Peer Review History

Original SubmissionJune 6, 2020
Decision Letter - Nicole J. Moreland, Editor

PONE-D-20-17248

Rheumatic Heart Disease is the Largest Complication Observed in Ethiopia

PLOS ONE

Dear Dr. Asmare,

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 Oct 02 2020 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:

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  • 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: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

We look forward to receiving your revised manuscript.

Kind regards,

Nicole J. Moreland

Academic Editor

PLOS ONE

Additional Editor Comments:

The comments from the reviewer around selection criteria are particularly important and should be considered.

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2. Thank you for including your ethics statement:  "The study protocol was approved by the Research Ethics Committee of the Department of Internal Medicine (Ethical Clearance No: 014/2018). ".   

Please amend your current ethics statement to include the full name of the ethics committee/institutional review board(s) that approved your specific study.

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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: No

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: 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: No

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: This manuscript was reviewed using the STROBE guideline for cross-sectional studies. I have major comments.

TITLE: The title of the maunscript is uninformative. It does not capture the study design. Also, the word "... Largest..." is not scientific. The titles would benefit from some modifications.

ABSTRACT

1. The statement "Rheumatic Heart Disease (RHD) remains the number one cause of death and disability in developing countries." is false. Yes, cardiovascular diseases are the leading cause of death in developing countries. But ischemic heart disease and stroke are the leading cardiovascular causes of death, not rheumatic heart disease as the authors claim (https://www.who.int/news-room/fact-sheets/detail/the-top-10-causes-of-death).

2. The abstract contain no information about the study design, inclusion criteria, the method used to sample records, method of statistical analysis used, and the tool used to analyse the data.

3. The results should be written in past tense.

MAIN TEXT

BACKGROUND:

1. The authors need to be more specific and avoid using colloquial languages. For example the sentence " Despite the fact that hundreds of thousands of people worldwide are a victim to this disease..." can be more specific. Also, "... the awareness of most people about the disease is very small." is very unspecific. What do the authors mean by very small?

2. The reference [23] comes immediately after reference [1]. Is this supposed to be a mistake?

3. The objective of the study is not clear. What do the authors mean by "burden"? This can range from prevalence, years of life lost to disability, or mortality. They need to be more specific.

METHODS

1. The study design is not mentioned.

2. The inclusion and exclusion criteria, if any, are not mentioned.

3. Ethical considerations should come at the end of the methods or in the declaration.

4. The methods should be written in the past tense.

5. This should fall under the results, not the methods: " A total of 8371(Male (40.5%) and Female (59.5%) data cards were encoded. 795 of the records were excluded due to incomplete information and exhibiting a non-cardiac diagnosis."

6. There is no information on how participants were selected.

7. What protocol was used by the health facility to diagnose different cardiac diseases?

7. There is no section on data analysis.

8. Again, this is supposed to fall under the results and not the methods: "The remaining 7576 records were statically analyzed. Table 1 shows the socio-demographic summarization of the data."

RESULTS

1. It is important to analyse data for paediatric and adult patients separately because the distribution of cardiovascular diseases differ between these two groups.

2. The prevalence of rheumatic heart disease in this study is surprising high. It is important for the authors to properly describe their study population for better interpretation of the results.

DISCUSSION

The authors do not provide a balanced discussion of their results. They did not compare or contrast their findings with other African literature published on the subject.

Reviewer #2: Authors should be congratulated for this research paper. Nicely written, methodology robust, and discussion/perspective well managed.This study is one of the contemporary studies conducted to assess the prevalence of difference cardiovascular diseases in Ethiopia. The study has been conducted in the biggest referral hospital in the country where patients are sent from every corner of the country. The study has analyzed patient cards over three year’s period. Last data on RHD from GBD project published in the NEJM as well as its editorial should be considered. In addition, relatively recent review on RHD published in The Lancet (PMID: 22405798) can be considered since the introduction. The importance of early diagnosis should be emphasised (and practical challenges of echo screening...Mirabel et al. Circ Imaging) as well as the cost effectiveness of antibioprophylaxis...

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Reviewer #1: Yes: Valirie Ndip Agbor

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.]

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Revision 1

Journal Requirements:

1. 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

Response: The paper is formatted accordingly

2. Thank you for including your ethics statement: "The study protocol was approved by the Research Ethics Committee of the Department of Internal Medicine (Ethical Clearance No: 014/2018). ".

Please amend your current ethics statement to include the full name of the ethics committee/institutional review board(s) that approved your specific study.

Response: full name of the ethics committee is included. Please refer page 6 line number 205-208 of the final manuscript.

3. Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly.

Response: The paper amended accordingly.

Reviewer Requirements

Reviewer #1

Reviewer #1: This manuscript was reviewed using the STROBE guideline for cross-sectional studies. I have major comments.

Response: Thank you very much for the detail review of the paper. The quality of the paper is now greatly improved. We have tried to address all of your comments accordingly.

TITLE: The title of the manuscript is uninformative. It does not capture the study design. Also, the word "... Largest..." is not scientific. The titles would benefit from some modifications.

Response: The paper has a new Title: Retrospective cross-sectional study of patient records in a cardiology clinic at a major Ethiopian referral hospital reveals that RHD is the most prevalent complication. Please refer page 1 line number 2-6 of the final manuscript.

ABSTRACT

1. The statement "Rheumatic Heart Disease (RHD) remains the number one cause of death and disability in developing countries." is false. Yes, cardiovascular diseases are the leading cause of death in developing countries. But ischemic heart disease and stroke are the leading cardiovascular causes of death, not rheumatic heart disease as the authors claim

(https://www.who.int/news-room/fact-sheets/detail/the-top-10-causes-of-death).

Response: It is now modified as : Rheumatic Heart Disease (RHD) remains one of the major cause of death and disability in developing countries. Please refer page 1 line number 24 of the final manuscript..

2. The abstract contain no information about the study design, inclusion criteria, the method used to sample records, method of statistical analysis used, and the tool used to analyse the data.

Response: A paragraph explaining the study design is now included.

It reads: This is a retrospective cross-sectional study of the spectrum of cardiovascular diseases at one of the major referral hospital in Ethiopia. A statistical analysis of the 7576 patient records who visited the cardiac clinic of Tikur Anbessa Referral Hospital is done. In this study all the patients who visited the cardiac from June 2015 to August 2018 and presented a cardiac problem. A predesigned and tested EXCEL form is used to collect the data. The data was encoded directly from the patient cards mainly focusing on ten variables which include diagnosis, sex, age, and address.

Please refer page 1 line number 29-36 of the final manuscript..

3. The results should be written in past tense.

Response: It is corrected accordingly.

MAIN TEXT

BACKGROUND:

1. The authors need to be more specific and avoid using colloquial languages. For example the sentence " Despite the fact that hundreds of thousands of people worldwide are a victim to this disease..." can be more specific. Also, "... the awareness of most people about the disease is very small." is very unspecific. What do the authors mean by very small?

Response: It is now corrected as : Although many people in the world suffer from this disease, there is minimal public knowledge about the disease.

Please refer page 2 line number 71-72 of the final manuscript..

2. The reference [23] comes immediately after reference [1]. Is this supposed to be a mistake?

Response: it was supposed to be [2,3], and it is corrected accordingly.

Please refer page 2 line number 62 of the final manuscript..

3. The objective of the study is not clear. What do the authors mean by "burden"? This can range from prevalence, years of life lost to disability, or mortality. They need to be more specific.

Response: In the context of this paper burden means prevalence. The objective has been corrected accordingly.

Please refer page 3 line number 99-101 of the final manuscript..

METHODS

1. The study design is not mentioned.

Response: under the section "Study design and setting", the study design is explained in detail as:

This is a retrospective cross-sectional study of the spectrum of cardiovascular diseases at one of the major referral hospitals in Ethiopia . An analysis of cardiovascular disease trends at Tikur Anbessa Referral Teaching Hospital, Adult Cardiac Clinic, Addis Ababa University, College of Health Sciences has been conducted. This is the biggest hospital in Ethiopia where the majority of referrals are made from all over of Ethiopia. The cardiac center manually records the admission and discharge diagnosis of inpatients and outpatients. A socio- demographic data which includes, sex, age group, and origin of all cardiac patients is collected. Reviewing these reports can provide information on the prevalence of different CVD cases.

. Please refer page 6 line number 195-203 of the final manuscript..

2. The inclusion and exclusion criteria, if any, are not mentioned.

Response: A separate section for inclusion and exclusion criteria is included which states the inclusion and exclusion criteria as:

The cards of all inpatients and outpatients who visited the cardiac clinic from June 2015 to August 2018 were included. Records exhibiting non cardiac diagnosis and those without a clear indication of diagnostic information were excluded from the study.

. Please refer page 7 line number 227-231 of the final manuscript..

3. Ethical considerations should come at the end of the methods or in the declaration.

Response: the full name of the ethics committee is included at the end of the first paragraph of the study design. Please refer page 6 line number 204-205 of the final manuscript.

4. The methods should be written in the past tense.

Response: corrected accordingly

5. This should fall under the results, not the methods: " A total of 8371(Male (40.5%) and Female (59.5%) data cards were encoded. 795 of the records were excluded due to incomplete information and exhibiting a non-cardiac diagnosis."

Response: corrected accordingly

Please refer page 8 line number 258-259 of the final manuscript..

6. There is no information on how participants were selected.

Response: This is a hospital record based study hence the cards of all inpatients and outpatients who visited the cardiac clinic from June 2015 to August 2018 were included.

Please refer page 7 line number 229-232 of the final manuscript..

7. What protocol was used by the health facility to diagnose different cardiac diseases?

Response: Diagnosis techniques for the major CVDs are now included in the manuscript.

Please refer page 7 -8 line number 207-225 of the final manuscript..

7. There is no section on data analysis.

Response: There is one under the section " Data collection process and data analysis", it reads:

A detailed descriptive statistics are performed for the data analysis. As cutoff points, 95 % confidence interval (CI) was used to assess the statistical significance of relationship tests of various variables with CVDs.

Please refer page 7-8 line number 234-245 of the final manuscript..

8. Again, this is supposed to fall under the results and not the methods: "The remaining 7576 records were statically analyzed. Table 1 shows the socio-demographic summarization of the data."

Response: Corrected accordingly

Please refer page 8 line number 251-252 of the final manuscript..

RESULTS

1. It is important to analyse data for paediatric and adult patients separately because the distribution of cardiovascular diseases differ between these two groups.

Response: corrected accordingly

Please refer page 9 line number 273-279 of the final manuscript and Table 2

2. The prevalence of rheumatic heart disease in this study is surprising high. It is important for the authors to properly describe their study population for better interpretation of the results.

Response: It is now demonstrated how RHD is consistently high in comparison with other Sub-Saharan996 countries. Different scenarios that can explain the high prevalence rate are now presented and discussed.

Please refer page 12 line number 335-375 of the final manuscript.

DISCUSSION

The authors do not provide a balanced discussion of their results. They did not compare or contrast their findings with other African literature published on the subject.

Response: A comparison with a previous study in Ethiopia, Cameron and Malawi and several other sub-Saharan countries is included now.

Please refer page 12 line number 329-342 of the final manuscript.

Reviewer #2

Reviewer #2: Authors should be congratulated for this research paper. Nicely written, methodology robust, and discussion/perspective well managed. This study is one of the contemporary studies conducted to assess the prevalence of difference cardiovascular diseases in Ethiopia. The study has been conducted in the biggest referral hospital in the country where patients are sent from every corner of the country. The study has analyzed patient cards over three year’s period. Last data on RHD from GBD project published in the NEJM as well as its editorial should be considered. In addition, relatively recent review on RHD published in The Lancet (PMID: 22405798) can be considered since the introduction. The importance of

early diagnosis should be emphasised (and practical challenges of echo screening...Mirabel et al. Circ Imaging) as well as the cost effectiveness of antibioprophylaxis...

Response: Thank you very much for the complement and the valuable discussion about the paper. The quality of the paper is greatly improved now.

The reference you stated are included as Reference 5 ,6 and 7.

Please refer page 2 line number 62-65 of the final manuscript.

An intervention recommendation is included at the end of the concluding remarks.

Please refer page 13 line number 389-395 of the final manuscript.

Attachments
Attachment
Submitted filename: Rebuta Letter.docx
Decision Letter - Nicole J. Moreland, Editor

PONE-D-20-17248R1

Retrospective cross-sectional study of patient records in a cardiology clinic at a major Ethiopian referral hospital reveals that RHD is the most prevalent complication

PLOS ONE

Dear Dr. Asmare,

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 06 2020 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: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

We look forward to receiving your revised manuscript.

Kind regards,

Nicole J. Moreland

Academic Editor

PLOS ONE

Additional Editor Comments (if provided):

Both reviewers have noted that some comments from the previous reviews have been addressed but further comments and questions remain.

[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: (No Response)

Reviewer #3: (No Response)

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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: Partly

Reviewer #3: Partly

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

Reviewer #1: Yes

Reviewer #3: I Don't Know

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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 Response)

Reviewer #3: 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: No

Reviewer #3: No

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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 thank the authors for taking the time to submit a revised version of their manuscript. They have addressed most of the comments that I raised in the previous version of their manuscript. I have some major comments.

TITLE:

1. I will suggest that the authors structure the title as such: "Prevalence of rheumatic heart disease in a major referral cardiology clinic in Ethiopia: a retrospective cross-sectional study"

ABSTRACT

a. BACKGROUND:

Please, include the objective of the study as the last sentence of the background section of the abstract. This would be something like " We sought to describe the prevalence of rheumatic heart disease at one of the major referral cardiology clinics in Ethiopia".

b. METHODS

1. The method is still written in the present. The methods should read something like this: "This was a retrospective cross-sectional chart review of all patients referred for a cardiopathy at the Tikur Anbessa Referral Cardiac Clinic from June 2015 to August 2018. We excluded records of patients with a non-cardiac diagnosis and those without a clear diagnosis." Do not mention the number of records that were included in the study at this stage. Please, reserve that for the results.

2. The authors mention that Microsoft Excel 2010 was used for data abstraction but did not provide any information on the software that was used for the Statistical analysis. Was the statistical analysis done in excel, or another statistical analysis program such as the Statistical Package for Social Sciences (SPSS), R or Stata?

c. Results

1. Generally, the median and interquartile range (Q1-Q3) will be reported as such: “median (interquartile range = Q1-Q3)”. For example, the median age was 30 years (interquartile range = 20-40). Please, correct throughout.

2. " followed by congenital heart disease with 9% incidence rate." This is a cross-sectional study; you cannot talk about incidence but prevalence. Period prevalence to be more specific. Please, correct.

d. Conclusion

The authors are making conclusions that are not supported by their data. For example: "Low-cost screening methods also help identify the disease early. " and "There is a backlog of patients waiting for surgery, so increasing this potential would be of utmost importance."

MAIN TEXT

a. Methods

1. This was a retrospective cross-sectional study of hospital records, not "This is..." Please, correct the tense here.

b. Results

1. Since Table 2 and 3 are describing the entire study population, they should be presented before Figure 1.

2. Table 1: There is no title for Table 1. There are no values for the number of patients according to residence; the authors just presented percentages.

3. Table 4 can be combined with Table 1 by presenting the frequency distribution table with percentages of sociodemographic characteristic by RHD status (those with RHD and those without) and for the total population.

4. Table 2: Please, present the percentages for Table 2. Once this is done, you can delete Figure 2 because it is presenting the same information as Table 2.

5. An alternative way to present the information in the resulting Table 2 is by using a bar chart to present the frequency (or percentage) of the different cardiac diseases by age group (so paediatric versus adults) and for the total population. This is just a suggestion, the authors can go with whatever option they are comfortable with.

6. Figure 1 is not a histogram but a bar chart.

7. Paragraph 3: "The hospital has separate cardiology services for pediatric and adults. The pediatric cardiac clinic primarily treats congenital and acquired heart disease patients who are younger than 18 years of age. There is an understanding, amid this distinction, that pediatric patients are treated in the adult wing. This is primarily due to cardiologist shortages; thus some pediatric outpatients might be referred to the adult cardiac clinic.". This is misplaced and should not be in the results. Please, move the sentence to the methods where you are supposed to describe the study setting.

8. In the statistical analysis, the authors mentioned: " As cutoff points, 95 % confidence interval (CI) and P-value < 0.05 were used to assess the statistical significance of relationship tests of various variables with CVDs.". Looking at the results, the authors did not report 95% confidence intervals, or p-value. I am not sure why the authors want to perform hypothesis testing, but I will not encourage them to do this. Rather, they should report the 95% confidence interval for the prevalence of RHD since this cardiac condition is the main focus of the paper.

c. Discussion

1. Line 1: Do the authors mean "different" instead of "difference"?

2. Paragraph 1: The authors should use the past tense to describe what they did.

3. "The findings of this study are a good indicator of how severe the burden of RHD is in Ethiopia" This statement is wrong. The sample is not representative of the Ethiopian population. The study was conducted in a referral hospital and in patients with suspected or established cardiac diseases. This group of patients would be systematically different from the Ethiopian population in terms of characteristics such as age and socioeconomic status. Therefore, it is difficult for the authors to generalise their results to the whole of Ethiopia. Again, it is unclear what the authors mean by "burden".

d. COnclusion

The conclusions of the authors should be supported by the data presented.

The manuscript will benefit from editing by a native English speaker.

Reviewer #3: This is an interesting piece of work on the prevalence of RHD in Ethiopia. While the authors have addressed some of the reviewer’s comments, the manuscript needs to clarify a few more details.

One of the main things that needs more information is around the dataset. The authors mention a "card" what is this? Can you please add in more details about what this "card" is. Does Ethiopia use ICD codes? How are the each of the diseases categorised? I understand that a cardiologist diagnoses the patient, but what happens to the data after that? Are the patients only coded if they stay in over-night or are day patients also included?

More specific comments are:

Title

While I really like the title, it is more suited to a media release than a journal article. I note that you have changed it from the previous version, I would suggest refining it further.

Abstract

Line 26 delete "the"

Line 27 what do you mean by misunderstanding of the burden? Who misunderstands? The general public? Drs? Other countries? Is the misunderstanding around the disease progression? I note you also mentioned this in lines 73/74. It is unclear exactly what is meant.

Line 29 hospital needs to be hospitals

Line 30 remove "the"

Line 31 is should be was

Background

Line 64 by hyper nutrition do you mean poor nutrition?

Line 66 I don't think you need this sentence.

Line 68 you need to add in that it is Group A streptococcal (GAS) infection. Delete "is called" and replace with "causes acute rheumatic fever (ARF). ARF can led to RHD and autoimmune disease.......

Line 70 delete "that"

Line 83 you mention western countries having no RHD. This is untrue, high-income countries with indigenous populations also suffer high rates of ARF/RHD.

Literature review

I am unsure what this is separate to the background. I would suggest combining the background and the literature review and making it an "introduction"

Your aim needs to be more specific. Something like "This study aimed to explore the spectrum of cardiovascular diseases through hospital discharge data from 2015-2018."

Methods

Line 199 replace "of the spectrum" with "investigating"

Line 200 delete "at one of the major referral hospitals in Ethiopia. An analysis of" it is a repeat of below.

Line 202 delete "has been conducted'

Where does the socio-economic data come from? The discharge data?

Line 205 is origin the region? Place of residence?

Line 206 delete "is"

I would have a separate sub heading for the "ethics" section

Lines 217-230 are not needed in the methods, they are background, rather than methods.

Line 233 - clarify what is meant by the "cards"

Line 242 delete this sentence it is not needed.

Line 247 replace "designed" with "used"

Line 250 what data was entered? Was it coded data? How was it coded?

Line 250 delete the words "ten required columns which are"

Line 252 Delete the part about optional columns, as I don't think you analyse these?

Line 255 Replace "patient name, contact number and card number were" with "All identificable information was"

Line 256 you need to say how the stats were analysed. Were they analysed in excel?

Results

Line 263 summarization should be summary.

You don't need to have Table 1 and Figure 1 they show the same information.

Lines 275-280 are not results. This is background information

Lines 300-305 belong with Table/Figure 1 you need to put them before you start talking about Table 2.

You only need Table2 or Figure 2 again they show the same information as each other. The same is true for Table3/Figure 3.

You have accidently put "Table 4" in the discussion, this is a double up of Table 1?

Discussion

You refer to another Ethiopian study, how was this done, what makes your study any different?

Line 362 add in GAS

Has the prevalence of RHD changed over time, if so this is something that should be discussed.

Line 383 you mention that hypertensive heart disease/etc was considered an ailment of the developed world. Why? What is the life expectancy difference between sub-Sahara Africa and high-income countries, does this explain the difference?

Line 388 you mention your limitation only used hospital data you need to say why this is a limitation. Because it doesn't capture those people who don't come to hospital - they may be too sick, too mild, live too far away?

**********

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.

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Reviewer #1: Yes: Valirie Ndip Agbor

Reviewer #3: No

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Revision 2

Authors' Responses to Reviewers

Reviewer #1:

I thank the authors for taking the time to submit a revised version of their manuscript. They have addressed most of the comments that I raised in the previous version of their manuscript. I have some major comments.

Response: Thank you very much for the detail review of the revised version of the paper. The quality of the paper is now greatly improved. We have tried to address all of your comments accordingly.

TITLE:

1. I will suggest that the authors structure the title as such: "Prevalence of rheumatic heart disease in a major referral cardiology clinic in Ethiopia: a retrospective cross-sectional study"

Response: Corrected accordingly

ABSTRACT

a. BACKGROUND:

Please, include the objective of the study as the last sentence of the background section of the abstract. This would be something like " We sought to describe the prevalence of rheumatic heart disease at one of the major referral cardiology clinics in Ethiopia".

Response: Corrected accordingly

b. METHODS

1. The method is still written in the present. The methods should read something like this: "This was a retrospective cross-sectional chart review of all patients referred for a cardiopathy at the Tikur Anbessa Referral Cardiac Clinic from June 2015 to August 2018. We excluded records of patients with a non-cardiac diagnosis and those without a clear diagnosis." Do not mention the number of records that were included in the study at this stage. Please, reserve that for the results.

Response: Corrected accordingly

2. The authors mention that Microsoft Excel 2010 was used for data abstraction but did not provide any information on the software that was used for the Statistical analysis. Was the statistical analysis done in excel, or another statistical analysis program such as the Statistical Package for Social Sciences (SPSS), R or Stata?

Response: Yes Excel was used for data abstraction and MATLAB Statistics toolbox (MATLAB2019b) was used for statistical analysis. This information is now included.

c. Results

1. Generally, the median and interquartile range (Q1-Q3) will be reported as such: “median (interquartile range = Q1-Q3)”. For example, the median age was 30 years (interquartile range = 20-40). Please, correct throughout.

Response: Corrected accordingly

2. " followed by congenital heart disease with 9% incidence rate." This is a cross-sectional study; you cannot talk about incidence but prevalence. Period prevalence to be more specific. Please, correct.

Response: Corrected accordingly

d. Conclusion

The authors are making conclusions that are not supported by their data. For example: "Low-cost screening methods also help identify the disease early. " and "There is a backlog of patients waiting for surgery, so increasing this potential would be of utmost importance."

Response: These statements are more of recommendation rather than conclusion. They are removed.

MAIN TEXT

a. Methods

1. This was a retrospective cross-sectional study of hospital records, not "This is..." Please, correct the tense here.

Response: corrected accordingly

b. Results

1. Since Table 2 and 3 are describing the entire study population, they should be presented before Figure 1.

Response: Figure 1 is now removed as it is redundant.

2. Table 1: There is no title for Table 1. There are no values for the number of patients according to residence; the authors just presented percentages.

Response: There is a title which is: Table 1. Socio-demographic characteristics of all the patients in the study

3. Table 4 can be combined with Table 1 by presenting the frequency distribution table with percentages of socio-demographic characteristic by RHD status (those with RHD and those without) and for the total population.

Response: Yes, it's possible to merge them, but the aim for separation is to give more emphasis to RHD hence they are separately presented RHD.

4. Table 2: Please, present the percentages for Table 2. Once this is done, you can delete Figure 2 because it is presenting the same information as Table 2.

Response: corrected accordingly. Figure 2 is now deleted.

5. An alternative way to present the information in the resulting Table 2 is by using a bar chart to present the frequency (or percentage) of the different cardiac diseases by age group (so paediatric versus adults) and for the total population. This is just a suggestion, the authors can go with whatever option they are comfortable with.

Response: Tabular representation is a better approach since there is a significant difference between the number of adult and pediatric case, as the bar chart couldn't display the small numbers clearly.

6. Figure 1 is not a histogram but a bar chart

Response: corrected accordingly. Figure 1 is removed now.

7. Paragraph 3: "The hospital has separate cardiology services for pediatric and adults. The pediatric cardiac clinic primarily treats congenital and acquired heart disease patients who are younger than 18 years of age. There is an understanding, amid this distinction, that pediatric patients are treated in the adult wing. This is primarily due to cardiologist shortages; thus some pediatric outpatients might be referred to the adult cardiac clinic.". This is misplaced and should not be in the results. Please, move the sentence to the methods where you are supposed to describe the study setting.

Response: Corrected accordingly

8. In the statistical analysis, the authors mentioned: " As cutoff points, 95 % confidence interval (CI) and P-value < 0.05 were used to assess the statistical significance of relationship tests of various variables with CVDs.". Looking at the results, the authors did not report 95% confidence intervals, or p-value. I am not sure why the authors want to perform hypothesis testing, but I will not encourage them to do this. Rather, they should report the 95% confidence interval for the prevalence of RHD since this cardiac condition is the main focus of the paper.

Response: Yes, that statement was mistakenly included in the first version however such statement is removed in the first revision and is no more there.

c. Discussion

1. Line 1: Do the authors mean "different" instead of "difference"?

Response: we meant different. corrected accordingly

. 2. Paragraph 1: The authors should use the past tense to describe what they did.

Response: corrected accordingly

3. "The findings of this study are a good indicator of how severe the burden of RHD is in Ethiopia" This statement is wrong. The sample is not representative of the Ethiopian population. The study was conducted in a referral hospital and in patients with suspected or established cardiac diseases. This group of patients would be systematically different from the Ethiopian population in terms of characteristics such as age and socioeconomic status. Therefore, it is difficult for the authors to generalise their results to the whole of Ethiopia. Again, it is unclear what the authors mean by "burden".

Response: The statement is now modified as: The findings of this study are a good indicator of how severe the prevalence of RHD is in Ethiopia's biggest referral hospital.

d. Conclusion

The conclusions of the authors should be supported by the data presented.

The manuscript will benefit from editing by a native English speaker.

Response: corrected accordingly

Reviewer #3:

This is an interesting piece of work on the prevalence of RHD in Ethiopia. While the authors have addressed some of the reviewer’s comments, the manuscript needs to clarify a few more details.

Response: Thank you very much for the detail review of the revised version of the paper. The quality of the paper is now greatly improved. We have tried to address all of your comments accordingly.

One of the main things that needs more information is around the dataset. The authors mention a "card" what is this? Can you please add in more details about what this "card" is. Does Ethiopia use ICD codes? How are the each of the diseases categorized? I understand that a cardiologist diagnoses the patient, but what happens to the data after that? Are the patients only coded if they stay in over-night or are day patients also included?

Response:

1. Card is essentially the word we use in the patient file folder where the medical record number (MRN) is issued for each file (MRN or card number is used synonymously). Each patient card typically contains the patient's medical history and symptoms, medical findings, results of diagnostic tests and procedures, and medicines and therapeutic procedures.

2. In Ethiopia, we use the ICD code for any disease and the disease is classified accordingly.

3. When a diagnosis has been made for a patient with cardiac problems, the patient will be treated with standard care in accordance with the national guidelines, including medical management, surgical procedures, psychosocial support and rehabilitation.

4. We included all patients seen as out-patients and treated as inpatients.

More specific comments are:

Title

While I really like the title, it is more suited to a media release than a journal article. I note that you have changed it from the previous version, I would suggest refining it further.

Response: the new title is: Prevalence of rheumatic heart disease in a major referral cardiology clinic in Ethiopia: a retrospective cross-sectional study

Abstract

Line 26 delete "the"

Response: corrected accordingly

Line 27 what do you mean by misunderstanding of the burden? Who misunderstands? The general public? Drs? Other countries? Is the misunderstanding around the disease progression? I note you also mentioned this in lines 73/74. It is unclear exactly what is meant.

Response: The statement means: The misunderstanding is actually for both the public and the health authorities. Community-level understanding of the cause and association between GAS pharyngitis and ARF/RHD is almost non-existent where as health authorities' commitment to this disease and subsequent resource allocation is poor.

Line 29 hospital needs to be hospitals

Response: corrected accordingly

Line 30 remove "the"

Response: corrected accordingly

Line 31 is should be was

Response: corrected accordingly

Background

Line 64 by hyper nutrition do you mean poor nutrition?

Response: No, hyper nutrition means over eating.

Line 66 I don't think you need this sentence.

Response: statement removed

Line 68 you need to add in that it is Group A streptococcal (GAS) infection. Delete "is called" and replace with "causes acute rheumatic fever (ARF). ARF can led to RHD and autoimmune disease.......

Line 70 delete "that"

Response: corrected accordingly

Line 83 you mention western countries having no RHD. This is untrue, high-income countries with indigenous populations also suffer high rates of ARF/RHD.

Response: Yes you are right the statement is now modified as :....Western Countries where there is no prevalence of RHD except in isolated impoverished pockets of these nations....

Literature review

I am unsure what this is separate to the background. I would suggest combining the background and the literature review and making it an "introduction"

Response: corrected accordingly

Your aim needs to be more specific. Something like "This study aimed to explore the spectrum of cardiovascular diseases through hospital discharge data from 2015-2018."

Response: corrected accordingly

Methods

Line 199 replace "of the spectrum" with "investigating"

Response: corrected accordingly

Line 200 delete "at one of the major referral hospitals in Ethiopia. An analysis of" it is a repeat of below.

Response: corrected accordingly

Line 202 delete "has been conducted'

Response: corrected accordingly

Where does the socio-economic data come from? The discharge data?

Response: The socio-demographic data came from the patient file folder which was referred as patent cards in the paper.

Line 205 is origin the region? Place of residence?

Response: Origin means place of residence and corrected accordingly

Line 206 delete "is"

Response: corrected accordingly

I would have a separate sub heading for the "ethics" section

Lines 217-230 are not needed in the methods, they are background, rather than methods.

Response: The ethics statement was placed in its current place, as recommended by the editor. The CVD diagnostic protocol was in its current position as suggested by the other reviewer.

Line 233 - clarify what is meant by the "cards"

Response: Card is essentially the word we use in the patient file folder.

Line 242 delete this sentence it is not needed.

Response: corrected accordingly

Line 247 replace "designed" with "used"

Response: corrected accordingly

Line 250 what data was entered? Was it coded data? How was it coded?

Response: socio-demographic data along with diagnosis and treatment information from the patient file folder ( which was referred as patient cards) is entered to the Excel form with 14 variables however only 10 of them were used in this analysis. The data is not coded.

Line 250 delete the words "ten required columns which are"

Response: corrected accordingly

Line 252 Delete the part about optional columns, as I don't think you analyse these?

Response: corrected accordingly

Line 255 Replace "patient name, contact number and card number were" with "All identifiable information was"

Response: corrected accordingly

Line 256 you need to say how the stats were analysed. Were they analysed in excel?

Response: MATLAB Statistics toolbox (MATLAB2019b) was used for statistical analysis. It is corrected accordingly.

Results

Line 263 summarization should be summary.

Response: corrected accordingly

You don't need to have Table 1 and Figure 1 they show the same information.

Response: Figure 1 is now removed.

Lines 275-280 are not results. This is background information

Response: corrected accordingly

Lines 300-305 belong with Table/Figure 1 you need to put them before you start talking about Table 2.

Response: This is due to the auto formatter where the position of Tables and Figures are set automatically to optimize space. It is now modified accordingly.

You only need Table2 or Figure 2 again they show the same information as each other. The same is true for Table3/Figure 3.

Response: corrected accordingly, Figure 2 and Figure 3 are now removed.

You have accidently put "Table 4" in the discussion, this is a double up of Table 1?

Response: They are actually different tables. Table 4 is for only RHD cases.

Discussion

You refer to another Ethiopian study, how was this done, what makes your study any different?

Response: The refereed Ethiopian study[16] studied from 1 January 2015 to 30 June 2015 and published in 2017 analyzing data from six university hospitals. They studied 6275 patients of which 58.5% were females and 61% of the patients were from urban areas with median age was 33 years. RHD was the most common diagnosis with 40.5% of the cases. However, the study period is limited to 6 months. They have only considered patients who visited the cardiac clinics in the study period.

Our study has on the other hand considered a relatively longer study period of 3 years (June 2015 to August 2018) and bigger data set (7576) to understand the pattern of cardiovascular diseases which will make it more representative. It also reports the contemporary scope of cardiovascular disease in the biggest hospital in the country. It has also found that there is an almost 11% increment of the incidence rate of RHD compared to a previous hospital-based study conducted in cardiology clinics.

Line 362 add in GAS

Response: corrected accordingly

Has the prevalence of RHD changed over time, if so this is something that should be discussed.

Response: Yes the prevalence has changed with 11% increment from previous study and it is discussed.

Line 383 you mention that hypertensive heart disease/etc was considered an ailment of the developed world. Why? What is the life expectancy difference between sub-Sahara Africa and high-income countries, does this explain the difference?

Response: No. The statement is to just to explain the incorrect assumption which tends to associate heart disease mainly with the sedentary lifestyle and hyper nutrition [2, 3]. It has nothing to do with life expectancy difference.

Line 388 you mention your limitation only used hospital data you need to say why this is a limitation. Because it doesn't capture those people who don't come to hospital - they may be too sick, too mild, live too far away?

Response: The main reason why this is a limitation is that the sample is not representative of Ethiopian population. The research was performed in a referral hospital and patients with suspected or confirmed heart disease. This category of patients will be systematically different from the Ethiopian population in terms of age and socioeconomic status. The authors therefore have difficulty generalizing our findings all over Ethiopia.

________________________________________

Attachments
Attachment
Submitted filename: Response to Reviewers.docx
Decision Letter - Nicole J. Moreland, Editor

PONE-D-20-17248R2

Prevalence of rheumatic heart disease in a major referral cardiology clinic in Ethiopia: a retrospective cross-sectional study

PLOS ONE

Dear Dr. Asmare,

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 Feb 20 2021 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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We look forward to receiving your revised manuscript.

Kind regards,

Nicole J. Moreland

Academic Editor

PLOS ONE

Additional Editor Comments (if provided):

As you can see one of the reviewers has suggested further changes for clarity that I also agree with.

[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: Partly

**********

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

Reviewer #1: Yes

Reviewer #3: I Don't Know

**********

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: No

**********

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 thank the authors for submitting a revised version of their work. The authors have addressed my concerns. I have no further comments.

Reviewer #3: This is a worthwhile piece of work and one that I am supportive of being published. The manuscript has improved however, it still needs further work to improve the quality.

The introduction needs to be shortened and only contain information that is directly relevant to the study topic.

Throughout the paper you need to be consistent with the use of acronyms. Once you have spelt out acute rheumatic fever you should use ARF from then on. The same is true for rheumatic heart disease (RHD).

For example a lot of the introduction can be deleted, Lines 78-85, Lines 91-94, lines 168-171.

Methods

You should delete lines 176-182 as they don’t provide the reader with any information about the study.

Line 191 data should be dataset

Line 192 replace collected with utilised

Line 234 ID needs to be identification

Line 241 in to should be into

Line 241 contains should be contained

Results

Line 250 there is a ( before Male that shouldn’t be there

Your tables need more descriptive titles, for example, Table 1 Socio-demographic characteristics of study participants with a hospital diagnosis of ARF/RHD, 2015-2018, Ethiopia

Is this what the table shows? Or is it all cardiovascular diagnoses? And Table 4 is just the RHD patients?

I am a bit confused as to the difference between tables 2 and 3? I think they should be combined by adding a Total column (N) and a column for the median age.

Again the Table needs a more descriptive title. Among which population? What years? Which age groups, etc.

I am unsure why Table 4 is in the discussion? I presume this is a formatting issue?

You need to be very careful with wording in your conclusions for example line 376 would be better worded something like:

In our study population, RHD was more prevalent in urban areas. These areas are associated with lower socio-economic status.

The reason that more women have RHD may be due to women being diagnosed more (they may seek help more than men). They may be picked up having a heart issue when pregnant. Be careful not to draw conclusions that your data doesn’t support. Simply say in our study population, twice as more women were diagnosed with RHD than men.

**********

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: 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.

Revision 3

Authors' Responses to Reviewers

Reviewer #1:

I thank the authors for submitting a revised version of their work. The authors have addressed my concerns. I have no further comments.

Response: Dear reviewer #1, thank you very much again for the detail review of the revised version of the paper. The quality of the paper has now greatly improved.

Reviewer #3:

This is a worthwhile piece of work and one that I am supportive of being published. The manuscript has improved however; it still needs further work to improve the quality.

Response: Dear reviewer #3, thank you very much again for the detail review of the revised version of the paper. The quality of the paper has now greatly improved. We have tried to address all of your comments accordingly.

Introduction

The introduction needs to be shortened and only contain information that is directly relevant to the study topic. Throughout the paper you need to be consistent with the use of acronyms. Once you have spelt out acute rheumatic fever you should use ARF from then on. The same is true for rheumatic heart disease (RHD).

Response: It is now corrected accordingly please check to Line 25, 56, 106 and 178 from the revised manuscript.

For example a lot of the introduction can be deleted, Lines 78-85, Lines 91-94, lines 168-171.

Response: It is now corrected accordingly. The paragraphs are now removed. Please refer to Line 75, line 80, line 154 respectively from the revised manuscript.

Methods

You should delete lines 176-182 as they don’t provide the reader with any information about the study.

Response: It is now corrected accordingly. The paragraphs are now removed. Please refer to Line 156 from the revised manuscript.

Line 191 data should be dataset

Response: It is now corrected accordingly. Please refer line to 164 from the revised manuscript.

Line 192 replace collected with utilised

Response: It is now corrected accordingly. Please refer line to 165 from the revised manuscript.

Line 234 ID needs to be identification

Response: It is now corrected accordingly. Please refer to line 206 from the revised manuscript.

Line 241 in to should be into

Response: It is now corrected accordingly. Please refer to line 213 from the revised manuscript.

Line 241 contains should be contained

Response: It is now corrected accordingly. Please refer to line 213 on the revised manuscript.

Results

Line 250 there is a ( before Male that shouldn’t be there

Response: It is now corrected accordingly. Please refer to line 222 on the revised manuscript.

Your tables need more descriptive titles, for example, Table 1 Socio-demographic characteristics of study participants with a hospital diagnosis of ARF/RHD, 2015-2018, Ethiopia

Response: It is now corrected accordingly. Please refer to line 227 on the revised manuscript.

Is this what the table shows? Or is it all cardiovascular diagnoses? And Table 4 is just the RHD patients?

Response: Yes you are right; Table 1 shows all participants in the study with a hospital diagnosis of cardiopathy; while Table 4 (now Table 3) is for RHD patients.

I am a bit confused as to the difference between tables 2 and 3? I think they should be combined by adding a Total column (N) and a column for the median age.

Response: It is now corrected accordingly. The two tables are now combined. Please refer to line 250 of the revised manuscript.

Again the Table needs a more descriptive title. Among which population? What years? Which age groups, etc. I am unsure why Table 4 is in the discussion? I presume this is a formatting issue?

Response: It is now corrected accordingly. The formatting issue is now sorted out and the title for the new table is now: Distribution of different cardiovascular diagnosis among pediatric an adult patients with their corresponding median age, 2015-2018, Ethiopia. Please refer to line 250 of the revised manuscript.

You need to be very careful with wording in your conclusions for example line 376 would be better worded something like: In our study population, RHD was more prevalent in urban areas. These areas are associated with lower socio-economic status.

Response: It is now corrected accordingly. Please refer to line 352 of the revised manuscript.

The reason that more women have RHD may be due to women being diagnosed more (they may seek help more than men). They may be picked up having a heart issue when pregnant. Be careful not to draw conclusions that your data doesn’t support. Simply say in our study population, twice as more women were diagnosed with RHD than men.

Response: It is now corrected accordingly. Please refer to line 253 of the revised manuscript.

Attachments
Attachment
Submitted filename: Response to Reviewers.docx
Decision Letter - Nicole J. Moreland, Editor

Prevalence of rheumatic heart disease in a major referral cardiology clinic in Ethiopia: a retrospective cross-sectional study

PONE-D-20-17248R3

Dear Dr. Asmare,

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 for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, 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,

Nicole J. Moreland

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

The reviewer has suggested some final minor revisions. However these are mostly editorial in nature and could be corrected during typesetting as needed.

Therefore I am pleased to accept this manuscript for publication.

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: This manuscript has greatly improved and is a lot easier to follow. Well done.

My comments are minor.

Line 57 - RHD needs be spelled out in full as it is the first time it is used.

Line 63 Acute rheumatic fever/rheumatic heart disease should be ARF/RHD as you have already used them.

Line 66 Group A streptococcus should be GAS

Lines 179-182 are not needed, please delete first two sentences. They are not methods.

Line 186 Delete first sentence as it is not methods.

Line 188 Delete the description of IHD it is not needed and is not methods.

Line 235 Delete the sentence "This was, in fact..... as this is not results.

Line 270 Delete "Next, the. Start the sentence with Data.

Line 276 Men should be men

Line 293 "said" should be reported.

Line 328/329 Use HHD and IHD.

**********

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Reviewer #3: No

Formally Accepted
Acceptance Letter - Nicole J. Moreland, Editor

PONE-D-20-17248R3

Prevalence of rheumatic heart disease in a major referral cardiology clinic in Ethiopia: a retrospective cross-sectional study

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