PONE-D-23-18085The Predicting formula and scoring system for cardiac iron overload for thalassemia children:  an urgent need in IndonesiaPLOS ONE

Dear Dr. Rohimi,

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.

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ACADEMIC EDITOR: 

It is undoubtedly a very good paper, so I urge the authors to consider the indications of the reviewers, especially, to deepen the discussion and the projections of the article.

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Academic Editor

PLOS ONE

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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: Yes

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

Reviewer #1: Yes

Reviewer #2: 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: No

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

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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: According to what was presented, conclusive data are obtained to estimate a score that correlates with iron overload. A correlation is also suggested between adherence to chelation treatment and number of transfusions, as it may bias the results.

Detailed demographic data is not found in the supplementary material. It is suggested to attach them to review the data tabulation.

Reviewer #2: Dear Authors,

I hope this letter finds you well. I am delighted to have the opportunity to review your exceptional research in the field of Thalassemia. Your findings are invaluable contributions to the scientific community and hold great significance for both researchers and patients alike. Please allow me to provide some constructive feedback aimed at enhancing the quality of your manuscript, organized according to each section:

1. Title: The title is informative and relevant, effectively capturing the essence of your study.

2. Abstract: I would kindly suggest mentioning the formula in the conclusion section of the abstract. Additionally, incorporating relevant keywords such as "MRI T2" could prove beneficial for indexing and discoverability purposes. Furthermore, I recommend replacing the term "thalassemia major" with the more encompassing "thalassemia" throughout the abstract. The remaining portions of the abstract effectively convey the study's findings and methodological approach.

3. Introduction: While conciseness is appreciated, a more substantial introduction could better communicate the importance and necessity of your research. The research question could be more firmly grounded in the existing literature, necessitating the inclusion of more up-to-date studies and references, particularly recently published works such as those by Meloni et al. and Fedai et al.

4. Methods: The subject selection process is clearly delineated. The variables are well-defined and measured appropriately, and the study methods are valid and reliable. The level of detail provided is sufficient to facilitate replication of the study by others.

5. Results: The presentation of data could be enhanced through the judicious use of visual aids, such as charts and graphs, which would effectively communicate the key findings of your research. A Receiver Operating Characteristic (ROC) graph is highly recommended. Appropriate labeling of columns and rows in tables is appreciated, but I would suggest removing any horizontal lines to enhance readability.

6. Discussion and Conclusions: A more comprehensive discussion, exploring the results from multiple perspectives, would be beneficial. Addressing the socioeconomic implications of your findings and the potential of the formula for early detection of cardiac iron overload in regions where MRI T2 is unavailable could broaden the impact of your work. Generalizing your results to low- and middle-income countries, where the problem you have identified is prevalent, would further underscore the global relevance of your research. The conclusions are well-supported by the results and effectively address the aims of the study. Additionally, the limitations acknowledged present opportunities for future research endeavors.

7. Overall: The study design is appropriate and effectively addresses the research aims, contributing novel insights to the existing body of knowledge on this topic.

I commend your exceptional work and look forward to the positive impact it will have on the scientific community and the lives of those affected by Thalassemia.

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Reviewer #1: Yes: Juan Carlos Rivera Fuentes

Reviewer #2: Yes: Amirreza Nasirzadeh

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The Predicting formula and scoring system for cardiac iron overload for thalassemia children:  study from a middle income country

PONE-D-23-18085R1

Dear Dr. Syarif Rohimi,

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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Kind regards,

Juan Luis Castillo-Navarrete, Ph.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Congratulations to the authors for the genesis of an excellent piece of writing.

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

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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: 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: No

Reviewer #2: Yes

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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: I would like to start by greeting the authors.

I suggest adding a table that organizes both the application of the formula along with the risk ranges of a simpler one so that clinicians can apply it. The constructed tables show the results obtained and validated, but one that simplifies their application is missing.

In the review they mention the preparation of OR graphs but they do not appear in the article. I suggest adding them.

When consulting the bibliography, an adequate focus on the topic in question is evident. I suggest updating it and strengthening the quotes used.

My most sincere congratulations for the work done.

Reviewer #2: Dear authors,

Thank you for applying the suggested comments. The present version of the manuscript is suitable for publication in PLOS ONE.

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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: Yes: Juan Carlos Rivera Fuentes

Reviewer #2: Yes: Amirreza Nasirzadeh

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