Reviewer's report
Title:Controlling on demand gastric acidity in obese subjects: a randomized
controlled trial comparing a single dose of rabeprazole 20 mg and omeprazole 20
mg.
Version:2Date:27 February 2014
Reviewer: Carmelo Scarpignato
Reviewer's report:
This is an important work addressing a clinically relevant clinical question, i.e.
pharmacodynamic activity of proton pump inhibitors (PPIs) in obese patients with
GERD and its potential therapeutic consequences.
The paper is well written, the methodology is suitable to the aims of the study
and described accurately, and data are presented and discussed clearly. In
addition, strengths and limitations of the study are honestly acknowledged.
I have no major criticism to this study, but would like to offer some suggestions in
the hope to improve the already good level of the paper:
1) Although the omeprazole dose (i.e. 20 mg daily) is the approved daily dose in
the treatment of GERD, several pharmacodynamics studies have shown that it is
NOT equivalent to the approved regimens of the other PPIs (namely
lansoprazole, pantoprazole and rabeprazole). In addition, the inter-individual
variability of the antisecretory action of the 20 mg dose of omeprazole has been
well described from its introduction in our therapeutic armamentarium. The
Authors should mention these findings together with the relevant references.
2) Although NAB was originally defined as the occurrence of intra-gastric pH<4
for more than 1 h from 10:00 PM to 08:00 AM, it was later observed that its
occurrence is more frequent after midnight, when the effect of (even a double
dose of) PPIs is vanished. It would interesting therefore to compare two periods
of observations, i.e. 10:00 PM to 08:00 AM and 00:00 AM to 08:00.
3) The Authors reported the occurrence of NAB but not its duration (min). These
data should be provided in the paper. I suspect that the difference between
rabeprazole and omeprazole will be significant also for this parameter.
4) The evaluation of antisecretory activity of rabeprazole and omeprazole
showed that the first PPI gave a more consistent acid inhibitory effect and this
was shown, statistically, by the fact that – for any period – variances for each
parameter were lower for rabeprazole than for omeprazole. An elegant (and very
convincing) way to show this is a graph, where the single values of different
parameters (e.g. time spent over pH 3 and intragastric pH) - before and after
treatment - are shown. Each individual value (on the left and right side of the
graph) should be joined by a line, so that the final result will give a clear picture of
the trend observed. A coefficient of variation should be calculated and given.
5) Discussion. It is evident that the final word on the obesity’s effect on PPI
pharmacokinetics and pharmacodynamics will be given by a study, investigating
both activities of a given PPI before and after weight reduction, be it obtained by
medical or surgical treatment. This perspective should be given in closing the
Discussion.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
Conflict of interest: NONE
Reviewer's report
Title:Controlling on demand gastric acidity in obese subjects: a randomized
controlled trial comparing a single dose of rabeprazole 20 mg and omeprazole 20
mg.
Version:2Date:27 February 2014
Reviewer: Carmelo Scarpignato
Reviewer's report:
This is an important work addressing a clinically relevant clinical question, i.e.
pharmacodynamic activity of proton pump inhibitors (PPIs) in obese patients with
GERD and its potential therapeutic consequences.
The paper is well written, the methodology is suitable to the aims of the study
and described accurately, and data are presented and discussed clearly. In
addition, strengths and limitations of the study are honestly acknowledged.
I have no major criticism to this study, but would like to offer some suggestions in
the hope to improve the already good level of the paper:
1) Although the omeprazole dose (i.e. 20 mg daily) is the approved daily dose in
the treatment of GERD, several pharmacodynamics studies have shown that it is
NOT equivalent to the approved regimens of the other PPIs (namely
lansoprazole, pantoprazole and rabeprazole). In addition, the inter-individual
variability of the antisecretory action of the 20 mg dose of omeprazole has been
well described from its introduction in our therapeutic armamentarium. The
Authors should mention these findings together with the relevant references.
2) Although NAB was originally defined as the occurrence of intra-gastric pH<4
for more than 1 h from 10:00 PM to 08:00 AM, it was later observed that its
occurrence is more frequent after midnight, when the effect of (even a double
dose of) PPIs is vanished. It would interesting therefore to compare two periods
of observations, i.e. 10:00 PM to 08:00 AM and 00:00 AM to 08:00.
3) The Authors reported the occurrence of NAB but not its duration (min). These
data should be provided in the paper. I suspect that the difference between
rabeprazole and omeprazole will be significant also for this parameter.
4) The evaluation of antisecretory activity of rabeprazole and omeprazole
showed that the first PPI gave a more consistent acid inhibitory effect and this
was shown, statistically, by the fact that – for any period – variances for each
parameter were lower for rabeprazole than for omeprazole. An elegant (and very
convincing) way to show this is a graph, where the single values of different
parameters (e.g. time spent over pH 3 and intragastric pH) - before and after
treatment - are shown. Each individual value (on the left and right side of the
graph) should be joined by a line, so that the final result will give a clear picture of
the trend observed. A coefficient of variation should be calculated and given.
5) Discussion. It is evident that the final word on the obesity’s effect on PPI
pharmacokinetics and pharmacodynamics will be given by a study, investigating
both activities of a given PPI before and after weight reduction, be it obtained by
medical or surgical treatment. This perspective should be given in closing the
Discussion.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
Conflict of interest: NONE
Please review this paper.
user
Reviewer's report
Title:Controlling on demand gastric acidity in obese subjects: a randomized
controlled trial comparing a single dose of rabeprazole 20 mg and omeprazole 20
mg.
Version:2Date:27 February 2014
Reviewer: Carmelo Scarpignato
Reviewer's report:
This is an important work addressing a clinically relevant clinical question, i.e.
pharmacodynamic activity of proton pump inhibitors (PPIs) in obese patients with
GERD and its potential therapeutic consequences.
The paper is well written, the methodology is suitable to the aims of the study
and described accurately, and data are presented and discussed clearly. In
addition, strengths and limitations of the study are honestly acknowledged.
I have no major criticism to this study, but would like to offer some suggestions in
the hope to improve the already good level of the paper:
1) Although the omeprazole dose (i.e. 20 mg daily) is the approved daily dose in
the treatment of GERD, several pharmacodynamics studies have shown that it is
NOT equivalent to the approved regimens of the other PPIs (namely
lansoprazole, pantoprazole and rabeprazole). In addition, the inter-individual
variability of the antisecretory action of the 20 mg dose of omeprazole has been
well described from its introduction in our therapeutic armamentarium. The
Authors should mention these findings together with the relevant references.
2) Although NAB was originally defined as the occurrence of intra-gastric pH<4
for more than 1 h from 10:00 PM to 08:00 AM, it was later observed that its
occurrence is more frequent after midnight, when the effect of (even a double
dose of) PPIs is vanished. It would interesting therefore to compare two periods
of observations, i.e. 10:00 PM to 08:00 AM and 00:00 AM to 08:00.
3) The Authors reported the occurrence of NAB but not its duration (min). These
data should be provided in the paper. I suspect that the difference between
rabeprazole and omeprazole will be significant also for this parameter.
4) The evaluation of antisecretory activity of rabeprazole and omeprazole
showed that the first PPI gave a more consistent acid inhibitory effect and this
was shown, statistically, by the fact that – for any period – variances for each
parameter were lower for rabeprazole than for omeprazole. An elegant (and very
convincing) way to show this is a graph, where the single values of different
parameters (e.g. time spent over pH 3 and intragastric pH) - before and after
treatment - are shown. Each individual value (on the left and right side of the
graph) should be joined by a line, so that the final result will give a clear picture of
the trend observed. A coefficient of variation should be calculated and given.
5) Discussion. It is evident that the final word on the obesity’s effect on PPI
pharmacokinetics and pharmacodynamics will be given by a study, investigating
both activities of a given PPI before and after weight reduction, be it obtained by
medical or surgical treatment. This perspective should be given in closing the
Discussion.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
Conflict of interest: NONE
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