PONE-D-19-23454

Actigraphy assessment of motor activity and sleep in patients with alcohol withdrawal syndrome and the effects of intranasal oxytocin

PLOS ONE

Dear Ms Melby,

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.

The manuscript has been assessed by two reviewers, their comments are available below.

The reviewers have raised some major concerns which need attention in a revision. The reviewers feel that the rationale for investigating sleep in this population should be further articulated and justified, and they recommend further discussion of how the study relates to earlier published work reporting the use of oxytocin on alcohol withdrawal symptoms. The reviewers note that the inclusion and exclusion criteria should be reported in greater detail and they raise questions about the sample size calculation.

Please carefully revise the manuscript to address the reviewers’ concerns. 

We would appreciate receiving your revised manuscript by Dec 09 2019 11:59PM. When you are 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,

Iratxe Puebla

Senior Managing Editor, PLOS ONE

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3. Thank you for including your ethics statement: The randomized controlled trial was approved by the Regional Ethics Committee (2016/45) and the Norwegian Medical Agency (2015-004463-37) and is registered in clinicaltrials.gov (identifier NCT02903251). It was also approved by the User Council at the addiction treatment center. The use of healthy individuals was approved by the Regional Ethics Committee in a separate application (2011/1668). All patients and controls gave their informed written consent prior to inclusion in the study.

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4. Thank you for submitting your manuscript for consideration by PLOS ONE.

We note that your study is closely related to the following publications, on which you are an author:

https://doi.org/10.1016/j.drugalcdep.2019.01.003

Please cite and discuss the above study in the introduction and discussion sections of your manuscript, clarifying how the present work is related to the previously published paper.

Please note that our second publication criterion states that "If a submitted study replicates or is very similar to previous work, authors must provide a sound scientific rationale for the submitted work and clearly reference and discuss the existing literature. Submissions that replicate or are derivative of existing work will likely be rejected if authors do not provide adequate justification." http://www.plosone.org/static/publication.action#results.

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We will update your Data Availability statement on your behalf to reflect the information you provide.

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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: Partly

Reviewer #2: Partly

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

Reviewer #1: Yes

Reviewer #2: No

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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: 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 could potentially present valuable data that could add to the literature in a meaningful way, however, I think the authors need to refine their presentation of this data to create a more logical rationale for investigating sleep in alcohol withdrawal in the context of an OT clinical trial. I have 3 major comments on this manuscript:

1 What is the rationale for expecting OT to affect actigraphy and sleep related outcome measures?

2 A more rational approach would be for Part 1 to establish group differences (AUD vs controls) in actigraphy/ sleep outcomes. Then look for an effect of OT on these outcomes in AUD patients in withdrawal with a rationale to do so. That is, there any evidence that OT affects motor activity or sleep (there is some literature on this).

3 This seems a lost opportunity to report whether this study replicated a previous study on the effect of OT on alcohol withdrawal symptoms, craving and benzo requirement during withdrawal (Pedersen et al. 2013). If it does not have an effect on withdrawal symptoms then why should it have an effect on activity and sleep disturbances related to alcohol withdrawal.

Reviewer #2: The manuscript entitled 'Actigraphy assessment of motor activity and sleep in patients with alcohol withdrawal syndrome and the effects of intranasal oxytocin' with the aims to explore whether 1) actigraphy could be used as a tool to register symptoms during detoxification, 2) oxytocin affected actigraphy variables related to motor activity and sleep compared to placebo during detoxification, and 3) actigraphy-recorded motor function during detoxification was different from that in healthy controls.

This is quite an interesting study but the manuscript requires further improvement.

Comments

Abstract

Line 53, the sentence requires revision.

Materials and Methods

Line 96-103, all the details to be labelled using the word inclusion and exclusion criteria. There was no information on the inclusion and exclusion criteria for the controls. What are the characteristics of these subjects i.e. medical history, social history, occupation, psychological (stress, anxiety etc) etc. More information to be provided on type of occupation.

Table 1 requires cosmetic changes. At least one decimal point for the percentages. The symbol % for individual figures to be omitted since it was stated on the left column. There was no alcohol level measurement for the healthy controls. The p value - for the number of subjects to be omitted.

Line 130, for from1. 1 to be spaced from the word from.

Line 189 - 194, these sections to be included in their respective part in the earlier section in Page 8.

Line 195, proper citation for the SPSS including the publisher name to be stated.

There was no consideration of the attrition rates in the sample size calculation to derive the sample size.

Results

Statistical test(s) to be denoted in all the tables.

Line 199-200, the word mean to be stated.

Line 216 & Line 217, p values to be stated.

Table 2, decimal points to be standardized. For standardization, the word mean to be written in all variables.

Table 3, 2 subjects who were not included in the analysis to be denoted in the table footnote. For the title, n=38 to be stated rather than 40. Please ensure all the numbers stated in the figures and tables title are correct.

Line 243. phosphatidylethanol blood, Oxazepam dose to be stated.

Line 250-152, p value to be provided.

Table 4 and Table 5, results to be presented according to oxytocin group, placebo group and overall group.

Table 6, separate group (oxytocin and placebo group) to be presented.

Figure 2, 3, n to be stated.

References to conform with the journal format.

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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

[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 to be viewed.]

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 us at figures@plos.org. Please note that Supporting Information files do not need this step.

PONE-D-19-23454R1

Actigraphy assessment of motor activity and sleep in patients with alcohol withdrawal syndrome and the effects of intranasal oxytocin

PLOS ONE

Dear Ms Melby,

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 address minor comments.

==============================

We would appreciate receiving your revised manuscript by Feb 29 2020 11:59PM. When you are 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.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter.

To enhance the reproducibility of your results, we recommend that if applicable you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

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). This letter should be uploaded as separate file and labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. This file should be uploaded as separate file and labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. This file should be uploaded as separate file and labeled 'Manuscript'.

Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out.

We look forward to receiving your revised manuscript.

Kind regards,

Shahrad Taheri

Academic Editor

PLOS ONE

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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 #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 #2: (No Response)

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

Reviewer #2: (No Response)

**********

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 #2: (No Response)

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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 #2: (No Response)

**********

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 #2: Authors have put in great effort to address the comments.

Minor comment(s)

Line 175, the symbol > and < for the power and alpha to be replaced with symbol = and the sentence to be rephrased.

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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 #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 to be viewed.]

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 us at figures@plos.org. Please note that Supporting Information files do not need this step.

Actigraphy assessment of motor activity and sleep in patients with alcohol withdrawal syndrome and the effects of intranasal oxytocin

PONE-D-19-23454R2

Dear Dr. Melby,

We are pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it complies with all outstanding technical requirements.

Within one week, you will receive an e-mail containing information on the amendments required prior to publication. When all required modifications have been addressed, you will receive a formal acceptance letter and your manuscript will proceed to our production department and be scheduled for publication.

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With kind regards,

Shahrad Taheri

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments: