PONE-D-24-46593Global burden and risk factors of peptic ulcer disease between 1990 and 2021: an analysis from the Global Burden of Disease Study 2021PLOS ONE

Dear Dr. Ma,

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Emmanuel O Adewuyi, BPharm, MPH, PhD

Academic Editor

PLOS ONE

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Additional Editor Comments:

The reviewers have provided feedback on this manuscript, highlighting several key issues. I invite the authors to revise their manuscript and respond comprehensively to all reviewer comments.

One reviewer has noted a similar publication on the same subject. The authors should clearly distinguish their work from the existing study, emphasizing how their research advances or builds upon previous findings.

Additionally, the reviewers have recommended improving the presentation of the manuscript, including grammatical refinements. Strengthening the literature review in the introduction section and expanding the discussion, including appropriate insight on the differences observed between male and female  would further enhance the quality of the work.

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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: Yes

Reviewer #2: Partly

Reviewer #3: Partly

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

Reviewer #1: Yes

Reviewer #2: I Don't Know

Reviewer #3: Yes

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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

Reviewer #3: 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

Reviewer #3: No

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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: Revisão PLOS ONE - PONE-D-24-46593 Research Article

Global burden and risk factors of peptic ulcer disease between 1990 and 2021: an analysis from the Global Burden of Disease Study 2021.

The manuscript is well written, the topic is highly relevant and the references used are current. However, I was disturbed by the large number of abbreviations in the text, and I had the impression that there was a lack of better discussion of the results found. Overall, this is promising work on a topic that is of great relevance to the population.

Major issues:

According to the submission guidelines:

Define abbreviations upon first appearance in the text. Do not use non-standard abbreviations unless they appear at least three times in the text. Keep abbreviations to a minimum.

Introduction

Few references in the introduction, the topic should be explored better in the literature.

Discussion

I had the impression that a better discussion of the results found was missing. The discussion is not a summary of the results. You should compare the results obtained with other results available in the literature and find associations that corroborate the data found.

Minor issues:

Correct minor errors according to the submission guidelines:

- Include page numbers and line numbers in the manuscript file. Use continuous line numbers (do not restart the numbering on each page).

- Figure captions are inserted immediately after the first paragraph in which the figure is cited. Figure files are uploaded separately.

- Use figure label with Arabic numerals, and “Figure” abbreviated to “Fig” (e.g. Fig 1, Fig 2, Fig 3, etc).

Materials and methods

Add the website as a reference instead of placing it in the middle of the text (https://vizhub.healthdata.org/gbd-results/).

Discussion

Please find a more recent reference to replace reference number 19.

"which indicated that the PUD burden was significantly heavier in males, potentially due to lower levels of estrogen" - This assumption needs a reference or better argumentation.

"which appeared to be associated with limited access to diagnostic services." - A reference is needed for this assumption.

Reviewer #2: Dear authors, congratulations on your significant contribution to advancing our understanding of the epidemiological characteristics and risk factors associated with peptic ulcer disease. Here are my comments:

Q0: A similar study using the same material was published in 2023: "Peptic ulcer disease burden, trends, and inequalities in 204 countries and territories, 1990–2019: a population-based study" ( doi: 10.1177/17562848231210375). Beyond sex (male patients being more vulnerable in terms of incidence, prevalence mortality and DALY) and smoking (a primary risk factor), were there any other notable findings comparing the 2023 study to the current one? Additionally, did the COVID-19 pandemic influence the epidemiological characteristics of peptic ulcer disease between 2020 and 2021? If not, what are the authors' perspectives on this

Q1: The authors noted in the Discussion section that 'the ASRs of PUD remain abnormally high in Taiwan.' However, in the 2023 study mentioned in Q0 stated that 'EAPCs of ASDR were significantly decreasing in ... Taiwan'. What are the authors' opinions on this?

Q2: The ASRs of incidence, prevalence, deaths and DALYs of PUD decrease more rapidly in males than in females. Please discuss the possible reasons for this phenomenon.

Q3: How can the causal relationship between peptic ulcer disease (PUD)-related disability-adjusted life years (DALYs) and cigarette smoking be determined?

Q4: In "Global and regional burden of PUD", the authors mentioned: "The Taiwan (Province of China) (335.31 (95% UI: 284.75 to 399.55) per 100,000) had the highest ASPR." Though this annotation '(Province of China)' was shown in IHME forms, Taiwan is not globally recognized as a province of China; if it were, China would not pursue its annexation. For instance, does China plan to annex Hebei or Guangdong (both Province of China) in the future? Please remove the annotation '(Province of China)' to avoid potential political issues in scientific research.

Reviewer #3: Dear Editor and Authors,

This manuscript presents an analysis of the global burden of peptic ulcer disease (PUD) from 1990 to 2021, using data from the Global Burden of Disease (GBD) Study 2021. The study examines incidence, prevalence, mortality, and disability-adjusted life years (DALYs), and explores the association with potential risk factors. The topic is relevant, given the clinical and economic impact of PUD worldwide. While the study has merit, there are several areas that require attention before it can be considered for publication.

The introduction, while providing necessary background, suffers from a lack of specific focus and a strong "hook" to immediately engage the reader. It lacks a clearly stated hypothesis and a concise explanation of the study's novel contributions to the existing literature. Furthermore, the objectives are stated too broadly. To improve, provide a brief "roadmap" of the paper's structure.

The manuscript uses an ARIMA model to predict PUD burden until 2050. Long-term epidemiological predictions are inherently unreliable due to numerous unpredictable factors (e.g., changes in healthcare policy, emergence of new treatments, shifts in risk factor prevalence, and unforeseen global events). The manuscript fails to adequately acknowledge and address these limitations.

The conclusion that smoking is the only primary risk factor associated with DALYs and deaths from PUD is an overstatement not supported by a comprehensive analysis. The authors present this conclusion without exploring potential confounding factors or interactions between different risk factors.

The manuscript reports gender differences in PUD burden but fails to provide a meaningful explanation for these disparities. Simply stating that males have higher rates than females is insufficient. The authors do not explore the underlying biological, behavioral, or socioeconomic factors that could explain these differences.

The conclusion states that "precise prevention strategies are essential to mitigate the disease burden of PUD," but this statement is generic and lacks specific, actionable recommendations. The manuscript does not provide a clear link between the study's findings and concrete policy implications. The authors do not discuss how the observed trends and risk factors should inform the development and implementation of targeted prevention programs.

Finally, while the language is generally understandable, the manuscript contains several minor grammatical and stylistic errors that detract from its overall clarity and professionalism. A thorough proofreading by a native English speaker is recommended to address these issues and ensure the manuscript meets the standards for publication.

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: No

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PONE-D-24-46593R1Global burden and risk factors of peptic ulcer disease between 1990 and 2021: an analysis from the Global Burden of Disease Study 2021PLOS ONE

Dear Dr. Ma,

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 May 26 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.

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,

Emmanuel O Adewuyi, BPharm, MPH, PhD

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.

Additional Editor Comments:

One of the reviewers has raised concerns regarding causality and adherence to the correction commitment. The authors need to respond to these comments and make corrections where necessary, or provide a rebuttal as appropriate. Additionally, the authors should carefully review their work sentence by sentence and fact-check every statement.

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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: All comments have been addressed

Reviewer #2: All comments have been addressed

Reviewer #3: All comments have been addressed

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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: Partly

Reviewer #3: Yes

**********

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

Reviewer #1: Yes

Reviewer #2: I Don't Know

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: (No Response)

Reviewer #2: Thank you for your response. I have the following comments:

Q1. In response to Q3 from the previous review — "How can the causal relationship between peptic ulcer disease (PUD)-related disability-adjusted life years (DALYs) and cigarette smoking be determined?" — the authors referred to the population attributable fraction (PAF) formula for explanation. However, it is important to note that a "risk factor" or the use of "PAF" does not inherently establish a causal relationship between the factor and the disease.

Q2. In the "Results" and "Discussion" sections (pages 23 and 33, respectively), the manuscript still contains the term "Taiwan (Province of China)," despite the authors' prior agreement in Q4 to remove the "Province of China" annotation. This inconsistency raises concerns about the authors' integrity and adherence to revision commitments. Given this, I recommend that the manuscript be rejected from publication.

Reviewer #3: (No Response)

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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 #2: No

Reviewer #3: No

**********

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

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

PONE-D-24-46593R2Global burden and risk factors of peptic ulcer disease between 1990 and 2021: an analysis from the Global Burden of Disease Study 2021PLOS ONE

Dear Dr. Ma,

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:

1. Incomplete Correction Regarding “Taiwan (Province of China)”

Despite the authors’ indication that all instances of 'Province of China' were removed from references to Taiwan, at least one instance remains in the main manuscript. We appreciate that such an error may have been unintentional. However, given this is the second or third time the issue is recurring, the sensitivity of the terminology and prior revision instructions, it is essential that all instances are carefully corrected in the next revision. Please comprehensively review the entire manuscript, including main text, figure captions, tables, and supplementary materials, to ensure full removal of ‘Province of China’ references, consistently referring to the location simply as ‘Taiwan’ as recommended by the reviewer.

2. Methodological Concern: ARIMA Model Projections

Authors use the ARIMA model to project the future burden of peptic ulcer disease up to 2050. However, some projections—notably age-standardised mortality rates (ASMR) and disability-adjusted life-years (ASDR) for females—predict negative rates by 2050. Negative incidence or mortality rates are biologically implausible. Authors need to revise the ARIMA modelling approach to either constrain the lower limit of projections to zero or explain the biological and methodological limitations of ARIMA predictions in the Discussion section and avoid interpreting negative projections literally.

3. Language and Grammar

Although the manuscript is generally understandable, several grammatical errors remain, including but not limited to: typographical errors, incorrect article usage, and redundant wording. A full, careful language edit (sentence-by-sentence) is necessary to ensure clarity and professional presentation. Authors may seek assistance from a professional editing service.

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

Please submit your revised manuscript by Jun 13 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.

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,

Emmanuel O Adewuyi, BPharm, MPH, PhD

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.

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

[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-24-46593R3Global burden and risk factors of peptic ulcer disease between 1990 and 2021: an analysis from the Global Burden of Disease Study 2021PLOS ONE

Dear Dr. Ma,

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: Thank you for your revised submission. The manuscript is greatly improved, and your responses have addressed the reviewers’ and editor’s concerns. However, a few minor issues remain that require correction before the manuscript can be accepted.

First, peptic ulcer disease (PUD) is described as a ‘prevalent acute abdominal condition’, which could be misleading. PUD is a chronic gastrointestinal condition that may present acutely when complications arise. Please revise this description for accuracy or provide justification for using ‘acute’.

Second, there are minor discrepancies between the structured abstract and the full abstract, including a spelling error (‘identifed’ should be ‘identified’) and some formatting inconsistencies.

Finally, please take this opportunity to review the manuscript sentence by sentence to ensure accuracy, clarity, and consistency throughout.

Please submit your revised manuscript by Jun 30 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.

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,

Emmanuel O Adewuyi, BPharm, MPH, PhD

Academic Editor

PLOS ONE

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Global burden and risk factors of  peptic ulcer disease between 1990 and 2021: an analysis from the Global Burden of Disease Study 2021

PONE-D-24-46593R4

Dear Dr. Ma,

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Kind regards,

Emmanuel O Adewuyi, BPharm, MPH, PhD

Academic Editor

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