Review for 10.1186/s12876-020-1173-z (2020)

Reviewer’s report
Title: Prevention and management of diarrhea associated with naldemedine among patients
receiving opioids: a retrospective cohort study
Version: 1 Date: 30 Sep 2019
Reviewer: Reviewer 2
Reviewer's report:
PEER REVIEWER ASSESSMENTS: 
OBJECTIVE - Full research articles: is there a clear objective that addresses  a testable research
question(s) (brief or other article types: is there a clear objective)?
Yes - there is a clear objective
DESIGN - Is the current approach (including controls and analysis protocols) appropriate for the
objective?
Yes - the approach is appropriate
EXECUTION - Are the experiments and analyses performed with technical rigor to allow confidence
in the results?
Yes - experiments and analyses were performed appropriately
STATISTICS - Is the use of statistics in the manuscript appropriate?
Yes - appropriate statistical analyses have been used in the study
INTERPRETATION  -  Is  the  current  interpretation/discussion  of  the  results  reasonable  and  not
overstated?
Yes - the author's interpretation is reasonable
OVERALL MANUSCRIPT POTENTIAL - Is the current version of this work technically sound? If
not, can revisions be made to make the work technically sound?
Yes - current version is technically sound
PEER REVIEWER COMMENTS: 
GENERAL COMMENTS: This is a multi-centre retrospective cohort study that demonstrated a good
clinical outcome in preventing/intervening OIC. 
Further  improvements  required  are  1.  Improve  the  flow  by  using,  e.g.  Summary  Tables  and  2.
Specifically, mention, discuss and summarise the risk factors for adverse events, which is the aim of
this study. 
REQUESTED REVISIONS: 
There are a couple of questions.
1. What is the reason/s that CTCAE, ECOG-PS scoring system were used? What are their relationships
in this study?
2. Authors should provide the ethnic backgrounds and BMI (if available) of the participants. 
3. Page 2, line 24: How did Authors decide "taken at least one dose of naldemedine between June 2017
and  March  2018"  criteria?  Was  the  dosing  regimen  for  the  opioid  treatments,  as  well  as
naldemedien/other laxatives of each patient documented and made available as supplementary info?
There are many patients with each received different opioid/laxatives treatments. It will be much easier
to read with a summarised table. 
4. Page 6, line 14: "A phase 3 randomized placebo-controlled trial of naldemedine for cancer patients
with OIC significantly increased spontaneous bowel movements". OIC is known evoked by two major
mechanisms, 1. Bowel movements and 2. Re-hydration of the stool. Has naldemedine also improved
opioids induced de-hydration of stool?  
5. Page 6, line 36: Under the Discussion/Conclusion sections, the risk factors for adverse events should
be mentioned, discussed and summarised. 
6.  Page  7,  line  27:  How  did  individual  physician  decide  when  to  start  and  discontinue  use  of
naldemedine or other laxatives?  Were these decisions based on the, e.g. CTCAE Grades? 
7. Page 9, lines: 12-13: "Data from patients without daily defecation counts from day -1 to day +1 from
the first naldemedine dose were excluded from analysis". Why excluded these patients? Is this to
exclude the non-responders? If yes, how many of them? 
8. Page 11, line 51: "female, 8 (47%)" should write as "female, 8/17 (47%)". This should be applied
throughout the entire manuscript. 
9.  What  are  the  perceived  benefits  of  using  naldemedine  as  a  prevention/intervention  treatment
compared to other laxatives?
Are the methods appropriate and well described?
If not, please specify what is required in your comments to the authors.
Yes
Does the work include the necessary controls?
If not, please specify which controls are required in your comments to the authors.
Yes
Are the conclusions drawn adequately supported by the data shown?
If not, please explain in your comments to the authors.
Yes
Are you able to assess any statistics in the manuscript or would you recommend an
additional statistical review?
If an additional statistical review is recommended, please specify what aspects require further
assessment in your comments to the editors.
I am able to assess the statistics
Quality of written English
Please indicate the quality of language in the manuscript:
Acceptable
Declaration of competing interests
Please complete a declaration of competing interests, considering the following questions:
1. Have you in the past five years received reimbursements, fees, funding, or salary from an
organisation that may in any way gain or lose financially from the publication of this
manuscript, either now or in the future?
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose
financially from the publication of this manuscript, either now or in the future?
3. Do you hold or are you currently applying for any patents relating to the content of the
manuscript?
4. Have you received reimbursements, fees, funding, or salary from an organization that holds
or has applied for patents relating to the content of the manuscript?
5. Do you have any other financial competing interests?
6. Do you have any non-financial competing interests in relation to this paper?
If you can answer no to all of the above, write 'I declare that I have no competing interests' below.
If your reply is yes to any, please give details below.
This reviewer has been recruited by a partner organization, Research Square. Reviewers with declared
or  apparent  competing  interests  are  not  utilized  for  these  reviews.  This  reviewer  has  agreed  to
publication of their comments online under a Creative Commons Attribution License attributed to
Research Square and was paid a small honorarium for completing the review  within a specified
timeframe. Honoraria for reviews such as this are paid regardless of the reviewer recommendation.
I agree to the open peer review policy of the journal. I understand that my name will be included
on my report to the authors and, if the manuscript is accepted for publication, my named report
including any attachments I upload will be posted on the website along with the authors'
responses. I agree for my report to be made available under an Open Access Creative Commons
CC-BY license (http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments
which I do not wish to be included in my named report can be included as confidential comments
to the editors, which will not be published.
I agree to the open peer review policy of the journal