********

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

**********