Dynamic SOFA score assessments to predict outcomes after acute admission of octogenarians to the intensive care unit

Emmanuelle Loyrion; Lydiane Agier; Thibaut Trouve-Buisson; Gaetan Gavazzi; Carole Schwebel; Jean-Luc Bosson; Jean-François Payen

doi:10.1371/journal.pone.0253077

Peer Review History

Original SubmissionMarch 30, 2021
11 May 2021 Decision Letter - Martina Crivellari, Editor PONE-D-21-10444 Which early indicators associated with outcomes in very old critically ill patients? PLOS ONE Dear Dr. Payen, 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 manuscript presents an intersting and relavant analysis. But the population is small and eterogeneous and there is not a sample size calculation. So the results should be interpreted with caution. Which type of study is this? cross-sectional study as defined in the abstract or a prospective observational cohort study? Some important informations about the reason for Admission and first therapy are also not so clear. 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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: Partly Reviewer #2: Partly ******** 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: The study "Which early indicators associated with outcomes in very old critically ill patients? presents an interesting Analysis on older patients admitted to ICU and Outcome prediction. The study is intersting a relevant but I'd like to highlight a number of issues thet should be adressed be the authors: The title should include "are". 1)I would suggest to use "octogenarians" intead of "very old patients". 2)How could a stay longer than 24 be predicted? 3) It is not clear how a "end of life" decision before 48 Hours excluded patients from the study and not when taken later during the Hospital stay. 4) The authors should specify the reason for Admission. When they stated Surgery, does it mean post surgical? Was it post emergency or planned surgery? 5) The Population is relatively small and Comes from four very different ICUS. 6) Th ereason for Admission to ICU may also have played a role an certaily would help to direct the Interpretation of the results. What was the main failure or combination of filures? What was the Treatment initiated (e.g. mechanical Ventilation/Dialysis) 7) I appreciated the idea of TLT. Did the Authors looked at SOFA Change and absolute number at 24 or 48 Hours? Would they expect them to be different? 7) Was there any power Analysis done? 8) How would this results practically Impact on clinical decision making? Reviewer #2: Thank you for asking me to review this exciting manuscript. Summary Payen et al. evaluated the association of early indicators, i.e., the SOFA score at admission (day 1) and day four, along with other factors, with long-term outcomes, i.e., 90-day mortality and functional status among ≥80-year-old patients. They found that the combination of day 4 SOFA score and other factors associated with mortality increased the prediction of death as evidenced by the AUROC of 0.81 compared to the only SOFA at day four is 0.72. In addition, they found that SOFA at day four, unlike at admission, was significantly associated with mortality. However, this asserts the message that predictive tools should not be used in isolation to determine outcomes for individual patients. Provision of a time-limited trial is, therefore, could potentially be justified; however, these results ought to be interpreted with caution because of the petite sample size. While there are ample studies on elderly patients and factors associated with their outcomes, both short- and long-term, this study focuses on using the SOFA score akin to a time-limited trial to assess association with long-term outcomes. While it’s not novel but highlights an important message, due to some of the methodological challenges, the validity of the results is in question, especially related to the functional assessment. Major comments 1. Methods a) The authors should highlight the sampling method used for this study. b) How did the authors arrive at the sample size they needed? There was no sample size calculation description made. The authors should perhaps give the reason for this. Sample size is essential for a study whose aim is to assess the predictive ability of tools like the SOFA score and other factors. c) The function assessment was both with regards to independence (self-sufficiency) and functional activity. However, the Katz Index of Independence in Activities of Daily Living (ADL) assesses independence, while the Lawton Instrumental Activities of Daily Living (IADL) assess functional activity. However, in lines 121-124, the authors indicate that the tools were assessing the opposite i.e., “An ADL score of 6 indicated full function, and a score of 2 or less severe functional impairment. Full independence was indicated with an IADL score of 8 and dependence with an IADL score of 0.” Perhaps the authors can provide clarification to this. Minor 1. General comments a) Some minor grammatical errors need to be fixed especially in the results section as well as clarity of writing for the reader to grasp the message e.g. Figure 1, “End-of-decision < 48h after admission” 2. Title a) The title doesn’t highlight the key aim of the research, which is to use SOFA score in conjunction with other variables in predicting long-term outcomes of very old critically ill patients. b) Perhaps the authors should consider highlighting the SOFA score in the title and including the study design in the title. 3. Abstract a) However, the abstract refers to it as a cross-sectional study (line 33), while the methods section, line 82, refers to it as a prospective observational cohort study. The authors should clarify this discrepancy; however, this is a prospective cohort study by design. 4. Methods a) It is clear how long the follow-up period was, i.e., 90 days after ICU admission; however, the authors should include how long the recruited patients. When did the recruitment end? b) It is unclear why night or weekend admissions were excluded. c) In Figure 1, Exclusion based on “Unknown reason” is unclear. Authors perhaps should explain these criteria with some examples if possible in the Results section. 5. Limitations a) Due to the petite sample size, the authors clearly state that their results ought to be interpreted with caution. ****** 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:** Massimiliano Meineri 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. 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Revision 1
26 May 2021 Author Response POINT-BY-POINT RESPONSE TO REVIEWERS We thank the reviewers for their constructive criticisms and suggestions that have helped us to clarify the paper and to enhance the quality of the message. Academic Editor The manuscript presents an interesting and relevant analysis. But the population is small and heterogeneous and there is not a sample size calculation. So the results should be interpreted with caution. Which type of study is this? cross-sectional study as defined in the abstract or a prospective observational cohort study? Some important information about the reason for Admission and first therapy are also not so clear. ANSWER: We thank you for these comments. These issues have been addressed accordingly. Please see our responses below to Rev#1 and 2. Reviewer #1 The study "Which early indicators associated with outcomes in very old critically ill patients?” presents an interesting Analysis on older patients admitted to ICU and Outcome prediction. The study is interesting a relevant but I'd like to highlight a number of issues they should be addressed be the authors. The title should include "are". ANSWER: As suggested by Rev#2, the title has been changed. 1) I would suggest to use "octogenarians" instead of "very old patients". ANSWER: Done. 2) How could a stay longer than 24 be predicted? ANSWER: More information about this point has been provided now (lines 95-96). 3) It is not clear how a "end of life" decision before 48 Hours excluded patients from the study and not when taken later during the Hospital stay. ANSWER: We have considered that early EOL decision was due to the extreme severity of illness on admission. This situation was similar to that of moribund patients staying in the ICU for less than 24h. However, EOL decisions could have been taken later if the medical team deemed that the patient’s condition worsened despite active therapies. These patients were then included in the study either in the primary analysis where EOL decision was taken after day 4 or in the sensitivity analysis with EOL decision between day 2 and day 4 (see Fig.1). 4) The authors should specify the reason for Admission. When they stated Surgery, does it mean post surgical? Was it post emergency or planned surgery? ANSWER: As mentioned in the MM section (line 98), patients were not included if they were admitted after elective surgery. The “unknown reason” term has been changed to “other reasons” with more information (lines 167-169). 5) The Population is relatively small and comes from four very different ICUS. ANSWER: This comment is right. This issue has been more discussed as a limit of the study (lines 338-342). 6) The reason for Admission to ICU may also have played a role and certainly would help to direct the Interpretation of the results. What was the main failure or combination of failures? What was the Treatment initiated (e.g. mechanical Ventilation/Dialysis). ANSWER: More information on the reasons for admission is provided now (lines 174-177). The most frequent organ failures and the most required treatments have been mentioned (please see Table 1 and lines 177-178). 7) I appreciated the idea of TLT. Did the Authors looked at SOFA Change and absolute number at 24 or 48 Hours? Would they expect them to be different? ANSWER: Unfortunately, we could not assess SOFA score on day 2 and day 3. However, serial measurements of SOFA score have been rarely performed in the literature. The use of changes in SOFA scores (delta SOFA) to predict mortality has been recently discussed (lines 75-76). 8) Was there any power Analysis done? ANSWER: As requested also by Rev.2, more information is provided regarding the estimation of the sample size (lines 157-162). 9) How would this results practically Impact on clinical decision making? ANSWER: We have added a summary statement from our results in the Discussion (lines 273-276). Reviewer #2 Thank you for asking me to review this exciting manuscript. Major comments 1. Methods a) The authors should highlight the sampling method used for this study. ANSWER: Data from unselected, consecutive patients were extracted during the study period. This point is mentioned now (lines 105-106). b) How did the authors arrive at the sample size they needed? There was no sample size calculation description made. The authors should perhaps give the reason for this. Sample size is essential for a study whose aim is to assess the predictive ability of tools like the SOFA score and other factors. ANSWER: This comment is right. As requested also by Rev.1, more information is provided regarding the estimation of the sample size (lines 157-162). c) The function assessment was both with regards to independence (self-sufficiency) and functional activity. However, the Katz Index of Independence in Activities of Daily Living (ADL) assesses independence, while the Lawton Instrumental Activities of Daily Living (IADL) assess functional activity. However, in lines 121-124, the authors indicate that the tools were assessing the opposite i.e., “An ADL score of 6 indicated full function, and a score of 2 or less severe functional impairment. Full independence was indicated with an IADL score of 8 and dependence with an IADL score of 0.” Perhaps the authors can provide clarification to this. ANSWER: This suggestion is correct. Wording regarding these scores has been changed accordingly (lines 125-126). Minor 1. General comments a) Some minor grammatical errors need to be fixed especially in the results section as well as clarity of writing for the reader to grasp the message e.g. Figure 1, “End-of-decision < 48h after admission” ANSWER: Please note that the manuscript had been reviewed and corrected by an English professional medical writer, who was not involved in the study. We have double-checked the material to prevent grammatical errors. Fig.1 has been corrected accordingly. 2. Title a) The title doesn’t highlight the key aim of the research, which is to use SOFA score in conjunction with other variables in predicting long-term outcomes of very old critically ill patients. ANSWER: The title has been changed as suggested. b) Perhaps the authors should consider highlighting the SOFA score in the title and including the study design in the title. ANSWER: Done. Due to the length of the new title, it was not possible to insert the study design. 3. Abstract a) However, the abstract refers to it as a cross-sectional study (line 33), while the methods section, line 82, refers to it as a prospective observational cohort study. The authors should clarify this discrepancy; however, this is a prospective cohort study by design. ANSWER: Abstract corrected. 4. Methods a) It is clear how long the follow-up period was, i.e., 90 days after ICU admission; however, the authors should include how long the recruited patients. When did the recruitment end? ANSWER: As mentioned in the MM section, the recruitment ended on 15 September 2018 (line 84). The status of the latest enrolled patient was assessed on day 90 after his/her admission, i.e. 15 January 2019. b) It is unclear why night or weekend admissions were excluded. ANSWER: Data had to be collected on real-time, in particular those regarding preadmission frailty and nutritional status. To do so, only one person (EL) was in charge of this task to ensure their reliability and consistency. This explains why inclusions during nights or weekends were not possible. c) In Figure 1, Exclusion based on “Unknown reason” is unclear. Authors perhaps should explain these criteria with some examples if possible in the Results section. ANSWER: The “unknown reason” term has been changed to “other reasons” with more information (lines 167-169). 5. Limitations a) Due to the petite sample size, the authors clearly state that their results ought to be interpreted with caution. ANSWER: This comment is right. This issue has been more discussed as a limit of the study (lines 338-342). https://doi.org/10.1371/journal.pone.0253077.r002
28 May 2021 Decision Letter - Martina Crivellari, Editor Dynamic SOFA score assessments to predict outcomes after acute admission of octogenarians to the intensive care unit PONE-D-21-10444R1 Dear Dr. Payen, 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, Martina Crivellari Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0253077.r003
Formally Accepted
22 Jul 2021 Acceptance Letter - Martina Crivellari, Editor PONE-D-21-10444R1 Dynamic SOFA score assessments to predict outcomes after acute admission of octogenarians to the intensive care unit Dear Dr. Payen: 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. Martina Crivellari Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0253077.r004

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