Added value of clinical prediction rules for bacteremia in hemodialysis patients: An external validation study

Sho Sasaki; Yoshihiko Raita; Minoru Murakami; Shungo Yamamoto; Kentaro Tochitani; Takeshi Hasegawa; Kiichiro Fujisaki; Shunichi Fukuhara

doi:10.1371/journal.pone.0247624

Peer Review History

Original SubmissionOctober 23, 2020
9 Dec 2020 Decision Letter - Tatsuo Shimosawa, Editor PONE-D-20-33423 Added value of clinical prediction rules for bacteremia in hemodialysis patients: An external validation study PLOS ONE Dear Dr. Sasaki, 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 topic is potentially interesting and important issue. The three experts raised some concerns and points to be clearly described. Please submit your revised manuscript by Jan 23 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: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols We look forward to receiving your revised manuscript. Kind regards, Tatsuo Shimosawa, M.D., Ph.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. Thank you for stating in the text of your manuscript The present study was approved by the ethics committee of Iizuka Hospital (17167-436), Okinawa Prefectural Chubu Hospital (H28-51) and Saku General Hospital (R201701-01). The study was conducted in accordance with the ethical standards of the Declaration of Helsinki." Please also add this information to your ethics statement in the online submission form. 3. Please confirm whether ethical approval was obtained for the original cohort and for the validation cohorts, or whether there was a different ethical approval for cohorts 1&2. 4. Thank you for stating in your manuscript "Since all patient information analyzed in this study was retrospective, participants’ written informed consent was not obtained." In your ethics statement in the Methods section and in the online submission form, please clarify whether all data were fully anonymized before or after you accessed them and/or whether the IRB or ethics committee waived the requirement for informed consent. 5. Please include the date(s) on which you accessed the databases or records to obtain the data used in your study. 6. 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 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 identifying or sensitive patient information) 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. Please see http://www.bmj.com/content/340/bmj.c181.long for guidelines on how to de-identify and prepare clinical data for publication. 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. [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 Reviewer #3: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes Reviewer #3: 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: No Reviewer #3: 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 Reviewer #3: 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: Dear authors, Predicting bacteria in in HD patients is important clinical tool to care for this patient population. The methodology is standard and statistical analysis is robust. Minor comments are as follows. 1- Why was the study design as a basic model and added models? Why not the comparison between the 2 final models? Was the basic model validated to start with? (To assess the value of reclassification) 2- A typo in second line of introduction (Key should be keys). 3- How does the lack of standard criteria for blood cultures make the 2 cohorts different in characteristics? 4- How did the expert panel exclude the contamination from retrospective data? 5- Please explain why difference in etiology (Gram-negative vs Gram-positive) between genera population and HD patient will render Shapro's score ineffective in predicting bacteremia. 6- Please explain the calibration plot. Regards Reviewer #2: This is an interesting study addressing the external validation of a novel clinical prediction rule (CPR) for bacteremia (BAC-HD score) which the authors have previously developed specifically for hemodialysis (HD) patients. They compared the diagnostic accuracy of BAC-HD score and the Shapiro’s criteria and reported that the former was better in the discrimination ability to predict bacteremia than the latter. The article is well drafted and certainly provides valuable information to supplement clinical judgment and treatment decision in the dialysis unit. The reviewer has a few comments as follows: 1) The indications for obtaining blood cultures are not presented, and the patient selection for the two cohorts cannot escape a certain degree of arbitrariness. There may have been patients with bacteremia who did not have a blood culture obtained and therefore were not included I the patient population. This point should be clearly stated as limitation in the manuscript. 2) The authors refer to the uniqueness of bacteria etiology of HD patients. Can the authors present data of the frequency of the organisms actually cultured from the blood culture of the patients? Can the authors present data concerning the suspected infectious foci of the patients as well? 3) Concerning the ‘false negative’ cases (i.e. score did not suggest a culture but the patient was found to be bacteremic), there seems to be seven patients in Model 2 and eight in Model 2. Do these patients of the two Models show considerable overlapping? Can the authors describe the clinical circumstances of these patients and comment on the reason why the patients were missed by the prediction rule? Reviewer #3: This study intends to provide exteral validation to a recently described prediction model for diagnosing bacteremia in hemodialysis patients. Further, the diagnostic yield of the new model is compared to an established model by Shapiro et al. Since bacteremia is an important problem and the diagnosis is not straight forward, this approach is relevant and interesting. The paper is well written. The study is retrospective in design, two validation cohorts were formed at two different hospitals. Patients were included if they were on maintenance hemodialysis and two blood cultures were drawn at hospital admission. The prediction models were compared with the results of the blood cultures. Both additive models improved prediction of positive blood cultures. The authors claim that their new score performed better than Shapiro's rule, however, the data suggest that both rules add similarly to the basic model. The authors should check if they really can assume superiority. Some suggestions to the authors: 1) line 61: fortunately bacteremia is not identical with sepsis, although it may lead to this severe complication. The mortality rates cited in #18 and #19 are for Sepsis. 2) lines 65 f: please consider rewording, this sentence is hard to understand. Further, at least with CVC the time point of dialysis is most likely irrelevant for the diagnostic yield of blood cultures when drawn from the catheter. 3) Would the addition of the condition "CVC present" further improve the BAC-HD score? This seems most likely given the numbers in Tbl. 1 ****** 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: No Reviewer #3: 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.0247624.r001
Revision 1
22 Jan 2021 Author Response RESPONSE TO EDITOR 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 RESPONSE: Thank you for your very clear guidance. We have referred to the guide and revised the manuscript accordingly. 2. Thank you for stating in the text of your manuscript The present study was approved by the ethics committee of Iizuka Hospital (17167-436), Okinawa Prefectural Chubu Hospital (H28-51) and Saku General Hospital (R201701-01). The study was conducted in accordance with the ethical standards of the Declaration of Helsinki." Please also add this information to your ethics statement in the online submission form. RESPONSE: Thank you for reminding us of this; we will include this on the submission form,. 3. Please confirm whether ethical approval was obtained for the original cohort and for the validation cohorts, or whether there was a different ethical approval for cohorts 1&2. RESPONSE: The validation cohort and the original cohort were separately approved by the ethics committees of the relevant institutions. In this article, we have provided the approval numbers for the validation cohort. 4. Thank you for stating in your manuscript "Since all patient information analyzed in this study was retrospective, participants’ written informed consent was not obtained." In your ethics statement in the Methods section and in the online submission form, please clarify whether all data were fully anonymized before or after you accessed them and/or whether the IRB or ethics committee waived the requirement for informed consent. Please include the date(s) on which you accessed the databases or records to obtain the data used in your study. RESPONSE: Thank you for your suggestion. We have revised the sentence in the Methods section. We will also include additional information on the submission form. Revised sentences (lines 83–87): Since all patient information analyzed in this study was retrospective, participants’ written informed consent was not required by the ethics committee. All data were fully anonymized before authors accessed them. We accessed the medical records at Okinawa Prefectural Chubu Hospital from February 9th to February 13th, 2017, and at Saku General Hospital from February 24th to 26th, 2017. 5. 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 information on unacceptable data access restrictions, please see http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions. RESPONSE: We have obtained permission to provide the minimal anonymized datasets from the ethical committees of participating facilities. REVIEWER 1: 1- Why was the study design as a basic model and added models? Why not the comparison between the 2 final models? Was the basic model validated to start with? (To assess the value of reclassification) REPONSE: We wish to express our appreciation to Reviewer 1 for his or her insightful comments, which have helped us significantly improve the paper. We appreciate your raising this important point. As you pointed out, we created a basic model to assess the added value of clinical prediction rules (CPRs). We referred to previous studies (Moons, 2012 #12226), (Takada, 2020 #12228) as a basis for considering that validation of the basic model is not necessary. We have revised line 141 as below: Revised sentence (lines 142–145): The basic model to assess the value of reclassification of CPRs was conducted using a logistic regression model with explanatory variables of sex (0: female, 1: male), age (y), mean arterial pressure (mmHg), heart rate, body temperature (°C), presence of diabetes mellitus, HD vintage (months), and white blood cell count (× 109/L). 2- A typo in second line of introduction (Key should be keys). RESPONSE: We apologize for our mistake and have corrected it (Line 55). 3- How does the lack of standard criteria for blood cultures make the 2 cohorts different in characteristics? RESPONSE: We appreciate your raising this important point. Unfortunately, it is difficult to provide data on the standard procedures for the drawing of blood cultures at different facilities. Clinically, the threshold for blood cultures being drawn varies among institutions. We have modified line 123 as follows: Revised sentence (line 128): Since there are no standard criteria for obtaining blood cultures, it was suspected that the selection of subjects may have differed depending on the facility. 4- How did the expert panel exclude the contamination from retrospective data? RESPONSE: We appreciate your important point. We apologize for the lack of explanation in the text. The expert panel, which was blinded to the study design, used the results of the blood cultures, as well as basic patient information and blood test results, to determine contamination. We have revised lines 117–121 accordingly: Revised sentences (lines 119–123): Finally, an external consensus panel of infectious disease physicians with > 10 y clinical experience and Japanese Board of Infectious Disease certification who were blinded to the present study design determined whether a culture was contaminated or not based on the above definitions and their clinical expertise. 5- Please explain why difference in etiology (Gram-negative vs Gram-positive) between genera population and HD patient will render Shapiro's score ineffective in predicting bacteremia. RESPONSE: We appreciate Reviewer 1’s pointing out this important issue. Unfortunately, we have not found adequate evidence that different species or foci of infection have different clinical presentations. We have revised accordingly: Revised text (lines 227–230): In our experience, UTIs and BSIs often have different clinical presentations. We therefore considered that Shapiro’s score, a CPR developed in a population with a high rate of UTIs, would be unable to predict bacteremia in maintenance HD patients with a high rate of cutaneous infections. 6- Please explain the calibration plot. We apologize to reviewer 1 for the lack of explanation. The calibration plot is a diagram for evaluating the calibration of a logistic regression model, checking the difference between the observed probability and the probability estimated by the regression model. Therefore, the closer the slope of the plot is to 1 and the closer the intercept is to 0, the better the calibration is. REVIEWER 2: 1) The indications for obtaining blood cultures are not presented, and the patient selection for the two cohorts cannot escape a certain degree of arbitrariness. There may have been patients with bacteremia who did not have a blood culture obtained and therefore were not included I the patient population. This point should be clearly stated as limitation in the manuscript. We wish to express our appreciation to Reviewer 2 for his or her insightful comments, which have helped us significantly improve the paper. RESPONSE TO REVIEWER 2: We appreciate your important point. We added the following to the limitations (line 261–267) as suggested by reviewer 2: Fourth, since there were no standard criteria for when to obtain blood cultures, the possibility that there was some degree of arbitrariness to the decision to draw blood cultures cannot be denied. However, since we used data before the development of the BAC-HD score, the items in the BAC-HD score could not have influenced the decision on whether or not to draw blood cultures. Furthermore, it is possible that some of the patients whose blood cultures were not drawn included cases of bacteremia. 2) The authors refer to the uniqueness of bacteria etiology of HD patients. Can the authors present data of the frequency of the organisms actually cultured from the blood culture of the patients? Can the authors present data concerning the suspected infectious foci of the patients as well? RESPONSE: We thank reviewer 2 for these important points. We have described the frequency of the causative organism in S1 Table. Unfortunately, we do not have reliable data on suspected infectious foci due to the fact that this is a retrospective study, so we are unable to provide data on this. New table: S1 Table. Pathogens involved in bacteremia in validation cohorts 1 and 2 Validation cohort 1 n = 37 Validation cohort 2 n = 16 Total n = 53 Staphylococcus aureus (S. aureus) 9 (24.4) 9 (56.2) 18 (34.0) [methicillin-resistant S. aureus] 5 2 7 coagulase negative Staphylococci 1 (2.7) 2 (12.5) 3 (5.7) Streptococcus spp. 2 (5.4) 2 (12.5) 4 (7.5) Enterococcus spp. 2 (5.4) 2 (12.5) 4 (7.5) Escherichia coli 11 (29.7) 0 11 (20.8) Klebsiella pneumoniae 4 (10.8) 1 (6.3) 5 (9.4) Others 8 (21.6) 0 8 (15.1) 3) Concerning the ‘false negative’ cases (i.e. score did not suggest a culture but the patient was found to be bacteremic), there seems to be seven patients in Model 2 and eight in Model 2. Do these patients of the two Models show considerable overlapping? Can the authors describe the clinical circumstances of these patients and comment on the reason why the patients were missed by the prediction rule? RESPONSE: We thank Reviewer 2 for these important questions. Two of the false-negative cases overlapped. Unfortunately, we could not find any similarities between these cases, and the reason why the predictive scores showed false negatives is unknown. REVIEWER 3: This study intends to provide external validation to a recently described prediction model for diagnosing bacteremia in hemodialysis patients. Further, the diagnostic yield of the new model is compared to an established model by Shapiro et al. Since bacteremia is an important problem and the diagnosis is not straight forward, this approach is relevant and interesting. The paper is well written. The study is retrospective in design, two validation cohorts were formed at two different hospitals. Patients were included if they were on maintenance hemodialysis and two blood cultures were drawn at hospital admission. The prediction models were compared with the results of the blood cultures. Both additive models improved prediction of positive blood cultures. The authors claim that their new score performed better than Shapiro's rule, however, the data suggest that both rules add similarly to the basic model. The authors should check if they really can assume superiority. We wish to express our appreciation to Reviewer 3 for his or her insightful comments, which have helped us significantly improve the paper. We appreciate your important point. As you noted, the interpretation of the results was incorrect. The following corrections have been made: Revised sentence (lines 47–49): Either the BAC-HD score or Shapiro’s score may improve the ability to diagnose bacteremia in HD patients. Reclassification was better with the BAC-HD score. Revised sentence (lines 274–276): We suggest that either the BAC-HD score or Shapiro’s score may improve the accuracy of predicting bacteremia in patients on HD. Reclassification was better with the BAC-HD score. Some suggestions to the authors: 1) line 61: fortunately bacteremia is not identical with sepsis, although it may lead to this severe complication. The mortality rates cited in #18 and #19 are for Sepsis. RESPONSE: We appreciate the important point made by reviewer 3. We apologize for our inaccurate description. We have revised line 65 as follows: The annual mortality due to sepsis, a severe complication of bacteremia, in HD patients is 50–100 times higher than that of the general population 2) lines 65 f: please consider rewording, this sentence is hard to understand. Further, at least with CVC the time point of dialysis is most likely irrelevant for the diagnostic yield of blood cultures when drawn from the catheter. RESPONSE: We appreciate your important point. We have revised lines 69–72. In addition, we added sentences to the limitations (line 257) that blood cultures may have been taken from the CVC. However, in our opinion, since only a small number of Japanese dialysis patients use CVC, the impact of CVC on the present study was small. Revised sentence (lines 69–72): Since many blood test findings in HD patients are often affected by dialysis, the accuracy of items included in existing CPRs developed in the general population, such as blood counts and serum creatinine levels, may be greatly affected New sentence (lines 267–271): Fifth, it is unclear whether blood cultures were collected from a central venous catheter (CVC) that was the site of vascular access. However, since it is unlikely that both sets of blood cultures were collected from the CVC, and the number of CVCs was small, we believe that the effect of this was not significant. 3) Would the addition of the condition "CVC present" further improve the BAC-HD score? This seems most likely given the numbers in Tbl. 1 RESPONSE: Thank you for pointing out this very important issue. In the BAC-HD development paper, we used “CVC use” as a candidate predictor, but it did not remain in the final model. Since the purpose of this study was to test external validity, we did not test the effect of CVC use on improving predictive ability. There are two reasons why CVC use was not included in the final model even though it is an important predictor, the first being that it was incompatible with other variables in multivariate models, and the second that the number of CVCs used was too small. https://doi.org/10.1371/journal.pone.0247624.r002
10 Feb 2021 Decision Letter - Tatsuo Shimosawa, Editor Added value of clinical prediction rules for bacteremia in hemodialysis patients: An external validation study PONE-D-20-33423R1 Dear Dr. Sasaki, 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, Tatsuo Shimosawa, M.D., Ph.D. 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: Yes ****** 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: Yes 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: Dear authors, Thank you for addressing my previous comments. I do not have any other comments at this point. Best, 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: Yes:** Islam M. Ghazi, PharmD Reviewer #2: No https://doi.org/10.1371/journal.pone.0247624.r003
Formally Accepted
12 Feb 2021 Acceptance Letter - Tatsuo Shimosawa, Editor PONE-D-20-33423R1 Added value of clinical prediction rules for bacteremia in hemodialysis patients: An external validation study Dear Dr. Sasaki: 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 Prof. Tatsuo Shimosawa Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0247624.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 .