Effects and predictors of intravenous lidocaine infusion for patients with fibromyalgia

Min Liu; Stephany Harris; Anna P. Andreou; Adnan Al-Kaisy; David Pang; Xuenong Bo

doi:10.1371/journal.pone.0320463

Peer Review History

Original SubmissionFebruary 18, 2025
Decision Letter - Wesam Gouda, Editor PONE-D-25-08401Effects and predictors of intravenous lidocaine infusion for patients with fibromyalgiaPLOS ONE Dear Dr. Bo, 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. ============================== Abstract: - Briefly give the key findings of your study. Include key numeric data (including confidence intervals or p values). Patients and Methods - How were the patients selected (e.g., consecutively, randomly, or selectively)? - All studies must be reported according to the relevant Equator network guideline: https://www.equator-network.org/ - In your manuscript, you need to state in the Methods section that you have followed relevant Equator guidelines. For example, if you use STROBE: ‘The reporting of this study conforms to STROBE guidelines. (Insert new reference number). - More details should be provided in terms of the IRB approval. Discussion - You concluded that IV lidocaine infusion showed higher effectiveness in female patients compared to male patients. A comparison of your results and the relevant previous studies showing gender difference in FM should be made. For examples: DOI:10.2147/OARRR.S358255 ============================== Please submit your revised manuscript by Jul 01 2025 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. 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Please also provide contact information for a data access committee, ethics committee, or other institutional body to which data requests may be sent. If data are owned by a third party, please indicate how others may request data access. [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: Yes 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: The references cited in the manuscript need revision. The author needs to ensure the PLOS ONE journal's guidelines. For proper formatting, I recommend the authors visit the journal's author guidelines. The authors identified 50% pain reduction as a reference for responders. I recommend the authors briefly justify the relevance and clinical significance of the 50% pain reduction criterion in the setting of fibromyalgia treatment. The manuscript did not reflect the characteristics of the control group. While there was mention of controls being matched for age , sex, etc., were there any other control group characteristics that could have had an effect on QST parameters? It would be interesting if there is a brief description of control group characteristics. Reviewer #2: This manuscript is commendably well-written, exhibiting a clear and coherent structure throughout. The statistical analyses used are appropriate, effectively supporting the study's conclusions. The results are presented with clarity and precision, facilitating easy comprehension of the findings. The discussion section is thoughtfully organized, providing insightful interpretations that are well-grounded in the data. For my specific suggestions, please refer to the PDF attached with this submission. Reviewer #3: The manuscript “Effects and predictors of intravenous lidocaine infusion for patients with fibromyalgia” by Liu et al. is a retrospective study describing the effect of systematic IV lidocaine infusion on pain relief in 132 patients with fibromyalgia using questionnaires and quantitative sensory testing. The authors identified 22% of patients as responders, with the criteria being patients who had a pain reduction of 50% or greater lasting for at least 3 weeks following an IV lidocaine infusion at a dose of 5 mg/kg; They also found that IV lidocaine infusion was especially effective for younger female patients. This discovery will be incredibly beneficial in designing an effective lidocaine clinical therapy protocol for fibromyalgia patients. Minor: 1. In the 2nd paragraph of Methods tilted “Questionnaires, screening blood tests, and clinical investigations”, there are no descriptions about the screening blood tests. 2. Due to the large number of abbreviations within the manuscript, it is advisable to have a table listing all of the abbreviations. 3. The authors set up the responder standard at 50% or greater pain reduction. According to the literature, the responder standards range from 20% to 50% pain reduction. It will be helpful to discuss how the responder standard was chosen to get clinically meaningful data. ****** 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: Vijaya Prasanna Parimi Reviewer #2: Yes: Clint Vaz 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. Attachments Attachment Submitted filename: PONE-D-25-08401.pdf Attachment Submitted filename: PONE-D-25-08401 edits.pdf https://doi.org/10.1371/journal.pone.0320463.r001
Revision 1
4 Jun 2025 Author Response Responses to the editor: 1. Abstract: Briefly give the key findings of your study. Include key numeric data (including confidence intervals or p values). Key numeric data and p-values have been added to the Abstract. 2. Patients and Methods. How were the patients selected (e.g., consecutively, randomly, or selectively)? The information on patient selection has been added to the Abstract and the Methods (1st paragraph on page 6). 3. All studies must be reported according to the relevant Equator network guideline: https://www.equator-network.org/ In your manuscript, you need to state in the Methods section that you have followed relevant Equator guidelines. For example, if you use STROBE: ‘The reporting of this study conforms to STROBE guidelines. (Insert new reference number). Please see the Abstract on page 2 “This study adheres to RECORD guidelines for reporting studies using observational routinely collected data. It was conducted retrospectively and employed data derived from clinical records of patients who received standard care.” and Methods on page 5 “We adhere to RECORD guidelines for reporting studies using observational routinely collected data [26].” 4. More details should be provided in terms of the IRB approval. Please see Methods on page 5 “This was an NHS registry study using routinely collected patients' data, which was approved by the R&D Lead of Guy's and St Thomas’ Hospital, London.” There isn’t a specific IRB number available. 5. Discussion: You concluded that IV lidocaine infusion showed higher effectiveness in female patients compared to male patients. A comparison of your results and the relevant previous studies showing gender differences in FM should be made. For example: DOI:10.2147/OARRR.S358255 We have added some more discussion. However, it is difficult to compare our results directly with those published in previous studies, as the protocols of lidocaine infusion and the parameters of assessments were different from one study to another. Response to Reviewers Reviewer #1: The references cited in the manuscript need revision. The author needs to ensure the PLOS ONE journal's guidelines. For proper formatting, I recommend the authors visit the journal's author guidelines. We have checked the format of our manuscript following the author’s guidelines closely and made the relevant changes where needed. The authors identified 50% pain reduction as a reference for responders. I recommend the authors briefly justify the relevance and clinical significance of the 50% pain reduction criterion in the setting of fibromyalgia treatment. Please see the Methods on page 8. “A clinically important difference is defined as a 30% pain reduction or a 2-point improvement on the NRS (0-10) [30]. We adopted a stringent 50% pain reduction to identify a group of patients that fell in the category of “very much improvement” and exceeded a 2-point pain reduction.” The manuscript did not reflect the characteristics of the control group. While there was mention of controls being matched for age, sex, etc., were there any other control group characteristics that could have had an effect on QST parameters? It would be interesting if there is a brief description of control group characteristics We have compared the two groups: responders and non-responders, based on the responses to IV lidocaine infusion. QST parameters and phenotypes were similar in responders and non-responders. Responders were mostly females and significantly younger than non-responders. The raw data of QST was transformed to Z scores. Please see the Methods on page 7. “The results of QST were transformed to Z-scores (patient measurement-mean of age- and gender-matched healthy controls )/SD” Minor: 1. In the 2nd paragraph of Methods titled “Questionnaires, screening blood tests, and clinical investigations”, there are no descriptions about the screening blood tests. Please see Methods on page 6. Screening blood tests, including full blood count, and renal and liver function tests, were performed. 2. Due to the large number of abbreviations within the manuscript, it is advisable to have a table listing all of the abbreviations. We have added a list of abbreviations based on the suggestions. Please see the abbreviations on page 3. 3. The authors set up the responder standard at 50% or greater pain reduction. According to the literature, the responder standards range from 20% to 50% pain reduction. It will be helpful to discuss how the responder standard was chosen to get clinically meaningful data. Please see the Methods on page 8. “A clinically important difference is defined as a 30% pain reduction or a 2-point improvement on the NRS (0-10) [30]. We adopted a stringent 50% pain reduction to identify a group of patients that fell in the category of “very much improvement” and exceeded a 2-point pain reduction.” Reviewer #2: We have made changes based on the comments made in the PDF file. Attachments Attachment Submitted filename: Response to editors and reviewers.docx https://doi.org/10.1371/journal.pone.0320463.r002
Decision Letter - Wesam Gouda, Editor Effects and predictors of intravenous lidocaine infusion for patients with fibromyalgia PONE-D-25-08401R1 Dear Dr. Bo, 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 will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager® and clicking the ‘Update My Information' link at the top of the page. If you have any questions relating to publication charges, 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, Wesam Gouda, MD,PhD Academic Editor PLOS ONE 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 Reviewer #3: 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 Reviewer #3: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes Reviewer #3: 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 Reviewer #3: 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 Reviewer #3: 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: ---------------------------------------------------- ----------------------------nil------------------------------------------------- Reviewer #2: The revised manuscript is now well written, clear, and methodologically sound. The authors have adequately addressed prior concerns, and the presentation of results is coherent and supported by appropriate references. The study offers meaningful insights and is suitable for publication in its current form. I have no concerns regarding dual publication, research ethics, or publication integrity. Reviewer #3: The authors already gave clear answers to all my questions including adding an abbreviation information.... I have no more questions. ****** 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: Vijaya Prasanna Parimi ---------------------------------------- Reviewer #2: Yes: Clint Vaz Reviewer #3: Yes: Gerald Z Zhuang ******** https://doi.org/10.1371/journal.pone.0320463.r003
Formally Accepted
Acceptance Letter - Wesam Gouda, Editor PONE-D-25-08401R1 PLOS ONE Dear Dr. Bo, I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now being handed over to our production team. At this stage, our production department will prepare your paper for publication. This includes ensuring the following: * All references, tables, and figures are properly cited * All relevant supporting information is included in the manuscript submission, * There are no issues that prevent the paper from being properly typeset You will receive further instructions from the production team, including instructions on how to review your proof when it is ready. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few days to review your paper and let you know the next and final steps. Lastly, 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 customercare@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. Wesam Gouda Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0320463.r004

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