PONE-D-24-13109Prognostic Value of Procalcitonin in Acute Exacerbation of Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-analysisPLOS ONE

Dear Dr. Xun,

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 manuscript is within the scope of the journal. However, there are a few major concerns related to the manuscript that needs to be addressed before final decision.

Major comments:

Manuscript concludes that the deceased patients has significantly higher PCT, whereas SMD between two groups is not statistically different (SMD 0.94, 95%CI 0.74-1.14). This needs to be addressed. Also, the manuscript did not provide any information regarding publication bias (Funnel plot). Also, authors need to include the clinical implication of the findings of this metanalysis. There are a few other issues raised by reviewers.Manuscript also requires a through check for grammar and typo errors.

Please submit your revised manuscript by Aug 09 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.

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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,

Vijay Hadda, MD

Academic Editor

PLOS ONE

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2. We noticed you have some minor occurrence of overlapping text with the following previous publication(s), which needs to be addressed:

- https://doi.org/10.1371/journal.pone.0129450

- https://doi.org/10.1016/j.ijcard.2015.05.006

(among others)

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"Open access funding provided by The Project of National Famous Traditional Chinese Medicine Practitioner Zhusheng Zhu Studio (No.2022-75). "

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7. Please include your tables as part of your main manuscript and remove the individual files. Please note that supplementary tables (should remain/ be uploaded) as separate "supporting information" files

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

Reviewer #2: Partly

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: In current metanalysis, the study question, study selection, data analysis and tests for heterogenity are performed as per standard protocol. However the studies included are quite heterogeneous and smaller studies or studies with less weight support the hypothesis better as compared to studies with higher weight. The funnel plot for heterogenity is not provided the authors. The actual cut off for PCT-Q for predicting the mortality is not mentioned. This metanaysis doesn't completely support the hypothesis.

Reviewer #2: The authors have highlighted the role of PCT at time of admission in predicting the mortality in patients with AECOPD. However, the following suggestions can be incorporated.

1. In the introduction (Line 51), grammatical errors are there. ‘Negatively impacts on health status’. It should be ‘negative impact on health’.

2. In the results, 8 clinical trials with 2085 patients are mentioned however, the authors have mentioned that fourteen clinical trials were taken into consideration for meta- analysis in the discussion. Pl clarify.

3. The discussion is not lucid as the authors have not clearly explained the results. The discussion meanders a bit and should be a bit more elaborate.

4. The authors have contradicted themselves. In the results, it is mentioned that no significant association between PCT levels and mortality was found. However, in the conclusion the authors have mentioned that PCT at the time of admission positively corelated with mortality. Please explain and clarify.

5. The Forest plots have not been labelled.

6. The authors have neither mentioned about the findings of sub- group analysis (as shown in the Forest plot) in the results nor have they discussed them in the discussion section.

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Reviewer #1: Yes: Dr Neetu Jain

Reviewer #2: No

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Attachments

Attachment

Submitted filename: Reviewer comments- PCT in AECOPD.docx

PONE-D-24-13109R1Prognostic Value of Procalcitonin in Acute Exacerbation of Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-analysisPLOS ONE

Dear Dr. Xun,

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.  Academic Editor's comments: 1. Line 81-82, mention “ the type of 82 study design was observational research”, table mention study design retrospective, prospective cohort or cohort study. Line 131 – 132 mention “Eight clinical trials [14-21] with a total of 2085 patients reported the level of PCT predicting mortality for patients with AECOPD”

It is confusing; authors must use uniform and standard terminology. RCT and cohort study are two different study designs.

2. Please clarify and modify in table whether clinical setting “Hospital” represent out patient department or hospitalized or both? Mild exacerbations usually donot require hospitalization. Hence, it will be good to include more clear information where the study was conducted – out patient department or hospitalized or both. This is essential, as authors concluded that PCT was correlated with increased mortality in mild to moderate.

3. Authors need to review for typo-errors

==============================

Please submit your revised manuscript by Oct 07 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,

Vijay Hadda, MD

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

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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)

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: Partly

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: 1. It is still not clear how 14 studies were selected and results are reported only for 8 studies

2. Conclusions should not be based on only on subgroup analysis but also included the whole analysis and language need revision and should mention if it statistically significant relationship.

3. The results stating that PCT levels are associated with high mortality in mild to moderate COPD are contradictory as mild to moderate COPD by definition doesn't even require hospitalization.

4. Discussion needs revision and should explain the results better.

5. There are many grammatical errors like Line 131-132 "Eight clinical trials [14-21] with a total of 2085 patients reported the level of PCT predicting mortality for patients with AECOPD " should be "Eight clinical trials [14-21] with a total of 2085 patients reported that the level of PCT predicts mortality in patients with AECOPD"

Reviewer #2: The authors have made significant changes in the MS and it has shaped up well.

The authors have mentioned in discussion section that COPD is a 'prevalent diagnosed chronic disease'. Please clarify what this implies?

**********

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: Dr Neetu Jain

Reviewer #2: No

**********

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

PONE-D-24-13109R2Prognostic Value of Procalcitonin in Acute Exacerbation of Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-analysisPLOS ONE

Dear Dr. Xun,

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 include the MOOSE checklist, mention how the publication bias was assessed/addressed, and the method section section needs more information (please check the comments of reviewer 3).

==============================

Please submit your revised manuscript by Nov 08 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,

Vijay Hadda, MD

Academic Editor

PLOS ONE

Additional Editor Comments:

There are certain important issues related the statistical part of the manuscript. Please refer to the comments from the reviewer provided below.

[Note: HTML markup is below. Please do not edit.]

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: (No Response)

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: line 33 (abstract) And deceased patients had 1-" remove And before the sentence

" line 50 pulmonary disease (AECOPD) play a singnificant role in the management of COPD, due to their " replace "their" with "its"

" line 167 (dicussion) please mention p-value when word "significant" is used

Reviewer #3: As a statistical reviewer I will focus on methods and reporting.

Major

1) MOOSE is a checklist for reporting meta analyses. The authors need to assess the risk of bias in the studies using an appropriate tool (see Cochrane ROBINS for example). they also say "The reviewers assessed the quality of the included studies according to Modifying the MOOSE item list." this needs to be corrected for grammar and also they need to explain why they had to use a modified version and who modified it.

2) In the statitical analyses section, list all the outcomes, primary and secondary, for clarity. Also are all outcomes reported in exactly the same scale, so there is no need for meta analysing as SMDs? please state that clearly as well. UPDATE: I see in the results SMDs are reported, that needs to be explained in the methods section.

3) Publication bias is one of the biggest risks in conducting meta analyses and it seems to be ignored. Publication bias tests and plots only relevant if you have >10 studies otherwise underpowered to detect much and tend to lead to conclusions that are not justified http://www.ncbi.nlm.nih.gov/pubmed/11106885. If you don’t have enough studies to assess you should discuss this as a major limitation. Even with 10 or 20 studies it is very difficult to visually assess. If you have 20 or more studies it is a considerable strength.

4) Avoid fixed effect models since they under-perform in the presence of ANY heterogeneity. Random-effects (RE) models are more conservative and provide better estimates with wider confidence intervals: http://www.ncbi.nlm.nih.gov/pubmed/11252006 and http://www.ncbi.nlm.nih.gov/pubmed/21148194 . What does the arbitrary 50% cut-off point add? Why is 49% fine and 51% an issue? My point is that a RE model will work better, in the presence of 5% heterogeneity, compared to a FE model!

5) Report the confidence intervals for I^2, since it is an estimate. A simple formula exists in the seminal 2002 Higgins paper that proposed I^2.

Minor

1) "Subgroup analysis was performed based on the severity of disease" please expand to clarify, what were the grouping for example.

2) Year may be worth considering in bias assessment, especially if you don't have enough studies for a formal test: http://www.ncbi.nlm.nih.gov/pubmed/25988604. With newer studies we would be more confident.

3) How was the random-effect model implemented, i.e. how was heterogeneity estimated? There are numerous ways to do so. Did they use the standard DerSimonian-Laird method? If so, please state so. Also there are better performing methods, for example please see https://www.ncbi.nlm.nih.gov/pubmed/28815652 (or http://www.ncbi.nlm.nih.gov/pubmed/23922860) and the metaan command in Stata where these are implemented (https://www.stata-journal.com/article.html?article=st0201).

**********

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: Dr Neetu Jain

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.

Prognostic Value of Procalcitonin in Acute Exacerbation of Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-analysis

PONE-D-24-13109R3

Dear Dr. Xun,

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.

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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,

Vijay Hadda, MD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Dear authors,

Thank you for addressing all reviewers comments satisfactorily. The manuscript has improved significantly.

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 #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 #3: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

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 #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 #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 #3: I am satisfied with the authors' responses and the resulting changes to the paper - some of the responses were difficult to follow (e.g. about MOOSE and the related action) but the paper has been amended satisfactorily.

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Reviewer #3: No

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