Reviewer’s report
Title: 
Premedication with reformulated simethicone and sodium bicarbonate
improves mucosal visibility during upper gastrointestinal endoscopy: A double-
blind, multicenter, randomized controlled trial
Version: 
1 
Date: 
10 Nov 2020
Reviewer's report:
I reviewed the submission by Chen et al on the 
role of simethicone formulation
to prevent white flocculate precipitation during upper GI endoscopy. In this
double-blind RCT (retrospectively registered under ChiCTR1900021689),
patients were randomised to 45ml of intervention (30ml 5% sodium bicarbonate
+ 15ml simethicone) vs 45ml of water. Outcomes studied include the presence of
"white precipitant", mucosal visibility (measured on a tool used by Lee et al),
flush volumes, procedure times, and patient outcomes of abdominal pain and
distension. Prior to the RCT, the authors conducted in vitro experiments and
found that intragastric pH >5.5 was associated with better views (less white
precipitation) which formed the composition used in the intervention arm. With
the exception of nausea, all outcomes studied were superior in favour of the
treatment arm, leading the authors to conclude that premedication with their
mixed solution can prevent white precipitation and enhance mucosal views. The
authors should be commended for their RCT. I have a few minor comments:
1) How many endoscopists were involved? Did they crossover between groups?
Did the outcomes vary by endoscopist? Mention under limitations if you don't
have this data.
2) It is arguable that the Scores of 2 or even 3 for each segment would not have
missed any pathology. What was the target level cleanliness which endoscopists
were instructed to achieve? This would have an impact on flush volumes and
procedure times. 
3) Given that the study is predicated on better mucosal visibility to reduce the
risk of missed cancers, what were the endoscopic findings and were they
different between groups?
4) Under methods, please comment how long patients were fasted before the
procedure.
5) Patients underwent procedures without sedation or anaesthesia. Did they
receive pharyngeal anaesthesia?
6) Many guidelines now mandate a minimum inspection time - would that have
influenced your inspection times in Groups A and B?
7) I suggest improving the title as the presence of white flocculate precipitation
was actually not reported in the results section. Instead, the results centred on
mucosal visualisation scores. Randomized controlled trial should also be
specified in the title.
8) If the data had not been previously published, I believe that the results of the
in vitro experiments to determine the optimal simethicone volume (summarised
above) are important and should be elaborated more in the results section and
even briefly in the abstract.
9) The reduction in abdominal pain is an important patient-centred outcome. I
could not find details on how this was measured in the paper or in the online trial
registration document. This should be specified under Methods to include the
scale used and how long after the procedure this was taken. The results have
enough importance to be emphasised in the Discussion, Abstract and perhaps
even the title. 
10) Under Discussion, a lot of weight has been given to the importance of
NaHCO3. You mentioned about your laboratory experiment and cited Reference
13. Please check if this is the correct reference. Has the addition of sodium
bicarbonate to simethicone been shown to be beneficial?
11) Please elaborate on NaHCO3 - I would suggest using sodium bicarbonate
instead.
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Yes
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.
None
Reviewer Publication Consent.
 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
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the editorial
office before completing the review.
If you wish, you can include your name in your published report. Please note
you must decide whether to include your name at the start of the process and
confirm this decision whenever prompted. If you change your decision later, we
will not be able to publish your name.
I agree to the terms of the CC-BY 4.0 license; please publish my name with my
report.
Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
Yes
Are the methods sufficiently described to allow the study to be repeated?
Yes
Is the use of statistics and treatment of uncertainties appropriate?
Yes
Is the presentation of the work clear?
Yes
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
Reviewer’s report
Title: 
Premedication with reformulated simethicone and sodium bicarbonate
improves mucosal visibility during upper gastrointestinal endoscopy: A double-
blind, multicenter, randomized controlled trial
Version: 
1 
Date: 
10 Nov 2020
Reviewer's report:
I reviewed the submission by Chen et al on the 
role of simethicone formulation
to prevent white flocculate precipitation during upper GI endoscopy. In this
double-blind RCT (retrospectively registered under ChiCTR1900021689),
patients were randomised to 45ml of intervention (30ml 5% sodium bicarbonate
+ 15ml simethicone) vs 45ml of water. Outcomes studied include the presence of
"white precipitant", mucosal visibility (measured on a tool used by Lee et al),
flush volumes, procedure times, and patient outcomes of abdominal pain and
distension. Prior to the RCT, the authors conducted in vitro experiments and
found that intragastric pH >5.5 was associated with better views (less white
precipitation) which formed the composition used in the intervention arm. With
the exception of nausea, all outcomes studied were superior in favour of the
treatment arm, leading the authors to conclude that premedication with their
mixed solution can prevent white precipitation and enhance mucosal views. The
authors should be commended for their RCT. I have a few minor comments:
1) How many endoscopists were involved? Did they crossover between groups?
Did the outcomes vary by endoscopist? Mention under limitations if you don't
have this data.
2) It is arguable that the Scores of 2 or even 3 for each segment would not have
missed any pathology. What was the target level cleanliness which endoscopists
were instructed to achieve? This would have an impact on flush volumes and
procedure times. 
3) Given that the study is predicated on better mucosal visibility to reduce the
risk of missed cancers, what were the endoscopic findings and were they
different between groups?
4) Under methods, please comment how long patients were fasted before the
procedure.
5) Patients underwent procedures without sedation or anaesthesia. Did they
receive pharyngeal anaesthesia?
6) Many guidelines now mandate a minimum inspection time - would that have
influenced your inspection times in Groups A and B?
7) I suggest improving the title as the presence of white flocculate precipitation
was actually not reported in the results section. Instead, the results centred on
mucosal visualisation scores. Randomized controlled trial should also be
specified in the title.
8) If the data had not been previously published, I believe that the results of the
in vitro experiments to determine the optimal simethicone volume (summarised
above) are important and should be elaborated more in the results section and
even briefly in the abstract.
9) The reduction in abdominal pain is an important patient-centred outcome. I
could not find details on how this was measured in the paper or in the online trial
registration document. This should be specified under Methods to include the
scale used and how long after the procedure this was taken. The results have
enough importance to be emphasised in the Discussion, Abstract and perhaps
even the title. 
10) Under Discussion, a lot of weight has been given to the importance of
NaHCO3. You mentioned about your laboratory experiment and cited Reference
13. Please check if this is the correct reference. Has the addition of sodium
bicarbonate to simethicone been shown to be beneficial?
11) Please elaborate on NaHCO3 - I would suggest using sodium bicarbonate
instead.
Publons Reviewer Recognition
. Springer Nature can send verification of this
review directly to Publons (a subsidiary of Clarivate Analytics). If you would
like to take advantage of this service, please click on the “Yes” option below.
Your name, email address, title of the reviewed manuscript, name of the journal,
and date of your review submission (the “Review Data”) will then be transmitted
to Publons upon publication of the manuscript. If you have already registered at
Publons, they will notify you of the receipt of this review and update your profile
as per your settings and their policy. If you are not registered with Publons, you
will receive an email from them asking you to register in order for them to be
able to recognize your review on your new profile page. Publons may use the
Review Data to generate derivative metadata for the benefit of Publons and you
as a reviewer, carefully considering the sensitivity of such information. For
example, Publons may verify your record as a reviewer by updating your profile
published on its webservice if you have registered for such service or help
editors to identify candidate reviewers. Please find the details of processing in
Publons’ privacy policy 
https://publons.com/about/terms
Yes
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.
None
Reviewer Publication Consent.
 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
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the editorial
office before completing the review.
If you wish, you can include your name in your published report. Please note
you must decide whether to include your name at the start of the process and
confirm this decision whenever prompted. If you change your decision later, we
will not be able to publish your name.
I agree to the terms of the CC-BY 4.0 license; please publish my name with my
report.
Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
Yes
Are the methods sufficiently described to allow the study to be repeated?
Yes
Is the use of statistics and treatment of uncertainties appropriate?
Yes
Is the presentation of the work clear?
Yes
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
Please review this paper.
user
Reviewer’s report
Title: 
Premedication with reformulated simethicone and sodium bicarbonate
improves mucosal visibility during upper gastrointestinal endoscopy: A double-
blind, multicenter, randomized controlled trial
Version: 
1 
Date: 
10 Nov 2020
Reviewer's report:
I reviewed the submission by Chen et al on the 
role of simethicone formulation
to prevent white flocculate precipitation during upper GI endoscopy. In this
double-blind RCT (retrospectively registered under ChiCTR1900021689),
patients were randomised to 45ml of intervention (30ml 5% sodium bicarbonate
+ 15ml simethicone) vs 45ml of water. Outcomes studied include the presence of
"white precipitant", mucosal visibility (measured on a tool used by Lee et al),
flush volumes, procedure times, and patient outcomes of abdominal pain and
distension. Prior to the RCT, the authors conducted in vitro experiments and
found that intragastric pH >5.5 was associated with better views (less white
precipitation) which formed the composition used in the intervention arm. With
the exception of nausea, all outcomes studied were superior in favour of the
treatment arm, leading the authors to conclude that premedication with their
mixed solution can prevent white precipitation and enhance mucosal views. The
authors should be commended for their RCT. I have a few minor comments:
1) How many endoscopists were involved? Did they crossover between groups?
Did the outcomes vary by endoscopist? Mention under limitations if you don't
have this data.
2) It is arguable that the Scores of 2 or even 3 for each segment would not have
missed any pathology. What was the target level cleanliness which endoscopists
were instructed to achieve? This would have an impact on flush volumes and
procedure times. 
3) Given that the study is predicated on better mucosal visibility to reduce the
risk of missed cancers, what were the endoscopic findings and were they
different between groups?
4) Under methods, please comment how long patients were fasted before the
procedure.
5) Patients underwent procedures without sedation or anaesthesia. Did they
receive pharyngeal anaesthesia?
6) Many guidelines now mandate a minimum inspection time - would that have
influenced your inspection times in Groups A and B?
7) I suggest improving the title as the presence of white flocculate precipitation
was actually not reported in the results section. Instead, the results centred on
mucosal visualisation scores. Randomized controlled trial should also be
specified in the title.
8) If the data had not been previously published, I believe that the results of the
in vitro experiments to determine the optimal simethicone volume (summarised
above) are important and should be elaborated more in the results section and
even briefly in the abstract.
9) The reduction in abdominal pain is an important patient-centred outcome. I
could not find details on how this was measured in the paper or in the online trial
registration document. This should be specified under Methods to include the
scale used and how long after the procedure this was taken. The results have
enough importance to be emphasised in the Discussion, Abstract and perhaps
even the title. 
10) Under Discussion, a lot of weight has been given to the importance of
NaHCO3. You mentioned about your laboratory experiment and cited Reference
13. Please check if this is the correct reference. Has the addition of sodium
bicarbonate to simethicone been shown to be beneficial?
11) Please elaborate on NaHCO3 - I would suggest using sodium bicarbonate
instead.
Publons Reviewer Recognition
. Springer Nature can send verification of this
review directly to Publons (a subsidiary of Clarivate Analytics). If you would
like to take advantage of this service, please click on the “Yes” option below.
Your name, email address, title of the reviewed manuscript, name of the journal,
and date of your review submission (the “Review Data”) will then be transmitted
to Publons upon publication of the manuscript. If you have already registered at
Publons, they will notify you of the receipt of this review and update your profile
as per your settings and their policy. If you are not registered with Publons, you
will receive an email from them asking you to register in order for them to be
able to recognize your review on your new profile page. Publons may use the
Review Data to generate derivative metadata for the benefit of Publons and you
as a reviewer, carefully considering the sensitivity of such information. For
example, Publons may verify your record as a reviewer by updating your profile
published on its webservice if you have registered for such service or help
editors to identify candidate reviewers. Please find the details of processing in
Publons’ privacy policy 
https://publons.com/about/terms
Yes
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.
None
Reviewer Publication Consent.
 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
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the editorial
office before completing the review.
If you wish, you can include your name in your published report. Please note
you must decide whether to include your name at the start of the process and
confirm this decision whenever prompted. If you change your decision later, we
will not be able to publish your name.
I agree to the terms of the CC-BY 4.0 license; please publish my name with my
report.
Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
Yes
Are the methods sufficiently described to allow the study to be repeated?
Yes
Is the use of statistics and treatment of uncertainties appropriate?
Yes
Is the presentation of the work clear?
Yes
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
assistant