PONE-D-24-08238End-of-Life Experiences in Individuals with Dementia with Lewy Bodies: a Mixed-Methods AnalysisPLOS ONE

Dear Dr. Armstrong,

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. 

Reviewer 1

Major Revision

Thank you for submitting an interesting manuscript that explores caregiver-reported end-of-life experiences in DLB. Please consider the following suggestions for improvement by section.

Title:

- Although the title references “End-of-Life Experiences in Individuals with Dementia with Lewy Bodies,” the majority of data are caregiver-reported and may not accurately reflect the patient experience. To avoid confusion, consider incorporating caregivers into the title (e.g., Caregiver-Reported End-of-Life Experiences in Individuals with DLB, End-of-Life Experiences among DLB Patients and Caregivers, Patient and Caregiver Experiences at End-of-Life in DLB, etc.)

Abstract:

- In the methods section, please clarify what data was collected from patients, if any

Introduction:

- You state: “Reported survival is longer in pathologic cohorts.” Please define the term “pathologic cohorts” for those that are unfamiliar. I assume these were patients who underwent post-mortem examination, but this was not immediately clear.

- You state, “Allowing for multiple categories, the most common cause of death in DLB is failure to thrive (65%), followed by pneumonia/swallowing difficulties (23%), medical conditions other than pneumonia (19%), and falls or complications from a fall (10%). How big was this cohort? The denominator will help put these figures into context, as death certificates are often unavailable when using national data.

- Similarly, when you state “In a 2017 survey conducted through the Lewy Body Dementia Association, only 40% of family members of individuals with DLB said their physician discussed what to expect at the end of life in DLB,” what was the sample size?

- You report that “The current mixed-methods analysis investigates end-of-life experiences for the first 50 study participants who died during the study.” Why are you reporting these data separately from the parent study?

Methods:

- The inclusion criteria includes persons with DLB expected to live at least 6 months. How was this determined?

Results:

- You present mean years between diagnosis and death. It would be helpful to present data on disease duration (symptom onset to death) if available.

- There were 37 male patients and 36 patients who identified as male. Was one patient transgender? Consider changing sex and gender to “biological sex” and “gender identity” to avoid confusion.

- Caregivers most commonly reported that individuals with DLB died from the DLB itself. How? Please elaborate.

- In the section “Healthcare factors associated with Positive or Negative Experiences,” please describe the negative factors in more detail. For example, what were the negative experiences surrounding hospice care?

Discussion:

- A 90% hospice utilization rate is quite high, even if initiated later than appropriate. Could the high utilization rate be based on referral patterns from outpatient doctors (more than 50% saw a DLB specialist) or due to participant bias, given that data were drawn from patients who were willing to participate in end-of-life care research? I would add this to study limitations since this affects generalizability.

General:

- Writing could be more concise, particularly in the introduction

Reviewer 2

Minor Revision

The paper is good and interesting but needs minor revision. See my comments below

Abstract

It does not have conclusion which should be strictly based on the results

Discussion should be deleted from the abstract

Introduction

DLB expand to full at the beginning of the statement

Study visits and measures

Correct priori

Please be specific of what you did in the research-visits were completed over multiple

days if needed

Data Availability

Indicate the author to contact for data availability

Sample size of 50

It is small, you would have followed more subjects

Conclusion

Remove the table you mentioned on the conclusion. The conclusion is too long. Kindly summarise the key findings and implications

Please submit your revised manuscript by Jul 31 2024 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

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We look forward to receiving your revised manuscript.

Kind regards,

Hope Onohuean, PhD

Academic Editor

PLOS ONE

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[I have read the journal's policy and the authors of this manuscript have the following competing interests: EW, BL, SMM, ZL, and HJF report no competing interests. HLP: HLP receives funding from the NIA (1P30AG053760) and is the local PI of a Lewy Body Dementia Association Research Center of Excellence. CM: CM receives research support from ACL/DHHS (90ALGG0014-01-00), NIA/NIH (2SB1AG037357-04A1, R01-AG-054435), HRSA (U1QHP287440400) and DoD (AZ190036). She is the local PI of a Lewy Body Dementia Association Research Center of Excellence. JAF: JAF receives research support from the NIA (U01NS100620, R01AG068128, R43AG65088). AL: AL receives research support from the NIA (P30AG62677, R43AG65088). She is a Program Coordinator for the local a Lewy Body Dementia Association Coordinating Center Research Center of Excellence. BFB: BFB has served as an investigator for clinical trials sponsored by Biogen, Alector, and EIP Pharma. He serves on the Scientific Advisory Board of the Lewy Body Dementia Association, Association for Frontotemporal Degeneration, and Tau Consortium. He is the site PI of a Lewy Body Dementia Association Research Center of Excellence program, as well as coordinating center PI of the program. He receives research support from the NIH, the Mayo Clinic Dorothy and Harry T. Mangurian Jr. Lewy Body Dementia Program, and the Little Family Foundation. JEG: JEG is the creator of the QDRS and the LBCRS. He is supported by grants from the National Institutes of Health (R01 AG069765, R01 AG057681, R01 NS101483, P30 AG059295, U54 AG06354, R01 AG056531, U01 NS100610, R01 AG056610, R01 AG054425, R01 AG068128) and the Leo and Anne Albert Charitable Trust. He is the local PI of the Lewy Body Dementia Association Research Center of Excellence at the University of Miami and serves on the Scientific Advisory Board of the Lewy Body Dementia Association. AST: AST is an employee of the Lewy Body Dementia Association. MJA: MJA receives research support from the NIH (R01AG068128, P30AG066506, R01NS121099, R44AG062072), the Florida Department of Health (grants 20A08, 24A14, 24A15), and as the local PI of a Lewy Body Dementia Association Research Center of Excellence. She serves on the DSMBs for the Alzheimer’s Therapeutic Research Institute/Alzheimer’s Clinical Trial Consortium and the Alzheimer’s Disease Cooperative Study. She has provided educational content for Medscape, Vindico CME, and Prime Inc.]. 

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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

**********

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

**********

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: Thank you for submitting an interesting manuscript that explores caregiver-reported end-of-life experiences in DLB. Please consider the following suggestions for improvement by section.

Title:

- Although the title references “End-of-Life Experiences in Individuals with Dementia with Lewy Bodies,” the majority of data are caregiver-reported and may not accurately reflect the patient experience. To avoid confusion, consider incorporating caregivers into the title (e.g., Caregiver-Reported End-of-Life Experiences in Individuals with DLB, End-of-Life Experiences among DLB Patients and Caregivers, Patient and Caregiver Experiences at End-of-Life in DLB, etc.)

Abstract:

- In the methods section, please clarify what data was collected from patients, if any

Introduction:

- You state: “Reported survival is longer in pathologic cohorts.” Please define the term “pathologic cohorts” for those that are unfamiliar. I assume these were patients who underwent post-mortem examination, but this was not immediately clear.

- You state, “Allowing for multiple categories, the most common cause of death in DLB is failure to thrive (65%), followed by pneumonia/swallowing difficulties (23%), medical conditions other than pneumonia (19%), and falls or complications from a fall (10%). How big was this cohort? The denominator will help put these figures into context, as death certificates are often unavailable when using national data.

- Similarly, when you state “In a 2017 survey conducted through the Lewy Body Dementia Association, only 40% of family members of individuals with DLB said their physician discussed what to expect at the end of life in DLB,” what was the sample size?

- You report that “The current mixed-methods analysis investigates end-of-life experiences for the first 50 study participants who died during the study.” Why are you reporting these data separately from the parent study?

Methods:

- The inclusion criteria includes persons with DLB expected to live at least 6 months. How was this determined?

Results:

- You present mean years between diagnosis and death. It would be helpful to present data on disease duration (symptom onset to death) if available.

- There were 37 male patients and 36 patients who identified as male. Was one patient transgender? Consider changing sex and gender to “biological sex” and “gender identity” to avoid confusion.

- Caregivers most commonly reported that individuals with DLB died from the DLB itself. How? Please elaborate.

- In the section “Healthcare factors associated with Positive or Negative Experiences,” please describe the negative factors in more detail. For example, what were the negative experiences surrounding hospice care?

Discussion:

- A 90% hospice utilization rate is quite high, even if initiated later than appropriate. Could the high utilization rate be based on referral patterns from outpatient doctors (more than 50% saw a DLB specialist) or due to participant bias, given that data were drawn from patients who were willing to participate in end-of-life care research? I would add this to study limitations since this affects generalizability.

General:

- Writing could be more concise, particularly in the introduction

Reviewer #2: The paper is good and interesting but needs minor revision. See my comments below

Abstract

It does not have conclusion which should be strictly based on the results

Discussion should be deleted from the abstract

Introduction

DLB expand to full at the beginning of the statement

Study visits and measures

Correct priori

Please be specific of what you did in the research-visits were completed over multiple

days if needed

Data Availability

Indicate the author to contact for data availability

Sample size of 50

It is small, you would have followed more subjects

Conclusion

Remove the table you mentioned on the conclusion. The conclusion is too long. Kindly summarise the key findings and implications

**********

6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

**********

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End-of-Life Experiences in Individuals with Dementia with Lewy Bodies and their Caregivers: a Mixed-Methods Analysis

PONE-D-24-08238R1

Dear Dr Melissa J. Armstrong.

Thank you for addressing the comments and resubmitting your interesting manuscript that explores caregiver-reported end-of-life experiences in DLB.

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,

Hope Onohuean, PhD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

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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: Yes

Reviewer #2: Yes

**********

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

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

Reviewer #1: Yes

Reviewer #2: Yes

**********

6. Review Comments to the Author

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

Reviewer #1: (No Response)

Reviewer #2: The comments have been addressed from the concerns raised in the reviews. The paper is interesting and highly recommnded

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: Yes: Emmanuel Ifeanyi Obeagu

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