Central nervous system infection in the intensive care unit: Development and validation of a multi-parameter diagnostic prediction tool to identify suspected patients

Hugo Boechat Andrade; Ivan Rocha Ferreira da Silva; Justin Lee Sim; José Henrique Mello-Neto; Pedro Henrique Nascimento Theodoro; Mayara Secco Torres da Silva; Margareth Catoia Varela; Grazielle Viana Ramos; Aline Ramos da Silva; Fernando Augusto Bozza; Jesus Soares; Ermias D. Belay; James J. Sejvar; José Cerbino-Neto; André Miguel Japiassú

doi:10.1371/journal.pone.0260551

Peer Review History

Original SubmissionJune 14, 2021
19 Oct 2021 Decision Letter - Andrea Cortegiani, Editor Transfer Alert This paper was transferred from another journal. As a result, its full editorial history (including decision letters, peer reviews and author responses) may not be present. PONE-D-21-19498Nervous system infection in the intensive care unit: development and validation of a multi-parameter diagnostic prediction tool to identify suspected patientsPLOS ONE Dear Dr. Andrade, 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 Dec 03 2021 11:59PM. 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Kind regards, Andrea Cortegiani, M.D. 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. 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 If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references.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 If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice. Additional Editor Comments (if provided): Two reviewers experts in the field underlined the quality of the paper and proposed some points to be improved. I agree on these points that should be addressed. [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: Partly Reviewer #2: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: I Don't Know 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 paper is well written. The authors specified a model to indicate the diagnosis of central nervous system infections. Their ultimate model included AIDS/HIV, Age, CSF WBC >2 cells/mm3, encephalopathy, fever, focal neurologic deficit, GCS <14 (points), seizures as the parameters to establish CNS diagnosis in suspected ICU patients. Frankly to say, I was not surprised with these results considering our daily medical practices. Anyway, it may contribute to the readers. On the other hand, it will be better if an expert statistician checks advanced mathematics in the paper. There are some minor points: Please revise NSI and replace it with central nervous system infections. The reference of erdem et al mentions all CNS infections, HIV positives are a subgroup in the paper and should be revised accordingly. Reviewer #2: In the article “Nervous system infection in the intensive care unit: development and validation of a multi-parameter diagnostic prediction tool to identify suspected patients” the authors present an interesting tool that could aid physicians screening patients for nervous system infections. The article is well presented, clear in the content and appropriate in the form. Results are clearly presented and there are not overstatements in the discussion. The study limitations and conclusions are adequate, reporting the need for this tool to be further validated in different contexts from the ones of this study. I do not have major concerns regarding the publication of this article. As a minor concern I noticed the absence of a protocol registration which might have been appropriate. Other comments: Line 144: please rephrase as the meaning of the sentence is unclear. Line 195: please rephrase as it follows: “The variables required for calculating theVC2 were collected and crosschecked by two of the authors (IRFDS and JLS)” ****** 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:** Hakan Erdem 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. https://doi.org/10.1371/journal.pone.0260551.r001
Revision 1
21 Oct 2021 Author Response PONE-D-21-19498 Nervous system infection in the intensive care unit: development and validation of a multi-parameter diagnostic prediction tool to identify suspected patients PLOS ONE New title after review: “Central nervous system infection in the intensive care unit: development and validation of a multi-parameter diagnostic prediction tool to identify suspected patients” Response to Reviewers “Dear Dr. Andrade, 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.” R: Thank you all for the attention and consideration. My answers are highlighted in blue. "If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results." R: Thank you for the information. There are no laboratory protocol for this study, so it's not applicable. “Additional Editor Comments (if provided): Two reviewers experts in the field underlined the quality of the paper and proposed some points to be improved. I agree on these points that should be addressed.” R: Thank you. We addressed the points to improve it. It is an honor to publish once again with such an internationally respected medical journal. “5. Review Comments to the Author Reviewer #1: The paper is well written. The authors specified a model to indicate the diagnosis of central nervous system infections. Their ultimate model included AIDS/HIV, Age, CSF WBC >2 cells/mm3, encephalopathy, fever, focal neurologic deficit, GCS <14 (points), seizures as the parameters to establish CNS diagnosis in suspected ICU patients. Frankly to say, I was not surprised with these results considering our daily medical practices. Anyway, it may contribute to the readers. R: Thank you very much for your time. Yes, our intention was to build a tool that could help general practice physicians screening patients for central nervous system infections. “On the other hand, it will be better if an expert statistician checks advanced mathematics in the paper.” R: Yes, good advice. Thank you. The advanced mathematics were really complex, so they were assessed by expert statisticians from our institutions before submission. There are some minor points: Please revise NSI and replace it with central nervous system infections. The reference of erdem et al mentions all CNS infections, HIV positives are a subgroup in the paper and should be revised accordingly.” R: We changed Nervous System Infection (NSI) for Central Nervous System Infection (CNSI) as recommended. Therefore, this led to the title of the article being changed to “Central nervous system infection in the intensive care unit: development and validation of a multi-parameter diagnostic prediction tool to identify suspected patients”. We also revised the text for the reference of Erdem et Al (lines 342-347) as follows: “The microbiological profile is compatible with the current international literature: in a multicenter international study to understand the burden of community acquired CNSI, Erdem et al. showed that the most frequent pathogens were Streptococcus pneumoniae (n=206; 8%) and Mycobacterium tuberculosis (n=152; 5.9%). Cryptococci were the leading pathogens in the subgroup of HIV-positive individuals. Ninety-six (8.9%) patients of INI's sample presented with clinical features of a subacute disease, suggestive of tuberculosis or neurosyphilis [31].” “Reviewer #2: In the article “Nervous system infection in the intensive care unit: development and validation of a multi-parameter diagnostic prediction tool to identify suspected patients” the authors present an interesting tool that could aid physicians screening patients for nervous system infections. The article is well presented, clear in the content and appropriate in the form. Results are clearly presented and there are not overstatements in the discussion. The study limitations and conclusions are adequate, reporting the need for this tool to be further validated in different contexts from the ones of this study. I do not have major concerns regarding the publication of this article. As a minor concern I noticed the absence of a protocol registration which might have been appropriate.” R: Thank you for your review. As an observational study with no interventions and no systematic reviews, we didn’t register the protocol. However, with your comment, we have only recently discovered that there is a possibility to register observational studies on the ClinicalTrials.gov website. Thank you for the advice. Next time we will proceed as recommended. “Other comments: Line 144: please rephrase as the meaning of the sentence is unclear.” R: We agree. We deleted part of it, as it was confusing. The new phrase is as follows: “Two physicians (HBA and JHN) independently reviewed the medical records. The diagnosis of CNSI was considered if it met at least two of…”. “Line 195: please rephrase as it follows: “The variables required for calculating theVC2 were collected and crosschecked by two of the authors (IRFDS and JLS)”’ R: Done. Rephrased. Sincerely, Hugo Boechat Andrade, MD, MSc Corresponding Author Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0260551.r002
12 Nov 2021 Decision Letter - Andrea Cortegiani, Editor Central nervous system infection in the intensive care unit: development and validation of a multi-parameter diagnostic prediction tool to identify suspected patients PONE-D-21-19498R1 Dear Dr. Andrade, 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, Andrea Cortegiani, M.D. Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0260551.r003
Formally Accepted
16 Nov 2021 Acceptance Letter - Andrea Cortegiani, Editor PONE-D-21-19498R1 Central nervous system infection in the intensive care unit: development and validation of a multi-parameter diagnostic prediction tool to identify suspected patients Dear Dr. Andrade: 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. Andrea Cortegiani Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0260551.r004

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