Rhabdomyolysis related to acute recreational drug toxicity—A Euro-DEN study

Wojciech Waldman; Piotr M. Kabata; Alison M. Dines; David M. Wood; Christopher Yates; Fridtjof Heyerdahl; Knut Erik Hovda; Isabelle Giraudon; Euro-DEN Research Group; Paul I. Dargan; Jacek Sein Anand

doi:10.1371/journal.pone.0246297

Peer Review History

Original SubmissionJuly 1, 2020
12 Aug 2020 Decision Letter - Muhammad Adrish, Editor PONE-D-20-18319 Rhabdomyolysis related to acute recreational drug toxicity – a Euro-DEN study. PLOS ONE Dear Dr. Kabata, 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. I have received the comments of the reviewers on your manuscript. The specific comments of the reviewers are included below. Please provide point by point response in your revised manuscript. Please submit your revised manuscript by due date. 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. 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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. 3. One of the noted authors is a group or consortium [Euro-DEN Research Group]. In addition to naming the author group, please list the individual authors and affiliations within this group in the acknowledgments section of your manuscript. Please also indicate clearly a lead author for this group along with a contact email address. 4. Your ethics statement must appear in the Methods section of your manuscript. If your ethics statement is written in any section besides the Methods, please move it to the Methods section and delete it from any other section. Please also ensure that your ethics statement is included in your manuscript, as the ethics section of your online submission will not be published alongside your manuscript. 5. Please include a copy of Table 2 which you refer to in your text (line 191). [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 ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: No ****** 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 ****** 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 ****** 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: In this retrospective analysis, the authors described cases of rhabdomyolysis in patients who presnted to the Emergency Department with severe acute recreational drug toxicity. The study presents an interesting perspective on the frequency of rhabdomyolysis related to different drugs of abuse. However, the manuscript will require a major revision to make it suitable for publication. Areas that require the authors’ attention are itemized below. Method 1. Page 10 line 129-Any justification for restricting the retrospective study to Oct 2013 to Sept 2014? Are there more recent data? 2. Page 11, line 165-168-Statistical analysis- The use of range and interquartile range as measures of data spread suggest that the data were not normally distributed. Therefore, the use of parametric test such as pearson's moment correlation and ANOVA for analysis may not be appropriated. The authors should consider the use of equivalent non parametric test for the analysis. Results 1. Page 12, line 177-192- Correlation between CK and creatinine. This analysis is not necessary, as both biochemical parameter are the result of massive breakdown of skeletal muscles which occurs in Rhabdomyolysis. Early detection of acute renal failure can be achieved by monitoring serum creatinine and serum creatine kinase. CK is a better predictor of ARF due to rhabdomyolysis than creatinine. Since CK and creatinine are usually highly correlated in rhabsomyolysis, an attempt to find the correlation between them in this study will result in multicollinearity. 2. The result tables are not properly labelled. Also, the table do not present a clear distinction between the exposure and outcome variables making them difficult to interpret. Discussion 1. The discussion needs to be better organized. There should be a clear pattern on how current findings connect to, support, elaborate on, or challenge conclusions of earlier studies. Others are highlighted on the attached manuscript. ****** 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:** ISAAC OKOH ABAH [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: PONE-D-20-18319_reviewer.pdf https://doi.org/10.1371/journal.pone.0246297.r001
Revision 1
14 Dec 2020 Author Response Dear Reviewers, we would like to thank you for your review of our manuscript. We hope, that you will find our responses and revisions of the document satisfactory to reconsider the publication of our paper. 1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The style has been adjusted. 2. We note that you have indicated that data from this study are available upon request. PLOS only allows data to be available upon request if there are legal or ethical restrictions on sharing data publicly. For 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. The dataset contains date and time of patients admission to the hospital, which could potentially identify a patient; furthermore recreational drug use is a sensitive area for many individuals and therefore the risks associated with identification are greater in this context. The data can be obtained from European Drug Emergencies Network steering committee. The restrictions have been imposed by the EuroDEN steering committee. For inquiries regarding data access, please contact Mrs Barbara Whetton, phone number: +44 (0)20 7188 5848 barbara.whetton@gstt.nhs.uk 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. 3. One of the noted authors is a group or consortium [Euro-DEN Research Group]. In addition to naming the author group, please list the individual authors and affiliations within this group in the acknowledgments section of your manuscript. Please also indicate clearly a lead author for this group along with a contact email address. Corrected 4. Your ethics statement must appear in the Methods section of your manuscript. If your ethics statement is written in any section besides the Methods, please move it to the Methods section and delete it from any other section. Please also ensure that your ethics statement is included in your manuscript, as the ethics section of your online submission will not be published alongside your manuscript. Corrected 5. Please include a copy of Table 2 which you refer to in your text (line 191). Added Reviewers' comments: Reviewer #1: In this retrospective analysis, the authors described cases of rhabdomyolysis in patients who presnted to the Emergency Department with severe acute recreational drug toxicity. The study presents an interesting perspective on the frequency of rhabdomyolysis related to different drugs of abuse. However, the manuscript will require a major revision to make it suitable for publication. Areas that require the authors’ attention are itemized below. Method 1. Page 10 line 129-Any justification for restricting the retrospective study to Oct 2013 to Sept 2014? Are there more recent data? Whilst Euro-DEN continued after Sept 2014 as the Euro-DEN Plus project creatinine concentration and CK activity are no longer collected therefore the data included in this study are only available for the period Oct 2013 – Sept 2014. We have clarification of this in the Materials and Methods. 2. Page 11, line 165-168-Statistical analysis- The use of range and interquartile range as measures of data spread suggest that the data were not normally distributed. Therefore, the use of parametric test such as pearson's moment correlation and ANOVA for analysis may not be appropriated. The authors should consider the use of equivalent non parametric test for the analysis. Thank you – we agree, we have adjusted the statistical tests for non-normally distributed data. Results 1. Page 12, line 177-192- Correlation between CK and creatinine. This analysis is not necessary, as both biochemical parameter are the result of massive breakdown of skeletal muscles which occurs in Rhabdomyolysis. Early detection of acute renal failure can be achieved by monitoring serum creatinine and serum creatine kinase. CK is a better predictor of ARF due to rhabdomyolysis than creatinine. Since CK and creatinine are usually highly correlated in rhabsomyolysis, an attempt to find the correlation between them in this study will result in multicollinearity. We are aware of the high correlation between CK activity and creatinine concentration. However our clinical experience has shown, that some of patients were have very high CK activity without significant kidney injury. The serum creatinine concentration in this study was used as the marker of kidney injury. Unfortunately, due to study design (patients were treated mainly in emergency departments and only the highest recorded creatinine concentration was recorded in the dataset) we could not apply KDIGO criteria for acute kidney injury. We have addressed this in revised limitations of the paper. 2. The result tables are not properly labelled. Also, the table do not present a clear distinction between the exposure and outcome variables making them difficult to interpret. Thank you - we corrected the labelling of the tables. Hopefully, this makes them more comprehensible. Discussion 1. The discussion needs to be better organized. There should be a clear pattern on how current findings connect to, support, elaborate on, or challenge conclusions of earlier studies. Thank you, we shortened the discussion and added connections to our study, to make it more clear and concise. Thank you for consideration of our paper, and we hope that the revised version presents a higher standard, that would be suitable for publication. Best regards Piotr Maciej Kabata, on behalf of Euro-DEN Research Group Attachments Attachment Submitted filename: Response_to_reviewers.doc https://doi.org/10.1371/journal.pone.0246297.r002
18 Jan 2021 Decision Letter - Muhammad Adrish, Editor Rhabdomyolysis related to acute recreational drug toxicity – a Euro-DEN study. PONE-D-20-18319R1 Dear Dr. Kabata, 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, Muhammad Adrish Academic Editor PLOS ONE Additional Editor Comments (optional): All recommended edits have been addressed. 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: (No Response) ******** 2. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes ****** 4. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes ****** 5. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: No ****** 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 sufficiently addressed the issues raised in the previous review, except that columns heading are missing in Table 1. Authors should ensure that Tables are formatted in line with the journal's style. For instance, the table titles should be at the top of the table and not at the bottom. ****** 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:** ISAAC OKOH ABAH https://doi.org/10.1371/journal.pone.0246297.r003
Formally Accepted
25 Jan 2021 Acceptance Letter - Muhammad Adrish, Editor PONE-D-20-18319R1 Rhabdomyolysis related to acute recreational drug toxicity – a Euro-DEN study. Dear Dr. Kabata: 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. Muhammad Adrish Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0246297.r004

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