PONE-D-20-40765

Anxiolytic benzodiazepines may induce severe delirium in patients with acute decompensated heart failure

PLOS ONE

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PLOS ONE

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Reviewers' comments:

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Comments to the Author

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Reviewer #1: Yes

Reviewer #2: Yes

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

Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: No

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Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

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

Reviewer #1: This study is aimed to evaluate the association of anxiolytic benzodiazepines use with delirium and their additive predictive value in models based on conventional risk factors. Data derived from a single-center, retrospective study, that enrolled 650 patients treated for ADHF. Fifty-nine patients (9.1%) had delirium. In multivariate analysis, anxiolytic benzodiazepines, mechanical ventilation or noninvasive positive pressure ventilation, depression, intensive care or high care unit admission, male sex, and age were independently associated with severe delirium. The predictive model that included anxiolytic benzodiazepines had a significantly better discriminatory ability for the incidence of

severe delirium than the conventional model.

The study is of great interest, even if data derived from a single-center study, results confirmed also in HF patients the use of anxiolytic benzodiazepines as risk factor for severe delirium. Table 1 and 2 should be better presented.

Reviewer #2: The authors retrospectively studied if delirium in patients with acute decompensated heart failure (ADHF) was associated with poor clinical outcomes in 650 patients treated for ADHF. Fifty-nine patients (9.1%) had delirium. In multivariate analysis, anxiolytic benzodiazepines [odds ratio (OR): 6.4, 95% confidence interval (CI): 2.8–15], mechanical ventilation or noninvasive positive pressure ventilation (OR: 6.0, 95% CI: 2.9–12), depression (OR: 3.2, 95% CI: 1.5–6.5), intensive care or high care unit admission (OR: 2.9, 95% CI: 1.5–5.6), male sex (OR: 2.0, 95% CI: 1–3.7), and age (OR: 1.1, 95% CI: 1–1.1) were independently associated with severe delirium. The predictive model that included anxiolytic benzodiazepines had a significantly better discriminatory ability for the incidence of severe delirium than the conventional model.

The manuscript is interesting and topic. However, I have some concerns about the precipitating factors for ADHF considered. Please see and discuss Testa G et al. Precipitating factors in younger and older adults with decompensated chronic heart failure: are they different? J Am Geriatr Soc. 2013 Oct;61(10):1827-8.

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Reviewer #1: Yes: Francesco Cacciatore

Reviewer #2: No

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Added value of anxiolytic benzodiazepines in predictive models on severe delirium in patients with acute decompensated heart failure: a retrospective analysis

PONE-D-20-40765R1

Dear Dr. KAWADA,

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.

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Kind regards,

Pasquale Abete

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

No further comments.

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

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

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

Reviewer #1: Yes

Reviewer #2: Yes

**********

6. Review Comments to the Author

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

Reviewer #1: (No Response)

Reviewer #2: The manuscript is really improved and all the questions are correctly answered. The manuscript merits to be published in PONE.

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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: francesco cacciatore

Reviewer #2: No