Post-Discharge non-invasive ventilation for hypercapnic respiratory failure: Outcomes in a Rural Cohort

Sunil Sharma; Robert Stansbury; Mayuri Mudgal; Priyanka Srinivasan; Edward Rojas; Kassandra K. Olgers; Scott Knollinger; Bernardo J. Selim; Sijin Wen

doi:10.1371/journal.pone.0321420

Peer Review History

Original SubmissionJanuary 5, 2025
5 Jan 2025 Author Response https://doi.org/10.1371/journal.pone.0321420.r001
4 Feb 2025 Decision Letter - Rabail Chaudhry, Editor PONE-D-24-60120Post-Discharge Non-Invasive Ventilation for Hypercapnic Respiratory Failure: Outcomes in a Rural CohortPLOS ONE Dear Dr. Sharma, 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 revise the limitations section of the manuscript to address issues raised by Reviewer 2 below. In addition, please clarify some of the questions raised regarding methodology. Please submit your revised manuscript by Mar 21 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 . 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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: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes ****** 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). 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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 would have liked more explanation on the randomization process- since the control group consisted of participants who "did not qualify for non-invasive ventilation at discharge," but the study group did not include that subset of patients then doesn't that naturally skew your results? Are the patients first randomized into control vs study groups and then determined if they met criteria for NIV at discharge? That way, there would naturally be patients in both control and study groups that did not end up meeting criteria for NIV at discharge and their data removed for purposes of this study. I would also have liked a breakdown for chief complaint causing the 12 month mortality and hospital readmissions out of curiosity to see what percentage were pulmonary related. Reviewer #2: The article is technically sound but has notable minor methodological limitations. Patients with a prior diagnosis of acute-on-chronic hypercapnic respiratory failure who were already on home NIV were excluded. This exclusion may bias the study population toward newly diagnosed or less severe cases, potentially limiting the applicability of the findings to patients with long-standing NIV use or more advanced disease. The retrospective data, relied on data extracted from electronic medical records and a sleep medicine registry and hence prone to selection bias, missing data, and inaccuracies in documentation. Adherence data obtained from durable medical equipment companies, may not capture the full picture of patient usage patterns and may not account for patient-reported barriers (e.g., discomfort, mask fit issues) or technical issues with the devices. Elaborating on the methods these equipment companies use to collect adherence data may provide helpful context for readers. Lastly, the study included patients admitted between January 2020 and July 2023, i.e. during the COVID-19 pandemic which most likely may have influenced hospitalization patterns, access to care, and outcomes, how were these factors addressed and adjusted for in the study? ****** 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: Ronald Tang Reviewer #2: Yes: Maaz Shah Khan ******** [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. https://doi.org/10.1371/journal.pone.0321420.r002
Revision 1
28 Feb 2025 Author Response Response to reviewers comments for NIV study Editorial comments Please remove any funding-related text from the manuscript and let us know how you would like to update your Funding Statement. Currently, your Funding Statement reads as follows: “The authors received no specific funding for this work.”. Please include your amended statements within your cover letter; we will change the online submission form on your behalf. Funding related text removed from the manuscript as advised. Please add the following funding information on the submission form: “Research reported in this publication was supported by the National Institute Of General Medical Sciences of the National Institutes of Health under Award Number 5U54GM104942-08. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.” Thank you. Please provide an amended Competing Interests Statement that explicitly states this commercial funder, along with any other relevant declarations relating to employment, consultancy, patents, products in development, marketed products, etc. Please include your amended Competing Interests Statement within your cover letter. We will change the online submission form on your behalf. Amended competing interests statement added to the manuscript and added the sentence “This does not alter our adherence to PLOS ONE policies on sharing data and materials.” Please review your reference list to ensure that it is complete and correct. Reference list is complete and correct. 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: I would have liked more explanation on the randomization process- since the control group consisted of participants who "did not qualify for non-invasive ventilation at discharge," but the study group did not include that subset of patients then doesn't that naturally skew your results? Are the patients first randomized into control vs study groups and then determined if they met criteria for NIV at discharge? That way, there would naturally be patients in both control and study groups that did not end up meeting criteria for NIV at discharge and their data removed for purposes of this study. We appreciate the reviewer’s observation. Most patients in the control group were admitted by the primary team for acute-on-chronic hypercapnic respiratory failure and were not evaluated by the hospital sleep medicine service. Additionally, we included patients who were consulted but were unable to be discharged on NIV. This approach was appropriate, as the study aimed to assess whether patients who were not discharged on therapy were at higher risk for poor outcomes. As noted in Table 1, there were no significant differences between the intervention and control groups. Since this is a retrospective study based on a prospective registry, the control group was not initially randomized. To clarify, we have updated the methodology as follows: “The control group consisted of hospitalized patients who had hypercapnia (PaCO2 ≥ 45 mmHg) on arterial blood gas or a VPaCO2 ≥ 51 mmHg from their venous blood gas, comorbidity of COPD or a BMI ≥ 30 Kg/m2 who were admitted during the same time period but the primary admitting team did not consult hospital sleep medicine service, and those who did not qualify for non-invasive ventilation at discharge or experienced insurance denial.” I would also have liked a breakdown for chief complaint causing the 12 month mortality and hospital readmissions out of curiosity to see what percentage were pulmonary related. Unfortunately, we could not determine specific causes of mortality as records from outside hospitals were not available. This has been listed in the limitations section. Prospective studies in on further delineation of causes for mortality are recommended. Reviewer #2: The article is technically sound but has notable minor methodological limitations. Patients with a prior diagnosis of acute-on-chronic hypercapnic respiratory failure who were already on home NIV were excluded. This exclusion may bias the study population toward newly diagnosed or less severe cases, potentially limiting the applicability of the findings to patients with long-standing NIV use or more advanced disease. We thank the reviewer for their excellent comments. We believe it was important to exclude patient already on NIV as the duration of use and hours of compliance could not be controlled. We agree with the reviewer that enrolling NIV naïve patients may have biased the cohort towards less severe cases. However our data shows that NIV was beneficial even in relatively less severe patients and supports the conclusion that more severe patients may also benefit. The retrospective data, relied on data extracted from electronic medical records and a sleep medicine registry and hence prone to selection bias, missing data, and inaccuracies in documentation. Adherence data obtained from durable medical equipment companies, may not capture the full picture of patient usage patterns and may not account for patient-reported barriers (e.g., discomfort, mask fit issues) or technical issues with the devices. Elaborating on the methods these equipment companies use to collect adherence data may provide helpful context for readers. We again thank the reviewer for their comments and agree with the observations. We have addressed this in the limitations section. Downloadable objective adherence data from the DME company was obtained and reviewed by the investigators and was not based solely on DME companies observations or documentation. Information on patient reported barriers was obtained from clinic notes and encounters. This has been added to the methodology section. Lastly, the study included patients admitted between January 2020 and July 2023, i.e. during the COVID-19 pandemic which most likely may have influenced hospitalization patterns, access to care, and outcomes, how were these factors addressed and adjusted for in the study? We agree with the reviewer that the COVID-19 pandemic affected all aspects of medical care, and the impact of these confounders is difficult to quantify. However, regarding acute-on-chronic hypercapnic respiratory failure, we did not observe a decrease in cases but rather a slight increase, likely due to the temporary closure of ambulatory clinics. Both the intervention and control groups were exposed to similar environmental influences. We have acknowledged the unknown impact of COVID-19 in the study’s limitations section. 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. Done Attachments Attachment Submitted filename: Reviewers comments for NIV study_Feb8.docx https://doi.org/10.1371/journal.pone.0321420.r003
7 Mar 2025 Decision Letter - Rabail Chaudhry, Editor Post-Discharge Non-Invasive Ventilation for Hypercapnic Respiratory Failure: Outcomes in a Rural Cohort PONE-D-24-60120R1 Dear Dr. Sharma, 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 will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager® and clicking the ‘Update My Information' link at the top of the page. If you have any questions relating to publication charges, 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, Rabail Chaudhry Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0321420.r004
Formally Accepted
Acceptance Letter - Rabail Chaudhry, Editor PONE-D-24-60120R1 PLOS ONE Dear Dr. Sharma, I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now being handed over to our production team. At this stage, our production department will prepare your paper for publication. This includes ensuring the following: * All references, tables, and figures are properly cited * All relevant supporting information is included in the manuscript submission, * There are no issues that prevent the paper from being properly typeset If revisions are needed, the production department will contact you directly to resolve them. If no revisions are needed, you will receive an email when the publication date has been set. At this time, we do not offer pre-publication proofs to authors during production of the accepted work. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few weeks to review your paper and let you know the next and final steps. Lastly, if your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. 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. If we can help with anything else, please email us at customercare@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Rabail Arif Chaudhry Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0321420.r005

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