Anticoagulants utilization in eight hospitals within the Luzhou region from 2019 to 2023

Wei Luo; Yan Li; Jiali Yang; Yang Liu; Yue Shi; Hongli Luo

doi:10.1371/journal.pone.0318463

Peer Review History

Original SubmissionSeptember 2, 2024
14 Nov 2024 Decision Letter - Mohammed Abutaleb, Editor PONE-D-24-36242Analysis of anticoagulant drug utilization in eight hospitals within the Luzhou region from 2019 to 2023PLOS ONE Dear Dr. Luo, 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 29 2024 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: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols. We look forward to receiving your revised manuscript. Kind regards, Mohammed Hussain Abutaleb, PhD Academic Editor PLOS ONE Journal Requirements: 1. When submitting your revision, we need you to address these additional requirements. 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 the following financial disclosure: Sichuan Provincial Department of Science and Technology project (No. 2023JDKP0040) Please state what role the funders took in the study. If the funders had no role, please state: "The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript." If this statement is not correct you must amend it as needed. Please include this amended Role of Funder statement in your cover letter; we will change the online submission form on your behalf. 3. In the online submission form, you indicated that The data that support the findings of this study are available from Hospital Information System and Prescription Automatic Screening System of Sichuan Medico Software Research and Development Co., Ltd. but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of Hospital Information System and Prescription Automatic Screening System of Sichuan Medico Software Research and Development Co., Ltd. All PLOS journals now require all data underlying the findings described in their manuscript to be freely available to other researchers, either a. In a public repository, b. Within the manuscript itself, or c. Uploaded as supplementary information. This policy applies to all data except where public deposition would breach compliance with the protocol approved by your research ethics board. If your data cannot be made publicly available for ethical or legal reasons (e.g., public availability would compromise patient privacy), please explain your reasons on resubmission and your exemption request will be escalated for approval. [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: Partly Reviewer #3: Yes Reviewer #4: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: No Reviewer #2: I Don't Know Reviewer #3: Yes Reviewer #4: N/A ****** 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: No Reviewer #3: Yes Reviewer #4: 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 Reviewer #4: 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: This article provides a valuable and timely analysis of anticoagulant drug utilization trends across multiple tertiary hospitals in the Luzhou region from 2019 to 2023. However, to strengthen the statistical rigor and enhance the interpretability of the results, I assert necessity to including inferential statistical tests where comparisons are made across groups (e.g., DDD trends, cost differences). Including appropriate inferential tests would allow the authors to draw more robust conclusions regarding observed trends and differences, enhancing the article's scientific validity. Ethically, the study appears to be conducted with attention to patient privacy, using anonymized data, and the authors have appropriately disclosed the lack of conflicts of interest. I did not observe any issues with dual publication or ethical concerns that would compromise the integrity of the research. Overall, this study is well-structured, addresses an important healthcare issue, and has the potential to contribute valuable insights to the field of anticoagulation therapy. With the addition of inferential statistics and some clarification in specific sections, this work would represent a strong and impactful addition to the literature. Reviewer #2: This study presented a descriptive analysis of anticoagulants use over 4 years duration in 8 hospitals in Luzhou region in China. The main idea of this study appears clear, but the poor quality of writing could make it challenging for readers to comprehend. I recommend that this study undergo Major editorial and language revisions to enhance clarity and readability. Find in the attached my comments. Reviewer #3: 1. Study aim statement - "This study aims to luzhou area through the analysis of the drug utilization research in tertiary hospital nearly five years of anticoagulant drugs usage, combining economics discussion and thinking of anticoagulant drugs selection and reasonable use." Need to rephrase the aim clearly and precisely. 2. Ethics statement - " The data used in this study were completely anonymized, did not require review and approval by ethics committees, and the requirement for informed consent was waived" - For retrospective analysis of drug utilization studies, ethical approval may still be needed despite the observational nature of the study. Hence it would be appropriate you declare the proof of waiver status, as confirmed by an ethics board. 3. Figures (ALL) - Please specify the X axis and also Y axis clearly. Also add a brief description on what the figure depicts? (Example: Figure 1: Usage of anticoagulant drugs at eight hospitals and DDDs: defined daily doses) Reviewer #4: Title: The title is concise and captures the manuscript appropriately. Abstract: This was well-written and sound. Methods: The methods does not quite capture a particular study design. The authors state that it was a retrospective multicenter study. As to whether it was retrospective cross-sectional or cohort. Results:This was well written and captures the objectives of the study. Conclusion:The conclusion is tied in with the initial study objectives. ****** 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: Yes: Alyaa M. Ajabnoor Reviewer #3: No Reviewer #4: 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: manuscript.docx Attachment Submitted filename: Alyaa Ajaboor (review for PLOS).docx Attachment Submitted filename: PONE-D-24-36242_reviewer.pdf https://doi.org/10.1371/journal.pone.0318463.r001
Revision 1
7 Dec 2024 Author Response Response to Reviewers Reviewer #1 Comments to the Author: This article provides a valuable and timely analysis of anticoagulant drug utilization trends across multiple tertiary hospitals in the Luzhou region from 2019 to 2023. However, to strengthen the statistical rigor and enhance the interpretability of the results, I assert necessity to including inferential statistical tests where comparisons are made across groups (e.g., DDD trends, cost differences). Including appropriate inferential tests would allow the authors to draw more robust conclusions regarding observed trends and differences, enhancing the article's scientific validity. Ethically, the study appears to be conducted with attention to patient privacy, using anonymized data, and the authors have appropriately disclosed the lack of conflicts of interest. I did not observe any issues with dual publication or ethical concerns that would compromise the integrity of the research. Overall, this study is well-structured, addresses an important healthcare issue, and has the potential to contribute valuable insights to the field of anticoagulation therapy. With the addition of inferential statistics and some clarification in specific sections, this work would represent a strong and impactful addition to the literature. Reply: Thank you for your valuable scientific comments and endorsement of our manuscript. With your help, we have added inferential statistical tests to enhance statistical rigor and improve the interpretability of the results. Thank you very much for your valuable suggestions on our manuscript. Comment 1. Line 19 to 20: “and provide valuable insights for their management and rational use”. Please clarify how this study contributes to existing literature on anticoagulant use in hospital settings. Reply: Thank you for your invaluable advice. We have revised the background of the abstract to explicitly highlight the implications of our article on anticoagulant use in various healthcare settings. The revised background (line:24-27) is as follows: With the increasing utilization of anticoagulants, the selection of appropriate anticoagulants has emerged as a significant quandary. The objective of this study was to evaluate recent trend in the utilization and expenditure of anticoagulants within a specific region, aiming to provide valuable insights into the optimal choice of anticoagulants across other healthcare facilities. Comment 2. Line 27: “The DDDC of rivaroxaban decreased”. Adding explanation of this unexpected findings would enlighten reader. Reply: Thank you for your invaluable advice. We have revised the results to provide a comprehensive explanation of the factors contributing to the decrease in DDC, aiming to enhance readers' comprehension of the article. The revised version (line: 36-41) is as follows: The implementation of the centralized procurement policy, however, resulted in a decline in the expenditure of rivaroxaban and LMWH in 2021 and 2022 respectively. The DDC value of rivaroxaban experienced a substantial decrease over the past five years (p = 0.020), declining from 55.20 Chinese Yuan (CNY) in 2019 to 4.28 CNY in 2023. Conversely, there was a slight increase noted in the DDC of heparin sodium during this time frame (p = 0.042). Comment 3. Line 28: “significantly”. Clarify any statistical tests used for comparing DDDC trends across hospitals, as this is not mentioned. Significance cannot be assessed using only descriptive statistics. Reply: Thank you for your valuable scientific comment. We sincerely apologize for the oversight that led to an error in this section. In order to address this issue, we have added linear regression analysis to the article in order to show the trend of defined daily doses (DDDs) and defined daily cost (DDC), which helps strengthen the scientific rigor of our study. For example (line:242-246): The DDC value of rivaroxaban exhibited a significant decrease over the past 5 years (p = 0.020), declining from 55.20 CNY in 2019 to 4.28 CNY in 2023. Furthermore, there was a slight increase observed in the DDC of heparin sodium during the same period (p = 0.042), rising from 5.79 CNY in 2019 to 9.67 CNY in 2023. However, the DDC values of warfarin (p = 0.793) and LMWH (p = 0.202) remained relatively stable throughout the past 5 years. Comment 4. Line 33-36. Conclusion did not reflect on the main results of the study. I think, your conclusion should more directly reflect the study’s key results, highlighting the observed trends in anticoagulant usage, etc. Especially highlighting and explaining the discrepancy found between DDDs and DDDC. Reply: Thank you for your valuable scientific comment. The conclusions in the abstract have been revised to more accurately reflect the key findings of the study, with the revised conclusions (line: 42-45) presented as follows: Over the past five years (2019-2023), there has been an increase in the utilization of rivaroxaban and LMWH. However, their expenditure has decreased. In addition, the utilization and expenditure of warfarin and heparin sodium remained relatively stable. The application prospects of rivaroxaban and LMWH are promising. Comment 5. Line 93-95. It’s helpful to highlight gaps this study fills regarding regional drug utilization. Consider suggesting more details on these gaps for the reader’s understanding. Also, please clarify the significance of selecting the Luzhou region and tertiary hospitals for this study. Reply: Thank you for your valuable advice. We have incorporated the rationales and significance behind the selection of tertiary-care hospitals in Luzhou, and the specific modifications (line:113-121) as follows: The city of Luzhou, situated in the southern region of Sichuan province, stands as a representative example with relatively high medical and economic standards within the province. Moreover, owing to factors such as advanced medical facilities and convenient transportation, tertiary-care hospitals are predominantly chosen by patients for their treatment needs. Consequently, this inclination towards tertiary-care hospitals results in a greater utilization of anticoagulant medications and facilitates a more comprehensive understanding of their usage trends. Therefore, the objective of this study is to provide an all-encompassing overview regarding the utilization and expenditure patterns of anticoagulant drugs in Luzhou's tertiary-care hospitals from 2019 to 2023 through DUR. Comment 6. Line 140: “luzhou”. Please Capitalize Luzhou wherever mentioned. Reply: We agree with you and apologize for our mistake. We have revised it. Thank you for your positive and progressive suggestions on our manuscript. Comment 7. Line 227: “An estimated 370,000 deaths related to VTE occur annually in six European countries”. Is there any estimation in China? Reply: Thank you for your valuable advice. We removed the VTE example from Europe and added the epidemiology of VTE in China, with the following changes (line:253-255): In China, the hospitalization crude rate of VTE was 2.9 in 2007 to 15.8 in 2016 per 100,000 population, with a relative increase of five-fold (p < 0.001)[1]. Reference [1].Zhang Z, Lei J, Shao X, Dong F, Wang J, Wang D, et al. Trends in Hospitalization and In-Hospital Mortality From VTE, 2007 to 2016, in China. Chest. 2019;155: 342–353. doi:10.1016/j.chest.2018.10.040 Comment 8. Line 228-235. These sentences present general information on VTE prevention and treatment, which does not directly explain or support your study’s findings. Consider moving it to the introduction if you feel it provides necessary background context. In the discussion, focus on interpreting your results in relation to existing research and highlighting specific insights drawn from your data. Reply: Thank you very much for your scientific comment. We omitted general information about VTE prevention and treatment and focused on explaining results relevant to existing research and highlighting specific insights. The specific changes are as follows (lines 255-259): Therefore, the utilization of anticoagulants is of utmost importance. The findings from this study demonstrate a notable increase in the utilization of rivaroxaban and LMWH over the past 5 years, accompanied by a decrease in expenditure due to changes in DDC. Simultaneously, their exceptional safety profile and high efficacy distinguish them as superior options among various anticoagulants. Comment 9. Line 241-242. What does “nationwide” mean in this context? This is confusing because apparently these two studies were not conducted in China. Please change the sentence to remove that ambiguity. Reply: We agree with you, and we apologize for this ambiguous sentence. The specific changes are as follows (line:265-267): In a UK national survey and a randomized, controlled trial, outpatient prophylaxis with LMWH demonstrated efficacy in mitigating the risk of VTE among patients with immobilization of the lower extremities. Comment 10. Line 265-267. The term 'AD' is unclear and should be defined for clarity, at least in the first appearance. Additionally, the inclusion of P-values and using the technical term “significant”, suggest inferential statistical analysis, yet your methodology states that only descriptive statistics were used. Please clarify if inferential tests were conducted and, if so, detail these methods in the methodology section. If not, consider removing the P-values and “significant(ly)” terms; to maintain consistency with your stated analysis approach. Reply: Thank you very much for your scientific comment. We have redefined 'AD' to make its meaning clearer to the reader. In addition, we added inferential statistical methods and included p values. Comment 11. Line 270-273. Again, as above. These are general knowledge, and suggested to be moved into background section if necessary. Reply: Thank you for your valuable advice. We also agree with you and have deleted most of the content. However, considering that the discussion in this section is mainly to analyze the specific indications for warfarin in order to determine the rationality of its prescription. We also retained some of the necessary content. The specific changes are as follows (line: 295-303): Warfarin is the most widely utilized oral anticoagulant globally for the prevention and treatment of various thrombotic events, including deep-vein thrombosis, atrial fibrillation, valvular heart disease and prosthetic valves, as well as peripheral vascular disease. However, according to the expert consensus statement on ICD therapy, administration of warfarin for anticoagulation purposes is not recommended following ICD surgery. Therefore, the use of warfarin after ICD implantation in our study was not justified; however, it constitutes a negligible proportion. Despite its flaws, the majority of warfarin diagnoses in this study were in accordance with the prescribed indications for warfarin. However, collaborative efforts are still required to further enhance the rationality of prescribing practices. Comment 12. Line 308-309. Is there any expected effect of COVID-19 on this trend? Reply: Reply: Thank you for your valuable scientific advice. Patients with COVID-19 have a certain risk of thrombosis, and the guidelines require that patients with COVID-19 need to use heparin drugs for anticoagulant therapy [2]. In addition, the duration of COVID-19 was from December 2019 to December 2022, which was the window period of our study. Thus, COVID-19 had an effect on trends in the use of heparin. Reference [2]. National Health Commission of the People’s Republic of China. Diagnosis and Treatment of COVID-19(Trial Version 10). Chinese Journal of Clinical Infectious Diseases. 2023;16(1):1-9. Doi:10.3760/cma.j.issn.1674-2397.2023.01.001 Comment 13. Line 319-334. Limitations have been addressed very well. However, it may be useful to recommend more specific future research directions, such as including secondary hospitals or exploring anticoagulant trends by patient demographics (age, comorbidities). Reply: Thank you for your valuable advice and affirmation. We have added more specific future research directions with the following modifications (line:352-354): In future studies, we will further investigate the adaptability of other anticoagulants in prescription and consider their inclusion in secondary hospitals or continue to explore trends in anticoagulants based on patient demographic characteristics such as age and comorbidities. Comment 14. Line 339-340:” The implementation of the centralized procurement policy has significantly reduced the prices of anticoagulant drugs”. Good point. Please point to it briefly in the abstract. Reply: Thank you for your valuable advice and affirmation. We have pointed out in the abstract. Thank you for your positive and progressive suggestions on our manuscript. Reviewer #2 Comments to the Author: This study presented a descriptive analysis of anticoagulants use over 4 years duration in 8 hospitals in Luzhou region in China. The main idea of this study appears clear, but the poor quality of writing could make it challenging for readers to comprehend. I recommend that this study undergo Major editorial and language revisions to enhance clarity and readability. Find in the attached my comments. Reply: Thank you very much for your scientific comment. We apologize for grammatical errors and poor writing quality. With your help, we made significant language changes to the manuscript to improve the readability of the article. Thank you for your positive suggestions on our manuscript. Comment 1. Line 1 to 2. I advise to change the title to: anticoagulants utilization in eight hospitals within the Luzhou region: descriptive study from 2019 to 2023. Reply: Thank you for your valuable advice. Integrating the opinions of multiple reviewers, the full text adds inferential statistical analysis on the basis of the first draft, which makes the article more convincing and rigorous. The title of this article is not suitable for descriptive analysis, but we have changed it accordingly (lines: 1-2): Anticoagulants utilization in eight hospitals within the Luzhou region from 2019 to 2023. Comment 2. Line 18 to 20: Rephrase the background of the abstract. It’s not supposed to state the objective but rather to highlight the gap in the literature and briefly mention the aim of the study Reply: Thank you very much for your scientific comment. We modified the background section so that it was no longer a description of the research purpose only, and the revised background was as follows (line:24-27): With the increasing utilization of anticoagulants, the selection of appropriate anticoagulants has emerged as a significant quandary. The objective of this study was to evaluate recent trend in the utilization and expenditure of anticoagulants within a specific region, aiming to provide valuable insights into the optimal choice of anticoagulants across other healthcare facilities. Comment 3. Line 22 to 23: “Data on the utilization of anticoagulant drugs in tertiary hospital within a district from 2019 to 2023 were collected” this sentence needs rewording. It’s clearer to say tertiary-care hospitals throughout. Reply: Thank you very much for your scientific comment. We modified the sentence to make it more colloquial. The specific changes are as follows (line:28-30): The data on anticoagulant utilizations in tertiary-care hospitals within a district were collected from January 2019 to December 2023. Comment 4. Line 24: “Diagrams illustrating the trend of change were generated”. Change in what? Either clarify the sentence or remove it if it’s not related to the main analysis of this study. Reply: Thank you for your valuable advice. What we intended to describe was to plot trends in the frequency of use (DDDs), DDC, and cost of anticoagulants. We apologize for any ambiguity. We modified it as follows (lines 31-32): The trends in the utilization and expenditure of anticoagulants were examined using linear regression analysis. Comment 5. Line 28: Define CNY on first mention in the abstract. Reply: We agree with you and have defined "CNY". Thank you for your positive suggestions on our manuscript Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0318463.r002
16 Jan 2025 Decision Letter - Mohammed Abutaleb, Editor Anticoagulants utilization in eight hospitals within the Luzhou region from 2019 to 2023 PONE-D-24-36242R1 Dear Dr. Hongli Luo, 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, Mohammed Abutaleb, PhD 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 #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 #3: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: 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 #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 #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: Authors made a great efforts to address my points. I recommend this manuscript for publication. Thanks for authors. Reviewer #3: The authors have addressed all issues raised in the previous review. The manuscript may be considered for publication. ****** 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: No Reviewer #3: Yes: Abdul Nazer Ali ******** Attachments Attachment Submitted filename: PONE-D-24-36242_reviewer.pdf https://doi.org/10.1371/journal.pone.0318463.r003
Formally Accepted
22 Jan 2025 Acceptance Letter - Mohammed Abutaleb, Editor PONE-D-24-36242R1 PLOS ONE Dear Dr. Luo, 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 If revisions are needed, the production department will contact you directly to resolve them. If no revisions are needed, you will receive an email when the publication date has been set. At this time, we do not offer pre-publication proofs to authors during production of the accepted work. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few weeks 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. Mohammed Abutaleb Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0318463.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 .