Review for 10.1186/s12876-021-01623-w (2021)

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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