PONE-D-24-27101Multimodal Prehabilitation in People Awaiting Acute Inpatient Cardiac Surgery:  Study Protocol for a Pilot Feasibility Trial (PreP-ACe)PLOS ONE

Dear Dr. Raut,

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 Oct 21 2024 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.

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We look forward to receiving your revised manuscript.

Kind regards,

Yashendra Sethi

Academic Editor

PLOS ONE

Journal Requirements:

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

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2. Please provide a complete Data Availability Statement in the submission form, ensuring you include all necessary access information or a reason for why you are unable to make your data freely accessible. If your research concerns only data provided within your submission, please write "All data are in the manuscript and/or supporting information files" as your Data Availability Statement.

3. We note that the original protocol that you have uploaded as a Supporting Information file contains an institutional logo. As this logo is likely copyrighted, we ask that you please remove it from this file and upload an updated version upon resubmission.

4. 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 If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references.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 If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field.

Reviewer #1: Yes

Reviewer #2: Yes

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2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses?

The manuscript should describe the methods in sufficient detail to prevent undisclosed flexibility in the experimental procedure or analysis pipeline, including sufficient outcome-neutral conditions (e.g. necessary controls, absence of floor or ceiling effects) to test the proposed hypotheses and a statistical power analysis where applicable. As there may be aspects of the methodology and analysis which can only be refined once the work is undertaken, authors should outline potential assumptions and explicitly describe what aspects of the proposed analyses, if any, are exploratory.

Reviewer #1: Yes

Reviewer #2: Partly

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3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable?

Descriptions of methods and materials in the protocol should be reported in sufficient detail for another researcher to reproduce all experiments and analyses. The protocol should describe the appropriate controls, sample size calculations, and replication needed to ensure that the data are robust and reproducible.

Reviewer #1: Yes

Reviewer #2: Yes

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4. Have the authors described where all data underlying the findings will be made available when the study is complete?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception, at the time of publication. 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

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics.

You may also provide optional suggestions and comments to authors that they might find helpful in planning their study.

(Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Thank you for the invitation to review this interesting study protocol. The rationale is clearly articulated that this is a novel intervention and important area of research. I have made a few comments below for your consideration.

Sample size - I understand approximately 100 patients were admitted to CHH per year and would be available for recruitment but what proportion of these would be likely to be eligible e.g. how many had a condition unlikely to be treated with surgery? How many underwent surgery in less than 5 days post-admission?

PPIE - As written it in unclear how feedback from PPIE members influenced the study or intervention design - for example did PPIE members feed into the content of the exercise programme? It may also be worth commenting on how representative PPIE members were of the population e.g. considering sex, race, economic status. Will PPIE members have a role throughout the trial?

Data collection - Would patients usually be referred to cardiac rehab on discharge from inpatient care? - if so it would be interesting to collect data on uptake. It is possible that those who receive prehab refuse cardiac rehab (this was observed by Greening et al 2018 with regards to pulmonary rehab), this would be an unintended consequence.

Data collection - the content of the intervention and the outcome measures do not appear to be completely aligned - The exercise intervention includes balance and strength training yet there is no outcome measures to assess strength (although grip strength could be a proxy for lower-limb strength) or balance (e.g. TUG, SLS). Did the authors considered assessing MIP as IMT is part of the intervention?

Intervention - please consider using thee TiDiER checklist. Currently there is no description of the balance/flexibility exercises to be performed.

In a feasibility trial I would expect to see "stop go criteria" or progression criteria?

End of study and Statistical analysis - this is the first time a qualitative component is mentioned? In the study design it should be clear that a mixed-methods approach is being applied. Who is conducting the interviews? Where? What is the purpose of the interviews? What analysis will be applied?

Reviewer #2: As a pilot feasibility study, no formal sample size calculation is required. However, since the primary objective of this study is to determine the feasibility of a prehabilitation programme, it is expected to see how the feasibility will be quantified. For example, how big of the enrollment rate or completion rate would establish the feasibility. Even though the statistical analysis for such a pilot study is mainly descriptive, it would be better to have more details such as all 95% confidence intervals will be reported for any rates. There would be longitudinal data (such as QoL) collected over time and hence proper models for such data should be used in order to better estimate the change in QoL after the programme. Consultation with and/or the involvement of a professional biostatistician in the study team is strongly recommended.

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Reviewer #1: Yes:  Samantha L Harrison

Reviewer #2: No

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PONE-D-24-27101R1Multimodal Prehabilitation in People Awaiting Acute Inpatient Cardiac Surgery:  Study Protocol for a Pilot Feasibility Trial (PreP-ACe)PLOS ONE

Dear Dr. Raut,

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: The reviewer have again raised some minor concerns. Please have a look and address them soon.

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

Please submit your revised manuscript by Jan 02 2025 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,

Yashendra Sethi

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.

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

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field.

Reviewer #3: Yes

**********

2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses?

The manuscript should describe the methods in sufficient detail to prevent undisclosed flexibility in the experimental procedure or analysis pipeline, including sufficient outcome-neutral conditions (e.g. necessary controls, absence of floor or ceiling effects) to test the proposed hypotheses and a statistical power analysis where applicable. As there may be aspects of the methodology and analysis which can only be refined once the work is undertaken, authors should outline potential assumptions and explicitly describe what aspects of the proposed analyses, if any, are exploratory.

Reviewer #3: Yes

**********

3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable?

Descriptions of methods and materials in the protocol should be reported in sufficient detail for another researcher to reproduce all experiments and analyses. The protocol should describe the appropriate controls, sample size calculations, and replication needed to ensure that the data are robust and reproducible.

Reviewer #3: Yes

**********

4. Have the authors described where all data underlying the findings will be made available when the study is complete?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception, at the time of publication. 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 #3: Yes

**********

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 #3: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics.

You may also provide optional suggestions and comments to authors that they might find helpful in planning their study.

(Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #3: Well thought out and good idea to consider prehabilitation in selected individuals waiting for cardiac surgery. I greatly appreciate the authors addressing previous reviewer comments. I would recommend to include the demographics of the patient population - age, sex, BMI; some of the common medical comorbidities that are associated with cardiac surgery - HTN, DM2, PAD, AKI or CKD, HLD, COPD, or on O2 at baseline; albumin level; LV function prior to surgery, presence of any IV or subcutaneous antiplatelets agents or anticoagulants, risk of falls/fragility, are they functionally independent prior to this admission. If they don't have these medical comorbidities, these patients would tend to participate more in the prehabilitation program and you would only have stable patients who would do well in the long run regardless if they undergo prehabilitation or not. It would be good to see these data in the feasibility study.

It is uncommon to wait beyond 7 days for an urgent cardiac surgery in US or some Asian countries.

"Only 34% of acute patients receive their surgery within 7 days in 2019/2020." Things are different post COVID - you can consider what's your current % of these patients getting their surgery within 7 days. If this % way higher than before, you may have difficulty recruiting patients beyond the feasibility trial.

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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 #3: 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.

Multimodal Prehabilitation in People Awaiting Acute Inpatient Cardiac Surgery:  Study Protocol for a Pilot Feasibility Trial (PreP-ACe)

PONE-D-24-27101R2

Dear Dr. Raut,

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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Kind regards,

Yashendra Sethi

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments: