PONE-D-23-24901Polypharmacy patterns and associated factors in South Korean elderly patients with dementia: An analysis using National Health Insurance claims dataPLOS ONE

Dear Dr. Lee,

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Muhammad Eid Akkawi

Academic Editor

PLOS ONE

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4. We are unable to open your Supporting Information file [Figure 1.pptx]. Please kindly revise as necessary and re-upload.

Additional Editor Comments:

- The use of the term "polypharmacy patterns" is not tally with the results and discussion. No results were reported about the types of medications or dosing regimens. Therefore, please remove the word patterns and stick to "polypharmacy" throughout the manuscript.

- L150: to stay consistent, please report the percentages for polypharmacy instead of non-polypharmacy.

- Do not repeat the results in the text and tables. Just highlight the important findings in the text or findings not stated in the tables.

- Table 1: Add a comparison of the mean age between the two groups.

- Include the number of patients in the table captions.

- Make the abstract structured with conclusion.

- English language proofreading is needed.

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

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

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

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

Reviewer #1: Partly

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: 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: I thank the author for this interesting work about polypharmacy and dementia. This work is relevant as it found consistent result with literature with over-prescription in patients suffering from dementia. A major strength of this study is that it was performed on a large sample of a national cohort. However, a better explanation of the method used, and an update of the organization of the results and discussion can improve this study quality and it's understanding.

Major comments:

1. The goal announced is “to discern patterns and associated factors of polypharmacy among outpatient suffering from dementia “. Results and discussion sections show first a comparison between dementia vs non-dementia patients then polypharmacy vs non-polypharmacy in patients suffering from dementia. Both groups can be compared to achieve the announced goal, but they answer different questions. Thus, the author should either improve the formulation of the goal/question and reorganize the methods, results, and discussion sections accordingly.

2. In line with the previous comment, the limit discussed l. 274 might be the most significant. Yet, it is discussed as the last one and the justification provided is not satisfactory. It would be possible either to attribute the value 0 for “Duration of dementia” to negate the variable for non-demented patients or to treat missing values for this variable as a level (if there are no missing values in the dementia patients’ group).

Minor comments

1. The manuscript should be reviewed by an English native speaker to improve its general understanding and quality.

2. The author should specify the ethic committee and its decision date and decision reference

3. The author used the codes F00, F01, F02, F03, G30 and G31.82, which refer mainly to Alzheimer’s disease However, these codes do not include cognitive disorder or impairment, which is a major selection bias. Is it possible for the author to include those missing patients? If not, could they provide justification and/or specify in the method section that these patients were not included?

4. The author defined disability using the disability grades used in South Korea. Can they provide how these grades are assessed?

5. Can the author precise the ranking of the quantiles used for the income level? It is only precise in the results section but a phrase such as (“the fifth quantile represents the highest income”) could be added in the method section.

6. In the table 1, the term Institutional care was used whereas “facility service” is used in the method. The authors should stay consistent.

7. Missing values assessment, analysis and consideration should be provided in the method section.

8. Can the author precise how the CCI variable was dichotomized? The result section shows 3 categories, but it was not specified why/how these cut-offs were chosen.

9. The models used may include redundant variables (CCI and dementia, disability, and dwelling accommodation, …). Have the authors assessed multicollinearity? If so, can they specify it in the method section?

10. The authors should provide in supplementary material comorbidities’ details (overall and groups/sub-groups)

11. In the discussion, the authors assumed that the difference of polypharmacy in dementia patients may be because of the prescription of BPSD controlling drugs. As the author have access to prescriptions records, it will strengthen authors’ conclusion if drug classes comparison was provided.

12. In the discussion, the authors discussed the issue of income when comparing Medical Aid vs NHI population. However, the analysis showed an OR 1 for NIH 1 to 3 compared when compared to NIH 5. Could this author add a section to discuss this result as well?

13. This author should give practical implication of their findings.

Reviewer #2: The article you've presented appears to be a comprehensive and methodologically sound study focusing on polypharmacy among elderly patients with dementia in South Korea. Here are some reviewer comments that could be helpful:

Strengths:

Relevance and Timeliness: The topic of polypharmacy in dementia patients is both timely and relevant, especially considering the aging population and the increase in dementia cases globally.

Data Source and Population: The use of the National Health Insurance Service-Senior cohort database provides a robust and representative sample for this type of research.

Methodological Rigor: The study's methodology, including the definition of polypharmacy and excessive polypharmacy, patient categorization, and statistical analysis, seems thorough and well-justified.

Policy Implications: The findings of this study have significant implications for healthcare policy and practice, particularly in countries with rapidly aging populations.

Areas for Improvement:

Clarity in Introduction: The introduction could benefit from a clearer articulation of the research gap. While it mentions the scarcity of studies in this area, a more explicit statement of what specifically this study adds would be helpful.

Broader Contextualization: The discussion could explore how these findings relate to or differ from studies in other countries, especially those with different healthcare systems or demographic profiles.

Addressing Limitations: While some limitations are implicit (such as the study's focus on South Korea), it would be beneficial for the authors to explicitly state these limitations and discuss how they might affect the generalizability of the findings.

Potential Biases: Any potential biases in the data source or methodology should be acknowledged and discussed, such as selection bias in the cohort or limitations in the diagnostic codes used.

Implications for Future Research: The article could offer more detailed suggestions for future research, such as exploring interventions to reduce polypharmacy risks or examining the impact of polypharmacy on specific outcomes in dementia patients.

Editorial Suggestions:

Abstract Structure: The abstract could be structured more clearly with distinct sections for background, methods, results, and conclusions to enhance readability.

Consistency in Terminology: Ensure consistency in the use of terms and definitions throughout the paper.

References: Check for the latest references, especially if there have been significant developments in the field since the original literature review was conducted.

Overall, the article contributes valuable insights into an under-researched area and has the potential to inform clinical practices and policy decisions in the care of dementia patients.

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Reviewer #1: Yes: Edouard Baudouin

Reviewer #2: Yes: Ali Haider Mohammed

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Polypharmacy and associated factors in South Korean elderly patients with dementia: An analysis using National Health Insurance claims data

PONE-D-23-24901R1

Dear Dr. Lee,

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,

Muhammad Eid Akkawi

Academic Editor

PLOS ONE

Additional Editor Comments:

In the future, please consider avoiding use of the term "elderly" as it may have negative connotation.

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

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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

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

Reviewer #1: 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

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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

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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: Thank you for your detailed answers and corrections. However, authors should be advised that the word "Elderly" can have a negative connation and should avoid its use in future papers

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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: Edouard Baudouin

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