Acute respiratory distress syndrome readmissions: A nationwide cross-sectional analysis of epidemiology and costs of care

Matthew T. Siuba; Divyajot Sadana; Shruti Gadre; David Bruckman; Abhijit Duggal

doi:10.1371/journal.pone.0263000

Peer Review History

Original SubmissionApril 25, 2021
27 Sep 2021 Decision Letter - Brenda M. Morrow, Editor PONE-D-21-13742Acute respiratory distress syndrome readmissions: a nationwide cross-sectional analysis of epidemiology and costs of carePLOS ONE Dear Dr. Siuba, 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 Nov 11 2021 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, Brenda M. Morrow, PhD 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. We note that you have indicated that data from this study are available upon request. PLOS only allows data to be available upon request if there are legal or ethical restrictions on sharing data publicly. For more information on unacceptable data access restrictions, please see http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions. In your revised cover letter, please address the following prompts: a) If there are ethical or legal restrictions on sharing a de-identified data set, please explain them in detail (e.g., data contain potentially sensitive information, data are owned by a third-party organization, etc.) and who has imposed them (e.g., an ethics committee). Please also provide contact information for a data access committee, ethics committee, or other institutional body to which data requests may be sent. b) If there are no restrictions, please upload the minimal anonymized data set necessary to replicate your study findings as either Supporting Information files or to a stable, public repository and provide us with the relevant URLs, DOIs, or accession numbers. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories. We will update your Data Availability statement on your behalf to reflect the information you provide. 3. 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. 4. We note you have included a table to which you do not refer in the text of your manuscript. Please ensure that you refer to Table 7e in your text; if accepted, production will need this reference to link the reader to the Table. [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: 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). 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 ****** 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 ****** 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: This manuscript presents the results of a cross-sectional analysis of a large, national, administrative database to evaluate ARDS. This study is the first of its kind to use data after the inclusion of ARDS as a distinct ICD-10 code, potentially improving its detection in administrative datasets. Strengths of the study include: 1) The findings of the study have strong face validity, with admission information, associated diagnoses, and mortality rate all in line with previous prospectively collected data. It is highly likely that the dataset has accurately identified the population of interest. 2) Statistical methods are clearly explained and are rigorous and appropriate for the use of the administrative dataset. Choices are explained thoroughly. 3) The writing is clear and concise, and the tables and figures add to the manuscript. Limitations of the study include: 1) The findings (or lack thereof) of ECLS in the database are concerning, though perhaps not surprising. Survival for ARDS requiring ECLS is lower than for those without. The authors only identified 339 cases of ECLS in the entire database for the year, suggesting a significant under-reporting. However, this does limit the potential generalizability to ARDS findings in general. Future work could include a possible link with ELSO database or analysis of later years within the NRD to identify trends in ECLS coding. 2) Page 5, Line 168: This sentence initially led me to think the patient had to also survive the readmission, however after further reading in the manuscript, it became clear this is not the case. I would advise simply clarifying this sentence to avoid confusion of the reader. Reviewer #2: Please see attached file. In this paper, Dr Siuba and colleagues have used the HCUP’s NRD, which contains discharge abstract data for over 36 million weighted discharges, to describe the rate of 30-day readmission after an admission to hospital with a diagnosis of ARDS (defined using ICD-10 codes and procedure codes for intubation or tracheostomy). They also sought to explore the costs associated with both the admission to hospital for ARDS and a subsequent readmission. They identified 25,170 index episodes, with 9,439 dying during index admission, and 2889 experiencing a readmission within 30 days. 14.3% of the readmissions occurred within the first two days following discharge, and most had codes for the same most responsible diagnosis as was noted for the index admission. They identified some predictors of readmission using a multivariable logistic regression model that notably demonstrated that older age, and longer stay in hospital were associated with higher hospital costs. They found that the mean cost of hospitalization for ARDS was $71,004, and the mean cost of readmission was 26,971. Costs stratified by age demonstrated that younger groups had higher costs as well as longer mean length of stays than older groups. They also conducted a regression analysis to predict readmission costs based on various covariates. ****** 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:** Thomas Bice, MD, MSc 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. Attachments Attachment Submitted filename: PLOS review.docx https://doi.org/10.1371/journal.pone.0263000.r001
Revision 1
23 Nov 2021 Author Response Dear Drs. Morrow, Bice, and Reviewer #2, Thank you kindly for the opportunity to revise this submission. Within the limitations of what can be achieved with this data set and timing of revision, we attempted to address every possible concern raised during the first review. We feel this version is improved significantly with your input and look forward to your feedback. Matthew Siuba, DO On behalf of the authors Reponse to Editor Comments: 1. All sections were formatted according to PLOS ONE guidelines. 2. We note that you have indicated that data from this study are available upon request. PLOS only allows data to be available upon request if there are legal or ethical restrictions on sharing data publicly. For more information on unacceptable data access restrictions, please see http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions. a) If there are ethical or legal restrictions on sharing a de-identified data set, please explain them in detail (e.g., data contain potentially sensitive information, data are owned by a third-party organization, etc.) and who has imposed them (e.g., an ethics committee). Please also provide contact information for a data access committee, ethics committee, or other institutional body to which data requests may be sent. With regards to the sharing of the de-identified data set, this information has been clarified in the main manuscript. HCUP NRD database is available on request from the publisher (HCUP), not from our team directly. The usage of the dataset requires completion of a data use agreement and fee paid to HCUP. b) If there are no restrictions, please upload the minimal anonymized data set necessary to replicate your study findings as either Supporting Information files or to a stable, public repository and provide us with the relevant URLs, DOIs, or accession numbers. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories. We will update your Data Availability statement on your behalf to reflect the information you provide. Please see the answer in 2a above. 3. 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. Thank you, captions have been added to the end of the manuscript, before references. 4. We note you have included a table to which you do not refer in the text of your manuscript. Please ensure that you refer to Table 7e in your text; if accepted, production will need this reference to link the reader to the Table. A reference to Table 7e (now S7 Table) is included at the end of the results section. Reviewer #1: This manuscript presents the results of a cross-sectional analysis of a large, national, administrative database to evaluate ARDS. This study is the first of its kind to use data after the inclusion of ARDS as a distinct ICD-10 code, potentially improving its detection in administrative datasets. Strengths of the study include: 1) The findings of the study have strong face validity, with admission information, associated diagnoses, and mortality rate all in line with previous prospectively collected data. It is highly likely that the dataset has accurately identified the population of interest. 2) Statistical methods are clearly explained and are rigorous and appropriate for the use of the administrative dataset. Choices are explained thoroughly. 3) The writing is clear and concise, and the tables and figures add to the manuscript. Thank you very much for the kind comments, we appreciate your attention to our choices and rigor. Limitations of the study include: 1) The findings (or lack thereof) of ECLS in the database are concerning, though perhaps not surprising. Survival for ARDS requiring ECLS is lower than for those without. The authors only identified 339 cases of ECLS in the entire database for the year, suggesting a significant under-reporting. However, this does limit the potential generalizability to ARDS findings in general. Future work could include a possible link with ELSO database or analysis of later years within the NRD to identify trends in ECLS coding. We agree that this is a significant limitation and the directions for future study mentioned are intriguing. In our discussion, we state: “Finally, no patients who received extracorporeal life support were identified, which likely leads to an underestimation of overall costs, mortality, and readmission rate.” 2) Page 5, Line 168: This sentence initially led me to think the patient had to also survive the readmission, however after further reading in the manuscript, it became clear this is not the case. I would advise simply clarifying this sentence to avoid confusion of the reader. Thank you for the important clarification. The sentence was revised: “For readmission analyses, complete length of stay information was required” Reviewer #2 Comments In this paper, Dr Siuba and colleagues have used the HCUP’s NRD, which contains discharge abstract data for over 36 million weighted discharges, to describe the rate of 30-day readmission after an admission to hospital with a diagnosis of ARDS (defined using ICD-10 codes and procedure codes for intubation or tracheostomy). They also sought to explore the costs associated with both the admission to hospital for ARDS and a subsequent readmission. They identified 25,170 index episodes, with 9,439 dying during index admission, and 2889 experiencing a readmission within 30 days. 14.3% of the readmissions occurred within the first two days following discharge, and most had codes for the same most responsible diagnosis as was noted for the index admission. They identified some predictors of readmission using a multivariable logistic regression model that notably demonstrated that older age, and longer stay in hospital were associated with higher hospital costs. They found that the mean cost of hospitalization for ARDS was $71,004, and the mean cost of readmission was 26,971. Costs stratified by age demonstrated that younger groups had higher costs as well as longer mean length of stays than older groups. They also conducted a regression analysis to predict readmission costs based on various covariates. The study question is important, and well-justified. Thank you for the summary and commentary. Major comments: 1. I would suggest that the authors rearrange the methods section slightly so that it follows more closely the EQUATOR checklist. I don’t see any descriptions of considerations of bias, or confounding, and these should be addressed. Thank you very much for pointing this out. The methods section has been rewritten accordingly to follow the EQUATOR STROBE checklist order as much as possible, without compromising clarity. 2. The authors have identified some interesting trends, particularly that costs were higher among younger patients, who also had longer lengths of stay. Do the authors have any thoughts on how age and length of stay might interact in the causal pathway to costs? We agree that this is an interesting finding. Please see the following commentary added in the discussion section: “We observed that younger patients incurred a higher cost on readmission, markedly so in those who died during readmission. This may be due to a higher propensity to escalate and sustain (rather than withdraw) aggressive care measures in younger people compared to those who were older. Of note, we did not capture any records of patients in this study who received extracorporeal life support. We did detect a longer length of stay in younger patients as well which could be the driver of the increased costs, for the same rationale of increased life-sustaining care. Further breakdown in the specific charges (in terms of services rendered) which led to the total costs was not possible in this database, however, beyond the data we presented.” 3. Does the database only provide the total cost for an admission, or are the costs broken down into categories of costs? If they can be broken down, I would suggest describing the breakdown for the total cohort, as well as for the group that die during index admission, discharged with no readmission and those with a readmission. You might want to also describe costs for readmission stratified by early versus later readmission. This is a great point. Unfortunately, we only see the total reported charges in this type of administrative dataset, so further cost breakdown is not possible. This limitation has been added to the discussion section as mentioned in 2. Above. 4. A significant limitation of this study is that health care utilization costs and readmission are likely predicted by previous healthcare use. Previous research has demonstrated that high-users of healthcare, and those who have higher health care costs (High cost users) are likely to remain high-cost users. Can they do a look back and identify previous healthcare utilization and costs for their cohort, and then either stratifiy or control for this in their models? Previous work (eg: https://www.cmaj.ca/content/188/3/182) has demonstrated that of 45% of high-cost users remain high-cost users over the next two years. Thank you for the insightful comment. This would be helpful but is not possible with the limitations of this particular dataset. We did demonstrate in the multivariable model (Table 3), however, that increased age and certain comorbidities made readmission more likely, which supports a similar message. A comment including your suggested citation is included in paragraph 2 of the discussion: “Finally, while we were not able to examine prior healthcare utilization specifically, our multivariable model supports a higher risk of readmission for those with certain comorbidities and increasing age, similar to prior work in more granular datasets[21].” 5. The authors have described total costs, but have not described the attributable costs of ARDS. These costs are heavily confounded by the costs associated with underlying medical comorbidities, previous healthcare spending, hospitalization in general, and are not described relative to the costs associated for other non-ARDS types of hospitalizations. They might want to consider a matched analysis comparing costs of hospitalization for ARDS to a group hospitalized for other causes. (See this as an example of costing study employing this methodology: 10.1097/CCM.0000000000004777) Thank you for the comment. We agree this would be a valuable comparison to make. Our linear regression cost model (see the supplement and specifically S6 Table) supports that comorbidities, insurance status, and age all impact the cost of readmissions. Unfortunately the statistical funding support for this study has ended so further analysis (e.g. with propensity matching) as suggested is not feasible at this time. Minor: 1. Is it possible that patients were readmitted to a hospital that might not have reported discharge abstract data to this data set, and thus had a missed readmission? Or does the dataset include all data from all hospitals? This is absolutely a concern, given the sampling procedure of HCUP’s NIS and NRD datasets. Fortunately, hospitals which are not eligible for HCUP reporting comprise a very small percentage of US hospitals. A note above this has been added to the new “Bias” section in the Methods section. 2. There is no mention of the cost findings in either the take-home section or the abstract. Thank you for pointing this out. The take-home section was removed to meet the formatting of the journal. The results section of the abstract was updated to mention readmission costs. Attachments Attachment Submitted filename: PLOS-cover-response.docx https://doi.org/10.1371/journal.pone.0263000.r002
11 Jan 2022 Decision Letter - Brenda M. Morrow, Editor Acute respiratory distress syndrome readmissions: a nationwide cross-sectional analysis of epidemiology and costs of care PONE-D-21-13742R1 Dear Dr. Siuba, 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, Brenda M. Morrow, PhD Academic Editor PLOS ONE Additional Editor Comments: The second reviewer was not available to re-review, but as the handling editor, I have reviewed the author responses and, together with reviewer #1 am satisfied with the responses and changes made. 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 ******** 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 ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: 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 ****** 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 ****** 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: Thank you for addressing my comments and the comments of the other reviewers. Thank you for your important work. ****** 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:** Thomas Bice, MD, MSc https://doi.org/10.1371/journal.pone.0263000.r003
Formally Accepted
13 Jan 2022 Acceptance Letter - Brenda M. Morrow, Editor PONE-D-21-13742R1 Acute respiratory distress syndrome readmissions: a nationwide cross-sectional analysis of epidemiology and costs of care Dear Dr. Siuba: I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. 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 plosone@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 Professor Brenda M. Morrow Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0263000.r004

Open letter on the publication of peer review reports

PLOS recognizes the benefits of transparency in the peer review process. Therefore, we enable the publication of all of the content of peer review and author responses alongside final, published articles. Reviewers remain anonymous, unless they choose to reveal their names.

We encourage other journals to join us in this initiative. We hope that our action inspires the community, including researchers, research funders, and research institutions, to recognize the benefits of published peer review reports for all parts of the research system.

Learn more at ASAPbio .