Frailty independently predicts unfavorable discharge in non-operative traumatic brain injury: A retrospective single-institution cohort study

Rahul A. Sastry; Josh R. Feler; Belinda Shao; Rohaid Ali; Lynn McNicoll; Albert E. Telfeian; Adetokunbo A. Oyelese; Robert J. Weil; Ziya L. Gokaslan

doi:10.1371/journal.pone.0275677

Peer Review History

Original SubmissionJuly 11, 2022
3 Aug 2022 Decision Letter - Yusuke Tsutsumi, Editor PONE-D-22-19585Frailty Independently Predicts Unfavorable Discharge in Non-Operative Traumatic Brain Injury: A Retrospective Single-Institution Cohort StudyPLOS ONE Dear Dr. Sastry, 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. The reviewer #1 raises several essential concerns before the paper can be accepted for publication. Especially, I agree with the major comments 2. As the reviewer #1 recommended, I suggest the authors exclude patients who came from the “unfavorable” facilities because these patients usually cannot avoid “unfavorable discharge”. Please submit your revised manuscript by Sep 17 2022 11:59PM. 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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: No 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: No 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: The authors investigated an association of frailty in elderly patients suffered traumatic brain injury with disposition after hospital discharge. They found an association between frailty and the deterioration of outcomes. This research topic is valuable because frailty is one of the most important and urgent issues in the trauma and critical care today. However, several significant modifications are required for acceptance. Major comments 1. The authors need to show the patient selection flow. Even if the study was conducted nonconsecutively, the total number of eligible patients needs to be shown first, then the number of patients who dropped out for each reason, and finally the number of patients included in the study. In addition, they should clearly indicate the number of patients excluded from the analysis due to in-hospital death. 2. I have concerns that the inclusion criteria may be inappropriate. To examine the association between frailty and unfavorable outcomes, they need to exclude patients admitted from facilities judged unfavorable. I think patients admitted from the Skilled Nursing Facility would not discharge home. 3. The authors treat the frail category as an ordinal variable. I am not sure if there is a difference between pre-frail and non-frail from this result. I perceive that the difference in the number of outcomes might just be based on differences in prehospital residence. Please clarify the characteristics of the distribution of those variables (and it would be better to exclude prehospital “unfavorable” facility). It might be better to treat frail as a binomial variable (non-frail or worse than prefrail) or as a categorical variable. 4. I recommend that variables for multivariate analysis be selected based on their clinical importance, not on their p-values. (Sun GW, Shook TL, Kay GL. Inappropriate use of bivariable analysis to screen risk factors for use in multivariable analysis. Journal of Clinical Epidemiology. 1996;49(8):907-916. doi:10.1016/0895-4356(96)00025-X) 5. In several places in the Abstract and Discussion, the authors describe primary outcomes, which are adjusted analyses, and secondary outcomes, which are unadjusted analyses, as being equivalent. I would suggest that the authors do not assert that the results of the unadjusted analysis are associated with the outcomes with the same strength as the results of the adjusted analysis. Line 37: “Frailty was not associated with increased readmission rate, LOS, or rate of complications.” Line 39: “Frailty is associated with increased odds of unfavorable discharge disposition but not with other major complications for geriatric patients admitted with TBI.” Line 165: ” In a cohort of patients older the age of 70 admitted to the neurosurgical　service at a Level I trauma center, we find that physiologic frailty was associated with unfavorable　discharge disposition independently of age. We did not, however, observe a relationship between physiologic frailty and major inpatient complications, consulting services per patient, LOS, discharge GCS, or readmission/re-presentation to acute care after discharge. “ L183: “Our finding that frail patients are at risk for unfavorable discharge disposition but not other adverse outcomes” L236: “Frailty is associated with increased odds of unfavorable discharge disposition but not with other major complications for geriatric patients admitted with TBI.” 6. Based on the journal's publication criteria, part of the conclusions would be inappropriate because it is unclear from which results they are derived. Line 238: “Our study suggests that increased attention to the development of inpatient and outpatient care pathways and patient medical and social navigation protocols that more carefully assess alterations in neurological and physiologic derangement, and which identify and insure more complete and durable return to an optimal level of function is warranted.” Minor comments 1. Line 21: The authors need to spell out “TBI”. 2. Line 22: It would be better to add elderly or geriatric patients as a target population. 3. Line 94: The authors need to define "number of consulting services provided to hospitalized patients". 4. Line 95: The citation for the definition of "major complications during hospitalization" needs to be mentioned. 5. The authors would do well to discuss the possibility that the indication for surgery causes selection bias (patients too severely ill to undergo surgery). 6. The authors need to describe that they treated GCS as categorical variables and the rationale of the category in Methods. 7. Please resubmit the Figure1 because of poor resolution. Reviewer #2: It is not surprising that the percentage of FRAIL increases with age. And it is also natural that the frail will have a nonfavorable discharge disposition. However, it is also important to show the obvious, as it will lead to the next study. As the author writes in LIMITATION, this study has very little external validity. ****** 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: No Reviewer #2: Yes: Fumihito Ito ******** [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: review_frail_tbi.docx https://doi.org/10.1371/journal.pone.0275677.r001
Revision 1
30 Aug 2022 Author Response Dear Dr. Tsutsumi, Thank you for considering our manuscript and for providing us with this specific feedback. We have made the following clarifications and/or improvements to the manuscript in order to appropriately address all the points that were raised. Specifically, we have attempted to ensure that the manuscript aligns with PLOS formatting requirements and that the statement regarding informed consent is appropriate. The authors received no specific funding for this work. We would like to note that, in response to comment #2, we have refined the inclusion criteria of this study to include only patients who were admitted from home (and thus excluding the small number of patients who came from locations that would have been classified as unfavorable discharge destinations). The authors would like to note that, at least for an American audience, discharge metrics such as percentage of patients discharged to nursing facilities are likely relevant regardless of what locations the patients arrive from. Nevertheless, the clinically relevant result of this study is robust to this change in cohort definition. The authors investigated an association of frailty in elderly patients suffered traumatic brain injury with disposition after hospital discharge. They found an association between frailty and the deterioration of outcomes. This research topic is valuable because frailty is one of the most important and urgent issues in the trauma and critical care today. However, several significant modifications are required for acceptance. Major comments 1. The authors need to show the patient selection flow. Even if the study was conducted nonconsecutively, the total number of eligible patients needs to be shown first, then the number of patients who dropped out for each reason, and finally the number of patients included in the study. In addition, they should clearly indicate the number of patients excluded from the analysis due to in-hospital death. A new figure 1, which demonstrates this patient selection flow, has been included. 2. I have concerns that the inclusion criteria may be inappropriate. To examine the association between frailty and unfavorable outcomes, they need to exclude patients admitted from facilities judged unfavorable. I think patients admitted from the Skilled Nursing Facility would not discharge home. As previously noted, the authors re-did the relevant analyses excluding patients who were admitted from unfavorable locations. While the fundamental conclusion of the analysis is unchanged, this change does eliminate a major potential source of bias in the results. As such, the authors have implemented this change as part of the cohort definition rather than a subgroup analysis. 3. The authors treat the frail category as an ordinal variable. I am not sure if there is a difference between pre-frail and non-frail from this result. I perceive that the difference in the number of outcomes might just be based on differences in prehospital residence. Please clarify the characteristics of the distribution of those variables (and it would be better to exclude prehospital “unfavorable” facility). It might be better to treat frail as a binomial variable (non-frail or worse than prefrail) or as a categorical variable. The authors have also implemented this change. Based on the distribution of FRAIL scores, we chose to dichotomize the population into low FRAIL (0-1) and high FRAIL (2-5) categories. As previously noted, patients with prehospital “unfavorable” status have been excluded. 4. I recommend that variables for multivariate analysis be selected based on their clinical importance, not on their p-values. (Sun GW, Shook TL, Kay GL. Inappropriate use of bivariable analysis to screen risk factors for use in multivariable analysis. Journal of Clinical Epidemiology. 1996;49(8):907-916. doi:10.1016/0895-4356(96)00025-X) The authors broadly agree with this statement, and have updated the chosen multivariate model to reflect this change. 5. In several places in the Abstract and Discussion, the authors describe primary outcomes, which are adjusted analyses, and secondary outcomes, which are unadjusted analyses, as being equivalent. I would suggest that the authors do not assert that the results of the unadjusted analysis are associated with the outcomes with the same strength as the results of the adjusted analysis. Line 37: “Frailty was not associated with increased readmission rate, LOS, or rate of complications.” Line 39: “Frailty is associated with increased odds of unfavorable discharge disposition but not with other major complications for geriatric patients admitted with TBI.” Line 165: ” In a cohort of patients older the age of 70 admitted to the neurosurgical　service at a Level I trauma center, we find that physiologic frailty was associated with unfavorable　discharge disposition independently of age. We did not, however, observe a relationship between physiologic frailty and major inpatient complications, consulting services per patient, LOS, discharge GCS, or readmission/re-presentation to acute care after discharge. “ L183: “Our finding that frail patients are at risk for unfavorable discharge disposition but not other adverse outcomes” L236: “Frailty is associated with increased odds of unfavorable discharge disposition but not with other major complications for geriatric patients admitted with TBI.” The language of these statements have been modified to more clearly distinguish between the primary result, which is controlled for on multivariate analysis, and the secondary results, which are not. 6. Based on the journal's publication criteria, part of the conclusions would be inappropriate because it is unclear from which results they are derived. Line 238: “Our study suggests that increased attention to the development of inpatient and outpatient care pathways and patient medical and social navigation protocols that more carefully assess alterations in neurological and physiologic derangement, and which identify and insure more complete and durable return to an optimal level of function is warranted.” The conclusion has also been amended, as above. Minor comments 1. Line 21: The authors need to spell out “TBI”. This abbreviation has now been spelled out. 2. Line 22: It would be better to add elderly or geriatric patients as a target population. This clarification has been added 3. Line 94: The authors need to define "number of consulting services provided to hospitalized patients". A parenthetical listing some possible consulting services has been added to clarify this statement. 4. Line 95: The citation for the definition of "major complications during hospitalization" needs to be mentioned. An appropriate citation has been included. 5. The authors would do well to discuss the possibility that the indication for surgery causes selection bias (patients too severely ill to undergo surgery). Additional discussion of this point has been added to the limitations section of the discussion 6. The authors need to describe that they treated GCS as categorical variables and the rationale of the category in Methods. This has been clarified in the manuscript 7. Please resubmit the Figure1 because of poor resolution. The old figure 1 (now figure 3) has been updated. The authors would again like to thank the editorial staff for giving them the chance to revise this manuscript. Sincerely, Rahul A Sastry On behalf of all other authors Attachments Attachment Submitted filename: fraity_revisions.docx https://doi.org/10.1371/journal.pone.0275677.r002
21 Sep 2022 Decision Letter - Yusuke Tsutsumi, Editor Frailty Independently Predicts Unfavorable Discharge in Non-Operative Traumatic Brain Injury: A Retrospective Single-Institution Cohort Study PONE-D-22-19585R1 Dear Dr. Sastry, 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, Yusuke Tsutsumi 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 #1: All comments have been addressed 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 #1: Yes Reviewer #2: Partly ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes 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 #1: No Reviewer #2: 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 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 #1: The authors have responded appropriately to the remarks made by the reviewer. No further comments are noted. 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 #1: No Reviewer #2: No ******** https://doi.org/10.1371/journal.pone.0275677.r003
Formally Accepted
27 Sep 2022 Acceptance Letter - Yusuke Tsutsumi, Editor PONE-D-22-19585R1 Frailty Independently Predicts Unfavorable Discharge in Non-Operative Traumatic Brain Injury: A Retrospective Single-Institution Cohort Study Dear Dr. Sastry: 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 Dr. Yusuke Tsutsumi Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0275677.r004

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